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): negative with and without activation in Salmonella typhimurium strains: TA 98, TA 100, TA 1535, and TA 1537 (similar to OECD TG 471).

Mammalian cytogenicity (Chinese hamster lung fibroblasts V79 cell chromosome aberration assay): negative with and without metabolic activation (according to OECD TG 473).

Mammalian cell gene mutation:

No measured data are available to assess the in vitro mammalian mutagenicity potential of the registered substance, however, reliable data are available for the structural analogue substance trichloro(phenyl)silane (CAS: 98-13-5).

negative in L5178Y mouse lymphoma cells with the structural analogue substance trichloro(phenyl)silane (CAS: 98 -13 -5) (according to OECD TG 476).

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A key bacterial reverse mutation assay according to OECD TG 471 and GLP is available for dichloro(diphenyl)silane. No evidence for a test-substance related increase in the number of revertants was observed in Salmonella typhimurium strains: TA 98, TA 100, TA 1535, and TA 1537. The strains were treated with doses of up to 1200 µg/plate with and without metabolic activation system. Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, dichloro(diphenyl)silane was concluded to be non-mutagenic in theSalmonella typhimurium strains tested (Herbold, B.1994). An additional key bacterial reverse mutation assay with the registered substance is also available. Where no evidence for a test-substance related increase in the number of revertants was observed in Salmonella typhimurium: TA 98, TA 100, TA 1535, TA 1537 and Escherichia coli WP2 strains.  The strains were treated with doses of 0.078 to 1.25 µg/plate with and without metabolic activation system. Appropriate positive and solvent controls were included and gave expected results ( Dow Corning Corporation, 1985). The results of both studies are in agreement and give evidence that the test substance is non-mutagenic in the bacterial reverse mutation assay under the applied test conditions.

 

The key in vitro cytogenicity study on dichloro(diphenyl)silane was conducted according to OECD TG 473 and to GLP. In the presence and absence of metabolic activation no biologically relevant increase in the frequencies of polyploidy cells was found after treatment with the test item in Chinese Hamster V79 cells as compared to the controls. Appropriate positive and solvent controls were included and gave expected results. The test substance was therefore considered to be non-clastogenic in Chinese Hamster V79 cells (Oppong-Nketiah, M. 2012).

No measured data are available to assess the in vitro mammalian mutagenicity potential of the registered substance, however, reliable data are available for the structural analogue substance trichloro(phenyl)silane (CAS: 98-13-5). Both substances hydrolyse in contact with water to generate structurally similar silanol hydrolysis products, diphenylsilanediol and phenylsilanetriol, and it is therefore considered that read-across between the substances is appropriate. The other hydrolysis product, hydrogen chloride is not genotoxic.

 

The key in vitro mammalian cell gene mutation study on the structural analogue substance trichlorophenylsilane (CAS: 98-13-5) was conducted according to OECD TG 476 and to GLP. No increase in mutant frequency was observed at any concentration with and without metabolic activation at 4 hours treatment and without metabolic activation at 24 hours treatment. Expected results were obtained with positive and negative controls. It was concluded that the structural analogue substance, trichlorophenylsilane is negative for the induction of mutations in L5178Y cells under the conditions of the test (Flanders, L.2010).

 

 

In vivo testing is not required as no evidence for genetic toxicity was found in the in vitro studies.

READ-ACROSS JUSTIFICATION

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint.  In the case of genotoxicity relevant properties are structural similarity as well as physical-chemical and basic toxicological parameters in the same range. Especially functional groups that are associated with genetic toxicity have to be compared. In the following paragraphs the read-across approach for dichloro(diphenyl)silane is evaluated point by point.

Read-across hypothesis

Data are available fordichloro(diphenyl)silane(CAS 80-10-4) from two reliablein vitrostudies for bacterial mutagenicity (Herbold, 1994 and Dow Corning, 1985) and chromosome aberration (Oppong-Nketiah, 2012). No mutagenic properties were observed in the Ames test and in the chromosome aberration assay. Based on the fact that dichloro(diphenyl)silane has no functional groups associated with genotoxicity in accordance with the other substances of the group and the substances have the same or similar hydrolysis products, read-across to the analogues is appropriate. No further data are available for the registered substance; however, reliable data are available for the related substance trichloro(phenyl)silane (CAS 98-13-5) from anin vitromammalian mutagenicity test (Flanders, 2010). The registered substance and the structurally-analogous substance trichloro(phenyl)silane hydrolyse to similar products, diphenylsilanediol and phenylsilanetriol. The other product of hydrolysis HCl is not genotoxic. Neither substance has any functional groups that are associated with genetic toxicity. The genetic toxicity data available for other read-across substances are summarised in Table 1. Additional information is given in a supporting report (PFA, 2013aa) attached in Section 13 of the IUCLID 6 dossier.


Table 1: Summary of available genotoxicity data forsubstances in theanalogue group phenylsilanes hydrolysing rapidly at pH7.

 

CAS

Name

Bacterial Mutagenicity

In VitroMammalian Cytogenicity

In VitroMammalian Mutagenicity

In VivoGenotox

003027-21-2

Dimethoxymethylphenylsilane

Negative

 

 

Negative in micronucleus test (Dow Corning, 1991)

002996-92-1

Trimethoxyphenylsilane

Negative

(Dow Corning, 1991)

Positive

(Hoffmann, 2008)

 

 

000780-69-8

Triethoxy(phenyl)silane

Negative (Wacker, 2002)

Negative (BSL, 2012)

 

 

006843-66-9

Dimethoxydiphenylsilane

Negative (Dow Corning, 1977; Hüls AG, 1995; SafePharm, 2002)

 

 

 

070131-69-0

Silsesquioxanes, Phenyl

Negative

 

Negative

 

000149-74-6

Dichloro(methyl)(phenyl)silane

Negative

 

 

 

000080-10-4

Dichloro(diphenyl)silane

Negative (Herbold, 1994; Dow Corning, 1985)

Negative (Oppong-Nketiah, 2012)

 

 

000098-13-5

Trichloro(phenyl)silane

Negative

 

Negative

(Flanders, 2010)

 

 

Justification for classification or non-classification

 Based on the available in vitro data on mutagenicity of the registered substance and the structural analogue substance, trichloro(phenyl)silane (CAS: 98-13-5, dichloro(diphenyl)silane is not classified for mutagenicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.