Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

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

Additional information

There are no reliable genetic toxicity data available for (chloromethyl)diethoxymethylsilane (CAS No. 2212-10-4), therefore good quality data for the structurally-related substance, Silane, (chloromethyl)triethoxymethyl- (CAS No. 15267-95-5), have been read across. Both substances hydrolyse to structurally-related silanol hydrolysis products, chloromethylsilanetriol and (chloromethyl)methylsilanediol, the other hydrolysis products being methanol and ethanol, respectively, which are not known to be genotoxic. The study is considered to be reliability 1 (reliable without restrictions); the read across of the result is considered to be reliability 2 (reliable with restrictions).

In the available read accross study on (chloromethyl)triethoxymethyl- (CAS No. 15267-95 -5) the test material was investigated for bacterial mutagenicity according to the OECD TG 471, and in compliance with GLP. Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and TA 102 were treated with the test material up to limit concentrations both with and without metabolic activation system for 48 h in two independent experiments. No increase in revertant colonies was observed in either of the tester strains with or without metabolic activation system up to cytotoxic concentrations. In conclusion, the test material can be considered to be not mutagenic to bacteria under the conditions of the test.


Short description of key information:
Gene mutation (Bacterial reverse mutation assay / Ames test): negative

Read-across justification genetic toxicity

 

There is one measured data available for (Chloromethyl)diethoxymethylsilane (CAS 2212-10-4) for acute toxicity. However, as the result is sourced from secondary literature (RTECS) only, without access to the original reference for review and no further information is available the reliability of the study is not assignable. This document describes the analogue approach for fulfilling this endpoint by read-across from a source substance (Chloromethyl)triethoxysilane (CAS 15267-95-5), according to the Read-across Assessment Framework (RAAF)[1].

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 5.6.4) 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 RAAF1

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 source substance, (Chloromethyl)triethoxysilane (CAS 15267-95-5) contains a chloromethyl silane group in addition with an ethoxy moiety. (Chloromethyl)triethoxysilane hydrolyses rapidly to form (chloromethyl)silanetriol (1 moles) and ethanol (3 moles) under conditions relevant in the environment or in vivo, with a half-life of 2.5 h. A half-life value of approximately 2.5 h at 20-25°C and pH 7 was obtained using an accepted validated QSAR method.

At pH 2 (the known pH of the stomach), the calculated hydrolysis rate is approximately 5 seconds.

The source substance has log Kow of 2.5 at 20°C (QSAR), water solubility of 1.1E+03 mg/l at 20°C (QSAR) and vapour pressure of 6.5 Pa at 25°C (QSAR).

 

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

The registration substance, (Chloromethyl)diethoxymethylsilane (CAS 2212-10-4), and the read-across substance, (Chloromethyl)triethoxysilane (CAS 15267-95-5), are structurally similar. (Chloromethyl)triethoxysilane (CAS 15267-95-5) contains a chloromethyl silane group in addition to three ethoxy-groups attached to the Si atom, while in (Chloromethyl)diethoxymethylsilane (CAS 2212-10-4) only two ethoxy-groups are attached to the Si atom of the chloromethyl silane group and the third ethoxy group is substituted by a methyl group.

This structural difference remains in the Si-containing hydrolysis product for the target and source substance. The Si hydrolysis product for the target substance is (chloromethyl)methylsilanediol while the Si hydrolysis product for the source substance is chloromethylsilanetriol.

 

Table 2: Physico-chemical properties

 

Property

 

Target substance

 

Source substance

 

Substance name

 

(Chloromethyl)diethoxymethylsilane

 

(Chloromethyl)triethoxysilane

 

CAS number

 

2212-10-4

 

15267-95-5

 

Hydrolysis half-life at pH 4 and 20 - 25°C

 

1.1 – 24 min (QSAR)

 

12 min (QSAR)

 

Silanol hydrolysis product

 

(chloromethyl)methylsilanediol

 

chloromethylsilanetriol

 

Non-Si hydrolysis product

 

Ethanol

 

Ethanol

 

LogKow Value

 

1.82 at 25°C (QSAR)

 

2.5 at 20°C (QSAR)

 

Vapour pressure

 

25.2 hPa at 25°C (measured)

 

6.5 Pa at 25°C (QSAR)

 

Water solubility

 

1487 mg/L at 25°C (QSAR)

 

1.1E+03 mg/l at 20°C (QSAR)

 

 

 

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

 

In the available read accross study on (chloromethyl)triethoxymethyl- (CAS No. 15267-95 -5) the test material was investigated for bacterial mutagenicity according to the OECD TG 471, and in compliance with GLP. Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and TA 102 were treated with the test material up to limit concentrations both with and without metabolic activation system for 48 h in two independent experiments. No increase in revertant colonies was observed in either of the tester strains with or without metabolic activation system up to cytotoxic concentrations. In conclusion, the test material can be considered to be not mutagenic to bacteria under the conditions of the test.

 

4. AE A.4 Bias that influences the prediction

 

Data on the source substance (Chloromethyl)triethoxysilane (CAS 15267-95-5) were read-across to the registered (target) substance (Chloromethyl)diethoxymethylsilane (CAS 2212-10-4). The source substance and the target substance have similar chemical structure and physico-chemical properties. Both substances hydrolyse at similar rate to a similar Si-containing hydrolysis product, chloromethylsilanetriol resp. (chloromethyl)methylsilanediol. The non-silanol hydrolysis product is the same, ethanol. Due to that, their toxicological properties are expected to be similar, with similar genetic toxicity concerning bacteria. No other data for relevant substances were available. This substance is the closest structural analogue to the target substance available.

 

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

 

Both substances hydrolyse very rapidly in contact with water under conditions relevant for this endpoint. Therefore, the test organism is mainly exposed to their hydrolysis products, (chloromethyl)methylsilanediol, resp. chloromethylsilanetriol. The source and target substances have been profiled using the OECD QSAR Toolbox v. 4.1. The two substances and their silanol hydrolysis products show similar profiles for all toxicological endpoints. No alert for genetic toxicity was detected by OECD QSAR Toolbox v.4.1. No classification for sensitization has been assigned to the substance.

 

 

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

 

No toxicity data are available for the target substance (Chloromethyl)diethoxymethylsilane (CAS 2212-10-4), therefore data are read-across from the structurally analogous substance (Chloromethyl)triethoxysilane (CAS 15267-95-5). Both substances hydrolyse at similar rate to a similar Si-containing hydrolysis product, chloromethylsilanetriol resp. (chloromethyl)methylsilanediol. The non-silanol hydrolysis product, ethanol, is not expected to be relevant for this endpoint. Moreover, they have similar physico-chemical 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 target substance, (Chloromethyl)diethoxymethylsilane (CAS 2212-10-4), does not have any impurities of toxicological concern. The source substance, (Chloromethyl)triethoxysilane (CAS 15267-95-5), has a named impurity of approx. 1% is Ethanol (CAS 64-17-5). It is not expected that the ethanol impurity will contribute to the genetic toxicity of the source substance. The test substance in the study with the source substance, (Chloromethyl)triethoxysilane (CAS 15267-95-5), has a purity of 97.3%.

 

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

 

Not relevant.

 

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

Justification for classification or non-classification

Data are insufficient for classification or non-classification.