Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial reverse mutation assay:
The read-across substance, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2), was negative with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102.
The read-across substance, 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), was negative with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102.

The studies were conducted according to an appropriate OECD test guideline, and in compliance with GLP.

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

Additional information

The read-across substance, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2), has been tested in a valid bacterial reverse mutation assay, according to the OECD test guideline 471 (1989), and under GLP, using Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (LPT, 2002). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive 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.

The read-across substance, 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), 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 1537, TA 98, TA 100 and TA 102 (LPT, 2002). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive 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.

The read-across substances,1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), contain no structural elements which may be of concern for potential mutagenic activity.

Bacterial mutagenicity in vitro tests are negative.

READ-ACROSS JUSTIFICATION

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.

Read across hypothesis

The read-across hypothesis is that the source and target substances have similar genetic toxicity properties because they are structurally similar and hydrolyse to similar products. None of the substances nor any of the hydrolysis products have structural alerts for genetic toxicity, therefore read across from the analogous substances with similar hydrolysis products is considered representative of the genetic toxicity of the target substance.

Tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9) hydrolyses slowly with a hydrolysis half-life of >200 h (>8.3 d) at pH 7 and 20-25°C (QSAR) to form phenylsilanetriol and trimethylsilanol.

1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) hydrolyses slowly with a hydrolysis half-life of >200 h at pH 7, 25°C to form diphenyl(methyl)silanol and methyl(phenyl)silanediol.

1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) hydrolyses slowly with a hydrolysis half-life of >200 h at pH 7, 25°C to form diphenyl(methyl)silanol and dimethylsilanediol.

Analogue approach justification

(a) Structural similarity

The registration and read-across substances are structurally similar and are members of an analogue group of alkoxysilanes and silanols. All three substances are linear or branched siloxanes. All silicon atoms present are fully substituted with methyl and phenyl groups. The registration substance, tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9) is a branched siloxane chain with four silicon atoms, connected by three oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are fully substituted with three methyl or one phenyl group.

The read-across substances are both linear siloxanes, with three silicon atoms connected by two oxygen atoms. The terminal silicon atoms are substituted with two phenyl and one methyl group. The substance 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) has one methyl and one phenyl groups on the central silicon atom; 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) has two methyl groups on the central silicon atom.

All three substances produce phenyl and/or methyl substituted silicon hydrolysis products. See table below for detail of hydrolysis products.

The differences in structure are not expected to affect genetic toxicity:

The structures differ in the number of silicon atoms and the nature of the substituting groups. Data are available for a number of siloxanes and cyclic siloxanes, of which only two gave positive results in bacterial mutagenicity assays, and these two substances are both epoxides, therefore have a structural alert for mutagenicity. The dataset includes substances with methyl and with phenyl substituted silicon atoms that do not give positive results in bacterial mutagenicity assays. This supports the conclusion that in the absence of structural alerts, the number of silicon atoms and the presence of methyl and phenyl groups does not affect bacterial mutagenicity. Additional information is given in a supporting report (PFA, 2013aa) attached in Section 13.

Si hydrolysis products of submission substance and relevant read-across substances

Substance

Phenylsilanetriol

Diphenyl(methyl)silanol

Methyl(phenyl)silanediol

Trimethylsilanol

Dimethylsilanediol

Tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9)

Yes

-

-

Yes

-

1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2)

-

Yes

Yes

-

-

1,3,3,5-Tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9)

-

Yes

-

-

Yes

(b) Structural alerts for genotoxicity

None of the substances tris(trimethylsiloxy)phenylsilane (CAS 2116-84-9), 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) have structural alerts for genotoxicity (Benigni et al., 2008).

(c) Results in bacterial mutagenicity assays

1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) have been tested for mutagenicity to bacteria with negative results.

The surrogate substance 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) has been tested in a valid bacterial reverse mutation assay according to OECD TG 471 and under GLP, using Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 (LPT, 2002). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive 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. The key study was selected because a fully-compliant range of strains was tested. The key study was considered reliability 1.

The surrogate substance 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9) has been tested in a valid bacterial reverse mutation assay according to OECD TG 471 and under GLP, using Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 (LTP, 2002). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive and solvent controls were used and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The result is supported by another study, which used E. coli CM891 strain as the fifth test strain. Both studies were considered reliability 1.

EU RAR (2003): EU Risk Assessment Report Volume 34, methyl acetate, CAS 79-20-9.

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

PFA (2013aa). Peter Fisk Associates, Genotox Analogue Report, PFA.300.004.001.


Justification for classification or non-classification

Based on the available data from the read-across substances, 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane (CAS 3390-61-2) and 1,3,3,5-tetramethyl-1,1,5,5-tetraphenyltrisiloxane (CAS 3982-82-9), no classification for genetic toxicity is required for the registered substance according to Regulation (EC) No. 1272/2008.