UNITED NATIONS RC
UNEP/FAO/RC/CRC.6/5/Add.1
Rotterdam Convention on the Prior Distr.: General 1 December 2009 Informed Consent Procedure for Certain Hazardous Chemicals and English only Pesticides in International Trade
Chemical Review Committee Sixth meeting Geneva, 15–19 March 2010 Item 5 (b) (i) of the provisional agenda* Listing of chemicals in Annex III to the Rotterdam Convention: review of notifications of final regulatory actions to ban or severely restrict a chemical: amitraz
Amitraz
Note by the Secretariat
Addendum
Supporting documentation provided by the European Community
The Secretariat has the honour to provide, in the annex to the present note, documentation received from the European Community to support its notification of final regulatory action for amitraz as a pesticide. The documentation has been reproduced as received, without formal editing by the Secretariat.
* UNEP/FAO/RC/CRC.6/1.
K0953651 040110
For reasons of economy, this document is printed in a limited number. Delegates are kindly requested to bring their copies to meetings and not to request additional copies.
UNEP/FAO/RC/CRC.6/5/Add.1
Annex
1. Commission decision of 12 February 2004 concerning the non-inclusion of amitraz in Annex I to Council Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing this active substance (2004/141/EC) Available at: http://ec.europa.eu/food/plant/protection/evaluation/existactive/oj_amitraz.pdf
2. Review report for the active substance amitraz: Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 4 July 2003 in support of a decision concerning the non-inclusion of amitraz in Annex I of Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing this active substance Available at: http://ec.europa.eu/food/plant/protection/evaluation/existactive/list_amitraz.pdf
3. Excerpt of a report of a tripartite meeting between the European Commission, Austria as Rapporteur Member State and the main data submitter: Amitraz
4. List of end points: Amitraz
5. Monograph prepared in the context of inclusion of following active substance in Annex I of the Council Directive 91/414/EEC: Amitraz. Volume 1: Report and proposed decision.
6. Amitraz: Addendum II to Volume 1 to the Draft Assessment Report and Proposed Decision of Austria prepared in the context of the possible inclusion of the above mentioned active substance in Annex I of Council Directive 91/414/EEC
7. Amitraz: Addendum II to Volume 3 Annex B: Summary, Scientific Evaluation and Assessment
8. Excerpt of the report of a European Commission Co-ordination (ECCO) peer review meeting: Concise outline report of ECCO 78 peer review meeting
9. Excerpt of the report of a European Commission Co-ordination (ECCO) peer review meeting: Concise outline report of ECCO 80 peer review meeting
10 Excerpt of the report of a European Commission Co-ordination (ECCO) peer review meeting: Concise outline report of ECCO 82 peer review meeting
11. Excerpt of the report of a European Commission Co-ordination (ECCO) peer review meeting: Concise outline report of ECCO 84 peer review meeting
2 17.2.2004 EN Official Journal of the European Union L 46/35
COMMISSION DECISION of 12 February 2004 concerning the non-inclusion of amitraz in Annex I to Council Directive 91/414/EEC and the with- drawal of authorisations for plant protection products containing this active substance (notified under document number C(2004) 332) (Text with EEA relevance)
(2004/141/EC)
THE COMMISSION OF THE EUROPEAN COMMUNITIES, (4) In accordance with Article 7(1)(c) of Regulation (EEC) No 3600/92, Austria, being the designated rapporteur Member State, submitted on 6 January 1998 to the Having regard to the Treaty establishing the European Commission the report of its assessment of the informa- Community, tion submitted by the notifiers in accordance with Article 6(1) of that Regulation. Having regard to Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on (5) On receipt of the report of the rapporteur Member 1 the market ( ), as last amended by Commission Directive 2003/ State, the Commission undertook consultations with 2 119/EC ( ), and in particular the third and the fourth sub- experts of the Member States as well as with the main paragraph of Article 8(2) thereof, notifier Bayer CropScience, as provided for in Article 7(3) of Regulation (EEC) No 3600/92. Having regard to Commission Regulation (EEC) No 3600/92 of 11 December 1992 laying down the detailed rules for the (6) The Commission organised two tripartite meeting with implementation of the first stage of the programme of work the main data submitter and the rapporteur Member referred to in Article 8(2) of Council Directive 91/414/EEC State for this active substance on 9 June 2000 and on concerning the placing of plant protection products on the 21 March 2003. market (3), as last amended by Regulation (EC) No 2266/ 2000 (4), and in particular Article 7(3A)(b) thereof, (7) The assessment report prepared by Austria has been reviewed by the Member States and the Commission Whereas: within the Standing Committee on the Food Chain and Animal Health. This review was finalised on 4 July 2003 in the format of the Commission review report for (1) Article 8(2) of Directive 91/414/EEC provided for the amitraz. Commission to carry out a programme of work for the examination of the active substances used in plant protection products which were already on the market (8) Assessments made on the basis of the information on 25 July 1993. Detailed rules for the carrying out of submitted have not demonstrated that it may be this programme were established in Regulation (EEC) No expected that, under the proposed conditions of use, 3600/92. plant protection products containing amitraz satisfy in general the requirements laid down in Article 5(1)(a) and (b) of Directive 91/414/EEC. In particular, Article 5(2)(b) (2) Commission Regulation (EC) No 933/94 of 27 April provides that an acceptable daily intake (ADI) for man 1994 laying down the active substances of plant protec- must be taken into account in deciding on the inclusion tion products and designating the rapporteur Member of an active substance in Annex I. In setting the ADI the States for the implementation of Commission Regulation possible neurological effects of amitraz had to be consid- 5 (EEC) No 3600/92 ( ), as last amended by Regulation ered. These effects were also considered for setting the 6 (EC) No 2230/95 ( ), designated the active substances Acute Reference Dose, i.e. the estimate of the amount of which should be assessed in the framework of Regu- the substance that can be ingested over a short period of lation (EEC) No 3600/92, designated a Member State to time without appreciable health risk to the consumer. It act as rapporteur in respect of the assessment of each has not been demonstrated for the proposed uses that substance and identified the producers of each active consumers might not be exposed to amitraz exceeding substance who submitted a notification in due time. the Acute Reference Dose. A probabilistic risk assess- ment was prepared by the notifier. It must however be taken into consideration that agreed criteria for the inter- (3) Amitraz is one of the 89 active substances designated in pretation of such a probabilistic risk assessment are not Regulation (EC) No 933/94. yet established and it would not be appropriate, in view of the possible risks, to delay decision-making further 1 ( ) OJ L 230, 19.8.1991, p. 1. until such criteria are agreed. (2) OJ L 325, 12.12.2003, p. 41. (3) OJ L 366, 15.12.1992, p. 10. (4) OJ L 259, 13.10.2000, p. 27. (5) OJ L 107, 28.4.1994, p. 8. (9) Amitraz should therefore not be included in Annex I to (6) OJ L 225, 22.9.1995, p. 1. Directive 91/414/EEC. L 46/36EN Official Journal of the European Union 17.2.2004
(10) Measures should be taken to ensure that existing author- 2. from 17 February 2004 no authorisations for plant protec- isations for plant protection products containing amitraz tion products containing amitraz are granted or renewed are withdrawn within a prescribed period and are not under the derogation provided for in Article 8(2) of Direc- renewed and that no new authorisations for such tive 91/414/EEC; products are granted. 3. in relation to the uses listed in column B of the Annex, a Member State specified in column A may maintain in force (11) In the light of the information submitted to the Commis- authorisations for plant protection products containing sion it appears that, in the absence of efficient alterna- amitraz until 30 June 2007 provided that it: tives for certain limited uses in certain Member States, there is a need for further use of the active substance so (a) ensures that such plant protection products remaining as to enable the development of alternatives. It is there- on the market are relabelled in order to match the fore justified in the present circumstances to prescribe restricted use conditions; under strict conditions aimed at minimising risk a longer (b) imposes all appropriate risk mitigation measures to period for the withdrawal of existing authorisations for reduce any possible risks in order to ensure the protec- the limited uses considered as essential for which no effi- tion of human and animal health and the environment; cient alternatives appear currently to be available for the and control of harmful organisms. (c) ensures that alternative products or methods for such uses are being seriously sought, in particular, by means (12) Any period of grace for disposal, storage, placing on the of action plans. market and use of existing stocks of plant protection products containing amitraz allowed by Member States, The Member State concerned shall inform the Commission on should be limited to a period no longer than 12 months 31 December 2004 at the latest on the application of this para- to allow existing stocks to be used in no more than one graph and in particular on the actions taken pursuant to points further growing season. (a) to (c) and provide on a yearly basis estimates of the amounts of amitraz used for essential uses pursuant to this (13) This Decision does not prejudice any action the Article. Commission may undertake at a later stage for this active substance within the framework of Council Direc- Article 3 tive 79/117/EEC of 21 December 1978 prohibiting the placing on the market and use of plant protection Any period of grace granted by Member States in accordance products containing certain active substances (1), as last with the provisions of Article 4(6) of Directive 91/414/EEC, amended by Regulation (EC) No 807/2003 (2). shall be as short as possible and:
(14) The measures provided for in this Decision are in (a) for the uses for which the authorisation is to be withdrawn accordance with the opinion of the Standing Committee on 12 August 2004, shall expire not later than 12 August on the Food Chain and Animal Health, 2005; (b) for the uses for which the authorisation is to be withdrawn by 30 June 2007, shall expire not later than 31 December HAS ADOPTED THIS DECISION: 2007.
Article 1 Article 4 This Decision is addressed to the Member States. Amitraz shall not be included as an active substance in Annex I to Directive 91/414/EEC.
Done at Brussels, 12 February 2004. Article 2 Member States shall ensure that: For the Commission 1. authorisations for plant protection products containing David BYRNE amitraz are withdrawn by 12 August 2004; Member of the Commission
(1) OJ L 33, 8.2.1979, p. 36. (2) OJ L 122, 16.5.2003, p. 36. 17.2.2004 EN Official Journal of the European Union L 46/37
ANNEX
List of authorisations referred to in Article 2(3)
Column A Column B
Member State Use
Greece Cotton
The Netherlands Tree nursery, strawberry (only propagating material), pear trees after harvest
United Kingdom Pear trees after harvest
Portugal Pear trees after harvest
EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL
Directorate E – Food Safety: plant health, animal health and welfare, international questions E1 - Plant health
Amitraz SANCO/10363/2003-final 6 June 2003
Review report for the active substance amitraz Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 4 July 2003 in support of a decision concerning the non-inclusion of amitraz in Annex I of Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing this active substance
1. Procedure followed for the re-evaluation process
This review report has been established as a result of the re-evaluation of amitraz, made in the context of the work programme for review of existing active substances provided for in Article 8(2) of Directive 91/414/EEC concerning the placing of plant protection products on the market, with a view to the possible inclusion of this substance in Annex I to the Directive.
Commission Regulation (EEC) No 3600/92(1) laying down the detailed rules for the implementation of the first stage of the programme of work referred to in Article 8(2) of Council Directive 91/414/EEC, as last amended by Regulation (EC) No 2266/2000(2), has laid down the detailed rules on the procedure according to which the re-evaluation has to be carried out. Amitraz is one of the 90 existing active substances covered by this Regulation.
In accordance with the provisions of Article 4 of Regulation (EEC) No 3600/92, AgrEvo GmbH (now Bayer CropScience) on 27 July 1993, Chimac-Agriphar SA on 27 July 1993, SANC on 23 July 1993, Iberotam on 26 July 1993, AgriChem on 15 July 1993, Industrias Afrasas on 27 July 1993 and B. V. Luxan on 21 July 1993 notified to the Commission of their wish to secure the inclusion of the active substance amitraz in Annex I to the Directive.
In accordance with the provisions of Article 5 of Regulation (EEC) No 3600/92, the Commission, by its Regulation (EEC) No 933/94(3), as last amended by Regulation (EC) No 2230/95(4), designated Austria as rapporteur Member State to carry out the assessment of amitraz on the basis of the dossiers submitted by the notifiers. In the same Regulation, the Commission specified furthermore the deadline for the notifiers with regard to the submission to the
1 OJ No L 366, 15.12.1992, p.10. 2 OJ No L 259, 13.10.2000, p.27. 3 OJ No L 107, 28.04.1994, p.8. 4 OJ No L 225, 22.09.1995, p.1. - 2 - rapporteur Member States of the dossiers required under Article 6(2) of Regulation (EEC) No 3600/92, as well as for other parties with regard to further technical and scientific information; for amitraz this deadline was 31 October 1995.
Only Bayer CropScience submitted in time a dossier to the rapporteur Member State which did not contain substantial data gaps, taking into account the supported uses. Therefore Bayer CropScience was considered to be the main data submitter. CHIMAC-AGRIPHAR S.A. and Industrias Afrasas did not submit complete dossiers. Information has furthermore been submitted by third parties, including the European Environmental Bureau and the World Wide Fund for Nature. In accordance with the provisions of Article 7(1) of Regulation (EEC) No 3600/92, Austria submitted on 6 January 1998 to the Commission the report of its examination, hereafter referred to as the draft assessment report, including, as required, a recommendation concerning the possible inclusion of amitraz in Annex I to the Directive. Moreover, in accordance with the same provisions, the Commission and the Member States received also the summary dossier on amitraz from Bayer CropScience, on 5 November 1998.
In accordance with the provisions of Article 7(3) of Regulation (EEC) No 3600/92, the Commission forwarded for consultation the draft assessment report to all the Member States on 14 April 1998 as well as to Bayer CropScience being the main data submitter, on 23 April 1998.
The Commission organised an intensive consultation of technical experts from a certain number of Member States, to review the draft assessment report and the comments received thereon (peer review), in particular on each of the following disciplines:
- identity and physical /chemical properties ; - fate and behaviour in the environment ; - ecotoxicology ; - mammalian toxicology ; - residues and analytical methods ; - regulatory questions.
The meetings for this consultation were organised on behalf of the Commission by the Pesticide Safety Directorate (PSD) in York, United Kingdom, from March to October 1999.
The report of the peer review (i.e. full report) was circulated, for further consultation, to Member States on 17 March 2000 and the main data submitter on 21 March 2000 for comments and further clarification.
In accordance with the provisions of Article 6(4) of Directive 91/414/EEC concerning consultation in the light of a possible unfavourable decision for the active substance the Commission organised a tripartite meeting with the main data submitter and the rapporteur Member State for this active substance on 9 June 2000 and on 21 March 2003.
In accordance with the provisions of Article 7(3) of Regulation (EEC) No 3600/92, the dossier, the draft assessment report, the peer review report (i.e. full report) and the comments and clarifications on the remaining issues, received after the peer review were referred to the Standing Committee on the Food Chain and Animal Health, and specialised working groups of this Committee, for final examination, with participation of experts from the 15 Member States. This final examination took place from October 2000 to July 2003, and was finalised in the meeting of the Standing Committee on 4 July 2003. - 3 -
The present review report contains the conclusions of the final examination; given the importance of the draft assessment report, the peer review report (i.e. full report) and the comments and clarifications submitted after the peer review as basic information for the final examination process, these documents are considered respectively as background documents A, B and C to this review report and are part of it.
2. Purposes of this review report
This review report including the background documents has been developed and finalised in support of Decision 2004/141/EC5 concerning the non-inclusion of amitraz in Annex I to Directive 91/414/EEC.
In accordance with the provisions of Article 7(6) of Regulation (EEC) No 3600/92, Member States will keep available or make available this review report for consultation by any interested parties or will make it available to them on their specific request. Moreover the Commission will send a copy of this review report (not including the background documents) to all operators having notified for this active substance under Article 4(1) of this Regulation.
3. Overall conclusion in the context of Directive 91/414/EEC
The overall conclusion of this evaluation, based on the information available and the proposed conditions of use, is that:
- the information available is insufficient to satisfy the requirements set out in Annex II and Annex III Directive 91/414/EEC in particular with regard to the acute exposure of consumers.
- concerns were identified with regard to
• The acceptability of acute exposure of consumers in view of the possible neurological effects of the active substance.
In conclusion from the assessments made on the basis of the submitted information, no plant protection products containing the active substance concerned is expected to satisfy in general the requirements laid down in Article 5 (1) (a) and (b) of Council Directive 91/414/EEC.
5 OJ L 46, 17.2.2004, p. 35 EUROPEAN COMMISSION DIRECTORATE-GENERAL HEALTH & CONSUMER PROTECTION
Directorate E - Public, animal and plant health Unit E1 Legislation relating to crop products and animal nutrition Amitraz Sanco/10194/2003-final 27 March 2003
DISCLAIMER
PLEASE NOTE THAT THIS DOCUMENT IS AN EXCERPT OF THE REPORT OF A TRIPARTITE MEETING BETWEEN THE EUROPEAN COMMISSION, AUSTRIA AS RAPPORTEUR MEMBER STATE AND THE MAIN DATA SUBMITTER
COMMISSION WORKING DOCUMENT - DOES NOT NECESSARILY REPRESENT THE VIEWS OF THE COMMISSION SERVICES
Amitraz
Report of a Tripartite Meeting between the European Commission, Austria as Rapporteur Member State and the main data submitter
Date and venue of Meeting: 21 March 2003, Vienna (Austria) Austrian Agency for Health and Food Safety
Attendance: European Commission Main data submitter: Bayer CropScience Rapporteur Member State: Austria - AGES
Introduction […..] No safe uses were identified, in particular with respect to the ecotoxicology and mammalian toxicology section. The peer review identified several data requirements. […..] […..] Problems, on the other hand, remain for the exposure to operators and consumers as well as the impact on non-target organisms, specially birds and mammals. The Commission pointed out that since safe use was not demonstrated for these points, it considers to propose a Decision for non-inclusion of amitraz in Annex I. […..]
Mammalian toxicology The notifier presented a brief overview on the effects of amitraz on mammalian toxicology. Both ADI and AOEL of 0.003 mg/kg/day were based on the NOEL from the 90-day and 2-year dog studies with a safety factor of 100 and presented no problems. The same values were also used by the Veterinary Committee. The notifier agreed to these values, although he expressed that the estimates were very conservative, since they did not take the human studies into account. In a human study two male volunteers were administered a single oral dose of 0.25 mg/kg. The subjects suffered under sedation and drowsiness, one for 60 and the other for 220 minutes. In another study six males received oral doses of 0.0625 mg/kg or 0.125 mg/kg, resulting in an NOEL of >0.125 mg/kg. A slight CNS depression was detected for dogs at 1 mg/kg/day, which was readily reversible. A NOAEL in dogs was seen at 0.25 mg/kg. The notifier pointed out that the effects on dogs and humans were very similar, while they were very different for rats. Therefore, dogs were considered good subjects to model the effects in humans. At a special Toxicology Meeting of the Working Group “Pesticides – Evaluation” on 16 May 2002, it was proposed to set the ARfD at 0.01 mg/kg/day, based on the NOEL of 0.25 mg/kg/day from dog studies and a safety factor of 25 in view of the circumstantial data from human studies covering an acute exposure situation. Concerns had been raised by several MS that for the ARfD the safety factor should not be reduced to 25 on the basis of the human study results. Also the Veterinary Committee argued that the human studies were not sufficient to lower the safety factor to set the ADI. A safety factor of 100 for setting the ArfD would mean that no safe use could be demonstrated for amitraz for acute consumer exposure. The notifier stressed it would be unreasonable to disregard the good data of the human studies on ethical and political grounds. He explained that while the effects for humans and dogs were very similar, the disadvantage of the dog study was its relatively old age and crude results. The human studies had been specifically designed to look for particular effects observed in the dog study. The Commission responded that the tendency is to use animal studies to get the required values and human studies for confirmation. The RMS stated that humans are the most sensitive species and thus a conservative calculation is needed. The Commission agreed and reminded the participants that the Directive provides that the protection of human health and the environment has precedence over agricultural interests.
Consumer risk assessment The notifier presented a NESTI calculation based on composite residue data, which included an empirically derived variability factor resulting in 121 % of the ARfD (apples) and 146 % of the ARfD (pears) for toddlers (the calculations have been performed using an ARfD of 0.01 mg/kg bw). With regard to individual fruit data (the residues expressed in mg/kg declined with the increase of the fruit size) and the possible reduction of the residues by processing the raw agricultural commodities the risk for toddlers can be reduced down to < 100 % of the ARfD. A probabilistic assessment of the dietary exposure in pears was carried out, estimated on the potential diet exposure to residues on individual commodities as consumed by adults and toddlers at a 99.9 percentile. The NESTI was 13% and 31% of ARfD, respectively. The RMS stated that these calculations were in line with the DAR. However, if the ARfD was set to 0.003 mg/kg, the NESTI would reach about 500% of the ARfD. The notifier agreed and expressed the need to use the individual fruit data, instead of the composite residue data, since it was more realistic. Nevertheless, with an ARfD of 0.003 mg/kg, the NESTI would still exceed the ARfD by 270-300%.
Operator exposure risk assessment With regard to operator exposure, the Commission stated that some acceptable scenarios seem to be available. Thus, no further problems are expected under this point. The notifier pointed out that the values were very conservative, since dermal contact is the main route of exposure and the uptake via the dermal route is very slow.
Long-term risk to birds Concerns had been expressed by several MS with regard to the chronic risk to breeding birds through the consumption of treated insects. The notifier presented a short overview of the chronic risk assessment for birds. He pointed out that a long-term exposure to amitraz was very unlikely, since the AS is metabolised rapidly. The risk assessment in orchards gave a TER > 5 for amitraz and the metabolite. The calculations were carried out according to the old guidance document. One MS had asked for the evaluation to be carried out according to the new guidance document. The notifier had expressed that he had completed all studies in good faith and to the protocols agreed in advance with the RMS. Thus, he felt that it would be unreasonable to carry out a risk assessment using the new guidance document. Nevertheless, the notifier carried out a refined risk assessment according to the new document, to demonstrate the validity of the first risk assessment. This included the assumption that birds spend only 10 % of their time in orchards (based upon data given by Crocker 1998) and resulted in a TER of 3.96. The notifier stressed, that it was very unlikely that birds would be exposed over such long time periods, due to the high degradation of the product. A discussion followed, whether the use of data limited to blue tits was enough to determine the risk of exposure of small birds. The notifier argued that other species generally spent less time in orchards or fed less on insects and that the data therefore presented no problems. Further, an MS’s concern was addressed on the NOEC of the metabolite BTS 27271 used for risk assessment. An increased incidence of mortality was observed in the 25 ppm treatment group. The notifier pointed out that this did, however, not differ significantly from controls. Moreover, the first bird to die in the 25 ppm group did so only after 51 days of continuous feeding on food containing BTS 27271. The remaining birds only died after 54 - 149 days after exposure had commenced. The notifier stated that the studies were over 10 years old and had not been designed to investigate the problem of mortality. Thus, it could not be determined how the birds died. No reproductive effects were observed at the NOEC, while a decreased reproduction was observed at higher concentrations. However, in the notifier´s view no effects were determined on fertility rate or embryo toxicity. The notifier agreed that further refinement of the data was needed, since not enough data was available in order to be able to carry out the risk assessment according to the new guidance document. He proposed that this data could be generated at MS-level.
Aquatic risk assessment Although some risk remains to aquatic organisms, the problem could be solved by employing appropriate mitigation measures.
Conclusion The Commission repeated the main concerns for amitraz, emphasising the proposal for non-inclusion that will be submitted to the Standing Committee on 14 April 2003 for discussion and to vote in June. This was particularly due to the problem of consumer exposure and the impact on non-target organisms. The Commission will inform the Member States on the outcome of this Tripartite Meeting by making the report, as well as the comments of the notifier available to them. The notifier was asked to submit any argumentation for further evaluation to the Commission and the RMS until latest noon 7 April 2003.
List of end points Amitraz (Ac, In) 1/28 RMS: AT April 2003
LIST OF END POINTS: AMITRAZ
1 Physical chemical properties section
Identity, Physical and Chemical Properties, Details of Uses, Further Information
Active substance AMITRAZ (ISO Common Name (ISO)
Function Insecticide, Acaricide
Rapporteur Member State AUSTRIA
Identity (Annex IIA, point 1) Chemical name (IUPAC) N-methylbis(2,4-xylyliminomethyl)amine
Chemical name (CA) N’-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl) imino] methyl]-N-methylmethaniminamide
CIPAC No 362
CAS No 33089-61-1
EEC No (EINECS or ELINCS) 2513574
FAO Specification (including year of - publication)
Minimum purity of the active substance as 970 g/kg manufactured (g/kg)
Identity of relevant impurities -
Molecular formula C19H23N3 Molecular mass 293.4
Structural formula CH3 CH3 CH3 NCHNCHN CH3
CH3
Physical-chemical properties (Annex IIA, point 2)
Melting point (state purity in not purified) 86°C (purity > 99.4 %:)
Boiling point (state purity if not purified) not relevant as substance decomposes with heat
Temperature of decomposition not relevant
Appearance (state purity if not purified) white (purified a.s.)
Relative density (state purity if not purified) 1.128 (purified a.s.) List of end points Amitraz (Ac, In) 2/28 RMS: AT April 2003
Surface tension not relevant
Vapour pressure (in Pa, state temperature) 3.4 x 10-4 Pa at 25°C
Henry's law constant (Pa m3 mol-1) 1.0 Pa m3 mol-1
Solubility in water (g/l or mg/l, state pH 6.5: 9.4 x 10-5 g/l at 25.5°C temperature pH 10.8: 0.22 x 10-3 g/l at 27°C
acid conditions: not stable
Solubility in organic solvents (in g/l of mg/l, Solubility at 25°C (g/l) state temperature) Acetone 300 to 600
Acetonitrile 60 to 75
Dichlormethane > 600
Dimethylsulfoxide 120 to 150
Ethanol 35.1
Ethylacetate 300 to 600
Hexane 21 to 25
Methanol 20.1
Propan-2-ol 21.5
Toluene 300 to 600
Partition co-efficient (log Pow) (state pH and pH log Pow temperature) 9 5.6 at 40°C 7 5.6 at 40°C 5.8: 5.5 at 25°C 6.14 5.96 at 22°C 5.51 5.98 at 22°C 5.29 6.00 at 22°C 5.25 6.01 at 22°C
Hydrolytic stability (DT50) (state pH and DT50 (at 25°C) temperature) pH 5: 2 h
pH 7: 22 h
pH 9: 26 h
Dissociation constant pKa = 4.2 ± 0.1 at 20°C UV/VIS absorption (max.) (if absorption absorption maxima at 202 nm and 288 nm >290 nm state λ)
Photostability (DT50) (aqueous, sunlight, DT50 = 46.5 h (corrected for hydrolysis) pH 7.13, 28°C, artificial state pH) light
Quantum yield of direct phototransformation Φ = 5.9 x 10-5 molecules degraded/photon absorbed in water at λ>290 nm
Flammability Not flammable List of end points Amitraz (Ac, In) 3/28 RMS: AT April 2003
Explosive properties No explosive properties
List of end points Amitraz (Ac, In) 4/28 RMS: AT April 2003
Analytical methods for the active substance (Annex IIA, point 4.1) Technical as (principle of method) Determination of the a.i. with GC/FID after addition of internal standard (CIPAC method 362/TC/M/3, company method no. 1800/02/05)
Impurities in technical as (principle of Determination of the impurities with GC/ECD (external standard method) technique)
Plant protection product (principle of Determination of the a.i. with GC/FID after addition of internal method) standard (CIPAC methods 362/EC/M/- and 362/WP/M/-, company method no. 1803/14/01)
Analytical methods for residues (Annex IIA, point 4.2) Food/feed of plant origin (principle of Acid hydrolysis, followed by base hydrolysis to release 2,4- method and LOQ for specific method) dimethylaniline, simultaneous steam distillation, clean-up by solvent partition, derivatisation with HFBA*), determination with GC/ECD LOQ: 0.05 mg/kg
Food/feed of plant origin (principle of see above method and LOQ for methods for monitoring purposes)
Food/feed of animal origin (principle of Acid hydrolysis, followed by base hydrolysis to release 2,4- method and LOQ for methods for dimethylaniline, simultaneous steam distillation, clean-up by monitoring purposes) solvent partition, derivatisation with HFBA*), determination with GC/ECD LOQ: milk and eggs: 0.01 mg/kg other products of animal origin: 0.05 mg/kg
Soil (principle of method and LOQ) Base hydrolysis to release 2,4-dimethylaniline with simultaneous steam distillation, clean-up by solvent partition, determination with GC/TID. LOQ: 0.01 mg/kg
Water (principle of method and LOQ) Drinking water: Conversion to 2,4-dimethylaniline by base hydrolysis with simultaneous steam distillation, clean-up by solvent partition, determination with GC/TID LOQ: 0.05 µg/L Surface water: Extraction of amitraz and metabolites, concentration, GC-MS-determination LOQ: 1 µg/L
Air (principle of method and LOQ) Sampling by adsorption in sampling cartridges filled with Tenax, desorption by ultrasonic extraction with acetone, determination by GC/MS LOQ: 0.1 µg/m3
Body fluids and tissues (principle of method Acid and base hydrolysis to release 2,4-dimethylaniline, and LOQ) simultaneous steam distillation, clean-up by solvent partition, List of end points Amitraz (Ac, In) 5/28 RMS: AT April 2003
derivatisatiom with HFBA*), determination with GC/ECD LOQ: 0.01 mg/kg
*) Heptafluorbutyric anhydride List of end points Amitraz (Ac, In) 6/28 RMS: AT April 2003
2 Fate and behaviour section
Route of degradation (aerobic) in soil (Annex IIA, point 7.1.1.1.1) 2-methyl radio-labelled amitraz in two soils, 6 mg/kg at 25°C ± 2°C and 50 % MHC
Mineralization after 100 days (90/120 d) 15-24 % / 20-27 %
Non-extractable residues after 100 days 61-78 % / 71-73 % (90/120 d)
Relevant metabolites- name and/or code- % N-Methyl-N'-(2,4-xylyl) formamidine (BTS 27271; of applied (range and maximum) active metabolite): 0.2-7 % (maximum day 2) Form-2', 4'-xylidine (BTS 27919): 0.2-34 % (maximum day 1) 2,4-Dimethylaniline (BTS 24868): 0.2-11 % (maximum 3 hrs)
Route of degradation in soil - Supplemental studies (Annex IIA, point 7.1.1.1.2) Anaerobic degradation Very rapidly degraded, DT50: <1 d Amitraz, radiolabelled in the 2-methyl- 1.5-2.5 % in water position of either phenyl ring 79 - 85 % soil ‘bound’ residues (maximum day 0) 6 mg/kg to two soils BTS 27919 (up to 13 %, day 30), aerobic 30 days at 25° C ± 2°C and 50 % BTS 27271 (up to 1.3 %, day 60) MHC BTS 24868 (up to 5.5 %, day 60)
Sterile degradation Chemical hydrolysis led to the rapid decay
25°C and 50 % MHC BTS 27919 (63 %, 14 d), BTS 27271 (6 %, 1 d), BTS 24868 (12 %, 0 d) Soil ‘bound’ residues (2-44 %, 30 d)
Soil photolysis Amitraz: DT50 = 7.7 minutes (dark controls: DT50 = 47.5 minutes) [14C]-ring labelled amitraz BTS 27919 (36 %, 30 min, in the dark: 27 %, 30 min), BTS 27271 (10 %, 30 min, in the dark: 8 %, 30 min)
Rate of degradation in soil (Annex IIA, point 7.1.1.2, Annex IIIA, point 9.1.1) Method of calculation TOPFIT version IBM 1.57E (two compartment model) Amitraz: Two soils, 50 % MHC, 25+/-2°C Two soils, 40 % MHC, 20+/-2°C Metabolites: Two soils, 50 % MHC, 25+/-2°C
Laboratory studies (range or median, with n DT50lab (20°C, aerobic): value, with r2 value Amitraz: 0.27 – 0.33 d
DT50lab (25°C, aerobic):
List of end points Amitraz (Ac, In) 7/28 RMS: AT April 2003
Amitraz: 0.08 – 0.17 d BTS 27271: 0.5 – 2.4 d BTS 27919: 4.1 – 6.4 d BTS 24868: 0.27 – 3.3 d
DT90lab (20°C, aerobic): Amitraz: 1.4 – 5.9 d
DT90lab (25°C, aerobic): Amitraz: 0.26 – 1.0 d BTS 27271: 11 - 29 d BTS 27919: 62 - 98 d BTS 24868: 1.2 - 51 d
DT50lab (10°C, aerobic): not submitted
DT50lab (25°C, anaerobic): Amitraz: < 1 d Field studies (state location, range or median with n value) no relevant information
Soil accumulation and plateau concentration --
Soil adsorption/desorption (Annex IIA, point 7.1.2)
Kf/Ko Amitraz: Kd: 8 – 60 KOC: not relevant 4 soils were tested: The slurries had been adjusted to pH 8 with 10 N sodium pH: 5.1 – 6.9 hydroxide solution to reduce the rate of hydrolysis of the parent %OC: 0.4 – 4.4 compound, because Amitraz hydrolyses rapidly in soil and water. pH 5.1 - 7.6 AE C427271: KF: 2.1 – 21.3 KOC: not relevant %OC: 0.53 - 2.83 AE C427919: KOC: 100 – 145
AE C424868: KOC: 107 estimated from the log POW of 2.2:log KOM = 0.52 x log POW + 0.65 and KOC = KOM x 1.72 pH dependence (yes/no) --
Mobility in soil (Annex IIA, point 7.1.3, Annex IIIA, point 9.1.2) Because of the rapid breakdown of amitraz in soil and water the mobility of amitraz has been investigated by soil thin layer chromatography. The bulk of the amitraz related material was of low mobility.
Column leaching BTS 27271: Less than 0.3 % was detected in the percolate. BTS 27919: 0.7 – 3.1 % of the applied radioactivity was detected in the leachate.
Aged residues leaching Of [14C]-ring labelled amitraz, ageing period: 3 d Radioactivity in the leachate: 1.1 – 5.0 % AR No Amitraz or known metabolites were detected, only polar
List of end points Amitraz (Ac, In) 8/28 RMS: AT April 2003
material was detected.
Lysimeter /field leaching studies --
PEC (soil) (Annex IIIA, point 9.1.3)
-k x t -ln2/DT50 x t Method of calculation actual: C(t) = C(0) x e = C(0) x e
(-t x ln2/DT50) time weighted: C(t) = C(0) x DT50/(t x ln2) x (1 - e ) Assumptions single application due to very low DT50; 50 % reaches the ground; soil density: 1.5 g/cm3; incorporation and homogenous distribution within 5 cm soil
DT50 Amitraz: 0.3 days
PEC (s) Actual Time weighted average µg/kg Application rate 800 g/ha initial 533.333 short term 24 h 52.913 207.929 2 d 5.249 114.279 4 d 0.521 57.702 long term 7 d 0.000 32.976 14 d 0.000 16.488 21 d 0.000 10.992 28 d 0.000 8.244 50 d 0.000 4.617 100d 0.000 2.308
Metabolites molec. weight maximum conc. in soil BTS 27271: 162 20.46 BTS 27919: 149 91.50 BTS 24868: 111 21.97
Route and rate of degradation in water (Annex IIA, point 7.2.1)
Hydrolysis of Amitraz (DT50) pH 5: 2 hrs 25° C pH 7: 22 hrs pH 9: 26 hrs
Hydrolysis of relevant metabolites (DT50) pH 5: BTS 27271: stable 25° C BTS 27919: 95 days
pH 7: BTS 27271: 14 days BTS 27919: 604 days
pH 9: BTS 27271: 5 hrs BTS 27919: 20.7 days
List of end points Amitraz (Ac, In) 9/28 RMS: AT April 2003
Photolytic degradation of Amitraz pH 7: 2 - 4 days
Quantum yield of Amitraz 5.93 x 10-5 (molecules degraded per photon absorbed)
Photolytic degradation of relevant BTS 27 271: stable metabolites BTS 27 919: stable
Readily biodegradable (yes/no) not readily biodegradable
Degradation in water/sediment- system: Water whole system sediment DT50 a.i.: 0.3-0.6 d 1.3-1.9 d 12-14 d (8° C)
1.7-3.4 hrs 3.6-6 hrs 4-20 d (25° C)
BTS 27 271 3.3-7 d 6.1-7.7 d - (25° C) 1.2 d 53 d - (25° C)* * after repeated applications BTS 27 919: 9-20 d 10-21 d 7-33 d (25° C) (data not used for calculations) 10 d 11 d - (25° C)* BTS 24868: ~24 d 32 d - (25° C)*
Distribution in water/sediment systems (as) Following repeated applications (% AR):
25° C Water Sediment 1 d 7.8 % 2.5 % 10 d n.d % 1.4 % 20 d n.d % 1.5 % 59 d n.d % 1.1 %
Distribution in water/sediment systems Following repeated applications (% AR): (metabolites) BTS 27919 BTS 27271 25° C Water Sediment Water Sediment 1 d 33.0 % 10.6 % n.d. 0.9 % 10 d 31.7 % 7.5 % n.d. 2.3 % 20 d 23.1 % 3.1 % 9.7 % 1.3 % 59 d 1.2 % 1.3 % 0.6 % 1.4 %
Distribution in water/sediment systems of Amitraz BTS 27919 BTS 27271 Amitraz and metabolites in % AR at Water Sedim. Water Sedim. Water Sedim. 8° C 1d 21-28 13-18 4-7 11-16 3-7 0.8-1 10d 0.8-4 9.7-13 11-21 12-13 1.5-5 0.5-1.8 30d n.d-1.9 2.6-3 20-25 8-10 nd-1.5 1.7-3.4
Field or mesocosm studies ---
PEC (surface water) (Annex IIIA, point 9.2.3)
-ln2/DT50*t Method of calculation Actual: C(t) = C(0)*e
List of end points Amitraz (Ac, In) 10/28 RMS: AT April 2003
(-t*ln2/DT50) time weighted: C(t) = C(0)*T50/(t*ln2)*(1 – e ) Application rate Orchards: 800 g/ha single application (due to rapid degradation) 30 cm water depth
Main routes of entry Spray drift: Orchards: 3 m (30 %); 50 m (0.2 %)
DT50 Amitraz 0.6 days (8°C)
PEC (sw) Actual Time weighted average µg/l
ORCHARDS 800 g/ha
Spray drift 30 % 0.2% 30 % 0.2 %
Initial 80.000 0.533 80.000 0.5333
Short term 24 h 25.198 0.168 47.437 0.316 2 d 7.937 0.053 31.189 0.208 4 d 0.787 0.005 17.142 0.114
Long term 7 d 0.025 0.000 9.889 0.066 14 d 0.000 0.000 4.946 0.033 21d 0.000 0.000 3.297 0.022 28 d 0.000 0.000 2.473 0.016 50 d 0.000 0.000 1.385 0.009 100 d 0.000 0.000 0.692 0.005
Metabolites
Application rate 800 g/ha 800 g/ha Spray drift (%) 30 % 0.2 %
Conc.max in water BTS 27271: 22.16 0.147 BTS 27919: 48.16 0.321 BTS 24868: 7.36 0.049
PEC (sediment) Method of calculation -ln2/DT50*t Actual: C(t) = C(0)*e
(-t*ln2/DT50) time weighted: C(t) = C(0)*T50/(t*ln2)*(1 – e ) Application rate Orchards: 2 x 800 g/ha; 14 day interval maximum concentration in sediment: 23 % AR incorporation into 3 cm sediment layer; density: 1.5
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DT50 Amitraz 14 days
PEC (SED) Actual Time weighted average µg/l
2 x 800 g/ha
Spray drift 0.2 % 30 % 0.2 % 30 %
Initial 0.82 122.67 0.82 122.67
Short term* 24 h 1.167 175.112 0.630 94.544 2 d 1.111 166.653 0.662 99.332 4 d 1.006 150.941 0.706 105.916
Long term* 7 d 0.867 130.107 0.739 110.832 14 d 0.613 92.000 0.737 110.606 21d 0.434 65.054 0.694 104.035 28 d 0.307 46.000 0.639 95.859 50 d 0.103 15.477 0.484 72.539 100 d 0.009 1.302 0.288 43.236 * after last application
PEC (ground water) (Annex IIIA, point 9.2.1) Method of calculation PELMO 3.00
Application rate 2x 0.8 kg ai/ha for pome fruit
PEC (gw) Maximum concentration
Average annual concentration over 20 years Amitraz: <0.001 µg/l AE C427271: <0.001 µg/l AE C427919: <0.001 µg/l AE C424868: <0.001 µg/l
Fate and behaviour in air (Annex IIA, point 7.2.2, Annex III, point 9.3) Direct photolysis in air no study submitted
Quantum yield 5.93 x 10-5 (molecules degraded per photon absorbed)
Photochemical oxidative degradation in air Amitraz: 2.9 h (DT50) BTS 24868 (AE C424868): 2.4 h BTS 27271 (AE C427271): 4.0 h BTS 27919 (AE C427919): 6.0 h
Volatilisation from plant surfaces: no study submitted
List of end points Amitraz (Ac, In) 12/28 RMS: AT April 2003
from soil: up to 12 % during 18 days
Vapour pressure (in Pa, state temperature) Amitraz 3.4 x 10-4 Pa at 25°C BTS 27271: 0.12 Pa (interpolated) BTS: 27919: 4.1 x 10-4 Pa (extrapolated)
PEC (air) Method of calculation no calculation
PEC (a)
Maximum concentration -
Definition of the Residues (Annex IIA, point 7.3 Relevant to the environment Soil: Amitraz, BTS 27271, BTS 27919, BTS 24868 Water: Amitraz, BTS 27271, BTS 27919, BTS 24868
Monitoring data (Annex IIA, point 7.4)
Soil Not submitted
Surface water Not submitted
Ground water Not submitted
Air Not submitted
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3 Ecotoxicology section
Effects on Non-target Species
Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3)
Acute toxicity to mammals Amitraz: LD50 (rat, male) = 600 mg/kg bw
BTS 27271: LD50 (mouse) = 100 mg/kg bw Amitraz: relev. NOAEC (rat, reproduction studies) = 50 ppm BTS27271: relev. NOAEC (rat, 90 d) = 45 ppm
Acute toxicity to birds Amitraz: LD50 (Bobwhite quail) = 788 mg/kg bw
BTS 27919: LD50 (Bobwhite quail) = 1827 mg/kg bw
BTS 27271.HCl LD50 (Bobwhite quail) = 71 mg/kg bw
Dietary toxicity to birds Amitraz: LC50 (Japanese quail) = 1800 ppm
BTS27919: LC50 (Bobwhite quail) > 5200 ppm
BTS 27271.HCl: LC50 (Bobwhite quail) = 1362 ppm Reproductive toxicity to birds Amitraz: NOAEC (Mallard duck) = 40 ppm BTS 27919: NOEC (Bobwhite quail) = 100 ppm BTS 27271.HCl: NOAEC (Mallard duck) = 25 ppm
Toxicity/exposure ratios for terrestrial vertebrates (Annex IIIA, points 10.1 and 10.3) Application Crop Category Time- TER Annex rate (e.g. insectivorous bird) scale VI (kg as/ha) Trigger ai BTS 27271 2*0.8 Orchards frugivorous bird Acute 1970 710 10 insectivorous bird Acute 114 65 10 2*0.8 Orchards insectivorous bird Chronic 20.5 5.07 5 grazing bird Chronic 19.84 6.03 5 earthworm/invertebrates eating bird Chronic 52 8.68 5 2*2.5 Orchards frugivorous mammal Acute 1500 1000 10 insectivorous mammal Acute 87 91 10 earthworm eating mammal Acute 54545 833 10 2*0.8 Orchards insectivorous mammal Chronic 26.6 5.5 5 grazing mammal Chronic 16.5 7.24 5 earthworm/invertebrates eating mammal Chronic 65 15.62 5
Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2, Annex IIIA, point 10.2) Group Test substance Time-scale Endpoint Toxicity LC50/EC50/NOEC (mg ai/l) Laboratory tests
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Group Test substance Time-scale Endpoint Toxicity LC50/EC50/NOEC (mg ai/l) Fish Amitraz 96h / flow through mortality 0.45 Invertebrates Mitac 20 EC 48h / sediment/water system immobilisation 1.05 Algae Amitraz 91h /static biomass, growth rate > 12 Fish BTS 27919 96h / static mortality 74 Invertebrates BTS 27919 48h /static immobilisation >100 Fish BTS 27271 96h / flow through mortality 27.9 Invertebrates BTS 27271 48h /static immobilisation 3.28 Fish Mitac 20 EC 96h / flow through mortality 0.348 Invertebrates Mitac 20 EC 48h /static immobilisation 0.0422 Algae Mitac 20 EC 89h /static biomass 0.1884 Fish Mitac 20 EC 34d, pulsed dose NOEC length 0.15 Invertebrates Mitac 20 EC 28d, sediment/water system NOEC reproduction 0.2 Invertebrates Mitac 20 EC 28 d, pulsed dose in a NOEC reproduction 0.2 sediment/water system NOEC mortality <0.025 Sediment dweller Amitraz 28d NOEC emerge 2 Microcosm or mesocosm tests No data
Toxicity/exposure ratios for the most sensitive aquatic organisms (Annex IIIA, point 10.2) Application Crop Organism Time-scale Distance TER Annex VI Rate (m) Trigger (kg as/ha)
2 * 0.8 orchards fish 96h 50 849 100 2 * 0.8 orchards invertebrates 48h 50 1981 100 2 * 0.8 orchards algae 91h 50 >11215 10 2 * 0.8 orchards fish 34d 50 283 10 2 * 0.8 orchards invertebrates 21d 50 377 10 2* 0.8 orchards invertebrates 21d 50 < 47 10 0.8 orchards invertebrates 21d 50 377 10 2 * 0.8 orchards sediment dwellers 21d 50 3773 10
Bioconcentration Bioconcentration factor (BCF) 1333 Annex VI Trigger:for the bioconcentration factor 100
Clearance time (CT50) After 14 days dissipation 8 % of the radioactivity remains in the fish (CT90)
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Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4) Acute oral toxicity LD50 (96h) = 20 µg Mitac/bee Acute contact toxicity LD50 (96h) = 27 µg Mitac/bee
Hazard quotients for honey bees (Annex IIIA, point 10.4) Application rate Crop Route Hazard quotient Annex VI (l Mitac/ha) Trigger Laboratory tests 4.0 Orchards Oral 200 50 4.0 Orchards Contact 148 50
Semi-field tests Application rate Crop Route Effects (l Mitac/ha) 0.5 % Phacelia Contact/Oral Adult bees and brood: No abnormal changes were observed
The possible effects of the metabolites are covered by the semi-fiels test
Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5) Species Stage Test Dose Endpoint Effect Annex VI Substance (l Mitac/ha) Trigger Laboratory tests Trichogr Adults Mitac 20 EC 3.5 Mortality 100 30 cacoeciae Trichogr Adults Mitac 20 EC 1.8 Reduction of 100 30 cacoeciae parasitism Encarsia Adults & Mitac 20 EC 1.8 Mortality & parasitism 100 30 formosa larvae Phygadeuon Adults & Mitac 20 EC 1.8 Reduction of 50-79 30 trichops larvae parasitism Phytosei Nymphs Mitac 20 EC 3.5 Mortality 100 30 persimilis Phytosei Nymphs Mitac 20 EC 5.0 Mortality 100 30 persimilis Phytosei Adults & Mitac 20 EC 1.8 Reduction of 100 30 persimilis eggs egg production Phytosei Nymphs Mitac 20 EC 3.5 Mortality 100 30 persimilis Amblyseius Adults & Mitac 20 EC 1.8 Mortality & egg 100 30 pottentillae eggs production, total effect Typhlodr Adults & Mitac 20 EC 1.8 Mortality & egg 100 30 pyri eggs production, total effect Anthocoris Nymphs Mitac 20 EC No details Mortality & fecundity 46 30 nemorum provided Chrysopa Larvae Mitac 20 EC 5.0 Mortality of larvae 58 30 carnea Chrysopa Larvae & Mitac 20 EC 1.8 Mortality & egg 80-99 30 carnea adults production total effect Coccinella Larvae Mitac 20 EC 1.8 Mortality of larvae & 80-99 30 7-punctata fecundity of adults Adalia Larvae & Mitac 5.0 Mortality of larvae and 0 30
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Species Stage Test Dose Endpoint Effect Annex VI Substance (l Mitac/ha) Trigger Laboratory tests bipunctata adults fecundity of adults Lepthypan- Adults Mitac 20 EC 1.8 Mortality & predation, 100 30 tes tenuis total effect Aleochara Adults & Mitac 20 EC 1.8 Egg production & 80-99 30 bilineata larvae parasitism, total effect Bembidion Adults Mitac 20 EC 1.8 Mortality 50-79 30 lampros Aleochara Adults Mitac 20 EC 0.00175 Mortality 15 30 bilineata Aleochara Adults Mitac 20 EC 1 Mortality 44 30 bilineata Aleochara Adults & Mitac 20 EC 0.00175 Egg production & +14 30 bilineata larvae parasitism, total effect Aleochara Adults & Mitac 20 EC 1 Egg production & 50 30 bilineata larvae parasitism, total effect
semi-field tests , initial and persistence Species Stage Test Dose Endpoint Effect Annex VI Substance (l Mitac/ha) Trigger Trichogr Susceptible Mitac 20 1.8 Duration of Persistent 25 cacoeciae stage EC harmful activity (> 30 d) Encarsia Susceptible & Mitac 20 1.8 Total effect > 75 25 formosa robust stage EC Encarsia Susceptible & Mitac 20 1.8 Duration of Short lived 25 formosa robust stage EC harmful activity (< 5 d) Phytosei Mitac 20 1.8 Total effect > 75 25 persimilis EC Typhlodromus Mitac 20 4 in crop Mortality and 56 d bioassay 25 pyri EC fecundity 9%, fecundity not affected Typhlodromus Mitac 20 4 off crop Mortality and 56 d bioassay 25 pyri EC (1.05) fecundity 9%, fecundity not affected Aphidius Mitac 20 4 in crop Mortality and 14 d bioassay 25 rhopalosiphi EC fecundity no mortality, fecundity not significant from control Aphidius Mitac 20 4 off crop Mortality and 7 d bioassay 25 rhopalosiphi EC (1.05) fecundity no mortality, fecundity not significant from control Episyrphus Mitac 20 4 in crop Mortality and 43 d bioassay 25 balteatus EC fecundity no mortality, fecundity of high viability Chrysoperla Mitac 20 4 in crop Mortality 39 d bioassay 25 carnea EC no mortality Field test Amblyseius Adults, Mitac 20 1.8 Mortality & > 75 25 finlandicus eggs & EC fecundity, juveniles total effect Typhlodr Adults, Mitac 20 1.8 Mortality & > 75 25 pyri eggs & EC fecundity,
List of end points Amitraz (Ac, In) 17/28 RMS: AT April 2003
juveniles total effect
Effects on earthworms (Annex IIA, point 8.4, Annex IIIA, point 10.6) Acute toxicity 14 days LC50 = 20 mg as/kg* Reproductive toxicity No data * According to the EPPO risk assessment scheme the toxicity data from laboratory tests in artificial soil are divided by the factor of 2 when the log Pow >2.
Toxicity/exposure ratios for earthworms (Annex IIIA, point 10.6) Application rate Crop Time-scale TER Annex VI (kg as/ha) Trigger 0.8 orchards 14 days 38 10
Effects on soil micro-organisms (Annex IIA, point 8.5, Annex IIIA, point 10.7) Nitrogen mineralization < 25 %, no significant effects at an application rate of 3.27 mg ai/kg > 25 %, effects at an application rate of 32.7 mg ai/ha Carbon mineralization < 25 %, no significant effects
Classification and proposed labelling (Annex IIA, point 10) with regard to ecotoxicological data N: Dangerous for the environment S 60: This material and its container must be disposed of as hazardous wastes S 61: Avoid release to the environment R 50/53: Very toxic to aquatic organisms and may cause long-term adverse effects in the aquatic environment
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4 Mammalian toxicology section
Impact on Human and Animal Health
Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1)
Rate and extent of absorption: rapid (80 % within 24h)
Distribution: Uniformly distributed; highest tissue levels found in thyroid, adrenals, liver and eyes
Potential for accumulation: no evidence for accumulation
Rate and extent of excretion: rapid and extensive, (approx. 94 %) within 96 hours; mainly via urine (82 %)
Metabolism in animals completely metabolized ; main metabolites “BTS 39098“ (4-formamido-m-toluic acid), “FBC 31158“ (4- acetomido-m-toluic acid), BTS 27271 (N-2,4- dimethylphenyl-N-methylformamidine) cleavage reactions and mainly oxidation reactions followed by conjugation
Toxicologically significant compounds (animals, plan parent compound; metabolite BTS 27271 and environment) (pharmacologically active);
Acute toxicity (Annex IIA, point 5.2)
Rat LD50 oral approx. 600 mg/kg bw Xn, R 22
Rat LD50 dermal > 1600 mg/kg bw
Rat LC50 inhalation 65 mg/l air (6 h; aerosol) Skin irritation (rabbit) not irritant
Eye irritation (rabbit) not irritant
Skin sensitization (test method used and result) sensitising (Maximisation test) Xi, R 43
Short term toxicity (Annex IIA, point 5.3) Target / critical effect body weight, liver; behavioural effects
Lowest relevant oral NOAEL / NOEL 0.25 mg/kg bw/d (90 days; dog) Xn, R48/22
Lowest relevant dermal NOEL / NOAEL no valid data, no data required Lowest relevant inhalation NOAEL / NOEL 0.01 mg/l air (3 weeks, rat); [1.26 mg/kg bw]
no genotoxic potential Genotoxicity (Annex IIA, point 5.4)
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Long term toxicity and carcinogenicity (Annex IIA, point 5.5) Target/critical effect decreased body weight gain, behavioural effects
Lowest relevant oral NOAEL / NOEL 0.25 mg/kg bw/d (2 years oral toxicity study in dogs)
Carcinogenicity overall no carcinogenic potential relevant for humans (but liver adenomas and carcinomas in female B6C3F1 mice and lymphoreticular tumours in female CFLP-mice (not classified)
Reproductive toxicity (Annex IIA, point 5.6) Reproduction target / critical effect adverse effect during lactation period and impaired parental care
Lowest relevant reproductive NOAEL / NOEL 1.3 mg/kg bw/d (rat)
Developmental target / critical effect no teratogenic potential but foetotoxic at maternal toxic dose
Lowest relevant developmental NOAEL /NOEL 6 mg/kg bw/d (rabbit)
Neurotoxicity / Delayed neurotoxicity (Annex IIA, point 5.7) Neuro-endocrine effects on behaviour, cardio-vascular parameters and hormone secretion after single and repeat dose administration. Impaired alertness in humans. Acute neurotoxic NOAEL: 0.125 mg/kg/day
Other toxicological studies (Annex IIA, point 5.8)
Competitive inhibition of the α2-adrenoreceptor functions, including CNS.
Acute human oral NOAEL for α2-adrenoreceptor agonist activity: 0.125 mg/kg bw/d
Acute human dermal NOAEL for α2-adrenoreceptor agonist activity: 24 mg/kg bw/d
metabolite 27271:acute oral LD50 approx. 200 mg/kg bw; no genotoxic potential; more active than parent compound in subchronic studies; NOAEL 0.1 mg/kg bw/d (90 day dog)
Medical data (Annex IIA, point 5.9) after direct skin contact: skin flushing effects and skin rashes after acute oral ingestion: CNS depression (ranging from sleepiness to deep coma)
Summary (Annex IIA, point 5.10) Value Study Safety factor ADI 0.003 mg/kg bw/d toxicity studies in dogs 100 (90 d and 2 year)
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AOEL (systemic) 0.003 mg/kg bw/d toxicity studies in dogs 100 (90 d and 2 year)
Drinking water limit 0.1 µg/l
ArfD (acute reference dose) 0.01 mg/kg bw *) based on the NOEL of 0.25 mg/kg bw in dogs. In view of the circumstantial data from humans covering an acute exposure situation, a SF of 25 is applied
*) At an expert group meeting (16. May 2002), the ADI and the systemic AOEL were set at 0.003 mg/kg bw/d, based on the NOAEL of 0.25 mg/kg bw/d in the 2-year dog study and the safety factor of 100. Concerning the ARfD assessment, it was agreed to use this dog study as basis, too, since acute effects (slight CNS depression) were seen on the first two days of treatment only 3 hours after dosing. These effects are in line with the known pharmacological activity of amitraz, an alpha-2-adrenoceptor agonist, producing symptoms such as CNS depression. Similar effects (CNS depression, sedation) were also seen ín a human volunteer study after single oral application of 0.25 mg/kg bw. However, in a 1992 double blind crossover study of sequential single oral doses study with six healthy male volunteers, no such effects were seen at 0.125 mg/kg bw. Consequently, it was proposed by the experts to use the NOAEL in dogs of 0.25 mg/kg bw as a basis for the ARfD, but in view of the circumstantial data from humans, which covers an acute exposure situation, to apply a Safety Factor of 25, and the ARfD was thus set at 0.01 mg/kg bw. Nevertheless, it has to be emphazised that the single oral dose of 0.25 mg/kg bw, which can be regarded a NOAEL in rats, produced CNS depression in humans and is an effect dose in this species therefore, indicating that humans are at least twofold sensitive than rats with respect to CNS effects.
However, some MS questioned the use of human data and requested that there should be a clear policy on the application of human studies, e.g. in order to get the required values like ARfD. The Commission is requested to give clear advice concerning the use of human data in general .
Dermal absorption (Annex IIIA, point 7.3) Concentrate 1% absorption rate, spray dilution 2 % absorption rate based on in vivo rat study and comparative in vitro human skin/rat skin
Acceptable exposure scenarios (including method of calculation) Operator recommended use (pome fruits) acceptable for tractor application only German model, with PPE
Workers no risk identified for proposed uses; PPE required
Bystanders unlikely to exceed AOEL
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Classification and proposed labelling (Annex IIA, point 10) with regard to toxicological data Xn, R22, R48/22, Xi, R43,
List of end points Amitraz (Ac, In) 22/28 RMS: AT April 2003
5 Residues
Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6) Plant groups covered grapes, apples, lemons, pears, cotton Rotational crops lettuce, radish, wheat Plant residue definition for monitoring Amitraz including the metabolites containing the 2,4-dimethylaniline moiety expressed as Amitraz Plant residue definition for risk assessment Amitraz including the metabolites containing the 2,4-dimethylaniline moiety expressed as Amitraz Conversion factor (monitoring to risk assessment) -
Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6) Animals covered lactating cow, laying hen Animal residue definition for monitoring due to the low intake by livestock, the residue definition for food of animal origin is not regarded necessary; if higher intake occurs (due to changing intended uses), the same residue definition as for food of plant origin should be used Animal residue definition for risk assessment due to the low intake by livestock, the residue definition for food of animal origin is not regarded necessary; if higher intake occurs (due to changing intended uses), the same residue definition as for food of plant origin should be used Conversion factor (monitoring to risk assessment) - Metabolism in rat and ruminant similar (yes/no) yes Fat soluble residue: (yes/no) no
Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5) no residues above the LOD expected ......
Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 introduction) stable for 2 years (oranges, tomatoes), 18 months (hops) ...... and 13 months (cottonseed); 1 year (muscle, liver, fat, milk)
Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3) Intakes by livestock ≥ 0.1 mg/kg diet/day: Ruminant: Poultry: Pig: yes/no yes/no not assessed Muscle 0.05 mg/kg* 0.05 mg/kg* - Liver 0.05 mg/kg* 0.05 mg/kg* - Kidney 0.05 mg/kg* 0.05 mg/kg* - Fat 0.05 mg/kg* 0.05 mg/kg* - Milk 0.01 mg/kg* - - Eggs - 0.01 mg/kg* -
List of end points Amitraz (Ac, In) 23/28 RMS: AT April 2003
Summary of critical residues data (Annex IIA, point 6.3, Annex IIIA, point 8.2) Crop Northern or Trials results relevant to the critical Recommendation/comments MRL1) STMR1 Mediterranean GAP/intended uses1) Region (b) (a) Oranges US-trials PHI = 14 d.: 0.33. 0.5, 0.45, 0.49, 1.1, 1.0, only US-trials (supporting 0.99, 0.71-0.74 (8 trials) information), the results were used 0.05* only for risk calculation; Grapefruits US-trials PHI = 14: 0.51 - 0.63 (1 trial) further trials are considered necessary; not further supported
not further supported by the notifier Mandarines - no adequate data submitted further trials are considered necessary 0.05* -
not further supported by the notifier not further supported Pome fruits Northern Region 10 trials (PHI = 33 – 50 days): 0.12; 2 x 0.15; 0.42, 0.48 (apples); 0.08, 2 x 0.10, 0.5 mg/kg 0.15 0.17; 0.20 (pears)
Southern Region 9 trials (PHI = 29 – 49 days): 2 x 0.14; 2 x 0.5 mg/kg 0.185 0.17; 0.19, 0.20; 2 x 0.34, 0.42 (pears)
Stone fruits: 0.05* - Peaches, Northern Region not intended in this region Apricots further trials are considered necessary not further Southern Region no adequate data submitted not further supported by the notifier supported Stone fruits: 0.05* - Cherries, Northern Region no adequate data submitted further trials are considered necessary; Plums not further supported by the notifier not further supported Southern Region no data submitted further trials are considered necessary; not further supported by the notifier
Strawberries Northern Region no data submitted trials are considered necessary; not 0.05* - further supported by the notifier not further
List of end points Amitraz (Ac, In) 24/28 RMS: AT April 2003
Crop Northern or Trials results relevant to the critical Recommendation/comments MRL1) STMR1 Mediterranean GAP/intended uses1) Region (b) (a) Southern Region no data submitted trials are considered necessary; not supported further supported by the notifier
glasshouse no data submitted trials are considered necessary; not further supported by the notifier Currants Northern Region no adequate data submitted further trials are considered necessary; 0.05* - not further supported by the notifier not further Southern Region no data submitted trials are considered necessary; not supported further supported by the notifier
glasshouse no adequate data submitted further trials are considered necessary; not further supported by the notifier Bananas Southern Region no data submitted trials are considered necessary; not 0.05* - supported by the notifier (AgrEvo) not further supported Tomatoes Northern Region no adequate data submitted further trials are considered necessary; 0.05* - not further supported by the notifier for this region not further Southern Region 1 x 1.2 kg a.i./ha; PHI = 3 d: 0.17, 0.37, 0.55 further trials are considered necessary supported for 1 x 1.4 kg a.i./ha; PHI = 3 d: 0.31 and planned by the notifier; the reports the evaluation 2 x 0.6 kg a.i./ha; PHI = 3 d: 0.41 of the 1999 trials will be available by under 2000 (including the analysis of the 91/414/EEC single fruit in order to derive a variability factor for the acute risk assessment); the 2000 trials will be reported during 2001
not further supported by the notifier for the evaluation under 91/414/EEC
Aubergines no trials on aubergines available Extrapolation from tomatoes 0.05* -
List of end points Amitraz (Ac, In) 25/28 RMS: AT April 2003
Crop Northern or Trials results relevant to the critical Recommendation/comments MRL1) STMR1 Mediterranean GAP/intended uses1) Region (b) (a) not further supported by the notifier not further for the evaluation under 91/414/EEC supported for the evaluation under 91/414/EEC Peppers Northern Region no data submitted trials are considered necessary; not 0.05* - further supported by the notifier for this region not further supported Southern Region 3 x 0.8 kg a.i./ha; PHI = 14 d: 0.33, 0.51 (2 2 trials (field) and 8 trials (protected); trials, field) the results from all trials show that 3 x 0.8 kg a.i./ha; PHI = 14 d: 2 x 0.29, 0.49, residues resulted from protected or 0.71, 0.72, 0.80, 0.89, 1.5 (8 trials, field use were not significantly protected) different not further supported by the notifier Cucurbits – Northern Region no data submitted trials are considered necessary; not 0.05* - edible peel supported by the notifier not further Southern Region no data submitted trials are considered necessary; not supported supported by the notifier Cucurbits – Northern Region no data submitted trials are considered necessary; not 0.05* - inedible peel further supported by the notifier for (melons) this region not further supported Southern Region 2 x 0.5 kg a.i./ha; PHI = 14 d: 0.06, 3 x 0.12, 0.14, 0.17, 0.25, 0.3, 0.31 (9 trials) not further supported by the notifier Cotton only intended in the 2 x 0.6 kg a.i./ha; PHI = 19-21 d; 0.62, 0.41, 9 trials; sufficient data 0.05* - Southern Region of 0.39, 0.47, 0.59, 0.42, 0.21, 0.20, 0.52 (9 Europe trials) not further supported by the notifier not further for the evaluation under 91/414/EEC supported
Hops Northern Region dried hops: 10 trials, sufficient data 0.1* - PHI = 26 d.: 9.3, 7.2, 6.1 PHI = 27 d.: 1.3, 1.4, 1.9-2.1 not further supported by the notifier not further
List of end points Amitraz (Ac, In) 26/28 RMS: AT April 2003
Crop Northern or Trials results relevant to the critical Recommendation/comments MRL1) STMR1 Mediterranean GAP/intended uses1) Region (b) (a) PHI = 29 d.: 4.5, 7.3, 24-25 (outlier; not for the evaluation under 91/414/EEC supported included in the MRL-calculation), 5.3 (a) Numbers of trials in which particular residue levels were reported e.g. 3 x <0.01, 1 x 0.01, 6 x 0.02, 1 x 0.04, 1 x 0.08, 2 x 0.1, 2 x 0.15, 1 x 0.17 (b) Supervised Trials Median Residue i.e. the median residue level estimated on the basis of supervised trials relating to the critical GAP (1) Amitraz and Amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of Amitraz (2) According to Council Directives 95/38/EC and 95/39/EC
List of end points Amitraz (Ac, In) 27/28 RMS: AT April 2003
Consumer risk assessment (Annex IIA, point 6.9, Annex IIIA, point 8.8) ADI 0.003 mg/kg bw/d TMDI (European Diet) (% ADI) European diet: 14.3 % (adults) German diet: 60 % (children) NEDI (% ADI) IEDI (European diet) 5.4 % IEDI (German diet) 22.8 % Factors included in NEDI Factors included in IEDI: • STMRs were used for the intake calculation ARfD 0.01 mg/kg bw Acute exposure (% ARfD) Apples: 31.8 % (adults); 117.8 % (toddler) Pears: 29 % (adults); 141.6 % (toddler)
Processing factors (Annex IIA, point 6.5, Annex IIIA, point 8.4) Crop/processed crop Number of studies Transfer factor % Transference *
Citrus (orange, tangerine): 3 whole fruit to juice <0.09 - <0.13 not calculated whole fruit to pomace 0.63 - 1.1 whole fruit to peeled fruit <0.09 - < 0.13 Apple: 2 whole fruit to juice 0.46 - 0.52 not calculated whole fruit to pomace 0.99 - 2.1 whole fruit to puree 0.23 - 0.28 Cottonseed: 2 cottonseed to delinted cottonseed 0.18 - 0.95 15.3 – 80.8 % cottonseed to meal 0.13 - 0.62 7.4 – 35.5 % cottonseed to crude oil <0.10 - 0.11 < 1.6 - 1.8 % cottonseed to refined oil <0.05 - <0.10 <0.3 - < 0.7% Hops 3 not calculated fresh hops to dried hops 2.8 - 3.3 fresh hops to spent hops 0.03 - 0.14 fresh hops to beer 0.003 - 0.02 * Calculated on the basis of distribution in the different portions, parts or products as determined through balance studies
Proposed MRLs (Annex IIA, point 6.7, Annex IIIA, point 8.6) citrus not further supported; 0.05 mg/kg*
pome fruits 0.5 mg/kg
stone fruits not further supported; 0.05 mg/kg*
strawberries not further supported; 0.05 mg/kg*
currants not further supported; 0.05 mg/kg*
bananas not further supported; 0.05 mg/kg*
List of end points Amitraz (Ac, In) 28/28 RMS: AT April 2003
tomatoes and aubergines not further supported for the evaluation under 91/414/EEC; 0.05 mg/kg* peppers not further supported; 0.05 mg/kg*
cucurbits-edible peel not further supported; 0.05 mg/kg*
cucurbits-inedible peel (melons) not further supported; 0.05 mg/kg* . Cotton not further supported for the evaluation under 91/414/EEC; 0.05 mg/kg* hops (dried) not further supported for the evaluation under 91/414/EEC; 0.1 mg/kg* * LoD
In addition to the MRL-proposals, there are existing MRLs for food of animal origin deriving from veterinary uses (Regulation 2393/1999; Regulation 508/1999):
honey 0.2 mg/kg
cattle: fat 0.2 mg/kg liver 0.2 mg/kg kidneys 0.2 mg/kg milk 0.01 mg/kg
sheep: fat 0.4 mg/kg liver 0.1 mg/kg kidneys 0.2 mg/kg milk 0.01 mg/kg
pig: skin and fat 0.4 mg/kg liver 0.2 mg/kg kidneys 0.2 mg/kg
A risk assesment including food of plant origin derived from plant protection uses (MRL-proposals) and food of animal origin deriving from veterinary uses (Regulation 2393/1999; Regulation 508/1999) have been performed: TMDI-calculations show 20.1 % of the ADI (adults) and 73 % of the ADI (children)
Federal Ministry of Agriculture and Forestry
Stubenring 1 1010 Vienna Austria
Monograph prepared in the context of inclusion of following active substance in Annex I of the Council Directive 91/414/EEC
Amitraz
Volume 1
Report and Proposed Decision
Draft: December 97
- i - Amitraz - Volume 1: Contents
Contents Page
1 Statement of Subject Matter and Purpose of Monograph 1 1.1 Purpose for which the monograph was prepared 2 1.2 Summary and assessment of information relating to the collective assessment of dossiers 2 1.3 Identity of the active substance 2 1.4a Identity of the plant protection product MITAC 20 EC (AgrEvo UK Ltd.) 3 1.5a Use of the plant protection product MITAC 20 EC (AgrEvo UK Ltd.) 4 1.4b Identity of the plant protection product AMITRAZ WDG (Chimac-Agriphar S.A.) 14 1.5b Use of the plant protection product AMITRAZ WDG (Chimac Agriphar S.A.) 14 1.4c Identity of the plant protection product NARVAL (Industrias Afrasa. S.A.) 18 1.5c Use of the plant protection product -NARVAL (Industrias Afrasa. S.A.) 18 2 Overall Conclusions 21 2.1 Identity 22 2.2 Physical and chemical properties 22 2.3 Details of uses and further information 24 2.4 Impact on human and animal health 24 2.5 Methods of analysis 32 2.6 Definition of residues 33 2.7 Residues 33 2.8. Fate and behaviour in the environment 36 2.9 Effects on non-target organisms 40 2.10 Classification and labelling 45 Appendix 1 48 Appendix 2 60 3 Proposal for the Decision with Respect to the Application for Inclusion of the Amitraz in Annex I 61 3.1 Background to the proposed decision 62 3.2 Proposed decision concerning inclusion in Annex I 65 3.3 Rational for the postponement of the decision to include the active substance in Annex I, or for the conditions and restrictions to be associated with a proposed inclusion in Annex I, as appropriate 66 4 Demand for Further Information 67 4.1 Identity of the active substance 68 4.2 Physical and chemical properties of the active substance 69 4.3 Data on application and further information 70 4.5 Toxicology and metabolism 71 4.6 Residue data 72 4.7 Environmental fate and behaviour 73 4.8 Ecotoxicology 74 4.9 Classification. packaging and labelling 74
Level 1
Amitraz
Statement of Subject Matter and Purpose of Monograph - 2 - Amitraz - Level 1: Statement of subject matter and purpose
1. Statement of subject matter and purpose for which the monograph was prepared
1.1 Purpose for which the monograph was prepared
This monograph is submitted to support first inclusion of the existing active substance Amitraz in Annex I of Council Directive 91/414/EEC, according to Commission Regulations (EEC) No. 3600/92 and 933/94.
1.2 Summary and assessment of information relating to the collective assessment of dossiers
See confidential information - Annex C (Volume 4)
1.3 Identity of the active substance
1.3.1 Name and address of applicant(s) for inclusion of the active substance in Annex I (Annex IIA 1.1)
First notifier: Central Address: Member State Address: AgrEvo UK Ltd. T.B. Agrartechnik Chesterford Park Sellnergasse 4 Saffron Walden A-2540 Bad Vöslau Essex Austria CB10 1XL England Primary contact: Dr. J P R Orme Primary contact: Ing. H. Koroschetz Telephone: +44 1799 573162 Telephone: +43 2252 76960 Telefax: +44 1799 573222 Telefax: +43 2252 71005
Second notifier: Central Address: Member State Address: CHIMAC-AGRIPHAR S.A. GIMENO CONSULTANTS Rue de Renory, 26 Pottensteinerstr.20A B-4102 Ougrée A-2560 Berndorf (Seraing) Austria Belgium Primary contact: Dr. G. Neumann Primary contact: Dr. Barbara Gimeno Telephone: +32 41 301711 Telephone: +43 2672 84810 Telefax: +32 41 301749 Telefax: +43 2672 848024
Third notifier: Central Address: Member State Address: INDUSTRIAS AFRASA, S.A. no designated representative Ciudad de Sevilla, 53 46988-Polígono Industrial Fuente del Jarro PATERNA (Valencia) SPAIN Primary contact: D.Fco. J.Fernandez Garcia Telephone: 34-6-1321700 Telefax: 34-6-1321716
- 1 - Amitraz - Level 1: Statement of subject matter and purpose
1.3.2 Common name and synonyms (Annex IIA 1.3)
ISO: Amitraz (no synonyms)
1.3.3 Chemical name (Annex IIA 1.4)
IUPAC: N-methylbis(2,4-xylyliminomethyl)amine CA: N’-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl)imino]methyl]-N- methylmethaniminamide
1.3.4 Manufacturer’s development code number (Annex IIA 1.5)
1.3.4a First notifier: AgrEvo UK Ltd.
code numbers: BTS 27419 (Boots Company Ltd.) U-36059 (Upjohn/USA) JA 119 (Japan) ZK 49974 (Schering/Germany) CR 17612 (Schering/UK)
1.3.4b Second notifier: Chimac-Agriphar S.A.
code numbers: no information provided
1.3.4c Third notifier: Industrias Afrasa, S.A.
code numbers: ZB/46275-89
1.3.5 CAS, EEC and CIPAC numbers (Annex IIA 1.6)
CAS No.: 33089-61-1 EINECS No.: 2513574 CIPAC: 362
1.3.6 Molecular formula, structural formula, molecular mass (Annex IIA 1.7)
Molecular formula: C19H23N3 Structural formula:
CH3 CH3 CH3 NCHNCHN CH3
CH 3
Molecular mass: 293.4 - 2 - Amitraz - Level 1: Statement of subject matter and purpose
1.3.7 Manufacturer or manufacturers of the active substance (Annex IIA 1.2)
1.3.7a First notifier: AgrEvo UK Ltd.
Address: AgrEvo UK Limited Hauxton Cambridge, CB2 5HU England Contact: Mr. M. Brown Telephone: +44 1223 870312 Telefax: +44 1223 872142
Manufacturing plant: Address: BASFIN Corporation, Knoll Pharmaceuticals Beeston Nottingham NG2 3AA England Manufactured by BASFIN Corporation, Knoll Pharmaceuticals on behalf of AgrEvo UK Limited in a plant owned by AgrEvo UK Limited.
1.3.7b Second notifier: Chimac-Agriphar S.A.:
Address: DEFENSA Puerto Alegre /RS Rua Padre Chagas, 79 - 7° Andar Caixa Postal: 10551 BRASIL Primary contact: Dr. Georges Neumann Telephone: 32-41-30.17.11 Telefax: 32-41-30.17.49
Manufacturing plant: DEFENSA S.A. Av. Júlio de Castilhos 2085 Taquari- RS BRASIL CEP 958600-000 Telephone: 00 55 51 653 1277 Telefax: 00 55 51 653 1100
1.3.7c Third notifier: Industrias Afrasa, S.A.
Address: HANGZHOU PESTICDES 277 Airport Road Hangzhou CHINA Primary contact: not designated Telephone: no adequate information provided Telefax: no adequate information provided
Manufacturing plant: no information
1.3.8 Method or methods of manufacture (Annex IIA 1.8)
Confidential Information - See Annex C
- 3 - Amitraz - Level 1: Statement of subject matter and purpose
1.3.9 Specification of purity of the active substance (Annex IIA 1.9)
1.3.9a First notifier: AgrEvo UK Ltd.
min. 970 g/kg
1.3.9b Second notifier: Chimac-Agriphar S.A.
The notifier suggested: min. 965 g/kg. (see confidential information- Annex C)
1.3.9c Third notifier: Industrias Afrasa, S.A.
The notifier suggested: min. 950 g/kg (see confidential information- Annex C)
1.3.10 Identity of isomers, impurities and additives (Annex IIA 1.10)
No inactive isomers Impurities: see confidential information - Annex C
1.3.11 Analytical profile of batches (Annex IIA 1.11)
see confidential information -Annex C
1.4a Identity of the plant protection product MITAC 20 EC (AgrEvo UK Ltd.)
1.4.1a Current, former and proposed trade names and development code numbers (Annex IIIA 1.3)
Trade names: Mitac® Maïtac® Bumetran Trazam Manufacturer's Code number: CR 19055 CR 17299 CR 18264 CR 19860 CR 17635 ‘FSN’ prefix used instead of ‘CR’ prefix when production material used for test purposes.
1.4.2a Manufacturer or manufacturers of the plant protection product - First notifier (Annex IIIA 1.2)
Central address: BASFIN Corporation, Knoll Pharmaceuticals Beeston Nottingham NG2 3AA England Primary contact: Mr. M. Brown Telephone: +44 1223 870312
- 4 - Amitraz - Level 1: Statement of subject matter and purpose
Telefax: +44 1223 872142
1.4.3a Type of the preparation and code (Annex IIIA 1.5)
Emulsifiable concentrate (EC)
1.4.4a Function (Annex IIA 3.1, Annex IIIA 1.6)
Acaricide / insecticide
1.4.5a Composition of the preparation (Annex IIIA 1.4)
Component g/l Chemical name CAS no. Function
Amitraz technical 200.4 N-methylbis(2,4- 33089-61-1 technical active (purity 99.8%) xylyliminomethyl)amine substance
Amitraz 200.0 pure active substance
A detailed specification, which includes details of the formulants in the preparation, is provided in Annex C.
1.5a Use of the plant protection product MITAC 20 EC (AgrEvo UK Ltd.)
1.5.1a Field of use (Annex IIA 3.3, Annex IIIA 3.1)
Agriculture, horticulture, orchards, forestry, amenity (public greens) Field use, protected crops (under glass / in greenhouse)
1.5.2a Effects on harmful organisms (Annex IIA 3.2, Annex IIIA 3.2)
Amitraz and its metabolite BTS 27271 (N, N’-bis(2,4-xylyl)formamidine ) are effective against insects and mites acting by contact. These substances act as an agonist of the insect neurtotransmitter octopamine by mimicking its actions at the insect neuromuscular junction. Amitraz is not translocated in plants but it does have translaminar activity.
1.5.3a Summary of intended uses (Annex IIA 3.4, Annex IIIA 3.3 to 3.7, 3.9)
Harmful organsisms controlled or other effects Insecticidal activity: Amitraz has been shown to give effective control of a number of hemipterous pests such as Psylla and whitefly and to suppress others such as scale insects and aphids. Also it gives activity against certain species of Lepidoptera at the egg and the first instar larval stage.
- 5 - Amitraz - Level 1: Statement of subject matter and purpose
Insects controlled: Psyllids: Agonoscena targionii Aphids: Aphis fabae Psylla mali Aphis gossyplii * Psylla pyri * Aphis porni Psylla pyricola Dysaphis plantaginea Whitefly: Bemisia tabaci * Dysaphis pyri Dialeurodes citri * Eriosoma lanigerum Jassids: Empoasca lybica Myzus persicae Erythroneura elegantula Phorodon humuli * Erythroneura variabilis Rhopalosiphum maidis Typhlocyba comes Toxoptera citricida Typhlocyba pomaria Lepidoptera: Bucculartix thurberiella Typhlocyba rosae Cydia pomonella Scale insects Ceroplastes rubens * Diparopsis castanea & mealy bugs: Ceroplastes rusci Earias spp. Ceroplastes sinensis Heliothis spp. * Gascardia destructor Leucoptera scitella * Planococcus citri * Lithocolletis blancardella * Quadraspidiotus perniciosus Pectinophora gossypiella Saissetia oleae * Perleucoptera coffeella Lepidosaphis ulmi Spodoptera spp. * * main uses
Acaricidal activity Amitraz is active against all stages of spider mite development except winter eggs of Panonychus ulmi. The notifier stated, that it is active against mites which have developed resistance to other acaricides. Mites controlled:
Aculus cornutus Panonychus ulmi * Aculus fockeui Phyllocoptruta oleivora * Aculus schlechtendali * Steneotarsonemus pallidus Brevipalpus lewisi Tetranychus cinnabarinus * Brevipalpus phoenicis Tetranychus evani Epitrimerus pyri Tetranychus kanzawai Eriophyes sheldoni Tetranychus lambi Eriophyes vitis Tetranychus mcdaniellii Eutetranychus banksi Tetranychus pacificus Hemitarsonemus latus Tetranychus urticae * Oligonychus ilicis * main uses Oligonychus yothersi Panonychus citri *
- 6 - Amitraz - Level 1: Statement of subject matter and purpose
Recommended time of application: For mite control apply at the start of mite infestation build-up before damage occurs. In strawberries use is restricted to pre-flowering or post-cropping only.
Table 1.5.3a-1 Summary of approved uses of MITAC 20 EC
Crop Country Maximum Maximum Spray No. of Pre- rate per rate per conc. applications harvest application season (g/l) (maximum interval (kg a.s./ha) (kg a.s./ha) per season) (days)
Citrus Greece 2.4 2.4 - 4.8 1 - 2 30
Italy 0.6 0.6 - 1.2 1 - 2 35
Spain 0.2 - as required 14 0.75
Pome fruit Austria 0.32 0.32 - 0.64 1 - 2 28
Greece 1.5 1.5 - 4.5 1 - 3 30
Spain 0.2 - as required 14 0.75
Apples Belgium 0.2 - 0.3 0.2 - 0.4 1 - 2 28
France 0. 8 30
Germany 0.75 0.75 - 1.5 1 - 2 28
Italy 0.7 0.7 - 1.4 1 - 2 28
Netherlands 0.6 0.6 - 1.8 1 - 3 28
Portugal 0.45 0.45 - 1.35 1 - 3 30
UK 0.3 - 0.7 0.3 - 1.4 1 - 2 14
Pears Belgium 0.2 - 0.3 0.2 - 0.4 1 - 2 28
France 0.8 30
Germany 0.75 0.75 - 1.5 1 - 2 28
Italy 0.9 0.9 - 1.8 1 - 2 28
Netherlands 0.6 0.6 - 1.2 1 - 2 28
Portugal 0.45 - 0.6 0.45 - 1.8 1 - 3 30
UK 0.7 0.7 - 1.4 1 - 2 14
Stone fruit Greece 1.5 1.5 - 4.5 1 - 3 30
Italy 0.6 0.6 - 1.2 1 - 2 28
Spain 0.2 - as required 14 0.75
Peaches France 0.8 30
Austria 0.32 - 0.4 0.32 - 0.8 1 - 2 28
Vines Greece 0.6 0.6 1 30
- 7 - Amitraz - Level 1: Subject matter and purpose
Crop Country Maximum Maximum Spray No. of Pre- rate per rate per conc. applications harvest application season (g/l) (maximum interval (kg a.s./ha) (kg a.s./ha) per season) (days)
Italy 0.5 0.5 1 35
Strawberries Belgium 0.4 0.4 1 (after picking. - after planting) Netherlands 0.2 - 1.0 2 - 5 - (pre blossom. post harvest) Spain 0.2 - as required 7 0.75
Vegetables Greece 0.4 - 0.6 7
Cucurbits Italy 0.5 0.5 1 28
Spain 0.2 - as required 14 0.75
Tomatoes Belgium 0.8 several 3
Netherlands 0.8 0.08 - 2.4 1 - 3 3
Spain 0.2 - as required 14 0.75
Aubergines Italy 0.5 0.5 1 28
Netherlands 0.8 0.8 - 2.4 1 - 3 3
Spain 0.2 - as required 14 0.75
Peppers Netherlands 0.8 0.8 - 2.4 1-3 3
Spain 0.2 - as required 14 0.75
Cotton Greece 0.6 0.6 - 1.2 1 - 2 30
Spain 0.2 - as required 30 0.75
Hops Germany 0.075 - 3.75 1 - 2 35
UK 0.7 0.7 - 1.4 1 - 2 49
Ornamentals Austria 0.32 0.32 - 0.64 1-2 -
Belgium 0.6 0.6 1 (before leaves) -
Denmark 0.5 -
Greece 0.4 - 0.6 1 - 2 -
Italy 0.5 as needed -
Spain 0.2 - as required - 0.75
Roses Netherlands 0.2 0.2 - 0.4 1 - 2 -
- 8 - Amitraz - Level 1: Subject matter and purpose
Crop Country Maximum Maximum Spray No. of Pre- rate per rate per conc. applications harvest application season (g/l) (maximum interval (kg a.s./ha) (kg a.s./ha) per season) (days)
Empty Belgium 2.0 1 - glasshouses (during winter)
Netherlands 0.2 0.2 1 (clean-up) -
Nursery crops Netherlands 0.2 0.2 1 (spent - (under glass) vegetables)
Tree nurseries Netherlands 0.2 0.2 - 0.4 1 - 2 -
Public greens Netherlands 0.2 0.2 - 0.4 1 - 2 -
- 9 - Amitraz - Level 1: Statement of subject matter and purpose
Table 1.5.3a-2 Summary of intended uses of MITAC 20 EC
Crop and/or F or G Pest/ Application Application rate per treatment PHI Northern Europe situation group of (N) pests Southern Europe (field/ Method Growth No. kg a.s./hl water l/ha kg days (S) glass) kind stage a.s./ha Oranges F Mites Spray Beginning of 2 0.04 2000 0.8 14 S Scales infestation Mandarines F Mites Spray Beginning of 2 0.04 2000 0.8 14 S Scales infestation Apples F Mites Spray Beginning of 2 0.08 1000 0.8 28 N / S Rust mites infestation Pears F Mites Spray Beginning of 2 0.08 1000 0.8 28 N / S infestation Cherries F Mites Spray Beginning of 2 0.08 1000 0.8 28 N / S Aphids infestation Plums F Mites Spray Beginning of 2 0.08 1000 0.8 28 N / S Aphids infestation Peaches F Mites Spray Beginning of 2 0.08 1000 0.8 28 S Aphids infestation Apricots F Mites Spray Beginning of 2 0.08 1000 0.8 28 S Aphids infestation Strawberries F/G Mites Spray Pre-blossom 2 0.15 500 0.8 35 N / S Rust mites post-harvest Blackcurrants F/G Mites Spray Pre-blossom 2 0.15 500 0.8 42 N Rust mites post-harvest Tomatoes F Mites Spray Beginning of 3 0.08 1000 0.8 14 N / S infestation Peppers F Mites Spray Beginning of 3 0.08 1000 0.8 14 N / S infestation
- 10 - Amitraz - Level 1: Subject matter and purpose
Crop and/or F or G Pest/ Application Application rate per treatment PHI Northern Europe situation group of (N) pests Southern Europe (field/ Method Growth No. kg a.s./hl water l/ha kg days (S) glass) kind stage a.s./ha Aubergines F Mites Spray Beginning of 1 0.05 1000 0.5 14 N / S infestation Cotton F Mites Spray All season 2 0.06 1000 0.6 21 S Insects Hops F Mites Spray Beginning of 2 0.05 2300 - 2.5 28 N Aphids infestation 5000 Mist 2 0.075 1500 - 2.5 28 blower 3300 Ornamentals F/G Mites Spray All season 2 0.06 1000 0.6 - N / S Insects Glass houses G Mites Spray Empty 1 - - 1 - N Insects greenhouses Tree nursery F Mites Spray All season 2 0.2 500 1 - N / S Insects Public green F Mites Spray All season 2 0.2 500 1 - N / S Insects
- 11 - Amitraz - Level 1: Statement of subject matter and purpose
1.5.4a Information on authorization in EU Member States (Annex IIIA 12.1)
Table 1.5.4a-1: Authorizations and Registrations in the EU - MITAC 20 EC
Country Type of authorization Crop/uses Authorization details
AUSTRIA Commercial Top fruits MITAC 20 EC Ornamentals EC 200 g/l Reg.No. 2329 Date of issue: 11.3.1987 Date of expiry: 31.7.2001
BELGIUM Commercial Orchards (apples & MITAC pears) EC Tomatoes in 200 g/l greenhouse Reg.No. 7389/B Strawberries Date of issue: 26.5.94 Empty greenhouses Date of expiry: 8.12.2003 Ornamental trees & bushes
DENMARK Commercial Indoor use on MITAC 20 ornamental trees EC 200 g/l Reg.No. 6-49 Date of issue: 8.1.1985 Date of expiry: non terminating
FRANCE Commercial Apples MITAC 20 Pears EC Peaches 200 g/l Reg.No. 7800210 Date of issue: to be advised Date of expiry: to be advised
MITAC 20 HF EC 200 g/l Reg.No. 9100572 Date of issue: to be advised Date of expiry: to be advised
GERMANY Commercial Apples MITAC Pears EC Hops 200 g/l Reg.No. 23302 Date of issue: 22.4.1992 Date of expiry: 31.12.2002
GREECE Commercial Pome fruit MITAC 20 EC Stone fruit EC Citrus 200 g/l Vines Reg.No. 2036 Cotton Date of issue: 26.1.1980 Vegetables Date of expiry: Application Ornamentals for renewal lodged
ITALY Commercial Apples BUMETRAN Pears EC Stone fruits (all) 200 g/l
- 12 - Amitraz - Level 1: Subject matter and purpose
Country Type of authorization Crop/uses Authorization details Citrus (all) Reg.No. 2505 Vines Date of issue: 4.4.1977 Cucurbits (all) Date of expiry: non Aubergines terminating Ornamentals BUMETRAN HF EC 200 g/l Reg.No. 8297 Date of issue: 4.6.1993 Date of expiry: non terminating MITAC 20 CE EC 200 g/l Reg.No. 8298 Date of issue: 4.6.1993 Date of expiry: non terminating ACATRAZ HF EC 200 g/l Reg.No. 6791 Date of issue: 1.10.1988 Date of expiry: non terminating
NETHERLANDS Commercial Apples MITAC Pears EC Strawberries 200 g/l Tomatoes Reg.No. 6904-N Aubergines Date of issue: Peppers Date of expiry: 1.8.1996 Ornamentals Empty glasshouses Tree nurseries Nursery crops
PORTUGAL Commercial Apples & Pears (mites) MITAC 20 EC 200 g/l Provisional sales permit Pears (Psylla) Reg.No. 2343 Date of issue: 1982 Date of expiry: 2.1.1996
SPAIN Commercial Pome fruit MITAC PLUS EC Stone fruit EC Tomatoes 200 g/l Peppers Reg.No. 12.215/02 Aubergines Date of issue: 18.11.1994 Cucurbits Date of expiry: 31.12.2002 Strawberries Ornamentals Citrus MITAC TOP EC Cotton EC Bananas 200 g/l Reg.No. 14.316/02 Date of issue: 20.2.1995
- 13 - Amitraz - Level 1: Subject matter and purpose
Country Type of authorization Crop/uses Authorization details Date of expiry: 31.12.2003
UNITED KINGDOM Commercial Apples MITAC Pears EC Hops 200 g/l Reg.No. 07265 Date of issue: 11.8.1989 Date of expiry: 25.7.2003
- 14 - Amitraz - Level 1: Subject matter and purpose
1.4b Identity of the plant protection product AMITRAZ WDG (Chimac-Agriphar S.A.)
1.4.1b Current. former and proposed trade names and development code numbers (Annex IIIA 1.3)
Trade name: AMITRAZ WDG Manufacturer's Code number: 501
1.4.2b Manufacturer or manufacturers of the plant protection product (Annex IIIA 1.2)
Central address: DEFENSA S.A. Av. Júlio de Castilhos, 2085 Taquari- RS BRAZIL CEP 95860-000 Telephone: 00 55 51 653 1277 Telefax: 00 55 51 653 1100
1.4.3b Type of the preparation and code (Annex IIIA 1.5)
Water dispersible granules (WG)
1.4.4b Function (Annex IIA 3.1. Annex IIIA 1.6)
Insecticide / acaricide
1.4.5b Composition of the preparation (Annex IIIA 1.4)
Component g/kg Chemical name CAS no. Function (dry base)
Amitraz technical 765 N-methylbis(2,4- 33089-61-1 technical active (purity 98%) xylyliminomethyl)amine substance
Amitraz 750 pure active substance
Further information on the composition of the formulation AMITRAZ WDG is provided in Annex C.
1.5b Use of the plant protection product AMITRAZ WDG (Chimac Agriphar S.A.)
1.5.1b Field of use (Annex IIA 3.3. Annex IIIA 3.1)
Field use
1.5.2b Effects on harmful organisms (Annex IIA 3.2. Annex IIIA 3.2)
see 1.5a
1.5.3b Summary of intended uses (Annex IIA 3.4. Annex IIIA 3.3 to 3.7. 3.9)
Harmful organsisms controlled or other effects: Amitraz is effective against a wide range of
- 15 - Amitraz - Level 1: Subject matter and purpose phytophagus mites and insects. Time of application: To control Panonychus ulmi start the application when the population reaches the average of 5 mites per leaf (consider only the adult females). Against Phyllocoptruta oleivora start spraying when on 20 % of fruits or leaves the mite is found. Brevipalpus phoenicis: start spraying when on 3% of fruits at least one mite is found. Cacopsylla pyri: to inhibit egg-laying psylla, apply as soon as first eggs are laid. Second application after 7 days if adults are still present. Better control is obtained when majority of insects are in adult or young nymphal stages of development.
- 16 - Amitraz - Level 1: Statement of subject matter and purpose
Table 1.5.3b-2 Summary of intended uses of AMITRAZ WDG
Crop and/or F or G Pest/ Application Application rate per treatment PHI Region (N/S) situation group of pests (field/ Method Growth No. kg a.s./hl water l/ha kg days Northern Europe glass) kind stage a.s./ha (N) Southern Europe (S) Citrus F Phyllocoptruta Spray Beginning of 2-3 0,030 - 200 - 2500 7 S oleivora , infestation 0,035 Brevipalpus phoenicis Apples F Panonychus Spray Beginning of 2 -3 0,04 200 - 2500 0,08 - 1 14 ulmi infestation Pears F Cacopsylla pyri Spray Beginning of 2 0,06 200 - 2500 0,12 - 1,5 14 infestation
- 17 - Amitraz - Level 1: Statement of subject matter and purpose
1.5.4b Information on authorization in EU Member States (Annex IIIA 12.1)
No information provided concerning the formulation Amitraz WDG for which the Annex III dossier has been submitted.
- 18 - Amitraz - Level 1: Subject matter and purpose
1.4c Identity of the plant protection product NARVAL (Industrias Afrasa. S.A.)
1.4.1c Current. former and proposed trade names and development code numbers (Annex IIIA 1.3)
Trade name: NARVAL Manufacturer's Code number: No information provided
1.4.2c Manufacturer or manufacturers of the plant protection product (Annex IIIA 1.2)
Address: INDUSTRIAS AFRASA, S.A. Ciudad de Sevilla, 53 46988-Polígono Industrial Fuente del Jarro PATERNA (Valencia) SPAIN Primary contact: D.Fco. Javier Fernandez Garcia Telephone: 34-6-1321700 Telefax: 34-6-1321716
1.4.3c Type of the preparation and code (Annex IIIA 1.5)
Emulsifiable concentrate (EC)
1.4.4c Function (Annex IIA 3.1. Annex IIIA 1.6)
Insecticide / acaricide
1.4.5c Composition of the preparation NARVAL (Annex IIIA 1.4)
Component g/l Chemical name CAS no. Function
Amitraz technical 206.0 N-methylbis(2,4- 33089-61-1 technical active (purity 97 %) xylyliminomethyl)amine substance
Amitraz 200.0 pure active substance
Further information on the composition of the formulation is provided in Annex C.
1.5c Use of the plant protection product NARVAL
1.5.1c Field of use (Annex IIA 3.3. Annex IIIA 3.1)
Field, greenhouse
1.5.2c Effects on harmful organisms (Annex IIA 3.2. Annex IIIA 3.2)
See 1.5.2a
- 19 - Amitraz - Level 1: Subject matter and purpose
1.5.3c Summary of intended uses (Annex IIA 3.4. Annex IIIA 3.3 to 3.7. 3.9)
Table 1.5.3c-1 Summary of indented uses of NARVAL
Crop Pests controlled
Seed and stone fruit trees Spider mites Panonychus ulmi Tetranychus urticae Bryobia rubriculus
Psila Psylla pyri
Citrus Spider mites Panonychus citri Tetranychus urticae
Cochineal insects Aspidiotus aurantii Aspidiotus nerii Leidosaphes beckii Parlatoria pergandii Ceroplastes sinensis Coccus hesperidum Saissetia oleae Planococcus citri Iceria purchasi
Banana tree Spider mites Tetranychus urticae Panonychus ulmi
Cucurbitaceae Spider mites Tetranychus urticae Tomato Tetranychus turkestani Pepper Aubergine
Strawberry Spider mites Tetaniquides and Eriophides mites
Ornamental Spider mites Tetaniquides and Flower plant Eriophides mites
Cotton Spider mites Heliothis armigera
Recommended time of application: Application of the crops should take place as soon as mites are first seen.
Table 1.5.3c-2 Summary of approved uses of NARVAL
Crop Country Maximum Maximum Maximum Pre-harvest rate per rate per number of interval in application season applications (days) (kg a.i./ha) (kg a.i./ha) per season
Seed and stone fruit Spain 0.2 - 0.6 1.8 3 14 trees
Banana trees 0.2 - 0.6 1.2 2 14
Citrus 0.2 - 0.3 0.3 1 14
Tomatoes 0.2 - 0.6 1.2 2 14
- 20 - Amitraz - Level 1: Subject matter and purpose
Crop Country Maximum Maximum Maximum Pre-harvest rate per rate per number of interval in application season applications (days) (kg a.i./ha) (kg a.i./ha) per season
Cucurbitaceae 0.2 - 0.6 1.2 2 14
Peppers 0.2 - 0.6 1.2 2 14
Aubergines 0.2 - 0.6 1.2 2 14
Strawberries 0.2 - 0.6 1.2 2 7
Ornamentals 0.2 - 0.6 1.2 2 14
Cotton 0.2 - 0.6 1.8 3 not applcable
The notifier stated, that the approved uses are identical with the intended uses.
1.5.4c Information on authorization in EU Member States (Annex IIIA 12.1)
Table 1.5.4c-1: Authorizations and Registrations in the EU - NARVAL
Country Type of authorization Crop/uses Authorization details
SPAIN Commercial Seed and stone fruit NARVAL trees EC Banana trees 20% Amitraz Citrus Reg.No.: 19094/94 Tomato Date of issue: 5.3.1993 Cucurbits Date of expiry: 5.3.1995 Peppers Aubergines Strawberries Ornamentals Flower plants
- 21 -
Level 2
Amitraz
Overall Conclusions
- 22 - Amitraz - Level 2: Reasoned statement of the overall conclusions
2. Reasoned statement of the overall conclusions drawn by the Rapporteur Member State
2.1 Identity
Amitraz is known by its IUPAC chemical name N-methylbis(2,4-xylyliminomethyl)amine. The three notifying companies apply different methods of manufacture, which - according to the partly weak database provided -indicate different profiles of impurities. However, this can only be confirmed after all information as specified in Volume 1, level 4 has been provided. AgrEvo UK Ltd: Sufficient information concerning the identity of the active substance, its impurities, the method of manufacture and the analytical methods for determination of the active substance and the impurities were submitted. The specified purity is greater than 970 g/kg. Chimac Agriphar S.A.: A summary description of the method of manufacture has been provided. The notifier identified six different impurities in the active substance, which have been characterized by means of HPLC-MS using atmospheric pressure ionization. The quantification of the different impurities was not reliable. The notifier suggested a minimum purity of 965 g/kg for the active substance as manufactured, but the data provided do not support this assigned minimum value. A reliable determination and quantification of the impurities is still required to characterise the active substance and to evaluate the comparability of the active substance produced on behalf of the notifier Chimac Agriphar S.A. with the products of the other notifiers. Industrias Afrasa S.A.: As there are possible variations in the manufacturing process, the notifier has to explain whether this has consequences with respect to the purity or the profile of impurities of the resulting active substance. The specification of the starting materials is required, too. The information about the impurities is equivocal and contradictory. The analytical method for the determination of the active substance and the impurities is not available. The information provided concerning the profile of batches as well as the identity and amount of impurities is insufficient. As the information provided by the notifier is incomplete and does not meet the requirements laid down in Annex II, the identity of the active substance as manufactured is not sufficiently characterized. No evaluation concerning the comparability of the active substance produced on behalf of the notifier Industrias Afrasa S.A. with the products of the other notifiers is possible.
2.2 Physical and chemical properties
2.2.1 Active substance
Amitraz is a white crystalline solid which is virtually odourless. It has a melting point of 86°C and is slightly volatile (vapour pressure: 3.4 x 10-4 Pa). At neutral and alkaline pH Amitraz is
- 23 - Amitraz - Level 2: Reasoned statement of the overall conclusions
very slightly soluble in water. Under acidic conditions Amitraz is not stable. It is readily soluble in organic solvent. The molecule is very rapidly hydrolysing at environmental pHs
and its degradation due to aqueous photolysis occurs rapidly with DT50 of about 2 days. The
log Po/w of 5.5 indicates that the molecule should be classified as fat soluble. Amitraz does not show explosive properties (with respect to thermal and mechanical sensitivity) or oxidizing properties. It has been proved that the test substance is neither flammable nor auto-flammable under the test conditions.
2.2.2 Formulation
2.2.2a MITAC 20 EC (AgrEvo UK Ltd.)
The notifier submitted information for the emulsifiable concentrate MITAC 20 EC, which contains 200 g active ingredient per litre. The detailed composition of the formulation is presented in Annex C, Confidential Information. The formulation was claimed to be stable for at least 2 years although some supporting data are still missing (see Level 4). Since data on explosive properties are missing, the evaluation of the product in the context of safety can not be finalised. Other data provided in accordance with Annex III indicate that there is no evidence of adverse physical or chemical properties. The notifier submitted information about the compatibility of MITAC 20 EC with a wide range of formulations. This information should be considered on member state level.
2.2.2b AMITRAZ WDG (Chimac Agriphar S.A.)
The notifier submitted information for the water dispersible granule AMITRAZ WDG with a content of active ingredient of 750 g/kg. The composition of the formulation has been submitted (see Annex C, Confidential Information). The formulation is a tan granule, which is not classified highly flammable or oxidizing. The autoignition temperature is high. The pH of a 1% solution is 10.31. The formulation showed acceptable physical and chemical properties both before and after the accelerated storage test. For an evaluation of the shelf life study, however, the storage-time has to be given. Studies that have to be submitted to finalize the evaluation are: explosive properties under friction condition, attrition, friability and flowability.
2.2.2c NARVAL (Industrias Afrasa, S.A.)
The notifier Industrias Afrasa, S.A. submitted an Annex III Dossier on the EC formulation NARVAL, which contains 200 g Amitraz per litre. The identity of the formulation has been specified (see Annex C, Confidential Information). As the studies on explosive properties, oxidizing properties, auto flammability and flash point are missing a classification with respect to safety aspects is not possible. The notifier submitted incomplete information on the physical chemical properties of the
- 24 - Amitraz - Level 2: Reasoned statement of the overall conclusions
formulation. An announcement that the missing studies and data will be provided later was made, but no time schedule for generating and submission of the new studies has been provided. Based on the information available at the moment it has to be concluded, that an evaluation of the product is not possible.
2.3 Details of uses and further information
2.3.1 Details of uses
Amitraz is used as insecticide and acaricide in agriculture, horticulture, orchards, forestry and amenity. It is also used in veterinary medicine as ectoparasiticide. The active substance and its metabolite N,N’-bis(2,4-xylyl)formamidine are effective against insects and mites acting by contact. These substances are agonists of the insect neurotransmitter octopamine. Amitraz can be formulated as emulsifiable concentrate or as solid preparation e.g. water dispersible granule.
2.3.2 Further information
Information on handling, storage, transport, fire, destruction or decontamination, emergency measures for the technical product and the EC formulation MITAC 20 EC have been supplied and are acceptable. For the formulations AMITRAZ WDG and NARVAL the information as specified in Volume 1, level 4 is still lacking.
2.4 Impact on human and animal health
2.4.1 Effects having relevance to human and animal health arising from exposure to the active substance or to impurities contained in the active substance or to their transformation products
After single oral administration of radiolabelled Amitraz to rats, mice, dogs, baboons and men it has been shown that the compound is well absorbed from the gastrointestinal tract and rapidly excreted via urine and to a lesser extent via the faeces; in rats, mice and dogs nearly 80 % of the applied dose are excreted in the first 24 hours after dosing and nearly 100 % after 72 and 96 hours respectively. In baboons, more than 80 % of the applied dose was detected in urine and faeces after a collection period of 72 hours. In human volunteers more than half of the applied dose was excreted in the urine in the first 24 hours, by 48 hours 77 % of the applied dose were detected in the urine and 82 % after 72 hours. Tissue residue levels in rats, mice, dogs and baboon after a single application were found to be highest in the liver and there were no differences between male and female animals in absorption, distribution and excretion. Repeated oral doses of 14 C-Amitraz to rats showed tissue residue levels being highest in thyroid, adrenal and liver after 7 and also after 28 days of treatment. Two days after final dosage a decrease in magnitude and distribution of
- 25 - Amitraz - Level 2: Reasoned statement of the overall conclusions residues was observed, showing the highest residue levels in the liver of both sexes.
After dermal application of 14 C-Amitraz to male rats, radioactivity was slowly absorbed and subsequently rapidly eliminated via urine and faeces. Absorption increased with application rate and contact time. Washing the application site effectively removed most of the applied dose (nearly 95 %). Residual radioactivity retained at the application site post-washings fell to < 3 % by 24 hours and to 1.4 resp. 0.6 % after five days. The absorption rate was between 3 and 12.4 %; the extent of absorption (as percent of the applied dose) fell with increasing dose rate. Absorbed radioactivity was primarily eliminated in urine with minor quantities detected in faeces. Levels of radioactivity in residual carcasses were low and were below the limit of detection after 5 days post application. 14 C-Amitraz in a diluted EC formulation applied to the skin of male and female pigs showed also a remote of 57 - 81 % after washing the skin 12 hours after application. Over a period of 60 hours after dosing, 6.7 ± 2.7 % of the applied radioactivity was detected in urine and faeces and it is reasoned that this is equivalent to the radioactivity absorbed through the skin. Based on these animal studies the absorption of Amitraz through skin was in a range of 3 - 12 % in rats and 4 - 9.5 % in pigs. The rate of absorption of 14C-Amitraz (as "Mitac W") was also determined through rat and human epidermis using an in vitro system (Ref.: John, 1997). The results demonstrated that rat skin is more permeable and shows a higher penetration rate than human skin under the same condintions. In summary it can be concluded that the dermal absorption rate of amitraz in rats ranges up to 12%. Therefore a mean dermaal absorption rate of Amitraz of 10% should be taken into account.
Studies on metabolism in rats, dogs and men have shown that the proportion of each metabolite was broadly similar. In the rat, the main metabolites found in urine after single and repeated oral administrations of 14 C-Amitraz were BTS 39098 [4-formamido-m-toluic acid], FBC 31158 [4-acetomido-m-toluic acid] and BTS 27271 [N’-(2,4-Dimethylphenyl)-N- Methylformamidine)], which together accounted for up to 32 % of the urinary excretion. A polar fraction contained conjugates of BTS 39098, FBC 31158, BTS 28369 [4-amino-3- methylbenzoic acid] and BTS 27271 and constituted 32-65 % of the excretion. These conjugates and the free BTS 39098 and FBC 31158 were converted by hydrolysis to BTS 28369. The minor metabolites BTS 27919 and BTS 28369 accounted for approximately 2% of the total excretion. Raising the dose rate from 1 to 100 mg 14 C-Amitraz/kg bw produced a marked increase in the proportion of the urinary radioactivity excreted as BTS 27271 (from 4 % up to 23-38 %). In dogs it has been demonstrated that the metabolism of 14 C-Amitraz is essentially the same by either oral or dermal administration, BTS 39098 was the predominant residue in blood and urine. The first formed hydrolysis products BTS 27271 and BTS 27919 were never observed at measurable levels in blood or urine in dogs treated either orally or dermally with
- 26 - Amitraz - Level 2: Reasoned statement of the overall conclusions
14 C-Amitraz. BTS 24868 was also found to be a negligible metabolic fate. The metabolites in human urine were mainly FBC 31158 and BTS 39098 which together contain 27.1 % of the excreted radioactivity. As in the case of rats, the fraction categorised as polar material consists mainly of conjugates of FBC 31158, BTS 39098 and BTS 28369 and accounted for nearly 60 %. BTS 27271 accounted for 5.8% of the human urinary excretion. The proportion of the minor metabolites BTS 27919 and BTS 28369 was slightly higher than in rats and accounted for 3.6-3.8 % of the urinary radioactivity.
Following oral administration, technical Amitraz is harmful to rats with a LD50-value of approximately 500 - 600 mg/kg bw.; mice seem to be less sensitive and dogs more sensitive
than rats. Clear LD50-values for these both animal species could not be established. Clinical symptomology in rats, mice and dogs consists principally of nerval symptoms. Evaluation of acute dermal toxicity was not possible due to a scientific invalid study. Therefore a limit test is required. The highest achievable concentration of 75 mg/l air in an acute inhalation toxicity study caused death among 7/12 rats; Amitraz is not classifiable as acute toxic to rats via inhalation route. Technical Amitraz does not cause skin irritation but elicits slight conjunctival irritancy in the rabbit eye. Although Amitraz is not a skin sensitiser following the test method of Buehler there is clear evidence of delayed contact hypersensitivity following the test method of Magnusson and Kligman. Additionally, direct skin contact to small amounts can produce "skin flushings" over a period of a few days to a few weeks, which is cause of the fact, that
Amitraz is an α2-receptor agonist and this symptoms are due to central and peripheral α2- adrenergic action.
Table 2.4.1-1 Acute toxicity data of Amitraz
Animal Type of exposure Results Comments species (LD50, LC50) rat acute oral toxicity appr. 600 mg/kg bw Xn, R22 mouse acute oral toxicity > 1600 mg/kg bw rat acute dermal toxicity > 1600 mg/kg bw not valid rat acute inhalative toxicity appr. 65 mg/l air (6 hours) rabbit skin irritation not to slight irritant rabbit eye irritation not to slight irritant guinea pig skin sensitization not sensitizing Buehler Test guinea pig skin sensitization sensitizing Xi, R43 Magnusson/Kligman
In short term toxicity experiments in rats, mice and dogs Amitraz showed clear evidence of CNS effects (disturbance of behaviour) after oral application. Comparable effects were seen
- 27 - Amitraz - Level 2: Reasoned statement of the overall conclusions in the subacute dermal study in rabbits and in a subacute inhalation study in rats. Histopathological alterations of the nerval system - as far as investigated - were not found. Additionally, signs of liver toxicity (enlargement of hepatocytes and increased liver weights) were seen in the oral rat and in the dog study. Due to the fact that the oral and dermal studies in this chapter are not in accordance with international accepted guidelines, a comprehensive evaluation of short term toxicity and establishment of clear oral and dermal NOELs respectively was not possible. In the short term inhalative study with a NOEC of 0.01 mg/l air study, additional clinical signs were indicative for irritation of the respiratory tract.
In chronic feeding studies Amitraz produced in all three species (rats, mice, dogs) signs of neuropharmacologic effects like behaviour disturbances and in mice effects in liver, pituitary, uterus and ovaries. Additionally, female mice treated with 400 ppm had an increased incidence of hepatocellular adenomas and carcinomas. It can be assumed that the increased incidence of liver tumours are not a result of a genotoxic mechanism but might be resulting from an indirect mechanism, probably due to the disturbance of hormonal balance. According to directive 67/548 EEC Amitraz should be classified as category 3 of carcinogenic substances and labelled with the risk phrase R 40 -"Possible risk for irreversible effects".
The mutagenic potential of Amitraz was studied in in-vitro test systems in bacteria (including two mouse host mediated assays) and mammalian cells and in vivo by means of a Micronucleus test and a Dominant lethal test. None of these test systems revealed any evidence of a mutagenic potential of technical Amitraz.
In the multigeneration study technical Amitraz did not effect fertility, gestation, parturition, organogenesis or growth and development of offspring over 3 generations in the rat up to a dose level of 20 mg/kg bw. Based on impaired lactation of the dams and consequently higher mortality in the offspring of both the highest and mid dose groups, the overall NOEL was 15 ppm, equivalent to a mean daily intake of 1.6 mg/kg bw. In the first teratogenic study in rats a conclusion, that developmental effect by Amitraz can be excluded, cannot be drawn on the basis of this study, because the period of major organogenesis was not covered. Also no data for mechanistic explanation of the shift in the male:female ratio, seen in the offsprings, was given. This study was therefore found to be not scientifically valid. In the second teratogenicity study in rats the highest dose level of 30 mg/kg bw/day caused a statistically significant increase of dilated ureters and a higher incidence of, although not statistically significant, bilaterally increased renal pelvic cavitation in the foetuses. Based on the fact that at a dose level of 15 mg/kg bw the incidence of bilaterally increased renal pelvic cavitation was statistically significantly higher than that of the concurrent control group the NOEL will be 7.5 mg/kg bw/day for the foetuses and 7.5 mg/kg bw/day for maternal toxicity.
- 28 - Amitraz - Level 2: Reasoned statement of the overall conclusions
Pregnancy rate, implantation rates, mean number of foetuses and mean foetal weights were uneffected. In the teratogenic study in rabbits maternally toxic dose levels of Amitraz up to 12 mg/kg bw were without effect on foetal morphology, so the NOEL for teratogenic effects was 12 mg/kg bw. Based on total litter loss in 3 females of the highest dosage group the NOEL for embryofoetal toxicity was 6 mg/kg bw. A NOEL for maternal toxicity could not be established but the LOEL was found to be 3 mg/kg bw.
Table 2.4.1-2 Summary results of mutagenicity, short term, chronic and reproductive toxicity studies Type of study Test system Results 90 day oral (gavage) rat NOEL 3 mg/kg bw LOAEL 12 mg/kg bw 90 day oral (feeding) mouse MTD 400 ppm 90 day oral (capsule) dog LOAEL 0.25 mg/kg bw 21 day dermal rabbit LOAEL 50 mg/kg bw 21 day inhalative rat NOEC 0.01 mg/l air mutagenicity bacteria, mammalian negative cells in vitro and in vivo 2 year oral (feeding) rat NOEL 2.5 mg/kg bw oncogenicity negative 2 year oral (feeding) mouse NOEL 2.3 mg/kg bw oncogenicity liver tumors in females at 400 ppm (50 mg) 2 years dog (capsule) dog NOEL 0.25 mg/kg bw 3 generation rat NOEL 15 ppm (1.6 mg/kg bw) reproduction teratogenicity rat NOEL 7.5 mg/kg bw maternal and fetal teratogenicity rabbit NOEL 6 mg/kg bw fetal LOEL 3 mg/kg bw maternal
The notifier pointed out that no delayed neurotoxicity studies have been conducted with Amitraz since it does not belong to a chemical class with a potential for delayed neurotoxic effects such as organophosphorous compounds. This statement is not accurate because of clear signs of clinical neurotoxic symptoms including also behavioural disturbances seen in subchronic and chronic studies. Regarding these findings in subchronic and chronic studies, the notifier stated in a comment (dated 24.10.1997) that typical neuropharmacological effects after application of Amitraz are possible.
Further studies to investigate some toxicological and pharmacological properties of Amitraz were submitted as additional information. In summary, it can be stated that the active substance is a competitive α2-receptor agonist and some intoxication symptoms are due to
- 29 - Amitraz - Level 2: Reasoned statement of the overall conclusions
central and peripheral α2-adrenergic action. It may be supposed that some of the pharmacological effects of Amitraz may be mediated by an action on the hypothalamus like other drugs, which act on the hypothalamus and affected the oestrus cycle of the rat and mice. In animal studies, it has been shown that Amitraz affects the oestrus cycle of rats and mice. Also cardiovascular, hyperglycaemic, CNS and gastrointestinal effects of Amitraz are
due to α2-adrenoceptor agonist activity whereas reduction of body temperature may be due to 5HT (serotonin) blockade. Each of these effects are only observed at exaggerated toxic dose levels. Additionally, some toxicological studies (acute, subchronic and mutagenicity studies) have been conducted with the metabolite BTS 27271, [N-methyl-N'-(2,4- dimethylphenyl)formamidine] (first metabolite of Amitraz in both animals and plants and also an impurity in technical Amitraz), BTS 28369 [4-amino-3-methylbenzoic acid] and BTS 27919, [N-(2,4-dimethylphenyl)formamide].
The results of the short term toxicity studies with BTS 28369 support that the biotransformation of Amitraz to this metabolite in animals will not be associated with any toxicity due to this metabolite, as it is less toxic than the parent compound. Studies with BTS 27271 showed similar results to those seen in studies with Amitraz technical although the NOELs of this metabolite was lower indicating a quantitatively greater activity for BTS 27271. This finding of a greater toxicity for BTS 27271 compared with Amitraz is also in accordance with the results of their comparative acute toxicity studies . The metabolites BTS 27271, BTS 28369 and BTS 24868 were negative in in vitro mutagenicity test systems conducted.
2.4.2 ADI
The calculation of the acceptable daily intake is based on the lowest no-observed -effect- level (NOEL) seen in all long-term toxicity, carcinogenicity and reproduction studies together. One notifier proposed 0.0125 mg/kg bw/d as an ADI based on a NOEL of 0.125 mg/kg bw taken from a double blind tolerance study of Amitraz in six adult volunteers (Cass, 1992). In this study, volunteers received only two single doses of Amitraz (0.0625 mg/kg and 0.125 mg/kg bw) within 2 to 3 weeks. Based on this a proposal and an evaluation of the long-term toxicity of Amitraz in humans are not possible. The other notifier proposed 0.003 mg/kg bw as an ADI without giving nearer justification for this decision.
In contrast to the notifiers’ proposals the following ADI was calculated: The lowest NOEL of Amitraz seen in the long-term toxicity studies is 0.25 mg/kg bw/day, which was observed in the long-term oral toxicity study in dogs (Morgan et al, 1973), the most sensitive species to Amitraz. For intra- and interspecies variations, a safety factor of 100 is justified for the transposition of the animal toxicity data to an estimate of the acceptable daily intake for human.
- 30 - Amitraz - Level 2: Reasoned statement of the overall conclusions
In his comments (dated 24.10.1997), the notifier pointed out that in the two year chronic study in dogs minor, acute, transient and reversible pharmacological effects were seen only on the first two days of dosing with 1.0 mg/kg bw, when all eight dogs had slight CNS depression and one male dog also had slight hypothermia. In the opinion of the notifier, the interpretation of the effects at this dose level are questionable because of lack of reproducibility of the CNS depression throughout the remaining time of the study. Therefore, the dose of 1.0 mg/kg bw should be taken as NOEL. This statement cannot be agreed upon as it has been reported in the subchronic study in dogs (which is of limited validity but of supporting evidence in connection with the results of long term study in dogs), dogs even dosed at the lowest level of 0.25 mg/kg bw Amitraz also showed slight CNS depression, a slight enlargement of the central and midzonal hepatozytes and a mild diffuse neutrophilia with an occasional lymphcytosis. Although these results (from a study of limited validity) would in fact lead to a conclusion that the NOAEL would be below 0.25 mg/kg bw, the same effects regarding CNS depression were only seen at a dose level of 0.1 mg/kg bw, and above- and not at the dose level of 0.25 mg/kg bw- in the long term toxicity study in dogs. Based on the results described above, the NOEL taken from the valid long term toxicity study in dogs as 0.25 mg/kg bw is seen as the best scientific judgement. At the same time this overall NOEL is justified as the basis for establishing the ADI.
Lowest NOEL: 0.25 mg/kg bw/d Safety factor: 100 ADI 0.0025 mg/kg bw/d
2.4.3 AOEL
The calculation of the acceptable operator exposure level (AOEL) can in principal be based on subacute toxicity, subchronic toxicity, long term, or reproduction studies. The long term studies and reproduction studies should be used if a relevant critical effect is observed in these studies and if it cannot be excluded that such an effect can be induced after repeated and longer exposure in humans or such an effect may appear only long after exposure has taken place. Another reason to use long term or reproduction studies is given in such cases, when foreseeable application of the substance in question will occur during all seasons of the year as it can be assumed for Amitraz. In contrast to the opinion of one notifier, who calculated the AOEL on the basis of a 90-day feeding study in dogs, it is justified on the reasons above to choose the long term toxicity studies for the calculation of an acceptable operator exposure level. The lowest no-observed-effect level derives from the long term oral toxicity study in dogs, the most sensitive species to Amitraz. 0.25 mg/kg bw/day was determined as a clear NOEL. (Morgan et al, 1973). For intra- and interspecies variations, a safety factor of 100 is justified for the calculation of the acceptable operator exposure level on the basis of animal data.
- 31 - Amitraz - Level 2: Reasoned statement of the overall conclusions
No suitable data for chronic toxicity of Amitraz via the dermal route are available. Therefore and for precaution, the NOEL from the oral toxicity study in dogs was used for the estimation of the dermal AOEL, assuming a 10 % absorption rate. (Explanation for this absorption rate is given in Chapter 5.12). The subacute inhalation study in rats (Berczy et al, 1973) is not suitable for the estimation of an inhalative AOEL because the duration of the study (6 hours per day, on 14 days over a period of three weeks) is fare too short compared with the frequency of exposure periods associated with the intended uses of Amitraz-containing pesticides. Therefore and for precautionary reasons the NOEL from the oral toxicity study in dogs was also used for the estimation of the inhalative AOEL, assuming a 100% absorption rate.
NOEL: 0,25 mg/kg bw/day Safety factor: 100 AOEL (systemic) 0,0025 mg/kg bw/day
2.4.4 Drinking water limit
According to directive 80/778/EEC a drinking water limit of 0.1 µg is legally established.
2.4.5 Impact on human or animal health arising from exposure to the active substance or to impurities contained in it
Based on all findings, the data suggest, that substance related effects which could be expected after normal use of Amitraz containing formulations are skin sensitization reactions. Additionally, direct skin contact to small amounts of Amitraz can produce "skin flushings" over a period of few days to few weeks, which is caused by the fact, that Amitraz
is an α2-receptor agonist and these symptoms are due to central and peripheral α2- adrenergic action. Considering the proposed ADI and AOEL, repeated exposure to small quantities should not lead to adverse health effects in terms of genotoxicity, reproductive toxicity or organ toxicity.
For the use of preparations containing Amitraz, estimations of potential operator exposure calculated based on the German BBA as well as on the UK POEM model have been submitted. The results show, that after application of Amitraz containing formulations to high cultivations the predicted operator exposure will exceed the proposed systemic AOEL, if no personal protective equipment is used. Calculations only for the BBA model, using as result a non sufficient protective equipment (gloves, mask, hood/visor and garments) also show an exceeding of the proposed AOEL. Calculations of the risk to the operator using Amitraz containing formulations in glass houses with hand held equipment or on public green were not submitted; additionally, for these two intended uses, health risk to workers and bystanders in term of establishing re-entry interval was not taken into sufficient consideration from the notifier.
- 32 - Amitraz - Level 2: Reasoned statement of the overall conclusions
Taking into account these comments, adverse health effects to operators cannot be excluded, when no sufficient protective equipment is used. Measurements of the operator exposure covering all intended applications and using sufficient protective equipment as well as re-entry intervals for workers and bystanders are required to evaluate if exposure to Amitraz presents no undue risk for human health.
2.5 Methods of analysis
2.5.1 Analytical method for analysis of the active substance as manufactured
For the determination of Amitraz in the active substance as manufactured a validated method, approved by CIPAC, is available. For the determination of impurities, which the notifier AgrEvo UK Ltd. considered to be of toxicological or ecotoxicological significance, validated methods are available, too. But no satisfying method has been submitted for the determination of significant and/or relevant impurities arising from the manufacturing processes applied by the manufacturer of Chimac Agriphar S.A. and Industrias Afrasa S.A.
2.5.2 Analytical method for formulation analysis
Applicable methods for the determination of Amitraz in EC and WP formulations, which can be performed with usual analytical instruments, are available.
2.5.3 Analytical method for residue analysis
Residues in plant material: The common moiety method provided allows to determine Amitraz and all metabolites containing 2,4-dimethylaniline, which were chosen as relevant substances in the definition of the residues in plant protection products. The limit of determination which can be achieved in monitoring routine is considered to be 0.05 mg/kg. For the sake of a full validation of the method, the notifier has to give evidence, that 2,4- dimethylanilinie is a specific moiety for the residue determination of Amitraz. The detection of the active substance by means of a multi-residue method is possible, but the metabolites included in the residue definition are not covered. Residues in food of animal origin: For food of animal origin the same residue definition as for food and feed of plant origin has been suggested. For monitoring purposes a common moiety method can be applied. The limits of determination are 0.01 for milk and eggs, and 0.05 for other products of animal origin. The validation with respect to the specifity of 2,4-dimethylaniline is also necessary for the food of animal origin. Soil: Methods have been submitted which allow to detect Amitraz and degradation products in soil, which have been included in the residue definition relevant for the environment. The methods fulfil the criteria and can be used in residue analysis work. Water:
- 33 - Amitraz - Level 2: Reasoned statement of the overall conclusions
The method suggested determines Amitraz and all metabolites containing 2,4-dimethylmine. But as there are interferences of the analyte signal with matrix compounds, a reliable determination of Amitraz derived residues in water at the EU-limit of 0.1 µg/kg is not possible. An adopted method including a full validation (also for surface water) has to be submitted. Air: The method fulfills the standard requirements for a residue analytical method with respect to recovery and relative standard deviation. Residues in animal and human fluids and tissues: In addition to the requirements for non-toxic substances, the notifier submitted a supplementary method for the determination of Amitraz and metabolites in animal tissues, which fulfils the general requirements for residue methods with respect to recovery.
2.6 Definition of residues
2.6.1 Definition of residues relevant to MRLs
Amitraz, its hydrolysis products BTS 27271 and BTS 27919 and the compounds containing the 2,4-dimethylaniline moiety are considered to be residues of concern. Therefore, based on the metabolism data submitted for the plants: grapes, apples, lemons, pears and cotton and the animals: cow, laying hens, residues in plants and in products of animal origin should be defined as Amitraz, including the metabolites containing the 2,4-dimethylaniline moiety, expressed as Amitraz.
2.6.2 Definition of residues relevant to the environment
In soil and surface water, amitraz, BTS 27271 and BTS 27919 and in minor amounts BTS 24868 are considered to be residues of concern. Neither amitraz nor its degradates are expected to leach to groundwater.
2.7 Residues
2.7.1 Residues relevant to consumer safety
The minimum and maximum residue levels found directly after the application (initial deposits) and at crop maturity (or at the end of the proposed preharvest interval) are compiled in the following table 2.7.1-1, whereby only the results of those trials which can be used for the MRL-estimation and which are therefore considered to be relevant are listed below.
Table 2.7.1-1 Key results of supervised crop residue trials with Amitraz
Crop Region No. of Minimum Maximum PHI Minimum Maximum trials Day 0 Day 0 [days] Harvest Harvest [mg/kg]*) [mg/kg]*) [mg/kg]*) [mg/kg]*) Oranges, S2) 9 -1) -1) 14 0.33 1.1
- 34 - Amitraz - Level 2: Reasoned statement of the overall conclusions
grapefruit Apples N 7 0.57 1.3 14-29 0.3 0.74 Pears S 5 -1) -1) 30-34 0.22 0.4 Pepper S, glass- 1 1.4 1.6 13 0.34 0.36 house Cotton S2) 13 -1) -1) 15-24 0.08 0.84 Hops (dried) N 17 2.0 76 26-28 1.30 24.5
*) Amitraz and Amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed as Amitraz 1) No data available at day 0 2) Trials conducted in the USA; the studies are considered to be relevant to the growing regions of Southern Europe where climatic conditions during the growing season are similar; nevertheless further trials conducted in the southern region of Europe are needed
To establish the residue behaviour of Amitraz and to provide data for establishing MRLs, the listed residue trials were carried out on crops to support the intended uses in the Northern and Southern Region of Europe. The data provided by the notifiers are not sufficient to set MRLs with the exception for hops (50 mg Amitraz/kg dried hops; Amitraz and Amitraz-derived metabolites containing the 2,4- dimethylaniline moiety are expressed in terms of Amitraz). Further residue data according to the intended uses on the following crops are therefore required: citrus fruits (Southern Region), pome fruits (Southern Region), stone fruits (Northern and Southern Region), strawberries (Northern and Southern Region, glasshouse), currants (Northern Region, glasshouse), bananas (Southern Region), tomatoes (Northern and Southern Region, glasshouse), aubergines (Northern and Southern Region, glasshouse), peppers (Northern and Southern Region, glasshouse), cucurbitacea (Northern and Southern Region, glasshouse) and cotton (Southern Region of Europe).
Concerning the effects of industrial processing on treated plant products (citrus fruit, apples, cotton and hops), the data received show that the majority of the residues occur primarily in the peel (citrus, apples) and in the hulls (cotton), which are removed in the processing procedures. Furthermore, it can be concluded, that the residue level in dried hops shows a 3-5 fold increase compared to fresh hops, but these residues become significantly diluted during the brewing process in beer. The data address all processed products which are likely to be generated from crops treated with Amitraz except from stone fruits, currants, strawberries and tomatoes where data on processing are still necessary (depending on the level of residues to be detected and the consumer risk assessment).
The results of the livestock feeding studies performed on lactating cows and laying hens demonstrate that levels of Amitraz expected to be present in animal feeding stuffs (fruit pomace: apples, citrus; meal, cake: cotton) will not be transferred to the resultant products of animal origin (dairy cattle: milk, fat, muscle, kidney, liver; laying hens: eggs, muscle, fat,
- 35 - Amitraz - Level 2: Reasoned statement of the overall conclusions liver). A further assessment of the likely levels of Amitraz-derived residues in food of animal origin could be necessary once residue data according to intended uses conducted in the European Region on citrus fruits, pome fruits and cotton which may contribute towards animal diets have been provided and assessed. The data available at the moment make it possible to estimate the MRLs for food of animal origin which can be set at the limit of determination of the relevant analytical methods (meat, fat and offals: 0.05 mg Amitraz/kg; milk and eggs: 0.01 mg Amitraz/kg; Amitraz and Amitraz-derived metabolites containing the 2,4-dimethylaniline moiety are expressed in terms of Amitraz).
Amitraz and its metabolites are not readily taken up from the soil by most plants, and corresponding residues (Amitraz and Amitraz-derived metabolites expressed as Amitraz) will not occur in edible parts of the crop tested.
In total, the Theoretical Maximum Daily Intake can be estimated as 0.36102 mg Amitraz derived residues expressed as Amitraz for an adult person and as 0.07182 mg for a 4-6 year old girl. These results are equivalent to 0.00602 mg/kg bw/day (in the case of an adult person, 60 kg bw.) and 0.00532 mg/kg bw/day (in the case of a child, 13.5 kg bw.). The Acceptable Daily Intake (ADI) of Amitraz based on the toxicological data provided is proposed to be 0.0025 mg/kg bw/day. Therefore, the Theoretical Maximum Daily Intake of Amitraz-derived residues through the relevant food items accounts for 240.7 % of the ADI (adult, 60 kg bw.) and 212.8 % of the ADI (4-6 year old girl, 13.5 kg bw.), respectively. The TMDI shows an excess of 140.7 % and 112.8 %, respectively. This may be even more severe if the calculation based on national diets or extreme categories of consumers are taken into account. It was therefore necessary to carry out additional EMDI-calculations.
In total the Estimated Maximum Daily Intake can be estimated as 0.08188 mg Amitraz- derived residues expressed as Amitraz for an adult person and as 0.06133 mg for a 4-6 year old girl. These results are equivalent to 0.00136 mg/kg bw/day (in the case of an adult person, 60 kg bw.) and 0.00454 mg/kg bw/day (in the case of a child, 13.5 kg bw.). Therefore, the Estimated Maximum Daily Intake of Amitraz-derived residues through the relevant food items accounts for 54.59 % of the ADI (adult, 60 kg bw.) and 181.72 % of the ADI (4-6 year old girl, 13.5 kg bw.), respectively.
The calculation of the EMDI for Amitraz takes into account the facts that citrus fruits are consumed mainly after discarding the peel, and that hops is consumed only as beer. In this case the EMDI is below the ADI for an adult person. But for a 4-6 year old girl the EMDI shows an excess of 81.72 % above the ADI. Therefore, additional residue data according to the intended uses conducted in the European Region on citrus fruits, pome fruits, stone fruits, strawberries, currants, bananas, tomatoes, aubergines, peppers and cotton have to be submitted in order to facilitate new
- 36 - Amitraz - Level 2: Reasoned statement of the overall conclusions
TMDI- and EMDI-calculations. Without these studies it must be stated that an excess (as TMDI and EMDI) of the ADI will take place for a 4-6 year old girl. Therefore, it may also be decided on a rationalisation or an amendment of the at the moment intended uses including e.g. reduction of the application rates, changing the time of the application (by increasing the PHI) and/or an otherwise adaptation of the intended uses in order to reduce the consumer exposure to an acceptable level.
2.7.2 Residues relevant to worker safety
See chapter 2.4.5 (a propose for re-entry interval for workers is required).
2.7.3 Proposed EU MRLs and compliance with existing MRLs
EU-MRLs have been set for Amitraz on following crops/food of animal origin: oranges (1 mg/kg), peaches incl. nectarines and similar hybrids (1 mg/kg), tomatoes (0.5 mg/kg) and hops (50 mg/kg). For certain groups the MRL has been set at the limit of determination of the analytical method: tree nuts, cane fruits, other small fruits and berries except currants, miscellaneous, root and tuber vegetables, bulb vegetables, sweetcorn, brassica vegetables, leaf vegetables and fresh herbs, legume vegetables, stem vegetables, fungi, pulses, oil seeds except cotton, potatoes, tea, cereals, poultry meat and eggs. Due to the lack of information provided by the notifier and insufficient data base MRLs could only estimated for hops and for food of animal origin.
The MRL proposal of 50 mg Amitraz/kg dried hops is in compliance with the EU-MRL published in Council Directives 95/38/EC.
The MRL proposal of poultry meat and eggs covers the EU-MRLs (limit of determination). There is still no EU-MRL existing for meat (other than poultry), offals and milk (open positions).
2.7.4 Proposed EU import tolerances and compliance with existing import tolerances
EU import tolerances are not regarded as relevant because the use of Amitraz containing plant protection products for all crops stated by the notifiers is intended within the European Community.
2.8. Fate and behaviour in the environment
The studies provided by the notifiers Chimac Agriphar S.A. and Industrias Afrasa, S.A. were incomplete and have therefore not been taken into consideration of the following evaluation.
2.8.1. Fate and behaviour in soil
It is concluded from tests covering rate and route of degradation under aerobic and anaerobic conditions (laboratory studies) that amitraz is very rapidly degraded to its primary
- 37 - Amitraz - Level 2: Reasoned statement of the overall conclusions soil degradation products, BTS 27919 and BTS 27271 with a half life < 0.33 day and DT90 values between 1 and 6 days. Degradation of BTS 27919 and BTS 27271 to BTS 24868 and mineralisation of all three metabolites occur in the next step. DT50 (DT90) values of the metabolites range from 6.4 (98) to 0.27 (1.2) days.
Under anaerobic conditions amitraz had an apparent half life of less than one day. Very little of the degradation products BTS 27919 and BTS 27271 (less than 10 %) remained after the aerobic pre-incubation period in soil. Due to variable data points no DT50(90) values have been calculated for anaerobic degradation of the metabolites.
The mineralisation to CO2 is supposed to be one endpoint of degradation. Significant amounts of CO2 were found in the laboratory studies (13-20 % after 60 days, 20-27 % after 120 days). The other endpoint is incorporation of carbon fragments into the natural carbon pool of soil. Soil ‘bound’ residues in this study were high, with maxima of 82.5 % of applied radioactivity after 7 days and 73.7 % after 30 days in sandy loam and silt loam soil, respectively. These residues declined gradually throughout the remainder of the year leaving 64.5 % and 52.9 % of applied radioactivity after 364 days in sandy loam and silt loam soil respectively. No further investigations of the bound residues were conducted (e.g. separation of residues bound to fulvo acids and humic acids) and no further degradation products were investigated. Due to the extraction by soxhlet with toluene the amount of more polar degradation products may have been underestimated with a corresponding over- estimate in the amount of soil bound residues.
It can be concluded that degradation at the soil surface is accelerated by photolysis. A DT50 value of < 10 min was estimated for degradation of amitraz on soil surfaces under irradiation. Amitraz was rapidly degraded to its primary hydrolysis products BTS 27271 and BTS 27919. No further degradation of the metabolites BTS 27271 and BTS 27919 was observed
Because of the very low DT50 values of amitraz and it's metabolites no field dissipation study was evaluated. A rotational crop study in the USA revealed that soil residues ranged from 0.08 to 0.15 mg /kg amitraz equivalents at the time of planting the first following crop and that in most crops no measurable uptake of soil residues was detected.
The results of these studies show that amitraz or its degradation products are not supposed to bear significant risk to persist or accumulate in soil under aerobic field conditions. The adsorption of [14C]-amitraz to 4 soil types was tested on sterile soil slurries. The Koc value of amitraz indicates that it will be of low to high mobility in soil. Due to the rapid breakdown of amitraz it was not practically possible to evaluate the desorption of amitraz from soil surfaces.
The rapid breakdown of amitraz in soil and water makes it difficult to measure its mobility in
- 38 - Amitraz - Level 2: Reasoned statement of the overall conclusions
soil using soil column techniques. However the mobility of amitraz has been investigated by soil thin layer chromatography. The mobility of its main hydrolysis products, BTS 27271 and BTS 27919 has been investigated using soil columns. But due to its rapid hydrolysis in soil the mobility of its hydrolysis products are of relevance; BTS 27271 is immobile in soil whilst BTS 27919 is mobile although it was not detected in leachate from an aged leaching study probably due to its short half-life in soil.
The mobility of [14C]-ring labelled amitraz aged in three soils, a sandy loam, a sand and a silty clay loam was investigated using soil columns (Leake, 1988). Amitraz rapidly degraded during the ‘ageing’ period, between 8 % and 19 % of the applied radioactivity remained as unchanged parent compound after 3 days. The major metabolites after ageing were BTS 27271 and BTS 27919. 1.1 to 5.0 % of applied radioactivity was detected in leachate collected from the soils. Analysis of the leachate detected no amitraz or known metabolites, only polar material was detected. Analysis of the soil after the leaching period detected the largest proportions of radioactivity in the top 5 cm of soil (the treated soil). Some radioactivity had leached into the next segment (5 to 10 cm) particularly in the more sandy soils. Very little material leached below 10 cm in any of the soil columns.
The ‘aged’ leaching study indicated that neither amitraz nor its primary metabolites (BTS 27271 and BTS 27919) are likely to be found in leachate.
Neither amitraz nor its metabolites BTS 27271 and BTS 27919 bear significant risk to persist or accumulate in soil or to have a significant potential to leach in soil and contaminate ground water if the compound is used according to good agricultural practice and proposed label recommendations.
2.8.2. Fate and behaviour in water
2.8.2.1 Ground water
Considering its rapid degradation in the environment and its leaching behaviour, the risk of amitraz to contaminate ground water is small. The metabolites BTS 27271 and BTS 27919 are more polar but are also rapidly degraded in soil. The behaviour of amitraz and its metabolites in soil were determined by degradation and adsorption studies, column leaching studies and aged column studies. The results of these studies suggest that the
environmental concentration in ground water (PECgw) for amitraz and its metabolites is smaller than 0.1 μg/l. Thus it can be concluded that amitraz does not bear any significant risk to leach into ground water if it is used according the proposed label recommendations and good agricultural practice.
2.8.2.2 Surface water
Amitraz rapidly hydrolyses at pH 5 - 9 with DT50 ranging from 0.97 to 32 hours, being slightly more stable under alkaline conditions. The hydrolysis products are less readily degraded.
- 39 - Amitraz - Level 2: Reasoned statement of the overall conclusions
BTS 27271 was hydrolysed very quickly at pH 9 to BTS 27919, but very slowly at pH 5. Degradation of amitraz in photolysis solution is due to photolysis as well as to dark reactions. The corresponding half life for the photolysis reaction is between 46.5 h and 4.2 days. In addition to hydrolytic degradation it is clear that amitraz is also rapidly degraded by photochemical processes in aqueous solution. No degradation of the metabolites BTS 27919 and BTS 27271 by photolysis could be observed.
Amitraz was rapidly degraded in water/sediment microcosms with a half-life of <12 hours at 25° C. Its rate of disappearance from the water was more rapid. The major metabolites detected were BTS 27271, BTS 27919 and BTS 24868. These were also relatively quickly
degraded with DT50 in whole water/sediment microcosms that ranged from 3.4 to 32 days at 25° C. Degradation of amitraz and its metabolites was generally slightly less rapid at lower
temperatures, where DT50 at 8° C ranged from <1 day for amitraz and between 4 and 64 days for the metabolites. Most of amitraz and its metabolites BTS 27271 and BTS 27919 remained in the water phase and were degraded there. Amitraz was found in the sediment in concentrations of up to 20 % and it was readily degraded there. A maximum sediment concentration of 19 % of applied radioactivity for BTS 27919 and of 3.5 % of applied radioactivity for BTS 27271 was reached. Both were readily degraded.
The predicted initial environmental concentrations were calculated for water depths of 0.3 m on the basis of maximum application rates for several intended uses and several distances. The spray drifts for each distance between field and water body were taken from Ganzelmeier H. et al., 1995. Time-weighted average concentrations of amitraz were calculated for selected time intervals taking into account the degradation in the water column of a water/sediment system (half-life 0.6 days at 8° C). The calculation of the predicted environmental concentration of the metabolites BTS 27271
and BTS 27919 in surface water was based on the assumption that the DT50 values for BTS 27271 (BTS 27919) are 7 (9) days and that the metabolites reach a maximum of 27.7 % (60.2 %) of the applied radioactivity in the water column after 1.9 (4.2) days. Maximum
concentrations and DT50 values for both metabolites were taken from degradation studies in a water/sediment system. At the highest proposed application rate of 2*2500g as/ha and a drift of 18 % the initial
PECsw is 0.15 mg as/l and the 21 day time-weighted average concentration is 0.01236 mg as/l. The maximum concentration of metabolites after repeated applications is 0.09 mg/l on day 16 (BTS 27271) and 0.12 mg/l on day 18 (BTS 27919), respectively.
2.8.3. Fate and behaviour in air
On soil amitraz was rapidly degraded, and it was not volatilised from the soil. An increment
- 40 - Amitraz - Level 2: Reasoned statement of the overall conclusions
calculation of the degradation of amitraz and its metabolite BTS 24868 in air according to Atkinson is required.
2.9 Effects on non-target organisms
The studies provided by the notifiers Chimac Agriphar S.A. and Industrias Afrasa, S.A. were incomplete and have therefore not been taken into consideration of the following evaluation.
2.9.1 Effects on terrestrial vertebrates
Acute risk Amitraz and even more its metabolite BTS 27271 are of high acute toxicity to birds and
mammals. Because of a lower toxicity of the metabolite BTS 27919 no TERa calculations were done. The plant protection product in question is used in crops the leaves of which are not consumed by animals. Thus terrestrial vertebrates might be exposed to amitraz by eating contaminated grass on the ground of the treated crops, insects, fruits, or earthworms. For a consideration of the worst case conditions it is assumed that the food of birds and mammals consists exclusively of contaminated material. 15 % of the initial concentration of amitraz were assumed as maximum concentration of the metabolite BTS 27271. Since there are between two and three applications, the half-life time for amitraz and BTS 27271 being assumed to be 7 and 21 days, it is to be expected that these substances will accumulate with every further treatment. Thus the maximum concentration of amitraz and BTS 27271
after the last application (PECmax) was used as predicted environmental concentration for the calculation of the acute maximum daily intake. Since insects are not expected to be treated
twice or three times, in this case the initial concentration (PECi) was used for the calculation
of the TERa-value. Earthworms were considered to have the same concentration of amitraz as the surrounding soil. Furthermore, for both insectivore and herbivore animals a daily food demand of 30 % of their body weight is assumed. According to these assumptions the maximum daily intake lies between 0.4 mg/kg bw and 53 mg/kg bw for amitraz and between 0.1 mg/kg bw and 13.2 mg/kg bw for BTS 27271.
Risk to birds:
For amitraz the TERa-values for birds are above the trigger given in Annex VI of Directive
91/414 EEC for all applications with a range between 15 and 1970. The TERa-value for BTS 27271 in public green for grass-eating birds is 9 and thus slightly below the trigger value of 10. Assuming that public green is no major feeding place for wild birds, this is an acceptable risk.
In hops the TERa for BTS 27271 is 5 for grass-eating birds. To assess the risk more seriously it should be clarified if the maximum concentration of the metabolite BTS 27271in the environment is 15 % of the initial concentration of amitraz.
In all other cases the TERa-value is above 10 ranging between 22 and 710.
- 41 - Amitraz - Level 2: Reasoned statement of the overall conclusions
For both amitraz and its metabolite, all calculated TERse-values are greater than the trigger value of 10 with a range between 12 and 1636 for amitraz and between 32 and 6810 for BTS 27271.
Risk to mammals:
In hops the TERa for the metabolite BTS 27271 is 7.7 which indicates an unacceptable risk to grass-eating mammals (if 15 % or more of the initial concentration of amitraz is the maximum concentration of the metabolite BTS 27271in the environment). For all other
applications the TERa-values are above the trigger value of 10 for unacceptable effects
given in Annex VI of 91/414 EEC for both amitraz and BTS 27271. For amitraz the TERa is
between 11 and 1500, for BTS 27271 the TERa-value is between 7.7 and 1000.
Summing up it can be said that the acute toxicity/exposure ratios for amitraz and its metabolites in all uses except hops are above the trigger of 10. Short term toxicity/exposure ratios indicates a low risk to birds in all crops.
Chronic risk Risk to birds and mammals:
For both amitraz and its metabolite BTS 27271 in all crops and application rates the TERlt for birds and mammals is below the trigger value of 5 given in Annex VI of Directive 91/414/EEC. This indicates a high risk to herbivore and insectivore birds. Only by consumption of fruits does not involve any risks. Since the initial concentrations were used in comparison with a NOEC of a 20 (22) week- study for birds and a 90-day study for mammals long-term risk might be less than expected on account of these calculations. To give an exact statement measurements of residues on wildlife food items (especially on insects) to determine the degradation of the as and its relevant metabolites are necessary. On basis of these data of measurements the decision should be made if further data (a field-test) are necessary to enable the assessment of the chronic risk to terrestrial vertebrates. Because of the rapid degradation of amitraz and its metabolites in soil the chronic risk to earthworm-eating animals is expected to be low.
2.9.2 Effects on aquatic species
The initial worst case route of surface water contamination to be considered in the aquatic risk assessment is spray drift. As worst case an application rate of 2*2500 g/kg in hops and a buffer zone of 5 m (18 % drift) is assumed. As a second standard calculation the assessment was carried out using 1 m buffer zones in strawberry culture (2*800 g/ha, 4 % drift).
Acute risk
- 42 - Amitraz - Level 2: Reasoned statement of the overall conclusions
The most sensitive aquatic species tested are daphnids with a LC50 of 0.035 mg as/l, 3.28 mg/l (metabolite BTS 27271) and 74 mg/l (metabolite BTS 27919).
The TERa for daphnids calculated for amitraz is 0.23 (hops) and 3 (strawberries) and therefore below the Annex IV trigger values.
Also TERa calculations for the metabolite BTS 27271 in hops indicate a risk to daphnids (the
TERa is 62). The acute TER calculated for the metabolite BTS 27919 indicates a low risk to daphnids.
Amitraz and its metabolites are also toxic to fish. The LC50-value of amitraz is 0.45 mg/l, the
LC50-value of the metabolite BTS 27271 is 27.9 mg/l and 74 mg/l for the metabolite BTS 27919. The acute TER'-s calculated for amitraz for fish in hops are 3, in strawberries 42, respectively. The acute TER'-s calculated for the metabolite BTS 27271 and BTS 27919 indicate a low risk to fish.
The TER for algae calculated from EC50-values of testing amitraz in hops is 80. It should be stressed that in algae the formulation Mitac 20 EC yields lower TERa-values than technical amitraz alone. Using data of the formulation the algal TERa calculated for application in hops is 1. No data have been submitted on the effects of the metabolite BTS 27271 on algae.
By rearranging the TER calculation it can be seen that a PECi of <0.0005 as/l would generate a TERa above the Annex IV trigger value of 100 for daphnids. Thus at application rates of 800 g/ha safety distances of between 20 and 50 m can reduce the risk to aquatic invertebrates. In hops the risk to aquatic organisms cannot be reduced by keeping safety distances from surface water because of the high application rate and drift values of 0.3 % in a distance of 50 m.
Amitraz (as and formulation) always shows much lower TERa values than its metabolites. Therefore, if amitraz concentrations in surface water are regarded as acceptable, no risk to aquatic organisms is expected even considering an accumulation of the metabolites due their DT50 of 7 or 9 days and repeated applications.
In conclusion it can be said that the acute risk to aquatic life will be acceptable if amitraz is used at application rates of 800 g or 500 g as/ha and drift values of 0.2 or 0.1 %. In case of higher application rates (in hops) or in case buffer zones are removed further information (eg. from a micro/mesocosm study) will be required to assess these risks. Data on the acute toxicity of the metabolite BTS 27271 on algae should be submitted.
Chronic risk
In strawberries (1 m distance, 4 % drift, 800 g as/ha) the TERlt calculated for amitraz is below the Annex IV trigger value of 10 in both fish and daphnia (3: fish, 1.3: daphnids).
Also in hops (5 m distance, 18 % drift, 2500 g as/ha) the TERlt is 0.014 for fish and 0.089 for daphnids and therefore far below the Annex IV trigger value. Using drift values of 0.2 % (the borderline for acute risk) the long-term risk for aquatic life is
- 43 - Amitraz - Level 2: Reasoned statement of the overall conclusions
acceptable (in tomatoes - 30 m distance, 0.2 % drift, 800 g as/ha - the TERlt is 21 for fish and 27.5 for daphnids). No tests investigating the long-term toxicity of the metabolites of amitraz were performed. It is not expected that the two main metabolites of amitraz BTS 27271 and BTS 27919 will be a risk for aquatic organisms because of their lower acute toxicity and lower concentration than the as. It can be concluded that assuming that amitraz is used repeatedly at application rates of 800 g or 500 g as/ha and drift values of 0.2 or 0.1 % the chronic risk to aquatic life is acceptable. In case of higher application rates (in hops) or if buffer zones are removed further information (eg. from a micro/mesocosm study) will be required to assess these risks.
Sediment dwelling organisms No data have been submitted on the effects of amitraz on sediment dwelling organisms. Amitraz partitions to sediment rapidly. Depending on the temperature of the test system more (8 °C) or less (25 °C) than 10 % of the applied radioactivity could be found in sediment after day 14 (see B.7.4). In cold water the extractable radioactivity on day 10 was 22 %, consisting of 10 % amitraz and 12 % BTS 27919. From day 1 to day 10 amitraz concentrations were stable in sediment with a decreasing trend afterwards. The metabolite BTS 27919 persisted over about 30 days in concentrations of 10 to 14 % in sediment. The
acute toxicity of this metabolite is low (LC50 >100 mg/l). Thus sediment dwelling organisms are only endangered by repeated applications of amitraz. Daphnids are very sensitive to amitraz. Therefore in case of repeated applications of amitraz an investigation of its toxicity to sediment dwelling organisms will be required. This study should be designed realistically and simulate 3 applications at an interval of 1 week, the test temperature should be 8° C. Thus a constant amitraz concentration in sediment over 3 weeks would be achieved which would enable an assessment of the chronic risks to sediment dwelling organisms.
Bioaccumulation The bioconcentration factor of amitraz in fish was determined as 1333 (whole fish) and about 90 % of the radioactivity was eliminated within 2 weeks, which indicates a risk of bioaccumulation. Rapid degradation of amitraz in water and its partitioning to sediment (the DT50 is 0.6 days in the watercolumn and 1.9 in the whole water/sediment-system) minimise
the risk. Furthermore the log Pow for both main metabolites is less than 3, which means that these substances have no significant bioaccumulation potential. With a view to these factors the bioaccumulation risk of amitraz and its metabolites is considered to be acceptable.
2.9.3 Effects on bees and other arthropod species
Bees: To assess the risk amitraz may have on honey bees only tests with Mitac 20 EC were
provided. According to the lab tests (LD50, oral 96 h = 20 µg Mitac/bee and LD50, contact 96 h = 27 µg Mitac/bee) Mitac 20 EC is slightly toxic to honey bees. Assuming that the
- 44 - Amitraz - Level 2: Reasoned statement of the overall conclusions
toxicity is produced by the active substance, amitraz must be labelled according to the council directive 67/548/EEC with the risk phrase R57 ("toxic to bees"). The hazard quotients for Mitac 20 EC applied in hop-yards (12.5 kg Mitac 20 EC/ha) and orchards (4.0 kg Mitac 20 EC/ha) exceed the threshold value of 50. Appropriate semi-field tests show that amitraz formulated as Mitac 20 EC seems not to be hazardous to honey bees if the application rate does not exceed 2.5 kg amitraz/ha in hop- yards and 0.8 kg amitraz/ha in orchards and vegetable-cultures. Additionally to the studies provided there is further requirement for clarification if any hazard to honey bees may arise out of the formation of the two major breakdown products of amitraz (BTS 27919 and BTS 27271). An appropriate test or a scientific explanation should be provided to answer this question. To avoid any impairment of honey bees until clarification on the effects of BTS 27919 and BTS 27271 on bees is provided, an appropriate labelling of Mitac 20 EC ("Do not use for the treatment of flowering crops or in their near vicinity") is recommended.
Non-target arthropods: According to the tests provided, amitraz formulated as Mitac 20 EC is toxic to non-target arthropods representing different groups of beneficial arthropods (parasitoids, predatory mites, foliage dwelling predators and ground dwelling predators). Since all dose rates tested are lower than the recommended ones harmful effects cannot be excluded for any of the arthropod species tested based on the lab test results provided. Therefore amitraz is not a selective insecticide but has a negative affect on a lot of non-target arthropods. In order to meet the requirements of Annex VI of the council directive 91/414/EEC appropriate risk mitigation strategies should be specified to avoid unacceptable effects on non-target arthropods especially to reduce the risk for off-crop arthropods.
2.9.4 Effects on earthworms and other soil macro-organisms
Earthworms may come into contact and incorporate amitraz that reaches the soil. According to the EPPO risk assessment scheme the toxicity data from laboratory tests in
artificial soil are divided by the factor of 2 when the log Pow >2.
For calculation of the TERa-value a LC50 of 20 mg/kg (a concentration of 200 mg Mitac 20 EC/kg corresponds to a concentration of 40 mg amitraz/kg, divided by the factor of 2) and a PEC of 1.7 were used. The PEC was calculated for day 0 of an application with the maximum rate (2.5 kg as/ha) and a soil depth of 5 cm.
For calculation of the TERlt-value a NOEC of 6,25 mg/kg (a concentration of 62.5 mg Mitac 20 EC/kg corresponds to a concentration of 12.5 mg amitraz/kg, divided by the factor of 2)
and a PEC of 0.057 calculated for day 14 (2.5 kg as/ha and DT50 of 0.33 days) were used.
The TERa-value is 12 and therefore above the trigger value of 10 for unacceptable short-
term effects given in Annex VI of 91/414 EEC. A calculated TERlt-value of 110 indicates that the long-term risk to earthworms is low.
- 45 - Amitraz - Level 2: Reasoned statement of the overall conclusions
Because of the rapid degradation of amitraz to its primary soil degradation products, BTS 27919 and BTS 27271 with a half life < 0.33 day and DT90 values between 1 and 6 days these metabolites are also tested within a test duration of 14 days. Thus no toxicity tests which the metabolites are required.
Based on the calculated TER-values no adverse effects of amitraz to earthworms, even if used with the highest intended concentration should be expected.
There is no further available data which provides information with respect to possible impact of amitraz on other non-target macro-organisms. Because of the low stability of amitraz and
its metabolites BTS 27919 and BTS 27271 in soil (DT50 < 100 d) no tests are required.
2.9.5 Effects on soil micro-organisms
There was only a negligible (<25 %) effect of Mitac 20 EC on soil respiration and nitrogen turnover at application rates up to ten times the maximum recommended application concentration of Mitac 20 EC. Therefore, amitraz is not expected to present a risk to microbial activity under the maximum recommended conditions of use of Mitac 20 EC.
2.9.6 Effects on other non-target organisms (flora and fauna)
Taking into account the high toxicity of amitraz and its matabolites (BTS 27919 and BTS 27271) to terrestrial and aquatic organisms, adverse effects on other non-target organisms cannot be excluded. In the absence of data and EU guidance it is proposed that individual Member States consider these issues at re-registration.
2.9.7 Effects on biological methods of sewage treatment
No significant contamination of sewage treatment plants is envisaged through the proposed use of the compound. No risk is identified and no data will be required.
2.10 Classification and labelling
2.10.1 Active Substance
On the basis of the available data the following classification and labelling is proposed according to Directive 67/548/EEC.
Hazard symbols: Xn N Indication of danger: Harmful Dangerous for the environment Risk phrases: R 22 Harmful if swallowed R 40 Possible risk of irreversible effects
- 46 - Amitraz - Level 2: Reasoned statement of the overall conclusions
R 43 May cause sensitization by skin contact R50/53 Very toxic to aquatic organisms, may cause long- term adverse effect in the aquatic environment. R57 Toxic to bees Safety phrases: S 13 Keep away from food, drink and animal feeding stuffs S 20/21 When using, do not eat, drink or smoke S 24 Avoid contact with skin S 36/37/39 Wear suitable protective clothing, gloves and eye/face protection S 45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible) S60 This material and its container must be disposed of as hazardous waste S61 Avoid release to the environment. Refer to special instructions / Safety data sheet
According to Directive 67/548 EEC, as amitraz has EC50 -values for fish and daphnids < 1
mg as/l and the log pow > 3 with a BCF >100, the active substance should be classified as above. On the basis of the R50/53 classification, amitraz should also carry the "N" symbol on the active substance level and the S60/61 phrases.
2.10.2 MITAC 20 EC (AgrEvo Uk Ltd.)
The following classification and labelling is proposed:
Hazard symbols: Xn N Indication of danger: Harmful Dangerous for the environment Risk phrases: R 22 Harmful if swallowed R 38 Irritant to skin R 40 Possible risk of irreversible effects R 43 May cause sensitization by skin contact R 50/53 Very toxic to aquatic organisms, may cause long term adverse effects in aquatic environment R 57 Toxic to bees Safety phrases: S 2 Keep out of children S 13 Keep away from food, drink and animal feeding stuffs S 20/21 When using, do not eat, drink or smoke
- 47 - Amitraz - Level 2: Reasoned statement of the overall conclusions
S 24 Avoid contact with skin S 36/37/39 Wear suitable protective clothing, gloves and eye/face protection S 45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible) S 60 This material and its container must be disposed of as hazardous waste S 61 Avoid release to the environment. Refer to special instructions / Safety data sheet Honey bees: To avoid any impairment of honey bees until clarification on the effects of BTS 27919 and BTS 27271 on bees is provided, an appropriate labelling of Mitac 20 EC ("Do not use for the treatment of flowering crops or in their near vicinity") is recommended.
2.10.3 NARVAL (Industrias Afrasa, S.A.)
Due to lack of data a proposal for classification and labelling for Narval is not possible.
2.10.4 AMITRAZ WDG (Chimac Agriphar, S.A.)
Due to lack of data a proposal for classification and labelling for Amitraz WDGl is not possible.
- 48 - Amitraz - Level 2: Appendix 1
Appendix 1
Standard Terms and Abbreviations
Part 1 Technical Terms
A ampere ACh acetylcholine AChE acetylcholinesterase ADI acceptable daily intake ADP adenosine diphosphate AFID alkali flame-ionization detector of detection A/G albumin/globulin ratio ai active ingredient ALD50 approximate median lethal dose, 50 % ALT alanine aminotransferase (SGPT) AMD automatic multiple development ANOVA analysis of variance AOEL acceptable operator exposure level AP alkaline phosphatase approx. approximate as active substance AST aspartate aminotransferase (SGOT) ASV air saturation value ATP adenosine triphosphate
BCF bioconcentration factor bfa body fluid assay BOD biological oxygen demand bp boiling point BSAF biota-sediment accumulation factor BSE bovine spongiform encephalopathie BSP bromosulfophthalein Bt bacillus thuringiensis Bti bacillus thuringiensis israelensis Btk bacillus thuringiensis kurstaki Btt bacillus thuringiensis tenebrionis BUN blood urea nitrogen bw body weight c centi- (x 10-2) °C degree Celsius (centigrade) CA controlled atmosphere CAD computer aided design CBI confidential business information cd candela CDA controlled drop(let) application cDNA complementary DNA CEC cation exchange capacity cf confer, compare to CFU colony forming units ChE cholinesterase CI confidence interval CL confidence limits cm centimetre CNS central nervous system COD chemical oxygen demand CPK creatine phosphatase
- 49 - Amitraz - Level 2:Appendix 1 cv coefficient of variation Cv ceiling value CXL Codex Maximum Residue Limit (Codex MRL) d day DES diethylstilboestrol DMSO dimethylsulfoxide DNA deoxyribonucleic Acid dna designated national authority DO dissolved oxygen DOC dissolved organic carbon dpi days pot inoculation DT50 period required for 50 percent dissipation (define method of estimation) DT90 period required for 50 percent dissipation (define method of estimation) dw dry weight DWQG drinking water quality guidelines
ε decadic molar extinction coefficient EC50 median effective concentration ECD electron capture detector ECU European currency unit ED50 median effective dose EDI estimated daily intake ELISA enzyme linked immunosorbent assay e-mail electronic mail EMDI estimated maximum daily intake EPMA electron probe micro analysis ERC environmentally relevant concentration ERL extraneous residue limit
F0 parental generation F1 filial generation, first F2 filial generation, second FIA fluorescence immuno assay FID flame ionization detector FOB functional observation battery fp freezing point FPD flame photometric detector FPLC fast protein liquid chromatography g gram GAP good agricultural practice GC gas chromatography GC-EC gas chromatography with electron capture detector GC-FID gas chromatography with flame ionization detector GC-MS gas chromatography-mass spectrometry GC-MSD gas chromatography with mass-selective detection GEP good experimental practice GFP good field practice GGT gamma glutamyl transferase GI gastro-intestinal GIT gastro-intestinal tract GL guideline level GLC gas liquid chromatography GLP good laboratory practice GMM genetically modified micro-organism GMO genetically modified organism GPC gel-permeation chromatography GPPP good plant protection practice GPS global positioning system GSH glutathion GV granulosevirus
- 50 - Amitraz - Level 2:Appendix 1
h hour(s) H Henry's Law constant (calculated as a unitless value), (see also K) ha hectare Hb haemoglobin HCG human chorionic gonadotropin Hct haemocrit HEED high energy electron diffraction HID helium ionization detector hl hectolitre hma host-mediated assay HPAEC high performance anion exchange chromatography HPLC high pressure liquid chromatography or high performance liquid chromatography HPLC-MS high pressure liquid chromatography -mass spectroscopy HPPLC high pressure planar liquid chromatography HPTLC high performance thin layer chromatography HRGC high resolution gas chromatography Hs Shannon-Weaver index Ht haematocrit
I50 inhibitory dose, 50 % IC50 median immobilization concentration ICM integrated crop management ID ionization detector IEDI international estimated daily intake IGR insect growth regulator im intramuscular inh inhalation ip intraperitoneal IPM integrated pest management IR infrared ISBN international standard book number ISSN international standard serial number iv intravenous IVF in vitro fertilization k kilo K Kelvin or Henry's Law constant (in atmospheres per cubic meter per mole) (see also H) Kads adsorption constant Kdes apparent desorption coefficient kg kilogram Koc organic carbon adsorption coefficient Kom organic matter adsorption coefficient kg kilogram
L litre LAN local area network LASER light amplification by stimulated emission of radiation LBC loosely bound capacity LC liquid chromatography LC-MS liquid chromatography-mass spectrometry LC-MS-MS liquid chromatography with tandem mass spectrometry LC50 lethal concentration, median LCA life cycle analysis LCLo lethal concentration low LD50 lethal dose, median; dosis letalis media LDLo lethal dose low LDH lactate dehydrogenase LOAEC lowest observable adverse effect concentration LOAEL lowest observable adverse effect level
- 51 - Amitraz - Level 2:Appendix 1
LOD limit of detection LOEC lowest observable effect concentration LOEL lowest observable effect level LOQ limit of quantification (determination) LPLC low pressure liquid chromatography LSC liquid scintillation counting or counter LSD least squared denominator multiple range test LSS liquid scintillation spectrometry LT lethal threshold m metre M molar µm micrometer (micron) MC moisture content MCH mean corpuscular haemoglobin MCHC mean corpuscular haemoglobin concentration MCV mean corpuscular volume MDL method detection limit MFO mixed function oxidase mg milligram µg microgram MHC moisture holding capacity min minute(s) mL millilitre MLD minimum lethal dose MLT median lethal time mm millimetre mo month(s) mol Mole(s) MOS margin of safety mp melting point MRE maximum residue expected MRL maximum residue level mRNA messenger ribonucleic acid MS mass spectrometry MSDS material safety data sheet MTD maximum tolerated dose n normal (defining isomeric configuration) or number of observations NAEL no adverse effect level nd not detected NEDI no effect daily intake (mg/kg body wt/day) NEL no effect level NERL no effect residue level ng nanogram nm nanometer NMR nuclear magnetic resonance no number NOAEC no observed adverse effect concentration NOAEL no observed adverse effect level NOEC no observed effect concentration NOED no observed effect dose NOEL no observed effect level NOIS notice of intent to suspend NPD nitrogen-phosphorus detector of detection NPV nuclear polyhedrosis virus NR not reported nse non standard exposure NTE neurotoxic target esterase
OC organic carbon content ODP ozone-depleting potential
- 52 - Amitraz - Level 2:Appendix 1
ODS ozone depleting substances OM organic matter content op organophosphorous pesticide
Pa Pascal PAD pulsed amperometric detection 2-PAM 2-pralidoxime pc paper chromatography PCV haematocrit (packed corpuscular volume) PEC predicted environmental concentration PECA predicted environmental concentration in air PECGW predicted environmental concentration in ground water PECs predicted environmental concentration in soil PECSW predicted environmental concentration in surface water PED plasma-emissions-detector pH pH-value PHI pre-harvest interval PIC prior informed consent pic phage inhibition capacity pic phage inhibitory capacity PIXE proton induced X-ray emission pKa negative logarithm (to the base 10) of the dissociation constant PNEC predicted no effect concentration po by mouth POW partition coefficient between n-octanol and water POP persistent organic pollutants ppb parts per billion (10-9) ppm parts per million (10-6) ppp plant protection products ppq parts per quadrillion (10-24) ppt parts per trillion (10-12) PSP phenolsulfophthalein PrT prothrombin time PRL practical residue limit PT prothrombin time PTDI provisional tolerable daily intake PTT partial thromboplastin time
QSAR quantitative structure-activity relationship r correlation coefficient r2 coefficient of determination RBC red blood cell REI restricted entry interval Rf ratio of fronts RfD reference dose RH relative humidity RL50 residual lifetime RNA ribonucleic acid RP reversed phase rpm rotations per minute rRNA ribosomal ribonucleic acid RRT relative retention time s seconds SAC strong adsorption capacity SAP serum alkaline phosphatase SAR structure/activity relationship SBLC shallow bed liquid chromatography sc subcutaneous sce sister chromatid exchange SD standard deviation
- 53 - Amitraz - Level 2:Appendix 1
SE standard error se standard error SEM standard error of the mean SEP standard evaluation procedure SF safety factor SFC supercritical fluid chromatography SFE supercritical fluid extraction SIMS secondary ion mass spectroscopy SOP standard operating procedures sp species (only after a generic name) SPE solid phase extraction SPF specific pathogen free spp subspecies sq square SSD sulphur specific detector SSMS spark source mass spectrometry STEL short term exposure limit STMR supervised trials median residue t tonne (metric ton) t1/2 half-life (define method of estimation) T3 tri-iodothyroxine T4 thyroxine TADI temporary acceptable daily intake TBC tightly bound capacity TCD thermal conductivity detector TCLo toxic concentration, low TDLo toxic dose low TDR time domain reflectrometry TER Toxicity Exposure Ratio TER toxicity exposure ratio TERI toxicity exposure ratio for initial exposure TERLT toxicity exposure ratio following chronic exposure TERST toxicity exposure ratio following repeated exposure tert tertiary (in a chemical name) TEP typical end-use product TGGE temperature gradient gel electrophoresis TID thermionic detector, alkali flame detector TLC thin layer chromatography Tlm median tolerance limit TLV threshold limit value TMDI theoretical maximum daily intake TMRC theoretical maximum residue contribution TMRL temporary maximum residue limit TOC total organic carbon Tremcard Transport emergency card tRNA transfer ribonucleic acid TSH thuroid stimulating hormone (thyrotropin) TWA time weighted average
UDS unscheduled DNA synthesis UF uncertainty factor (safety factor) ULV ultra low volume UV ultraviolet v/v volume ratio (volume per volume)
WBC white blood cell wk week wt weight w/v weight per volume w/w weight per weight
- 54 - Amitraz - Level 2:Appendix 1 ww wet weight
XRFA X-ray fluorescence analysis yr year
≤ less than or equal to ≥ greater than or equal to < less than > greater than
Part 2 Organisations and Publications
ASTM American Society for Testing and Materials
BA Biological Abstracts (Philadelphia) BART Beneficial Arthropod Registration Testing Group
CA Chemical Abstracts CAB Centre for Agriculture and Biosciences International CAC Codex Alimentarius Commission CAS Chemical Abstracts Service CCFAC Codex Committee on Food Additives and Contaminants CCGP Codex Committee on General Principles CCPR Codex Committee on Pesticide Residues CE Council of Europe CIPAC Collaborative International Pesticides Analytical Council Ltd COREPER Comite des Representants Permanents
EC European Commission ECB European Chemical Bureau ECCA European Crop Care Association ECDIN Environmental Chemicals Data and Information Network of the European Communities ECDIS European Environmental Chemicals Data and Information System ECE Economic Commission for Europe ECETOC European Chemical Industry Ecology and Toxicology Centre ECLO Emergency Centre for Locust Operations ECMWF European Centre for Medium Range Weather Forecasting ECPA European Crop Protection Association EDEXIM European Database on Export and Import of Dangerous Chemicals EHC Environmental Health Criteria (number) (number) EINECS European Inventory of Existing Commercial Chemical Substances ELINCS European List of New Chemical Substances EMIC Environmental Mutagens Information Centre EPA Environmental Protection Agency EPO European Patent Office EPPO European and Mediterranean Plant Protection Organization ESCORT European Standard Characteristics of Beneficials Regulatory Testing EU European Union EUPHIDS European Pesticide Hazard Information and Decision Support System EUROPOEM European Predictive Operator Exposure Model
FAO Food and Agriculture Organization of the UN FOCUS Forum for the Co-ordination of Pesticide Fate Models and their Use
- 55 - Amitraz - Level 2:Appendix 1
GATT General Agreement on Tariffs and Trade GAW Global Atmosphere Watch GCOS Global Climate Observing System GCPF Global Crop Protection Federation (formerly known as GIFAP) GEDD Global Environmental Data Directory GEMS Global Environmental Monitoring System GIEWS Global Information and Early Warning System for Food and Agriculture GIFAP Groupement International des Associations Nationales de Fabricants de Produits Agrochimiques GRIN Germplasm Resources Information Network
HRAC Herbicide Resistance Action Committee
IARC International Agency for Research on Cancer IATS International Academy of Toxicological Science IBT Industrial Bio-Test Laboratories ICBB International Commission of Bee Botany ICBP International Council for Bird Preservation ICES International Council for the Exploration of the Seas ICPBR International Commission for Plant-Bee Relationships ILO International Labour Organisation IMO International Maritime Organisation IOBC International Organization for Biological Control of Noxious Animals and Plants IPCS International Programme on Chemical Safety IRAC Insecticide Resistance Action Committee IRC International Rice Commission ISCO International Soil Conservation Organization ISO International Organization for Standardization IUPAC International Union of Pure and Applied Chemistry
JECFA FAO/WHO Joint Expert Committee on Food Additives JFCMP Joint FAO/WHO Food and Animal Feed Contamination Monitoring Programme JMP Joint Meeting on Pesticides (WHO/FAO) JMPR Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues (Joint Meeting on Pesticide Residues)
NAFTA North American Free Trade Agreement NATO North Atlantic Treaty Organisation NCI National Cancer Institute (USA) NCTR National Center for Toxicological Research (USA) NGO non-governmental organization NTP National Toxicology Programme (USA)
OECD Organization for Economic Cooperation and Development OLIS On-line Information Service of OECD
PAN Pesticide Action Network
RNN Re-registration Notification Network RTECS Registry of Toxic Effects of Chemical Substances (USA)
SCPH Standing Committee on Plant Health SETAC Society of Environmental Toxicology and Chemistry SI Systeme International d’Unites SITC Standard International Trade Classification
Toxline Toxicology Information On-line UN United Nations UNEP United Nations Environment Programme
- 56 - Amitraz - Level 2:Appendix 1
WCDP World Climate Data Programme WCP World Climate Programme WCRP World Climate Research Programme WFP World Food Programme WHO World Health Organization WTO World Trade Organization WWF World Wildlife Fund
Part 3 Preparation (Formulation) Types and Codes *
Code Description Definition
AB Grain bait Special forms of bait.
AE Aerosol dispenser A container-held preparation which is dispersed generally by a propellant as fine droplets/particles upon actuation of a valve.
AL Other liquids to be applied Self defining. undiluted
BB Block baits Special forms of bait.
BR Briquette Solid block designed for controlled release of active ingredient into water.
CB Bait concentrate A solid or liquid intended for dilution before use as a bait.
CG Encapsulated granule A granule with a protective or release controlling coating.
CS Capsule suspension A stable suspension of capsules in a fluid normally intended for dilution with water before use.
DC Dispersible concentrate A liquid homogeneous preparation to be applied as a solid dispersion after dilution in water.
DP Dustable powder A free-flowing powder suitable for dusting.
DS Powder for dry seed treatment A powder for application in the dry state directly to seed.
EC Emulsifiable concentrate A liquid, homogenous preparation to be applied as an emulsion after dilution in water.
ED Electrochargeable liquid Special liquid preparation for electrostatic (electrodynamic) spraying.
EO Emulsion, water in oil A fluid, heterogeneous preparation consisting of a dispersion of fine globules of pesticide in water in a continuous organic liquid phase. ES Emulsion for seed treatment A stable emulsion for application to the seed either directly or after dilution.
* based upon the catalogue of Pesticide Formulation types and International Coding Systems, developed by GIFAP in co-operation with the German working group on documentaion questions (Arbeitsgruppe EDV Pflanzenschutz Versuchswesen). GIFAP Technical Monograph No 2, 1989.
- 57 - Amitraz - Level 2:Appendix 1
Code Description Definition
EW Emulsion, oil in water A fluid, heterogeneous preparation consisting of a dispersion of fine globules of pesticide in an organic liquid in a continuous water phase.
FD Smoke tin Special form of smoke generator.
FG Fine granule A granule in the particle size range from 300 to 2500µ.
FK Smoke candle A smoke generator in the form of a candle.
FP Smoke cartridge Special form of smoke generator.
FR Smoke rodlet Special form of smoke generator.
FS Flowable concentrate for seed A stable suspension for application to the seed either directly treatment or after dilution.
FT Smoke tablet Special form of smoke generator.
FU Smoke generator A combustible preparation generally solid, which upon ignitionreleases the active substances in the form of a smoke.
FW Smoke pellet Special form of smoke generator.
GA Gas A gas packed in pressure bottle or pressure tank.
GB Granular bait Special forms of bait.
GE Gas generating product A preparation which generates a gas by chemical reaction.
GG Macrogranule A granule in the particle size range from 2000 to 6000 µ.
GP Flo-dust Very fine dustable powder for pneumatic application in glass- houses.
GR Granule A free-flowing solid preparation of a defined granule size range ready for use.
GS Grease Very viscous preparation based on oil or fat.
HN Hot fogging concentrate A preparation suitable for application by fogging equipment either directly or after dilution.
KN Cold fogging concentrate A preparation suitable for application by cold fogging equipment, either directly or after dilution.
LA Lacquer A solvent based film-forming preparation.
LS Solution for seed treatment A solution for application to the seed either directly or after dilution.
MG Microgranule A granule in the particle size range from 100 to 600 µ.
OF Oil miscible flowable (=oil A stable suspension of concentrate fluid intended for dilution active substances in a inan organic liquid before use. miscible suspension)
- 58 - Amitraz - Level 2:Appendix 1
Code Description Definition
OL Oil miscible liquid A liquid, homogenous preparation to be applied as a homogenous liquid after dilution in an organic liquid.
OP Oil dispersible powder A powder preparation to be applied as a suspension after dispersion in an organic liquid.
PA Paste A water based film forming preparation.
PB Plate bait Special forms of bait.
PC Gel or paste concentrate A solid preparation to be applied as a gel or a paste after dilution with water.
PR Plant rodlet A small rodlet, usually a few centimetres in length and a few millimetres in diameter containing active substance.
PS Seed coated with a pesticide Self defining.
RB Bait (ready for use) A preparation designed to attract and be eaten by the target species.
SB Scrap bait Special forms of bait.
SC Suspension concentrate A stable suspension of active substance(s) in a fluid intended (= flowable concentrate) for dilution with water before use.
SE Suspo-emulsion A fluid, heterogeneous preparation consisting of a stable dispersion of active substance(s) in the form of solid particles and of fine globules in a continuous water phase.
SG Water soluble granules A preparation consisting of granules to be applied as a true solution of active substance after dissolution in water but may contain insoluble inert ingredients.
SL Soluble concentrate A liquid homogenous preparation to be applied as a true solution of the active substance after dilution with water.
SO Spreading oil A preparation designed to form a surface layer on application to water.
SP Water soluble powder A powder preparation to be applied as a true solution of the active substance after solution in water but which may contain insoluble inert ingredients.
SS Water soluble powder for A powder to be dissolved in water before application to the seed treatment seed.
SU Ultra low volume (ULV) A suspension ready for use through ULV equipment. suspension
TB Tablet Solid preparation in the form of small, flat plates for dissolution in water.
- 59 - Amitraz - Level 2:Appendix 1
Code Description Definition
TP Tracking powder A rodenticidal contact preparation in powder form.
UL Ultra low volume (ULV) liquid A homogenous liquid ready for use through ULV equipment.
VP Vapour releasing product A preparation containing one or more volatile ingredients, the vapours of which are released into the air. Evaporation rate normally is controlled by using suitable preparations and/or dispensers.
WG Water dispersible A preparation granule consisting of granules to be applied after disintegration and dispersion in water.
WP Wettable powder A powder preparation to be applied as a suspension after dispersion in water.
WS Water dispersible powder for A powder to be dispersed at high concentration in water slurry seed treatment before application as a slurry to the seed.
XX Others
- 60 - Amitraz - Level 2:Appendix 1
Appendix 2
Specific Terms and Abbreviations
- 61 -
Level 3
Amitraz
Proposal for the Decision with Respect to the Application for Inclusion of the Amitraz in Annex I
- 62 - Amitraz - Level 3: Proposed decision
3 Proposed decision with respect to the application for inclusion of the active substance in Annex I
3.1 Background to the proposed decision
Amitraz is an insecticide and acaricide with a broad spectrum of activity used in agriculture, horticulture, orchards, forestry and amenity and as ectoparasiticide in veterinary medicine. The notifier AgrEvo UK Ltd. supports the crops listed up in the following table.
Table 3.1-1 Intended uses of Mitac 20 EC, AgrEvo UK Ltd.
Crop Region Use Application No. of Time of PHI Northern rate per Appli- application (days) Europe(N)/ treatment cation (growth Southern [kg a.i./ha] stage) Europe(S)
Citrus fruit Oranges S field 0.8 2 beginning of 14 infestation Mandarines S field 0.8 2 beginning of 14 infestation
Pome fruit Apples N/S field 0.8 2 beginning of 28 infestation Pears N/S field 0.8 beginning of 28 2 infestation
Stone fruit Cherries N/S field 0.8 2 beginning of 28 infestation Plums N/S field 0.8 2 beginning of 28 infestation Peaches S field 0.8 2 beginning of 28 infestation Apricots S field 0.8 2 beginning of 28 infestation
Berries and small fruit Strawberries N/S field/glass- 0.8 2 pre blossom, 35 house post harvest Currants N field/glass- 0.8 2 pre blossom, 42 house post harvest
Solanacea Tomatoes N/S field 0.8 3 beginning of 14 infestation Peppers N/S field 0.8 3 beginning of 14 infestation Aubergines N/S field 0.5 1 beginning of 14 infestation
Oil seed Cotton S field 0.6 2 all season 21
Hops N field 2.5 2 beginning of 28
- 63 - Amitraz - Level 3: Proposed decision
Crop Region Use Application No. of Time of PHI Northern rate per Appli- application (days) Europe(N)/ treatment cation (growth Southern [kg a.i./ha] stage) Europe(S) infestation
Ornamentals N/S field/glass- 0.6 2 all season - house
Glasshouses N/S glasshouse 1 1 empty glass- - houses
Tree nursery N/S field 1 2 all season -
Public green N/S field 1 2 all season -
The information submitted by the notifier Chimac Agriphar S.A. concerning the intended uses of the product Amitraz WDG is listed up in Table 3.1-2 .
Table 3.1-2 Intended uses of Amitraz WDG
Crop Region Use Application No. of Time of PHI Northern rate per Appli- application (days) Europe(N)/ treatment [kg cation (growth Southern a.i./ha] stage) Europe(S)
Citrus S field 30 - 35 g 2 - 3 beginning of 7 a.i. /hl infestation *)
Apples field 0.08 - 1.0 2 -3 when mite 14 population >5 mites per leaf
Pears field 0.12 - 1,5 2 when first 14 egg is laid
The notifier Industrias Afrasa, S.A. provided the authorized use of NARVAL in Spain which are supported by the notifier.
Table 3.1-3 Approved (supported) uses of Narval
Crop Region Use Application No. of Time of PHI Northern rate per Appli- application (days) Europe(N)/ treatment [kg cation (growth Southern a.i./ha] stage) Europe(S) Citrus fruit S field 0.3 1 beginning of 14 infestation Stone fruit S field 0.6 3 beginning of 14 infestation Berries and
- 64 - Amitraz - Level 3: Proposed decision
Crop Region Use Application No. of Time of PHI Northern rate per Appli- application (days) Europe(N)/ treatment [kg cation (growth Southern a.i./ha] stage) Europe(S) small fruit Strawberries S field/glass- 0.6 2 beginning of 7 house infestation Miscellaneous Bananas S field 0.6 2 beginning of 14 infestation Solanacea Tomatoes S field/glass- 0.6 2 beginning of 14 house infestation
Peppers S field/glass- 0.6 2 beginning of 14 house infestation
Aubergines S field/glass- 0.6 2 beginning of 14 house infestation Cucurbitacea S field/glass- 0.6 2 beginning of 14 house infestation Cotton S field 0.6 3 beginning of not infestation applicabl e Ornamentals S field/glass- 0.6 2 beginning of 14 house infestation
Residues of Amitraz and metabolites, which may occur in plants, products of plant origin animal tissues and soil are determinable with adequate analytical methodology. Confirmatory data, however, concerning the specifity of the methods based on the determination of 2,4-dimethylaniline should be submitted. The method for the determination of Amitraz in water does not meet the requirement to detect residue levels of 0.1 µg/l and has to be therefore improved.
After proper use of Amitraz containing formulations skin sensitization reactions can be expected. Additionally, direct skin contact with small amounts can produce "skin flushings"
as a consequence, that Amitraz is an α2-receptor agonist and this symptoms are due to central and peripheral α2-adrenergic action. Considering the proposed ADI and AOEL of 0,0025 mg/kg bw respectively, repeated exposure to small quantities should not lead to adverse health effects under the limited
- 65 - Amitraz - Level 3: Proposed decision
circumstances given below.
On the other hand, estimations of the potential operator exposure, based on the German BBA as well as the UK POEM model show, that after application of Amitraz containing formulations to high cultivations the predicted operator exposure will exceed the proposed systemic AOEL, if no or a non-sufficient personal protective equipment is used. Calculations of the risks to the operator using Amitraz containing formulations in glass houses with hand held equipment or on public green were not submitted. Additionally, for these two intended uses, health risk to workers and bystanders in term of re-entry interval was not taken into sufficient consideration from the notifier. Taking into account these comments, adverse health effects to operators cannot be excluded, when no sufficient protective equipment is used. Therefore, measurements of the operator exposure covering all intended applications and using sufficient protective equipment as well as re-entry intervals for workers and bystanders are required to evaluate if exposure to Amitraz presents no undue risk for human health.
At the moment, there are insufficient residue data available for establishing MRLs for all intended uses except for hops and for food of animal origin. In addition, it must be stated that in spite of further residue data an excess (as TMDI and EMDI) of the ADI will take place and it may therefore also be decided on a rationalisation or an amendment of the at the moment intended uses including e.g. reduction of the application rates, changing the time of the application (by increasing the PHI) and/or otherwise adaptation of the intended uses in order to reduce the consumer exposure to an acceptable level. At present, the data provided indicate that the residues of Amitraz may present a risk to human health through residues in food (the TMDI-calculation shows an excess of the ADI for an adult person and for a 4-6 year old girl, respectively; the EMDI-calculation shows still an excess of the ADI for a 4-6 year old girl).
Although the environmental fate data submitted are still not sufficient for a definitive assessment of the route and rate of degradation in air it can be concluded on the basis of the environmental data given that an accumulation in soil and water as well as a contamination of ground water are not to be expected. Further ecotoxicological data are required to assess whether the use of amitraz and its degradation products will have any harmful effects on terrestrial and aquatic organisms.
3.2 Proposed decision concerning inclusion in Annex I
Amitraz is the ISO- common name for N-methylbis(2,4-xylyliminomethy)amine (IUPAC) or N’-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl)imino]methyl]-N-methylmethaniminamide (CA), respectively. One notifier has definitively demonstrated that the minimum purity of the active substance is
- 66 - Amitraz - Level 3: Proposed decision
> 970 g/kg. It is proposed to postpone the inclusion of the above characterized activce substance Amitraz in Annex I of Council Directive 91/414 EEC pending the receipt and evaluation of the data listed in Section 4.
If in the future, Amitraz is included in Annex I of Council Directive 91/414/EEC, Member states should be advised that: i) Risk mitigation to minimise the risk on aquatic life is necessary. ii) The impact on non-target organisms should be assessed. iii) As long as the effects of BTS 27919 and BTS 27271 on bees have not been fully clarified an appropriate labelling of formulated amitraz is recommended (i.e. "Do not use for the treatment of flowering crops or in their near vicinity").
3.3 Rational for the postponement of the decision to include the active substance in Annex I, or for the conditions and restrictions to be associated with a proposed inclusion in Annex I, as appropriate
The data provided till now indicate that there are some specific health and environmental concerns with the use of Amitraz in plant protection products. Additional data are required to complete the assessment of wether the conditions laid down in Article 5(1) of Council Directive 91/414 EEC are satisfied.
- 67 -
Level 4
Amitraz
Demand for Further Information
- 68 - Amitraz - Level 4: Demand for further information
4 Further information to permit a decision to be made. or to support a review of the conditions and restrictions associated with the proposed inclusion in Annex I
4.1 Identity of the active substance
4.1.1 Active substance
4.1.1a AgrEvo UK Ltd.
The information provided is sufficient.
4.1.1b Chimac Agriphar S.A.
IIA 1.9 Specification of purity of the active substance: A justified specification of the minimum purity of the active substance has to be provided. IIA 1.10 and IIA 1.11 Identity of isomers, impurities and additives, analytical profile of batches A reliable quantification of the impurities is required.
4.1.1c Industrias Afrasa, S.A.
IIA 1.2 Manufacturer: A contact point (incl. telefone number) has to be provided. Information concerning the location of the manufacturing plant is missing. IIA 1.8 Method of manufacture: The specification of the starting materials is missing. As there are possible variations in the manufacturing process the notifier has to explain whether these variations influence the purity or the profile of impurities. IIA 1.10 Identity of isomers, impurities and additives: The information concerning the identity and amount of impurities is required. IIA 1.11 Analytical profile of batches: The results of analyses of batches and the validated methods for the determination of the active substance and the impurities are required.
4.1.2 Formulation
4.1.2a MITAC 20 EC, emulsifiable concentrate, 200 g/l
The information supplied is sufficient.
4.1.2b AMITRAZ WDG, water dispersible granule, 750 g/kg
The information supplied is sufficient.
- 69 - Amitraz - Level 4: Demand for further information
4.2.2c NARVAL, emulsifiable concentrate, 200 g/l
The information supplied is sufficient.
4.2 Physical and chemical properties of the active substance
4.2.1 Active substance
The following studies are missing or have been submitted in an unacceptable quality (details can be found in Annex B): IIA 2.10 Stability in air, photochemical oxidative degradation: A study is required. IIA 2.13 Explosive properties:
The DSC report referenced has to be provided for the evaluation.
4.2.2 Formulation
The following studies are missing or have been submitted in an unacceptable quality (details can be found in Annex B):
4.2.2a MITAC 20 EC, emulsifiable concentrate, 200 g/l
IIIA 2.2.1 Explosive properties IIIA 2.3 Auto-flammability IIIA 2.3 Flash point a GLP study is required. IIIA 2.7.1 Stability after storage for 14 days at 54°C according to CIPAC MT 46 IIIA 2.8.7.1 Emulsifiability, re-emulsifiability and emulsion stability
4.2.2b AMITRAZ WDG, water dispersible granule, 750 g/kg,
IIIA 2.7.3 Shelf life: The notifier submitted a study but did not specify the storage time that has been tested. IIIA 2.8.6.3 Attrition and friability IIIA 2.8.8.1 Flowability IIIA 2.9.1 Physical and chemical compatibility of tank mixes: Member state level
4.2.2c NARVAL, emulsifiable concentrate, 200 g/l
IIIA 2.2.1 Explosive properties IIIA 2.2.2 Oxidizing properties IIIA 2.3 Autoflammability IIIA 2.3 Flash point IIIA 2.4 pH of 1 % aqueous dilution, emulsion or dispersion IIIA 2.5.2 Viscosity: The full study incl. raw data have to be submitted IIIA 2.5.3 Surface tension IIIA 2.6.1 Relative density IIIA 2.7.1 Stability after storage for 14 days at 54°C
- 70 - Amitraz - Level 4: Demand for further information
IIIA 2.7.2 Effect of low temperature on stability IIIA 2.7.3 Shelf life IIIA 2.8.2 Persistent foaming IIIA 2.8.7.1 Emulsifiabilty, re-emulsifiabilty and emulsion stability: a complete study has to be provided IIIA 2.8.7.2 Stability of dilute emulsions IIIA 2.9.1 Physical and chemical compatibility of tank mixes: Member state level The notifier informed the rapporteur that these studies will be supplied. But to perform the studies and to prepare the report according to the guidelines and criteria requested the notifier needs an extra period of time. No schedule has been submitted.
4.3 Data on application and further information
4.3a AgrEvo UK Ltd.
IIA 3.7 No information has been supplied about storage, handling and transport of stabilised product packed with paraformaldehyde sachets.
4.3b Chimac Agriphar S.A.
IIIA 4.1 Description and specification of the packaging and materials used in packaging, resistance of the packaging material to its content: The notifier did not provide information on this section.
4.3c Industrias Afrasa, S.A.
IIIA 4.4 Regulations concerning transport of the product.
4.4 Methods of analysis
IIA 4.1.2 Analytical method for the determination of impurities No satisfying methods for the determination of significant and/or relevant impurities arising from the manufacturing processes applied by the manufacturer of Chimac Agriphar S.A. and Industrias Afrasa S.A. have been submitted. For the evaluation of the validity of the batch analysis and for monitoring purposes, the methods for the determination of impurities are an absolute necessity.
IIIA 5.1 The notiffiers Chimac Agriphar S.A. and Industrias Afrasa S.A. have to provide validation data to allow an estimation of the applicability of the CIPAC methods for the determination of Amitraz in the WG and EC formulation, respectively.
IIA 4.2.1 Aanalytical methods (residue) for plants and plant products A common moiety method has been suggested for the determination of Amitraz derived residues. The notifier is asked to provide information about the specifity of the analyte 2,4-dimethylaniline as a characteristic moiety for Amitraz.
- 71 - Amitraz - Level 4: Demand for further information
IIA 4.2.3, IIIA 5.2.3 Analytical method for analysis of water for parent compound and toxicologically, ecotoxicologically or environmentally significant impurities As there are interferences of the analyte signal with matrix compounds, which can not be neglected, a reliable determination of Amitraz derived residues in water at the EU-limit of 0.1 µg/kg is not possible. An adopted method (including a full validation for ground water and for surface water) has to be submitted.
4.5 Toxicology and metabolism
IIA, 5.2.2 Three studies for the estimation of the acute dermal toxicity of Amitraz have been submitted; due to the limited validity of all three studies, a clear assessment of the acute dermal toxicity
cannot be made and LD50 values cannot be calculated. Therefore, a limit test for the clarification of the acute dermal toxicity is required. Deadline: 3 months
IIIA. 7.1 For the formulation NARVAL no detailed studies for the evaluation of the acute profile including irritancy and skin sensitization have been submitted. Therefore, these studies are required. Additionally, the classification and labelling, proposed from the notifier for the formulation NARVAL includes the risk phrases R 20 and R 36 without giving any explanation. Therefore a justification for classification and labelling of this formulation, based on relevant data is necessary. Deadline: 6 months
IIIA, 7.3 The results of all model calculations submitted show that the predicted operator exposure will exceed the proposed systemic AOEL of 0.0025 mg/kg bw, if no personal protective equipment is used. Even calculation using protective equipment (gloves, mask, hood/visor and garments) only for the BBA model also shows an excess of the proposed AOEL. Additionally, no model calculations covering the application under glass house conditions using a hand held equipment were submitted. Therefore measurements including the usage of sufficient protective equipment for all intended uses are required. Due to the fact that Amitraz containing formulations are also intended for an application on public green, a calculation of the bystander exposure and of a re-entry interval for this use is required. In this case special care should also be taken of children, e.g. playing on treated public green. Amitraz containing formulations are also used under glass house conditions. Therefore, a
- 72 - Amitraz - Level 4: Demand for further information
statement on worker exposure (especially through glass house application) and a re-entry interval based on calculation data are required Deadline: 3 months
4.6 Residue data
II A, 6.1 One further metabolism study will be needed (e.g. one study conducted on one representative of the crop group "leafy vegetables" like brassica vegetables) in order to estimate the conformity or similarity of the route of degradation in all intended crops. Deadline: 6 months
II A, 6.3; A III, 8.1 The residue data provided by the notifiers are not sufficient to propose EU wide MRLs for all intended uses with the exception of hops. Therefore, further data according to the intended uses are necessary (the requirements listed below do not distinguish between the notifiers aand their different plant protection products): Citrus fruit: a) oranges, grapefruits, pomelos: 8 trials (Southern Region of Europe) b) lemons, mandarines, (including clementines and similar hybrids) and limes: 8 trials (Southern Region of Europe) Pome fruit: apples, pears: 3 trials (Southern Region of Europe) Stone fruit: a) peaches, apricots, nectarines and other peach hybrids: 8 trials (Southern Region of Europe) b) cherries, plums, mirabelles and other plum hybrids: 8 trials (Northern Region of Europe) 4 trials (Southern Region of Europe) Berries and small fruit: a) strawberries: 8 trials (Northern Region of Europe) 8 trials (Southern Region of Europe) 8 trials (glasshouse) b) currants: 4 trials (Northern Region of Europe) 4 trials (glasshouse) Miscellaneous: bananas: 8 trials (Southern Region of Europe) Solanacea: a) tomatoes: 8 trials (Northern Region of Europe) 8 trials (Southern Region of Europe) 8 trials (glasshouse) b) aubergines: 8 trials (Northern Region of Europe)
- 73 - Amitraz - Level 4: Demand for further information
8 trials (Southern Region of Europe) 8 trials (glasshouse) c) peppers 4 trials (Northern Region of Europe) 8 trials (Southern Region of Europe) 7 trials (glasshouse) Cucurbitaceae: a) cucurbits with edible peel: 8 trials (Northern Region of Europe) 8 trials (Southern Region of Europe) 8 trials (glasshouse) b) cucurbits with inedible peel: 4 trials (Northern Region of Europe) 8 trials (Southern Region of Europe) 8 trials (glasshouse) Cottonseed: 8 trials (Southern Region of Europe) Deadline: max. 3 years, for individual crops in the shortest period possible
II A, 6.5 Data on processing may be required depending on the level of residues to be detected and on the relevant consumer risk assessment (EMDI) for following crops: stone fruits, currants, strawberries and tomatoes. These data are necessary for calculating the transfer factors and for estimating further consumer risk assessments. Deadline: in connection with the deadline under point IIA, 6.3 and IIIA, 8.1
II A, 6.9 The Theoretical Maximum Daily Intake of Amitraz-derived residues through the relevant food items accounts for 240.7 % of the ADI (adult, 60 kg bw.) and 212.8 % of the ADI (4-6 year old girl, 13.5 kg bw.), respectively. The Estimated Maximum Daily Intake of Amitraz-derived residues through relevant food items accounts for 181.7 % of the ADI (4-6 year old girl, 13.5 kg bw.). It must be stated that in spite of further residue data an excess (as the TMDI and the EMDI) of the ADI will take place and it may also be decided on a rationalisation or an amendment of the at the moment intended uses including e.g. reduction of the application rates, changing the time of application (by increasing the PHI) and/or an otherwise adaptation of the intended uses in order to reduce the consumer exposure to an acceptable level. Deadline: in connection with the deadlines under points IIA, 6.3; IIIA, 8.1 and IIA, 6.5
4.7 Environmental fate and behaviour
IIA, 7.2.2 An increment calculation of the degradation of amitraz and its metabolite BTS 24868 in air according to Atkinson is required.
- 74 - Amitraz - Level 4: Demand for further information
For the formulations NARVAL and AMITRAZ WDG no studies for the evaluation of fate and bahaviour in the environment have been submitted. These studies are required.
4.8 Ecotoxicology
IIA, 8.1.3, III, 10.3 Measurements of residues on wildlife food items (especially on insects) to determine the degradation of amitraz and its relevant metabolites.
IIA 8.1.3, IIIA 10.3 A field-test to determine the long-term toxicity of amitraz and its metabolites to terrestrial vertebrates in case that results of the measurements of residues on wildlife food items indicate an exposure risk to terrestrial vertebrates
IIA, 8.2 A microcosm/mesocosm study to investigate the acute and long-term risk to aquatic life (especially to invertebrates) if amitraz is used at application rates higher than 800 g as/ha and drift values of less than 0.2 %. Data on the toxicity of amitraz to sediment dwelling organisms in case of repeated applications in northern European countries where the temperature of surface water is mainly closer to 8° C than 25° C. This study should be designed realistically and simulate 3 applications at an interval of 1 week, the test temperature should be 8° C. Thus a constant amitraz concentration in sediment over 3 weeks would be achieved which would enable an assessment of the chronic risks to sediment dwelling organisms.
IIA 8.3.1 Additionally to the studies provided for honey bees there is further requirement for clarification if any hazard to honey bees may arise out of the formation of the two major breakdown products of amitraz (BTS 27919 and BTS 27271). An appropriate test or a scientific explanation should be provided to answer this question. For the formulations NARVAL and AMITRAZ WDG no studies for the evaluation of ecotoxicology have been submitted. These studies are required. Data submission deadline: 3 years
4.9 Classification. packaging and labelling
See section 4.2 (physical and chemical properties)
Federal Ministry of Agriculture, Forestry, Environment and Water Management
Stubenring 1 1010 Vienna Austria
Amitraz
Addendum II
to Volume 1
to the Draft Assessment Report and Proposed Decision of Austria prepared in the context of the possible inclusion of the above mentioned active substance in Annex I of Council Directive 91/414/EEC
December 09
13859 /ECCO/BBA/02 - i - Amitraz – Addendum II: Contents February 2002
Contents Page Addendum II to Level 1 5 Statement of Subject Matter and Purpose of Monograph 5 1.3.1 Name and address of applicant(s) for inclusion of the active substance in Annex I (Annex IIA 1.1) 6 Table 1.5.3a-2 Summary of uses supported by available data (Mitac 20EC) 5 Addendum II to Level 2 7 Proposed Decision 7 2.1 Background to the proposed decision 8 2.2 Proposed decision concerning inclusion in Annex I 9
Amitraz
Addendum II to Level 1
Statement of Subject Matter and Purpose of Monograph
- 6 - Amitraz – Addendum II to Level 1: Statement of subject matter and purpose
1. Statement of subject matter and purpose for which the monograph was prepared
1.3.1 Name and address of applicant(s) for inclusion of the active substance in Annex I (Annex IIA 1.1)
1.3.1.1 First notifier:
The notifier Bayer CropScience GmbH (former AgrEvo UK Ltd.) informed the Rapporteur Member State that the central address for all matters concerning the review of Amitraz has changed.
New Central Address: Member State Address: Bayer CropScience GmbH T.B. Agrartechnik Industriepark Hoechst Sellnergasse 4 Gebäude K 607, A-2540 Bad Vöslau D-65926 Frankfurt am Main Austria Germany
Primary contact: Berthold Krebs Primary contact: Anita Olson Telephone: +49 69 305 3844 Telephone: +43 2252 76960 Telefax: +49 69 305 3826 Telefax: +43 2252 71005
- - Amitraz – Addendum II to Level 1: Statement of subject matter and purpose September 2000
Table 1.5.3a-2 Summary of uses supported by available data (Mitac 20EC)
Crop and/or F or G Pest or group Formulation Application Application rate per treatment PHI Region (N/S) situation of pests *Minor crops (field/ Type Conc. of Method Growth Number kg a.s./hl water l/ha Kg days N=North Europe glass) a.s. (g/l) kind stage a.s./ha S=South Europe Pome fruit - F Mites EC 200 Spray Beginning of 2 0.05 500 - 1500 0.75 42 N Apples Rust mites infestation Pome fruit - F Mites EC 200 Spray Beginning of 2 0.08 1000 0.8 35 S Apples Rust mites infestation Pome fruit - F Mites EC 200 Spray Beginning of 2 0.05 500 - 1500 0.75 42 N Pears Pear suckers infestation Pome fruit - F Mites EC 200 Spray Beginning of 2 0.08 1000 0.8 35 S Pears Pear suckers infestation
Amitraz
Addendum II to Level 2
Proposed Decision
- 8 - Amitraz – Addendum II to Level 2: Proposed Decision
2 Proposed decision with respect to the application for inclusion of the active substance in Annex I
2.1 Background to the proposed decision
The information submitted concerning the physical and chemical properties is complete and acceptable.
The analytical methods proposed for the technical active substance and the plant protection products are acceptable and validated.
The Committee for Veterinary Medicinal Products (CVMP) has evaluated Amitraz and has proposed an ADI of 0.003 mg/kg b.w./day based on the NOEL in dogs of 0.25 mg/kg b.w. and a Safety Factor of 100. In order to avoid inconsistencies in the evaluation, this ADI has been endorsed in an expert working group (pesticides - evaluation) held on 16. May 2002. In view of the fact that operator exposure scenarios might be not strictly acute, the same value of 0,003 mg/kg b.w. is proposed for the Acceptable Operator Exposure Level (AOEL). An Acute Reference Dose (ARfD) of 0.01 mg/kg b.w. is proposed for Amitraz. The basis for this ARfD is the NOEL in dogs (0.25 mg/kg b.w.). In view of the circumstantial data for humans, which covers an acute exposure situation, it is proposed to apply a Safety Factor of 25.
The operator exposure for the use of Amitraz in high corps with application rates of 0.8 kg a.i./ha can be considered acceptable if extensive PPE and additionally a closed tractor cabin is used. This issue has to be addressed in the decision for Annex I inclusion.
The chronic dietary risk assessment reveals that acceptable margins of safety exist for dietary exposure to residues of Amitraz. In the acute risk assessment for adults the intake of Amitraz is below the Acute Reference Dose. For children a refined calculation of the acute intake gives an exceedance of the Acute Reference Dose (118 % for apples and 142% for pears), however this could be accepted as the model is based on a conservative, worst case approach which is unlikely to happen in reality. In practice additional reduction factors might be applied, e.g. processing factors for production of juice and reduction factors for washing and peeling, which is routinely done especially for children. From metabolism studies in pome fruit it is known that a high percentage of the residues are found in the peel (peel: 70%, pulp: 30% of the residues, expressed in % of radioactivity after 21 days). Taking all these aspects into account the acute risk assessment for children might be acceptable.
Following normal usage, Amitraz and its metabolites are not expected to cause damage to the environment.
- 9 - Amitraz – Addendum II to Level 2: Proposed Decision
Detailed studies and evaluation of ecotoxicological aspects allow to conclude that risk assessment is acceptable for non-target organisms, if appropriate risk mitigation measures are taken.
Final conclusion: On the basis of the proposed and supported uses it is expected that the use of Amitraz and the residues resulting form this use are unlikely to have harmful effects on human and animal health, groundwater, or have unacceptable influence on non-target organisms. Risk mitigation measures are necessary with regard to appropriate protective equipment for the operators and aquatic organisms.
2.2 Proposed decision concerning inclusion in Annex I
The inclusion of the active substance Amitraz in Annex I of the Directive 91/414/EEC is proposed.
Federal Ministry of Agriculture, Forestry, Environment and Water Management
Stubenring 1 1010 Vienna Austria
Amitraz
Addendum II
to Volume 3 Annex B
Summary, Scientific Evaluation and Assessment
Draft: July 2002
13860 /ECCO/BBA/02 - i - Amitraz – Addendum II: Contents February 2002
Contents
page
Contents i B.2 Physical and chemical properties 2 B.2.1 Physical and chemical properties of the active substance (Annex IIA 2) 3 B.2.3 Summary of physical, chemical and technical properties 4 B.2.3.1 Active substance 4 B.2.3.2 Plant protection product 4 B.2.4 References relied on 4 B.4 Methods of analysis 5 B.4.3 Analytical methods (residue) for soil, water and air 6 B.4.3.2 Water (including drinking water (Annex IIA 4.2.3, Annex IIIA 5.2.3) 6 B.4.6 References relied on 8 B.6 Residue data 9 B.6 Residue data 9 B.6.4 Use pattern 10 B.6.6 Residues resulting from supervised trials (Annex IIA 6.3; Annex IIIA 8.1) 10 B.6.6.1 Pome fruit 10 B.6.12 Proposed EU-MRLs and justification for the acceptability of those MRLs (Annex IIA, 6.7; Annex IIIA, 6.8) 12 B.6.15 Estimates of potential and actual dietary exposure through diet and other means (Annex IIA, 6.9; Annex IIIA, 8.8) 12 B.6.15.1 Chronic risk assessment 12 B.6.15.2 Acute risk assessment 15 B.6.17 References relied on 18 B.8 Ecotoxicology 30 B.8.1 Effects on birds (Annex IIA 8.1; Annex IIIA 10.1, 10.3) 30 B.8.1.1 Determination of residues 30 B.8.1.2 Field studies 33 B.8.2 Effect on aquatic organisms 37 B.8.2.1 Acute toxicity (Annex II A 8.2; Annex IIIA 10.2) 37 B.8.2.2 Chronic toxicity (Annex II A 8.2.2, Annex III A 10.2) 40 B.8.2.3 Effects on sediment dwelling organisms (Annex IIA 8.2.7) 42 B.8.2.4 Risk assessment (Annex III A 10.2) 43 B.8.3 Effects on bees (Annex III A, 10.4.1, Annex II A, 8.3.1) 45 B.8.3.1 Acute toxicity 45 B.8.3.2 Risk assessment 45 B.8.4 Effects on other arthropod species (Annex II A, 8.3.2, Annex III A, 10.5.1;) 46 B.8.4.1. Laboratory tests 46 8.4.2.2 Semi-field studies 47 B.4.8.3 Risk assessment: 50 B.8.5 References relied on 52
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Annex B
Amitraz
B.2 Physical and chemical properties
- 3 - Amitraz – Addendum II to Annex B - 2: Physical and chemical properties July 2002
B. 2 Physical and chemical properties
B.2.1 Physical and chemical properties of the active substance (Annex IIA 2)
Table B.2.1-1 Summary of the physical and chemical properties of the active substance (studies were completed to an acceptable standard and results were considered to be valid unless specified otherwise) Data requirement 1.4 in Doc 6493/VI/99: The data requirement was confirmed by the evaluation group on 4.10.2001.
Study Method Results Comment Reference
B.2.1.14 EEC method A 8 Amitraz (purity 98% w/w) There was no Mühlberger, B., 2001 Partition coefficient HPLC procedure dependence of partition n-octanol/water pH log Pow coefficient on pH (IIA 2.8) between pH 7 and 9. 7.0 5.6 From this study and the 9.0 5.6 studies evaluated in the
draft monograph (Bright column temperature: 40°C and Stalker, 1990) and in addendum I (Bright, 2000) the overall conclusion is that the log Pow ranges form 5.5 to 6.0 with no relationship to pH.
- 4 - Amitraz – Addendum II to Annex B - 2: Physical and chemical properties July 2002
B.2.3 Summary of physical, chemical and technical properties
B.2.3.1 Active substance
All data requirements mentioned in the draft monograph, Volume 1, level 4.2.1. and the data requirements raised in the Evaluation table (doc. 6493/VI/99) concerning the active substance produced by Aventis CropScience (main data submitter) have been addressed adequately. The data requirements for this section have been fulfilled.
B.2.3.2 Plant protection product
All data requirements mentioned in the draft monograph, Volume 1, level 4.2.2.a and the data requirements raised in the Evaluation table (doc. 6493/VI/99, data requirement no. 1.6 to 1.12 and 1.22 have been addressed adequately by the main data submitter. All data requirements for this section are fulfilled.
B.2.4 References relied on
Annex Author(s) Year Title Data Owner point / Source (where different from company) Protection reference Company, Report No Claimed number GLP or GEP status (where relevant), Published or not Y/N IIA, 2.8 Muehlbeerger 2001 Partition coefficient n-octanol /water (HPLC- Y AVO B. method) Amitraz Code AE B049974 00 1D98 0001 Aventis CropScience GmbH, DEU Rep.No. PA00/041 Doc.No. C012650 GLP study not published
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Annex B
Amitraz
B.4 Methods of analysis
- 6 - Amitraz – Addendum II to Annex B - 4: Methods of analysis July 2002
B.4 Methods of analysis
B.4.3 Analytical methods (residue) for soil, water and air
B.4.3.2 Water (including drinking water (Annex IIA 4.2.3, Annex IIIA 5.2.3)
B.4.3.2.1 Drinking water Principle of the method In drinking water, the total amitraz-derived residue is determined. This is achieved by base hydrolysis of all the residue components to AE C424868 (2,4-Dimethylaniline) which is subsequently steam distilled into hexane prior to GC-MS quantification.
Validation
Determination of Amitraz (AE B049974) and the metabolites containing the common moiety AE C424686 in drinking water to give a total amitraz-derived residue
Specifity No interferences (interferences)
Linearity Calibration range: 0.01 µg/ml – 0.2 µg/ml for AE C424868 (analytical standard) calibration curve second order quadratic, forced through the origin)
Precision – RSD% n=10 Repeatability AE B049974 * 8.9% AE C427271 * 14% AE C427919 * 16% AE C424868 * 19% * determined as AE C424868
LOQ 0,05 µg/L
Limit of detection 0.025 µg/L
Accuracy – Recorery efficiency of amitraz and metabolites
Compound Fortification level Recovery efficiency (%) (mg/kg)
Amitraz 0.05 µg/L 86 % (n=5) AE B049974 * 0.5 µg/L 83% (n=5)
AE C427271 * 0.05 µg/L 91 % (n=5) (BTS 27271) 0.5 µg/L 81% (n=5)
AE C427919 * 0.05 µg/L 88 % (n=5) (BTS 27919) 0.5 µg/L 78% (n=5)
- 7 - Amitraz – Addendum II to Annex B - 4: Methods of analysis July 2002
AE C424686 * 0.05 µg/L 72 % (n=5) (BTS 24868) 0.5 µg/L 97 % (n=5)
* determined as AE C424868 Conclusion The analytical method is suitable for enforcement purposes to determine amitraz and the metabolites in drinking water. The validation was carried out for the parent compound and the metabolites and gives acceptable results.
B.4.3.2.2 Surface water Principle of the method In surface water, the residue components are determined separately. The AE B049974 (Amitraz), AE C427919 (BTS 27919)) and AE C424868 (BTS 24868) are extracted from the aqueous phase with toluene, and then the AE C427271 (BTS 27271) is partitioned into ethyl acetate from the same water. After concentration, the two organic phases are combined to enable all four components to be quantified in one GC-MS chromatogramm
Determination of Amitraz (AE B049974) , AE C427919 (BTS 27919)) and AE C424868 (BTS 24868)and AE C427271 (BTS 27271) in surface water
Specifity No interferences (interferences)
Linearity Calibration range: 0.02 µg/ml – 0.4 µg/ml for AE B049974 , (analytical standard) AE C427919, AE C424868 and AE C427271, resp. calibration curve second order quadratic, forced through the origin)
Precision – RSD% (n=10) Repeatability AE B049974 23% AE C427271 10% AE C427919 18% AE C424868 8.3%
LOQ 1 µg/L
Limit of detection 0.5 µg/L
Accuracy – Recorery efficiency of amitraz and metabolites
Compound Fortification level Recovery efficiency (%) (mg/kg)
Amitraz 1 µg/L 80 % (n=5) AE B049974 10 µg/L 116% (n=5)
- 8 - Amitraz – Addendum II to Annex B - 4: Methods of analysis July 2002
AE C427271 1 µg/L 90 % (n=5) (BTS 27271) 10 µg/L 81% (n=5)
AE C427919 1 µg/L 74 % (n=5) (BTS 27919) 10 µg/L 102% (n=5)
AE C424686 1 µg/L 87 % (n=5) (BTS 24868) 10 µg/L 89 % (n=5)
Ref.: Garner M.A., Taylor N.W., 1999
Conclusion This GLP study presents a method for the determination of amitraz derived residues in surface water. The active substance and the metabolites are determined separately. The performance data of the method are acceptable.
B.4.6 References relied on
Title Data Owner Annex point/ Author(s) Year Source (where different from company) Protection reference Company, Report No Claimed number GLP or GEP status (where relevant), Published or not Y/N-R/NR
IIA 4.2.3, Garner M.A., 1999 Enforcement Method with Validation for Y AVO IIIA 5.2.3 Taylor N.W. Surface and Drinking Water by GC-MS. Amitraz (AE B0479974), AE C427271, AE C427919, AE C424868 Rep.No. EM C04/99-0 Doc.No. C003685 GLP not published
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Annex B
Amitraz
B.6 Residue data
B.6 Residue data
For pome fruits, residue trials reflecting changed GAPs (i.e. PHIs) have been conducted in order to reduce residues on apples and pears and the acute risk. The results of the trials including single fruit analysis in order to derive a variability factor (20 trials in the Northern European Region and 20 trials in the Southern European Region) conducted in 1999 and 2000 were submitted and evaluated herewith.
Trials conducted on tomatoes (5 trials performed under field conditions in the Southern Region of Europe; 9 trials performed under protected conditions) during 1999, 2000 and 2001 (including analysis of the single fruit in order to derive a variability factor for the acute risk assessment) were reported. These residue trials have not been evaluated since pome fruits are the only uses to be representative for Annex I inclusion (as stated by the notifier by 30 August 2001).
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B.6.4 Use pattern
The intended uses are summarised in table B.6.4-1:
Table B.6.4-1: Intended uses of amitraz Crop Region Use Application Water No. of Time of PHI [days] rate per [l/ha] appli- application treatment cations (growth stage) [kg a.i./ha] Apples N Field 0.75 500 - 2 beginning of 42 1000 infestation Pears N Field 0.75 500 - 2 Beginning of 42 1000 infestation Apples S Field 0.8 1000 2 beginning of 35 infestation Pears S Field 0.8 1000 2 beginning of 35 infestation
B.6.6 Residues resulting from supervised trials (Annex IIA 6.3; Annex IIIA 8.1)
B.6.6.1 Pome fruit
For pome fruits, new residue trials reflecting changed GAPs (i.e. PHIs) have been conducted in order to reduce residues on apples and pears. The results of the trials (20 trials in the Northern European Region and 20 trials in the Southern European Region) conducted in 1999 and 2000 were submitted and evaluated herewith.
For the Northern Region, 20 trials (apples, pears) have been performed in Germany, North of France and United Kingdom; amitraz was applied 2 or 3 times at nominal application rates of 644 - 885 g a.i./ha whereby the last treatment has been performed between growth stage BBCH 74 (fruit diameter up to 40 mm) and BBCH 79 (fruit about 90 % of final size). The first samples were taken for analysis within three hours after the last application; the second sampling took place at harvest, i.e. 33 – 83 days after the last treatment. At the second sampling, additional single fruits were taken in order to derive a variability factor for the acute risk assessment (1999 trials); these results have been presented in a separate study and were described in chapter B.6.15.2.1.1. All samples were analysed using a method in which all amitraz derived residues are converted to a common moiety and expressed in terms of amitraz. According to the intended uses (PHI = 42 days), 10 trials are regarded relevant for establishing MRLs for pome fruits. At harvest (PHI = 33 - 50 days), apple samples contained residues between 0.12 and 0.48 mg/kg and pear samples between 0,08 and 0,10 mg/kg.
For detailed information see Annex 1a.
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MRL-calculation (pome fruit; based on data conducted in the Northern Region): Based on all data conducted in the Northern Region of Europe (apples and pears), the MRL was calculated to be 0.5 mg/kg (amitraz and amitraz derived metabolites containing the 2,4- dimethylaniline moiety expressed in terms of amitraz).
Individual data points are: • Apples: 0.12 mg/kg, 0.15 mg/kg, 0.15 mg/kg (1999 trials) 0.42 mg/kg, 0.48 mg/kg (2000 trials) • Pears: 0.17 mg/kg, 0.2 mg/kg (1999 trials) 0.08 mg/kg, 0.10 mg/kg, 0.10 mg/kg (2000 trials)
STMR-calculation (pome fruit; based on data conducted in the Northern Region): Based on the data conducted in the Northern Region of Europe, a STMR can be calculated to be 0.15 mg/kg (amitraz and amitraz derived metabolites containing the 2,4- dimethylaniline moiety expressed in terms of amitraz).
For the Southern Region, 20 trials (pears) have been performed in Spain, Italy and the South of France; amitraz was applied 2 times at nominal application rates of 800 g a.i./ha whereby the second treatment took place between growth stage BBCH 72 (fruit size up to 20 mm) and BBCH 77 (fruit about 70 % of final size). The first sampling was done within three hours after the final treatment ; the second sampling took place at harvest, i.e. 12 – 58 days after the last treatment. At the second sampling, additional single fruits were taken in order to derive a variability factor for the acute risk assessment (1999 trials); these results have been presented in a separate study and were described in chapter B.6.15.2.1.1. According to the intended uses (PHI = 35 days), 9 trials are regarded relevant for establishing MRLs for pome fruits. At harvest (PHI = 29 - 49 days), pear samples contained between 0.14 and 0.42 mg/kg. The residues of 2 trials performed in Spain (1999 trials) were rather high (0.59 – 0.61 mg/kg) taking into account the application made in the earliest growth stages (PHI = 28 days); it was assumed, that the samples were mislabelled in the field or contaminated by later applications to other plots. It is acceptable not to include these values in the evaluation.
For detailed information see Annex 1b.
MRL-calculation (pome fruit; based on data conducted in the Southern Region): Based on the data conducted in the Southern Region of Europe, an MRL can be calculated to be 0.5 mg/kg (amitraz and amitraz derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz).
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Individual data points are: • Pears: 0.14 mg/kg, 0.17 mg/kg, 0.2 mg/kg, 0.34 mg/kg (1999 trials) 0.14 mg/kg, 0.17 mg/kg 0.19 mg/kg, 0.34 mg/kg, 0.42 mg/kg (2000 trials)
STMR-calculation (pome fruit; based on data conducted in the Southern Region): Based on the data conducted in the Southern Region of Europe, a STMR can be calculated to be 0.19 mg/kg (amitraz and amitraz derived metabolites containing the 2,4- dimethylaniline moiety expressed in terms of amitraz).
Conclusion: Based on the residue trial data made available (10 trials conducted in the Northern Region of Europe and 9 trials conducted in the Southern Region of Europe) a MRL for pome fruits can be proposed to be set at 0.5 mg/kg (amitraz and amitraz derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz).
B.6.12 Proposed EU-MRLs and justification for the acceptability of those MRLs (Annex IIA, 6.7; Annex IIIA, 6.8)
For pome fruit (apples, pears), a MRL of 0.5 mg/kg (amitraz and amitraz derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz) can be proposed.
B.6.15 Estimates of potential and actual dietary exposure through diet and other means (Annex IIA, 6.9; Annex IIIA, 8.8)
The chronic risk assessment has been performed based on the intended uses (representative use), i.e. pome fruit only.
B.6.15.1 Chronic risk assessment
a) TMDI-calculations: TMDI-calculation (diet consumption data obtained from the European Diet compiled in the WHO-publication on Cultural and Global Diets, 1994): The results of the estimation of the Theoretical Maximum Daily Intake of the amitraz-derived residues through the consumption of the different edible crops are summarised in table 7.15.1-1:
Table 7.15.1-1: Theoretical Maximum Daily Intake (TMDI) of amitraz-derived residues Food Average daily MRL Theoretical maximum consumption of food [mg/kg]1) daily intake item [mg/day]
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[g/day] Pome fruit 51.3 0.5 0.02565 TMDI [mg/day] 0.02565 TMDI [mg/kg bw/day] 0.00043 1) Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
Intake total: 0.00043 mg/kg bw/day Percent of ADI (0.003 mg/kg bw/day): 14.3 %
TMDI-calculation (diet consumption data obtained from the BBA Guideline Part IV, 3-7, 1993): The results of the estimation of the Theoretical Maximum Daily Intake of the amitraz-derived residues through the consumption of the different edible crops are summarised in table 7.15.1-2. The mean consumption intake data of a 4 - 6 year girl (13.5 kg bodyweight) were chosen as a worst case scenario.
Table 7.15.1-2: Theoretical Maximum Daily Intake (TMDI) of amitraz-derived residues Food Average daily MRL Theoretical maximum consumption of food [mg/kg]1) daily intake item [mg/day] [g/day] Pome fruit 48.6 0.5 0.02430 TMDI [mg/day] 0.02430 TMDI [mg/kg bw/day] 0.00180 1) Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
Intake total: 0.00180 mg/kg bw/day Percent of ADI (0.003 mg/kg bw/day): 60 %
b) IEDI-calculations: IEDI-calculation (diet consumption data obtained from the European Diet compiled in the WHO-publication on Cultural and Global Diets, 1994): The results of the IEDI of the amitraz-derived residues through the consumption of the different edible crops are summarised in table 7.15.1-3:
Table 7.15.1-3: IEDI of amitraz-derived residues Food Average daily STMR International consumption of food [mg/kg]1) estimated daily intake item [mg/day] [g/day] Pome fruit 51.3 0.19 0.00975 TMDI [mg/day] 0.00975 TMDI [mg/kg bw/day] 0.00016 1) Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
- 14 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Intake total: 0.00016 mg/kg bw/day Percent of ADI (0.003 mg/kg bw/day): 5.4 %
IEDI-calculation (diet consumption data obtained from the BBA Guideline Part IV, 3-7, 1993): The results of the IEDI of the amitraz-derived residues through the consumption of the different edible crops are summarised in table 7.15.1-4. The mean consumption intake data of a 4 - 6 year girl (13.5 kg bodyweight) were chosen as a worst case scenario.
Table 7.15.1-4: IEDI of amitraz-derived residues Food Average daily STMR International consumption of food [mg/kg]1) estimated daily intake item [mg/day] [g/day] Pome fruit 48.6 0.19 0.00923 TMDI [mg/day] 0.00923 TMDI [mg/kg bw/day] 0.00068 1) Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
Intake total: 0.00068 mg/kg bw/day Percent of ADI (0.003 mg/kg bw/day): 22.8 %
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B.6.15.2 Acute risk assessment
B.6.15.2.1 Variability factor
B.6.15.2.1.1 Pome fruit In order to determine an empirically derived variability factor for pome fruit (with regard to refined acute risk calculation), amitraz derived residues were investigated on a single fruit residue basis. Samples (pears) were taken from 6 trials (Italy, North and South France, Germany) conducted as a part of studies ER 99 ECN 737 (Ref.: Hees, 2000b) and ER 99 ECS 738 (Ref.: Hees, 2000a): amitraz was applied 2 times at nominal application rates of 750 – 800 g a.i./ha whereby the last treatment have been performed between growth stage BBCH 75 (fruit about half final size) and BBCH 77 (fruit about 70 % of final size). The sampling (24 samples from each trial) took place at harvest, i.e. 35 – 50 days after the last treatment. The single fruits were quartered and the two opposite quarters were analysed for total amitraz-derived residues containing the 2,4-dimethylaniline moiety.
Results: The variability between the highest residue level found in any single fruit from a particular data set divided by the mean residue from the data set (i.e. the variability factor) was calculated for each of the 6 trials. The maximum residue levels range from 0.23 mg/kg to 0.57 mg/kg and the mean residues from 0.13 mg/kg to 0.21 mg/kg; the variability factor was calculated to be 2 – 3. The results are summarised in the following table:
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Table 7.15.2.1.1-1: Maximum residues, mean residues and variability factors based on single fruit residues (pears) Trial Application PHI Maximum residue1) Mean residue1) Variability regime [days} factor
Cento – Ferrara 2 x 0.8 kg a.i./ha 37 0.57 0.18 3 ITALY 1000 l water/ha last treatment: fruit about 70 % of final size
Doue la Fontaine 2 x 0.75 kg a.i./ha 49 0.34 0.15 2 FRANCE NORTH 1453 l water/ha last treatment: fruit about 70 % of final size
Meckenheim – 2 x 0.75 kg a.i./ha 35 0.55 0.21 3 Altendorf 1453 l water/ha GERMANY last treatment: fruit about 70 % of final size
Saint Vincent de 2 x 0.8 kg a.i./ha 50 0.23 0.13 2 Paul 1005-1025 l FRANCE SOUTH water/ha last treatment: fruit about half final size
Portomagiore – 2 x 0.8 kg a.i./ha 49 0.34 0.15 2 Ferrara 1000 l water/ha ITALY last treatment: fruit about half final size
Portomagiore – 2 x 0.8 kg a.i./ha 42 0.53 0.16 3 Ferrara 1000 l water/ha ITALY last treatment: fruit about half final size
1) Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
Conclusion: The results from the first year residue trials (6 trials) on a single fruit basis show variabilty factors ranging from 2 – 3; a mean variability factor of 2.4 could be calculated and have been used for the acute risk assessment performed in chapter B.6.15.2.2. Ref.: Taylor, 2000
B.6.15.2.2 Estimation of the acute risk The estimation of acute dietary intakes of pesticide residues (risk assessment) has been performed based on proposed calculations described in FAO manual on the submission and
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evaluation of pesticide residues data for the estimation of maximum residue levels in food and feed, Food and Agriculture Organisation of the United Nations 1997 and UK technical policy on the estimation of acute dietary intakes of pesticide residues, PSD Jan. 1998 and Report of the JMPR – 2000.
The estimation have been carried out for apples using the results taken from the Northern European Region that are regarded to be more critical than the results from the Southern trials; for pears the data taken from the Southern region of Europe were used as regarded more critical than the data from the Northern trials.
Apples: The following values were used for risk calculation: Commodity size for whole raw product: 112 g RL: 0.48 mg/kg Variability factor: 2.4 Consumption by adults aged 16-64 years:308 g (97.5th percentile) Consumption by toddlers aged 1 ½ - 4 ½ years: 199 g (97.5th percentile) STMR (based on adequate residue trials data): 0.15 mg/kg Mean body weight (adult): 70.1 kg Mean body weight (toddler): 14.5 kg
Table B.6.15.2.2-1: Acute risk assessment for amitraz (apples: variability factor: 2.4); ARfD: 0.01 mg/kg bw/d. The STMR is used for the second part of the equation Commodity RL1) STMR1) Acute intake % of ArfD [mg/kg bw/d] Adult Toddler Adult Toddler Apples 0.48 0.15 0.00226 0.00980 22.6 98 1 Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
Table B.6.15.2.2-2: Acute risk assessment for amitraz (apples: variability factor: 2.4); ARfD: 0.01 mg/kg bw/d. The HRL is used for the second part of the equation Commodity RL1) STMR1) Acute intake % of ArfD [mg/kg bw/d] Adult Toddler Adult Toddler Apples 0.48 0.15 0.00318 0.01178 31.8 117.8 1 Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
Pears: The following values were used for risk calculation: Commodity size for whole raw product: 150 g RL: 0.42 mg/kg Variability factor: 2.4
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Consumption by adults aged 16-64 years: 274 g (97.5th percentile) Consumption by toddlers aged 1 ½ - 4 ½ years: 279 g (97.5th percentile) STMR (based on adequate residue trials data): 0.19 mg/kg Mean body weight (adult): 70.1 kg Mean body weight (toddler): 14.5 kg
Table B.6.15.2.2-3: Acute risk assessment for amitraz (pears: variability factor: 2.4); ARfD: 0.01 mg/kg bw/d. The STMR is used for the second part of the equation Commodity RL1) STMR1) Acute intake % of ArfD [mg/kg bw/d] Adult Toddler Adult Toddler Pears 0.42 0.19 0.00249 0.01212 24.9 121.2 1 Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
Table B.6.15.2.2-4: Acute risk assessment for amitraz (pears: variability factor: 2.4); ARfD: 0.01 mg/kg bw/d. The HRL is used for the second part of the equation Commodity RL1) STMR1) Acute intake % of ArfD [mg/kg bw/d] Adult Toddler Adult Toddler Pears 0.42 0.19 0.00290 0.01416 29 141.6 1 Amitraz and amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
B.6.17 References relied on
Annex Author(s) Year Title Data Owner point Source (where different from protection company) claimed Company, Report No. GLP or GEP (status where relevant) Y/N Published or not IIA, 7.3, IIIA, Hees, M.S. 2000a Residue study in pome fruit; European Y AVO 8.1 Union [Southern zone], 1999 Aventis CropScience UK Limited Study No. ER 99 ECS 738 GLP not published
IIA, 7.3, IIIA, Hees, M.S. 2000b Residue study in pome fruit; European Y AVO 8.1 Union [Northern zone], 1999 Aventis CropScience UK Limited Study No. ER 99 ECN 737 GLP not published
IIA, 7.3, IIIA, Neuß, B.; 2001a Decline of residues in pome fruit Y AVO 8.1 Sonder, K.; European Union [northern zone] 2000 Werner, H.-J. Amitraz, AE B049974, Emulsifiable Concentrate (EC) 200 g/l Aventis Crop Science GmbH Study No. DR 00 EUN 220 GLP not published
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Annex Author(s) Year Title Data Owner point Source (where different from protection company) claimed Company, Report No. GLP or GEP (status where relevant) Y/N Published or not IIA, 7.3, IIIA, Neuß, B.; 2001b Decline of residues in pears Y AVO 8.1 Sonder, K.; European Union [southern zone] 2000 Werner, H.-J. Amitraz, AE B049974, Emulsifiable Concentrate (EC) 200 g/l Aventis Crop Science GmbH Study No. DR 00 EUS 221 GLP not published
IIA, 7.3, IIIA, Taylor, N.W. 2000 Amitraz: EC (emulsifable concentrate) Y AVO 8.1 200 g/l Code: AE B049974 00 EC20 B104 Residues of amitraz and metabolites in single pome fruit Aventis CropScience UK Limited Study No. 082/03/145 GLP not published
- 20 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
ANNEX 1a: Summary of residue data: pome fruit (Northern region of Europe):
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha Water kg and last date 3. harvest l/ha a.i./hl
C009137 Apple 1. 1960 0.75 1505 2 fruit half final size whole fruit 1.1 0 field Mühlhausen Golden 2. 10/4/99 – 22/6/99 whole fruit 0.10 83 GERMANY Delicious 24/4/99 3. 13/9/99
C009137 Apple 1. 1960 0.75 1505 2 fruit 70 % of final whole fruit 0.51 0 field Mühlhausen Golden 2. 10/4/99 – 12/7/99 size whole fruit 0.07 63 GERMANY Delicious 24/4/99 3. 13/9/99
C009137 Apple 1. 1960 0.75 1505 3 fruit 70 % of final whole fruit 1.0 0 field Mühlhausen Golden 2. 10/4/99 – 12/7/99 size whole fruit 0.08 63 GERMANY Delicious 24/4/99 3. 13/9/99
C009137 Pear 1. 1968 0.75 1507 – 2 fruit half final size whole fruit 0.43 0 field Meckenheim- Alexander 2. 22/4/99 – 1525 13/7/99 whole fruit <0.05 58 Altendorf Lukas 13/5/99 GERMANY 3. 9/9/99
- 21 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha Water kg and last date 3. harvest l/ha a.i./hl
C009137 Pear 1. 1968 0.75 1507 2 fruit 70 % of final whole fruit 0.45 0 field
Meckenheim- Alexander 2. 22/4/99 – 5/8/99 size whole fruit 0.17 35 Altendorf Lukas 13/5/99 GERMANY 3. 9/9/99
C009137 Pear 1. 1968 0.75 1507 – 3 fruit 70 % of final whole fruit 1.6 0 field Meckenheim- Alexander 2. 22/4/99 – 1525 5/8/99 size whole fruit 0.29 35 Altendorf Lukas 13/5/99 GERMANY 3. 9/9/99
C009137 Apple 1. 1989 0.75 1463 - 2 fruit half final size whole fruit 0.41 0 field
Wurzen- Rubin 2. 1/5/99 – 1518 22/7/99 whole fruit 0.15 50 Roitzsch 15/5/99 GERMANY 3. 10/9/99
C009137 Apple 1. 1989 0.75 1463 – 2 fruit 70 % of final whole fruit 0.47 0 field
Wurzen- Rubin 2. 1/5/99 – 1537 2/8/99 size whole fruit 0.12 39 Roitzsch 15/5/99 GERMANY 3. 10/9/99
C009137 Apple 1. 1989 0.75 1463 – 3 fruit 70 % of final whole fruit 1.0 0 field Wurzen- Rubin 2. 1/5/99 – 1533 2/8/99 size whole fruit 0.2 39 Roitzsch 15/5/99 GERMANY 3. 10/9/99
- 22 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha Water kg and last date 3. harvest l/ha a.i./hl
C009137 Pear 1. 1995 0.75 1556 2 fruit half final size whole fruit 2.5 0 field Doue la William 2. 18/3/99 – 16/6/99 whole fruit 0.1 68 Fontaine 17/4/99 FRANCE 3. 23/8/99
C009137 Pear 1. 1995 0.75 1453 2 fruit 70 % of final whole fruit 1.8 0 field
Doue la William 2. 18/3/99 – 5/7/99 size whole fruit 0.2 49 Fontaine 17/4/99 FRANCE 3. 23/8/99
C009137 Pear 1. 1995 0.75 1453 3 fruit 70 % of final whole fruit 2.9 0 field Doue la William 2. 18/3/99 – 5/7/99 size whole fruit 0.28 49 Fontaine 17/4/99 FRANCE 3. 23/8/99
C009137 Apple 1. 1968 0.75 1000 2 fruit half final size whole fruit 0.94 0 field Great Chishill Bramley 2. 23/4/99 – 30/7/99 whole fruit 0.24 66 United Kingdom 21/5/99 3. 4/10/99
C009137 Apple 1. 1968 0.75 1000 2 fruit 70 % of final whole fruit 0.43 0 field
Great Chishill Bramley 2. 23/4/99 – 1/9/99 size whole fruit 0.15 33 United Kingdom 21/5/99 3. 4/10/99
- 23 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha Water kg and last date 3. harvest l/ha a.i./hl
C009137 Apple 1. 1968 0.75 1000 3 fruit 70 % of final whole fruit 1.1 0 field Great Chishill Bramley 2. 23/4/99 – 1/9/99 size whole fruit 0.43 33 United Kingdom 21/5/99 3. 4/10/99
C011949 Pear 1. 1984 0.75 770 2 fruit 90 % of final whole fruit 1.32 0 field Geisenheim Gellerts 2. 12/4/00 – 3/8/00 size whole fruit 0.28 21 GERMANY Butterbirne 26/4/00 whole fruit 0.41 35 3. 14/9/00 whole fruit 0.08 42 whole fruit 0.16 49
C011949 Pear 1. 1993 0.75 714 - 2 fruit about half whole fruit 0.26 0 field Dürrweitzschen Conference 2. 25/4/00 – 744 21/7/00 final size whole fruit 0.30 21 GERMANY 1/5/00 whole fruit 0.06 35 3. 1/9/00 whole fruit 0.10 42 whole fruit <0.04 49
C011949 Apple 1. 1992 0.75 – 437 - 2 fruit diameter up whole fruit 2.88 0 field Great Chishill Jonathan 2. 1/4/00 – 0.885 516 11/8/00 to 40 mm whole fruit 0.96 21
UK 31/5/00 whole fruit 0.48 41 3. 1/9/00
C011949 Apple 1. 1992 0.75 804 2 fruit about half whole fruit 0.59 0 field Ongar Cox 2. 1/4/00 – 9/8/00 final size whole fruit 0.36 20
UK 30/5/00 whole fruit 0.42 44 3. 22/9/00
- 24 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha Water kg and last date 3. harvest l/ha a.i./hl
C011949 Pear 1. 1985 0.644 - 498 - 2 fruit about half whole fruit 0.91 0 field Ecquevilly Conference 2. 10/4/00 – 0.75 666 2/8/00 final size whole fruit 0.77 21 FRANCE 2/5/00 whole fruit 0.20 35 3. 11/9/00 whole fruit 0.10 40 whole fruit 0.25 49 1) Amitraz and amitraz derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
- 25 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
ANNEX 1b: Summary of residue data: pome fruit (Southern region of Europe):
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha water kg and last date 3. harvest l/ha a.i./hl
C009138 Pear 1. 1981 0.8 1000 2 fruit diameter up whole fruit 1.9 0 field Palau de Blanquilla 2. 10/3/99 – 29/6/99 to 40 mm whole fruit 0.61 28 these values were not Anglesola 20/3/99 included in the SPAIN 3. 27/7/99 evaluation because the values are abnormally high due to contamination or mislabelling
C009138 Pear 1. 1981 0.8 1000 2 fruit half final size whole fruit 0.73 0 field Palau de Blanquilla 2. 10/3/99 – 7/7/99 whole fruit 0.36 20 Anglesola 20/3/99 SPAIN 3. 27/7/99
C009138 Pear 1. 1981 0.8 1000 2 fruit 70 % final whole fruit 0.77 0 field Palau de Blanquilla 2. 10/3/99 – 15/7/99 size whole fruit 0.26 12 Anglesola 20/3/99 SPAIN 3. 27/7/99
- 26 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha water kg and last date 3. harvest l/ha a.i./hl
C009138 Pear 1. 1988 0.8 1000 2 fruit diameter up whole fruit 2.1 0 field La Devoe 2. 10/3/99 – 29/6/99 to 40 mm whole fruit 0.59 28 these values were not Granjad`Escarp 25/3/99 included in the SPAIN 3. 27/7/99 evaluation because the values are abnormally high due to contamination or mislabelling
C009138 Pear 1. 1988 0.8 1000 2 fruit half final size whole fruit 0.79 0 field La Devoe 2. 10/3/99 – 7/7/99 whole fruit 0.33 20 Granjad`Escarp 25/3/99 SPAIN 3. 27/7/99
C009138 Pear 1. 1988 0.8 1000 2 fruit 70 % final whole fruit 0.50 0 field La Devoe 2. 10/3/99 – 15/7/99 size whole fruit 0.30 12 Granjad`Escarp 25/3/99 SPAIN 3. 27/7/99
C009138 Pear 1. 1969 0.8 1013 - 2 fruit diameter up whole fruit 1.6 0 field Saint Vincentde Williams 2. 15/5/99 – 1024 15/6/99 to 40 mm whole fruit 0.19 58 Paul 25/5/99 FRANCE 3. 12/8/99
C009138 Pear 1. 1969 0.8 1005 – 2 fruit half final size whole fruit 1.4 0 field Saint Vincentde Williams 2. 15/5/99 – 1025 23/6/99 whole fruit 0.17 50 Paul 25/5/99 FRANCE 3. 12/8/99
- 27 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha water kg and last date 3. harvest l/ha a.i./hl
C009138 Pear 1. 1969 0.8 981 – 2 fruit 70 % final whole fruit 0.59 0 field Saint Vincentde Williams 2. 15/5/99 – 1015 22/7/99 size whole fruit 0.18 21 Paul 25/5/99 FRANCE 3. 12/8/99
C009138 Pear 1. 1991 0.8 1000 2 fruit diameter up whole fruit 2.4 0 field Portomagiore – Conference 2. 1/4/99 – 24/6/99 to 40 mm whole fruit 0.15 57 Ferrara 15/4/99 ITALY 3. 20/8/99
C009138 Pear 1. 1991 0.8 1000 2 fruit half final size whole fruit 1.9 0 field Portomagiore – Conference 2. 1/4/99 – 2/7/99 whole fruit 0.14 49 Ferrara 15/4/99 ITALY 3. 20/8/99
C009138 Pear 1. 1991 0.8 1000 2 fruit 70 % final whole fruit 1.9 0 field Portomagiore – Conference 2. 1/4/99 – 29/7/99 size whole fruit 0.17 42 Ferrara 15/4/99 ITALY 3. 20/8/99
C009138 Pear 1. 1994 0.8 1000 2 fruit diameter up whole fruit 1.8 0 field Cento – Ferrara S. Maria 2. 1/4/99 – 22/6/99 to 40 mm whole fruit 0.20 37 ITALY 15/4/99 3. 29/7/99
C009138 Pear 1. 1994 0.8 1000 2 fruit half final size whole fruit 1.8 0 field Cento – Ferrara S. Maria 2. 1/4/99 – 30/6/99 whole fruit 0.34 29 ITALY 15/4/99 3. 29/7/99
- 28 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha water kg and last date 3. harvest l/ha a.i./hl
C009138 Pear 1. 1994 0.8 1000 2 fruit 70 % final whole fruit 1.1 0 field Cento – Ferrara S. Maria 2. 1/4/99 – 9/7/99 size whole fruit 0.24 20 ITALY 15/4/99 3. 29/7/99
C011950 Pear 1. 1971 0.8 500 2 fruit half final size Whole fruit 0.80 0 field Saint Pardoux William 2. 10/4/00 – 26/7/00 whole fruit 0.31 20 FRANCE 20/4/00 Whole fruit 0.17 35 3. 17/8/00 Whole fruit 0.13 42 Whole fruit 0.11 49
C011950 Pear 1. 1996 0.8 1000 2 fruit half final size Whole fruit 1.68 0 field Bologna William 2. 1/4/00 – 28/6/00 whole fruit 0.32 22 heavy rainfall occured ITALY 20/4/00 Whole fruit 0.19 36 10 hours after last 3. 9/8/00 Whole fruit 0.22 42 application Whole fruit 0.20 49
C011950 Pear 1. 1979 0.8 1026 2 fruit 70 % final Whole fruit 1.01 0 field Ferrara Abate Fetel 2. 1/4/00 – 28/7/00 size whole fruit 1.19 21 ITALY 16/4/00 Whole fruit 0.14 35 3. 8/9/00 Whole fruit 0.23 42 Whole fruit 0.26 49
C011950 Pear 1. 1986 0.8 1500 2 fruit half final size Whole fruit 1.68 0 field Nisi Highland 2. 25/3/00 – 28/6/00 whole fruit 0.18 21 GREECE 15/4/00 Whole fruit 0.42 35 3. 9/8/00 Whole fruit 0.14 42 Whole fruit 0.25 49
- 29 - Amitraz – Addendum II to Annex B - 6: Residue data July 2002
Report No. Commodity/ Date of Dates of Growth stage at Portion analysed Residues PHI Remarks Variety 1. sowing or Application rate treatment(s) or last treatment or [mg/kg]1) [days] Location planting per treatment no. of treatment date 2. flowering kg a.i./ha water kg and last date 3. harvest l/ha a.i./hl
C011950 Pear 1. 1981 0.8 1500 2 fruit half final size Whole fruit 0.58 0 field Paleo Skilitsi William 2. 20/3/00 – 28/6/00 whole fruit 0.31 21 GREECE 10/4/00 Whole fruit 0.34 35 3. 9/8/00 Whole fruit 0.14 42 Whole fruit 0.13 49 1) Amitraz and amitraz derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of amitraz
- 30 -
Annex B
Amitraz
B.8 Ecotoxicology
B.8. Ecotoxicology
B.8.1 Effects on birds (Annex IIA 8.1; Annex IIIA 10.1, 10.3)
B.8.1.1 Determination of residues
The aim of the study was to quantify residues of amitraz and its toxicological relevant metabolites in invertebrates and grass, following an application of Mitac (20% EC- formulation of amitraz) in a mature apple orchard. The orchard was located in Cambridgeshire, UK (Forster, 2001 a). The study was done in compliance with GLP requirements. In July 2000, Mitac was applied once to a plot of approximately 0.4 ha at the maximum recommended rate for hops, 2.5 kg ai/ha. A single untreated plot of similar size was sampled in order to provide a comparative matrix for analytical work.
- 31 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
Six pitfall traps were set on each day of the sampling occasions (day 0, 3, 10 and 28 after treatment) to collect surface-active invertebrates. Traps were set for a seven day period on each occasion. On the same occasion, foliar-dwelling invertebrates were collected from each plot by inventory sampling using an insecticide to collect fauna from the whole trees. Foliar dwelling invertebrates were separated into two groups: winged and wingless. Between ten and twenty-one families were identified in pitfall trap samples. On all but one occasion slugs, predatory beetles and spiders were the dominant group. Wasps and springtails were also found. The foliar dwelling fauna represented a typical UK orchard fauna. Winged invertebrates included a number of adult beetles, earwigs, booklice and bugs. Wingless families included spiders, beetle larvae and Leidoptera larvae. Following sampling, all samples were shipped frozen to the laboratories for determination.
Report on the analytical phase The analytical part of this study was conducted in compliance with GLP requirements (Laporte and Snowdon (2001)).
Blank values: All analyses of foliar-dwelling control-invertebrates contained apparent residues. This could be caused by the free movement of invertebrates between the treated and the untreated plots. But similar values were found in wingless as well as winged species. Overall, values reached levels up to 4.6 mg/kg for total equivalent amitraz (24 h after treatment) and 7.8 mg/kg for BTS 27271. Nevertheless, all values remained significantly below concentrations found in invertebrates actually sampled from the treated plot at the corresponding time points. Apparent residues in control samples of ground dwelling invertebrates remained non detectable.
Residues in grass: Samples of grass from between the rows in the orchards were taken at the day of treatment and at intervals of 3, 10 and 28 days. The residues measured on day 1 were 105, on day 3: 130, day 10: 54 and day 28: 3.5 mg amitraz equivalents/kg, respectively. The corresponding half live is 5.4 days. It is assumed that the total equivalent of amitraz measured on day 1 consists on the active ingridient. Considering the available data on fate and behaviour and residue measurements, amitraz seems to be converted very quickly into its metabolites. For this reason, residues measured on day 3 are supposed to consist mainly on the two metabolites. The molecular weights of amitraz are 293, of the metabolite BTS 27919 149 and of BTS 27271 162, respectively. The residues measured on day 3 (amitraz equivalents) correspond to 72 ppm BTS 27271.
Residues in foliar dwelling invertebrates: Samples were collected 2, 8 and 24 hours after application and then again 8 and 24 hours after each of the 3, 10 and 28 day sampling
- 32 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002 intervals. Some samples were combined for analyses to provide sufficient weight for analyses. For residue levels see tables 8.1-1 and 8.1-2
Table 8.1-1 Summary of residues in wingless invertebrates (values given in mg/kg) Sampling interval (days) Timepoint Total equivalent amitraz BTS 27271 Day 0 /1 2-hour 61 63 Day 0 /1 8-hour 67
Day 0 /1 24-hour 25 42 Day 3 /4 8-hour 22 Day 3 /4 8 + 24-hour 64
Day 10/11 24-hour 23 Day 10/11 8 + 24-hour 31 Day 28/29 24-hour 3.3
Day 28/29 8 + 24-hour 46
Table 8.1-2 Summary of residues in winged invertebrates (values given in mg/kg)
Sampling interval (days) Timepoint Total equivalent amitraz BTS 27271
Day 0 /1 2+8 -hour 112
Day 0 /1 24-hour 35
Day 3/ 4 8 + 24-hour 42 Day 10/11 8 + 24-hour 21 Day 28/29 8-hour 17
Day 28/29 8 + 24-hour 10
A calculation of half lives of amitraz is not possible on bases of these data. Because of the high amounts of the metabolite BTS 27271 measured, a rapid degradation of the parent could be assumed (50% reduction within 1 day). It is assumed that the total equivalent of amitraz measured on day 0 in wingless invertebrates consists of the active ingredient. Because of the lack of sufficient data, the same amount is assumed in winged vertebrates.
The C0 for foliar dwelling invertebrates of 61 ppm is used for TER calculations.
For the metabolite the following DT50 is calculated: 1.8 days in winged invertebrates and
52.1 days in wingless invertebrates. C0 – values for TER calculations are the residues on day 0.
Residues in ground-dwelling invertebrates: Pitfall traps were set on six replicate sampling positions and left for a seven day period on each sampling occasion. For residue concentration of the metabolites see table 8.1-3
- 33 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
Table 8.1-3 Summary of residues in ground dwelling invertebrates (values given in mg/kg) Sampling interval (days) BTS 27271 (mean) BTS 27919 Day 0 6 3 Day 3 18 4 Day 10 14 4.6 Day 28 9.2 2.8
Because of the 7-day trap placement periods and due to the instability of amitraz under the conditions of sampling, it is very likely that the two metabolites constituted the entire
residues in these samples. The DT50 calculated for BTS 27271 is 25.7 days (first order degradation assumed, time window: day 3 to day 28). Calculations of the residues of amitraz: Summing up the concentration of the metabolites on day 3 (maximum residues) and correction for mol weight: (22 x 1.8) 39.6 mg amitraz/kg.
B.8.1.2 Field studies
A radio-telemetry monitoring study was conducted by Crocker (1998). The aim of the study was to track common bird species in a range of orchards. The data were collected in 21 orchards over a 3 year period between April and September 1995 - 1997. The habitat was classified as central (among orchard fruit trees), edge (orchard hedgerows) and non-orchard habitat. A total of 130 birds (43 blackbirds, 23 blue tits, 43 chaffinches and 30 robins) were each monitored through radio-telemetry. The birds were monitored over 8 hours average between dawn and dusk. Birds were visible for little more than 10% of contact time. It was not possible to observe the birds behaviour, but the bird could be classified as active or inactive (foraging or potentially not foraging). On average, birds spent 67% of their time active. The time spent in orchards is a reliable measure of food obtained there. Most birds spent less than a quarter of their active time among orchard fruit trees. 95% of blue tits in this study spent less than 61% of potential foraging time among orchard trees. The 95% quantiles for the other species were: blackbirds 82%, chaffinches 81% and robbins 64%.
B.8.1.3 Risk assessment (Annex II A 8.1.3, 10.1) Long-term risk to birds The chronic risk to breeding birds from the consumption of treated insects and the long term risk from the metabolite BTS 27271 should be addressed by evaluating new data using more realistic assumptions about the exposure and effects to birds. A re-evaluation of the toxicity figures in the existing studies result in new values of the endpoints. Amitraz: In the study with mallard duck (Beavers et al, 1992 b) at 80 ppm the body weight of males was increased at termination and in females between weeks 4 and 8. Effects on reproductive parameters were reductions in the number of eggs laid during the first 4 weeks
- 34 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
of egg laying at both 40 and 80 ppm. But the effects were not statistically significant. The lowest effect level (LOEL) of 80 ppm amitraz caused a slight reduction in the number of offspring produced per female or reductions in hatchling bodyweight. No mortality effects were seen in adults at the highest doses tested (up to 250 ppm) amitraz. Therefore the ecologically relevant long-term NOAEC for amitraz is 40 ppm.
BTS 27271: In mallard duck treated with BTS 27271.HCl (Hakin et al, 1993 b) mortality of adult animals was dose-related (25 to 400 ppm). Mortality incidences were 21, 36 and 67% at 25, 100 and 400 ppm respectively. Body weight was reduced at 400 ppm, but food consumption was not affected in all groups. Although an increased death rate was already observed in the group treated with 25 ppm, effects on reproductive parameters were only observed at 100 and 400 ppm. In the groups treated with 25, 100 and 400 ppm death occurred 30 - 50 days after start of the study (in the 25 ppm group after day 51 continuous exposure). Focussing on realistic reproduction parameters, the ecologically relevant long-term NOAEC for BTS 27271 is 25 ppm.
Table 8.1.3-1 Avian long-term Ecologically relevant No Observed Adverse Effect Concentrations (NOAEC) for amitraz and BTS 27271.
amitraz (ppm diet) BTS 27271 (ppm diet) Birds 40 25
The revised risk assessment is based on the re-assessed NOAEC values and the residue data on food items and half-lifes for amitraz and BTS 27271 given above. The values are corrected for the application rate in pome fruits (2 x 800 g ai/ha). The radio-telemetry monitoring study conducted by Crocker 1998, gives also further aspects for refinement.
Since there are two applications, it is to be expected that amitraz and its metabolites will accumulate. Thus a MAF factor of 1.2 was used for calculation of the maximum concentration of amitraz and BTS 27271 in grass.
Table B.8.1.3.-2 Estimated initial concentrations, maximum actual concentrations, food demand and daily intake of amitraz and BTS 27271 for birds
Appl. food Residues (ppm) NOEC (ppm) TERlt rate in pome fruits (kg ai/ha) 2*0.8 amitraz BTS 27271 amitraz BTS 27271 amitraz BTS 27271
insects 1.95 1) 4.93 2) 40 25 20.5 5.07
grass 2.016 3) 4.14 4) 19.84 6.03
invertebrates 0.765 5) 2.88 6) 52 8.68
- 35 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
1) C0 for foliar dwelling invertebrates, corrected for appl. rate x f twa (DT50 = 1 d, f twa = 0.1), MAF = 1 in insects, 2) C0 for winged invertebrates, corrected for appl. rate x f twa (DT50 = 1.8 d, f twa = 0.1), MAF = 1 in insects, 50% of daily intake consists on winged invertebrates C0 for wingless invertebrates, corrected for appl. rate x f twa (DT50 = 52 d, f twa = 0.9), MAF = 1 in insects, 50% of daily intake consists on wingless invertebrates C for wingless and winged insects summed up: 10.8. Further refinement: Radio-tracking data indicates that blue tits find less than 61% of their food in orchards. C: 6.58 Assuming that small insect eating birds spent only 75% of their time during a 3 week period in the treated area: C = 4.93 3) Residues in grass on day 1, corrected for appl. rate x f twa (DT50 =1 d, f twa = 0.1), MAF = 1,2 Assuming that grass eating birds spent only 50% of their time during a 3 week period in the treated area: C = 2.016 4) Residues of BTS 27271 in grass on day 3, corrected for appl. rate x f twa (DT50 = 5.4 d, f twa = 0.3), MAF = 1,2 Assuming that grass eating birds spent only 50% of their time during a 3 week period in the treated area: C = 4.14 5) C0 for grounddwelling invertebrates, corrected for appl. rate x f twa (DT50 =1d, f twa =0.1), MAF = 1.2, 50% of daily food consumption 0.76 mg/kg PECtwa (soil) for earthworms (earthworms were considered to have the same concentration of amitraz as the surrounding soil, see endpoint list: 0.011 mg/kg) 50% of daily food consumption C = 0.005 C for grounddwelling invertebrates and earthworms summed up: 0.765 mg/kg 6) C0 max for grounddwelling invertebrates, corrected for appl. rate x f twa (DT50 =25.7d, f twa =0.8), MAF = 1.2, 50% of daily food consumption: 2.76 mg/kg PEC(metabolite)-soil for earthworms (earthworms were considered to have the same concentration of amitraz as the surrounding soil, see endpoint list: 0.237mg/kg) 50% of daily food consumption 0.12 mg/kg C for grounddwelling invertebrates and earthworms summed up: 2.88 mg/kg
The TERlt-values are above the trigger-value of 5 for unacceptable chronic effects given in Annex VI of 91/414 EEC. Thus, no unacceptable chronic risk from the use of amitraz in orchards is to be expected.
Long-term risk to wild mammals (Annex II A 10.3)
The chronic risk to breeding wild mammals from the consumption of treated insects and the long term risk from the metabolite BTS 27271 should be addressed by evaluating new data using more realistic assumptions concerning the exposure and effects to birds. A re-evaluation of the toxicity figures in the existing studies result in new values of endpoints. Amitraz:: In mammals, the most sensitive ecologically relevant end-point observed in reproduction studies is increased maternal aggression, which in extreme conditions can lead to pup death. This behavioural response to amitraz seen in rodents has been investigated further in a rat dietary mechanistic reproduction study (Harvey, 2000). In this study, female rats fed amitraz in the diet over 28 days, incorporating the gestation period, showed maternal aggression towards the pups (recorded as bite marks), leading to infant neglect. This effect was confirmed for female rats fed 200 ppm amitraz in the diet. The effects was not significant in rats fed 50 ppm amitraz over the same period, and is consistent with a lack of effects seen at 50 ppm after one generation in the original multigeneration study. Effects observed in later generations are not relevant to a wild mammal risk assessment as no situation will occur where wild mammals will be continuously exposed to amitraz residues
- 36 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
over 3 generations. Therefore, for the purposes of risk assessment for wild mammals the long-term ecologically relevant NOAEC for mammals is 50 ppm. However, it should be noted that this aggressive behaviour has been shown in previous studies to be reversible. Within one week of ceasing dosing the behaviour was no longer observed. BTS 27271: The only effects noted in rats fed by oral intubation for 90 days at 3 mg/kg/day (equivalent to approx. 45 ppm diet, factor 15: Lehmann, 59) was transient reduction in weight gain in males. This occurred only during the first week of dosing, possibly due to unpalatability (Shaw and Williams, 1975). At the higher dose, (12 mg/kg/day equivalent to approx. 180 ppm diet) the rats were aggressive (nervous and difficult to handle) during the first nine weeks, although they subsequently recovered and appeared normal. No mammalian reproduction studies have been conducted with BTS 27271 since acute and dietary studies in birds and mammals consistently indicate that amitraz is rapidly metabolised to BTS 27271, and that amitraz and BTS 27271 are of similar toxicity. Furthermore, the characteristic aggressiveness of rodents dosed with amitraz was also seen with BTS 27271 during the 90-day rat subchronic study. Since this behavioural response was the most sensitive ecologically relevant end-point for amitraz, and the effect was seen in the 90-day study with BTS 27271, it is reasonable to assume that the 90-day NOAEC for the metabolite reflects its (indirect) reproductive toxicity to rodents. Thus, for the purposes of risk assessment the long-term ecologically relevant NOAEC for wild mammals is 45 ppm.
Table 8.1.3-3 mammal long-term Ecologically relevant No Observed Adverse Effect Concentrations (NOAEC) for amitraz and BTS 27271.
amitraz (ppm diet) BTS 27271 (ppm diet)
mammals 50 45
The revised risk assessment is based on the re-assessed NOAEC values as well as the residue data on food items and half-lifes for amitraz and BTS 27271 given above. The values are corrected for the application rate in pome fruits (2 x 800 g ai/ha).
Since there are two applications, it is to be expected that amitraz and its metabolites will accumulate. Thus a MAF factor of 1.2 was used for calculation of the maximum concentration of amitraz and BTS 27271 in grass.
Table B.8.1.3-4 Estimated initial concentrations, maximum actual concentrations, food demand and daily intake of amitraz and BTS 27271 for mammals
Appl. food Residues (ppm) NOEC (ppm) TERlt rate in pome fruits (kg ai/ha)
- 37 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
2*0.8 amitraz BTS 27271 amitraz BTS 27271 amitraz BTS 27271
insects 1.95 1) 8.12) 50 45 25.6 5.5
grass 3.024 3) 6.21 4) 16.5 7.24
invertebrates 0.765 5) 2.88 6) 65 15.62
1) C0 for foliar dwelling invertebrates, corrected for appl. rate x f twa (DT50 = 1 d, f twa = 0.1), MAF = 1 in insects, 2) C0 for winged invertebrates, corrected for appl. rate x f twa (DT50 = 1.8 d, f twa = 0.1), MAF = 1 in insects, 50% of daily intake consists on winged invertebrates C0 for wingless invertebrates, corrected for appl. rate x f twa (DT50 = 52 d, f twa = 0.9), MAF = 1 in insects, 50% of daily intake consists on wingless invertebrates C for wingless and winged insects summed up: 10.8. Assuming that small insect eating mammals spent only 75% of their time during a 3 week period in the treated area: C= 4.93 3) Residues in grass on day 1, corrected for appl. rate x f twa (DT50 =1 d, f twa = 0.1), MAF = 1,2 Assuming that grass eating mammals spent only 75% of their time during a 3 week period in the treated area: C = 3.024 4) Residues of BTS 27271 in grass on day 3, corrected for appl. rate x f twa (DT50 = 5.4 d, f twa = 0.3), MAF = 1,2 Assuming that grass eating mammals spent only 75% of their time during a 3 week period in the treated area: C = 6.21 5) C0 for grounddwelling invertebrates, corrected for appl. rate x f twa (DT50 =1d, f twa =0.1), MAF = 1.2, 50% of daily food consumption 0.76 mg/kg PECtwa (soil) for earthworms (earthworms were considered to have the same concentration of amitraz as the surroundig soil, see endpoint list: 0.011 mg/kg) 50% of daily food consumption 0.005 C for grounddwelling invertebrates and earthworms summed up: 0.765 mg/kg 6) C0 max for grounddwelling invertebrates, corrected for appl. rate x f twa (DT50 =25.7d, f twa =0.8), MAF = 1.2, 50% of daily food consumption: 2.76 mg/kg PEC(metabolite)-soil for earthworms (earthworms were considered to have the same concentration of amitraz as the surrounding soil, see endpoint list: 0.237mg/kg) 50% of daily food consumption: 0.12 mg/kg C for grounddwelling invertebrates and earthworms summed up: 2.88 mg/kg
The TERlt-values are above the trigger-value of 5 for unacceptable chronic effects given in Annex VI of 91/414 EEC. Thus, no unacceptable chronic risk from the use of amitraz in orchards is to be expected.
B.8.2 Effect on aquatic organisms
B.8.2.1 Acute toxicity (Annex II A 8.2; Annex IIIA 10.2)
Acute toxicity of amitraz technical to fish The acute toxicity of amitraz technical to Harlequin fish in a flow-through system was not conducted according to a validated guideline nor GLP requirements) (Fraser and Jenkins, 1973).
Results: 96-hour LC50: 0.3.2 – 4.3 mg/l; 96-hour LC100: 4.3 mg/l (see Table B.8.2.1.-1)
Table B.8.2.1-1 Acute toxicity of amitraz technical to aquatic organisms (values are given as average of measurements at the beginning and the end of the test in mg/l)
Species NOEC LOEC LC50 mg/l Exposure duration (h) Guideline Reference mg/l mg/l / design
Fish
- 38 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
Harlequin fish 1.8 2.4 3.2 – 4.3 96/ flow through None (1) (1) Fraser and Jenkins, 1973
Acute toxicity of metabolites BTS 27271 and BTS 27919 to aquatic invertebrates
The acute toxicity of BTS 27919 to Mysid shrimp (Mysidopis bahia) was determined according FIFRA guideline in a static test system and in compliance with GLP, Schupner 1991, (see Table B.8.2.1.-2). 4 days old juvenile mysid shrimps were exposed to nominal concentrations of 8, 14, 23, 39 and 65 mg BTS 27919/l for 96 hours.
Results: 96-hour LC50: 25 mg/l (based on mean measured concentrations)
The acute toxicity of BTS 27271 to mysid shrimp (Mysidopis bahia) was determined according EPA guideline 72-3 in a flow through system and in compliance with GLP, Ward 1991 (see Table B.8.2.1-2). Less than 24 hours old mysid shrimps were exposed to nominal concentrations of 1.6, 2.6, 4.3, 7.2 and 12 mg BTS 27271/l for 96 hours.
Results: 96-hour LC50: 4.74 mg/l (based on mean measured concentrations)
Table B.8.2.1.-2 Acute toxicity of BTS 27919 and BTS 27271 to mysid shrimp
Species Substance NOEC LOEC EC50 Exposure Guideline Reference mg/l mg/l mg/l duration (h) / design
Invertebrates
Mysid shrimp BTS 27919 8 14 25 96/static FIFRA (1)
Mysid shrimp BTS 27271 1.47 2.46 4.74 96/flow-through EPA 72-3 (2) (1) Schupner and Stachura, 1991 (2) Ward, 1991
Acute toxicity of amitraz formulation to aquatic organisms For acute toxicity of amitraz formulation (Mitac 20 EC - containing 20% amitraz) to aquatic organisms see Table B.8.2.1-3. Acute toxicity of amitraz formulation to aquatic invertebrates:
The acute toxicity of amitraz 20 EC to mysid shrimp (Mysidopis bahia) was determined according EPA guideline 72-3 in a flow through system and in compliance with GLP (Smyth, 1988). Less than 48 hours old mysid shrimps were exposed to nominal concentrations of 0.1, 0.18, 0.32, 0.56, 1.0, 1.8 and 3.2 mg amitraz for 96 hours.
Results: 96-hour EC50: 0.48 mg/l (based on mean measured concentrations)
- 39 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
The acute toxicity of amitraz EC 200 g/l to freshwater invertebrates was determined in a static screening test in compliance with GLP (Mattock, 2000 a). Test concentrations: nominal 21, 105, 210, 1050 and 2100 µg amitraz/l, test duration: 48 hours Test organisms: Daphnia magna < 24 h old Daphnia magna 6 d Daphnia magna 14 d Baetis rhodani Asellus aquaticus Gammarus pulex Calanoid Copepod Chironimus riparius Brachionus calyciforus
Results: 48-hour EC50: based on nominal values and given in amitraz equivalents Daphnia magna < 24 h old: 194 µg/l Daphnia magna 6 d 270 µg/l Daphnia magna 14 d 101 µg/l Baetis rhodani 306 µg/l Asellus aquaticus 191 µg/l Gammarus pulex 233 µg/l Calanoid Copepod 42 µg/l Chironimus riparius < 21 µg/l
Brachionus calyciforus 942 µg/l (24-hour EC50)
Acute toxicity of amitraz 20 EC to daphnids in a modified system
The acute toxicity of Mitac EC (200 g ai /L) to daphnia magna was estimated in a sediment– water exposure system (Final report and amendment, Mattock, 2000 b+c). The study was designed to met the known requirements of the OECD guideline for testing of chemicals No 202 Part I and performed according GLP requirements. The test was carried out in the presence of sediment without renewal of the test media for 48h. The test vessels were 150 ml glass crystallising dishes containing 100 ml of test medium and approximately 50 g (wet weight) of sediment (depth approximately 1 cm). The test sediment (91% sand) was natural sediment collected from the Lake at Fountains Abbey, containing 0.9% organic carbon. The pH in water was 7.9. The test vessels were left to equilibrate for 24 days. Daphnia magna, less than 24 h old, were added afterwards. After 24 and 48 h the number of immobilised daphnids were recorded. Test concentrations: 0.8,
- 40 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
1.575, 3.125, 6.25 and 12.5 mg Mitac/l (amitraz equivalents: 0,16, 0.315, 0.625, 1.25 and 2.5 mg ai/L). The initial measured concentrations of amitraz ranged between 64 and 150%, after 48 h the measured amitraz concentrations had declined to between 7 and 14% of nominal.
Results: 48-hour EC50: 1.05 mg ai/l (48 h) Following NOEC is given: 0.625 mg ai/l, EC100: 2.5 mg ai/l
Table B.8.2.1.-3 Acute toxicity of amitraz 20 EC to aquatic invertebrates, values given in nominal amitraz equivalents
Species NOEC LOEC LC50 Exposure duration (h) Guideline Reference µg/l µg/l µg/l / design
Invertebrates
Mysid shrimp 120* 390* 480* 96/flow through FIFRA (1)
Daphnia magna < 24 h old 105 210 194 48/static none (2)
Daphnia magna 6 d 105 210 270
Daphnia magna 14 d 21 105 101
Baetis rhodani 210 1050 306
Asellus aquaticus 21 105 191
Gammarus pulex < 21 21 233
Calanoid Copepod < 21 21 42
Chironimus riparius < 21 < 21 < 21
Brachionus calyciforus 210 1050 942
Daphnia magna 625 1250 1050 48-hour, sediment OECD (3) water system 202 (1) Smyth, Comber and Hill, 1988 (2) Mattock, 2000 a (3) Mattock, 2000 b+c
* values given in mg amitraz 20 EC/L
B.8.2.2 Chronic toxicity (Annex II A 8.2.2, Annex III A 10.2)
Chronic toxicity of amitraz formulation to fish
Fish early life stage (IIA 8.2.2.2) simulating a pulsed dose application
The chronic toxicity of amitraz EC 200 g/L to embryos and larvae of the fathead minnow (Pimephales promelas) was determined following OECD 210 recommendations and was in compliance with GLP requirements (Sewell, Mullee, 2001). Newly hatched fathead minnow larvae were exposed to a single or double simulated pulse of test material over a range of test concentrations: 0.015, 0.032, 0.07 and 0.15 mg active ingredient (amitraz). Two test sets of the test concentrations (each concentration in
- 41 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002 duplicate) were subjected to a single simulated pulse of test material upon completion of hatching and one of these concentration sets was then subjected to a second simulated pulse dose of test material 14 days after the initial dose. Water quality parameters during the test were: pH 7.8, dissolved oxygen greater or equal 6.6 mg/l O2, temperature 25 ± 2°C and water hardness of approximately 100 mg/l as CaCO3. Chemical analyses of the test samples at 0 hours from the initial simulated pulse dose showed that measured concentrations of amitraz ranged from 78% to 93% of nominal. Analyses for amitraz at 6 hours ranged from 36% to 41% of nominal. Analyses at 24, 48 and 72 hours showed measured concentrations of amitraz to be less than the limit of quantification. Analyses of the test samples from the second simulated pulse dose showed that measured concentrations of amitraz at 0 hours ranged from 82% to 88% of nominal, 24% to 35% of nominal at 6 hours and less the limit of quantification after 24, 48 and 72 hours. Analysis of the metabolites BTS 27271 and BTS 27919 showed the measured concentrations to be less than the limit of quantification on all occasions. The numbers of mortalities or any sublethal effects were recorded daily until termination of the test (28 days post hatch). At termination the length, wet weight and dry weight of the surviving fish were measured. Findings: The mean hatching rate ranged from 75% to 92% and the mean survival rate ranged from 95% to 100%. Fish length, wet weight and dry weight data showed significant differences between the control group and some test concentrations, however, none of these differences indicated any treatment related trends and so cannot be attributed to the test material. Assessment: NOEC (34 d) = 0.15 mg ai/l
Chronic toxicity of amitraz formulation to aquatic invertebrates
Reproduction test with Daphnia magna in a sediment-water system
The chronic toxicity of amitraz EC 200 g/L to first instar larvae of Daphnia magna was determined following modified OECD 202 part 2 recommendations and in compliance with GLP requirements (Mattock, 2001). Eight replicates of 10 daphnids (< 24 hours old) were incubated in a static system until 28 days with daily feeding and observation on the survival, growth and reproduction. The nominal concentration range used in this study was 25, 50, 100, 200 and 400 µg/l (expressed as amitraz). After fourteen days, Mitac was applied at the same rates to half of the test vessels. Chemical analyses of the test samples at day 0 showed that measured concentrations of amitraz ranged from 73% to 88% of nominal. After 14 days, amitraz was only detected in the 200 µg amitraz/L treatment at amounts of 5% of the initial concentration. Analyses of the test samples from the second simulated pulse dose showed that measured concentrations of amitraz at day 0 ranged from 61% to 76% of nominal, and less the limit of
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quantification at the end of the exposure period. Analysis of the metabolites BTS 27271 and BTS 27919 showed the measured concentrations to be less than the limit of quantification on all occasions. Further, five control vessels were prepared. Test temperature of the test media ranged from 20 to 21.5°C and the pH-values ranged from 7.8 to 8.8. Dissolved oxygen content was between 81 to 96 (% ASV). Each test vessel contained approximately 150 g of sediment (loamy sand, 1.9% organic carbon) to a depth of approximately 2 cm and approximately 400 ml of overlaying water. The test sediment was natural sediment collected from a lake in North Yorkshire. Findings: At the end of the test survival, growth and reproduction (young per adult) of treated groups were compared to the control group. One application group (day 0): At the highest concentration level (2000 µg Mitac/l) no effects on survival or growth were observed, while reproduction was significant (< 25%) reduced. Therefore the 28 d NOEC was 1000 µg Mitac/l (200 µg ai). Two applications group (days 0 and 14): Significant effects were observed at all application levels with 30% mortality at the lowest treatment and 75% mortality at the highest. The surviving daphnids showed significant effects on growth at 2000 µg/l and reproduction was reduced by ca. 50% at 2000 µg/l.
Assessment: NOEC (28 d) = < 125 µg Mitac/l (25 µg ai/l) and LC50 = 732 µg Mitac/l (nominal concentration at application)
Table B.8.2.2.-1 Chronic toxicity of amitraz formulation on aquatic organisms (values given in mg ai)
Species Test type Parameter NOEC LOEC LC50 Exposure Guideline Ref mg/l mg/l mg/l duration/design
Fish
Fathead early life Survival 0.15 > 0.15 > 0.15 34 d (28 d post OECD 210 (1) minnow stage hatchability hatch)/ pulsed modified length dose weight
Invertebrates EC50
Daphnia Reproduction survival < 0.025 0.025 0.146 28d/ pulsed OECD 202 (2) magna test growth 0.4 > 0.4 dose in a modified reproduction 0.2 0.4 sediment water system (1) Sewell and Mullee, 2001 (2) Mattock,2001
B.8.2.3 Effects on sediment dwelling organisms (Annex IIA 8.2.7)
Toxicity of amitraz technical to Chironomus riparius
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A 28 day static study was undertaken with Chironomus riparius using (14C)-amitraz (purity: 99%). The study was undertaken in accordance with GLP and using the BBA method for plant protection products (1995) (Mattock, 2000 d). 25 larvae (first instar stage) for each test concentration were used. The test vessels were 3000 ml volume glass beakers containing 300 g of test sediment (equivalent to 194 dry sediment) and 2250 ml overlying water. The nominal initial concentrations in the water fraction were 0.125, 0.225, 0.5, 1, and 2 mg ai/l. Five replicates were prepared for each treatment, additional to one water and one solvent control. The test sediment was artificial soil prepared according the recipe in OECD guideline 207, the pH was adjusted within 6.0 ± 0.5
with CaCO3.
The analytical findings of the overlaying water at 1h sampling time indicated that the nominal initial concentrations were archived, therefore results were based on nominal initial concentrations. The concentration of radio labelled amitraz in the water phase declined over the course of the study. On day 28 approximately 10% of the nominal initial values were found. The initial concentrations of radio labelled amitraz in the pore water were 4, 10, 20, 72 and 65 µg/l, respectively. These values increased to 355 µg after 7 days (2000 µg/l samples) and decreased by the end of the study: 65 µg/l in 2000 µg/l samples. Recorded temperatures, pH values and oxygen levels were similar between the different treatments and the control.
During the study, number and time of emergence of the midges were determined daily. Emergence of adult midges was first observed on day 14. At day 17 emergence had occurred in all replicates. By day 25 emergence of C. riparius was complete with 3 exceptions (emergence on day 27). There were no apparent effects on the development of male and female midges.
The 28-d EC50 for total emergence based on the nominal amitraz exposure concentrations was > 2 mg/l. Assessment: NOEC (28 d) = 2 mg (14C)-amitraz/l
B.8.2.4 Risk assessment (Annex III A 10.2)
For the supported use in pome fruits (apple and pears) the application rate is 2 x 800 g ai/ha, interval 14 days. It is assumed that the contamination of surface water is exclusively caused by spray drift. Acute toxicity Fish: The most sensitive fish species is bluegill sunfish (see monograph). For this reason the
risk assessment is based on the corresponding LC50 of 0.45 mg/l and PECi (first tier approach). Invertebrates: A lot of data were provided showing the acute toxicity of amitraz formulation to invertebrates. For investigation of the risk under more realistic conditions, a new modified
- 44 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002 toxicity test was conducted using daphnids and a static sediment/water system. According the outcome of this test, the toxicity to daphnids was reduced by a factor of 5.5. The risk assessment was based on these higher tier data and the PECi (see table B.8.2.4) Chronic toxicity
The TERlt-values were estimated for fish and daphnids as the ratio of chronic toxicity
(NOEC) in the modified tests and PECi. The use of the initial PEC is appropriate because of the test design (single dose or double pulsed dose in a static system). For TER values see table B.8.2.4-1
For PEC see Monograph, B.7.6. The PECi at a distance of 3 m and 50 m to surface waters is 0.08 and 0.00053 mg/l respectively.
Table B.8.2.4-1: TERa and TERlt calculations for aquatic organisms
Substance species EC/LC50 PECi (mg ai/l) TERa PECi (mg ai/l) TERa (mg ai/l) 3m 50 m
Amitraz Bluegill sunfish 1 0.45 0.08 5.6 0.00053 849
Daphnia 2 1.05 13 1981
Substance Species NOEC PECi (mg ai/l) TERlt PECi (mg ai/l) TERlt 3m 50 m
Amitraz Fish 3 0.15 0.08 1.9 0.00053 283
Daphnia 4 0.2 2.5 377
Daph. Mort. 5 < 0.025 < 47
Daph. Reprod. 5 0.2 377
Chironimus 2 25 3773 1 most sensitive species (see monograph) 2 tested in a sediment/ water-system 3 pulsed dose test in sediment/water-system 4 pulsed dose test in sediment/water-system, one application 5 pulsed dose test in sediment/water-system, two applications
In the case of Chironomus, first instar larvae were more sensitive than daphnid neonates when exposed in water-only systems. But the toxicity to these organisms was significantly lower in the presence of sediment. The TERlt indicates no risk for sediment dwelling species.
TERa and TERlt are sufficient to protect aquatic invertebrates if amitraz is applied once and risk mitigation measures are used. In the modified tests no NOEC could be seen when the test substance is applied twice, but the lowest concentration tested is approximately 50 times higher than the initial PEC. At 0.025 mg/l (lowest concentration tested) 30% mortality occurred, at 0.0053 mg/l (PEC x 10, taking the uncertainty factor of 10 given in Annex IV into account), the percentage of mortality would be less. Furthermore, reproduction was not
affected up to concentrations of 0.2 mg ai/l. The corresponding TERlt of 377 indicates the
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possibility of recovery. Thus, no unacceptable effects on aquatic invertebrates are expected when amitraz is applied twice a year and risk mitigation measures are used..
B.8.3 Effects on bees (Annex III A, 10.4.1, Annex II A, 8.3.1)
B.8.3.1 Acute toxicity
The toxicity of amitraz EC 20%-formulation and amitraz metabolites BTS 27919 and BTS 27271 to bees was addressed. The studies on the acute oral and contact toxicity to honeybees are summarised in table B.8.3.1-1 and B.8.3.1-2. All tests were carried out in accordance with GLP.
Table B.8.3.1-1 The acute toxicity of amitraz EC 20%-formulation to honeybees.
Test type substance LD50 (µg form/bee) Test guideline Ref acute oral, 96 h amitraz 20% EC 43 EPPO 170 (1)
acute contact, 72 h amitraz 20% EC > 505 EPPO 170 (2) (1) Waltersdorfer, A. (2000 a) (2) Waltersdorfer, A. (2000 b)
Table B.8.3.1-2 The acute toxicity of amitraz metabolites to honeybees.
Test type substance LD50 (µg as/bee) Test guideline Ref .
acute oral, 72h BTS 27 919 > 93 EPPO 170 (1)
acute contact, 72 h BTS 27 919 > 100 EPPO 170 (2)
acute oral, 72 h BTS 27 271 4 EPPO 170 (3)
acute contact, 72 h BTS 27 271 18.67 EPPO 170 (4) (1) Waltersdorfer, A. (2000 c) (2) Waltersdorfer, A. (2000 d) (3) Waltersdorfer, A. (2000 e) (4) Waltersdorfer, A. (2000 f)
B.8.3.2 Risk assessment
Honey-bees may be exposed to formulated amitraz by direct spraying when foraging on flowers or weeds present in the crops to be treated through contact with fresh or dry residues or by oral uptake of contaminated pollen, nectar and honey dew.
Table B.8.3.2-1 Hazard quotients (QHC and QHO) for Mitac 20 EC applied in orchards (4.0 l Mitac/ha)
Test Route of LD50 Crop Field rate Hazard substance Exposure [µg Mitac/bee] [g Mitac/ha] quotient1
Mitac 20 EC oral 43 orchards 4000 QHO = 93
contact > 505 4000 QHC = < 7.9
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2 BTS 27 919 oral > 93 407 QHO = < 4.3
2 contact > 100 407 QHC = < 4
2 BTS 27 271 oral 4 442 QHO = 110.5
2 contact 18.67 442 QHC = 23.6 1 Hazard quotient: QH = max. field rate [g /ha] / LD50 [µg /bee] (according to EPPO risk assessment scheme) 2 4000g Mitac/ha, corrected for molecular weight (The molecular weight of amitraz is 293, of the metabolite BTS 27919 149 and of BTS 27271 162)
The hazard quotient indicates a risk to bees on the oral route of exposure for the formulation and the metabolite BTS 27271. In a higher tier study Mitac 20 EC was evaluated under semi-field conditions on foraging bees. According to the results of the cage tests, it was concluded that the application of amitraz formulation is not hazardous to honey-bees at all intended uses. However, no data on the metabolites are given. As the relevant metabolites are formed quickly (see B.8., residues in grass and insects) and the test duration of the semi-field test was 96 h, it can be assumed that the semi-field test covers the effects of the metabolites, too. Therefore, it can be concluded that a repeated application of 0.8 kg amitraz/ha in orchards does not bear an unacceptable risk to honey bees.
B.8.4 Effects on other arthropod species (Annex II A, 8.3.2, Annex III A, 10.5.1;)
B.8.4.1. Laboratory tests
Plant protection product (Karathane LC)
Ground dwelling predators The toxicity of amitraz 200 g/l emulsifiable concentrate to the ground active beetle Aleochara bilineata has been investigated in the laboratory following recommendations of Naton (1988) and was in compliance with GLP requirements (Taruza, 2000). In this study, the amitraz formulation was evaluated at two rates, equivalent to 1 l and 1.75 ml formulation/ha. A toxic reference was testet and tap water as control as well. Adult rove beetles of equal sex ratio were placed in batches of 20 in boxes of damp sand with four replicates. Treatments were then applied to the boxes. The beetles were provided with food and their survival monitored over 28 d. In order to assess the fecundity of these beetles, onion fly pupae were buried in the sand in each box. At day 28, the sand-filled arenas were turned out and the adult beetles were removed and host fly pupae were sieved out. They were stored and the numbers of emerged adult (F1) rove beetles emerging from the fly pupae were recorded up to day 72.
Results:
Table B.8.4.1-1 Effects of Mitac to Aleochara bilineata in the laboratory
Species Category Dose Effects Classification stage
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Ground Aleochara 1.75 ml/ha 15% mortality* harmless dwellinging bilineata 1 l/ha 44% slightly harmful predators adults 1.75 ml/ha + 14% fecundity harmless 1 l/ha - 50% slightly harmful
*Abbott-corrected mortality
The combined effect was not reported.
Conclusion: The dose rates tested are lower than the recommended rate in orchards (4 l Mitac /ha). Based on the test results provided the effects Mitac EC on ground dwelling arthropods under the proposed conditions of use cannot be clear stated.
B.8.4.2 Semi-field studies
Predatory mites, parasitoids, foliage dwellers
A semi-field study was conducted to evaluate the effects of fresh and aged residues of Mitac to predatory mites, parasitoids and foliage dwellers in apple trees in Devon, UK (Forster, 2001 b). The study was conducted according GLP requirements and refers to the ESCORT guidance documents (Barret et al. 1994 and Candolfi et al. 2001)and Mead-briggs (1996). The study was of a randomized block design with four replicates of 6 treatments as summarized below: Water control and toxic standard, A) 800 g ai/ha in 1000 l volume (representing field application rate in orchards) = 0.08% w/v B) 210 g ai/ha in 1000 l volume (representing 26% drift at 3 m and two applications from crop in orchards) = 0.021% w/v C) 500 g ai/ha in 5000 l volume (representing 20% drift at 3 m from crop in hops) = 0.01% w/v = 12.5% drift rate = appr. 5 m from crops in orchards D) 2.5 kg ai /ha in 5000 l volume (representing field application rate in hops) = 0.05% w/v
To simulate worst-case conditions, Mitac was applied twice with an interval of 19 days, before any bioassay was initiated. Following the second treatment, branch tips and/or leaves were removed from the trees at different time points, taken to the laboratory, and series of bioassays carried out under laboratory conditions with four indicator species: T. pyri, A. rhopalosiphi, E. balteaus and C. carnea.
For T. pyri, survival was assessed for fresh residues immediately after the last application of the test substance and then for the 7, 14, 28 , 42 and 56-day aged residues. Ten T. pyri protonymphs were introduced to the leaf material collected on day 7, 14, 28 , 42 and 56. Mortality was assessed on day 1, 3 and 7 after introduction of the protonymphs. All rates of
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Mitac were evaluated in each mortality bioassay. Fecundity was assessed on each bioassay occasion when mortality was less than 50% in any treatment. Assessment of the effects on reproduction were carried out on day 10, 12 and 14. For each fecundity bioassay, the mean number of eggs produced per female was calculated and results analysed by statistics to assign any significant differences between treatments.
For A. rhopalosiphi, survival and fecundity were assessed for fresh residues immediately after the last application of the test substance (day 0), and then for the 7, 14, and 28-day aged residues. Assessments for mortality were carried out 24 and 48 hours after the adult wasps were introduced into the test chamber. All rates of Mitac were evaluated in each bioassay. The bioassays initiated on days 0, 7, 14 and 28 were continued to the fecundity phase for control and test substance treatment only. After the final mortality assessments, surviving wasps were introduced into fertility chambers containing aphid infested barley seedlings. Adult wasps were removed after 24 hours and the number of mummies present on the barley seedlings was recorded after 12 days. The mean number of mummies produced per adult female was calculated and the data were analysed using analyses of variance (Tukey test).
For E. balteaus survival and fecundity were assessed for the 43-day aged residues. Only the in-crop application rates of Mitac were evaluated. For fecundity assessment, emerged adults were pooled within the treatment groups and introduced into fecundity enclosures. Pollen, a honey water solution and a bean plant with aphid infestation was also placed inside the enclosure. The first fecundity assessment period started 29 days after introduction of the introduction of E. balteaus larvae and approximately fifteen days after the majority of adults had emerged. The number of eggs produced by each female and the percentage of viable eggs were calculated.
For C. carnea, larval survival through to pupation was assessed for the 39-days old residues only. Only the in-crop application rates of Mitac were evaluated.
Results: Typhlodromus pyri : mortality assessed on day 7 : day 0 : all groups: 100% 7 d bioassay: group A), D) 100% group B) 90% group C) 30% 14 d bioassay: group A), D) 100% group B) 83% group C) 26% 28 d bioassay: group A) 74% group D) 40%
- 49 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
group B) 17% group C) 15.7% 42 d bioassay: group A) 65% group D) 50% group B) 12.5% group C) - 3% 56 d bioassay: group A) 9% group D) 21% group B) -18% group C) - 1% fecundity: 7 d bioassay: only group C) was continued to the fecundity phase: significant different from control 14 d bioassay: only group C) was continued to the fecundity phase: significant different from control 28 d bioassay: only groups C) B) D) were continued to the fecundity phase: significant different from control 42 d bioassay: evaluation not possible because of low control values 56 d bioassay: groups A), B), C) D) not significantly different from control
Aphidius rhopalosiphi: mortality after 48 h 0 d bioassay: group A) 29% B) 12% C) 33% D) 4.2% 7 d bioassay: group A) -33% B) -15% C) -21% D) 19% Fecundity on day 12 : 0 d bioassay: all groups significant different from control 7 d bioassay: D), A) significant different from control 14 d bioassay: A) different from control, but not significant
Episyrphus balteatus: only one bioassay was initiated on day 43 for groups D) and A): Mortality not significant from control group: D) and A)
- 50 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
fecundity: no statistical evaluation because of high variability. Qualitative assessment indicated that there might be slight reduction in fecundity in group A), but no clear treatment-related effect was indicated. Animals exposed to amitraz showed a lower egg production compared with control but this was compensated by higher viability Chrysoperla carnea: only one bioassay was initiated on day 39 for groups D) and A): Mortality: no significant from control fecundity: not evaluated
Conclusion: Residues of amitraz applied as 20% EC formulation caused high mortality (>50%) to Typhlodromus pyri at the in-crop rate of 800 g ai/ha, even in bioassays conducted with 42-day aged residues. At off-crop rates, the mortality in the 28-day bioassay was < 17%. Fecundity was significantly effected in both in-crop and off-crop treatments up to the bioassays conducted with 42-day aged residues. The 56-d bioassay showed no significant differences to the controls. The Aphidius rhopalosiphi mortality was less than 50% at all application rates in the 0 d bioassay. At in-crop rate, fecundity was very low up to the 14-d bioassay, but only statistically significant on the 7 d bioassay. For the off-crop application rate, the 7 d bioassay was significant from control, too. For Episyrphus balteatus and Chrysoperla carnea only one bioassay was initiated, but no effects on survival or reproduction could be seen at the in-crop treatment group (the off-crop concentration was not tested with these species).
B4.8.4.3 Risk assessment:
Since amitraz is an insecticide, its toxicity to non target insects is not unexpected. Dose- response testing on glass plates has illustrated that with regard to survival, mites are significantly more sensitive than the other non-target arthropods groups tested, being ca. 600-fold more sensitive than the wasp Aphidius (see Addendum I Annex B, Sept. 2000; Vinall, 2000, Baxter 2000). Being one of the two indicator species, Aphidius is more or at least as sensitive as other non-target arthropod species (foliage dwelling predators and ground dwelling predators (Phillips, 2000 , Addendum I and Taruza, 2000). Taking Aphidius as representative surrogate of the other non target species it can be concluded that the semi field-test with Aphidius covers the possible effects on ground dwelling predators, which were not further tested. The foliage dwellers Episyrphus balteatus and Chrysoperla carnea are less sensitive under semi field conditions, too, compared with Aphidius. Based on the results obtained with mites as worst-case assessment, the persistence of ecologically relevant residues on foliage following two applications of Mitac will be between 0 –and 56 days in the in-crop and the immediate off-crop area (assuming the maximum drift within a distance of 3 m). More typically however, based on the results with parasitoids, the persistence of ecologically relevant residues for most other non target arthropods will be
- 51 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002 between 0-14 days in crop and no more than 7 days in the immediate off-crop area. The data on Episyrphus balteatus and Chrysoperla carnea indicate that there are no effects on foliar dwelling predators 43 and 39 days after the second use of Mitac in orchards, respectively. Summed up, the potential for recovery for the most sensitive species is shown in-crop as well as off-crop at the latest 56 days after the second application.
- 52 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
B.8.5 References relied on
Annex point/ Author(s) Year Title Data Owner reference Source (where different from company) Protection number Company, Report No Claimed GLP or GEP status (where relevant), Published or not Y/N
IIA 8.1.3 Forster A. 2001 a Determination of residues of amitraz (AE Y AVO B049974 00 EC20 B1) and its toxicologically relevant metabolites in invertebrates collected from an orchard in Cambridgeshire, UK, Interim report Ecotox Limited Rep.No. ER-01-KCB135 GLP, unpublished
IIA 8.1.3 Laporte, F., 2001 Determination of amitraz and its metabolites Y AVO IIIA 10.1 Snowdon, AE C427271 and AE C427919 in IIIA 10.3 P.J. invertebrates and grass Aventis CropScience GmbH, DEU Rep.No. CR00/032 GLP, unpublished
IIA 8.1.3 Crocker, D.R., 1998 Improving the Assessment of Pesticide Risk N IIIA 10.1 et al to Birds in Orchards Objective 1: Use of IIIA 10.3 Radio-Telemetry to Monitor Birds’ Use of Orchards Central Science Laboratory, Sand Hutton, York Rep.No. EH18/02 not GLP, published
IIA 8.2.2.1 Fraser W.H., 1973 The acute toxicities of technical and N AVO Jenkins G. formulated BTS 27419 to harlequin fish (Rasbora heteromorpha) under continuous flow conditions Huntigdon Research Centre Rep.No. BTS 73117 not GLP, unpublished
IIA 8.2.4 Smyth D.V., 1988 Amitraz 20 EC Formulation: Determination Y AVO IIIA 10.2 Comber of acute toxicity to mysid shrip (Mysdopsis M.H.I., bahia) Hill R.W. ICI Brixham Laboratory, GBR Rep.No. BL/B/3219, GLP, unpublished
IIA 8.2.4 Schuppner 1991 The static acute toxicity of BTS 27919 to the Y AVO J.K., mysid shrip, Mysidopsis bahia Stachura B.J. Nor-Am Chemical Co Rep.No. 502L GLP, unpublished
IIA 8.2.4 Scott Ward G. 1991 BTS 27271: Acute toxicity to the mysid, Y AVO Mysidopsis bahia, under flow-throough test conditions Nor-Am Chemical Co, Rep.No. 514L GLP, unpublished
- 53 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
Annex point/ Author(s) Year Title Data Owner reference Source (where different from company) Protection number Company, Report No Claimed GLP or GEP status (where relevant), Published or not Y/N
IIA 8.2.4 Mattock S.D. 2000 a Acute Toxicity Tests with Freshwater Y AVO IIIA 10.2 Invertebrates amitraz Emulsifiable Concentrate 200 g/L Aventis CropScience USA LP, Rep.No. ENVIR/00/55 GLP, unpublished
IIA 8.2.4 Mattock S.D. 2000 b Acute toxicity to Daphnia magna in a Y AVO IIIA 10.2 sediment-water exposure system amitraz EC 200 g/L Code: AE B049974 00 EC20 B1 Convance Laboratories, Harrogate, North Yorks, GBR Rep.No. 194/213-D2145 GLP, unpublished
IIA 8.2.4 Mattock S.D. 2000 c Report Amendment 1: Acute toxicity to Y AVO IIIA 10.2 Daphnia magna in a sediment-water exposure system Code: AE B049974 00 EC20 B1 Convance Laboratories, Harrogate, North Yorks, GBR Rep.No. ENVIR/00/042 not GLP, unpublished
IIA 8.2.2.2 Sewell I., 2001 Fish Early Life Stage Toxicity Test: Amitraz Y AVO Mullee D. Enulsifiable concentrate 200 g/L AE B049974 00 EC20 B1 Safepharm Laboratories Limited, Derby GBR Rep.No. 1457/002 GLP, unpublished
IIA 8.2.5 Mattock S. 2001 Reproduction test with Daphnia magna in a Y AVO sediment-water exposure system amitraz emulsifiable concentrate 200/g/L Covance Laboratories, Harrogate, North Yorks Rep.No. 194/214-D2149 GLP, unpublished
IIA 8.2.7 Mattock S. 2000 d 14-C amitraz: Effects on Sediment Dwelling Y AVO Chironomus riparius in a Water-sediment System, amitraz 99% substance Technical Aventis CropScience USA LP Rep.No. ENVIR/00/053 GLP, unpublished
IIA 8.3.1 Waltersdorfer 2000 b Contact toxicity (LD50) to honey bees (Apis Y AVO IIIA 10.4.1 A. mellifera L.) amitraz Emulsibable concentrate 200 g/l substance pure Code: AE B049974 00 EC20 B 104 Aventis CropScience GmbH, DEU Rep.No. CW99/094 GLP, unpublished
- 54 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
Annex point/ Author(s) Year Title Data Owner reference Source (where different from company) Protection number Company, Report No Claimed GLP or GEP status (where relevant), Published or not Y/N
IIA 8.3.1 Waltersdorfer 2000 f Contact toxicity (LD50) to honey bees (Apis Y AVO A. mellifera L.) substance pure Code: AE B049844 00 1B99 0001 (= BTS27271-HCl) Aventis CropScience GmbH, DEU Rep.No. CW00/064 GLP, unpublished
IIA 8.3.1 Waltersdorfer 2000 d Contact toxicity (LD50) to honey bees (Apis Y AVO A. mellifera L.) substance pure Code: AE C427919 00 1B99 0003 (formerly BTS27919) Aventis CropScience GmbH, DEU Rep.No. CW00/063 GLP, unpublished
IIA 8.3.1 Waltersdorfer 2000 a Oral toxicity (LD50) to honey bees (Apis Y AVO IIIA 10.4.1 A. mellifera L.) amitraz Emulsibable concentrate 200 g/l substance pure Code: AE B049974 00 EC20 B 104 Aventis CropScience GmbH, DEU Rep.No. CW99/134 GLP, unpublished
IIA 8.3.1 Waltersdorfer 2000 c Oral toxicity (LD50) to honey bees (Apis Y AVO A. mellifera L.) substance pure Code: AE C427919 00 1B99 0003 (formerly BTS27919) Aventis CropScience GmbH, DEU Rep.No. CW00/069 GLP, unpublished
IIA 8.3.1 Waltersdorfer 2000 e Oral toxicity (LD50) to honey bees (Apis Y AVO A. mellifera L.) substance pure Code: AE B049844 00 1B99 0001 (= BTS27271-HCl) Aventis CropScience GmbH, DEU Rep.No. CW00/070 GLP, unpublished
IIIA 10.5 Forster A. 2001 b A semi-field study to evaluate the effects of Y AVO fresh and aged residues of MITAC (AE B049974 00 EC20 B1) on the non-target arthropod species Typhlodroms pyri (Acari: Phytoseiidae), Aphidius sp. (Hymenoptera: Braconidae), Episyrphus balteatus (Diptera: Syrph) Ecotox Limited Rep.No. ER-01-KCB136 GLP, unpublished
IIIA 10.5 Taruza, S. 2000 Amitraz, 200 g/L emulsifiable concentrate Y AVO Toxicity of AE B049974 00 EC20 B1 to the ground active beetle, Aleochara bilineata in a laboratory test Rep.No. ENVIR/00/039 GLP, unpublished
- 55 - Amitraz – Addendum II Annex B - 8: Ecotoxicology July 2002
Report from ECCO 78 - amitraz / 6391/ECCO/PSD/99 15 June 1999
DISCLAIMER
PLEASE NOTE THAT THIS DOCUMENT IS AN EXCERPT OF THE REPORT OF AN ECCO (European Commission Co-ordination) PEER REVIEW MEETING
CONCISE OUTLINE REPORT OF ECCO 78 PEER REVIEW MEETING
Peer Review Programme under Directive 91/414/EEC
Subject: Meeting to discuss Mammalian toxicology, chapter 2.4 ”Impact on human and animal health”, chapter 2.7.2 ”Residues relevant to worker safety” and chapter 2.10 ”Classification and labelling” (Volume 1) of the monographs on
- famoxadone (NAS) NAS = new active substance - CGA 245 704 (NAS) EAS = existing active substance - thiram (EAS) - ziram (EAS) - amitraz (EAS)
Date: 26 - 30 April 1999
Venue: PSD/York
Attendance: Mr. Warren (Chairperson) Mr. Bergmann (Austria) Ms. Duverger (Belgium) Mr. Solecki (Germany) Mr. Pelfrene (France) Ms. Machera (Greece) Mr. Maier (European Commission, DG VI) Ms. Fassold (ECB, Ispra, on behalf of the European Commission, DG XI) Ms. Barling (ECCO-TEAM (PSD)/Report)
Summary of the meeting: The experts identified and discussed the list of end points for mammalian toxicology using templates provided by the corresponding rapporteur Member State. Where appropriate, separate lists of data requirements and studies relied upon (for which data protection has been claimed) were agreed on. The proposals for ”residues relevant to worker safety” and for ”classification/labelling” have been reviewed. Areas of concern related to each active substance and restricted to the section ”mammalian toxicology” were pointed out. Specific comments on the monographs were added and several general issues have been discussed as detailed below.
1 Report from ECCO 78 - amitraz / 6391/ECCO/PSD/99 15 June 1999
General comments concerning study requirements and evaluation of studies in the section Mammalian toxicology are listed below.
1. With regard to acute toxicity, the ECCO meeting considered that where there is a marked difference in toxicity between male and female rats then the LD50 for both sexes should be given on the end points sheet. In addition, with regard to the rat LC50 inhalation, it would be useful to indicate the nature of application used in the study (dust, aerosol, vapour, whole body).
2. The procedure by which shorter and longer-term studies in the same species and strain (e.g. 13- and 52-week dog studies) might be combined to arrive at an appropriate reference dose (e.g. ADI) was discussed. Where the longer study had a higher NOAEL than the shorter study but was of adequate design to ensure that the critical effect in the shorter study would be detected in the longer study, then it was agreed to be appropriate to use the higher NOAEL from the longer study. Also, if there was no evidence of toxicity increasing with duration of treatment (i.e. that at comparable dose-levels the severity of effects remained constant) it might be appropriate to select the NOAEL from the higher of both studies. However, for an ADI it would usually not be appropriate to select a short-term NOAEL in preference to a longer-term, lower NOAEL. This was particularly the case if there was evidence of chronicity (effect levels becoming lower with increasing duration of treatment). 3. It was noted that the submission of a list of literature citations in place of comments was unhelpful, since experts would not be able to evaluate the information at the meeting. Without a brief statement of the value and significance of the information, or provision of a copy of the articles in time to be evaluated before the meeting, such a submission could only delay decision-making. This point should be made clear to potential commentators. 4. It was helpful to the meeting when the rapporteur had an up-to-date recommendation on the list of studies to be granted data protection. 5. In a meeting considering 8 monographs in 5 days, experts found it necessary to work undesirably long hours in order to give an appropriate level of attention to the evaluations. The experts recommended this level of loading to be excessive.
The following documents were tabled at the meeting:
Date Supplier Content ECCO Ref No. 28 April 1999 ECCO 76 amitraz – information 6384/ECCO/PSD/99 and questions 29 April 1999 Mr Pelfrene amitraz – French 6387/ECCO/PSD/99 comments
2 Report from ECCO 78 - amitraz 6391/ECCO/PSD/99 15 June 1999
Specific comments on the active substances in the section Mammalian toxicology are listed below. The conclusions of the meeting were as follows:
AMITRAZ
Rapporteur Member State: Austria
1. All comments received were discussed: Date Supplier ECCO Ref No. 19 April 1999 AgrEvo 6357/ECCO/PSD/99 19 April 1999 United Kingdom 6358/ECCO/PSD/99 19 April 1999 Netherlands 6359/ECCO/PSD/99 19 April 1999 Belgium 6360/ECCO/PSD/99 19 April 1999 France 6361/ECCO/PSD/99 19 April 1999 Sweden 6362/ECCO/PSD/99 20 April 1999 AgrEvo 6363/ECCO/PSD/99 20 April 1999 Austria 6364/ECCO/PSD/99 21 April 1999 Germany 6367/ECCO/PSD/99 28 April 1999 ECCO 76 6384/ECCO/PSD/99 29 April 1999 France 6387/ECCO/PSD/99 July 1997 European Environmental 5601/ECCO/PSD/97 Bureau 5602/ECCO/PSD/97 5603/ECCO/PSD/97 28 August 1998 World Wide Fund for Nature 6006/ECCO/PSD/98
2. Residues relevant to worker safety: Revised calculations of operator, worker and bystander exposure are required.
3. Data on preparations: The data package submitted for NARVAL was considered complete.
4. Classification and labelling: The experts proposed hazard classification as Xn, Xi and risk phrases R22, R43, R48/22, R64. The need for classification as R40 to be considered following submission of the re-evaluation of the long term studies.
5. Claims for data protection: See Appendix 3.
3 Report from ECCO 78 - amitraz 6391/ECCO/PSD/99 15 June 1999
6. Recommended restrictions/conditions for use: None.
Areas of concern: 1. Impaired lactation was observed in the rat reproductive toxicity study, however, it was not clear whether this was an effect on dams or directly on the pups. Therefore, in the absence of mechanistic information it was considered that amitraz should be classified as R64. 2. Classification for R40 to be considered following re-evaluation of the long term toxicity studies. 3. Provisional ADI proposed based on the NOAEL from the chronic dog toxicity study and applying a safety factor of 100. This value was supported by the human volunteer study (applying a safety factor of 25). In the event that mechanistic information are provided which demonstrate that the lactation effect in the rat reproductive toxicity study is parental then it may be possible to re-consider setting the ADI on the basis of the NOAEL from that study (1mg/kg bw/day) and applying a safety factor of 100.
Appendix 1: ECCO 78 reporting table: amitraz
Appendix 2: List of end points: amitraz
Appendix 3: List of studies for which the main submitter has claimed data protection and which during the re-evaluation process were considered as essential for the evaluation with a view to Annex I inclusion: amitraz
Appendix 4: Suggested classification and labelling: amitraz
4 Report from ECCO 78 - / amitraz / 6391/ECCO/PSD/99 15 June 1999
Appendix 1: ECCO 78 reporting table Amitraz (Ac, In)
4. Mammalian toxicology
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(i) Toxicologically In response to a question from ECCO 76 the meeting commented that BTS significant 27271 is toxicologically significant , however, in view of the fact that the level compounds of activity (as reflected by the NOAEL) is similar to that of the parent it was not considered necessary to set separate end points. With regard to impurities, the meeting concluded that the significance of the impurities in the source considered was adequately addressed by the data package, however, if the impurity profile differed in other sources then the relevance of these differences would need to be addressed. (ii) Short term toxicity: The Rapporteur explained that there had been mortalities in all doses in the lowest relevant dermal study due to an infection, it was therefore not an appropriate study on dermal which to base a dermal NOAEL. However, given the dermal absorption data NOEL/NOAEL available, the meeting concluded that it was not necessary to request a repeat study. (iii) Short term toxicity: On the basis of the findings in the 90-day dog study it was concluded that lowest relevant oral R48/22 was appropriate. NOEL/NOAEL (iv) Genotoxicity In response to a comment on the potential genotoxicity of the metabolites BTS 4.1 Studies on the mutagenicity 28369 and BTS 24868, the Rapporteur explained that the BTS 24868 may be of metabolites (as cited in merely an artefact since it had also been found in tests in which urine was spiked JMPR/Hayes & Laws) with amitraz. With regard to BTS 28369, it was concluded that since this should be submitted. metabolite was found in rats, mice and plants following very low dosing then its toxicity would be covered by the toxicology data package. Studies on the mutagenicity of metabolites (as cited in JMPR/Hayes & Laws) should be submitted and evaluated.
5 Report from ECCO 78 - / amitraz / 6391/ECCO/PSD/99 15 June 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(v) Carcinogenicity There was discussion of the relevance of the hepatocellular adenomas found in 4.2 Rapporteur to provide an females in the top dose group in the long-term mouse study. The Rapporteur evaluation of the second reported that the main data submitter considered that classification was not long-term mouse study required because B C F mice are sensitive to tumours, and adenomas were (Burnett et al). 6 3 1 found in females only at dose levels above the MTD. The Rapporteur reported 4.3 that the main data submitter had also recently submitted a further study giving a Main data submitter to
NOAEL of 2.8 mg/kg bw/day, although lymphoreticular tumours were seen in provide a pathology re- females at 400ppm. Although this was not a new study the Rapporteur agreed to evaluation of all long term provide an evaluation for the overview meeting. In order to determine whether studies, in particular to R40 classification was required the meeting agreed that the main data submitter differentiate between the should provide a pathology re-evaluation of all of the available long-term lymphoreticular tumour studies. In particular, it was important to differentiate between the types found in females, and lymphoreticular tumours observed in females since the criteria for include a comparison with lymphoreticular tumours had only comparatively recently been defined (the detailed historical control study was conducted in 1976). In addition, it was agreed that the re-evaluation data from the laboratory should provide a comparison with detailed historical control data from the
laboratory. (vi) Reproductive toxicity The Rapporteur reported that the study was terminated at 200ppm due to loss of pups at that dose level. At the mid dose level (50ppm) there was high pup mortality, and increased aggressiveness and impaired lactation in maternal parents. The meeting discussed the relevance of the effects on lactation. If this was a behavioural effect on the mother then it would not warrant classification. It was possible, however, that this was an effect on the young failing to elicit appropriate maternal behaviour, which would necessitate classification as R64. Therefore, in the absence of mechanistic information it was appropriate to classify as R64 based on the effects on lactation. It was commented that where new reproductive toxicity studies were available then these should be submitted to the Rapporteur.
6 Report from ECCO 78 - / amitraz / 6391/ECCO/PSD/99 15 June 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(vii) Lowest relevant It was noted that the main data submitter had submitted a copy of the JMPR 4.4 Main data submitter to developmental review of amitraz. Since the JMPR review concluded a different NOAEL provide a copy of the NOAEL/NOEL (5mg/kg bw/day) to that proposed by the Rapporteur, it was agreed that the main second rabbit teratology data submitter should provide the Rapporteur with a copy of the second rabbit study referenced in the teratology study referenced in the JMPR review. JMPR review. (viii ADI The meeting discussed the relevant basis on which to set the ADI. The main ) data submitter had proposed to set an ADI on the same basis as that adopted in the JMPR review (0.01 mg/kg bw/day based on the human volunteer study and applying a safety factor of 10). The meeting did not accept this proposal as only 6 individuals (all males) had been tested, and although it was acknowledged to have been a double-blind study, the meeting had a significant concern on effects in females and it was considered that a safety factor of 25 was more appropriate. Given the conclusion regarding reproductive toxicity, it was considered more appropriate to adopt the Rapporteur’s proposal to set a provisional ADI on the basis of the NOAEL from the chronic dog toxicity study, and applying a safety factor of 100. It was noted that this ADI value was also supported by the NOAEL from the human volunteer study when applying a safety factor of 25. It was agreed that if mechanistic information is provided which demonstrates that the effects on lactation in the rat reproductive toxicity study are maternal only then it would be possible to re-consider setting the ADI on the basis of the NOAEL from that study (1 mg/kg bw/day) and applying a safety factor of 100. (ix) ARfD Since the provisional ADI was supported by the findings from an acute human volunteer study it was considered appropriate to set the ARfD at the same value. ECCO 82 – Residues meeting to note revised ARfD (x) Dermal penetration The meeting agreed dermal penetration of 1% for the concentrate and 10% for spray dilution
7 Report from ECCO 78 - / amitraz / 6391/ECCO/PSD/99 15 June 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(xi) Acceptable exposure The meeting agreed that the main data submitter should provide revised 4.5 Revised estimates of scenarios calculations of operator, worker and bystander exposure using the revised operator, worker and dermal penetration values. bystander exposure are required (IIIA 7.2)
8 Report from ECCO 78 - / amitraz /
Appendix 2
LIST OF END POINTS: AMITRAZ
4 Mammalian toxicology section
Impact on Human and Animal Health
Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1)
Rate and extent of absorption: rapid (80 % within 24h)
Distribution: Uniformly distributed; highest tissue levels found in thyroid, adrenals, liver and eyes
Potential for accumulation: no evidence for accumulation
Rate and extent of excretion: rapid and extensive, (approx. 94 %) within 96 hours; mainly via urine (82 %)
Metabolism in animals completely metabolized ; main metabolites “BTS 39098“ (4-formamido-m-toluic acid), “FBC 31158“ (4- acetomido-m-toluic acid), BTS 27271 (N-2,4- dimethylphenyl-N-methylformamidine) cleavage reactions and mainly oxidation reactions followed by conjugation
Toxicologically significant compounds (animals, parent compound; metabolite BTS 27271 plants and environment) (pharmacologically active);
Acute toxicity (Annex IIA, point 5.2)
Rat LD50 oral approx. 600 mg/kg bw Xn, R 22
Rat LD50 dermal > 1600 mg/kg bw
Rat LC50 inhalation 65 mg/l air (6 h; aerosol) Skin irritation (rabbit) not irritant
Eye irritation (rabbit) not irritant
Skin sensitization (test method used and result) sensitising (Maximisation test) Xi, R 43
Short term toxicity (Annex IIA, point 5.3)
Target / critical effect body weight, liver; behavioural effects
Lowest relevant oral NOAEL / NOEL 0.25 mg/kg bw/d (90 days; dog) Xn, R48/22
Lowest relevant dermal NOEL / NOAEL no valid data, no data required Lowest relevant inhalation NOAEL / 0.01 mg/l air (3 weeks, rat); [1.26 mg/kg bw] NOEL
Genotoxicity (Annex IIA, point 5.4) no genotoxic potential
9 Report from ECCO 78 - / amitraz /
Long term toxicity and carcinogenicity (Annex IIA, point 5.5)
Target/critical effect decreased body weight gain, behavioural effects
Lowest relevant oral NOAEL / NOEL 0.25 mg/kg bw/d (2 years oral toxicity study in dogs)
Carcinogenicity liver adenomas and carcinomas in female B6C3F1 -mice lymphoreticular tumours in female CFLP-mice further information required for classification
Reproductive toxicity (Annex IIA, point 5.6)
Reproduction target / critical effect adverse effect during lactation period and impaired parental care R 64
Lowest relevant reproductive NOAEL / NOEL 1.3 mg/kg bw/d (rat)
Developmental target / critical effect no teratogenic potential but foetotoxic at maternal toxic dose
Lowest relevant developmental NOAEL /NOEL 6 mg/kg bw/d (rabbit)
Neurotoxicity / Delayed neurotoxicity (Annex IIA, point 5.7) Neuro-endocrine effects on behaviour, cardio-vascular parameters and hormone secretion after single and repeat dose administration. Impaired alertness in humans. Acute neurotoxic NOAEL: 0.1 mg/kg/day
Other toxicological studies (Annex IIA, point 5.8)
Competitive inhibition of the a2-adrenoreceptor functions, including CNS.
metabolite 27271:acute oral LD50 approx. 200 mg/kg bw; no genotoxic potential; more active than parent compound in subchronic studies; NOAEL 0.1 mg/kg bw/d (90 day dog)
10 Report from ECCO 78 - / amitraz /
Medical data (Annex IIA, point 5.9) after direct skin contact: skin flushing effects and skin rashes after acute oral ingestion: CNS depression (ranging from sleepiness to deep coma
Summary (Annex IIA, point Value Study Safety factor 5.10) ADI (provisional) 0.0025 mg/kg bw/d chronic toxicity dog 100
AOEL (systemic; provisional) 0.0025 mg/kg bw/d chronic toxicity dog 100
Drinking water limit 0.1 µg/l
ARfD (acute reference dose) in the same order of magnitude as the ADI (0.0025 mg/kg bw/d)
Dermal absorption (Annex IIIA, point 7.3) concentrate: 1% absorption rate spray dilution: 10 % absorption rate
Acceptable exposure scenarios (including method of calculation) Operator to be re-calculated
Workers to be re-calculated
Bystanders to be re-calculated
Classification and proposed labelling (Annex IIA, point 10) with regard to toxicological data Xn, R22, R48/22, R64, Xi R43,
11 Report from ECCO 78 - / amitraz /
Appendix 4
SUGGESTED CLASSIFICATION AND LABELLING: AMITRAZ
4 Mammalian toxicology section
Hazard symbol Xn Harmful Xi Irritant Risk phrase R22 Harmful if swallowed R43 May cause sensitisation by skin contact R48/22 Harmful, danger of serious damage to health by prolonged exposure if swallowed R64 May cause harm to breastfed babies
Classification for R40 to be considered following submission of the re-evaluation of the long term studies by the main data submitter.
12 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
DISCLAIMER
PLEASE NOTE THAT THIS DOCUMENT IS AN EXCERPT OF THE REPORT OF AN ECCO (European Commission Co-ordination) PEER REVIEW MEETING
CONCISE OUTLINE REPORT OF ECCO 80 PEER REVIEW MEETING
Peer Review Programme under Directive 91/414/EEC
Subject: Meeting to discuss Fate and Behaviour, chapter 2.6.2 ”Definition of the residues relevant to the environment”, chapter 2.8 ”Fate and behaviour in the environment” and chapter 2.10 "classification and labelling" (Volume 1), of the monographs on
- famoxadone (NAS) NAS = new active substance - CGA 245 704 (NAS) EAS = existing active substance - thiram (EAS) - ziram (EAS) - amitraz (EAS)
Date: 25 - 28 May 1999
Venue: PSD/York
Attendance: Mr. Griffin (Chairperson) Ms. Ecker (Austria) Mr. Pussemier (Belgium) Mr. Schinkel (Germany) Mr. Soulas (France) Mr. Hansen (Denmark) Mr. Maier (European Commission, DGVI) Ms. Riley (ECCO-TEAM (PSD)/Report)
Summary of the meeting: The experts identified and discussed the lists of end points of the compartments soil, water and air using templates provided by the corresponding rapporteur Member State. Where appropriate, separate lists of data requirements and studies relied upon for which data protection has been claimed (for existing active substances only) were agreed on. The proposals for “definition of the residues relevant to the environment” and for “classification/labelling” have been reviewed. Areas of concern related to each active substance and restricted to this section were pointed out where necessary. Specific comments on the monographs were added and several general issues have been discussed as detailed below.
1 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
General comments concerning study requirements and evaluation of studies in the section Fate and Behaviour are listed below.
1. For calculations of PECs the group agreed in general to follow the assumption that the active substance was incorporated into the first 5 cm of top soil, as recommended in Directive 91/414/EEC. 2. General comments were made with regard to the End point sheets; where values were reported as atypical, a footnote, containing an explanation, should be included. o 3. Regarding route of degradation in soil, where DT50lab data at 10 C had not been generated, the group noted the draft findings of the Focus Group which concluded that extrapolation might be possible from data obtained at 20 oC. However, the group agreed that extrapolation may not be appropriate for every pesticide. 4. The group noted that for rate of degradation in soil where there were a large number of results, it would be useful to quote the range of DT50 values together with the median DT50 value, in the End point sheets. 5. Where a compound appeared to be strongly absorbed and persistent, although leaching to ground water was very unlikely, it might still be possible. The group considered that a standardised phrase be adopted in such circumstances to report the findings in the End point sheets: “On the basis of current knowledge it is considered unlikely that parent or relevant metabolites will leach to ground water. Therefore contamination of ground water in excess of 0.1 μg/l is not expected”. 6. Regarding soil adsorption and desorption, when commenting on pH dependence of particular compounds, it was considered preferable to state ‘not apparent’, rather than ‘no pH dependence’, where the data provided were limited.
7. When calculating PECs values, where the pesticide application was pre-emergence or early post-emergence, the percentage plant cover was assumed to be 0%. However, for applications later than early post-emergence, the group agreed that a default of 50% plant cover should be assumed in all cases.
8. The group agreed that when calculating PEC values, where the DT50 was ≤ 2 days, it was not necessary to calculate PEC values using time weighted averages (TWA’s). Also, for multiple applications where the DT90 value was greater than the interval between applications, it was considered useful to give PEC values for both single and multiple applications. The group also noted that there were no standard guidelines for calculating plateau concentrations, although plateau concentrations would only be required where a compound appeared to be persistent. 9. The group noted that at the completeness check stage, the dossier (particularly for review active substances) could appear to be complete. However, upon evaluation, substantial data gaps might become apparent. A more thorough completeness check could possibly identify these data gaps, although this would take more time and resource. 10. Regarding route of degradation in soil, where high levels of ‘bound’ residues were observed, the group considered that further guidance on residues associated with the biomass would be useful. 11. The information reported in the End point sheets for PEC values, such as method of calculation information, should be concise and kept to the minimum relevant information. The group considered that standard assumptions and additional relevant information relating to the calculation of PEC values should be reported in the monograph only.
12. Although the main data submitter/applicant should propose DT50 values, it was the responsibility of the rapporteur to consider whether the DT50 values were representative
2 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
of the data presented. If not, then the DT50 values should be recalculated by the rapporteur. The group noted that DT50 values were normally calculated by linear regression analysis, although first order kinetics should not automatically be assumed.
13. The group suggested that in the future, the End point sheets include a section for DT50sed and DT90sed (in addition to DT50/90 values for water and the whole system, as was already reported in the End point sheets) as this information might be useful to the Ecotoxicology ECCO meetings. 14. As the PEC calculations made reference to the agreed application rates, until the GAP for all the discussed active substances had been confirmed by the relevant ECCO meeting, the PEC values could not be confirmed.
The following documents were tabled at the meeting: Date Supplier Content ECCO Ref No. 25 May 1999 ECCO 76 CGA 245 704/Thiram/ 6439/ECCO/PSD/99 Ziram/Amitraz/Lindane/ Glyphosate: Questions and Information 26 May 1999 Ms. Ecker Amitraz: 6442/ECCO/PSD/99 water/sediment studies 26 May 1999 Ms. Ecker Amitraz: 6443/ECCO/PSD/99 PEC surface water calculations
3 Report from ECCO 80 - / amitraz / 6441/ECCO/PSD/99 2 June 1999
Specific comments on the active substances in the section Fate and Behaviour are listed below. The conclusions of the meeting were as follows:
AMITRAZ
Rapporteur Member State: Austria
1. All comments received were discussed: Date Supplier ECCO Ref No. 19 April 1999 UK 6436/ECCO/PSD/99 22 April 1999 The Netherlands 6437/ECCO/PSD/99
2. Definition of the residues relevant to the environment: Amitraz, BTS 27271, BTS 27919 and BTS 24868 (soil and water).
3. Data on preparations: The data set were considered almost complete, except for minor data gaps – e.g. The main data submitter must address the possibility of leaching to ground water from amitraz and all relevant metabolites.
4. Classification and labelling: No proposal was made at the meeting.
5. Claims for data protection: The group agreed to the list proposed by the rapporteur Member State (see Appendix 3).
6. Recommended restrictions/conditions for use: No proposal was made at the meeting.
Areas of concern: None
Appendix 1: ECCO 80 reporting table: amitraz
Appendix 2: List of end points: amitraz
Appendix 3: List of studies for which the main submitter has claimed data protection and which during the re-evaluation process were considered as essential for the evaluation with a view to Annex I inclusion: amitraz
Appendix 4: Suggested classification and labelling: amitraz
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Appendix 1: ECCO 80 reporting table Amitraz (Ac, In)
2. Environmental Fate and Behaviour
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(i) Route of degradation The group noted that amitraz was quickly degraded, therefore although there in soil were high levels of unextractable bound residues, they were unlikely to consist of parent compound. They agreed that there was sufficient information on non- extractable residues, and bound residues were not of concern.
(ii) Rate of degradation in soil The End point sheet should be amended to reflect the soil studies conducted, i.e. Open point: RMS to amend (lab) 4 soils for parent compound, 2 soils for the 3 major metabolites (BTS 27271, End point sheet; refer to BTS 27919, BTS 24868). The group were content to accept only 2 soil studies number of soil studies for for the major metabolites, as the results were consistent. amitraz and major o The DT50lab at 10 C had not been provided. Therefore the DT50lab for amitraz metabolites; extrapolate the and the major metabolites must be extrapolated from the data available at other DT50lab for amitraz and temperatures. major metabolites.
For anaerobic degradation, the DT50 was reported as >1 day. This was incorrect Open point: RMS to amend and should be amended to <1 day. the End point sheet; anaerobic DT50 should be < 1 day. (iii) Rate of degradation As the field data were not relevant, the group agreed that the results be removed Open point: RMS to delete in soil (field) from the End point sheet and state ‘no relevant information’ instead. field results from End point sheet and state ‘no relevant information’.
5 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(iv) Soil adsorption/ The group considered that the adsorption / desorption studies were questionable Open point: RMS to amend desorption and due to the instability of amitraz. Also, the group agreed that the Koc values were End point sheet to state that mobility unreliable. However, although it was not possible to quantify the mobility of Koc values for amitraz are amitraz and the major metabolites, Koc values for amitraz were not relevant, as ‘not relevant’. it degraded quickly, therefore was likely to be of low mobility. There was sufficient information on amitraz and the major metabolites to conclude that leaching was not of concern. (v) PECs Due to the rapid degradation of amitraz, together with an application interval of 2 weeks, the Open point: RMS to report group considered it relevant to report only PEC values for a single application. End points only single application PEC should be amended accordingly. calculations. Report only The meeting agreed that for the major metabolites (BTS 27271, BTS 27919 and BTS 24868), only the maximum concentration reached needed to be reported in the End point sheet. The % of the maximum concentration applied amitraz, should be deleted. for major metabolites (BTS
The group also considered that the maximum concentration and DT50 for metabolite BTS 24868 27271, BTS 27919 and BTS should be calculated. 24868) and delete the % amount. Also report the DT50 for BTS 24868. (vi) Route and rate of The hydrolysis rates for amitraz should be added to the End point sheet. As the Open point: RMS to update degradation in water values were high, they should be reported as days or years (not hours). End point sheet to include Also, the results for readily biodegradable should be changed to ‘not readily hydrolysis rates and change biodegradable’. units to days/years. Report as ‘not readily biodegradable’.
(vii) Water/ sediment As DT50sed was available, as agreed by the meeting, where available, this should Open point: RMS to report systems be reported in the End point sheet as it may be of use to the Ecotoxicology DT50sed in End point sheet. ECCO meeting.
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No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(viii PECsw The group considered that the worst case use scenario should be used to Open point: RMS to amend ) calculate PECsw values. They agreed that both hops and orchard uses were worst the End point sheet; case uses, therefore the End point sheet should be amended to report PEC values calculate PECsw for hops for hops and orchard use. For the method of calculation, a DT50 of 0.6 days was and orchard uses, assuming considered appropriate. a DT50 of 0.6 days.
(ix) PECsw (metabolites) From the table reported in the End point sheet, it was not possible to calculate Open point: RMS to the maximum concentration where the results were reported as ‘increasing’. calculate PECsw metabolites Therefore, the PEC value should be taken from the actual maximum using the maximum concentration reported in the tables. The PEC values should be amended and the concentration reported in DT50 values reported also. the tables; report DT50 values also.
(x) PECgw As there was no reliable information, the PECgw maximum concentration and 2.1 Address the possibility of average annual concentration should be deleted from the End point sheet. leaching to ground water Where the method of calculation referred to ‘no calculation necessary’, the from amitraz and major group agreed this should also be deleted. metabolites. PECgw values The group agreed that the main data submitter must address the possibility of should be calculated using leaching to ground water from the parent compound and other relevant an appropriate method. metabolites. (IIIA, 9.2.1) Open point: RMS to delete results for PECgw maximum concentration and average annual concentration; the method of calculation should state ‘no calculation submitted’.
7 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(xi) PECa The group agreed that the main data submitter should provide the Atkinson 2.2 Provide the Atkinson calculation for amitraz and the 3 major metabolites (BTS 27271, BTS 27919, calculation for amitraz, BTS BTS 24868). 27271, BTS 27919 and BTS The RMS should also state the vapour pressure (if available) in the End point 24868. (IIA, 7.2.2) sheet, for amitraz, BTS 27271, BTS 27919 and BTS 24868. Regarding direct Open point: RMS to report photolysis in air, the quantum yield for amitraz must also be reported here. vapour pressure in the End point sheet for amitraz, BTS 27271, BTS 27919 and BTS 24868 (if available). Also, report the quantum yield for amitraz. (xii) Monitoring data The results should be amended to state ‘not submitted’, instead of ‘not submitted Open point: RMS to remove and not necessary’. the statement ‘and not necessary’ from the monitoring results as reported in the End point sheet. (xiii Definition of the The agreed residue definition must be reported in the End point sheet. Soil and Open point: RMS to report ) residue surface water: amitraz, BTS 27271, BTS 27919 and BTS 24868. residue definition in the End point sheet. Soil and surface water: amitraz, BTS 27271, BTS 27919 and BTS 24868.
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Appendix 2
LIST OF END POINTS: AMITRAZ
2 Fate and behaviour section
Route of degradation (aerobic) in soil (Annex IIA, point 7.1.1.1.1) 2-methyl radiolabelled amitraz in two soils, 6 mg/kg at 25°C ± 2°C and 50 % MHC
Mineralization after 100 days (90/120 d) 15-24 % / 20-27 %
Non-extractable residues after 100 days 61-78 % / 71-73 % (90/120 d)
Relevant metabolites- name and/or N-Methyl-N'-(2,4-xylyl) formamidine (BTS 27271; code- % of applied (range and active metabolite): 0,2-7 % (maximum day 2) maximum) Form-2', 4'-xylidine (BTS 27919): 0,2-34 % (maximum day 1) 2,4-Dimethylaniline (BTS 24868): 0,2-11 % (maximum 3 hrs)
Route of degradation in soil - Supplemental studies (Annex IIA, point 7.1.1.1.2) Anaerobic degradation Very rapidly degraded, DT50: <1 d Amitraz, radiolabelled in the 2-methyl- 1,5-2,5 % in water position of either phenyl ring 79 - 85 % soil ‘bound’ residues (maximum day 0) 6 mg/kg to two soils BTS 27919 (up to 13 %, day 30), aerobic 30 days at 25° C ± 2°C and 50 BTS 27271 (up to 1,3 %, day 60) % MHC BTS 24868 (up to 5,5 %, day 60)
Sterile degradation Chemical hydrolysis led to the rapid decay
25°C and 50 % MHC BTS 27919 (63 %, 14 d), BTS 27271 (6 %, 1 d), BTS 24868 (12 %, 0 d) Soil ‘bound’ residues (2-44 %, 30 d)
Soil photolysis Amitraz: DT50 = 7.7 minutes (dark controls: DT50 = 47.5 minutes) [14C]-ring labelled amitraz BTS 27919 (36 %, 30 min, in the dark: 27 %, 30 min), BTS 27271 (10 %, 30 min, in the dark: 8 %, 30 min)
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Rate of degradation in soil (Annex IIA, point 7.1.1.2, Annex IIIA, point 9.1.1) Method of calculation TOPFIT version IBM 1.57E (two compartment model) Amitraz: Two soils, 50 % MHC, 25+/-2°C Two soils, 40 % MHC, 20+/-2°C Metabolites: Two soils, 50 % MHC, 25+/-2°C
Laboratory studies (range or median, DT50lab (20°C, aerobic): with n value, with r2 value Amitraz: 0,27 - 0,33 d
DT50lab (25°C, aerobic): Amitraz: 0,08 - 0,17 d BTS 27271: 0,5 - 2,4 d BTS 27919: 4,1 - 6,4 d BTS 24868: 0,27 - 3,3 d
DT90lab (20°C, aerobic): Amitraz: 1,4 - 5,9 d
DT90lab (25°C, aerobic): Amitraz: 0,26 - 1,0 d BTS 27271: 11 - 29 d BTS 27919: 62 - 98 d BTS 24868: 1,2 - 51 d
DT50lab (10°C, aerobic): not submitted
DT50lab (25°C, anaerobic): Amitraz: < 1 d Field studies (state location, range or median with n value) no relevant information
Soil accumulation and plateau -- concentration
Soil adsorption/desorption (Annex IIA, point 7.1.2)
Kf/Koc Kd: 8 – 60 4 soils were tested: The slurries had been adjusted to pH 8 with 10 N sodium hydroxide solution to reduce the rate of hydrolysis of the pH: 5,1 - 6,9 parent compound, because Amitraz hydrolyses rapidly in %OC: 0,4 - 4,4 soil and water. pH dependence (yes/no) --
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Mobility in soil (Annex IIA, point 7.1.3, Annex IIIA, point 9.1.2) Because of the rapid breakdown of amitraz in soil and water the mobility of amitraz has been investigated by soil thin layer chromatography. The bulk of the amitraz related material was of low mobility.
Column leaching BTS 27271: Less than 0.3 % was detected in the percolate. BTS 27919: 0.7 – 3.1 % of the applied radioactivity was detected in the leachate.
Aged residues leaching Of [14C]-ring labelled amitraz, ageing period: 3 d Radioactivity in the leachate: 1,1 - 5,0 % AR No Amitraz or known metabolites were detected, only polar material was detected.
Lysimeter /field leaching studies --
PEC (soil) (Annex IIIA, point 9.1.3) -k x t -ln2/DT50 x t Method of calculation actual: C(t) = C(0) x e = C(0) x e
(-t x ln2/DT50) time weighted: C(t) = C(0) x DT50/(t x ln2) x (1 - e ) Assumptions single application due to very low DT50; 50 % reaches the ground; soil density: 1.5 g/cm3; incorporation and homogenous distribution within 5 cm soil
DT50 Amitraz: 0.3 days
PEC (s) Actual Time Actual Time Actual Time weighted weighted weighted µg/kg average average average Application rate 600 g/ha 800 g/ha 2 500 g/ha initial 400.000 533.333 1666.666 short term 24 h 39.685 155.947 52.913 207.929 165.354 649.781 2 d 3.937 85.709 5.249 114.279 16.405 357.124 4 d 0.000 43.277 0.521 57.702 0.161 180.319 long term 7 d 0.000 24.732 0.000 32.976 0.000 103.049 14 d 0.000 12.366 0.000 16.488 0.000 51.525 21 d 0.000 8.244 0.000 10.992 0.000 34.349 28 d 0.000 6.183 0.000 8.244 0.000 25.672 50 d 0.000 3.462 0.000 4.617 0.000 14.427 100 d 0.000 1.731 0.000 2.308 0.000 7.213
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PEC (s) Actual Time Actual Time Actual Time weighted weighted weighted µg/kg average average average Application rate 600 g/ha 800 g/ha 2 500 g/ha
Metabolites molec. weight maximum conc. in soil day when max. reached DT50 (d) BTS 27271 162.2 0.237 mg/kg 0 0.5 - 2.4 BTS 27919 131.4 1 0.526 mg/kg 4.1 - 6.4 BTS 24868 101.2 0 0.156 mg/kg 0.3 - 3.3
Route and rate of degradation in water (Annex IIA, point 7.2.1)
Hydrolysis of Amitraz (DT50) pH 5 : 2 hrs 25° C pH 7 : 22 hrs pH 9 : 26 hrs
Hydrolysis of relevant metabolites (DT50) pH 5 : BTS 27271: stable 25° C BTS 27919: 95 days
pH 7 : BTS 27271: 14 days BTS 27919: 604 days
pH 9 : BTS 27271: 5 hrs BTS 27919: 20.7 days
Photolytic degradation of Amitraz pH 7 : 2 - 4 days
Quantum yield of Amitraz 5.93 x 10-5 (molecules degraded per photon absorbed)
Photolytic degradation of relevant BTS 27 271: stable metabolites BTS 27 919: stable
Readily biodegradable (yes/no) no
Degradation in water/sediment- system: Water whole system sediment
DT50 a.i.: 0.3-0.6 d 1.3-1.9 d 12-14 d (8° C)
1.7-3.4 hrs 3.6-6 hrs 4-20 d (25° C) BTS 27 271: 3.3-7 d 6.1-7.7 d - “
* after repeated applications 1.2 d 53 d - (25° C)* (data not used for calculations) BTS 27 919: 9-20 d 10-21 d 7-33 d (25° C) 10 d 11 d - (25° C)* BTS 24 868: ~24 d 32 d - “
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Distribution in water/sediment systems Following repeated applications (% AR): (as) Water Sediment 25° C 1 d 7.8 % 2.5 % 10 d n.d % 1.4 % 20 d n.d % 1.5 % 59 d n.d % 1.1 %
Distribution in water/sediment systems Following repeated applications (% AR): (metabolites) BTS 27919 BTS 27271 25° C Water Sediment Water Sediment 1 d 33 % 10.6 % n.d. 0.9 % 10 d 31.7 % 7.5 % n.d. 2.3 % 20 d 23.1 % 3.1 % 9.7 % 1.3 % 59 d 1.2 % 1.3 % 0.6 % 1.4 %
Distribution in water/sediment systems Amitraz BTS 27919 BTS 27271 of Amitraz and metabolites in % AR at Water Sedim. Water Sedim. Water Sedim.
8° C 1d 21-28 13-18 4-7 11-16 3-7 0.8-1 10d 0.8-4 9.7-13 11-21 12-13 1.5-5 0.5-1.8 30d n.d-1.9 2.6-3 20-25 8-10 nd-1.5 1.7-3.4
Field or mesocosm studies ---
PEC (surface water) (Annex IIIA, point 9.2.3) -ln2/DT50*t Method of calculation Actual: C(t) = C(0)*e
(-t*ln2/DT50) time weighted: C(t) = C(0)*T50/(t*ln2)*(1 – e ) Application rate Hops: 2,5 kg/ha Vegetables, ornamentals: 800 g/ha single application (due to rapid degradation) 30 cm water depth
Main routes of entry Spray drift: Hops: 5 m distance (12.5 %), 50 m distance (0.3 %) Vegetables, ornamentals (>50 cm): 5 m (5 %); 20 m (0.4 %)
DT50 Amitraz 0.6 days
13 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
PEC (sw) Actual Time weighted Actual Time weighted average average µg/l
2 500 g/ha 800 g/ha
12.5 % 0.3 % 12.5 % 0.3 % 5 % 0.4 % 5 % 0.4 %
Initial 104.167 2.500 104.167 2.500 13.333 1.067 13.333 1.067
Short term 24 h 32.810 0.787 61.767 1.482 4.199 0.336 7.906 0.632 2 d 10.335 0.248 40.611 0.975 1.323 0.106 5.198 0.416 4 d 1.025 0.025 22.320 0.536 0.131 0.010 2.857 0.228
Long term 7 d 0.032 0.001 12.877 0.309 0.004 0.000 1.648 0.132 14 d 0.000 0.000 6.441 0.155 0.000 0.000 0.824 0.066 21d 0.000 0.000 4.294 0.103 0.000 0.000 0.549 0.044 28 d 0.000 0.000 3.220 0.077 0.000 0.000 0.412 0.033 50 d 0.000 0.000 1.803 0.043 0.000 0.000 0.231 0.018 100 d 0.000 0.000 0.902 0.022 0.000 0.000 0.115 0.009
Metabolites BTS 27271: DT50 = 7 days (Maximum concentration on day 3)
BTS 27919 : DT50 = 20 days (Maximum concentration on day 3 or 7) BTS 24868 : >10 % only at 1 measurement point (day 14)
Conc.max in water µg/l µg/l µg/l µg/l BTS 27271 31.1 0.75 3.98 0.33 BTS 27919 50.4 1.21 6.45 0.53 BTS 24868 9.5 0.23 1.22 0.1
PEC (sediment) -ln2/DT50*t Method of calculation Actual: C(t) = C(0)*e
(-t*ln2/DT50) time weighted: C(t) = C(0)*T50/(t*ln2)*(1 – e ) Application rate Hops: 2 x 2,5 kg/ha Vegetables: 3 x 800 g/ha; 14 day interval maximum concentration in sediment: 23 % AR incorporation into 3 cm sediment layer; density: 1.5
DT50 Amitraz 14 days
PEC (SED) Actual Time weighted Actual Time weighted average average µg/l
2 x 2 500 g/ha 3 x 800 g/ha
Spray drift 12.5 % 0.3 % 12.5 % 0.3 % 5 % 0.4 % 5 % 0.4 %
Initial 243.750 5.850 - - 42.862 3.429 - -
14 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
PEC (SED) Actual Time weighted Actual Time weighted average average µg/l
Short term* 24 h 231.976 5.567 125.258 3.006 40.791 3.263 19.838 1.587 2 d 220.770 5.298 131.575 3.158 38.821 3.106 20.706 1.656 4 d 199.957 4.799 140.311 3.367 35.161 2.813 22.007 1.761
Long term* 7 d 172.357 4.137 146.811 3.523 30.308 2.425 23.149 1.852 14 d 121.875 2.925 146.524 3.517 21.431 1.714 23.642 1.891 21d 86.179 2.068 137.819 3.308 15.154 1.212 22.721 1.818 28 d 60.938 1.462 126.987 3.048 10.715 0.857 21.304 1.704 50 d 20.504 0.492 96.096 2.306 3.605 0.288 16.726 1.338 100 d 1.725 0.041 57.276 1.374 0.303 0.024 10.365 0.829
Metabolites BTS 27919: DT50 = 33 days (Maximum concentration on day 0-1) BTS 27271: minor BTS 24868: minor
Conc.max sediment µg/kg µg/kg µg/kg µg/kg **BTS 27919 13.999 0.336 1.791 0.148 * nach der letzten Anwendung ** nach einmaliger Applikation
PEC (ground water) (Annex IIIA, point 9.2.1) Method of calculation No calculation submitted
Application rate --
PEC (gw) Maximum concentration -
Average annual concentration -
Fate and behaviour in air (Annex IIA, point 7.2.2, Annex III, point 9.3) Direct photolysis in air no study submitted
Quantum yield 5.93 x 10-5 (molecules degraded per photon absorbed)
Photochemical oxidative degradation in no calculation submitted air (DT50) Volatilisation from plant surfaces: no study submitted
from soil: up to 12 % during 18 days
Vapour pressure (in Pa, state Amitraz: 3.4 x 10-4 Pa at 25°C temperature) BTS 27271: 0.12 Pa (interpolated) BTS: 27919: 4.1 x 10-4 Pa (extrapolated)
PEC (air) Method of calculation no calculation
15 Report from ECCO 80 - amitraz / 6441/ECCO/PSD/99 2 June 1999
PEC (a)
Maximum concentration -
Definition of the Residues (Annex IIA, point 7.3 Relevant to the environment Soil: Amitraz, BTS 27271, BTS 27919, BTS 24868 Water: Amitraz, BTS 27271, BTS 27919, BTS 24868
Monitoring data (Annex IIA, point 7.4)
Soil Not submitted
Surface water Not submitted
Ground water Not submitted
Air Not submitted
Appendix 4
SUGGESTED CLASSIFICATION AND LABELLING: AMITRAZ
2 Fate and behaviour section
No proposal was made at the meeting.
16 Report from ECCO 82 - amitraz / 6441/ECCO/PSD/99 July 1999
Page 1 of 15 DISCLAIMER
PLEASE NOTE THAT THIS DOCUMENT IS AN EXCERPT OF THE REPORT OF AN ECCO (European Commission Co-ordination) PEER REVIEW MEETING
CONCISE OUTLINE REPORT OF ECCO 82 PEER REVIEW MEETING
Peer Review Programme under Directive 91/414/EEC
Subject: Meeting to discuss Residues, chapter 2.6 ”Definition of the residues” and chapter 2.7 ”Residues” (Volume 1), of the monographs on:
- famoxadone (NAS) NAS = new active substance - CGA 245 704 (NAS) EAS = existing active substance - thiram (EAS) - ziram (EAS) - amitraz (EAS)
Date: 29 June – 2 July 1999
Venue: PSD/York
Attendance: Ms Harris (Chairperson) Ms Bosman-Hoefakker (The Netherlands) Mr Declercq (France) Mr Mohimont (Belgium) Mr Prohaska (Austria) Mr Storzer (Germany) Mr Nolan (Commission DGVI) Ms Bartlett (ECCO-TEAM (PSD)/Report)
Summary of the meeting: The experts identified and discussed the end points of famoxadone, CGA 245 704, thiram, ziram, amitraz, lindane, glyphosate and glyphosate-trimesium using templates provided by the corresponding rapporteur Member State. Where appropriate, separate lists of data requirements and studies relied upon (for which data protection has been claimed) were agreed on. Areas of concern related to each active substance and restricted to the section ”Residues” were pointed out. Specific comments on the monographs were added and several general issues have been discussed as detailed below.
Report from ECCO 82 - amitraz / 6441/ECCO/PSD/99 July 1999
Page 2 of 15
Specific comments on the active substances in the section Residues are listed below. The conclusions of the meeting were as follows:
AMITRAZ
Rapporteur Member State: Austria
1. All comments received were discussed: Date Supplier ECCO Ref No. 22.6.99 The Netherlands 6501/ECCO/PSD/99 22.6.99 AgrEvo 6502/ECCO/PSD/99 22.6.99 Germany 6503/ECCO/PSD/99 22.6.99 UK 6504/ECCO/PSD/99 1.7.99 Austria 6534/ECCO/PSD/99 2.7.99 Austria 6537/ECCO/PSD/99 2.7.99 ECCO 82 6538/ECCO/PSD/99
2. Definition of the residues: Amitraz.
3. Classification and labelling: No proposal was made at the meeting.
4. Claims for data protection: All data relied on by the Rapporteur were considered as essential except 8 studies (which did not support intended uses or the relevant end point).
5. Recommended restrictions/conditions for use: None proposed at meeting.
Areas of concern: Initial calculations by the RMS indicated that the acute reference dose was significantly exceeded for all commodities.
Appendix 1: ECCO 82 reporting table: amitraz
Appendix 2: List of end points: amitraz
Appendix 3: List of studies for which the main submitter has claimed data protection and which during the re-evaluation process were considered as essential for the evaluation with a view to Annex I inclusion: amitraz
Appendix 4: Suggested classification and labelling: amitraz
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Page 3 of 15 Appendix 1: ECCO 82 reporting table Amitraz (Ac, In)
5. Residues
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(i) Metabolism – plants It was noted that for the intended use of amitraz on hops, a metabolism study - - was not submitted as the notifier considered hops to be in the fruit crop group (following guidance from Germany). However, the meeting agreed that sufficient information was available on leaves from the cotton metabolism study to indicate the metabolic pathway of hops and that no further information was required. (ii) Residue definition The meeting agreed the residue definition as stated in the end points although it - - – plants was noted that the common moiety method of analysis may not be appropriate for enforcement purposes. (iii) Metabolism – The animal metabolism studies were on the border of acceptability. However, given the - - animals expected low intakes from the animal diet the meeting did not propose a residue definition for products of animal origin. If future changes are made to the GAP which would result in significant intakes by animals, further data would be required although the animal residue definition was likely to be as stated in the end points. (iv) MRLs – plants For those intended uses where an MRL has already been set in the legislation, 5.1 For those intended uses data to confirm the MRL are required. where an MRL has already been set in the legislation, data to confirm the MRL are required. (IIA 6.3) (v) MRLs – citrus US trials data were submitted. These data do not represent EU GAP so can only - - except oranges be used to set an STMR for risk assessment purposes. An MRL at the limit of determination of 0.05 mg/kg was set as the notifier does not intend to support these uses any further.
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Page 4 of 15 No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(vi) MRLs – oranges US trials data were submitted. These data do not represent EU GAP so can only be used to set 5.2 Further data are required to an STMR for risk assessment purposes. Further data are required to set an MRL. set an MRL for the intended use of amitraz on oranges. (IIA 6.3) (vii) MRLs – pome fruits Further residues trials to support the intended use of pome fruits are required. 5.3 The GAP for pome fruits will need to be revised to In the comments submitted by the notifier referring to new residue trials on pome fruit, it was support a lower MRL and noted that in order to reduce residues the latest application was to be no later than growth stage reduce unacceptable 77 (fruit 70% of final diameter). The meeting did not consider this approach to be acceptable and concluded that to reduce residue levels a longer pre harvest interval should be stated instead consumer exposure levels. of a latest time of application. The GAP for pome fruits will need to be revised to support a (IIIA 3.3) lower MRL and reduce unacceptable consumer exposure levels. (viii) stone fruits An MRL at the limit of determination of 0.05 mg/kg was proposed as the notifier does not intend - - berries and to support these uses any further. soft fruit bananas (ix) MRLs – tomatoes Further data are being generated on tomatoes to support the amended intended use (2 5.4 Further data in support of and aubergines applications of 0.6 kg ai/ha). The intended use for aubergines has been amended and is now the amended GAP for equivalent to the GAP for tomatoes. Therefore, tomato data can be extrapolated to aubergines. Further data in support of the amended GAP for tomato are required to propose an MRL for tomato are required to set an tomatoes and aubergines. MRL for the intended use of amitraz on tomatoes and aubergines. (IIA 6.3) (x) MRLs – pepper The intended use for peppers is in the field, yet the critical GAP is for glasshouse use. The data - - submitted (2 x field trials, 8 x protected trials) were sufficient to propose an MRL of 2 mg/kg in line with that for the open position. (xi) MRLs – cucurbits An MRL at the limit of determination of 0.05 mg/kg was proposed, as the - - – edible peel notifier does not intend to support this use any further.
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Page 5 of 15 No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(xii) MRLs – cucurbits It was noted that the number of applications and PHI used in the data submitted in support of the 5.5 Clarification of the GAP for – inedible peel amended GAP for use of amitraz on melons differs from the intended use. However, the time of melons is required. application and PHI supports the critical GAP (Spanish) therefore allowing an MRL of 0.5 mg/kg to be proposed. Clarification of the GAP for melons is required. (IIIA 3.3) (xiii) MRLs – cotton Only US trials data were submitted. Further data have been submitted reflecting EU GAP. Open point: These data must be evaluated by the RMS and reported in the evaluation table and an MRL proposed accordingly. Residues trials data for cotton must be evaluated by the RMS and an MRL proposed. (xiv) MRLs – hops The current MRL is 50mg/kg. However, according to the Dixon test the results of 24 and 25 - - mg/kg are outliers and can be excluded from calculations. Therefore, an MRL of 20 mg/kg can be proposed. (xvi) Residues – honey The meeting sought information on the veterinary uses of amitraz, particularly 5.6 Information on the with regard to bees and possible residues of amitraz in honey. veterinary uses of amitraz, particularly with regard to bees and possible residues in honey is required. (xvii) Succeeding crops The 2 studies undertaken on succeeding crops showed high levels of - - uncharacterised bound residues. However, the meeting concluded that residues in succeeding crops were unlikely to be a problem given that no residues above the LOQ are expected. (xviii) Effects of In the processing trial on citrus, it was noted that despite amitraz having 5.7 Clarification is required of processing systemic activity, positive residues were found in pulp. Clarification is therefore which parts of the fruit were required of which parts of the fruit were analysed as ‘pulp’. analysed as ‘pulp’ in the processing study on citrus. (IIA 6.5)
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Page 6 of 15 No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(xix) Effects of The RMS must amend the end points to reflect the raw agricultural commodity Open point: processing for the processing factors e.g. dried hops to beer, whole fruit to juice. RMS to amend the end points to reflect the raw agricultural commodity for the processing factors e.g. dried hops to beer, whole fruit to juice. (xx) Effects of It was noted that the cattle in the livestock feeding study were not dosed with - - processing metabolites. However, the meeting concluded that the animals will have been sufficiently exposed to the metabolites during the study and therefore no further data are required. (xxi) Storage stability Difficulties were seen in storage of liver prior to analysis. Since intakes by animals are low and - - MRLs have not been proposed, this is not of concern. (xxii) Dietary intakes – The RMS must update the end points with the recalculations reflecting the newly Open point: chronic agreed MRL for hops. The RMS must update the end points with the recalculations of dietary intake reflecting the newly agreed MRL for hops. (xxiii) Dietary intakes – Recalculations using the revised consumption data indicate that the chronic Open point: chronic intakes are acceptable. The RMS must update the end points with the recalculations of dietary intakes (chronic) using the revised consumption data.
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Page 7 of 15 No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(xxiv) Dietary intakes – Initial calculation by the RMS indicated that the acute reference dose was Open point: acute significantly exceeded for all commodities. Recalculations using the revised The RMS must update the consumption data indicate that the acute reference dose is still significantly end points with the exceeded. The RMS must update the end points with these recalculations. recalculations of dietary Confirmation of the derivation of the acute reference dose value is sought from intakes (acute) using the the Overview meeting. The notifier must address the exceedence of the acute revised consumption data. reference dose. 5.8 The exceedence of the acute reference dose must be addressed. (IIA 6.9) Open point: Confirmation of the derivation of the acute reference dose value is sought from the Overview meeting.
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Page 8 of 15 Appendix 2
LIST OF END POINTS: AMITRAZ
5 Residues section
Residues
Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6) Plant groups covered grapes, apples, lemons, pears, cotton Rotational crops lettuce, radish, wheat Plant residue definition for monitoring Amitraz including the metabolites containing the 2,4-dimethylaniline moiety expressed as Amitraz Plant residue definition for risk assessment Amitraz including the metabolites containing the 2,4-dimethylaniline moiety expressed as Amitraz Conversion factor (monitoring to risk - assessment)
Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6) Animals covered lactating cow, laying hen Animal residue definition for monitoring due to the low intake by livestock, the residue definition for food of animal origin is not regarded necessary; if higher intake occurs (due to changing intended uses), the same residue definition as for food of plant origin should be used Animal residue definition for risk due to the low intake by livestock, the residue definition for food of animal origin is not assessment regarded necessary; if higher intake occurs (due to changing intended uses), the same residue definition as for food of plant origin should be used Conversion factor (monitoring to risk - assessment) Metabolism in rat and ruminant similar yes (yes/no) Fat soluble residue: (yes/no) Amitraz
Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5) no residues above the LoD expected ......
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Page 9 of 15
Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 introduction) stable for 2 years (oranges, tomatoes), 18 ...... months (hops) and 13 months (cottonseed); 1 ...... year (muscle, liver, fat, milk)
Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3) Intakes by livestock ≥ 0.1 mg/kg diet/day: Ruminant: Poultry: Pig: yes/no yes/no not assessed Muscle 0.05 mg/kg* 0.05 mg/kg* - Liver 0.05 mg/kg* 0.05 mg/kg* - Kidney 0.05 mg/kg* 0.05 mg/kg* - Fat 0.05 mg/kg* 0.05 mg/kg* - Milk 0.01 mg/kg* - - Eggs - 0.01 mg/kg* -
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Page 10 of 15 Summary of critical residues data (Annex IIA, point 6.3, Annex IIIA, point 8.2)
Crop Northern or Trials results relevant to the Recommendation/comments MRL1) STM Mediterranean critical GAP/intended uses1) R1 Region (a) (b) oranges US-trials PHI = 14 d.: 0.33. 0.5, 0.45, 0.49, 1.1, only US-trials (supporting further data 0.57 1.0, 0.99, 0.71-0.74 (8 trials) information), the results were used required to only for risk calculation; confirm the grapefruits US-trials PHI = 14: 0.51 - 0.63 (1 trial) further trials are considered already necessary; established EU-MRL2) further trials (oranges) are planned by the notifier; other citrus (like lemons) are not further supported by the notifier mandarines - no adequate data submitted further trials are considered 0.05* - necessary not further supported by the notifier pome fruits Northern Region apples: further data 0.36 PHI = 28 d.: 0.30-0.36, 0.74, 0.43, 0.32, are required 1.0 to confirm PHI = 29 d.: 0.25-0.31 the already 1 US-trial (New York): PHI = 14 d.: established 0.46-0.64 EU-MRL2) Southern Region pears: trials conducted in the Southern PHI = 30d.: 0.22, 0.36 Region are only useful in a limited PHI = 32 d.: 0.4 way (smaller amounts of a.i./ha and PHI = 34 d.: 0.26-0.28 longer PHIs than intended); further trials conducted in the Southern Region are required
the results were used only for risk calculation; with respect to the
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Page 11 of 15 Crop Northern or Trials results relevant to the Recommendation/comments MRL1) STM Mediterranean critical GAP/intended uses1) R1 Region (a) (b) acute risk assessment, further trials are planned by the notifier with changed application regime; it should be noted that lower amounts of a.i. and number of applications and a longer PHI are considered useful in order to reduce the residues of Amitraz stone fruits: 0.05* - peaches, Northern Region not intended in this region apricots Southern Region no adequate data submitted further trials are considered necessary not further supported by the notifier stone fruits: 0.05* - cherries, Northern Region no adequate data submitted further trials are considered plums necessary; not further supported by the notifier Southern Region no data submitted further trials are considered necessary; not further supported by the notifier strawberries Northern Region no data submitted trials are considered necessary; not 0.05* - further supported by the notifier Southern Region no data submitted trials are considered necessary; not further supported by the notifier glasshouse no data submitted trials are considered necessary; not further supported by the notifier currants Northern Region no adequate data submitted further trials are considered 0.05* - necessary; not further supported by
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Page 12 of 15 Crop Northern or Trials results relevant to the Recommendation/comments MRL1) STM Mediterranean critical GAP/intended uses1) R1 Region (a) (b) the notifier Southern Region no data submitted trials are considered necessary; not further supported by the notifier glasshouse no adequate data submitted further trials are considered necessary; not further supported by the notifier bananas Southern Region no data submitted trials are considered necessary; not 0.05* - supported by the notifier (AgrEvo) tomatoes Northern Region no adequate data submitted further trials are considered further data 0.37 necessary; not further supported by required to the notifier for this region confirm the Southern Region 1 x 1.2 kg a.i./ha; PHI = 3 d: 0.17, 0.37, further trials are considered already 0.55 necessary and planned by the established 1 x 1.4 kg a.i./ha; PHI = 3 d: 0.31 notifier EU-MRL2) 2 x 0.6 kg a.i./ha; PHI = 3 d: 0.41 aubergines no trials on aubergines available extrapolation from tomatoes peppers Northern Region no data submitted trials are considered necessary; not 2 0.61 further supported by the notifier for this region
Southern Region 3 x 0.8 kg a.i./ha; PHI = 14 d: 0.33, 0.51 2 trials (field) and 8 trials (2 trials, field) (protected); the results from all 3 x 0.8 kg a.i./ha; PHI = 14 d: 2 x 0.29, trials show that residues resulted 0.49, 0.71, 0.72, 0.80, 0.89, 1.5 (8 trials, from protected or field use were not protected) significantly different cucurbits - Northern Region no data submitted trials are considered necessary; not 0.05* - edible peel supported by the notifier Southern Region no data submitted trials are considered necessary; not supported by the notifier cucurbits - Northern Region no data submitted trials are considered necessary; not further 0.14
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Page 13 of 15 Crop Northern or Trials results relevant to the Recommendation/comments MRL1) STM Mediterranean critical GAP/intended uses1) R1 Region (a) (b) inedible peel further supported by the notifier for clarification (melons) this region required in order to Southern Region 2 x 0.5 kg a.i./ha; PHI = 14 d: 0.06, 3 x all trials conducted with 2 x 0.5 kg establish a 0.12, 0.14, 0.17, 0.25, 0.3, 0.31 (9 trials) a.i./ha (PHI = 14 d); the intended MRL of 0.5 use is stated by the notifier as 1 x 0.5 kg a.i./ha, PHI = 28 d; therefore, the intended use has to be clarified by the notifier; furthermore, the transfer of residues into the flesh/pulp has to be clarified cotton only intended in US-trials: only US-trials (supporting new data 0.3 the Southern PHI = 15 d.: 0.33, 0.21, 0.29, 0.81, 0.31, information); submitted (US Region of Europe 0.16, 0.32 further trials are considered have to be trials PHI = 20 d.: 0.33, 0.17, 0.41, 0.84, 0.29, necessary; evaluated in only) 0.41 the results of new trials were order to PHI = 23 d.: 0.08, 0.09 submitted by May 1999, but not yet establish a the results of new trials were not yet evaluated MRL evaluated hops Northern Region dried hops: 10 trials, sufficient data 20 5.3 PHI = 26 d.: 9.3, 7.2, 6.1 PHI = 27 d.: 1.3, 1.4, 1.9-2.1 PHI = 29 d.: 4.5, 7.3, 24-25 (outlier; not included in the MRL-calculation), 5.3 (a) Numbers of trials in which particular residue levels were reported e.g. 3 x <0.01, 1 x 0.01, 6 x 0.02, 1 x 0.04, 1 x 0.08, 2 x 0.1, 2 x 0.15, 1 x 0.17 (b) Supervised Trials Median Residue i.e. the median residue level estimated on the basis of supervised trials relating to the critical GAP (1) Amitraz and Amitraz-derived metabolites containing the 2,4-dimethylaniline moiety expressed in terms of Amitraz (2) According to Council Directives 95/38/EC and 95/39/EC
Report from ECCO 82 - amitraz / 6441/ECCO/PSD/99 July 1999
Page 14 of 15 Consumer risk assessment (Annex IIA, point 6.9, Annex IIIA, point 8.8) ADI 0.0025 mg/kg bw/d TMDI (European Diet) (% ADI) European diet: 156.8 % German diet: 212.8 % NEDI (% ADI) IEDI (European diet) 49.9 % (5 g hops/d) and 70.3 % (1000 g beer/d) IEDI (German diet) 57.9 % Factors included in NEDI factors included in IEDI: • peeling of citrus. factor of 0.1 • processing of cottonseed into oil: factor of 0.05 ARfD 0.0025 mg/kg bw Acute exposure (% ARfD) Oranges: 104 % (adults); 224 % (toddler) Apples: 520 % (adults); 2373 % (toddler) Pears: 640 % (adults); 3190 % (toddler) Tomatoes: 282 % (adults); 243 % (toddler) Pepper: 812 % (adult); 1228 % (toddler) Melons: 108 % (adult); 627 %
Processing factors (Annex IIA, point 6.5, Annex IIIA, point 8.4) Crop/processed crop Number of Transfer factor % Transference studies * citrus (orange, tangerine): 3 juice <0.09 - <0.13 <9 - <13 % pomace 0.63 - 1.1 63 - 110 % peeled fruit <0.09 - < 0.13 <9 - <13 % apple: 2 juice 0.46 - 0.52 46 - 52 % pomace 0.99 - 2.1 99 - 210 % puree 0.23 - 0.28 23 - 28 % cottonseed: 2 delinted cottonseed 0.18 - 0.95 18 - 95 % meal 0.13 - 0.62 13 - 62 % crude oil <0.10 - 0.11 < 10 - 11 % refined oil <0.05 - <0.10 <5 - <10 % hops 3 dried hops 2.8 - 3.3 280 - 330 % spent hops 0.03 - 0.14 3 - 14 % beer 0.003 - 0.02 0.3 - 2 % * Calculated on the basis of distribution in the different portions, parts or products as determined through balance studies
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Page 15 of 15 Proposed MRLs (Annex IIA, point 6.7, Annex IIIA, point 8.6)
citrus (other than oranges) 0.05 mg/kg* ...... stone fruits 0.05 mg/kg* ...... strawberries 0.05 mg/kg* ...... currants 0.05 mg/kg* ...... bananas 0.05 mg/kg* ...... peppers 2 mg/kg ...... cucurbits-edible peel 0.05 mg/kg* ...... hops (dried) 20 mg/kg
Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
DISCLAIMER
PLEASE NOTE THAT THIS DOCUMENT IS AN EXCERPT OF THE REPORT OF AN ECCO (European Commission Co-ordination) PEER REVIEW MEETING
CONCISE OUTLINE REPORT OF ECCO 84 PEER REVIEW MEETING
Peer Review Programme under Directive 91/414/EEC
Subject: Meeting to discuss Ecotoxicology, chapter 2.6.2 ”Definition of the residues relevant to the environment”, chapter 2.9 ”Effects on non-target species” and chapter 2.10 ”Classification and labelling” (Volume 1), of the monographs on
- famoxadone (NAS) NAS = new active substance - CGA 245 704 (NAS) EAS = existing active substance - thiram (EAS) - ziram (EAS) - amitraz (EAS)
Date: 20 - 23 July 1999
Venue: PSD/York
Attendance: Mr Clook (Chairperson) Ms. Grimm (Austria) Mr. Hucorne (Belgium) Ms. Jung (Germany) Ms. Vergnet (France) Ms. Mattsoff (Finland) Mr. Smeets (European Commission, DG VI) Ms. Godson (ECCO-TEAM (PSD)/Report)
Summary of the meeting: The experts identified and discussed the end points for ecotoxicology using templates provided by the corresponding rapporteur Member State. Where appropriate, separate lists of data requirements and studies relied upon (for which data protection has been claimed) were agreed on. The definition of the residues relevant to the environment and classification/labelling of these active substances were reviewed. Areas of concern related to each active substance and restricted to the section ”Ecotoxicology” were identified. Specific comments on the monographs were added and several general issues have been discussed as detailed below.
Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
Specific comments on the active substances in the section Ecotoxicology are listed below. The conclusions of the meeting were as follows:
AMITRAZ
Rapporteur Member State: Austria
1. All comments received were discussed: Date Supplier ECCO Ref No. 14.7.99 Finland 6569/ECCO/PSD/99 14.7.99 Germany 6570/ECCO/PSD/99 14.7.99 Denmark 6571/ECCO/PSD/99 14.7.99 Sweden 6572/ECCO/PSD/99 14.7.99 AgrEvo 6573/ECCO/PSD/99 15.7.99 The Netherlands 6581/ECCO/PSD/99 16.7.99 UK 6582/ECCO/PSD/99
2. Definition of the residues relevant to the environment: soil (parent), water (parent and metabolites BTS 27271 and BTS 27919.
3. Data on preparations: the data set was considered incomplete. Data requirements are listed below.
4. Classification and labelling: proposal of rapporteur Member State (R50/R53) agreed on.
5. Claims for data protection: the rapporteur MS provided a list containing only those studies for which the main data submitter has claimed data protection. All data claims were agreed on.
6. Recommended restrictions/conditions for use: No safe use could be identified on hops and orchards.
Areas of concern: Substantial number of data gaps and an incomplete assessment of risk, therefore no safe use could be identified.
Appendix 1: ECCO 84 reporting table: amitraz
Appendix 2: List of end points: amitraz
Appendix 3: List of studies for which the main submitter has claimed data protection and which during the re-evaluation process were considered as essential for the evaluation with a view to Annex I inclusion: amitraz
Appendix 4: Suggested classification and labelling: amitraz
Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
Appendix 1: ECCO 84 reporting table Amitraz (Ac, In)
3. Ecotoxicology
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(i) Intended uses The application rate had been amended by the main data submitter. The risk assessment has therefore now been based on the following maximum application rates: Hops - 2.5 kg a.s/ha (2 applications) Orchards – 0.8 kg a.s/ha (2 applications) Tomatoes – 0.6 kg a.s/ha (2 applications) Curcurbits – 0.5 kg a.s/ha (2 applications) Glasshouse – (empty) 1.0 kg a.s/ha (1 application) Applications every 10-14 days. The end point sheet has been updated to take account of these revised GAPs. (ii) Risk assessment for For risk assessment purposes, the group assumed that birds and mammals would be exposed to Open point: rapporteur MS to terrestrial vertebrates the active substance in the first instance on treated insects and vegetation. Due to rapid include mammalian degradation of the active substance to the two metabolites (BTS 27919 and BTS 27271), the multigeneration study in end point group assumed that both birds and mammals would also be exposed to these in significant sheet. quantities as well. It was noted that acute, dietary and reproductive toxicity data had been submitted on the active substance as well as the metabolites. It was noted that the parent was of low acute and dietary toxicity, BTS 27919 was of lower acute and dietary toxicity, whilst BTS 27271 was significantly more toxic via the acute oral route but not the dietary route. It was also noted that the data on the effects for the active substance and the metabolites on reproduction were inconsistent and that the reproductive effects of BTS 27271 had not been fully addressed due to excessive parent bird mortality. It was agreed that the main data submitter should be asked to explain the apparent discrepancy in the avian toxicity data set.
A long-term end point for mammals has not been included in the end point sheet. Rapporteur to update the end point sheet. The group noted that hydrolysis of amitraz is rapid, after 7d metabolites can be detected. Most of the residue studies submitted were carried out 80d or so after application. Therefore it can be assumed that birds and mammals will be exposed to both the parent compound and the metabolites. Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(iii) Birds The acute and short-term risk for the parent is considered to be acceptable. The group 3.1 Address the chronic risk to highlighted a chronic risk to breeding birds from use of the active substance in hops and orchards breeding birds from the via the consumption of treated insects. Further data are required to address this risk. consumption of treated insects. (IIA 8.1.3) (iv) Mammals The acute and short-term risk is considered to be acceptable. The group highlighted a chronic 3.2 Address the chronic risk to risk to breeding mammals from use of the active substance in hops and orchards via the breeding mammals from the consumption of treated insects. Further data are required to address this risk consumption of treated insects. (IIIA, 10.3) (v) Metabolites BTS 27271 was considered to be the most toxic metabolite. This was shown to be stable over 3 3.3 Address the long-term risk to weeks. The group identified a long-term risk to both birds and mammals from this metabolite birds and mammals from the and requested that further data be submitted. Note that this data point is linked to point (ii) metabolite BTS 27271. above. (IIIA, 10.1, 10.3)
The rapporteur MS is to carry out a risk assessment for the metabolite in soil to determine the Open point: rapporteur MS to long-term risk to birds and mammals from the consumption of earthworms. calculate the long-term risk to birds and mammals from the metabolite BTS 27271 through the consumption of earthworms. (vi) Toxicity to aquatic life The metabolites were found not to be as toxic to aquatic life as the parent compound. The acute risk from the active substance and the formulation was considered to be acceptable. With regard to chronic toxicity the group agreed that further data on the toxicity of the metabolite BTS 27919 to algae were not required because the difference in toxicity between the active substance and metabolite BTS 27271 in aquatic invertebrates was >100. Algae were clearly less sensitive.
Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(vii) Fish High acute risk to fish from the hop use at the default value of 5m. Safe use requires a default 3.4 Fish early life stage study is distance of 50m. required addressing both the Chronic studies had been submitted which assessed the long-term risk to fish (15µg/l) and active substance and metabolites invertebrates (11µg/l). However it was not clear whether the effect was attributable to the active using 2 applications. (IIA 8.2.2.2) substance or the metabolites. Following in-depth discussion the group agreed that whilst amitraz has a very short half-life in surface waters and normally chronic data would not be requested, the data submitted by the main data submitter indicates potential long-term effects, however the relevance of this assessment is unclear. The main data submitter has suggested a way of addressing this issue by carrying out a fish early life stage study with a single application made at a relevant point during the study. The group agreed that this study should be carried out but that it should address both amitraz and the metabolites and use 2 applications at relevant points during the study. (viii) Daphnia Due to the acute and chronic risk there is currently no safe use for Daphnia. 3.5 Address the chronic risk to The main data submitter has proposed to carry out repeat Daphnia acute and chronic toxicity Daphnia from the active tests in the presence of sediment. The group questioned the need for conducting such a study in substance and metabolites the presence of sediment since amitraz does not appear to partition to sediment (2.5-18% on Day following two applications. 1) particularly at the temperature that such studies are carried out at. The group agreed that a (IIA, 8.2.5) repeat 21d study should be carried out but requested that the main data submitter justify the proposed use of sediment. Main data submitter to justify the use of sediment in a repeat acute and chronic test with aquatic invertebrates. (ix) Sediment dwelling Due to the potential high chronic toxicity of amitraz data are required to address the risk to 3.6 Address the chronic risk to organisms sediment dwelling organisms. It was noted that the main data submitter was currently sediment dwelling organisms undertaking such a study which would be completed in 1999. from amitraz. (IIA, 8.2.7)
(x) Bioconcentration One study had been submitted which gave a BCF of 1300. The clearance time had not been determined but CT90 indicated that after 14 days dissipation, 8% of the radioactivity remained in fish. However the group agreed that there was no concern because of the rapid half life of amitraz in water and the low log Pow for metabolites which was <3. Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(xi) Bees Laboratory tests indicated that amitraz was higly acutely toxic to bees. Semi-field tests showed 3.7 Address the risk to bees from the no significant difference to the control. The group referred back to the data and noted that two metabolites BTS 27919 and studies had been carried out, one 6.25 times the recommended application rate and the other 2.5 27271. (IIA, 8.3.1) times the application rate. Therefore in both cases the crop had been overdosed. In the first study the first run was not considered to be valid because the number of treated bees present was low. In the second study four runs with 10-12 bees were used. There was no significant difference in mortality between the formulation and the control. It was therefore agreed that the risk to bees was acceptable. However, the data provided did not address the risk to bees from the two metabolites BTS 27919 and 27271 which appeared to be relatively stable in plants. Further data are required. (xii) Non-target arthropods Initial laboratory and semi-field data indicate a high risk to all non-target arthropods. The 3.8 Potential recovery in non-target maximum application rates for the formulation were not used, however significant effects were arthropod populations in crop still seen. The group noted that the data generated only demonstrated that there was an effect, no over a season using the maximum information had been provided on the potential for recovery. It was not possible to make an application rate should be assessment of the impact and duration of the effects based on the incomplete data set. Therefore addressed. (IIIA, 10.5) the main data submitter should provide data on potential recovery in crop over a season at the maximum application rate. No safe use for non-target arthropods at present. (xiii) Earthworms The acute toxicity of amitraz to earthworms was considered to be acceptable. No reproductive toxicity data were submitted. The group agreed that further data were not required since the DT50 for the three metabolites (BTS 27919, 27271 and 27868) were all approximately 6d. (xiv) Soil macro-organisms Further data not required due to rapid degradation of the active substance and its metabolites.
(xv) Sewage treatment No studies have been provided. The meeting requested that data be submitted as amitraz can be 3.9 Effects on biological methods for used in glasshouses. sewage treatment. (IIA, 8.7)
(xvi) Non-target flora and Data are required where available. 3.10 Effects on other non-target fauna organisms (flora and fauna) believed to be at risk. (IIA, 8.6)
(xvii) Endocrine disruption According to a literature survey carried out by the WWF amitraz has been reported to have 3.11 Address the concern that amitraz several endocrine disrupting effects. The group agreed that main data submitter should be asked may exhibit endocrine disrupting to comment on these findings. effects. Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
No. Subject Discussion ECCO-Peer Review Meeting Recommendations ECCO-Peer Review Meeting (Annex point)
(xviii) Data protection The rapporteur MS provided a list containing only those studies for which the main data submitter has claimed data protection. All data claims were agreed on.
Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
Appendix 2
LIST OF END POINTS: AMITRAZ
3 Ecotoxicology section
Active substance (ISO Common Name) Amitraz Function (e.g. fungicide) Acaricide/insecticide
Rapporteur Member State Austria
Chapter 2.6 Effects on Non-target Species
Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3) Acute toxicity to mammals Amitraz: LD50 (rat, male) = 600 mg/kg bw BTS 27271: LD50 (mouse) = 100 mg/kg bw Amitraz: NOAEL (rat, multigeration study) = 1.3 mg/kg bw BTS27271: NOAEL (rat, 90 d) = 1 mg/kg bw Acute toxicity to birds Amitraz: LD50 (Bobwhite quail) = 788 mg/kg bw BTS 27919: LD50 (Bobwhite quail) = 1827 mg/kg bw BTS 27271.HCl LD50 (Bobwhite quail) = 71 mg/kg bw Dietary toxicity to birds Amitraz: LC50 (Japanese quail) = 1800 ppm BTS27919: LC50 (Bobwhite quail) > 5200 ppm BTS 27271.HCl: LC50 (Bobwhite quail) = 1362 ppm Reproductive toxicity to birds Amitraz: NOEC (Mallard duck) = 20 ppm BTS 27919: NOEC (Bobwhite quail) = 100 ppm BTS 27271.HCl: NOEC (Mallard duck) = 5 ppm
Toxicity/exposure ratios for terrestrial vertebrates (Annex IIIA, points 10.1 and 10.3) Application Crop Category Time-scale TER Annex rate (e.g. insectivorous bird) VI (kg as/ha) Trigger ai met 2*2,5 Hops grazing bird Acute 15 5 10 insectivorous bird Acute 36 22 10 earth worm eating bird Acute 1576 101 10 4 2*0,8 Orchards frugivorous bird Acute 1970 710 10 insectivorous bird Acute 114 65 10 2*2,5 Hops grazing bird Subacute 12 32 10 insectivorous bird Subacute 25 124 10 Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
earth worm eating bird Subacute 1058 574 10 6 2*2,5 Hops grazing bird Chronic 0.14 0.24 5 insectivorous bird Chronic 0.27 0.45 5 earth worm eating bird Chronic 12 21 5 2*0,8 Orchards frugivorous bird Chronic 20 25 5 insectivorous bird Chronic 0,9 1,4 5 1*0,5 Cucurbits insectivorous bird Chronic 1,4 2,3 5 2*2,5 Hops grazing mammal Acute 11 7,7 10 insectivorous mammal Acute 27 30 10 earthworm eating mammal Acute 1200 1000 10 2*2,5 Hops grazing mammal Chronic 0,03 0,16 5 insectivorous mammal Chronic 0,06 0,3 5 earthworm eating mammal Chronic 2.6 14 5 2*0,8 Orchards frugivorous mammal Chronic 4,3 16 5 insectivorous mammal Chronic 0,17 1 5 earthworm eating mammal Chronic 8 14 5 1*0,5 Aubergines insectivorous mammal Chronic 0,29 0,4 5 met: BTS 27271, 15 % of applied ai.
Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2, Annex IIIA, point 10.2) Group Test substance Time-scale Endpoint Toxicity LC50/EC50/NOEC (mg ai/l) Laboratory tests Fish Amitraz 96h / flow through mortality 0.45 Invertebrates Amitraz 48h /static immobilisation 0.035 Algae Amitraz 91h /static biomass, growth rate > 12 Fish BTS 27919 96h / static mortality 74 Invertebrates BTS 27919 48h /static immobilisation >100 Fish BTS 27271 96h / flow through mortality 27.9 Invertebrates BTS 27271 48h /static immobilisation 3.28 Fish Mitac 20 EC 96h / flow through mortality 0.348 ai Invertebrates Mitac 20 EC 48h /static immobilisation 0.0422 ai Algae Mitac 20 EC 89h /static biomass 0.1884 ai Fish Amitraz 36d/ flow through NOEC Length 0.0015 * Invertebrates Amitraz 21d / flow through NOEC reproduction 0.0011** Microcosm or mesocosm tests No data
* C 14 measurement, data expressed in Amitraz equivalents (ai and metabolites), % of amitraz not mentioned ** C 14 measurement, data expressed in Amitraz equivalents (ai and metabolites), mean of amitraz 54.7 % ⇒ PECi used for calculation of long term toxicity Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
Toxicity/exposure ratios for the most sensitive aquatic organisms (Annex IIIA, point 10.2) Application Crop Organism Time-scale Distance TER Annex Rate (m) VI (kg as/ha) ai met/ Trigger *Mitac 2.5 hops fish 96 h 5 4.32 897 100 2.5 hops invertebrates 48 h 5 0.33 105 100 2.5 hops algae 91 h 5 >115 *1.8 10 2.5 hops fish 96 h 50 180 100 2.5 hops invertebrates 48 h 50 12.8 100 2.5 hops algae 91 h 50 >4800 *75.2 10 0.8 orchards fish 96 h 40 420 100 0.8 orchards invertebrates 48 h 40 32.7 100 0.8 orchards algae 91 h 40 >11215 10 2.5 hops fish 36d 5 0.014 10 2.5 hops invertebrates 21d 5 0.01 10 2.5 hops fish 36d 50 0.6 10 2.5 hops invertebrates 21d 50 0.44 10 0.8 orchards fish 36d 40 1.4 10 0.8 orchards invertebrates 21d 40 1.03 10
Met: BTS 27271; BTS 27919 is less toxic (no calculations) Mitac: *
Bioconcentration Bioconcentration factor (BCF) 1333 Annex VI Trigger:for the bioconcentration factor 100
Clearance time (CT50) After 14 days dissipation 8 % of the (CT90) radioactivity remains in the fish
Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4) Acute oral toxicity LD50 (96h) = 20 µg Mitac/bee Acute contact toxicity LD50 (96h) = 27 µg Mitac/bee
Hazard quotients for honey bees (Annex IIIA, point 10.4) Application rate Crop Route Hazard quotient Annex VI (l Mitac/ha) Trigger Laboratory tests 12.5 Hop Oral 625 50 4.0 Orchards Oral 200 50 4.0 Vegetables Oral 200 50 12.5 Hop Contact 463 50 4.0 Orchards Contact 148 50 4.0 Vegetables Contact 148 50
Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
Semi-field tests Application rate Crop Route Effects (l Mitac/ha) 0.5 % Phacelia Contact/Oral Adult bees and brood: No abnormal changes were observed
Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5) Species Stage Test Dose Endpoint Effect Annex VI Substance (l Mitac/ha) Trigger Laboratory tests Trichogr Adults Mitac 20 EC 3.5 Mortality 100 30 cacoeciae Trichogr Adults Mitac 20 EC 1.8 Reduction of 100 30 cacoeciae parasitism Encarsia Adults & Mitac 20 EC 1.8 Mortality & parasitism 100 30 formosa larvae Phygadeuon Adults & Mitac 20 EC 1.8 Reduction of 50-79 30 trichops larvae parasitism Phytosei Nymphs Mitac 20 EC 3.5 Mortality 100 30 persimilis Phytosei Nymphs Mitac 20 EC 5.0 Mortality 100 30 persimilis Phytosei Adults & Mitac 20 EC 1.8 Reduction of 100 30 persimilis eggs egg production Phytosei Nymphs Mitac 20 EC 3.5 Mortality 100 30 persimilis Amblyseius Adults & Mitac 20 EC 1.8 Mortality & egg 100 30 pottentillae eggs production, total effect Typhlodr Adults & Mitac 20 EC 1.8 Mortality & egg 100 30 pyri eggs production, total effect Anthocoris Nymphs Mitac 20 EC No details Mortality & fecundity 46 30 nemorum provided Chrysopa Larvae Mitac 20 EC 5.0 Mortality of larvae 58 30 carnea Chrysopa Larvae & Mitac 20 EC 1.8 Mortality & egg 80-99 30 carnea adults production total effect Coccinella Larvae Mitac 20 EC 1.8 Mortality of larvae & 80-99 30 7-punctata fecundity of adults Adalia Larvae & Mitac 5.0 Mortality of larvae and 0 30 bipunctata adults fecundity of adults Lepthypan- Adults Mitac 20 EC 1.8 Mortality & predation, 100 30 tes tenuis total effect Aleochara Adults & Mitac 20 EC 1.8 Egg production & 80-99 30 bilineata larvae parasitism, total effect Bembidion Adults Mitac 20 EC 1.8 Mortality 50-79 30 lampros
semi-field tests , initial and persistance Species Stage Test Dose Endpoint Effect Annex VI Substance (l Mitac/ha) Trigger Trichogr Susceptible Mitac 20 EC 1.8 Duration of harmful Persistent cacoeciae stage activity (> 30 d) Encarsia Susceptible & Mitac 20 EC 1.8 Total effect > 75 25 Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
formosa robust stage Encarsia Susceptible & Mitac 20 EC 1.8 Duration of harmful Short lived formosa robust stage activity (< 5 d) Phytosei Mitac 20 EC 1.8 Total effect > 75 25 persimilis Field test Amblyseius Adults, Mitac 20 EC 1.8 Mortality & > 75 25 finlandicus eggs & fecundity, juveniles total effect Typhlodr Adults, Mitac 20 EC 1.8 Mortality & > 75 25 pyri eggs & fecundity, juveniles total effect
Effects on earthworms (Annex IIA, point 8.4, Annex IIIA, point 10.6) Acute toxicity 14 days LC50 = 20 mg as/kg* Reproductive toxicity No data * According to the EPPO risk assessment scheme the toxicity data from laboratory tests in artificial soil are divided by the factor of 2 when the log Pow >2.
Toxicity/exposure ratios for earthworms (Annex IIIA, point 10.6) Application rate Crop Time-scale TER Annex VI (kg as/ha) Trigger 2,5 hops 14 days 12 10
Effects on soil micro-organisms (Annex IIA, point 8.5, Annex IIIA, point 10.7) Nitrogen mineralization < 25 %, no significant effects at an application rate of 3.27 mg ai/kg > 25 %, effects at an application rate of 32.7 mg ai/ha Carbon mineralization < 25 %, no significant effects
Classification and proposed labelling (Annex IIA, point 10) with regard to ecotoxicological data N: Dangerous for the environment S 60: This material and its container must be disposed of as hazardous wastes S 61: Avoid release to the environment R 50/53: Very toxic to aquatic organisms and may cause long-term adverse effects in the aquatic environment
Report from ECCO 84 - amitraz / 6587/ECCO/PSD/99 xx July 1999
Appendix 4
SUGGESTED CLASSIFICATION AND LABELLING: AMITRAZ
3 Ecotoxicology section
Hazard symbol N Dangerous for the environment
Risk phrase R50 Very toxic to aquatic organisms
R53 May cause long-term adverse effects in the aquatic environment Safety phrase S60 This material and its container must be disposed of as hazardous wastes S61 Avoid release to the environment, refer to special instructions/safety data sheets