Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): read-across from structural analogue [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6): negative with and without activation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (OECD TG 471) (LPT, 2002).
Gene mutation (Bacterial reverse mutation assay / Ames test): read-across from structural analogue dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7): negative with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, and TA 100 (similar to OECD TG 471) (Dow Corning Corporation 1979).
Mammalian cytogenicity (chromosome aberration assay): read across from structural analogue dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7): negative with and without metabolic activation in Chinese hamster V79 cells (OECD TG 473) (BSL BIOSERVICE, 2012b).
Mammalian mutagenicity (Mouse Lymphoma Assay): read across from structural analogue dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7): negative with and without metabolic activation (OECD TG 476) (BSL BIOSERVICE, 2012a)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No data are available for the genetic toxicity of [2-(perfluorohexyl)ethyl]trichlorosilane, therefore reliable data are read across from bacterial mutagenicity studies with the structural analogues [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6) and dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7), and from in vitro cytogenicity and mutagenicity studies in mammalian cells with dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7). The results of all the studies are negative

Non-testing methods including read-across from surrogate substances are able to provide information on genetic toxicity (REACH Guidance part 07a, R.7.7.3). In the case of genetic toxicity the presence or absence of functional groups that are known to be related to genetic toxicity is considered important, as the presence or absence of reactive groups and molecular substructures is associated with mutagenic and carcinogenic properties of chemicals (Benigni and Bossa, 2006). Consideration is therefore given to the structural similarity, particularly presence or absence of structural alerts for genetic toxicity, when selecting surrogate substances for genetic toxicity endpoints. Additional information is given in a supporting report (PFA 2013aa) attached in Section 13.

Read-across justification

There are no available measured data for trichloro(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane (CAS 78560-45-9) for in vitro genetic toxicity. Therefore, the Annex requirements are fulfilled with data on two structurally analogous substances. This document describes the analogue approach for fulfilling bacterial mutagenicity endpoint by read-across from the source substances, [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6) and dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7), and mammalian cytogenicity and mutagenicity by read-across from dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7 according to the Read-across Assessment Framework (RAAF) .

Read-across is proposed in accordance with RAAF Scenario 2: “This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst case.”

The read-across justification is presented (Table 1) according to RAAF scenario 2 assessment elements (AE) as outlined in Table B1 of the RAAF1:

Table 1: RAAF scenario 2 assessment elements (AE) as given in Appendix B (Table B1) of the RAAF

AE A.1

Characterisation of source substance

AE A.2

Link of structural similarity and differences with the proposed Prediction

AE A.3

Reliability and adequacy of the source study

AE 2.1

Compounds the test organism is exposed to

AE 2.2

Common underlying mechanism, qualitative aspects

AE 2.3

Common underlying mechanism, quantitative aspects

AE 2.4

Exposure to other compounds than to those linked to the prediction

AE 2.5

Occurrence of other effects than covered by the hypothesis and Justification

AE A.4

Bias that influences the prediction

1. AE A.1 Identity and characterisation of the source substance

The first source substance, [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6), belongs to an analogue group of organosilicon substances with highly (but no fully) fluorinated side chains. Apart from being attached to a highly fluorinated side chain, the silicon atom is also attached to a methyl group and two chlorine groups. The substance hydrolyses rapidly in contact with water and the hydrolysis products are hydrogen chloride and [2‑(perfluorohexyl)ethyl]methylsilanediol.  The predicted half-lives of hydrolysis are approximately 5 seconds as a worst case at 25°C and pH 4, 7 and 9 (analogue read-across).

The values for logKow and water solubility for the source substance are not relevant as the substance is hydrolyses rapidly in water. The vapour pressure of the source substance is 0.04 Pa at 20°C, 30 Pa at 50°C (EU Method A.4).

The second source substance, dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7), belongs to the same analogue group and has a shorter highly (but not fully) fluorinated side chain and two chlorine and one methyl groups attached to the silicon. It also hydrolyses rapidly to give hydrogen chloride and methyl(3,3,3-trifluoropropyl)silanediol. Half-life estimates are < 17 seconds for pH 4, 7, and 9 at 1.5°C.

The values for logKow and water solubility for the source substance are not relevant as the substance is hydrolyses rapidly in water. The vapour pressure of the source substance is 740 Pa at 25°C  (QSAR).

2. AE A.2 Link of structural similarities and differences with the proposed prediction

The registration and read-across substances belong to an analogue group of organosilicon substances with highly (but no fully) fluorinated side chains. The substances hydrolyse very rapidly to produce the corresponding Si-hydrolysis products and hydrochloric acid. The reaction is typically so rapid that its precise half-life is not significant (in some cases, it is so fast that it cannot be quantified). As the hydrolysis reaction may be acid or base-catalysed, the rate of reaction is expected to be slowest at around pH 7 and increase as the pH is raised or lowered.

The registration substance, trichloro(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane (CAS 78560-45-9) hydrolyses very rapidly, with a hydrolysis half-life of approximately 5 seconds at 25°C and pH 4, 7 and 9. At physiologically relevant conditions, the rate of hydrolysis would be faster, therefore a hydrolysis half-life at pH 7 and 37.5 °C has been estimated  to be < 5 seconds. The products of hydrolysis are hydrochloric acid and [2-(perfluorohexyl)ethyl]silanetriol.

The source substances [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6) and  dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7) hydrolyse very rapidly to produce [2‑(perfluorohexyl)ethyl]methylsilanediol, methyl(3,3,3-trifluoropropyl)silanediol and hydrochloric acid. None of the substances or hydrolysis products has structural alerts for genotoxicity (Benigni et al., 2008). The reaction is typically so rapid that its precise half-life is not significant (in some cases, it is so fast that it cannot be quantified). The source substances estimated hydrolysis half-lives at pH 7 are approximately 5 and 17 seconds. At physiologically-relevant conditions the calculated hydrolysis half-lives are expected to be faster.  

Table 2: Physicochemical properties

Property

Target substance

Source substance

Source substance

Substance name

trichloro(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane

[2-(perfluorohexyl)ethyl]dichloro(methyl)silane

dichloromethyl(3,3,3-trifluoropropyl)silane

CAS number

78560-45-9

73609-36-6

675-62-7

Hydrolysis half-life at pH 7 and 25°C

5 seconds

5 seconds

< 17 seconds

Hydrolysis half-life at pH 7 and 37.5°C

<5 seconds

<5 seconds

< 17 seconds

Silanol hydrolysis product

[2-(perfluorohexyl)ethyl]silanetriol

[2(perfluorohexyl)ethyl]methylsilanediol

methyl(3,3,3-trifluoropropyl)silanediol

Non-Si hydrolysis products

hydrogen chloride

hydrogen chloride

hydrogen chloride

LogKow value (parent)

Not relevant

Not relevant

Not relevant

LogKow value (silanol hydrolysis product)

2.7 at 20°C (QSAR)

4.6 at 20°C (QSAR)

1.0

Vapour pressure (parent)

30 Pa at 25°C (QSAR)

0.04 Pa at 20°C, 30 Pa at 50°C (EU Method A.4)

740 Pa at 25°C (QSAR)

Vapour pressure (silanol hydrolysis product)

6.9E-03 Pa at 25°C (QSAR)

0.38 Pa at 25°C (QSAR)

1.3 Pa at 25°C (QSAR)

Water solubility (parent)

Not relevant

Not relevant

Not relevant

Water solubility (silanol hydrolysis product)

0.58 mg/l at 20°C (QSAR)

0.0048 mg/l at 20°C (QSAR)

1.35E+04 mg/l (very soluble) (QSAR)

3. AE A.3 Reliability and adequacy of the source study

There are no available data for in vitro genetic toxicity for the registered substance. Therefore, data were read-across from structurally analogous substances.

Dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7) has been tested for bacterial mutagenicity (Ames Test) in a study conducted according to a protocol similar to the OECD TG 471 which predates GLP (Dow Corning Corporation 1979). The Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100 were exposed to the test material both in absence and presence of a metabolic activation system. An additional strain for the detection of cross-linking agents was not included into the test. No treatment related increase in the number of revertants was observed in any of the tester strains. Appropriate solvent and positive controls were included into the test and gave the expected results. Hence, the test item was considered to be non-mutagenic to bacteria under the conditions of the test.

Dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7) was tested for in vitro cytogenicity to mammalian cells according to the OECD TG 473 and in compliance with GLP (BSL BIOSERVICE, 2012b). The test item did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line with and without metabolic activation up to cytotoxic concentrations. Appropriate positive and solvent controls were included into the study and gave the expected results. The test item is therefore considered to be non-clastogenic under the conditions of the test.

Dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7) has been tested for mutagenicity to mammalian cells in a study conducted according to OECD 476 and GLP (BSL BIOSERVICE, 2012a). No increase in mutant frequency was observed in the presence or absence of metabolic activation. It is concluded that, under the experimental conditions reported, the test substance is non-mutagenic in the in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells.

4. AE A.4 Bias that influences the prediction

Data on the source substances, [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6) and dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7), were read-across to the registered (target) substance trichloro(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane (CAS 78560-45-9). The source substances and the target substance have similar chemical structure and physicochemical properties. All three substances are members of the analogue group of organosilicon substances with highly (but no fully) fluorinated side chains. The substances hydrolyse very rapidly to produce the corresponding Si-hydrolysis products and hydrochloric acid. None of the substances or hydrolysis products has structural alerts for genotoxicity (Benigni et al., 2008). The silanol hydrolysis products are also structurally similar. Therefore, the substances’ toxicological properties are expected to be similar, with similar genotoxic potential. No other data for relevant substances were available.

5. AE A.2.1 Compounds the test organism is exposed to

The source substances as well as the target substance hydrolyse at similar rate and very rapidly in contact with water. The rate of hydrolysis is fast in physiologically relevant conditions (approx. 5 seconds at pH7 and 37°C), therefore it is considered that the test organism would predominantely be exposed to the hydrolysis products. All three substances produce the same non-silanol hydrolysis product, hydrochloric acid, which is known for its corrosive properties. The silanol hydrolysis products for both substances are not expected to affect this assessment.

Hydrogen chloride gave negative results in the most reliable of the bacterial mutagenicity studies. Positive results were obtained in mutagenicity and cytogenicity assays using mammalian cells (OECD, 2002; ECHA disseminated dossier for hydrogen chloride). The positive results were associated with decrease in pH, and it is considered that the positive results were likely to have been caused by reduced pH. Positive results caused by high or low pH effects are considered not to be relevant for in vivo situations (ECHA guidance Chapter R.07a), and testing should be carried out at neutral pH.

6. AE A.2.2 and A.2.3 Common underlying mechanism, qualitative and quantitative aspects

No in vitro genetic toxicity data are available for the target substance trichloro(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane (CAS 78560-45-9), therefore data are read-across from the structurally analogous substances [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6) and dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7). Both substances hydrolyse very fast to produce acetic acid which has corrosive properties. The silanol hydrolysis products are not considered to be relevant for this endpoint. Moreover, they have similar physicochemical properties. Thus, both substances are expected to have similar toxicity profiles.

7. AE 2.4 Exposure to other compounds than to those linked to the prediction

The purity of the registration substance, trichloro(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane (CAS 78560-45-9), is greater than 90 % with no impurities present at concentration greater than 1%.

Purity of test substance in the bacterial mutagenicity study with the source substance, [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6), was reported to be 99.8%.

Purity of test substance in the bacterial mutagenicity study with the source substance, dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7), was not reported.

Purity of test substance in the mammalian cytogenicity study with the source substance, dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7), was reported to be 99.8%.

Purity of test substance in the mammalian mutagenicity study with the source substance, dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7), was reported to be 99.8%.

8. AE 2.5 Occurrence of Other Effects than Covered by the Hypothesis and Justification

Not relevant.

References:

Benigni and Bossa (2006). Current Computer-Aided Drug Design 2, (2), 169-176.

European Chemicals Agency (ECHA) (2015) Read-across Assessment Framework. Appendix B, Scenario 2.

Benigni et al (2008).The Benigni/Bossa rule base for mutagenicity and carcinogenicity JR Scientific report EUR 23241 EN.

OECD (2004b): SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 19-22 October 2004, Ethanol, CAS 64-17-5.

Justification for classification or non-classification

Based on the available read-across data on [2-(perfluorohexyl)ethyl]dichloro(methyl)silane and dichloromethyl(3,3,3-trifluoropropyl)silane, no classification is required for mutagenicity for [2-(perfluorohexyl)ethyl]trichlorosilane according to Regulation (EC) No. 1272/2008.