3-(chlorodimethylsilyl)propyl methacrylate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial mutagenicity (Ames test): read-across from [dimethoxy(methyl)silyl]methyl methacrylate; negative, with or without metabolic activation in Salmonella typhimurium strains TA 1535, TA 98, TA 97a, TA 100 and TA 102 (OECD 471) (Bioservice, 2003).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

[Dimethoxy(methyl)silyl]methyl methacrylate ( CAS No. 121177-93-3) has been tested in a valid bacterial reverse mutation assay, according to the OECD TG 471 (1989), and under GLP, using Salmonella typhimurium strains TA 1535, TA 98, TA 97a, TA 100 and TA 102 (Bioservice, 2003).

No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive, negative and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

A supporting study was also available. 3-[Dimethoxy(methyl)silyl)propyl acrylate (CAS No. 13732-00-8) has been tested for mutagenicity to bacteria (Shin Etsu, 1990). No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or E. coli WP2 uvrA in the initial or the repeat experiments up to limit concentrations. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Read-across justification

There are no available measured data for 3-(chlorodimethylsilyl)propyl methacrylate (CAS 24636-31-5) for genetic toxicity. This document describes the analogue approach for fulfilling this endpoint by read-across from two source substances, 3-[dimethoxy(methyl)silyl]propyl acrylate (CAS 13732-00-8) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), 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 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 first source substance, 3-[dimethoxy(methyl)silyl]propyl acrylate (CAS 13732-00-8), has a silicon atom bound to two methoxy groups, one methyl group and one propyl acrylate group. Its predicted hydrolysis half-lives are 0.2 h at pH 4, 1.7 h at pH 7 and 0.04 h at pH 9 and 20-25°C.

The half-life at 7 and 37.5°C, relevant to human exposure, is 0.63 h.

The hydrolysis products in this case are 3-[dihydroxy(methyl)silyl]propyl acrylate and methanol.

The source substance has log Kow of 2.9 at 20°C and vapour pressure of 4.1 Pa at 25°C.

The second source substance [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), has a silicon atom bound to two methoxy groups, one methyl group and one methyl methacrylate group. Its predicted hydrolysis half-lives are 0.2 h at pH 4, 0.2 h at pH 5, 1.8 h at pH 7 and 0.04 h at pH 9 and 20-25°C

The hydrolysis products in this case are [dihydroxy(methyl)silyl]methyl methacrylate and methanol. The source substance has a log Kow of 2.4 at 20°C, vapour pressure of 37 Pa at 25°C and water solubility of 2500 mg/l. The silanol hydrolysis product has log Kow of 0.0 at 20°C, water solubility of 410000 mg/L at 20-25°C and vapour pressure of 0.0052 Pa at 25°C.

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

The source substances, 3-[dimethoxy(methyl)silyl]propyl acrylate (CAS 13732-00-8), and the target substance, 3-(chlorodimethylsilyl)propyl methacrylate (CAS 24636-31-5) are structurally similar because they are organosilicon compounds with one propyl(meth)acrylate side-chain, one or two methyl side-chains and one or two hydrolytically unstable groups at silicon. The differences are:

• The source substance has a propylacrylate side-chain, whereas the target substance has an additional methyl group at the end of the side-chain, making it propylmethacrylate.

• The target substance has two methyl groups bound to silicon; the source substance has one.

• The target substance has a Si-Cl group; the source substance has two Si-OMe groups.

The Si-Cl and Si-OMe groups both hydrolyse to give silanols, Si-OH.

Both hydrolyse rapidly to give structurally similar hydrolysis products. The hydrolysis products of these two substances are structurally similar in that they both have a (meth)acrylate side-chain, one or two methyl groups and one or two silanol groups at a silicon centre. The differences are:

• The source substance has a propylacrylate side-chain, whereas the target substance has an additional methyl group at the end of the side-chain, making it propylmethacrylate.

• The target substance has two methyl groups and one silanol group bound to silicon; the source substance has one methyl group and two silanol groups.

The source substance, [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), and the target substance, 3-(chlorodimethylsilyl)propyl methacrylate (CAS 24636-31-5) are structurally similar. They are both organosilicon compounds with one methacrylate side-chain. The differences are:

• The source substance has a methyl methacrylate side-chain attached to the silicon atom, while the target substance has a propyl methacrylate side-chain instead.

• The target substance has two methyl groups bound to silicon; the source substance has one.

• The target substance has a Si-Cl group; the source substance has two Si-OMe groups.

Both hydrolyse rapidly to give structurally similar hydrolysis products. The hydrolysis products of these two substances are structurally similar in that they both have a methacrylate side chain, one or two methyl groups and one or two silanol groups at a silicon centre. The differences are:

• The source substance has a methyl methacrylate side chain  attached to the silicon atom, while the target substance has a propyl methacrylate side-chain instead.

• The target substance has two methyl groups and one silanol group bound to silicon; the source substance has one methyl group and two silanol groups.

Table 2: Physico-chemical properties

Property	Target substance	Source substance	Source substance
Substance name	3-(chlorodimethylsilyl)propyl methacrylate	3-[dimethoxy(methyl)silyl]propyl acrylate	[dimethoxy(methyl)silyl]methyl methacrylate
CAS number	24636-31-5	13732-00-8	121177-93-3
Hydrolysis half-life	< 1 min at pH 7 and 25ºC	1.7 h at pH 7 and 20-25ºC	1.7 h at pH 7 and 20-25ºC
Silanol hydrolysis product	3-[hydroxy(dimethyl)silyl]propyl methacrylate	3-[dihydroxy(methyl)silyl]propyl acrylate	[dihydroxy(methyl)silyl]methyl methacrylate
Non-Si hydrolysis product	hydrochloric acid	methanol	methanol
LogKow value	2.6  at 20  °C	2.9  at 20  °C (QSAR)	2.4 at 20°C (QSAR)
Vapour pressure	9.6 Pa at 25°C (QSAR)	4.1 Pa	37 Pa at 25°C (QSAR)
Water solubility	Not available	Not available	2500 mg/l
LogKow value (silanol hydrolysis product)	2.6  at 20  °C	0.5 (QSAR)	0.0 at 20°C
Vapour pressure (silanol hydrolysis product)	0.048 Pa at 25°C	0.0013 Pa at 25°C (QSAR)	0.0052 Pa at 25°C

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

3-[Dimethoxy(methyl)silyl]propyl acrylate has been tested for mutagenicity to bacteria. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or E. coli WP2 uvrA in the initial or the repeat experiments up to limit concentrations (Shin Etsu, 1990). Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

[Dimethoxy(methyl)silyl]methyl methacrylate has been tested in a valid bacterial reverse mutation assay, according to the OECD TG 471 (1989), and under GLP, using Salmonella typhimurium strains TA 1535, TA 98, TA 97a, TA 100 and TA 102 (Bioservice, 2003). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive, negative and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

4. AE A.4 Bias that influences the prediction

Data on the source substances 3-[dimethoxy(methyl)silyl]propyl acrylate (CAS 13732-00-8) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3)  were read-across to the registered (target) substance 3-(chlorodimethylsilyl)propyl methacrylate (CAS 24636-31-5). The source substances and the target substance have similar chemical structure and physico-chemical properties. All three substances hydrolyse at similar rate, and produce 3-[hydroxy(dimethyl)silyl]propyl methacrylate, 3-[dihydroxy(methyl)silyl]propyl acrylate and [dihydroxy(methyl)silyl]methyl methacrylate as silicon-containing hydrolysis products. Their non-silanol hydrolysis products are hydrochloric acid and methanol. Therefore, their toxicological properties are expected to be similar, with similar genotoxic effects. No other data for relevant substances were available.

There is an ongoing Comet Assay study for another structural analogue 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0). Read-across strategy for the registered substance would be reconsidered once results from this ongoing study are available.

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

The source substances as well as the target substance hydrolyse very rapidly in contact with water. Therefore, the test organism is exposed to both the parent substances and their hydrolysis products, 3-[hydroxy(dimethyl)silyl]propyl methacrylate, 3-[dihydroxy(methyl)silyl]propyl acrylate, [dihydroxy(methyl)silyl]methyl methacrylate and methanol.   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:

• All show an alert for DNA binding by OECD, due to the presence of the (meth)acrylate groups. This is relevant for genetic toxicity

• They all have no alerts in other profilers relevant for genetic toxicity including DNA alerts for AMES by OASIS v.1.4, DNA alerts for CA and MNT by OASIS v.1.1, in vitro mutagenicity (Ames test) alerts by ISS, in vivo mutagenicity (Micronucleus) by ISS, Keratinocyte gene expression, Protein binding alerts for Chromosomal aberration by OASIS v.1.2, or DNA binding by OASIS v.1.4.

• Profiles for other toxicological endpoints are also consistent

Additionally, presence of the O-C-Si-O fragment is detected in [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3). This substance is a methylmethacrylate rather than propylmethacrylate, which means that it has an alert for in vivo mutagenicity (Micronucleus) by ISS (H-accepter-path3-H-acceptor). This alert explores the possibility that a chemical interacts with DNA and/or proteins via non-covalent binding, such as DNA intercalation or groove-binding (Snyder et al. 2006). Structures of the type HbondAcc-A-A-HbondAcc are selected, where HbondAcc is any atom that is potentially a hydrogen-bond acceptor and A is any other atom. The substances with a propyl (meth)acrylate side-chain do not show this alert. The presence of this additional alert for one of the source substances makes the read-across conservative.

The non-silanol hydrolysis product methanol has been tested for mutagenicity to bacteria in seven Ames tests. No evidence of a test-substance related increase in the number of revertants was observed in any of these studies. Therefore, methanol was concluded to be negative for mutagenicity to bacteria.

The non-silanol hydrolysis product hydrochloric acid has been tested for mutagenicity to bacteria in six studies. No evidence of a test-substance related increase in the number of revertants was observed in any of these studies. Therefore, hydrochloric acid was concluded to be negative for mutagenicity to bacteria.

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 3-(chlorodimethylsilyl)propyl methacrylate therefore data are read-across from the structurally analogous substances 3-[dimethoxy(methyl)silyl]propyl acrylate and [dihydroxy(methyl)silyl]methyl methacrylate. All three substances hydrolyse at similar rates, and produce 3-[hydroxy(dimethyl)silyl]propyl methacrylate, 3-[dihydroxy(methyl)silyl]propyl acrylate and {dimethoxy(methyl)silyl]methyl methacrylate as silicon-containing hydrolysis products. Moreover, they have similar physico-chemical properties. Thus, both substances are expected to have similar toxicity profiles. The non-silanol hydrolysis products, hydrochloric acid and methanol, have been shown not to be genotoxic.

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

Neither the target substance, 3-(chlorodimethylsilyl)propyl methacrylate nor the source substances, 3-[dimethoxy(methyl)silyl]propyl acrylate and  [dimethoxy(methyl)silyl]methyl methacrylate, have impurities of toxicological concern.

The test substance in the study with the source substance, 3-[dimethoxy(methyl)silyl]propyl acrylate,  has a purity of 100%.

The test substance in the study with the second source substance, [dimethoxy(methyl)silyl]methyl methacrylate, has a purity of 98.6%.

The target substance is >95% pure; a disiloxane dimer of the parent substance has been identified as an impurity above 1%. No impurities that may be SVHC or impact the classification and labelling have been identified.

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

Not relevant

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

Justification for classification or non-classification

Based on the available data for 3-[chloro(dimethyl)silyl]propyl methacrylate, no classification for genetic toxicity is required according to Regulation (EC) No 1272/2008.