CA-Sept12-Doc.3.6a
Directive 98/8/EC concerning the placing biocidal products on the market
Inclusion of active substances in Annex I to Directive 98/8/EC
Assessment Report
Didecyldimethylammonium chloride Product-type PT 8 (Wood preservative)
date SCB
Annex I – Italy Didecyldimethylammonium Product-type 8 Chloride
Didecyldimethylammonium Chloride (PT 8)
Finalised in the Standing Committee on Biocidal Products at its meeting on date SCB in view of its inclusion in Annex I to Directive 98/8/EC
CONTENTS
1. STATEMENT OF SUBJECT MATTER AND PURPOSE...... 4 1.1. Procedure followed...... 4 1.2. Purpose of the assessment report...... 5 1.3. Overall conclusion in the context of Directive 98/8/EC...... 6 2. OVERALL SUMMARY AND CONCLUSIONS...... 7 2.1. Presentation of the Active Substance...... 7 2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis...... 7 2.1.2. Intended Uses and Efficacy...... 11 2.1.3. Classification and Labelling...... 12 2.2. Summary of the Risk Assessment...... 15 2.2.1. Human Health Risk Assessment...... 15 2.2.1.1. Hazard identification...... 15 2.2.1.2. Effects assessment...... 16 2.2.1.3. Exposure assessment...... 18 2.2.1.4. Risk characterization...... 26 2.2.2. Environmental Risk Assessment...... 38 2.2.2.1. Fate and distribution in the environment...... 38 2.2.2.2. Effects Assessment...... 42 2.2.2.3. PBT assessment...... 44 2.2.2.4. Exposure assessment...... 45 2.2.2.5. Risk characterisation...... 48 3. DECISION...... 53
3.1. BACKGROUND TO THE PROPOSED DECISION...... 53
3.2. PROPOSED DECISION REGARDING INCLUSION IN ANNEX I...... 55
2 Didecyldimethylammonium Product-type 8 Chloride
3.3. ELEMENTS TO BE TAKEN INTO ACCOUNT BY MEMBER STATES WHEN AUTHORISING PRODUCTS...... 57
3.4. REQUIREMENT FOR FURTHER INFORMATION...... 59
3.5. UPDATING THIS ASSESSMENT REPORT...... 60 APPENDIX I: LIST OF END POINTS...... 61 Chapter 1: Identity, Physical and Chemical Properties, Details of Uses, Further Information, and Proposed Classification and Labelling...... 61 Chapter 2: Methods of Analysis...... 64 Chapter 3: Impact on Human Health...... 65 Chapter 4: Fate and Behaviour in the Environment...... 71 Chapter 5: Effects on Non-target Species...... 73 Chapter 6: Other End Points...... 74 APPENDIX II: LIST OF INTENDED USES...... 75 APPENDIX III: LIST OF STUDIES...... 76
3 Didecyldimethylammonium Product-type 8 Chloride
1. STATEMENT OF SUBJECT MATTER AND PURPOSE
1.1. Procedure followed
This assessment report has been established as a result of the evaluation of Didecyldimethylammonium Chloride as product-type 8 (wood preservative), carried out in the context of the work programme for the review of existing active substances provided for in Article 16(2) of Directive 98/8/EC concerning the placing of biocidal products on the market 1, with a view to the possible inclusion of this substance into Annex I or IA to the Directive.
Didecyldimethylammonium Chloride (CAS no. 7173-51-5) was notified as an existing active substance, by Lonza Cologne GmbH, Stepan Europe, Mason Europe Limited, hereafter referred to as the applicant, in product-type 8. Commission Regulation (EC) No 2032/2003 of 4 November 20032 lays down the detailed rules for the evaluation of dossiers and for the decision-making process in order to include or not an existing active substance into Annex I or IA to the Directive.
In accordance with the provisions of Article 5(2) of that Regulation, Italy was designated as Rapporteur Member State to carry out the assessment on the basis of the dossier submitted by the applicant. The deadline for submission of a complete dossier for Didecyldimethylammonium Chloride as an active substance in Product Type 8 was 28th March 2004, in accordance with Annex V of Regulation (EC) No 2032/2003.
On 28th March 2004, the Italian Competent Authority received a dossier from the applicant. The Rapporteur Member State accepted the dossier as complete for the purpose of the evaluation on 28th September 2004. On 27th June 2005 the time period was suspended and the evaluation taken up again on 27th March 2006 after the applicant has submitted the necessary data. After that, the evaluation phase was suspended again on the 17th July 2006 and taken up on 18th July 2007. On 31st July 2007, the Rapporteur Member State submitted, in accordance with the provisions of Article 10(5) and (7) of Regulation (EC) No 2032/2003, to the Commission and the applicant a copy of the evaluation report, hereafter referred to as the competent authority report. The Commission made the report available to all Member States by electronic means on 20th September 2007. The competent authority report included a recommendation for the inclusion of Didecyldimethylammonium Chloride in Annex I to the Directive for PT 8.
In accordance with Article 12 of Regulation (EC) No 2032/2003, the Commission made the competent authority report publicly available by electronic means on 10th October 2007. This report
1 Directive 98/8/EC of the European Parliament and of the Council of 16 February 1998 concerning the placing biocidal products on the market. OJ L 123, 24.4.98, p.1 2 Commission Regulation (EC) No 2032/2003 of 4 November 2003 on the second phase of the 10-year work programme referred to in Article 16(2) of Directive 98/8/EC of the European Parliament and of the Council concerning the placing of biocidal products on the market and amending Regulation (EC) No 1896/2000. OJ L 307, 24.11.2003, p. 1
4 Didecyldimethylammonium Product-type 8 Chloride did not include such information that was to be treated as confidential in accordance with Article 19 of Directive 98/8/EC.
In order to review the competent authority report and the comments received on it, consultations of technical experts from all Member States (peer review) were organised by the Commission. Revisions agreed upon were presented at technical and competent authority meetings and the competent authority report was amended accordingly.
On the basis of the final competent authority report, the Commission proposed the inclusion of Didecyldimethylammonium Chloride in Annex I to Directive 98/8/EC and consulted the Standing Committee on Biocidal Product on date.
In accordance with Article 11(4) of Regulation (EC) No 2032/2003, the present assessment report contains the conclusions of the Standing Committee on Biocidal Products, as finalised during its meeting held on date.
1.2. Purpose of the assessment report
This assessment report has been developed and finalised in support of the decision to include Didecyldimethylammonium Chloride in Annex I to Directive 98/8/EC for product-type 8. The aim of the assessment report is to facilitate the authorisation in Member States of individual biocidal products in product-type 8 that contain Didecyldimethylammonium Chloride. In their evaluation, Member States shall apply the provisions of Directive 98/8/EC, in particular the provisions of Article 5 as well as the common principles laid down in Annex VI.
For the implementation of the common principles of Annex VI, the content and conclusions of this assessment report, which is available at the Commission website3, shall be taken into account.
However, where conclusions of this assessment report are based on data protected under the provisions of Directive 98/8/EC, such conclusions may not be used to the benefit of another applicant, unless access to these data has been granted.
3 http://ec.europa.eu/comm/environment/biocides/index.htm
5 Didecyldimethylammonium Product-type 8 Chloride
1.3. Overall conclusion in the context of Directive 98/8/EC
The overall conclusion from the evaluation is that it may be expected that there are products containing Didecyldimethylammonium Chloride for the product-type 8, which will fulfil the requirements laid down in Article 10(1) and (2) of Directive 98/8/EC. This conclusion is however subject to:
i. compliance with the particular requirements in the following sections of this assessment report,
ii. the implementation of the provisions of Article 5(1) of Directive 98/8/EC, and
iii. the common principles laid down in Annex VI to Directive 98/8/EC.
Furthermore, these conclusions were reached within the framework of the uses that were proposed and supported by the applicant (see Appendix II). Extension of the use patternscenario beyond those described will require an evaluation at product authorisation level in order to establish whether the proposed extensions of use will satisfy the requirements of Article 5(1) and of the common principles laid down in Annex VI to Directive 98/8/EC.
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2. OVERALL SUMMARY AND CONCLUSIONS
1.4. Presentation of the Active Substance
1.4.1. Identity, Physico-Chemical Properties & Methods of Analysis
Identification of the active substance
CAS No. 7173-51-5 EINECS No. 230-525-2 Other substance No.: 612-131-00-6 (Annex I Index number) IUPAC Name N,N-Didecyl-N,N-dimethylammonium Chloride Common name, synonyms Didecyldimethylammonium Chloride; DDAC N-Decyl-N,N-dimethyl-1-decanaminium chloride Ammonium, didecyldimethyl-, chloride Chemical name (CA) 1-Decanaminium, N-decyl-N,N-dimethyl-, chloride
Molecular formula C22H48N.Cl Structural formula - R Cl
N+ R
R = C10H21 Molecular weight (g/mol) 362.1
Purity 87.0-99.5% w/w dry weight (*) Impurities See Confidential Data (*) Didecyldimethylammonium Chloride (DDAC) is not manufactured solvent-free but always exists in process solvents
Didecyldimethylammonium Chloride (DDAC) does not contain additives or impurities that would be of toxicological or environmental concern.
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Identification of the representative product
Trade name BC-25 Manufacturers development code number Not assigned Active substance Didecyldimethylammonium Chloride Content of the active substance 25% Function Fungicide, insecticide Physical state of preparation Liquid Nature of preparation Solution The product does not contain substances of concern.
Physico-chemical properties
The active substance Didecyldimethylammonium Chloride (DDAC) is a light-coloured solid with melting point between 188 and 205°C. Decomposition was observed at approximately 280°C before boiling. Its relative density was determined to be 0.902 at 20°C.
Its vapour pressure was calculated to be 5.9E-06 Pa at 20°C, 1.1E-05 at 25°C and 2.3E-04 at 3 –1 50°C, with a Henry’s Law constant of 4.27E-09 Pa m mol at 20°C.
DDAC is highly soluble in water (water solubility at 20°C is 500 g/l at pH 2.2 and at pH 9.2). Furthermore, it is readily soluble in Acetone (>600 g/l at 20°C), Methanol (>600 g/l at 20°C) and Octanol (>250 g/l at 20°C).
The partition coefficient n-octanol/water is not determinable since the active substance is a surfactant in the octanol/water system, thus preventing the use of the shake-flask method. The HPLC Method is not applicable either, due to the absence of suitable calibration compounds and to the fact that ionic compounds interact with the HPLC column by forces other than partitioning. Also the log Pow assessment by KOWWIN is deemed inaccurate, being the software database very limited for surface active substances. On the other hand, log Pow could be roughly obtained from solubility in n-octanol and water (Pow ≈ 1, log Pow ≈ 0). However, this result is of no use with regard to environmental fate and behaviour and secondary poisoning risk assessment, since there is an experimental BCF available.
DDAC does not exhibit hazardous physico-chemical properties. It has a low vapour pressure and it is highly soluble in water. It is thermally stable and does not show explosive or oxidising properties. DDAC is not classified as highly flammable, self-ignition temperature being 195°C. There is no risk to be expected due to the physico-chemical properties of the product, either.
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Analytical methods
Analysis of the active substance as manufactured
Both studies summarised in Doc. IIIA Sections 4.1 (1) and (2) were found not compliant with Technical Notes for Guidance requirements and were not considered acceptable by the RMS. Hence, fully validated analytical methods for the active substance as well as for impurities were required by the RMS. The notifier was requested to perform these methods before the completion of the present CAR.
An additional analytical method (“Kurz M. and Ranft V. (2007), “Determination of quaternary ammonium compounds and related quaternary impurities by HPLC-ELSD”, Section 4.1(3) Doc. IIIA) was submitted at the mid-July 2007. The method was not deemed acceptable by the RMS, due to the deficiencies/mistakes affecting both the validation work and the original study report. Hence, the RMS required the full validation of the developed method for both Didecyldimethylammonium Chloride (DDAC) and impurities > 0.1% w/w, in compliance with SANCO/3030/99 rev.4 11/07/00. Anyway, at the TMIV08 it was concluded that the HPLC- ELSD method could be considered acceptable for DDAC. It was also agreed that the Applicant should have provided further information and considered the possibility to use an internal standard for quantitative analysis as suggested by AT.
In 2011, a new study (Zehr, P.S. (2010), “Methods Validation for the Preliminary Characterization Analyses of Dialkyldimethyl Ammonium Chlorides”) for the determination of DDAC, impurities and process solvents in commercially available technical concentrate Bardac 22 (nominal DDAC content: 50% w/w) was submitted by the Applicant, superseding Doc. IIIA Sections 4.1(1), (2) and (3). Results are now summarized in Section 4.1(4)(a) in Doc. IIIA and Section 4.1(4)(b)-(c) in the Confidential Data. Valid analytical methods are available for impurities and process solvents in 50% w/w DDAC-based technical concentrate, but additional information/clarification must be provided in any case (please refer to the RMS comments/requests in the evaluation box of the relevant study summaries).
Following the submission of Zehr, P.S. (2010), in April 2011 an additional study addressing batch-analysis (Zehr, P.S. (2011), “Batch analysis of Didecyldimethyl Ammonium Chloride”) was presented. Only two batches per Notifier have been investigated, whereas the TNsG for on the assessment of technical equivalence of substances regulated under 98/8/EC require the analytical profile of at least five different representative batches of each source for the purpose of Tier I assessment. In conclusion, a new five-batch analysis for each source of the active substance must be submitted to allow the assessment of the technical equivalence of the three joint Notifiers supporting DDAC and also to confirm the active substance specification under Sec. 2 Doc. IIIA. Data should be submitted prior to product authorization phase at national level.
Residues
As regards the analysis of DDAC residues, LC-MS methods have been used in soil and water (drinking-, ground- and surface water) with a LOQ of 0.01 mg/kg and 0.1 mg/l, respectively. Only one mass fragment was used for the purpose of validation. During the evaluation of the Dossier in 2006, these methods were considered sufficiently specific, linear, accurate and precise by the RMS and were therefore accepted. At that time, the Addendum to TNsG on Data
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Requirements Analytical Methods (based on SANCO/825/00) had not been endorsed yet and the conclusion on the specificity of the methods had been drawn by the RMS on the following grounds:
- no further fragmentation was likely to occur under the LC-MS experimental conditions adopted;
- the chromatograms of untreated matrices showed no interferences;
- the m/z of the ion monitored ([DDA]+, m/z = 326.3) was sufficiently high that in the RMS opinion LC-MS could be reasonably considered specific enough.
On the contrary, the Addendum (adopted in May 2009) states that a confirmatory method is not necessary in case of a highly specific technique, which means the use of three fragment ions (possibly with m/z ratio >100) when MS detection is carried out. So, according to the Addendum, the available data (given for one LC-MS ion only) are not actually sufficient to prove the specificity of the submitted methods, which are necessary for post-authorization control and monitoring purposes.
Furthermore, a bilateral discussion with DE-CA occurred in 2010 on analogous LC-MS analytical methods for residues in soil and water for structurally-related quaternary ammonium compounds, with only one mass fragment (instead of three) validated. It was agreed that highly specific confirmatory methods for residues in soil and water were necessary and were to be submitted for the product authorization phase at national level. The same position (i.e. the request for additional validation data) has been recently agreed with DE-CA in the commenting step for the very same substance (CAS 7173-51-5) notified by another Applicant. In that case, LC/MS-MS analytical methods for residues in soil and water (both drinking- and surface- water) were available, with only one mass transition (instead of two) validated. In conclusion, in line with the Addendum to TNsG on Data Requirements Analytical Methods and also for the sake of consistency with the approach adopted for structurally-related quaternary ammonium compounds and for the same active substance notified by another Applicant, additional highly- specific confirmatory methods for DDAC residues in soil and water (both drinking- and surface-water) are to be submitted at the product authorization phase at national level.
No analytical method is required for the determination of residues in air, since the a.s. is non- volatile and will not be used in spray application.
No analytical method is deemed necessary for the determination of residues in body fluids and tissues, being the a.s. neither toxic nor highly toxic.
Wood treated with DDAC-containing biocidal product is not intended for and contains label restrictions against use in areas where food for human consumption is prepared, consumed or stored, or where the feedingstuff for livestock is prepared, consumed or stored. Therefore, no analytical method for the determination of residues in food/feed of plant/animal origin is required, either.
1.4.2. Intended Uses and Efficacy
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Didecyldimethylammonium Chloride (DDAC) is a wood preservative used for preventive protection of wood and constructional timbers in Hazard Classes 1 to 4A against wood destroying organisms and wood discolouring moulds and fungi.
Effectiveness
DDAC has properties similar to the benzyl QUATS but with Organic Soil and Hard Water Tolerance.
DDAC is a cationic surfactant type active substance. Due to its interaction with phospholipid- bilayer structures, it severely alters the cell wall permeability, disturbs membrane-bound ion- translocation mechanisms, and may facilitate the uptake of other biocides.
The use concentration depends on the type of application technique, use class required and on additional formulation components. Against fungi, there exists a selective activity spectrum.
The biocidal product (BC-25) contains 25% DDAC in water. It is a wood preservative with preventive efficacy against wood-destroying fungi (basidiomycetes) and insects and against soft rot fungi. It is used in drenching/dipping and vacuum pressure process applications. In practice it is always used in formulations in combination with other active substances.
The degree of dilution will vary depending on the wood species, type of wood product and anticipated use. The requirements for the final concentration of Didecyldimethylammonium Chloride vary between 0.3% and 1.8%. The application rate of DDAC in wood is 1.8 kg/m3.
Number and timing of applications depends on application technique, wood species, moisture and hazard class. An uptake of approximately 1.8 kg/m3 should be achieved by these application methods in order to ensure the protection level for the different use classes required.
Since after approx. 40 years of use worldwide no reports of selective acquisition of DDAC- resistance in the field of wood protection exists the risk of development of resistance to is considered negligible. On the other hand, DDAC acts as a wood preservative, i.e. works by preventing growth of organisms, not by killing organisms that are present thus reducing the potential for resistant organisms to develop. In addition, for hard surface sanitization/disinfection (where antimicrobial activity is based on direct killing of organisms present on surfaces), investigations on exposure of domestic microbial communities to quaternary ammonium biocidal substances showed no increased antimicrobial resistance (McBain A.J. et al. 2004). Therefore, we can agree that development of resistance can be considered negligible.
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1.4.3. Classification and Labelling
The Current Classification Classification as in Directive 67/548/EEC Class of danger Xn; R22 C; R34 R phrases R22 Harmful if swallowed R34 Causes burns S phrases S2 Keep out of the reach of children S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice S36/37/39 Wear suitable protective clothing, gloves and eye/face protection S45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible)
The proposed Classification and Labelling of the substance based on Directive 67/548/EEC Classification Class of danger Xn; R22 C; R34 N; R50 Labelling: Symbol C ; N R phrases R22 Harmful if swallowed R34 Causes burns R50 Very toxic to aquatic organisms S phrases S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice S28 After contact with skin, wash immediately with plenty of… S36/37/39 Wear suitable protective clothing, gloves and eye/face protection S45 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 into the environment. Refer to special instructions/safety data sheets. Specific Cn ≥ 2.5 %: N; R50 concentration limits for the environmental classification
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Justification for the proposal
The substance is currently classified according to Annex I of Council Directive 67/548/EC (with amendments and adaptations).
On basis of the results from studies presented in the dossier, classification of DDAC was proposed according to principles detailed in Annex VI of Council Directive 67/548/EEC (with amendments and adaptations).
Related to N; R 50, LC50 is below 1 mg/l with proposal for specific concentration limits and the substance is readily biodegradable.
Proposed Classification and labelling of the active substance based on Regulation EC 1272/2008: Classification: Hazard Class and Acute toxicity (oral), Hazard Category 3* Category Skin Corrosion Hazard Category 1B_ Aquatic Acute 1_ Hazard Statement H301 Codes H314 H400 Labelling: GHS Pictogram GHS05, GHS06, GHS09 Signal Word Danger Hazard Statement H301:Toxic if swallowed. H314: Causes severe skin burns and eye damage H400: Very toxic to aquatic life. Specific M factor=10 concentration limits for the aquatic hazard classification As precautionary statements are not included in Annex VI of Regulation EC 1272/2008, no proposal is made.
Classification by Acute Tox 3 is based on the lowest determined oral LD50 for DDAC: 238 mg/kg
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Proposed classification of the DDAC-based product BC-25 based on Directive 99/45/EEC with amendments and adaptations, on basis of study results presented and by calculation.
Classification
Class of danger Xn R22
C R34
N R50
R phrases R22 Harmful if swallowed R34 Causes burns R50 Very toxic to aquatic organisms S phrases S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice
S28 After contact with skin, wash immediately with plenty of …
S36/37/39 Wear suitable protective clothing, gloves and eye/face protection
S45 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 sheets Classification and labelling for the mixture according to Regulation EC 1272/2008 is required from June 2015.
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1.5. Summary of the Risk Assessment
1.5.1. Human Health Risk Assessment
2.2.1.1. Hazard identification
DDAC is highly ionic and, therefore, it is expected not to be readily absorbed from the gastrointestinal tract or skin. As indicated in a toxicokinetics study on rats, the majority (>90%) of orally administered DDAC is excreted very likely unabsorbed via the faeces. Based on data on urine excretion (3%) and tissue residues (<1%), and on the 90% recovery of radioactivity obtained in the available toxicokinetic study, it is expected that DDAC oral absorption is limited to 10%). The majority of DDAC metabolism, accounting for 40% of total administered dose is expected to be carried out by intestinal flora giving rise to hydroxylation products in the alkyl chain, none of them exceeding 10%.
About 0.1% of a DDAC dose delivered as aqueous solution fully penetrated human skin in vitro in 24 h; mean total absorbable DDAC was 9.41% (rounded to 10% for risk characterization purposes), including the radioactivity present in the dermis and epidermis at the dose site.
The lowest determined oral LD50 for DDAC is 238 mg/kg. No clinical signs or mortality were observed until a dosage or a concentration is attained that causes irritation of the gut mucosa or affects the gastrointestinal flora. According to Annex VI of Commission Directive 2001/59/EC, DDAC requires classification “Xn/R22 “Harmful if swallowed”.
The rabbit acute dermal LD50 of DDAC is 3342 mg/kg.and no classification is required for the dermal route (LD50 = 3342mg/kg bw).Inhalation of DDAC is not considered a potential route of exposure based on use patternscenarios and vapour pressure 2.3x10-4 Pa at 50ºC.
DDAC is is a severe skin and eye irritant. According to the requirement specified by Commission Directive 2001/59/EC, DDAC requires classification with the symbol “C” and the risk phrase R34 “Cause burns”.On the basis of the available data DDAC is not a skin sensitiser.
From a two-week skin irritation study in rats, it can be derived a NOAEL/NOAEC of 0.6% active substance in water at 2.0 ml/kg body weight per day after a 5 day application and a NOAEL/NOAEC of 0.3% active substance in water at 2.0 ml/kg body weight per day after 2- week application.
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2.2.1.2. Effects assessment
As with acute exposure, DDAC repeated intake results in death in rodents at a concentration that affects the gastrointestinal mucosa or microflora. The subchronic oral NOAELs were 107- 134 mg/kg/day in male and female mice and 61-74 mg/kg/day in male and female rats mainly based on aspecific effects, such as decreased body weights, considered to be secondary to local effects on gut mucosa and intestinal microflora. No organ specific toxicity was evidenced. With both rodent species high mortality (80% and 96% of treated rats and mice) occurred in animals given DDAC fortified diets at the highest dose tested; death was attributed to gastrointestinal alterations resulting in dehydration and wasting. The exposure to the immediately lower dose caused only minimal body weight effects (10-15% decrease). The steepness of the dose-response curve (from no effects to high % mortality caused by 3-fold higher dose) is also indicative of the mechanism of action through irritation/corrosive properties of DDAC
In a 1-year feeding study in dogs with DDAC, the two highest doses (10 and 20 mg/kg/day) resulted in g.i.-related complications including emesis and abnormal faeces. The clinical signs observed in all the animals treated at 10 mg/kg/d (emesis, salivation, soft/loose faeces) persisted for the entire study duration; taking into account that the treatment dosage is reached with 2 different administrations within the day (lowering the entity of the bolus dose achievable with a single administration-possibly giving rise to more severe effects) this dosage cannot be considered as the NOAEL derived from the study. The NO(A)EL should be fixed equal to 3 mg/kg/d, related to local effects on gut mucosa. The clinical signs reported at 10 mg/kg/d, on which the NOAEL derivation is based, are consistent with the irritation/corrosive properties of the test item : only a small amount of DDAC becomes systemically available, without giving rise to any significant systemic effects. The systemic effects (10-15% decrease in body weight), were seen at 20/30 mg/kg/d, although secondary to effects in the gut. Therefore it is not appropriate to use 3 mg/kg/d to derive a systemic AEL and consequently for AEL calculation it is proposed to use the immediately higher value (systemic NOAEL=10 mg/kg/d).
In a 90-day subchronic dermal study, no effects were seen at the highest dose that could be applied without excessive skin irritation. Therefore the systemic NOAEL was 12 mg/kg /d (highest dose tested) and the local NOAEL was 2 mg/kg/d.
The NOAELs for non neoplastic effects after chronic dietary DDAC administration were 32-41 mg/kg/day for rats and 76 – 93 mg/kg/day for mice. NOAELs values derivation was mainly based on aspecific unspecific effects, such as decreased body weights, considered to be secondary to local effects on gut mucosa and intestinal microflora. No organ specific toxicity was evidenced. In line with the fact that the main outcome directly derives from the irritative/corrosive properties of the active substance, the subchronic and chronic NOAELs are similar in rodents, and little difference is expected between the 2 exposure scenario.
Didecyldimethylammonium Chloride displayed no genotoxic activity in the three mutagenicity tests required for the authorisation of Biocidal Products: in-vitro gene mutation assay in S. typhimurium (Ames test), in vitro chromosomal aberrations assay in CHO cells and
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CHO/HGPRT forward mutation assay. Moreover, no clastogenic activity was observed in chromosomal aberration test in rat bone marrow in vivo. Therefore DDAC can be considered not genotoxic.
Didecyldimethylammonium Chloride is not carcinogenic and does not affect reproduction or development at doses that are not toxic to the mother. The NOAEL from maternal toxicity in the reproductive toxicity study was 1 mg/kg/d. It is not considered appropriate to use that NOAEL for systemic AEL derivation, since the administration was by gavage, and considering the local effects on the gut mucosa, it is obvious that a bolus dose is more irritant than the same amount taken slowly and mixed with the other dietary components, as it was in the 1-year dog study from which the relevant NOAEL is taken for risk characterization.
The lack of any structural similarity to known neurotoxins or of any alert for neurotoxic effects shown by quaternary ammonium chemicals in general together with no indication of neurotoxic effects in any of the performed toxicological studies support the conclusion that DDAC has no neurotoxic potential.
Medical data
No medical reports on the manufacturing personnel have been submitted.
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2.2.1.3. Exposure assessment
The biocidal product containing the active substance is used in two wood preservative treatment applications: dipping and vacuum pressure processes. For both processes, the preservative is delivered to the processing plant by tanker in the form of a concentrate. The concentrate contains 25% of the active substance Didecyldimethylammonium Chloride. It is diluted down to a suitable working strength with water. The degree of dilution varies depending on the wood species, type of wood product and anticipated use. Didecyldimethylammonium Chloride concentrations in both processes vary between 0.3% and 1.8%.
Furthermore, the use classes 1 to 4A are envisaged for the Didecyldimethylammonium Chloride containing wood preservative product.
Due to the irritant/corrosive properties of DDAC, the systemic effects can be considered as secondary in comparison to the local ones. Nevertheless, a small amount of active substance becomes systematically available and gives rise to some non significant systemic effects, such as decreasing of body weight. Therefore, both a systemic and a local exposure assessment have been connsidered so as to provide a comprehensive overview of the effects resulting from the use of DDAC.
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2.2.1.3.1 LOCAL EXPOSURE ASSESSMENT
DDAC exhibits irritant/corrosive properties which mainly affect the human exposure. In order to quantify the local exposure, the scenarios adopted have been selected from TNsG on Human Exposure and RISKOFDERM Model. In this context, it has not been taken into consideration any reduction factors from wearing clothes and/or Personal Protective Equipments; no dermal penetration has been considered, either.
DDAC is a non-volatile active substance and therefore the inhalation uptake can be considered as negligible in assessing the exposure due to the local effects.
Industrial users (primary exposure)
In the local exposure assessment the dermal route is deemed to be the most relevant one for industrial users handling both concentrated (Mixing and loading process) and diluted DDAC- based solutions (dipping and vacuum-pressure applications). The resulted exposure values are reported below. Information on assumptions and input values used in the relevant scenarios are provided in Doc. IIB.
Table 2.2.1.3.1-1 Summary of the exposure local dose for industrial users
EXPOSURE MODEL Hands exposure Body exposure Feet exposure
mg/cm2 mg/cm2 mg/cm2
MIXING&LOADING Riskofderm Connecting 0.000275 - - lines
APPLICATION PHASE (Dipping treatment): 0.0555 0.0044 0.032 Handling Model1
APPLICATION PHASE (Vacuum Pressure 0.069 0.008 0.024 treatment): Handling Model1
19 Didecyldimethylammonium Chloride Product-type 8 date SCB
Secondary exposure: Child playing on weathered structure and mouthing – ingestion (Local Exposure due to irritant effect)
The local irritant effect of the DDAC deems to be more relevant in the case of the secondary exposure than the systemic effect. In particular, this is the case of the scenario in which has taking into account the exposure for child chewing wood. Therefore it has been drafted an exposure scenario considering that the maximum absorption of product is 1.8 mg/cm3 (see above).
The volume of the timber chips is 16 cm3 (4 cm x 4 cm x 1 cm) as reported in the TNsG, Part 3, p. 50 and User Guidance, p. 52.
The fraction extracted by chewing is 10% as reported in User Guidance, p. 52.
The amount of saliva produced is 1.5 ml/min median value reported for stimulated saliva production (http://www.scopevic.org.au/therapy_crc_research_saliva_anatomy.html) .
A maximum absorption a.s mg/cm3 1.8 B size of chewed timber cut-off (chip) cm2 16 C depth of chewed timber cut-off (chip) cm 1 D = B x C volume of chip cm3 16 E a.s. extracted by chewing fraction 0.1 F = A x D x E a.s. in the mouth mg 2.88 G Amount of saliva produced ml/min 1.5 H Event duration min 1
The event duration has been conservatively assumed to be of 1 min. Any increase in duration time is associated with an higher production of saliva and consequently with an higher dilution. Anyhow this has to be considered a very worst case scenario, as the release of the 10% of the active substance in a very short time (i.e., 1 min) has to be considered unrealistic.
The estimate of the concentration in the mouth has been derived with the above reported parameters revealing the following exposure calculation:
Amount of active substance in the mouth:
F. = A x D x E = 2.88 mg
Concentration in the mouth = F/(G x H) = 1.92 mg/ml = 1920 mg/kg
Local dose expressed as percentage of active substance = 0.192 %
20 Didecyldimethylammonium Chloride Product-type 8 date SCB
2.2.1.3.2 SYSTEMIC EXPOSURE ASSESSMENT
Industrial/Professional exposure (Primary Exposure)
There are four main strata of workers that may potentially be exposed to the wood preservative in the process plant: workers that handle wet treated lumber, workers that handle treated wood after drying, maintenance workers of equipment, forklift operators.
Professional exposure from the use processes has been estimated using the scenarios reported in the Technical Notes for Guidance on Human Exposure to Biocidal Products. In a TIER 1 evaluation, representing a worst-case estimate, only the default values have been taken into account. As general assumptions, it was agreed that in the Tier 1 the estimate of the primary exposure has been carried without considering the use of the personal protective equipment (PPE) or a 100% clothing penetration with old gloves. A correction is applied for the maximum dermal absorption of 9.41% (rounded to 10%). As concerns the inhalation exposure, an agreed default value for inhalation uptake of 100% has been taken into account.
Furthermore, the value of 1.25 m3/hour for the inhalation rate, due to moderate physical activity, has been used. Furthermore, as a worst case scenario, all calculations are based on the wood treatment solution employed containing 1.8% a.s. The neat concentrate of the substance (containing 25% a.s.) is only handled under closed conditions during the Mixing and loading process.
The scenarios in TIER 1 predict potential exposure assuming that no PPE is employed. In reality due to the irritant/corrosive properties of the active substance, PPE will be worn, hence the estimates reported below have to be considered as overestimates.
In TIER 2, refined values have been considered and the assessment has been conducted assuming use of personal protective equipment including protective clothing, gloves and footwear. The exposure calculations were performed according to the recommendations of the TNsG (Human Exposure to Biocidal Products, as revised by User Guidance version 1 (EC, 2002a). Model calculations have been undertaken using measured data given in the TNsG as revised in the user guidance and are considered to represent a reasonable scenario for risk assessment purposes. For vacuum/pressure treatment, dermal exposure has been assessed assuming clothing penetration of 10% (User Guidance version 1, p42), except for certain exposure scenarios (dipping and cleaning out dipping tank) where it is assumed that impermeable coveralls will be worn (penetration = 4%; TNsG - Part 3, p60). Also, to reduce exposure via the hands, operators would be required to wear new protective gloves at the start of each daily dipping session. New gloves reduce hand-in-glove exposure by a factor of 0.6 (TNsG, Part 2, p.192). The dermal penetration of DDAC used for this assessment is 9.41% (rounded to 10%), as discussed in Section 4.1 of document IIB.
In TIER 2, for the Mixing and Loading process has been considered also the exposure scenario of RISKOFDERM Toolkit (Connecting lines). For automated transfer/pumping the Human Exposure Expert Group (HEEG) has concluded that in case of evaluated available data and models for the assessment of the exposure to operators during the loading of products into vessels or systems in industrial scale the exposure could be considered as negligible, with a
21 Didecyldimethylammonium Chloride Product-type 8 date SCB very low or accidental exposure during connecting lines. Alternatively, the RISKOFDERM Connecting lines could be used. (Opinion presented and accepted at the March meeting (2008) in the Technical Meeting in the Biocides Group). Indicative dermal exposure values for RISKOFDERM Toolkit Connecting lines referred in the HEEG document are 0.066 mg/cm2/h (0.92 mg/min) for hands. The model is a semi-quantitative model and assumes that small contaminations and no body exposure take place during the task.
Being the Mixing and Loading an automated task, only the exposure assessment carried out by using RISKOFDERM should be taken into consideration for the purpose of Annex I inclusion.
For both the Tiers, the default value for body weight of an exposed adult is assumed to be 60 kg in order to include women (50th Percentile = 60.3 kg according to ECETOC, 2001).
22 Didecyldimethylammonium Chloride Product-type 8 date SCB
In the following tables the estimates calculated on the basis of the TNsG scenarios for Total Exposure to Didecyldimethylammonium Chloride in Wood Preservation are reported.
Table 2.2.1.3.2-1- Exposure to Didecyldimethylammonium Chloride in Wood Preservation (Tiers 1-2)
Inhalation Total Total Systemic Dermal Exposure scenario Exposure (mg) Exposure dose Exposure (mg) (mg) (mg/kg/d) Tier Tier 2 Tier 2 Tier Tier Tier 2 Tier 1 Tier 1 1 1 2 Dipping Mixing and loading concentrate 0.15 0.15 0.205 0.205 0.35 0.35 0.0059 0.0059 (25% solution)(Model 7)* Dipping Mixing and loading concentrate 0.23 - - - - 0.23 - 0.004 (25% solution)(RISKOFDERM toolkit) Dipping Application 69.5 7.1 - - 69.5 7.1 1.16 0.12 (1.8% solution) Dipping Application 11.6 - - 11.6 0.2 0.02 1.2 1.2 (0.3% solution) Vacuum/pressure treatment (1.8% solution)(including feet 55 13 0.38 0.38 55.4 13.4 0.92 0.22 exposure assessment) Vacuum/pressure treatment (0.3% solution) (including feet 9.2 2.2 0.06 0.06 9.26 2.26 0.15 0.04 exposure assessment) *This Model refers to a manual task. Being the mixing and loading for DDAC an automated task, only the RISKOFDERM model should be taken into account.
23 Didecyldimethylammonium Chloride Product-type 8 date SCB
Non-professional exposure (Consumers) (Primary Exposure)
Consumers are not involved in the application (wood treatment) stage. Consumer exposure is restricted to handling of treated lumber in operations such as erecting fences. Consumers are not involved in the application stage. The level of exposure is considered to be comparable to (or less than) occupation exposure to workers that handle treated wood after it is dry.
Indirect exposure as a result of use of the active substance in biocidal product
The secondary human exposure estimates consider the potential for the exposure of professional adults, infants and children in a number of possible scenarios in which they may come into contact with DDAC treated timber.
The scenarios used in this assessment are described in the TNsG on Human Exposure to Biocidal Products Part 3, p50-51 as revised by User Guidance version 1 p50-54 (EC, 2002a).
For non-professional exposure (consumers) the following scenarios have been considered:
Acute phase reference scenarios
Adult (professionals): sanding treated wood from vacuum/pressure impregnated timber - inhalation and dermal route.
Adult (non-professionals): sanding treated wood from vacuum/pressure impregnated timber - inhalation and dermal route.
Infant: chewing wood off-cut – oral route (wood from vacuum/pressure impregnated timber)
Child not relevant.
Chronic phase reference scenarios
Adult inhalation route – not relevant
Child playing on playground structure outdoors - dermal route.
Infant playing on weathered structure and mouthing - dermal and ingestion.
24 Didecyldimethylammonium Chloride Product-type 8 date SCB
In the following table are reported the systemic exposure values of total uptake for humans.
Table 2.2.1.3.2-2- Summary of the total systemic uptake for the secondary exposure.
Oral Dermal Inhalation Combined Acute Non-professionals Adult 0.05087 -- 0.0504 mg/kg/day 0.00047 mg/kg bw sanding mg/kg/day Infant 0.288 ------mouthing mg/kg/day Chronic Professionals Adult 0.053 -- 0.0504 mg/kg/day 0.0028 mg/kg bw sanding mg/kg/day Non-professionals Child 0.0096 mg/kg bw/day -- playing Infant 0.018 0.0324mg/kg 0.0144 mg/kg/day playing mg/kg/day day
25 Didecyldimethylammonium Chloride Product-type 8 date SCB
2.2.1.4. Risk characterization
2.2.1.4.1 Risk Characterisation for local effects
Considering the repeated dose studies, the main critical effects associated with DDAC are due to its corrosive prosperities. In this context, the systemic effects such as the reduction of body weight and food consumption can be considered secondary compared to the corrosive properties of DDAC. It can be concluded that DDAC actually does not cause ‘true’ systemic effects and the derivation of a systemic AEL is not considered as relevant.
As regards the operators dermal exposure, a dermal AEL could possibly be considered. In the 2-week skin irritation study with rats, no systemic effects were observed and the NOAEL for local effects has been set at 6 mg/kg bw/day (0.3% DDAC).
However, based on the new guideline for the Risk characterisation of local effects, it was agreed (TMIII09) to include also a quantitative assessment for the secondary exposure scenario (child mouthing treated wood). Therefore, the AEC for dermal route was derived as follows.
Local NOEC derivation – Dermal route
The NOEC derived for the DDAC is of 0.3% of active substance in water (i.e., 3 g/l or 3000 mg/l or 3mg/ml). The total volume applied is of 2 ml/kg bw per day. Therefore, the resulted NOEL is of 6 mg/kg bw/day (=3mg/ml x 2ml/kg bw per day).
In the skin irritation study the treated body surface has not been well defined and therefore, the assumption of 10% coverage of the animal body could be made based on the guideline recommendations. According to the TGD, the total surface body of rat (male and female) is 400 cm2 and the mean body weight is 300g. Assuming that 10% of the body surface has been exposed to the test substance, the resulting exposed area is of 40cm2.
For the characterization of the risk due to the local dermal effects a NO(A)EC (expressed in mg/cm2) has to be derived following the formula below:
Total dose applied in mg NOAEC in mg / cm2 Treated surface in cm² (average animal weight in kg) (dose in mg / kg bw) Treated surface in cm2
NOEC = (0.3kg x 6 mg/kg bw/day) / 40cm2 = 0.045mg/cm2
The NOEC value of 0.045 mg/cm2 is equivalent to a NOEC of 0.3%.
26 Didecyldimethylammonium Chloride Product-type 8 date SCB
Selection of Assessment Factor for the dermal route (AF)
Given that local toxicity based on the chemical reactivity of QUATs is the basis for the risk characterization, a reduced inter-species AFs when extrapolating data obtained in rats to humans could be used. In fact, for the local effects the QUATs show its effects at port of entry and therefore, it is justified to assume that both the components (toxicokinetic and -dynamic) do not contribute to interspecies differences.
Regarding intra-species differences it could be acceptable to lower the default factor disregarding the TK contribution (again 3.16 ≈ 3.2), given that chemical reactivity is the principle concern. Therefore, for the intraspecies AF only the Toxicodynamic component (3.16 ≈ 3.2) could be taken into consideration.
Therefore, for the dermal route the overall AF turns out to be AF: 3.2 = 1x, interspecies; 3.2x, human variability.
AEC derivation
Based on the NOEC and the AF derived, the calculated AEC for dermal route is 0.014 mg/cm2 (0.045 mg/cm2 / 3.2) or 0.094% (0. 3% / 3.2).
Text revised following a request raised during the first discussion at CA meeting (May 2012) (ADDED) Local AEC derivation – Oral route
Following a UK proposal to consider what was accepted for a structurally similar compound (DDACarbonate) for deriving the oral AEC for the local effects in the perspective of characterizing the risks for children chewing/sucking treated wood, the RMS would like to highlight that in the DDAC CAR, for local effects an oral NOAEL has been set at 3 mg/kg bw/d from a 52-week feeding study in dogs. This NOAEL is particularly relevant since from the same study it was possible to differentiate a NOAEL for local effects on the g.i. mucosa (3 mg/kg bw/d) on the basis of emesis present at the higher dose (10 mg/kg bw/d), which was on the other hand considered as a systemic NOAEL, based on decrease body weight at the immediately higher dose. This value has been included in the Listing of Endpoints (from the very beginning) and the RMS does intend to derive the oral AEC from this endpoint, rather than from the reproductive toxicity studies on rats. This taking into consideration that also in the DDACarbonate CAR it is stated that “(…) dogs appear to be more sensitive to the adverse effects of repeated oral exposure to DDAC than rats and mice and toxicity occurs at lower doses in gavage studies compared to dietary studies (…)” (Draft Final CAR – Doc.I, p.11/59). Although an oral NOAEL for local effects had been set by the RMS, the oral AEC was not derived due to the fact that the Technical Meeting did not consider the administration by oral gavage to be fully representative of a realistic exposure route for the children scenario under evaluation. However, this conclusion was changed during the peer review of DDACarbonate and CAR report as follows: “(…) Given the underlying mode of action of DDAC/DDACarbonate toxicity (i.e., irritation/corrosion) and the anticipated pattern of oral exposure in humans (infant chewing wood), gavage administration is considered a relevant exposure route for use in the risk characterisation of DDACarbonate (…)” (Draft Final CAR – Doc.I, pp.11-12/59).
27 Didecyldimethylammonium Chloride Product-type 8 date SCB
Using the NOAEL for local effects from the dog study as point of departure for the oral AEC for local effects for DDAC, an AEC value for acute, medium-term and chronic oral exposure scenarios of 0.09 mg/ml (equivalent to 0.94 mg/kg bw/day) is proposed (based on the NOAEL of 3 mg/kg bw/day from the 52-week gavage study in dogs) and an intraspecies toxicodynamic assessment factor of 3.2. Deriving the oral AEC, the information from the original study has been considered such as the fixed dose volume of 10 ml/kg dose used for dog body weight of 10kg. In conclusion, the oral AEC results to be of 0.09 mg/ml (equivalent to 0.94 mg/kg bw/day) .
28 Didecyldimethylammonium Chloride Product-type 8 date SCB
Exposure and risk from use of the product
For industrial users, the risk resulting from the direct use of biocidal products containing DDAC has been assessed by applying the AEC approach. Therefore, the dermal loads have been compared to the calculated dermal AEC of 0.014 mg/cm2.
Hands Body exposure Feet exposure AEChands% AECbody% exposure AECfeet% EXPOSURE MODEL mg/cm2 mg/cm2 mg/cm2
MIXING&LOADING Riskofderm Connecting 0.000275 1.96 - - - - lines
APPLICATION PHASE (Dipping 0.0555 396 0.0044 31 0.032 228 treatment): Handling Model1
APPLICATION PHASE (Vacuum 0.069 493 0.008 57 0.024 172 Pressure treatment): Handling Model1
AEC% = (Exposure x 100)/AEC
Conclusion: for local effects, no unacceptable risk can occurs for industrial users handling concentrate biocidal product during the mixing and loading phase. As regards, the application stage, no risk has been highlighted for body. On the other hand, an unacceptable risk can be envisaged for both hands and feet during the application phase. Anyway, feet contamination can be reduced by prescribing that suitable impermeable boots are worn. In addition to that, the risk for hands can be lowered by using appropriate and suitable gloves. Furthermore, the gloves should be frequently replaced.
However, for the risk assessment this discussion is not really relevant, since the formulation BC-25 contains 25% DDAC, and in practice solutions of 1.8% and 0.3% DDAC are used. Therefore, at 0.3% DDAC (6 mg/kg bw/day) clear local effects are not observed in the study. For DDAC the primary effects are the local effects, hence for the risk assessment of DDAC it is more relevant to take into account the concentration of the active substance on the skin than the dose expressed in mg/kg bw/day (systemic effects). Being the concentrations of the DDAC solutions applied are equal or higher than the (marginal) NOEL from the 2-week skin irritation study, for all intended uses listed in the CAR, personal protective equipments (PPEs) should be used to protect operators against the local effects of DDAC. The conclusion from the qualitative risk assessment due to the corrosive properties of DDAC is that PPE are per definition required when applying DDAC.
29 Didecyldimethylammonium Chloride Product-type 8 date SCB
Exposure and risk from indirect exposure to the product
As concerns the risks arising from the secondary exposure, the only scenario considered as relevant is child mouthing treated wood. The resulting local dose is 0.192% DDAC (1.92 mg/ml). This value is well below the derived NOEL for local effect (i.e., 0.3%DDAC). Therefore, it can be concluded that no risk occurs due to the secondary exposure. (DELETED)
Text revised following a German comment raised during the 60-day commenting period:
( ADDED ) Being the skin less sensitive than the mucosa membrane of the digestive tract, RMS agrees with Germany that the dermal 2-week study in rats is not fully representative of the oral local effects and therefore a route-to-route extrapolation without correction with an additional AF (although discussed and accepted during the TM) can lead to an underestimation of the AECoral. A NOAEL related to local effects due to gastro intestinal mucosa irritation can be derived from the repeated oral toxicity dog study, but again is not fully representative of an AECoral. Therefore, RMS agrees with the German proposal to include an use restriction for DDAC-treated wood possibly entering into contact with children.
Following a request raised during the first discussion at CA meeting (May 2012), by a comparison of the exposure external concentrations estimated of 1.92 mg/ml DDAC with the oral AEC 0.09mg/ml a potential risk is still highlighted for children chewing and sucking timber treated cut-off being the calculated oral concentration above the oral AEC value of 0.09 mg a.s./ml therefore the risk is not acceptable.
In conclusion, as a potential risk can occur not being fully addressed the risk arising from child sucking and mouthing treated wood, the scenario has not been assessed. Therefore, the use of DDAC treated wood has to be restricted to applications where biocidal treatment is unavoidable (e.g., construction) but definitely excludes applications to treated wood composites which would otherwise come into contact with children. In order to overruled the use restriction at product authorization level an AECoral should be derived by either using an oral toxicity study for the local effects or considering an additional assessment factors when the dermal 2-week study in rats is used.
The scenario estimated for the secondary exposure was agreed during the Technical Meetings when no specific guidelines were available on the risk characterization for the local effects. The assessment should not be considered as comprehensive of the overall exposure pathways. Thus, additional exposure scenarios covering any relevant exposure scenarios should be estimated at Product Authorization stage when the guidelines on the risk characterization for the local effects are finalized, depending on the use patterns.
Therefore, based on the above discussion, it is considered inappropriate to use an AEL approach for DDAC and similar quaternary amines, because there is no true systemic toxicity. DDAC, and other quaternary amine biocides, do not exhibit “systemic toxicity” as based on changes to organs or effects on reproduction, development, mutagenicity, carcinogenicity, neurobehavior or other key toxicological endpoints. Rather, effects observed in toxicity studies occur only at irritant doses and general effects, including body weight changes at lower doses and death at high doses, are secondary to these irritant responses.
30 Didecyldimethylammonium Chloride Product-type 8 date SCB
2.2.1.4.2 Risk characterization for systemic effects
AEL (Acceptable exposure level) approach
The lowest systemic NOAEL in a repeated dose study is the one of 10 mg/kg b.w/day derived from the 52 weeks study on dogs. This value is then used in deriving the AEL. An assessment factor of 10 is used for interspecies variability and an assessment factor of 10 for taking into account intraspecies variability.
For the systemic AEL derivation was not deemed to be estimated as internal dose by including the oral absorption factor in the calculations. In fact, DDAC acts mainly on gut mucosa or at the site of application due to its corrosive effects: the effects seen in the toxicological studies are mainly secondary to this mode of action. For this reason in the CAR, it is proposed not to calculate any internal dose (correcting exposure value for the very low oral absorption). Indeed, due to its corrosive characteristics, DDAC will react immediately and only a limited amount of the active substance become systemically available. Based on these considerations, derivation of a systemic internal dose is not considered appropriate.
Exposure and risk from use of the product
Total systemic dose values are taken from the calculations presented in Document IIB. For the Mixing and Loading stage, only the data derived by using the RISKOFDERM, have been considered. In Tier 2 a realistic approach is assumed. Therefore PPE (gloves 12% penetration) are considered to be worn.
Risk characterisation is expressed as the systemic dose as a percentage of the AEL% (exposure x 100/ AEL).
Risk Characterisation Calculations for Professional Users to Didecyldimethylammonium Chloride in Wood Preservation (Tier 2).
%AEL = Total Systemic Exposure scenario dose (mg/kg/d) (Exposure x 100)/AEL (0.1 mg/kg bw/d) Dipping Mixing and loading concentrate 0.0059 5.9 (25% solution)(Model 7)* Dipping Mixing and loading concentrate 0.004 4 (25% solution)(RISKOFDERM toolkit) Dipping Application 0.12 120 (1.8% solution) Dipping 0.02 20
31 Didecyldimethylammonium Chloride Product-type 8 date SCB
Application (0.3% solution) Vacuum/pressure treatment 0.22 220 (1.8% solution)(including feet exposure assessment) Vacuum/pressure treatment (0.3% solution) (including feet exposure 0.04 40 assessment) *This Model refers to a manual task. Being the mixing and loading for DDAC an automated task, only the RISKOFDERM model should be taken into account.
A potential risk has been identified for both automated dipping and vacuum/pressure treatments using a 1.8% of DDAC-based solution. The risk will be avoided prescribing the Personal Protective Equipments as mandatory.
The DDAC-based products are not authorized to the general public so the risk from the primary exposure to consumers and man via the environment can be predicted as negligible exposure is predicted for.
Margin of Exposure (MOE) approach
Exposure and risk from use of the product
The NOAEL for dermal sub-chronic effects (12 mg a.i./kg/day – highest possible dose that could be applied but no systemic toxicity observed) is used to determine the Margin of Exposure for dermal exposure. Anyway this value does not consider the dermal absorption/penetration of 9.41% (rounded to 10%). Therefore, NOAELdermal results to be 1.2 mg a.i./kg/day). A safety factor of 100 (10 for interspecies difference x 10 for intraspecies difference) is used, although there is no evidence of systemic toxicity from dermal application of DDAC. Therefore, the MOE (NOAEL/exposure) should be equal to or greater than 100 in order to determine no risk to human health.
The NOAEL for oral sub-chronic effects (10 mg a.i./kg/day) is used to determine the Margins of Exposure for inhalation exposure in the absence of sub-chronic inhalation toxicity data. A safety factor of 100 (10 for interspecies difference x 10 for intraspecies difference) is applied. Therefore, MOE (NOAEL/exposure) should be equal to or greater than 100 in order to determine no risk to human health.
Exposure scenario MOE = MOE = Dermal NOAEL (1.2 Inhalation NOAEL (10 Systemic mg/kg/d)/ Systemic mg/kg/d) / uptake Exposure uptake Exposure (mg/kg/day) (mg/kg (mg/kg/day) (mg/kg bw/day) bw/day) Dipping Mixing and loading 0.0025 480 0.0034 2941 concentrate (25% solution)(Model 7)* Dipping 0.004 300 - -
32 Didecyldimethylammonium Chloride Product-type 8 date SCB
Mixing and loading concentrate (25% solution) (RISKOFDERM toolkit) Automated Dipping Application 0.12 10 - - (1.8% solution) Automated Dipping Application 0.02 60 - - (0.3% solution) Vacuum/pressure treatment 0.22 5 0.0057 1754 (1.8% solution)(including feet exposure assessment) Vacuum/pressure treatment 0.036 33 0.001 10000 (0.3% solution) (including feet exposure assessment) *This Model refers to a manual task. Being the mixing and loading for DDAC an automated task, only the RISKOFDERM model should be taken into account.
For industrial workers there is a concern from dermal exposure during the application of the DDAC-based products in the automated dipping and vacuum pressure treatments. Hence, to avoid any risk, the use of Personal Protective Equipments has to be prescribe as mandatory by the RMS. On the other hand, DDAC does not pose any risk to industrial workers with regard to inhalation effects.
Workers are not expected to be exposed by the oral route to the product. Although the active substance is harmful by acute oral exposure (LD50 rat, oral = 238 mg/kg), good industrial hygiene, such as washing before eating or smoking, will reduce the risk of accidental oral exposure. In conclusion, DDAC or BC-25 is not a risk to industrial workers with regard to oral exposure effects.
33 Didecyldimethylammonium Chloride Product-type 8 date SCB
Indirect/Secondary exposure as a result of use
Indirect exposure to construction timber treated with wood preservatives is not directly related to the use of the wood preservative during application or handling of the wet treated wood, but to secondary exposure to the treated ready-to use wooden articles.
Three main exposure paths were identified that are (a) acute by adults sanding treated timber, (b) acute by children ingesting wood particles and (c) chronic by being exposed to the wood surface. The calculations were performed only for the highest loading rates (retentions) of 2.0 g/m2 and 2.0 kg/m3. For the contact assessment of treated timber a worst case leaching rate of 10% per day was chosen.
Acute:
Oral acute NOEL = 10 mg/kg bw/d
Inhalation acute = use oral NOEL = 10 mg/kg bw/d
Dermal acute NOEL = 6 mg/kg/day; the main acute effect is due to the irritant/corrosive properties of DDAC, the NOEL was set from a two-week skin irritation study
Chronic:
Dermal NOAEL = 1.2 mg/kg/day
Inhalation = use oral NOAEL = 10 mg/kg/day
Intermediate-term risk calculations will use the same NOAEL as the long-term assessments resulting in the same assessments. Therefore, the intermediate-term assessments have not calculated.
34 Didecyldimethylammonium Chloride Product-type 8 date SCB
Following are reported the secondary exposure for Professional and non-professional users – MOEs for indirect exposure.
Oral Dermal Inhalation Combined NOEL/NOAEL MOE
Acute
NON-PROFESSIONALS
Adult Oral/Inhalation: Dermal: sanding 0.00047 0.05087 10 mg/kg bw/d 119 -- 0.0504 mg/kg bw mg/kg bw mg/kg bw Dermal: Inhalation: 6 mg/kg bw/day 21276 Infant 0.288 Oral/Inhalation: ------Oral: 35 mouthing mg/kg bw 10 mg/kg bw/d Chronic
PROFESSIONALS Adult Oral/Inhalation: Dermal: sanding 10 mg/kg bw/d 0.0028 0.053 24 -- 0.0504 mg/kg bw Dermal: mg/kg bw mg/kg bw Inhalation: 1.2 mg/kg 3571 bw/day NON-PROFESSIONALS Dermal: Dermal: Child 0.0096 mg/kg bw/day -- 1.2 mg/kg playing bw/day 125 Oral: Oral: 10 mg/kg 555 Infant 0.018 0.194mg/kg bw/day 0.0144 mg/kg/day playing mg/kg/day day Dermal: Dermal: 1.2 mg/kg 83 bw/day
Conclusion: according to the TNsG exposure scenarios, a risk can be highlighted for professionals (during sanding treated wood) and infants (playing with treated wood) chronically exposed to wood treated with DDAC-based products (dermal exposure). Furthermore, a risk can occur also for infant mouthing wood treated with DDAC-based products (oral acute exposure).
35 Didecyldimethylammonium Chloride Product-type 8 date SCB
Combined exposure
Combined exposure to Didecyldimethylammonium Chloride used in a wood preservative product is not expected to occur, since only industrial use is envisaged. Theoretically, a combined exposure scenario is possible when an operator, after the working day, inhales the volatile residues indoors at home. However, due to the low vapour pressure of the active substance, this latter exposure can be considered as negligible. For this reason combined exposure has not been quantitatively evaluated in this dossier.
Biocidal Product
An in vitro dermal absorption study showed that less than 0.1% DDAC fully penetrate human skin in 24 h; considering also epidermis and dermis material at the dose site, receptor fluid and rinse receptor fluid, 9.41% of total absorption can be assumed.
An acute oral toxicity study has been performed on 5% aqueous dilutions of DDAC resulting in an LD50 = 238 mg/kg and leading to the classification Xn, R22 being applied. According to the provisions of directive 1999/45/EC, this product is also classified as Xn, R22 (trigger concentration is 25%).
An acute dermal toxicity study has been performed on an 80% solution of DDAC resulting in an LD50 = 3342 mg/kg. According to the provisions of directive 1999/45/EC this product is also not classified for dermal toxicity.
This product contains 25% DDAC in water and no other components. DDAC is not volatile as the vapour pressure is 2.3E-04 Pa at 50°C. Therefore there is no concern for inhalation exposure.
Skin and eye irritation studies have been performed on an 80% dilution of DDAC, which lead to the classification as corrosive, R34 being applied. According to the provisions of directive 1999/45/EC, this product is also classified as C, R34 (trigger concentration is 10%)
An aqueous dilution of DDAC, at a higher concentration than BC-25, did not show any sensitizing potential.
Summary and conclusion
Based on the toxicological and ecotoxicological properties, the active substance Didecyldimethylammonium Chloride is classified as harmful if swallowed, causes burns and very toxic to aquatic organisms. Furthermore, the active substance is thermally stable, not classified as flammable and does not show explosive or oxidising properties.
Therefore, no risk is to be expected due to the physical-chemical properties both of the active substance and product.
Furthermore, no risk is expected due to exposure to Didecyldimethylammonium Chloride during its use both for professional and non-professional users. In conclusion, risk for consumers and man indirectly exposed via the environment is not expected, as well.
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1.5.2. Environmental Risk Assessment
1.5.2.1. Fate and distribution in the environment
Biodegradation
Didecyldimethylammonium Chloride can be considered readily biodegradable
A study to measure biodegradation in seawater was not conducted as Didecyldimethylammonium Chloride used as a wood preservative will not be released to the marine environment in considerable amounts.
Didecyldimethylammonium Chloride biodegraded in aerobic conditions. At test termination (28 days), 93.3% of the radioactivity was evolved as 14CO2 , 1.32% was recovered in the extracts and 3.28% remained in the solid. In the abiotic sample 92.22% of the radioactivity was recovered in the extracts and 1.5% remained in the solid.
For consideration of anaerobic degradation, Didecyldimethylammonium Chloride is readily biodegradable, will be used in wood preservative products, and is being supported as a biocidal active substance under Product Type 8. Due to the fact that Didecyldimethylammonium Chloride was readily biodegradable, field studies on accumulation in the sediment, aerobic degradation studies in soil, field soil dissipation and accumulation studies were not needed. However a biodegradation study in two water/sediment systems has been performed and shoed that the substance easily migrates from the aqueous phase to the sediment phase and is also easily adsorbed to sediments (high Koc). The study has a reliability indicator of 3, is not considered a key study, it has been used in support of the risk assessment. The degradation in the sediment phase did not increase very much after the first month and the DT50 of the total system was not reached within the 120 days test duration.
Abiotic Degradation
Didecyldimethylammonium Chloride was hydrolytically stable during the 30-day hydrolysis study at pH 5, 7 or 9 at 25°C.
Didecyldimethylammonium Chloride was found to be photolytically stable in the absence of a photosensitiser. An accurate estimate of the photolysis rate constants and the half-life for solutions containing no photosensitiser and all dark controls (both sensitised and nonsensitised) could not be determined since no significant degradation of the test substance was detected during the 30-day evaluation period The half-life of the test compound was determined to be 227 days with 7% degradation after 30 days.
The test substance was stable and not subject to photodegradation on soil. Extractable residues decreased from 90.5% to 80.8% (exposed) and 81.1% (non-exposed). Soil bound residues increased from 9.48% to 25.2% (exposed) and 20.9% (non-exposed). 73.8 to 74% of activity was recovered in the extractable bound residues. Half-lives were calculated as t1/2 = 132 days
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(exposed) and t1/2 = 169 days (non-exposed). Rate constants were calculated as 5.26 E-03/days (exposed) and 4.11E-03/days (non-exposed).
Estimation of Photodegradation in air was calculated using the Atmospheric Oxidation Program (AOPWIN) (Howes, D. 2004) Mean atmospheric half life = 0.367 days (8.8 hours).
Distribution
Didecyldimethylammonium Chloride can be considered as immobile in four soil/sediment types with the adsorption (Ka) and mobility (Kaoc) coefficients of Ka=1,095 and Kaoc=437,805 for sand, Ka=8,179 and Kaoc=908,757 for sandy loam, Ka=32,791 and Kaoc=1,599,564 for silty clay loam, and Ka=30,851 and Kaoc=1,469,081 for silt loam. The desorption (Kd) and mobility (Kdoc) coefficients are following reported: Kd=591 and Kdoc=236473 for sand, Kd=2074 and Kdoc=230498 for sandy loam, Kd=8309 and Kdoc=405328 for silty clay loam, and Kd=7714 and Kdoc=367334 for silt loam.
It is well known that because of their positive charge, the cationic surfactants adsorb strongly to the negatively charged surfaces of sludge, soil and sediments.
The average Koc is 1.10 106.
Mobility
The results of this study indicated that Didecyldimethylammonium Chloride had little or no potential for mobility in soil and should not pose an environmental risk for contamination of ground water. Therefore, mobility-lysimeter studies were not justified.
Bioconcentration
The bioconcentration potential of DDAC in fish was investigated in a flow through test with bluegill (28 d exposure + 18 d depuration). Based on the measured 14C residues, the steady-state BCF (whole fish) was 81, indicating that DDAC has a low potential for bioaccumulation..
No data are available on the BCFearthworm and calculation according to TGD (eq. 82d) is not applicable to ionic substances, therefore bioaccumulation by terrestrial organisms cannot be estimated with the data available. Nevertheless, it has been calculated that bioaccumulation in the terrestrial food chain would pose birds and mammals at risk of secondary poisoning in case of BCFearthworm in excess of 4000 (see IIA, 4.1.3; IIB, 3.3.5; IIIA, 7.5.5.1). In conclusion, the measurement of a terrestrial BCF is deemed not necessary.
Leaching study
The leaching values used in the calculation of Predicted Environmental Concentrations (PECs) are derived from laboratory tests, which were conducted according to the American Wood-Preserver’s Association Standard Method E11-97 being different from the OECD guidelines. The RMS considered this study acceptable, without an assessment factor, because it resembles a worst- case as the wooden blocks are continuously submerged in water taking into account the high water solubility for DDAC, that was accepted at TM level (TMI 09 and TMII 09). The leaching
38 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force study provided a worst-case leaching value that was used for Risk Assessment. No assessment factors are applied to the leaching rate of 0.19% per day (i.e. 2.6% in 14 days) because higher leaching rates would indicate a commercially non-viable situation in which the wood preservative would not be retained for sufficient time to warrant the expense of the treatment.
The FLUX and Q*Leach have been calculated according to the Appendices I and II of the OECD ESD. The FLUX and Q*Leach values are following reported: Daily FLUX (TIME1) = 1.56 x 10 -5 kg/m 2/d Daily FLUX (TIME2) = 1.52 x 10 -7 kg/m 2/d Q*Leach (TIME1) = 5.52 x 10 -4 kg/m 2 Q*Leach (TIME2) = 1.19 x 10 -3 kg/m 2
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1.5.2.2. Effects Assessment
Aquatic Compartment
The toxicity of DDAC to aquatic organisms is documented by short- and long-term studies with fresh water species belonging to three trophic levels.
The results of short-term toxicity studies indicate that DDAC is very toxic to fish, daphnia and algae. The most sensitive group is algae (Selenastrum capricornutum) with a 96 h ErC50 = 0.026 mg a.s./l. The chronic toxicity of DDAC is < 10 times higher than the acute toxicity. In long-term tests, Daphnia magna and algae, with a 21d NOEC of 0.010 mg a.s./L and a 96h NOEC = 0.014 mg a.s./L, respectively, were more sensitive than fish.
The PNEC aquatic is derived from the Daphnia NOEC, applying a factor of 10, therefore:
PNEC water = 0.001 mg a.s./l.
The hazard of DDAC to sediment dwelling organisms is based on a chronic sediment spiked test with Chironomus tentans from which a 28 d NOEC was 530 mg a.s./kg dw was derived (equivalent to 356.16 mg/kg wwt). Anyhow, it should be noted that in this test midge larvae were fed with fresh food and Chironomus is not a true endobenthic ingester, hence the toxicity of DDAC might have been underestimated, because of its high adsorption potential. The PNECsediment is calculated applying an assessment factor of 100 to this NOEC, therefore:
PNEC sediments = 3.56 mg a.s./kg wwt.
The effects of DDAC on the respiration of activated sewage sludge has been investigated in one 3 hours study. Because of the lack of statistical analysis of data, the EC50 = 11 mg a.s./l was retrieved as more robust endpoint. The lowest PNEC is obtained from this endpoint appying an assessment factor of 100:
PNECmicroorganisms = 0.11 mg/l
Metabolites
No metabolites are known, following the degradation of DDAC in water.
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Terrestrial Compartment
Acute toxicity tests have been conducted on soil dwelling invertebrates (earthworms) and three species of plants (mustard, wheat and mung bean). A 28d test on nitrogen and carbon transformation is also available.
The 14-day LC50 for earthworms (E. foetida) is > 1000 mg/kg dry soil and no effect of DDAC on nitrite, nitrate, ammonium and carbon dioxide formation is observed at a concentration of 1000 mg/kg dry soil. The most sensitive organisms were plants, with the lowest EC50 = 283 mg a.s./kg dw (equivalent to 281 mg/kg ww) relative to mustard. The PNECsoil is derived from the lowest EC50 based on wet weight and the application of an assessment factor of 1000, leading to:
PNECsoil = 0.281 mg/kg wwt.
The acute toxicity of DDAC to birds has been measured on northern bobwhite quail and provided a LD50 = 229 mg/kg bw. In the two short term dietary toxicity tests, the lowest endpoint was retrieved for mallard duck, and was LC50 > 1633 mg/kg. This estimate represents the concentration, corrected to take into account the observed food avoidance, at which no mortality was recorded; therefore it is still a conservative estimate of the acute toxicity to birds. A factor of 3000 was used to derive the PNEC:
PNECbirds = >1633 mg a.s./kg food / 3000 = > 0.54 mg/kg.
From the several studies with mammals available, the relevant lowest NOEC = 500 mg/Kg food was derived from a 18 months oral feed repeated doses study with mouse. Applying an assessment factor of 30 the following PNEC results:
PNECmammals = 500 mg/kg / 30 = 17 mg/kg.
Endocrine effects.
Based on available experimental results, there is no indication that DDAC affects the endocrine system. Structural characteristics and SAR do not hint to possible effects of DDAC as endocrine disruptor.
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1.5.2.3. PBT assessment
P criterion: Half life > >120 d in freshwater sediment.
From data of hydrolysis: DDAC is hydrolytically stable over an environmentally relevant pH range of 5-9.
From data of photolysis in water: DDAC was found to be photolytically stable in the absence of a photosensitiser.
DDAC is ready biodegradable therefore, according to the screening criteria for P, vP (ECHA Guidance on information requirements and chemical safety assessment Chapter R.11: PBT Assessment), the P criterion is not fulfilled .
B criterion: BCF > 2000
For DDAC the calculated bioconcentration factor in fish is 81. Therefore, the B criterion is not fulfilled.
T criterion: Chronic NOEC < 0.01 mg/L or CMR or endocrine disrupting effects, other evidence
The substance is classified as Xn;R22 C;R34 N;R50.
The most sensitive species is Daphnia Magna for which a NOEC of 0.01 mg/l has been derived from a 21 d reproduction study.
The whole evidence of the available information indicates that the T criterion is fulfilled.
Conclusion: The active substance DDAC does not meet the PBT criteria.
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1.5.2.4. Exposure assessment
Aquatic Compartment Exposure assessment
PECs have been calculated according to the OECD Emission Scenario Document for Wood Preservatives (ESD).
Local PEC Scenario 1: Dipping treatment during application PEClocalwater STP 0.0079 mg/l PEClocalsed STP 189.5 mg/kgwwt PECmicroorganism STP 0.21 mg/l Scenario 2: Dipping treatment during storage PEClocalwater run-off 2.3 x 10-3 mg/l PEClocalsed run-off 51 mg/kgwwt Scenario 3: Vacuum pressure treatment during application PEClocalwater STP 0.0024 mg/l PEClocalsed STP 56.3 mg/kgwwt PECmicroorganism STP 0.06 mg/l Scenario 4: Vacuum pressure treatment during storage PEClocalwater 1.7 x 10-3 mg/l PEClocalsed 40.8 mg/kgwwt *Scenario 65: Bridge over pond PEClocalwater STP Time1 0.09 mg/l Time2 0.00006 mg/l PEClocalsed STP Time1 2152 mg/kgwwt Time2 1.4 mg/kgwwt Scenario 6: Noise Barrier PEClocalwater STP Time1 0.0025 mg/l Time2 0.00002 mg/l PEClocalsed STP Time1 60 mg/kgwwt Time2 0.5 mg/kgwwt
PECSTP Time1 0.02 mg/l
PECSTP Time2 0.00017 mg/l *Not being supported by the Applicant, the risks occurring from the in situ application have not been evaluated. Consequently, the risk assessment for the use scenario 5 has been overruled.
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Terrestrial Compartment Exposure assessment
In the following table has been reported the PECs calculated using the OECD Emission Scenario Document for Wood Preservatives (ESD).
The leaching values used in the calculation of Predicted Environmental Concentrations (PECs) are derived from laboratory tests, which were conducted according to the American Wood-Preserver’s Association Standard Method E11-97 being different from the OECD guidelines. The RMS considered this study acceptable, without an assessment factor, because it resembles a worst- case as the wooden blocks are continuously submerged in water taking into account the high water solubility for DDAC, that was accepted at TM level (TMI 09 and TMII 09). The leaching study provided a worst-case leaching value that was used for Risk Assessment. No assessment factors are applied to the leaching rate of 0.19% per day (i.e. 2.6% in 14 days) because higher leaching rates would indicate a commercially non-viable situation in which the wood preservative would not be retained for sufficient time to warrant the expense of the treatment.
Local PEC
Scenario 2: Dipping treatment during storage
PEClocalsoil (TIME 1) 3.0 mg/kg PEClocalsoil (TIME 2) 0.6 mg/kg PEClocalsoil, porew (TIME 1) 1.5 x 10-4 mg/l PEClocalsoil, porew (TIME 2) 3.0 x 10-5 mg/l Scenario 4: Vacuum pressure treatment during storage
PEClocalsoil (TIME 1) 3.0 mg/kg PEClocalsoil (TIME 2) 7.2 mg/kg PEClocalsoil, porew (TIME 1) 1.5 x 10-4 mg/l PEClocalsoil, porew (TIME 2) 3.7 x 10-4 mg/l Use patternScenario 6: Treated wood in service Noise barrier
PEClocalsoil (TIME 1) 1.2 mg/kg PEClocalsoil (TIME 2) 2.5 mg/kg PEClocalsoil (TIME 2) refined including degradation* 0.5 mg/kg PECgw 6.0 x 10-5 mg/l Use patternScenario 7: Treated wood in service Fence
PEClocalsoil (TIME 1) 2.6 mg/kg PEClocalsoil (TIME 2) 5.6 mg/kg PEClocalsoil (TIME 2) refined including degradation* 0.3 mg/kg PECgw max 1.3 x 10-4 mg/l Use patternScenario 8: Treated wood in service House
PEClocalsoil (TIME 1) 3.1 mg/kg PEClocalsoil (TIME 2) 6.7 mg/kg PEClocalsoil (TIME 2) refined including degradation* 0.4 mg/kg PECgw max 1.6 x 10-4 mg/l Use patternScenario 9: Treated wood in service Transmission pole
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PEClocalsoil (TIME 1) 0.4 mg/kg PEClocalsoil (TIME 2) 1.0 mg/kg PEClocalsoil (TIME 2) refined including degradation* 0.05 mg/kg PECgw max 2.0 x 10-5 mg/l Use patternScenario 10: Treated wood in service fence post
PEClocalsoil (TIME 1) 0.4 mg/kg PEClocalsoil (TIME 2) 0.8 mg/kg PEClocalsoil (TIME 2) refined including degradation* 0.04 mg/kg PECgw max 2.0 x 10-5 mg/l * the equations available in the OECD ESD document (Chapter 7, Removal processes in the receiving compartment, p.115).
Atmospheric Compartment Exposure assessment
In the following table has been reported the PECs calculated using the default values (worst- case).
Local PEC (OECD ESD) Use patternScenario 1: Dipping application Annual average local PEC in air 3.98 x 10-5 mg/m3 Use patternScenario3: Vacuum pressure application: Annual average local PEC in air 1.2 x 10 -5mg/m3
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1.5.2.5. Risk characterisation
Aquatic Compartment
Use patternScenario PEC/PNEC values
Water Sediment Sewage compartment compartment treatment plant
Use scenario 1 (dipping treatment during application) 7.9 53.2 1.91
Use scenario 2 (dipping treatment during storage) 2.3 14.3 - Use scenario 3 (Vacuum pressure treatment during 2.4 15.8 0.55 application) Use scenario 4 (Vacuum pressure treatment during storage) 1.7 11.4 - Use scenario 6 TIME 1 TIME 1 =2 TIME 1 =16.8 0.18 Noise Barrier TIME 2 TIME 2 =0.04 TIME 2 =0.13 1.5 x 10 -3
The PEC/PNEC ratios for the water and sediment compartments in the use scenario 1, 2, 3 and 3 4 (dipping treatment during application and storage, vacuum pressure treatment during application and storage) are higher than 1. For the use scenario 1, the PEC/PNEC value is higher than the trigger value of 1 also for the sediment and sewage treatment plant. In the use scenario 4 (Vacuum pressure treatment during storage) the PEC/PNEC ratio is higher than 1 even though close to the trigger value. . The PEC/PNEC values for the water compartment for the in situ application and subsequent in- service leaching of a wood preservative from a bridge over a pond scenario suggest that this use pattern would be unacceptable for DDAC. The Applicant does not support the in situ use of DDAC-containing wood preservatives. It is suggested to restrict the in situ application of DDAC-containing wood preservative to prevent its use on structures where direct losses to water cannot be prevented. For the water and sediment compartments in the use in Noise barrier scenario the PEC/PNEC values are higher than 1 in the short-term use whilst the long- term use does not pose any risk. In conclusion, in order to reduce emissions from the application and storage phases for aquatic compartment, the dipping and vacuum pressure treatment must be performed only by those plants where significant losses can be contained (e.g., no drain connections to storm drains or STP) and appropriately recycled/disposed.
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Terrestrial Compartment including Groundwater
Summary of PEC/PNEC values for terrestrial compartment
Use patternScenario PEC/PNEC values Terrestrial compartment Scenario 2: Storage of dipped/ immersed wood After 30 days 10.67 After 15 years 2.14 Scenario 4: Storage of vacuum-pressure-treated wood: After 30 days 10.67 After 20 years 25.6 Scenario 6: Treated wood in service: Noise barrier After 30 days 4.27 After 20 years 1.77
Scenario 7: Treated wood in service: Fence After 30 days 9.25 After 20 years 1.07
Scenario 8: Treated wood in service: House After 30 days 11.03 After 20 years 1.42
Scenario 9: Treated wood in service: Transmission pole After 30 days 1.42 After 20 years 0.18
Scenario 10: Treated wood in service: Fence post After 30 days 1.42 After 20 years 0.14
For use patternscenarios 2 and 4 the PEC/PNEC values are higher than 1 suggesting that there is unacceptable risk for the terrestrial compartment. Furthermore, an increasing risk over time has been predicted for the use patternscenario 4. Therefore, all timber treated by dipping and vacuum pressure applications should be stored on impermeable hard standing surfaces so as to prevent direct losses to soil and allow losses to be collected for re-use or disposal. For use patternscenarios 6, 7, and 8 the PEC/PNEC values are higher than 1 only in the longshort-term whilst for the shortlong-term use the PEC/PNEC values are round 1 does not pose any risk. For use patternscenario 9 and 10 the PEC/PNEC values are higher than 1 in the short-term whilst the long-term use does not pose any risk.
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For use patterns 6, 7, 8, 9 and 10 the PEC/PNEC values are higher than 1 in the short-term whilst the PEC/PNEC values are lower or round 1 in the long-term. Being a potential risk identified for a number of the terrestrial compartments, the use products should be restricted to prevent the use for treatment of wood in contact with fresh water or used for outdoor constructions near or above water, or for treatment by dipping of wood that will be continually exposed to the weather or subject to frequent wetting. Therefore, the product should be restricted to prevent use on wood in use class 3 unless, a safe use of the product is also demonstrated by providing data such as an additional leaching study at product authorization stage. In fact, the leaching data currently used for the derivation of the PEC values were generated with a worst-case leaching value. Particularly, the leaching study simulates worst- case conditions being the wooden blocks continuously submerged in water, for a period of 14 days, taking into account the high water solubility for DDAC, that was accepted at TM level (TMI 09 and TMII 09). Finally, although a potential risk has been highlighted for some of the terrestrial compartments, it has to be considered that the leaching data used for the derivation of the PEC values were generated with a worst-case leaching valuea simple aqueous dilution of the active substance, following continuous 14-day immersion of the wood, and with much higher loading rates than that proposed in this dossier. The leaching study resembles a worst-case as the wooden blocks are continuously submerged in water, for a period of 14 days, taking into account the high water solubility for DDAC, that was accepted at TM level (TMI 09 and TMII 09).
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Summary of PEC/PNEC values for groundwater
As an indication for potential groundwater levels, the concentration in porewater of agricultural soil is taken, according to the TGD equations 67 and 68. It should be noted that this is a worst- case assumption, neglecting transformation and dilution in deeper soil layers.
As an indication for potential groundwater levels, the concentration in porewater of agricultural soil is taken, according to the TGD equations 67 and 68. It should be noted that this is a worst- case assumption, neglecting transformation and dilution in deeper soil layers. Use patternScenario PEC Limit value PEC/ Limit value mg/l Scenario 2: Storage of dipped/ immersed 0.00015 mg/l 1.5 wood
Scenario 4: Storage of vacuum-pressure- 0.00015 mg/l 1.5 treated wood: Scenario 6: Treated wood in service: Noise 0.00006 mg/l 0.6 barrier 0.0001 Scenario 7: Treated wood in service: Fence 0.00013 mg/l 1.3 Scenario 8: Treated wood in service: House 0.00016 mg/l 1.6 Scenario 9: Treated wood in service: 0.00002 mg/l 0.2 Transmission pole Scenario 10: Treated wood in service: Fence 0.00002 mg/l 0.2 post For scenarios 2 and 4, PEC/PNEC ratios higher than 1 are indicating a potential risk for groundwater. AnywayHowever, in order to reduce emissions from the storage phases for aquatic compartment, the dipping and vacuum pressure treatment must be performed only by those plants where significant losses can be contained (e.g no drain connections to storm drains or STP) and appropriately recycled/disposed.
Also for scenarios 7 and 8 PEC/ PNEC ratios higher than 1 are indicating a potential risk for groundwater. The treated wood is not placed on the market until it is dry. Consequently, exposure through release in groundwater of treated wet surfaces is considered to be an unlikely exposure scenario. However, for in-service use of treated wood mitigation measures are proposed which would restrict the use of the DDAC wood preservative products as to prevent use on treatment of wood in UC 3.
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Environmental risk in the atmosphere
For the atmosphere compartment no PNEC values are available. However, for all use patternscenarios, the PEC in air is considered to be negligible (≤ 1E-04) suggesting that there is no concern for this compartment.
Primary and secondary poisoning (non-compartment specific effects relevant to the food chain)
Use patternScenario PEC/PNEC values Fish-eating mammals Fish-eating birds Use scenario 1 (dipping 0.0619 treatment during application) <1.95 Use scenario 2 (dipping 0.012 treatment during storage) <0.38 Use scenario 3 (Vacuum pressure treatment during <0.6 application) 0.019 Use scenario 4 (Vacuum pressure treatment during 0.0081 <0.26 storage) Thus, the PEC/PNEC value for the scenario 1 for fish-eating birds is above the trigger value of 1. Anyhow, this ratio has been derived from a very worst-case NOEC and applying a factor of 3000. Therefore, this ratio can likely overestimate the real risk coming from this scenario.
As for the other PEC/PNEC values, they are < 1 for all use patternscenarios, there is no concern with regard to non-compartment specific effects relevant to the food chain (secondary poisoning via aquatic food chain).
The risk of secondary poisoning via the terrestrial food chain is considered be highly unlikely.
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3. DECISION
1.6. Background to the Proposed Decision
On the basis of the proposed and supported uses and the evaluation conducted as summarised in chapter 2 of this document, it can be concluded that under the conditions listed in chapter 3.2 Didecyldimethylammonium Chloride fulfils the requirements laid down in Article 5(1) (b), (c), and (d) of Directive 98/8/EC, apart from those corresponding to the list in chapter 3.4 below. Didecyldimethylammonium Chloride is proposed to be included in Annex I of the Directive provided that data/information required by RMS under chapter 3.4 are submitted by the Applicant.
The overall conclusion from the human health evaluation of Didecyldimethylammonium Chloride, for use in product type 8 (wood preservatives) is that the active substance in biocidal products containing 1.8% w/w Didecyldimethylammonium Chloride will not present an unacceptable risk to humans during the proposed normal use. This conclusion relies on the fact that users will be applying the basic principles of good practice and using appropriate and obligatory PPE (as identified in Document II-C and below); in particular for the vacuum pressure treatment where considerable contamination of the operator can be anticipated, a higher degree of protection than typical work clothing is warranted. Consequently, it is assumed impermeable coveralls will be worn. Also, to reduce exposure via the hands, operators would be required to wear new protective gloves at the start of each daily dipping session.
Also fFor the secondary exposure assessment no risks have been identified for the exposed population. Therefore, mitigation measure is proposed in order to prevent that children enter in direct contact with treated wood.
As regards the environmental risk assessment, unacceptable risks have been identified for the aquatic compartment due to the industrial applications (dipping and vacuum pressure treatments) ,and storage and in situ application of products containing 1.8% w/w Didecyldimethylammonium Chloride. However, the Applicant does not support the in situ use of DDAC wood preservatives. Therefore, for in situ treatment by brush (professional or amateur),the wood preservative products containing Didecyldimethylammonium Chloride at 1.8% w/w must not be used to treat wooden structures located where direct losses to water cannot be prevented. For the water and sediment compartments in the use in Noise barrier scenario the PEC/PNEC values are higher than 1 in the short-term use whilst the long-term use doeses not pose any risk. For the other scenarios presenting a concern risk mitigation measures are proposed. For the terrestrial compartment unacceptable risks have been identified following storage on site and, wood in service and in situ application. For the Noise Barrier, Fence and House scenarios the PEC/PNEC values are higher than 1 only in the shortlong-term whilst for the longshort-term use the PEC/PNEC values are round 1. does not pose any riskTherefore the product should be restricted to prevent use for treatment of wood in Use Class 3. For TrasmissionTransmission Pole and Fence Post scenarios the PEC/PNEC values are higher than 1 in the short-term whilst the long-term use does not pose any risk.
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For these scenarios presenting a concern risk reduction measures are proposed in order to prevent the direct losses to the soil. For the groundwater compartment, unacceptable risks have been identified following storage on site and wood in service. For the storage scenarios presenting a concern risk reduction measures is proposed in order to prevent losses which would be collected for re-use or disposal. For in-service use of treated wood mitigation measures are proposed which would restrict the use of the DDAC wood preservative products as to prevent use on treatment of wood in UC 3.
The Annex I – entry should, however, only include the intended uses with the conditions and restrictions proposed in this report.
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1.7. Proposed Decision regarding Inclusion in Annex I
The Italian CA recommends that Didecyldimethylammonium Chloride is included in Annex I to Directive 98/8/EC as an active substance for use in wood preservative products (Product- type 8), subject to the following specific provisions:
Common name: Didecyldimethylammonium Chloride
IUPAC name: N,N-Didecyl-N,N-dimethylammonium Chloride
CAS No.: 7173-51-5
EC No.: 230-525-2
Minimum degree of purity of the active substance:
The active substance as manufactured shall have a minimum purity of 87% (w/w) dry weight.
Identity and maximum content of impurities:
The identity and maximum content of impurities must not differ in such a way as to invalidate the assessment for the inclusion of the active substance on to Annex I.
Product types:
Wood preservative (product-type 8)
Specific provisions
Member States shall ensure that authorisations are subject to the following condition:
In order to reduce emissions from the application and storage phases for aquatic compartment, the dipping and vacuum pressure treatment must be performed only by those plants where significant losses can be contained (e.g no drain connections to storm drains or STP) and appropriately recycled/disposed.
Wood products treated with Didecyldimethylammonium Chloride must not come in contact with food or feedstuffs. Since neither analytical methods nor toxicological risk assessment for Didecyldimethylammonium Chloride contamination in food and feedstuffs has been carried out, the use of Didecyldimethylammonium Chloride- based wood preservative must exclude applications that may lead to contact with food and feedstuffs and contaminants thereof, unless a risk assessment is made at the stage of product authorisation.
Since the risk assessment did not address use by non-professionals, products shall not be authorised for such use unless a risk assessment is made at the stage of product authorisation.
54 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
All timber treated by automated dipping and vacuum pressure applications should be stored on impermeable hard standing surfaces to prevent direct losses to soil and allow losses to be collected for re-use or disposal. This is also important considering the potential risks identified for the groundwater related scenarios and considering the possibility of an increasing risk over the time for the terrestrial compartment for the storage scenarios.
Labels and/or safety data sheets of products authorised for industrial use should indicate that freshly timber treated by dipping and vacuum pressure applications should be stored after treatment on impermeable hard standing surfaces to prevent direct losses to soil and that any losses must be collected for re-use or disposal.
For the local effects it is not possible to characterize the risk identified for children chewing treated wood and therefore products shall not be used for the treatment of wood that may enter in direct contact with children.
.
Due to the irritant/corrosive properties, labels and/or safety data sheets of products authorised for industrial use should indicate the need of specific Personal Protective Equipments, . in according to the following characteristics:
Hygiene measures
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.
Respiratory protection
In the case of vapour formation, use a respirator with an approved filter. Respirator with a vapour filter of the following type should be used: EN 141.
Hand protection for long-term exposure
Suitable material for gloves: Nitrile rubber
Break through time / glove: > 480 min
Minimal thickness / glove: 0.7 mm
Take note of the information given by the producer concerning permeability and break through times, and of special workplace conditions (mechanical strain, duration of contact).
Hand protection for short-term exposure (e.g. accidental aerosols from splashing etc.)
Suitable material for gloves: Nitrile rubber
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Break through time / glove: > 30 min
Minimal thickness / glove: 0.4 mm
Take note of the information given by the producer concerning permeability and break through times, and of special workplace conditions (mechanical strain, duration of contact).
Eye protection
Tightly fitting safety goggles; Face-shield.
Skin and body protection
Choose body protection according to the amount and concentration of the dangerous substance at the work place, Rubber or plastic apron, Rubber or plastic boots.
Moreover due to the possibility of systemic effects the use new gloves on each working day in order to benefit of an extra protection, is strongly recommended.
In addition, for industrial/professionals, operational procedures shall be established for the manipulation of treated wood (ex: sanding wood), and industrial/professionals shall wear appropriate personal protective equipment, unless it can be demonstrated in the application for product authorization that risks can be reduced to an acceptable level by other means.
Unacceptable risks for the environment were identified for in-service use of wood treated in UC 3. It is therefore appropriate to require that products shall not be authorised for the treatment of wood that will be in contact with fresh water or used for outdoor constructions near or above water, or for treatment by dipping of wood that will be continually exposed to the weather or subject to frequent wetting, unless data is submitted to demonstrate that the product will meet the requirements of Article 5 and Annex VI, if necessary by the application of appropriate mitigation measures.
1.8. Elements to be taken into account by Member States when authorising products
Products containing Didecyldimethylammonium Chloride are intended to be used in the treatment of wood by dipping/immersion process and vacuum pressure application by professional users only. Indeed in consideration of the potential risk derived for the in-situ treatment scenarios this application shall not be authorised.
56 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
Human Health and Environmental Risk Assessment has been performed on the knowledge that the wood treatment solution employed contains 1.8% active substance. Therefore any deviation from the value of 1.8% increasing the concentration of the substance in the final treatment solution, must undergo through a specific risk assessment.
When authorising the product use Member States Authorities should ensure that the Risk Reduction Measure described in Sections 3.2 and 3.5 are applied. In particular, due to the irritant/corrosive properties, labels and/or safety data sheets of products authorised for industrial use should indicate the need of specific Personal Protective Equipments in according to the following characteristics:
Hygiene measures
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.
Respiratory protection
In the case of vapour formation, use a respirator with an approved filter. Respirator with a vapour filter of the following type should be used: EN 141.
Hand protection for long-term exposure
Suitable material for gloves: Nitrile rubber
Break through time / glove: > 480 min
Minimal thickness / glove: 0.7 mm
Take note of the information given by the producer concerning permeability and break through times, and of special workplace conditions (mechanical strain, duration of contact).
Hand protection for short-term exposure (e.g. accidental aerosols from splashing etc.)
Suitable material for gloves: Nitrile rubber
Break through time / glove: > 30 min
Minimal thickness / glove: 0.4 mm
Take note of the information given by the producer concerning permeability and break through times, and of special workplace conditions (mechanical strain, duration of contact).
Eye protection
Tightly fitting safety goggles; Face-shield.
57 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
Skin and body protection
Choose body protection according to the amount and concentration of the dangerous substance at the work place, Rubber or plastic apron, Rubber or plastic boots.
Moreover due to the possibility of systemic effects the use new gloves on each working day in order to benefit of an extra protection, is strongly recommended.
As the assessment should not be considered as comprehensive of the overall exposure pathways, additional exposure scenarios covering overall exposure pathways should be estimated at Product Authorization stage when the guidelines on the risk characterization for the local effects are finalized, depending on the use patterns.
Additional leaching data should be submitted at the product authorisation stage in order to demonstrate that use class 3 (treatment of wood exposed to weathering).
1.9. Requirement for further information
The need for the following studies should be considered:
Five-batch analysis data supporting each source of DDAC are required prior to product authorization. These data must be generated on representative batches of the technical concentrate and quantify the active substance, significant and relevant impurities. The batch analysis data must be supported by fully validated methods of analysis. Though valid analytical methods were concerned for Annex I inclusion for the active substance, impurities and process solvents in the technical concentrate, additional information/clarification must be provided for these methods if they are used to support the new batch analysis data (please refer to the RMS specific requests in the evaluation box of the relevant study summaries under Doc. IIIA).
Additional highly-specific confirmatory methods for DDAC residues in soil and water (both drinking- and surface-water) are required. These methods can be provided at the product authorization stage at national level.
For the risk characterization of the local effects, sufficient data on inhalation toxicity for DDAC should be submitted at Product Authorization stage depending on the scenarios of the biocidal product.
1.10. Recommended Measures
Due to the fact that for the representative wood preservative, different intended uses (dipping and vacuum pressure treatment) should be conducted with formulations which are containing
58 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force the active substance in a concentration no higher than 1.8% w/w, measures for a good application should be prescribed. As regards occupational safety measures it suggested that PPE should be worn for minimizing exposure. For the environment as risk scenarios have been identified for on-site storage, timber treated with Didecyldimethylammonium Chloride wood preservative formulations must be stored on impermeable grounds.
1.11. Updating this Assessment Report
This assessment report may need to be updated periodically in order to take account of scientific developments and results from the examination of any of the information referred to in Articles 7, 10.4 and 14 of Directive 98/8/EC. Such adaptations will be examined and finalised in connection with any amendment of the conditions for the inclusion of Didecyldimethylammonium Chloride in Annex I to the Directive.
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Appendix I: List of end points
Chapter 1: Identity, Physical and Chemical Properties, Details of Uses, Further Information, and Proposed Classification and Labelling
Active substance (ISO Common Name) Not available Registered in EINECS as Didecyldimethylammonium Chloride Function (e.g. fungicide) Fungicide and insecticide
Rapporteur Member State Italy
Identity (Annex IIA, point II.)
Chemical name (IUPAC) N,N-Didecyl-N,N-dimethylammonium Chloride Chemical name (CA) 1-Decanaminium, N-decyl-N,N-dimethyl-, chloride CAS No 7173-51-5 EC No 230-525-2 Other substance No. 612-131-00-6 (Annex I Index number) Minimum purity of the active substance as 870 g/kg dry weight manufactured (g/kg or g/l) Identity of relevant impurities and additives None (substances of concern) in the active substance as manufactured (g/kg)
Molecular formula C22H48N.Cl Molecular mass 362.1 g/mol Structural formula - R Cl
N+ R
R = C10H21
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Physical and chemical properties (Annex IIA, point III., unless otherwise indicated)
Melting point (state purity) The melting range is from 188 to 205°C (98.2 %) Boiling point (state purity) The substance decomposed before boiling (98.2%) Temperature of decomposition 280°C (98.2%) Appearance (state purity) Light-coloured solid (98.2 %) Relative density (state purity) 0.902 at 20°C (98.2 %) Surface tension 27.0 mN/m at 20°C (test solution: 1 g/l aqueous solution). Vapour pressure (in Pa, state temperature) 5.9E-06 Pa @ 20C (calculated) 1.1E-05 Pa @ 25C (calculated) 2.3E-04 Pa @ 50ºC (calculated) Henry’s law constant (Pa m3 mol -1) 4.27E-09 Pa m3 mol -1 @ 20C Solubility in water (g/l or mg/l, state temperature) pH 2.2: 500 g/l at 20 °C pH 9.2: 500 g/l at 20 °C pH: Solubility in organic solvents (in g/l or mg/l, state Acetone: > 600 g/l @ 20ºC temperature) (Annex IIIA, point III.1) Methanol: > 600 g/l @ 20ºC Octanol: > 250 g/l @ 20ºC Stability in organic solvents used in biocidal Ethanol: Stable < 5% loss for 14 days at 55°C products including relevant breakdown products (IIIA, point III.2) Isopropanol: Stable < 5% loss for 14 days at 55°C
Partition coefficient (log POW) (state temperature) Not determined (EC methods A.8 not applicable for surfactants). Assessment by KOWWIN is inaccurate (software database very limited for surfactants). log Pow could be roughly obtained from solubility in n-octanol and water. However, this calculation is of no use with regard to environmental fate and behaviour and secondary poisoning risk assessment (experimental BCF available) Dissociation constant (not stated in Annex IIA or Not applicable: the substance is irreversibly ionized IIIA; additional data requirement from TNsG) UV/VIS absorption (max.) (if absorption > 290 nm The ultraviolet/visible absorption spectra were consistent state at wavelength) with the assigned structure of DDAC. No maxima determined due to lack of chromophores in the molecular structure Flammability Not highly flammable (self-ignition temperature: 195°C) Explosive properties Not explosive
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Classification and proposed labelling (Annex IIA, point IX.)
The Current Classification as in Directive 67/548/EEC
with regard to physical/chemical data No classification with regard to toxicological data C- Corrosive R22; R34; S2; S26, S36/37/39; S45 with regard to fate and behaviour data No classification with regard to ecotoxicological data No classification
The proposed Classification and labelling as in Directive 67/548/EEC
with regard to physical/chemical data No classification with regard to toxicological data C- Corrosive R22; R34; S26, S28; S36/37/39; S45 with regard to fate and behaviour data No classification with regard to ecotoxicological data N- Dangerous for the environment R50; S60; S61 Specific concentration limits for the environmental Cn ≥ 2.5 %: N; R50 classification
The proposed Classification and labelling based on Regulation EC 1272/2008
GHS Pictogram GHS05, GHS06, GHS09
Signal Word Danger
Hazard Statement H301; H314; H400
Specific concentration limits for the environmental M= 10 classification
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Chapter 2: Methods of Analysis
Analytical methods for the active substance
Technical active substance (principle of method) HPLC with evaporative light scattering detection (Annex IIA, point 4.1) (ELSD). Confirmation by LC-MS
5-batch analysis from each source supporting DDAC should be provided prior to product authorization phase Impurities in technical active substance (principle HPLC-ELSD (identification by LC-MS) of method) (Annex IIA, point 4.1) Titration method IC coupled with conductivity detector
Karl-Fischer titration and GC/FID for process solvents
Analytical methods for residues
Soil (principle of method and LOQ) (Annex IIA, Extraction with methanol:water (90:10 v/v) containing point 4.2) 0.01 M ammonium formate and 0.1% formic acid. Analysis by LC-MS (m/z = 326.3). LOQ = 0.01 mg/kg Confirmatory method should be provided for the product authorization phase at national level Air (principle of method and LOQ) (Annex IIA, Not required. The a.s. is non-volatile; it will not be used point 4.2) by spray application; measurable concentrations in the air under normal use will not occur and are highly unlikely even under unusual circumstances (e.g. accidental release) Water (principle of method and LOQ) (Annex IIA, Partition with 0.1 M heptanesulfonic acid and point 4.2) dichloromethane. Concentration by rotary evaporation and re-dissolution in 0.1% formic acid in methanol. Analysis by LC-MS (m/z = 326.3). LOQ = 0.1 µg/l Confirmatory method should be provided for the product authorization phase at national level Body fluids and tissues (principle of method and The a.s. is neither toxic nor highly toxic LOQ) (Annex IIA, point 4.2) Food/feed of plant origin (principle of method and Not required. Wood treated with DDAC-containing LOQ for methods for monitoring purposes) (Annex biocidal product is not intended for and contains label IIIA, point IV.1) restrictions against use in areas where food for human consumption is prepared, consumed or stored, or where the feedingstuff for livestock is prepared, consumed or stored Food/feed of animal origin (principle of method Not required. Wood treated with DDAC-containing and LOQ for methods for monitoring purposes) biocidal product is not intended for and contains label (Annex IIIA, point IV.1) restrictions against use in areas where food for human consumption is prepared, consumed or stored, or where the feedingstuff for livestock is prepared, consumed or stored
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Chapter 3: Impact on Human Health
Absorption, distribution, metabolism and excretion in mammals (Annex IIA, point 6.2)
Rate and extent of oral absorption: The majority (>90% )of orally administered a.s is excreted very likely unabsorbed via the faeces. Based on data on urine excretion (<3%) and tissue residues (<1%), and on the highly ionic nature of the a.s., it is expected that its oral absorption is limited to 10%). Rate and extent of dermal absorption: Less than 0.1% of the applied 14C-DDAC dose dissolved in water fully penetrated human skin in 24 h. The total dermal absorption is evaluated equal to 9.41% (rounded to 10%), summing up also radioactivity present in the dermis and epidermis at the application site. Distribution: Following oral administration, tissue residues were less than 1%. Potential for accumulation: None Metabolism Four major metabolites of DDAC were identified, accounting for 40% of the administered dose, as the product of alkyl chain hydroxylation. It can be hypothesized that DDAC metabolism is carried out by gut microflora. Rate and extent of excretion: Following oral administration in rats: 89 – 99% excreted in faeces, 2.5-3% excreted in urine Toxicologically significant metabolite None
Acute toxicity (Annex IIA, point 6.1)
Rat LD50 oral 238 mg/kg bw
Rat LD50 dermal 3342 mg/kg bw (rabbit)
Rat LC50 inhalation Study not conducted- not relevant Skin irritation Corrosive NOAEL/NOAEC for 5 day-application =0.6%; NOAEL/NOAEC for 2week-application =0.3% Eye irritation Corrosive Skin sensitisation (test method used and result) Epicutaneous maximization test – Not sensitising Buehler Method – Not sensitising
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Repeated dose toxicity (Annex IIA, point 6.3)
Species/ target / critical effect Rat/Dog / GI tract/ severe irritation of g.i. mucosa- emesis Lowest relevant oral NOAEL / LOAEL NOAEL 3 mg/kg bw/day (Dog – 1 year) for local effects NOAEL 10 mg/kg bw/day (Dog – 1 year) for systemic effects Lowest relevant dermal NOAEL / LOAEL Systemic NOAEL = 12 mg/kg bw/day (Highest dose tested Rat 90 days) Local NOAEL=2 mg/kg bw/day ( Rat 90 days) Lowest relevant inhalation NOAEL / LOAEL Not conducted – not relevant
Genotoxicity (Annex IIA, point 6.6)
In-vitro: Ames test – negative (with and without metabolic activation) Chromosomal aberration test – negative (with and without metabolic activation) Mammalian cell gene mutation assay – negative (with and without metabolic activation) In-vivo: Chromosomal aberration test in rat bone marrow - negative
Carcinogenicity (Annex IIA, point 6.4)
Species/type of tumour Rat/none, Mouse/none lowest dose with tumours Negative
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Reproductive toxicity (Annex IIA, point 6.8)
Species/ Reproduction target / critical effect Rat /NOEL/reduced body weight and food consumption in parental and F1-F2 animals Lowest relevant reproductive NOAEL / LOAEL LOAEL/NOAEL parental = 1500/750 mg/kg food (> 64 mg/kg bw/day / > 31 mg/kg bw/day) LOAEL/NOAEL F1 offspring = 1500/750 mg/kg food (> 64 mg/kg bw/day / > 31 mg/kg bw/day) LOAEL/NOAEL F2 offspring = 1500/750 mg/kg food (> 64 mg/kg bw/day / > 31 mg/kg bw/day) Species/Developmental target / critical effect Rat / NOAEL / maternal toxicity Lowest relevant developmental NOAEL / LOAEL LOAEL/NOAEL maternal = 8.1 mg/kg bw/day / 0.8 mg/kg bw/day NOAEL developmental ≥ 16.2 mg/kg bw/day Species/Developmental target / critical effect Rabbit / NOAEL /maternal toxicity Lowest relevant developmental NOAEL / LOAEL LOAEL/NOAEL maternal = 3.0 mg/kg bw/day / 1.0 mg/kg bw/day NOAEL developmental ≥ 3 mg/kg bw/day
Neurotoxicity / Delayed neurotoxicity (Annex IIIA, point VI.1)
Species/ target/critical effect Lowest relevant developmental NOAEL / LOAEL Study not conducted- not relevant
Other toxicological studies (Annex IIIA, VI/XI)
...... None required
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Medical data (Annex IIA, point 6.9)
...... No substance-specific effects have been noted. No .... specific observations or sensitivity/allergenicity have been reported
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Summary for local effects
Value Study Safety factor Professional/Non-Professional users ADI (if residues in food or feed) Not applicable
2 AEC (Acceptable Exposure 0.014 mg/cm 2-week skin irritation 3.2 Concentration) study in rats Reference value for dermal absorption Not applicable Drinking water limit Not applicable ARfD (acute reference dose) Not applicable
Acceptable exposure scenarios for local effects (including method of calculation) Professional users Hands: 0.000275 mg/cm2 (MIXING&LOADING Riskofderm Connecting lines); 0.069 mg/cm2 (Vacuum pressure treatment - Handling Model1) Body: 0.0044mg/cm2 (Dipping treatment - Handling Model1) - 0.008mg/cm2 (Vacuum pressure treatment - Handling Model1) Feet: 0.024mg/cm2 (Vacuum pressure treatment - Handling Model1) - 0.032mg/cm2 (Dipping treatment - Handling Model1) Production of active substance: Not applicable Formulation of biocidal product Not applicable Intended uses Dipping and Vacuum pressure industrial application Secondary exposure Not applicable Non-professional users Not applicable Indirect exposure as a result of use Dermal: 0.192% a.s.
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Summary for systemic effects
Value Study Safety factor Professional/Non-Professional users ADI (if residues in food or feed) Not applicable
AEL (Acceptable Exposure Level) 0.10 52 week oral study in dogs 100 mg/kg/day
Reference value for dermal 10 % In vitro on human skin absorption Drinking water limit 0.1 g/L As set by EU drinking water Directive 98/83/EC ARfD (acute reference dose) Not applicable
Acceptable exposure scenarios for systemic effects (including method of calculation)
Professional users AEL%= 4-220
Production of active substance: Not applicable Formulation of biocidal product Not applicable Secondary exposure Not applicable Non-professional users Not applicable Indirect exposure as a result of use MOE(dermal) = 24 – 119 MOE(inhalation) = 3571 – 21276 MOE(oral) = 35 - 555
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Chapter 4: Fate and Behaviour in the Environment
Route and rate of degradation in water (Annex IIA, point 7.6, IIIA, point XII.2.1, 2.2) Hydrolysis of active substance and relevant pH___5___: >30 days at 25°C metabolites (DT ) (state pH and temperature) 50 pH___7___: >30 days at 25°C pH___9___: >30 days at 25°C Photolytic / photo-oxidative degradation of active ca. 0% after 30 days (direct) substance and resulting relevant metabolites ca. 7% after 30 days (indirect) Readily biodegradable (yes/no) Yes Biodegradation in seawater Not used in seawater Non-extractable residues Not applicable Distribution in water / sediment systems (active A biodegradation study in two water/sediment systems substance) has been performed and shoed that the substance easily migrates from the aqueous phase to the sediment phase and is also easily adsorbed to sediments (high Koc). The degradation in the sediment phase did not increase very much after the first month and the DT50 of the total system was not reached within the 120 days test duration Distribution in water / sediment systems Not applicable (metabolites) Amount of 14C-DDAC as mean percentageof the recovered radioactivity in the TNO and Kromme Rijn water/sediment system. Days 0 1 2 7 14 28 42 56 84 120 TNO 97.9 93.9 91.7 91.3 77.4 69.2 70.6 67.8 76.1 69.5 Kromme 97.0 94.5 94.5 87.0 68.8 54.3 57.9 54.8 64.7 54.4 Rijn
Route and rate of degradation in soil (Annex IIIA, point VII.4, XII.1.1, XII.1.4; Annex VI, para. 85) Mineralization (aerobic) No data available Laboratory studies (range or median, with number For readily biodegradable substances, TGD recommend of measurements, with regression coefficient) 15 days for surface water and 300 days for soil if Kp >1000 Field studies (state location, range or median with Not applicable number of measurements) Anaerobic degradation Active substance is readily biodegradable; Soil photolysis Stable, not subject to photogradation in soil Non-extractable residues No data available Relevant metabolites - name and/or code, % of Not measured applied a.i. (range and maximum) Soil accumulation and plateau concentration No data available
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Adsorption/desorption (Annex IIA, point XII.7.7; Annex IIIA, point XII.1.2)
Ka , Kd Ka (Kaoc) values for four soil types: Sand: 1’095 (437’805) Kaoc , Kdoc Sandy loam: 8’179 (908’757) pH dependence (yes / no) (if yes type of Silty clay loam: 32’791 (1’599’564) dependence) Silt loam: 30’851 (1’469’081)
Kd (Kdoc) values for four soil types: Sand: 591 (236’473) Sandy loam: 2074 (230’498) Silty Clay loam: 8309 (405’328) Silt loam: 7714 (367’334)
No pH dependence
Fate and behaviour in air (Annex IIIA, point VII.3, VII.5) Direct photolysis in air Atmospheric t½ = 2.8 hr (AOPWIN) Quantum yield of direct photolysis Not specified Photo-oxidative degradation in air Latitude: ...... Season: ......
DT50 ...... Volatilization Not volatile [vapour pressure 2.3 E-06 hPa (2.3E-04 Pa) @ 50°C]
Monitoring data, if available (Annex VI, para. 44) Soil (indicate location and type of study) No data available Surface water (indicate location and type of No data available study) Ground water (indicate location and type of No data available study) Air (indicate location and type of study) No data available
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Chapter 5: Effects on Non-target Species
Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2, Annex IIIA, point 10.2) Species Time-scale Endpoint Toxicity
Fish Fathead Minnow 96h Mortality LC50 = 0.19 mg a.s./L (Pimephales promelas) Zebra fish (Brachydanio 34d Growth NOEC = 0.0322 mg rerio) a.s./L Invertebrates
Daphnia magna 48h Immobilisation EC50 = 0.062 mg a.s./l Daphnia magna 21d Reproduction NOEC = 0.010 mg a.s./L (survival of parent animals) Chironomus tentans 28d Mortality and growth NOEC = 530 mg a.s./kg dw (equivalent to 356.16 mg/Kg wwt) Algae 1
Selenastrum 96h Biomass production ErC50 = 0.026 mg capricornutum and cell density a.s./L;
NOErC = 0.014 mg a.s./L L (based on initial measured conc.)
ErC50 = 0.021 mg a.s./L; NOErC = 0.011 mg a.s./L (based on mean measured conc.) Microorganisms
Activated sewage sludge 3h Respiration EC50 = 11.0 mg a.s./L inhibition 1) Algae are target organisms for DDAC.
Effects on earthworms or other soil non-target organisms
Acute toxicity to Eisenia foetida 14d LC50 > 1000 mg a.s./kg, in artificial soil (Annex IIIA, point XIII.3.2) NOEC ≥1000 mg a.s./kg, in artificial soil Reproductive toxicity to No data available. ………………………… (Annex IIIA, point XIII.3.2)
Acute toxicity to plants EC50 = 283 mg a.s./kg dw soil (mustard, dry weight)
(Annex Point IIA 7.5.1.3) (equivalent to EC50 =281 mg/kg ww soil).
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Effects on soil micro-organisms (Annex IIA, point 7.4)
Nitrogen mineralization EC50 > 1000 mg a.s./kg Carbon mineralization EC50 > 1000 mg a.s./kg
Effects on terrestrial vertebrates
Repeated dose toxicity to mammals 18 months NOEC = 500 mg a.s./kg food (mouse) (Annex Point IIA6.3) Acute toxicity to birds Northern bobwhite quail
(Annex IIIA, point XIII.1.1) LD50 = 229 mg a.s./kg bw Dietary toxicity to birds Northern bobwhite quail (Annex IIIA, point XIII.1.2) LC50 = >5620 mg a.s./kg a.s. food Dietary toxicity to birds Mallard duck (Annex IIIA, point XIII.1.2) LC50 = >1633 mg a.s./kg a.s. food Reproductive toxicity to birds Not available (Annex IIIA, point XIII.1.3)
Effects on honeybees (Annex IIIA, point XIII.3.1)
Acute oral toxicity No data available nor required Acute contact toxicity No data available nor required
Effects on other beneficial arthropods (Annex IIIA, point XIII.3.1)
Acute oral toxicity No data available nor required Acute contact toxicity No data available nor required Acute toxicity to No data available nor required …………………………………..
Bioconcentration (Annex IIA, point 7.5)
Bioconcentration factor (BCF) Measured BCFfish whole body = 81 BCFearthworm not available
Depuration time (DT50) 7-14d whole body. (DT90) Level of metabolites (%) in organisms No data available accounting for > 10 % of residues
Chapter 6: Other End Points
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Appendix II: List of Intended Uses
Summary of intended uses The biocidal product containing the active substance is used in two wood preservative treatment applications: dipping and vacuum pressure processes. For both processes the preservative is delivered to the processing plant by tanker in the form of a concentrate. The concentrate contains 25% of the active substance Didecyldimethylammonium Chloride. It is diluted to a suitable working strength with water. The degree of dilution varies depending on the wood species, type of wood product and anticipated use. The requirements for Didecyldimethylammonium Chloride concentration in both processes vary between 0.3% and 1.8%. Dipping/ immersion process Application rate: 1.8 kg a.s./m3 (worst case site-specific information) Total amount of a.s. processed per site per day: 3.6 kg Total tonnage of a.s. processed per site per year: Confidential (Reference B) (worst case) Total tonnage of a.s. used in region: Confidential (Reference C) (widespread use, 10% of tonnage used in default region) Vacuum pressure process Application rate: 1.8 kg a.s./m3 (worst-case site-specific information) Total amount of a.s. processed per day: Confidential (Reference E) Total tonnage of a.s. processed per site per year: Confidential (Reference F) (worst case) Total tonnage of a.s. used in region: Confidential (Reference C) (widespread use, 10% of tonnage used in default region) Organisms to be controlled Wood destroying basidiomycetes (Coniophora puteana / Coniophora spec., Coriolus versicolor, Gloephyllum trabeum, Poria vaillantii / Poria spec., Fomes spec., Trametes spec., etc.) Wood staining molds (Aureobasidium pullulans, Sclerophoma pityopila, Ophistostoma piliferum, Aspergillus niger, Aspergillus terreus, Chaetomium globosum, Paecilomyces variotii, Penicillium funicolosum, Trichoderma viridae, etc.) Wood boring insects (Hylotrupes bajulus, Anobium punctatum, Lyctus brunneus, termites, etc.) Products to be protected Wood, use classes 1 to 4A according to ISO draft standard (see Document IIIA Section 2 Table 2.10.2.2.2-1) Use concentration The use concentration depends on the type of application technique, use class required and on additional formulation components. For details see exposure-scenarios in the Risk Assessments.
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Appendix III: List of Studies
Document III A
Endpoint Reference Reference No. Non-Key Studies are italicized. 3.1.1 – Melting point D47 Schneider, S. (2000) Determination of the melting temperature (LON 3256) of Dodigen 1881 AS (pure active substance of Bardac 22) in accordance with OECD-Guideline 102 and according to EEC Guideline A.1. Clariant GmbH - Werk Cassella-Offenbach, Analytische und Physikalische Abteilung, Frankfurt, Germany. Report No. B 077/2000 (unpublished). 3.1.3 – Density D48 Schneider, S. (2000) Determination of the density of (LON 3257) Dodigen 1881 AS (pure active substance of Bardac22) in accordance with OECD-Guideline 109 and according to EEC-Guideline A.3. Clariant GmbH - Werk Cassella- Offenbach, Analytische und Physikalische Abteilung, Frankfurt, Germany. Report No. B079/2000 (unpublished). 3.2 – Vapor pressure D49 Smeykal, H. (2000) Dodigen 1881 AS - DD 00/004: Vapour (LON 3275) pressure. Siemens Axiva GmbH & Co. KG, Frankfurt, Germany. Report No. SI092-00 (unpublished). 3.4.1 – UV/VIS D93 Petrovic P. (2000) Characterization of the structure of 3.4.2 – IR (LON 3278) Dodigen1881 AS. Clariant GmbH - Werk Cassella-Offenbach, 3.4.3 – NMR Analytische 3.4.4 – MS und Physikalische Abteilung, Frankfurt, Germany. Report No. B 085/2000 (unpublished). 3.5 – Solubility in water D51 Schneider, S. (2000) Determination of the water solubility of (LON 3280) Dodigen 1881 AS (pure active substance of Bardac 22) in accordance with EEC-Guideline A.6. Clariant GmbH - Werk Cassella-Offenbach, Analytische und Physikalische Abteilung, Frankfurt, Germany. Report No. B 080/2000(unpublished). 3.7(1) – Solubility in organic D101 Schneider, S. (2001) Determination of the solubility of Dodigen solvents (LON 3279) 1881 AS [pure active substance of Bardac22] in organic solvents. AllessaChemie GmbH - Werk Cassella-Offenbach, Analytik, Frankfurt, Germany. Report No. B 084/2000 (unpublished). 3.7(2) – Solubility in organic D92 Young S. (2004) N,N-Didecyl-N,N-dimethylammonium solvents (LON 3802) chloride (DDAC): Solubility in octanol. Huntingdon Life Sciences, Huntingdon, Cambridgeshire, England. Report No. DKG/011 033992 (unpublished). 3.8 – Stability in organic D94 Young, S. (2004) N,N-Didecyl-N,N-dimethylammonium solvents (LON 3803) chloride (DDAC): Stability in ethanol and isopropanol. Huntingdon Life Sciences, Huntingdon, Cambridgeshire, England. Report No. DKG/012 042290 (unpublished). 3.9 – Partition coefficient D137 Nixon, W.B. (1998) DDAC octanol/water partition coefficient test. Unpublished letter report dated August 14, 1998; from Wildlife International, Ltd., Easton, MD, USA. (unpublished). 3.9 – Partition coefficient D92 Young, S. (2004) N,N-Didecyl-N,N-dimethylammonium 75 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
(LON 3802) chloride (DDAC): Solubility in octanol. Huntingdon Life Sciences, Huntingdon, Cambridgeshire, England. Report No. DKG/011 033992 (unpublished). [REPORT FILED UNDER ENDPOINT 3.7] 3.10 – Thermal stability D95 Keipert, W. (2001) Determination of the thermal stability and (LON 3449) stability in air of Dodigen 1881 AS (Bardac 22 AS) in accordance with OECD-Guideline 113. AllessaChemie GmbH - Werk Cassella-Offenbach, Analytik, Frankfurt, Germany. Report No. B 012/2001 (unpublished). 3.11(1) – Flammability D96 Keipert, W. (2001) Determination of the relative self ignition (solids) & Autoflammability (LON 3446) temperature of Dodigen 1881 AS (Bardac 22 AS) in accordance with EEC-Guideline A.16. AllessaChemie GmbH - Werk Cassella-Offenbach, Analytik, Frankfurt, Germany. Report No. B 022/2001 (unpublished). 3.11(2) – Flammability D97 Keipert, W. (2001) Determination of the flammability of (solids) & Autoflammability (LON 3447) Dodigen 1881 AS (Bardac 22 AS) in accordance with EEC-Guideline A.10. AllessaChemie GmbH - Werk Cassella-Offenbach, Analytik, Frankfurt, Germany. Report No. B 021/2001 (unpublished). 3.13 – Surface tension D98 Schneider, S. (2001) Determination of the surface tension of an (LON 3448) aqueous solution of Dodigen 1881 AS (Bardac 22 AS) in accordance with OECD-Guideline 115. AllessaChemie GmbH, Analytik, Frankfurt, Germany. Report No. B 023/2001 (unpublished). 3.14 – Viscosity D135 Keipert, W. (2003) Determination of the viscosity of Bardac (LON 3660) 22/Dodigen 1881 in accordance with OECD-Guideline 114. AllessaChemie GmbH, Analytik, Frankfurt, Germany. Report No. B 019/2003 (unpublished). 3.15(1) – Explosive D99 Dodigen 1881 AS (Bardac 22 AS) in accordance with properties (LON 3445) EECGuideline A.14. AllessaChemie GmbH - Werk Cassella- Offenbach, Analytik, Frankfurt, Germany. Report No. B 024/2001 (unpublished). 3.15(2) – Explosive D100 Tremain, S.P. (2002) Didecyl dimethylammonium chloride properties (LON 3612) (DDAC): Determination of explosive and oxidising properties, expert statement. Safepharm Laboratories Ltd., Shardlow, Derbyshire, England. SPL Project No. 102/438 (unpublished). 3.16 – Oxidising properties D100 Tremain, S.P. (2002) Didecyl dimethylammonium chloride (LON 3612) (DDAC): Determination of explosive and oxidising properties, expert statement. Safepharm Laboratories Ltd., Shardlow, Derbyshire, England. SPL Project No. 102/438 (unpublished). [REPORT FILED UNDER ENDPOINT 3.15] 4.1(1) – Analytical methods D136 Sloan, R. (1994) Bardac 2280 - Characterization of the test for purity/impurity (LON 3843) substance. Huntingdon Life Sciences, Huntingdon, Cambridgeshire, England. Report No. 94-013 (unpublished).
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4.1(2) – Analytical methods D91 Young, S. (2003) Didecyldimethylammonium chloride (DDAC; for purity/impurity (LON 3804) CAS RN 7173-51-5): Screening by ion chromatography. Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, England. Study No. DKG/010 (unpublished). 4.1(3) – Analytical methods Lonza Report Kurz M. and Ranft V. (2007) Determination of quaternary for purity/impurity (new No. 4134 ammonium compounds and related quaternary impurities by submission) HPLC-ELSD. Study No.CSPE-44/BS-07-70. Lonza AG. (Unpublished).
4.2 (a) – Analytical methods D46 Brewin, S. (2003) Didecyldimethylammonium chloride (DDAC; for determination of residues (LON 3701) CAS RN 7173-51-5): Validation of methodology for the in soil determination of residues in soil. Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, England. Report No. ADB/014 033180 (unpublished). 4.2 (c) – Analytical methods D90 Brewin, S. (2003) Didecyldimethylammonium chloride (DDAC; for determination of residues (LON 3702) CAS RN 7173-51-5): Validation of methodology for the in water determination of residues in drinking, ground and surface water. Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, England. Report No. ADB/015 033168 (unpublished). 5.3.1 – Effects on Target D139 Archer, K., Nicholas, D.D. and T.P. Schultz (1995) Screening of Organisms wood preservatives: Comparison of the soil block, agar block and agar plate tests. Forest Prod. J. 45(1): 86-89. D142 Linfield, W.M. (1969) Chapter 2: Straight-chain alkylammonium compounds. In E. Jungermann (Ed.), Cationic Surfactants. Marcel Dekker: New York, NY, USA, pp 9-70. D151 Wazny, J. and L.J. Cookson (1993) A comparison of Coniophora olivacea and Coniophora puteana test strains. International Research Group on Wood Preservation Document No. IRG/WP/20004. D152 Wazny, J. and L.J. Cookson (1994) Comparison of the agar block and soil block methods used for evaluation of fungitoxic value of QAC and CCA wood preservatives. International Research Group on Wood Preservation Document No. IRG/WP/20039. 6.1.1 – Acute oral toxicity D9 Morris, T.D. (1992) Acute oral toxicity in rats – Median lethal (LON 3746) dosage determination with didecyldimethylammonium chloride (DDAC). Hill Top Biolabs, Inc., Miamiville, Ohio, USA. Study No. 91-8114-21(A) (unpublished). 6.1.1 – Acute oral toxicity D102 Ullman, L. and R. Sacher (1983) Acute oral toxicity study (LON 1239) (LD50) with P 0151 in rats. Research & Consulting Company AG, Itingen, Switzerland. Project No. 021532 (unpublished). 6.1.2 – Acute dermal toxicity D85 Siglin, J.C. (1987) Acute dermal toxicity study in rabbits LD50 (LON 3805) test (EPA) with DMD10AC. Springborn Institute for Bioresearch, Inc., Spencerville, OH, USA. Study No. 3165.1.2C 77 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
(unpublished). 6.1.2 – Acute dermal toxicity D71 Nitka S. (1980) An acute dermal LD50 study in albino rabbits (LON 1237) Consumer Product Testing, Fairfield, NJ, USA. Report No 8044- 10 (unpublished). 6.1.4(1) – Skin irritation D103 Jones, J.R. and T.A. Collier (1986) P0151: OECD 404 Acute (LON 1241) dermal irritation/corrosion test in the rabbit. Safepharm Laboratories Ltd., Derbyshire, England. Project No. 102/1 (unpublished). 6.1.4 – Skin irritation D104 Allan, D.J. (1995) P4289: Acute dermal irritation test in rabbits (LON 2424) Safepharm Laboratories Ltd., Derbyshire, England. Project No. 102/1908 (unpublished). 6.1.4 – Skin irritation D11 Morris, T.D. (1991) Primary skin irritation study in rabbits with (LON 3807) didecyldimethylammoniumchloride (DDAC). Hilltop Biolabs, Inc., Miamiville, OH, USA. Study No. 91-8114-2 (B) (unpublished). 6.1.4(2) – Eye irritation D10 Morris, T.D. (1991) Primary eye irritation study in rabbits with (LON 3806) didecyldimethylammonium chloride (DDAC). Hill Top Biolabs, Inc., Cincinnati, OH, USA. Study No. 91-8114-21 (unpublished). 6.1.5(1) – Skin sensitisation D105 Clement, C. (1992) BARDAC-22: Test to evaluate the (LON 1243) sensitizing potential by topical applications in the guinea pig. Hazleton- Institute Français de Toxicologie, L’Arbresle, France. Report No. 704323 RE (unpublished). 6.1.5(2) – Skin sensitisation D155 Kukulinski, M. (2003) Skin sensitization study of Maquat 4480- (LON 4003) E, Batch #30717J5, OPPTS 870.2600. Tox Monitor Laboratories, Inc., Oak Park, IL, USA. Project No. 03-092-5 (unpublished). 6.1.5(3) – Skin sensitisation D154 Merkel, D.J. (2004) Bardac 2280: Dermal sensitization test in (LON 4005) guinea pigs (Buehler method). Product Safety Laboratories, Dayton, NJ, USA. Study No. 15512 (unpublished). 6.1.5 – Skin sensitisation D12 Morris T.D. (1991) Photoallergy study in guinea pigs with (LON 3808) didecyldimethylammoniumchloride (DDAC). Hill Top Biolabs, Cincinnati, OH , USA. Study No. 91-8114-21(D) (unpublished). 6.2(1) – Metabolism in D45 Roper, C.S. (2001) The in vitro percutaneous absorption of mammals (toxicokinetics; (LON 3329) [14C]- dermal absorption) Didecyldimethylammonium chloride (DDAC) through human skin. Inveresk Research, Tranent, Scotland. Report No. 19128 (unpublished). 6.2(2) – Metabolism in D34, D35 Selim, S. (1989) Absorption, distribution, metabolism and mammals (toxicokinetics; (LON 1779) excretion studies of didecyldimethylammoniumchloride dermal absorption) (DDAC) in the rat. Biological Test Center, Irvine, CA, USA. Study No. P01421 (unpublished). 6.4.1(1) – Subchronic oral D27 Van Miller, J.P. (1988) Ninety-day dietary subchronic oral toxicity (rat) (LON 1257) toxicity study with didecyldimethylammoniumchloride in rats. Union Carbide, Bushy Run Research Center, Export, PA, USA. Report No. 51-506 (unpublished).
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6.4.1(2) – Subchronic oral D16 Osheroff, M.R. (1990) Subchronic oral toxicity study of toxicity (dog) (LON 1256) didecyldimethylammonium chloride in dogs. Hazelton Laboratories America, Inc., Vienna, VA, USA. Study No. 2545- 100 (unpublished). 6.4.1(3) – Subchronic oral D19 Van Miller, J.P. (1988) Subchronic dietary dose range finding toxicity (mouse) (LON 1775) study with didecyldimethylammonium chloride in mice. Union Carbide, Bushy Run Research Center, Export, PA, USA. Report No. 51-507 (unpublished). 6.4.1 – Subchronic oral D108 Cox, G.E. and Bailey, D. (1975) 90-Day feeding study in dogs toxicity (LON 1256A) with a quaternary ammonium sanitizer BARDAC-22. Food and Drug Research Laboratories, Inc., Waverly, NY, USA. (unpublished). 6.4.2 – Subchronic dermal D14 Gill, M.W. and J.P. Van Miller (1988) Ninety-day subchronic toxicity test (rat) (LON 1255) dermal toxicity study with didecyldimethylammonium chloride in rats. Union Carbide, Bushy Run Research Center, Export, PA, USA. Project No. 51-554 (unpublished). 6.5(1) – Chronic toxicity D18 Schulze, G.E. (1991) Chronic oral toxicity study of (dog) (LON 1778) didecyldimethylammoniumchloride in dogs. Hazelton Washington, Inc., Vienna, VA, USA. Study No. 2545-102 (unpublished). 6.5(2) – Chronic toxicity (rat) D30 Gill, M.W., Chun, J.S. and C.L. Wagner (1991) Chronic dietary (LON 1755) toxicity/oncogenicity study with didecyldimethylammoniumchloride in rats. Union Carbide, Bushy Run Research Center, Export, PA, USA. Report No. 53-566 (unpublished). 6.6.1 – In vitro gene mutation D87 Thompson, P.W. (2001) LZ1043 (Didecyldimethylammonium study in bacteria (LON 3341) chloride): Reverse mutation assay "Ames Test" using Salmonella typhimurium. Safepharm Laboratories Ltd., Derby, England. Project No. 102/368 (unpublished). 6.6.2 – In vitro cytogenicity D31 Holmstrom, M., Leftwich, D.J. and I.A. Leddy (1986) PO151: study in mammalian cells (LON 1253) Chromosomal aberrations assay with Chinese hamster ovary cells in vitro. Inveresk Research International, Musselburgh, Scotland. Report No. 4236 (unpublished). 6.6.3 – In vitro gene mutation D32 Young, R.R. (1988) Mutagenicity test on assay in mammalian cells (LON 1254) didecyldimethylammoniumchloride (DDAC) in the CHO/HGPRT forward mutation assay. Hazleton Laboratories America, Inc., Kensington, MD, USA. Report No. 10141-0-435 (unpublished). 6.6.4 – In vivo Mutagenicity D84 Allen, J.A., Proudlock R.J. and P.C. Brooker (1987) Analysis of (conditional) (LON 1252) metaphase chromosomes obtained from bone marrow of rats treated with P0151 (Bardac 22). Report No. LZA 24/8761. Huntingdon Research Centre, Ltd., Huntingdon, England. (unpublished). 6.6.5 – In vivo Mutagenicity D33 Cifone, M.A. (1988) Mutagenicity test on didecyldimethyl – (conditional) (LON 1499) ammoniumchloride (DDAC) in the rat primary hepatocyte unscheduled DNA synthesis assay. Hazleton Laboratories America, 79 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
Inc., Kensington, MD, USA. Study No. 10141-0-447 (unpublished). 6.7(1) – Carcinogenicity D21 Gill, M.W., Hermansky, S.J. and C.L. Wagner (1991) Chronic (mouse) (LON 1776) dietary oncogenicity study with didecyldimethylammonium chloride in mice. Union Carbide, Bushy Run Research Center, Export, PA, USA. Report No. 53-528 (unpublished). 6.7(2) – Carcinogenicity (rat) D30 Gill, M.W., Chun, J.S. and C.L. Wagner (1991) Chronic dietary (LON 1755) toxicity/oncogenicity study with didecyldimethylammonium chloride in rats. Union Carbide, Bushy Run Research Center, Export, PA, USA. Report No. 53-566 (unpublished). [REPORT FILED UNDER 6.5] 6.8.1(1) – Teratogenicity, rat D23 Neeper-Bradley, T.L. (1991) Developmental toxicity evaluation (LON 1781) of didecyldimethylammoniumchloride administered by gavage to CD® (Sprague-Dawley) rats. Union Carbide, Bushy Run Research Center, Export, PA, USA. Project No: 53-534 (unpublished). 6.8.1(2) – Teratogenicity, D26 Tyl, R.W. (1989) Developmental toxicity study of rabbit (LON 1770) didecyldimethylammoniumchloride administered by gavage to New Zealand white rabbits. Union Carbide, Bushy Run Research Center, Export, PA, USA. Project No. 51-590 (unpublished). 6.8.2 – Two generation D29 Neeper-Bradley, T. L. (1991) Two-generation reproduction reproduction study (LON 1777) study in Sprague-Dawley (CD) rats with didecyldimethylammonium chloride administered in the diet. Union Carbide, Bushy Run Research Center, Export, PA, USA. Report No. 52-648 (unpublished). 6.11 – Studies on other D106 Duprey, L.P. and J.O. Hoppe (1967) TS 19: Toxicity and routes of administration (LON 1248) irritation studies on quarternary ammonium compounds. (parenteral routes) – Acute Sterling IV study in rats Winthrop Research Institute, Renssalaer, NY, USA. (unpublished).
7.1.1.1.1 – Hydrolysis D36 Dykes, J. and M. Fennessey (1989) Hydrolysis of (LON 1791) didecyldimethylammoniumchloride (DDAC) as a function of pH at 25°C. ABC Laboratories Inc., Columbia, MO, USA. Report No. 37004 (unpublished). 7.1.1.1.2 – D37 Dykes, J. and M. Fennessey (1989) Determination of the Phototransformation (LON 1793) photolysis rate of didecyldimethylammoniumchloride (DDAC) in water in pH 7 buffered solution at 25°C. ABC Laboratories Inc., Columbia, MO, USA. Report No. 37005 (unpublished). 7.1.1.2.1(1) – Ready D52 Downing, J.L. (1993) Aerobic aquatic biodegradation of biodegradability (LON 2305) didecyldimethylammonium chloride using a shake flask test system. ABC Laboratories, Inc., Environmental Fate and Assessment Division, Columbia, MO, USA. Report No. 40687 (unpublished). 7.1.1.2.1(2) – Ready D61a Schaefer E.C. (1996) Aerobic aquatic biodegradation test with biodegradability (LON 2923) didecyldimethylammoniumchloride (DDAC) and a bentonite 80 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
clay:DDAC complex conducted with natural sediment and site water. Wildlife International Ltd., Easton, MD, USA. Project No. 434E-101 (unpublished). 7.1.1.2.1(3) – Ready D110 Hirschen, D.M., Ziemer, M. and D. Seifert (1998) Bardac 22: biodegradability (LON 2970) DOC die-away test OECD 301 A with pre-adapted inoculum. Clariant GmbH, Frankfurt, Germany. Report No. D0094-1 (unpublished). 7.1.1.2.1(4) – Ready D134 Bazzon, M and F. Deschamps (2002) Biotic degradation biodegradability (LON 3796) biodegradability evaluation on aqueous medium ultimate aerobia of the referenced compounds, CATIGENE T 50. INERIS, Vert- lepetit, France. Study No. 506223 (unpublished). 7.1.1.2.1(5) – Ready D159 Fiebig, S. (2006) Dodigen 1881: Ready Biodegradability: biodegradability (LON 4031) Modified Sturm Test. Dr. U. Noack-Laboratorien, Germany. Study No. AST97952 (unpublished).
7.1.1.2.2 – Inherent D110 Hirschen, D.M., Ziemer, M. and D. Seifert (1998) Bardac 22: biodegradability (LON 2970) DOC die-away test OECD 301 A with pre-adapted inoculum. Clariant GmbH, Frankfurt, Germany. Report No. D0094-1 (unpublished). [REPORT FILED UNDER ENDPOINT 7.1.1.2.1] 7.1.2.1.1 – Aerobic D60 Schaefer, E.C. (2001) Didecyldimethylammonium chloride biodegradation (LON 3438) (DDAC): Dieaway in activated sludge. Wildlife International, Inc., Easton, MA, USA. Project No. 289E-112 (unpublished). Other Non-Key D111 Bücking H. -W. (1989) Prüfung des biologischen Abbaus von Biodegradability Report(s) (LON 1266) BARDAC 22 im OECD-Confirmatory-Test. Hoechst, Frankfurt, Included in This Submission Germany. Report No. 95/89(B) (unpublished). D40 Cranor, W. (1991) Anaerobic aquatic metabolism of (LON 1798) 14CDidecyldimethylammoniumchloride (14C-DDAC) ABC Laboratories, Inc., Columbia, MO, USA. Report No. 37007 (unpublished). D41 Cranor, W. (1991) Aerobic aquatic metabolism of (LON 1794) 14CDidecyldimethylammoniumchloride (14C-DDAC) ABC Laboratories, Inc., Columbia, MO, USA. Report No. 37008 (unpublished). D65 de Vette, H.Q.M., van Asten, J.G. and A.O. Hanstveit (2000) A (LON 3255) water/sediment study of didecyldimethylammonium chloride (DDAC) using [14C]-DDAC. TNO Nutrition and Food Research, Delft, The Netherlands. Study No. IMW-99-9048-01 (unpublished). D39 Cranor, W. (1991) Aerobic soil metabolism of 14C (LON 1796) -Didecyldimethylammonium chloride (14C-DDAC). ABC Laboratories, Columbia, MO, USA. Report No. 37006(unpublished).
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D120 Todt K. (1991) Abbau von Didecydimethylammoniumchlorid im (LON 1957) Boden unter Praxisbedingungen. Natec, Hamburg, Deutschland. Abschlußbericht NA 91 9601 (unpublished). 7.2.2.4 – Other soil D38 Schmidt, J. (1992) Determination of the photolysis rate of degradation studies (LON 3069) didecyldimethylammonium chloride on the surface of soil. ABC Laboratories, Columbia, MO, USA. Report No. 39505 (unpublished). 7.2.3.1 – Adsorption and D42 Daly, D. (1989) Soil/sediment adsorption-desorption of 14C - desorption (LON 1792) Didecyldimethylammoniumchloride(DDAC). Analytical Bio- Chemistry Laboratories, Inc., Columbia, MO, USA. Report No. 37009 (unpublished). 7.4.1.1(1) – Acute toxicity to D5 LeLievre, M.K. (1990) Evaluation of fish (Oncorhynchus kisutch) (LON 1788) didecyldimethylammonium chloride (DDAC) in a static acute toxicity test with Coho salmon, Oncorhynchus kisutch. Springborn Laboratories, Inc., Wareham, MA, USA. SLI Report No. 90-4-3290 (unpublished). 7.4.1.1(2) – Acute toxicity to D4 LeLievre, M.K. (1990) Evaluation of Didecyldimethylammonium fish (Lepomis macrochirus) (LON 1786) chloride (DDAC) in a static acute toxicity test with bluegill sunfish, Lepomis macrochirus. Springborn Laboratories, Inc., Wareham, MA, USA. SLI Report No. 89-10-3111 (unpublished). 7.4.1.1(3) – Acute toxicity to D56 Putt, A.E. (1994) Didecyldimethylammoniumchloride (DDAC): fish (Pimephales promelas) (LON 2937) Static acute toxicity to fathead minnow (Pimephales promelas) with and without the presence of humic acid. Springborn Laboratories, Inc., Wareham, MA, USA. Report No. 94-1-5122 (unpublished). 7.4.1.1(4) – Acute toxicity to D68 Swigert, J.P., Graves, W.C. and M.A. Mank (1995) An fish (Pimephales promelas) (LON 3087) evaluation of didecyldimethylammoniumchloride (DDAC) in a 96-hour flowthrough acute toxicity study with the fathead minnow (Pimephales promelas). Wildlife International Ltd., Easton, MD, USA. Project No. 289A-124 (unpublished). 7.4.1.1(5) – Acute toxicity to D69 Swigert, J.P., W.C. Graves and M.A. Mank (1995) An fish (Oncorhynchus mykiss) (LON 3809) evaluation of didecyldimethylammonium chloride (DDAC) in a 96-hour flowthrough acute toxicity study with the rainbow trout (Oncorhynchus mykiss). Wildlife International Ltd., Easton, MD, USA. Project No. 289A-125 (unpublished). 7.4.1.1 – Acute toxicity to fish D54 Collins, M.K. (1994) Didecyldimethylammonium-chloride (Cyprinodon variegatus) (LON 3166) (DDAC): Evaluation in a static acute toxicity test with sheepshead minnow (Cyprinodon variegatus). Springborn Laboratories, Inc., Wareham, MA, USA. SLI Report No. 93-6-4833 (unpublished). 7.4.1.1 – Acute toxicity to fish D55 Miller, J.L. (1997) Evaluation of Bardac 2280 in a static- (Acipenser transmontanus) (LON 2948) renewal acute toxicity test with juvenile white sturgeon, Acipenser transmontanus. Aqua-Science Environmental Toxicology 82 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
Specialists, Davis, CA, USA. (unpublished). 7.4.1.1 – Acute toxicity to fish D112 Luy, T. and S. Frances (1971) Report on fish (rainbow trout) (Oncorhynchus mykiss) (LON 1270) toxicity testing using BARDAC 22. Wells Laboratories, Inc., Jersey City, NJ, USA. (unpublished). 7.4.1.1 – Acute toxicity to fish D113 Adema, D.M.M. (1978) The acute toxicity of Barquat MB 50, (Poecilia reticulata) (ON 1268) Barquat 4250 and Bardac 22 to young guppies. Centraal Laboratorium TNO, Delft, The Netherlands. Report No. CL 78/34 (unpublished). 7.4.1.1 – Acute toxicity to fish D64 Miller, J.L. (1997) Evaluation of Bardac 2280 in a static- (Acipenser transmontanus) in (LON 2950) renewal the presence of Fraser River acute toxicity test with juvenile white sturgeon Acipenser sediment transmontanus, in the presence of Fraser River sediment. Aqua- Science, Davis, CA, USA. (unpublished). 7.4.1.1 – Acute toxicity to fish D70 Swigert, J.P., Graves, W.C. and M.A. Mank (1995) Evaluation (Oncorhynchus mykiss) (LON 2938) of a Bentonite clay:didecyldimethylammoniumchloride (DDAC) complex in a 96-hour static acute toxicity study with the rainbow trout (Oncorhynchus mykiss). Wildlife Internationl, Ltd., Easton, MD, USA. Project No. 289A-121 (unpublished). 7.4.1.2(1) – Acute toxicity to D6 LeLievre, M.K. (1990) Evaluation of invertebrates (Daphnia (LON 1787) didecyldimethylammonium magna) chloride (DDAC) in a static acute toxicity test with daphnids, Daphnia magna. Springborn Laboratories, Inc., Wareham, MA, USA. Report No. 89-10-3112 (unpublished). 7.4.1.2(2) – Acute toxicity to D67 Swigert, J.P., Graves, W.C. and M.A. Mank (1995) An invertebrates (Daphnia (LON 2939) evaluation magna) of didecyldimethylammoniumchloride (DDAC) in a 48-hour flowthrough acute toxicity study with the cladoceran (Daphnia magna). Wildlife International Ltd., Easton, MD, USA. Project No. 289A- 122 (unpublished). 7.4.1.2 – Acute toxicity to D8 LeLievre, M.K. (1990) Evaluation of didecyldimethylammonium invertebrates (Mysidopsis (LON 1789) chloride (DDAC) in a static acute toxicity test with mysid bahia) shrimp, Mysidopsis bahia. Springborn Laboratories, Inc., Wareham, MA, USA. Report No. 90-2-3233 (unpublished). 7.4.1.2 – Acute toxicity to D59 Dionne, E. (1994) Didecyldimethylammoniumchloride (DDAC): invertebrates (Crassostrea Evaluation in a static (recirculated) acute toxicity test with virginica) Eastern oysters (Crassostrea virginica) using [14C]-DDAC. Springborn Laboratories, Inc., Environmental Sciences Division, Wareham, MA, USA. Report No: 93-12-5079 (unpublished). 7.4.1.2 – Acute toxicity to D58 Dionne, E. (1994) Didecyldimethylammoniumchloride (DDAC): invertebrates (Crassostrea (LON 3167) Evaluation in a static (recirculated) acute toxicity test with virginica) Eastern oysters (Crassostrea virginica) using [14C]-DDAC. Springborn Laboratories, Inc., Environmental Sciences Division, Wareham, 83 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
MA, USA. Report No. 93-6-4854 (unpublished). 7.4.1.3(1) – Growth D57 Desjardins, D., Kendall, T.Z., Van Hoven, R.L. and H.O. inhibition test on algae (LON 3433) Krueger (Selenastrum capricornutum) (2003) Bardac 2280: A 96-hour toxicity test with the freshwater alga (Selenastrum capricornutum). Wildlife International, Ltd., Easton, MD, USA. Project No. 289A-152 (unpublished).
7.4.1.3(2) – Growth D115 Scheerbaum, D. (1998) Bardac 22: Alga, growth inhibition test inhibition test on algae (LON 3011) (72hr). Dr.U.Noack-Laboratorium fur Angewandte Biologie, (Scenedesmus subspicatus) Sarstedt, Germany. Study No. SS061301 (unpublished). 7.4.1.3(3) – Growth D66 Desjardins, D., Kendall, T.Z., Van Hoven, R.L. and H.O. inhibition test on algae (LON 3659) Krueger (Selenastrum capricornutum) (2003) Bardac 2280: A 96-hour toxicity test with the freshwater in Natural Surface Water alga (Selenastrum capricornutum) using natural surface water. Wildlife International, Ltd., Easton, MD, USA. Project No. 289A- 153 (unpublished). 7.4.1.4 – Inhibition to D117 Mead, C. (2001) LZ1043 (Didecyldimethylammounium microbiological activity (LON 3330) chloride): Assessment of the inhibitory effect on the respiration of activated sewage sludge. Safepharm Laboratories Ltd., Derby, England. Project No. 102-369 (unpublished). 7.4.1.4 – Inhibition to D116 Vonk, J.W. (1989) Biodegradability of Bardac-22. Netherlands microbiological activity (LON 1265) Organization for Applied Scientific Research, TNO Division of Technology for Society, Delft, The Netherlands. Report No. R89/252 (unpublished). 7.4.2– Bioconcentration D43 Fackler, P.H. (1990) Bioconcentration and elimination of (Lepomis machrochirus) (LON 1790) 14Cresidues by bluegill (Lepomis machrochirus) exposed to didecyldimethylammonium chloride (DDAC). Springborn Laboratories, Inc., Wareham, MA, USA. Report No. 89-7-3043 (unpublished). 7.4.3.2 – Reproduction and D118 Hooftman, R.N., de Vette, H.Q.M. and B. Borst (2001) Early growth in fish (Brachydanio (LON 3373) life rerio) stage test under intermittent flow-through conditions with didecyldimethylammounium chloride and the fish species, Brachydanio rerio (OECD Guideline No. 210). TNO Chemistry, Delft, The Netherlands. Report No. V99.1173 (unpublished).
7.4.3.4 – Reproduction and D7 Hooftman, R.N. and H.Q.M. de Vette (2001) Intermittent growth in invertebrates (LON 3323) flowthrough (Daphnia magna) reproduction test with didecyldimethylammonium chloride and Daphnia magna. TNO Nutrition and Food Research, Department of Environmental Toxicology, Delft, The Netherlands. Report No. V99.1171 (unpublished). 7.4.3.4 – Reproduction and D121 Jonas, W. (1992) Bardac 2270: Reproduktionstest an Daphnia growth in invertebrates (LON 1953) magna. (unpublished). 84 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
(Daphnia magna) 7.4.3.5.1 – Effects on D63 England, D.C. and T. Leak (1995) Chronic toxicity of sediment dwelling organisms (LON 2941) sedimentincorporated (Chironomus tentans) didecyldimethylammoniumchloride (DDAC) to Chironomus tentans. ABC Laboratories, Columbia, MO, USA. Report No. 41005 (unpublished). 7.5.1.1 – Inhibition to D119 DeVette, H.Q.M., Hanstveit, R. and J.A. Schoonmade (2001) microbiological activity (LON 3378) The assessment of the ecological effects of didecyldimethylammounium chloride (Guidelines OPPTS 850.5100 Soil Microbial Community Test, OECD 216 and OECD 217 and CTB Section H.4.1). TNO Chemistry, Delft, The Netherlands. Study No. IMW- 99-9048-05 (unpublished). 7.5.1.2(1) – Acute toxicity to D88 Henzen, L. (1999) The acute toxicity of DDAC to the worm earthworms (LON 3153) species Eisenia fetida in a 14-day test (OECD Guideline No. 207). TNO Nutrition and Food Research Institute, Delft, The Netherlands. Report No. V99.160 (unpublished). 7.5.1.2(2) – Acute toxicity to D133 Rodgers, M.H. (2004) N-Alkyl (C12-16)-N,N-dimethyl- earthworms (LON 3799) Nbenzylammonium chloride (ADBAC): Acute toxicity (LC50) to the earthworm. Huntingdon Life Sciences, Huntingdon, Cambridgeshire, England. Report No. ADB/023 033976 (unpublished). 7.5.1.3 – Acute toxicity to D114 Gray, J. (2004) N,N-Didecyl-N,N-dimethylammonium chloride plants (LON 3811) (DDAC): Acute toxicity to terrestrial plants. Huntingdon Life Sciences, Huntingdon, Cambridgeshire, England. Study No. DKG/014 (unpublished). 7.5.3.1.1 – Acute oral D1 Campbell, S., Hoxter, K.A. and G.J. Smith (1991) toxicity (Bobwhite Quail) (LON 1784) Didecyldimethylammonium chloride: An acute oral toxicity study with the northern bobwhite. Wildlife International Ltd., Easton, MD, USA. Project No. 289-103A (unpublished). 7.5.3.1.2(1) – Short-term D2 Long, R.D., Hoxter, K.A. and G.J. Smith (1991) toxicity (Bobwhite Quail) (LON 1785) Didecyldimethylammonium chloride: A dietary LC50 Study with the northern bobwhite. Wildlife International Ltd., Easton, MD, USA. Project No. 289-101 (unpublished). 7.5.3.1.2(2) – Short-term D3 Long, R.D., Hoxter, K.A. and G.J. Smith (1991) toxicity (Mallard duck) (LON 1783) Didecyldimethylammoniumchloride: A dietary LC50 study with the mallard. Wildlife International Ltd., Easton, MD, USA. Project No. 289-102 (unpublished). Other Non-Key Report(s) D53 Bestari, K. (2001) Determination of the leachability of Bardac Included in This Submission (LON 3815) 2280 from treated wood. Centre for Toxicology, University of Guelph, Guelph, Ontario, Canada. Study No. 200-CT-WL-B22 (unpublished).
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References Supporting D138 Ruddick, J.N.R. (1984) Appendix C – Alkylammonium Summaries Found in compounds Document III-A, Section 5 as wood preservatives. Proc. Am. Wood. Pres. Assn. 80, 191- 204 and Appendix D – Field testing of alkylammonium wood preservatives, pp. 206-210. D139 Archer, K., Nicholas, D.D. and T.P. Schultz (1995) Screening of wood preservatives: Comparison of the soil block, agar block and agar plate tests. Forest Prod. J. 45(1): 86-89. D140 Creffield, J.W. (1993) A study on the effectiveness of DDAC to protect wood from attack by termites. IRG Document No. IRG/WP/93-30009. D141 Graf, E. (1987) Determination of the protective effectiveness of Bardac 22 against wood destroying basidiomycetes after leaching procedure. Swiss Federal Laboratories for Materials Testing and Research, EMPA St. Gallen, Switzerland. Report No. 2311491 (unpublished). [Ref. No. D132 (LON 3819), English translation of the German original test report (Bestimmung der Wirksamkeitsgrenze von Bardac 22 gegen holzzerstörende Basidiomyceten) attached as Annex. D142 Linfield, W.M. (1969) In E. Jungermann, Ed., “Cationic Surfactants”, Marcel Dekker, New York, N.Y. Chapter 2, “Straight-Chain Alkylammonium Compounds, pages 9-70.
D144 Molnar, S., Dickinson, D.J. and R.J. Murphy (1996) Accelerated testing for out-of-ground contact using natural biological preconditioning. International Research Group on Wood Preservation Document No. IRG/WP 96-20088. D145 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997a) Accelerated testing for out-of-ground contact using natural biological preconditioning. International Research Group on Wood Preservation Document No. IRG/WP 97-20108. D146 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997b) Microbial ecology of treated lap-joints at Hilo, Hawaii for 24 months. International Research Group on Wood Preservation Document No. IRG/WP 97-20107. D147 Preston, A.F., McKaig, P.A. and P.J. Walcheski (1986) Termite resistance of treated wood in an above ground field test. International Research Group on Wood Preservation Document No. IRG/WP 1300. D148 Preston, A.F., Walcheski, P.J., McKaig, P.A. and D.D. Nicholas (1987) Recent research on alkylammonium compounds in the U.S. Proc. Am. Wood Pres. Assn. 83, 331-347.
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D149/D150 Walker, L.E. (1999) Waterproofing and preservative compounds and preparation thereo. U.S. Patent 5,855,817; and Walker L.E. (1998) Waterproofing and preservative composition for wood. U.S. Patent 5,833,741. D151 Wazny, J. and L.J. Cookson (1993) A comparison of Coniophora olivacea and Coniophora puteana test strains. International Research Group on Wood Preservation Document No. IRG/WP/20004. D152 Wazny, J. and L.J. Cookson (1994) Comparison of the agar block and soil block methods used for evaluation of fungitoxic value of QAC and CCA wood preservatives. International Research Group on Wood Preservation Document No. IRG/WP/20039. D153 Zahora, A., Jin, L., Cui, F., Walcheski, P. and K. Archer (2000) E-mail communication of June 9, 2000 and attached memo to AWPA Formosan Subterranean Task Force.
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Document III B
Endpoint Reference Reference No. Non-Key Studies are italicized. 3.5(1) – Acidity/alkalinity D156 Sydney, P. (2006) BC-25: Physicochemical properties. and if necessary pH value (LON 4006) Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, (1% in water) England. Report No. DKG0018/062229 (unpublished). 3.6(1) – Relative Density D156 Sydney, P. (2006) BC-25: Physicochemical properties. (LON 4006) Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, England. Report No. DKG0018/062229 (unpublished). 3.8(1) – Technical D156 Sydney, P. (2006) BC-25: Physicochemical properties. characteristics of the biocidal (LON 4006) Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, product: Persistent foaming England. Report No. DKG0018/062229 (unpublished). 3.10.2(1) – Viscosity D156 Sydney, P. (2006) BC-25: Physicochemical properties. (LON 4006) Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, England. Report No. DKG0018/062229 (unpublished). References Supporting D139 Archer, K., Nicholas, D.D. and T.P. Schultz (1995) Screening of Summaries Found in wood preservatives: Comparison of the soil block, agar block Document III-B, Section 5 and agar plate tests. Forest Prod. J. 45(1): 86-89. D143 Moffat, A.R. (1994) A determination of the toxic level of ACQ2100 wood preservative for the powder post borer Lyctus brunneus (Stephens). International Research Group on Wood Preservation Document No. IRG/WP 94-20029. D144 Molnar, S., Dickinson, D.J. and R.J. Murphy (1996) Accelerated testing for out-of-ground contact using natural biological preconditioning. International Research Group on Wood Preservation Document No. IRG/WP 96-20088. D145 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997a) Accelerated testing for out-of-ground contact using natural biological preconditioning. International Research Group on Wood Preservation Document No. IRG/WP 97-20108. D146 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997b) Microbial ecology of treated lap-joints at Hilo, Hawaii for 24 months. International Research Group on Wood Preservation Document No. IRG/WP 97-20107. D148 Preston, A.F., Walcheski, P.J., McKaig, P.A. and D.D. Nicholas (1987) Recent research on alkylammonium compounds in the U.S. Proc. Am. Wood Pres. Assn. 83, 331-347. D153 Zahora, A., Jin, L., Cui, F., Walcheski, P. and K. Archer (2000) E-mail communication of June 9, 2000 and attached memo to AWPA Formosan Subterranean Task Force.
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Appendix IV: List of standard terms and abbreviations
Stand. term / Explanation Abbreviation A Ampere ACh Acetylcholine AChE Acetylcholinesterase ADBAC Alkyldimethylbenzylammonium Chloride ADI acceptable daily intake ADME administration distribution metabolism and excretion ADP adenosine diphosphate AE acid equivalent AF assessment factor AFID alkali flame-ionisation detector or detection A/G albumin/globulin ratio ai active ingredient
ALD50 approximate median lethal dose, 50% ALT alanine aminotransferase (SGPT) Ann. Annex AOEL acceptable operator exposure level AMD automatic multiple development ANOVA analysis of variance AP alkaline phosphatase approx Approximate ARC anticipated residue contribution ARfD acute reference dose as active substance AST aspartate aminotransferase (SGOT) ASV air saturation value ATP adenosine triphosphate BAF bioaccumulation factor BCF bioconcentration factor bfa body fluid assay BOD biological oxygen demand bp boiling point BPD Biocidal Products Directive BSAF biota-sediment accumulation factor BSE bovine spongiform encephalopathy BSP bromosulfophthalein BUN blood urea nitrogen bw body weight c centi- (x 10 –2 ) °C degrees Celsius (centigrade) CA controlled atmosphere CAD computer aided design cd candela CDA controlled drop(let) application cDNA complementary DANN CEC cation exchange capacity cf confer, compare to
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Stand. term / Explanation Abbreviation CFU colony forming units ChE cholinesterase CI confidence interval CL confidence limits cm centimetre CNS central nervous system COD chemical oxygen demand Conc Concentration CPK creatinine phosphatase cv coefficient of variation Cv ceiling value d day(s) DDAC Didecyldimethylammonium Chloride DES diethylstilboestrol DIS draft international standard (ISO) DMSO dimethylsulfoxide DNA deoxyribonucleic acid dna designated national authority DO dissolved oxygen DOC dissolved organic carbon dpi days post inoculation DRP detailed review paper (OECD)
DT50(lab) period required for 50 percent dissipation (under laboratory conditions) (define method of estimation)
DT90(field) period required for 90 percent dissipation (under field conditions) (define method of estimation) dw dry weight DWQG drinking water quality guidelines decadic molar extinction coefficient EASE Estimation and Assessment of Substance Exposure
EC50 median effective concentration ECD electron capture detector
ED50 median effective dose EDI estimated daily intake EINECS European inventory of existing commercial substances ELINCS European list of notified chemical substances ELISA enzyme linked immunosorbent assay e-mail electronic mail EMDI estimated maximum daily intake EN European norm EPMA electron probe micro-analysis ERL extraneous residue limit ESD Emission Scenario Document ESPE46/51 evaluation system for pesticides EUSES European Union system for the evaluation of substances F Field F0 parental generation F1 filial generation, first
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Stand. term / Explanation Abbreviation F2 filial generation, second FBS full base set FELS fish early-life stage FIA fluorescence immuno-assay FID flame ionisation detector
Fmol fractional equivalent of the metabolite´s molecular weight compared to the active substance FOB functional observation battery foc organic carbon factor (compartment dependent) fp freezing point FPD flame photometric detector FPLC fast protein liquid chromatography g gram(s) gd gestation day GAP good agricultural practice GC gas chromatography GC-EC gas chromatography with electron capture detector GC-FID gas chromatography with flame ionisation 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 GM geometric mean GMO genetically modified organism GMM genetically modified micro-organism GPC gel-permeation chromatography GPS global positioning system GSH Glutathione GV Granulosevirus h hour(s) H Henry’s Law constant (calculated as a unitless value) ha hectare(s) Hb Haemoglobin HC5 concentration which will be harmless to at least 95 % of the species present with a given level of confidence (usually 95 %) HCG human chorionic gonadotropin Hct Haematocrit HDT highest dose tested hL Hectolitre HEED high energy electron diffraction HID helium ionisation detector HPAEC high performance anion exchange chromatography
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Stand. term / Explanation Abbreviation HPLC high pressure liquid chromatography or high performance liquid chromatography HPLC-MS high pressure liquid chromatography - mass spectrometry HPPLC high pressure planar liquid chromatography HPTLC high performance thin layer chromatography HRGC high resolution gas chromatography
HS Shannon-Weaver index Ht Haematocrit HUSS human and use safety standard I Indoor
I50 inhibitory dose, 50%
IC50 median immobilisation concentration or median inhibitory concentration 1 ICM integrated crop management ID ionisation detector IEDI international estimated daily intake IGR insect growth regulator im intramuscular inh inhalation INT 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazoliumchloride testing method ip intraperitoneal IPM integrated pest management IR infrared ISBN international standard book number ISSN international standard serial number IUCLID International Uniform Chemical Information Database iv intravenous IVF in vitro fertilisation k (in combination) kilo k rate constant for biodegradation K Kelvin Ka acid dissociation constant Kb base dissociation constant
Kads adsorption constant
Kdes apparent desorption coefficient kg kilogram
KH Henry´s Law constant (in atmosphere per cubic metre per mole)
Koc organic carbon adsorption coefficient
Kom organic matter adsorption coefficient
Kow octanol-water partition coefficient Kp solid-water partition coefficient kPa kilopascal(s) l, 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
LC50 lethal concentration, median LCA life cycle analysis
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Stand. term / Explanation Abbreviation LC-MS-MS liquid chromatography with tandem mass spectrometry
LD50 lethal dose, median; dosis letalis media LDH lactate dehydrogenase ln natural logarithm LOAEC lowest observable adverse effect concentration LOAEL lowest observable adverse effect level LOD limit of detection LOEC lowest observable effect concentration LOEL lowest observable effect level log logarithm to the base 10 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 micrometre (micron) MAC maximum allowable concentration MAK maximum allowable concentration MC moisture content MCH mean corpuscular haemoglobin MCHC mean corpuscular haemoglobin concentration MCV mean corpuscular volume MDL method detection limit MFO mixed function oxidase µg microgram mg milligram MHC moisture holding capacity MIC minimum inhibitory concentration min minute(s) MKC minimum killing concentration mL millilitre MLT median lethal time MLD minimum lethal dose mm millimetre MMAD mass median aerodynamic diameter mo month(s) MOE margin of exposure mol mole(s) MOS margin of safety mp melting point MRE maximum residue expected MRL maximum residue level or limit mRNA messenger ribonucleic acid MS mass spectrometry MSDS material safety data sheet
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Stand. term / Explanation Abbreviation MTD maximum tolerated dose MT material test MW molecular weight n.a. not applicable n- normal (defining isomeric configuration) n number of observations NAEL no adverse effect level nd not detected NEDI national estimated daily intake NEL no effect level NERL no effect residue level ng Nanogram nm Nanometre NMR nuclear magnetic resonance no, n° 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 or detection NPV nuclear polyhedrosis virus NR not reported NTE neurotoxic target esterase OC organic carbon content OCR optical character recognition ODP ozone-depleting potential ODS ozone-depleting substances OEL occupational exposure limit OH Hydroxide OJ Official Journal OM organic matter content 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
PECS predicted environmental concentration in soil
PECSW predicted environmental concentration in surface water
PECGW predicted environmental concentration in ground water PED plasma-emissions-detector pH pH-value PHED pesticide handler’s exposure data PIC prior informed consent pic phage inhibitory capacity
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Stand. term / Explanation Abbreviation PIXE proton induced X-ray emission pKa negative logarithm (to the base 10) of the acid dissociation constant pKb negative logarithm (to the base 10) of the base dissociation constant PNEC predicted no effect concentration (compartment to be added as subscript) po by mouth POP persistent organic pollutants ppb parts per billion (10-9 ) PPE personal protective equipment ppm parts per million (10-6 ) PPP plant protection product ppq parts per quadrillion (10-24 ) ppt parts per trillion (10-12 ) PSP phenolsulfophthalein PrT prothrombin time PRL practical residue limit PT product type PT(CEN) project team CEN PTDI provisional tolerable daily intake PTT partial thromboplastin time QA quality assurance QAU quality assurance unit (Q)SAR quantitative structure-activity relationship r correlation coefficient r 2 coefficient of determination RA risk assessment RBC red blood cell REI restricted entry interval RENI Registry Nomenclature Information System Rf retardation factor RfD reference dose RH relative humidity
RL50 median residual lifetime RNA ribonucleic acid RP reversed phase rpm revolutions per minute rRNA ribosomal ribonucleic acid RRT relative retention time RSD relative standard deviation s Second S Solubility SAC strong adsorption capacity SAP serum alkaline phosphatase SAR structure/activity relationship SBLC shallow bed liquid chromatography sc Subcutaneous sce sister chromatid exchange SCAS semi-continuous activated sludge SCTER smallest chronic toxicity exposure ratio (TER)
95 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
Stand. term / Explanation Abbreviation SD standard deviation 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 S/L short term to long term ratio SMEs small and medium sized enterprises SOP standard operating procedures sp species (only after a generic name) SPE solid phase extraction SPF specific pathogen free spp subspecies SSD sulphur specific detector SSMS spark source mass spectrometry STEL short term exposure limit STER smallest toxicity exposure ratio (TER) STMR supervised trials median residue STP sewage treatment plant t tonne(s) (metric ton) t½ half-life (define method of estimation)
T3 tri-iodothyroxine
T4 thyroxine
T25 tumorigenic dose that causes tumours in 25% of the test animals TADI temporary acceptable daily intake TBC tightly bound capacity TCD thermal conductivity detector TG technical guideline, technical group TGD Technical guidance document TID thermionic detector, alkali flame detector TDR time domain reflectrometry TER toxicity exposure ratio
TERI toxicity exposure ratio for initial exposure
TERST toxicity exposure ratio following repeated exposure
TERLT toxicity exposure ratio following chronic exposure tert tertiary (in a chemical name) TEP typical end-use product TGGE temperature gradient gel electrophoresis TIFF tag image file format 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 TNsG technical notes for guidance
96 Company Name The Activa / Pelgar BQ- Name of A.S. BQ-25 Month/Year: June 2005 25 and Difenacoum Task Force
Stand. term / Explanation Abbreviation TOC total organic carbon Tremcard transport emergency card tRNA transfer ribonucleic acid TSH thyroid stimulating hormone (thyrotropin) TTC 2,3,5-triphenylterazoliumchloride testing method TWA time weighted average UDS unscheduled DNA synthesis UF uncertainty factor (safety factor) ULV ultra low volume UR unit risk UV Ultraviolet UVC unknown or variable composition, complex reaction products UVCB undefined or variable composition, complex reaction products in biological material v/v volume ratio (volume per volume) vis Visible WBC white blood cell wk Week wt Weight w/v weight per volume ww wet weight w/w weight per weight XRFA X-ray fluorescence analysis yr year < less than less than or equal to > greater than greater than or equal to
97