3-(dimethoxymethylsilyl)propanethiol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in strains TA98, TA100, TA1535 and TA1537, and Escherichia coli WP2 uvrA (OECD TG 471) (BioReliance, 2001). The selected key study was chosen because it is the most reliable and recent available study for the appropriate read-across substance. It was conducted according to appropriate OECD guidelines and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The data for genetic toxicity are read across from the analogous substance 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0).

3-trimethoxysilylpropane-1-thiol has been tested for mutagenicity to bacteria which was conducted according to OECD guideline and in compliance with GLP (BioReliance, 2001). Appropriate positive and solvent controls were included and gave expected results. Under test conditions, the test substance did not produce a mutagenic effect in strains TA98, TA100, TA1535, TA1537 or Escherichia coli WP2 uvrA in the presence or the absence of metabolic activation. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Read-across approach

Non-testing methods including read-across from surrogate substances are able to provide information on mutagenic 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 et al, 2008). 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 on read across approach is given in a supporting report (PFA 2013aa) attached in Section 13. In the following paragraphs the proposed read-across for the above endpoints from 3 -trimethoxysilylpropane-1-thiol (CAS 4420-74-0) to 3-[dimethoxy(methyl)silyl]propane--thiol (CAS 31001-77-1) is evaluated point by point.

Read-across hypothesis

The read-across hypothesis is that the source and target substances have similar genetic toxicity properties because they are structurally very similar.

They contain an identical propanethiol side chain attached to silicon and hydrolyse to analogous silicon-containing hydrolysis products. Neither substance nor any of the hydrolysis products have structural alerts for genetic toxicity, therefore read across from the analogous substance, 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0) with a similar hydrolysis product is considered representative of the toxicity of the target substance 3-[dimethoxy(methyl)silyl]propane-1-thiol (CAS 31001-77-1). They share the common hydrolysis product methanol, which does not contribute to genotoxicity based on publicly available information. This is discussed further below.

Read-across justification

The predicted half-lives of the registered substance, 3-[dimethoxy(methyl)silyl]propane-1-thiol (CAS 31001-77-1), are 1.4 hours at pH 7, 0.1 hours at pH 4, 0.03 hours at pH 9 and 20-25°C (QSAR). At 37.5°C and pH 7 (relevant for lungs and blood and genotoxicity testing), the half-life is 0.52 hour. The products of hydrolysis are 3-(dihydroxymethylsilyl)propanethiol and methanol.

The read-across substance, 3 -trimethoxysilylpropane-1-thiol (CAS 4420-74-0), has a predicted hydrolysis half-life of 2.6 hours at pH 7, 0.2 hours at pH 4, and 0.1 hours at pH 9 and 20-25C (QSAR). At 37.5ºC and pH 7, the calculated half-life is 1.0 hours. The products of hydrolysis are 3-(trihydroxysilyl)propanethiol and methanol.

 

Analogue approach justification

(a) Structural similarity

The registration and read-across substances are structurally similar and are members of an analogue group of alkoxysilane substances containing a thiol functional group. Both contain a silicon atom to which is attached to a propanethiol side chain. The propanethiol side chains of the two substances are identical. The registered substance has two methoxy groups and a methyl group bound to silicon. The only difference in the read across substance is that all three groups bound to the silicon are methoxy groups. Both hydrolyse rapidly to produce similar silicon-containing hydrolysis products, 3-(dihydroxymethylsilyl)propanethiol and 3-(trihydroxysilyl)propanethiol, and the same non-silicon hydrolysis product, methanol.

(b) Structural alerts for genotoxicity

Neither 3-[dimethoxy(methyl)silyl]propane-1-thiol (CAS 31001-77-1) nor 3 -trimethoxysilylpropane-1 -thiol (CAS 4420-74-0) has structural alerts for genotoxicity (Benigni et al, 2008).

 

(c) Discussion of toxicity of the non-silanol hydrolysis product

 

Methanol has been tested in vitro in bacterial and mammalian mutagenicity assays and in micronucleus and chromosome aberration assays. The majority of the results were negative (OECD 2004). In the ECHA disseminated dossier for methanol, the conclusions of all the key in vitro studies and the weight of evidence of the in vivo assays are negative.

References:

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

 

OECD (2004): SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 18-20 October 2004, Methanol, CAS 67-56-1.

Justification for classification or non-classification

The available information on the read across substance 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0) indicates that when tested in vitro, the substance does not induce mutations in bacterial cells.

Based on the available information 3-[dimethoxy(methyl)silyl]propane-1-thiol (CAS 31001-77-1) is not classified for genetic toxicity according to Regulation (EC) No 1272/2008.