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CA-July12-Doc.3.3a

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

Company Name The Activa / Pelgar BQ-25 and Difenacoum Task Force

Name of A.S. BQ-25 Month/Year: June 2005

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Didecyldimethylammonium Chloride

Product-type 8

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.....................................................36

2.2.2.1. Fate and distribution in the environment..........................................36

2.2.2.2. Effects Assessment..........................................................................38

2.2.2.3. PBT assessment...............................................................................40

2.2.2.4. Exposure assessment.......................................................................41

2.2.2.5. Risk characterisation........................................................................44

3. DECISION............................................................................................................ 48

3.1. BACKGROUND TO THE PROPOSED DECISION.........................................48

3.2. PROPOSED DECISION REGARDING INCLUSION IN ANNEX I................49

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Product-type 8

3.3. ELEMENTS TO BE TAKEN INTO ACCOUNT BY MEMBER STATES WHEN AUTHORISING PRODUCTS.............................................................................51

3.4. REQUIREMENT FOR FURTHER INFORMATION.......................................51

3.5. RECOMMENDED MEASURES.........................................................................52

3.6. UPDATING THIS ASSESSMENT REPORT.....................................................52

APPENDIX I: LIST OF END POINTS...............................................................53

Chapter 1: Identity, Physical and Chemical Properties, Details of Uses, Further Information, and Proposed Classification and Labelling........................................................................................53

Chapter 2: Methods of Analysis.......................................................56

Chapter 3: Impact on Human Health..............................................57

Chapter 4: Fate and Behaviour in the Environment......................63

Chapter 5: Effects on Non-target Species........................................65

Chapter 6: Other End Points...........................................................66

APPENDIX II: LIST OF INTENDED USES......................................................67

APPENDIX III: LIST OF STUDIES...................................................................68

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Product-type 8

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 market1, 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 28 th

September 2004.

On 27th June 2005 the time period was suspended and the evaluation taken up again on 27 th 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.

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

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Product-type 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 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

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http://ec.europa.eu/comm/environment/biocides/index.htm


Product-type 8

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 pattern 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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Didecyldimethylammonium Chloride Product-type 8 date SCB

2. OVERALL SUMMARY AND CONCLUSIONS

2.1. Presentation of the Active Substance

2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis

Identification of the active substance

CAS No. 7173-51-5EINECS No. 230-525-2Other substance No.: 612-131-00-6 (Annex I Index number)IUPAC Name N,N-Didecyl-N,N-dimethylammonium ChlorideCommon name, synonyms Didecyldimethylammonium Chloride;

DDACN-Decyl-N,N-dimethyl-1-decanaminium chlorideAmmonium, didecyldimethyl-, chloride

Chemical name (CA) 1-Decanaminium, N-decyl-N,N-dimethyl-, chlorideMolecular formula C22H48N.ClStructural formula

N+

R Cl-

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-25Manufacturers development code number Not assignedActive substance Didecyldimethylammonium ChlorideContent of the active substance 25%Function Fungicide, insecticidePhysical state of preparation LiquidNature of preparation SolutionThe 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 50°C, with a Henry’s Law constant of 4.27E-09 Pa m3 mol–1at 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

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precise by the RMS and were therefore accepted. At that time, the Addendum to TNsG on Data 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.

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2.1.2. Intended Uses and Efficacy

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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2.1.3. Classification and Labelling

The Current ClassificationClassification as in Directive 67/548/EECClass of danger Xn; R22

C; R34R phrases R22 Harmful if swallowed

R34 Causes burnsS 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 adviceS36/37/39 Wear suitable protective clothing, gloves and eye/face protectionS45 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/EECClassification Class of danger Xn; R22

C; R34N; R50

Labelling:Symbol C ; NR phrases R22 Harmful if swallowed

R34 Causes burnsR50 Very toxic to aquatic organisms

S phrases S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical adviceS28 After contact with skin, wash immediately with plenty of…S36/37/39 Wear suitable protective clothing, gloves and eye/face protectionS45 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 concentration limits for the environmental classification

Cn ≥ 2.5 %: N; R50

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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 andCategory

Acute toxicity (oral), Hazard Category 3*Skin Corrosion Hazard Category 1B_ Aquatic Acute 1_

Hazard Statement Codes

H301H314H400

Labelling:GHS Pictogram GHS05, GHS06, GHS09Signal Word DangerHazard Statement H301:Toxic if swallowed.

H314: Causes severe skin burns and eye damageH400: Very toxic to aquatic life.

Specific concentration limits for the aquatic hazard classification

M factor=10

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 swallowedR34 Causes burnsR50 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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2.2. Summary of the Risk Assessment

2.2.1. 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 patterns 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 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.

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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 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

lines0.000275 - -

APPLICATION PHASE (Dipping treatment):

Handling Model10.0555 0.0044 0.032

APPLICATION PHASE (Vacuum Pressure

treatment): Handling Model1

0.069 0.008 0.024

20


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/cm 3 (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 1.8B size of chewed timber cut-off (chip) cm2 16C depth of chewed timber cut-off (chip) cm 1D = B x C volume of chip cm3 16E a.s. extracted by chewing fraction 0.1F = A x D x E a.s. in the mouth mg 2.88G Amount of saliva produced ml/min 1.5H 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 %

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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

22


vessels or systems in industrial scale the exposure could be considered as negligible, with a 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).

23


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)

Exposure scenario Dermal Exposure (mg)

Inhalation Exposure (mg)

Total Exposure

(mg)

Total Systemic dose

(mg/kg/d)Tier

1Tier 2 Tier 1 Tier 2 Tier

1Tier

2 Tier 1 Tier 2

DippingMixing and loading concentrate(25% solution)(Model 7)*

0.15 0.15 0.205 0.205 0.35 0.35 0.0059 0.0059

DippingMixing and loading concentrate(25% solution)(RISKOFDERM toolkit)

-0.23

- - - 0.23 - 0.004

DippingApplication(1.8% solution)

69.5 7.1 - - 69.5 7.1 1.16 0.12


11.61.2

- - 11.61.2

0.2 0.02

Vacuum/pressure treatment(1.8% solution)(including feet exposure assessment)

55 13 0.38 0.38 55.4 13.4 0.92 0.22

Vacuum/pressure treatment(0.3% solution) (including feet exposure assessment)

9.2 2.2 0.06 0.06 9.26 2.26 0.15 0.04

*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.

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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.

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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 CombinedAcute

Non-professionalsAdult

sanding-- 0.0504 mg/kg/day 0.00047 mg/kg bw

0.05087mg/kg/day

Infant mouthing

0.288 mg/kg/day

-- -- --

ChronicProfessionals

Adult sanding

-- 0.0504 mg/kg/day 0.0028 mg/kg bw0.053

mg/kg/dayNon-professionals

Child playing

0.0096 mg/kg bw/day --

Infant playing

0.018 mg/kg/day

0.0144 mg/kg/day0.0324mg/kg

day

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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:

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%.

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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

28


exposure route for use in the risk characterisation of DDACarbonate (…)” (Draft Final CAR – Doc.I, pp.11-12/59).

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)

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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 AEC of 0.014 mg/cm2.

EXPOSURE MODEL

Hands exposure mg/cm2

AEChands%Body exposure

mg/cm2AECbody%

Feet exposure mg/cm2

AECfeet%

MIXING&LOADING Riskofderm Connecting

lines0.000275 1.96 - - - -

APPLICATION PHASE (Dipping

treatment): Handling Model1

0.0555 396 0.0044 31 0.032 228

APPLICATION PHASE (Vacuum

Pressure treatment): Handling Model1

0.069 493 0.008 57 0.024 172

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.

30


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 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.

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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.


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).

Exposure scenario Total Systemic dose (mg/kg/d)

%AEL = (Exposure x 100)/AEL

(0.1 mg/kg bw/d)DippingMixing and loading concentrate(25% solution)(Model 7)*

0.0059 5.9


0.004 4


0.12 120


0.02 20

Vacuum/pressure treatment(1.8% solution)(including feet exposure assessment)

0.22 220

Vacuum/pressure treatment(0.3% solution) (including feet exposure assessment)

0.04 40


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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


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 scenarioDermal

Systemic uptake

(mg/kg/day)

MOE =NOAEL (1.2

mg/kg/d)/ Exposure

(mg/kg bw/day)

Inhalation Systemic uptake

(mg/kg/day)

MOE =NOAEL (10 mg/kg/d) / Exposure

(mg/kg bw/day)

DippingMixing and loading concentrate(25% solution)(Model 7)*

0.0025 480 0.0034 2941


0.004 300 - -

Automated DippingApplication(1.8% solution)

0.12 10 - -

Automated DippingApplication(0.3% solution)

0.02 60 - -

Vacuum/pressure treatment(1.8% solution)(including

0.22 5 0.0057 1754

33


feet exposure assessment)Vacuum/pressure treatment(0.3% solution) (including feet exposure assessment)

0.036 33 0.001 10000


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.

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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.

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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 sanding

-- 0.0504 mg/kg bw 0.00047 mg/kg bw

0.05087mg/kg bw

Oral/Inhalation:10 mg/kg bw/d

Dermal:6 mg/kg bw/day

Dermal:119

Inhalation:21276

Infantmouthing

0.288 mg/kg bw -- -- -- Oral/Inhalation:

10 mg/kg bw/d Oral: 35

Chronic

PROFESSIONALS

Adult sanding

-- 0.0504 mg/kg bw 0.0028 mg/kg bw

0.053mg/kg bw

Oral/Inhalation:10 mg/kg bw/d

Dermal:1.2 mg/kg

bw/day

Dermal:24

Inhalation:3571

NON-PROFESSIONALS

Child playing

0.0096 mg/kg bw/day --

Dermal:1.2 mg/kg

bw/day

Dermal:

125

Infant playing

0.018 mg/kg/da

y0.0144 mg/kg/day 0.194mg/

kg day

Oral:10 mg/kg bw/dayDermal:

1.2 mg/kg bw/day

Oral:555

Dermal:83

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).

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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.

37

Didecyldimethylammonium Chloride Product-type 8

2.2.2. Environmental Risk Assessment

2.2.2.1. 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 (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).

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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 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

39


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 10-5 kg/m2 /d

Daily FLUX (TIME2) = 1.52 10-7 kg/m2 /d

Q*Leach (TIME1) = 5.52 10-4 kg/m2

Q*Leach (TIME2) = 1.19 10-3 kg/m2

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2.2.2.2. 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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2.2.2.3. 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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2.2.2.4. Exposure assessment

Aquatic Compartment Exposure assessment

PECs have been calculated according to the OECD Emission Scenario Document for Wood Preservatives (ESD).

Local PECScenario 1: Dipping treatment during applicationPEClocalwater STP 0.0079 mg/lPEClocalsed STP 189.5 mg/kgwwtPECmicroorganism STP 0.21 mg/lScenario 2: Dipping treatment during storagePEClocalwater run-off 2.3 10-3 mg/lPEClocalsed run-off 51 mg/kgwwtScenario 3: Vacuum pressure treatment during applicationPEClocalwater STP 0.0024 mg/lPEClocalsed STP 56.3 mg/kgwwtPECmicroorganism STP 0.06 mg/lScenario 4: Vacuum pressure treatment during storage PEClocalwater 1.7 10-3 mg/lPEClocalsed 40.8 mg/kgwwtScenario 65: Bridge over pondPEClocalwater STP Time1 0.09 mg/l

Time2 0.00006 mg/lPEClocalsed STP Time1 2152 mg/kgwwt

Time2 1.4 mg/kgwwtScenario 6: Noise BarrierPEClocalwater STP Time1 0.0025 mg/l

Time2 0.00002 mg/lPEClocalsed STP Time1 60 mg/kgwwt

Time2 0.5 mg/kgwwtPECSTP Time1 0.02 mg/l

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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/kgPEClocalsoil (TIME 2) 0.6 mg/kgPEClocalsoil, porew (TIME 1) 1.5 10-4 mg/lPEClocalsoil, porew (TIME 2) 3.0 10-5 mg/lScenario 4: Vacuum pressure treatment during storage

PEClocalsoil (TIME 1) 3.0 mg/kgPEClocalsoil (TIME 2) 7.2 mg/kgPEClocalsoil, porew (TIME 1) 1.5 10-4 mg/l PEClocalsoil, porew (TIME 2) 3.7 10-4 mg/lUse pattern 6: Treated wood in service Noise barrier

PEClocalsoil (TIME 1) 1.2 mg/kgPEClocalsoil (TIME 2) 2.5 mg/kgPEClocalsoil (TIME 2) refined including degradation* 0.5 mg/kgPECgw 6.0 10-5 mg/lUse pattern 7: Treated wood in service Fence

PEClocalsoil (TIME 1) 2.6 mg/kgPEClocalsoil (TIME 2) 5.6 mg/kgPEClocalsoil (TIME 2) refined including degradation* 0.3 mg/kgPECgw max 1.3 10-4 mg/lUse pattern 8: Treated wood in service House

PEClocalsoil (TIME 1) 3.1 mg/kgPEClocalsoil (TIME 2) 6.7 mg/kgPEClocalsoil (TIME 2) refined including degradation* 0.4 mg/kgPECgw max 1.6 10-4 mg/lUse pattern 9: Treated wood in service Transmission pole

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PEClocalsoil (TIME 1) 0.4 mg/kgPEClocalsoil (TIME 2) 1.0 mg/kgPEClocalsoil (TIME 2) refined including degradation* 0.05 mg/kgPECgw max 2.0 10-5 mg/lUse pattern 10: Treated wood in service fence post

PEClocalsoil (TIME 1) 0.4 mg/kgPEClocalsoil (TIME 2) 0.8 mg/kgPEClocalsoil (TIME 2) refined including degradation* 0.04 mg/kgPECgw max 2.0 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 pattern 1: Dipping applicationAnnual average local PEC in air 3.98 10-5 mg/m3

Use pattern3: Vacuum pressure application:Annual average local PEC in air 1.2 10 -5mg/m3

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2.2.2.5. Risk characterisation

Aquatic Compartment

Use pattern PEC/PNEC values

Water compartmen

t

Sediment compartmen

t

Sewage treatmen

t 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 application) 2.4 15.8 0.55

Use scenario 4 (Vacuum pressure treatment during storage) 1.7 11.4 -

Use scenario 6Noise Barrier

TIME 1 TIME 1 =2 TIME 1 =16.8 0.18

TIME 2 TIME 2 =0.04

TIME 2 =0.13

The PEC/PNEC ratios for the water and sediment compartments in the use scenario 1, 2 and 3 (dipping treatment during application and storage, vacuum pressure treatment during application) 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 use in Noise barrier 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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Terrestrial Compartment including Groundwater

Summary of PEC/PNEC values for terrestrial compartment


Terrestrial compartmentScenario 2: Storage of dipped/ immersed wood After 30 days 10.67

After 15 years 2.14Scenario 4: Storage of vacuum-pressure-treated wood: After 30 days 10.67

After 20 years 25.6Scenario 6: Treated wood in service: Noise barrier After 30 days

After 20 years

4.27

1.77

Scenario 7: Treated wood in service: Fence After 30 days

After 20 years

9.25

1.07

Scenario 8: Treated wood in service: House After 30 days

After 20 years

11.03

1.42

Scenario 9: Treated wood in service: Transmission pole After 30 days

After 20 years

1.42

0.18

Scenario 10: Treated wood in service: Fence post After 30 days

After 20 years

1.42

0.14

For use patterns 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 use pattern 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 patterns 6, 7, and 8 the PEC/PNEC values are higher than 1 only in the long-term whilst for the short-term use the PEC/PNEC values are round 1 does not pose any risk. For use pattern 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.

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

TGD s 67 and 68

Use pattern PEC Limit value PEC/ Limit value

mg/lScenario 2: Storage of dipped/ immersed wood

0.00015 mg/l

0.0001

1.5

Scenario 4: Storage of vacuum-pressure-treated wood:

0.00015 mg/l 1.5

Scenario 6: Treated wood in service: Noise barrier

0.00006 mg/l 0.6

Scenario 7: Treated wood in service: Fence 0.00013 mg/l 1.3Scenario 8: Treated wood in service: House 0.00016 mg/l 1.6Scenario 9: Treated wood in service: Transmission pole

0.00002 mg/l 0.2

Scenario 10: Treated wood in service: Fence post

0.00002 mg/l 0.2

For scenarios 2 and 4, PEC/PNEC ratios higher than 1 are indicating a potential risk for groundwater. Anyway, 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.

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Environmental risk in the atmosphere

For the atmosphere compartment no PNEC values are available. However, for all use patterns, 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)


Fish-eating mammals Fish-eating birdsUse scenario 1 (dipping treatment during application) 0.0619

<1.95Use scenario 2 (dipping treatment during storage) 0.012

<0.38Use scenario 3 (Vacuum pressure treatment during application) 0.019

<0.6

Use scenario 4 (Vacuum pressure treatment during storage) 0.0081 <0.26

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 patterns, 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

3.1. 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 for the secondary exposure assessment no risks have been identified for the exposed population.

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), 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), 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 use in Noise barrier the PEC/PNEC values are higher than 1 in the short-term whilst the long-term use does 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, 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 short-term whilst for the long-term use the PEC/PNEC values are round 1 does not pose any risk. For Trasmission 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.For these scenarios risk reduction measures are proposed in order to prevent the direct losses to the soil.

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The Annex I – entry should, however, only include the intended uses with the conditions and restrictions proposed in this report.

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3.2. 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.

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

54


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

Break through time / glove: > 30 min

Minimal thickness / glove: 0.4 mm

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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.

3.3. 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.

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.

3.4. 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

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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 use patterns of the biocidal product.

3.5. 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 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.

3.6. 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 manufactured (g/kg or g/l)

870 g/kg dry weight

Identity of relevant impurities and additives (substances of concern) in the active substance as manufactured (g/kg)

None

Molecular formula C22H48N.Cl

Molecular mass 362.1 g/mol

Structural formula

N+

R Cl-

R

R = C10H21

58


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 temperature) (Annex IIIA, point III.1)

Acetone: > 600 g/l @ 20ºC

Methanol: > 600 g/l @ 20ºC

Octanol: > 250 g/l @ 20ºC

Stability in organic solvents used in biocidal products including relevant breakdown products (IIIA, point III.2)

Ethanol: Stable < 5% loss for 14 days at 55°C

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 IIIA; additional data requirement from TNsG)

Not applicable: the substance is irreversibly ionized

UV/VIS absorption (max.) (if absorption > 290 nm state at wavelength)

The ultraviolet/visible absorption spectra were consistent 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

59


Classification and proposed labelling (Annex IIA, point IX.)

The Current Classification as in Directive 67/548/EEC

with regard to physical/chemical data No classificationwith regard to toxicological data C- Corrosive

R22; R34; S2; S26, S36/37/39; S45with regard to fate and behaviour data No classificationwith regard to ecotoxicological data No classification

The proposed Classification and labelling as in Directive 67/548/EEC

with regard to physical/chemical data No classificationwith regard to toxicological data C- Corrosive

R22; R34; S26, S28; S36/37/39; S45

with regard to fate and behaviour data No classificationwith regard to ecotoxicological data N- Dangerous for the environment

R50; S60; S61


Cn ≥ 2.5 %: N; R50

The proposed Classification and labelling based on Regulation EC 1272/2008

GHS Pictogram GHS05, GHS06, GHS09

Signal Word Danger

Hazard Statement H301; H314; H400


M= 10

60


Chapter 2: Methods of Analysis

Analytical methods for the active substance

Technical active substance (principle of method) (Annex IIA, point 4.1)

HPLC with evaporative light scattering detection (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 of method) (Annex IIA, point 4.1)

HPLC-ELSD (identification by LC-MS) 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, point 4.2)

Extraction with methanol:water (90:10 v/v) containing 0.01 M ammonium formate and 0.1% formic acid. Analysis by LC-MS (m/z = 326.3).LOQ = 0.01 mg/kgConfirmatory method should be provided for the product authorization phase at national level

Air (principle of method and LOQ) (Annex IIA, point 4.2)

Not required. The a.s. is non-volatile; it will not be used 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, point 4.2)

Partition with 0.1 M heptanesulfonic acid and 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/lConfirmatory method should be provided for the product authorization phase at national level

Body fluids and tissues (principle of method and LOQ) (Annex IIA, point 4.2)

The a.s. is neither toxic nor highly toxic

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes) (Annex IIIA, point IV.1)

Not required. 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

Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes) (Annex IIIA, point IV.1)

Not required. 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

61


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

62


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

63


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

64


Medical data (Annex IIA, point 6.9)

........................................................................

.......No substance-specific effects have been noted. No specific observations or sensitivity/allergenicity have been reported

65


Summary for local effects

Value Study Safety factor

Professional/Non-Professional users

ADI (if residues in food or feed) Not applicable

AEC (Acceptable Exposure Concentration)

0.014 mg/cm22-week skin irritation study in rats

3.2

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.

66


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 mg/kg/day

52 week oral study in dogs 100

Reference value for dermal absorption

10 % In vitro on human skin

Drinking water limit 0.1 mg/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

67


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 metabolites (DT50) (state pH and temperature)

pH___5___: >30 days at 25°C

pH___7___: >30 days at 25°C

pH___9___: >30 days at 25°C

Photolytic / photo-oxidative degradation of active substance and resulting relevant metabolites

ca. 0% after 30 days (direct)

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 substance)

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 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 (metabolites)

Not applicable

Amount of 14C-DDAC as mean percentageof the recovered radioactivity in the TNO and Kromme Rijn water/sediment system.

Days0 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 69.5Kromme Rijn

97.0 94.5 94.5 87.0 68.8 54.3 57.9 54.8 64.7 54.4

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 of measurements, with regression coefficient)

For readily biodegradable substances, TGD recommend 15 days for surface water and 300 days for soil if Kp >1000

Field studies (state location, range or median with number of measurements)

Not applicable

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 applied a.i. (range and maximum)

Not measured

Soil accumulation and plateau concentration No data available

68


Adsorption/desorption (Annex IIA, point XII.7.7; Annex IIIA, point XII.1.2)

Ka , Kd

Kaoc , Kdoc

pH dependence (yes / no) (if yes type of dependence)

Ka (Kaoc) values for four soil types:Sand: 1’095 (437’805)Sandy loam: 8’179 (908’757)Silty clay loam: 32’791 (1’599’564)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 study)

No data available

Ground water (indicate location and type of study)

No data available

Air (indicate location and type of study) No data available

69


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

FishFathead Minnow (Pimephales promelas)

96h Mortality LC50 = 0.19 mg a.s./L

Zebra fish (Brachydanio rerio)

34d Growth NOEC = 0.0322 mg a.s./L

InvertebratesDaphnia magna 48h Immobilisation EC50 = 0.062 mg a.s./lDaphnia 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 capricornutum

96h Biomass production and cell density

ErC50 = 0.026 mg 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.)

MicroorganismsActivated sewage sludge 3h Respiration

inhibitionEC50 = 11.0 mg a.s./L

1) Algae are target organisms for DDAC.

Effects on earthworms or other soil non-target organisms

Acute toxicity to Eisenia foetida(Annex IIIA, point XIII.3.2)

14d LC50 > 1000 mg a.s./kg, in artificial soilNOEC ≥1000 mg a.s./kg, in artificial soil

Reproductive toxicity to …………………………(Annex IIIA, point XIII.3.2)

No data available.

Acute toxicity to plants(Annex Point IIA 7.5.1.3)

EC50 = 283 mg a.s./kg dw soil (mustard, dry weight) (equivalent to EC50 =281 mg/kg ww soil).

70

Lara Hall, 03/11/09,

Results based on initial measured concentration should be retained here, as reported, regardless of whether mean measured concentrations are also reported (e.g. for comparison purposes).


Effects on soil micro-organisms (Annex IIA, point 7.4)

Nitrogen mineralization EC50 > 1000 mg a.s./kgCarbon mineralization EC50 > 1000 mg a.s./kg

Effects on terrestrial vertebrates

Repeated dose toxicity to mammals(Annex Point IIA6.3)

18 months NOEC = 500 mg a.s./kg food (mouse)

Acute toxicity to birds(Annex IIIA, point XIII.1.1)

Northern bobwhite quailLD50 = 229 mg a.s./kg bw

Dietary toxicity to birds(Annex IIIA, point XIII.1.2)

Northern bobwhite quailLC50 = >5620 mg a.s./kg a.s. food

Dietary toxicity to birds(Annex IIIA, point XIII.1.2)

Mallard duckLC50 = >1633 mg a.s./kg a.s. food

Reproductive toxicity to birds(Annex IIIA, point XIII.1.3)

Not available

Effects on honeybees (Annex IIIA, point XIII.3.1)

Acute oral toxicity No data available nor requiredAcute 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 requiredAcute contact toxicity No data available nor requiredAcute toxicity to…………………………………..

No data available nor required

Bioconcentration (Annex IIA, point 7.5)Bioconcentration factor (BCF) Measured BCFfish whole body = 81

BCFearthworm not availableDepuration time (DT50)

(DT90)7-14d whole body.

Level of metabolites (%) in organisms accounting for > 10 % of residues

No data available

Chapter 6: Other End Points

71


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 kgTotal 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.

72


Appendix III: List of Studies

Document III A

Endpoint ReferenceNo.

ReferenceNon-Key Studies are italicized.

3.1.1 – Melting point D47(LON 3256)

Schneider, S. (2000) Determination of the melting temperature of Dodigen 1881 AS (pure active substance of Bardac 22) in accordance with OECD-Guideline 102 and according to EECGuideline A.1. Clariant GmbH - Werk Cassella-Offenbach, Analytische und Physikalische Abteilung, Frankfurt, Germany.Report No. B 077/2000 (unpublished).

3.1.3 – Density D48(LON 3257)

Schneider, S. (2000) Determination of the density of Dodigen 1881 AS (pure active substance of Bardac22) inaccordance with OECD-Guideline 109 and according toEEC-Guideline A.3. Clariant GmbH - Werk Cassella-Offenbach, Analytische und Physikalische Abteilung, Frankfurt, Germany.Report No. B079/2000 (unpublished).

3.2 – Vapor pressure D49(LON 3275)

Smeykal, H. (2000) Dodigen 1881 AS - DD 00/004: Vapour pressure. Siemens Axiva GmbH & Co. KG, Frankfurt, Germany.Report No. SI092-00 (unpublished).

3.4.1 – UV/VIS3.4.2 – IR3.4.3 – NMR3.4.4 – MS

D93(LON 3278)

Petrovic P. (2000) Characterization of the structure of Dodigen1881 AS. Clariant GmbH - Werk Cassella-Offenbach, Analytischeund Physikalische Abteilung, Frankfurt, Germany. Report No. B 085/2000 (unpublished).

3.5 – Solubility in water D51(LON 3280)

Schneider, S. (2000) Determination of the water solubility ofDodigen 1881 AS (pure active substance of Bardac 22) inaccordance with EEC-Guideline A.6. Clariant GmbH - WerkCassella-Offenbach, Analytische und Physikalische Abteilung, Frankfurt, Germany. Report No. B 080/2000(unpublished).

3.7(1) – Solubility in organicsolvents

D101(LON 3279)

Schneider, S. (2001) Determination of the solubility of Dodigen 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 organicsolvents

D92(LON 3802)

Young S. (2004) N,N-Didecyl-N,N-dimethylammonium chloride(DDAC): Solubility in octanol. Huntingdon Life Sciences,Huntingdon, Cambridgeshire, England. Report No. DKG/011033992 (unpublished).

3.8 – Stability in organicsolvents

D94(LON 3803)

Young, S. (2004) N,N-Didecyl-N,N-dimethylammonium chloride(DDAC): Stability in ethanol and isopropanol. Huntingdon LifeSciences, Huntingdon, Cambridgeshire, England. Report No.DKG/012 042290 (unpublished).

3.9 – Partition coefficient D137 Nixon, W.B. (1998) DDAC octanol/water partition coefficienttest. Unpublished letter report dated August 14, 1998; fromWildlife International, Ltd., Easton, MD, USA. (unpublished).

73


3.9 – Partition coefficient D92(LON 3802)

Young, S. (2004) N,N-Didecyl-N,N-dimethylammonium chloride(DDAC): Solubility in octanol. Huntingdon Life Sciences,Huntingdon, Cambridgeshire, England. Report No. DKG/011033992 (unpublished).[REPORT FILED UNDER ENDPOINT 3.7]

3.10 – Thermal stability D95(LON 3449)

Keipert, W. (2001) Determination of the thermal stability andstability in air of Dodigen 1881 AS (Bardac 22 AS) in accordancewith OECD-Guideline 113. AllessaChemie GmbH - WerkCassella-Offenbach, Analytik, Frankfurt, Germany. Report No. B012/2001 (unpublished).

3.11(1) – Flammability(solids) & Autoflammability

D96(LON 3446)

Keipert, W. (2001) Determination of the relative self ignitiontemperature of Dodigen 1881 AS (Bardac 22 AS) in accordancewith EEC-Guideline A.16. AllessaChemie GmbH - WerkCassella-Offenbach, Analytik, Frankfurt, Germany. Report No. B022/2001 (unpublished).

3.11(2) – Flammability(solids) & Autoflammability

D97(LON 3447)

Keipert, W. (2001) Determination of the flammability of Dodigen1881 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(LON 3448)

Schneider, S. (2001) Determination of the surface tension of anaqueous solution of Dodigen 1881 AS (Bardac 22 AS) inaccordance with OECD-Guideline 115. AllessaChemie GmbH,Analytik, Frankfurt, Germany. Report No. B 023/2001(unpublished).

3.14 – Viscosity D135(LON 3660)

Keipert, W. (2003) Determination of the viscosity of Bardac22/Dodigen 1881 in accordance with OECD-Guideline 114.AllessaChemie GmbH, Analytik, Frankfurt, Germany. Report No.B 019/2003 (unpublished).

3.15(1) – Explosiveproperties

D99(LON 3445)

Dodigen 1881 AS (Bardac 22 AS) in accordance with EECGuideline A.14. AllessaChemie GmbH - Werk Cassella-Offenbach, Analytik, Frankfurt, Germany. Report No. B 024/2001(unpublished).

3.15(2) – Explosiveproperties

D100(LON 3612)

Tremain, S.P. (2002) Didecyl dimethylammonium chloride(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(LON 3612)

Tremain, S.P. (2002) Didecyl dimethylammonium chloride(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 methodsfor purity/impurity

D136(LON 3843)

Sloan, R. (1994) Bardac 2280 - Characterization of the testsubstance. Huntingdon Life Sciences, Huntingdon,

74


Cambridgeshire, England. Report No. 94-013 (unpublished).4.1(2) – Analytical methodsfor purity/impurity

D91(LON 3804)

Young, S. (2003) Didecyldimethylammonium chloride (DDAC;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 methodsfor purity/impurity (new submission)

Lonza Report No. 4134

Kurz M. and Ranft V. (2007) Determination of quaternary ammonium compounds and related quaternary impurities by HPLC-ELSD. Study No.CSPE-44/BS-07-70. Lonza AG. (Unpublished).

4.2 (a) – Analytical methodsfor determination of residuesin soil

D46(LON 3701)

Brewin, S. (2003) Didecyldimethylammonium chloride (DDAC;CAS RN 7173-51-5): Validation of methodology for thedetermination of residues in soil. Huntingdon Life Sciences Ltd.,Huntingdon, Cambridgeshire, England. Report No. ADB/014033180 (unpublished).

4.2 (c) – Analytical methodsfor determination of residuesin water

D90(LON 3702)

Brewin, S. (2003) Didecyldimethylammonium chloride (DDAC;CAS RN 7173-51-5): Validation of methodology for thedetermination 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 TargetOrganisms

D139 Archer, K., Nicholas, D.D. and T.P. Schultz (1995) Screening ofwood preservatives: Comparison of the soil block, agar block andagar plate tests. Forest Prod. J. 45(1): 86-89.

D142 Linfield, W.M. (1969) Chapter 2: Straight-chain alkylammoniumcompounds. In E. Jungermann (Ed.), CationicSurfactants. Marcel Dekker: New York, NY, USA, pp 9-70.

D151 Wazny, J. and L.J. Cookson (1993) A comparison of Coniophoraolivacea and Coniophora puteana test strains. InternationalResearch Group on Wood Preservation Document No.IRG/WP/20004.

D152 Wazny, J. and L.J. Cookson (1994) Comparison of the agar blockand soil block methods used for evaluation of fungitoxic value ofQAC and CCA wood preservatives. International Research Groupon Wood Preservation Document No. IRG/WP/20039.

6.1.1 – Acute oral toxicity D9(LON 3746)

Morris, T.D. (1992) Acute oral toxicity in rats – Median lethaldosage determination with didecyldimethylammonium chloride(DDAC). Hill Top Biolabs, Inc., Miamiville, Ohio, USA. StudyNo. 91-8114-21(A) (unpublished).

75


6.1.1 – Acute oral toxicity D102(LON 1239)

Ullman, L. and R. Sacher (1983) Acute oral toxicity study (LD50)with P 0151 in rats. Research & Consulting Company AG, Itingen,Switzerland. Project No. 021532 (unpublished).

6.1.2 – Acute dermal toxicity D85(LON 3805)

Siglin, J.C. (1987) Acute dermal toxicity study in rabbits LD50test (EPA) with DMD10AC. Springborn Institute for Bioresearch,Inc., Spencerville, OH, USA. Study No. 3165.1.2C (unpublished).

6.1.2 – Acute dermal toxicity D71(LON 1237)

Nitka S. (1980) An acute dermal LD50 study in albino rabbitsConsumer Product Testing, Fairfield, NJ, USA. Report No 8044-10 (unpublished).

6.1.4(1) – Skin irritation D103(LON 1241)

Jones, J.R. and T.A. Collier (1986) P0151: OECD 404 Acutedermal irritation/corrosion test in the rabbit. SafepharmLaboratories Ltd., Derbyshire, England. Project No. 102/1(unpublished).

6.1.4 – Skin irritation D104(LON 2424)

Allan, D.J. (1995) P4289: Acute dermal irritation test in rabbitsSafepharm Laboratories Ltd., Derbyshire, England. Project No.102/1908 (unpublished).

6.1.4 – Skin irritation D11(LON 3807)

Morris, T.D. (1991) Primary skin irritation study in rabbits withdidecyldimethylammoniumchloride (DDAC). Hilltop Biolabs, Inc.,Miamiville, OH, USA. Study No. 91-8114-2 (B) (unpublished).

6.1.4(2) – Eye irritation D10(LON 3806)

Morris, T.D. (1991) Primary eye irritation study in rabbits withdidecyldimethylammonium chloride (DDAC). Hill Top Biolabs,Inc., Cincinnati, OH, USA. Study No. 91-8114-21 (unpublished).

6.1.5(1) – Skin sensitisation D105(LON 1243)

Clement, C. (1992) BARDAC-22: Test to evaluate the sensitizingpotential by topical applications in the guinea pig. Hazleton-Institute Français de Toxicologie, L’Arbresle, France. Report No.704323 RE (unpublished).


Kukulinski, M. (2003) Skin sensitization study of Maquat 4480-E,Batch #30717J5, OPPTS 870.2600. Tox Monitor Laboratories,Inc., Oak Park, IL, USA. Project No. 03-092-5 (unpublished).


Merkel, D.J. (2004) Bardac 2280: Dermal sensitization test inguinea pigs (Buehler method). Product Safety Laboratories,Dayton, NJ, USA. Study No. 15512 (unpublished).

6.1.5 – Skin sensitisation D12(LON 3808)

Morris T.D. (1991) Photoallergy study in guinea pigs withdidecyldimethylammoniumchloride (DDAC). Hill Top Biolabs,Cincinnati, OH , USA. Study No. 91-8114-21(D) (unpublished).

76


6.2(1) – Metabolism inmammals (toxicokinetics;dermal absorption)

D45(LON 3329)

Roper, C.S. (2001) The in vitro percutaneous absorption of [14C]-Didecyldimethylammonium chloride (DDAC) through human skin.Inveresk Research, Tranent, Scotland. Report No. 19128(unpublished).

6.2(2) – Metabolism inmammals (toxicokinetics;dermal absorption)

D34, D35(LON 1779)

Selim, S. (1989) Absorption, distribution, metabolism andexcretion studies of didecyldimethylammoniumchloride (DDAC)in the rat. Biological Test Center, Irvine, CA, USA. Study No.P01421 (unpublished).

6.4.1(1) – Subchronic oraltoxicity (rat)

D27(LON 1257)

Van Miller, J.P. (1988) Ninety-day dietary subchronic oraltoxicity study with didecyldimethylammoniumchloride in rats.Union Carbide, Bushy Run Research Center, Export, PA, USA.Report No. 51-506 (unpublished).

6.4.1(2) – Subchronic oraltoxicity (dog)

D16(LON 1256)

Osheroff, M.R. (1990) Subchronic oral toxicity study ofdidecyldimethylammonium chloride in dogs. HazeltonLaboratories America, Inc., Vienna, VA, USA. Study No. 2545-100 (unpublished).

6.4.1(3) – Subchronic oraltoxicity (mouse)

D19(LON 1775)

Van Miller, J.P. (1988) Subchronic dietary dose range findingstudy with didecyldimethylammonium chloride in mice. UnionCarbide, Bushy Run Research Center, Export, PA, USA. ReportNo. 51-507 (unpublished).

6.4.1 – Subchronic oraltoxicity

D108(LON 1256A)

Cox, G.E. and Bailey, D. (1975) 90-Day feeding study in dogswith a quaternary ammonium sanitizer BARDAC-22. Food andDrug Research Laboratories, Inc., Waverly, NY, USA.(unpublished).

6.4.2 – Subchronic dermaltoxicity test (rat)

D14(LON 1255)

Gill, M.W. and J.P. Van Miller (1988) Ninety-day subchronicdermal toxicity study with didecyldimethylammonium chloride inrats. Union Carbide, Bushy Run Research Center, Export, PA,USA. Project No. 51-554 (unpublished).

6.5(1) – Chronic toxicity(dog)

D18(LON 1778)

Schulze, G.E. (1991) Chronic oral toxicity study of didecyldimethylammoniumchloridein dogs. Hazelton Washington, Inc.,Vienna, VA, USA. Study No. 2545-102 (unpublished).

6.5(2) – Chronic toxicity (rat) D30(LON 1755)

Gill, M.W., Chun, J.S. and C.L. Wagner (1991) Chronic dietarytoxicity/oncogenicity study with didecyldimethylammoniumchloridein rats. Union Carbide, Bushy Run Research Center,Export, PA, USA. Report No. 53-566 (unpublished).

6.6.1 – In vitro gene mutationstudy in bacteria

D87(LON 3341)

Thompson, P.W. (2001) LZ1043 (Didecyldimethylammoniumchloride): Reverse mutation assay "Ames Test" using Salmonellatyphimurium. Safepharm Laboratories Ltd., Derby, England.Project No. 102/368 (unpublished).

77


6.6.2 – In vitro cytogenicitystudy in mammalian cells

D31(LON 1253)

Holmstrom, M., Leftwich, D.J. and I.A. Leddy (1986) PO151:Chromosomal aberrations assay with Chinese hamster ovary cellsin vitro. Inveresk Research International, Musselburgh, Scotland.Report No. 4236 (unpublished).

6.6.3 – In vitro gene mutationassay in mammalian cells

D32(LON 1254)

Young, R.R. (1988) Mutagenicity test on didecyldimethylammoniumchloride(DDAC) in the CHO/HGPRT forwardmutation assay. Hazleton Laboratories America, Inc., Kensington,MD, USA. Report No. 10141-0-435 (unpublished).

6.6.4 – In vivo Mutagenicity(conditional)

D84(LON 1252)

Allen, J.A., Proudlock R.J. and P.C. Brooker (1987) Analysis ofmetaphase chromosomes obtained from bone marrow of ratstreated with P0151 (Bardac 22). Report No. LZA 24/8761.Huntingdon Research Centre, Ltd., Huntingdon, England.(unpublished).

6.6.5 – In vivo Mutagenicity(conditional)

D33(LON 1499)

Cifone, M.A. (1988) Mutagenicity test on didecyldimethyl –ammoniumchloride (DDAC) in the rat primary hepatocyteunscheduled DNA synthesis assay. Hazleton Laboratories America,Inc., Kensington, MD, USA. Study No. 10141-0-447 (unpublished).

6.7(1) – Carcinogenicity(mouse)

D21(LON 1776)

Gill, M.W., Hermansky, S.J. and C.L. Wagner (1991) Chronicdietary oncogenicity study with didecyldimethylammoniumchloride in mice. Union Carbide, Bushy Run Research Center,Export, PA, USA. Report No. 53-528 (unpublished).

6.7(2) – Carcinogenicity (rat) D30(LON 1755)

Gill, M.W., Chun, J.S. and C.L. Wagner (1991) Chronic dietarytoxicity/oncogenicity study with didecyldimethylammoniumchloride 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(LON 1781)

Neeper-Bradley, T.L. (1991) Developmental toxicity evaluationof didecyldimethylammoniumchloride administered by gavage toCD® (Sprague-Dawley) rats. Union Carbide, Bushy Run ResearchCenter, Export, PA, USA. Project No: 53-534 (unpublished).

6.8.1(2) – Teratogenicity,rabbit

D26(LON 1770)

Tyl, R.W. (1989) Developmental toxicity study ofdidecyldimethylammoniumchloride administered by gavage toNew Zealand white rabbits. Union Carbide, Bushy Run ResearchCenter, Export, PA, USA. Project No. 51-590 (unpublished).

6.8.2 – Two generationreproduction study

D29(LON 1777)

Neeper-Bradley, T. L. (1991) Two-generation reproduction studyin Sprague-Dawley (CD) rats with didecyldimethylammoniumchloride administered in the diet. Union Carbide, Bushy RunResearch Center, Export, PA, USA. Report No. 52-648(unpublished).

78


6.11 – Studies on otherroutes of administration(parenteral routes) – AcuteIV study in rats

D106(LON 1248)

Duprey, L.P. and J.O. Hoppe (1967) TS 19: Toxicity andirritation studies on quarternary ammonium compounds. SterlingWinthrop Research Institute, Renssalaer, NY, USA. (unpublished).

7.1.1.1.1 – Hydrolysis D36(LON 1791)

Dykes, J. and M. Fennessey (1989) Hydrolysis ofdidecyldimethylammoniumchloride (DDAC) as a function of pH at25°C. ABC Laboratories Inc., Columbia, MO, USA. Report No.37004 (unpublished).

7.1.1.1.2 –Phototransformationin water

D37(LON 1793)

Dykes, J. and M. Fennessey (1989) Determination of thephotolysis rate of didecyldimethylammoniumchloride (DDAC) inpH 7 buffered solution at 25°C. ABC Laboratories Inc., Columbia,MO, USA. Report No. 37005 (unpublished).

7.1.1.2.1(1) – Readybiodegradability

D52(LON 2305)

Downing, J.L. (1993) Aerobic aquatic biodegradation ofdidecyldimethylammonium chloride using a shake flask testsystem. ABC Laboratories, Inc., Environmental Fate andAssessment Division, Columbia, MO, USA. Report No. 40687(unpublished).


D61a(LON 2923)

Schaefer E.C. (1996) Aerobic aquatic biodegradation test withdidecyldimethylammoniumchloride (DDAC) and a bentoniteclay:DDAC complex conducted with natural sediment and sitewater. Wildlife International Ltd., Easton, MD, USA. Project No.434E-101 (unpublished).


D110(LON 2970)

Hirschen, D.M., Ziemer, M. and D. Seifert (1998) Bardac 22:DOC die-away test OECD 301 A with pre-adapted inoculum.Clariant GmbH, Frankfurt, Germany. Report No. D0094-1(unpublished).


D134(LON 3796)

Bazzon, M and F. Deschamps (2002) Biotic degradationbiodegradability evaluation on aqueous medium ultimate aerobia ofthe referenced compounds, CATIGENE T 50. INERIS, Vert-lepetit,France. Study No. 506223 (unpublished).


D159 (LON 4031)

Fiebig, S. (2006) Dodigen 1881: Ready Biodegradability: Modified Sturm Test. Dr. U. Noack-Laboratorien, Germany. Study No. AST97952 (unpublished).

7.1.1.2.2 – Inherentbiodegradability

D110(LON 2970)

Hirschen, D.M., Ziemer, M. and D. Seifert (1998) Bardac 22: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 – Aerobicbiodegradation

D60(LON 3438)

Schaefer, E.C. (2001) Didecyldimethylammonium chloride(DDAC): Dieaway in activated sludge. Wildlife International,Inc., Easton, MA, USA. Project No. 289E-112 (unpublished).

79


Other Non-KeyBiodegradability Report(s)Included in This Submission

D111(LON 1266)

Bücking H. -W. (1989) Prüfung des biologischen Abbaus vonBARDAC 22 im OECD-Confirmatory-Test. Hoechst, Frankfurt,Germany. Report No. 95/89(B) (unpublished).

D40(LON 1798)

Cranor, W. (1991) Anaerobic aquatic metabolism of 14CDidecyldimethylammoniumchloride(14C-DDAC) ABCLaboratories, Inc., Columbia, MO, USA. Report No. 37007(unpublished).

D41(LON 1794)

Cranor, W. (1991) Aerobic aquatic metabolism of 14CDidecyldimethylammoniumchloride(14C-DDAC) ABCLaboratories, Inc., Columbia, MO, USA. Report No. 37008(unpublished).

D65(LON 3255)

de Vette, H.Q.M., van Asten, J.G. and A.O. Hanstveit (2000) Awater/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(LON 1796)

Cranor, W. (1991) Aerobic soil metabolism of 14C -Didecyldimethylammonium chloride (14C-DDAC). ABCLaboratories, Columbia, MO, USA. Report No. 37006(unpublished).

D120(LON 1957)

Todt K. (1991) Abbau von Didecydimethylammoniumchlorid imBoden unter Praxisbedingungen. Natec, Hamburg, Deutschland.Abschlußbericht NA 91 9601 (unpublished).

7.2.2.4 – Other soildegradation studies

D38(LON 3069)

Schmidt, J. (1992) Determination of the photolysis rate ofdidecyldimethylammonium chloride on the surface of soil. ABCLaboratories, Columbia, MO, USA. Report No. 39505(unpublished).

7.2.3.1 – Adsorption anddesorption

D42(LON 1792)

Daly, D. (1989) Soil/sediment adsorption-desorption of 14C - Didecyldimethylammoniumchloride(DDAC). Analytical Bio-Chemistry Laboratories, Inc., Columbia, MO, USA. Report No.37009 (unpublished).

7.4.1.1(1) – Acute toxicity tofish (Oncorhynchus kisutch)

D5(LON 1788)

LeLievre, M.K. (1990) Evaluation of didecyldimethylammoniumchloride (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 tofish (Lepomis macrochirus)

D4(LON 1786)

LeLievre, M.K. (1990) Evaluation of Didecyldimethylammoniumchloride (DDAC) in a static acute toxicity test with bluegillsunfish, Lepomis macrochirus. Springborn Laboratories, Inc.,Wareham, MA, USA. SLI Report No. 89-10-3111 (unpublished).

80


7.4.1.1(3) – Acute toxicity tofish (Pimephales promelas)

D56(LON 2937)

Putt, A.E. (1994) Didecyldimethylammoniumchloride (DDAC):Static acute toxicity to fathead minnow (Pimephales promelas)with and without the presence of humic acid. SpringbornLaboratories, Inc., Wareham, MA, USA. Report No. 94-1-5122(unpublished).

7.4.1.1(4) – Acute toxicity tofish (Pimephales promelas)

D68(LON 3087)

Swigert, J.P., Graves, W.C. and M.A. Mank (1995) An evaluationof didecyldimethylammoniumchloride (DDAC) in a 96-hour flowthroughacute toxicity study with the fathead minnow (Pimephalespromelas). Wildlife International Ltd., Easton, MD, USA. ProjectNo. 289A-124 (unpublished).

7.4.1.1(5) – Acute toxicity tofish (Oncorhynchus mykiss)

D69(LON 3809)

Swigert, J.P., W.C. Graves and M.A. Mank (1995) An evaluationof didecyldimethylammonium chloride (DDAC) in a 96-hour flowthroughacute toxicity study with the rainbow trout (Oncorhynchusmykiss). Wildlife International Ltd., Easton, MD, USA. ProjectNo. 289A-125 (unpublished).

7.4.1.1 – Acute toxicity to fish(Cyprinodon variegatus)

D54(LON 3166)

Collins, M.K. (1994) Didecyldimethylammonium-chloride(DDAC): Evaluation in a static acute toxicity test with sheepsheadminnow (Cyprinodon variegatus). Springborn Laboratories, Inc.,Wareham, MA, USA. SLI Report No. 93-6-4833 (unpublished).

7.4.1.1 – Acute toxicity to fish(Acipenser transmontanus)

D55(LON 2948)

Miller, J.L. (1997) Evaluation of Bardac 2280 in a static-renewalacute toxicity test with juvenile white sturgeon, Acipensertransmontanus. Aqua-Science Environmental ToxicologySpecialists, Davis, CA, USA. (unpublished).

7.4.1.1 – Acute toxicity to fish(Oncorhynchus mykiss)

D112(LON 1270)

Luy, T. and S. Frances (1971) Report on fish (rainbow trout)toxicity testing using BARDAC 22. Wells Laboratories, Inc.,Jersey City, NJ, USA. (unpublished).

7.4.1.1 – Acute toxicity to fish(Poecilia reticulata)

D113(ON 1268)

Adema, D.M.M. (1978) The acute toxicity of Barquat MB 50,Barquat 4250 and Bardac 22 to young guppies. CentraalLaboratorium TNO, Delft, The Netherlands. Report No. CL 78/34(unpublished).

7.4.1.1 – Acute toxicity to fish(Acipenser transmontanus) inthe presence of Fraser Riversediment

D64(LON 2950)

Miller, J.L. (1997) Evaluation of Bardac 2280 in a static-renewalacute toxicity test with juvenile white sturgeon Acipensertransmontanus, in the presence of Fraser River sediment. Aqua-Science, Davis, CA, USA. (unpublished).

7.4.1.1 – Acute toxicity to fish(Oncorhynchus mykiss)

D70(LON 2938)

Swigert, J.P., Graves, W.C. and M.A. Mank (1995) Evaluation ofa Bentonite clay:didecyldimethylammoniumchloride (DDAC)complex in a 96-hour static acute toxicity study with the rainbowtrout (Oncorhynchus mykiss). Wildlife Internationl, Ltd., Easton,

81


MD, USA. Project No. 289A-121 (unpublished).7.4.1.2(1) – Acute toxicity toinvertebrates (Daphniamagna)

D6(LON 1787)

LeLievre, M.K. (1990) Evaluation of didecyldimethylammoniumchloride (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 toinvertebrates (Daphniamagna)

D67(LON 2939)

Swigert, J.P., Graves, W.C. and M.A. Mank (1995) An evaluationof didecyldimethylammoniumchloride (DDAC) in a 48-hour flowthroughacute toxicity study with the cladoceran (Daphnia magna).Wildlife International Ltd., Easton, MD, USA. Project No. 289A-122 (unpublished).

7.4.1.2 – Acute toxicity toinvertebrates (Mysidopsisbahia)

D8(LON 1789)

LeLievre, M.K. (1990) Evaluation of didecyldimethylammoniumchloride (DDAC) in a static acute toxicity test with mysid shrimp,Mysidopsis bahia. Springborn Laboratories, Inc., Wareham, MA,USA. Report No. 90-2-3233 (unpublished).

7.4.1.2 – Acute toxicity toinvertebrates (Crassostreavirginica)

D59 Dionne, E. (1994) Didecyldimethylammoniumchloride (DDAC):Evaluation in a static (recirculated) acute toxicity test with Easternoysters (Crassostrea virginica) using [14C]-DDAC. SpringbornLaboratories, Inc., Environmental Sciences Division, Wareham,MA, USA. Report No: 93-12-5079 (unpublished).

7.4.1.2 – Acute toxicity toinvertebrates (Crassostreavirginica)

D58(LON 3167)

Dionne, E. (1994) Didecyldimethylammoniumchloride (DDAC):Evaluation in a static (recirculated) acute toxicity test with Easternoysters (Crassostrea virginica) using [14C]-DDAC. SpringbornLaboratories, Inc., Environmental Sciences Division, Wareham,MA, USA. Report No. 93-6-4854 (unpublished).

7.4.1.3(1) – Growthinhibition test on algae(Selenastrum capricornutum)

D57(LON 3433)

Desjardins, D., Kendall, T.Z., Van Hoven, R.L. and H.O. Krueger(2003) Bardac 2280: A 96-hour toxicity test with the freshwateralga (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

82


inhibition test on algae(Scenedesmus subspicatus)

(LON 3011) test(72hr). Dr.U.Noack-Laboratorium fur Angewandte Biologie,Sarstedt, Germany. Study No. SS061301 (unpublished).

7.4.1.3(3) – Growthinhibition test on algae(Selenastrum capricornutum)in Natural Surface Water

D66(LON 3659)

Desjardins, D., Kendall, T.Z., Van Hoven, R.L. and H.O. Krueger(2003) Bardac 2280: A 96-hour toxicity test with the freshwateralga (Selenastrum capricornutum) using natural surface water.Wildlife International, Ltd., Easton, MD, USA. Project No. 289A-153 (unpublished).

7.4.1.4 – Inhibition tomicrobiological activity

D117(LON 3330)

Mead, C. (2001) LZ1043 (Didecyldimethylammounium chloride):Assessment of the inhibitory effect on the respiration of activatedsewage sludge. Safepharm Laboratories Ltd., Derby, England.Project No. 102-369 (unpublished).

7.4.1.4 – Inhibition tomicrobiological activity

D116(LON 1265)

Vonk, J.W. (1989) Biodegradability of Bardac-22. NetherlandsOrganization for Applied Scientific Research, TNO Division ofTechnology for Society, Delft, The Netherlands. Report No.R89/252 (unpublished).

7.4.2– Bioconcentration(Lepomis machrochirus)

D43(LON 1790)

Fackler, P.H. (1990) Bioconcentration and elimination of 14Cresidues by bluegill (Lepomis machrochirus) exposed todidecyldimethylammonium chloride (DDAC). SpringbornLaboratories, Inc., Wareham, MA, USA. Report No. 89-7-3043(unpublished).

7.4.3.2 – Reproduction andgrowth in fish (Brachydaniorerio)

D118(LON 3373)

Hooftman, R.N., de Vette, H.Q.M. and B. Borst (2001) Early lifestage test under intermittent flow-through conditions withdidecyldimethylammounium 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 andgrowth in invertebrates(Daphnia magna)

D7(LON 3323)

Hooftman, R.N. and H.Q.M. de Vette (2001) Intermittent flowthroughreproduction test with didecyldimethylammonium chlorideand Daphnia magna. TNO Nutrition and Food Research,Department of Environmental Toxicology, Delft, The Netherlands.Report No. V99.1171 (unpublished).

7.4.3.4 – Reproduction andgrowth in invertebrates(Daphnia magna)

D121(LON 1953)

Jonas, W. (1992) Bardac 2270: Reproduktionstest an Daphniamagna. (unpublished).

7.4.3.5.1 – Effects onsediment dwelling organisms(Chironomus tentans)

D63(LON 2941)

England, D.C. and T. Leak (1995) Chronic toxicity of sedimentincorporateddidecyldimethylammoniumchloride (DDAC) toChironomus 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) 83


microbiological activity (LON 3378) Theassessment of the ecological effects of didecyldimethylammouniumchloride (Guidelines OPPTS 850.5100 Soil MicrobialCommunity Test, OECD 216 and OECD 217 and CTB SectionH.4.1). TNO Chemistry, Delft, The Netherlands. Study No. IMW-99-9048-05 (unpublished).

7.5.1.2(1) – Acute toxicity toearthworms

D88(LON 3153)

Henzen, L. (1999) The acute toxicity of DDAC to the wormspecies Eisenia fetida in a 14-day test (OECD Guideline No. 207).TNO Nutrition and Food Research Institute, Delft, TheNetherlands. Report No. V99.160 (unpublished).

7.5.1.2(2) – Acute toxicity toearthworms

D133(LON 3799)

Rodgers, M.H. (2004) N-Alkyl (C12-16)-N,N-dimethyl-Nbenzylammoniumchloride (ADBAC): Acute toxicity (LC50) to theearthworm. Huntingdon Life Sciences, Huntingdon,Cambridgeshire, England. Report No. ADB/023 033976(unpublished).

7.5.1.3 – Acute toxicity toplants

D114(LON 3811)

Gray, J. (2004) N,N-Didecyl-N,N-dimethylammonium chloride(DDAC): Acute toxicity to terrestrial plants. Huntingdon LifeSciences, Huntingdon, Cambridgeshire, England. Study No.DKG/014 (unpublished).

7.5.3.1.1 – Acute oraltoxicity (Bobwhite Quail)

D1(LON 1784)

Campbell, S., Hoxter, K.A. and G.J. Smith (1991)Didecyldimethylammonium chloride: An acute oral toxicity studywith the northern bobwhite. Wildlife International Ltd., Easton,MD, USA. Project No. 289-103A (unpublished).

7.5.3.1.2(1) – Short-termtoxicity (Bobwhite Quail)

D2(LON 1785)

Long, R.D., Hoxter, K.A. and G.J. Smith (1991)Didecyldimethylammonium chloride: A dietary LC50 Study withthe northern bobwhite. Wildlife International Ltd., Easton, MD,USA. Project No. 289-101 (unpublished).

7.5.3.1.2(2) – Short-termtoxicity (Mallard duck)

D3(LON 1783)

Long, R.D., Hoxter, K.A. and G.J. Smith (1991)Didecyldimethylammoniumchloride: A dietary LC50 study with themallard. Wildlife International Ltd., Easton, MD, USA. ProjectNo. 289-102 (unpublished).

Other Non-Key Report(s)Included in This Submission

D53(LON 3815)

Bestari, K. (2001) Determination of the leachability of Bardac2280 from treated wood. Centre for Toxicology, University ofGuelph, Guelph, Ontario, Canada. Study No. 200-CT-WL-B22(unpublished).

References SupportingSummaries Found inDocument III-A, Section 5

D138 Ruddick, J.N.R. (1984) Appendix C – Alkylammonium compoundsas wood preservatives. Proc. Am. Wood. Pres. Assn. 80, 191-204and Appendix D – Field testing of alkylammonium woodpreservatives, pp. 206-210.

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D140 Creffield, J.W. (1993) A study on the effectiveness of DDAC toprotect wood from attack by termites. IRG Document No.IRG/WP/93-30009.

D141 Graf, E. (1987) Determination of the protective effectiveness ofBardac 22 against wood destroying basidiomycetes after leachingprocedure. Swiss Federal Laboratories for Materials Testing andResearch, EMPA St. Gallen, Switzerland. Report No. 2311491(unpublished). [Ref. No. D132 (LON 3819), English translation ofthe German original test report (Bestimmung derWirksamkeitsgrenze von Bardac 22 gegen holzzerstörendeBasidiomyceten) attached as Annex.

D142 Linfield, W.M. (1969) In E. Jungermann, Ed., “CationicSurfactants”, 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) Acceleratedtesting for out-of-ground contact using natural biologicalpreconditioning. International Research Group on WoodPreservation Document No. IRG/WP 96-20088.

D145 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997a) Acceleratedtesting for out-of-ground contact using natural biologicalpreconditioning. International Research Group on WoodPreservation Document No. IRG/WP 97-20108.

D146 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997b) Microbialecology of treated lap-joints at Hilo, Hawaii for 24 months.International Research Group on Wood Preservation DocumentNo. IRG/WP 97-20107.

D147 Preston, A.F., McKaig, P.A. and P.J. Walcheski (1986) Termiteresistance of treated wood in an above ground field test.International Research Group on Wood Preservation DocumentNo. 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 compoundsand 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 Coniophoraolivacea and Coniophora puteana test strains. InternationalResearch Group on Wood Preservation Document No.IRG/WP/20004.

D152 Wazny, J. and L.J. Cookson (1994) Comparison of the agar blockand soil block methods used for evaluation of fungitoxic value ofQAC and CCA wood preservatives. International Research Groupon 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 toAWPA Formosan Subterranean Task Force.

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Document III B

Endpoint ReferenceNo.

ReferenceNon-Key Studies are italicized.

3.5(1) – Acidity/alkalinityand if necessary pH value(1% in water)

D156(LON 4006)

Sydney, P. (2006) BC-25: Physicochemical properties.Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire,England. Report No. DKG0018/062229 (unpublished).

3.6(1) – Relative Density D156(LON 4006)


3.8(1) – Technicalcharacteristics of the biocidalproduct: Persistent foaming

D156(LON 4006)


3.10.2(1) – Viscosity D156(LON 4006)


References SupportingSummaries Found inDocument III-B, Section 5


D143 Moffat, A.R. (1994) A determination of the toxic level ofACQ2100 wood preservative for the powder post borer Lyctusbrunneus (Stephens). International Research Group on WoodPreservation Document No. IRG/WP 94-20029.

D144 Molnar, S., Dickinson, D.J. and R.J. Murphy (1996) Acceleratedtesting for out-of-ground contact using natural biologicalpreconditioning. International Research Group on WoodPreservation Document No. IRG/WP 96-20088.

D145 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997a) Acceleratedtesting for out-of-ground contact using natural biologicalpreconditioning. International Research Group on WoodPreservation Document No. IRG/WP 97-20108.

D146 Molnar, S., Dickinson, D.J. and R.J. Murphy (1997b) Microbialecology of treated lap-joints at Hilo, Hawaii for 24 months.International Research Group on Wood Preservation DocumentNo. 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 toAWPA Formosan Subterranean Task Force.

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Appendix IV: List of standard terms and abbreviations

Stand. term / Abbreviation

Explanation

A AmpereACh AcetylcholineAChE AcetylcholinesteraseADBAC Alkyldimethylbenzylammonium ChlorideADI acceptable daily intakeADME administration distribution metabolism and excretionADP adenosine diphosphateAE acid equivalentAF assessment factorAFID alkali flame-ionisation detector or detectionA/G albumin/globulin ratioai active ingredientALD50 approximate median lethal dose, 50%ALT alanine aminotransferase (SGPT)Ann. AnnexAOEL acceptable operator exposure levelAMD automatic multiple developmentANOVA analysis of varianceAP alkaline phosphataseapprox ApproximateARC anticipated residue contributionARfD acute reference doseas active substanceAST aspartate aminotransferase (SGOT)ASV air saturation valueATP adenosine triphosphateBAF bioaccumulation factorBCF bioconcentration factorbfa body fluid assayBOD biological oxygen demandbp boiling pointBPD Biocidal Products DirectiveBSAF biota-sediment accumulation factorBSE bovine spongiform encephalopathyBSP bromosulfophthaleinBUN blood urea nitrogenbw body weightc centi- (x 10 –2 )°C degrees Celsius (centigrade)CA controlled atmosphereCAD computer aided designcd candelaCDA controlled drop(let) applicationcDNA complementary DANNCEC cation exchange capacitycf confer, compare toCFU colony forming units

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Explanation

ChE cholinesteraseCI confidence intervalCL confidence limitscm centimetreCNS central nervous systemCOD chemical oxygen demandConc ConcentrationCPK creatinine phosphatasecv coefficient of variationCv ceiling valued day(s)DDAC Didecyldimethylammonium ChlorideDES diethylstilboestrolDIS draft international standard (ISO)DMSO dimethylsulfoxideDNA deoxyribonucleic aciddna designated national authorityDO dissolved oxygenDOC dissolved organic carbondpi days post inoculationDRP 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 weightDWQG drinking water quality guidelines decadic molar extinction coefficientEASE Estimation and Assessment of Substance ExposureEC50 median effective concentrationECD electron capture detectorED50 median effective doseEDI estimated daily intakeEINECS European inventory of existing commercial substancesELINCS European list of notified chemical substancesELISA enzyme linked immunosorbent assaye-mail electronic mailEMDI estimated maximum daily intakeEN European normEPMA electron probe micro-analysisERL extraneous residue limitESD Emission Scenario DocumentESPE46/51 evaluation system for pesticidesEUSES European Union system for the evaluation of substancesF FieldF0 parental generationF1 filial generation, firstF2 filial generation, secondFBS full base set

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Explanation

FELS fish early-life stageFIA fluorescence immuno-assayFID flame ionisation detectorFmol fractional equivalent of the metabolite´s molecular weight compared to the

active substanceFOB functional observation batteryfoc organic carbon factor (compartment dependent) fp freezing pointFPD flame photometric detectorFPLC fast protein liquid chromatographyg gram(s)gd gestation dayGAP good agricultural practiceGC gas chromatographyGC-EC gas chromatography with electron capture detectorGC-FID gas chromatography with flame ionisation detectorGC-MS gas chromatography-mass spectrometryGC-MSD gas chromatography with mass-selective detectionGEP good experimental practiceGFP good field practiceGGT gamma glutamyl transferaseGI gastro-intestinalGIT gastro-intestinal tractGL guideline levelGLC gas liquid chromatographyGLP good laboratory practiceGM geometric meanGMO genetically modified organismGMM genetically modified micro-organismGPC gel-permeation chromatographyGPS global positioning systemGSH GlutathioneGV Granulosevirush hour(s)H Henry’s Law constant (calculated as a unitless value) ha hectare(s)Hb HaemoglobinHC5 concentration which will be harmless to at least 95 % of the species present with

a given level of confidence (usually 95 %)HCG human chorionic gonadotropinHct HaematocritHDT highest dose testedhL HectolitreHEED high energy electron diffractionHID helium ionisation detectorHPAEC high performance anion exchange chromatographyHPLC high pressure liquid chromatography or high performance liquid

chromatographyHPLC-MS high pressure liquid chromatography - mass spectrometry

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Explanation

HPPLC high pressure planar liquid chromatographyHPTLC high performance thin layer chromatographyHRGC high resolution gas chromatographyHS Shannon-Weaver indexHt HaematocritHUSS human and use safety standard I IndoorI50 inhibitory dose, 50%IC50 median immobilisation concentration or median inhibitory concentration 1ICM integrated crop managementID ionisation detectorIEDI international estimated daily intakeIGR insect growth regulatorim intramuscularinh inhalationINT 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazoliumchloride testing methodip intraperitonealIPM integrated pest managementIR infraredISBN international standard book numberISSN international standard serial numberIUCLID International Uniform Chemical Information Databaseiv intravenousIVF in vitro fertilisationk (in combination) kilok rate constant for biodegradationK Kelvin Ka acid dissociation constantKb base dissociation constantKads adsorption constantKdes apparent desorption coefficientkg kilogramKH Henry´s Law constant (in atmosphere per cubic metre per mole)Koc organic carbon adsorption coefficientKom organic matter adsorption coefficientKow octanol-water partition coefficientKp solid-water partition coefficientkPa kilopascal(s)l, L litreLAN local area networkLASER light amplification by stimulated emission of radiationLBC loosely bound capacityLC liquid chromatographyLC-MS liquid chromatography- mass spectrometryLC50 lethal concentration, medianLCA life cycle analysisLC-MS-MS liquid chromatography with tandem mass spectrometryLD50 lethal dose, median; dosis letalis media

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Explanation

LDH lactate dehydrogenaseln natural logarithmLOAEC lowest observable adverse effect concentrationLOAEL lowest observable adverse effect levelLOD limit of detectionLOEC lowest observable effect concentrationLOEL lowest observable effect levellog logarithm to the base 10LOQ limit of quantification (determination)LPLC low pressure liquid chromatographyLSC liquid scintillation counting or counterLSD least squared denominator multiple range testLSS liquid scintillation spectrometryLT lethal thresholdm MetreM Molarµm micrometre (micron)MAC maximum allowable concentration MAK maximum allowable concentration MC moisture contentMCH mean corpuscular haemoglobinMCHC mean corpuscular haemoglobin concentrationMCV mean corpuscular volumeMDL method detection limitMFO mixed function oxidaseµg microgrammg milligramMHC moisture holding capacityMIC minimum inhibitory concentration min minute(s)MKC minimum killing concentrationmL millilitreMLT median lethal timeMLD minimum lethal dosemm millimetreMMAD mass median aerodynamic diametermo month(s)MOE margin of exposuremol mole(s)MOS margin of safetymp melting pointMRE maximum residue expectedMRL maximum residue level or limitmRNA messenger ribonucleic acidMS mass spectrometryMSDS material safety data sheetMTD maximum tolerated doseMT material test

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Explanation

MW molecular weightn.a. not applicablen- normal (defining isomeric configuration)n number of observationsNAEL no adverse effect levelnd not detectedNEDI national estimated daily intakeNEL no effect levelNERL no effect residue levelng Nanogramnm NanometreNMR nuclear magnetic resonanceno, n° NumberNOAEC no observed adverse effect concentrationNOAEL no observed adverse effect levelNOEC no observed effect concentrationNOED no observed effect doseNOEL no observed effect levelNOIS notice of intent to suspendNPD nitrogen-phosphorus detector or detectionNPV nuclear polyhedrosis virusNR not reportedNTE neurotoxic target esteraseOC organic carbon contentOCR optical character recognitionODP ozone-depleting potentialODS ozone-depleting substancesOEL occupational exposure limit OH HydroxideOJ Official JournalOM organic matter contentPa PascalPAD pulsed amperometric detection2-PAM 2-pralidoximepc paper chromatographyPCV haematocrit (packed corpuscular volume)PEC predicted environmental concentrationPECA predicted environmental concentration in airPECS predicted environmental concentration in soilPECSW predicted environmental concentration in surface waterPECGW predicted environmental concentration in ground waterPED plasma-emissions-detectorpH pH-valuePHED pesticide handler’s exposure dataPIC prior informed consentpic phage inhibitory capacityPIXE proton induced X-ray emissionpKa negative logarithm (to the base 10) of the acid dissociation constant

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Explanation

pKb negative logarithm (to the base 10) of the base dissociation constantPNEC predicted no effect concentration (compartment to be added as subscript)po by mouthPOP persistent organic pollutantsppb parts per billion (10-9 )PPE personal protective equipmentppm parts per million (10-6 )PPP plant protection productppq parts per quadrillion (10-24 )ppt parts per trillion (10-12 )PSP phenolsulfophthaleinPrT prothrombin timePRL practical residue limitPT product typePT(CEN) project team CENPTDI provisional tolerable daily intakePTT partial thromboplastin timeQA quality assuranceQAU quality assurance unit(Q)SAR quantitative structure-activity relationshipr correlation coefficientr 2 coefficient of determinationRA risk assessmentRBC red blood cellREI restricted entry intervalRENI Registry Nomenclature Information SystemRf retardation factorRfD reference doseRH relative humidityRL50 median residual lifetimeRNA ribonucleic acidRP reversed phaserpm revolutions per minuterRNA ribosomal ribonucleic acidRRT relative retention timeRSD relative standard deviations SecondS SolubilitySAC strong adsorption capacitySAP serum alkaline phosphataseSAR structure/activity relationshipSBLC shallow bed liquid chromatographysc Subcutaneoussce sister chromatid exchangeSCAS semi-continuous activated sludgeSCTER smallest chronic toxicity exposure ratio (TER)SD standard deviationse standard error

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Explanation

SEM standard error of the meanSEP standard evaluation procedureSF safety factorSFC supercritical fluid chromatographySFE supercritical fluid extractionSIMS secondary ion mass spectroscopyS/L short term to long term ratioSMEs small and medium sized enterprisesSOP standard operating proceduressp species (only after a generic name)SPE solid phase extractionSPF specific pathogen freespp subspeciesSSD sulphur specific detectorSSMS spark source mass spectrometrySTEL short term exposure limitSTER smallest toxicity exposure ratio (TER)STMR supervised trials median residueSTP sewage treatment plantt tonne(s) (metric ton)t½ half-life (define method of estimation)T3 tri-iodothyroxineT4 thyroxineT25 tumorigenic dose that causes tumours in 25% of the test animals TADI temporary acceptable daily intakeTBC tightly bound capacityTCD thermal conductivity detectorTG technical guideline, technical groupTGD Technical guidance documentTID thermionic detector, alkali flame detectorTDR time domain reflectrometryTER toxicity exposure ratioTERI toxicity exposure ratio for initial exposureTERST toxicity exposure ratio following repeated exposureTERLT toxicity exposure ratio following chronic exposuretert tertiary (in a chemical name)TEP typical end-use productTGGE temperature gradient gel electrophoresisTIFF tag image file formatTLC thin layer chromatographyTlm median tolerance limitTLV threshold limit valueTMDI theoretical maximum daily intakeTMRC theoretical maximum residue contributionTMRL temporary maximum residue limitTNsG technical notes for guidanceTOC total organic carbonTremcard transport emergency card

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Explanation

tRNA transfer ribonucleic acidTSH thyroid stimulating hormone (thyrotropin)TTC 2,3,5-triphenylterazoliumchloride testing methodTWA time weighted averageUDS unscheduled DNA synthesisUF uncertainty factor (safety factor)ULV ultra low volumeUR unit riskUV UltravioletUVC unknown or variable composition, complex reaction productsUVCB undefined or variable composition, complex reaction products in biological

materialv/v volume ratio (volume per volume)vis VisibleWBC white blood cellwk Weekwt Weightw/v weight per volumeww wet weightw/w weight per weightXRFA X-ray fluorescence analysisyr year< less than less than or equal to> greater than greater than or equal to

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