6-Benzyladenine Final RR 1107 EXILIS Part B Section 7

Part A Exilis Registration Report - Central Zone National Assessment – Germany Page 1 of 21

REGISTRATION REPORT Part A

Risk Management

Product code: Exilis Active Substance: 6-Benzyladenine (20 g/L)

COUNTRY: Germany Central Zone Zonal Rapporteur Member State: Germany

NATIONAL ASSESSMENT UPDATE 15/06/2017

Applicant: Fine Agrochemicals Limited Date: 18/02/2013

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Table of Contents

PART A – Risk Management 4 1 Details of the application 4 1.1 Application background 4 1.2 Annex I inclusion 5 1.3 Regulatory approach 5 1.4 Data protection claims 5 1.5 Letters of Access 5 2 Details of the authorisation 6 2.1 Product identity 6 2.2 Classification and labelling 6 2.2.1 Classification and labelling under Directive 99/45/EC 6 2.2.2 R and S phrases under Directive 2003/82/EC (Annex IV and V) 6 2.2.3 Other phrases 6 2.2.3.1 Restrictions linked to the PPP 6 2.2.3.2 Specific restrictions linked to the intended uses 7 2.3 Product uses 8 3 Risk management 10 3.1 Reasoned statement of the overall conclusions taken in accordance with the Uniform Principles 10 3.1.1 Physical and chemical properties (Part B, Section 1, Points 2 and 4) 10 3.1.2 Methods of analysis (Part B, Section 2, Point 5) 10 3.1.2.1 Analytical method for the formulation (Part B, Section 2, Point 5.2) 10 3.1.2.2 Analytical methods for residues (Part B, Section 2, Points 5.3 – 5.8) 10 3.1.3 Mammalian Toxicology (Part B, Section 3, Point 7) 11 3.1.3.1 Acute Toxicity (Part B, Section 3, Point 7.1) 11 3.1.3.2 Operator Exposure (Part B, Section 3, Point 7.4) 11 3.1.3.3 Bystander and Resident Exposure (Part B, Section 3, Point 7.4) 11 3.1.3.4 Worker Exposure (Part B, Section 3, Point 7.4) 11 3.1.4 Residues and Consumer Exposure (Part B, Section 4, Point 8) 12 3.1.4.1 Residues (Part B, Section 4, Points 8.2) 12 3.1.4.2 Consumer exposure (Part B, Section 4, Point 8.3) 12 3.1.5 Environmental fate and behaviour (Part B, Section 5, Point 9) 12 3.1.6 Ecotoxicology (Part B, Section 6, Point 10) 14 3.1.6.2 Effects on Aquatic Species (Part B, Section 6, Point 10.2) 14

Applicant: Fine Agrochemicals Limited Evaluator: DE Date: 18/02/2013

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3.1.6.3 Effects on Bees and Other Arthropod Species (Part B, Section 6, Points 10.4 and 10.5) 15 3.1.6.4 Effects on Earthworms and Other Soil Macro-organisms (Part B, Section 6, Point 10.6) 15 3.1.6.5 Effects on organic matter breakdown (Part B, Section 6, Point 10.6) 16 3.1.6.6 Effects on Soil Non-target Micro-organisms (Part B, Section 6, Point 10.7) 16 3.1.6.7 Assessment of Potential for Effects on Other Non-target Organisms (Flora and Fauna) (Part B, Section 6, Point 10.8) 16 3.1.7 Efficacy (Part B, Section 7, Point 8) 16 3.1.8 Adverse Effects 18 3.2 Conclusions 19 3.3 Further information to permit a decision to be made or to support a review of the conditions and restrictions associated with the authorisation 19 Appendix 1 – Copy of the product authorisation 20 Appendix 2 – Copy of the product label 20 Appendix 3 – Letter of Access 20 Appendix 4 – Additional Report 21

Applicant: Fine Agrochemicals Limited Evaluator: DE Date: 18/02/2013

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PART A – Risk Management This document describes the acceptable use conditions required for the re-registration/registration of Exilis containing 6-Benzyladenine in Germany. This evaluation is required subsequent to the inclusion of 6-Benzyladenine on Annex 1.

The risk assessment conclusions are based on the information, data and assessments provided in Registration Report, Part B Sections 1-7 and Part C and the addendum for Germany. The information, data and assessments provided in Registration Report, Parts B includes assessment of further data or information as required at national re-registration/registration by the EU review. It also includes assessment of data and information relating to Exilis where that data has not been considered in the EU review. Otherwise assessments for the safe use Exilis have been made using endpoints agreed in the EU review of 6-Benzyladenine.

This document describes the specific conditions of use and labelling required for Germany for the re- registration/registration of Exilis.

Appendix 1 of this document provides a copy of the final product authorisation for Germany.

Appendix 2 of this document is a copy of the approved product label for Germany.

The submitted draft product label has been checked by the competent authority. The applicant is requested to amend the product label in accordance with the decisions drawn by the competent authority. The final version of the label is not available, because the layout is the sole responsibility of the applicant and will not be checked again.

Appendix 3 of this document contains copies of the letters of access to the protected data / third party data that was needed for evaluation of the formulation.

Letter(s) of access is/are classified as confidential and, thus, are not attached to this document.

Amendment: Based on a notification of the applicant dated 29/09/2015 accompanied by a report (*) concerning applicability of 75 day PHI the GAP on pome fruit and the respective PHI became re-evaluated. As a result PHI was changed to F (**) and the growth stage of the crops was set to 71 – 72. For further Details, see chapters 2.3 (Product uses), 3.1.4.1 (Residues) and 3.1.7 (Efficacy).

(*) Stephenson, C. and Gill, P., 2015, Justification for a 75 day PHI for the use of 6-benzyladenine (6-BA) on pome fruit. Report Number: 0800299.UK0 – 8179, Exponent International Ltd. (BVL code: 2930762) – see Appendix 4 (**) The PHI is covered by the conditions of use and/or the vegetation period remaining between the application of the plant protection product and the use of the product (e. g. harvest) or the setting of a PHI in days is not required resp.)

1 Details of the application

1.1 Application background This application was submitted by Fine Agrochemicals Limited on 11/10/2011.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013 Part A Exilis Registration Report - Central Zone National Assessment – Germany Page 5 of 21

The application was for approval of Exilis, a soluble concentrate containing 20 g/l 6-Benzyladenine for use as a plant growth regulator for apple and pear orchards.

1.2 Annex I inclusion 6-Benzyladenine was included on Annex I of Directive 91/414/EEC on 3 January 2011 under Inclusion Directive 2011/1/EC and implemented under Regulation (EU) No 540/2011.

The Annex I Inclusion Directive for 6-Benzyladenine (2011/1/EC) provides specific provisions under Part B which need to be considered by the applicant in the preparation of their submission and by the MS prior to granting an authorisation.

For the implementation of the uniform principles of Annex VI, the conclusions of the review report on 6- Benzyladenine, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 23/11/2010 shall be taken into account.

In this overall assessment Member States shall pay particular attention to the: • protection of aquatic organisms. Risk mitigation measures such as buffer zones shall be applied, where appropriate.

These concerns were all addressed in the decision. Expiration of approval: 31/05/2021

1.3 Regulatory approach To obtain approval the product Exilis must meet the conditions of Annex I inclusion and be supported by dossiers satisfying the requirements of Annex II and Annex III, with an assessment to Uniform Principles, using Annex I agreed end-points.

This application was submitted in order to allow the first approval of this product/use in Germany in accordance with the above.

1.4 Data protection claims Where protection for data is being claimed for information supporting registration of Exilis, it is indicated in the reference lists in Appendix I of the Registration Report, Part B, sections 1 - 7 and Part C.

1.5 Letters of Access In the EU Review Report for 6-Benzyladenine (SANCO/12667/2010 final of 4 January 2011) it is indicated that subsequent to the Commission decision 2008/941/EC and in accordance with Article 13 of Regulation (EC) No 33/2008 Fine and Valent Biosciences Corporation (VBC) were the sole data submitters who presented a dossier on 5 May 2009 to the UK as the designated RMS for the active substance. The RMS finalised their examination in October 2009 in the form of an Additional Report to the original Draft Assessment Report. The Additional Report concluded with a recommendation to include 6-benzyladenine in Annex I on the basis of the evaluated uses. Fine and VBC collaborated from the outset of the original dossier submission to the RMS within the framework of an EU Task Force (TF) and an EU TF agreement. It is therefore implicit that Fine as a data submitter and full TF member has full access to the requisite data supporting the Annex I inclusion. This position is substantiated by LOA issued

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2 Details of the authorisation

2.1 Product identity

Product Name Exilis Authorization Number 007524-00/00 (for re-registration) Function growth regulator Applicant Fine Agrochemicals Limited Composition 20 g/L 6-benzyladenine Formulation type Soluble concentrate [Code: SL] Packaging co-extruded PE: 5 and 10 L fluorinated HDPE: 20 L

2.2 Classification and labelling

2.2.1 Classification and labelling under Directive 99/45/EC The following is proposed in accordance with Directive 99/45/EC in combination with the latest classification and labelling guidance under Directive 67/548/EEC (i.e. in the 18th ATP published as Directive 93/21/EEC):

Hazard Symbol: Indication of danger: Risk Phrases: R52 Safety Phrases: S35

2.2.2 R and S phrases under Directive 2003/82/EC (Annex IV and V) Risk Phrases: Safety Phrases:

2.2.3 Other phrases

2.2.3.1 Restrictions linked to the PPP The authorization of the PPP is linked to the following conditions (mandatory labelling):

SB001 Avoid any unnecessary contact with the product. Misuse can lead to health damage. SB010 Keep out of the reach of children.

Applicant: Fine Agrochemicals Limited Evaluator: DE Date: 18/02/2013

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SB110 The directive concerning requirements for personal protective gear in plant protection, "Personal protective gear for handling plant protection products" of the Federal Office of Consumer Protection and Food Safety must be observed. SF245-01 Treated areas/crops may not be entered until the spray coating has dried. SS110 Wear standard protective gloves (plant protection) when handling the undiluted product. NW 262 The product is toxic for algae. [6-benzyladenine: EbC50 = 7.6 mg/L (N. pelliculosa)] NW 264 The product is toxic for fish and aquatic invertebrates. [6-benzyladenine: LC50 > 2.03 mg/L (O. mykiss), EC50 > 2.03 mg/L (Daphnia magna)] NW 265 The product is toxic for higher aquatic plants. [6-benzyladenine: EbC50 = 0,31 mg/L (Lemna gibba)] NW 468 Fluids left over from application and their remains, products and their remains, empty containers and packaging, and cleansing and rinsing fluids must not be dumped in water. This also applies to indirect entry via the urban or agrarian drainage system and to rain-water and sewage canals. WH963 The use of plant growth modifiers can cause undesired side effects depending on the species and variety of the crops and also external conditions. It is recommended to apply the product according to the advice of the plant protection service and taking into consideration the instructions given.

The authorization of the PPP is linked to the following conditions (voluntory labelling):

NB6641 The product is classified as non-hazardous to bees, even when the maximum application rate, or concentration if no application rate is stipulated, as stated for authorisation is applied. (B4) NN1001 The product is classified as non-harmful for populations of relevant beneficial insects.

2.2.3.2 Specific restrictions linked to the intended uses Some of the authorized uses are linked to the following conditions (mandatory labelling): See 2.3 (Product uses)

NW 642-1 The product may not be applied in or in the immediate vicinity of surface or coastal waters. Irrespective of this, the minimum buffer zone from surface waters stipulated by state law must be observed. Violations may be punished by fines of up to 50 000 EUR.

Applicant: Fine Agrochemicals Limited Evaluator: DE Date: 18/02/2013

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2.3 Product uses PPP (product name/code) Exilis (007524-00) Formulation type: SL active substance 6-Benzyladenin Conc. of as 1: 20 g/L

Applicant: Fine Agrochemicals Ltd. professional use X Zone(s): central non professional use

Verified by MS: y

1 2 3 4 5 6 7 8 10 11 12 13 14 Use- Member Crop and/ F Pests or Group of pests Application Application rate PHI Remarks: No. state(s) or situation G controlled (days) or Method / Timing / Growth Max. number kg, L product / g, kg as/ha Water L/ha e.g. safener/synergist per ha (crop destination / I (additionally: Kind stage of crop & (min. interval ha purpose of crop) developmental stages of season between a) max. rate per a) max. rate min / max e.g. recommended or mandatory tank the pest or pest group) applications) appl. per appl. mixtures a) per use b) max. total rate b) max. total b) per crop/ per crop/season rate per season crop/season 001 DE Apple F Enhancing fruit size, spraying 71 - 7172 a) 1 a) 3,75 L/ha and a) 0.075 kg 500 L/ha 90 NW642 Thinning of fruit b) 1 per m crown a.i./ha and per and per m *) The PHI is covered by the conditions height m crown crown F *) of use and/or the vegetation period b) 7,5 L/ha height height remaining between the application of b) 0,15 kg the plant protection product and the use a.i./ha of the product (e. g. harvest) or the setting of a PHI in days is not required resp. 002 DE Pear F Enhancing fruit size, spraying 71 - 7172 a) 1 a) 3,75 L/ha and a) 0.075 kg 500 L/ha 90 NW642 Thinning of fruit b) 1 per m crown a.i./ha and per and per m height m crown crown F *) b) 7,5 L/ha height height b) 0,15 kg a.i./ha

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

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Remarks: (a) For crops, the EU and Codex classifications (both) should be used; where relevant, the use (i) g/kg or g/l situation should be described (e.g. fumigation of a structure) (j) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) Blackwell, ISBN 3-8263-3152-4), including where relevant, information on season at time of (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds application (d) e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) (k) The minimum and maximum number of application possible under practical conditions of use (e) GCPF Codes - GIFAP Technical Monograph No 2, 1989 must be provided (f) All abbreviations used must be explained (l) PHI - minimum pre-harvest interval (g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (m) Remarks may include: Extent of use/economic importance/restrictions (h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

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3 Risk management

3.1 Reasoned statement of the overall conclusions taken in accordance with the Uniform Principles

3.1.1 Physical and chemical properties (Part B, Section 1, Points 2 and 4) Overall Summary: All studies have been performed in accordance with the current requirements and the results are deemed to be acceptable. The appearance of the product is that of clear liquid with a slightly sweet odour. It has no explosive or oxidising properties, the self ignition temperature is above 400 °C. In aqueous solution, it has a pH value around 4.4. The stability data indicate a shelf life of at least 2 years at ambient temperature. The technical characteristics are acceptable for a soluble concentrate formulation.

Implications for labelling: none

Compliance with FAO specifications: There is no FAO specification for 6-benzyladenine.

Compliance with FAO guidelines: The product Exilis complies with the general requirements of the FAO/WHO manual (2010).

Compatibility of mixtures: There are no recommendations for tank mixtures.

Nature and characteristics of the packaging: Information with regard to type, dimensions, capacity, size of opening, type of closure, strength, leakproofness, resistance to normal transport & handling, resistance to & compatibility with the contents of the packaging, have been submitted, evaluated and is considered to be acceptable.

Nature and characteristics of the protective clothing and equipment: Information regarding the required protective clothing and equipment for the safe handling of Exilis has been provided and is considered to be acceptable.

3.1.2 Methods of analysis (Part B, Section 2, Point 5)

3.1.2.1 Analytical method for the formulation (Part B, Section 2, Point 5.2) A method using analysis by HPLC-UV is provided. Linearity, Precision, Accuracy and Specificity have been checked and found acceptable. According to the data, the method for the determination of the active substance in the formulated product is validated. No further data are required.

3.1.2.2 Analytical methods for residues (Part B, Section 2, Points 5.3 – 5.8) Sufficiently sensitive and selective analytical methods are not available for all for kinds of food and feed of plant origin. Based on the Guidance Document SANCO/825/00 (rev. 8.1 of 2010-11-16) independently validated analytical methods and confirmatory methods have to be provided for all matrix groups. This general requirement is independent from the intended use.

Applicant: Fine Agrochemicals Limited Evaluator: DE Date: 18/02/2013

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Noticed data gaps are: 1. An analytical method for the determination of residues of 6-benzyladenine in commodities with high oil content has to be provided. 2. Independent validations of analytical methods for the determination of residues of 6-benzyladenine in dry commodities and in commodities with high oil content have to be provided. 3. Confirmatory methods for the determination of residues of 6-benzyladenine in commodities with high oil content and commodities with high acid content have to be provided.

3.1.3 Mammalian Toxicology (Part B, Section 3, Point 7)

3.1.3.1 Acute Toxicity (Part B, Section 3, Point 7.1) Acute toxicity studies for Exilis were not evaluated as part of the EU review of the 6-benzyladenine. The relevant data were provided and are considered adequate. Exilis, containing 20 g/L 6-benzyladenine, has a low toxicity in respect to acute oral, dermal and inhalation toxicity and is not irritating to the rabbit skin and eye. It is not found to be a skin sensitiser to the guinea pig. Taking into account all submitted data no classification or labelling including risk- and safety-phrases is necessary.

3.1.3.2 Operator Exposure (Part B, Section 3, Point 7.4) The risk assessment according to the German model has shown that the estimated exposure towards 6- benzyladenine in Exilis will not exceed the systemic AOEL (0.03 mg/kg bw/d) for operators if prescribed PPE (gloves during mixing/loading) is worn. The risk assessment according to the UK-POEM has shown that the estimated exposure towards 6- benzyladenine in Exilis will not exceed the systemic AOEL for operators if hand-held equipment is used. To achieve this, the use of PPE (gloves during mixing/loading and application as well as with impermeable coverall) is mandatory for operators. In the case of tractor-mounted equipment, the systemic AOEL will be exceeded referred to the UK POEM even if PPE is used.

3.1.3.3 Bystander and Resident Exposure (Part B, Section 3, Point 7.4) The risk assessment has shown that the estimated exposure towards 6-benzyladenine in Exilis will not exceed the systemic AOEL for bystanders and residents.

3.1.3.4 Worker Exposure (Part B, Section 3, Point 7.4) The risk assessment has shown that the estimated exposure towards 6-benzyladenine in Exilis will not exceed the systemic AOEL for workers. No specific PPE is necessary for workers.

Implications for labelling resulting from operator, worker, bystander assessments: Hazard Symbol: -- Indication of danger: -- Risk Phrases: -- Safety Phrases: -- SP001: To avoid risks to man and the environment, comply with the instructions for use.

For mandatory labelling specifying the PPE required, please refer to 2.2.3.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

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3.1.4 Residues and Consumer Exposure (Part B, Section 4, Point 8) The data available is considered sufficient for risk assessment. An exceedance of the default MRL of 0.01*mg/kg for 6-benzyladenine is not expected (no MRLs set in Reg. (EC) No 396/2005 yet). The chronic and the short-term intake of 6-benzyladenine residues are both unlikely to present a public health concern.

3.1.4.1 Residues (Part B, Section 4, Points 8.2) Sufficient residue trial data are available indicating that no residues above LOQ (<0.005 mg/kg) are to be expected following the GAP applied for. Therefore an exceedance of the default MRL of 0.01*mg/kg for 6-benzyladenine is not expected. Based on a notification of the applicant dated 29/09/2015 accompanied by a report concerning applicability of 75 day PHI a change of the PHI from 90 days to “F” (*) and an amendment of the growth stage of the uses in pome fruit was requested. As documented in the report additionally submitted (Stephenson, C. and Gill, P., 2015) following an extrapolation approach no residues above the MRL of 0.01*mg/kg for 6-benzyladenine are expected after application until growth stage 72 representing a PHI of 75 days. Thus PHI “F” is acceptable. Based on expert judgement Germany agrees with the approach documented and amended the PHI accordingly.

(*)The PHI is covered by the conditions of use and/or the vegetation period remaining between the application of the plant protection product and the use of the product (e. g. harvest) or the setting of a PHI in days is not required resp.

3.1.4.2 Consumer exposure (Part B, Section 4, Point 8.3) The chronic and the short-term intake of 6-benzyladenine residues are both unlikely to present a public health concern when applied according to the recommendations whereas no ARfD was allocated for 6- benzyladenine. Further details are shown in IIIA Fehler! Kein Text mit angegebener Formatvorlage im Dokument.-1 of Part B, Section 4.

3.1.5 Environmental fate and behaviour (Part B, Section 5, Point 9) The environmental fate and behaviour of the active substance 6-benzyladenin was assessed in the context of Annex I inclusion and the results of the peer review are summed up in the Review Reports (SANCO/12667/2010 final, 04/01/2011). All environmental fate studies performed with the active substance or metabolites for Annex I inclusion are adequate to evaluate the proposed use of the formulation product Exilis. New environmental fate studies were performed and evaluated in the core assessment (Section 5, Appendix 2). Based on the data provided in this submission, appropriate endpoints were used to calculate PEC values for Exilis and 6-benzyladenine and its metabolite M8 in soil, surface water, ground water and air for the intended use patterns.

3.1.5.1 Predicted Environmental Concentration in Soil (PECsoil) (Part B, Section 5, Points 9.4 and 9.5) For German exposure assessment the applied soil depth is based on experimental data (Fent, Löffler, Kubiak: Ermittlung der Eindringtiefe und Konzentrationsverteilung gesprühter Pflanzenschutzmittel- wirkstoffe in den Boden zur Berechnung des PEC-Boden. Abschlussbericht zum Forschungsvorhaben FKZ 360 03 018, UBA, Berlin 1999). Generally for active substances with a Kf,oc < 500 a soil depth of 2.5 cm is applied whereas for active substances with a Kf,oc > 500 a soil depth of 1 cm is applied.

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Using a soil bulk density of 1.5 g cm-3 and a DT50 of 8 d (SFO, Maximum, Field studies, non- normalized), a PECact of 0,3 mg/kg soil and a PECtwa (21 d) of 0,1382 mg/kg soil were calculated for 6- benzyladenin. Due to the fast degradation of 6-benzyladenine in soil (DT90 < 365 d, SFO, laboratory data) the accumulation potential of 6-benzyladenine does not need to be considered.

3.1.5.2 Predicted Environmental Concentration in Ground Water (PECGW) (Part B, Section 5, Point 9.6) For authorization in Germany exposure assessment of surface water the routes of entry (spraydrift and deposition following volatilisation; run-off, drainage) are considered separately to derive risk mitigation measures separately for each entry route. For the intended use pattern, no entries of 6-benzyladenine and its metabolite M8 into the groundwater with concentrations ≥ 0.1 µg/L are expected. Thus, no risk management measures for groundwater protection are required for the intended use pattern.

3.1.5.3 Predicted Environmental Concentration in Surface Water (PECSW) (Part B, Section 5, Points 9.7 and 9.8) The calculation of concentrations in surface water is based on spray drift data by Rautmann and Ganzelmeier. The vapour pressure at 20 °C of the active substance 6-benzyladenine is < 10-5 Pa. Hence the active substance 6-benzyladenine is regarded as non-volatile. Therefore exposure of surface water by the active substance 6-benzyladenine due to deposition following volatilization does not need to be considered. The calculation of PECsw after exposure by spraydrift and deposition following volatilization using the model EVA 2.1 is not required. The concentration of the active substance 6-benzyladenine in adjacent ditch due to surface runoff and drainage is shown in the following table as calculated using the model EXPOSIT 3.01.

Exposure by surface runoff vegetated buffer strip (m) PECsw in adjacent ditch (µg/L) 0 0.27 5 0.24 10 0.20 20 0.14 Exposure by drainage Time of application PECsw in adjacent ditch (µg/L) Autumn/winter/early spring 0.33 Spring/summer 0.11

3.1.5.4 Predicted Environmental Concentration in Air (PECAir) (Part B, Section 5, Point 9.9) The vapour pressure at 20 °C of the active substance 6-benzyladenine is < 10-5 Pa. Hence the active substance 6-benzyladenine is regarded as non-volatile. Therefore volatilization does not need to be considered.

3.1.5.5 Implications for labelling resulting from environmental fate assessment: none

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3.1.6 Ecotoxicology (Part B, Section 6, Point 10) Only information relevant for the prescription of national labelling and environmental restrictions are mentioned in the following chapters. Details of ecotoxicological studies are described in the National Addendum of Germany. Risk assessment is presented in the National Addendum Germany, Part B, Section 6.

3.1.6.1 Effects on Terrestrial Vertebrates (Part B, Section 6, Points 10.1 and 10.3) The risk assessment of the effects on birds and mammals was carried out according to the Guidance Document on Risk Assessment for Birds & Mammals on request from EFSA”, EFSA Journal 2009; 7(12):1438 (EFSA/2009/1438). Birds Based on the highly conservative presumptions of the screening step, the acute risk of exposure of birds to the active ingredient 6-benzyladenine according to the GAP of the formulation Exilis achieves the acceptability criteria TER ≥ 10, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for acute effects. Based on the highly conservative presumptions of the screening step, the long term risk of exposure of birds to 6-benzyladenine at the submitted GAP of the formulation Exilis achieves the acceptability criteria TER ≥ 5, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for long term effects. Mammals Based on the highly conservative presumptions of the screening step, the acute risk of exposure of terrestrial vertebrates to the active ingredient 6-benzyladenine according to the GAP of the formulation Exilis achieves the acceptability criteria TER ≥ 10, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for acute effects no further refinement is necessary. Based on the highly conservative presumptions of the screening step, the long-term risk of exposure of mammals to 6-benzyladenine when applied according to the GAP achieves the acceptability criteria TER ≥ 5, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for long term effects. Birds and mammals: Secondary poisening The EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) states that a log Kow ≥3 is used to indicate that there might be a potential for bioaccumulation (see Section 5.6

Bioaccumulation and food chain behaviour). The log Kow of 6-benzyladenine is 2.16, so this active substances has a (negligible) potential to bioaccumulate in animal tissues.

3.1.6.2 Effects on Aquatic Species (Part B, Section 6, Point 10.2)

For the active ingredient the most sensitive endpoint divided by the safety factor is EC50 = 0.31 mg/L (Lemna gibba). Exilis was not the representative formulation during the EU Review of 6-benzyladenine, but its active ingredient concentration and proposed use (1 x 150 g a.s. on apples and pears) are within what was considered for Annex I inclusion of 6-benzyladenine. However, the EFSA Conclusion (EFSA Journal 2010; 8(9):1716) states that the risk assessment for aquatic organisms could not be finalised. This was driven by the formulated product MaxCel being significantly more toxic than expected based on the content of the active substance. The toxicity data which are available show that Exilis is less toxic for aquatic organisms compared to 6-benzyladenine.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

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For 6-benzyladenine as active substances the calculated TER values are above the trigger of 10 therefore a buffer zone and spray drift reduction is not considered necessary. Regarding the entry pathway spray drift and run-off or drainage it is concluded by the MS that the proposed use of Exilis will not pose an unacceptable risk to aquatic organisms, if applied according to the recommended use pattern. Therefore a low risk to aquatic organism is indicated. Based on the intrinsic property of the active substance 6-benzyladenine, the national labellings and restrictions NW262, NW264, NW265 and NW642 are prescribed as mandatory.

Based on the toxicity of the product to Lemna gibba (EC50: 29.62 mg/L), the classification and Labelling R52 according to Guideline 1999/45/EC is assigned.

3.1.6.3 Effects on Bees and Other Arthropod Species (Part B, Section 6, Points 10.4 and 10.5) Bees The proposed use of Exilis in orchards fits within the risk envelope of the uses that were assessed under the EU Review of 6-benzyladenine. Showing an oral or contact toxicity of 260.8 µg as/bee or 69.0 µg as/bee Exilis is less toxic than the product evaluated during EU assessment. The resulting Hazard Quotients (HQs) were substantially below the trigger of 50, indicating an acceptable risk. Even at the maximum application rate the product is non-hazardous to bees. The national labeling NB6641 is assigned.

Other non-target arthropods Toxicity Exposure Ratios (TER) are calculated for the off-field exposure of non-target arthropods via spray drift, following the application of “Exilis” according to the submitted use patterns.The off-field TER values for A. rhopalosiphi and T. pyri are above the trigger value, indicating that Exilis does not pose an unacceptable risk to non-target arthropods in off-field areas. The risk for Orius laevigatus is slightly below the trigger value. But due to the conservative first tier assessment this deemed to be acceptable. The application of Exilis according to good agricultural practice will cause no unacceptable risk to non- target arthropods. The national labeling NN1001 is assigned. There is no need of additional specific mitigation measures.

3.1.6.4 Effects on Earthworms and Other Soil Macro-organisms (Part B, Section 6, Point 10.6)

In conclusion, all acute TERs for the active and major soil degradation products are above the respective trigger values. Earthworms and other soil non-target macro-organisms are not at risk following treatment with Exilis. There is no need to address the long term risk of the active substance 6-benzyladenine and its metabolite M8 for earthworms, because their degradation in soil (DT90 < 365 d, Kinetic, laboratory/field data) is fast. 6-benzyladenine forms one major metabolite in soil: M8 (9.9 % at day 3). There are no toxicological studies for the metabolite M8 available. The metabolite reaches his maximum at day 3 after the application. Therefore the ZRMS considers the risk from the Metabolite M8 covered with the studies from the parent compound 6-benzyladenine.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

Part A Exilis Registration Report - Central Zone National Assessment – Germany Page 16 of 21

According to SANCO/10329/2002 rev2 final tests on other soil non-target organisms are triggered by breaching the soil persistence criteria (DT90 > 365 d). This is not the case for the major soil degradation product M8. For the parent compounds, studies on other non-target soil macro-organisms are not triggered. It is concluded that the application of Exilis according to good agricultural practice will cause no unacceptable risk to earthworms and other soil macro organism. There is no need of additional specific mitigation measures. No risk management measures are required for the protection of earthworms and other soil macro- organisms for the intended use pattern.

3.1.6.5 Effects on organic matter breakdown (Part B, Section 6, Point 10.6) For 6-benzyladenine, no study on organic matter breakdown is triggered. Therefore, the risk of Exilis to soil-dwelling organism communities is considered to be low and application according to good agricultural practice will not cause unacceptable risk to organic matter decomposition. There is no need of additional specific mitigation measures.

3.1.6.6 Effects on Soil Non-target Micro-organisms (Part B, Section 6, Point 10.7) The results of these studies showed no effects of > 25% compared to the control (trigger value as according to SANCO/10329/2002 ) on soil microbial activity up to a maximum tested concentration of 1.0 mg a.s./kg soil, after 28 days. As this maximum tested concentration was much higher than the maximum initial PEC from the proposed use of 6-benzyladenine l (0.040 mg a.s./kg, EFSA Journal 2010; 8(9):1716), as assessed under the EU Review, an acceptable risk to soil microbial activity was concluded. As the proposed use of Exilis in orchards fits within the risk envelope of the uses that were assessed during the EU Review of 6-benzyladenine the risk to soil micro-organisms is considered to be acceptable. No risk management measures are required for the protection of non-target soil micro-organisms for the intended use pattern.

3.1.6.7 Assessment of Potential for Effects on Other Non-target Organisms (Flora and Fauna) (Part B, Section 6, Point 10.8) Based on the worst case risk assessment it can be concluded that the proposed use of Exilis poses no unacceptable risk to non-target terrestrial plants. No risk management measures are required for the protection of other non-target organisms (Flora and Fauna) for the intended use pattern.

Implications for labelling resulting from ecotoxicological assessment: see 2.2

3.1.7 Efficacy (Part B, Section 7, Point 8) Following a notification of the applicant dated 29/09/2015 the growth stage for effective application on pome fruit was re-evaluated. Based on expert judgement taking into consideration efficacy data available it was concluded that an application up to stage 72 (20 mm diameter) would be appropriate. The GAP table in chapter 2.3 (Product uses) was corrected accordingly.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

Part A Exilis Registration Report - Central Zone National Assessment – Germany Page 17 of 21

3.1.7.1 Minimum effective dose tests (IIIA1 6.1.2) Results from the Maritime, the Mediterranean, the North Eastern and the North Western EPPO zone from the years 2003 to 2010 were submitted and analysed together to assess and compare the performance and efficacy of Exilis under the various regional climatic conditions within the EU. There is a clear tendency of fruit set reduction with increasing dose rate over all climatic zones and no discrete clouds of data points originating from a specific climatic zone are shown. It is therefore reasoned that the comparability of Exilis trial data is not intrinsically dependent on the climatic zone in which the product was evaluated, but rather on the weather conditions at and directly following application.

Apple Rates from 2.5 to 5 L/ha showed good results with an average reduction in fruit set of 10% in comparison with the untreated, but data on varieties which are very difficult to thin like were not sufficient or no efficacy was observed in too many trials. The rate of 7.5 L/ha presented an average fruit set index of 84, i.e. a fruit set reduction of 16 %. and in only 3 of 28 situations where this rate was tested, no reduction in fruit set was reported. Higher rate of 10 L/ha does not show any further efficacy

The same analysis was performed on relative mean fruit weight in comparison with the untreated. This comparison does not show any clear dose effect between the different tested rates, with a fruit weight increase in the order of 6-9% in average in comparison to the untreated:

Pear A similar analysis of the data obtained in pear was performed. Even if the number of data available on pear is lower than on apple, the same conclusion can be drawn: 7.5 L/ha is required to ensure at least 10% fruit set reduction in most of the situations: The average fruit weight increase is 3% when Exilis is applied at 7.5 L/ha:

Final considerations about minimum effective dose for apple and pear Overall, results presented in the previous tables indicate that an average crop load reduction of 15% (compared to the untreated) and a fruit size increase of >10% are obtained in most of the situations when Exilis is applied at 7.5 L/ha on apple and pear. All the results exposed in this section indicate that the minimum effective dose of Exilis is 7.5 L/ha.

3.1.7.2 Efficacy tests (IIIA1 6.1.3) For the assessment of efficacy the same trials from all zones were considered as in the previous chapter. Exilis at 7.5 L/ha (without adjuvant) was tested in a total of 33 trials, with 22 in apple and 11 in pear (Table 20). Two trials were carried out on apple by non GEP official institutes (1 in Spain and 1 in Southern France) but all other trials were GEP-compliant. These trials cover a large period of time and different climatic conditions. In apple as well as in pear, the trials show the same level of activity of Exilis in the Maritime and Mediterranean zone, as already proved in the previous section. The results confirm that Exilis at 7.5 L/ha ensures an average reduction in fruit set of 10 to 15 % on apple and about 10 % on pear. At the same time, fruit weight is increased by about 5 % in apple and 3 % in pear (more limited set of data).

A number of trials also showed that Exilis could be successfully used in the frame of a thinning programme including other chemical thinners.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

Part A Exilis Registration Report - Central Zone National Assessment – Germany Page 18 of 21

3.1.7.3 Effects on yield and quality (IIIA1 6.1.4) Impact of treatment with Exilis on quality of plants and plant products was evaluated in the efficacy trials presented in section 6.1.2 where different parameters were assessed. Main findings are summarised in the following. Exilis did not have any negative effect on leaf quality, shoot growth, fruit shape or the ratio between fruit length and fruit diameter, fruit skin quality, fruit colour, fruit firmness, An improved flowering in the year following the application of Exilis was observed in some trials, probably as a side effect of thinning. No increase of the production of pygmy fruit was in comparison with the untreated control was observed using Exilis alone or mixed with an adjuvant. However, when Exilis is combined with NAA or NAD at a late timing of treatment, it seems to amplify the production of pygmy fruit induced by auxin application. Therefore, a warning will be included in the label recommending not to mix Exilis with NAD or NAA (where available) on apple cultivars known to be prone to produce pygmy fruit. Therefore, a warning will be included in the label recommending not to mix Exilis with NAD or NAA (where available) on apple cultivars known to be prone to produce pygmy fruit. Based on all the facts exposed above, it can be considered that Exilis applied at 7.5 L/ha in apple and pear will not have any negative impact on quality of plant and plant products. On the contrary, it will have a positive impact on fruit quality by improving fruit size and weight on the year of treatment.

3.1.7.4 Effects on the processing procedure Because the residues in fruit are not significant (< 0.1 mg/kg=LOQ), processing study was not required. However, a study with another 6-benzyladenine formulation was performed with apples which were processed into juice or wet pomace. No concentration of residues during processing. As 6-BA is very similar to natural cytokinins, it can be concluded that use of Exilis in apple will not have any negative impact on fruit processing and on the quality of the final product. Because of the similarities between apple and pear uses, this also applies for processed pears.

3.1.7.4 Effects on the yield of treated plants or plant products No specific trials were conducted to assess the decrease in yield as quantitative assessments of crop load are an essential part of standard fruit thinning trials for product registration. Most of the trials did only show a limited or no difference in yield between the Exilis treated trees and the untreated, because the reduction in fruit number was compensated for by better fruit growth of the remaining fruit.

3.1.8 Adverse Effects

3.1.8.1 Phytotoxicity to host crop (IIIA 6.2.1) The active substance of Exilis, 6-BA is similar to a naturally occurring plant hormone and at the rates of use recommended for Exilis, no serious levels of phytotoxicity is to be expected. This is supported by the absence of phytotoxicity in the field trials described in section 6.1.2 and 6.1.3. No phytotoxic effects on the target plant product like skin or stem end russet or reduction of red pigmentation of the fruit have been reported in the efficacy and crop safety trials included in this dossier. No impact on vegetative growth was observed either.

3.1.8.2 Adverse effects on beneficial organisms (other than bees) (IIIA1 6.2.4) Effects on relevant beneficial organisms

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

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Laboratory tests (glass-plate and extended) with several non-target species. No harmful effects were observed on Aphidius rhopalosiphi, Typhlodromus pyri and Orius laevigatus. Results to sublethal effects of Exilis on Typhlodromus pyri are not available. Therefore, the effect of Exilis on the predatory mite Typhlodromus pyri cannot be evaluated finally. Exilis can be classified as not harmful for populations of relevant beneficial insect species.

Effects on soil quality The acute TER for earthworms based on the active substance data is greatly in excess of the trigger value (>2500). Studies on the formulated product or long-term studies are not considered necessary. The results of studies on soil microbial activity showed no effects of > ± 25% compared to the control. It was agreed during the EU Review that studies on other non-target macro-organisms or organic matter breakdown are not required. There is no indication of any unacceptable adverse effects on soil macro- or soil micro-organisms relevant for the maintenance of soil quality.

3.1.8.3 Impact on succeeding crops (IIIA1 6.2.6) Given the rapid degradation of the active substance in soil, no effect of the treatment on succeeding crops is expected, even if treated trees would be removed and replaced by a young orchard or any other crop.

3.1.8.4 Impact on other plants including adjacent crops (IIIA1 6.2.7) Exilis applied on pome fruit tree will not have any detrimental effect on neighbouring crop because of spray drift or volatilisation, because the TER ratio is well above the trigger value for non-target plants.

3.1.8.5 Possible development of resistance or cross-resistance (IIIA1 6.2.8) 6-BA is a naturally occurring plant hormone. 6-BA resistant plant phenotypes will have a very low fitness as normal plant growth and development will be severely affected. Resistance development is therefore not relevant.

3.2 Conclusions

Considering an application in accordance with the evaluated use pattern and good agricultural practice as well as strict observance of the conditions of use no harmful effects on groundwater or adverse effects on the ecosystem are to be apprehended. Further, no adverse health effects for operators, workers, bystanders and residents are to be expected if used properly and according to the intended conditions of use. The intended use in apples and pears will not result in residues above the default MRLs. A risk for consumers through consumption of food with residues of 6-BA is not expected.

An authorisation can be granted.

3.3 Further information to permit a decision to be made or to support a review of the conditions and restrictions associated with the authorisation No further data are required. Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

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Appendix 1 – Copy of the product authorisation See below.

Appendix 2 – Copy of the product label The submitted draft product label has been checked by the competent authority. The applicant is requested to amend the product label in accordance with the decisions drawn by the competent authority. The final version of the label is not available, because the layout is the sole responsibility of the applicant and will not be checked again.

Appendix 3 – Letter of Access Letter(s) of access is/are classified as confidential and, thus, are not attached to this document.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

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Appendix 4 – Additional Report

Stephenson, C. and Gill, P., 2015, Justification for a 75 day PHI for the use of 6-benzyladenine (6-BA) on pome fruit.

Applicant: Fine Agrochemicals Limited Evaluator: Germany Date: 18/02/2013

CENTRE FOR CHEMICAL REGULATION AND FOOD SAFETY (EUROPE) The Lenz, Hornbeam Business Park, Harrogate. HG2 8RE UK T (+44) 1423 853200 F (+44) 1423 810431 [email protected]

Report Number: 0800299.UK0 – 8179

Justification for a 75 day PHI for the use of 6-benzyladenine (6- BA) on pome fruit

Prepared by: Claire Stephenson & Philip Gill Exponent International Ltd. The Lenz, Hornbeam Business Park Harrogate, Yorkshire, HG2 8RE, UK

Prepared for:

Fine Agrochemicals Ltd

Exponent Project Number: 0800299.UK0

19 June 2015 Justification for a 75 day PHI for the use of 6-benzyladenine (6-BA) on pome fruit

Background

6-BA was included in Annex I of Directive 91/414/EEC for use as a plant growth regulator via Commission Directive 2011/1/EU of 3 January 2011. France was the original Rapporteur Member State (RMS) and prepared the initial Draft Assessment Report (DAR) dated September 2007. Subsequently the active substance was voluntarily withdrawn and resubmitted in accordance with the procedures outlined in Commission Regulation (EC) No. 33/2008. The RMS for the resubmission was the UK who prepared the Additional Report (AR) dated November 2009.

With respect to residues, the Inclusion Directive for 6-BA highlights no specific provisions which need to be considered by the Member States prior to granting an authorisation.

Summary

The GAP for the representative use on apples is provided in Table 1. The timing of the application for apples was initially proposed at BBCH 74 (approximately 2.5 months before harvest). During the evaluation the RMS proposed a PHI of 90 days which, with a 25 % deviation (range: 68 to 112 days), allowed reference to six supervised residues trials performed in northern Europe and four residues trials performed in southern Europe. Since all residues from all ten trials were below the analytical limit of quantification (LOQ) these trials were sufficient in support of the amended GAP.

Table 1 Representative GAP from the EU review

Crop F, G Use Method Growth Application PHI or I stage No. g Water g as/ha (days) as/hL (L/ha) Apple F Fruit Spray BBCH 1 7.5-15 1000 75-150 90 thinning 71-74

The growth stage at which 6-benzyladenine is applied is critical to the intended effect. However for some apple varieties the interval between BBCH 74 and normal commercial harvest (NCH) is less than the 90 day PHI established by the RMS during the EU review. A PHI of 75 days would be more in line with agronomic requirements and therefore the existing residues data package has been re- evaluated in support of the proposed reduction of the PHI from 90 to 75 days.

The current EU MRLs for 6-benzyladenine in all commodities are 0.01* mg/kg according to Article 18(1)(b) of Regulation (EC) No 396/2005, where the asterisk denotes an MRL set at the limit of quantification (for monitoring methods).

The full assessment of the residues data below demonstrates that a reduction in the PHI from 90 to 75 days will not lead to measurable residues (above the analytical LOQ of 0.005 mg/kg) in the treated fruit. 6-Benzyladenine is not acutely toxic and therefore an ARfD was not considered necessary. An ADI of 0.01 mg/kg bw/day is given in the Review Report (SANCO/12667/2010). Based on the HR of 0.005 mg/kg, the worst-case dietary intake is 0.6 % ADI (for the German child). Therefore there are no concerns for consumer health based on the proposed reduction in PHI.

As residues are below the LOQ at either a 90 or 75 day PHI and there are no MRL or dietary risk assessment implications, it is considered appropriate that authorisation may be given for uses based on an amended PHI of 75 days, rather than the existing 90 day restriction. Assessment

During the EU review, a total of 24 studies were assessed in apple. The studies were located in France (16 trials), Germany (2 trials), Spain (3 trials), United Kingdom (2 trials) and Italy (1 trial); they were performed during 2000 (8 trials), 2001 (8 trials) and 2002 (8 trials). The trials all gave residues of <0.005 mg/kg. The trials were conducted with either of two formulations, Maxcel and Excel, both of which are SL formulations containing 20 g/L 6-BA.

The majority of these trials were overdosed compared to the intended GAP; either one application made at a nominal rate of 200 g as/ha, or four applications with applications 1 and 2 made at a nominal rate of 40 g as/ha and applications 3 and 4 made nominally at 200 g as/ha. The exaggerated dose rates may be accepted since residues at a PHI of 75 days are demonstrated to be below the LOQ. Four of the trials made applications at less than 100 g as/ha and are therefore excluded from further consideration. An additional seven trials were conducted as harvest trials with only one sampling interval greater than 75 days by which time residues were below the LOQ and therefore cannot be used to estimate the residues at 75 days. A summary of the trials is provided in Table 2.

Of the trials which were not excluded for the reasons given above (7 N-EU and 5 S-EU), residues were found to be below the LOQ of 0.005 mg/kg in six trials within 10 to 40 days. In the remaining six trials, residues were 0.007 to 0.022 mg/kg at 28 days after application (5 trials) and 0.006 mg/kg at 40 days after application (1 trial). Residues at the final sampling interval (83 to 146 days after application) were all below the LOQ. In order to determine the expected residue levels at 75 days after application, a DT50 was calculated for each trial and this rate of decline was used to calculate the expected day 75 residue. The DT50 values were calculated using SFO kinetics (with the FOCUS_DEGKIN v1 tool). Chi2 statistics indicate a good fit (Chi2 <20) for all except one trial (Chi2 = 22.2), however in all cases the visual fit was good. All kinetic fits are therefore considered to be acceptable due to the high variability associated with residues in field trials. Calculated DT50 values ranged from 1.9 to 11.2 days.

On the basis of the residues measured at day 0, and separately at the preceding time interval (28 or 40 days after application), the DT50 for each trial was used to determine the day 75 residue. In all cases, the residue at day 75 was predicted to be significantly below the LOQ, whether estimated from the initial residues value or that measured at the preceding interval. Furthermore the application rates in these trials were all overdosed (1 to 4 applications with a final application of approximately 200 g ai/ha) compared to the GAP of one application of 150 g ai/ha. This provides further evidence that residues would not be expected at the proposed GAP.

Conclusion

The available residues trials show that, following application of 6-benzyladenine at exaggerated rates, residues in treated fruit are below the LOQ of 0.005 mg/kg by 40 days following the final application in all but one trial (0.006 mg/kg at day 40 following application at 1.4N). On the basis of these data (4 N-EU trials and 2 S-EU trials) it can be concluded that measurable residues would not be expected in apples treated 75 days before harvest. In order to provide further evidence, the DT50 values were estimated for trials where positive residues were measured at the penultimate interval and these were used to estimate the likely residues at day 75. In all cases the residues would be below 0.005 mg/kg at day 75. Therefore it is concluded that the existing PHI of 90 can be reduced to 75 days and the non- residue situation will be maintained. Residues of <0.005 mg/kg are in accordance with the current EU MRL and do not lead to concerns for consumer health.

Table 2 A summary of the supervised residues trials presented in the DAR (September 2007) Shaded trials not used for PHI comparision

Residues Variety Application Portion mg/kg Country, Year Comments analysed PHI Reference g a.s./ha g a.s./hL 6-BA (d) Northern Europe -0 0.026 40.8 4 +0 0.115 Gala 38.8 4 Whole 7 0.036 Residue <0.005 mg/kg by 14 day 1 N France, 2001 206.2 20 fruit 14 <0.005 PHI. AF/5573/VB/3 207.6 20 28 <0.005 93 <0.005 38.7 4 Jonica, 38.5 4 Whole 2 Germany, 2001 92 <0.005 No decline data 192.6 20 fruit AF/5573/VB/1 196.6 20 -0 0.029 42.4 4 +0 0.203 DT = 3.8 days Golden delicious 50 40.0 4 Whole 7 0.050 (k = 0.184; Chi2 = 8.0) 3 N France, 2001 191.2 20 fruit 14 0.025 Based on rate of decline residues AF/5573/VB/4 206.6 20 28 0.007 will be <0.005 mg/kg at 75 days. 111 <0.005 -0 0.054 38.2 4 +0 0.261 Gala 36.8 4 Whole 7 0.032 Residue <0.005 mg/kg by 28 day 4 N France, 2002 163.0 20 fruit 14 0.014 PHI. AF/6229/VB/3 190.0 20 28 <0.005 105 <0.005 40.8 4 Golden Delicious 38.7 4 Whole 5 N France, 2002 130 <0.005 No decline data 200.0 20 fruit AF/6229/VB/2 202.0 20 37.8 4 Jonagold 39.3 4 Whole 6 Germany, 2002 112 <0.005 No decline data 193.6 20 fruit AF/6229/VB/4 199.6 20 -0 0.032 36.6 4 +0 0.070 DT = 11.2 days Braeburn 50 40.7 4 Whole 7 0.051 (k = 0.062; Chi2 = 18.6) 7 N France, 2002 180.6 20 fruit 14 0.017 Based on rate of decline residues AF/6229/VB/5 186.2 20 28 0.022 will be <0.005 mg/kg at 75 days. 146 <0.005 Residues Variety Application mg/kg Country, Year Portion Comments analysed PHI Reference g a.s./ha g a.s./hL 6-BA (d) 0- < 0.005 0+ 0.100 Golden Delicious Whole 10 0.012 8 UK, 2000 93.3 - Underdosed fruit 19 0.008 AF/5294/FC/1 40 < 0.005 109 < 0.005 0- < 0.005 0+ 0.172 DT = 12.5 days Golden Delicious 50 Whole 10 0.032 (k = 0.148; Chi2 = 12.5) 9 UK, 2000 209.2 - fruit 19 0.024 Based on rate of decline residues AF/5294/FC/1 40 0.006 will be <0.005 mg/kg at 75 days. 109 < 0.005 0- < 0.005 0+ 0.067 Golden Whole 10 0.009 10 N France, 2000 97.7 - Underdosed fruit 20 < 0.005 AF/5294/FC/2 40 < 0.005 119 < 0.005 0- < 0.005 0+ 0.167 Golden Whole 10 0.040 Residue <0.005 mg/kg by 40 day 11 N France, 2000 204.6 - fruit 20 0.007 PHI. AF/5294/FC/2 40 < 0.005 119 < 0.005 0- < 0.005 0+ 0.082 Golden Whole 10 < 0.005 12 N France, 2000 106.4 - Underdosed fruit 20 < 0.005 AF/5294/FC/3 40 < 0.005 122 < 0.005 0- < 0.005 0+ 0.082 Golden Whole 10 < 0.005 Residue <0.005 mg/kg by 10 day 13 N France, 2000 211.2 - fruit 20 < 0.005 PHI. AF/5294/FC/3 40 < 0.005 122 < 0.005 Southern Europe -0 0.027 40.7 4 +0 0.214 DT = 2.9 days Early red one 50 43.3 4 Whole 7 0.040 (k = 0.242; Chi2 = 5.0) 1 Spain, 2001 201.6 20 fruit 14 <0.005 Based on rate of decline residues AF/5574/VB/6 201. 6 20 28 0.007 will be <0.005 mg/kg at 75 days. 106 <0.005 Residues Variety Application mg/kg Country, Year Portion Comments analysed PHI Reference g a.s./ha g a.s./hL 6-BA (d) 38.9 4 Golden smoothee 40.1 4 Whole 2 S France, 2001 111 <0.005 No decline data 197.6 20 fruit AF/5574/VB/1 211.4 20 41.5 4 Royal Gala 43.4 4 Whole 3 Spain, 2001 113 <0.005 No decline data 229.8 20 fruit AF/5574/VB/5 204.4 20 -0 0.068 41.8 4 +0 0.366 DT = 3.6 days Royal Gala 50 42.0 4 Whole 7 0.068 (k = 0.194; Chi2 = 19.1) 4 S France, 2001 201.0 20 fruit 14 0.071 Based on rate of decline residues AF/5574/VB/7 199.8 20 28 0.018 will be <0.005 mg/kg at 75 days. 83 <0.005 16.0 4 Jonagold 41.4 4 Whole 5 S France, 2001 116 <0.005 No decline data 209.6 20 fruit AF/5573/VB/2 190.4 20 -0 0.072 38.6 4 +0 0.175 DT = 1.9 days Golden Delicious 50 39.9 4 Whole 7 0.010 (k = 0.361; Chi2 = 22.2) 6 S France, 2002 199.0 20 fruit 14 0.026 Based on rate of decline residues AF/6230/VB/1 202.6 20 28 0.012 will be <0.005 mg/kg at 75 days. 118 <0.005 40.3 4 Golden Delicious 41.0 4 Whole 7 S France, 2002 119 <0.005 No decline data 200.6 20 fruit AF/6230/VB/2 198.0 20 39.2 4 Double red 39.3 4 Whole 8 Italy, 2002 133 <0.005 No decline data 192.0 20 fruit AF/6230/VB/4 195.2 20 -0 0.099 42.2 4 +0 0.261 Royal Gala 42.2 4 Whole 7 0.045 Residue <0.005 mg/kg by 28 day 9 Spain, 2002 191.6 20 fruit 14 0.117 PHI. AF/6230/VB/6 198.8 20 28 <0.005 104 <0.005 0- < 0.005 0+ 0.072 Ozarn Gold Whole 10 0.007 10 S France, 2000 97.5 - Underdosed fruit 20 < 0.005 AF/5294/FC/4 40 < 0.005 120 < 0.005 Residues Variety Application mg/kg Country, Year Portion Comments analysed PHI Reference g a.s./ha g a.s./hL 6-BA (d) -0- < 0.005 0+ 0.092 Ozarn Gold Whole 10 0.013 Residue <0.005 mg/kg by 40 day 11 S France, 2000 206.2 - fruit 20 0.006 PHI. AF/5294/FC/4 40 < 0.005 120 < 0.005

Bundesamt für Verbraucherschutz und Lebensmittelsicherheit Dr. Dietmar Gottschild Dienstsitz Braunschweig • Postfach 15 64 • 38005 Braunschweig Referent Einschreiben mit Rückschein TELEFON +49 (0)531 299-3512 TELEFAX +49 (0)531 299-3002 E-MAIL [email protected] Fine Agrochemicals Ltd. INTERNET www.bvl.bund.de Hill End House WR5 2RQ Worcester IHR ZEICHEN IHRE NACHRICHT VOM VEREINIGTES KÖNIGREICH (UK) AKTENZEICHEN 200.22100.007524-00/00.61553 (bitte bei Antwort angeben)

DATUM 25. Februar 2013

ZV1 007524-00/00 Exilis Zulassungsverfahren für Pflanzenschutzmittel Bescheid

Das oben genannte Pflanzenschutzmittel

mit dem Wirkstoff: 20 g/l 6-Benzyladenin

Zulassungsnummer: 007524-00

Versuchsbezeichnung: FIN-30001-W-0-SL

Antrag vom: 11. Oktober 2011

wird auf der Grundlage von Art. 29 der Verordnung (EG) Nr. 1107/2009 des Europäischen Parlaments und des Rates vom 21. Oktober 2009 über das Inverkehrbringen von Pflanzen- schutzmitteln und zur Aufhebung der Richtlinien 79/117/EWG und 91/414/EWG des Rates (ABl. L 309 vom 24.11.2009, S. 1), wie folgt zugelassen:

Zulassungsende

Die Zulassung endet am 31. Mai 2022. BVL_FO_05_2437_200_V1.1

Dienstsitz Braunschweig Abt. Pflanzenschutzmittel Dienststelle Berlin Referatsgr. Untersuchungen Bundesallee 50, Geb. 247 Messeweg 11/12 Mauerstraße 39-42 Diedersdorfer Weg 1 38116 Braunschweig 38104 Braunschweig 10117 Berlin 12277 Berlin Tel: +49 (0)531 21497-0 Tel: +49 (0)531 299-5 Tel: +49 (0)30 18444-000 Tel: +49 (0)30 18412-0 Fax: +49 (0)531 21497-299 Fax: +49 (0)531 299-3002 Fax: +49 (0)30 18444-89999 Fax: +49 (0)30 18412-2955 SEITE 2 VON 9

Festgesetzte Anwendungsgebiete bzw. Anwendungen

Es werden folgende Anwendungsgebiete bzw. Anwendungen festgesetzt (siehe Anlage 1):

Anwendungs- Schadorganismus/ Pflanzen/-erzeugnisse/ Verwendungszweck nummer Zweckbestimmung Objekte 007524-00/00-001 Förderung der Apfel Fruchtgröße, Frucht- ausdünnung 007524-00/00-002 Förderung der Birne Fruchtgröße, Frucht- ausdünnung

Festgesetzte Anwendungsbestimmungen

Es werden folgende Anwendungsbestimmungen gemäß § 36 Abs. 1 S. 1 des Gesetzes zum Schutz der Kulturpflanzen (Pflanzenschutzgesetz - PflSchG) vom 6. Februar 2012 (BGBl. I S. 148, 1281) festgesetzt: (NW468) Anwendungsflüssigkeiten und deren Reste, Mittel und dessen Reste, entleerte Behältnisse oder Packungen sowie Reinigungs- und Spülflüssigkeiten nicht in Gewässer gelangen las- sen. Dies gilt auch für indirekte Einträge über die Kanalisation, Hof- und Straßenabläufe sowie Regen- und Abwasserkanäle.

Siehe anwendungsbezogene Anwendungsbestimmungen in Anlage 1, jeweils unter Nr. 3.

Verpackungen

Gemäß § 36 Abs. 1 S. 2 Nr. 1 PflSchG sind für das Pflanzenschutzmittel die nachfolgend näher beschriebenen Verpackungen für den beruflichen Anwender zugelassen:

Verpackungs- Verpackungs- Anzahl Inhalt art material von bis von bis Einheit Kanister Coex 1 5,00 10,00 l Kanister HDPE, fluoriert 1 20,00 l

Die Verpackungen für den beruflichen Anwender sind wie folgt zu kennzeichnen: Anwendung nur durch berufliche Anwender zulässig.

Auflagen

BVL_FO_05_2437_200_V1.1 Die Zulassung wird mit folgenden Auflagen gemäß § 36 Abs. 3 S. 1 PflSchG verbunden: SEITE 3 VON 9

Kennzeichnungsauflagen: (NW262) Das Mittel ist giftig für Algen.

(NW264) Das Mittel ist giftig für Fische und Fischnährtiere.

(NW265) Das Mittel ist giftig für höhere Wasserpflanzen.

(SB001) Jeden unnötigen Kontakt mit dem Mittel vermeiden. Missbrauch kann zu Gesundheitsschä- den führen.

(SB010) Für Kinder unzugänglich aufbewahren.

(SB110) Die Richtlinie für die Anforderungen an die persönliche Schutzausrüstung im Pflanzenschutz "Persönliche Schutzausrüstung beim Umgang mit Pflanzenschutzmitteln" des Bundesamtes für Verbraucherschutz und Lebensmittelsicherheit ist zu beachten.

(SF245-01) Behandelte Flächen/Kulturen erst nach dem Abtrocknen des Spritzbelages wieder betreten.

(SS110) Universal-Schutzhandschuhe (Pflanzenschutz) tragen beim Umgang mit dem unverdünnten Mittel.

Siehe anwendungsbezogene Kennzeichnungsauflagen in Anlage 1, jeweils unter Nr. 2.

Sonstige Auflagen: (WH963) Die Anwendung von Wachstumsregulatoren kann in Abhängigkeit von Art und Sorte der Kul- turpflanzen sowie von äußeren Rahmenbedingungen unerwünschte Nebenwirkungen mit sich bringen. Es wird empfohlen, die Anwendung gemäß der Beratung durch den Pflanzen- schutzdienst und unter Beachtung der dabei gegebenen Anweisungen vorzunehmen. BVL_FO_05_2437_200_V1.1 SEITE 4 VON 9

Vorbehalt

Dieser Bescheid wird mit dem Vorbehalt der nachträglichen Aufnahme, Änderung oder Ergänzung von Anwendungsbestimmungen und Auflagen verbunden.

Angaben zur Einstufung und Kennzeichnung gemäß § 4 Gefahrstoffverordnung

Gefahrenhinweise (R-Sätze): R 52 : Schädlich für Wasserorganismen

Sicherheitshinweise (S-Sätze): S 35: Abfälle und Behälter müssen in gesicherter Weise beseitigt werden

Zur Vermeidung von Risiken für Mensch und Umwelt ist die Gebrauchsanleitung einzuhalten.

Angaben zur Einstufung und Kennzeichnung gemäß Verordnung (EG) Nr. 1272/2008

- keine -

Abgelehnte Anwendungsgebiete bzw. Anwendungen

Für folgende Anwendungsgebiete bzw. Anwendungen lehne ich Ihren Antrag ab (siehe Anlage 2): - keine -

Hinweise

Auf dem Etikett und in der Gebrauchsanleitung kann angegeben werden: (NB6641) Das Mittel wird bis zu der höchsten durch die Zulassung festgelegten Aufwandmenge oder Anwendungskonzentration, falls eine Aufwandmenge nicht vorgesehen ist, als nicht bienen- gefährlich eingestuft (B4).

(NN1001) Das Mittel wird als nicht schädigend für Populationen relevanter Nutzinsekten eingestuft.

Weitere Hinweise und Bemerkungen Vorsorglich weise ich darauf hin, dass bisher mitgeteilte Forderungen bestehen bleiben, soweit sie noch nicht erfüllt sind. BVL_FO_05_2437_200_V1.1 SEITE 5 VON 9

Unterbleibt eine Beanstandung der vorgelegten Gebrauchsanleitung, so ist daraus nicht zu schließen, dass sie als ordnungsgemäß angesehen wird. Die Verantwortung des Zulas- sungsinhabers für die Übereinstimmung mit dem Zulassungsbescheid bleibt bestehen.

Hinsichtlich der Gebühren erhalten Sie einen gesonderten Bescheid.

Rechtsbehelfsbelehrung

Gegen diesen Bescheid kann innerhalb eines Monats nach Bekanntgabe Widerspruch erhoben werden. Der Widerspruch ist bei dem Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Messeweg 11/12, 38104 Braunschweig, schriftlich oder zur Niederschrift einzulegen.

Mit freundlichen Grüßen im Auftrag

gez. Dr. Hans-Gerd Nolting Abteilungsleiter

Dieses Schreiben wurde maschinell erstellt und ist daher ohne Unterschrift gültig.

Anlage BVL_FO_05_2437_200_V1.1 SEITE 6 VON 9

Anlage 1 zugelassene Anwendung: 007524-00/00-001 1 Anwendungsgebiet Schadorganismus/Zweckbestimmung: Förderung der Fruchtgröße, Fruchtausdünnung Pflanzen/-erzeugnisse/Objekte: Apfel Verwendungszweck:

2 Kennzeichnungsauflagen 2.1 Angaben zur sachgerechten Anwendung Einsatzgebiet: Obstbau Anwendungsbereich: Freiland - Erläuterungen: Anwendung im Haus- und Kleingartenbereich: Nein Erläuterung zum Schadorganismus: Stadium des Schadorganismus: - Erläuterungen: Erläuterung zur Kultur: Stadium der Kultur: 71 - Erläuterungen: Anwendungszeitpunkt: - Erläuterungen: Maximale Zahl der Behandlungen - in dieser Anwendung: 1 - für die Kultur bzw. je Jahr: 1 - Abstand: - Erläuterungen Anzahl Behandlungen: Mischungspartner: - Erläuterungen: Anwendungstechnik: spritzen - Erläuterungen: Aufwand: - 3,75 l/ha und je m Kronenhöhe bei maximal 2 m Kro- nenhöhe in maximal 500 l Wasser/ha und je m Kro- nenhöhe

- Erläuterungen: Sonstige Ergänzungen und Hinweise: - keine - BVL_FO_05_2437_200_V1.1 SEITE 7 VON 9

2.2 Sonstige Kennzeichnungsauflagen (NW642-1) Die Anwendung des Mittels in oder unmittelbar an oberirdischen Gewässern oder Küstenge- wässern ist nicht zulässig. Unabhängig davon ist der gemäß Länderrecht verbindlich vorge- gebene Mindestabstand zu Oberflächengewässern einzuhalten. Zuwiderhandlungen können mit einem Bußgeld bis zu einer Höhe von 50.000 Euro geahndet werden.

2.3 Wartezeiten 90 Tage Freiland: Apfel

3 Anwendungsbezogene Anwendungsbestimmungen - keine - BVL_FO_05_2437_200_V1.1 SEITE 8 VON 9

Anlage 1 zugelassene Anwendung: 007524-00/00-002 1 Anwendungsgebiet Schadorganismus/Zweckbestimmung: Förderung der Fruchtgröße, Fruchtausdünnung Pflanzen/-erzeugnisse/Objekte: Birne Verwendungszweck:

- Erläuterungen: Sonstige Ergänzungen und Hinweise: - keine - BVL_FO_05_2437_200_V1.1 SEITE 9 VON 9

2.3 Wartezeiten 90 Tage Freiland: Birne

3 Anwendungsbezogene Anwendungsbestimmungen - keine - BVL_FO_05_2437_200_V1.1 Bundesamt für Verbraucherschutz und Lebensmittelsicherheit Dr. Dietmar Gottschild Dienstsitz Braunschweig • Postfach 15 64 • 38005 Braunschweig Referent

TELEFON +49 (0)531 299-3512 Fine Agrochemicals Ltd. TELEFAX +49 (0)531 299-3002 Hill End House, Whittington E-MAIL [email protected] WR5 2RQ Worcester IHR ZEICHEN VEREINIGTES KÖNIGREICH (UK) IHRE NACHRICHT VOM

AKTENZEICHEN 200.22100.007524-00/00.61553 (bitte bei Antwort angeben)

DATUM 18. Januar 2016

ZV1 007524-00/00 Exilis Zulassungsverfahren für Pflanzenschutzmittel Änderungsbescheid

Die Zulassung des oben genannten Pflanzenschutzmittels

mit dem Wirkstoff: 20 g/l 6-Benzyladenin

Zulassungsnummer: 007524-00

Versuchsbezeichnungen: FIN-30001-W-0-SL

Antrag vom: 11. Oktober 2011

Zulassungsbescheid vom: 25. Februar 2013

ändere ich wie folgt:

Zusätzliche Anwendungsgebiete bzw. Anwendungen

Die Zulassung wird um folgende Anwendungsgebiete bzw. Anwendungen erweitert (siehe Anlage 1): - keine - BVL_FO_05_2470_200_V1.6

Das Bundesamt für Verbraucherschutz und Lebensmittelsicherheit im Internet: www.bvl.bund.de SEITE 2 VON 5

Nicht mehr zugelassene Anwendungsgebiete bzw. Anwendungen

Folgende Anwendungsgebiete bzw. Anwendungen werden aus den in Anlage 2 genannten Gründen bei der Zulassung nicht mehr vorgesehen: - keine -

Abgelehnte Anwendungsgebiete bzw. Anwendungen

Für folgende Anwendungsgebiete bzw. Anwendungen lehne ich Ihren Antrag ab (siehe Anlage 2): - keine -

Anwendungsgebiete bzw. Anwendungen in geänderter Fassung

Folgende Anwendungsgebiete bzw. Anwendungen werden aufgehoben und durch die in der Anlage 1 beschriebenen ersetzt:

Festgesetzte Anwendungsbestimmungen

Anwendungsbestimmungen gemäß § 36 Abs. 1 S. 1 des Gesetzes zum Schutz der Kultur- pflanzen (Pflanzenschutzgesetz - PflSchG) vom 6. Februar 2012 (BGBl. I S. 148, 1281), zuletzt geändert durch Artikel 375 der Verordnung vom 31. August 2015 (BGBl. I S. 1474): Folgende Anwendungsbestimmungen werden zusätzlich festgesetzt: - keine -

Folgende Anwendungsbestimmungen sind nicht mehr festgesetzt: - keine -

Siehe anwendungsbezogene Anwendungsbestimmungen in Anlage 1, jeweils unter Nr. 3.

Auflagen

Auflagen gemäß § 36 Abs. 3 S. 1 PflSchG: BVL_FO_05_2470_200_V1.6 SEITE 3 VON 5

Siehe anwendungsbezogene Kennzeichnungsauflagen in Anlage 1, jeweils unter Nr. 2.

Angaben zur Einstufung und Kennzeichnung gemäß Verordnung (EG) Nr. 1272/2008

- keine Änderung -

Hinweise

Auf dem Etikett und in der Gebrauchsanleitung kann zusätzlich angegeben werden: - entfällt -

Auf dem Etikett und in der Gebrauchsanleitung ist nicht mehr anzugeben: - entfällt -

Weitere Hinweise und Bemerkungen Vorsorglich weise ich darauf hin, dass bisher mitgeteilte Forderungen bestehen bleiben, soweit sie noch nicht erfüllt sind.

Hinsichtlich der Gebühren erhalten Sie einen gesonderten Bescheid.

Rechtsbehelfsbelehrung

Mit freundlichen Grüßen im Auftrag

gez. Dr. Martin Streloke Abteilungsleiter

Dieses Schreiben wurde maschinell erstellt und ist daher ohne Unterschrift gültig.

Anlage BVL_FO_05_2470_200_V1.6 SEITE 4 VON 5

2 Kennzeichnungsauflagen 2.1 Angaben zur sachgerechten Anwendung

Einsatzgebiet: Obstbau Anwendungsbereich: Freiland Anwendung im Haus- und Kleingartenbereich: Nein Stadium der Kultur: 71 bis 72 Maximale Zahl der Behandlungen - in dieser Anwendung: 1 - für die Kultur bzw. je Jahr: 1 Anwendungstechnik: spritzen Aufwand: - 3,75 l/ha und je m Kronenhöhe bei maximal 2 m Kro- nenhöhe in maximal 500 l Wasser/ha und je m Kro- nenhöhe

2.3 Wartezeiten (F) Freiland: Apfel Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich.

3 Anwendungsbezogene Anwendungsbestimmungen - keine - BVL_FO_05_2470_200_V1.6 SEITE 5 VON 5

2 Kennzeichnungsauflagen 2.1 Angaben zur sachgerechten Anwendung

2.3 Wartezeiten (F) Freiland: Birne Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich.

3 Anwendungsbezogene Anwendungsbestimmungen - keine - BVL_FO_05_2470_200_V1.6 Bundesamt für Verbraucherschutz und Lebensmittelsicherheit Dr. Dietmar Gottschild Dienstsitz Braunschweig • Postfach 15 64 • 38005 Braunschweig Referent

AKTENZEICHEN 200.22100.007524-00/00.61553 (bitte bei Antwort angeben)

DATUM 18. Januar 2016

ZV1 007524-00/00 Exilis Zulassungsverfahren für Pflanzenschutzmittel Änderungsbescheid

Die Zulassung des oben genannten Pflanzenschutzmittels

mit dem Wirkstoff: 20 g/l 6-Benzyladenin

Zulassungsnummer: 007524-00

Versuchsbezeichnungen: FIN-30001-W-0-SL

Antrag vom: 11. Oktober 2011

Zulassungsbescheid vom: 25. Februar 2013

ändere ich wie folgt:

Zusätzliche Anwendungsgebiete bzw. Anwendungen

Die Zulassung wird um folgende Anwendungsgebiete bzw. Anwendungen erweitert (siehe Anlage 1): - keine - BVL_FO_05_2470_200_V1.6

Das Bundesamt für Verbraucherschutz und Lebensmittelsicherheit im Internet: www.bvl.bund.de SEITE 2 VON 5

Nicht mehr zugelassene Anwendungsgebiete bzw. Anwendungen

Folgende Anwendungsgebiete bzw. Anwendungen werden aus den in Anlage 2 genannten Gründen bei der Zulassung nicht mehr vorgesehen: - keine -

Abgelehnte Anwendungsgebiete bzw. Anwendungen

Für folgende Anwendungsgebiete bzw. Anwendungen lehne ich Ihren Antrag ab (siehe Anlage 2): - keine -

Anwendungsgebiete bzw. Anwendungen in geänderter Fassung

Folgende Anwendungsgebiete bzw. Anwendungen werden aufgehoben und durch die in der Anlage 1 beschriebenen ersetzt:

Festgesetzte Anwendungsbestimmungen

Folgende Anwendungsbestimmungen sind nicht mehr festgesetzt: - keine -

Siehe anwendungsbezogene Anwendungsbestimmungen in Anlage 1, jeweils unter Nr. 3.

Auflagen

Auflagen gemäß § 36 Abs. 3 S. 1 PflSchG: BVL_FO_05_2470_200_V1.6 SEITE 3 VON 5

Siehe anwendungsbezogene Kennzeichnungsauflagen in Anlage 1, jeweils unter Nr. 2.

Angaben zur Einstufung und Kennzeichnung gemäß Verordnung (EG) Nr. 1272/2008

- keine Änderung -

Hinweise

Auf dem Etikett und in der Gebrauchsanleitung kann zusätzlich angegeben werden: - entfällt -

Auf dem Etikett und in der Gebrauchsanleitung ist nicht mehr anzugeben: - entfällt -

Weitere Hinweise und Bemerkungen Vorsorglich weise ich darauf hin, dass bisher mitgeteilte Forderungen bestehen bleiben, soweit sie noch nicht erfüllt sind.

Hinsichtlich der Gebühren erhalten Sie einen gesonderten Bescheid.

Rechtsbehelfsbelehrung

Mit freundlichen Grüßen im Auftrag

gez. Dr. Martin Streloke Abteilungsleiter

Dieses Schreiben wurde maschinell erstellt und ist daher ohne Unterschrift gültig.

Anlage BVL_FO_05_2470_200_V1.6 SEITE 4 VON 5

2 Kennzeichnungsauflagen 2.1 Angaben zur sachgerechten Anwendung

3 Anwendungsbezogene Anwendungsbestimmungen - keine - BVL_FO_05_2470_200_V1.6 SEITE 5 VON 5

2 Kennzeichnungsauflagen 2.1 Angaben zur sachgerechten Anwendung

3 Anwendungsbezogene Anwendungsbestimmungen - keine - BVL_FO_05_2470_200_V1.6 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 1 of 29

REGISTRATION REPORT Part B

Section 1: Identity, physical and chemical properties, other information Detailed summary of the risk assessment

Product code: Exilis Active Substance: 6-Benzyladenine 20.0 g/L

Central Zone Rapporteur Member State: Germany

CORE ASSESSMENT

Applicant: Fine Agrochemicals Limited Date: 18/02/2013

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 2 of 29

Table of Contents

IIIA 1 IDENTITY OF THE PLANT PROTECTION PRODUCT ...... 7 IIIA 1.1 Applicant...... 7 IIIA 1.2 Manufacturer of the Preparation, Manufacturer and Purity of the Active Substance(s) ...... 7 IIIA 1.2.1 Manufacturer(s) of the preparation ...... 7 IIIA 1.2.2 Manufacturer(s) of the active substance(s)...... 7 IIIA 1.2.3 Statement of purity (and detailed information on impurities) of the active substance(s)...... 7 IIIA 1.3 Trade Names and Manufacturer’s Code Numbers for the Preparation...... 7 IIIA 1.4 Detailed Quantitative and Qualitative Information on the Composition of the Preparation ...... 7 IIIA 1.4.1 Content of active substance and formulants...... 7 IIIA 1.4.2 Certified limits of each component ...... 8 IIIA 1.4.3 Common names and code numbers for the active substance(s)...... 8 IIIA 1.4.4 Co-formulant details: identity, structure, codes, trade name, specification and function...... 8 IIIA 1.4.5 Formulation process...... 8 IIIA 1.4.5.1 Description of formulation process...... 8 IIIA 1.4.5.2 Discussion of the formation of impurities of toxicological concern ...... 9 IIIA 1.5 Type of Preparation and Code...... 9 IIIA 1.6 Function ...... 9 IIIA 1.7 Other/Special Studies...... 9 IIIA 2 PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF THE PLANT PROTECTION PRODUCT ...... 10 IIIA 2.16 Summary and Evaluation of Data Presented Under Points 2.1 to 2.15...... 17 IIIA 3 DATA ON APPLICATION OF THE PLANT PROTECTION PRODUCT...... 17 IIIA 3.1 Field of Use...... 17 IIIA 3.2 Nature of the Effects on Harmful Organisms...... 17 IIIA 3.3 Details of Intended Use ...... 17 IIIA 3.3.1 Details of existing and intended uses ...... 17 IIIA 3.3.2 Details of harmful organisms against which protection is afforded ...... 17 IIIA 3.3.3 Effects achieved ...... 18

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 3 of 29

IIIA 3.4 Proposed Application Rates (Active Substance and Preparation)...... 18 IIIA 3.5 Concentration of the Active Substance in the Material Used...... 18 IIIA 3.6 Method of Application, Type of Equipment Used and Volume of Diluent ...... 18 IIIA 3.7 Number and Timings of Applications, Timing, Growth Stages (of Crop and Harmful Organism) and Duration of Protection...... 18 IIIA 3.7.1 Maximum number of applications and their timings ...... 18 IIIA 3.7.2 Growth stages of crops or plants to be protected...... 18 IIIA 3.7.3 Development stages of the harmful organism concerned ...... 18 IIIA 3.7.4 Duration of protection afforded by each application...... 18 IIIA 3.7.5 Duration of protection afforded by the maximum number of applications...... 18 IIIA 3.8 Necessary Waiting Periods or Other Precautions to Avoid Phytotoxic Effects on Succeeding Crops ...... 18 IIIA 3.8.1 Minimum waiting periods or other precautions between last application and sowing or planting succeeding crops ...... 18 IIIA 3.8.2 Limitations on choice of succeeding crops ...... 18 IIIA 3.8.3 Description of damage to rotational crops...... 18 IIIA 3.9 Proposed Instructions for Use as Printed on Labels...... 18 IIIA 3.10 Other/Special Studies...... 19 IIIA 4 FURTHER INFORMATION ON THE PLANT PROTECTION PRODUCT ...... 20 IIIA 4.1 Packaging and Compatibility with the Preparation ...... 20 IIIA 4.1.1 Description and specification of the packaging ...... 20 IIIA 4.1.2 Suitability of the packaging and closures...... 20 IIIA 4.1.3 Resistance of the packaging material to its contents...... 21 IIIA 4.2 Procedures for Cleaning Application Equipment ...... 21 IIIA 4.2.1 Procedures for cleaning application equipment and protective clothing...... 21 IIIA 4.2.2 Effectiveness of the cleaning procedures...... 21 IIIA 4.3 Re-entry Periods to Protect Man, Livestock and the Environment...... 21 IIIA 4.3.1 Pre-harvest interval (in days) for each relevant crop ...... 21 IIIA 4.3.2 Re-entry period (in days) for livestock, to areas to be grazed...... 21 IIIA 4.3.3 Re-entry period (in hours or days) for man to crops, buildings or spaces treated....21 IIIA 4.3.4 Withholding period (in days) for animal feeding stuffs...... 21 IIIA 4.3.5 Waiting period (in days) between application and handling of treated products .....22 IIIA 4.3.6 Waiting period (in days) between last application and sowing or planting succeeding crops ...... 22

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 4 of 29

IIIA 4.3.7 Information on specific conditions under which the preparation may or may not be used...... 22 IIIA 4.4 Statement of the Risks Arising and the Recommended Methods and Precautions and Handling Procedures to Minimise Those Risks ...... 22 IIIA 4.4.1 Warehouse storage...... 22 IIIA 4.4.2 User level storage...... 22 IIIA 4.4.3 Transport ...... 22 IIIA 4.4.4 Fire...... 22 IIIA 4.4.5 Nature of protective clothing proposed...... 22 IIIA 4.4.6 Characteristics of protective clothing proposed...... 22 IIIA 4.4.7 Suitability and effectiveness of protective clothing and equipment...... 22 IIIA 4.4.8 Procedures to minimise the generation of waste ...... 22 IIIA 4.4.9 Combustion products likely to be generated in the event of fire ...... 23 IIIA 4.5 Detailed Procedures for Use in the Event of an Accident During Transport, Storage or Use...... 23 IIIA 4.5.1 Containment of spillages...... 23 IIIA 4.5.2 Decontamination of areas, vehicles and buildings...... 23 IIIA 4.5.3 Disposal of damaged packaging, adsorbents and other materials...... 23 IIIA 4.5.4 Protection of emergency workers and bystanders ...... 23 IIIA 4.5.5 First aid measures ...... 23 IIIA 4.6 Neutralisation Procedure for Use in the Event of Accidental Spillage...... 23 IIIA 4.6.1 Details of proposed procedures for small quantities...... 24 IIIA 4.6.2 Evaluation of products of neutralization (small quantities)...... 24 IIIA 4.6.3 Procedures for disposal of small quantities of neutralized waste ...... 24 IIIA 4.6.4 Details of proposed procedures for large quantities ...... 24 IIIA 4.6.5 Evaluation of products of neutralization (large quantities) ...... 24 IIIA 4.6.6 Procedures for disposal of large quantities of neutralized waste...... 24 IIIA 4.7 Pyrolytic Behaviour of the Active Substance...... 24 IIIA 4.8 Disposal Procedures for the Plant Protection Product ...... 24 IIIA 4.8.1 Detailed instructions for safe disposal of product and its packaging ...... 24 IIIA 4.8.2 Methods other than controlled incineration for disposal ...... 24 IIIA 4.9 Other/Special Studies...... 25 IIIA 11 FURTHER INFORMATION...... 25 IIIA 11.1 Information of Authorisations in Other Countries...... 25 IIIA 11.2 Information on Established Maximum Residue Limits (MRL) in Other Countries 25

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 5 of 29

IIIA 11.3 Justified Proposals for Classification and Labelling...... 25 IIIA 11.4 Proposals for Risk and Safety Phrases...... Fehler! Textmarke nicht definiert. IIIA 11.5 Proposed Label...... 25 IIIA 11.6 Specimens of Proposed Packaging...... 25 Appendix 1: List of data used in support of the evaluation...... 26 Appendix 2: Critical Uses – justification and GAP tables...... 27 Appendix 3: Experimental testing of the product's physico-chemical and technical characteristics:...... 29

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 6 of 29

Introduction This document summarises the information related to the identity, the physical and chemical properties, the data on application, further information and the classification for the product Exilis containing the active substance 6-benzyladenine which was approved according to Regulation (EC) No 1107/2009.

Exilis was not the representative formulation reviewed in the DAR and AR but is very similar in that it contains a nominal 20 g/l 6-benzyladenine and is a soluble concentrate (SL).

The following table provides the EU endpoints to be used in the evaluation.

Agreed EU End-points

End point 6-Benzyladenin (540/2011/EU)

Purity of active substance min 973 g/kg

Appendix 1 of this document contains the list of references included in this document for support of the evaluation. Appendix 2 of this document is the table of intended uses for Exilis.

Information on the detailed composition of Exilis can be found in the confidential dossier of this submission (Registration Report - Part C).

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 7 of 29

IIIA 1 IDENTITY OF THE PLANT PROTECTION PRODUCT IIIA 1.1 Applicant

Name: Fine Agrochemicals Limited Address: Hill End House, Whittington, Worcester, WORCS. WR5 2RQ

Contact : Miss Maria McKelvie Telephone number: +44 (0) 1905 361800 Fax: +44 (0) 1905 361810 E-mail: [email protected]

IIIA 1.2 Manufacturer of the Preparation, Manufacturer and Purity of the Active Substance(s) IIIA 1.2.1 Manufacturer(s) of the preparation Confidential information - data provided separately (Part C). IIIA 1.2.2 Manufacturer(s) of the active substance(s) Confidential information - data provided separately (Part C). IIIA 1.2.3 Statement of purity (and detailed information on impurities) of the active substance(s) 6-Benzyladenin: minimum 973 g/kg Detailed information is provided in Part C. IIIA 1.3 Trade Names and Manufacturer’s Code Numbers for the Preparation Trade name: Exilis Company code number: no one mentioned

IIIA 1.4 Detailed Quantitative and Qualitative Information on the Composition of the Preparation IIIA 1.4.1 Content of active substance and formulants The formulation was not the representative formulation.

Pure active substance:

content of pure 6-benzyladenine 20 g/L

limits 6-benzyladenine 17.0 – 23.0 g/L (± 15 % according FAO/WHO):

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 8 of 29

Technical active substance:

content of technical 6-benzyladenine 20.2 g/L at typical purity (99 %):

The active substance is not present in the formulation in the form of a salt, ester, anion or cation.

Further information on the active substances and on the certified limits of formulants is considered confidential and is provided separately (Part C).

IIIA 1.4.2 Certified limits of each component This is not an EC data requirement/ not required by regulation (EU) 2011/545.

IIIA 1.4.3 Common names and code numbers for the active substance(s)

Data Type Name/Code Number Point

1.4.3.1 ISO common name none

1.4.3.2 CAS No. 1214-39-7

1.4.3.2 EINECS No. 214-927-5

1.4.3.2 CIPAC No. 829

1.4.3.2 ELINCS –

1.4.3.3 Salt, ester anion or cation – present

IIIA 1.4.4 Co-formulant details: identity, structure, codes, trade name, specification and function. CONFIDENTIAL information - data provided separately (Part C).

IIIA 1.4.5 Formulation process IIIA 1.4.5.1 Description of formulation process This is not an EC data requirement/ not required regulation (EU) 2011/545.

Applicant Fine Agrochemicals Limited Evaluator: DE / BVL Date: 18/02/2013 Part B – Section 1 Exilis Registration Report – Central Zone Core Assessment – Germany Page 9 of 29

IIIA 1.4.5.2 Discussion of the formation of impurities of toxicological concern There are no impurities of toxicological concern in the active substance 6-benzyladenine.

IIIA 1.5 Type of Preparation and Code Type : Soluble concentrate Code : SL

IIIA 1.6 Function The product will be used as growth regulator.

IIIA 1.7 Other/Special Studies None.

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IIIA 2 PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF THE PLANT PROTECTION PRODUCT All studies have been performed in accordance with the current requirements and the results are deemed to be acceptable. The appearance of the product is that of clear liquid, with a slightly sweet odour. It has no explosive or oxidising properties, the self ignition temperature is above 400 °C. In aqueous solution, it has a pH value around 4.4. The stability data indicate a shelf life of at least 2 years at ambient temperature. Its technical characteristics are acceptable for a soluble concentrate formulation.

Tabelle 1: Summary of the physical, chemical and technical properties of the plant protection product

Test or study & Method used / Test material purity Findings GLP Reference Acceptability / Annex point deviations and specification comments Y/N

Colour, odour and visual Nominal 20 g/l ± Clear liquid, no separated material. Y Knowles, R.J (2009), Acceptable physical state 15% (Actual batch = Slightly sweet odour. KIIIA1 2.1/01 (IIIA 2.1) 19 g/l 6- benzyladenine) LOT No SAF7B265CB

Explosive properties By calculation and see above non explosive – Y Knowles, R.J (2009), Acceptable. DSC data (ASTM KIIIA1 2.2.1/01 (IIIA 2.2.1) no exothermic peak E537-02) Formulation has no explosive properties.

Oxidizing properties By calculation and see above Non oxidising Y Knowles, R.J (2009), Acceptable. (IIIA 2.2.2) DSC data KIIIA1 2.2.2/01 Formulation has no oxidising properties.

Flash point EEC A9, see above 104 °C Y Knowles, R.J (2009), Acceptable. KIIIA1 2.3.1/01 (IIIA 2.3.1) CIPAC MT 12.3

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Test or study & Method used / Test material purity Findings GLP Reference Acceptability / Annex point deviations and specification comments Y/N

Flammability - - Not relevant since the formulation is - - Acceptable. (IIIA 2.3.2) a liquid

Auto-flammability EEC A15 see above None below 400 °C Y Knowles, R.J (2009), Acceptable. (IIIA 2.3.3) KIIIA1 2.3.3/01

Acidity or alkalinity CIPAC MT 31.1 see above 0.143 % m/m H2SO4 Y Knowles, R.J (2009), Acceptable. and pH KIIIA1 2.4.1/01 (IIIA 2.4.1) pH of a 1% aqueous CIPAC MT 75.3 see above 4.4 (1 % dilution) Y Knowles, R.J (2009), Acceptable. KIIIA1 2.4.2/01 dilution, emulsion or 4.2 (neat formulation) dispersion (IIIA 2.4.2)

Kinematic viscosity - - Not relevant - - Acceptable. (IIIA 2.5.1)

Dynamic viscosity OECD 114 Brookfield see above 60 mPa.s to 94.2 mPa.s Y Knowles, R.J (2009), Acceptable. (IIIA 2.5.2) viscometer, spindle 1 KIIIA1 2.5.2/01 (10 to 100 rpm)

Surface tension EEC A5 see above 65.2 mN/m (1 % in water) at 20 °C Y Knowles, R.J (2009), Acceptable. (IIIA 2.5.3) KIIIA1 2.5.3/01

Relative density EEC A3 see above 1.04 g/ml Y Knowles, R.J (2009), Acceptable. (IIIA 2.6.1) KIIIA1 2.6.1/01

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Test or study & Method used / Test material purity Findings GLP Reference Acceptability / Annex point deviations and specification comments Y/N

Bulk or tap density - - Not relevant since the formulation is - - Acceptable. (IIIA 2.6.2) a liquid

Storage Stability after CIPAC MT 46 see above Storage material: fluorinated HDPE Y Knowles, R.J (2009), Proposed packaging 14 days at 54º C KIIIA1 2.7.1/01 is also made of Coex, (IIIA 2.7.1) Physically and chemically stable. which is more resistant according to the applicant.

Stability after storage - - not relevant - - Acceptable. for other periods and/or temperatures (IIIA 2.7.2)

Minimum content - - Not necessary, since the decrease of - - Acceptable. after heat stability the active substance did not exceed testing 5 %. (IIIA 2.7.3)

Effect of low CIPAC MT 39.1 see above Solution remained clear, no Y Knowles, R.J (2009), Acceptable. temperatures on separated material KIIIA1 2.7.4/01 stability (IIIA 2.7.4)

Ambient temperature see above Physically and chemically stable Y Knowles, R.J (2009), Acceptable. shelf life when stored for 24 months at KIIIA1 2.7.5/01 (IIIA 2.7.5) ambient temperatures in the commercial pack

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Test or study & Method used / Test material purity Findings GLP Reference Acceptability / Annex point deviations and specification comments Y/N

Shelf life in months - - Please refer to 2.7.5 - - Acceptable. (if less than 2 years) (IIIA 2.7.6)

Wettability - - not relevant as the formulation is a - - Acceptable. (IIIA 2.8.1) liquid

Persistence of CIPAC MT 47.2 see above no foam produced (1 % dilution in Y Knowles, R.J (2009), Acceptable. foaming water) KIIIA1 2.8.2/01 (IIIA 2.8.2)

Suspensibility - - not relevant for SL formulations - - Acceptable. (IIIA 2.8.3.1)

Spontaneity of - - not relevant for SL formulations - - Acceptable. dispersion (IIIA 2.8.3.2)

Dilution stability CIPAC MT 41 see above < 1 ml separated material, Y Knowles, R.J (2009), Acceptable. (IIIA 2.8.4) remaining solution appears clear KIIIA1 2.8.4/01 ( 1 % dilution in water)

Dry sieve test - - not relevant for SL formulations - - Acceptable. (IIIA 2.8.5.1)

Wet sieve test - - not relevant for SL formulations - - Acceptable. (IIIA 2.8.5.2)

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Test or study & Method used / Test material purity Findings GLP Reference Acceptability / Annex point deviations and specification comments Y/N

Particle size - - not relevant for SL formulations - - Acceptable. distribution (IIIA 2.8.6.1)

Nominal size range of - - not relevant for SL formulations - - Acceptable. granules (IIIA 2.8.6.2)

Dust content - - not relevant for SL formulations - - Acceptable. (IIIA 2.8.6.3)

Particle size of dust - - not relevant for SL formulations - - Acceptable. (IIIA 2.8.6.4)

Friability and attrition - - not relevant for SL formulations - - Acceptable. (IIIA 2.8.6.5)

Emulsifiability - - not relevant for SL formulations Acceptable. (IIIA 2.8.7.1)

Dispersibility - - not relevant for SL formulations Acceptable. (IIIA 2.8.7.1)

Flowability - - not relevant for SL formulations Acceptable. (IIIA 2.8.8.1)

Pourability (including - - not relevant for SL formulations Acceptable. rinsed residue)

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Test or study & Method used / Test material purity Findings GLP Reference Acceptability / Annex point deviations and specification comments Y/N (IIIA 2.8.8.2)

Dustability following - - not relevant for SL formulations Acceptable. accelerated storage (IIIA 2.8.8.3)

Physical - - Not relevant since no tank mixes - - Acceptable. compatibility of tank recommended mixes (IIIA 2.9.1)

Chemical - - Not relevant since no tank mixes - - Acceptable. compatibility of tank recommended mixes (IIIA 2.9.2)

Distribution to seed - - Not relevant since the formulation is - - Acceptable (IIIA 2.10.1) not to be used as a seed treatment

Adhesion to seeds - - Not relevant since the formulation is - - Acceptable (IIIA 2.10.2) not to be used as a seed treatment

Miscibility - - Not required by regulation (EU) - - Acceptable. (IIIA 2.11) 2011/545.

Dielectric breakdown - - Not required by regulation (EU) - - Acceptable. (IIIA 2.12) 2011/545.

Corrosion - - Not required by regulation (EU) - - Acceptable. characteristics 2011/545.

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Test or study & Method used / Test material purity Findings GLP Reference Acceptability / Annex point deviations and specification comments Y/N (IIIA 2.13)

Container material - - Not required by regulation (EU) - - Acceptable. (IIIA 2.14) 2011/545.

Other/special studies - - Not required by regulation (EU) - - Acceptable. (IIIA 2.15) 2011/545.

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IIIA 2.16 Summary and Evaluation of Data Presented Under Points 2.1 to 2.15 All studies have been performed in accordance with the current requirements and the results are deemed to be acceptable. The appearance of the product is that of clear liquid, with a slightly sweet odour. It has no explosive or oxidising properties, the self ignition temperature is above 400 °C. In aqueous solution, it has a pH value around 4.4. The stability data indicate a shelf life of at least 2 years at ambient temperature. Its technical characteristics are acceptable for a soluble concentrate formulation.

Experimental testing of the product's physico-chemical and technical characteristics: See Appendix 3

Implications for labelling: No implications for labelling due to physical or chemical properties.

IIIA 3 DATA ON APPLICATION OF THE PLANT PROTECTION PRODUCT IIIA 3.1 Field of Use Exilis is a Plant Growth Regulator (PGR) containing the active substance 6-benzyladenine. It is used as a post-bloom thinning agent with an additional effect on fruit size above and beyond the direct thinning effect. IIIA 3.2 Nature of the Effects on Harmful Organisms The mode of action of 6-BA in pome fruit thinning is to promote the abscission of fruits at the early stages of fruitlet development. The uptake of 6-BA is mainly through leaves and fruitlets. 6-BA is locally translocated in the foliage and the fruit and is therefore not regarded as a PGR with systemic activity. Following application and uptake, the PGR modulates photosynthesis and cell respiration in the developing fruit. In the days following application, the net photosynthesis is reduced while the net mitochondrial cell respiration is increased. The combined effect of a reduced carbohydrate production and accelerated cell respiration in the developing fruit enhances the competition for nutrients and promotes the abscission of less fit fruit. In addition, 6-BA promotes cell division in the developing fruit, leading to a higher cell count in fruit and creating the potential for bigger fruit independently from the thinning efficacy.. IIIA 3.3 Details of Intended Use IIIA 3.3.1 Details of existing and intended uses The present application is provided as a national application for Germany. Germany as zRMS belongs to the central registration zone (zone B). The Netherlands are involved in the registration procedure as cMS. According to EPPO standard PP1/241 (zones of comparable climate in the EPPO region), Germany is part of the maritime EPPO zone. In Germany, the present request for authorization as PGR in apples and pears for thinning is applied for the first time. Currently no other product is registered for comparable use containing 6-BA. According to the notification form, comparable products are registered in France, UK, Italy, Greece and Spain.

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IIIA 3.3.2 Details of harmful organisms against which protection is afforded The aim is to promote the abscission of fruits at the early stages of fruitlet development to allow for better development of the remainig fruit. IIIA 3.3.3 Effects achieved An effective fruit set reduction and potential for bigger fruit is to be ensured. IIIA 3.4 Proposed Application Rates (Active Substance and Preparation) The proposed target dosage of 7,5 L/ha can be said to be the minimum effective rate for Exilis to ensure an effective fruit set reduction and potential for bigger fruit. IIIA 3.5 Concentration of the Active Substance in the Material Used Exilis is formulated as a 2% (i.e. 20 gram/litre) 6-BA soluble concentrate. IIIA 3.6 Method of Application, Type of Equipment Used and Volume of Diluent Foliar spray using 500 L/ha water IIIA 3.7 Number and Timings of Applications, Timing, Growth Stages (of Crop and Harmful Organism) and Duration of Protection IIIA 3.7.1 Maximum number of applications and their timings One application per year and crop IIIA 3.7.2 Growth stages of crops or plants to be protected Application at the end of blooming (BBCH 71). IIIA 3.7.3 Development stages of the harmful organism concerned Not relevant. IIIA 3.7.4 Duration of protection afforded by each application Not relevant. IIIA 3.7.5 Duration of protection afforded by the maximum number of applications Not relevant. IIIA 3.8 Necessary Waiting Periods or Other Precautions to Avoid Phytotoxic Effects on Succeeding Crops IIIA 3.8.1 Minimum waiting periods or other precautions between last application and sowing or planting succeeding crops None IIIA 3.8.2 Limitations on choice of succeeding crops None IIIA 3.8.3 Description of damage to rotational crops Not relevant.

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IIIA 3.9 Proposed Instructions for Use as Printed on Labels Please refer to Registration Report – Part A IIIA 3.10 Other/Special Studies This is not an EC data requirement/ not required by Directive 91/414/EEC.

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IIIA 4 FURTHER INFORMATION ON THE PLANT PROTECTION PRODUCT IIIA 4.1 Packaging and Compatibility with the Preparation Packaging Summary Information with regard to type, dimensions, capacity, size of opening, type of closure, strength, leakproofness, resistance to normal transport & handling, resistance to & compatibility with the contents of the packaging, have been submitted, evaluated and is considered to be acceptable.

IIIA 4.1.1 Description and specification of the packaging Exilis is to be marketed in high-density polyethylene containers with an inner barrier, e.g., polyamide (PA/PE). They are sealed by foil seals, protected by screw caps of polyethylene.

5 L container material: PA/PE (Coex)

shape/size: 190 x 140 x 307 mm

opening: 54.5 mm

closure: 63 mm induction heat sealed white cap

10 L container material: PA/PE (Coex)

shape/size: 230 x 165 x 375 mm

opening: 54.5 mm

closure: 63 mm induction heat sealed white cap

20 L container material: fluorinated HDPE

shape/size: 259 x 237 x 415 mm

opening: 54.5 mm inner neck diameter

closure: 63 mm induction heat sealed white cap

IIIA 4.1.2 Suitability of the packaging and closures Exilis has been demonstrated as having good storage stability when packed in fluorinated high density polyethylene (F-HDPE) and as COEX-HDPE is of a superior quality no problems are perceived with the suitability of packing Exilis in COEX-HDPE.

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The packaging is designed for agrochemical use and is acceptable for the subsidiary regulations for the transport of dangerous goods. All bottles contain a heat sealed induction cap.

IIIA 4.1.3 Resistance of the packaging material to its contents Exilis has been found to be physically and chemically stable when stored in the F-HDPE container for up to 24 months and as COEX-HDPE is of a superior quality no problems are perceived with the suitability of packing Exilis in COEX-HDPE.

IIIA 4.2 Procedures for Cleaning Application Equipment IIIA 4.2.1 Procedures for cleaning application equipment and protective clothing Immediately after use, clean the spray equipment thoroughly. Drain the system completely and rinse spray tank, boom and nozzles two to three times with clean water until all traces of product have been removed.

IIIA 4.2.2 Effectiveness of the cleaning procedures Exilis is a soluble concentrate formulation, effective cleaning can be obtained by rinsing with water. No specific data to assess the effectiveness of cleaning procedures are available or deemed necessary.

IIIA 4.3 Re-entry Periods to Protect Man, Livestock and the Environment IIIA 4.3.1 Pre-harvest interval (in days) for each relevant crop 90 days for apples and pears.

IIIA 4.3.2 Re-entry period (in days) for livestock, to areas to be grazed Not applicable.

IIIA 4.3.3 Re-entry period (in hours or days) for man to crops, buildings or spaces treated Please refer to Registration Report – Part A, classification and labelling.

IIIA 4.3.4 Withholding period (in days) for animal feeding stuffs

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Not applicable.

IIIA 4.3.5 Waiting period (in days) between application and handling of treated products Not applicable – early application.

IIIA 4.3.6 Waiting period (in days) between last application and sowing or planting succeeding crops Not applicable.

IIIA 4.3.7 Information on specific conditions under which the preparation may or may not be used Please refer to Registration Report – Part A.

IIIA 4.4 Statement of the Risks Arising and the Recommended Methods and Precautions and Handling Procedures to Minimise Those Risks

IIIA 4.4.1 Warehouse storage Store in cool dry conditions in original well marked containers. IIIA 4.4.2 User level storage Store in cool dry conditions in original well marked containers. Keep away from drink and foodstuffs. IIIA 4.4.3 Transport Not classified IIIA 4.4.4 Fire

Use dry chemical, foam, CO2, water mist

IIIA 4.4.5 Nature of protective clothing proposed Please refer to Registration Report – Part A.

IIIA 4.4.6 Characteristics of protective clothing proposed Please refer to Registration Report – Part A.

IIIA 4.4.7 Suitability and effectiveness of protective clothing and equipment Exilis is not an eye or skin irritant but recommendations are that personal protective clothing is worn.

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IIIA 4.4.8 Procedures to minimise the generation of waste Dispose or recycle the empty and clean container according to the national regulations. Avoid contamination of any water supply with chemical or empty container. IIIA 4.4.9 Combustion products likely to be generated in the event of fire At very high temperatures Exilis will decompose to form carbon, chlorine, nitrogen and sulphur compounds. Combustion of monopropylene glycol may produce aldehydes.

IIIA 4.5 Detailed Procedures for Use in the Event of an Accident During Transport, Storage or Use

IIIA 4.5.1 Containment of spillages Isolate spilled material for safe disposal and collect in sealable polylined containers, clean contaminated area with water. Prevent contaminated water entering drains.

IIIA 4.5.2 Decontamination of areas, vehicles and buildings May be taken to waste disposal site or incineration plant when in compliance with local regulations refer to the local waste regulations authority.

IIIA 4.5.3 Disposal of damaged packaging, adsorbents and other materials May be taken to waste disposal site or incineration plant when in compliance with local regulations refer to the local waste regulations authority. IIIA 4.5.4 Protection of emergency workers and bystanders There are no specific hazards associated with Exilis to emergency workers and bystanders but spilled material should be isolated and collected in sealable polylined containers for safe disposal.

IIIA 4.5.5 First aid measures After inhalation: Remove the person to a well ventilated area. Ensure the person is warm and comfortable. Obtain immediate medical attention.

After skin contact: Remove contaminated clothing. Wash the affected area thoroughly with soap and water. Obtain medical attention if irritation occurs.

After eye contact: Irrigate eyes with running water for at least 15 minutes.

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After swallowing: Do not induce vomiting, give water or milk to dilute and seek medical advice.

IIIA 4.6 Neutralisation Procedure for Use in the Event of Accidental Spillage

IIIA 4.6.1 Details of proposed procedures for small quantities No specific requirements

IIIA 4.6.2 Evaluation of products of neutralization (small quantities) None IIIA 4.6.3 Procedures for disposal of small quantities of neutralized waste Not relevant.

IIIA 4.6.4 Details of proposed procedures for large quantities Not relevant.

IIIA 4.6.5 Evaluation of products of neutralization (large quantities) not relevant

IIIA 4.6.6 Procedures for disposal of large quantities of neutralized waste not relevant.

IIIA 4.7 Pyrolytic Behaviour of the Active Substance Not applicable since 6-BA is unlikely to form polyhalogenated dibenzo-p-dioxins under pyrolysis at 8000C IIIA 4.8 Disposal Procedures for the Plant Protection Product IIIA 4.8.1 Detailed instructions for safe disposal of product and its packaging Product - May be taken to waste disposal site or incineration plant when in compliance with local regulations refer to the local waste regulation authority. Packaging - Empty containers can be land filled when in accordance with local regulation.

IIIA 4.8.2 Methods other than controlled incineration for disposal Not relevant.

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IIIA 4.9 Other/Special Studies Not relevant.

IIIA 11 FURTHER INFORMATION IIIA 11.1 Information of Authorisations in Other Countries see EU pesticide data base (http://ec.europa.eu/sanco_pesticides/public/ )

IIIA 11.2 Information on Established Maximum Residue Limits (MRL) in Other Countries No MRLs are currently set. No residues at or above the default MRL of 0.01*mg/kg are expected in apples and pears at harvest.

IIIA 11.3 Justified Proposals for Classification and Labelling The product is not classified. For further details please refer to Registration Report – Part A, classification and labelling.

IIIA 11.5 Proposed Label Please refer to Registration Report – Part A.

IIIA 11.6 Specimens of Proposed Packaging Specimens of the packaging were not provided as there was no request.

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Appendix 1: List of data used in support of the evaluation

Annex point/ Author(s) Year Title Data Owner How considered in reference No Source (where different from protection dRR company) claimed Study-Status / Usage* Report-No. GLP or GEP status (where relevant), Published or not Authority registration No KIIIA1 2.1/01 Knowles, 2009 Accelerated and 2 years at Y Fine 1 2.2.1 R.J Ambient Storage Stability on Agrochemi Exilis, G C Laboratories cals 2.2.2 Limited, Stotfold, Hitchin, UK, Limited 2.3.1 Report Number; J16294, GLP, 2.3.3 unpublished 2.4.1 2.4.2 2.5.2 2.5.3 2.6.1 2.7.1 2.7.3 2.7.4 2.7.5 2.8.2 2.8.4

KIIIA1 4.1/01 anonymous 2012 Statement for Coex packaging Y Fine 1 Agrochemi cals Limited

KIIIA1 4.1/02 anonymous 2012 Packaging information 5 L- Y Fine 1 Container Agrochemi cals Limited

KIIIA1 4.1/03 anonymous 2012 Packaging information 10 L- Y Fine 1 Container Agrochemi cals Limited

KIIIA1 4.1/04 anonymous 2012 Packaging information 20 L- Y Fine 1 Container Agrochemi cals Limited

* 1 accepted (study valid and considered for evaluation) 2 not accepted (study not valid and not considered for evaluation) 3 not considered (study not relevant for evaluation) 4 not submitted but necessary (study not submitted by applicant but necessary for evaluation) 5 supplemental (additional information, alone not sufficient to fulfil a data requirement, considered for evaluation)

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Appendix 2: Critical Uses – justification and GAP tables PPP (product name/code) Exilis (007524-00) Formulation type: SL active substance 6-Benzyladenin Conc. of as 1: 20 g/L

Applicant: Fine Agrochemicals Ltd. professional use X Zone(s): central non professional use

Verified by MS: y

1 2 3 4 5 6 7 8 10 11 12 13 14 Use- Member Crop and/ F Pests or Group of pests Application Application rate PHI Remarks: No. state(s) or situation G controlled (days) or Method / Timing / Growth Max. number kg, L product / g, kg as/ha Water L/ha e.g. safener/synergist per ha (crop destination / I (additionally: Kind stage of crop & (min. interval ha purpose of crop) developmental stages of season between a) max. rate per a) max. rate min / max e.g. recommended or mandatory tank the pest or pest group) applications) appl. per appl. mixtures a) per use b) max. total rate b) max. total per crop/season rate per b) per crop/ crop/season season 001 DE Apple F Enhancing fruit size, spraying 71 - 71 a) 1 a) 3,75 L/ha and a) 0.075 kg 500 L/ha 90 NW642 Thinning of fruit b) 1 per m crown a.i./ha and per and per m height m crown crown b) 7,5 L/ha height height b) 0,15 kg a.i./ha 002 DE Pear F Enhancing fruit size, spraying 71 - 71 a) 1 a) 3,75 L/ha and a) 0.075 kg 500 L/ha 90 NW642 Thinning of fruit b) 1 per m crown a.i./ha and per and per m height m crown crown b) 7,5 L/ha height height b) 0,15 kg a.i./ha NL Apple F Fruit thinning and fruit spraying Fruit between 7 a) 1 a) 7,5 L/ha a) 0,15 kg 300 – 1000 90 Max. 3.75 L product/ha/m crown height size in improvement and 15 mm (BBCH b) 1 b) 7,5 L/ha a.i./ha L 71-74) b) 0,15 kg a.i./ha

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NL Pear F Fruit thinning and fruit spraying Fruit between 7 a) 1 a) 7,5 L/ha a) 0,15 kg 300 – 1000 90 Max. 3.75 L product/ha/m crown height size in improvement and 15 mm (BBCH b) 1 b) 7,5 L/ha a.i./ha L 71-74) b) 0,15 kg a.i./ha Remarks: (a) For crops, the EU and Codex classifications (both) should be used; where relevant, the use (i) g/kg or g/l situation should be described (e.g. fumigation of a structure) (j) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) Blackwell, ISBN 3-8263-3152-4), including where relevant, information on season at time (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds of application (d) e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) (k) The minimum and maximum number of application possible under practical conditions of (e) GCPF Codes - GIFAP Technical Monograph No 2, 1989 use must be provided (f) All abbreviations used must be explained (l) PHI - minimum pre-harvest interval (g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (m) Remarks may include: Extent of use/economic importance/restrictions (h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated

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Appendix 3: Experimental testing of the product's physico-chemical and technical characteristics: The following physical, chemical and technical properties of the plant protection product were experimentally tested: density, colour, pH, surface tension, storage stability at high temperatures (14 d at 54 °C), low temperature stability (7 d at 0 °C), persistent foaming and dilution stability. No significant deviations from the data submitted by the applicant were detected. The formulation complies with the chemical, physical and technical criteria which are stated for this type of formulation in the FAO/WHO manual (2010).

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REGISTRATION REPORT Part B

Section 2: Analytical Methods Detailed summary of the risk assessment

Product code: Exilis Active Substance: 6-benzyladenine 20.0 g/L

Central Zone Rapporteur Member State: Germany

CORE ASSESSMENT

Applicant: Fine Agrochemicals Limited Date: 18/02/2013

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Table of Contents

IIIA 5 METHODS OF ANALYSIS...... 4

IIIA 5.1 Analytical Standards and Samples ...... 4

IIIA 5.1.1 Samples of the preparation...... 4

IIIA 5.1.2 Analytical standards for the pure active substance ...... 4

IIIA 5.1.3 Samples of the active substance as manufactured...... 4

IIIA 5.1.4 Analytical standards for relevant metabolites and all other components included in the residue definition...... 4

IIIA 5.1.5 Samples of reference substances for relevant impurities ...... 4

IIIA 5.2 Methods for the Analysis of the Plant Protection Product...... 4

IIIA 5.2.1 Description of the analytical methods for the determination of the active substance in the plant protection product...... 4

IIIA 5.2.2 For preparations containing more than one active substance, description of method for determining each in the presence of the other ...... 5

IIIA 5.2.3 Applicability of existing CIPAC methods ...... 5

IIIA 5.2.4 Description of analytical methods for the determination of relevant impurities ...... 6

IIIA 5.2.5 Description of analytical methods for the determination of formulants...... 6 IIIA 5.3 Description of Analytical Methods for the Determination of Residues...... 6 IIIA 5.3.1 Evaluation of 6-benzyladenine ...... 6 IIIA 5.3.1.1 Overview of residue definitions and levels for which compliance is required...... 7 IIIA 5.3.1.2 Description of Analytical Methods for the Determination of Residues of 6-benzyladenine in Plant Matrices (OECD KIII A 5.3.1)...... 8 IIIA 5.3.1.3 Description of Analytical Methods for the Determination of Residues of 6-benzyladenine in Animal Matrices (OECD KIII A 5.3.1)...... 9 IIIA 5.3.1.4 Description of Methods for the Analysis of 6-benzyladenine in Soil (OECD KIII A 5.4)...... 9 IIIA 5.3.1.5 Description of Methods for the Analysis of 6-benzyladenine in Water (OECD KIII A 5.6)...... 9 IIIA 5.3.1.6 Description of Methods for the Analysis of 6-benzyladenine in Air (OECD KIII A 5.7)...... 10 Applicant: Fine Agrochemicals Limited Evaluator: DE / BVL Date : 18/02/2013

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IIIA 5.3.1.7 Description of Methods for the Analysis of 6-benzyladenine in Body Fluids and Tissues (OECD KIII A 5.8) ...... 10 IIIA 5.3.1.8 Other Studies/ Information ...... 10

Appendix 1 – List of data submitted in support of the evaluation ...... 12

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IIIA 5 METHODS OF ANALYSIS This document summarises the information related to the analytical methods for the product Exilis containing the active substance 6-benzyladenine which was approved according to Regulation (EC) No 1107/2009.

This product was not the representative formulation. The product has not been previously evaluated according to Uniform Principles.

Appendix 1 of this document contains the list of references included in this document for support of the evaluation.

Information on the detailed composition of Exilis can be found in the confidential dossier of this submission (Registration Report - Part C).

IIIA 5.1 Analytical Standards and Samples

IIIA 5.1.1 Samples of the preparation A sample of the preparation was provided by the applicant but no analysis of the content of the active substance was performed.

IIIA 5.1.2 Analytical standards for the pure active substance An analytical standard of 6-benzyladenine was provided.

IIIA 5.1.3 Samples of the active substance as manufactured No samples were provided because there was no request.

IIIA 5.1.4 Analytical standards for relevant metabolites and all other components included in the residue definition No samples were provided because there was no request.

IIIA 5.1.5 Samples of reference substances for relevant impurities No samples were provided because there was no request. 6-benzyladenine does not contain any impurity of toxicological or ecotoxicological concern.

IIIA 5.2 Methods for the Analysis of the Plant Protection Product Analytical methods for the determination of 6-benzyladenine, impurities and relevance of CIPAC methods were not evaluated as part in the EU review. Therefore all relevant data are provided and are considered adequate.

IIIA 5.2.1 Description of the analytical methods for the determination of the active substance in the plant protection product

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The following analytical method and validation for the determination of the active substance in the plant protection product performed on Exilis has not previously been reviewed.

Report: KIIIA1 5.2.1/01, Parsons, A.H, 2005 Title: Validation of analytical method M496 ‘ HPLC determination of 6-benzyladenine (BAP) in formulations and technical material’ for the ‘Exilis Formulation’. Document No: K2 Guidelines: OPPTS 830.1700 + 830.1800 GLP Yes, certified laboratory

Method description The samples are diluted with methanol and then mixed in an ultrasonic bath. A dilution is performed to obtain a compatibility with the chromatographic solvent. The analyses have been performed using reverse phase, High Performance Liquid Chromatography system for separation (mobile phase : 0.2 % perchloric acid in water / methanol 55 / 45%) and UV/vis detection at 215 nm. Dimethyl phthalate has been used as the internal standard.

Method validation

Table containing the methods and validation of the methods (formulation Exilis) Analyte Linearity Accuracy Repeatability n = Specificity/Inteferences n = 5 n = 5 5

6- 0.5 – 1.5 times of mean RSD = 0.45 % No interferences were noted. benzyladenine expected recovery acceptable acc. Chromatograms of formulation with and concentration 100.5 % Horwitz: 2.44 % without active ingredients present were r2 = 0.9994 submitted. acceptable: Specifity was confirmed by identity of (97 – 103 UV-spectrum with an analytical standard. %)

Summary A method using analysis by HPLC-UV is provided. Linearity, Precision, Accuracy and Specificity have been checked and found acceptable. According to the data, the method for the determination of the active substance in the formulated product is validated. No further data are required.

IIIA 5.2.2 For preparations containing more than one active substance, description of method for determining each in the presence of the other Not relevant, Exilis contains only one active substance.

IIIA 5.2.3 Applicability of existing CIPAC methods There is no CIPAC method available for the determination of 6-benzyladenine.

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IIIA 5.2.4 Description of analytical methods for the determination of relevant impurities 6-benzyladenine does not contain any relevant impurity.

IIIA 5.2.5 Description of analytical methods for the determination of formulants No formulants with toxicological or ecotoxicological relevant compounds are present in the formulation. Therefore, no analytical methods for the determination of formulants are necessary.

IIIA 5.3 Description of Analytical Methods for the Determination of Residues

Based on the information submitted the applicant has full access to methods evaluated in the DAR.

Conclusion

Sufficiently sensitive and selective analytical methods are not available for all for kinds of food and feed of plant origin. Based on the Guidance Document on Pesticide Residue Analytical Methods (SANCO/825/00 rev. 8.1 of 2010-11-16) independently validated analytical methods and confirmatory methods have to be provided for all matrix groups. This general requirement is independent from the intended use.

Noticed data gaps are: 1. An analytical method for the determination of residues of 6-benzyladenine in commodities with high oil content has to be provided. 2. Independent validations of analytical methods for the determination of residues of 6- benzyladenine in dry commodities and in commodities with high oil content have to be provided. 3. Confirmatory methods for the determination of residues of 6-benzyladenine in commodities with high oil content and commodities with high acid content have to be provided.

IIIA 5.3.1 Evaluation of 6-benzyladenine The conclusion regarding the peer review of the analytical methods for residues of 6-benzyladenine are summarized in EFSA Journal 2010; 8(10) 1716.

Name of component of residue definiton Structural formula substance code IUPAC name formula 6-benzyladenine N6-benzyladenine or N-benzyl-1H-purin-6-amine C12H11N5

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IIIA 5.3.1.1 Overview of residue definitions and levels for which compliance is required Compared to the residue definition proposed in the Draft Assessment Report (incl. its addenda) the current legal residue definition (based on article 18 (1) b) is the same.

Table IIIA 5.3-1: Relevant residue definitions

Matrix Relevant residue Reference Remarks plant material 6-benzyladenine EFSA Journal 2010; 8(10) 1716 foodstuff of animal origin not relevant EFSA Journal 2010; 8(10) 1716 soil ecotoxicology 6-benzyladenine EFSA Journal 2010; 8(10) 1716 water ecotoxicology 6-benzyladenine EFSA Journal 2010; 8(10) 1716 human toxicology 6-benzyladenine EFSA Journal 2010; 8(10) 1716 air 6-benzyladenine generally defined body fluids/tissue not relevant not classified as T / T+

Table IIIA 5.3-2: Levels for which compliance is required

Matrix MRL Reference for MRL/level Remarks Plant, high water content 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) Plant, acidic commodities 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) Plant, dry commodities 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) Plant, high oil content 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) Plant, difficult matrices (hops, 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 spices, tea) (1) (b) meat 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) milk 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) eggs 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) fat 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) liver, kidney 0.01 mg/kg Regulation (EC) No 396/2005; Art. 18 (1) (b) soil 0.05 mg/kg common limit drinking water 0.1 µg/L general limit for drinking water

surface water 310 µg/L EC50 Lemna gibba, EFSA Journal 2010; 8(10) 1716

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air 9 µg/m3 AOEL sys/AOEL inhal: 0.03 mg/kg bw/d, EFSA Journal 2010; 8(10) 1716 tissue (meat or liver) not required not classified as T / T+ blood not required not classified as T / T+

IIIA 5.3.1.2 Description of Analytical Methods for the Determination of Residues of 6- benzyladenine in Plant Matrices (OECD KIII A 5.3.1) An overview of the acceptable methods and possible data gaps for analysis of 6-benzyladenine in plant matrices is given in the following tables. New studies were not provided.

Table IIIA 5.3-3: Overview of independently validated methods and confirmatory methods for food and feed of plant origin (always required for first 4 matrix types)

Matrix type Primary method ILV Confirmatory method high water content Kruplak, 2000*; Stevenson, 2001* Wolf, 2004* Wolf, 2004* acidic Kruplak, 2000* Stevenson, 2001* missing fatty missing missing missing dry Wolf, 2004* missing Wolf, 2004* difficult not required for the intended not required for the not required for the GAP intended GAP intended GAP * EU-agreed method (see Draft Assessment Report)

Table IIIA 5.3-4: Statement on extraction efficiency

Method for products of plant origin Required, available from: Not required, because: no residues expected

Table IIIA 5.3-5: Methods suitable for the determination of residues (enforcement) in products of plant origin

Author(s), year Matrix Method LOQ Principle of Comment Evaluated in group method Kruplak J.F., high water 0.005 mg/kg GC-NPD after very laborious DAR Vol. 3 B.5.2, 2000 content, derivatization, method Additional Report acidic RTX-5 and Addendum 1 to the AR (ASB2011-10201) Wolf S., 2004 high water 0.01 mg/kg LC-MS/MS; confirmation DAR Vol. 3 B.5.2 content, dry ESI+; C18; m/z with phenyl- and Additional 226→91 hexyl column is Report included (ASB2011-10199) Stevenson K., high water 0.005 mg/kg GC-NPD after ILV of Kruplak, DAR Vol. 3 B.5.2, 2001 content derivatization, 2000 Additional Report RTX-5 and Addendum 1 to the AR

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(ASB2011-10200)

IIIA 5.3.1.3 Description of Analytical Methods for the Determination of Residues of 6- benzyladenine in Animal Matrices (OECD KIII A 5.3.1) The intended use of the plant protection product does not lead to residues in crops. Therefore, analytical methods for animal matrices are not required.

IIIA 5.3.1.4 Description of Methods for the Analysis of 6-benzyladenine in Soil (OECD KIII A 5.4) An overview of the acceptable methods and possible data gaps for analysis of 6-benzyladenine in soil is given in the following tables. New studies were not provided.

Table IIIA 5.3-6: Overview of suitable primary and confirmatory methods for soil

Component(s) of residue definition Primary method Confirmatory method 6-benzyladenine Wolf, 2004* Wolf, 2004* 6-benzyladenine Burton, 2008* Burton, 2008* * EU-agreed method (see Draft Assessment Report)

Table IIIA 5.3-7: Methods for soil

Author(s), year Method LOQ Principle of method Comment Evaluated in Wolf S., 2004 0.01 mg/kg LC-MS/MS, C18, confirmation DAR Vol. 3 B.5.3 ESI+, m/z 226→91 with phenyl- and Additional hexyl column Report column (ASB2011-10198) Burton D., 2008 0.01 mg/kg LC-MS/MS, C18, m/z confirmation Additional Report 226→91, 226→148 with 2nd MRM (ASB2011-10216) transition

IIIA 5.3.1.5 Description of Methods for the Analysis of 6-benzyladenine in Water (OECD KIII A 5.6) An overview of the acceptable methods and possible data gaps for analysis of 6-benzyladenine in surface and drinking water is given in the following table. New studies were not provided.

Table IIIA 5.3-8: Overview of suitable primary and confirmatory methods for water

Component(s) of residue Matrix Primary method Confirmatory method definition 6-benzyladenine drinking water/ surface Wolf, 2004* Kruplak, 2003* water * EU-agreed method (see Draft Assessment Report)

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Table IIIA 5.3-9: Methods for drinking water and surface water

Author(s), year Method LOQ Principle of method Comment Evaluated in Wolf S., 2004 0.05 µg/L LC-MS/MS, C18, direct injection; DAR Vol. 3 B.5.3 ESI+, m/z 226→91 confirmation and Additional with 2nd column Report (Phenyl-hexyl) (ASB2011-10196) Kruplak J.F., 2003 0.01 µg/L LC-MS/MS, confirmation DAR Vol. 3 B.5.3 Aminopropyl column, not included and Additional ESI-, m/z 224→133 Report (ASB2011-10202)

IIIA 5.3.1.6 Description of Methods for the Analysis of 6-benzyladenine in Air (OECD KIII A 5.7) An overview of the acceptable methods and possible data gaps for analysis of 6-benzyladenine in air is given in the following table. New studies were not provided.

Table IIIA 5.3-10: Overview of suitable primary and confirmatory methods for air

Component(s) of residue definition Primary method Confirmatory method 6-benzyladenine Burton, 2009* Burton, 2009* * EU-agreed method (see Draft Assessment Report)

Table IIIA 5.3-11: Methods for air

Author(s), year Method LOQ Principle of method Comment Evaluated in Burton D., 2009 0.023 µg/m3 LC-MS/MS, C18, m/z confirmation Additional Report 226→91, 226→148 with 2nd MRM and Addendum 1 to transition the AR (ASB2011-10217)

IIIA 5.3.1.7 Description of Methods for the Analysis of 6-benzyladenine in Body Fluids and Tissues (OECD KIII A 5.8) Methods for body fluids and tissues are not required, because 6-benzyladenine is not considered as toxic or very toxic (T / T+) nor is it classified according to GHS as follows: Acute toxicity (cat. 1 - 3), CMR (cat. 1) or STOT (cat. 1).

IIIA 5.3.1.8 Other Studies/ Information Further studies were provided for 6-benzyladenine, but not considered for the following reasons:

• The study of Carlo G.G., 1996 (ASB2011-10209) concerning Determination of 6-Benzyladenine residues on apple and pear was insufficiently validated with two replicates per level (minimum requirement is five replicates). • The study of Stearns J, 2009 (ASB2011-10212) cannot be considered as independent laboratory validation of the method of Carlo G.G., 1996, because an additional cleanup was needed. • The study of Ingelse B.A., 2000 (ASB2011-10213) concerning a method of analysis of 6-BA in water using HPLC could not be evaluated with regard to the selectivity. Indispensable

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chromatograms of blank samples are missing.

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Appendix 1 – List of data submitted in support of the evaluation Annex point/ Author(s) Year Title Data Owner How considered in reference No Source (where different from company) protection dRR Report-No. claimed Study-Status / Usage* GLP or GEP status (where relevant), Published or not Authority registration No KIIIA 5.2.1/01 Parsons, A.H, 2005 Validation of analytical method M496 ‘ Y Fine Y HPLC determination of 6-benzyladenine Agrochemical (BAP) in formulations and technical Limited material’ for the ‘Exilis Formulation’ G C Laboratories Limited, Stotfold, Hitchin, UK, Report Number; J15472, GLP, unpublished

OECD: KIIA 4.3 Carlo, G. G. 1996 Determination of 6-Benzyladenine N residues on apple and pear - Report of analytical method validation in compliance with GLP regulations NEOT/GLP/LN52B-95 BVL-2197678, ASB2011-10209 OECD: KIIA 4.3 Kruplak, J. F. 2000 Validation of the method for quantitation Y of 6-Benzyladenine (6BA) in apples, apple juice and wet apple pomace ADC 1766V-1 BVL-2197681, ASB2011-10201 OECD: KIIA 4.3 Stearns, J. 2009 Independent Laboratory Validation of the N method described in Determination of 6- BA on Apple & Pear Valent USA Corporation V-32888 BVL-2197686, ASB2011-10212 OECD: KIIA 4.3 Stevenson, K. 2001 Independent laboratory validation of Y Valent Bioscience analytical method 1766V-1 for the analysis of 6-BA in apples, apple juice, and wet apple pomace (2001) (incl. amendment no. 1 dated 27.06.2003) AD/5576/VB BVL-2197680, ASB2011-10200 OECD: KIIA 4.3 Wolf, S. 2004 Development and validation of a residue Y analytical method for 6- Benzylaminopurine in maize (grain and silage) 854457 BVL-2197679, ASB2011-10199 OECD: KIIA 4.4 Burton, D. 2008 6-BA: Validation of Methodology for the Y Determination of Residues in Two soil types. Valent/Fine Agrochemicals ZAB0094 BVL-2197687, ASB2011-10216 OECD: KIIA 4.4 Wolf, F. 2004 Development and validation of a residue Y analytical method for 6- Benzylaminopurine in soil 854380 BVL-2197694, ASB2011-10198 OECD: KIIA 4.5 Ingelse, BA 2000 Validation of the analysis of 6-BA in N water using HPLC for Valent biosciences V2953 BVL-2197696, ASB2011-10213 OECD: KIIA 4.5 Kruplak, J. F. 2003 Validation of a method for the Y determination of 6-Benzyladenine (6BA) in surface water ADC 1879-1 BVL-2197685, ASB2011-10202

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Annex point/ Author(s) Year Title Data Owner How considered in reference No Source (where different from company) protection dRR Report-No. claimed Study-Status / Usage* GLP or GEP status (where relevant), Published or not Authority registration No OECD: KIIA 4.5 Wolf, S. 2004 Development and validation of a residue Y analytical method for 6- Benzylaminopurine in drinking, ground, and surface water 854381 BVL-2197695, ASB2011-10196 OECD: KIIA 4.7 Burton, D. 2009 6-Benzyladenine: Validation of Y methodology for the determination of residues of 6-Benzyladenine in air HLS, Cambridgeshire, UK ZAB0096 BVL-2197688, ASB2011-10217 All EFSA 2010 Conclusion on the peer review of the Used pesticide risk assessment of the active substance 6-benzyladenine EFSA Journal 2010; 8(10):1716; ASB2012-1116

* Y: Yes, relied on N: No, not relied on Add: Relied on, study not submitted but necessary for evaluation

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REGISTRATION REPORT Part B

Section 3: Mammalian Toxicology Detailed summary of the risk assessment

Product code: Exilis Active Substance: 6-Benzyladenine (20 g/L)

Central Zone Zonal Rapporteur Member State: Germany

CORE ASSESSMENT

Applicant: Agrochemicals Limited Date: 12/04/2012

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Table of Contents

IIIA 7 Mammalian Toxicology ...... 3 IIIA 7.1 Toxicological Evaluation of Active Substance 6- Benzyladenine...... 3 IIIA 7.2 Toxicological Evaluation of Pesticide...... 3 IIIA 7.3 Dermal Absorption ...... 4 IIIA 7.4 Safety Assessment of Pesticide Application...... 5 IIIA 7.4.1 Selection of critical use(s) and justification...... 5 IIIA 7.4.2 Evaluation of the Active Substance 6-Benzyladenine...... 7 IIIA 7.4.2.1 Operator exposure and risk assessment ...... 7 IIIA 7.4.2.2 Worker exposure and risk assessment ...... 8 IIIA 7.4.2.3 Bystander and resident exposure and risk assessment...... 9 IIIA 7.4.3 Conclusion of Exposure Estimation and Risk Assessment ...... 9 IIIA 7.5 Justified Proposals for Classification and Labelling and Safety Instructions...... 10 Appendix 1 List of Data Submitted in Support of the Evaluation...... 12 Appendix 2 Detailed Evaluation of the Studies Relied upon...... 13 A 2.1 Acute Oral Toxicity...... 13 A 2.2 Acute Percutaneous (Dermal) Toxicity ...... 14 A 2.3 Acute Inhalation Toxicity...... 15 A 2.4 Skin Irritation...... 17 A 2.5 Eye Irritation...... 18 A 2.6 Skin Sensitisation ...... 19 A 2.7 Supplementary Studies for Combinations of Plant Protection Products ...... 21 A 2.8 Short-Term Toxicity Studies ...... 21 A 2.9 Data on Formulants ...... 21 A 2.9.1 Material safety data sheet for each formulant...... 21 A 2.9.2 Available toxicological data for each formulant...... 21 A 2.10 Studies on Dermal Absorption...... 21 A 2.11 Other/Special Studies ...... 21 Appendix 3 Exposure Calculations ...... 22 A 3.1 Exposure Calculations for 6-Benzyladenine...... 22 A 3.1.1 Operator exposure calculations...... 22 A 3.1.2 Worker exposure calculations...... 30 A 3.1.3 Bystander and resident exposure calculations ...... 31

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IIIA 7 Mammalian Toxicology

IIIA 7.1 Toxicological Evaluation of Active Substance

Table IIIA 7.1-1: Agreed EU endpoints for 6-benzyladenine

Value Reference

ADI 0.01 mg/kg bw SANCO/12667/2010 final (2011-01-04)

AOEL systemic 0.03 mg/kg bw/d EFSA Journal 2010; 8(10):1716 (2010-08-27)

ARfD (acute reference dose) n.n. (no exposure) EFSA Journal 2010; 8(10):1716 (2010-08-27)

Table IIIA 7.1-2: Classification and proposed labelling for 6-benzyladenine

Regulation (EC) No 1272/2008 (Table 3.2): substance not listed up to and including 1st ATP with regard to toxicological data Proposal DE: (according to the criteria in Dir. 67/548/EEC) Xn - Harmful R22 - Harmful if swallowed R63 - Possible risk of harm to the unborn child

with regard to toxicological data Regulation (EC) No 1272/2008 (Table 3.1): substance not (according to the criteria in Reg. 1272/2008) listed up to and including 1st ATP Proposal DE: Acute toxicity, cat. 4 Reproductive toxicity, cat. 2 H302 - Harmful if swallowed H361d - Suspected of damaging the unborn child

IIIA 7.2 Toxicological Evaluation of Pesticide

Table IIIA 7.2-1: General information on Exilis

Product name and code Exilis (FIN-30001-W-0-SL) Formulation type SL (Water soluble concentrate) Active substance 6-Benzyladenine (20 g/L) (incl. content) Category Plant growth regulator Statement as to whether the product was already Yes evaluated as the ‘representative formulation’ during the Annex I inclusion or has been previously evaluated in an other MS according to Uniform Principles

Information on the detailed composition of Exilis can be found in the confidential dossier of this submission (Registration Report - Part C).

A summary of the toxicological evaluation for Exilis is given in Table IIIA 7.2-2. Full summaries of studies on the product Exilis are presented in Appendix 2.

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Table IIIA 7.2-2: Summary of evaluation of the studies on acute toxicity including irritancy and skin sensitisation for Exilis

Classification Classification Type of test, species Result (acc. to the (acc. to the Acceptability Reference (Guideline) criteria in Dir. criteria in Reg. 67/548/EEC) 1272/2008)

LD50 oral, rat > 2000 mg/kg Yes None None Farkas, B., (OECD 423) bw/day (2007)

LD50 dermal, rat > 2000 mg/kg Yes None None Farkas, B., (OECD 402) bw/day (2007)

LC50 inhalation, rat > 5.02 mg/L air Yes None None Wesson, C., (OECD 403) (2007) Skin irritation, rabbit Non-irritant Yes None None Stahl, J., (OECD 404) (2007) Eye irritation, rabbit Non-irritant Yes None None Stahl, J., (OECD 405) (2007) Skin sensitisation, Non-sensitising Yes None None Stahl, J., guinea pig (2007) (OECD 406, M&K) Supplementary studies No data – not for combinations of required plant protection products

Table IIIA 7.2-3: Additional relevant toxicological information

Classification of the Classification of Exilis Substance substance (acc. to the criteria in Type of test, species (Concentration (acc. to the criteria in Dir. Reference Dir. 67/548/EEC, in (Guideline) in product, 67/548/EEC and/or in Dir. 1999/45/EC and/or % w/w) Reg. 1272/2008) in Reg. 1272/2008)

Short-term toxicity No data – not studies required Toxicological data on None active substance (not tested with the preparation) Toxicological data on None non-active substances (not tested with the preparation) Further relevant No data – not toxicological required information

An overview on the classification and labelling of the preparation is given in paragraph IIIA 7.5.

IIIA 7.3 Dermal Absorption

No in vivo or in vitro study conducted with Exilis were submitted for the evaluation of this application.

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Exilis is very similar to the product Maxcel that contains 20 g/l 6-benzyladenine and is also a soluble concentrate formulation. The dermal absorption studies performed on MAXCEL SL are summarized in Table IIIA 7.3-1. No detailed summaries are provided as the studies have already been assessed and accepted at EU level. The dermal absorption values quoted for Maxcel at EU level can also be used for Exilis.

Table IIIA 7.3-1: Agreed EU end-points for dermal absorption of 6-benzyladenine, which were also used for evaluation of Exilis

Information on dermal absorption rate of MAXCEL SL 20 g/L: 6-benzyladenine 13 % for the concentrate (19 g/L, applied dose appr. 0.19 mg/cm2) and 7 % for the dilution (0.19 g/L, applied dose appr. 1.9 µg/cm2) based on rat in vivo (EFSA Journal 2010; 8(10):1716 (2010-08-27), ASB2011-10254)

IIIA 7.4 Safety Assessment of Pesticide Application

Table IIIA 7.4-1: Product information and toxicological reference values used for safety assessment of pesticide application

Product name and code Exilis (FIN-30001-W-0-SL) Formulation type SL (Water soluble concentrate) Active substance 6-Benzyladenine (20 g/L) (incl. content) Category Plant growth regulator Container sizes, short Containers 5 L, 10 L and 20 L; HDPE, COEX description with wide necks (min. 63 mm) and screw caps Statement as to whether the No product was already evaluated as the ‘representative formulation’ during the Annex I inclusion AOEL systemic 0.03 mg/kg bw/d Oral absorption 100 % Inhalative absorption 100 % Dermal absorption Concentrate: 13 % Dilution: 7 % based on: SL formulation containing 20 g/L a.s. (MAXCEL)

IIIA 7.4.1 Selection of critical use(s) and justification The critical GAPs used for the safety assessment of pesticide application are presented in Table IIIA 7.4-2.

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Table IIIA 7.4-2: Critical Use (worst case) used for safety assessment of pesticide application

1 2 3 4 5 6 7 8 9 10 11 12 13 Use- Member Crop and/ F Pests or Group of pests Application Application rate PHI Remarks: No. state(s) or situation G controlled (days) or Method / Timing / Growth Max. number L product / ha kg as/ha Water L/ha (i) (j) I Kind stage of crop & (min. interval (a) (b) (c) season between min / max (d-f) (g) applications) 1 DE Apple F Fruit thinning and fruit Spraying BBCH 71 1 3.75 l/ha per m 0.075 kg 300 – 1000 90 Max. 3.75 L product/ha per size development crown height as/ha per m crown height with maximum m crown crown height of height 2 m max. 7.5 l/ha 2 DE Pear F Fruit thinning and fruit Spraying BBCH 71 1 3.75 l/ha per m 0.075 kg 300 – 1000 90 Max. 3.75 L product/ha per size development crown height as/ha per m crown height with maximum m crown crown height of height 2 m max. 7.5 l/ha

Remarks: (a) For crops, the EU and Codex classifications (both) should be used; where relevant, (g) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, the use situation should be described (e.g. fumigation of a structure) Blackwell, ISBN 3-8263-3152-4), including where relevant, information on season (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) at time of application (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds (h) The minimum and maximum number of application possible under practical (d) All abbreviations used must be explained conditions of use must be provided (e) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, (i) PHI - minimum pre-harvest interval drench (j) Remarks may include: Extent of use/economic importance/restrictions (f) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated

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IIIA 7.4.2 Evaluation of the Active Substance 6-Benzyladenine

IIIA 7.4.2.1 Operator exposure and risk assessment

Estimation of operator exposure and risk assessment

Table IIIA 7.4-3: Exposure models for intended uses

Critical uses Apples and pears (max. 1 x 3.75 L Exilis/ha per metre crown height, 2 m assumed) Model German model (available on http://www.bfr.bund.de/cm/343/anwendersicherheit_deutsches_modell_v1.xls) [Uniform Principles for Safeguarding the Health of Applicators of Plant Protection Products (Uniform Principles for Operator Protection), Mitteilungen aus der Biologischen Bundesanstalt für Land-und Forstwirtschaft, Berlin-Dahlem, Heft 277, 1992] Critical uses Apples and pears (max. 1 x 3.75 L Exilis/ha per metre crown height, 2 m assumed) Model Revised UK-POEM, (available on http://www.pesticides.gov.uk/uploadedfiles/Web_Assets/PSD/UK_POEM1.xls) [Estimation of Exposure and Absorption of Pesticides by Spray Operators, Scientific subcommittee on Pesticides and British Agrochemical Association Joint Medical Panel Report (UK MAFF), 1986 and the Predictive Operator Exposure Model (POEM) V 1.0, (UK MAFF), 1992]

Table IIIA 7.4-4: Estimated operator exposure towards 6-benzyladenine

Total absorbed dose Model data Level of PPE % of systemic AOEL (mg/kg/day)

Tractor mounted spray applications outdoors to high crops Application rate: 0.15 kg a.s./ha German Model no PPE 1) 0.0195 64.9 Body weight: 70 kg with PPE 2) 0.0142 47.2 UK POEM no PPE 4) 0.0992 330.7 Application volume: 300 L/ha 3) Container: 10 litres 63 mm with PPE 5) 0.0535 178.3 closure (‘worst case’) Body weight: 60 kg Hand held spray applications outdoors to high crops Application rate: 0.15 kg a.s./ha German Model no PPE 1) 0.0639 213.1 Body weight: 70 kg with PPE 2) 0.0074 24.6 UK POEM no PPE 4) 0.0958 319.4 Application volume: 300 L/ha 3) Container: 5 litres 45 or 63 with PPE 6) 0.0127 42.4 mm closure 7) Body weight: 60 kg 1) no PPE: Operator wearing T-shirt and shorts 2) with PPE: gloves during mixing/loading (PPE acc. to the Federal Office of Consumer Protection and Food Safety (BVL); 2006; Personal protective equipment for handling plant protection products - Guidelines for requirements concerning

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personal protective equipment in plant protection) 3) minimum volume applied according to GAP given by the notifier 4) no PPE: Operator wearing long sleeved shirt, long trousers (‘permeable’) but no gloves 5) with PPE: gloves during mixing/loading and application 6) with PPE: gloves during mixing/loading and application as well as with impermeable coverall 7) realistic worst case, since max. 7.5 L Exilis/day are needed for this scenario

For the detailed calculations it is referred to Appendix 3.

Measurement of operator exposure and risk assessment

Applying the UK POEM the acceptable operator exposure level (AOEL) will be exceeded in the case of tractor-mounted equipment even if PPE is used. On the other hand, operator exposure is acceptable according to the UK POEM if hand-held equipment and PPE are applied.

According to the German model the acceptable operator exposure level will not be exceeded under conditions of intended uses if PPE is worn. Therefore, a study to provide measurements of operator exposure was not necessary and was not performed.

IIIA 7.4.2.2 Worker exposure and risk assessment

Estimation of worker exposure and risk assessment

Table IIIA 7.4-5: Exposure models for intended uses

Critical uses Apples and pears (max. 1 x 3.75 L Exilis/ha per metre crown height, 2 m assumed) Model German re-entry model, Krebs et al. (2000) (available on http://www.bfr.bund.de/cm/343/schutz_von_personen_bei_nachfolgearbeiten_v1.xls) [Uniform Principles for Safeguarding the Health of Workers Re-entering Crop Growing Areas after Application of Plant Protection Products, Nachrichtenbl. Deut. Pflanzenschutzdienst., 52(1), p. 5-9]

Table IIIA 7.4-6: Estimated worker exposure towards 6-benzyladenine Total absorbed % of systemic Model data Level of PPE dose (mg/kg/day) AOEL Number of applications and application rate: 1 x 0.15 kg a.s./ha German re-entry model no PPE 3) 0.0117 5) 39 8 hours/day 1), TC: 4500 cm2/person/h 2) with PPE 4) 0.0006 5) 2 Body weight: 60 kg 1) 8 h/day for professional applications for harvesting, pruning, tying, thinning or weeding activities etc. 2) EUROPOEM II, 2002, Post-Application Exposure of Workers to Pesticides in Agriculture 3) no PPE: Worker wearing long-sleeved shirt, long trousers (“permeable”) but no gloves 4) with PPE: see 'Instructions for use' 5) calculated using the dermal absorption value for the concentrate (‘worst case’)

For the detailed calculations it is referred to Appendix 3.

Measurement of worker exposure and risk assessment

Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL)

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IIIA 7.4.2.3 Bystander and resident exposure and risk assessment

Estimation of bystander and resident exposure and risk assessment

Table IIIA 7.4-7: Exposure models for intended uses

Critical use(s) Apples and pears (max. 1 x 3.75 L Exilis/ha per metre crown height, 2 m assumed) Model Martin, S. et al. (2008) (available on http://www.bfr.bund.de/cm/343/schutz_von_nebenstehenden_und_anwohnern_v1.xls) [Guidance for Exposure and Risk Evaluation for Bystanders and Residents Exposed to Plant Protection Products During and After Application; J. Verbr. Lebensm. 3 (2008): 272-281 Birkhäuser Verlag Basel and Bundesanzeiger (BAnz), 06 January 2012, Issue No. 4, pp. 75-76]

Table IIIA 7.4-8: Estimated bystander and resident exposure towards 6-benzyladenine Total absorbed dose Model data % of systemic AOEL (mg/kg/day) Air assisted spray applications outdoors to high crops ('worst case') Number of applications and application rate: 1 x 0.15 kg a.s./ha Bystanders (adult) Drift rate: 15.73 % (HC, 3 m) 0.005123 1) 17.1 Body weight: 60 kg Bystanders (children) Drift rate: 15.73 % (HC, 3 m) 0.004011 1) 13.4 Body weight: 16.15 kg Residents (adult) Drift rate: 15.73 % (HC, 3 m) 0.000373 1) 1.2 Body weight: 60 kg Residents (children) Drift rate: 15.73 % (HC, 3 m) 0.000859 1) 2.9 Body weight: 16.15 kg 1) calculated using the dermal absorption value for the concentrate (‘worst case’)

For the detailed calculations it is referred to Appendix 3.

Measurement of bystander and resident exposure and risk assessment

Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of bystander or resident exposure was not necessary and was therefore not performed.

IIIA 7.4.3 Conclusion of Exposure Estimation and Risk Assessment The risk assessment according to the German model has shown that the estimated exposure towards 6- benzyladenine in Exilis will not exceed the systemic AOEL for operators, workers, bystanders and residents. Operator exposure will be below the systemic AOEL only, if prescribed PPE is worn. No specific PPE is necessary for workers.

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The risk assessment according to the UK-POEM has shown that the estimated exposure towards 6- benzyladenine in Exilis will not exceed the systemic AOEL for operators, workers, bystanders and residents if hand-held equipment is used. To achieve this the use of PPE is mandatory for operators. In the case of tractor-mounted equipment, the systemic AOEL will be exceeded referred to the UK POEM even if PPE is used.

If used properly and according to the intended conditions of use, adverse health effects for operators, workers, bystanders and residents will not be expected.

IIIA 7.5 Justified Proposals for Classification and Labelling and Safety Instructions

Justified proposals for classification and labelling

In accordance with Directives 67/548/EEC and 1999/45/EC the following classification and labelling with regard to toxicological data is proposed for the preparation:

Table IIIA 7.5-1: Classification and labelling according to Directives 67/548/EEC and 1999/45/EC

Hazard symbols: None Indications of danger: None Risk phrases: None Safety phrases: None Labelling texts and restrictions: To avoid risks to man and the environment, comply with the instructions for use.

According to the criteria given in Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, the following classification for toxicological hazards of the preparation according to GHS would be proposed:

Table IIIA 7.5-2: Classification and labelling according to Regulation (EC) No 1272/2008

Hazard classes, categories: None Signal word: None Hazard statements: None Labelling texts and restrictions: To avoid risks to man and the environment, comply with the instructions for use.

Safety instructions

Table IIIA 7.5-3: Safety phrases for use instructions

Safety instructions (codes according to BVL 1)) Justification 2) SB001 Avoid any unnecessary contact with the product. Misuse can lead to health 1 damage. SB010 Keep out of the reach of children. 2 SB110 The directive concerning requirements for personal protective gear in plant 1 protection, "Personal protective gear for handling plant protection products" of

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the Federal Office of Consumer Protection and Food Safety must be observed. SF245-01 Treated areas/crops may not be entered until the spray coating has dried. 2 SS110 Wear standard protective gloves (plant protection) when handling the undiluted 4 product. Wear protective gloves when handling the undiluted product. – corresponds 5 approximately to S37 Wear protective gloves when handling/applying the product ready for 5 application. – corresponds approximately to S37 Wear an impermeable coverall when applying/handling the product ready for 5 application. – corresponds approximately to S36 1) http://www.bvl.bund.de/SharedDocs/Downloads/04_Pflanzenschutzmittel/eAntrag-Codelisten- EN.pdf?__blob=publicationFile&v=6 2) Justification: 1 Mandatory for plant protection products 2 With regard to preventive health protection and good agricultural practice 3 Based on BBA-Guideline Part I, 3-3 (1993) with regard to the dangerous substance directive (Biologische Bundesanstalt für Land- und Forstwirtschaft, Richtlinen für die Prüfung von Pflanzenschutzmitteln – Kennzeichnung von Pflanzenschutzmitteln (Gesundheitsschutz) (Federal Biological Research Centre for Agriculture and Forestry, Guidelines for Evaluation of Plant Protection Products – Labelling of Plant Protection Products (Human Health)): None 4 Based on the exposure estimation according to the German model for the operator and the uniform principles for the protection of workers 5 Based on the exposure estimation according to the UK-POEM for the operator using hand-held equipment and the uniform principles for the protection of workers Please note: Application using tractor-mounted equipment cannot be supported due to excess of systemic AOEL by estimated operator exposure (UK POEM)

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Appendix 1 List of Data Submitted in Support of the Evaluation

Table A 1: List of data submitted in support of the evaluation Annex point/ Author Year Title Data Owner How considered reference No Report-No. protection in dRR Authority Registration-No. claimed Study-Status / Usage*

OECD: KIIIA1- Farkas, B. 2007 Acute oral toxicity study (Acute Y 7.1.1 toxic class method) of test item Exilis 2% SL formulation in rats, Report-No.: 07/394-001P, ASB2011-14765 OECD: KIIIA1- Farkas, B. 2007 Acute dermal toxicity study of Y 7.1.2 test item Exilis 2% SL formulation in rats, Report-No.: 07/394-002P, ASB2011-14766 OECD: KIIIA1- Wesson, 2007 Acute inhalation toxicity study Y 7.1.3 C. (Nose only) in the rats, Report-No.: 07/394-004P ASB2011-14767 OECD: KIIIA1- Stahl, J. 2007 Acute skin irritation study of Y 7.1.4 Exilis 2% SL formulation in rabbits, Report-No.: 07/394-006N, ASB2011-14768 OECD: KIIIA1- Stahl, J. 2007 Acute eye irritation study of Y 7.1.5 Exilis 2% SL formulation in rabbits, Report-No.: 07/394-005N, ASB2011-14769 OECD: KIIIA1- Stahl, J. 2007 Skin Sensitisation of Exilis 2% Y 7.1.6 SL formulation in guinea pigs by Magnusson and Kligman, Report-No.: 07/394-104T, ASB2011-14770 OECD: KIIIA1- Smith, A. 2006 6-Benzyladenine: In vivo Y 7.6 D. dermal absorption study in rats Report-No.: URL0907-REG, ASB2011-10254 * Y: Yes, relied on N: No, not relied on Add: Relied on, study not submitted but necessary for evaluation

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Appendix 2 Detailed Evaluation of the Studies Relied upon

A 2.1 Acute Oral Toxicity

Reference: KIIIA1-7.1.1 Report Acute oral toxicity study (Acute toxic class method) of test item Exilis 2% SL formulation in rats Farkas, B., 2007, report-no. 07/394-001P, ASB2011-14765 Guidelines: OECD 423 Directive 2004/73/EEC B.1 tris OPPTS Guideline 870.1100 Deviations: No GLP: Yes Acceptability: Yes

Materials and methods The acute oral toxicity of Exilis (Batch number: W0655B, clear liquid which contains 20.8 g/L 6- benzyladenine (a.i.) as the active ingredient) was tested in 12 female Wistar rats (CRL:(WI) BR) at dose levels of 300 mg/kg bw (2 x 3 animals) and 2000 mg/kg bw (2 x 3 animals) according to the acute toxic class method.

Following an overnight fast, three rats were given a single dose of Exilis (300 mg/kg/body weight, i.e. 10 mL/kg body weight) by gavage as the first step of the procedure. Since no animal died a second group of three rats was dosed alike. Again no mortality occurred. Therefore, successively two additional groups of three rats were given 2000 mg/kg bw Exilis. After treatment the rats were observed daily for mortality, signs of gross toxicity, behavioral changes and weighed weekly for 14 days. At the end of the study survivors were sacrificed and necropsy was performed.

Results and discussions Table A 2: Results of acute oral toxicity study in rats of Exilis

Dose LD (mg/kg bw) Toxicological results 1) Duration of signs Time of death 50 (mg/kg bw) (14 days)

female rats 300 0 / 0 / 3 -- -- 300 0 / 0 / 3 -- -- 2000 0 / 2 / 3 3 h or 3 days, respectively -- > 2000 2000 0 / 0 / 3 -- > 2000 1) Number of animals which died/number of animals with clinical signs/number of animals used

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Table A 3: Summary of findings of acute oral toxicity study in rats of Exilis

Mortality: No Clinical signs: Hunched back and dyspnoea in 2/3 animals in one of the groups at a concentration of 2000 mg/kg bw Exilis Body weight: Not reduced in the 300 mg/kg bw dose groups, but two animals did not gain weight in the second week (d 7 - d 14), two rats at the high concentration slightly lost weight in week 2. Macroscopic Haemorrhages in pinprick size: 5/6 rats at 300 mg/kg bw, examination: 1/6 animals at 2000 mg/kg bw: hydrometra Both alterations considered not test item related: haemorrhages due to method of termination (exsanguination procedure) and hydrometra as a consequence of normal oestrus cycle among female rats at this age according to the applicant.

Conclusion

Under the experimental conditions, the oral LD50 of Exilis is greater than 2000 mg/kg bw in rats. Thus, no classification is required according to the classification criteria of Council Directive 67/548/EEC and subsequent regulations as well as according to Regulation (EC) No. 1272/2008.

Comments of zRMS: Acceptable used for evaluation, applicant’s description modified by the zRMS

A 2.2 Acute Percutaneous (Dermal) Toxicity

Reference: KIIIA1-7.1.2 Report Acute dermal toxicity study of test item Exilis 2% SL formulation in rats Farkas, B., 2007, report-no. 07/394-002P, ASB2011-14766 Guideline(s): OECD 402 Directive 92/69/EEC B.3 OPPTS Guideline 870.1200 Deviations: No GLP: Yes Acceptability: Yes

Materials and methods The acute dermal toxicity of Exilis (Batch number: W0655B, clear liquid which contains 20.8 g/L 6- benzyladenine as the active ingredient) was tested in 5 female and 5 male Wistar rats (CRL:(WI) BR) at a dose level of 2000 mg/kg bw using undiluted test substance.

24 hours prior to the start of the treatment period the trunk of the animals was shaven. The test item was applied as a single dose uniformly over an area of approximately 10 per cent of the total body surface for a 24-hour exposure period.

Clinical examinations were performed on the day of treatment 1 h and 5 h after application of the test item, and once a day for 14 days thereafter. Body weights of the animals were recorded prior to dosing

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Results and discussions Table A 4: Results of acute dermal toxicity study in rats of Exilis

Dose LD (mg/kg bw) Toxicological results 1) Duration of signs Time of death 50 (mg/kg bw) (14 days)

male rats 2000 0 / 0 / 5 -- -- > 2000 female rats 2000 0 / 0 / 5 -- -- > 2000 1) Number of animals which died/number of animals with clinical signs/number of animals used

Table A 5: Summary of findings of acute dermal toxicity study in rats of Exilis

Mortality: No Clinical signs: No Body weight: Not reduced Macroscopic Haemorrhages in pinprick size: 4/5 males and 1/5 females; examination: 3/5 females: hydrometra Both alterations considered not test item related: haemorrhages due to method of termination (exsanguination procedure) and hydrometra as a consequence of normal oestrus cycle among female rats at this age according to the applicant.

Conclusion

Under the experimental conditions, the dermal LD50 of Exilis is greater than 2000 mg/kg bw in rats. Thus, no classification is required according to the classification criteria of Council Directive 67/548/EEC and subsequent regulations as well as according to Regulation (EC) No. 1272/2008.

Comments of zRMS: Acceptable (no deviations from above mentioned test guideline), used for evaluation, applicant’s description modified by the zRMS

A 2.3 Acute Inhalation Toxicity

Reference: KIIIA1-7.1.3 Report Exilis 2% SL formulation: Acute inhalation toxicity study (nose only) in the rat Wesson, C., 2007; report-no. 07/394-004P, ASB2011-14767 Guidelines: OECD 403 Directive 92/69/EEC B.2 OPPTS Guideline 870.1300 Deviations: No GLP: Yes Acceptability: Yes

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Materials and methods The acute inhalation toxicity of Exilis (Batch number: W0655B, clear liquid which contains 20.8 g/L 6- benzyladenine as the active ingredient) was tested using 5 female and 5 male Wistar rats (CRL:(WI) BR). The rats were exposed to a liquid aerosol of the product at a target concentration of 5.0 mg/L air via nose- only inhalation equipment for 4-hours.

The test item was aerosolised using a stainless steel concentric jet nebuliser (TSE Systems GmbH, Germany) located at the top of the nose-only exposure chamber (TSE Rodent Exposure System, Germany). The animals were individually held in tapered polycarbonate restraining tubes, so that only the nose was exposed to the test atmosphere. Airflow and relative pressure within the exposure chamber were constantly monitored and adjusted by the computer system. Samples of the test atmosphere were taken at regular intervals during exposure and the concentration of the test item was determined gravimetrically. The particle size of the test atmosphere was analysed three times during exposure using a 7-stage impactor of Mercer style (TSE Systems GmbH, Germany). Other parameters of the test atmosphere, such as temperature, or relative humidity were monitored continuously during the exposure period.

Animals were checked twice daily for mortality during the observation period of 14 days and were observed for signs of toxicity during exposure, 1 h after exposure and subsequently once daily. Individual body weights were recorded prior to treatment on the day of exposure and on days 7 and 14. At the end of the 14 days observation period the animals were killed by exsanguination under anaethesia and gross necropsies were carried out.

Results and discussions Table A 6: Concentrations and exposure conditions

Target conc. Nominal conc. [mg/L Analytical conc. MMAD 1) GSD 2) [mg/L air] air] [mg/L air] [µm]

5 42.0 3) 5.02 3.31 2.33 1) MMAD = Mass Median Aerodynamic Diameter 2) GSD = Geometric Standard Deviation 3) Due to spillage this value is considered to be artificially high according to the applicant.

Table A 7: Results of acute inhalation toxicity study in rats of Exilis

Dose LC (mg/L air) Toxicological results 1) Duration of signs Time of death 50 (mg/kg bw) (14 days)

male rats 5.02 0 / 5 / 5 1 day 2) -- > 5.02 female rats 5.02 0 / 5 / 5 1 day 2) -- > 5.02 1) Number of animals which died/number of animals with clinical signs/number of animals used 2) Refers to increased respiratory rate, fur staining disappeared by day 2 in all animals

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Table A 8: Summary of findings of acute inhalation toxicity study in rats of Exilis

Mortality: No Clinical signs: Wet fur, fur staining, mild to laboured respiration and increased respiratory rate Body weight: 2 females slightly lost weight during week 2. Macroscopic Haemorrhages in pinprick size in 2/5 males and 2/5 females; examination: 1/5 females: hydrometra Both alterations considered not test item related: haemorrhages due to method of termination (exsanguination procedure) and hydrometra as a consequence of normal oestrus cycle among female rats at this age according to the applicant.

Conclusion

Under the experimental conditions, the acute inhalation LC50 of Exilis is greater than 5.02 mg/L air in rats. Thus, no classification is required according to the classification criteria of Council Directive 67/548/EEC and subsequent regulations as well as according to Regulation (EC) No. 1272/2008.

Comments of zRMS: Acceptable (no deviations from above mentioned test guideline), used for evaluation, applicant’s description modified by the zRMS

A 2.4 Skin Irritation

Reference: KIIIA1-7.1.4 Report Acute skin irritation study of Exilis 2% SL formulation in rabbits Stahl, J., 2007, report-no. 07/394-006N, ASB2011-14768 Guidelines: OECD 404 Directive 2004/73/EEC B.4 OPPTS Guideline 870.2500 Deviations: No GLP: Yes Acceptability: Yes

Materials and methods The skin irritation potential of Exilis (Batch number: W0655B, clear liquid which contains 20.8 g/L 6- benzyladenine as the active ingredient) was evaluated in 3 healthy male New Zealand white rabbits.

Approximately 24 hours prior to the test, the hair was clipped off the back and flanks of the animals. The test item, i.e. 0.5 mL of neat Exilis, was evenly applied to approximately 6 cm2 of intact skin. Untreated skin of each animal served as a control. Sterile gauze pads were place on the skin of the treated rabbits and the entire trunks of the animals were wrapped with plastic wrap for 4 hours. After 4 hours of exposure, the rest of the test item was removed with body temperature water. Animals were examined for signs of erythema and oedema at 1, 24, 48 and 72 hours after patch removal. The dermal irritation scores were evaluated according to the Draize system. Body weights were recorded at the beginning and at the end of the experiment.

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Results and discussions Table A 9: Skin irritation of Exilis

1) Animal Scores after treatment Mean scores Reversible

No. (24-72 h) [day] 1 h 24 h 48 h 72 h

1 Erythema 0 0 0 0 0.0 -- Oedema 0 0 0 0 2 Erythema 0 0 0 0 0.0 -- Oedema 0 0 0 0 3 Erythema 0 0 0 0 0.0 -- Oedema 0 0 0 0 1) scores in the range of 0 to 4

Clinical signs: No

Conclusion Under the experimental conditions, Exilis is not a skin irritant. Thus, no classification is required according to the classification criteria of Council Directive 67/548/EEC and subsequent regulations as well as according to Regulation (EC) No. 1272/2008.

Comments of zRMS: Acceptable (no deviations from above mentioned test guideline), used for evaluation, applicant’s description modified by the zRMS

A 2.5 Eye Irritation

Reference: KIIIA1-7.1.5 Report Acute eye irritation study of Exilis 2% SL formulation in rabbits Stahl, J., 2007, report-no. 07/394-005N, ASB2011-14769 Guideline(s): OECD 405 Directive 2004/73/EEC B.5 OPPTS Guideline 870.2400 Deviations: No GLP: Yes Acceptability: Yes

Materials and methods The eye irritation potential of Exilis (Batch number: W0655B, clear liquid which contains 20.8 g/L 6- benzyladenine as the active ingredient) was evaluated in 3 healthy male New Zealand white rabbits.

In the first step only one animal was used. The test item, i.e. 0.1 mL of neat Exilis was instilled into the conjunctival sac of the left eye. The eyelids were held closed gently for several seconds to prevent the loss of the test item. The contralateral eye served as a control. Immediately after administration of the test substance, initial pain reaction was recorded according to the six point scale. After consideration of the

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Exilis – 007524-00/00 Part B – Section 3 - Core Assessment ZRMS Version ocular response produced in the first animal, two additional animals were treated. Prior to administration of Exilis the eyes of the animals were not anaesthetised, because the score of initial pain was 1 in the first animal. The eyes were examined at 1, 24, 48 and 72 hours after treatment. All clinical signs of toxicity or signs of impaired health were recorded during the study. Scoring was carried out according to the Draize system.

Results and discussions Table A 10: Eye irritation of Exilis

1) Animal Scores after treatment Mean scores Reversible

No. (24-72 h) [day] 1 h 24 h 48 h 72 h

1 Corneal opacity 0 0 0 0 0.0 Iritis 0 0 0 0 0.0 Redness conjunctivae 1 0 0 0 0.0 day 2 Chemosis conjunctivae 0 0 0 0 0.0 Discharge 3 1 0 0 0.3 2 Corneal opacity 0 0 0 0 0.0 Iritis 0 0 0 0 0.0 Redness conjunctivae 2 0 0 0 0.0 day 1 Chemosis conjunctivae 0 0 0 0 0.0 Discharge 3 0 0 0 0.0 3 Corneal opacity 0 0 0 0 0.0 Iritis 0 0 0 0 0.0 Redness conjunctivae 1 0 0 0 0.0 day 2 Chemosis conjunctivae 0 0 0 0 0.0 Discharge 3 1 0 0 0.3 1) scores in the range of 0 to 4 for cornea opacity and chemosis, 0 to 3 for redness of conjunctiva and discharge, 0 to 2 for iritis

Clinical signs: No

Conclusion Under the experimental conditions, Exilis is not an eye irritant. Thus, no classification is required according to the classification criteria of Council Directive 67/548/EEC and subsequent regulations as well as according to Regulation (EC) No. 1272/2008.

Comments of zRMS: Acceptable (no deviations from above mentioned test guideline), used for evaluation, applicant’s description modified by the zRMS

A 2.6 Skin Sensitisation

Reference: KIIIA1-7.1.6 Report Skin sensitisation of Exilis 2% SL formulation in Guinea Pigs by Magnusson and Kligman Stahl, J., 2007, report-no. 07/394-104T ASB2011-14770 Guidelines: OECD 406 Directive 96/54/EEC B.6

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OPPTS Guideline 870.2600 Deviations: No GLP: Yes Acceptability: Yes

Materials and methods The skin sensitisation potential of Exilis (Batch number: W0655B, clear liquid which contains 20.8 g/L 6- benzyladenine as the active ingredient) was evaluated in 10 Dunkin/Hartley guinea pigs according to Magnusson and Kligman.

According to the test method the animals were subjected to a two-stage induction procedure, involving an intra-dermal injection of the test item and a topical application. On the basis of results of preliminary tests the most suitable concentration for injection was 5 % of Exilis in 1 % methyl cellulose using Freund’s complete adjuvant as well as neat Exilis for the topical induction. Two weeks after the topical induction application challenge was performed using Exilis at a concentration of 50 % (in 1 % methyl cellulose). 5 control animals were treated alike without having received Exilis during the induction phase. Skin reactions were examined 1 h, 24h, 48 h and 72 h after removal of the challenge application and scored according to Draize. Positive controls checking reliability and sensitivity of the procedure were carried out twice a year by the use of 2-mercaptobenzothiazole (intra-dermal: 0.1 % (w/v), topical: 75 % (w/v), challenge: 25 % (w/v)).

Body weights of the guinea pigs were checked on day 0 and day 25.

Results and discussions Table A 11: Results of skin sensitisation study of Exilis

Test Substance Group 1) Test Vehicle 2) Control Group 1)

24 hours 48 hours 24 hours 48 hours after challenge Exilis, 0 / 10 0 / 10 0 / 5 0 / 5 50 % Positive control (2-Mercaptobenzothiazole, 6 / 10 4 / 10 0 / 5 0 / 5 25 %) 1) Number of animals with positive dermal response (scores of 1-4) / number of animals in dose group 2) Vehicle: 1 % aqueous methyl cellulose

Clinical signs: No

Conclusion Under the experimental conditions, Exilis is not a skin sensitiser. Thus, no classification is required according to the classification criteria of Council Directive 67/548/EEC and subsequent regulations as well as according to Regulation (EC) No. 1272/2008.

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Comments of zRMS: Since all scores of the 10 treated animals were 0 after challenge, no further animals have to be tested.

Acceptable (no deviations from above mentioned test guideline), used for evaluation, applicant’s description modified by the zRMS

A 2.7 Supplementary Studies for Combinations of Plant Protection Products Exilis is not intended to be tank mixed with other plant growth regulators, pesticides or fertilizers. Therefore, no additional studies for combinations of plant protection products are necessary.

A 2.8 Short-Term Toxicity Studies This is not an EC data requirement / not required by Regulation (EC) No 1107/2009.

A 2.9 Data on Formulants

A 2.9.1 Material safety data sheet for each formulant Material safety data sheets of the formulants can be found in the confidential dossier of this submission (Registration Report - Part C).

A 2.9.2 Available toxicological data for each formulant Available toxicological data for each formulant can be found in the confidential dossier of this submission (Registration Report - Part C).

A 2.10 Studies on Dermal Absorption No new study has been submitted.

A 2.11 Other/Special Studies None.

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Appendix 3 Exposure Calculations

A 3.1 Exposure Calculations for 6-Benzyladenine

A 3.1.1 Operator exposure calculations

Table A 12: Estimation of operator exposure towards 6-benzyladenine using the German model, high crop tractor-mounted Input parameters considered for the estimation of operator exposure Formulation type: SL Application High Crop Tractor Mounted Application rate (AR): 0.15 kg a.s./ha technique: (HCTM) Dermal hands mg/person/kg Area treated per day (A): 8 ha 2.4 m/l (DM(H)): a.s. Dermal hands mg/person/kg 13 % (concentr.) 0.7 appl. (D ): a.s. Dermal absorption (DA): A(H) Dermal body mg/person/kg 7 % (dilution) 9.6 appl. (DA(B)): a.s. Inhalation absorption Dermal head mg/person/kg 100 % 1.2 (IA): appl. (DA(C)): a.s. Inhalation m/l mg/person/kg Body weight (BW): 70 kg/person 0.0006 (IM): a.s. Inhalation appl. mg/person/kg AOEL 0.03 mg/kg bw/d 0.018 (IA): a.s.

Operator exposure towards 6-benzyladenine Without PPE With PPE Operators: Systemic dermal exposure after application in apples, pears Dermal exposure during mixing/loading Hands Hands 1) SDEOM(H) = (DM(H) x AR x A x DA) / BW SDEOM(H) = (DM(H) x AR x A x PPE x DA) / BW (2.4 x 0.15 x 8 x 13%) / 70 (2.4 x 0.15 x 8 x 0.01 x 13%) / 70 External dermal External dermal exposure 2.88 mg/person 0.0288 mg/person exposure External dermal External dermal exposure 0.041143 mg/kg bw/d 0.000411 mg/kg bw/d exposure Systemic dermal Systemic dermal 0.005349 mg/kg bw/d 0.000053 mg/kg bw/d exposure exposure Dermal exposure during application Hands Hands

SDEOA(H) = (DA(H) x AR x A x DA) / BW SDEOA(H) = (DA(H) x AR x A x PPE x DA) / BW (0.7 x 0.15 x 8 x 7%) / 70 (0.7 x 0.15 x 8 x 1 x 7%) / 70 External dermal External dermal exposure 0.84 mg/person 0.84 mg/person exposure External dermal External dermal exposure 0.012 mg/kg bw/d 0.012 mg/kg bw/d exposure Systemic dermal Systemic dermal 0.00084 mg/kg bw/d 0.00084 mg/kg bw/d exposure exposure Body Body

SDEOA(B) = (DA(B) x AR x A x DA) / BW SDEOA(B) = (DA(B) x AR x A x PPE x DA) / BW (9.6 x 0.15 x 8 x 7%) / 70 (9.6 x 0.15 x 8 x 1 x 7%) / 70 External dermal External dermal exposure 11.52 mg/person 11.52 mg/person exposure External dermal exposure 0.164571 mg/kg bw/d External dermal 0.164571 mg/kg bw/d

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exposure Systemic dermal Systemic dermal 0.01152 mg/kg bw/d 0.01152 mg/kg bw/d exposure exposure Head Head

SDEOA(C) = (DA(C) x AR x A x DA) / BW SDEOA(C) = (DA(C) x AR x A x PPE x DA) / BW (1.2 x 0.15 x 8 x 7%) / 70 (1.2 x 0.15 x 8 x 1 x 7%) / 70 External dermal External dermal exposure 1.44 mg/person 1.44 mg/person exposure External dermal External dermal exposure 0.020571 mg/kg bw/d 0.020571 mg/kg bw/d exposure Systemic dermal Systemic dermal 0.00144 mg/kg bw/d 0.00144 mg/kg bw/d exposure exposure Total systemic dermal exposure: SDEO = SDEOM(H) + SDEOA(H) Total systemic dermal exposure: SDEO = SDEOM(H) + + SDEOA(B) + SDEOA(C) SDEOA(H) + SDEOA(B) + SDEOA(C) Total external dermal Total external 16.68 mg/person 13.8288 mg/person exposure dermal exposure Total external dermal Total external 0.238286 mg/kg bw/d 0.197554 mg/kg bw/d exposure dermal exposure Total systemic dermal Total systemic 0.019149 mg/kg bw/d 0.013853 mg/kg bw/d exposure dermal exposure Operators: Systemic inhalation exposure after application

in apples, pears Inhalation exposure during mixing/loading

SIEOM = (IM x AR x A x IA) / BW SIEOM = (IM x AR x A x PPE x IA) / BW (0.0006 x 0.15 x 8 x 100%) / 70 (0.0006 x 0.15 x 8 x 1 x 100%) / 70 External External inhalation 0.00072 mg/person inhalation 0.00072 mg/person exposure exposure External External inhalation 0.00001 mg/kg bw/d inhalation 0.00001 mg/kg bw/d exposure exposure Systemic Systemic inhalation 0.00001 mg/kg bw/d inhalation 0.00001 mg/kg bw/d exposure exposure Inhalation exposure during application

SIEOA = (IA x AR x A x IA) / BW SIEOA = (IA x AR x A x PPE x IA) / BW (0.018 x 0.15 x 8 x 100%) / 70 (0.018 x 0.15 x 8 x 1 x 100%) / 70 External External inhalation 0.0216 mg/person inhalation 0.0216 mg/person exposure exposure External External inhalation 0.000309 mg/kg bw/d inhalation 0.000309 mg/kg bw/d exposure exposure Systemic Systemic inhalation 0.000309 mg/kg bw/d inhalation 0.000309 mg/kg bw/d exposure exposure Total systemic inhalation exposure: SIEO = SIEOM + Total systemic inhalation exposure: SIEO = SIEOM + SIEOA SIEOA Total external Total external inhalation 0.02232 mg/person inhalation 0.02232 mg/person exposure exposure Total external Total external inhalation 0.000319 mg/kg bw/d inhalation 0.000319 mg/kg bw/d exposure exposure Total systemic Total systemic inhalation 0.000319 mg/kg bw/d inhalation 0.000319 mg/kg bw/d exposure exposure

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Total systemic exposure: SEO = SDEO + SIEO Total systemic exposure: SEO = SDEO + SIEO Total systemic Total systemic exposure 1.36272 mg/person 0.992064 mg/person exposure Total systemic Total systemic exposure 0.019467 mg/kg bw/d 0.014172 mg/kg bw/d exposure % of AOEL 64.9 % % of AOEL 47.2 % 1) reduction factor for gloves is 0.01 (professional appl.)

Table A 13: Estimation of operator exposure towards 6-benzyladenine using the German model, high crop hand-held Input parameters considered for the estimation of operator exposure Formulation type: SL Application High Crop Hand Held (HCHH) Application rate (AR): 0.15 kg a.s./ha technique: Dermal hands mg/person/kg Area treated per day (A): 1 ha 205 m/l (DM(H)): a.s. Dermal hands mg/person/kg 13 % (concentr.) 10.6 appl. (D ): a.s. Dermal absorption (DA): A(H) Dermal body mg/person/kg 7 % (dilution) 25 appl. (DA(B)): a.s. Inhalation absorption Dermal head mg/person/kg 100 % 4.8 (IA): appl. (DA(C)): a.s. Inhalation m/l mg/person/kg Body weight (BW): 70 kg/person 0.05 (IM): a.s. Inhalation appl. mg/person/kg AOEL 0.03 mg/kg bw/d 0.3 (IA): a.s.

Operator exposure towards 6-benzyladenine Without PPE With PPE Operators: Systemic dermal exposure after application in apples, pears Dermal exposure during mixing/loading Hands Hands 1) SDEOM(H) = (DM(H) x AR x A x DA) / BW SDEOM(H) = (DM(H) x AR x A x PPE x DA) / BW (205 x 0.15 x 1 x 13%) / 70 (205 x 0.15 x 1 x 0.01 x 13%) / 70 External dermal External dermal exposure 30.75 mg/person 0.3075 mg/person exposure External dermal External dermal exposure 0.439286 mg/kg bw/d 0.004393 mg/kg bw/d exposure Systemic dermal Systemic dermal 0.057107 mg/kg bw/d 0.000571 mg/kg bw/d exposure exposure Dermal exposure during application Hands Hands

SDEOA(H) = (DA(H) x AR x A x DA) / BW SDEOA(H) = (DA(H) x AR x A x PPE x DA) / BW (10.6 x 0.15 x 1 x 7%) / 70 (10.6 x 0.15 x 1 x 1 x 7%) / 70 External dermal External dermal exposure 1.59 mg/person 1.59 mg/person exposure External dermal External dermal exposure 0.022714 mg/kg bw/d 0.022714 mg/kg bw/d exposure Systemic dermal Systemic dermal 0.00159 mg/kg bw/d 0.00159 mg/kg bw/d exposure exposure Body Body

SDEOA(B) = (DA(B) x AR x A x DA) / BW SDEOA(B) = (DA(B) x AR x A x PPE x DA) / BW (25 x 0.15 x 1 x 7%) / 70 (25 x 0.15 x 1 x 1 x 7%) / 70 External dermal External dermal exposure 3.75 mg/person 3.75 mg/person exposure

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External dermal External dermal exposure 0.053571 mg/kg bw/d 0.053571 mg/kg bw/d exposure Systemic dermal Systemic dermal 0.00375 mg/kg bw/d 0.00375 mg/kg bw/d exposure exposure Head Head

SDEOA(C) = (DA(C) x AR x A x DA) / BW SDEOA(C) = (DA(C) x AR x A x PPE x DA) / BW (4.8 x 0.15 x 1 x 7%) / 70 (4.8 x 0.15 x 1 x 1 x 7%) / 70 External dermal External dermal exposure 0.72 mg/person 0.72 mg/person exposure External dermal External dermal exposure 0.010286 mg/kg bw/d 0.010286 mg/kg bw/d exposure Systemic dermal Systemic dermal 0.00072 mg/kg bw/d 0.00072 mg/kg bw/d exposure exposure Total systemic dermal exposure: SDEO = SDEOM(H) + SDEOA(H) Total systemic dermal exposure: SDEO = SDEOM(H) + + SDEOA(B) + SDEOA(C) SDEOA(H) + SDEOA(B) + SDEOA(C) Total external dermal Total external 36.81 mg/person 6.3675 mg/person exposure dermal exposure Total external dermal Total external 0.525857 mg/kg bw/d 0.090964 mg/kg bw/d exposure dermal exposure Total systemic dermal Total systemic 0.063167 mg/kg bw/d 0.006631 mg/kg bw/d exposure dermal exposure Operators: Systemic inhalation exposure after application

in apples, pears Inhalation exposure during mixing/loading

SIEOM = (IM x AR x A x IA) / BW SIEOM = (IM x AR x A x PPE x IA) / BW (0.05 x 0.15 x 1 x 100%) / 70 (0.05 x 0.15 x 1 x 1 x 100%) / 70 External External inhalation 0.0075 mg/person inhalation 0.0075 mg/person exposure exposure External External inhalation 0.000107 mg/kg bw/d inhalation 0.000107 mg/kg bw/d exposure exposure Systemic Systemic inhalation 0.000107 mg/kg bw/d inhalation 0.000107 mg/kg bw/d exposure exposure Inhalation exposure during application

SIEOA = (IA x AR x A x IA) / BW SIEOA = (IA x AR x A x PPE x IA) / BW (0.3 x 0.15 x 1 x 100%) / 70 (0.3 x 0.15 x 1 x 1 x 100%) / 70 External External inhalation 0.045 mg/person inhalation 0.045 mg/person exposure exposure External External inhalation 0.000643 mg/kg bw/d inhalation 0.000643 mg/kg bw/d exposure exposure Systemic Systemic inhalation 0.000643 mg/kg bw/d inhalation 0.000643 mg/kg bw/d exposure exposure Total systemic inhalation exposure: SIEO = SIEOM + Total systemic inhalation exposure: SIEO = SIEOM + SIEOA SIEOA Total external Total external inhalation 0.0525 mg/person inhalation 0.0525 mg/person exposure exposure Total external Total external inhalation 0.00075 mg/kg bw/d inhalation 0.00075 mg/kg bw/d exposure exposure Total systemic inhalation Total systemic 0.00075 mg/kg bw/d 0.00075 mg/kg bw/d exposure inhalation

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exposure

Total systemic exposure: SEO = SDEO + SIEO Total systemic exposure: SEO = SDEO + SIEO Total systemic Total systemic exposure 4.4742 mg/person 0.516675 mg/person exposure Total systemic Total systemic exposure 0.063917 mg/kg bw/d 0.007381 mg/kg bw/d exposure % of AOEL 213.1 % % of AOEL 24.6 % 1) reduction factor for gloves is 0.01 (professional appl.)

Table A 14: Estimation of operator exposure towards 6-benzyladenine using the UK- POEM, high crop tractor-mounted Without PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance 6-benzyladenine Product Exilis Formulation type water-based Concentration of a.s. 20 mg/mL Dose 7.5 L preparation/ha (0.15 kg a.s./ha) Application volume 300 L/ha Application method Tractor-mounted/trailed broadcast air-assisted sprayer: 500 L/ha Container 10 litres 63 mm closure Work rate/day 15 ha Duration of spraying 6 h PPE during mix./loading None PPE during application None Dermal absorption from product 13 % Dermal absorption from spray 7 % EXPOSURE DURING MIXING AND LOADING Container size 10 Litres Hand contamination/operation 0,05 mL Application dose 7.5 Litres product/ha Work rate 15 ha/day Number of operations 12 /day Hand contamination 0.6 mL/day Protective clothing None Transmission to skin 100 % Dermal exposure to formulation 0.6 mL/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Tractor-mounted/trailed broadcast air-assisted sprayer: 500 L/ha Application volume 300 spray/ha Volume of surface contamination 400 mL/h Distribution Hands Trunk Legs 10% 65% 25% Clothing None Permeable Permeable Penetration 100% 2% 5% Dermal exposure 10 5.2 5 mL/h Duration of exposure 6 h Total dermal exposure to spray 121.2 mL/day ABSORBED DERMAL DOSE Mix/load Application Dermal exposure 0.6 mL/day 121.2 mL/day Concen. of a.s. product or spray 20 mg/mL 0.5 mg/mL Dermal exposure to a.s. 12 mg/day 60.6 mg/day Percent absorbed 13 % 7 % Absorbed dose 1.56 mg/day 4.242 mg/day

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INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.05 mL/h Duration of exposure 6 h Concentration of a.s. in spray 0.5 mg/mL Inhalation exposure to a.s. 0.15 mg/day Percent absorbed 100 % Absorbed dose 0.15 mg/day PREDICTED EXPOSURE Total absorbed dose 5.952 mg/day Operator body weight 60 kg Operator exposure 0.099 mg/kg bw/day Amount of AOEL 330.7 %

With PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance 6-benzyladenine Product Exilis Formulation type water-based Concentration of a.s. 20 mg/mL Dose 7.5 L preparation/ha (0.15 kg a.s./ha) Application volume 300 L/ha Application method Tractor-mounted/trailed broadcast air-assisted sprayer: 500 L/ha Container 10 litres 63 mm closure Work rate/day 15 ha Duration of spraying 6 h PPE during mix./loading Gloves PPE during application Gloves Dermal absorption from product 13 % Dermal absorption from spray 7 % EXPOSURE DURING MIXING AND LOADING Container size 10 Litres Hand contamination/operation 0,05 mL Application dose 7.5 Litres product/ha Work rate 15 ha/day Number of operations 12 /day Hand contamination 0.6 mL/day Protective clothing Gloves Transmission to skin 5 % Dermal exposure to formulation 0.03 mL/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Tractor-mounted/trailed broadcast air-assisted sprayer: 500 L/ha Application volume 300 spray/ha Volume of surface contamination 400 mL/h Distribution Hands Trunk Legs 10% 65% 25% Clothing Gloves Permeable Permeable Penetration 10% 2% 5% Dermal exposure 4 5.2 5 mL/h Duration of exposure 6 h Total dermal exposure to spray 85.2 mL/day ABSORBED DERMAL DOSE Mix/load Application Dermal exposure 0.03 mL/day 85.2 mL/day Concen. of a.s. product or spray 20 mg/mL 0.5 mg/mL Dermal exposure to a.s. 0.6 mg/day 42.6 mg/day Percent absorbed 13 % 7 %

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Absorbed dose 0.078 mg/day 2.982 mg/day INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.05 mL/h Duration of exposure 6 h Concentration of a.s. in spray 0.5 mg/mL Inhalation exposure to a.s. 0.15 mg/day Percent absorbed 100 % Absorbed dose 0.15 mg/day PREDICTED EXPOSURE Total absorbed dose 3.21 mg/day Operator body weight 60 kg Operator exposure 0.054 mg/kg bw/day Amount of AOEL 178.3 %

Table A 15: Estimation of operator exposure towards 6-benzyladenine using the UK- POEM, high crop hand-held Without PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance 6-benzyladenine Product Exilis Formulation type water-based Concentration of a.s. 20 mg/mL Dose 7.5 L preparation/ha (0.15 kg a.s./ha) Application volume 300 L/ha Application method Hand-held rotary atomiser equipment (2.5 L tank). Outdoor, high level target Container 5 litres 45 or 63 mm closure Work rate/day 1 ha Duration of spraying 6 h PPE during mix./loading None PPE during application None Dermal absorption from product 13 % Dermal absorption from spray 7 % EXPOSURE DURING MIXING AND LOADING Container size 5 Litres Hand contamination/operation 0,01 mL Application dose 7.5 Litres product/ha Work rate 1 ha/day Number of operations 120 /day Hand contamination 1.2 mL/day Protective clothing None Transmission to skin 100 % Dermal exposure to formulation 1.2 mL/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Hand-held rotary atomiser equipment (2.5 L tank). Outdoor, high level target Application volume 300 spray/ha Volume of surface contamination 50 mL/h Distribution Hands Trunk Legs 10% 65% 25% Clothing None Permeable Permeable Penetration 100% 15% 20% Dermal exposure 5 4.875 2.5 mL/h Duration of exposure 6 h Total dermal exposure to spray 74.25 mL/day ABSORBED DERMAL DOSE Mix/load Application

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Dermal exposure 1.2 mL/day 74.25 mL/day Concen. of a.s. product or spray 20 mg/mL 0.5 mg/mL Dermal exposure to a.s. 24 mg/day 37.125 mg/day Percent absorbed 13 % 7 % Absorbed dose 3.12 mg/day 2.599 mg/day INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.01 mL/h Duration of exposure 6 h Concentration of a.s. in spray 0.5 mg/mL Inhalation exposure to a.s. 0.03 mg/day Percent absorbed 100 % Absorbed dose 0.03 mg/day PREDICTED EXPOSURE Total absorbed dose 5.749 mg/day Operator body weight 60 kg Operator exposure 0.096 mg/kg bw/day Amount of AOEL 319.4 %

With PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance 6-benzyladenine Product Exilis Formulation type water-based Concentration of a.s. 20 mg/mL Dose 7.5 L preparation/ha (0.15 kg a.s./ha) Application volume 300 L/ha Application method Hand-held rotary atomiser equipment (2.5 L tank). Outdoor, high level target Container 5 litres 45 or 63 mm closure Work rate/day 1 ha Duration of spraying 6 h PPE during mix./loading Gloves PPE during application Gloves and impermeable coveralls Dermal absorption from product 13 % Dermal absorption from spray 7 % EXPOSURE DURING MIXING AND LOADING Container size 5 Litres Hand contamination/operation 0,01 mL Application dose 7.5 Litres product/ha Work rate 1 ha/day Number of operations 120 /day Hand contamination 1.2 mL/day Protective clothing Gloves Transmission to skin 5 % Dermal exposure to formulation 0.06 mL/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Hand-held rotary atomiser equipment (2.5 L tank). Outdoor, high level target Application volume 300 spray/ha Volume of surface contamination 50 mL/h Distribution Hands Trunk Legs 10% 65% 25% Clothing Gloves Impermeable Impermeable Penetration 10% 5% 5% Dermal exposure 0.5 1.625 0.625 mL/h Duration of exposure 6 h Total dermal exposure to spray 16.5 mL/day ABSORBED DERMAL DOSE

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Mix/load Application Dermal exposure 0.06 mL/day 16.5 mL/day Concen. of a.s. product or spray 20 mg/mL 0.5 mg/mL Dermal exposure to a.s. 1.2 mg/day 8.25 mg/day Percent absorbed 13 % 7 % Absorbed dose 0.156 mg/day 0.578 mg/day INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.01 mL/h Duration of exposure 6 h Concentration of a.s. in spray 0.5 mg/mL Inhalation exposure to a.s. 0.03 mg/day Percent absorbed 100 % Absorbed dose 0.03 mg/day PREDICTED EXPOSURE Total absorbed dose 0.764 mg/day Operator body weight 60 kg Operator exposure 0.013 mg/kg bw/day Amount of AOEL 42.4 %

A 3.1.2 Worker exposure calculations

Table A 16: Estimation of worker exposure towards 6-benzyladenine using the German re- entry model Input parameters considered for the estimation of worker exposure Dislodgeable Intended use(s): Apples and pears foliar residues 1 µg/cm2/kg a.s. (DFR): Transfer Application rate (AR): 0.15 kg a.s./ha coefficient 4500 cm2/person/h (TC): Number of applications Work rate per 1 8 h/d (NA): day (WR): Body weight (BW): 60 kg/person PPE 5 % Dermal absorption (DA): 13 % ('worst case') AOEL 0.03 mg/kg bw/d

Worker exposure towards 6-benzyladenine Without PPE 1) With PPE 2) Worker (re-entry): Systemic dermal exposure after

application in apples and pears SDE = (DFR x TC x WR x AR x NA x PPE x SDE = (DFR x TC x WR x AR x NA x DA) / BW W W DA) / BW (1 x 4500 x 8 x 0.15 x 1 x 13%) / 60 (1 x 4500 x 8 x 0.15 x 1 x 5% x 13%) / 60 External dermal External dermal exposure 5.4 mg/person 0.27 mg/person exposure External dermal External dermal exposure 0.09 mg/kg bw/d 0.0045 mg/kg bw/d exposure Total systemic Total systemic exposure 0.702 mg/person 0.0351 mg/person exposure Total systemic Total systemic exposure 0.0117 mg/kg bw/d 0.0006 mg/kg bw/d exposure % of AOEL 39 % % of AOEL 2 % 1) acceptable without PPE: allocation of BVL code SF245-01 for spray applications 2) with PPE: allocation of BVL code SF1891 for professional applications (cf. Krebs et al., 2000)

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A 3.1.3 Bystander and resident exposure calculations

Table A 17: Estimation of bystander exposure towards 6-benzyladenineduring application in high crops, hand-held Input parameters considered for the estimation of bystander exposure Intended uses: Apples and pears Drift (D): 15.73 % (HC, late; 3 m) Exposed body Application rate 0.15 kg a.s./ha 1 m² (adults) surface area (AR): 15 mg/m2 0.21 m² (children) (BSA): kg/person mg/kg a.s. (6 60 Specific 0.3 Body weight (adults) hours, adults) Inhalation (BW): kg/person mg/kg a.s. (6 16.15 Exposure (I* ): 0.172414 (children) A hours, children) Dermal 13 % ('worst case') absorption (DA): ha/d (based on Area Treated (A): 1 Inhalation HCHH) 100 % absorption (IA): Exposure AOEL: 0.03 mg/kg bw/d 5 min duration (T):

Bystander exposure towards 6-benzyladenine Adults Children Bystander: Systemic dermal exposure during/after application in apples and pears (via spray drift)

SDEB = (AR x D x BSA x DA) / BW SDEB = (AR x D x BSA x DA) / BW (15 x 15.73% x 1 x 13%) / 60 (15 x 15.73% x 0.21 x 13%) / 16.15 External dermal External dermal 2.3595 mg/person 0.495495 mg/person exposure exposure External dermal External dermal 0.039325 mg/kg bw/d 0.030681 mg/kg bw/d exposure exposure Systemic dermal Systemic dermal 0.005112 mg/kg bw/d 0.003989 mg/kg bw/d exposure exposure Bystander: Systemic inhalation exposure during/after application in apples and pears (via spray drift)

SIEB = (I*A x AR x A x T x IA) / BW SIEB = (I*A x AR x A x T x IA) / BW (0.3 / 360 x 0.15 x 1 x 5 x 100%) / 60 (0.172414 / 360 x 0.15 x 1 x 5 x 100%) / 16.15 External inhalation External inhalation 0.000625 mg/person 0.000359 mg/person exposure exposure External inhalation External inhalation 0.00001 mg/kg bw/d 0.000022 mg/kg bw/d exposure exposure Systemic Systemic inhalation 0.00001 mg/kg bw/d inhalation 0.000022 mg/kg bw/d exposure exposure

Total systemic exposure: SEB = SDEB + SIEB Total systemic exposure: SEB = SDEB + SIEB Total systemic Total systemic 0.30736 mg/person 0.064774 mg/person exposure exposure Total systemic Total systemic 0.005123 mg/kg bw/d 0.004011 mg/kg bw/d exposure exposure % of AOEL 17.1 % % of AOEL 13.4 %

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Table A 18: Estimation of resident exposure towards 6-benzyladenine after application in high crops, hand-held Input parameters considered for the estimation of resident exposure Intended uses: Apples and pears Drift (D): 15.73 % (HC, late; 3 m) Application rate 0.15 kg a.s./ha Transfer 7300 cm2/h (adults) (AR): 0.0015 mg/cm2 coefficient (TC): 2600 cm2/h (children) Turf Number of 1 Transferable 5 % applications (NA): Residues (TTR): kg/person Exposure 60 2 h (adults) Duration (H): Body weight (BW): Airborne kg/person 16.15 Concentration of 0 mg/m3 (children) Vapour (ACV): Dermal absorption 13 % ('worst case') 16.57 m3/d (adults) (DA): Inhalation Rate Inhalation (IR): 100 % 8.31 m3/d (children) absorption (IA): Oral absorption Saliva Extraction 100 % 50 % (OA): Factor (SE): Surface Area of AOEL: 0.03 mg/kg bw/d 20 cm2 Hands (SA): Frequency of Hand to Mouth 20 events/h (Freq): Dislodgeable foliar residues 20 % (DFR): Ingestion Rate for Mouthing of 25 cm2/d Grass/Day (IgR):

Resident exposure towards 6-benzyladenine Adults Children Residents: Systemic dermal exposure after application in apples and pears (via deposits caused by spray drift) SDE = (AR x NA x D x TTR x TC x H x DA) / SDE = (AR x NA x D x TTR x TC x H x DA) / BW R R BW (0.0015 x 1 x % x 5% x 7300 x 2 x 13%) / 60 (0.0015 x 1 x % x 5% x 2600 x 2 x 13%) / 16.15 External dermal External dermal 0.172244 mg/person 0.061347 mg/person exposure exposure External dermal External dermal 0.002871 mg/kg bw/d 0.003799 mg/kg bw/d exposure exposure Systemic dermal Systemic dermal 0.000373 mg/kg bw/d 0.000494 mg/kg bw/d exposure exposure Residents: Systemic inhalation exposure after application in apples and pears (via vapour)

SIER = (ACV x IR x IA) / BW SIER = (ACV x IR x IA) / BW (0 x 16.57 x 100%) / 60 (0 x 8.31 x 100%) / 16.15 External inhalation External inhalation mg/person mg/person exposure exposure External inhalation External inhalation mg/kg bw/d mg/kg bw/d exposure exposure Systemic inhalation Systemic none none exposure inhalation

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exposure Residents: Systemic oral exposure (hand-to- mouth transfer) SOER(H) = (AR x NA x D x TTR x SE x SA x Freq x H x OA) / BW (0.0015 x 1 x % x 5% x 50% x 20 x 20 x 2 x 100%) / 16.15 External oral 0.004719 mg/person exposure External oral 0.000292 mg/kg bw/d exposure Systemic oral 0.000292 mg/kg bw/d exposure Residents: Systemic oral exposure (object-to- mouth transfer)

SOER(O) = (AR x NA x D x DFR x IgR x OA) / BW (0.0015 x 1 x % x 20% x 25 x 100%) / 16.15 External oral 0.00118 mg/person exposure External oral 0.000073 mg/kg bw/d exposure Systemic oral 0.000073 mg/kg bw/d exposure

Total systemic exposure: SER = SDER + SIER + Total systemic exposure: SER = SDER + SIER SOER(H) + SOER(O) Total systemic Total systemic 0.022392 mg/person 0.013874 mg/person exposure exposure Total systemic Total systemic 0.000373 mg/kg bw/d 0.000859 mg/kg bw/d exposure exposure % of AOEL 1.2 % % of AOEL 2.9 %

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REGISTRATION REPORT Part B

Section 4: Metabolism and Residues Detailed summary of the risk assessment

Product code: Exilis Active Substance: 6-Benzyladenine (20 g/L)

Central Zone Zonal Rapporteur Member State: Germany

CORE ASSESSMENT

Applicant: Fine Agrochemicals Limited Date: 13/07/2012

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Table of Contents

IIIA 8 METABOLISM AND RESIDUES DATA...... 3 IIIA 8.1 Evaluation of the active substances ...... 3 IIIA 8.1.1 6-Benzyladenine ...... 3 IIIA 8.1.1.1 Storage stability...... 3 IIIA 8.1.1.2 Metabolism in plants and plant residue definitions ...... 3 IIIA 8.1.1.3 Metabolism in livestock and animal residue definition(s)...... 4 IIIA 8.1.1.4 Residues in rotational crops...... 4 IIIA 8.1.1.5 Residues in livestock ...... 4 IIIA 8.2 Evaluation of the intended use(s) ...... 4 IIIA 8.2.1 Selection of critical use and justification...... 4 IIIA 8.2.2 Apples, pears ...... 6 IIIA 8.2.2.1 Residues in primary crops ...... 6 IIIA 8.2.2.2 Distribution of the residue in peel/pulp ...... 6 IIIA 8.2.2.3 Residues in processed commodities ...... 7 IIIA 8.2.2.4 Proposed pre-harvest intervals, withholding periods...... 7 IIIA 8.3 Consumer intake and risk assessment...... 7 IIIA 8.4 Proposed maximum residue levels (MRLs) ...... 7 IIIA 8.5 Conclusion...... 7 Appendix 1 List of data submitted in support of the evaluation ...... 8 Appendix 2 Detailed evaluation of the additional studies relied upon...... 8 A 2.1 Storage stability...... 8 A 2.2 Residues in primary crops ...... 8 A 2.2.1 Nature of residues...... 8 A 2.2.2 Magnitude of residues in apple...... 9 A 2.3 Residues in processed commodities ...... 17 A 2.4 Residues in rotational crops...... 17 A 2.5 Residues in livestock ...... 17 A 2.6 Other studies/information...... 17 Appendix 3 Pesticide Residue Intake Modell (PRIMo)...... 18

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IIIA 8 METABOLISM AND RESIDUES DATA

IIIA 8.1 Evaluation of the active substance(s)

IIIA 8.1.1 6-Benzyladenine

Table IIIA 8.1-1: Identity of the active substance H N H N N Structural formula

N N

Common Name 6-Benzyladenine (6-BA) CAS number 1214-39-7

IIIA 8.1.1.1 Storage stability A brief summary of the storage stability data on 6-BA is given in the following table. Data, which has been previously evaluated at EU level is described in detail in the DAR (2007; RMS FR; ASB2010- 10154).

Table IIIA 8.1-2: Stability of residues (Annex IIA, point 6.1)

No indications of instability during storage of apples at -18°C: Stability of 6-Benzyladenine >12 months at 0.025 mg/kg level >18 months at 0.25 mg/kg level

IIIA 8.1.1.2 Metabolism in plants and plant residue definitions A brief summary of the metabolism of 6-BA in plants is given in the following table. Data, which has been previously evaluated at EU level is described in detail in the DAR (ASB2010-10154).

Table IIIA 8.1-3: Metabolism in plants (Annex IIA, point 6.2.1; 6.5.1, 6.5.2, 6.6.2 and 6.7.1)

Metabolism study on apples are available together with Plant groups covered scientific review reports on root vegetables, cereals, pulses and oilseeds (EFSA Conclusion, ASB2012-1116).

Rotational crops No study available and none required, since DT50 in soil is 1 - 1.2 days. Metabolism in rotational crops similar to metabolism Not applicable in primary crops? (yes/no) Distribution of the residue in peel/ pulp Not relevant. Processed commodities (nature of residue) No data required, since residues in harvested products are not significant (< 0.1 mg/kg). Residue pattern in raw and processed commodities Not applicable similar? Plant residue definition for monitoring 6-Benzyladenine

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Plant residue definition for risk assessment 6-Benzyladenine Conversion factor(s) (monitoring to risk assessment) None

IIIA 8.1.1.3 Metabolism in livestock and animal residue definition(s)

Table IIIA 8.1-4: Metabolism in livestock (Annex IIA, point 6.2.2 to 6.2.5 and 6.7.1)

No livestock metabolism data is available and none is Animals covered required. Time needed to reach a plateau concentration in milk Not applicable and eggs Animal residue definition for monitoring not relevant, no MRLs required Animal residue definition for risk assessment not relevant, no residues expected Conversion factor(s) (monitoring to risk assessment) Not applicable Metabolism in rat and ruminant similar (yes/no) Not applicable Fat soluble residue: (yes/no) Not applicable

IIIA 8.1.1.4 Residues in rotational crops No field rotational crop studies are available and none are required.

IIIA 8.1.1.5 Residues in livestock No significant intake of 6-BA by livestock is expected, therefore no dietary burden calculation has been conducted.

Table IIIA 8.1-5: Conditions of requirement of livestock feeding studies on 6-BA

Ruminant: Poultry: Pig: Expected intake by livestock ≥0.1 mg/kg diet (dry no no no weight basis) (yes/no – If yes, specify the level) Potential for accumulation (yes/no): No data No data No data Metabolism studies indicate potential level of No data No data No data residues ≥0.01 mg/kg in edible tissues (yes/no)

No livestock feeding studies are available and none are required.

IIIA 8.2 Evaluation of the intended use(s)

IIIA 8.2.1 Selection of critical use and justification The critical GAP used for consumer intake and risk assessment is presented in Table IIIA 8.2-1. Except for a higher application rate the proposed use of Exilis® on apples and pears is basically similar to one of the representative uses which were assessed in the framework of Annex I inclusion of 6-BA, (1 x 150 g as/ha, BBCH 74, PHI 90 days). Further information can be found in the DAR (ASB2010-10154) and the conclusion on the peer review of the active substance 6-benzyladenine (ASB2012-1116).

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Table IIIA 8.2-1: Critical Use (worst case) used for consumer intake and risk assessment

1 2 3 4 5 6 7 8 9 10 11 12 13 Use- Member Crop and/ F Pests or Group of pests Application Application rate PHI Remarks: No. state(s) or situation G controlled (days) or Method / Timing / Growth Max. number L product / ha kg as/ha Water L/ha (i) (j) I Kind stage of crop & (min. interval (a) (b) (c) season between min / max (d-f) (g) applications) 1 DE Apple F Fruit thinning and fruit Spraying BBCH 71 1 3.75 l/ha per m 0.075 kg 500 l/ha per m 90 Max. 3.75 L product/ha per size development crown height as/ha per crown height m crown height with maximum m crown crown height of height 2 m max. 7.5 l/ha 2 DE Pear F Fruit thinning and fruit Spraying BBCH 71 1 3.75 l/ha per m 0.075 kg 500 l/ha per m 90 Max. 3.75 L product/ha per size development crown height as/ha per crown height m crown height with maximum m crown crown height of height 2 m max. 7.5 l/ha

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IIIA 8.2.2 Apples, pears

IIIA 8.2.2.1 Residues in primary crops Since i) the critical GAP for pears is identical to that for apples; ii) EU Guidance Documents allow for extrapolation of residue data from apple to pear; iii) available basic information on analytical method, plant metabolism etc. covers the uses in apples as well as in pears, the evaluation of both uses relies on the available residue trials on apples.

A set of eight residue trials was available (ASB2011-10203, ASB2011-10205) which does not fully reflect the conditions of the intended use (2 x 0.04 + 2 x 0.2 kg as/ha instead of 1 x 0.15 kg as/ha). The analyte was determined according to the EU agreed residue definition (parent by default). Despite of potential overdosing effects, five out of the eight trials were considered acceptable to support the EU GAP since residues in fruits were seen below the LOQ (<0.005 mg/kg) 92 to 112 days after the last application. In addition, a set of four trials was available (AF/5294/FC, ASB2012-9257) with a single application of 0.209 kg as/ha, out of which only one trial was also in compliance with the GAP in terms of the intended PHI (±25%). Nonetheless, since residue levels seen in apples of the other three trials (PHI 119-120) were below the LOQ of 0.005 mg/kg already 40 DALA, they were regarded as acceptable for purposes of evaluation of the GAP. Finally, a total of nine trials were selected from the available studies which were used to estimate 6-benzyladenine residues in apples and pears, consequent to the notified GAP.

The following table summarizes the results of the supervised field residue trials selected for the assessment of 6-benzyladenine residues in apples and pears when applied in compliance with the GAP for which approval is sought. The studies have also been reported in the DAR (2007; RMS FR; ASB2010- 10154).

Table IIIA 8.2-2: Overview of the selected supervised residue trials for 6-benzyladenine in apples

Commodity Region (a) Outdoor/ Individual trial results (mg/kg) STMR HR Median CF (d) Indoor (mg/kg) (b) (mg/kg) (c) Enforcement Risk assessment (parent 6-BA) (parent 6-BA) Apple NEU Outdoor <0.005 (9) <0.005 (9) 0.005 0.005 1 Underline median value from trial results (based on DoR for risk assessment) (a): NEU, SEU, EU or Import (country code). In the case of indoor uses there is no necessity to differentiate between NEU and SEU. (b): Median value of the individual trial results according to the risk assessment residue definition. (c): Highest value of the individual trial results according to the risk assessment residue definition. (d): The median conversion factor for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors for each residues trial.

Procedural recoveries detected alongside the treated sample analyses were acceptable for all fortification levels. In study ASB2011-10203, recoveries in one out of two samples were unacceptable (32% and 74% at 0.005 mg/kg). However, this is not considered to compromise the validity of the study as such, since all other recoveries in this study were acceptable (around 100% at default MRL level of 0.01 mg/kg and at 0.1 mg/kg) and the treated sample results (<0.005 mg/kg) are in accordance with the available data from other trials and the metabolism study in apples. No residues were detected in the corresponding untreated control samples. The maximum storage period of deep frozen samples is covered by storage stability studies. IIIA 8.2.2.2 Distribution of the residue in peel/pulp No data.

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IIIA 8.2.2.3 Residues in processed commodities Not relevant. Due to low residues at harvest, no processing studies are required. IIIA 8.2.2.4 Proposed pre-harvest intervals, withholding periods The proposed use of Exilis on apples and pears is identical to the GAP that was assessed for Annex I inclusion of 6-BA where apple was one of the representative uses. A pre-harvest interval of 90 days applies and is considered appropriate.

IIIA 8.3 Consumer intake and risk assessment

The consumer intake and risk assessment is based on the appropriate input values given in Table IIIA 8.3-1 and the toxicological reference values stated in Table 8.3-2. For the detailed calculation results it is referred to Appendix 3.

Table IIIA 8.3-1: Residue input values for the consumer risk assessment

Commodity Chronic risk assessment Acute risk assessment Input value Comment Input value Comment (mg/kg) (mg/kg) Apples 0.005 “No residue” situation n.n. No ARfD allocated at harvest. Pears 0.005 n.n. All other commodities of 0.01 default MRL -- -- plant origin

Table IIIA 8.3-2: Consumer risk assessment (Annex IIA, point 6.9, Annex IIIA, point 8.8)

ADI 0.01 mg/kg bw TMDI (% ADI) according to EFSA PRIMo 4.4 % (based on UK toddlers) NTMDI (% ADI) according to German NVS II 4.1 % (based on DE children 2 to 4 years) model IEDI (% ADI) according to EFSA PRIMo Not calculated NEDI (% ADI) according to German NVS II model Not calculated Factors included in IEDI and NEDI none ARfD Not allocated IESTI (% ARfD) according to EFSA PRIMo Not calculated NESTI (% ARfD) according to German NVS II Not calculated model Factors included in IESTI and NESTI none

IIIA 8.4 Proposed maximum residue levels (MRLs)

No MRLs are currently set. No residues at or above the default MRL of 0.01*mg/kg are expected in apples and pears at harvest.

IIIA 8.5 Conclusion

The data available is considered sufficient for risk assessment. An exceedance of the default MRL of 0.01*mg/kg for 6-benzyladenine is not expected (no MRLs set in Reg. (EC) No 396/2005 yet).

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The chronic and the short-term intake of 6-benzyladenine residues are both unlikely to present a public health concern.

As far as consumer health protection is concerned, BfR/Germany agrees with the authorization of the intended uses.

Appendix 1 List of data submitted in support of the evaluation

Table A 1: List of data submitted in support of the evaluation Annex point/ Author(s) Year Title Data Owner How considered in reference No Source (where different from protection dRR* company) claimed Report-No. GLP or GEP status (where relevant), Published or not Authority registration No OECD KIIA 6.3 Oxspring, S. 2003 VBC 30001: Residue levels in apples Y from trials carried out in Northern France and Germany during 2001, Report No. AF/5573/VB ASB2011-10203 OECD KIIA 6.3 Oxspring, S. 2003 VBC 30001: Residue levels in apples Y from trials carried out in Northern France and Germany during 2002; AF/6229/VB ASB2011-10205 OECD KIIA 6.3 Harrison, C. 2001 To determine the magnitude of N6- Y benzyladenine residues at intervals in the raw agricultural commodity apples resulting from a single directed application of EXILIS, in Northern France and the UK (2000-2001) ASB2012-9257 All RMS FR 2007 DAR (Draft assessment report prepared Used in the context of the possible inclusion of the following active substance in Annex I of Council Directive 91/414/EEC: 6-Benzyladenine) ASB2010-10154) All EFSA 2010 Conclusion on the peer review of the Used pesticide risk assessment of the active substance 6-benzyladenine EFSA Journal 2010; 8(10):1716 ASB2012-1116 * Y: Yes, relied on N: No, not relied on Add: Relied on, study not submitted but necessary for evaluation

Appendix 2 Detailed evaluation of the additional studies relied upon

A 2.1 Storage stability No further study on storage stability submitted/needed.

A 2.2 Residues in primary crops

A 2.2.1 Nature of residues No further study on nature of residues submitted/needed.

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A 2.2.2 Magnitude of residues in apple Reference: OECD KIIA 6.3 Report Oxspring, S. (2003):VBC 30001: Residue levels in apples from trials carried out in Northern France and Germany during 2001, Report No. AF/5573/VB; ASB2011-10203 Guideline(s): Yes. Deviations: None. GLP: Yes. Acceptability: Fully acceptable.

Table A 2: Residues of 6-benzyladenine in apples – study 1 RESIDUES DATA SUMMARY FROM SUPERVISED TRIALS (SUMMARY) Active ingredient : 6-Benzyladenine (Application on agricultural and horticultural crops) Crop / crop group : Apple

Federal Institute for Risk Assessment, Berlin Federal Republic of Germany Submission date : 2011-08-31

Content of a.i. (g/kg or g/l) : 18.9 g/l Indoors / outdoors : Outdoors (European North) Formulation (e.g. WP) : SL Other a.i. in formulation Commercial product (name) : VBC 30001 SL (submitted to MaxCel 006968-00) (content and common name) : treated with formulation VBC 30001 SL (actual 18.9 g/l 6-Benzyladenine, 6-BA) Applicant : Valent BioSciences Residues calculated as : 6-Benzyladenine

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1 2 3 4 5 6 7 8 9 10 Report-No. Commodity/ Date of Application Dates of Growth Portion Residues PHI Remarks Location Variety 1) Sowing or rate per treatment treatments stage analysed (mg/kg) (days) incl. planting kg or no. of at last Postal code 2) Flowering a.i./ha Water kg treatments treatment and date 3) Harvest l/ha a.i./hl and last date or date (a) (b) (c) (a) (d) (e) AF/5573/VB/1 apples / 1) 1988 0.039 968 0.0040 2001-05-14 BBCH 73 fruit <0.005 92 4) spraying (planting) 0.038 963 0.0040 2001-05-21 VP01-2-25D1 Jonica 2) 2001-04-26 0.19 963 0.020 2001-05-28 height of crown: no data, - 2001-05-12 0.20 983 0.020 2001-06-054) analytical method: Agrisearch Germany 3) 2001-10-01 6BA/Pome Fruit/KLS/01/1 69168 - 2001-10-10 (GC-NPD), Klingenbruchhof 1 LOQ: 0.005 mg/kg, recovery fruit 0.005 mg/kg 2003-01-27 53%, max. sample storage: 11 months

ASB2011-10203

AF/5573/VB/2 apples / 1) 1988 0.016 399 0.0040 2001-05-04 BBCH 72 fruit <0.005 116 4) spraying (planting) 0.041 1035 0.0040 2001-05-10 France (North) Oregon 2) 0.21 1048 0.020 2001-05-18 height of crown: no data, 41250 Beauregard, 3) 2001-09-18 0.19 952 0.020 2001-05-254) analytical method: Agrisearch Loir-et-Cher 6BA/Pome Fruit/KLS/01/1 (GC-NPD), LOQ: 0.005 2003-01-27 mg/kg, recovery fruit 0.005 mg/kg 53%, max. sample storage: 11 months

ASB2011-10203

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1 2 3 4 5 6 7 8 9 10 Report-No. Commodity/ Date of Application Dates of Growth Portion Residues PHI Remarks Location Variety 1) Sowing or rate per treatment treatments stage analysed (mg/kg) (days) incl. planting kg or no. of at last Postal code 2) Flowering a.i./ha Water kg treatments treatment and date 3) Harvest l/ha a.i./hl and last date or date (a) (b) (c) (a) (d) (e) AF/5573/VB/3 apples / 1) 1996 0.041 1019 0.0040 2001-05-09 BBCH 71-74 fruit 0.026 -0 4) spraying (planting) 0.039 969 0.0040 2001-05-16 0.12 0 France (North) Gala 2) 0.21 1031 0.020 2001-05-23 0.036 7 height of crown: no data, 45590 St Cyr en Val, 3) 2001-09-01 0.21 1038 0.020 2001-05-314) <0.005 14 analytical method: Agrisearch Loiret <0.005 28 6BA/Pome Fruit/KLS/01/1 <0.005 93 (GC-NPD), LOQ: 0.005 2003-01-27 mg/kg, recovery fruit 0.005 mg/kg max. storage: 15 months single recoveries: 32%, 74% (0.005) 108% (0.01) 100% (0.1) ASB2011-10203

AF/5573/VB, apples / 1) 1991 0.042 1059 0.0040 2001-05-10 BBCH 72 fruit 0.029 -0 4) spraying trial AF/5573/VB/4 (planting) 0.040 1000 0.0040 2001-05-17 fruit 0.20 0 Golden 2) 0.19 956 0.020 2001-05-23 fruit 0.050 7 height of crown: no data, France (North) Delicious 3) 2001-09-18 0.21 1033 0.020 2001-05-304) 0.025 14 analytical method: Agrisearch 45560 St Denis en 0.007 28 6BA/Pome Fruit/KLS/01/1 Val, Loiret <0.005 111 (GC-NPD), LOQ: 0.005 mg/kg, 2003-01-27 recovery fruit 0.005 mg/kg max. storage: 15 months single recoveries: 32%, 74% (0.005) 108% (0.01) 100% (0.1) ASB2011-10203 Remarks: (a) According to CODEX Classification / Guide (b) Only if relevant (c) Year must be indicated (d) Days after last application (Label pre-harvest interval, PHI, underline) (e) Remarks may include: Climatic conditions; Reference to analytical method and information which metabolites are included Note: All entries to be filled in as appropriate

Comments of zRMS: The study is acceptable

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Reference: OECD KIIA 6.3 Report Oxspring, S. (2003): VBC 30001: Residue levels in apples from trials carried out in Northern France and Germany during 2002; AF/6229/VB; ASB2011-10205 Guideline(s): Yes Deviations: None GLP: Yes Acceptability: Fully acceptable

Table A 3: Residues of 6-benzyladenine in apples – study 2 RESIDUES DATA SUMMARY FROM SUPERVISED TRIALS (SUMMARY) Active ingredient : 6-Benzyladenine (Application on agricultural and horticultural crops) Crop / crop group : Apple

Federal Institute for Risk Assessment, Berlin Federal Republic of Germany Submission date : 2011-08-31

1 2 3 4 5 6 7 8 9 10 Report-No. Commodity/ Date of Application Dates of Growth Portion Residues PHI Remarks Location Variety 1) Sowing or rate per treatment treatments stage analysed (mg/kg) (days) incl. planting kg Water kg or no. of at last Postal code 2) Flowering a.i./ha l/ha a.i./hl treatments treatment and date 3) Harvest and last date or date (a) (b) (c) (a) (d) (e) AF/6229/VB, apples / 1) 1991 0.040 1020 0.0039 2002-04-15 BBCH 71 fruit <0.005 130 4) spraying trial AF/6229/VB/2 (planting) 0.040 967 0.0041 2002-04-23 Golden 2) 0.20 1000 0.020 2002-04-29 height of crown: no data, France (North) Delicious 3) 2002-09-13 0.20 1010 0.020 2002-05-064) analytical method: Agrisearch 45560 St Denis en 6BA/Pome Fruit/KLS/01/1 Val (GC-NPD), LOQ: 0.005 mg/kg, max. sample storage: 2003-08-08 11 months ASB2011-10205

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1 2 3 4 5 6 7 8 9 10 Report-No. Commodity/ Date of Application Dates of Growth Portion Residues PHI Remarks Location Variety 1) Sowing or rate per treatment treatments stage analysed (mg/kg) (days) incl. planting kg Water kg or no. of at last Postal code 2) Flowering a.i./ha l/ha a.i./hl treatments treatment and date 3) Harvest and last date or date (a) (b) (c) (a) (d) (e) AF/6229/VB, apples / 1) 1996 0.040 955 0.0042 2002-04-16 BBCH 72 fruit 0.054 -0 4) spraying trial AF/6229/VB/3 (planting) 0.040 920 0.0044 2002-04-23 0.26 0 Gala 2) 0.20 915 0.022 2002-04-30 0.032 7 height of crown: no data, France (North) 3) 2002-08-20 0.20 950 0.021 2002-05-074) 0.014 14 analytical method: Agrisearch 45590 St-Cyr-en- <0.005 28 6BA/Pome Fruit/KLS/01/1 Val <0.005 105 (GC-NPD), LOQ: 0.005 mg/kg, max. sample storage: 2003-08-08 15 months ASB2011-10205

AF/6229/VB, apples / 1) 1992 0.040 945 0.0042 2002-05-07 BBCH 72 fruit <0.005 112 4) spraying trial AF/6229/VB/4 (planting) 0.040 983 0.0041 2002-05-15 Jonagold 2) 0.20 968 0.021 2002-05-21 height of crown: no data, Germany 3) 2002-09-17 0.20 998 0.020 2002-05-284) analytical method: Agrisearch 69234 Horrenberg 6BA/Pome Fruit/KLS/01/1 (GC-NPD), LOQ: 0.005 2003-08-08 mg/kg, max. sample storage: 10 months ASB2011-10205

AF/6229/VB, apples / 1) 1996 0.040 916 0.0044 2002-04-18 BBCH 72 fruit 0.032 -0 4) spraying trial AF/6229/VB/5 (planting) 0.040 1017 0.0039 2002-04-25 0.070 0 Braeburn 2) 0.20 903 0.022 2002-05-03 0.051 7 height of crown: no data, France (North) 3) 2002-10-03 0.20 931 0.021 2002-05-104) 0.017 14 analytical method: Agrisearch 91150 Etampes 0.022 28 6BA/Pome Fruit/KLS/01/1 <0.005 146 (GC-NPD), LOQ: 0.005 2003-08-08 mg/kg, max. sample storage: 14 months ASB2011-10205

Remarks: (a) According to CODEX Classification / Guide (b) Only if relevant (c) Year must be indicated (d) Days after last application (Label pre-harvest interval, PHI, underline) (e) Remarks may include: Climatic conditions; Reference to analytical method and information which metabolites are included Note: All entries to be filled in as appropriate

Comments of zRMS: The study is acceptable

Page 13 / 18 Exilis – 007524-00/00 Part B – Section 4 - Core Assessment ZRMS Version

Reference: OECD KIIA 6.3 Report Harrison, C. (2001) To determine the magnitude of N6-benzyladenine residues at intervals in the raw agricultural commodity apples resulting from a single directed application of EXILIS, in Northern France and the UK (2000-2001), Harrison, C., 2001, AF/5294/FC, FAL REF 194, ASB2012-9257 Guideline(s): yes Guidelines for the generation of data concerning residues as provided in Annex II part A, section 6 and Annex III, part A, section 8 of Directive 91/414/EEC concerning the placing of plant protection products on the market (Commission of the European Communities, 1607/VI/97), 1997 Deviations: no GLP: Yes Acceptability: acceptable

Table A 4: Residues of 6-benzyladenine in apples – study 3 RESIDUES DATA SUMMARY FROM SUPERVISED TRIALS (SUMMARY) Active ingredient : 6-Benzyladenine (Application on agricultural and horticultural crops) Crop / crop group : Apple

Federal Institute for Risk Assessment, Berlin Federal Republic of Germany Submission date : 2012-06-22

Content of a.i. (g/kg or g/l) : 20 g/l Indoors / outdoors : Outdoors (European North) Formulation (e.g. WP) : SL Other a.i. in formulation Commercial product (name) : Exilis 007524-00 (submitted to ZV1 007524-00) (content and common name) : Applicant : Fine Agrochemicals Ltd. Residues calculated as : 6-Benzyladenine

Page 14 / 18 Exilis – 007524-00/00 Part B – Section 4 - Core Assessment ZRMS Version

1 2 3 4 5 6 7 8 9 10 Report-No. Commodity/ Date of Application Dates of Growth Portion Residues PHI Remarks Location Variety 1) Sowing or rate per treatment treatments stage analysed (mg/kg) (days) incl. planting kg Water kg or no. of at last Postal code 2) Flowering a.i./ha l/ha a.i./hl treatments treatment and date 3) Harvest and last date or date (a) (b) (c) (a) (d) (e) AF/5294/FC/1, plot 3 apples / 1) 1990 0.21 1043 0.020 2000-06-114) BBCH 71 fruit <0.005 -0 4) spraying (planting) 0.17 0 United Kingdom Acton Golden 2) 0.032 10 height of crop: 2.0-2.5 m, Beauchamp, Hereford Delicious 3) 2000-09-28 0.024 19 analytical method: Agrisearch 0.006 40 BAP/POME FRUIT/DB/01/1 2001-09-28 <0.005 109 (GC-MS), LOQ: 0.005 mg/kg, max. sample storage: 12 months

ASB2012-9257

AF/5294/FC/2, plot 3 apples / 1) 1992 0.20 1020 0.020 2000-05-154) BBCH 71 fruit <0.005 -0 4) spraying (planting) 0.17 0 France (North) Golden 2) 0.040 10 height of crop: 3.0 m, 18330 La Chapelle 3) 2000-09-11 0.007 20 analytical method: Agrisearch Angillon <0.005 40 BAP/POME FRUIT/DB/01/1 <0.005 119 (GC-MS), LOQ: 0.005 mg/kg, 2001-09-28 max. sample storage: 13 months

ASB2012-9257

AF/5294/FC/3, plot 3 apples / 1) 1993 0.21 1053 0.020 2000-05-164) BBCH 71 fruit <0.005 -0 4) spraying (planting) 0.11 0 France (North) Golden 2) 0.007 10 height of crop: 3.0 m, 45160 St. Hilaire-St. 3) 2000-09-15 <0.005 20 analytical method: Agrisearch Mesmin <0.005 40 BAP/POME FRUIT/DB/01/1 <0.005 122 (GC-MS), LOQ: 0.005 mg/kg, 2001-09-28 max. sample storage: 13 months

ASB2012-9257

Page 15 / 18 Exilis – 007524-00/00 Part B – Section 4 - Core Assessment ZRMS Version

1 2 3 4 5 6 7 8 9 10 Report-No. Commodity/ Date of Application Dates of Growth Portion Residues PHI Remarks Location Variety 1) Sowing or rate per treatment treatments stage analysed (mg/kg) (days) incl. planting kg Water kg or no. of at last Postal code 2) Flowering a.i./ha l/ha a.i./hl treatments treatment and date 3) Harvest and last date or date (a) (b) (c) (a) (d) (e) AF/5294/FC/4, plot 3 apples / 1) 1986 0.21 1028 0.020 2000-05-154) BBCH 71 fruit <0.005 -0 4) spraying (planting) 0.092 0 France (North) Ozarn Gold 2) 0.013 10 height of crop: 3.5 m, 41250 Beauregard 3) 2000-09-12 0.006 20 analytical method: Agrisearch <0.005 40 BAP/POME FRUIT/DB/01/1 2001-09-28 <0.005 120 (GC-MS), LOQ: 0.005 mg/kg, max. sample storage: 13 months

ASB2012-9257

Note: All entries to be filled in as appropriate

Comments of zRMS: The study is acceptable

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A 2.3 Residues in processed commodities No new study on residues in processed commodities has been submitted/(and) none is needed due to low residues at harvest. A 2.4 Residues in rotational crops No new study on residues in rotational crops has been submitted. A 2.5 Residues in livestock No new study on residues in livestock has been submitted. A 2.6 Other studies/information None

Page 17 / 18 Exilis – 007524-00/00 Part B – Section 4 - Core Assessment ZRMS Version

Appendix 3 Pesticide Residue Intake Modell (PRIMo)

6-benzyladenine Status of the active substance: Code no. LOQ (mg/kg bw): proposed LOQ: Toxicological end points ADI (mg/kg bw/day): 0,01 ARfD (mg/kg bw): n.n. Source of ADI: Review report Source of ARfD: Review report 2011 Year of evaluation: 2010 Year of evaluation: 2010 Explain choice of toxicological reference values. The risk assessment has been performed on the basis of the MRLs collected from Member States in April 2006. For each pesticide/commodity the highest national MRL was identified (proposed temporary MRL = pTMRL). The pTMRLs have been submitted to EFSA in September 2006. Chronic risk assessment TMDI (range) in % of ADI minimum - maximum 1 4 No of diets exceeding ADI: --- Highest calculated Highest contributor 2nd contributor to 3rd contributor to pTMRLs at TMDI values in % to MS diet Commodity / MS diet Commodity / MS diet Commodity / LOQ of ADI MS Diet (in % of ADI) group of commodities (in % of ADI) group of commodities (in % of ADI) group of commodities (in % of ADI) 4,4 UK Toddler 2,3 SUGAR PLANTS 0,6 FRUIT (FRESH OR FROZEN) 0,6 VEGETABLES 3,9 WHO Cluster diet B 1,4 VEGETABLES 1,2 CEREALS 0,7 FRUIT (FRESH OR FROZEN) 3,7 FR infant 2,1 VEGETABLES 1,5 FRUIT (FRESH OR FROZEN) 0,1 CEREALS 3,6 DE child 2,3 FRUIT (FRESH OR FROZEN) 0,7 VEGETABLES 0,6 CEREALS 3,3 NL child 1,5 FRUIT (FRESH OR FROZEN) 1,1 VEGETABLES 0,6 CEREALS 3,3 FR toddler 1,7 VEGETABLES 1,2 FRUIT (FRESH OR FROZEN) 0,3 CEREALS 2,9 UK Infant 1,0 SUGAR PLANTS 0,7 VEGETABLES 0,6 FRUIT (FRESH OR FROZEN) 2,8 IE adult 1,1 FRUIT (FRESH OR FROZEN) 0,9 VEGETABLES 0,7 CEREALS 2,4 WHO cluster diet E 0,9 VEGETABLES 0,6 CEREALS 0,6 FRUIT (FRESH OR FROZEN) 2,3 DK child 1,0 CEREALS 0,7 VEGETABLES 0,5 FRUIT (FRESH OR FROZEN) 2,2 WHO cluster diet D 0,9 VEGETABLES 0,8 CEREALS 0,3 FRUIT (FRESH OR FROZEN) 2,1 SE general population 90th percentile 1,0 VEGETABLES 0,6 FRUIT (FRESH OR FROZEN) 0,5 CEREALS 1,8 PT General population 0,6 FRUIT (FRESH OR FROZEN) 0,5 VEGETABLES 0,5 CEREALS 1,8 WHO Cluster diet F 0,7 VEGETABLES 0,5 CEREALS 0,4 FRUIT (FRESH OR FROZEN) 1,8 ES child 0,6 FRUIT (FRESH OR FROZEN) 0,5 CEREALS 0,5 VEGETABLES 1,7 WHO regional European diet 0,9 VEGETABLES 0,4 CEREALS 0,3 FRUIT (FRESH OR FROZEN) 1,6 IT kids/toddler 0,8 CEREALS 0,4 VEGETABLES 0,4 FRUIT (FRESH OR FROZEN) 1,6 UK vegetarian 0,4 SUGAR PLANTS 0,4 VEGETABLES 0,3 FRUIT (FRESH OR FROZEN) 1,4 FR all population 0,6 FRUIT (FRESH OR FROZEN) 0,4 VEGETABLES 0,3 CEREALS 1,4 NL general 0,6 VEGETABLES 0,5 FRUIT (FRESH OR FROZEN) 0,3 CEREALS 1,4 UK Adult 0,4 SUGAR PLANTS 0,3 VEGETABLES 0,3 FRUIT (FRESH OR FROZEN) 1,2 ES adult 0,4 FRUIT (FRESH OR FROZEN) 0,4 VEGETABLES 0,3 CEREALS 1,2 IT adult 0,5 CEREALS 0,4 VEGETABLES 0,3 FRUIT (FRESH OR FROZEN) 1,0 LT adult 0,5 VEGETABLES 0,3 CEREALS 0,2 FRUIT (FRESH OR FROZEN) 1,0 DK adult 0,4 VEGETABLES 0,3 FRUIT (FRESH OR FROZEN) 0,3 CEREALS 1,0 PL general population 0,6 VEGETABLES 0,3 FRUIT (FRESH OR FROZEN) 0,0 PULSES, DRY 0,7 FI adult 0,3 VEGETABLES 0,3 FRUIT (FRESH OR FROZEN) 0,2 CEREALS

Conclusion: The estimated Theoretical Maximum Daily Intakes (TMDI), based on pTMRLs were below the ADI. A long-term intake of residues of 6-benzyladenine is unlikely to present a public health concern.

Page 18 / 18 Part B – Section 5 Exilis Registration Report Core Assessment Central Zone

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REGISTRATION REPORT Part B

Section 5 Environmental Fate Detailed summary of the risk assessment

Product code: Exilis Active Substance(s): 6-benzyladenine 20 g/L

Central Zone Zonal Rapporteur Member State: Germany

CORE ASSESSMENT

Applicant: Fine Agrochemicals Limited Date: 08/08/2012

Applicant: Fine Agrochemicals Limited Evaluator ZRMS Germany Applicant Document ID (insert company doc ID) 08/08/2012 Applicant Author (applicant author) Part B – Section 5 Exilis Registration Report Core Assessment Central Zone

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Table of Contents TABLE OF CONTENTS...... 2 SEC 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) ...... 3 5.1 GENERAL INFORMATION ON THE FORMULATION ...... 3 5.2 PROPOSED USE PATTERN ...... 3 5.3 INFORMATION ON THE ACTIVE SUBSTANCES 6-BENZYLADENINE...... 4 5.3.1 Identity, further information of 6-benzyladenine ...... 4 5.3.2 Physical and chemical properties of 6-benzyladenine...... 4 5.3.3 Metabolites of 6-benzyladenine ...... 5 5.4 SUMMARY ON INPUT PARAMETERS FOR ENVIRONMENTAL EXPOSURE ASSESSMENT ...... 5 5.4.1 Rate of degradation in soil...... 5 5.4.2 Adsorption/desorption...... 6 5.4.3 Rate of degradation in water ...... 7 5.5 ESTIMATION OF CONCENTRATIONS IN SOIL (KIIIA1 9.4)...... 7 5.6 ESTIMATION OF CONCENTRATIONS IN SURFACE WATER AND SEDIMENT (KIIIA1 9.7)...... 8 5.7 ESTIMATION OF CONCENTRATIONS IN GROUNDWATER (KIIIA1 9.6)...... 10 5.7.1 PECgw calculation for active substance and its metabolites (Tier 1) ...... 10 5.7.2 Summary Estimation of concentrations in groundwater ...... 11

5.1 PECAIR ...... 12 APPENDIX 1 LIST OF DATA SUBMITTED IN SUPPORT OF THE EVALUATION ...... 13 APPENDIX 2 DETAILED EVALUATION OF STUDIES RELIED UPON...... 14 KIIA 7 FATE AND BEHAVIOUR IN THE ENVIRONMENT ...... 14 KIIA 7.1 ...... 14 KIIA 7.4 ...... 19 KIIA 7.8.3 ...... 24

Page 3 of 34

Sec 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) This document comprises the risk assessment for groundwater and the exposure assessment of surface water and soil for the plant protection product Exilis containing the active substance 6-benzyladenine in its intended uses in apples and pears according to Part B, Section 1, Appendix 2. National Addenda are included containing country specific assessments for some annex points.

5.1 General Information on the formulation

Table 5-1: General information on the formulation Exilis

Code Exilis plant protection product Exilis applicant Fine Agrochemicals Limited date of application 31/08/2011 Formulation type Soluble concentrate (SL) active substance 6-benzyladenine Concentration of as 20 g/l codes of as CAS No. 1214-39-7 EINECS No. 214-92-7-5 CIPAC No. 8029

5.2 Proposed use pattern

The gaps classified according the soil effective application rate (cumulative, disregarding degradation in soil) is presented in Table 5-2. A list of all intended uses within the zone is given in Appendix 2 of section 1. Table 5-2: Classification of uses regarding soil effective concentration

Group Use-No. Crop Application rate Application date Soil effective (g/ha) (crop interception) application rate cumulative, disregarding degradation in soil

1 00-001 Apples, 150 13.06. – 06.07. 45 00-002 Pears (70% interception at BBCH 71-74)

Page 4 of 34

5.3 Information on the active substances 6-benzyladenine

5.3.1 Identity, further information of 6-benzyladenine Table 5-3: Identity, further information on 6-benzyladenine

Active substance (ISO common name) 6-benzyladenine IUPAC N-(phenylmethyl)-1H-purin-6-amine Function (e.g. fungicide) Plant growth regulator Status under Reg. (EC) No 1107/2009 Approved Date of approval 01/06/2011 Conditions of approval PART A Only uses as plant growth regulator may be authorised. PART B For the implementation of the uniform principles of Annex VI, the conclusions of the review report on 6-Benzyladenine, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 23 November 2010 shall be taken into account. In this overall assessment Member States shall pay particular attention to the protection of aquatic organisms. Risk mitigation measures such as buffer zones shall be applied, where appropriate.’ Confirmatory data - RMS FR Minimum purity of the active substance 973 g/kg (combined task force specification) as manufactured (g/kg) Molecular formula C12H11N5 Molecular mass 225.26 g/mol Structural formula

5.3.2 Physical and chemical properties of 6-benzyladenine Physical and chemical properties of 6-benzyladenine as agreed at EU level (see EFSA Journal 2010; 8(10):1716) and considered relevant for the exposure assessment are listed in Table 5-4. Table 5-4: EU agreed physical chemical properties of 6-benzyladenine relevant for exposure assessment

Value Reference Melting point (° C) 229°C to 230.5°C (99%) LoEP Vapour pressure (Pa) 6 x 10-7 Pa (98.5%) at 25°C LoEP ³ -1 Henry’s law constant (Pa × m × mol ) 1.77 x 10-6 at 25 °C (QSAR) LoEP Calculated to be 2.98 x 10-6 at 20 °C

Page 5 of 34

Solubility in water (mg/L) at 20°C (99%) LoEP pH Solubility (mg/L) Pure water 65.7 mg/L pH 4.0 Buffer 116 mg/L pH 7.0 Buffer 64.5 mg/L pH 9.0 Buffer 77.8 mg/L

Partition co-efficient, log KOW at 20°C (99%). LoEP

Tested solution Log Pow PH 4.0 buffer solution 1.86 PH 7.0 buffer solution 2.16 PH 9.0 buffer solution 2.13

Dissociation constant, pKa pKa1 = 9.4 LoEP pKa2 = 7.3

5.3.3 Metabolites of 6-benzyladenine In the assessment of 6-benzyladenine on EU-Level no environmentally occurring metabolites were identified. The ZRMS has taken note of one new study on the degradation in soil of 6-benzyladenine. Hence one new metabolite (M8) needs to be considered (Table 5-5). The leaching potential into groundwater of the soil metabolite M8 will be assessed for the application of the plant protection product and its intended uses. Table 5-5: Metabolites of 6-benzyladenine considered in the exposure assessment

Metabolit Structural Maximum occurence in Ecotoxicologically relevant formula/Molecular compartements (see Core Assessment Section formula 6) M8 unknown 9.9 % in soil Not relevant

5.4 Summary on input parameters for environmental exposure assessment

5.4.1 Rate of degradation in soil 6-benzyladenine The ZRMS has taken note of one new study (Völkel, 2009) on the soil degradation of 6- benzyladenine. A detailed evaluation of this study is presented in appendix 2. The DT50 values of the new study together with the DT50 values from the EU assessment are summarized in Table 5-6.

Table 5-6: Summary of aerobic degradation rates for 6-benzyladenine - laboratory studies

Soil type pH T Moisture DT50 (d) DT50 (d) Method of Reference (°C) 20 °°°C calculation pF2/10kPa Sandy loam 4.4 20 50% MWHC 1.0 1.0 SFO McCorquodale and Coyle Silty clay loam 5.7 20 50% MWHC 1.0 1.0 SFO (2004) Sandy loam 7.4 20 50% MWHC 1.2 1.2 SFO

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Clay loam 7.4 20 50% MWHC 1.1 1.1 SFO LoEP

Sandy loam 4.4 10 50% MWHC 2.9 1.3 SFO LoEP Sand Label 1 5.53 20 pF 2.5 5.1 5.05 3.5* 3.45* SFO Völkel (2009) Label 2 5.53 20 pF 2.5 5.0 3.4* SFO Silt Label 1 7.3 20 pF 2.5 1.5 1.6 1.3* 1.40* SFO loam Label 2 7.3 20 pF 2.5 1.7 1.5* SFO Clay Label 1 7.2 20 pF 2.5 5.3 5.0 4.9* 4.65* SFO Label 2 7.2 20 pF 2.5 4.7 4.4* SFO Loamy Label 1 5.4 20 pF 2.5 3.3 3.25 2.4* 2.35* SFO sand Label 2 5.4 20 pF 2.5 3.2 2.3* SFO geom. mean 1.6 median 1.3

In the degradation study by Völkel (2009) the potentially relevant metabolite M8 was observed to account for more than 5 % of the amount of active substance in two sequential measurements in one soil. The calculated DT50 for this soil is outlined in Table 5-7. Table 5-7: Summary of aerobic degradation rates for metabolite M8 - laboratory studies DT (d) 50 Method of Soil type pH T (°C) Moisture DT50 (d) 20 °C Reference °° calculation pF2/10kPa Loamy Völkel 5.4 20 pF2,5 6.8 5.0 SFO sand (2009)

Field studies from Korea were submitted as part of the EU review although they are not required as the laboratory DT50 is <<60 days. Though there is no evidence for these soils being representative for European soils, the longest field DT50 (8 d) was used in PEC soil calculations since it is more conservative than the data obtained from laboratory studies. The DT50 values of the field studies are summarized in Table 5-6. Table 5-8: Summary of aerobic degradation rates for 6-benzyladenine - field studies b Soil type Location pH Depth DT50 (d) DT90 (d) DT50 (d) Method of (cm) actual actual actual calculation Soil K/ Loam Korea 5.6 0 - 10 7 n/a n/a SFO Soil P/ Loam Korea 5.1 0 - 10 8 n/a n/a SFO

5.4.2 Adsorption/desorption 6-benzyladenine The ZRMS has taken note of one new study (Walther, 2009) on the adsorption and desorption of 6- benzyladenine. A detailed evaluation of this study is presented in appendix 2. The Kfoc values of the new study together with those values from the EU assessment are summarized in Table 5-9.

Page 7 of 34

Table 5-9: Kf, Kfoc and 1/n (Freundlich exponent) values for 6-benzyladenine

Soil Type OC pH Kf Kfoc 1/n Reference (%) (-) (mL g-1 (mL g-1) (-) SK961089, clay loam 4.8 7.5 21.62 451 0.79 Brice and Scholey SK104691, silty clay loam 2.7 6.1 24.43 905 0.76 (2005) LoEP SK179618, clay loam 3.8 5.5 10.73 282 0.79

SK566696 0.8 4.2 15.56 1945 0.82 Loamy sand 2.29 5.4 18.55 810 0.73 Walther (2009) Silt loam 1.43 7.46 10.15 710 0.84

Sandy clay loam 1.19 7.62 11.7 984 0.85

Clay 1.79 7.2 23.18 1295 0.86

Loam 1.32 7.05 7.53 570 0.84

Arithmetic mean 884 0.81

5.4.3 Rate of degradation in water The ZRMS has taken note of one new study (Völkel, 2009) on the degradation of 6-benzyladenine in aerobic water/sediment-systems. A detailed evaluation of this study is presented in appendix 2. The exposure modeling is based on the results of the water/sediment study of 6-benzyladenine reviewed in the DAR and the new study. The results of the water/sediment studies are summarized in Table 5-10. Table 5-10: Degradation in water/sediment of 6-benzyladenine

Water/ DegT50 Fit, DT50 Fit, DT50 Fit, Method Reference sediment whole Method of water Method of sed. of calculation system system calculation calculation TNO 17.1 d SFO 2.4 d SFO na na De Vette (2001) Kromme Rijn 8.6 d SFO 4.1 d SFO na na LoEP

River 9.25 d SFO na na na na Völkel (2009) Pond 7.65 d SFO na na na na

Geomean 10.1 d 3.1 d

5.5 Estimation of concentrations in soil (KIIIA1 9.4)

PECsoil calculations are based on the recommendations of the FOCUS workgroup on degradation kinetics. A soil bulk density of 1.5 g cm-3, a soil depth of 5 cm and a tillage depth 5 cm (permanent crops) were assumed. The PECsoil calculations were performed with ESCAPE 2.0 based on the input parameters for 6-benzaladenine as presented in Table 5-11.

Page 8 of 34

Table 5-11: Input parameter for active substance for PECsoil calculation

Active substance DT50

6-benzaladenine 8 d (SFO, Maximum, Field studies, see Table 5-8)

Due to the fast degradation of 6-benzyladenine in soil (DT90 < 365 d, SFO, laboratory data) the accumulation potential of 6-benzyladenine does not need to be considered.

Beside PECact values also PECtwa, 21 d values are required for risk assessment. PECtwa,21 d values are also presented in Table 5-12. Table 5-12: Results of PECsoil calculation (soil bulk density 1.5 g/cm-3, soil depth 5 cm)

plant protection product Exilis use 00-001 and 00-002 Number of applications 1 application rate Preparation Exilis: 7800 g/ha (Appl.: 7.5 l/ha, rel. density: 1040 g/l) Active substance 6-benzyladenine: 150 g/ha crop interception 70

active substance/ soil relevant PECact PECtwa 21 d tillage depth preparation application rate (mg/kg) (mg/kg) (cm) (g/ha) Active substance 45 0.06 0.0276 5 6-benzyladenine Metabolite M8 45 (worst case) 0.06 0.0276 5 Preparation Exilis 2340 3.12 - 5

5.6 Estimation of concentrations in surface water and sediment (KIIIA1 9.7)

PECsw and PECsed calculations are provided according to the recommendations of the FOCUS working group on surface water scenarios in a stepwise approach considering the pathways drainage and runoff. As risk mitigation measures differ within the central zone no FOCUS Step 4 calculations are performed. However, in case risk mitigation measures are necessary for authorization of Exilis risk mitigation measures applicable in Germany based on the German approach of PECsw and PECsed calculation are provided in the national addendum. The relevant input parameters for the 6-benzyladenine used for PEC calculation are summarized in Table 5-13.

Table 5-13: Input parameters for active substance for PECsw/sed calculations

Plant protection product: Exilis Use No evaluated 00-001 and 00-002 Crop Pome, stone fruit, late application Application method (-) Spray Growth stage at first 71 application (BBCH) Applicant: Fine Agrochemicals Limited Evaluator ZRMS Germany Applicant Document ID (insert company doc ID) 08/08/2012 Applicant Author (applicant author) Part B – Section 5 Exilis Registration Report Core Assessment Central Zone

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Crop interception: 70 Number of applications 1 Application rate: 150 Active Substance 6-benzyladenine Parameter Endpoint used for Values in Remarks PECsw/sed calculation accordance to EU endpoint in LoEP Molecular mass 225.26 yes LoEP Vapour pressure (Pa) 6 * 10-7 at 25°C yes LoEP Extrapolated to 20°C with EVA 2.1: 3.12 * 10-7 at 20°C

DT50,soil (d) 1.6 no geom. mean (see Table 5-6)

DT50,wholesystem (d) 10.1 no geom. mean (see Table 5-6)

DT50,water (d) 3.1 yes geom. mean (see Table 5-6)

DT50,sed (d) default (1000) default (1000) according to FOCUS 2006 -1 Kf,oc (mL g ) 884 no arithm. mean (see Table 5-9) 1/n (-) 0.81 no arithm. mean (see Table 5-9) Max. occurrence sediment 51.5 - - (%) Solubility in water (mg l-1) 64.5 (pH 7) yes LoEP

Results of FOCUS SW calculations for the worst-case application scenario of Exilis are summarized in Table 5-14 - Table 5-16. Beside PECact value also PECtwa, 21 d is given as it is necessary for risk assessment for birds and mammals.

Table 5-14 Summary of highest global maximum FOCUS PECsw and PECsed values at Step 1.

Active Substance 6-benzyladenine

FOCUS STEP 1 PECSW (µg/L) PECSED (µg/kg)

Actual, 0 h TWA, 21 d Actual, 0 h 30.81 14.17 202.88

Table 5-15 Summary of highest global maximum FOCUS PECsw and PECsed values at Step 2.

Active Substance 6-benzyladenine

FOCUS STEP 2 PECSW (µg/L) PECSED (µg/kg)

Actual, 0 h TWA, 21 d Actual, 0 h North Europe 7.86 2.30 24.64 (June-September) South Europe 7.86 2.42 26.65 (March-May)

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Table 5-16: Summary of highest global maximum FOCUS PECsw and PECsed values at Step 3.

Active Substance 6-benzyladenine

FOCUS STEP 3 Water body Application dates PECSW (µg/L) PECSED Scenario (µg/kg)

Actual, 0 h TWA, 21 d Actual, 0 h D3 Ditch 21.06. 5.504 0.390 4.242 D4 Pond 04.07. 0.246 0.129 0.819 D4 Ditch 04.07. 5.500 0.0672 1.003 D5 Pond 30.05. 0.246 0.138 0.874 D5 Ditch 30.05. 5.861 0.0642 0.960 R1 Pond 29.06. 0.246 0.129 0.823 R1 Ditch 29.06. 4.224 0.0472 0.656 R2 Ditch 20.05. 5.651 0.0292 0.443 R3 Ditch 02.06. 5.955 0.106 1.536 R4 Ditch 27.05. 4.129 0.0244 0.375

5.7 Estimation of concentrations in groundwater (KIIIA1 9.6)

5.7.1 PECgw calculation for active substance and its metabolites (Tier 1) Groundwater contamination by direct leaching of the active substance and its metabolites, degradation or reaction products through soil is generally assessed by groundwater model calculations. The PECs of 6-benzyladenine and its metabolite M8 in ground water have been assessed with standard FOCUS scenarios to obtain outputs from FOCUSPELMO 4.4.3. The FOCUS calculation was performed by ZRMS. 6-benzyladenine

Table 5-17: Input parameters related to application for PECgw modelling

use evaluated 00-001 and 00-002 application rate (kg as/ha) 150 crop (crop rotation) Apples date of application 13.06. interception (%) 70 soil moisture 100 % FC Q10-factor 2.58 moisture exponent 0.7 plant uptake 0 simulation period (years) 10

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Table 5-18: Input parameters related to active substance for PECgw modelling

Parent 6-benzyladenine Remarks/Reference molecular mass 225.26 LoEP

DT50 in soil (d) 1.6 see Table 5-6

Kfoc 884 see Table 5-9 1/n 0.81 see Table 5-9

Table 5-19: Input parameters related to metabolites of 6-benzyladenine for PECGW modelling

Metabolite 1 M8 Remarks/Reference molecular mass 225.26 molecular mass of active substance Formation fraction 1 worst case default

DT50 in soil (d) 5.0 see Table 5-7

Kfoc 1.0 worst case default 1/n 1.0 worst case default

Table 5-20: PECGW at 1 m soil depth for 6-benzyladenine and its metabolites

th -1 Use No /crop Szenario 80 Percentile PECGW at 1 m Soil Depth (µµµg L ) groundwater model: FOCUSPELMO 4.4.3 6-benzyladenine Metabolit M8 00-001 Châteaudun, <0.001 0.014 00-002 irrigation Hamburg <0.001 0.035 Kremsmünster <0.001 0.052 Okehampton <0.001 0.047 Piacenza, irrigation <0.001 0.026 Porto, irrigation <0.001 0.002

According to the PECGW modeling with FOCUSPELMO 4.4.3 a groundwater contamination of the active substance 6-benzyladenine at a concentration of ≥ 0.1 µg/L is not expected. For metabolite M8 a groundwater concentration of ≥ 0.1 µg/L can be excluded.

5.7.2 Summary Estimation of concentrations in groundwater Results of modeling with FOCUSPELMO 4.4.3 show that the active substance 6-benzyladenine is not expected to penetrate into groundwater at concentrations of ≥ 0.1 µg/L in the intended uses in apples. For the metabolite M8 concentrations of ≥ 0.1 µg/L in groundwater can be excluded.

Consequences for authorization: None

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5.1 PECair The vapour pressure at 20 °C of the active substance 6-benzyladenine is < 10-5 Pa. Hence the active substance 6-benzyladenine is regarded as non-volatile. Therefore exposure of surface water by the active substance 6-benzyladenine due to deposition following volatilization should be considered.

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Appendix 1 List of data submitted in support of the evaluation Table A 5-1: List of data submitted in support of the evaluation

Annex point/ Author(s) Year Title Data Owner How considered reference No Source (where different from protection in dRR company) claimed Study- Report-No. Status/Usage* GLP or GEP status (where relevant), Published or not Authority registration No OECD: Völkel, W. 2009 14C-6-benzyladenine – Yes Globachem 4) KIIA 7.1 Degradation and Metabolism in Four Soils Incubated under Aerobic Conditions B84587 GLP 1830967 OECD: Walther, 2009 14C-6-Benzyladenine - Yes Globachem 4) KIIA 7.4.1 D. Adsorption/Desorption on soil B84565 GLP 1830949 OECD: Völkel, W. 2009 14C-6-Benzyladenine - Route Yes Globachem 4) KIIA 7.8.3 and rate of degradation in aerobic aquatic sediment systems B84576 GLP 1830951

* 1) accepted (study valid and considered for evaluation) 2) not accepted (study not valid and not considered for evaluation) 3) not considered (study not relevant for evaluation) 4) not submitted but necessary (study not submitted by applicant but necessary for evaluation) 5) supplemental (additional information, alone not sufficient to fulfil a data requirement, considered for evaluation)

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Appendix 2 Detailed evaluation of studies relied upon Report only studies, which have not previously been evaluated within a peer reviewed process at EU level (Annex I inclusion of active substance). Present the authority's evaluation of the study in a box below each individual study. KIIA 7 Fate and Behaviour in the Environment KIIA 7.1

Reference: KIIA 7.1 Report 14C-6-Benzyladenine - Degradation and Metabolism in Four Soils Incubated under Aerobic Conditions Völkel, W. 05.02.2009 B84587 1830967 Guideline(s): Yes OECD Guideline 307: Aerobic and Anaerobic Transformation in Soil Deviations: No GLP: Yes Acceptability: Yes

Materials and methods Four representative fresh field soils I (Stolpe, Germany; sand); II (Fislis, France; silt loam), III (Speyer 6S, Germany; clay) and IV (Speyer 2.2, Germany; loamy sand) were used in the study. The soils were passed through a 2 mm sieve prior to testing, and characterized for particle size distribution, percent moisture at water holding capacity, pH, % organic matter, cation exchange capacity and microbial biomass. The parameters of the freshly sampled soils are shown in Table A 5-2. Table A 5-2 Soil types and their characteristics Parameters Soil I Soil II Soil III Soil IV Site Location Stolpe Fislis Speyer 6S Speyer 2.2 (Germany) (France) (Germany) (Germany) Soil Characteristics pH 5.53 7,3 7,2 5,4 OC (%) 0.86 1,57 1,75 2,16 CEC (meq/100g soil) 7.3 19,62 22 10 Soil Type Sand Silt Loam Clay Loamy Sand Particle Size Analysis (USDA) <0.002 (clay) (%) 4,80 22,68 42,1 6,4 0.002-0.05 (silt) (%) 4,69 60,67 36,0 12,2 >0.05 (sand) (%) 90,51 16,65 21,9 81,4 MWHC (g water/100g soil) At pF 1.0 31,99 55,77 55,4 48,8 At pF 2.0 10,45 36,08 36,2 18,7 At pF 2.5 6,93 29,26 39,9 14,4 Biomass (mg micr. C/kg dry soil) Applicant: Fine Agrochemicals Limited Evaluator ZRMS Germany Applicant Document ID (insert company doc ID) 08/08/2012 Applicant Author (applicant author) Part B – Section 5 Exilis Registration Report Core Assessment Central Zone

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Start and end of 95/92 527/497 343/295 268/222 incubation

The test item was then applied to 100 g soil samples at a concentration of about 0.20 mg/kg dry soil. This rate corresponds to a field rate of 200 g a.i./ha, based on the assumption that the test item is homogeneously distributed in the upper 10 cm of the soil layer with a soil density of 1.0 g/cm3. The treated soil samples were incubated at 20 ± 2 °C in the dark under continuous ventilation with moistened air. The exiting air was passed through a trapping system consisting of flasks of sodium hydroxide and ethylene glycol in series. Prior to treatment and at the end of the incubation period, the microbial biomass was determined for each soil. The results showed that the soils were viable during the study. Duplicate samples treated with the test item labeled at two different positions (phenyl- and adenine- label) were taken immediately from each soil after treatment (day 0) and after 1, 3, 7, 14, 28 and 59 days. Each sample was submitted to the following extraction procedure: room temperature extraction using acetonitrile/water (4: 1; v/v) for up to four times, followed by Soxhlet extraction using acetonitrile/water (4: 1; v/v) for 4 hours. The individual extracts were measured by LSC and combined. The samples were then analyzed for the test item and degradation products by TLC on normal phase plates. In order to confirm these TLC results, TLC analysis were conducted on selected samples and additionally by HPLC where possible. It was not possible to concentrate the extracts without degradation of the test item.

Results and discussions Radiochemical Purity and Stability of the Test Item The purity of 14C-6-Benzyladenine in the application solution was determined by HPLC after treatment to be 95.5% (P-label) and 100% (A-label) . Stability tests before and after the treatment procedure indicated that the test item was stable during application.

Material Balance (Overall Recovery of Radioactivity) The total mean recoveries were 95.3-97% (label P) and 99.0-101.5% (label A) of the applied radioactivity for all soils.

Characterization of Radioactivity Immediately after treatment (day 0), 97.7-102% of the applied radioactivity could be extracted from the soils (Table A 5-3 to Table A 5-6). The amount of extractable radioactivity decreased rapidly to 50.1 % (soil I), 13.5% (soil 11),39.6% (soil III) and 32.1 % (soil IV) of the applied radioactivity (day 7, mean values). By the end of the study (day 59), extractables accounted for between 3.7-7.2% of applied. The amount of bound residues was high, increasing from levels of 2.0-6.0% on day 0 to values of 35.8%, 43.0%, 36.6% and 43.6% of the applied radioactivity for the P-label in soils I, II, III and IV, respectively on day 28. At the same interval the amount of bound residues for the A- label amounted to 27.1%, 25.9, 23.4%, and 24.2% of the applied radioactivity. By the end of the study (day 59), the level of bound residues had declined to 33.6-23.0%, 40.8-23.3%, 35.1-19.5% and 38.8-22.6% of applied for labels P and A in the corresponding soils.

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Table A 5-3 Balance of the applied radioactivity in soil I treated with 14C-6-Benzyladenine 6- Incubation time in days Benzyladenine Sample Soil Stolpe 0 1 3 7 14 28 59 (% AR) P 97.9 80.5 62.0 39.1 18.4 6.4 4.1 Extractables A 106.0 79.2 67.2 37.4 16.8 4.2 2.0 P n.p. 7.3 40.7 11.2 8.5 7.9 5.2 Soxhlet A n.p. 8.3 6.7 12.5 6.0 4.2 3.0 P 97.9 87.9 72.7 50.3 26.8 14.3 9.3 Total A 406.0 87.6 73.9 49.9 22.8 8.4 5.1 Extractables Mean 102.0 97.7 73.3 50.1 24.8 11.4 7.2 P 1.9 6.9 13.2 26.2 33.5 35.8 33.6 Non- A 2.0 4.1 14.1 15.4 26.3 27.1 23.0 extractables Mean 2.0 5.5 13.6 20.8 29.9 31.5 28.3 P n.p. 4.1 9.3 19.1 34.3 45.1 55.0 14 CO2 A n.p. 3.7 15.2 31.6 52.1 66.5 76.0 Mean n.p. 3.9 12.3 25.4 43.2 55.8 65.5 P n.p. n.p. <0.1 <0.1 <0.1 <0.1 <0.1 Other volatiles A n.p. n.p. <0.1 <0.1 <0.1 <0.1 <0.1 in EG Mean n.p. n.p. <0.1 <0.1 <0.1 <0.1 <0.1 P 99.8 98.8 95.1 95.6 94.6 95.2 97.9 Total A 108.0 95.4 103.2 96.9 101.2 102.0 104.1 P 96.7 ± 2.1 Mean SD A 101.5 ± 4.3

Table A 5-4 Balance of the applied radioactivity in soil II treated with 14C-6-Benzyladenine 6- Incubation time in days Benzyladenine Sample Soil Stolpe 0 1 3 7 14 28 59 (% AR) P 97.7 56.2 34.6 10.3 5.9 2.9 2.8 Extractables A 102.1 59.3 37.4 7.2 2.3 1.1 0.9 P n.p. 5.0 4.9 3.7 7.9 3.2 2.7 Soxhlet A n.p. 4.6 2.6 5.9 2.0 1.3 1.0 P 97.7 61.2 39.5 14.0 13.8 6.1 5.5 Total A 102.1 63.9 40.0 13.1 4.2 2.4 1.9 Extractables Mean 99.9 62.5 39.7 13.5 9.0 4.2 3.7 P 2.7 21.0 30.8 43.8 42.0 43.0 40.8 Non- A 2.1 11.1 19.3 26.8 25.8 25.9 23.3 extractables Mean 2.4 16.1 25.1 35.3 33.9 34.4 32.1 P n.p. 3.5 24.1 37.20 41.6 48.7 50.7 14 CO2 A n.p. 17.6 40.0 53.4 68.7 75.2 76.1 Mean n.p. 10.5 32.0 45.3 55.1 62.0 63.4 P n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 Other volatiles A <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 in EG n.p. Mean n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 P 100.4 85.7* 94.4 94.9 97.3 97.7 97.0 Total A 104.3 92.6 99.3 93.3 98.8 103.6 101.3 P 95.3 ± 4.5 Mean SD A 99.0 ± 4.6 14 * Incomplete balance due to loss of CO2

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Table A 5-5 Balance of the applied radioactivity in soil III treated with 14C-6-Benzyladenine 6- Incubation time in days Benzyladenine Sample Soil Stolpe 0 1 3 7 14 28 59 (% AR) P 96.9 71.5 53.6 31.3 18.6 7.2 5.2 Extractables A 103.9 77.5 57.8 31.7 17.4 6.6 4.3 P n.p. 8.9 10.6 9.4 7.9 8.5 5.6 Soxhlet A n.p. 9.4 4.3 6.7 4.3 6.2 4.4 P 96.9 80.4 64.1 40.7 26.6 15.7 10.7 Total A 103.9 86.9 62.1 38.5 21.7 12.8 8.8 Extractables Mean 100.4 83.6 63.1 39.6 24.1 14.2 9.7 P 4.6 10.7 18.4 29.9 29.6 36.6 35.1 Non- A 4.5 4.8 15.3 21.7 20.3 23.4 19.5 extractables Mean 4.6 7.7 16.9 25.8 24.9 30.0 27.3 P n.p. 5.2 15.0 24.3 36.2 45.4 51.9 14 CO2 A n.p. 7.8 21.0 35.7 57.5 66.9 74.3 Mean n.p. 6.5 18.0 30.0 46.8 56.1 63.1 P n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 Other volatiles A n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 in EG Mean n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 P 101.6 96.3 97.6 95.0 92.3 97.6 97.7 Total A 108.4 99.5 98.3 95.8 99.5 103.1 102.6 96.9 ± 2.8 Mean SD P 101.0 ± 4.1

Table A 5-6 Balance of the applied radioactivity in soil IV treated with 14C-6-Benzyladenine 6- Incubation time in days Benzyladenine Sample Soil Stolpe 0 1 3 7 14 28 59 (% AR) P 95.5 74.1 52.6 23.6 7.4 3.8 2.7 Extractables A 99.8 76.4 53.6 23.4 5.8 2.5 1.4 P n.p. 9.1 12.9 11.5 7.7 6.9 4.3 Soxhlet A n.p. 8.7 10.6 5.6 6.6 3.8 2.5 P 95.5 83.2 65.5 35.1 15.1 10.7 7.0 Total A 99.8 85.1 64.2 39.0 12.4 6.4 3.9 Extractables Mean 97.7 84.1 64.8 32.1 13.7 8.6 5.4 P 6.2 10.6 19.8 35.8 44.1 43.6 38.8 Non- A 5.8 8.7 16.5 26.8 28.2 24.2 22.6 extractables Mean 6.0 9.6 18.2 31.3 36.1 33.9 30.7 P n.p. 4.3 11.6 24.1 34.2 43.8 50.4 14 CO2 A n.p. 6.3 18.7 40.0 60.6 70.7 70.5 Mean n.p. 5.3 15.2 32.0 47.4 57.2 60.4 P n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 Other volatiles A n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 in EG Mean n.p. <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 P 101.7 98.0 96.9 95.0 93.4 98.1 96.1 Total A 105.6 100.1 99.4 95.8 101.1 101.3 97.0 97.0 ± 2.7 Mean SD P 100.0 ± 3.2

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The microbial biomass determined prior to the start of incubation was 9.5 mg, 52.7 mg, 34.3 mg and 26.8 mg microbial C/100 g dry soil for soils I, II, III and IV, respectively (Table A 5-2). At the end of incubation, the corresponding values were 9.2 mg, 49.7 mg, 29.5 mg and 22.2 mg microbial C/100g dry soil, respectively. Pattern of Metabolite Formation The amounts of metabolite fractions are based on the results obtained by TLC analysis using silica plates. They were confirmed by HPLC and TLC on reversed phase plates. The quantitative determination was carried out based on the results of TLC analysis. A proposed pathway for the degradation of 6-Benzyladenine in soil incubated under aerobic conditions is shown in Figure A 5-1.

Figure A 5-1 Proposed metabolic pathway of 14C-Benzyladenine in soil incubated under aerobic conditions.

14C-6-Benzyladenine degraded very rapidly in soil with its amount declining from initial levels of 91.8-95.3% to 35.0%, 7.1%, 31.2% and 17.7% of applied on day 7 in soils I to IV, respectively. At the last interval (day 59), it accounted for 2.6%,0.9%,4.6% of applied in soils I to III, respectively. For soil IV it amounted to 4.6% of applied on day 28 and was not analyzed on day 59 due to the low radioactivity in the extract. 6-Benzyladenine was degraded to at least eleven minor radioactive fractions. The most significant metabolite formed was M 1 accounting for a maximum in soil I of 13.1% (day 1, both labels), in soil II 10.7% (day 0, label A) and 8.0% (day 1, label P), in soil III 9.3% (day 1, label P) and 8.5% (day 1, label A) and for soil IV 8.7% (day 1, label P) and 8.5% (day 1, label A) of the applied radioactivity. By day 59 it had declined to 2.7% of applied or less for all soils. M 1 corresponds to the radioactivity at the origin of the TLC plate using the solvent system selected for the evaluation. However M1 consists of at least three sub-fractions. No single fraction exceeds 10% of the applied radioactivity. Another significant degradate was M8 amounting to maximum values of 2.6% (Soil I, day 3), 4.7% (Soil II, day 3), 2.4% (soil III, day 3) and 9.9% (soil IV, day 3).

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Rate of Degradation of 6-Benzyladenine in Soil The rate of disappearance of 14C-6-Benzyladenine from soil was described using simple first order kinetics. The results are depicted in Table A 5-7.

Table A 5-7 Calculated DT50 and DT90 values for the aerobic degradation of 6-Benzyladenine 6-Benzyladenine Soil I Soil II Soil III Soil IV Label P A P A P A P A DT50 5.1 5.0 1.5 1.7 5.3 4.7 3.3 3.2 DT90 17.0 16.7 5.0 5.7 17.5 17.5 10.9 10.5 r2 0.9921 0.9900 0.9906 0.9938 0.9791 0.9826 0.9907 0.9931

Conclusion

14C-6-Benzyladenine degraded rapidly in all four soils with DT50 values of 5, 1.5, 5 and 3 days in soils I, II, III and IV, respectively (for both labels). 6-Benzyladenine was degraded to several minor non-characterized radioactive fractions. All radioactive fractions except for M1 and M8 were either transient or did not exceed 3% of the applied radioactivity at two consecutive sampling intervals. M1 accounted in soils I and II 13.1% and 10.7% at one single interval above 10% of applied. In all other soils and intervals it remained below and degraded rapidly. M8 amounted once in soil IV to 9.9% of applied and remained in all other soils below 4.7%. High mineralization of the radioactive residues was observed in all soils, with radiolabelled carbon dioxide reaching levels of 55-76%, 51-76%, 52-74% and 50-71 % of the applied radioactivity in soils I to IV, respectively, for labels P and A after 59 days of incubation. The amount of non-extractable radioactivity was also significant, amounting to maximum values of 20% to 41 % of the applied radioactivity during the 59-day incubation period. Organic matter fractionation indicated that the majority of the non-extractable radioactivity was bound to the immobile humic acids and humins (13-20% of the applied radioactivity). Only minor amounts of radioactivity (6-10% of applied) were detected in the more mobile fulvic acid fraction. The main degradation pathway of 6-Benzyladenine in soil proceeds via biodegradation to carbon dioxide and non-extractable residues and the formation of numerous minor and transient fractions.

Comments of zRMS The study is acceptable. It fulfills the requirements of OECD Guideline 307. The results are valid and plausible and are used in the evaluation.

KIIA 7.4

Reference: KIIA 7.4.1 Report 14C-6-Benzyladenine - Adsorption/Desorption on soil Walther, D. 30.01.2009 B84565 1830949 Applicant: Fine Agrochemicals Limited Evaluator ZRMS Germany Applicant Document ID (insert company doc ID) 08/08/2012 Applicant Author (applicant author) Part B – Section 5 Exilis Registration Report Core Assessment Central Zone

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Guideline(s): Yes OECD Guideline 307: Adsorption/Desorption using a Batch Equilibrium Method (2000). Deviations: No GLP: Yes Acceptability: Yes

Materials and methods Soil: The soils were collected from different agricultural areas (Table A 5-8). None of the soils had been fertilized or treated with pesticides for at least 12 months prior to sampling. After sampling aliquots of the soils were air dried and stored in a closed container at room temperature. The soils, sieved to 2-mm, were air-dried at room temperature and homogenized. Disaggregation was performed with minimal force, so that the original texture of the soil was changed as little as possible.

Table A 5-8 Soil types and their characteristics Soil I Soil II Soil III Soil IV Soil V Site Loacation Speyer 2.2 Attenschwiller Spra 03 Speyer 6S Mechtildshausen Country Germany France Spain Germany Germany pH (0.01 M CaCl2) 5,4 7,47 7,62 7,2 7,05 OC (%) 2,29 1,43 1,19 1,79 1,32 Clay Content (%) 6,7 20,07 21,91 42,6 16,97 Texture (USDA) Loamy Silt Loam Sandy Clay Clay Loam Sand Loam

Experimental design

All adsorption/desorption tests were conducted in duplicates in sealed teflon centrifuge tubes placed on a shaker in the dark at 20 ± 2°C. All test soils were pre-equilibrated with 0.01 M CaCl2 for more than 12 hours prior to addition of the test substance (from a stock solution, containing 6-benzyladenine in 0.01 M CaCl2 solution.). The soils were equilibrated with approximately 90% of the final volume of the aqueous phase. The study followed the three-tiered approach with a preliminary test (Tier 1), a screening test (Tier 2) and an adsorption isotherm test (Tier 3). The preliminary test (using five soils at one concentration) was conducted to determine the optimal soil:solution ratio, equilibration time, stability of the test substance and mass balance of the system. The screening test (using five soils at a single concentration) was conducted to establish the partition coefficients Kd and KOC for adsorption and desorption in all soils at equilibrium. The adsorption isotherms were determined in the advanced test using the same five soils, five test item concentrations (0.873, 0.272, 0.081, 0.033, 0.008 mgIL), a soil-to- solution ratio of 3/25 and an agitation time of 24 hours. After 24 hours of shaking, duplicate tubes were sampled and the supernatants and soil extracts were measured by LSC and analyzed by HPLC. The pH of the aqueous phase was measured before and after contact with the soils in the advanced test. Analytical methods The aqueous samples obtained from the soil after adsorption and desorption were analyzed by LSC Aqueous and organic (extracts) samples of up to 1 mL were mixed with 10 mL of scintillation mixture and their radioactivity measured in the scintillation counter.

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After all extractions (mass balance tubes), soil aliquots from each mass balance sample were air dried ground and then placed into ceramic sample boats and were combusted by an OX 500 sample oxidizer (Zinsser Analytic; Frankfurt/Germany) in a stream of nitrogen and oxygen gas. 14 All determinations were done in triplicate. Evolved C02 was absorbed in 9 mL of a 1:3 (v/v) mixture of ethanolamine/methoxyethanol. The resulting absorption solution was mixed with 10 mL of the scintillation mixture mentioned above and the radioactivity was quantified by LSC. Aliquots of calibration standard solutions were combusted at the beginning of each series. The yield of combustion of calibration standards solution was approximately 100%.

Results and discussions Radiochemical Purity and Stability of the Test Item The purity of 14C-6-Benzyladenine was determined to be >95% by HPLC analysis of the application solution before and after treatment in the advanced test. Its stability during the test procedure was demonstrated by HPLC analysis of a control sample after 24 hours of agitation. PRELIMINARY TEST Adsorption Based on the preliminary/screening test results, the 24-hour interval was considered as the time for all soils to reach adequate adsorption equilibrium. The adsorption depended on the relative amount of soil; i.e. it increased proportionally to the amount of soil. After 24 hours of adsorption, 35%, 85% and 88% of the applied test-item was absorbed at the ratios 1/25, 3/25 and 5/25 g dry soil/mL, respectively, for soil I. Corresponding values were 32%, 63% and 76% for soil II, 40%, 70% and 74% for soil III, 48%, 79% and 88% for soil IV and 26%, 56% and 68% for soil V. The entire applied radioactivity was recovered in the control samples (99% to 100%) throughout the incubation time. After addition of 13.12 µg 6-Benzyladenine, 10.88 µg, 7.88 µg, 7.63 µg, 9.99 µg and 6.86 µg were adsorbed to soils I to V, respectively. The resulting Kd values were 50 mL/g, 15 ml/g, 18 mL/g, 32 mL/g and 11 mL/g for soils I to V, respectively. Degradation of the test item, as observed in the advanced test, was accounted for in the calculation of the adsorption parameters. Desorption The amount of test item desorbed remained nearly constant within the 48-hour desorption for soil III (about 14%) and decreased for the other soils from 11 % to 8% (soil I), from 29% to 26% (soil II), from 16% to 14% (soil IV) and from 33% to 26% (soil V). These amounts are lower than those found in the supernatant during the adsorption phase, therefore a fraction of the test item was shown to be irreversibly bound to the soil. The distribution of the desorbed radioactivity between the aqueous phase and the soils is presented in Table 6. The resulting Kdes values were 71 mL/g, 23 mL/g, 120 mL/g, 64 mL/g and 19 mL/g for soils I to V, respectively. Degradation of the test item was accounted for in the calculation of the desorption parameters. Mass Balance The entire radioactivity was recovered from the soil samples, with recoveries ranging from 91 % to 103% for all soils. For soil III, similar amounts of radioactivity were detected in the supernatant (30%), soil extracts (35%) or bound to the soil (27%). For the other soils, the highest portion of the radioactivity was found in the extract followed by the supernatant and the bound residues.

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ADVANCED TEST For the advanced test, the soil-to-solution ratio of 3/25 and a maximum agitation time of 24 hours (for both adsorption and desorption) were used. Adsorption Isotherms The distribution of 14C-6-Benzyladenine between the aqueous phase and soil after 24 hours of adsorption in the advanced test is presented in Table A 5-9. Adsorption increased with decreasing test item concentration for all soils. At the highest concentration of 0.873 mg/L, amounts of 75%, 52%, 47%, 74% and 50% of the test item (non-degraded fraction) were adsorbed to soils I to V, respectively. At the lowest concentration, the corresponding values were 91 %, 68%, 60%, 84% and 66% of applied. Table A 5-9 Distribution of 14C-6-Benzyladenine between the aqueous phase and soil after 24 hours of adsorption in soils I to V. Evaluation according to the linear Freundlich adsorption isotherm at a soil-to-solution ratio of 3/25. Soil I (loamy sand) (Speyer 2.2) Concentration Ci (mg/L) 0.873 0.272 0.081 0.033 0.008 m(ads)s (µg) Sample A 16.627 5.487 1.843 0.765 0.192 Sample B 15.946 5.357 1.768 0.759 0.192 Mean (µg) 16.287 5.423 1.806 0.762 0.192 Mean (% of applied) 74.6 79.6 85.6 89.6 91.1 m(ads)s / m(soil) (µg/g) 5.4289 1.8077 0.6020 0.2540 0.0639 log (m(ads)s / m(soil)) 0.735 0.257 -0.220 -0.595 -1.194 C(ads)aq (µg/mL) 0.1836 0.0444 0.0090 0.0023 0.0005 Log(c(ads)aq) -0.736 -1.353 -2.046 -2.630 -3.330

Soil II (silt loam) (Attenschwiler) Concentration Ci (mg/L) 0.873 0.272 0.081 0.033 0.008 m(ads)s (µg) Sample A 11.364 3.974 1.315 0.552 0.144 Sample B 11.251 3.952 1.352 0.558 0.143 Mean (µg) 11.307 3.963 1.333 0.555 0.143 Mean (% of applied) 51.8 58.2 63.2 65.3 68.1 m(ads)s / m(soil) (µg/g) 3.7691 1.3211 0.4444 0.1850 0.0478 log (m(ads)s / m(soil)) 0.576 0.121 -0.352 -0.733 -1.321 C(ads)aq (µg/mL) 0.3311 0.0864 0.0227 0.0085 0.0019 Log(c(ads)aq) -0.480 -1.063 -1.645 -2.073 -2.729

Soil III (sandy clay loam) (Spra 03) Concentration Ci (mg/L) 0.873 0.272 0.081 0.033 0.008 m(ads)s (µg) Sample A 10.152 3.940 1.219 0.519 0.128 Sample B 10.539 3.805 1.275 0.525 0.126 Mean (µg) 10.345 3.873 1.247 0.522 0.127 Mean (% of applied) 47.4 56.9 59.1 61.4 60.4 m(ads)s / m(soil) (µg/g) 3.4485 1.2910 0.4156 0.1740 0.0424 log (m(ads)s / m(soil)) 0.538 0.111 -0.381 -0.759 -1.372 C(ads)aq (µg/mL) 0.2901 0.0633 0.0176 0.0063 0.0016 Log(c(ads)aq) -0.537 -1.198 -1.754 -2.202 -2.785

Soil IV (c1ay) (Speyer 6S)

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Concentration Ci (mg/L) 0.873 0.272 0.081 0.033 0.008 m(ads)s (µg) Sample A 16.16 5.20 1.72 0.70 0.018 Sample B 16.19 5.27 1.72 0.71 0.018 Mean (µg) 16.18 5.23 1.72 0.70 0.018 Mean (% of applied) 74.1 76.8 81.4 82.9 83.7 m(ads)s / m(soil) (µg/g) 5.392 1.744 0.572 0.235 0.059 log (m(ads)s / m(soil)) 0.732 0.242 -0.243 -0.629 -1.231 C(ads)aq (µg/mL) 0.1874 0.0511 0.0121 0.0044 0.0010 Log(c(ads)aq) -0.727 -1.291 -1.918 -2.361 -2.993

Soil V (Ioam) (Mechthildshausen) Concentration Ci (mg/L) 0.873 0.272 0.081 0.033 0.008 m(ads)s (µg) Sample A 10.53 3.26 1.25 0.53 0.14 Sample B 11.09 3.55 1.24 0.52 0.14 Mean (µg) 10.81 3.41 1.25 0.53 0.14 Mean (% of applied) 49.5 50.0 59.2 61.9 65.8 m(ads)s / m(soil) (µg/g) 3.603 1.135 0.416 0.175 0.046 log (m(ads)s / m(soil)) 0.557 0.055 -0.381 -0.756 -1.336 C(ads)aq (µg/mL) 0.3932 0.1212 0.0299 0.0112 0.0024 Log(c(ads)aq) -0.405 -0.916 -1.525 -1.953 -2.614

Recovered radioactivity in the control samples ranged from 99% to 106%. RPLC analysis showed that the test item was unstable in the aqueous phases and soil extracts. These values were used as correction factors to calculate the adsorption parameters. The results obtained were evaluated by applying the linear Freundlich equation. The resulting 2 constants Kf, Kfoc and l/n are presented in Table A 5-10. The coefficients of determination (r ) for the linear regression of the Freundlich equation were above 0.99. The 1/n values showed non-linearity for all soils. Table A 5-10 Freundlich isotherm parameters after 24 hours of adsorption at a soil-to-solution ratio of 3/25. Parameter Soil I Soil II Soil III Soil IV Soil V pH (0.01 M CaCl2) 5,40 7,47 7,62 7,20 7,25 % OC 2,29 1,43 1,19 1,79 1,32 Kf 18,55 10,15 11,70 23,18 7,53 Kfoc 810 710 984 1295 570 1/n 0,73 0,84 0,85 0,86 0,84 r2 0,9979 0,9989 0,9918 0,9985 0,9982

Desorption Isotherms Subsequent to 24 hours of adsorption, the desorption test was performed at the same initial test item concentrations as for the adsorption isotherms. At the highest concentration of 0.873 mg/L, mean amounts of 8%, 15%, 6%, 67% and 33% of the adsorbed radioactivity desorbed (non-degraded fraction of test item) from soils I to V, respectively. The corresponding values for the lowest concentration of 0.008 mg/L were 4%, 14%, 8%, 79% and 48%. HPLC analysis showed that the test item was unstable in the aqueous phases and soil extracts (Table A 5-11). These values were used as correction factors to calculate the Kfoc value.

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Table A 5-11 Percentage of 14C-6-Benzyladenine in the supernatants after 24 hours of adsorption and desorption. Adsorption Percent of 14C-6-Benzyladenine Soil I II III IV V Supernatant 91 88 83 94 94 Extract 97 91 79 96 95

Desorption Percent of 14C-6-Benzyladenine Soil I II III IV V Supernatant 90 91 48 89 88 Extract 95 92 76 98 92

The calculated Kdes,foc values exceeded those obtained for the adsorption isotherms indicating a partially irreversible adsorption process. The correlation coefficients (r2) for the linear regression of the Freundlich equation were higher than 0.99. The 1/n values were similar for both adsorption and desorption (0.82 and 0.90, respectively), reflecting a similar desorption behaviour as found for the adsorption process. Except for soil III, desorption was non-linear.

Conclusion The adsorption/desorption behaviour of 14C-6-Benzyladenine on soil was investigated using five different soil types covering a range of soil properties: Speyer 2.2 (soil I, loamy sand), Attenschwiller (soil II, silt loam), Spra 03 (soil III, sandy clay loam), Speyer 6S (soil IV, clay) and Mechthildshausen (soil V, loam). Five test concentrations were used for both adsorption and desorption covering two orders of magnitude.

The mean values for the adsorption and desorption Freundlich coefficients Kfoc and Kdes,foc were 874 mL/g and 2427 mL/g, respectively. The higher Freundlich isotherm coefficients for desorption indicate a partly irreversible sorption process. The mean l/n values were similar for both adsorption and desorption (0.82 and 0.90, respectively). Non-linear adsorption was observed in all soils i.e. adsorption was dependent of the test item concentration. Desorption was also non-linear except for soil III where desorption was independent of the test item concentration.

Comments of zRMS The study is acceptable. It fulfills the requirements of OECD Guideline 106. The results are valid and plausible and are used in the evaluation.

KIIA 7.8.3

Reference: KIIA 7.8.3 Report 14C-6-Benzyladenine - Route and rate of degradation in aerobic aquatic sediment systems Völkel, W. 05.02.2009 B84576 1830951 Guideline(s): Aerobic and Anaerobic Transformation in Aquatic Sediment Systems Deviations: No Applicant: Fine Agrochemicals Limited Evaluator ZRMS Germany Applicant Document ID (insert company doc ID) 08/08/2012 Applicant Author (applicant author) Part B – Section 5 Exilis Registration Report Core Assessment Central Zone

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GLP: Yes Acceptability: Yes

Materials and methods

Experimental design Water and sediment were sampled from natural river and pond systems (river Rhine and pond Fröschweiher). The sediments were characterized once transported to the laboratory for their pH, organic carbon content, particle size distribution and dry weight. The water-sediment systems were stored for 3 days at the test facility before use. The experiment was performed in open gas-flow-systems in 1000 mL glass metabolism flasks (inner diameter: approximately 10.6 cm, surface area: approximately 88.2 cm2). The sediments were added to the flasks to a depth of approx. 2.3 cm, corresponding to a wet weight of approximately 180-220 g. A water volume of 600 mL was added to the sediment to reach a depth of 7.1-7.3 cm. The sediment / water volume ratio was between 1:4 and 1:3. The flasks were incubated under continuous ventilation with moistened air at 20 ± 2°C in the dark. The water phases were slightly agitated from the top without disturbing the sediment. The target was to apply 14C-6-Benzyladenine to the aerobic aquatic systems at a quantity corresponding to 0.17 mg/L water. This rate was also considered sufficient to enable analysis of the parent compound and its degradation products. The water-sediment samples were applied time- delayed and each time fresh application solutions were prepared for both labels. The purity and stability of the test item were tested during the treatment procedure. The applied amount and its corresponding concentrations are presented in Table A 5-12. Table A 5-12 Applied amount of 14C-6-Benzyladenine and its corresponding concentrations Amount of 14C-6-Benzyladenine Aquatic System Mg/sample Mg/L water Mg/kg sediment Mg/kg total system River, P-label 0.099 0.166 0.452 0.121 River, A-label 0.102 0.170 0.465 0.125 Pond, P-label 0.101 0.168 0.561 0.130 Pond, A-label 0.102 0.170 0.566 0.131

After treatment, the samples were connected to the flow-through system and incubated at 20 ± 2°C in the dark. During incubation, the water was gently agitated without disturbing the sediment.

Sampling and extraction Duplicate samples per test system were taken for analysis immediately after application (time 0) and on days 1, 3, 7, 14, 28 and 56 of incubation. Ethylene glycol and sodium hydroxide (NaOH) traps were monitored for radioactivity by LSC, and exchanged at every sampling interval or every two to four weeks, if necessary. The actual volume of ethylene glycol and sodium hydroxide solutions was determined and their radioactivity content was measured separately for each trap. The radioactive content in the sodium hydroxide traps was checked 14 for the presence of CO2 by precipitation with barium hydroxide. A pool of the NaOH solutions from several exchanged traps for each system (river and pond) was used. For this purpose, 0.5 mL of the 14 alkaline solutions was diluted with 3 mL of bi-distilled water and the precipitation of C02 was induced by addition of 6 mL of saturated barium hydroxide solution. The suspensions were centrifuged for 5 min and the supernatants were tested for quantitative precipitation by adding another

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one to two drops of the saturated Ba(OH)2 solution. If no turbidity developed upon the second addition of Ba(OH)2, the supematants were counted by LSC measurement. If turbidity was observed, LSC measurements were performed after another precipitation step. The absence of radioactivity in the 14 supernatants after precipitation was taken as proof that only C02 was present in the sodium hydroxide solutions. At each sampling interval, the pH and oxygen content in the water phase and redox-potential in water and sediment were determined in the treated samples taken and corresponding control samples. The supernatant water phase was removed from the sediment with a pipette without disturbing the underlying sediment. Practically the total amount of water was removed. The small quantity of residual sediment pore water was treated as sediment in further processing as well as in material balance calculations. The amount of radioactivity in the water was determined by LSC and chromatographic methods. After removing the water phase from the test system, the sediment was submitted to up to three extraction steps using acetonitrile/water (4: I; viv) at room temperature followed by soxhlet extraction using acetonitrile/water (4: 1; viv) during 4 hours. With two duplicate samples reflux extraction was done (river day 28, pond day 14). Extractions at room temperature were performed in a shaker at about 200-250 strokes per minute each for about 30 minutes. The amount of solvent used was in general about 1 mL/g sediment (wet weight basis). The radioactivity in the individual extracts was quantified by LSC. The extracts were then combined and submitted to chromatographic analysis (TLC). After all extractions, the residual sediments were dried, weighed, homogenized and their radiocarbon content was determined by LSC after combustion of up to 1.0 g aliquots. After the room temperature extractions, the sediment samples showing the highest amount of non- extracted residues, i.e. pond at interval day 14 and river at interval day 28, were additionally submitted to the following harsh extraction procedure. The sediments were extracted with acetonitrile/0.1 M hydrochloric acid (1: 1; v, v) under reflux conditions for about 4 hours. The radioactivity content in the reflux extracts was determined by LSC. The reflux extracts were analyzed by TLC. The non-extractable residues were then submitted to organic matter fractionation to investigate the nature of the remaining non-extractable radioactivity. Fractionation of the sediment organic matter was performed in order to determine the percentage of the applied radioactivity bound to the humic and fulvic acids as well as the humin fraction of the sediment. The fractionation consisted of the extraction of sediment with 0.5 M NaOH solution, and subsequent precipitation of the humic acids by reducing to pH 1. Centrifugation permits separation of the fulvic acids, which remain in the liquid-phase. The humin fraction remains nondissolved together with the c1ay minerals and aluminium oxides.

Analytical methods The quantity of radioactivity was determined on Packard liquid scintillation counters equipped with dpm and luminescence options. All measurements were performed at least in duplicate, corrected for background, and counted for a time interval allowing a counting error below 5%. After extractions, sediment samples were homogenized, placed into ceramic sample boats and were combusted by an OX 500 sampie oxidiser (Zinsser Analytic; Frankfurt/Germany) in a stream of nitrogen and oxygen gas. The combustion temperature was 900°C. The combustion products were passed through a series of catalysts at 680°C. All determinations were done in triplicate. Evolved 14 CO2 was absorbed in 10 mL of a 1:3 (v/v) mixture of ethanolamine/methoxyethanol. The resulting absorption solution was mixed with 10 mL of scintilation mixture and the radioactivity was quantified by LSC. Aliquots of test solutions were combusted at the beginning of each series. The yield of combustion of a test solution was approximately 100%.

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Aliquots of 1 mL of the sodium hydroxide solutions from the CO2 absorption bottles and ethylene glycol (containing water from the moistened air) were mixed with 10 mL of scintillation mixture and the radioactivity measured by LSC. Aqueous and organic samples of up to 1.0 mL were mixed with 10 mL of scintillation mixture and the radioactivity measured by LSC.

Results and discussions Radiochemical Purity and Stability of the Test Item The radiochemical purity of 14C-6-Benzyladenine was determined by HPLC analysis. Before treatment the purity was 96.1% for the P-label and 99.5% for the A-label. After treatment the purity was 95.8% (P-label) and 99.7% (A-label), showing thereby the stability of the test item during the application procedure.

Physico-Chemical and Biological Parameters of the Test Systems During the acclimation and incubation periods, the pH, oxygen content and redox potential were measured in the water phase of both systems. In addition, the sediment was monitored for redox potential. During the acclimation period, pH and redox potential reached equilibrium. The water phase was always under aerobic conditions. The pH values of the river water phase of all samples measured one to three days before application ranged from 8.13 to 8.61. Corresponding values for the oxygen concentration ranged from 8.1 to 8.9 mg/L. The values for the redox potential in water ranged from 117 to 196 mV and from -158 to -100 mV in the sediment. The pH values of the pond water phase of all samples measured one to three days before application ranged from 8.27 to 8.55. The corresponding values for the oxygen concentration ranged from 8.2 to 8.8 mg/L. The values for the redox potential in water ranged from 87 to 179 mV and from -150 to -91 mV in the sediment. During incubation, redox potential was always indicative of aerobic conditions in the water phase and of reducing conditions in the sediment. The pH value of the river water phase of the treated samples during incubation was on average 8.46. The corresponding value for the oxygen concentration was 8.6 mg/L. The mean value for the redox potential was 139 mV in water and -120 mV in the sediment. The pH value of the pond water phase of the treated samples during incubation was on average 8.41. The corresponding value for the oxygen concentration was 8.4 mg/L. The mean value for the redox potential in water was 139 mV and -110 mV in the sediment. Very similar values were found in the untreated controls indicating that the test item had no measurable effect on the physico-chemical parameters of the test system. As an indicator of the microbial activity of the test system, the microbial biomass was determined in the sediment post-handling and at the start and end of the incubation period. The results showed that both sediments were viable throughout the study.

Material Balance (Overall Recovery of Radioactivity)

The results are reported in percent of the applied radioactivity in Table A 5-14 - Table A 5-17. The total mean recovery for all samples was on average 98.4% ± 3.6% (P-label) and 98.5% ± 2.4% (A- label) of the applied radioactivity for the river system and 97.9% ± 2.8% (P-label) and 96.2%±4.0% (A-label) of the applied radioactivity for the pond system.

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Distribution of Radioactivity The values are expressed as the mean of the P- and A-labeled samples, since the values for the individual samples were very similar. The radioactivity detected in the water phases decreased continuously during the study, reaching levels of 64% of applied radioactivity after 3 days and 2.1 % at the end of the study in the river system and 48.8% after 3 days and 0.7% at the end of the study in the pond system. The amount of total radioactivity in the sediment reached 41.3% of applied after 7 days and then decreased to 21.5% at the end of the study in the river system. In the pond system it reached 49.8% after 3 days and decreased thereafter to 18.4% at the end of the study. The total amount of extractables increased to 34.7% (day 7) in the river system and to 42.6% (day 3) in the pond system. Thereafter the radioactivity extracted decreased continuously to less than 4% at the end of incubation. The amount of non-extractable radioactivity in the sediments reached a maximum amount of 22.4% (day 28) and 27.4% (day 14) of applied radioactivity in the river and pond systems, respectively. Acidic harsh extraction under reflux followed by organic matter fractions were conducted on the non- extracted residues from days 28 (river) and 14 (pond). Reflux extraction released between 1.2% and 3.1 % of the applied radioactivity for both aquatic systems. Subsequent organic matter fractionation of the remaining non-extractable radioactivity showed that the majority of the non-extractable radioactivity was bound to the immobile humic acids and humin fraction amounting to mean amounts of 15.8% and 18.6% ofthe applied radioactivity for river and pond, respectively (Table 9). The corresponding range for the fulvic acids was low i.e. 5.2% (river) and 5.7% (pond) of applied. High levels of mineralization of the radioactive residues were observed for the river and pond systems. Radioactive carbon dioxide reached maximum levels of 76.6% (river) and 77.6% (pond) of the applied 14 radioactivity at the end of the study. The identity of CO2 was confirmed by precipitation with barium 14 hydroxide. The formation of other organic volatiles than CO2 was insignificant (less than 0.1 % of applied radioactivity).

Rate and Pattern of Degradation of 14C-6-Benzyladenine in Aerobic Aquatic Systems 14 The dissipation half-lives DT50 and DT90 (Table A 5-13) were calculated for C-6-Benzyladenine using the experimental values reported in Table A 5-14 - Table A 5-17 and single first order (SFO) kinetics using the Origin calculation software.

14 Table A 5-13 DT50 and DT90 for C-6-Benzyladenine. 14C-6-Benzyladenine Total system River Pond P-Label A-Label P-Label A-Label

DT50 9.7 8.8 6.9 8.4

DT90 32.3 29.2 23.0 28.0 r2 0.96 0.96 0.99 0.99 Model used SFO

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Table A 5-14 Distribution of 14C-6-Benzyladenine (P-label) and its degradates in the water phase, sediment extracts and the entire aerobic river test system. Values are given in percent of the applied radioactivity. Aerobic River (20°C) Incubation time (d) Pattern P-Label (% of applied) 0 1 3 7 14 28 56 6-Benzyladenine Water 95.9 77.7 59.1 44.7 20.7 * * Extr. na 12.0 21.7 30.7 11.2 3.4 2.4 Total 95.9 89.7 80.8 75.4 31.9 3.4 2.4 M1 Water * 3.5 1.9 2.3 3.6 * * Extr. * 0.5 0.8 1.3 0.9 1.9 0.8 Total * 4.1 2.7 3.6 4.5 1.9 0.8 M2 Water * * * * * * * Extr. * 0.5 * * 1.4 0.5 0.2 Total * 0.5 * * 1.4 0.5 0.2 M3 Water 1.5 * * * * * * Extr. * * * 0.1 0.4 * * Total 1.5 * * 0.1 0.4 * * M4 Water 2.8 * * * 1.5 * * Extr. * * * 0.2 0.4 0.6 0.4 Total 2.8 * * 0.2 1.9 0.6 0.4 M5 Water * * * * * * * Extr. * * * 0.4 * * * Total * * * 0.4 * * * M6 Water * * * * * * * Extr. * * * 0.5 * * * Total * * * 0.5 * * * M8 Water * * * * * * * Extr. * * * * * 0.4 * Total * * * * * 0.4 * M9 Water * * * * * * * Extr. * 0.3 1.4 * 0.6 * * Total * 0.3 1.4 * 0.6 * * M10 Water * * * * * * * Extr. * 0.1 * * 0.9 0.4 0.5 Total * 0.1 * * 0.9 0.4 0.5 M12 Water * * * * * * * Extr. * * * * 0.2 * * Total * * * * 0.2 * * M13 Water * * * * * * * Extr. * 0.1 * * 0.2 * 0.1 Total * 0.1 * * 0.2 * 0.1 M14 Water * * * * * * * Extr. * * * * 0.4 0.2 0.2 Total * * * * 0.4 0.2 0.2 M15 Water * * 3.1 * * * * Extr. * * * * * * * Total * * 3.1 * * * * Not analyzed Water * * * * * 3.3 3.5 Extr. < 0.1 * * * * * * Total < 0.1 * * * * 3.3 3.5 14 CO2 na 0.4 4.0 5.5 27.8 62.7 65.6 Other volatiles in EG na < 0.1 < 0.1 < 0.1 < 0.1 < 0.1 < 0.1 Non-extractables < 0.1 3.1 7.8 7.9 23.1 29.4 26.9 Total 100.2 98.2 99.8 93.6 93.3 102.8 100.6

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Table A 5-15 Distribution of 14C-6-Benzyladenine (A-label) and its degradates in the water phase. sediment extracts and the entire aerobic river test system. Values are given in percent of the applied radioactivity. Aerobic River (20°C) Incubation time (d) Pattern P-Label (% of applied) 0 1 3 7 14 28 56 6-Benzyladenine Water 99.2 79.1 63.9 41.9 15.0 * * Extr. na 13.0 28.5 32.4 10.3 2.8 1.0 Total 99.2 92.0 92.3 74.3 25.3 2.8 1.0 M1 Water * 3.2 * 3.9 2.9 * * Extr. * 0.5 0.7 1.4 0.8 1.0 0.3 Total * 3.7 0.7 5.3 3.7 1.0 0.3 M2 Water * * * * 0.9 * * Extr. * 0.1 0.2 0.4 0.6 1.3 0.2 Total * 0.1 0.2 0.4 1.5 1.3 0.2 M3 Water * * * * * * * Extr. * <0.1 * 0.4 0.4 0.3 0.1 Total * <0.1 * 0.4 0.4 0.3 0.1 M4 Water * * * * * * * Extr. * 0.1 * 0.3 0.3 0.4 0.2 Total * 0.1 * 0.3 0.3 0.4 0.2 M5 Water * * * * * * * Extr. * 0.1 * 0.5 * 0.2 * Total * 0.1 * 0.5 * 0.2 * M6 Water * * * * * * * Extr. * * * 0.7 * * * Total * * * 0.7 * * * M10 Water * * * * * * * Extr. * * * * 0.1 * 0.1 Total * * * * 0.1 * 0.1 M13 Water * * * * * * * Extr. * * * * 0.1 * <0.1 Total * * * * 0.1 * <0.1 Not analyzed Water * * * * * 1.3 0.7 Extr. <0.1 * * * * * * Total <0.1 * * * * 1.3 0.7 14 CO2 na 0.5 3.9 9.6 50.3 77.5 87.7 Other volatiles in EG na <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 Non-extractables <0.1 2.0 3.5 5.4 12.0 15.5 9.4 Total 99.2 98.6 100.7 96.9 93.7 100.2 99.8

Table A 5-16 Distribution of 14C-6-Benzyladenine (P-label) and its degradates in the sediment extracts of the aerobic pond test system. Mean values are given in percent of the applied radioactivity. Aerobic River (20°C) Incubation time (d) Pattern P-Label (% of applied) 0 1 3 7 14 28 56 6-Benzyladenine Water 94.7 72.9 44.9 16.2 9.8 * * Extr. na 13.3 37.5 29.8 12.7 3.0 1,6 Total 94.7 86.2 82.4 46.0 22.5 3.0 1,6 M1 Water * 2.6 1.9 6.6 2.9 * * Extr. * 0.1 2.1 1.3 0.8 0.4 0,8

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Total * 2.7 4.0 7.9 3.7 0.4 0,8 M2 Water * * * * * * * Extr. * 0.4 * * 1.1 1.1 0,2 Total * 0.4 * * 1.1 1.1 0,2 M3 Water 1.4 * * * * * * Extr. * * 0.2 0.1 0.3 0.1 0,1 Total 1.4 * 0.2 0.1 0.3 0.1 0,1 M4 Water 1.8 * * * 0.2 * * Extr. * * 0.4 0.1 0.3 0.1 0,2 Total 1.8 * 0.4 0.1 0.5 0.1 0,2 M5 Water * * * * * * * Extr. * * 0.9 0.3 0.2 0.1 * Total * * 0.9 0.3 0.2 0.1 * M6 Water * * * * * * * Extr. * * * 0.4 * * * Total * * * 0.4 * * * M7 Water * * * * * * * Extr. * 0.1 * * * * * Total * 0.1 * * * * * M8 Water * * * * * * * Extr. * 0.3 * * * 0.3 * Total * 0.3 * * * 0.3 * M9 Water * * * * * * * Extr. * 0.3 0.8 * 0.6 0.3 0,1 Total * 0.3 0.8 * 0.6 0.3 0,1 M10 Water * * * * * * * Extr. * 0.1 * 0.4 1.6 0.9 0,5 Total * 0.1 * 0.4 1.6 0.9 0,5 M12 Water * * * * * * * Extr. * * * * 0.3 * * Total * * * * 0.3 * * M13 Water * * * * * * * Extr. * 0.1 * * 0.2 0.2 0,1 Total * 0.1 * * 0.2 0.2 0,1 M14 Water * * * * * * * Extr. * * * * 0.3 0.2 0,1 Total * * * * 0.3 0.2 0,1 M16 Water * * 1.5 * * * * Extr. * * * * * * * Total * * 1.5 * * * * Not analyzed Water * * * * * 1.9 0,7 Extr. <0.1 * * * * * * Total <0.1 * * * * 1.9 0,7 14 CO2 na 0.1 1.6 16.0 29.5 63.6 75.0 Other volatiles in EG na <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 Non-extractables <0,1 5.4 8.3 22.7 35.2 27.1 22.6 Total 98,0 95.8 100.1 93.8 96.1 99.2 102.1

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Table A 5-17 Distribution of 14C-6-Benzyladenine (A-label) and its degradates in the sediment extracts of the aerobic pond test system. Mean values are given in percent of the applied radioactivity. Aerobic River (20°C) Incubation time (d) Pattern P-Label (% of applied) 0 1 3 7 14 28 56 6-Benzyladenine Water 98.2 84.0 44.2 32.1 21.9 1.3 * Extr. na 9.5 40.4 23.3 13.0 2.6 * Total 98.2 93.5 84.7 55.4 34.9 3.9 * M1 Water * * 2.8 2.9 4.7 8.3 * Extr. * 0.1 1.7 2.3 1.1 0.3 * Total * 0.1 4.4 5.2 5.8 8.6 * M2 Water * * * * * * * Extr. * 0.1 0.2 0.3 0.5 0.4 * Total * 0.1 0.2 0.3 0.5 0.4 * M3 Water * * * * * * * Extr. * * 0.2 * 0.3 0.1 * Total * * 0.2 * 0.3 0.1 * M4 Water * * * * 2.0 * * Extr. * <0.1 0.2 * 0.2 0.2 * Total * <0.1 0.2 * 2.2 0.2 * M5 Water * * * * * * * Extr. * * 0.2 * * * * Total * * 0.2 * * * * M6 Water * * * * * * * Extr. * * 0.4 * * * * Total * * 0.4 * * * * M7 Water * * * * * * * Extr. * <0.1 * * * * * Total * <0.1 * * * * * M8 Water * * * * * * * Extr. * 0.2 * * * 0.2 * Total * 0.2 * * * 0.2 * M10 Water * * * * * * * Extr. * 0.2 * 0.1 0.1 0.2 * Total * 0.2 * 0.1 0.1 0.2 * M16 Water * * 2.2 * * * * Extr. * * * * * * * Total * * 2.2 * * * * Not analyzed Water * * * * * * 0,7 Extr. <0.1 * * * * * 2,9 Total <0.1 * * * * * 3,7 14 CO2 na <0.1 2.0 14.8 31.8 73.2 80.2 Other volatiles in EG na <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 Non-extractables <0,1 3.1 6.1 14.7 19.5 13.2 7.5 Total 98,2 97.2 100.6 90.6 95.2 100.1 91.3

Pattern of Degradation Products

Page 33 of 34

The amounts of 14C-6-Benzyladenine and degradates present in the sediment extracts were based on TLC analysis. Chromatographic profiling by HPLC was used on selected samples in order to confirm the TLC results. The results are shown in percent of the applied radioactivity in Table A 5-14 - Table A 5-17. Based on the results obtained a proposed metabolic pathway for 6-Benzyladenine in aerobic aquatic systems is presented in Figure A 5-2.

Figure A 5-2 Pathway of degradation of 14C-6-Benzyladenine in aerobic aquatic systems.

River system (Table A 5-14 - Table A 5-15) The level of parent substance in the river decreased continuously with time, from an initial level of 95.9% (P-label) and 99.2% (A-label) of the applied radioactivity to 2.4% (P-label) and 1.0% (A-label). Besides the parent compound, thirteen minor degradation products were detected, not exceeding 5.3% of applied radioactivity (M1. A-label). Pond system (Table A 5-16 - Table A 5-17) The level of parent substance in the pond decreased continuously with time, from an initial level of 94.7% (P-label) and 98.2% (A-label) of the applied radioactivity to 1.6% or less. Besides the parent compound, one major (M1) and several minor degradation products were detected. The degradation product M1 reached maximum levels from 7.9% after 7 days (P-label) and 8.6% after 28 days (A- label). The minor degradates reached not more than 2.2% of applied radioactivity (M4 and M16, A- label).

Conclusion The route and rate of degradation of 14C-6-Benzyladenine in two aquatic systems (river and pond) under aerobic conditions were investigated at 20°C in the dark.

6-Benzyladenine degradated rapidly to carbon dioxide, several degradates and bound residues. DT50 values between 6.9 and 9.7 days were calculated for the river and pond total systems.

Page 34 of 34

One major metabolite was formed, reaching maximum levels of 8.6% of applied radioactivity in the pond system and 5.3% in the river system. Of the minor metabolites none exceeded 3.1 % of applied in either total aquatic system. Comments of zRMS The study is acceptable. It fulfills the requirements of OECD Guideline 308. The results are valid and plausible and are used in the evaluation.

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REGISTRATION REPORT Part B

Section 5 Environmental Fate Detailed summary of the risk assessment

Product code: Exilis Active Substance(s): 6-benzyladenine 20 g/L

Central Zone Zonal Rapporteur Member State: Germany

NATIONAL ADDENDUM - Germany

Applicant: Fine Agrochemicals Limited Date: 08/08/2012

Page 2 of 9

Table of Contents TABLE OF CONTENTS...... 2 SEC 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) ...... 3 5.1 GENERAL INFORMATION ON THE FORMULATION ...... 3 5.2 PROPOSED USE PATTERN ...... 3 5.3 INFORMATION ON THE ACTIVE SUBSTANCES 6-BENZYLADENINE...... 3 5.3.1 Physical and chemical properties of 6-benzyladenine...... 3 5.3.2 Metabolites of 6-benzyladenine ...... 3 5.4 SUMMARY ON INPUT PARAMETERS FOR ENVIRONMENTAL EXPOSURE ASSESSMENT ...... 3 5.4.1 Rate of degradation in soil...... 3 5.4.2 Adsorption/desorption...... 3 5.4.3 Rate of degradation in water ...... 3 5.5 ESTIMATION OF CONCENTRATIONS IN SOIL (KIIIA1 9.4)...... 4 5.6 ESTIMATION OF CONCENTRATIONS IN SURFACE WATER AND SEDIMENT (KIIIA1 9.7)...... 4 5.6.1 PECSW after exposure by spraydrift and deposition following volatilization...... 5 5.6.2 PECSW after exposure by surface run-off and drainage...... 5 Table 5-4 PECSW after exposure by surface run-off and drainage ...... 5 5.7 ESTIMATION OF CONCENTRATIONS IN GROUNDWATER (KIIIA1 9.6)...... 6 5.7.1 PECgw calculation for active substance and its metabolites (Tier 1) ...... 6 5.7.1 PECGW bank filtration ...... 6 Table 5-6 PECGW by bank filtration due to surface run-off and drainage...... 6 APPENDIX 1 LIST OF DATA SUBMITTED IN SUPPORT OF THE EVALUATION ...... 9

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Sec 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) The exposure assessment of the plant protection product Exilis in its intended for uses in apples and pears is documented in detail in the core assessment of the plant protection product Exilis dated from 08/08/2012 performed by Germany.

This document contains the specific exposure assessment regarding PECsoil, PECgw and PECsw for authorization of the plant protection product Exilis in Germany according to the above listed intended uses in apples and pears based on the results of the core assessment of the plant protection product Exilis dated from 08/08/2012 performed by Germany.

Regarding PECgw relevant risk mitigation measures, if necessary, are documented in this document. PECsoil, PECsw are used for risk assessment to derive specific risk mitigation measures if necessary (see Part B section 6 and Part A).

In the EU assessment soil Metabolite M8 has not been taken into account. Thus, this metabolite was assessed in the core assessment and in this document.

5.1 General Information on the formulation

See core assessment

5.2 Proposed use pattern

See core assessment

5.3 Information on the active substances 6-benzyladenine

See core assessment

5.3.1 Physical and chemical properties of 6-benzyladenine See core assessment

5.3.2 Metabolites of 6-benzyladenine See core assessment

5.4 Summary on input parameters for environmental exposure assessment

5.4.1 Rate of degradation in soil See core assessment

5.4.2 Adsorption/desorption See core assessment

5.4.3 Rate of degradation in water See core assessment

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5.5 Estimation of concentrations in soil (KIIIA1 9.4)

Results of PECsoil calculation for 6-benzyladenine according to EU assessment considering 5 cm soil depth are given in Table 5-12 of Part B, Section 5.5 of the core assessment.

For German exposure assessment the applied soil depth is based on experimental data (Fent, Löffler, Kubiak: Ermittlung der Eindringtiefe und Konzentrationsverteilung gesprühter Pflanzenschutzmittelwirkstoffe in den Boden zur Berechnung des PEC-Boden. Abschlussbericht zum Forschungsvorhaben FKZ 360 03 018, UBA, Berlin 1999). Generally for active substances with a Kf,oc < 500 a soil depth of 2.5 cm is applied whereas for active substances with a Kf,oc > 500 a soil depth of 1 cm is applied. The soil bulk density is 1.5 g cm-3. Due to the fast degradation of 6-benzyladenine in soil (DT90 < 365 d, SFO, laboratory data) the accumulation potential of 6-benzyladenine does not need to be considered.

Table 5-1: Input parameter for active substance for PECsoil calculation

Active substance DT50

6-benzaladenine 8 d (SFO, Maximum, Field studies, non-normalized)

Due to the fast degradation of 6-benzyladenine in soil (DT90 < 365 d, SFO, laboratory data) the accumulation potential of 6-benzyladenine does not need to be considered.

Beside PECact values also PECtwa, 21 d values are required for risk assessment. PECtwa, 21 d values are also presented in Table 5-2. Table 5-2: Results of PECsoil calculation (soil bulk density 1.5 g/cm-3, soil depth 1 cm)

active substance/ soil relevant PECact PECtwa 21 d tillage depth preparation application rate (mg/kg) (mg/kg) (cm) (g/ha) Active substance 45 0.3 0.1382 5 6-benzyladenine Metabolite M8 45 (worst case) 0.3 0.1382 5 Preparation Exilis 2340 15.6 - 5

5.6 Estimation of concentrations in surface water and sediment (KIIIA1 9.7)

Results of PECsw calculation of 6-benzyladenine for the intended uses of Exilis in apples and pears using FOCUS Surface Water are given in Tables 5-14 – 5-16 of Part B, Section 5.6 of the core assessment.

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For authorization in Germany exposure assessment of surface water considers the routes of entry (spraydrift and deposition following volatilisation; run-off, drainage) separately to derive risk mitigation measures separately for each entry route. The German surface water exposure assessment is outlined in the following chapters.

5.6.1 PECSW after exposure by spraydrift and deposition following volatilization The calculation of concentrations in surface water is based on spray drift data by Rautmann and Ganzelmeier. The vapour pressure at 20 °C of the active substance 6-benzyladenine is < 10-5 Pa. Hence the active substance 6-benzyladenine is regarded as non-volatile. Therefore exposure of surface water by the active substance 6-benzyladenine due to deposition following volatilization does not need to be considered. The calculation of PECsw after exposure by spraydrift and deposition following volatilization using the model EVA 2.1 is not required.

5.6.2 PECSW after exposure by surface run-off and drainage The concentration of the active substance 6-benzyladenine in adjacent ditch due to surface runoff and drainage is calculated using den model EXPOSIT 3.01.

Table 5-3 Input parameters for EXPOSIT 3.01 active substance 6-benzyladenine Solubility in water (mg/L) 64.5

DT50 soil (d) 8

KOC 884

(KOC value drives the proportion of the active substance that is potentially effective ) mobility class IV Active substance: 6-benzyladenine use pattern/gap: Apples and pears Application rate: 150 g ai/ha (worst case) Interception: 70 %

The PECsw values due to surface run-off and drainage are calculated for the active substance 6- benzyladenine for the intended use in apples and pears (worst case application rate).

Table 5-4 PECSW after exposure by surface run-off and drainage Exposure by surface runoff vegetated buffer strip (m) PECsw in adjacent ditch (µg/L) 0 0.27 5 0.24 10 0.20 20 0.14 Exposure by drainage Drainage Time of application PECsw in adjacent ditch (µg/L)

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Autumn/winter/early spring 0.33 Spring/summer 0.11

5.7 Estimation of concentrations in groundwater (KIIIA1 9.6)

5.7.1 PECgw calculation for active substance and its metabolites (Tier 1) See core assessment

5.7.1 PECGW bank filtration Groundwater contamination by bank filtration due to surface run-off and drainage of the active substance 6-benzyladenine into the adjacent ditch is estimated by the model EXPOSIT 3.01.

Table 5-5 Input parameters for EXPOSIT 3.01 Groundwater exposure assessment due to surface run-off and drainage with subsequent bank filtration (modelling with Exposit 3.0) Active substance 6-benzyladenine Solubility in water (mg/L) 64.5

DT50 soil (d) 8

KOC 884

(KOC value drives the proportion of the active substance that is potentially effective ) mobility class IV elimination rate during bank 100 % (default) filtration

Table 5-6 PECGW by bank filtration due to surface run-off and drainage use application PECgw due to rate run-off drainage interception vegetated buffer bank filtrate Time of bank filtrate strip (µg/L) application (µg/L) (m) 00-001 and 150 g ai/ha 0 0.000 autumn/winter/ 0.000 00-002 70 % 5 0.000 early spring 10 0.000 spring/summer 0.000 20 0.000 required labelling none

According to modeling results with EXPOSIT 3.01 groundwater exposure of the active substance 6- benzyladenine by bank filtration due to surface run-off and drainage into the adjacent ditch at concentration ≥ 0.1 µg/L can be excluded.

Page 7 of 9

Consequences for authorization: The authorization of the plant protection product Exilis is linked with following labeling: none

Applicant: Fine Agrochemicals Limited Evaluator ZRMS Germany Applicant Document ID (insert company doc ID) 08/08/2012 Applicant Author (applicant author)

Part B – Section 5 Exilis Registration Report National Addendum Germany

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Appendix 1 List of data submitted in support of the evaluation none

Applicant: Fine Agrochemicals Limited Evaluator ZRMS Germany Applicant Document ID (insert company doc ID) 08/08/2012 Applicant Author (applicant author) Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 1 of 74

REGISTRATION REPORT Part B

Section 6: Ecotoxicological Studies Detailed summary of the risk assessment

Product code Exilis

Active Substance 6-benzyladenine 20 g/L

Member State: Germany Central Zone

CORE ASSESSMENT

Applicant Fine Agrochemicals Limited Date 08. August 2012

Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date: 08. August 2012 Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 2 of 74

Table of Contents TABLE OF CONTENTS...... 2 SEC 6 ECOTOXICOLOGICAL STUDIES...... 5 6.1 PROPOSED USE PATTERNS...... 5 6.2 EFFECTS ON BIRDS (IIIA1 10.2)...... 7 6.2.1 Overview and summary ...... 7 6.2.2 Toxicity exposure ratios for birds (IIIA 10.2.1)...... 8 6.2.3 Drinking water exposure ...... 11 6.2.4 Details on formulation type in proportion per item...... 11 6.2.5 Effects of secondary poisoning (IIIA1 10.1.9)...... 11 6.3 EFFECTS ON TERRESTRIAL VERTEBRATES OTHER THAN BIRDS (IIIA1 10.3)...... 11 6.3.1 Overview and summary ...... 11 6.3.2 Toxicity exposure ratios (IIIA1 10.3.1)...... 13 6.3.3 Drinking water exposure ...... 15 6.3.4 Details on formulation type in proportion per item (IIIA 10.3.2) ...... 15 6.3.5 Effects of secondary poisoning (IIIA1 10.3.2.3)...... 15 6.3.6 Supervised cage or field trials (IIIA 10.3.3)...... 15 6.4 EFFECTS ON AQUATIC ORGANISMS (IIIA1 10.2) ...... 15 6.4.1 Overview and summary ...... 15 6.4.2 Toxicity exposure ratios (IIIA1 10.2.1)...... 19 6.4.3 Risk from metabolites ...... 20 6.4.4 Acute toxicity of the formulation (IIIA1 10.2.2)...... 21 6.4.5 Chronic toxicity to fish (IIIA1 10.2.5) ...... 21 6.4.6 Chronic toxicity to aquatic invertebrates (IIIA1 10.2.6) ...... 21 6.4.7 Accumulation in aquatic non-target organisms (IIIA1 10.2.7)...... 21 6.5 EFFECTS ON BEES (IIIA 10.4)...... 22 6.5.1 Overview and Summary...... 22 6.5.2 Toxicity ...... 22 6.5.3 Exposure...... 22 6.5.4 Hazard quotients...... 23 6.5.5 Risk assessment...... 23 6.5.6 Overall conclusion: ...... 23 6.6 EFFECTS ON ARTHROPODS OTHER THAN BEES (IIIA 10.5) ...... 24 6.6.1 Overview and summary ...... 24 6.6.2 Risk Assessment for Arthropods other than Bees ...... 26 6.6.3 Using artificial substrates...... 28 6.6.4 Extended laboratory studies (IIIA 10.5.2)...... 28 6.6.5 Semi-field tests (IIIA 10.5.3) ...... 28 6.6.6 Field tests (IIIA 10.5.4)...... 28 6.7 EFFECTS ON EARTHWORMS AND OTHER SOIL NON-TARGET MACRO-ORGANISMS (IIIA 10.6)...... 29 6.7.1 Overview and summary ...... 29 6.7.2 Toxicity exposure ratios for earthworms, TERA and TERLT (IIIA 10.6.1)...... 30 6.7.3 Acute toxicity (IIIA 10.6.2)...... 31 6.7.4 Sublethal effects (IIIA 10.6.3)...... 31 6.7.5 Field tests (IIIA 10.6.4)...... 31 6.7.6 Residue content of earthworms (IIIA 10.6.5)...... 31 6.7.7 Effects on other non-target macro-organisms (IIIA 10.6.6)...... 31 6.7.8 Effects on organic matter breakdown (IIIA 10.6.7) ...... 31 6.8 EFFECTS ON SOIL MICROBIAL ACTIVITY (IIIA 10.7)...... 32 6.8.1 Overview and summary ...... 32 6.8.2 Laboratory testing (IIIA 10.7.1)...... 33 6.8.3 Additional testing (IIIA 10.7.2)...... 33 6.9 EFFECTS ON NON-TARGET PLANTS (IIIA 10.8)...... 34 6.9.1 Terrestrial plants (IIIA 10.8.1) ...... 34 6.9.2 Effects on non-target aquatic plants (IIIA 10.8.2)...... 37 6.10 OTHER NON-TARGET SPECIES (FLORA AND FAUNA) (IIIA 10.9) ...... 38 6.11 SUMMARY AND EVALUATION OF POINTS 9 AND 10.1-10.10...... 39 6.11.1 Predicted distribution and fate in the environment and time courses involved (IIIA 10.11.1) ...... 39 Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date: 08. August 2012 Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 3 of 74

6.11.2 Non-target species at risk and extent of potential exposure (IIIA1 10.11.2)...... 39 6.11.3 Short and long term risks for non-target species, populations, communities and processes (IIIA 10.11.3) 39 6.11.4 Risk of fish kills and fatalities in large vertebrates or terrestrial predators (IIIA 10.11.4) ...... 39 6.11.5 Precautions necessary to avoid/minimise environmental contamination and to protect non-target species (IIIA 10.11.5)...... 39 APPENDIX 1 LIST OF DATA SUBMITTED IN SUPPORT OF THE EVALUATION...... 41 APPENDIX 2 DETAILED EVALUATION OF STUDIES RELIED UPON...... 43 A2-1 6-BENZYLADENINE ...... 43 A2-2 FORMULATION...... 43 IIIA 10.2 Effects on aquatic organisms...... 43 IIIA 10.4 Effects on Bees...... 53 IIIA 10.4.2 Acute toxicity of the formulation to bees ...... 53 IIIA 10.5 Effects on arthropods other than bees...... 56 IIIA 10.8 Effects on non-target plants...... 68 APPENDIX 3 TABLE OF INTENDED USES JUSTIFICATION AND GAP TABLES...... 73

Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date: 08. August 2012

Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 5 of 74

Sec 6 ECOTOXICOLOGICAL STUDIES

This document reviews the ecotoxicological studies for the product Exilis containing the active substance 6-benzyladenine, which was included into Annex I of Directive 91/414 3 January 2011, reference Commission Directive 2011/1/EU. Exilis was not the representative formulation considered in the EU review process as part of Annex I inclusion A full risk assessment according to Uniform Principles is provided which predicts acceptable environmental risks for the product if applied according to the proposed uses. Addenda are included containing country specific assessments for some annex points. In those cases this document should be read in conjunction with the relevant addenda. Where appropriate, this document refers to the conclusions of the EFSA, especially when data on the active substance is relied upon in the risk assessment of the formulation. Each section will begin with a table providing the EU endpoints used in this evaluation. Appendix 1 of this document contains the list of references included in this document in support of the evaluation. Appendix 2 of this document reports the detailed evaluation of studies relied upon. Appendix 3 of this document is the table of intended uses for Exilis.

Information on the detailed composition of Exilis can be found in the confidential dossier of this submission (Registration Report - Part C).

6.1 Proposed use patterns

Introduction This section of the submission summarises the ecotoxicological effects of the formulation Exilis and evaluates the potential risk to various representatives of terrestrial, aquatic and soil organisms. Full details or the proposed use pattern that will be assessed are shown in Appendix 2 of this document and summarized in the table below.

Table 6.1-1: Critical use pattern of Exilis

Crop Application Max. Number of Maximum Minimum Application method individual applications total application timing application application interval e.g. BBCH rate [kg rate [kg (days) a.s./ha] a.s./ha] Apples/Pears Spraying 0.075-0.150 1 0.075-0.150 not relevant Fruit between 7 and 15 mm (BBCH 71- 74)

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Table 6.1-2: Metabolites of 6-benzyladenine Parent compound Compound found in Maximal percentage of occurrence [% of applied, lab. studies] M8 soil Max. 9.9% at day 3 (day 14 < 2%)

Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date: 08. August 2012 Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 7 of 74

6.2 Effects on birds (IIIA1 10.2)

6.2.1 Overview and summary Effects on birds for Exilis were not evaluated as part of the EU review of 6-benzyladrin, but its active ingredient concentration and proposed use (1 x 150 g a.s. on apples and pears) are the same as for MaxCel which was the representative product.

The risk assessment for effects on birds and other terrestrial vertebrates is carried out according to the European Food Safety Authority Guidance Document on Risk Assessment for Birds and Mammals on request from EFSA (EFSA Journal 2009; 7(12): 1438).

6.2.1.1 Toxicity The endpoints employed in the risk assessment for birds are indicated in the following Table. Table 6.2-1: Summary of avian toxicity endpoints for 6-benzyladenine

Species Test substance Timescale Endpoint Reference ICS-No. (test type) Toxicity Author (mg/kg Bw) code Colinus virgianus 6-benzyladenin 1 d LD50 : 1599 mg EFSA --- akut a.s./kg bw Conclusion on Mortalität the Peer Review of 6- benzyladenine (EFSA Journal 2010; 8(9):1716) Colinus virgianus 6-benzyladenin 161 d, NOEC : 41,3 mg XXX 74121 chronic a.s./kg bw/d 27.02.2009 reproduction 529-118

An acute oral study with the formulated product has not been conducted. Consequently, the toxicity of Exilis has been assessed considering data generated on the individual active substance. 6.2.1.2 Exposure Exposure to standard generic focal species was estimated according to the “EC Guidance Document on Risk Assessment for Birds and Mammals Council EFSA/2009/1438”. Regarding the basic approach this EFSA-Guidance is in accordance with the previous “Guidance Document on Risk Assessment for Birds and Mammals“(EFSA 1438/2009):

PD × FIR DDD = ∑ i total × RUD × AR × PT bw i FIR = ∑ i × RUD × AR × PT i bw

DDD Daily dietary dose (mg/kg bw/day)

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PDi composition of diet obtained from treated area FIRi Food intake rate of indicator species i (g fresh weight/d) bw Bodyweight (g) RUD Residue per unit dose, bases on an application rate of 1 kg a.s./ha and assuming broadcast seedling AR Application rate (kg/ha) PT Proportion of diet obtained in the treated area (0…1)

In Tier 1 assessment, it is assumed that birds do not avoid contaminated food items, that they feed exclusively in the treated area and on a single food type. Factors AV, PT and PD are therefore equal to 1. The risk assessments were conducted in accordance with the new Guidance Document on Risk Assessment for Birds and Mammals on request from EFSA (EFSA, 1438/2009) and follow a stepwise approach. The screening step involves standard scenarios and default values for the exposure estimate, representing a “reasonable worst case”. If a potential risk is indicated in the screening step, then one or several refinement steps (Tier 1, Tier 2) follow. According to the new Guidance Document, no further assessment is required if all uses are safe in the screening step.

6.2.1.3 Overall conclusion The results of the acute and reproductive risk assessments are summarized in the following Table: Table 6.2-2: Minimum TERs for birds after uses of Exilis in pomme fruit.

Substance Risk assessment Indicator bird Timescale TER TER risk level assessment trigger 6- Screening small insectivorous bird Acute 228 10 benzyladenin Screening small insectivorous bird Long-term 29 5 TERs shown in bold fall below the relevant trigger.

Drinking water risk assessment Drinking water assessments are not required as the ratio of effective treatment rate to toxicological endpoint does not exceed the trigger.

Food chain behaviour An assessment of the risk from secondary poisoning is not required due to log POW values below the trigger.

6.2.2 Toxicity exposure ratios for birds (IIIA 10.2.1) 6.2.2.1 Acute toxicity exposure ratio (TERA) (IIIA1 10.2.1.1) Screening step

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Indicator species are used in the screening step. These are no real species but by size and feeding habits are considered to have higher exposure than other species occurring in a specific crop at a particular time, representing a worst case scenario. The indicator species for the intended uses are listed in the following Table:

Table 6.2-3: Avian indicator species for the use of 6-benzyladenine and shortcut values

Szenario Crop Indicator species Shortcut value (90th percentile RUD Fruit between 7 and 15 Orchards Small insectivorous bird 46.8 mm (BBCH 71-74)

The following equations were used:

Daily dietary dose:

DDDsingle application = application rate [kg/ha] × shortcut value* * see section 4.1 of EFSA/2009/1438

Toxicity exposure ratio (acute):

LD 50 (mg/kg bw/day) TER A = Acute DDD (mg/kg bw/day)

The resulting TERA values are summarised in the following Table:

Table 6.2-4: Acute screening risk assessment (TERA) for birds from 6-benzyladenine uses

Substance Indicator bird App. rate Shortcut MAF DDD LD50 TERA (kg/ha) value (mg/kg bw) (mg/kg bw) (acute) 6- Small 0.150 46.8 - 7.02 1599 228 benzyladenin insectivorous bird e TERs shown in bold fall below the relevant trigger.

Based on the highly conservative presumptions of the screening step, the acute risk of exposure of birds to the active ingredient 6-benzyladenine according to the GAP of the formulation Exilis achieves the acceptability criteria TER ≥ 10, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for acute effects /, further refinement is necessary.

6.2.2.2 Short-term toxicity exposure ratios (TERST) (IIIA1 10.1.2)

There is no requirement for the calculation of TERST for birds under the EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) and, consequently, a risk assessment for short- term toxicity has not been conducted.

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6.2.2.3 Long-term toxicity exposure ratio (TERLT) (IIIA1 10.1.3) Screening step

For the reproductive risk assessment, the calculation of the long-term toxicity exposure ratio (TERLT) in principle follows the same procedure as for the acute risk assessment. However, the defined daily dose is obtained by multiplying the application rate with the mean short-cut values (based on mean RUD according to the new Guidance Document (EFSA, 2009)) as summarized in the following Table:

Scenario Crop Indicator Species Shortcut value (mean RUD) Fruit between 7 and 15 Orchards Small insectivorous bird 18.2 mm (BBCH 71-74)

In accordance with the guidance document, it is justified to apply a time-weighted average (TWA) factor of 0.53 based on the default observation interval of 21 days and a default DT50 of 10 days for the calculation of the DDD (daily dietary dose):

DDDsingle application = application rate [kg/ha] × shortcut value × TWA* * see section 4.3 of EFSA/2009/1438

Toxicity exposure ratio (long-term): NOEL ( mg/kg bw/day) TER = LT Long - term DDD (mg/kg bw/day)

Long-term toxicity exposure ratios (TERLT) for 6-benzyladenine following applications of Exilis were calculated and results are summarised in the following Table.

Table 6.2-5: Long-term screening risk assessment (TERLT) for birds from 6-benzyladenine uses

a Substance Indicator App. rate Shortcut fTWA MAF DDD NOEC TERLT bird (kg/ha) value (mg/kg (mg/kg (long-term) bw/day) bw/day) 6- Small 0.150 18.2 0.53 - 1.45 41.3 28.5 benzyladenin insectivorous e bird TERs shown in bold fall below the relevant trigger.

Based on the highly conservative presumptions of the screening step, the long term risk of exposure of birds to 6-benzyladenine at the submitted GAP of the formulation Exilis achieves the acceptability criteria TER ≥ 5, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for long term effects. Therefore, refinements are (not) necessary.

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6.2.3 Drinking water exposure In case of early post-emergence uses as intend for 6-benzyladenine birds might be exposed via drinking water from puddles. According to the new Guidance Document (EFSA, 2009), no specific calculations of drinking water exposure and TER are necessary when the ratio of effective application rate (in g/ha) to the relevant endpoint (in mg/kg bw/d) does not exceed 50 in the case of less sorptive substances (Koc < 500 L/kg) or 3000 in the case of more sorptive substances (Koc ≥ 500 L/kg). This is due to the characteristics of the exposure scenario in connection with the standard assumptions for water uptake by birds (for further details please refer to chapter 5.5. of the Guidance Document). The puddle scenario has been taken into account to calculate the exposure concentration of 6- benzyladenine formed on a field after rainfall. The ratios do not exceed the value of 3000 (Koc = 896 L/kg), thus it is not necessary to conduct a drinking water risk assessment for birds.

6.2.4 Details on formulation type in proportion per item 6.2.4.1 Baits: Concentration of active substance in bait in mg/kg (IIIA1 10.1.3) Exilis is not formulated as bait. 6.2.4.2 Pellets, granules, prills or treated seed (IIIA1 10.1.4) Exilis.is not formulated as pellets, granules, prills or treated seeds. 6.2.4.3 Amount of active substance in or on each item (IIIA1 10.1.4) Not applicable. 6.2.4.4 Proportion of active substance LD50 per 100 items and per gram of items (IIIA1 10.1.4.2) Not applicable. 6.2.4.5 Size and shape of pellet, granule or prill (IIIA1 10.1.5) Not applicable.

6.2.5 Effects of secondary poisoning (IIIA1 10.1.9) The EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) states that a log Kow ≥3 is used to indicate that there might be a potential for bioaccumulation (see Section 5.6 Bioaccumulation and food chain behaviour). The log Kow of 6-benzyladenine is 2.16, so this active substances has a (negligible) potential to bioaccumulate in animal tissues. No formal risk assessment from secondary poisoning is therefore required.

6.3 Effects on Terrestrial Vertebrates Other Than Birds (IIIA1 10.3)

6.3.1 Overview and summary The risk assessment for effects on mammals is carried out according to the European Food Safety Authority Guidance Document on Risk Assessment for Birds and Mammals on request from EFSA (EFSA Journal 2009; 7(12): 1438). 6.3.1.1 Toxicity The endpoints employed in the risk assessment for mammals are indicated in the following Tables: Table 6.3-1: Toxicity of 6-benzyladenine to mammals

Species Test substance Timescale Endpoint Reference ICS- (test type) Toxicity Author No.

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(mg/kg Bw) code

rat 6-benzyladenine Acute, oral LD50 : 1584 mg a.s./kg EFSA --- bw Conclusion on the Peer Review of 6- benzyladenine (EFSA Journal 2010; 8(9):1716)

rat Exilis Acute LD50 > 2000 mg XXX 77681 product/kg bw 18.06.2007 07/394-001P rat 6-benzyladenine Long term NOAEL : 400 mg a.s./kg XXX 77963 feed = 30 mg a.s./kg bw/d 18.08.2003 492942

6.3.1.2 Exposure Exposure to standard generic indicator species was estimated according to the ‘EC Guidance Document on Risk Assessment for Birds and Mammals Council (EFSA/2009/1438) (see chapter 6.2.1.2 for detailed information of calculation of TER and mixture toxicity).

6.3.1.3 Overall conclusion

The resulting TERvalues are represented in the following table: The results of the acute and reproductive risk assessments are summarized in the following Table: Table 6.3-2: Minimum TERs for terrestrial vertebrates after uses of Exilis in orchards

Substance Risk assessment Indicator mammal Timescale TER TER risk level assessment trigger 6- Screening Small herbivorous mammal Acute 77.4 10 benzyladenine Screening Small herbivorous mammal Long-term 5.2 5 TERs shown in bold fall below the relevant trigger.

Drinking water risk assessment Drinking water assessments are not required as the ratio of effective treatment rate to toxicological endpoint does not exceed the trigger.

Food chain behaviour An assessment of the risk from secondary poisoning is not required due to log POW values below the trigger.

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6.3.2 Toxicity exposure ratios (IIIA1 10.3.1) 6.3.2.1 Acute toxicity exposure ratio (TERA) (IIIA1 10.3.1.1) Screening step Indicator species are used in the screening step. These are no real species but by size and feeding habits are considered to have higher exposure than other species occurring in a specific crop at a particular time. The indicator species for the intended uses are listed in the following Table:

Table 6.3-3: Terrestrial vertebrates indicator species for the use of 6-benzyladenine and shortcut values

Scenario Crop Indicator species Shortcut value (90th percentile RUD) Fruit between 7 and 15 Orchards Small herbivorous 136.4 mm (BBCH 71-74) mammal

The following equations were used: Daily dietary dose:

DDDsingle application = application rate [kg/ha] × shortcut value* * see section 4.1 of EFSA/2009/1438 Toxicity exposure ratio (acute):

LD50 (mg/kg bw/day) TER A = Acute DDD (mg/kg bw/day)

The resulting TERA values are summarised in the following Table:

Table 6.3-4: Acute screening risk assessment (TERA) for terrestrial vertebrates from 6- benzyladenine uses

Substance Indicator App. rate Shortcut MAF DDD LD50 TERA mammal (kg/ha) value (mg/kg bw) (mg/kg bw) (acute) 6- Small 1 x 0.150 136.4 - 20.46 1584 77.4 benzyladenin herbivorous e mammal TERs shown in bold fall below the relevant trigger.

Based on the highly conservative presumptions of the screening step, the acute risk of exposure of terrestrial vertebrates to the active ingredient 6-benzyladenine according to the GAP of the formulation Exilis achieves the acceptability criteria TER ≥ 10, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for acute effects no further refinement is necessary.

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6.3.2.2 Short-term toxicity exposure ratio (TERST) (IIIA1 10.3.1.2)

There is no requirement for the calculation of TERST for mammals under the EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) and, consequently, a risk assessment for short-term toxicity has not been conducted. 6.3.2.3 Long-term toxicity exposure ratio (TERLT) (IIIA1 10.3.1.3) Screening step

For the reproductive risk assessment, the calculation of the long-term toxicity exposure ratio (TERLT) in principle follows the same procedure as for the acute risk assessment. However, the defined daily dietary dose is obtained by multiplying the application rate with the mean short-cut value (based on the mean RUD according to the new Guidance Document (EFSA, 2009)) as summarized in the following Table:

Szenario Crop Indicator species Shortcut value (90th percentile RUD Fruit between 7 and 15 Orchards Small herbivorous 72.3 mm (BBCH 71-74) mammal

The following equations were used: Daily dietary dose: * DDDsingle application = application rate [kg/ha] × shortcut value* × TWA * see section 4.1 of EFSA/2009/1438 Toxicity exposure ratio (acute): NOEL(mg/kg bw/day) TER = LT Long - term DDD (mg/kg bw/day)

The resulting TERLT values for 6-benzyladenine are summarised in the following Table:

Table 6.3-5: Long-term risk assessment (TERLT) for mammals from 6-benzyladenine uses

Substance Indicator App. rate Shortcut fTWA MAF DDD NOEC TERLT mammal (kg/ha) value (mg/kg (mg/kg (long-term) bw/day) bw/day) 6- Small 1 x 0.150 72.3 0.53 - 5.75 30 5.2 benzyladeni herbivorous ne mammal N/A not applicable. TERs shown in bold fall below the relevant trigger.

Based on the highly conservative presumptions of the screening step, the long-term risk of exposure of mammals to 6-benzyladenine when applied according to the GAP achieves the acceptability criteria TER ≥ 5, according to directive 1107/2009 (EG), Annex IV, uniform principles, point 2.5.2.1 for long term effects. Therefore, refinements are not necessary.

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6.3.3 Drinking water exposure In case of early post-emergence uses as intended for 6-benzyladenine mammals might be exposed via drinking water from puddles. According to the new Guidance Document (EFSA, 2009), no specific calculations of drinking water exposure and TER are necessary when the ratio of effective application rate (in g/ha) to the relevant endpoint (in mg/kg bw/d) does not exceed 50 in the case of less sorptive substances (Koc < 500 L/kg) or 3000 in the case of more sorptive substances (Koc ≥ 500 L/kg). This is due to the characteristics of the exposure scenario in connection with the standard assumptions for water uptake by mammals (for further details please refer to chapter 5.5. of the Guidance Document). The puddle scenario has been taken into account to calculate the exposure concentration of 6- benzyladenine formed on a field after rainfall. The ratios do not exceed the value of 50 for 6- benzyladenine (Koc = 896 L/kg), thus it is not necessary to conduct a drinking water risk assessment for mammals.

6.3.4 Details on formulation type in proportion per item (IIIA 10.3.2) 6.3.4.1 Acute oral toxicity of the preparation (IIIA 10.3.2.1) The first screening step with the acute toxicity endpoint of the product Exilis does not achieve (TER of 1.96) the acceptability criteria (TER ≥ 10). But taking the highly conservative presumptions of the screening step and the fact that the LD50 of > 2000 mg product/kg bw is in fact a NOEC into consideration, it is acceptable to base the risk assessment on the endpoint with the active substance 6- benzyladenine. 6.3.4.2 Acceptance of bait, granules or treated seeds by terrestrial vertebrates (palatibility test (IIIA1 10.3.2.2) Exilis is not formulated as a bait.

6.3.5 Effects of secondary poisoning (IIIA1 10.3.2.3) The EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) states that a log Kow ≥3 is used to indicate that there might be a potential for bioaccumulation (see Section 5.6 Bioaccumulation and food chain behaviour). The log Kow of 6-benzyladenine is 2.16, so this active substances has a (negligible) potential to bioaccumulate in animal tissues.

6.3.6 Supervised cage or field trials (IIIA 10.3.3) Supervised cage/field trials with the formulation were not performed, since low risk to mammals indicates that further studies are not required.

6.4 Effects on Aquatic Organisms (IIIA1 10.2)

6.4.1 Overview and summary Effects on aquatic organisms for Exilis were not evaluated as part of the EU review of 6- benzyladenine. Data on Exilis is evaluated here, and risk assessments for 6-benzyladenine with the proposed use pattern are provided here.

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6.4.1.1 Toxicity The endpoints employed in the risk assessment for aquatic organisms are indicated in the following Tables. Table 6.4-1: Ecotoxicological endpoints of 6-benzyladenine to aquatic species

Species Test substance Timescale Endpoint Reference ICS-No. (test type) Toxicity Author (mg/L) code Fish, acute toxicity

Brachydanio rerio 6-Benzyladenin 4 d LC50 = 42 mg XXX 77606 semistatic a.s./L 20.11.2000 V2365/01

Oncorhynchus Exilis 2% SL 4 d, static LC50 > 100 mg XXX 77680 mykiss formulation preparation /L 20.06.2007 (> 2.03 mg 07/394-023DA a.s./L) Fish, long-term toxicity --- Invertebrates, acute toxicity

Daphnia magna 6-Benzyladenin 2 d EC50 = 28 mg Hooftman R.N., 77605 statisch a.s./L Borst B., Akdenir A. 20.11.2000 V2365/02

Daphnia magna Exilis 2% 2 d EC50 > 100 mg Hernadi, D. 77679 Formulation statisch preparation/L 20.06.2007 nom. 07/394-023DA (> 2.03 mg a.s./L) Invertebrates, long-term toxicity Daphnia magna 6-Benzyladenin 21 d, semistatic NOEC : 4 mg Gallagher S. et 74286 a.s./L al. EC50 (Reprod.): 03.12..2008 6,8 mg a.s./L 529A-107 Sediment dwelling organisms C. riparius 6-Benzyladerin 28 d, static, NOEC : 4.52 Burke, J. 74123 application to the mg a.s./L real 03.08.2007 water phase ZAB0073/07290 7 Algae

Pseudokirchneriella 6- 3 d, static EbC50: 36 mg/L Mayer P., 77604 subcapitata Benzyladerin ErC50: 45.1 Oldersma H., mg/Lnom. Hanstveit A.O. NOEC:1 mg/L 20.11.2000 nom. V2365/03

Navicula pelliculosa 6- 3 d, static EbC50: 7.6 mg Sindermann, A.B. 74122 Benzyladerin a.s./L nom. et al. ErC50: 15 mg 13.03.2008 a.s./L nom. 529A-106

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Species Test substance Timescale Endpoint Reference ICS-No. (test type) Toxicity Author (mg/L) code

Pseudokirchneriella Exilis 2% 3 d, static EbC50/ ErC50: > Hernadi, D. 77616 subcapitata Formulation 100 mg product 04.02.2008 /L 07/394-022ALR (> 2.03 mg a.s./L) nom. NOEC: 100 mg product /L (2.03 mg a.s./L nom.)

Navicula pelliculosa Exilis 2% 3 d, static EyC50: 367 mg Vryenhoef, H, 77617 Formulation product/L Mullee, D.M. (7.6 mg a.s./L 18.02.2011 nom) 41004731 ErC50: 820 mg product/L (17 mg a.s./L nom.) NOEC: 155 mg product/L (3.2 mg a.s./L nom.) Aquatic higher plants

Lemna gibba 6-Benzyladenin 7 d, static EC50 = 0.31 mg EFSA - a.s./L nom Conclusion on the Peer Review of 6- benzyladenine (EFSA Journal 2010; 8(9):1716)

Lemna gibba Exilis 2% 7 d, static EyC50: 29.62 Agh, I. 77618 Formulation mg product/L 27.11.2009 nom. 09/078-029BL (0.6 mg as/L)

NOEC: 0.5 mg product/L nom. (0,01 mg as/L) Mesocosm study --- 1) indicate with bold letters if endpoint deviates from EU agreed endpoint or represents new data e.g. study with new formulation 2) indicate whether based on nominal (nom = analytically confirmed), mean measured (mm) or time- weighted concentrations (twa). In the case of preparations indicate whether endpoints are presented as units of preparation or as. No indication means effects related to compound indicated in column ”Test substance”.

For the active ingredient the most sensitive endpoint divided by the safety factor is EC50 = 0.31 mg/L (Lemna gibba).

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Exilis was not the representative formulation during the EU Review of 6-benzyladenine, but its active ingredient concentration and proposed use (1 x 150 g a.s. on apples and pears) are within what was considered for Annex I inclusion of 6-benzyladenine. However, the EFSA Conclusion (EFSA Journal 2010; 8(9):1716) states that the risk assessment for aquatic organisms could not be finalised. This was driven by the formulated product MaxCel being significantly more toxic than expected based on the content of the active substance. The toxicity data which are available for Exilis show that Exilis is less toxic for aquatic organism compared to 6-benzyladenine (see Table 6.4-2).

Therefore the risk assessment is done only for this endpoint. 6.4.1.2 Exposure Following the dilution and spraying of the formulated product, much of the formulation constituents are likely to be lost by volatilisation. Therefore, shortly after application of a formulated product, aquatic organisms are mainly exposed to the single active substances present in the formulation. An evaluation of the risk posed by the intact formulation is therefore relevant only for the acute assessment. The long-term risk will be assessed considering data for the active substances in the formulation. 6-benzyladenine forms one major metabolites in soil: M8 (9.9 % at day 3). Contamination via run-off and drainage cannot be excluded. There are no toxicological studies for the metabolite M8 available. The metabolite reaches his maximum at day 3 after the application. Therefore the ZRMS considers the risk from the Metabolite M8 covered with the studies from the parent compound 6-benzyladenine. The risk posed by this metabolite to aquatic organisms is addressed. Calculations of PECsw and PECsed were performed with Focus surface water. For details see CA Part B, Section 5.7

Table 6.4-2: Summary of highest global maximum FOCUS surface water PECsw and PECsed values

Plant protection product: Exilis Use No evaluated 00-001 and 00-002 Crop Pome, stone fruit, late application Application method (-) Spray Growth stage at first application 71 (BBCH) Application time 13.06. – 06.07. Crop interception: 70% Number of applications/intervall 1 Application rate: 150 g a.s./ha Active Substance 6-benzyladenine

FOCUS STEP 2 PECSW (µg/L) PECSED (µg/kg) Scenario Actual, 0 h TWA, 21 d Actual, 0 h Northern Europe, Mar.-May 7.86 2.30 24.64 Southern Europe, Mar.-May 7.86 2.42 26.65

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6.4.1.3 Overall conclusions

TERs based on the PECSW provided in Table 6.4-2 are summarised in the following Table.

Table 6.4-3: Aquatic higher plant TER values for Lemna gibba after applications of 6- benzyladenine/Exilis. Scenario Critical Drift reducing PECSW (µg/L) TERact TER risk endpoint nozzles assessment (µg/L) trigger Northern Europe 310 - 7.86 39.44 10 Southern Europe 310 - 7.86 39.44 10

6.4.2 Toxicity exposure ratios (IIIA1 10.2.1) The risk assessment for 6-benzyladenine and his metabolites was carried out following application according to the proposed uses. The initial risk assessments were carried out by comparing the initial maximum PECSW values with the acute and long-term toxicity endpoints. Based on all aquatic studies as well as the corresponding safety factors the relevant Endpoint for the active ingredient 6- benzyladenine is EC50 = 0.31 mg/L (Lemna gibba). Risk assessment is done only for this organism because the endpoints/by the corresponding safety factor for the other organisms are higher.

6.4.2.1 TERA for fish (IIIA1 10.2.1) See above point 6.4.2.

6.4.2.2 TERLT for fish (IIIA1 10.2.1.1)

The active substance, 6-benzyladenine, degrades rapidly in water (DT50 of 2.4 – 4.1 days). Moreover, it should be used with only one application per year. Therefore, continued or repeated exposure to the active substance is unlikely. Thus, in line with the conclusions drawn in the EU Review of 6- benyladenine, a chronic fish toxicity study is not required and calculations of TERLT are not relevant.

6.4.2.3 TERA for Daphnia (IIIA1 10.2.1.2) See above point 6.4.2.

6.4.2.4 TERLT for Daphnia (IIIA1 10.2.1.3) See above point 6.4.2.

6.4.2.5 TERA for aquatic insect (IIIA1 10.2.1.5) See above point 6.4.2.

6.4.2.6 TERLT for aquatic insect (IIIA1 10.2.1.6) See above point 6.4.2.

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6.4.2.7 TERA for aquatic crustacean (IIIA1 10.2.1.7) See above point 6.4.2.

6.4.2.8 TERLT for aquatic crustacean (IIIA1 10.2.1.8) See above point 6.4.2.

6.4.2.9 TERA for aquatic gastropod mollusc (IIIA1 10.2.1.9) See above point 6.4.2.

6.4.2.10 TERLT for aquatic gastropod mollusc (IIIA1 10.2.1.10) See above point 6.4.2.

6.4.2.11 TERLT for algae (IIIA1 10.2.1.11) See above point 6.4.2.

6.4.2.12 TERLT for aquatic higher plant (IIIA1 10.8.2.1) The long-term risk assessment for aquatic higher plant is summarised in the following table, considering the lowest relevant endpoints and the maximum PECSW.

Table 6.4-4: Aquatic higher plant TER values for Lemna gibba after applications of 6- benzyladenine.

Scenario Critical Drift reducing PECSW (µg/L) TERact TER risk endpoint nozzles assessment (µg/L) trigger Northern Europe 310 - 7.86 39.44 10 Southern Europe 310 - 7.86 39.44 10

The TERLT values are greater than the Annex VI trigger value of 10. This indicates that the active substances 6-benzyladenine contained in Exilis pose low long-term risk to aquatic organisms at the proposed application rates.

6.4.3 Risk from metabolites Metabolite M8 6-benzyladenine forms one major metabolite in soil: M8 (9.9 % at day 3). Contamination via run-off and drainage cannot be excluded. There are no toxicological studies for the metabolite M8 available. The metabolite reaches his maximum at day 3 after the application. Therefore the ZRMS considers the risk from the Metabolite M8 covered with the studies from the parent compound 6-benzyladenine. The risk posed by this metabolite to aquatic organisms is addressed..

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6.4.4 Acute toxicity of the formulation (IIIA1 10.2.2) 6.4.4.1 Fish (IIIA1 10.2.2.1) Please refer to appendix 2 of this document.

6.4.4.2 Aquatic invertebrates (Daphnia) (IIIA1 10.2.2.2) Please refer to appendix 2 of this document..

6.4.4.3 Algae (IIIA1 10.2.2.3) Please refer to appendix 2 of this document.

6.4.4.4 Marine or estuarine organisms (IIIA1 10.2.2.4) No studies are submitted as this is not an EC data requirement.

6.4.4.5 Marine sediment invertebrates (IIIA1 10.2.2.5) No studies are submitted as this is not an EC data requirement.

6.4.4.6 Microcosm or mesocosm study (IIIA1 10.2.3)

Since all TERA and TERLT values exceed their respective Annex VI triggers, microcosm and/or mesocosm studies are not required.

6.4.4.7 Residue data in fish (IIIA1 10.2.4)

The log Kow of 6-benzyladenine is 2.1, so this active substance has a negligible potential to bioaccumulate in animal tissues. Data to evaluate the residues of 6-benzyladenine in fish have therefore not been generated.

6.4.5 Chronic toxicity to fish (IIIA1 10.2.5) Chronic toxicity tests with the formulated product were considered to be unnecessary since there is no evidence from the existing acute data for non-target organisms to suggest that the chronic toxicity of the formulated product cannot be assessed on the basis of the active substance contents alone.

6.4.6 Chronic toxicity to aquatic invertebrates (IIIA1 10.2.6) Chronic toxicity tests with the formulated product were considered to be unnecessary since there is no evidence from the existing acute data for non-target organisms that the chronic toxicity of the formulated product cannot be assessed on the basis of the active substance contents alone.

6.4.7 Accumulation in aquatic non-target organisms (IIIA1 10.2.7) Bioaccumulation of the active substance under natural conditions is not expected to occur and a study is not necessary to determine bioaccumulation in aquatic non-target organisms.

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6.5 Effects on Bees (IIIA 10.4)

6.5.1 Overview and Summary

The proposed use of Exilis in orchards fits within the risk envelope of the uses that were assessed for MaxCel under the EU Review of 6-benzyladenine as shown in Table 10.4-1. The EU risk assessment for bees was conducted in line with SANCO/10329/2002, based on an application rate of 150 g a.s./ha and the acute oral and contact LD50 values for both the active substance and the formulated product MaxCel. The resulting Hazard Quotients (HQs) were substantially below the trigger of 50, thereby indicating an acceptable risk. Therefore the risk to bees from technical 6-benzlyadenine is covered by the EU assessment and no further assessment is required. Furthermore as Exilis is less toxic than MaxCel (48 h acute and contact LD50 > 7.3 µg as/bee), the risk to bees from exposure to the formulated product is also covered by the EU assessment and no further consideration is required. However, for completeness a hazard quotient based risk assessment has been presented for Exilis.

6.5.2 Toxicity

The following table presents the results of bee toxicity studies. Further details regarding the test with the formulation are provided in section.

Table 6.5-1: Results of laboratory bee toxicity studies

Test substance Exposure LD50 Reference route 13410.4 µg product/bee oral 48 h Sipos, K. (2007); (260.8 µg as/bee) Exilis 07/394-116MT 3549.0 µg product/bee contact 48 h IIIA 10.4.2.1/01 (69.0 µg as/bee) oral 48 h > 58.7 µg/bee * EFSA Conclusion on the Peer Review of 6- 6-benzyladenine contact 48 h > 100 µg/bee * benzyladenine (EFSA Journal 2010; 8(9):1716)

* EU agreed endpoint

6.5.3 Exposure

Bees may be exposed by direct spraying while bees are foraging on flowers and weeds, through contact with fresh or dried residues or by oral uptake of contaminated pollen, nectar and honey dew.

The recommended use pattern for Exilis includes application in orchards at a maximum application rate of up to 3.75 L/ha per meter crown height, resulting in 7.5 L/ha

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(corresponding to 150 g as/ha) taking into account a mean crown height of 2 meter. This maximum single application rate is equivalent to 7500 g product/ha.

6.5.4 Hazard quotients

Hazard quotients for oral and contact exposure according to EPPO (2003) Environmental risk assessment scheme for plant protection products (Chapter 10: Honeybees (PP 3/10(2)). Bulletin OEPP/EPPO Bulletin 33: 141-145) were calculated as follows:

Hazard Quotient = max. application rate [g product/ha] / LD50 [µg product/bee]

Table 6.5-2: Hazard quotients for honeybees

Max. single Hazard HQ Exposure LD Test substance 50 application quotient assessment route rate (HQ) trigger oral 13410.4 µg product/bee 7500 g < 1 50 Exilis contact 3549.0 µg product/bee product/ha < 3 50

6.5.5 Risk assessment

Due to the results of laboratory tests Exilis is considered to be practically non-toxic to bees. All hazard quotients are clearly below the trigger of 50, indicating that the intended use of Exilis poses a low risk to bees in the field. Bee brood testing is not required since Exilis is not an IGR.

6.5.6 Overall conclusion: It is concluded that Exilis (20 g/L 6-Benzyladenin) will not adversely affect bees or bee colonies when used as recommended. No special labelling is necessary.

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6.6 Effects on Arthropods Other Than Bees (IIIA 10.5)

6.6.1 Overview and summary Effects on arthropods other than bees for Exilis were not evaluated as part of the EU review of 6- benzyladenin Data on Exilis is evaluated here, and risk assessments for non target arthropods with the proposed use pattern are provided here and are considered adequate. The critical endpoints employed in the risk assessment for non-target arthropods are indicated in the table below.

6.6.1.1 Toxicity Table 6.6-1: Toxicity of Exilis to arthropods other than bees

Species Test substance Timescale Endpoint Reference ICS- (test type) Toxicity Author No. (g/ha) code

Typhlodromus pyri Exilis 2% SL glass plate, LR50 > 7.5 L/ha Sipos, K. 77686 Formulation 7 d (> 152.25 g a.s./ha) 21.08.2007 07/394-335RA Aphidius rhopalosiphi Exilis 2% SL Glass LR50 (ER50, Reprod.) Kimmel, S. 77684 Formulation plate, 2 d > 76.8 kg/ha 27.04.2011 (13 d) (> 1536 g a.s./ha) D25464 Orius laevigatus Exilis 2% SL 2D, leaves LR50 = 2.2 L/ha Kimmel, S. 77683 Formulation 10 d (44.5 g a.s./ha) 27.04.2011 D13180 Orius laevigatus Exilis 2% SL 2D, leaves ER50 / LR50 > 7.5 L/ha Vinall, S. 77685 Formulation (aged (> 150 g a.s./ha) 01.11.2011 residue FIN-11-1 test)

6.6.1.2 Exposure In field Non-target arthropods inhabiting the crop can be exposed to residues from 6-benzyladenine by direct exposure or through contact with residues on plants and soil or in food items. According to the GAP, Exilis is intended to be applied only once per year with a maximum application rate of 7.5 L product/ha, corresponding to 150 g a.s./ha for all uses. As a worst-case assumption, the maximum in- field exposure (Predicted Environmental Rate, PER) to arthropods is therefore 7.5 L formulation/ha, assuming 0% crop interception. The in-field exposure (predicted environmental rate, PER) is calculated according to ESCORT 2 using the following equation:

PER = Application rate (g a.s./ha)×MAF in−field

Where:

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MAF is a generic multiple application factor, which is used to take into account the potential build-up of applied substances between applications based on the application interval, DT50 value and number of applications. Default foliar and soil MAF values following multiple applications are given in the ESCORT 2 Guidance Document.

Since Exilis is applied only once a season, the multiple application factor MAF, can be omitted. The maximum predicted environmental rate (PER) occurring within the field after application of Exilis at the maximum application rate are presented in Table the following table:

Table 6.6-2: In-field foliar Predicted environmental rates (PER)

Substance Application rate PER (foliar) PER (soil) 6-benzyladenine 150 g a.s./ha 150 g a.s./ha 150 g a.s./ha

Off-field The risk assessment for areas immediately surrounding the crop is considered important since these areas represent a natural reservoir for immigration, emigration and reproduction of arthropod populations and provide increased species diversity. Exposure of non-target arthropods living in off- field areas to 6-benzyladenine will mainly be due to spray drift from field applications. Off-field PER values were calculated from in-field PERs in conjunction with drift values published by the BBA (2000) as shown in the following equation:

Maximum -in field PER x (% drift/100) Off - field foliar PER = vegetation distribution factor

Vegetation distribution factor: The model used to estimate spray drift was developed for drift onto a two-dimensional water surface and, as such, does not account for interception and dilution by three- dimensional vegetation in off-crop areas. Therefore, a vegetation distribution or dilution factor is incorporated into the equation when calculating PERs to be used in conjunction with toxicity endpoints derived from two-dimensional (glass plate or leaf disc) studies. A dilution factor of 10 is recommended by ESCORT 2. For 3-dimensional studies, i.e. where spray treatment is applied onto whole plants, the dilution factor of 10 is not used, as any dilution over the 3-dimensional vegetation surface is accounted for in the study design. The ZRMS prefers a Vdf of 5 for 2-demensional studies, based on experimental data (See although national addenda). A vegetation distribution factor was applied for the assessment for all endpoints accounting for the 2- dimensional structure treated in the tests on these species

The resulting PERoff-field value is shown in the following Table:

Table 6.6-3: Off-field foliar Predicted environmental rates (PER)

Study type Maximum in-field Drift factor Vegetation Off-field PER PER (g a.s./ha)/(L (%dirft / 100) distribution factor (g a.s./ha)/ )/(L product/ha) product/ha) 3-dimensional 150/7.5 0.1573 1 236/1.18

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2-dimensional 150/7.5 0.1573 10 23.6/0.12

6.6.1.3 Overall Conclusion The risk assessment is considered below. HQs resulting from the risk envelope are summarized in the following table: Table 6.6-4: Maximum HQ values for arthropod species other than bees after uses of Exilis in pomme fruit Substance Study type Indicator species Scenario HQ HQ risk assessment trigger 6- glass plate, 7 d Typhlodromus pyri In-field 1 2 benzyladenin glass plate, 7 d Typhlodromus pyri Off-field 0.16 2 e 2D, leaves Orius laevigatus Off-field 0.27 10 d HQs shown in bold are above the relevant trigger.

6.6.2 Risk Assessment for Arthropods other than Bees 6.6.2.1 In-field The potential risk of 6-benzyladenine to in-field non-target arthropods was assessed by calculation of the hazard quotient (HQ = exposure/toxicity) with the predicted environmental rate (PER) and the lowest lethal rate (LR50) values according to the formula:

-In field PER In field HQ = LR 50

The resulting HQin-field values for the standard species are presented in the following table. The HQ trigger is 2.

Table 6.6-5: Tier 1 in-field HQs for non-target arthropods

Species ER50 [mL PER [mL In-field HQ Trigger value product/ha] product/ha]

Typhlodromus pyri LR50 > 7.5 L/ha 7.5 1 2 (> 152.25 g a.s./ha) Aphidius LR50 (ER50, 7.5 0.1 2 rhopalosiphi Reprod.) > 76.8 kg/ha (> 1536 g a.s./ha)

Orius laevigatus LR50 = 2.2 L/ha 7.5 3.4 (44.5 g a.s./ha)

The in-field HQ values for exposure to maximum residues for the representative species Typhlodromus pyri and Aphidius rhopalosiphi are less than the ESCORT 2 trigger value of 2. Thus,

Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date: 08. August 2012 Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 27 of 74 the results indicate that Exilis poses low risk to in-field non-target arthropods following application according to the proposed use patterns.

Additional species Data on one additional species Orius laevigatus have been presented by the Notifier. An extended laboratory test was conducted in which the predatory bug Orius laevigatus was exposed to bean leaf discs treated with Exilis up to 2.5 L product/ha (equivalent to 50 g a.s./ha). There was ≤ 50% lethal effects at up to 1.25 L product/ha (equivalent to 25 g a.s./ha). Effects on reproduction were only assessed at the two lowest rates, of 0.156 and 0.312 L product/ha (equivalent to 3.125 and 6.25 g a.s./ha), where there was only 2% and 10% reduction in the number of fertile eggs compared to the control, respectively.

The 50% effects on survival at an exposure level of 44.5 g a.s./ha (LR50), which is 3 times less than the in-field exposure level from the proposed use of Exilis (i.e. 150 g a.s./ha), indicates a potential concern for Orius following the proposed use of Exilis to apples and pears. The very rapid dissipation of the active substance 6-benzyladenine on foliage, along with the single application of Exilis in orchards, will facilitate the recovery and recolonisation of in-field non-target arthropod populations well within one year in apples and pears (the proposed ESCORT 2 in–field trigger). Indeed, analysis of radioactive residues in apple leaves treated with [14C]6-BA showed 86.8 and 99.7% decline after 7 and 90 DAT, respectively (see Table 7.4 in Section B.7.1.1 of the Additional Report, 2009). Therefore, if adverse effects on Orius laevigatus were to occur, these effects would be short-lived and rapid recolonisation and recovery would take place.

To support the risk assessment for Orius laevigatus, the most sensitive of the three non-target organisms, a higher tier extended laboratory study was conducted. In this study, whole bean plants were sprayed with Exilis, instead of spraying bean leaf discs. This is a more realistic exposure scenario. Bean plants were treated with Exilis at rates of 7500 and 1200 mL/ha, corresponding to 150 and 24 g a.s./ha, respectively. The bugs were then exposed to leaf discs with freshly-dried residues (DAT 0) taken from the treated plants. The corrected mortality was less than 50% (11% for the high treatment rate and 13% for the low treatment rate) and the reproduction assay showed no significant reduction of reproduction (2.3% for the high treatment rate and -25.6% for the low treatment rate).

Therefore, although a possible in-field risk for Orius laevigatus is indicated based on the extended laboratory test, the higher tier test with a realistic application and exposure scenario shows that the in- field risk for Orius laevigatus is acceptable when Exilis is applied at an application rate of 150 g a.s./ha. 6.6.2.2 Off field In order to assess the potential risk of Exilis to off-field non-target arthropods, the predicted environmental rate is compared with the toxicity endpoints according to the following formula and the result is compared to the trigger of 2:

PER (g/ha) Off - field HQ = off −field × Correction factor LR (g/ha) 50 Correction factor: ESCORT 2 recommends that a correction factor of 5 be used when assessing Tier II data or 10 for Tier I data, to account for extrapolation from testing just 2 representative species, to the species diversity expected in off-crop areas.

HQoff-field values are given in the following Table:

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Table 6.6-6: Tier 1 off-field HQs for non-target arthropods

Species ER50 [mL Test type / Off-field PER Correction Off-field HQ Trigger value product/ha] treatment [mL factor scheme product/ha]

Typhlodromus LR50 > 7.5 glass plate, 7 d 0.12 10 0.16 2 pyri L/ha (> 152.25 g a.s./ha)

Aphidius LR50 (ER50, glass plate, 2 d 0.12 10 0.016 2 rhopalosiphi Reprod.) > (13 d) 76.8 kg/ha (> 1536 g a.s./ha)

Orius LR50 = 2.2 2D, leaves 0.12 5 0.27 - laevigatus L/ha 10 d (44.5 g a.s./ha)

The off-field HQ values for Typhlodromus pyri, Aphidius rhopalosiphi as well as for the additional species Orius laevigatus are below the trigger value, indicating that Exilis does not pose an unacceptable risk to non-target arthropods in off-field areas.

6.6.3 Using artificial substrates Please refer to appendix 2 of this document.

6.6.4 Extended laboratory studies (IIIA 10.5.2) Please refer to appendix 2 of this document.

6.6.5 Semi-field tests (IIIA 10.5.3) Acceptable risk to in- and off-field communities of non-target terrestrial arthropods was indicated in the risk assessment and consequently no semi-field testing is necessary.

6.6.6 Field tests (IIIA 10.5.4) Acceptable risk to in- and off-field communities of non-target terrestrial arthropods was indicated in the risk assessment and consequently no field testing is necessary.

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6.7 Effects on Earthworms and Other Soil Non-target Macro-organisms (IIIA 10.6)

6.7.1 Overview and summary Effects on earthworms and other soil non-target macro-organisms for Exilis were not evaluated as part of the EU review of 6-benzyladenine. Therefore, all relevant study data for this risk assessment are provided here and are considered valid and acceptable by the ZRMS.

6.7.1.1 Toxicity Table 6.7-1: Studies on earthworms

Species Test substance Timescale Endpoint Reference ICS-No. (test type) Toxicity Author (mg/kg dw) code

Eisenia foetida 6-benzyladenine 14 d, artifical LC50 > 1340 Sacker, D. 73964 soil, 10% peat mg/kg d.w. soil 24.04.2008 Corrected: ENV8195/110708 LC50 > 670 mg/kg d.w. soil

6.7.1.2 Exposure According to the GAP, Exilis is intended to be applied once in spring with a maximum application rate of 7.5 L formulation/ha (equivalent to 150 g 6-benzyladenin /ha). For PEC calculations reference is made to the environmental fate section (Part B, Section 5) of this submission. The resulting maximum PECsoil values for the active substances 6-benzyladenin and the major soil degradation products are presented in the following Table 6.7-2. Calculations considered the maximum application rate of 150 g 6-benzyladenin/ha (i.e. a single application at 7.5 L Exilis/ha) and a minimum of 70% foliar interception for applications to apples and pears at BBCH 71-74. PEC values for the soil metabolites were calculated considering the maximum percentage of their formation observed in either the aerobic or anaerobic soil degradation studies and correcting for molecular weight. Calculations assumed an even distribution of the substances in the top 5 cm horizon with a soil bulk density of 1.5 g/mL.

Table 6.7-2: Maximum PECS for 6-Benzyladenin and Exilis after applications of 6- benzyladenin (expressed as a.s.)

Substance Maximum instantaneous PECS (mg/kg), 25% foliar interception 6-benzyladenine 0.06 M8 (worst case) 0.06

6.7.1.3 Overall conclusion All acute TERs for the active substances and the major soil degradation products are above the respective trigger values indicating that the acute and chronic risk to earthworms and other soil non-

Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date: 08. August 2012 Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 30 of 74 target macro-organisms following treatment with 6-benzyladenine.is low and acceptable at the intended worst-case uses. The risk from the major degradation product metabolite M8 is regarded as covered by the toxicity endpoint of the parent compound, because M8 reaches its degradation maximum in soil with 9.9% at day 3. At day 14 only 2.2% of the metabolite could be detected. The risk assessment results are summarized in the following Table: Table 6.7-3: Toxicity/exposure ratios for earthworms (Eisenia foetida) after applications of Exilis in pomme fruit

Test Worst-case use Timescale Endpoint PEC TER TER risk substance pattern (mg/kg dw (mg/kg assessment soil) dw soil trigger

6- 1 x 150 g a.s./ha Acute LC50 > 670 0.06 > 1000 10 benzyladenine mg/kg d.w. soil Long-term - - 5 TERs shown in bold fall below the relevant trigger.

6.7.2 Toxicity exposure ratios for earthworms, TERA and TERLT (IIIA 10.6.1) 6.7.2.1 Acute risk The potential acute risk of Exilis and the active substances 6-benzyladenine was assessed by comparing the maximum instantaneous PECsoil with the 14-day LC50 value to generate acute TER values. The log KOW value for 6-benzyladenine, is > 2. Therefore, a correction of the endpoints is required in order to account for the relatively high organic matter content of the artificial test soil compared to agricultural soils.

The TERA was calculated as follows:

LC50 (mg/kg) TER A = PECsoil (mg/kg)

The resulting TERA values are shown in the following Table, considering the highest initial PEC in soil (i.e70% interception during applications):

Table 6.7-4: Acute TER values for earthworms following applications of 6-benzyladenine.

Test substance Maximum initial Timescale LC50 or NOEC TER PEC (mg/kg) (mg/kg)

6-benzyladenine 0.06 Acute, 14 d LC50 > 670 mg/kg > 1000 d.w. soil TERs shown in bold fall below the relevant trigger.

Based on the worst case scenario, the acceptability criteria TER ≥ 10 for acute effects, according to Annex VI to directive 1107/2009 (EG), uniform principles, point 2.5.2.5 is reached.

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6.7.2.2 Long-term risk There is no need to address the long term risk of the active substances 6-benzyladenine and for the major metabolite M8 for earthworms, because their degradation in soil (DT90 < 365 d, Kinetic, laboratory/field data) is fast.

6.7.3 Acute toxicity (IIIA 10.6.2) No additional studies are considered necessary, due to the large margins of safety demonstrated based on data for the technical active substance.

6.7.4 Sublethal effects (IIIA 10.6.3) It was agreed during the EU Review that a study assessing the sublethal effects of 6-benzyladenine on earthworms was not required. The critical GAP for the proposed use of Exilis (Table 10-1) is within the risk envelope of the EU assessment and hence such a study is considered not necessary.

6.7.5 Field tests (IIIA 10.6.4) Not required as an acceptable risk to earthworms was identified, based on the laboratory studies available.

6.7.6 Residue content of earthworms (IIIA 10.6.5)

The log Kow values of 6-benzyladenine are < 3. Thus, it is very unlikely for both active substances to bioaccumulate in earthworms, as indicated by their low log Pow value (less than 3) in combination with its low toxicity and extensive metabolism. Therefore, studies determining residue content of earthworms are not necessary.

6.7.7 Effects on other non-target macro-organisms (IIIA 10.6.6) According to SANCO/10329/2002 rev2 final tests on other soil non-target organisms are triggered by breaching the soil persistence criteria (DT90 > 365 d). This is not the case for the major soil degradation product M8. For the parent compounds, studies on other non-target soil macro-organisms are not triggered.

6.7.8 Effects on organic matter breakdown (IIIA 10.6.7) According to SANCO/10329/2002 rev2 final a test for assessing effects on organic matter breakdown (litterbag) is required where:

• DT90f > 365 days or

• DT90f is between 100 and 365 days and

• Effects on soil microflora > 25 % or TERLT earthworm < 5

• or Collembola TERLT < 5

None of these criteria is met for 6-benzyladenine. DT90f values are less than 365 days and no risk was identified for earthworms, soil micro-organisms and non-target arthropods from the use of this product.

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6.8 Effects on Soil Microbial Activity (IIIA 10.7)

6.8.1 Overview and summary Effects on soil micro-organisms for 6-benzyladenine were evaluated as part of the EU review Therefore, all relevant data and assessments are provided here and are considered adequate.

6.8.1.1 Toxicity Table 6.8-1: Relevant studies on soil microbial activity

Species Test substance Timescale Endpoint Reference ICS-No. (test type) Toxicity Author (mg/kg dw) code Nitrogen 6-benzyladenine 0.2 mg 2.93% effect at day- Carter, J. 74305 mineralisation a.s./kg dw 28 24.07.2008 soil 1.1% effect at day-28 ZAB0091 1.0 mg (both <25% Annex VI a.s./kg dw trigger) soil Carbon mineralisation 6-benzyladenine 0.2 mg 2.4% effect at day-28 Carter, J. 74305 a.s./kg dw at 0.2 mg a.s./kg dw 24.07.2008 soil soil ZAB0091 1.0 mg -19.9% effect at day- a.s./kg dw 28 at 1.0 mg a.s./kg soil dw soil (both <25% Annex VI trigger)

The results of these studies showed no effects of > 25% compared to the control (trigger value as according to SANCO/10329/2002 ) on soil microbial activity up to a maximum tested concentration of 1.0 mg a.s./kg soil, after 28 days. As this maximum tested concentration was much higher than the maximum initial PEC from the proposed use of 6-benzyladenine l (0.040 mg a.s./kg, EFSA Journal 2010; 8(9):1716), as assessed under the EU Review, an acceptable risk to soil microbial activity was concluded. As the proposed use of Exilis in orchards fits within the risk envelope of the uses that were assessed during the EU Review of 6-benzyladenine (Table 6-1) the risk to soil micro-organisms is considered to be acceptable. 6.8.1.2 Exposure See section 6.7.1.2 of this document for the PECsoil values. 6.8.1.3 Overall conclusion The risk assessment results are summarized in the following Table:

Table 6.8-2: Relevant studies on soil microbial activity

Substance NOEC PECS (mg/kg), 25% MoS (< 25% effect at 28 d) foliar interception 6-benzyladenine 1.0 0.06 16.7

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6-benzyladenine applied at the proposed worst-case use patterns does not pose an unacceptable risk to soil microorganisms.

6.8.1.4 Toxicity exposure ratios SANCO/10329/2002 rev 2-final states that testing soil micro-organisms is always required when contamination of the soil is possible. The Predicted Environmental Concentrations of the formulation, the active substance(s) is below the concentrations at which no unacceptable effects (< 25%) were observed after 28 days of exposure. The results of the comparison expressed as Margin of Safety (MoS) is presented in the following Table:

Table 6.8-3: Risk assessment to soil micro-organisms

Substance Test type Maximum initial PEC Effects <25% MoS (mg/kg) (mg/kg) 6-benzyladenine N transformation 0.06 1.0 16.7

C transformation 1.0 16.7 TERs shown in bold fall below the relevant trigger.

The risk from the major degradation product metabolite M8 is regarded as covered by the toxicity endpoint of the parent compound, because M8 reaches its degradation maximum in soil with 9.9% at day 3. At day 14 only 2.2% of the metabolite could be detected For the active ingredients in Exilis, 6-benzyladenine and the metabolite M8 the soil concentrations which caused no deviations greater than ±25% in the micro-organism studies are at least 10-times higher than the corresponding maximum PEC in soil. Based on the worst case scenario, the acceptability criteria according to directive 1107/2009 (EG), Annex VI, uniform principles, point 2.5.2.6 is reached.

6.8.2 Laboratory testing (IIIA 10.7.1) Please refer to appendix 2 of this document.

6.8.3 Additional testing (IIIA 10.7.2) Additional testing on soil micro-organisms is not necessary since the studies performed on a worst- case formulation for Exilis, the active substance 6-benzyladenine resulted in no effects greater than ±25%.

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6.9 Effects on Non-Target Plants (IIIA 10.8)

6.9.1 Terrestrial plants (IIIA 10.8.1) 6.9.1.1 Overview and summary An EU agreed endpoint from a standard laboratory seedling emergence/growth study conducted with technical 6-benzyladenine is available. Data on Exilis is evaluated here, and risk assessments for 6- benzyladenine with the proposed use pattern are provided here and are considered adequate. 6.9.1.2 Toxicity Table 6.9-1: Relevant studies to terrestrial non-target plants

Species Test substance Timescale Endpoint Reference ICS-No. (test type) Toxicity Author (g/ha) code Seedling emergence

Lolium perenne (3 6-benzyladenine 28 d ER50 = 1.27 Gray, J. 74288 monokotyle und 4 di- mg a.s./kg soil 14.07.2008 kotyle Spezies) = 476 g a.i./ha ZAB0084 Vegetative vigour

Beta vulgaris Exilis 21 d EC50 > 300 g Bramby- 77682 Brassica oleracea (3 a.s./ha Gunary, J. monokotyle und 4 di- 16.12.2009 kotyle Spezies)

The data on the formulated product and 6-benzyladenine are most relevant for the risk assessments.

6.9.1.3 Exposure Effects on non-target plants are of concern in the off-field environment, where they may be exposed to spray drift. The amount of spray drift reaching off-crop habitats is calculated using the 90th percentile estimates derived by the BBA (2000)1 from the spray-drift predictions of Ganzelmeier & Rautmann (2000)2. Any dilution over the 3-dimensional vegetation surface is accounted for in the study design. Therefore, in contrast to the assessment of risks to arthropods from standard laboratory tests, no vegetation distribution factor is considered here. PECoff-field= Maximum in-field PER x (%DRIFT/100) The exposure assessment for the intended uses, due to the ground-directed application of Exilis, which is a plant growth regulator in pome fruits is most appropriately addressed by the drift values for

1 BBA (2000) Bundesanzeiger Jg. 52 (Official Gazette), Nr 100, S. 9879-9880 (25.05.2000) Bekanntmachung über die Abtrifteckwerte, die bei der Prüfung und Zulassung von Pflanzenschutzmitteln herangezogen werden. Public domain. 2 Ganzelmeier H., Rautmann D. (2000) Drift, drift-reducing sprayers and sprayer testing. Aspects of Applied Biology 57, 2000, Pesticide Application. Public domain.

Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date: 08. August 2012 Part B – Section 6 Exilis Registration Report Core Assessment Germany – Central Zone Page 35 of 74 orchards. The highest single application rate of Exilis is 7.5 L product/ha corresponding to 150 g 6- benzyladenine/ha. The resulting maximum off-field predicted environmental rates (PERoff-field) are summarized in the following Table: Table 6.9-2: Maximum off-field predicted environmental rates of 6-benzyladenine/Exilis

Maximum intended in- Maximum PERoff-field Maximum PERoff-field Maximum PERoff-field field rate (PECin-field) at 1m (15.73% drift) at 5m (8.41% drift) at 10m (3.60% drift) 150 g a.s./ha 23.6 g a.s./ha 12.6 g a.s./ha 5.4 g a.s./ha 7.5 L product/ha 1.18 L product/ha 0.63 L product/ha 0.27 L product/ha

6.9.1.4 Overall conclusion The risk assessment results are summarized in the following Table: Table 6.9-3: Risk assessment for terrestrial non-target plants exposed to Exilis

Effect endpoint Effect rate PERin-field Distance Exposure TER [mL [mL PERoff-field product/ha] product/ha] [mL (ER50) product/ha]

Seedling ER50 = 1.27 mg 150 g a.s./ha 3 23.6 g a.s./ha 20.2 emergence a.s./kg soil 7.5 L product/ha - - - = 476 g a.i./ha - -- -

Vegetative EC50 > 300 g 3 23.6 g a.s./ha 12.7 vigour a.s./ha ------Figures in bold indicate acceptable risk. Based on the most sensitive endpoints for seedling emergence and vegetative vigour, treatment of Exilis according to the proposed uses, poses an acceptable risk to terrestrial non-target plants.

6.9.1.5 Toxicity exposure ratios For plant protection products exerting effects of more than 50% at the maximum application rate a quantitative second tier risk assessment based on dose-response endpoints represented by ER50 values is required according to the Terrestrial Guidance Document. The risk assessment based on the overall lowest effect endpoint for seedling emergence and vegetative vigour for the actual formulation Exilis and the relevant predicted environmental rates in the off-field area after treatment with Exilis in accordance to the maximum proposed use rate of 7.5 L product/ha is presented in the following Table:

Table 6.9-4: Risk assessment for non-target plants after applications of Exilis

Study type Critical Distance (m) Drift reducing PER TER endpoint nozzles (mL/ha) (mL/ha)

Vegetative EC50 > 300 g 3 0% 23.6 g a.s./ha 12.7 vigour a.s./ha 50% - - 75% - - 90% - -

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5 0% - - 50% - - 10 0% - - Seedling ER50 = 1.27 mg 3 0% 23.6 g a.s./ha 20.2 emergence a.s./kg soil 50% - - = 476 g a.i./ha 5 0% - - TERs shown in bold are below the relevant trigger.

TER values based on the most sensitive species identified in the vegetative vigour study for Exilis are higher than the proposed Annex VI trigger of 5 at a distance of 3 m using standard application nozzles.

6.9.1.6 Seed germination (IIIA 10.8.1.1) This is not required by Directive Nr 1107/2009 (EG).

6.9.1.7 Vegetative vigour (IIIA 10.8.1.2) Please refer to appendix 2 of this document.

6.9.1.8 Seedling emergence (IIIA 10.8.1.3) Please refer to appendix 2 of this document.

6.9.1.9 Field testing (IIIA 10.8.1.4) No study submitted.

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6.9.2 Effects on non-target aquatic plants (IIIA 10.8.2) Please refer to assessment made under chapter 6.4.

6.9.2.1 Lemna growth test (IIIA 10.8.2.1) Please refer to appendix 2 of this document.

6.9.2.2 Field tests (IIIA 10.8.2.2) Due to the acceptable risk at lower tier, no aquatic field tests are required.

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6.10 Other Non-Target Species (Flora and Fauna) (IIIA 10.9)

Not relevant.

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6.11 Summary and Evaluation of Points 9 and 10.1-10.10

6.11.1 Predicted distribution and fate in the environment and time courses involved (IIIA 10.11.1) The predicted distribution and fate of Exilis in the environment is described in Part B, Section 5.

6.11.2 Non-target species at risk and extent of potential exposure (IIIA1 10.11.2) Please refer to chapter 6.11.3

6.11.3 Short and long term risks for non-target species, populations, communities and processes (IIIA 10.11.3) The above risk assessments demonstrate an acceptable risk to all wildlife groups from the proposed uses of Exilis, without the need for risk mitigation measures.

6.11.4 Risk of fish kills and fatalities in large vertebrates or terrestrial predators (IIIA 10.11.4) In view of the generally low acute and chronic toxicity of 6-benzyladenine and its active substances to vertebrates (i.e. fish, birds and mammals) and the fact that 6-benzyladenine is applied only once per year, the likelihood of fish kills or fatalities in large vertebrates or terrestrial vertebrates occurring is considered to be negligible.

6.11.5 Precautions necessary to avoid/minimise environmental contamination and to protect non-target species (IIIA 10.11.5) As with any application of pesticides not intended for direct application to water, direct overspray of water bodies with Exilis should be strictly avoided.

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Appendix 1 List of data submitted in support of the evaluation

Table A1: List of data submitted in support of the evaluation

Annex Author(s) Year Title Data Owner How considered point/referenc Source (where different from protection in dRR e No company) claimed Study- Report-No. Status/Usage* GLP or GEP status (where relevant), Published or not Authority registration No OECD: K IIIA XXX 2007 Fish acute toxicity study with 1) 10.2.2.1 Exilis 2% SL formulation on Rainbow trout (Oncorhynchus mykiss) Document No.: 07/394-009H

OECD: K IIIA Hernádi, D 2007 Acute immobilisation test 1) 10.2.2.2 with Exilis 2% SL formulation on Daphnia Magna Document No: 07/394-023DA

OECD: KIIIA Hernádi, D 2008 Exilis 2% SL formulation 1) 10.2.2.3 Growth Inhibition test on Algae (Pseudokirchneriella subcapitata) Document No: 07/394- 022ALR OECD: KIIIA Vryenhoef, 2011 Exilis: Navicula Pelliculosa: 1) 10.2.2.3 H. and Algal growth inhibition test Mullee, D. Document No: Project No. M. 41004731 OECD: KIIIA Sipos, K. 2007 Acute contact and oral 1) 10.4.2 toxicity of Exilis 2 % SL formulation on honey bees (Apis mellifera) OECD: KIIIA Agh, I. 2009 Growth Inhibition Test with 1) 10.8.2.1 Exilis on Lemna (Lemna gibba) Document No: 09/078-029BL OECD: KIIIA Sipos, K. 2007 Effects of Exilis 2% SL 1) 10.5.1 formulation on the Predatory Mite (Typhlodromus pyri) in a laboratory trial Document No: 07/394-335RA OECD: KIIIA Kimmel, S. 2011 Exilis: Toxicity to Adults of 1) 10.5.1 the Parasitoid Wasp Aphidius rhopalosiphi (Hymenoptera: Braconidae) under Worst- Case Conditions in the Laboratory

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Document No: D25464 OECD: KIIIA Kimmel, S. 2011 Exilis: Toxicity to the 1) 10.5.2 Predatory bug Orius laevigatus (Heteroptera: Anthocoridae) under Extended Laboratory Conditions. Document No: D13180 OECD: KIIIA Vinall, S. 2011 Aged-residue extended 1) 10.5.2 laboratory test to determine the effects of Exilis (2 g/L 6- benzyladenine) on the predatory mite Orius laevigatus Fieber (Hemiptera: Anthocoridae). Document No: FIN-11-1 IIIA 10.8.1.2 Bramby- 2009 Evaluation of the 1) Gunary, J. Phytotoxicity of Exilis. Non Target Terrestrial Plant Vegetative Vigour Test Document No: ACE-09-133

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Appendix 2 Detailed evaluation of studies relied upon Report only studies, which (a) have not previously been evaluated within a peer reviewed process at EU level (Annex I inclusion of 6-benzyladenine) or (b) have been evaluated in a peer reviewed process at EU level but where in exceptional cases derived endpoints have to be revised in the light of current scientific and technical knowledge. Studies evaluation is ordered according to OECD code numbers. For the report of study summaries, the applicant should use the OECD study evaluation templates. Indicate if original study evaluation from the notifier is acceptable or not acceptable without revision. Use commenting box below each study to indicate agreed endpoints and in case of a revision of the original study evaluation by the zRMS a short summary of the type of the authority's corrections to the original evaluation of the applicant.

A2-1 6-benzyladenine No studies with 6-benzyladenine were submitted after the Annex I inclusion.

A2-2 Formulation IIIA 10.2 Effects on aquatic organisms IIIA 10.2.2 Acute toxicity (aquatic) of the preparation IIIA 10.2.2.1 Fish acute toxicity LC50, freshwater, cold-water species

Reference: IIIA 10.2.2.1 Fish

Report IIIA 10.2.2.1/01, Hernádi, D, 2007a, Document No: 07/394-009H

Guideline(s): Yes, OECD 203 (1992); Directive 92/69/EC, C.1 (1992); OPPTS 850.1075

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and methods Test Material Exilis 2% SL formulation Description: Clear liquid Lot/Batch #: W0655B Active substance: 6-benzylaminopurine Content: 20.3 g a.s./L (measured)

Test animals

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Species: Rainbow trout (Oncorhynchus mykiss) Source: Piscicultura Ltd., Tapolca, Hungary Number: 7 fish in the test item and control group Age: Juvenile Length: 4.5 – 6.0 cm Weight: 2.57 – 2.66 g Acclimation period: From 24 January to 14 May 2007 (start of the study) Feeding: The fish were not fed during the test.

Test design System: Static system Duration: 96 hours Test vessel: 25-L aquaria containing 20 L of test solution Dilution water: Aquarium water (circulated, filter and cooled) Concentrations: 0 (control) and 100 mg/L (nominal concentration)

Environmental conditions Oxygen content: 91 – 93 % Temperature: 14.8 – 15.2 °C pH: 8.07 – 8.50

Hardness: 169.4 mg/L as CaCO3 Photoperiod: 16 hours of light / 8 hours of darkness daily

Animal assignment and treatment Two aquaria, each with seven fish were prepared for the treatment and control group. The nominal concentration of Exilis 2% SL formulation was (on the basis of the preliminary study) 100.0 mg/L.

Dose preparations The test medium was prepared just before introduction of the fish. The test item was dissolved into the test water as homogeneously as possible by intense stirring. No solvent substance was used. The control consisted of dilution water only.

Measurements/observations Observations were performed at 3, 6, 24, 48, 72 and 96 hours after the start of the test. Mortality was determined at each observation period. The water temperature, pH values and dissolved oxygen concentrations were determined daily in the test medium of the treatment and control group. Water samples were collected from the treatment group and the control group at the start and at the end of the test to determine concentrations of the test substance. The samples were diluted and analysed by high performance liquid chromatography (HPLC) with UV detection at 270 nm.

Statistics Probit analysis as well statistical comparisons was not deemed appropriate as no mortality occurred at the test concentration of 100 mg/L.

RESULTS AND DISCUSSION

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The measured concentration in the test group was 102 mg/L at the start and 102 mg/L at the end of the study. The results of the study were based on the nominal concentration of the test item. Daily observations of mortality during the test are presented in Table 10.2.2.1-1 below. No mortalities or symptoms of intoxication were observed in the control group and in the 100 mg/L treatment throughout the test. Therefore, the 96h-LC50 was estimated to be > 100 mg test item/L. The NOEC was 100 mg test item/L (based on the nominal concentrations).

Table A2-1Fehler! Kein Text mit angegebener Formatvorlage im Dokument.: Summary of results from acute fish toxicity study with Exilis 2% SL formulation

Mean measured Nominal conc. Mortality rate of treated fish (dead fish/treated fish) conc. (mg/L) (mg/L) 3 h 6h 24 h 48 h 72 h 96 h Control - 0/7 0/7 0/7 0/7 0/7 0/7 100 102 0/7 0/7 0/7 0/7 0/7 0/7

CONCLUSIONS

Rainbow trout (Oncorhynchus mykiss) were exposed for 96 hours under static conditions to Exilis 2% SL formulation at the limit test concentration of 100 mg/L (mean measured concentration of

102 mg/L). The 96-hour LC50 value was estimated to be > 100 mg/L. The no mortality concentration and the NOEC were found to be 100 mg/L.

Study Comments: The underlying study and the risk assessments is acceptable. The acute risk to fish is acceptable. Agreed Endpoints: In a 96-h acute toxicity study, rainbow trout (Oncorhynchus mykiss) were exposed to Exilis 2% SL formulation at the limit test concentration of 100 mg/L and a control under static conditions. One aquarium was maintained in each treatment and control group, with seven trouts per test chamber. Observations for mortality were performed 3, 6, 24, 48, 72 and 96 hours after the start of the test. The numbers of individuals exhibiting signs of toxicity or abnormal behavior also were evaluated. The 96-hour LC50 value was estimated to be > 100 mg test item/L. The no mortality concentration and the NOEC were 100 mg/L. Endpoints were based on the nominal concentration.

IIIA 10.2.2.2 Acute toxicity (24 & 48 h) for Daphnia preferably Daphnia magna

Reference: IIIA 10.2.2.2 Aquatic invertebrates (Daphnia)

Report IIIA 10.2.2.2/01, Hernádi, D, 2007b, Document No: 07/394-023DA

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Guideline(s): Yes, OECD 202 (2004); OPPTS 850.1010

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and methods Test Material Exilis 2% SL formulation Description: Clear liquid Lot/Batch #: W0655B Active substance: 6-benzylaminopurine Content: 20.3 g a.s./L (measured)

Test animals Species: Daphnia magna Source: National Institute of Public Health, Budapest, Hungary Number: 20 animals in the item and control group Age: < 24 h old at the beginning of the test Acclimation period: No acclimatisation as the water used was similar to the culture water Feeding: The test animals were not fed during the test

Test design System: Static system Duration: 48 hours Test vessel: Glass beakers (50 ml), containing 40 ml test media Dilution water: ISO medium Concentrations: 0 (control) and 100 mg/L (nominal concentration)

Environmental conditions Oxygen content: 6.6 – 6.9 mg/L Temperature: 19.8 – 20.2 °C pH: 6.77– 6.91 Photoperiod: 16 hours of light / 8 hours of darkness daily

Animal assignment and treatment Four vessels were used in the test item and control group. Each group comprised of twenty Daphnia, five in each of the four replicate vessels, each containing 40 ml test dilution. The nominal concentration of Exilis 2% SL formulation was (on the basis of the preliminary study) 100.0 mg/L.

Dose preparations

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The test medium was prepared just before introduction of the daphnids. The test item was dissolved into the test water as homogeneously as possible by intense stirring and by means of ultrasonic treatment. No solvent substance was used. The control consisted of dilution water only.

Measurements/observations The number of mobile and immobilised test animals was observed and recorded 24 and 48 hours after the start of the test. The oxygen concentrations and pH values of the control and the test solution were measured at the beginning and at the end of the test. The water temperature was measured daily. Water samples were taken from each test group at the start and from each replicates of the test and control group at the end of the test, to determine concentrations of the test substance. The samples were diluted and analysed by high performance liquid chromatography (HPLC) with UV detection at 270 nm.

Statistics

Statistical analysis of the results as well as calculations of the EC50 was not deemed appropriate as no immobilisation occurred at the test concentration of 100 mg/L.

RESULTS AND DISCUSSION

The measured concentration was 108 mg/L at the start and 112 mg/L at the end of the study. The results of the study were based on the nominal concentration of the test item. Daily observations of immobility during the test are presented in Table 10.2.2.2-1 below. No immobility was observed in the control group and in the 100 mg/L treatment throughout the test.

Therefore, the 48-hour-EC50 was estimated to be > 100 mg test item/L. The NOEC was 100 mg test item/L (based on the nominal concentration).

Table A2-2: Summary of results from acute Daphnia toxicity study with Exilis 2% SL formulation Mean measured Nominal conc. No. of treated Number of immobilised animals conc. (mg/L) animals (mg/L) 24 h 48 h Control - 20 0 0 100 110 20 0 0

CONCLUSIONS

The cladoceran, Daphnia magna, was exposed for 48 hours under static conditions to Exilis 2% SL formulation at the limit test concentration of 100 mg/L (mean measured concentration of 110 mg/L). The 48-hour EC50 value was estimated to be > 100 mg/L. The no immobility concentration and the NOEC were found to be 100 mg/L.

Study Comments: The underlying study and the risk assessments is acceptable. The acute risk to daphnia is acceptable.

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Agreed Endpoints: In a 48-h acute toxicity study, Daphnia magna were exposed to Exilis 2% SL formulation at the limit test concentration of 100 mg/L and a control under static conditions. There were 20 daphnids, divided into 5 replicates, in the concentration and control group. Immobilisation was observed 24 and 48 hours after the start of the test. The 48-hour EC50 value was estimated to be > 100 mg test item/L. The no immobility concentration and the NOEC were 100 mg/L. Endpoints were based on the nominal concentration.

IIIA 10.2.2.3 Effects on algal growth and growth rate

Reference: IIIA 10.2.2.3 Algae

Report IIIA 10.2.2.2/01, Hernádi, D, 2008, Document No: 07/394-022ALR

Guideline(s): Yes, OECD 201 (2006); OPPTS 850.5400 (1996); Directive 92/69/EC, C.3 (1992)

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and methods Test Material Exilis 2% SL formulation Description: Clear liquid Lot/Batch #: W0655B Active substance: 6-benzylaminopurine Content: 20.3 g a.s./L (measured)

Test organisms Species: Pseudokirchneriella subcapitata (strain No. ASAG 0109PS 070816) Source: Georg-August-Universität Göttingen, Germany Cell concentration: Initially cell concentration = 1 x 104 cells/ml.

Test design System: Static system Duration: 72 hours Test vessel: 250 ml glass flask each containing 100 ml of medium Dilution water: Algal Mineral Salts Test Medium (OECD 201 medium) Concentrations: 0 (control), 6.25, 12.5, 25, 50 and 100 mg/L (nominal concentration)

Environmental conditions Temperature: 22.6 – 24.0 °C

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pH: 7.79 – 8.54 Photoperiod: Continuous illumination (8166.64 lux) Agitation: Shaking at approximately 150 rpm

Assignment and treatment On the basis of a preliminary range finding study, Pseudokirchneriella subcapitata were exposed to Exilis 2% SL formulation at nominal concentrations of 6.25, 12.5, 25, 50 and 100 mg/L. An untreated control group (algal mineral medium with inoculum and without test item) was tested in parallel. The test design included three replicates at each test concentration and six replicates for the untreated control. At the start of the study the alga cell concentration was 104 cells/ml in each of the test cultures. To keep the algae in suspension, test flasks were placed on an orbital shaker table at approximately 150 rpm into the climate chamber.

Dose preparations A 100 mg/L stock solution was prepared by dispersing 0.100 g Exilis 2% SL formulation in 1000 ml of algal medium. The remaining test solutions were prepared from this stock solution by serial dilution and distributed into the appropriate test flasks.

Measurements/observations The cell numbers were counted, using a microscope, in each testing flask during the 72-hour test, at 24 hour intervals. The pH was recorded at the beginning and at the end of the test in the controls and at each test concentration. The temperature was checked at the beginning of the study and every 24 hours thereafter. In addition, the temperature was continuously measured within the climate chamber. For analytical determination of the test concentrations samples were taken from each concentration level at the start of the test and from each testing flask at the end of the test. Three samples were taken from the test solutions and one sample was taken from the control at the start and at the end of the test to determine the concentration of the 6-benzylaminopurine in the test solutions. The samples were diluted and analysed by high performance liquid chromatography (HPLC) with UV detection at 270 nm.

Statistics Probit analysis was not deemed appropriate as no inhibition occurred even at the highest test item concentration of 100 mg/L. Statistical comparisons of average specific growth rates, area under the growth curves and yield in control and in the treated groups were carried out using analysis of variance (ANOVA) and Bonferroni t-Test (α = 0.05) by TOXSTAT software. The percentage reduction of average specific growth rates, areas under the growth curve and yield compared to the control was plotted against the logarithm of nominal concentration using EXCEL for windows software.

RESULTS AND DISCUSSION

The analysed test item concentrations varied between 97 and 106 percent of the nominal concentrations at the test start and between 96 and 103 percent at the end of the test. As the deviations from the nominal concentrations were less than 20 percent in the analysed concentrations; the biological results are based on nominal concentrations of the formulation.

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No toxic effects of the test item on the growth of Pseudokirchneriella subcapitata were observed at any test concentration up to and including the highest test concentration of 100 mg/L. The 0-72 h average specific growth rates, the 0-72 h areas under the growth curve and the 0-72 h yield were not statistically significanty different from the untreated control value at any concentration level (Bonferroni t-Test; α = 0.05). A summary of the endpoints from this study are presented in the table below.

Table A2-3: Toxicity of Exilis 2% SL formulation on the growth of Pseudokirchneriella subcapitata (based on nominal concentrations)

Biological parameter Endpoints (mg formulation/L) (0-72 h) EC50 NOEC LOEC Biomass (b) > 100.0 100.0 > 100.0 Calculation based on > 100.0 100.0 > 100.0 Growth rate (r) Yield (y) > 100.0 100.0 > 100.0

CONCLUSIONS

No toxic effects of Exilis 2% SL formulation on the growth of Pseudokirchneriella subcapitata were observed at any test concentration up to and including the highest test concentration of 100 mg/L. The 0-72 h ErC50, EbC50 and EybC50 were >100 mg/L and the corresponding NOEC values were 100 mg/L (based on nominal concentrations).

Study Comments: The underlying study and the risk assessments is acceptable. The acute risk to algae is acceptable. Agreed Endpoints: Exponentially growing cultures of the unicellular green alga Pseudokirchneriella subcapitata were exposed to Exilis 2% SL formulation at nominal concentrations of 0 (control), 6.25, 12.5, 25, 50 and 100 mg/L under static conditions. The inhibition of growth compared to the control was determined over a period of 72 hours. The results of the test are based on the nominal concentrations. The 72 h ErC50, the 72 h EbC50 and the 72 h EyC50 were all estimated to be > 100 mg product/L and the corresponding NOEC values were determined to be 100 mg product/L.

Reference: IIIA 10.2.2.3 Algae

Report IIIA 10.2.2.2/02, Vryenhoef, H. and Mullee D. M., 2011, Document No: Project No. 41004731

Guideline(s): Yes, OECD 201 (2006), Commission Regulation (EC) 440/2008, Method C.3

Deviations: None

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GLP: Yes, certified laboratory

Acceptability: Yes

Original study evaluation Yes, indicates that study evaluation was corrected. revised by RMS

Materials and methods Test Material Exilis Description: Clear colourless liquid Lot/Batch #: 1401440004 Active substance: 6-benzylaminopurine Content: 20.73 g a.s./L (measured)

Test organisms Species: Navicula pelliculosa (strain SAG 1050-3) Source: Collection of Algae Cultures Inst. Plant Pysiologie, University of Göttingen, Germany Cell density: Initial nominal cell density of 5 x 103 cells/ml

Test design System: Static system Duration: 72 hours Test vessel: 250 ml glass conical flask each containing 100 ml of test preparation Dilution water: Algal culture medium Concentrations: 0 (control), 1.0, 3.2, 10, 32 and 100 mg a.s./L (nominal concentration)

Environmental conditions Temperature: 24 ±1 °C pH: 7.2 – 7.8 Photoperiod: continuous illumination (approximately 7000 lux) Agitation: constant shaking (approximately 150 rpm)

Assignment and treatment On the basis of a preliminary range finding study, the freshwater alga Navicula pelliculosa were exposed to Exilis at nominal concentrations of 1.0, 3.2, 10, 32 and 100 mg a.s./L. The control group was maintained under identical conditions but not exposed to the test item. Six flasks each containing 100 ml of test media were used for the control and three flasks each containing 100 ml were used for each treatment group. Pre-culture conditions gave an algal suspension in log phase growth characterized by a cell density of 1.54 x 105 cells/ml. Inoculation of 500 ml of test medium with 16 ml of this algal suspension gave an initial nominal cell density of 5 x 103 cells/ml and had no significant dilution effect on the final test concentration. The flasks were plugged with polyurethane foam bungs and incubated at 24 ± 1°C under continuous illumination and constantly shaken at 150 rpm for 72 hours.

Dose preparations

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Stock solutions 100 and 32 mg a.s./L were prepared by dissolving 4824 and 1544 mg EXILIS in culture medium with the aid of ultrasonication and vigorous shaking by hand for approximately 60 minutes and the volumes adjusted to 1 L. A series of dilutions were made from these stock solutions to give further stock solutions of 10, 3.2 and 1.0 mg a.s./L. An aliquot (500 mL) of each of the stock solutions was separately inoculated with algal suspension (16 mL) to give the required test concentrations of 1.0, 3.2, 10, 32 and 100 mg a.s./L.

Measurements/observations Samples were taken at 0, 24, 48 and 72 hours and the cell densities determined, using a coulter multisizer particle counter. The pH of each control and test flask was determined at initiation of the test and after 72 hours of exposure. The temperature within the incubator was recorded daily. For analytical determination of the test concentrations samples were taken from the control (6 replicates) and each concentration level (3 replicates) at the start at the end of the test. The samples were analysed by high performance liquid chromatography with a mass selective detector (HPLC-MS).

Statistics One way analysis of variance incorporating Bartlett’s test for homogeneity of variance (Sokal and Rohlf 1981) and Dunnett’s multiple comparison procedure for comparing several treatments with a control (Dunnett 1955) was carried out on the growth rate and yield data after 72 hours for the control and all test concentrations to determine any statistically significant differences between the test and control groups.

RESULTS AND DISCUSSION

Analysis of the test preparations at 0 and 72 hours showed measured test concentrations to range from 88% to 101% of nominal and so the results are based on nominal test concentrations only. There were no statistically significant differences in the growth rate and yield of Navicula pelliculosa between the control and the test concentrations of 1.0 and 3.2 mg a.s./L (p≥0.05). However, the test concentrations of 10, 32 and 100 mg a.s./L were significantly different from the control (p<0.05). Therefore, the NOEC and LOEC values based on growth rate and yield were determined to be 3.2 and 10 mg a.s./L, respectively.

The 0-72 h ErC50 was determined to be 17 mg a.s./L with a 95% confidence interval of 13 to 21 mg a.s./L and the 0-72 h EyC50 was determined 7.6 mg a.s./L with a 95% confidence interval of 6.7 to 8.6 mg a.s./L. A summary of the calculated endpoints from this study are presented in the table below.

Table A2-4: Toxicity of Exilis on the growth of Navicula pelliculosa (based on nominal concentrations)

Biological parameter Endpoints (mg a.s./L) (0-72 h) EC50 NOEC LOEC 17 Growth rate (r) 3.2 10 (13 – 21)

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7.6 Yield (y) 3.2 10 (6.7 – 8.6) (95% confidence interval)

CONCLUSIONS

No effects of Exilis on the growth rate and yield of Navicula pelliculosa were observed at test concentrations up to 3.2 mg a.s./L. The 0-72 h ErC50 was determined to be 17 mg a.s./L with a 95% confidence interval of 13 to 21 mg a.s./L and the 0-72 h EyC50 was determined to be 7.6 mg a.s./L with a 95% confidence interval of 6.7 to 8.6 mg a.s./L. The NOEC and LOEC values based on growth rate and yield were determined to be 3.2 and 10 mg a.s./L, respectively (based on nominal concentrations).

Study Comments: The underlying study and the risk assessments is acceptable. The acute risk to algae is acceptable. Agreed Endpoints: The effects of Exilis on the growth of the freshwater alga Navicula pelliculosa exposed to nominal concentrations of 0 (control), 1.0, 3.2, 10, 32 and 100 mg a.s./L (three replicates per test item concentration and six replicates for the control) were investigated under static conditions for 72 hours. Samples of the algal populations were removed daily and cell concentrations determined for each control and treatment group, using a coulter multisizer particle counter. The results of the test are based on nominal test concentrations. The 0-72 h ErC50 was determined to be 17 mg a.s./L with a 95% confidence interval of 13 to 21 mg a.s./L and the 0-72 h EyC50 was determined to be 7.6 mg a.s./L with a 95% confidence interval of 6.7 to 8.6 mg a.s./L. The NOEC and LOEC values based on growth rate and yield were determined to be 3.2 and 10 mg a.s./L, respectively.

IIIA 10.4 Effects on Bees IIIA 10.4.2 Acute toxicity of the formulation to bees The following bee acute oral and contact study performed on Exilis is provided in support of the assessment.

Table A2-5: Toxicity of Exilis to bees Report: IIIA 10.4.2.1/01, Sipos, K, 2007a Title: Acute contact and oral toxicity of EXILIS 2% SL formulation on Honey Bees (Apis Mellifera) Document No: 07/394-116MT Guidelines: OECD 213 and 214 (1998) Deviations: None GLP Yes

Executive Summary

The objective of the study was to determine the acute oral and contact toxicity of Exilis 2% SL formulation to honeybees. According to the range finding tests the following

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doses were used in the main oral study: 375, 750, 1500, 3000 and 6000 µg test item/bee, and in the main contact test: 187.5, 375, 750, 1500, 3000 µg test item/bee. In oral test one control group (sucrose solution only) was allocated, and in the contact test two control groups (with deionised water and acetone) were allocated, each with three replicates. Each replicate consisted of 10 bees. For the oral treatment the test item was diluted in 50% w/v sucrose solution and was offered to the bees in a volume of 20 µl/bee. For the contact treatment the test item was diluted in acetone and was dropped onto the thorax of the bees in a volume of 3 µl/bee. Results indicated that the 48-hour oral LD50 was 13410.4 µg test item/bee with 95% confidence limits of 4794.6 to 37508.5 µg test item/bee (equivalent to 260.81 µg a.s./bee with 95% confidence limits of 93.25 to 729.48 µg a.s./bee) and the 48-hour contact LD50 was 3549 µg test item/bee with 95% confidence limits of 2465.5 to 5108.8 µg test item/bee (equivalent to 69.02 µg a.s./bee with 95% confidence limits of 47.95 to 99.36 µg a.s./bee). A separate test with the reference item was carried out at four dose levels for both the oral and contact tests, at 0.07, 0.12, 0.19 and 0.30 µg a.s./bee, each in three replicates. The test with the reference item met the expected values (oral LD50-24h: 0.13 µg a.s./bee, contact LD50-24h: 0.12 µg a.s./bee).

Materials and methods

Test Material Exilis 2% SL Formulation Description: Clear liquid Lot/Batch #: W0655B Active substance: 6-benzylaminopurine Content: 20.3 g a.s./L (measured)

Reference substance: BAS 152 11 I (dimethoate 400 g/L)

Test species: adult honeybees (Apis mellifera) Number: 3 replicates of 10 bees each

Study design and methods

Duration: 48 hours Test cage: cylindrical cages with a circular mesh insert (9 cm diameter, 30 cm long and 3.5 cm wide) Vehicles: oral: sucrose solution (50% w/v), contact: acetone Concentrations: - Contact dose: 0 (sucrose solution), 187.5, 375, 750, 1500, 3000 µg/bee - Oral dosing solution: 0 (deionised water), 0 (acetone), 375, 750, 1500, 3000 and 6000 µg/bee - Reference item (BAS 152 11 I): 0.07, 0.12, 0.19, and 0.30 µg a.s./bee Temperature: 24.1 – 26.1 °C Relative humidity: 50 – 67% Photoperiod: The bees were kept in the dark except during the checking and feeding

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Animal assignment and treatment

According to the range finding tests the following doses were used in the main oral study: 375, 750, 1500, 3000 and 6000 µg test item/bee, and in the main contact test: 187.5, 375, 750, 1500, 3000 µg test item/bee. Three replicates of 10 bees per test item and control group were used. In the oral test one control group (sucrose solution only) was allocated, and in the contact test two control groups (with deionised water and acetone) were allocated, each with three replicates. The duration of the study was 48 hours. Oral test: the bees were starved for up to 2 hours, then in each feeding tube 200 µl of sucrose solution mixed with the test item was injected (20 µl/bee). By group feeding bees shared the test solution between themselves and so received similar volume of 20 µl/bee. Following exposure fresh sucrose solution was provided ad libitum in clean feeding tubes. The control groups received vehicles, such as sucrose solution in volume of 20 µl/10 bees (20 µl/bee). Contact test: the bees were lightly anaesthetised with CO2, then 3 µl of the test solution was applied to the thorax of each bee using a micropipette. After application, the bees were allocated to test cages and supplied with sucrose solution, ad libitum.

Dose preparations

Test solutions were prepared immediately prior to the treatment. The stock solution for the oral test was prepared by dissolving 1500 mg of the test item in 5 ml sucrose solution (50% w/v). A series of dilutions were made from this stock solution to obtain the following doses: 375, 750, 1500, 3000 and 6000 µg test item/bee. The stock solution for the contact test was prepared by dissolving 2000 mg of the test item in 2 ml acetone. A series of dilutions were made from this stock solution to obtain the following doses: 187.5, 375, 750, 1500 and 3000 µg test item/bee.

Observations

Mortalities and toxic symptoms were assessed at 4, 24 and 48 hours post treatment. In the oral test consumption of the test solution was registered at 4-6 hours after the start of the experiment.

Statistics

The 24-h and 48-h oral and contact LD50 were calculated using Probit-analysis.

Results and discussion

The mortality in the control groups in both the oral and contact tests was at an acceptable level (≤10%).

In the oral test, toxic symptoms such as decreased activity, partial paralysis, total paralysis and excitement were observed. No toxic symptoms appeared at the lowest dose of 375 µg test item/bee. The treated groups consumed the test solution during 4-6 hours

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of exposure. In the treated groups the percentage mortality at 48 hours was 3.3, 3.3, 6.7, 10 and 36.7% at the nominal doses of 375, 750, 1500, 3000 and 6000 µg test item/bee, respectively. Accordingly, the 48-hour oral LD50 was 13410.4 µg test item/bee with 95% confidence limits of 4794.6 to 37508.5 µg test item/bee (equivalent to 260.81 µg a.s./bee with 95% confidence limits of 93.25 to 729.48 µg a.s./bee). The NOEL was determined to be <375.0 µg test item/bee (equivalent to <7.29 µg a.s./bee). Control mortality was 3.3 %.

In the contact test, toxic symptoms such as decreased activity, partial paralysis, total paralysis and excitement were observed. No toxic symptoms appeared at the doses of 187.5, 375 and 750 µg test item/bee. In the treated groups the percentage mortality at 48 hours was 0, 0, 3.3, 6.7 and 43.3% at the nominal doses of 187.5, 375, 750, 1500 and 3000 µg test item/bee, respectively. Accordingly, the 48-hour contact LD50 was 3549 µg test item/bee with 95% confidence limits of 2465.5 to 5108.8 µg test item/bee (equivalent to 69.02 µg a.s./bee with 95% confidence limits of 47.95 to 99.36 µg a.s./bee). The NOEL was determined to be 375.0 µg test item/bee (equivalent to 7.29 µg a.s./bee). The test with the reference item met the expected values (oral LD50-24h: 0.13 µg a.s./bee, contact LD50-24h: 0.12 µg a.s./bee). Mortality was 0 % and 3.3 % in the water and acetone control, respectively.

Conclusions

The 48 hour LD50 for bees from oral exposure Exilis 2% SL formulation was 13410.4 µg/bee. The 48 hour contact LD50 was 3549 µg/bee. LD50 values of the reference item were in the expected range. No deviations from the guideline were reported. Control mortality was < 10 %. The test is considered valid.

IIIA 10.5 Effects on arthropods other than bees IIIA 10.5.1 Effects on sensitive species already tested, using artificial substrates

Reference: IIIA 10.5.1 Effects on Arthropods Other Than Bees

Report IIIA 10.5.1 /02, Sipos, K, 2011, Document No: D25464

Guideline(s): Yes, Mead-Briggs, M.A. et al., 2000 Grimm, C., M.P. Candolfi & R. Fisch, 2002

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and methods

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Test Material Exilis Description: Clear liquid Lot/Batch #: 1401440004 Active substance: 6-benzylaminopurine Content: 20.73 g a.s./L (measured) Reference substance: Roxion (Dimethoate 375 g/L EC formulation)

Test animals Species: Aphidius rhopalosiphi (DeStefani-Perez) (Hymenoptera : Braconidae) Source: Katz Biotech AG, An der Birkenpfuhlheide 10, 15837 Baruth/Germany Age: Adults (not older than 24 hours) Number: 5 males and 5 females per replicate, four replicates per test item treatment, 15 replicates per treatment for the reproduction assessment

Test design Duration: 14 days (reproduction) Test units: Glass plates (dimension) Concentrations: - Control: deionised water applied at 200 L/ha - Test substance: 230, 735, 2345, 7500, 24000 and 76800 g Exilis/ha (equivalent to 4.6, 14.7, 46.9, 150, 480 and 1536 g a.s./ha) applied at 200 L/ha - Toxic standard: 0.3 ml product/ha Application: With a calibrated sprayer (Schachtner Spray-Lab) at 2 mg/cm2 Food: Plug of cotton wool soaked in 1:3 honey-water solution

Environmental conditions Temperature: 19.3 – 20.1 °C Relative humidity: 74 – 88% Photoperiod: 850 – 1630 lux (mortality) and 4500 – 5300 lux (reproduction)

Animal assignment and treatment After spray application, the spray residues were allowed to dry. Then, adult wasps were introduced into the chambers and exposed to fresh residues during 48 hours. After this period, surviving females were transferred individually to cages with potted barley plants infested with the aphid species Rhopalosiphun padi (L.) as host for a period of 24 hours. The rate of reproduction of the parasitoids was evaluated after 11 days.

Dose preparations Prior to test start, the highest test rate of the test item Exilis was prepared by mixing 201.06 g of test item in 500 mL deionized water. An aliquot of this application solution was further diluted with deionized water to obtain the application solutions for the lower test rates.

Table A2-6: Application rates of Exilis Treatment (nominal rate)

Application g a.s./ha mL Exilis/ha g Exilis/L a Preparation of dilution series solution A 1536 76800 402 Undiluted application solution

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B 480 24000 126 156.25 mL of A ad 500 mL deion. H2O

C 150 7500 39 156.25 mL of B ad 500 mL deion. H2O

D 46.9 2345 12 156.33 mL of C ad 500 mL deion. H2O

E 14.7 735 3.8 156.72 mL of D ad 500 mL deion. H2O

F 4.6 230 1.2 156.46 mL of E ad 500 mL deion. H2O a: Based on a spray volume of 200 L/ha and a density of 1.0472 g/cm³.

Then, adequate volumes of these application solutions were sprayed onto the glass plates of each replicate by means of an adequate spraying apparatus (i.e. Spray Lab from Schachtner, Germany). The sprayer was calibrated to deliver a target of 2.0 ± 0.2 mg spray solution/cm², corresponding to 200 L/ha, by weighing the amount of water delivered. Before application, spray patterns were checked visually for uniformity. Uniform volumes of application solutions were used in the sprayer for all test rates.

The reference item treatment was prepared by mixing 75 µL of the reference item in 500 mL deionized water and subsequent dilution of this stock solution. The study also included a control, where only deionized water was applied, following the same procedure as for the test and reference item rates.

Observations The condition (mortality, signs of irritability, uncoordinated movement etc.) of each wasp was inspected at 2, 24 and 48 h. The number of mummies was counted and the number of parasitised aphids per female was calculated.

Statistical analysis Due to the low toxicity in the test item treatments, the LR50 and ER50 was determined directly from the raw data.

RESULTS AND DISCUSSION

After 48 hours of exposure (endpoint of the mortality assessment), the mean overall mortality in the control and in the reference item treatment was 7.5% and 100%, respectively. These mortality values were within the set validity limits (i.e mean mortality in the control: up to and including 13%; mean mortality in the reference item treatment: between 50 and 100%).

In the test item treatments, the mean mortality varied between 0 and 25% after 48 hours of exposure. In replicate four of the lowest test item treatment of 4.6 g a.s./ha and in replicate three of the second lowest test item treatment of 14.7 g a.s./ha, three and six wasps escaped after 24 hours, respectively, by a technical mistake (gap between glass plates and metal frame) and were therefore not taken into account. In the highest test item treatment of 1536 g a.s./ha, two and three wasps were drowned in the water supply (cotton wick) after 24 and 48 hours, respectively. Since this was not considered to be a substance-related effect, these drowned wasps were therefore also not taken into account. Since no mortality above 50% could be detected in all test item treatments up to and including the highest tested rate, the 48 hour LR50 for mortality was determined directly from the raw data to be > 1536 g a.s./ha.

The mean parasitisation success of the wasps was 11 parasitized aphids per female in the control and thus fulfilled the validity criterion for reproduction (i.e at least 5 mummies per female).

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Table A2-7: Effects of Exilis on mortality and reproduction of Aphidius rhopalosiphi in the laboratory

Mortality after 48 h of Treatment Reproduction after 13 days exposure Mean number of g Mean (%) g a.s./ha Corrected1 mummies/female % of control product/ha (SD) (SD) 7.5 11 Control - - - (9.6) (8.7) 10 4.6 230 n.d. n.d. (14) 23 7.9 14.7 735 72 (25) (6.0) 25 6.9 46.9 2345 63 (5.8) (9.2) 2.5 12 150 7500 106 (5.0) (6.6) 0 9.4 480 24000 87 (0) (5.0) 7.5 13 1536 76800 123 (15) (6.8) Roxion: 16 mL 100 n.a. Dimethoate/ha (0) 1 Calculated using Abbott’s formula. n.d. = not determined due to absence of toxicity in all tested rates in the mortality phase SD = Standard deviation

The mean parasitisation success of the wasps in the test item treatments ranged between 6.9 and 13 mummies per wasp. Since only minor toxicity (i.e no LR50) was found in the mortality phase in all tested rates, the lowest testing rate was left out for the reproduction phase. As reduction in reproduction in the test item treatments did not exceed 50% as compared to the control, the corresponding ER50 was determined directly from the raw data. A summary of the results obtained for mortality and reproduction is given in Table 10.5.1-2.

CONCLUSIONS

The 48-hour LR50 and the ER50 for reproduction was estimated to be > 76800 g Exilis applied at 200 L/ha (equivalent to > 1536 g a.s./ha).

Study Comments: The underlying study and the risk assessments is acceptable. The risk to athropods is acceptable. Agreed Endpoints: The toxicity of Exilis to the parasitoid wasp Aphidius rhopalosiphi was determined in a 48-hour mortality test under worst case laboratory conditions (i.e glass plates as substrate) and a subsequent 13-day fecundity test on non-treated barley plants infested with aphids, according to the IOBC/WPRS Guideline. Organisms were exposed to dried spray deposits of Exilis applied on glass surfaces at rates of 230, 735, 2345, 7500, 24000 and 76800 g product/ha (equivalent to 4.6, 14.7, 46.9, 150, 480 and 1536 g a.s./ha) at a volume of

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200L/ha. A control (deionised water) and a reference item (i.e Roxion, containing 375 g/L Dimethoate) were tested in parallel. Four replicates per test item treatment, control and reference item treatment were set up for the mortality assessment, 15 replicates per treatment for the reproduction assessment. Mortality and fecundity values of the control as well as mortality values of the reference item treatment were within the study validity criteria. The 48-hour LR50 and the ER50 for reproduction was estimated to be > 76800 g Exilis applied at 200 L/ha (equivalent to > 1536 g a.s./ha).

Reference: IIIA 10.5.1 Effects on Arthropods Other Than Bees

Report IIIA 10.5.1 /01, Sipos, K, 2007b, Document No: 07/394-335RA

Guideline(s): Yes Blumel et al. (2000)

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and methods Test Material Exilis 2% SL Formulation Description: Clear liquid Lot/Batch #: W0655B Active substance: 6-benzylaminopurine Content: 20.3 g a.s./L (measured) Reference substance: BAS 152 11 I (Dimethoate 400 g/L EC formulation)

Test animals Species: Predatory mites Typhlodromus pyri Source: Ecotoxicological Laboratory, LAB International Hungary Ltd. Age: Protonymphs, < 24 hours old after the moulting of the larvae Number: 100 mites per treatment, reference substance and control (5 replicates of 20 protonymphs)

Test design Duration: 7 days (mortality) Test units: Glass cover slides (60 x 60 mm; thickness 0.13-0.17 mm) attached with a glass bar in the horizontal direction with a square test arena of 10-13 cm2 made of pure tangle-foot-glue in which the mites were confined. The test units were placed individually on a layer of wet filter paper covering a glass plate on a water soaked foam sponge.

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Concentrations: - Control: deionised water applied at 200 L/ha - Test substance: 7.5 L Exilis 2% SL formulation/ha applied at 200 L/ha - Toxic standard: 15 ml/ha applied at 200 L/ha Application: With a calibrated sprayer (Schachtner Spray-Lab) at 2 mg/cm2 Food: Pollen from Pinus sp. was supplied every 3 days and tap water was provided ad libitum

Environmental conditions Temperature: 23.2 – 26.4 °C Relative humidity: 62 – 88% Photoperiod: 16 hours light : 8 hours dark (892 lux)

Animal assignment and treatment The test units were treated and placed separately in a tray with tap water. After the spray residue had dried (no later than 1.5 hours) the protonymphs were transferred to test arenas and left to develop under continuous exposure to the residue.

Dose preparations The test substance (7.8225 g) was diluted in 200 ml deionised water shortly before treatment to achieve an application rate of 7.5 L Exilis 2% SL formulation/ha in 200 L water/ha. The reference substance, BAS 152 11 I (Dimethoate 400 g/L EC formulation) was tested at 15 ml product/ha in 200 L water/ha. The treatments were applied with calibrated spraying equipment.

Observations The number of living, dead and escaped mites was counted on days 1, 3 and 7 after application. A reproduction phase was not performed.

Statistics The percentage mortality in the test substance and the reference treatment groups was corrected for mortality in the control group using Abbott’s formula (Abbott, 1925). The mean values of mortality were analysed by Dunnett’s Test.

RESULTS AND DISCUSSION

The cumulative mean mortality after 7 days was 2% in the water control group and 100% in the toxic reference group. The corrected mortality in the test substance treatment was -1.02% after 7 days. A summary of the results obtained for mortality is given in the following table. The 7-day

LR50 value was estimated to be higher than 7.5 L/ha Exilis 2% SL formulation.

Table A2-8: Mortality of Typhlodromus pyri exposed to fresh residues Exilis 2% SL formulation in the laboratory Mean mortality (%) Treatment (SD) Corrected mortality (%) 1 Day 1 Day 3 Day 7 0 2 2 Control - (0) (2.74) (2.74)

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Exilis 2% SL formulation: 0 0 1 -1.02 7.5L/ha (0) (0) (2.24) BAS 152 11 I: 15 mL 96 100* 100* 100 Dimethoate/ha (4.18) (0) (0) 1 Calculated using Abbott’s formula. * Statistically different to the control (ANOVA and Dunnett’s Test (α = 0.05)) SD = Standard deviation

CONCLUSIONS

In a worst case laboratory study with Typhlodromus pyri the 7-day LR50 value was estimated to be higher than 7.5 L/ha Exilis 2% SL formulation applied at 200 L water/ha.

Study Comments: The underlying study and the risk assessments is acceptable. The risk to athropods is acceptable. Agreed Endpoints: In a worst case laboratory study, Typhlodromus pyri (Acarina Phytoseiidae) were exposed to dried residues of Exilis 2% SL formulation on glass plates at a single concentration of 7.5 L product/ha applied at 200 L water/ha. The endpoints of the study were mortality after 7 days of exposure, including determination of the LR50. Assessment of mortality was carried out 1, 3 and 7 days after application. No reproduction phase was performed. After 7 days, mortality in the test item treatment was 1% (corrected mortality to the control: -1.02%). The LR50 could not be calculated and was determined to be higher than 7.5 L Exilis 2% SL formulation/ha.

IIIA 10.5.2 Effects on non-target terrestrial arthropods in extended laboratory tests

Reference: IIIA 10.5.2 Extended laboratory studies

Report IIIA 10.5.2/02, Vinall, S., 2011, Document No: FIN-11-1

Guideline(s): Yes, Bakker, et al (2000)

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and methods

Test Material Exilis 2% SL Formulation Description: Clear liquid Lot/Batch #: 1026359002 Active substance: 6-benzyladenine

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Content: 20.3 g a.s./L (measured) Reference substance: BAS 152 11 I (Perfekthion) batch 90924-06

Test animals Species: Orius laevigatus (Fieber) (Hemiptera: Anthocoridae) Source: BCP Certis, Asford, Kent, UK Age: Nymphs in the second nymphal stage Number: In each bioassay, there were ten replicate arenas per treatment, each containing 5 bugs (i.e. a total of 50 per treatment). For the reproduction assessments, 10 adult female bugs per treatment were confined individually, depending on the number of insects still available.

Test design Duration: Bug mortality 9 days Reproductive capacity of surviving bugs 4 days

Test units: Mortality assessments The test insects were exposed to residues on 38-mm-diameter leaf discs taken from the treated bean leaves. These discs were laid onto a double layer (approximately 20 mm in depth) of freshly-prepared agar medium (1% w/v agar in water). The top layer of agar (approximately 2 mm deep) was added shortly before the arenas were assembled, so that it was close to setting. The agar was contained in clear, slightly-tapering, plastic pots (35 mm deep x 35 mm internal diameter at the base and 40 mm internal diameter at the top). The top 1.5 cm of the internal walls of the pots had been treated with an aqueous suspension of Fluon® (polytetrafluoroethylene, ICI), so as to create a near-frictionless surface, to deter bugs from climbing upwards. To prevent the bugs from becoming stuck on the agar, silver sand was sprinkled onto any agar exposed between the leaf disc and pot wall and the excess then tipped away. The central area of the lids (nominally a 2 cm-diameter circle) had been removed and replaced with nylon netting (0.1 mm x 0.1 mm mesh), to allow ventilation.

Reproduction assessments Adult holding arenas: Between the mortality and reproduction assessments, the surviving bugs from each treatment were stored in 1-L-capacity, lidded, plastic bottles lined with tissue paper. The pots were fitted with clip-on lids, the centre of which was replaced with nylon netting (0.1 mm x 0.1 mm mesh) to allow ventilation. An untreated dwarf French bean seedpod (Phaseolus vulgaris L. The Prince) was provided for the adults and flour-moth eggs were supplied as food. Oviposition arenas: For the reproduction assessments, female bugs were individually confined in the same type of arena as used for the mortality assessments. However, the leaf discs laid on the agar were taken from untreated sweet-pepper plants (Capsicum sp. var. Bellboy). The abaxial (lower) surface of the leaf discs was set uppermost so that the midrib was exposed for the bugs to lay eggs in. Flour-moth eggs were provided as food.

Concentrations: - Control: purified water applied at 400 L/ha - Test substance: 7500 mL/ha (150 g a.s./ha) and 1200 mL/ha (24 g a.s./ha) applied at 400 L/ha - Toxic standard: 60 ml product/400 L water/ha Application: With a calibrated laboratory track-sprayer (Schachtner) at 4 mg/cm2 Food: Fed ad libitum with a supply of Ephestia kuehniella and sitotroga

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cerealetta. eggs

Environmental conditions Temperature: 25 – 26 °C Relative humidity: 65 – 78% RH Photoperiod: 1180 – 1500 lux, 16 hour photoperiod

Endpoints

Mortality assessments The percentage mortality of bugs in each treatment at 9 DAT was calculated, both before and after correction for control treatment losses using Abbott’s formula (Abbott, 1925). Any bugs that were missing by the end of the assessment period were reclassified as being dead, if there was no evidence of their having escaped from a faulty arena. The mortality in the individual test item treatments was compared to that in the control treatment by Fisher’s Exact Test (α = 0.05) (Sokal & Rohlf, 1981; SPSS, 2009).

Reproduction assessments The numbers of eggs assessed as ‘hatched’ or ‘unhatched’ at day 21 or day 23, for the two respective sample batches, were used to determine values for the mean number of eggs produced per female per day and the mean number of viable eggs/female/day. Where a bug had died during a 2-day assessment period, the data for this replicate and time period were excluded from any calculations.

The mean numbers of viable eggs/female/day were analysed using one-way analysis of variance (ANOVA) (α = 0.05) (Fowler & Cohen, 1990; SPSS, 2010). The percentage change in numbers of viable egg production in individual test item treatments, relative to the control, was also calculated using the equation:

% change = (1-Rt/Rc) * 100

where Rt and Rc are the absolute values for viable eggs observed in the treatment and control groups, respectively.

Statistical analysis The results were determined directly from the raw data.

RESULTS AND DISCUSSION

Mortality assessments The results of the bioassay on freshly-dried residues (initiated at 0 DAT) are summarised in Table 10.5.2-1. At 9 days of exposure to freshly-dried residues, the percentage mortality in the control treatment was 10%, which compared with 20% and 22% mortality in the 7500 and 1200 mL/ha treatment rates of Exilis, respectively. When corrected for control treatment losses, the percentage mortality in the respective test-item treatment rates was 11% and 13%. The toxic reference treatment resulted in 92% mortality (91% corrected).

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Table A2-9: The percentage mortality of bugs (n = 80 bugs per treatment) after 9 days

Treatment Rate [mL/ha] % mortality a Corrected % mortality b Control - 10 - 7500 20 11 Exilis 1200 22 13 Toxic reference 150 92 * 91 a the results for individual treatments were compared to the control using Fisher’s Exact Test (α= 0.05). Treatments that differed significantly from the control are marked with an asterisk (*). b Corrected mortality values calculated using Abbott’s formula (Abbott, 1925)

Reproduction assessments The results of assessments of egg production and viability in the bioassay on freshly-dried residues (initiated at 0 DAT) are summarised in Table 10.5.2-2. In the control treatment, there was a mean of 5.9 viable eggs laid per female per day. This compared with values of 5.7 and 7.4 viable eggs per female per day in the 7500 and 1200 mL/ha treatment rates of Exilis, respectively. None of the results differed significantly (ANOVA, α = 0.05).

Table A2-10: Summary of the reproductive performance of individually confined female bugs over a 4-day period Mean number Mean number of viable % change in viable Rate of eggs laid eggs per female per day Treatment a eggs relative to control [mL/ha] per female b per day Control - 6.3 5.9 - 7500 6.0 5.7 2.3 Exilis 1200 7.8 7.4 -25.6 a the results were compared by one-way ANOVA (α = 0.05), but there were no significant differences between treatments. b A positive value indicates a decrease and a negative value indicates an increase in reproduction, relative to control

Since both treatment rates of Exilis resulted in < 30% corrected mortality and < 30% reduction in reproduction, relative to the control during the bioassay with freshly-dried residues (bioassay initiated 0 DAT), the test with aged residues (initiated at 14 DAT) was ended without being completed.

CONCLUSIONS

The effects of Exilis on the predatory bug, Orius laevigatus, were evaluated under extended laboratory test conditions. No unacceptable effects on either survival or reproduction of the bugs were observed when they were exposed to freshly-dried residues (bioassay at 0 DAT) of Exilis applied at rates of 7500 and 1200 mL/ha (corresponding to 150 and 24 g a.s./ha, respectively) in 400 L water/ha.

Study Comments: The underlying study and the risk assessments is acceptable. The risk to athropods is acceptable. Agreed Endpoints: The effects of Exilis on the predatory bug, Orius laevigatus, were evaluated under

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extended laboratory test conditions. No unacceptable effects on either survival or reproduction of the bugs were observed when they were exposed to freshly-dried residues (bioassay at 0 DAT) of Exilis applied at rates of 7500 mL/ha (150 g a.s./ha) and 1200 mL/ha (24 g a.s./ha) in 400 L water/ha.

Reference: IIIA 10.5.2 Extended laboratory studies

Report IIIA 10.2.2.1/01, Kimmel, S., 2011b, Document No: D13180

Guideline(s): Yes, Hassan, S.A (1992) (7), Barrett, K.L. et al (1994) (3), Bakker, F.M et al (2000) (2)

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and methods Test Material Exilis 2% SL Formulation Description: Clear liquid Lot/Batch #: 1401440004 Active substance: 6-benzylaminopurine Content: 20.73 g a.s./L (measured) Reference substance: Dimethoate 375 g/L EC formulation, batch G339A

Test animals Species: Orius laevigatus (Fieber) (Heteroptera: Anthocoridae) Source: Katz Biotech AG, An der Birkenpfuhlheide 10, 15837 aruth/Germany Age: Nymphs in the second nymphal stage Number: 5 nymphs, 8 replicates for each treatment group in the exposure phase, one mated O. laevigatus female, 15 replicates per treatment for the reproduction phase.

Test design Duration: 10 days Test units: The test units used to assess effects of the test item consisted of small plastic petri dishes covered with a lid. The inner part of the lid was cut out and covered with a fine mesh netting to allow air exchange in the test unit The test unit was filled up with 20 mL of agar. Afterwards a bean leaf disc (French bean, Phaseolus vulgaris L., Fabaceae) was fixed on a solidified agar with a thin layer of fresh agar. The leaf was positioned with the lower leaf side facing upwards. Concentrations: - Control: deionised water applied at 200 L/ha

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- Test substance: 3.125, 6.25, 12.5, 25 and 50 g a.s./ha applied at 200 L/ha - Toxic standard: 30 mL product/ha Application: With a calibrated sprayer (Schachtner Spray-Lab) at 2 mg/cm2 Food: Fed ad libitum with a supply of Ephestia sp. eggs

Environmental conditions Temperature: 25 ± 2°C Relative humidity: 75 ± 15% Photoperiod: 2500 - 3000 lux, 1:8 day/dark rhythm

Endpoints Test organisms were counted as dead when they were motionless even after touching them with a fine hairbrush. Mortality was calculated by adding the number of bugs which had escaped to the number of those that had died.

Statistical analysis

The LR50 and ER50 was determined directly from the raw data.

RESULTS AND DISCUSSION

After 10 days exposure (endpoint of the mortality assessment), the mean mortality values in the control and in the reference item treatment were 20 and 100%, respectively, and were therefore within the set validity criteria (i.e. mean mortality in the control: up to and including 25%; mean mortality in the reference item treatment: between 50 and 100%).

The mean corrected mortality in the test item treatments was -3.1% in the second lowest test item treatment of 6.25 g a.s./ha, varied between 3.1 and 50% in the treatments from 3.125 to 25 g a.s./ha and was 56% in the highest test item rate with 50 g a.s./ha.

The LR50 was calculated to be 45 g a.s./ha (95% confidence interval: 22 – 89 g a.s./ha).

Mean egg production in the control was 11.2 eggs per female and per two days and was therefore within the validity criterion for fecundity (i.e. at least 2 eggs per female per day). The hatch of the larvae from eggs in the control was 85.4% equally to 9.6 successfully hatched larvae per female and was therefore within the validity criterion for fertility (i.e. at least 70% hatching success in the control).

The overall reproduction values in the test item treatments up to and including 6.25 g a.s./ha ranged between 8.7 and 9.5 fertile eggs per female resulting to 90 – 98% of the control values. In all higher treatment rates up to and including 25 g a.s./ha, no reproduction assessment was performed in the treatment with the highest test item rate of 50 g a.s./ha since mortality was > 50% in this treatment.

The ER50 and its 95% confidence interval could not be calculated since no reproduction values < 50 % of the control were observed. Therefore, the ER50 was determined to be > 6.25 g a.s./ha.

CONCLUSIONS

The 10 day LR50 and ER50 were estimated to be 2.2 L Exilis/ha and > 0.31 L Exilis/ha, respectively, corresponding to 45 g a.s./ha and > 6.25 g a.s./ha, respectively.

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Study Comments: The underlying study and the risk assessments is acceptable. The risk to athropods is acceptable. Agreed Endpoints: The toxicity of Exilis to the predatory bug Orius laevigatus was determined in 10 days of exposure to the test item under extended laboratory conditions i.e. bean leaf discs as substrate, according to the IOBC/WPRS Guideline. The test item rate were 3.125, 6.25, 12.5, 25 and 50 g a.s/ha, corresponding to 156.25, 312.5, 625, 1250 and 2500 ml Exilis/ha. A control, deionised water, and a reference item treatment, Roxion, containing 375 g Dimethoate/L, were tested in parallel. Eight replicates per treatment were set up. The mortality and reproduction values of the control and reference item were within the study validity criteria. The 10 day LR50 and ER50 were estimated to be 2.2 L Exilis/ha and >0.31 L Exilis/ha respectively.

IIIA 10.8 Effects on non-target plants IIIA 10.8.1.2 Vegetative vigour

Reference: IIIA 10. 8.1.2 Vegetative vigour

Report IIIA 10.8.1.2/01, Bramby-Gunary J , 2009, Document No: ACE-09- 133

Guideline(s): Yes, OECD 227

Deviations: None

GLP: Yes, certified laboratory

Acceptability: Yes

Original study Yes, indicates that study evaluation was corrected. evaluation revised by RMS

Materials and method: Test Material Exilis Description: Clear liquid Lot/Batch #: 1401440002 Active substance: 6-benzyladenine Content: 20.29 g a.s./L (measured) Vehicle and/or positive control: Deionised water Test species:

Class Species Family Common Variety BBCH growth name stage & mean height at appl. Monocot- Lolium -1 13-14 Graminae Ryegrass yledonae perenne 17.3 cm

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Triticum XU 193 14 Graminae Wheat aestivum 39.7 cm Mini pop2 14 Zea mays Graminae Maize 36.7 cm Dicot- Salvador4 12 Beta vulgaris Chenopodiaceae Sugar beet yledonae 13.2 cm Brassica Golden acre2 13 Brassicaceae Cabbage oleracea 15.7 cm Vigna radiata5 13 Vigna radiata Fabaceae Mung bean 39.4 cm Lycopersicon Moneymaker2 13 Solonaceae Tomato esculentum 17.4 cm

Source: 1) Herbiseed Ltd., Twyford, RG10 0NJ, UK. 2) E. W. King & CO. Ltd., Kelvedon, CO5 9PG, UK. 3) Walnes Seeds Ltd., Framlingham, IP13 9EE, UK. 4) Danisco Seed, Højbygårdvej 31, DK 4960, Holeby 5) Thompson & Morgan UK Ltd., Poplar Lane, Ipswich, England, IP8 3BU. Soil: The soil mix had been previously characterised as a sandy loam with an organic carbon content of ≤ 1.5% and pH of 7.4. Water: All pots were placed in saucers filled with enough water to ensure that the pots were kept moist at all time. Housing: Test plants were grown in non-porous plastic pots (volume of 0.525 L) from seedlings at BBCH growth stage 10. There were 20 plants per treatment and control for each species. Environmental conditions Temperature: 13.0 – 30.5 °C Humidity: 36.1 – 90.6% Photoperiod: 16 hours light : 8 hours dark (29800 lux)

Assignment and treatment: All the species were germinated in seed trays of Levingtons F1 compost and transplanted shortly after emergence at BBCH Growth Stage 10. The seeds were not coated with an insecticide or fungicide. Four seedlings per pot of each species were transplanted into 60 pots (9 x 9 x 10 cm). From the 60 pots per species, 40 pots were chosen for the application of the test item, each containing 4 uniform live plants, giving 20 plants per treatment. These 40 pots made five replicate pots per treatment for each plant species. Plants were grown in non porous pots containing the following soil mix: 20 litres of sterile loam + 10 litres of sand + 4 litres of coarse grit (washed quartzite, nominal 4 mm) + 100 g of slow release fertiliser. The soil mix has been previously characterised as a sandy loam with an organic carbon content of not more than 1.5% and the pH was determined as 7.4.

Dose preparation and application The highest concentration of spray solution was prepared by weighing 15.463 g Exilis and diluting with tap water to 1000 ml for the first application. For the second application 14.350 g Exilis was weighed and diluted with tap water to 1000 ml. Lower concentrations were prepared by serial dilution with tap water. Seven test item treatments (0.617, 1.85, 5.56, 16.7, 50, 150 and 300 g a.s./ha) and a water control were applied to each species. Applications were made at

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growth stage BBCH 12-14 at volume rates of 990.82 L/ha (ryegrass, wheat, maize and sugar beet) and 1067.68 L/ha (cabbage, mung bean and tomato). After application, the pots were placed on benches in glasshouse in blocks of species. Randomised assignment of the pots was used within each replicate.

Measurements/observations Prior to each of the two separate applications two aliquots, each approximately 50 ml, were taken from the highest rate of the test. One aliquot from each application was analysed using high performance liquid chromatography (HPLC).

The plants were assessed for visual injury expressed as a percentage of healthy untreated control plants, (0 % = no injury, 1 - 39 % = slight injury, 40 - 69 % = moderate injury, 70 - 99 % = severe injury and 100 % = all plants dead) and mortality at 14 and 21 days after application. Total foliar fresh weight (biomass per pot above soil level) was measured immediately after harvest at 21 days after application.

Statistics The descriptive statistics for calculating Analysis of Variance (AOV) Means were Least Significant Difference (LSD) with 5% significance level. EC50 values were calculated using audited mean values of final fresh weight per treatment and using simple probit – maximum likelihood estimation method with 95% confidence level. The No Observed Effect Rate (NOER) is the highest concentration at which no statistically significant adverse effect was observed (p < 0.05) when compared with the control.

RESULTS AND DISCUSSION

Chemical analysis The recovery rates for the active ingredient ranged from 103-108% and indicate that the spray solution was prepared to an acceptable level of accuracy.

Effects on plant survival No dead plants (i.e. 100 % survival) were recorded for Lolium perenne, Triticum aestivum, Zea mays, Brassica oleracea and Vigna radiate at all application rates and in the control. 95% survival was recorded for Beta vulgaris and Lycopersicon esculentum at 50 g a.s./ha and 1.85 g a.s./ha, respectively. The mean plant survival in the control treatment was 100% for all plant species.

The plants showed the following symptoms: Lolium perenne: Stunting, Triticum aestivum: Slight stunting, Zea mays: Stunting, Beta vulgaris: Stunting and leaf distortion, Brassica oleracea: Stunting, Vigna radiata: None and Lycopersicon esculentum: Stunting and slight distortion. No injuries were observed in the control plants. The mean level of injury observed at the highest tested dose rates ranged from slight injury for Lolium perenne, Triticum aestivum, Zea mays, Brassica oleracea, Vigna radiata and Lycopersicon esculentum (32%, 10%, 22%, 39% 2% and 34% injury respectively) to moderate injury for Beta vulgaris (54% injury). The percentage survival and visual injury expressed as a percentage of healthy untreated control plants are given in Tables 10.8.1.2-2 and 10.8.1.1-3.

Table A2-11: Mean survival and visual injury of the monocotyledon plant species

Rate Lolium perenne Triticum aestivum Zea mays (g a.s./ha) Ryegrass Wheat Maize

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Visual injury Visual injury Visual injury Survival Survival Survival (% of (% of (% of (%) (%) (%) control)* control)* control)* 0 (water) 100 0 100 0 100 0 0.617 100 6 100 0 100 0 1.85 100 16 100 0 100 2 5.56 100 28 100 2 100 10 16.7 100 20 100 0 100 8 50 100 16 100 4 100 14 150 100 22 100 6 100 28 300 100 32 100 10 100 22 * 0 % = no injury, 1 - 39 % = slight injury, 40 - 69 % = moderate injury, 70 - 99 % = severe injury and 100 % = all plants dead

Table A2-12: Mean survival and visual injury of the dicotyledon plant species Lycopersicon Beta vulgaris Brassica oleracea Vigna radiate esculentum Sugar beet Cabbage Mung bean Rate Tomato (g Visual Visual Visual Visual a.s./ha injury injury injury injury Surviva Surviva Surviva Surviva ) (% of (% of (% of (% of l (%) l (%) l (%) l (%) control) control) control) control) * * * * 0 (water 100 0 100 0 100 0 100 0 ) 0.617 100 4 100 2 100 0 100 4 1.85 100 8 100 2 100 0 95 12 5.56 100 16 100 8 100 2 100 16 16.7 100 24 100 8 100 6 100 18 50 95 32 100 18 100 2 100 16 150 100 36 100 16 100 0 100 19 300 100 54 100 39 100 2 100 34 * 0 % = no injury, 1 - 39 % = slight injury, 40 - 69 % = moderate injury, 70 - 99 % = severe injury and 100 % = all plants dead

Effects on foliar fresh weight The mean foliar fresh weights for the monocotyledonous and the dicotyledonous species are given in Tables 10.8.1.2-4 and 10.8.1.2-5, respectively.

Table A2-13: Mean foliar fresh weights for the monocotyledon plant species

Lolium perenne Triticum aestivum Zea mays Rate Ryegrass Wheat Maize (g a.s./ha) % of % of % of Mean (g) Mean (g) Mean (g) control control control 0 (water) 8.81 - 27.9 - 109 - 0.617 6.77 77 27.6 99 114 100 1.85 6.50 74 27.6 99 106 98 5.56 5.22* 59 27.1 97 105 96 16.7 6.93 79 27.7 99 99.6 92

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50 8.28 94 25.4 91 97.4 90 150 7.29 83 27.2 98 80.9* 74 300 6.93 79 26.8 96 96.1 89 * statistically significantly different from the control (p < 0.05)

Table A2-14: Mean foliar fresh weights for the dicotyledon plant species Lycopersicon Beta vulgaris Brassica oleracea Vigna radiate esculentum Rate Sugar beet Cabbage Mung bean Tomato (g a.s./ha) Mean % of Mean % of Mean % of Mean % of (g) control (g) control (g) control (g) control 0 (water) 68.7 - 105 - 37.2 - 97.2 - 0.617 63.4 92 102 97 33.2 89 73.6 76 1.85 62.4 91 94.3 90 34.9 94 78.4 81 5.56 57.1 83 92.6 88 35.6 96 69.4 71 16.7 51.0* 74 85.1* 81 32.2 87 67.0 69 50 48.8* 71 84.3* 80 33.8 91 67.9 70 150 53.1* 77 79.6* 76 39.1 100 65.2 67 300 35.6* 52 70.4* 67 35.7 96 58.9* 61 * statistically significantly different from the control (p < 0.05)

The ER50 and NOER values based on fresh weight are summarised in Table 10.8.1.2-1.

CONCLUSIONS

The results for all the tested species demonstrate a high tolerance to post-emergence application of Exilis. The ER50 values based on fresh weight data are therefore concluded to be greater than the highest concentration of Exilis tested, i.e. > 300 g a.s./ha. The fresh weight data for all of the monocotyledonous species tested (Lolium perenne, Triticum aestivum and Zea mays) indicates a high tolerance to post-emergence application of Exilis. Therefore, the NOER is determined to be 300 g a.s./ha. Of the dicotyledonous species tested in post-emergence application of Exilis, mung bean (Vigna radiata) has a NOER value based on fresh weight data equal to the highest concentration of Exilis tested (i.e. 300 g a.s./ha) demonstrating a high tolerance of Exilis. Of the remaining dicotyledonous species tested a NOER value based on fresh weight data for both Beta vulgaris and Brassica oleracea of 5.56 g a.s./ha indicates that these species are the most sensitive of dicotyledonous species tested in post-emergence application of Exilis followed by Lycopersicon esculentum with a NOER value based on fresh weight data of 150 g a.s./ha.

Study Comments: The underlying study and the risk assessments is acceptable. The risk to athropods is acceptable.

Agreed Endpoints: The ER50 values based on fresh weight data are therefore concluded to be greater than the highest concentration of Exilis tested, i.e. > 300 g a.s./ha

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Appendix 3 Table of Intended Uses justification and GAP tables

Crop and/ Zone Product code F Pests or PHI Remarks: or situation G Group of pests Formulation Application Application rate per treatment (days) or controlled (a) I (b) (c) (l) (m) Type Conc. method growth number interval kg as/hL water kg as/ha of as kind stage & min max between L/ha season applications min max min max (d-f) (i) (f-h) (j) (k) (min) min max

Apple Central Exilis F Fruit thinning and fruit SL 20 g/l Spraying Fruit between 7 1 Not relevant 0.0075 – 0.050 300 – 1000 0.075 – 90 days sizin improvement and 15 mm L 0.150 (BBCH 71-74)

Pear Central Exilis F Fruit thinning and fruit SL 20 g/l Spraying Fruit between 7 1 Not relevant 0.01-0.05 300 – 1000 0.10-0.150 90 days sizin improvement and 15 mm L (BBCH 71-74)

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Page 74 of 74

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REGISTRATION REPORT Part B

Section 6: Ecotoxicological Studies Detailed summary of the risk assessment

Product code Exilis

Active Substance 6-benzyladenine 20 g/L

Central Zone Zonal Rapporteur Member State: Germany

NATIONAL ADDENDA – Germany

Applicant Fine Agrochemicals Limited Date 12/2012

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Table of Contents TABLE OF CONTENTS...... 2 SEC 6 ECOTOXICOLOGICAL STUDIES...... 3 6.1 PROPOSED USE PATTERNS ...... 3 6.2 EFFECTS ON BIRDS (IIIA1 10.2) ...... 4 6.3 EFFECTS ON TERRESTRIAL VERTEBRATES OTHER THAN BIRDS (IIIA1 10.3) ...... 4 6.4 EFFECTS ON AQUATIC ORGANISMS (IIIA1 10.2)...... 4 6.4.1 Overview and summary ...... 4 6.4.2 Toxicity exposure ratios (IIIA1 10.2.1) ...... 4 14.1.2 Risk from metabolites...... 8 14.1.3 Acute toxicity of the preparation (IIIA1 10.2.2) ...... 8 14.1.4 Chronic toxicity to fish (IIIA1 10.2.5)...... 8 14.1.5 Chronic toxicity to aquatic invertebrates (IIIA1 10.2.6)...... 8 14.1.6 Accumulation in aquatic non-target organisms (IIIA1 10.2.7) ...... 8 14.2 EFFECTS ON BEES (IIIA 10.4) ...... 9 14.3 EFFECTS ON ARTHROPODS OTHER THAN BEES (IIIA 10.5)...... 9 14.3.1 Overview and summary ...... 9 14.3.2 Risk Assessment for Arthropods other than Bees...... 10 14.3.3 Using artificial substrates...... 11 14.3.4 Extended laboratory studies (IIIA 10.5.2)...... 11 14.3.5 Semi-field tests (IIIA 10.5.3) ...... 11 14.3.6 Field tests (IIIA 10.5.4)...... 11 14.4 EFFECTS ON EARTHWORMS AND OTHER SOIL NON-TARGET MACRO-ORGANISMS (IIIA 10.6) ...... 12 14.4.1 Overview and summary ...... 12 14.4.2 Toxicity exposure ratios for earthworms, TERA and TERLT (IIIA 10.6.1)...... 13 14.4.3 Acute toxicity (IIIA 10.6.2) ...... 14 14.4.4 Sublethal effects (IIIA 10.6.3) ...... 14 14.4.5 Field tests (IIIA 10.6.4)...... 14 14.4.6 Residue content of earthworms (IIIA 10.6.5) ...... 14 14.4.7 Effects on other non-target macro-organisms (IIIA 10.6.6)...... 14 14.4.8 Effects on organic matter breakdown (IIIA 10.6.7)...... 14 14.5 EFFECTS ON SOIL MICROBIAL ACTIVITY (IIIA 10.7) ...... 15 14.5.1 Overview and summary ...... 15 14.5.2 Laboratory testing (IIIA 10.7.1)...... 16 14.5.3 Additional testing (IIIA 10.7.2) ...... 16 14.6 EFFECTS ON NON-TARGET PLANTS (IIIA 10.8) ...... 17 14.6.1 Terrestrial plants (IIIA 10.8.1)...... 17 14.6.2 Effects on non-target aquatic plants (IIIA 10.8.2) ...... 19 14.7 OTHER NON-TARGET SPECIES (FLORA AND FAUNA) (IIIA 10.9)...... 20 14.8 SUMMARY AND EVALUATION OF POINTS 9 AND 10.1-10.10 ...... 21 14.8.1 Predicted distribution and fate in the environment and time courses involved (IIIA 10.11.1) ...... 21 14.8.2 Non-target species at risk and extent of potential exposure (IIIA1 10.11.2)...... 21 14.8.3 Short and long term risks for non-target species, populations, communities and processes (IIIA 10.11.3)...... 21 14.8.4 Risk of fish kills and fatalities in large vertebrates or terrestrial predators (IIIA 10.11.4)...... 21 14.8.5 Precautions necessary to avoid/minimise environmental contamination and to protect non-target species (IIIA 10.11.5) ...... 21 APPENDIX 1 LIST OF DATA SUBMITTED IN SUPPORT OF THE EVALUATION...... 23 APPENDIX 2 DETAILED EVALUATION OF STUDIES RELIED UPON...... 24 APPENDIX 3 RISK ENVELOPE RATIONALE FOR ECOTOXICOLOGICAL RISK ASSESSMENT FEHLER! TEXTMARKE NICHT DEFINIERT. Risk envelope for Soil:...... Fehler! Textmarke nicht definiert. Groundwater ...... Fehler! Textmarke nicht definiert. Surface water ...... Fehler! Textmarke nicht definiert.

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Sec 6 ECOTOXICOLOGICAL STUDIES Please refer to the core dossier for the central zone.

6.1 Proposed use patterns

Table 6.1-1: Critical use pattern of Exilis

Crop Application Max. individual Number of Minimum Application method application rate applications application timing [kg a.s./ha] interval (days) e.g. BBCH Apples/pears spraying 0.150 1 Not relevant Fruit between 7 and 15 mm (BBCH 71-74)

Consideration of metabolites No relevant metabolites were identified in the EU Review of 6-benzyladenine. The ZRMS has taken note of one new study on the degradation in soil of 6-benzyladenine. Hence one new metabolite (M8) needs to be considered. The metabolites to which non-target organisms could be exposed are presented in the table below. No relevant metabolites were identified in the EU Review of 6-benzyladenine. Therefore, the ecotoxicological risk has been considered for the active substance and the formulated product only. Table 6.1-2: Metabolites of 6-benzyladenine

Parent compound Compound found in Maximal percentage of occurrence [% of applied, lab. studies] M8 soil Max. 9.9% at day 3 (day 14 < 2%)

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6.2 Effects on birds (IIIA1 10.2)

Please refer to the core dossier for the central zone.

6.3 Effects on Terrestrial Vertebrates Other Than Birds (IIIA1 10.3)

Please refer to the core dossier for the central zone.

6.4 Effects on Aquatic Organisms (IIIA1 10.2)

6.4.1 Overview and summary Please refer to the core dossier for the central zone.

6.4.1.1 Toxicity Please refer to the core dossier for the central zone.

6.4.1.2 Exposure Calculations of PECsw for the active substance 6-benzyladenine was performed with Drifttox. The concentration of the active substances in adjacent ditch due to surface water runoff and drainage is calculated using den model EXPOSIT 3.0. For details see NA Part B, Section 5.6.

6.4.1.3 Overall conclusions For 6-benzyladenine as active substances the calculated TER values are above the trigger of 10 a buffer zone and spray drift reduction is not considered necessary. Regarding the entry pathway spray drift, it is concluded by the MS that the proposed use of Exilis will not pose an unacceptable risk to aquatic organism, if applied according to the recommended use pattern.

6.4.2 Toxicity exposure ratios (IIIA1 10.2.1)

For the active ingredient the most sensitive endpoint divided by the safety factor is EC50 = 0.31 mg/L (Lemna gibba). Exilis was not the representative formulation during the EU Review of 6-benzyladenine, but its active ingredient concentration and proposed use (1 x 150 g a.s. on apples and pears) are within what was considered for Annex I inclusion of 6-benzyladenine. However, the EFSA Conclusion (EFSA Journal 2010; 8(9):1716) states that the risk assessment for aquatic organisms could not be finalised. This was driven by the formulated product MaxCel being significantly more toxic than expected based on the content of the active substance. The toxicity data which are available for Exilis show that Exilis is less toxic for aquatic organism compared to the a.s. (see Table6.4-1 in the core dossier for the central zone).

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6.4.2.1 TER: Entry pathway spray drift and volatilization/deposition The calculation of concentrations in surface water is based on spray drift data by Rautmann and Ganzelmeier. The vapour pressure at 20 °C of the active substance 6-benzyladenine is < 10-5 Pa. Hence the active substance 6-benzyladenine is regarded as non-volatile. Therefore exposure of surface water by the active substance 6-benzyladenine due to deposition following volatilization does not need to be considered. The calculation of PECsw after exposure by spraydrift and deposition following volatilization using the model EVA 2.1 is not required.

The PECsw values after exposure by spraydrift and deposition following volatilization are calculated for the active substance 6-benzyladenine for the intended use in apples and pears (worst case application rate). The following table shows the calculated TER-values regarding the entry pathway deposition. Calculation is based on the model DRIFTOX 4.0 a.

6.4-1: Calculated TER-values regarding the entry pathway spray drift (Model: DRIFTOX 4.0 a)

Test compound: 6-benzyladenine Application rate: 1 x 150 g a.s./ha

DT50 (SFO): 3.1 d

PEC-selection: PECact Drift-Percentile: 90stes percentil, orchards late

Buffer zone Entry via deposition Entry via PECsw,max [µg/L]; ΣΣΣ Entry D + V [m] (D) volatilization (V)*) [%] [µg/L] [%] [µg/L] 0% red. 90% red. 75% red. 50% red. 0 100.00 50.00 - - 50.00 5.00 12.50 25.00 3 15.73 7.87 - - 7.87 0.79 1.97 3.93 5 8.41 4.21 - - 4.21 0.42 1.05 2.10 10 3.60 1.80 - - 1.80 0.18 0.45 0.90 15 1.81 0.91 - - 0.91 0.09 0.23 0.45 20 1.09 0.55 - - 0.55 0.05 0.14 0.27

Endpoint: EC50 = 310 µg/L (Lemna gibba) TER risk assessment trigger: 10 Buffer zone [m] TER 0 6.20 62.00 24.80 12.40 3 39.42 394.15 157.66 78.83 5 73.72 737.22 294.89 147.44 10 172.22 1722.22 688.89 344.44 15 342.54 3425.41 1370.17 685.08 20 568.81 5688.07 2275.23 1137.61 Risk mitigation measures : None * Not necessary since 6-benzyladenine is not volatile For 6-benzyladenine as active substances the calculated TER values are above the trigger of 10 a buffer zone and spray drift reduction is not considered necessary. Regarding the entry pathway spray

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6.4.2.2 TER: Entry pathway run-off and drainage The 6.4-3show the calculated TER-values regarding the entry pathways run-off and drainage. Calculation is based on the model Exposit 3.01. Risk assessment for these entry pathways is based on the crucial toxicity endpoint for 6-benzyladenine (EC50 = 310 µg/L, see above). For the input parameter see Table 6.4-2.

6.4-2: Input parameters for Exposit 3.01 6-benzyladenine Solubility in water (mg/L) 64.5

DT50 soil (d) 8

KOC 884

6.4-3: Calculated TER-values for diflufenican regarding the entry pathways run-off and drainage (Model: Exposit 3.01) compound: 6-benzyladenine Application rate: 1 x 150 g a.s./ha

Endpoint: EC50 = 310 µg/L TER risk assessment trigger: 10 Entry pathway run-off Buffer zone [m] PEC [µg/L] TER 0 0.27 1139 5 0.24 1314 10 0.20 1533 20 0.14 2190 Entry pathway drainage Time of application PEC [µg/L] TER Spring/summer 0.11 2859 Risk mitigation measures : None

For 6-benzyladenine as active substances the calculated TER values are above the trigger of 10. Regarding the entry pathways run-off and drainage, it is concluded by the MS that the proposed use of

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Exilis will not pose an unacceptable risk to aquatic organism, if applied according to the recommended use pattern.

6.4.2.3 TERA for fish (IIIA1 10.2.1) See above point 6.4.2.1

6.4.2.4 TERLT for fish (IIIA1 10.2.1.1) See above point 6.4.2.1

6.4.2.5 TERA for Daphnia (IIIA1 10.2.1.2) See above point 6.4.2.1

6.4.2.6 TERLT for Daphnia (IIIA1 10.2.1.3) See above point 6.4.2.1

6.4.2.7 TERA for aquatic insect (IIIA1 10.2.1.5) See above point 6.4.2.1

6.4.2.8 TERLT for aquatic insect (IIIA1 10.2.1.6) See above point 6.4.2.1

6.4.2.9 TERA for aquatic crustacean (IIIA1 10.2.1.7) See above point 6.4.2.1

6.4.2.10 TERLT for aquatic crustacean (IIIA1 10.2.1.8) See above point 6.4.2.1

6.4.2.11 TERA for aquatic gastropod mollusc (IIIA1 10.2.1.9) See above point 6.4.2.1

6.4.2.12 TERLT for aquatic gastropod mollusc (IIIA1 10.2.1.10) See above point 6.4.2.1

6.4.2.13 TERLT for algae (IIIA1 10.2.1.11) See above point 6.4.2.1

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6.4.2.14 TERLT for aquatic higher plant (IIIA1 10.8.2.1) See above point 6.4.2.1

6.4.4 Acute toxicity of the preparation (IIIA1 10.2.2)

Please refer to the core dossier for the central zone (IIIA 10.2.2.1 - IIIA 10.2.2.5).

6.4.4.1 Microcosm or mesocosm study (IIIA1 10.2.3)

Since all TERA and TERLT values exceed their respective Annex VI triggers, microcosm and/or mesocosm studies are not required.

6.4.4.2 Residue data in fish (IIIA1 10.2.4) Please refer to the core dossier for the central zone.

6.4.5 Chronic toxicity to fish (IIIA1 10.2.5) Please refer to the core dossier for the central zone.

6.4.6 Chronic toxicity to aquatic invertebrates (IIIA1 10.2.6) Please refer to the core dossier for the central zone.

6.4.7 Accumulation in aquatic non-target organisms (IIIA1 10.2.7) Please refer to the core dossier for the central zone.

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6.5 Effects on Bees (IIIA 10.4)

Please refer to the core dossier for the central zone.

6.6 Effects on Arthropods Other Than Bees (IIIA 10.5)

6.6.1 Overview and summary Please refer to the core dossier for the central zone.

6.6.1.1 Toxicity Please refer to the core dossier for the central zone. 6.6.1.2 Exposure Off-field The risk assessment for areas immediately surrounding the crop is considered important since these areas represent a natural reservoir for immigration, emigration and reproduction of arthropod populations and provide increased species diversity. Exposure of non-target arthropods living in off- field areas to Exilis will mainly be due to spray drift from field applications. Off-field PER values were calculated from in-field PERs in conjunction with drift values published by the BBA (2000)1 as shown in the following equation:

Maximum -in field PER x (% drift/100) Off - field foliar PER = vegetation distribution factor

A vegetation distribution factor was applied for the assessment for Typhlodromus pyri, Aphidius rhopalosiphi and Orius laevigatus accounting for the 2-dimensional structure treated in the test on this species. The most sensitive endpoint is the LR50 of44.5 g a.s./ha from the extended test with Orius laevigatus.

The drift value at 3 m distance is 15.73% of the application rate (90th percentile drift). The drift factor (% drift/100) is therefore 15.73/100 = 0.1573.

1 90th percentile drift according to BBA (2000): Bundesanzeiger Jg. 52 (Official Gazette), Nr 100, S. 9879-9880 (25.05.2000) Bekanntmachung über die Abtrifteckwerte, die bei der Prüfung und Zulassung von Pflanzenschutzmitteln herangezogen werden

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The resulting PERoff-field value is shown in the following Table:

Table 6.6-1: Off-field foliar Predicted environmental rates (PER)

Maximum in-field drift factor Vegetation Off-field PER Study type PER (% distribution (g a.s./ha) (g /ha) drift/100) factor 3-dimensional 1 23.6 150 g a.s./ha 0.1573 2-dimensional 5 4.72

6.6.1.3 Overall Conclusion With off-field TERs based on standard laboratory data above the trigger, no unacceptable risk of treatment with Exilis for non-target arthropods is indicated without any risk mitigation.

Table 6.6-2: Tier 1 off-field TER values for non target arthropods

Worst-case PER off- Trigger Endpoint Off- Test field Species Test type ER field value substance 50 (3 m) [g/ha] TER [ml product a.s./ha]

extended = 44.5 g Exilis Orius laevigatus laboratory, 2- 4.72 9.43 10* a.s./ha dimensional** *Tier 1 data **VDF = 5

Thus, based on the standard laboratory data for Exilis, a low off-field risk to non-target arthropods is indicated without risk mitigation measures.

6.6.2 Risk Assessment for Arthropods other than Bees 6.6.2.1 Off-field

The risk assessment for non-target arthropods is done on basis of the calculation of toxicity-exposure ratio (TER) values as in line with German national requirements according the following formula:

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TER = LR50 / ER50 [L product/ha] . max. exposure level x MAF x (% drift / 100 x correction factor “5”) [L product/ha]

The risk is considered acceptable if the off-field TER obtained is > 10 (tier 1) or > 5 (higher tier assessment).

The resulting TERoff-field values are given in the following Table:

Table 6.6-3: Tier 1 off-field HQs for non-target arthropods

Worst-case PER off- Trigger Endpoint Off- Test field Species Test type ER field value substance 50 (3 m) [g a.s./ha] TER [ml a.s./ha]**

Aphidius Glass plate, 2 d Exilis 1536 4.72 325 10 rhopalosiphi (13 d)

Typhlodromus pyri glass plate, 7 d 152.25 4.72 32.3 10 2D, leaves 44.5 4.72 9.43 10 Orius laevigatus 10 d **VDF = 5

The off-field TER values for A. rhopalosiphi and T. pyri are above the trigger value, indicating that Exilis does not pose an unacceptable risk to non-target arthropods in off-field areas. The risk for Orius laevigatus is slightly below the trigger value. But due to the conservative first tier assessment this deemed to be acceptable. Thus, based on the standard laboratory data for Exilis, a low off-field risk to non-target arthropods is indicated without risk mitigation measures.

6.6.3 Using artificial substrates Please refer to the core dossier for the central zone.

6.6.4 Extended laboratory studies (IIIA 10.5.2) Please refer to the core dossier for the central zone.

6.6.5 Semi-field tests (IIIA 10.5.3) Please refer to the core dossier for the central zone.

6.6.6 Field tests (IIIA 10.5.4) Please refer to the core dossier for the central zone.

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6.7 Effects on Earthworms and Other Soil Non-target Macro-organisms (IIIA 10.6)

6.7.1 Overview and summary Please refer to the core dossier for the central zone.

6.7.1.1 Toxicity Information about ecotoxicological endpoints for earthworms and other soil non-target macro- organisms is considered to be relevant for all countries. Therefore please refer to the core assessment Part B, section 6, chapter 6.7.1.1.

6.7.1.2 Exposure The risk assessments is conducted for an application rate of 150 g 6-benzyladenine/ha. For PEC calculations reference is made to the environmental fate section (Part B, Section 5, chapter 5.5 of the national addenda) of this submission. The worst-case PEC in soil is, in accordance with national requirements, calculated for the maximum concentration in the top 1-cm of soil (based on a KOC > 500 3 L/kg) or 2.5-cm of soil (based on KOC < 500 L/kg) with a soil density of 1.5 g/cm . As for the two parent compounds the KOC is above 500 L/kg, PECs are calculated for 1 cm soil depth.

The resulting maximum instantaneous PECsoil values for the active substance 6-benzyladenine and the major soil degradation product M8 are presented in the Table below.

Table 6.7-1: Maximum peak soil PEC values for CHA 1270 (expressed as a.s.), and the major soil metabolites

Relevance of metabolites 6-benzyladenine forms one major metabolite in soil: M8 (9.9 % at day 3). There are no toxicological studies for the metabolite M8 available. The metabolite reaches his maximum at day 3 after the application. Therefore the ZRMS considers the risk from the Metabolite M8 covered with the studies from the parent compound 6-benzyladenine.

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6.7.1.3 Overall conclusion The risk assessment results are summarized in the Table below. PECs were calculated in line with German national requirements.

Table 6.7-2: Toxicity/exposure ratios for soil-m0.3akroorganism after applications of 6- benzyladenine in orchards. soil relevant Endpoint PEC TER risk Test substance application Species (mg/kg (mg/kg TER assessment rate dw soil) dw soil) trigger (g/ha) Earthworms - acute 6-benzyladenine 150 E. fetida > 670 0.3 > 1000 10 mg/kg d.w. soil Earthworms – chronic n.n. Other soil makro-organisms n.n. TERs shown in bold fall below the relevant trigger. In conclusion, all TERs for the major soil degradation products are above the respective trigger values. Other soil non-target macro-organisms are not at risk following treatment with Exilis.

6.7.2 Toxicity exposure ratios for earthworms, TERA and TERLT (IIIA 10.6.1) 6.7.2.1 Acute risk The potential acute risk of Exilis and the active substance 6-benzyladenine as well as the major soil degradation products M8was assessed by comparing the maximum instantaneous PECsoil with the 14- day LC50 value to generate acute TER values. The log KOW value for 6-benzyladenine is above 2. Therefore, a correction of the endpoints is required in order to account for the relatively high organic matter content of the artificial test soil compared to agricultural soils.

The TERA was calculated as follows:

LC50 (mg/kg) TER A = PECsoil (mg/kg)

The resulting TERA values are shown in the following Table, considering the highest initial PEC in soil (i.e 70% interception during application):

Table 6.7-3: Acute TER values for earthworms following applications of 6-benzyladenine

Test substance Maximum initial Timescale LC50 or NOEC TER PEC (mg/kg) (mg/kg)

6-benzyladenine 0.3 14d acute LC50 > 1340 mg/kg > 1000 d.w. soil Corrected: LC50 > 670 mg/kg d.w. soil TERs shown in bold fall below the relevant trigger.

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Based on the worst case scenario, the acceptability criteria TER ≥ 10 for acute effects, according to Annex VI to directive 1107/2009 (EG), uniform principles, point 2.5.2.5 is reached.

6.7.2.2 Long-term risk There is no need to address the long term risk of the active substance 6-benzyladenine and its metabolite M8 for earthworms, because their degradation in soil (DT90 < 365 d, Kinetic, laboratory/field data) is fast.

6.7.3 Acute toxicity (IIIA 10.6.2) Please refer to the core dossier for the central zone.

6.7.4 Sublethal effects (IIIA 10.6.3) Please refer to the core dossier for the central zone.

6.7.5 Field tests (IIIA 10.6.4) Please refer to the core dossier for the central zone.

6.7.6 Residue content of earthworms (IIIA 10.6.5) Please refer to the core dossier for the central zone.

6.7.8 Effects on organic matter breakdown (IIIA 10.6.7) Please refer to the core dossier for the central zone.

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6.8 Effects on Soil Microbial Activity (IIIA 10.7)

6.8.1 Overview and summary Please refer to the core dossier for the central zone.

6.8.1.1 Toxicity Please refer to the core dossier for the central zone. 6.8.1.2 Exposure See section 6.7.1.2 of this document for the PECsoil values. 6.8.1.3 Overall conclusion The risk assessment results are summarized in the following Table:

Table 6.8-1: Relevant studies on soil microbial activity

Substance NOEC PECS (mg/kg), 25% MoS (< 25% effect at 28 d) foliar interception 6-benzyladenine 1.0 mg a.s./kg dw soil 0.3 3.33

Exilis applied at the proposed worst-case use patterns does not pose an unacceptable risk to soil microorganisms.

6.8.1.4 Toxicity exposure ratios SANCO/10329/2002 rev 2-final states that testing soil micro-organisms is always required when contamination of the soil is possible. The Predicted Environmental Concentrations of the formulation, the active substance and the major soil degradation product Exilis are below the concentrations at which no unacceptable effects (< 25%) were observed after 28 days of exposure. The results of the comparison expressed as Margin of Safety (MoS) is presented in the following Table:

Table 6.8-2: Risk assessment to soil micro-organisms

Substance Test type Maximum initial PEC Effects <25% MoS (mg/kg) (mg/kg) 6-benzyladenine N transformation 0.3 1.0 mg a.s./kg dw soil 3.33 C transformation 1.0 mg a.s./kg dw soil TERs shown in bold fall below the relevant trigger.

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For the active ingredient in Exilis, 6-benzyladenine ,and his metabolite the soil concentrations which caused no deviations greater than ±25% in the micro-organism studies are at least 10-times higher than the corresponding maximum PEC in soil. Based on the worst case scenario, the acceptability criteria according to directive 1107/2009 (EG), Annex VI, uniform principles, point 2.5.2.6 is reached.

6.8.2 Laboratory testing (IIIA 10.7.1) Please refer to the core dossier for the central zone.

6.8.3 Additional testing (IIIA 10.7.2) Please refer to the core dossier for the central zone.

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6.9 Effects on Non-Target Plants (IIIA 10.8)

6.9.1 Terrestrial plants (IIIA 10.8.1) 6.9.1.1 Overview and summary Please refer to the core dossier for the central zone. 6.9.1.2 Toxicity Please refer to the core dossier for the central zone. 6.9.1.3 Exposure Please refer to the core dossier for the central zone. 6.9.1.4 Overall conclusion The risk assessment results are summarized in the following Table: Table 6.9-1: Risk assessment for terrestrial non-target plants exposed to Exilis

Substance: Exilis Indication: 00-001 and 00-002 GAP: 1 x 150 g a.s./ha MAF: 1 Scenario/Percentile: 90.s Interception: None Distance Drift Volatilisation/ PECact (g/ha) (m) Deposition (incl. Volatilisation, Interception) (%) (g/ha) (%) (g/ha) konv. T. 90% Red. 75% Red. 50% Red. 3 15.73 23.6 - - 23.6 5 8.41 12.6 - - 12.6 relevant toxiciy: ER50 > 300 g/ha, sugar beet (veg. vigour test) relevant TER: 10 Distance (m) TER-values (calculated) 3 12.7 5 23.8 Risk mitigation: None

An acceptable risk to terrestrial non-target plants of treatments with Exilis in accordance with the proposed worst-case use pattern is indicated by TERs above the trigger of 5 at a distance of 3 m using standard application nozzles.

6.9.1.5 Toxicity exposure ratios For plant protection products exerting effects of more than 50% at the maximum application rate a quantitative second tier risk assessment based on dose-response endpoints represented by ER50 values is required according to the Terrestrial Guidance Document. The risk assessment based on the overall lowest effect endpoint for vegetative vigour for the actual formulation Exilis and the relevant predicted environmental rates in the off-field area after treatment with Exilis in accordance to the maximum proposed use rate of 7.5 L product/ha is presented in the following Table:

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Table 6.9-2: Risk assessment for non-target plants after applications of Exilis Substance: Exilis Indication: 00-001 and 00-002 GAP: 1 x 150 g/ha MAF: 1 Scenario/Percentile: 90stes Interception: None Distance Drift Volatilisation/ PECact (g/ha) (m) Deposition (incl. Volatilisation, Interception) (%) (g/ha) (%) (g/ha) konv. T. 90% Red. 75% Red. 50% Red. 3 15.73 23.6 - - 23.6 5 8.41 12.6 - - 12.6 relevant toxiciy: ER50 > 300 g/ha, sugar beet (veg. vigour test) relevant TER: 10 Distance (m) TER-values (calculated) 3 12.7 5 23.8 Risk mitigation: None

6.9.1.6 Seed germination (IIIA 10.8.1.1) Please refer to the core dossier for the central zone.

6.9.1.7 Vegetative vigour (IIIA 10.8.1.2) Please refer to the core dossier for the central zone.

6.9.1.8 Seedling emergence (IIIA 10.8.1.3) Please refer to the core dossier for the central zone.

6.9.1.9 Field testing (IIIA 10.8.1.4) Please refer to the core dossier for the central zone.

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6.9.2 Effects on non-target aquatic plants (IIIA 10.8.2) Please refer to assessment made under chapter 6.4.

6.9.2.1 Lemna growth test (IIIA 10.8.2.1) Please refer to the core dossier for the central zone.

6.9.2.2 Field tests (IIIA 10.8.2.2) Due to the acceptable risk at lower tier, no aquatic field tests are required.

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6.10 Other Non-Target Species (Flora and Fauna) (IIIA 10.9)

Not relevant.

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6.11 Summary and Evaluation of Points 9 and 10.1-10.10

6.11.1 Predicted distribution and fate in the environment and time courses involved (IIIA 10.11.1) The predicted distribution and fate of 6-benzyladenine in the environment is described in Part B, Section 5.

6.11.2 Non-target species at risk and extent of potential exposure (IIIA1 10.11.2) Please refer to chapter 6.11.3

6.11.4 Risk of fish kills and fatalities in large vertebrates or terrestrial predators (IIIA 10.11.4) Please refer to the core dossier for the central zone.

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Appendix 1 List of data submitted in support of the evaluation Please refer to the core dossier for the central zone.

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Appendix 2 Detailed evaluation of studies relied upon Please refer to the core dossier for the central zone.

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Appendix 3 Table of Intended Uses in Germany (according to BVL 19. December 2012)

PPP (product name/code) Exilis Formulation type: SL active substance 1 6-benzyladenine Conc. of as 1: 20 g/L

1 2 3 4 5 6 7 8 10 11 12 13 14

Use- Member Crop and/ F Pests or Group of pests Application Application rate PHI Remarks: No. state(s) or situation G controlled (days) or Method / Timing / Growth Max. number kg, L product / kg as/ha Water L/ha e.g. safener/synergist per ha (crop destination / I (additionally: Kind stage of crop & (min. interval ha purpose of crop) developmental stages of season between a) max. rate per a) max. rate max e.g. recommended or mandatory tank the pest or pest group) applications) appl. per appl. mixtures a) per use b) max. total rate b) max. total b) per crop/ per crop/season rate per season crop/season

00- DE Apple F Fruit thinning and fruit Spraying Fruit between 7 a) 1 a) 3.75 L/ha a) 0.150 kg/ha 500 90 and 15 mm (BBCH 001 sizin improvement days 71) b) 1

00- DE Pear F Fruit thinning and fruit Spraying Fruit between 7 a) 1 a) 3.75 L/ha a) 0.150 kg/ha 500 90 and 15 mm (BBCH 002 sizin improvement days 71) b) 1

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Applicant: Fine Agrochemicals Limited Evaluator: ZRMS Germany Date:12/2012 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 1 of 48

REGISTRATION REPORT Part B Section 7: Efficacy Data and Information Detailed Summary

Product Code: Exilis Reg. No.: 007524-00/00 Active Substance: 6-Benzyladenin 20 g/L

Central Zone Zonal Rapporteur Member State: Germany

CORE ASSESSMENT

Applicant: Scientific Consulting Company Date: 2011-10-11

Evaluator: Julius Kühn-Institut Date: 2012-07-30

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Table of Contents

IIIA1 6 Efficacy Data and Information on the Plant Protection Product...... 4 General information...... 4 Description of the plant protection product ...... 4 IIIA1 6.1 Efficacy data...... 4 Efficacy and climate ...... 4 IIIA1 6.1.1 Preliminary range-finding tests ...... 7 IIIA1 6.1.2 Minimum effective dose tests ...... 7 Trials from the Maritime zone ...... 7 Trials from the Mediterranean zone...... 12 Trials from the North Eastern zone...... 16 Trials from the South Eastern zone ...... 16 Synthesis across zones...... 17 IIIA1 6.1.3 Efficacy tests...... 20 IIIA1 6.1.4 Effects on yield and quality...... 21 Impact on the quality of plants or plant products...... 21 Effects on the processing procedure ...... 23 Effects on the yield of treated plants or plant products ...... 23 IIIA1 6.2 Adverse effects ...... 24 IIIA1 6.2.1 Phytotoxicity to host crop...... 24 IIIA1 6.2.2 Adverse effects on health of host animals ...... 24 IIIA1 6.2.3 Adverse effects on site of application ...... 25 IIIA1 6.2.4 Adverse effects on beneficial organisms (other than bees)...... 25 IIIA1 6.2.5 Adverse effect on parts of plants used for propagating...... 29 IIIA1 6.2.6 Impact on succeeding crops...... 29 IIIA1 6.2.7 Impact on other plants including adjacent crops ...... 30 IIIA1 6.2.8 Possible development of resistance or cross-resistance ...... 30 IIIA1 6.3 Economics ...... 30 IIIA1 6.4 Benefits...... 30 IIIA1 6.4.1 Survey of alternative pest control measures...... 30 IIIA1 6.4.2 Compatibility with current management practices including IPM...... 30 IIIA1 6.4.3 Contribution to risk reduction...... 30 IIIA1 6.5 Other / special studies...... 30 Procedures for cleaning application equipment ...... 30 IIIA1 6.6 Summary and evaluation of data presented ...... 33 IIIA1 6.7 List of test facilities including corresponding certificates ...... 33

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Appendix 1 List of data submitted in support of the evaluation...... 34 Appendix 2 GAP tables...... 46

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IIIA1 6 Efficacy Data and Information on the Plant Protection Product

General information This document summarises the information related to the efficacy data of the plant protection product Exilis containing 6-benzyladenine (6-BA) which was included into Annex I of Council Directive 91/414/EEC (Commission Directive 2011/1/EU of 3 January 2011). There are no concerns to address arising from the inclusion directive of 6-benzyladenine relating to efficacy.

6-BA was on List 4A of the list of existing active substances and was supported by a task force made of Valent Biosciences and Fine Agrochemicals Limited. A first Draft Assessment Report was produced in September 2007 and a Final Addendum to the Additional Report was published in July 2010. These documents are considered to provide the relevant review information.

6-BA containing products were registered in some European countries prior to the implementation of Directive 91/414/EEC and are therefore considered as ‘established’ products. In particular, Exilis is already registered in Greece, Italy and Spain for use as an apple thinner. It is also authorised in other countries like the United States, Canada, Argentina, South Africa, New Zea- land and Australia. It is under development in many other countries, especially in Europe. In France and the UK, it was granted a temporary use permit for 120 days in 2010 and 2011. Since this application, Exilis got registrations in several new countries: UK (apple and pear), France and Belgium as well as in Turkey.

Description of the plant protection product Exilis is a Plant Growth Regulator (PGR) containing the active substance 6-benzyladenine, a naturally occurring compound from the cytokinin family which is produced chemically. Exilis is formulated as a 2% (i.e. 20 gram/litre) 6-BA soluble concentrate. In pome fruit, Exilis is used as a post-bloom thinning agent with an additional effect on fruit size above and beyond the direct thinning effect. The mode of action of 6-BA in pome fruit thinning is to promote the abscission of fruits at the early stages of fruitlet development. The uptake of 6-BA is mainly through leaves and fruitlets. 6-BA is locally translocated in the foliage and the fruit and is therefore not regarded as a PGR with systemic activity. Following application and uptake, the PGR modulates photosynthesis and cell respiration in the developing fruit. In the days following application, the net photosynthesis is reduced while the net mitochondrial cell respiration is increased. The combined effect of a reduced carbohydrate production and accelerated cell respiration in the developing fruit enhances the competition for nutrients and promotes the abscission of less fit fruit. In addition, 6-BA promotes cell division in the developing fruit, leading to a higher cell count in fruit and creating the potential for bigger fruit independently from the thinning efficacy. Proposed uses of Exilis are supplied in the GAP table in Appendix 2.

IIIA1 6.1 Efficacy data

Efficacy and climate Exilis application timing for thinning and size improvement in apple and pear crops is related to the mode of action of the active substance 6-BA. It is determined (and limited) by 2 factors:

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- The developmental stage of the fruit: the crop load reducing and fruit size enhancing activity of 6-BA has been shown to be maximal when fruit are rapidly expanding and cell divisions are occurring at a fast pace. The fruit is very susceptible to carbohydrate starva- tion during this growth stage, leading to fruit abscission and fruit drop. In parallel, fruit that show extensive cell division activity benefit from the 6-BA application through an increase in cell count, thereby increasing the growth potential of the fruit. The proper fruit stage at treatment is therefore a key factor for the success of the treatment and this is not dependant on any climatic zone. - The average day temperature in the first 3-5 days following application: in order to maximise the competition between fruitlets, cell metabolism should be at a high level. At higher temperatures, cell respiration is increased and a more severe competition for carbohydrates is achieved. It has been reported that average day temperatures exceeding 15°C facilitate an effective thinning activity of 6-BA (Buban, 2000). Extremely high average day temperatures exceeding 25°C may lead to over thinning. Thus, the conditions required for a good efficacy of Exilis are simply conditions where trees are actively growing and this again is not dependant on a specific climatic zone.

The efficacy of Exilis as a post-bloom thinning product in top fruit is therefore not dependent on the climate zone in which the product is applied, but rather on the actual weather conditions at and just after the application of the product.

Based on a comparative study of existing agro-climatic studies developed for the EPPO region, Bouma (2005) identified four climatic zones within the EU: Maritime, North-East, South-East and Mediterranean. Within each region, it is considered that climate, soil and agronomical conditions are similar and results of efficacy and crop safety testing can be considered comparable. Nevertheless, based on the specific conditions of application of Exilis, larger zones can be considered as similar. In fact, apples and pears are produced under temperate climatic conditions. In Southern Europe, they are typically grown at higher altitudes or in other locations where moderate climatic conditions support the production of these fruit crops. Timing of flowering and fruit set will vary between locations and European regions, but the actual climate during the early stages of flowering, fruit set and physiological fruit drop will differ less than proposed by Bouma. Exilis is typically applied in early spring, usually within one month after full bloom. Treatment takes place from end of April until early June. Effect of the treatment is observed at the time of physiological fruit drop which usually occurs during June until early July. As far as climatic conditions are concerned, the main parameter influencing Exilis thinning efficiency is temperature at the time and just after the treatment, i.e. in May and early June. A comparison of the weather conditions and in particular the average minimum and maximum temperatures in different European areas where apples and pears are produced shows quite similar temperature conditions in the four EPPO zones, with rather limited differences (see Figure 1 below). Thus, results from each of the four zones as defined by Bouma can be used as supportive information for the application for Exilis in the Central zone.

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Figure 1: Average temperatures in April, May and June (based on Meteo France data)

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IIIA1 6.1.1 Preliminary range-finding tests The cytokinin 6-BA has been extensively evaluated for use in post-bloom thinning in pome fruit by various research stations throughout the European Union. Literature data support the fact that efficient rates of Exilis are in the range 5 to 10 L/ha (100 to 200 g/ha 6-BA) based on a water volume of 1000 L/ha (Buban, 2000; Wertheim, 2000; Lafer, 2006). Furthermore, post-bloom fruit thinners based on 6-BA have been commercially used for stimulating natural fruit drop for more than 10 years. Exilis has been on the market in several EU countries prior to the introduction of harmonised rules and well before the Annex I inclusion of 6-BA. Exilis and other 6-BA based PGR’s have been, and continue to be, used successfully to reduce crop load and increase fruit size in apple production. Most common use rates for Exilis are in the range of 5 to 7.5 L/ha. Based on these facts, the inclusion of preliminary range-finding tests for an established product was not considered as relevant.

IIIA1 6.1.2 Minimum effective dose tests Minimum effective dose tests have been carried out on apple and pear and are summarised hereafter by EPPO zone and by crop.

Trials from the Maritime zone Apple A total of 14 GEP trials and 6 non GEP trials were carried out with Exilis on apple between 1999 and 2010. They were located in Belgium, the Netherlands, Northern France, Germany or in the United Kingdom and were carried out by the official technical institutes and GEP certified organisations listed in the next table (see Table 1). All the trials were carried out according to national requirements for agrochemical product registrations as formulated by the various National Pesticides Agencies. The vast majority of trials were conducted according to widely recognised experimental practices which included a proper experimental setup with a fully randomised block design featuring at least 4 independent replicates per treatment. A full statistical analysis is presented in all trial reports where these statistical inferences were appropriate to calculate. The most recent trials were set up according to the EPPO guidelines and in particular EPPO 1/158 (3). Main deviations from EPPO guidelines were as follows:

Table 1: Testing facilities for the apple trials in Maritime zone Country Organisation Deviations from the EPPO guidelines GEP status Belgium PCFruit / Proefcentrum Fruitteelt No GEP (4 trials) + 1 non (former Research station of Gorsem) GEP trial from 1999 France La Morinière In some of the trials no formal statistical analysis GEP (3 trials) + 1 non (Northern was perfor-med and assessments on return bloom GEP trial from 2001 zone) were not always repor-ted. This has no impact on the quality of the available trial data. Germany LWK Niedersachsen OVA No GEP (2 trials) Netherlands Agro Research International No GEP (2 trials) Netherlands Applied Plant Research (PPO) Trial design consisted in 8 blocks of 1 tree. This 4 non GEP trials has no consequence on the quality of the trial: applications were performed using a shield and the higher number of replicates compensates the lower number of trees per replicate. United East Malling Research No GEP (3 trials) Kingdom

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Two parameters are used in this summary: fruit set and mean fruit weight. Those parameters were recorded in almost all the trials and give a clear reflection of product effect on fruit load and fruit size. For each parameter, results were transformed into a relative value towards the untreated, which made it possible to compare the efficacy of Exilis across trials, years and locations. The general formula used to calculate the indexes is as follows: Index = (value in the treatment / value in the untreated) x 100.

Exilis was tested on different varieties including: ‘Ariane’, ‘Braeburn’, ‘Bramley’, ‘Cox’, ‘El- star’, ‘Gala’, ‘Golden’, ‘Jonagold’, ‘Rubens’ and ‘Tentation’. Exilis, alone or in a programme, was applied at rates ranging from 2.5 to 20 L/ha and using a water colume comprised between 300 and 1000 L/ha. Exilis was diluted in water only or in conditioned water (mainly with LI700, an acidifying adjuvant, but Agral and Designer were respectively used in the Dutch trials from 1999-2000 and in the English trials). Exilis was typically applied when fruitlet diameter was between 7 and 14 mm.

Fruit set expressed as the number of fruits per 100 clusters was assessed in 17 trials on 10 cultivars. Relative fruit set was calculated. For each trial, only the assessment realised after June drop (or at the latest at harvest) was taken into account for this synthesis. In Table 2, results obtained with Exilis or Exilis + adjuvant are grouped as it is believed that adjuvant only improves product penetration in case of adverse conditions like low relative humidity at the time of treatment but does not allow a reduction of the rate of Exilis. The low rates of Exilis up to 5 L/ha showed a very limited reduction in fruit set in average in comparison with the untreated. At 7.5 L/ha, the average reduction in fruit set after Exilis application is in the order of 15%. The higher rates do not bring more efficacy on fruit set.

Table 2: Average relative fruit set in the apple trials in Maritime zone Treatment Dose FP/ha Dose AS/ha Average Min-Max Number of data Untreated 100.0 100-100 17 Exilis 2.5 L 50 g 94.1 92.3-96.6 4 Exilis 3.75 L 75 g 92.1 91.1-93.0 2 Exilis 5 L 100 g 96.7 78.2-107.3 12 Exilis 7.5 L 150 g 85.3 58.6-117.6 22 Exilis 10 L 200 g 97.7 93.2-102.2 4 Exilis 15 L 300 g 84.0 66.1-98.4 6 Exilis 20 L 400 g 89.5 89.5-89.5 1

The second parameter is mean fruit weight at harvest. It was assessed or could be calculated for 16 trials. In order to make the comparison between trials easier, a relative fruit weight index was calculated. On all the 9 cultivars tested, mean fruit weight was numerically improved by the Ex- ilis treatments. The summary by Exilis rate (pulling together data with and without adjuvant) in the following table shows that Exilis at 5 to 7.5 L/ha induces an increase in mean fruit weight of 7-8% in average in comparison with the untreated.

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Table 3: Average relative fruit weight in the apple trials in Maritime zone Treatment Dose FP/ha Dose AS/ha Average Min-Max Number of data Untreated 100.0 100.0-100.0 13 Exilis 2.5 L 50 g 102.6 94.4-112.3 4 Exilis 3.75 L 75 g 101.8 101.6-101.9 2 Exilis 4.8 L 96 g 112.0 112.0-112.0 1 Exilis 5 L 100 g 107.0 99.2-116.8 11 Exilis 7.5 L 150 g 108.4 95.6-142.6 21 Exilis 10 L 200 g 106.8 103.2-111.4 4 Exilis 15 L 300 g 104.3 90.3-116.8 6 Exilis 20 L 400 g 111.8 111.8-111.8 1

All those results indicate that rates lower than 5 L/ha did not provide a sufficient thinning effect while a dose of 7.5 L/ha of Exilis was able to induce a fruit load reduction in most of the situations and improved fruit weight (and size) by 5-10%.

Five trials allowed a comparison between Exilis without adjuvant at 5 and 7.5 L/ha and an untreated (see Table 4). A statistical analysis was run ( followed by N&K test at 5%) and showed a slight reduction in fruit set with both rates of Exilis, despite the bad results recorded in trial 6- BA182 (treatment on a day with average temperature <15°C). A reduction in the number of fruit at harvest in the order of 10% was obtained with both rates but there was a trend towards a better fruit size increase with the rate of 7.5 L/ha of Exilis, which increased fruit weight by 16% in average when the lower rate only brought a 7% increase even when no thinning effect was observed (6-BA182).

Table 4: Effect of Exilis at 5 and 7.5 L/ha on fruit set on apple in Maritime zone Internal report 6-BA182 6-BA183 6-BA175 6-BA177 6-BA188 average comparison number /untreated Country / Year Germany, UK, Belgium, Belgium, NL, 2010 2010 2008 2009 2010 Status GEP GEP GEP GEP GEP Cultivar Braeburn M. Gala Rubens Rubens G. Delicious Stage at treatment 6-8 mm 12 mm 12 mm 8 mm 12 mm Temperature n.a. OK OK OK OK around treatment Criteria: fruit set NS NS NS NS S NS CV=12.0 F treatment = 0.92 (F table 4.46) HS block effect Untreated 116.2 182 52.14 124.4 106.2 116.2 - Exilis 5 L/ha 102.9 178 50.14 120.3 86.2 107.5 -7.5% Exilis 7.5 L/ha 136.6 173.3 45.26 110.5 62.2 105.6 -9.1% Criteria: mean S S NS NS S NS fruit weight CV=8.6 F treatment = 3.98 (F table 4.46) HS block effect Untreated 99.3 97.6 175 149.1 150.8 134.4 - Exilis 5 L/ha 116 98.3 173.8 151.4 177.2 143.3 +6.6% Exilis 7.5 L/ha 116.7 109.5 182.1 158.5 215.0 156.4 +16.4%

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Pear A total of 6 GEP trials and 1 non GEP trials were carried out on pear since 2007. They were located in Belgium, the Netherlands, or Northern France and carried out by the official technical institutes or GEP certified organisations listed in the following table. The vast majority of trials were conducted according to widely recognised experimental practices which included a proper experimental setup with a fully randomised block design featuring at least 4 independent replicates per treatment. A full statistical analysis was presented in all trial reports where these statistical inferences were appropriate to calculate. Most of the trials were in line with the EPPO guidelines and in particular EPPO 1/158 (3). Main deviations from EPPO guidelines were as follows:

Table 5: Testing facilities for the pear trials in Maritime zone Country Organisation Deviations from the EPPO guidelines GEP status Belgium PCFruit No GEP (2 trials)

France (North- La Morinière No return bloom assessment available. This has no impact GEP (4 trials) ern zone) on the quality of the available trial data. Netherlands Applied Plant No return bloom assessment available. This has no impact 1 non GEP Research (PPO) on the quality of the available trial data. trial Trial design consisted in 8 blocks of 1 tree, but this has no consequence on the quality of the trial: applications were performed using a shield and the higher number of replicates compensates the lower number of trees per replicate.

The same efficacy criteria were used as for the apple trials, i.e.: fruit set and mean fruit weight. Those parameters were recorded in almost all the trials and give a clear reflection of product effect on fruit load and fruit size. For each parameter, results were transformed into a relative value towards the untreated, which made it possible to compare the efficacy of Exilis across trials, years and locations. The general formula used to calculate the indexes is as follows: Index = (value in the treatment / value in the untreated) x 100.

Exilis was mainly tested on Conference variety and also on Williams in one trial. Exilis was applied at rates ranging from 3.75 to 20 L/ha, alone or in a programme, and using a water colume of 1000 L/ha. Exilis was diluted in water only or in conditioned water (with LI700, an acidifying adjuvant). Exilis was typically applied when fruitlet diameter was between 7 and 12 mm. Exilis was mainly compared with the untreated plot in the trials.

Fruit set could be summarized from 5 trials, 4 on ‘Conference’ and 1 on ‘Williams’. Most of the trials showed some reduction in fruit set: significant differences between Exilis and the untreated could be observed in trial 6-BA106. In trial 6-BA136, no reduction in fruit set was observed, but it has to be highlighted that fruit set was very low as a consequence of the very severe physiological fruit drop which did not allow seeing the impact of the treatments. Average relative fruit set was calculated for each product rate over the 5 trials; calculation only took into account the latest assessments. The results showed a mean reduction in fruit set of 12% when Exilis was applied at 7.5 L/ha with or without adjuvant (see Table 6).

Table 6: Average relative fruit set in the pear trials in Maritime zone Treatment Dose FP/ha Dose AS/ha Average Min-Max Number of data Untreated 100.0 100.0-100.0 5 Exilis 5 L 100 g 107.7 107.7-107.7 1 Exilis 7.5 L 150 g 87.7 64.4-120.7 7

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Exilis 10 L 200 g 100.8 100.8-100.8 1 Exilis 20 L 400 g 95.5 95.5-95.5 1

Mean fruit weight was assessed or calculated in the 7 trials. An increase in mean fruit weight appeared in most of the trials. Indeed only 2 trials (6-BA180 and 6-BA136) do not show any improvement of the mean fruit weight. This could be explained by the climatic conditions during the experiments: treatments were applied during a cool and wet period in trial 6-BA180 which probably did not allow the product to work properly; in contrast, trial 6-BA184 was sprayed at the end of the cool and rainy period and showed particularly good results, both in terms of reduction in the number of fruit at harvest and in the mean fruit weight. In trial 6-BA136, a drought and a very hot period during summer was reported and resulted in small sized fruit in general. In this trial, it can be considered that Exilis probably exerted its effect by increasing the number of cells in fruit but it did not result in improvement in fruit size because of the growth conditions which were not in favour of fruit growth. Calculation of the average relative mean fruit weight in the next table confirms the previous comments.

Table 7: Average relative mean fruit weight in the pear trials in Maritime zone Treatment Dose FP/ha Dose AS/ha Average Min-Max Number of data Untreated 100.0 100.0-100.0 7 Hand thinning 114.8 114.8-114.8 1 Exilis 5 L 100 g 105.9 101.1-112.4 3 Exilis 7.5 L 150 g 104.4 92.7-116.5 10 Exilis 10 L 200 g 101.8 98.3-105.4 2 Exilis 15 L 300 g 115.0 115.0-115.0 1 Exilis 20 L 400 g 107.1 101.7-112.5 2

The results obtained in the pear trials confirmed those in apple in the Maritime zone: the dose of 7.5 L/ha of Exilis was able to induce a fruit load reduction in most of the situations and improved fruit weight.

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Trials from the Mediterranean zone Apple A total of 12 GEP trials and 18 non GEP trials were carried out on apple since 2000. They were located in Greece, Italy, Spain and Southern France and were carried out by the official technical institutes or GEP certified organisations listed below in Table 8. All the trials were carried out according to national requirements for agrochemical product registrations as formulated by the various National Pesticides Agencies. The vast majority of trials were conducted according to widely recognised experimental practices which included a proper experimental setup with a fully randomised block design featuring at least 4 independent replicates per treatment. A full statistical analysis is presented in all trial reports where these statistical inferences were appropriate to calculate. The most recent trials were set up according to the EPPO guidelines and in particular EPPO 1/158 (3). The most important parameters were recorded in the large majority of the trials even if assessments on return bloom were often not reported. However, this has no impact for the evaluation of product efficacy. Main other deviations from EPPO guidelines were as follows:

Table 8: Testing facilities for the apple trials in Mediterranean zone Country Organisation Deviations from EPPO guidelines GEP status France CEFEL No 1 non GEP trial France CEHM No GEP (1 trial) + 7 non GEP trials Greece Hellafarm S.A. No GEP (5 trials) Italy Cooperativa Ter- Only 3 blocks but no consequence on the quality of the GEP (1 trial) remerse assessments performed because the trial has a quite high number of treatments (> 7), therefore it was considered that there would not be any consequence on the statistical analysis. Italy Rivoira No 1 non GEP trial Italy University of Bo- Only 3 blocks but no consequence on the quality of the 1 non GEP trial logna assessments performed because the trial has a quite high number of treatments (> 7), therefore it was considered that there would not be any consequence on the statistical analysis. Spain Anadiag Ibérica No GEP (2 trials) Spain Fitoexpert No GEP (2 trials) Spain Fundacio Mas No 1 non GEP trial Badia Spain Inveresk Research No GEP (1 trial) Spain IRTA No 7 non GEP trials

Exilis was applied, alone or in programme, at rates ranging from 2.5 to 20 L/ha using water volumes comprised between 300 and 1700 L/ha. Exilis was diluted in water or in conditioned water depending on the trials (various adjuvants including LI700, ammonium sulphate, Silwet L-77, non ionic adjuvant, Sipcamol, Tween 20, Ovipron top, Agral, Tecnil, Mojarin). Fruitlet stage at the time of treatment was in the range 6-15 mm. Exilis was tested on different varieties including the ‘Golden’ group, the ‘Gala’ group, ‘Red Chief’, ‘Ariane’, Fuji’, ‘Hillwell’ ‘Hidala’, ‘Granny Smith’ and ‘Pink Lady’.

Main parameters used for the synthesis are the same as previously.

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Fruit set was calculated in 17 trials and 8 cultivars. Calculation of the average fruit set index over the whole set of trials is presented in table 11. It shows a mean reduction in fruit of 15% when Exilis is applied at 5 L/ha and 18% when it is used at 7.5 L/ha. The dose of 7.5 L/ha is the one that reduced fruit set in almost all the trials, which was not the case of the lower rates. Higher rates had a stronger effect on fruit set but risks of overthinning in case of hot conditions are pretty high as demonstrated by the minimum index value of 47.7 recorded with Exilis at 10 L/ha.

Table 9: Average relative fruit set in the apple trials in Mediterranean zone Treatment Dose FP/ha Dose AS/ha Average Min- Max Number of data Untreated 100.0 100.0- 100.0 15 Exilis 2.5 L 50 g 85.7 65.1- 99.4 4 Exilis 3.4 L 68 g 87.7 76.8- 98.6 2 Exilis 3.75 L 75 g 110.8 110.8- 110.8 1 Exilis 4.5 L 90 g 106.7 106.7- 106.7 1 Exilis 5 L 100 g 85.9 59.4- 112.6 7 Exilis 6.75-6.8 L 135 g 90.3 69.9- 105.1 3 Exilis 7.5 L 150 g 82.2 68.0- 100.6 16 Exilis 8 L 160 g 70.6 70.6- 70.6 1 Exilis 9 L 180 g 103.3 103.3- 103.3 1 Exilis 10 L 200 g 70.6 47.7- 87.9 4 Exilis 13.2-13.5 L 264-270 g 80.3 64.8- 95.8 2 Exilis 20 L 400 g 73.1 67.6- 78.6 2

Assessments on mean fruit weight were performed in 24 trials on 8 varieties. Almost all the trials showed some increase in fruit weight. In particular, statistical fruit weight increase was found in trials on ’Fuji’ and in some of the trials on ‘Golden’ and ‘Gala’. Calculation of the average relative fruit weight confirmed that a rate of 5-7.5 L/ha of Exilis allowed a fruit weight improvement of 5% in average in comparison with the untreated:

Table 10: Average relative fruit weight in the apple trials in Mediterranean zone Treatment Dose FP/ha Dose AS/ha Average Min - Max Number of data Untreated 100 100- 100 23 Exilis 2.5 L 50 g 104.7 98.8- 113.2 9 Exilis 3 L 60 g 102.3 99.3- 105.2 2 Exilis 3.4 L 68 g 100.7 100.3- 101.2 2 Exilis 3.75 L 75 g 102.4 100.5- 104.4 2 Exilis 4.5 L 90 g 101.0 100.0- 103.4 4 Exilis 5 L 100 g 106.4 100- 119 12 Exilis 6 L 120 g 105.9 100.4- 111.4 2 Exilis 6.75-6.8 L 135-136 g 102.7 96.4- 115.4 4 Exilis 7.5 L 150 g 105.1 96.6- 114.7 20 Exilis 8 L 160 g 123.3 123.3- 123.3 1 Exilis 9 L 180 g 117.6 100.3- 137.2 3 Exilis 10 L 200 g 111.7 102.1- 129.5 5 Exilis 13.2-13.5 L 264-270 g 101.5 99.9- 103.0 2 Exilis 20 L 400 g 112.9 108.4- 117.4 2

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Comparison between Exilis at 5 and 7.5 L/ha and the untreated was possible in few trials. For each of the parameters, a statistical analysis was done with a N&K test at 5%. Results are presented in the following tables (see Tables 11 and 12). Trial 6-BA057 was characterised by extremely high rate of blossom and fruit set, which placed the thinning product in a difficult situation. Nevertheless, even with a limited effect on fruit set, fruit weight was nicely increased in that trial. Overall, a slight numerical dose effect could be found for the 3 parameters and showed a fruit set reduction of respectively 4 and 7% at 5 L/ha and 7.5 L/ha. A more important reduction in the number of fruit at harvest was shown, with respectively 13% and 17% reduction in comparison with the untreated, resulting in a fruit weight increase of 5-6%. This clearly confirms the previous analysis.

Table 11: Effect of Exilis at 5 and 7.5 L/ha on fruit set in the apple trials in Mediterranean zone Treatment 6-BA057 6-BA103 average reduction/ untreated Untreated 156 158 157.0 - Exilis 5 L/ha 159.0 143 151.0 -3.8% Exilis 7.5 L/ha 148.0 143 145.5 -7.3% NS Statistical analysis CV=4.2 F treatment= 1.6 (Ftable= 19)

Table 12: Effect of Exilis at 5 and 7.5 L/ha on the mean fruit weight in the apple trials in Mediterranean zone Treatment average increase/untre 6-BA100 6-BA047 6-BA046 6-BA057 6-BA103 6-BA104 6-BA098 ated Untreated 177.1 119 133.15 121 104 154 165 139.0 b - Exilis 5 L/ha 180.6 136 146.92 127 108 158 165 145.9 a +5% Exilis 7.5 L/ha 171.1 135 152.71 134 118 157 163 147.3 a +6% Statistical analysis S CV=3.8 Ftreatment=4.6 (Ftable=3.9) HS block effect

Pear A total of 8 GEP trials were carried out on pear since 2007 but 6-BA187 was stopped before the normal end and was therefore not taken into account in this synthesis. In addition, trial 6-BA159 also suffered from hail storm damages and only the assessments before harvest could be considered. Trials were located in Italy, Southern France and Spain and were carried out by the official technical institutes or GEP certified organisations listed below. All the trials were carried out according to national requirements for agrochemical product registrations as formulated by the various National Pesticides Agencies and the EPPO guidelines, in particular EPPO 1/158 (3). This included a proper experimental setup with a fully randomised block design featuring 4 independent replicates per treatment. A full statistical analysis is presented in all trial reports where these statistical inferences were appropriate to calculate. Assess- ments on return bloom were not always reported. This has no impact on the quality of the trial data. Main other deviations from EPPO guidelines were as follows:

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Table 13: Testing facilities for the pear trials in Mediterranean zone Country Organisation Deviations from EPPO guidelines GEP status France La Pugère No GEP (4 trials) Italy Eurofins Agro- No GEP (1 trial) science Services Spain Anadiag Ibérica Trial design consisted in 4 trees per elementary plot and GEP (4 trials) assessments were performed on the 2 central trees, which slightly reduces the accuracy of the trial but does not have any consequence on the quality of the collected data.

Exilis was applied alone or in a programme at rates ranging from 3.75 to 15 L/ha using 1000 L/ha of water. It was applied on various cultivars (‘Blanquilla’, ‘Conference’, ‘Ercolini’, ‘Guyot’, ‘Louise Bonne d’Avranches’, ‘Williams’) when fruitlet stage was 8-14 mm. Exilis was diluted in water only or using LI700 in few trials.

Same parameters as previously are exposed hereafter. Fruit set was evaluated in 7 trials on 6 varieties. Five trials exhibited a numerical reduction in fruit set. Trial 6-BA145 did not present any decrease in fruit set, but this particular trial was characterised by a very important physiological fruit fall which may have resulted from the many rainy days in April and May where 200 mm were recorded. These conditions did not allow seeing the effect of the treatments. Also in trial 6-BA138 where target rates were not achieved (error at the time of application), no reduction in fruit set could be found. Average relative fruit set was determined for each Exilis rate based on the whole set of data and shows a 13% reduction in fruit set with Exilis at 7.5 L/ha in comparison with the untreated:

Table 14: Average relative fruit set in the pear trials in Mediterranean zone Treatment Dose FP/ha Dose AS/ha Average Min- Max Number of data Untreated 100.0 100- 100 7 Exilis 3.75 L 75 g 88.8 81.7- 95.8 2 Exilis 5 L 100 g 91.7 91. 7- 91. 7 1 Exilis 7.5 L 150 g 86.7 73.2- 110.2 11 Exilis 10 L 200 g 78.7 78.7- 78.7 1 Exilis 15 L 300 g 92.5 92.5- 92.5 1

Mean fruit weight was determined in 6 trials on 5 varieties. All the trials but one showed a slight fruit weight increase after treatment with Exilis at 7.5 L/ha. Synthesis of the results by Ex- ilis rate confirms a slight increase in fruit weight after Exilis application. It should be highlighted that the effect was not reached in all the trials and strongly depends on the weather conditions at the time of treatment and after the treatment: the first ones may limit product penetration and activity on the number of cells in the fruit, the latter ones can limit fruit growth in case of drought or extreme temperature conditions.

Table 15: Average relative mean fruit weight in the pear trials in Mediterranean zone Treatment Dose FP/ha Dose AS/ha Average Min- Max Number of data Untreated 100.0 100.0- 100.0 6 Exilis 3.75 L 75 g 103.0 98.9- 107.0 2 Exilis 5 L 100 g 98.8 98.8- 98.8 1 Exilis 7.5 L 150 g 102.0 93.8- 109.6 11 Exilis 15 L 300 g 100.4 100.4- 100.4 1

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The results obtained in the pear trials confirmed those in apple in the Mediterranean zone: the dose of 7.5 L/ha of Exilis was able to induce a fruit load reduction in most of the situations and slightly improved fruit weight.

Trials from the North Eastern zone Two trials were carried out in Poland in 1999 by the Research Institute of Pomology and Flori- culture from Skierniewice before the implementation of GEP certification in Poland. Neverthe- less they were conducted according to widely recognised guidelines and can therefore be used for registration purpose. Trials were conducted with a fully randomised block design featuring 6-12 independent replicates per treatment, each elementary plot consisting of 1 tree. Statistical analysis was presented when appropriate. Main deviations from EPPO guidelines 1/158(3) were as follows: - Assessments on return bloom were not performed in these trials. This has no impact on the quality of the other trial data. - Trial design consisted in 6-12 blocks of 1 tree, but this also has no consequence on the quality of the trial: the higher number of replicates compensates the lower number of trees per replicate. Exilis was applied at 7.05 or 8.9 L/ha with a spray to run-off on ‘Gala’ and ‘Jonagold’. Applica- tion took place at 10 mm king fruit diameter.

Relative fruit set: even if no statistical difference could be found on ‘Gala’, a numerical reduction in fruit set was observed after treatment with Exilis, which showed similar final level of fruit set as the reference. On ‘Jonagold’, Exilis appeared significantly different from the untreated. This could be explained by the lower initial number of fruit in the Exilis plots and the frost which drastically reduced fruit set despite an abundant bloom. Under such conditions, the volume of treatment solution applied, and by so doing the rate of Exilis applied, should have been adapted and lowered.

The thinning effect observed on ‘Gala’ resulted in a clear increase in mean fruit weight, at least equivalent to that of the references. On ‘Jonagold’ however, Exilis did not improve fruit weight.

Trials from the South Eastern zone A total of 4 trials were carried out on apple in 2003 in Slovenia, before the implementation of GEP certifications. Trials were set up by the Agricultural Institute of Slovenia. Trials were conducted with a fully randomised block design featuring 6-8 independent replicates per treatment, each elementary plot consisting of 1 tree. Main deviations from EPPO guidelines 1/158(3) were as follows: - Assessments on return bloom were not performed in these trials. This has no impact on the quality of the collected data. - Trial design consisted in 6-8 blocks of 1 tree, but this has no consequence on the quality of the trial: the higher number of replicates compensates the lower number of trees per replicate.

Exilis was tested on ‘Golden’ ‘Delicious’, ‘Idared’ and ‘Gala’. It was applied at various timings, from full bloom to fruit diameter of 25 mm, with a spray to run-off limit. With the assumption of a water volume of about 1000 L/ha which is reasonable for trees of 2-2.5 m height, rates of 1.25 to 20 L/ha were employed.

Fruit set assessment in ‘Gala’ did not show any impact of the treatments. This was probably due to the young trees used which suffered from drought. Results on ‘Golden’ ‘Delicious’ showed a very good efficacy on fruit set for all the treatments at 5 L/ha applied from end of bloom to

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 17 of 48 fruitlets of 20 mm in diameter. Variations could be observed but were probably more related to differences in the climatic conditions around treatments. In the other trial on ‘Golden’, Exilis rates of 1.25 and 2.5 L/ha proved not sufficient while 5 L/ha gave good results. On ‘Idared’, a slight numerical reduction in fruit set was obtained with the treatments applied between bloom and fruitlet diameterof 15 mm, however this did not reach the significance level, probably because of the very low rates of Exilis used in this trial.

Mean fruit weight was a reflection of the previous results and confirmed that the best position- ing of Exilis was on young fruitlets until 15 mm in diameter:

Synthesis across zones Apple To assess and compare the performance and efficacy of Exilis under the various regional climatic conditions within the EU, all available efficacy trial data were pulled together and graphically presented. In Figures 2 and 3, the data are represented in a scatter diagram showing the relation- ship between the dose of Exilis applied and the observed thinning effect respectively measured by the relative fruit set and the relative mean fruit weight. Individual data points represent the result of a unique trial/treatment/crop event while the four symbols used represent the climatic zone in which the trial was conducted. From Figure 2, it can be deduced that there is a clear tendency that an increase in dose rate does reduce fruit set. Both figures also show that no discrete clouds of data points originating from trials performed in a specific climatic zone within the EU can be observed. This observation im- plies that the efficacy of Exilis for thinning in apple and pear is not dependent on the geographic location or climate zone defined by Bouma or the EU. Interestingly, the data do support the view that the efficacy of Exilis is not dependent on the climatic zone in which a particular trial was performed. It is therefore reasoned that the comparability of Exilis trial data is not intrinsically dependent on the climatic zone in which the product was evaluated, but rather on the weather conditions at and directly following application.

Figure 2: Relation between relative fruit set and dose in the EPPO zones

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Figure 3: Relation between relative mean fruit weight and dose in the EPPO zone

Following this rationale, all the trials from the four EPPO zones presented in the previous pages were pulled together to present the final synthesis of Exilis efficacy on apple, focusing on two parameters: fruit set and mean fruit weight.

The following table shows how relative fruit set varies with the different rates of Exilis. Rate of 2.5 L/ha shows surprisingly good results with an average reduction in fruit set of 10% in comparison with the untreated, although it has to be highlighted that this rate was not tested on varieties which are very difficult to thin like ’Fuji’ or ‘Red Delicious’. The rate of 5 L/ha also provided 9% fruit set reduction in average, but it had no efficacy in 25% of the cases and reduced fruit set by more than 10% in 11 situations out of 28.

Table 16: Exilis application dose and relative fruit set (100= value in the untreated) in apple Exilis rate Average of fruit set Min Max Number of Number of Number of data (L/ha) index data data (>=100 <90 1.25 100.3 83.0 117.6 2 1 1 2.5 89.7 65.1 113.1 17 2 9 3.4 87.7 76.8 98.6 2 0 1 3.75 98.3 91.1 110.8 3 1 0 4.5 106.7 106.7 106.7 1 1 0 5 91.0 59.4 123.3 28 7 11 6.75-6.8 90.4 69.9 105.1 3 1 1 7 75.8 75.8 75.8 1 0 1 7.5 84.0 57.9 117.6 38 3 26 8 70.6 70.6 70.6 1 0 1 8.9-9 74.0 44.7 103.3 2 1 1 10 86.7 47.7 117.6 10 2 5 13.2-13.5 80.3 64.8 95.8 2 0 1 15 84.0 66.1 98.4 6 0 4 20 82.3 67.6 100.0 5 1 4

The rate of 7.5 L/ha presented an average fruit set index of 84, i.e. a fruit set reduction of 16%. Among the 28 situations where this rate was tested, no reduction in fruit set was reported in only

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3 cases while more than 10% fruit set reduction was achieved in 26 situations out of 38. Higher rate of 10 L/ha does not show any further efficacy

The same analysis was performed on relative mean fruit weight in comparison with the untreated. This comparison does not show any clear dose effect between the different tested rates, with a fruit weight increase in the order of 6-9% in average in comparison to the untreated:

Table 17: Exilis dose and relative mean fruit weight (100= value in the untreated) in apple Number of data (number of data Exilis rate (L/ha) Average of fruit weight index Min Max <=100) 1.25 106.1 100.0 112.1 2 (1) 2.5 106.0 90.0 119.8 22 (6) 3 102.3 99.3 105.2 2 (1) 3.4 100.8 100.3 101.2 2 (0) 3.75 102.1 100.5 104.4 4 (0) 4.5 101.0 100.0 103.4 4 (2) 4.8 112.0 112.0 112.0 1 (0) 5 106.2 94.6 119.0 32 (7) 6 105.9 100.4 111.4 2 (0) 6.75-6.8 102.7 96.4 115.4 4 (3) 7 118.2 118.2 118.2 1 (0) 7.5 106.8 95.6 142.6 41 (8) 8 123.3 123.3 123.3 1 (0) 8.9-9 112.8 98.3 137.2 4 (1) 10 108.8 100.0 129.5 11 (1) 13.2-13.5 101.5 99.9 103.0 2 (1) 15 104.4 90.3 116.8 6 (2) 20 108.2 94.3 117.4 5 (1)

Pear A similar analysis of the data obtained in pear was performed. Even if the number of data available on pear is lower than on apple, the same conclusion can be drawn: 7.5 L/ha is required to ensure at least 10% fruit set reduction in most of the situations:

Table 18: Exilis dose and relative fruit set (100= value in the untreated) in pear Exilis rate Average of fruit Min Max Number of Number of Number of (L/ha) set index data data (>=100 data <90 3.75 88.8 81.7 95.8 2 0 1 5 99.7 91.7 107.7 2 1 0 7.5 87.1 64.4 120.7 18 4 11 10 89.8 78.7 100.8 2 1 1 15 92.5 92.5 92.5 1 0 0 20 95.5 95.5 95.5 1 0 0

The average fruit weight increase is 3% when Exilis is applied at 7.5 L/ha:

Table 19: Exilis dose and relative mean fruit weight (100= value in the untreated) in pear Exilis rate (L/ha) Average of fruit weight index Min Max Number of data (number of data <=100) 3.75 103.0 98.9 107.0 2 (1) 5 104.1 98.8 112.4 4 (1) 7.5 103.2 92.7 116.5 21 (5) 10 101.9 98.3 105.4 2 (1) 15 107.7 100.4 115.0 2 (0) 20 107.1 101.7 112.5 2 (0) Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 20 of 48

IIIA1 6.1.3 Efficacy tests The same trials were used to demonstrate the efficacy of Exilis applied at 7.5 L/ha as in the previous section 6.1.2. All the results from the different EPPO zones were taken into account. Exilis at 7.5 L/ha (without adjuvant) was tested in a total of 33 trials, with 22 in apple and 11 in pear (Table 20). Two trials were carried out on apple by non GEP official institutes (1 in Spain and 1 in Southern France) but all other trials were GEP-compliant.

Table 20: Number and EPPO zone of the efficacy trials with Exilis applied at 7.5 L/ha Crop Year EPPO zone/country 2003 2004 2006 2007 2008 2009 2010 Total Apple Total Maritime 1 1 2 1 10 15 Belgium 1 1 1 3 France 1 1 Germany 1 1 2 Netherlands 1 3 4 UK 5 5 Total Mediterranean 1 1 2 3 7 France 2 3 5 Spain 1 1 2 Pear Total Maritime 2 1 1 2 6 Belgium 1 1 2 France 1 1 1 1 4 Total Mediterranean 1 2 2 5 France 1 1 1 3 Spain 1 1 2 Total 1 1 1 6 5 2 17 33

Table 21 shows a summary of Exilis efficacy to reduce fruit set and improve fruit weight in apple and pear. Results are expressed as indexes (untreated set to 100):

Table 21: Efficacy of Exilis at 7.5 L/ha (no adjuvant) Criteria Crop Fruit set index Fruit weight index EPPO zone No. data Average Min Max No. data Average Min Max Apple Maritime 15 87.9 62.1 117.6 14 105.7 95.6 117.5 Mediterranean 6 86.9 81.3 94.9 7 103.8 96.6 110.7 Grand Total 21 87.6 62.1 117.6 21 105.1 95.6 117.5

Fruit set Fruit weight index Row Labels No. data Average Min Max No. data Average Min Max Pear Maritime 4 93.7 73.0 120.7 6 102.6 92.7 113.6 Mediterranean 5 90.2 76.7 102.0 5 102.9 97.9 105.1 Grand Total 9 91.7 73.0 120.7 11 102.8 92.7 113.6

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These trials cover a large period of time and different climatic conditions. In apple as well as in pear, the trials show the same level of activity of Exilis in the Maritime and Mediterranean zone, as already proved in previous section. The results confirm that Exilis at 7.5 L/ha ensures an average reduction in fruit set of 10 to 15% on apple and about 10% on pear. In the mean time, fruit weight is increased by about 5% in apple and 3% in pear (more limited set of data).

A number of trials also showed that Exilis could be successfully used in the frame of a thinning programme including other chemical thinners.

IIIA1 6.1.4 Effects on yield and quality

Impact on the quality of plants or plant products Exilis is used as a plant growth regulator to reduce crop load in apples and pears through stimulation of fruit abscission and fruit drop. Applications of Exilis also lead to a potential increase in fruit size and weight but the actual effect achieved is dependent on the local climatic conditions and other fruit growth limiting factors like available water for root uptake etc. The product is used specifically for the purpose of improving fruit quality, indirectly through mild crop thinning and directly through the stimulating effect on cell division in developing fruit.

Impact of treatment with Exilis on quality of plants and plant products was evaluated in many individual efficacy trials presented in section 6.1.2 where one or more of the following parameters were assessed: leaf quality, pygmy fruit, fruit size and fruit weight, fruit shape, russet incidence, fruit quality parameters (firmness, sugar content, acidity, starch content, fruit mineral analysis...) at harvest or after few months storage, fruit coloration, number of seeds, return bloom in the year after the treatment. Main findings are summarised hereafter.

Leaf quality was assessed or described in 4 trials on apple and 2 on pear where Exilis was applied at rates up to 15 L/ha, alone or within a thinning programme. All trials demonstrated that Exilis did not have any impact on leaf quality.

Shoot growth was also assessed in 2 trials in apple and did not show any significant difference between the untreated and the trees treated with Exilis.

Pygmy fruit are small fruit which do not grow to normal size. Some apple cultivars are prone to produce pygmy fruit, even in the absence of thinning treatment. Impact of Exilis and thinning programmes on this parameter was evaluated in 4 trials (on ‘Ariane’, ‘Hillwell’ ‘Hidala’, ‘Red Chief’ and ‘Rubens’). Results show that Exilis does not increase the production of pygmy fruit in comparison with the untreated when it is applied straight or mixed with an adjuvant, even at rates much higher than the target rate of 7.5 L/ha. Increase in the number of pygmy fruit was found in ‘Red Chief’ and ‘Ariane’ when Exilis was combined with NAA or NAD with a late timing of treatment. In that last case, Exilis seems to amplify the production of pygmy fruit induced by auxin application. Therefore, a warning will be included in the label recommending not to mix Exilis with NAD or NAA (where available) on apple cultivars known to be prone to produce pygmy fruit.

Fruit size and fruit weight are correlated and important parameters to determine fruit selling price. Applications of Exilis lead to fruit abscission and drop but also to a potential increase in fruit size and weight. Nevertheless, the actual effect achieved is dependent on the local climatic

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 22 of 48 conditions and other fruit growth limiting factors like availability of water for root uptake etc. It was demonstrated in section 6.1.2 and 6.1.3 that Exilis had a beneficial effect on apple and pear fruit weight in most of the situations. Impact of Exilis on fruit size was also found in many trials with a shift in fruit size towards higher fruit diameters.

Fruit shape or a ratio fruit length / fruit diameter was evaluated in several trials on apple (14) and on pear (2) and did not show significant impact of the treatment with Exilis. A very slight fruit elongation was reported in few trials, which is considered of no impact on fruit quality.

Fruit skin quality and in particular russet incidence was evaluated in many trials in all the 4 zones (9 trials from Maritime zone, 4 from Mediterranean zone, 3 from the South East zone and 1 from the North East zone). These assessments showed no negative influence of Exilis on skin russeting on apple. This was verified when product is applied alone or in combination with an adjuvant or other thinning products containing NAA for example. In pear also, incidence of treatments on fruit skin quality was assessed in two trials and did not reveal any significant influence. The improved skin firmness may well be associated with the promotion of cell division in the developing fruit. An enlarged cell number is likely to have a positive effect on the structural strength of the fruit.

Fruit coloration was observed in 16 apple trials where Exilis was applied straight or in the frame of a thinning programme and did not show any significant effect of the treatment with Ex- ilis in comparison with the untreated.

Different parameters related to fruit quality analysis were assessed in the trials. Apple firmness at harvest or after few months’ storage was assessed in 9 trials and did not show any negative impact of Exilis on this parameter. Fruit firmness was also measured in 2 trials on pear and confirmed the observations in apple. Exilis does not have any negative impact on fruit firmness. Fruit acidity was measured in 5 trials in apple and soluble solid content was determined in 7 trials: neither of these parameters showed an alteration after Exilis application. In addition, starch index was assessed in 2 trials, mineral analysis was performed in one trial and storage disorders were evaluated in 2 trials. All those data show that Exilis does not alter fruit quality and fruit behaviour during storage.

Assessments on return bloom in the year after the treatment are reported in 8 trials in apple and 5 in pear: they show that Exilis had no negative effect on return bloom of apple and pear trees. Several trials even show an improved flowering in the year after the treatment with Exilis applied alone or within a thinning programme (1 trial on each of the following varieties: ‘Rubens’, ‘Golden’ Reinders’, ‘Elstar’, ‘Hillwell’ ‘Hidala’, ‘Louise Bonne d’Avranches’, and ‘Guyot’). The increase in flower bud formation (return bloom) may not represent a direct effect of 6-BA, but is rather a positive side effect of thinning, especially on the varieties prone to biennial bearing. It represents one of the principal reasons for thinning. The positive effect on return bloom was also reported in the literature in pear (Chabikwa, 2008).

Greene (2005) evaluated also the effect of several fruit thinners on return bloom and other side effects. Based on field trials over a 4-year period, he concluded that there are no direct adverse effects following repeated use of 6-BA in apple. This is confirmed by two 2-year trials carried out in the recent years in Belgium.

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Based on all the facts exposed above, it can be considered that Exilis applied at 7.5 L/ha in apple and pear will not have any negative impact on quality of plant and plant products. On the contrary, it will have a positive impact on fruit quality by improving fruit size and weight on the year of treatment.

Effects on the processing procedure Treatments with Exilis take place at an early stage of fruit development and do not leave any residue in pome fruit, as shown in the numerous residue trials presented for Annex I inclusion: all 24 European trials show less than 0.005 mg/kg at harvest and 35 US trials give similar results, even when product was applied at a higher rate than the target 7.5 l/ha (see DAR). A metabolism study on apple (MacKinnon I, 2008; see Part B Section 4 point 8.2) showed that main residue in the majority of the samples was 6-BA, with the only exception of fruit where 6- BA was no more detected 90 days after treatment. All metabolites were < 0.010 mg equiv/kg. Because the residues in fruit are not significant (< 0.1 mg/kg=LOQ), processing study was not required. However, a study was performed with apples (non protected study, see DAR). Product used for this study was Maxcel. Samples were harvested 80 days after the last of four applications, two applications at a rate of 74 g a.i./ha then two applications at a rate of 395 g a.i./ha. Part of the samples were processed into juice or wet pomace. Sample specimens were analysed with a method validated by ADC to the Agrisearch Method “6BA/Pome fruit/KLS/01/1” (LOQ of the analytical method: 0.005 mg/kg). The level of 6-BA was determined in apples and apple processed fractions and 6-BA levels in the edible processed fraction were found the same as in whole apple, so there was no concentration of residues during processing: residues < LOQ. The results of this study carried out with a higher rate of 6-BA can be extrapolated to Exilis, which formulation is similar to that of Maxcel (20 g/l 6-BA, SL formulation). It can be concluded that use of Exilis following the GAPs exposed in this dossier will not have any negative impact on pome fruit processing.

All these elements clearly indicate that there is no residue in fruit when Exilis is applied according to the proposed GAPs. As 6-BA is very similar to natural cytokinins, it can be concluded that use of Exilis in apple will not have any negative impact on fruit processing and on the quality of the final product. Exilis use is recommended on cider apple in France (Dupont, 2009). Because of the similarities between apple and pear uses, this also applies for processed pears.

Effects on the yield of treated plants or plant products One of the principal objectives for application of Exilis in apples and pears is to reduce the yield by reducing the total number of fruit per tree. No specific trials were conducted to assess the decrease in yield as quantitative assessments of crop load are an essential part of standard fruit thinning trials for product registration. The yield results obtained after one treatment with Exilis straight at 7.5 L/ha are presented hereafter (Table 22). Exilis impact in comparison to the untreated is in the range -18%-+20.6% in apple, and -21%-+7% in pear. Some clear differences in yield were recorded in few trials but most of the trials did only show a limited or no difference in yield between the Exilis treated trees and the untreated. This is in fact a consequence of the treatments which reduced slightly the number of fruit in trees, allowing a better fruit growth of the remaining fruit. This finally resulted in not much difference in yield, except in cases of over thinning.

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Table 22: Effect of Exilis at 7.5 L/ha on yield in the efficacy trials Crop EPPO zone No. trials untreated Exilis 7.5 L/ha Average value Min – Max Average rela- Min – Max (kg/tree) (kg/tree) tive value relative value Apple Maritime 11 27.6 12.92-51.01 97.3 82.4-120.6 Mediterranean 2 45.6 38.6-52.7 99.5 90.2-108.5 Pear Maritime 6 23.3 16.9-35.4 95.7 79.4-107.1 Mediterranean 5 40.8 18.5-54.4 96.9 91.5-102.7

On apple and pear, Exilis applied at 7.5 L/ha usually reduced crop yield very slightly, which is desired for a thinning product.

IIIA1 6.2 Adverse effects

IIIA1 6.2.1 Phytotoxicity to host crop The active substance of Exilis, 6-BA is similar to a naturally occurring plant hormone and at the rates of use recommended for Exilis, no serious levels of phytotoxicity is to be expected. This is supported by the absence of phytotoxicity in the field trials described in section 6.1.2 and 6.1.3.

Phytotoxicity to target plant products (fruit) In the literature, a potential negative effect of 6-BA application as a post-bloom thinner on apple skin russet has been reported (Wertheim, 2000). No significant increase in skin or stem end russet has been described in any of the Exilis registration trials. It is conceivable that the potential increase in russet incidence or severity is not directly influenced by either the active substance or co-formulant(s) of Exilis, but is more likely to be associated with the application of a significant water volume to the developing fruits, thereby inducing russet. A potential reduction of red pigmentation of the fruit is also reported as a negative side effect of 6-BA applications. This effect has not been reported in any of the trial reports. No other phytotoxic effects on the target plant product have been reported in the efficacy and crop safety trials included in this dossier.

Phytotoxicity to non target plant products (foliage) In the literature, more vegetative growth has been found associated with 6-BA applications when applied at dose rates of 100 mg/L or higher (Wertheim, 2000). Indeed, in non-bearing apple tree nurseries, 6-BA can be applied to improve feathering in young trees (Buban, 2000). For lateral shoot development, 2 to 4 sequential sprays of 6-BA are applied in a weekly interval at a rate ranging from 100 to 400 mg/L. Typically, these applications are targeted during exponential growth of the trees, which is usually in May or June, depending on the climate zone. The total dose applied for shoot development is 1.5 to 10 times higher compared to the top rate for 6-BA that is proposed for thinning in apple and pear. Based on these calculations, it is concluded that a potential negative impact of Exilis on off target vegetative growth is negligible. Given all these elements and trial results as well as the almost ten years of use of Exilis under field conditions in Spain and Italy, it can be concluded that Exilis will not induce phytotoxicity in the treated apple. It can be extrapolated that the risk of phytotoxicity on pear trees is extremely limited as well.

IIIA1 6.2.2 Adverse effects on health of host animals No data submitted by the applicant, due to not being an EC data requirement / not required by Directive 91/414/EEC.

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IIIA1 6.2.3 Adverse effects on site of application No data submitted by the applicant, due to not being an EC data requirement / not required by Directive 91/414/EEC.

IIIA1 6.2.4 Adverse effects on beneficial organisms (other than bees) Effects on relevant beneficial organism Results from laboratory tests with the tow standard test species (Aphidius rhopalosiphi and Ty- phlodromus pyri) and from extended laboratory tests with Orius laevigatus were submitted. In the test with Typhlodromus pyri 7.5 L/ha Exilis (corresponding to 2.0-fold recommended field application rate/ha and m crown) were applied on glass plates. This application rate led to no lethal effect. Investigations to sublethal effects (reduction of the number of eggs/female) did not take place in this test (Reference: Sipos, K., 2007; study code: 07/394-335RA). The results of the laboratory test with Aphidius rhopalosiphi and of the extended laboratory tests with Orius laevigatus are shown in Table 6.2.4-1 and 6.2.4-2. At the recommended application rate of 3.75 L/ha Exilis is not harmful (effect < 25%) for Aphi- dius rhopalosiphi. With Orius laevigatus no unacceptable effects (≥ 25%) on either survival or reproduction of the bugs were observed in the higher tier test (using leaves from treated bean plants) when Exilis was applied at 2.0-fold recommended field rate/ha and m crown. Aphidius rhopalosiphi (indicator species) and Orius laevigatus are not relevant antagonists for the proposed crops (apple and pear), however. Results to sublethal effects of Exilis on Typhlodromus pyri are not available. Therefore, the effect of Exilis on the predatory mite Typhlodromus pyri cannot be evaluated finally.

Table 6.2.4-1: Effects of Exilis on Aphidius rhopalosiphi (exposed stage: adult animals) in a laboratory test (substrate: glass) Application rate Corrected mortality Effect on capacity of para- Reference sitism [L/ha] [%] [%]

0.230 -4.5 - Kimmel, S., 2011;

0.735 2.7 28.2 D25464

2.345 18.9 37.3

7.500 -5.4 -9.1

24.000 -8.1 14.5

76.800 -8.1 -18.2

Table 6.2.4-2: Effects of Exilis on Orius laevigatus (exposed stage: nymphs) Application rate Corrected mortality Effect on fertility Reference [L/ha] [%] [%]

1 Laboratory test using bean leaves

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0.156 3.1 1.0 Kimmel, S., 2011;

0.312 -3.1 9.4 D13180

0.625 50.0 -

1.25 34.4 -

2.5 56.3 -

LR50 = 2.2 L/ha (95% confidence limits: 1.1 L/ha – 4.5 L/ha)

2 Laboratory test using leaves from treated bean plants Vinall, S.;

FIN-11-1

1.2 13.0 -25.6

7.5 11.0 2.3

Conclusion Exilis is classified as not harmful for populations of relevant beneficial insect species.

Effects on soil quality

Effects on soil macro-organisms being used as indicators of soil quality

Effects on earthworms Duration, Test product Endpoint Value Dimension Reference organism ZAB 023/022953; Acute, 14 d Mortality 6-benzyladenine > 1000 mg/kg soil EFSA Journal Eisenia fetida LC 50 2010; 8(9):1716

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Exposure

Proposed use pattern Application rate per treatment Number of Growth stage Crop Active substance applications (BBCH) Product (l/ha) (g a.s./ha) Pome fruit 1 71 150 3,75

Description of the PECs assessment

Predicted environmental concentrations in soil (PECsoil) have been calculated assuming that residues were evenly distributed through the upper 1 cm (as the mean Koc is 896 mL/g) of soil and the soil had a bulk density of 1.5 g/cm³. Full details of these calculations can be found in Section 5, IIIA 9.4.

The following risk assessment has been conducted in line with SANCO/10329/2002, on the basis of one application to apples and pears at an application rate of 150 g a.s./ha, at a growth stage BBCH 71 (development of fruit) and assuming that only 20% of the applied dose reaches the soil surface. The acute TER was calculated by comparing the maximum initial PECsoil assuming distribution to 1 cm depth, with the acute toxicity endpoint.

Proposed crop interception: 80%

Risk assessment (Toxicity exposure ratios, TERA and TERLT)

Acute risk

The potential acute risk of the parent compound and its metabolites to earthworms was assessed by comparing the maximum instantaneous PECS with the 14-day LC50 value to generate acute TER values. The log POW value of the active substance/compound is below 2, and hence there was no need to reduce the LC50 by a factor of 2 in order to account for the relatively high organic matter content of the artificial test soil compared to agricultural soils.

The TERA was calculated as follows:

LC (mg/kg) TER = 50 A PEC (mg/kg) S

The resulting TERA values are shown in the following Table.

During the EU Review of 6-benzyladenine it was concluded that as the acute TER based on the active substance data was greatly in excess of the trigger value (e.g. 100 fold) studies on the formulated product were not considered necessary. This scientific argument remains true and studies on the formulated product Exilis are not required.

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Acute TER values for earthworms LC Maximum PEC Risk assess- Parent com- 50 S Test substance (mg/kg dry (mg/kg dry soil) TER ment trigger pound A soil) 1 cm Active sub- 6-benzyladenine > 500 1) 0,200 > 2500 10 stance 1 ) The LC50 value has been divided by 2, since the log Pow for of 6-benzyladenine is > 2

Long-term risk It was agreed during the EU Review that a study assessing the sublethal effects of 6- benzyladenine on earthworms was not required. The critical GAP for the proposed use of Exilis is within the risk envelope of the EU assessment and hence such a study is considered not necessary.

Conclusion The above acute TER value greatly exceeds the trigger value of 10. Thus, the risk to earthworms from the proposed uses of Exilis is considered to be acceptable, without any further consideration required.

Field tests Not required as an acceptable risk to earthworms was identified, based on the laboratory studies available.

Effects on other non-target macro-organisms It was agreed during the EU Review that a study assessing the effects of 6-benzyladenine on other non-target macro-organisms was not required. The critical GAP for the proposed use of Exilis is within the risk envelope of the EU assessment and hence such a study is considered not necessary.

Effects on organic matter breakdown It was agreed during the EU Review that a study assessing the effects of 6-benzyladenine on organic matter breakdown was not required. The critical GAP for the proposed use of Exilis is within the risk envelope of the EU assessment and hence such a study is considered not necessary.

Overall conclusion with respect to effects on soil macro-organisms It is concluded that the proposed use of EXILIS will not pose an unacceptable risk to populations of earthworms or other soil macro-organisms, when applied according to the recommended use pattern.

Instructions and information: None

Effects on soil micro-organisms being used as indicators of soil quality

Effects on soil non-target micro-organisms exposed to Exilis

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Effects on soil non-target micro-organisms exposed to (a.s.) and (product) Test concen- Test material tration (mg/kg Result Reference soil)* 0.2 – 1.0 C-mineralization – no effect after 28 d EFSA Scientific Report 6-benzyladenine EFSA Journal 2010; 0.2 – 1.0 N-transformation – no effect after 28 d 8(9):1716

Risk assessment for soil microflora functions The results of these studies showed no effects of > ± 25% compared to the control on soil microbial activity up to a maximum tested concentration of 1.0 mg a.s./kg soil, after 28 days. As this maximum tested concentration was much higher than the maximum initial PECsoil (0.200 mg a.s./kg) calculated based on the specific requirements for Germany. As the proposed use of Exilis an acceptable risk to soil microbial activity can be concluded.

Overall conclusion with respect to effects on soil quality There is no indication of any unacceptable adverse effects on soil macro- or soil micro- organisms relevant for the maintenance of soil quality.

IIIA1 6.2.5 Adverse effect on parts of plants used for propagating Propagation of apple (Malus domestica) and pear (Pyrus communis) is exclusively done through clonal reproduction. This propagation is usually controlled by specialised nurseries where certified, disease free twigs of a specific cultivar are grafted onto specifically produced rootstock. In commercial apple and pear production within the EU, plant material from bearing trees in commercial orchards is not used for grafting. Any exposure of 6-BA to orchard trees will therefore not be linked to the propagation cycle in apple or pear. Even in the very unlikely case where plant material of bearing trees will be used for propagation, it is not likely that Exilis applications will have an effect on propagation. Given the natural occurrence of cytokinin plant hormones in apple and pear, it is highly unlikely that exogenously applied 6-BA will have a notable effect on propagation as the timing of Exilis 6-BA application for post-bloom thinning in apple and pear is in early spring while grafting onto rootstock is typically done in winter. Given the lack of persistence of 6-BA in the plant, it is not likely that there will be an effect on (flower) bud development on the grafted plant. For all these reasons, Exilis applied at 7.5 L/ha will not have adverse effect on parts of plants used for propagating.

IIIA1 6.2.6 Impact on succeeding crops Exilis is sprayed on to perennial tree foliage. The active ingredient 6-BA is characterised by a short half-life in soil (DT50 in soil of 8 days) and PHI will be 90 days. Therefore, there is no risk of negative impact on the perennial tree the year after the treatment with Exilis. This was confirmed by the 2 trials carried out on the same trees for 2 years. In case when the treated trees would be removed and replaced by a young orchard or any other crop, no effect of the treatment is expected on the new crop given the rapid degradation of the active substance in soil. Based on the available literature and the trial results, it is concluded that Exilis can be safely applied as a post-bloom thinning product without having a negative impact on return bloom and alternate bearing. Moreover, there is no risk of significant residues of 6-benzyladenine in succeeding crops. Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 30 of 48

IIIA1 6.2.7 Impact on other plants including adjacent crops Exilis is applied on orchard at a maximum dose of 7.5 L/ha. Taking into account the spray drift data in fruit crop for a late application and the minimum distance of 3 meters (15.73%), the TER ratio appeared to be well above the trigger value for both the seedling emergence and the vegetative vigour. It can then be concluded that in the worse case, Exilis application is not going to cause damage to adjacent crop because of drift. -6 Furthermore, pure 6-benzyl adenine vapour pressure (5.5.10 Pa) is low, indicating that it has a very low possibility to volatilise from soil to air. The active substance also has a very low possibility to volatilise from water to air. Thus, Exilis applied on pome fruit tree will not have any detrimental effect on neighbouring crop because of volatilisation.

IIIA1 6.2.8 Possible development of resistance or cross-resistance Exilis is used as a plant growth regulator reducing crop load in apple and pear by stimulation of natural fruit drop (June drop). The product contains the cytokinin 6-BA as sole active substance. 6-BA is a naturally occurring plant hormone. Most mutations leading to resistance (or in this case rather increased tolerance) to cytokinins in general or 6-BA specifically will be of a recessive nature and will not be expressed in plants. New genotypes that have either dominant alleles or homozygous recessive alleles leading to 6-BA resistant plant phenotypes will have a very low fitness as normal plant growth and development will be severely affected. Plants with increased tolerance to cytokinins are therefore not viable from an agronomic point of view. It is considered that the possible occurrence of resistance is therefore not relevant.

IIIA1 6.3 Economics No data submitted by the applicant, due to not being an EC data requirement / not required by Directive 91/414/EEC.

IIIA1 6.4 Benefits

IIIA1 6.4.1 Survey of alternative pest control measures No data submitted by the applicant, due to not being an EC data requirement / not required by Directive 91/414/EEC.

IIIA1 6.4.2 Compatibility with current management practices including IPM No data submitted by the applicant, due to not being an EC data requirement / not required by Directive 91/414/EEC.

IIIA1 6.4.3 Contribution to risk reduction No data submitted by the applicant, due to not being an EC data requirement / not required by Directive 91/414/EEC.

IIIA1 6.5 Other / special studies

Procedures for cleaning application equipment 6-BA is readily degraded when kept in a spray tank in pH neutral to alkaline conditions. There- fore, 6-BA residues in spray tanks will either be inactivated or diluted to such a concentration

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 31 of 48 where no biological effect on plants is to be expected. No risk to non-target plants is therefore expected from carry-over of residues in spray tanks. Normal cleaning procedure will therefore be recommended after the application of Exilis, i.e. rinsing the tank with clear water.

Dose expression in Germany Rate expression in Germany is in L/ha per metre of crown height. Therefore, the rate of Exilis in L/ha/ meter of tree height was calculated wherever possible and summarised in classes by round- ing to the lower ¼ L. Results in apple are shown in Table 23. They show that a rate of 2.5 L/ha/m crown height or lower is not always sufficient to get enough thinning efficacy. Two results are recorded with this rate: in trial 6-BA182 on ‘Braeburn’ where Exilis at 2.5 L/ha/m crown height reduces fruit set by 12% towards the untreated whereas no thinning effect is achieved with the same rate applied on a more difficult to thin variety, ‘Gala’, in trial 6-BA063. It can be observed that the rate of 1 and 2 L/ha/m crown height showed quite good results in terms of fruit set. This can be explained by the very good results obtained in the Slovenian trials at low rate on easy-to-thin varieties, however results obtained with higher rates of 3.25 or 3.75 L/ha/m crown were usually better and more consistent, with mean fruit weight increase of 9.5-12% in comparison with the untreated. The lower rate does also bring some fruit weight increase but this remains around 6-7%.

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 32 of 48

Table 23: Fruit set and mean fruit weight indexes in relation to Exilis rate in the apple trials from the 4 EPPO zones (100= value in the untreated) Fruit set Mean fruit weight Rate (L/ha/m tree Number Number height) Average Min Max of data Average Min Max of data 0.5 100.3 83.0 117.6 2 106.1 100.0 112.1 2 0.75 92.9 92.9 92.9 1 112.3 112.3 112.3 1 1 87.0 65.1 100.0 12 107.3 94.4 119.8 13 1.25 105.7 96.6 113.1 3 101.9 90.0 112.0 4 1.5 96.9 91.1 106.7 3 101.0 100.0 101.9 4 1.75 99.8 96.7 102.3 3 105.9 100.5 114.0 4 2 86.2 59.4 102.9 16 105.9 94.6 119.0 16 2.25 92.3 75.8 105.1 3 104.4 99.4 118.2 4 2.5 106.0 88.6 123.3 2 106.0 100.0 116.8 3 2.75 88.9 88.9 88.9 1 106.3 106.3 106.3 1 3 103.3 103.3 103.3 1 100.3 100.3 100.3 1 3.25 84.9 58.6 97.3 14 109.5 99.5 142.6 13 3.5 96.3 96.3 96.3 1 111.4 111.4 111.4 1 3.75 78.8 57.9 117.6 4 112.0 97.3 122.6 4 4 76.3 76.3 76.3 1 100.0 100.0 100.0 1 4.25 77.3 47.7 102.2 4 108.3 96.5 129.5 4 4.5 95.8 95.8 95.8 1 99.9 99.9 99.9 1 5 81.2 44.7 117.6 2 104.9 98.3 111.4 2 5.75 98.4 98.4 98.4 1 104.4 104.4 104.4 1 6.5 84.2 78.6 89.7 2 103.6 90.3 116.8 2 7.5 85.7 73.8 97.5 2 109.1 105.3 112.8 2 8 75.6 75.6 75.6 1 109.1 109.1 109.1 1 10 100.0 100.0 100.0 1 94.3 94.3 94.3 1

Results on pear are summarised in Table 24 and confirm previous conclusions: rates comprised between 2 and 4 L/ha/m crown height seem to be quite satisfactory in terms of fruit set index and mean fruit weight index, the rate of 4 L/ha/m crown being maybe a bit high:

Table 24: Fruit set and mean fruit weight indexes in relation to Exilis rate in the pear trials in 2 EPPO zones (100= value in the untreated) Fruit set Mean fruit weight Rate (L/ha/m tree Number Number height) Average Min Max of data Average Min Max of data 1.25 95.8 95.8 95.8 1 105.2 98.9 112.4 3 1.5 91.7 91.7 91.7 1 98.8 98.8 98.8 1 2 112.2 106.5 116.5 3 2.5 87.1 82.5 91.7 2 95.9 93.8 97.9 2 2.75 105.4 105.4 105.4 1 4 78.7 78.7 78.7 1 115.0 115.0 115.0 1 5 92.5 92.5 92.5 1 100.4 100.4 100.4 1 5.5 112.5 112.5 112.5 1

Based on all the results, it can be concluded that a rate of Exilis in the range 2.5-3.75 L/ha/m crown height will provide growers with sufficient thinning efficacy when it is applied under good climatic conditions on apple and pear. It will allow a reduction in fruit set of about 15% and a fruit weight increase of about 10% in comparison to the untreated.

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 33 of 48

IIIA1 6.6 Summary and evaluation of data presented The efficacy of the product has been shown for all tested zones. The minimum effective dose has been defined. Generally, unwanted side effects of growth regulator use can occur depending on the plant cultivar.

Table 25: Proposed uses Crop Target Application rate Spray vol- Number of ap- Method and timing of L/hL L/ha ume L/ha plications (max.), application interval (days) Apple Thinning, fruit size 0.375- 3.75-7.5 1000 1 Foliar spray between improvement 0.75 king fruit size 7-15 mm Pear Thinning, fruit size 0.5-0.75 5.0-7.5 1000 1 Foliar spray between improvement king fruit size 7-15 mm

IIIA1 6.7 List of test facilities including corresponding certificates Non GEP trials Country Organisation Netherlands Applied Plant Research (PPO) France (Mediterranean) CEFEL France (Mediterranean) CEHM Italy Rivoira Giovanni & Figli S.p.A. Italy University of Bologna Department of Fruit Tree and Woody Plant Science Spain Fundacio Mas Badia Spain IRTA, Estacion Experimental de Lleida Poland Research Institute of Pomology and Floriculture Slovenia Agricultural Institute of Slovenia

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Appendix 1 List of data submitted in support of the evaluation

Annex Author Title Year Ref. App.

Point Ref. JKI

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 6 - 2011 6 Agrochemica Ecotoxicology - National addendum ls Ltd. 240673

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 7 - 2011 7 Agrochemica Efficacy Data and Information - National addendum ls Ltd. 240674

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - NL - Section 6 - 2011 6 Agrochemica Ecotoxicology - National addendum ls Ltd. 240678

Document D Anonymous Document D 2011

240680

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 6 - 2011 6 Agrochemica Ecotoxicology -- Core assessment ls Ltd. 240687

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 7 - 2011 7 Agrochemica Efficacy Data and Information - Core assessment ls Ltd. 240688

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 6 - 2011 6 Agrochemica Ecotoxicology - National addendum (word) ls Ltd. 240695

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - NL - Section 6 - 2011 6 Agrochemica Ecotoxicology - National addendum (word) ls Ltd. 240696

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 6 - 2011 6 Agrochemica Ecotoxicology - Core assessment (word) ls Ltd. 240697

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 7 - 2011 7 Agrochemica Efficacy Data and Information - National addendum (word) ls Ltd. 240698

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 35 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis - DE - Section 7 - 2011 7 Agrochemica Efficacy Data and Information - Core assessment (word) ls Ltd. 240699

KIIIA1 6.1.2 Creemers, Biological efficacy evaluation of Exilis (21.0 SL of 6- 2007 6-BA062a P., Deckers, benzyladenine) on fruit thinning on apple cv. Golden T. Delicious. 240700

KIIIA1 6.1.2 Creemers, Biological efficacy evaluation of Exilis (21.0 SL of 6- 2007 6-BA062b P., Deckers, benzyladenine) on fruit thinning on apple cv. Golden T. Delicious. 240701

KIIIA1 6.1.2 Anonymous Efficacy of BA as a fruit-thinner in apple 2007 6-BA096 ! ARI-06-D- 018

240702

KIIIA1 6.1.2 Wichura, A. Fruit thinning of apples 2009 6-BA127 ! 08127WFS0 07

240703

KIIIA1 6.1.2 Creemers, Biological efficacy evaluation of Exilis (20.0 SL) and Fixor 2009 6-BA132 ! P., Deckers, (100.0 SL) on fruit thinning on apple cv. "Golden Delicious" 20090917 T. 796 BE 628

240704

KIIIA1 6.1.2 Lavoisier, C., Eclaircissage - Adjuvant LI700. Efficacité - Ariane c.o.v. 2009 6-BA155 ! Coureau, C. 2009 LI700 2009.doc

240705

KIIIA1 6.1.2 Creemers, Biological Efficacy Evaluation of 6-BA, Exilis (20.0 SL) and 2010 6-BA175 ! P., Deckers, NAA, Fixor (100.0 SL) on fruit thinning on apple, cv. 20100527 T. "Rubens". 921 BE 709

240706

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 36 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1.2 Creemers, Biological Efficacy Evaluation of Exilis (20.0 SL) Fixor 2011 6-BA177 ! P., Deckers, (100.0 SL) on fruit thinning on apple, cv. "Rubens" 20100928 T. 1085 BE 826

240707

KIIIA1 6.1.2 Lavoisier, C. Etude vraie grandeur de programmes à base d'EXILIS® 2010 6-BA178 ! sur l'éclaircissage chimique du pommier, variété Mondial 7RC 11 910 Gala 240708

KIIIA1 6.1.2 Lavoisier, C. Evaluation de l'efficacité du LI700 associé à l'EXILIS® sur 2010 6-BA179 ! l'éclaircissage chimique du pommier, variété Ariane 2RC 119 10

240709

KIIIA1 6.1.2 Saunders, Evaluation of the effect of Exilis as a thinning agent on 2010 6-BA183 G. Gala apple (interim) 240710

KIIIA1 6.1.2 Anonymous Evaluation of the effect of Exilis as a thinning agent on 2010 6-BA182 - Braeburn apple (interim) - Teil 1 Teil 1

240711

KIIIA1 6.1.2 Anonymous Evaluation of the effect of Exilis as a thinning agent on 2010 6-BA182 - Braeburn apple (interim) Teil 2 Teil 2

240712

KIIIA1 6.1.2 Lavoisier, C. Etude d'efficacité du BAP sur l'éclaircissage chimique du 2001 6-BA006 ! 2 pommier RC 119 2001

240713

KIIIA1 6.1.2 Maas F. Report thinning trial 2000 Elstar. Report thinning trial 2000 2000 6- BA052!137- Ex00014!15 2-Ex0001

240714

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 37 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1.2 Maas, F., Report thinning trial Elstar 137 Ex 99028 combinations BA 1999 6- van der NAA.Report thinning trial Elstar 137 Ze 99045 Ethephon BA053!137E Steeg, P. BA sequences. x99028!137 Ze99045

240715

KIIIA1 6.1.2 Deckers, T., Thinning of Jonagold 1999 in Belgium 1999 6-BA055 Daemen, E., Schoofs, H. 240716

KIIIA1 6.1.2 Saunders, Evaluation of the effect of Exilis as a thinning agent on 2010 6-BA185 G. Bramley and Cox apple (interim) 240717

KIIIA1 6.1.2 Anonymous 6-BA - Apple thinning - Maritime zone 2011 6-BA188 ! ARI-10-D- 025

240718

KIIIA1 6.1.2 Chourdas, Efficacy evaluation of Exilis (2% w/v 6-BA)SL on fruit 2007 6-BA008 ! M. thinning in apples HL- Gef/1/07/07- 1

240719

KIIIA1 6.1.2 Marti, S. Evaluation of the efficacy of Exilis for fruit thinning on apple 2002 6-BA046 ! 22048

240721

KIIIA1 6.1.2 Puig Aclareo de frutos, Exilis, manzano, variedad Gala 2003 6-BA047 ! Sentanes, CQM0303 J.M. 240722

KIIIA1 6.1.2 Puig Aclareo de frutos, Exilis, manzano, variedad Gala 2002 6-BA098 ! Sentanes, CQM0202 J.M. 240723

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 38 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1.2 Torres, J.L.J. Evaluation of the efficacy and selectivity of EXILIS as apple 2004 6-BA100 ! thinning chemical agent in apple trees 04018/JL/A CL/MAS

240724

KIIIA1 6.1.2 Pujol Evaluation of the efficacy of different rates of EXILIS as 2005 6-BA105 ! Planella, X. apple thinning chemical agent in apple trees 05038/XP/A CL/MAS

240725

KIIIA1 6.1.2 Chourdas, Efficacy evaluation of Exilis (2% w/v 6-BA) SL on fruit 2008 6-BA161 ! M. thinning in apples HL- Gef/1/07/08- 1

240726

KIIIA1 6.1.2 Chourdas, Efficacy evaluation of Exilis (2% w/v 6-BA) SL on fruit 2008 6-BA162 ! M. thinning in apples HL- Gef/1/07/08- 2

240727

KIIIA1 6.1.2 Chourdas, Efficacy evaluation of Exilis (2% w/v 6-BA) SL on fruit 2009 6-BA163 ! M. thinning in apples HL- Gef/1/07/09- 1

240728

KIIIA1 6.1.2 Bouniol, M., Comparaison de programmes d'éclaircissages sur 2010 6-BA090 ! Ferré, G. pommier GFP1003

240729

KIIIA1 6.1.2 Hourda, M. Efficacy evaluation of the plant growth regulatory product 2011 6-BA181 ! Exilis (6-BA 2.1% w/v) SL on apple thinning. HL- Gef/1/10/10- 1

240730

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 39 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1.2 Ferré, G. Eclaircissage chimique Etude de l'efficacité de la 6 BA - 2001 6-BA003a ! Variété Hillwell CEHM 12/2001

240731

KIIIA1 6.1.2 Ferré, G. Eclaircissage chimique Etude de l'efficacité de la 6 BA - 2002 6-BA003b ! Variété Hillwell CEHM 12/2001

240732

KIIIA1 6.1.2 Saint-Hilary, Pommier Eclaircissage Chimique avec BAP 2001 6-BA004 ! J.F. 01 POM- Ecl.222

240733

KIIIA1 6.1.2 Costa, G., Efficacy study of Exilis on apple thinning 2004 6-BA050 Bregoli, A.M., 240734 Ciccioni, M., Fiori, G., Fabbroni, C., Nardozza, S., Noferini, M.

KIIIA1 6.1.2 Bonamy, J., Formulation examination of Exilis 2005 6-BA056 Carbo, J., Casals, M. 240735

KIIIA1 6.1.2 Alegre Avaluació de l'eficácia d'exilis per a l'aclareig de la poma 2003 6-BA057 Castellvi, S., golden Dalmau 240736 Barbarroja, R.

KIIIA1 6.1.2 Ferré, G. Evaluation de l'intérêt d'adjoindre un adjuvant mouillant- 2009 6-BA085 pénétrant et acidifiant à la 6-BA 240737

KIIIA1 6.1.2 Carbo, J., Report thinning trial "SMOOTHEE" International Eufrin 2000 6-BA089 Vilardell, P., thinning trial Guanter, G., 240738 Bonamy, J.

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 40 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1.2 Ferré G. Compte-rendu 2009. Evaluation desperformances de 2009 6-BA102 différents programmes d'éclaircissage. Variétés Gala, Granny Smith, Pink Lady. 240739

KIIA 8.9.1 Rodgers ABG-3191 Acute toxicity (LC50) to the Earthworm 2002 ZAB M.H. 023/022953

240745

KIIIA1 Sipos, K. Effects of Exilis 2 % SL formulation on the Predatory Mite 2007 07/394- 10.5.1 (Typhlodromus pyri) in a laboratory trial 335RA

240747

KIIIA1 Kimmel, S. Exilis: Toxicity to the adults of the parasitic wasps Aphidius 2011 D25464 10.5.1 rhopalosiphi (Hymenoptera: Braconidae) under worst-case condition in the laboratory 240748

KIIIA1 Kimmel, S. Exilis: Toxicity to the predatory bug Orius laevigatus 2011 D13180 10.5.2 (Heteroptera: Anthocoridae) under extended laboratory condition 240749

KIIIA1 6.1.2 Alegre Avaluació de l'eficácia d'Exilis per a l'aclareig de la poma 2006 6-BA103 Castellvi, S. mondial gala 240758

KIIIA1 6.1.2 Alegre Avaluació de l'eficácia d'Exilis per a l'aclareig de la poma 2005 6-BA104 Castellvi, S. mondial gala 240759

KIIIA1 6.1.2 Ferré, G. Evaluer l'efficacité de deux substances d'éclaircissage 2007 6-BA133 chimique : ANA (de Sangosse) & Exilis (Fine). 240760

KIIIA1 6.1.2 Ferré, G. Comparaison de programmes d'éclaircissage chimique du 2008 6-BA139 pommier Amid Thin W, Etifix, Exilis 240761

KIIIA1 6.1.2 Rivoira Prova Dirado chimico del melo Red Delicious 2008 6-BA140

240762

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 41 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1.2 Donati, G. Valutazione dell'efficacia diradante e della selettività di 2008 6-BA142 diversi prodotti a base di 6-Benziladenina su Fuji, clone Kiku 8. 240763

KIIIA1 6.1.2 Alegre Avaluació de l'eficàcia d'exilis per a l'aclareig de la poma 2006 6-BA160 Castellvi, S. mondial gala 240764

KIIIA1 6.1.2 Basak A. European Fruit Research Institutes Network (EUFRIN) 1999 6-BA016

240765

KIIIA1 6.1.2 Basak, A. European Fruit Research Institute Network (EUFRIN) 1999 6-BA017

240766

KIIIA1 6.1.2 Stopar, M. Poroilo o preiskuanju rastnega regulatorja "Exilis" 2004 6-BA063

240767

KIIIA1 6.1.2 Guignebault, Evaluation de l'efficacité de l'Exilis et d'une formulation 2007 6-BA106 P. d'ANA sur l'éclaircissage du poirier. Mesurer l'efficacité du mouillant LI700. 240768

KIIIA1 6.1.2 Guignebault, Evaluation de lefficacité de lExilis et de lEtifix sur 2009 6-BA136 P. léclaircissage du poirier. 240769

KIIIA1 6.1.2 Deckers, T., Biological efficacy evaluation of Exilis (20.0 SL) and Fixor 2009 6-BA146 Creemers, (100.0 SL) on fruit thinning on pear, cv. Conference P. 240771

KIIIA1 6.1.2 Maas, F.M., Thinning of Conference pear. Report of a trial with different 2007 6-BA109b Balkhoven, concentrations of Exilis in 2007 J.T.M., 240772 Kanne, H.J.

KIIIA1 6.1.2 Guignebault, Evaluation de l'efficacité de l-Exilis associé ou non au 2008 6-BA144 P. mouillant LI700 sur l'éclaircissage du poirier. 240773

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 42 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1.2 Guignebault, Evaluation de l'Exilis® et de l'Etifix sur l'éclaircissage du 2010 6-BA180 P. poirier. 240774

KIIIA1 6.1.2 Deckers, T., Biological efficacy evaluation of Exilis (20.0 SL) and Fixor 2011 6-BA184 Creemers, (100.0 SL) on fruit thinning on pear, cv. Conference P. 240775

KIIIA1 6.1.2 Florens, B., Eclaircissage du Poirier - Efficacité des spécialités Exilis et 2010 6-BA049 Coupard, H., Etifix utilisées seules ou en association sur la variété Reynier, C. Williams 240776

KIIIA1 6.1.2 Florens, B., Eclaircissage du Poirier Efficacité des spécialités Etifix et 2007 6-BA107 Coupard, H., Exilis sur la variété Louise Bonne dAvranches Reynier, C., 240777 Anthoine, J., Reynaud, F.

KIIIA1 6.1.2 Florens, B., Eclaircissage du Poirier - Efficacité de la spécialité Exilis 2008 6-BA138 Coupard, H., sur la variété Guyot Reynier, C. 240778

KIIIA1 6.1.2 Florens, B., Eclaircissage du Poirier - Etude de l'efficacité des 2010 6-BA002 Coupard, H., spécialités Exilis et Rhodofix pour un éclaircissage Reynier, C., chimique du poirier 240779 Delannoy, S., Fieyre, A.

KIIIA1 6.1.2 Blay Coll, J. Evaluation of Exilis for fruit thinning in Blanquilla pear 2009 6-BA145

240780

KIIIA1 6.1.2 Blay Coll, J. Evaluation of Exilis for fruit thinning in Conference pear 2010 6-BA159

240781

KIIIA1 6.1.2 Anonymous Field study to evaluate the thinning efficacy of Exilis on 2010 6-BA187 pear var. Conference, 1 site in Italy 2010 240782

KIIIA1 6.1.2 Blay Coll, J. Evaluation of Exilis for fruit thinning in Ercolini pear 2011 6-BA186

240783

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 43 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1 Basak, A. The effect of fruitlet thinning on fruit quality parameters in 2006 the apple cultivar "Gala" 240784

KIIIA1 6.1 Basak, A. Search for safe and efficient methods of chemical thinning 2006 by improving absorption of preparations and their subsequent use. Proc. Xth IS on Plant Bioregulators in 240785 Fruit

KIIIA1 6.1 Bouma, E. Development of comparable agro-climatic zones for the 2005 international exchange of data on the efficacy and crop safety of plant protection products. 240787

KIIIA1 6.1 Buban, T. The use of benzyladenine in orchard fruit growing: a mini 2000 review. 240790

KIIIA1 6.1 Chabikwa, Chemical thinning of European pear cultivars (Pyrus 2008 T.G. communis L.). 240791

KIIIA1 6.1 Costa G Fruit Chemical Thinning 2005

240793

KIIIA1 6.1 Dennis, F.G. Mechanisms of action of apple thinning chemicals 2002 Jr. 240795

KIIIA1 6.1 Dupont, N. La gestion de l'alternance: de nouvelles voies à explorer 2009

240796

KIIIA1 6.1 Anonymous Commission Directive 2011/1/EU of 3 January 2011 2011 amending Council Directive 91/414/EEC to include 6- Benzyladenine as active substance and amending Decision 240798 2008/941/EC.

KIIIA1 6.1 Greene, D. Effects of repeated yearly application of chemical thinners 2005 on "McIntosh" apples 240799

Julius Kühn-Institut 2012-07-30 Part B – Section 7 Exilis Registration Report Core Assessment 007524-00/00 Central Zone Page 44 of 48

Annex Author Title Year Ref. App.

Point Ref. JKI

KIIIA1 6.1 Lafer, G. Zulassungssituation und Strategien fur die chemische 2006 Ausdünnung 2006: auf die richtige Dosiering zum richtigen Zeitpunkt achten 240800

KIIIA1 6.1 Robinson, North East PGR Meeting 2010 T., Lakso, A., Hoying, 240802 S., Fargione, M., Iungerman, K., Miranda, M., Dominguez, L.

KIIIA1 6.1 Sakakibara, Cytokinins: Activity, biosynthesis, and translocation 2006 H. 240804

KIIIA1 6.1 Stern, R.A., Cytokinins increase fruit size of "Delicious" and "Golden 2006 Ben-Arie, R., Delicious" (Malus domestica) apple in a warm climate Applebaum, 240805 S., Flaishman, M.

KIIIA1 6.1 Van Staden, Benzyladenine and derivatives - their significance and 1996 J., Crouch, interconversion in plants N.R. 240807

KIIIA1 6.1 Wertheim, Developments in the chemical thinning of apple and pear. 2000 S.J. 240808

KIIIA1 6.1 Yuan, R., Benzyladenine as a chemical thinner for 'McIntosh' apples. 2000 Greene, I. Fruit thinning effect-s and associated relationships with D.W. photosynthesis, assimilate translocation, and non-structural 240810 carbohydrates

KIIIA1 Vinall, S. Aged-residue extended laboratory test to determine the 2011 FIN-11-1 10.5.2 effects of Exilis (2 g/l 6-benzyladenine) on the predatory mite Orius laevigatus Fieber (Hemiptera: Anthocoridae) 240815

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis -DE- Section 6- 2011 6 Agrochemica Ecotoxicology - Core assessment ls Limited 240817

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Annex Author Title Year Ref. App.

Point Ref. JKI

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis -DE- Section 6- 2011 6 Agrochemica Ecotoxicology - National addendum ls Limited 240818

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis -NL- Section 6- 2011 6 Agrochemica Ecotoxicology - National addendum ls Limited 240820

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis -DE- Section 6- 2011 6 Agrochemica Ecotoxicology - Core assessment (word) ls Limited 240822

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis -DE- Section 6- 2011 6 Agrochemica Ecotoxicology - National addendum (word) ls Limited 240824

MIIIA1 Sec Fine Draft Registration Report - Part B - Exilis -NL- Section 6- 2011 6 Agrochemica Ecotoxicology - National addendum (word) ls Limited 240826

KIIA 8.8.1.2 Gray, J. VBC 30001: Acute toxicity to Typhlodromus pyri in the 2006 ZAB laboratory 022/023059

265768

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Appendix 2 GAP tables

SUMMARY OF GOOD AGRICULTURAL PRACTICES FOR PESTICIDE USES (Application on agricultural and horticultural crops)

Federal Office of Consumer Protection and Food Safety Date : 2012-JAN-05 Department 2 - Plant Protection Product - Unit 207 D-38104 Braunschweig, Messeweg 11 - 12 Country : Federal Republic of Germany

Pesticide(s) (common name(s)) : 6-Benzyladenin EEC, CIPAC and CCPR No(s). : 214-927-5 , , Trade name(s) : Exilis (007524-00) Main uses e.g. insecticide, fungicide : Plant growth regulator Applicant : Fine Agrochemicals Ltd.

Use Pattern 1 2 3 4 5 6 7 8 9 Crop and / or F, Pest or Formulation Application Application rate per treatment PHI Remarks: situation G group of pests Type Conc. of method, kind growth stage number kg a.i./hl water l/ha kg a.i./ha (days) or controlled a.i. (range) I (a) (b) (c) (d - f) (i) (f - h) (j) (k) (l) Apple F Enhancing fruit SL 20 spraying 71 - 71 1 ; 1 0.015 kg 500 l/ha 0.075 kg ? size, g/l a.i./l/ha and and per m a.i./l/ha and Thinning of fruit per m crown per m crown height crown height height Pear F Enhancing fruit SL 20 spraying 71 - 71 1 ; 1 0.015 kg 500 l/ha 0.075 kg ? size, g/l a.i./l/ha and and per m a.i./l/ha and Thinning of fruit per m crown per m crown height crown height height

Remarks: (a) In case of group of crops the Codex classification should be used (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) (c) e.g. biting and sucking insects, soil born insects, foliar fungi (d) Soluble concentrate (SL) (e) Use CIPAC/FAO Codes where appropriate (f) All abbreviations used must be explained (g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants

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(i) g/kg or g/l (j) Growth stage at last treatment (k) PHI = Pre-harvest interval

(l) Remarks may include: Extent of use/economic importance/restrictions (e.g. feeding,grazing)/minimal intervals between applications

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