Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

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No measured data are available to assess the genetic toxicity of the registered substance, however, data are available for bacterial mutagenicity and in vitro cytogenicity from the structural analogue dichloro(diphenyl)silane (CAS 80-10-4) and for in vitro mammalian mutagenicity from the structural analogue trichloro(phenyl)silane (CAS 98-13-5).

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 of the IUCLID 5 dossier.

Read-across hypothesis

The read-across hypothesis is that genetic toxicity depends on the molecular species to which the organism is exposed and the registered substance is the silicon containing hydrolysis product of one structural analogue, and is closely related to the silicon containing hydrolysis product of the second surrogate.

Dichloro(diphenyl)silane hydrolyses rapidly, being fully hydrolysed within a few minutes at pH 4, 7 and 9 and 1.5 °C (measured). The products of hydrolysis are diphenylsilanediol and hydrogen chloride.

Trichloro(phenyl)silane also hydrolyses rapidly, with a hydrolysis half-life of <1 minute at pH 7 and 1.5°C, read-across from trichloro(methyl)silane. The products of hydrolysis are phenylsilanetriol and hydrogen chloride.

Hydrogen chloride gave negative results in the most reliable of the bacterial mutagenicity studies. Positive results were obtained in mutagenicity and cytogenicity assays using mammalian cells (OECD, 2002; ECHA disseminated dossier for hydrogen chloride). The positive results were associated with decrease in pH, and it is considered that the positive results were likely to have been caused by reduced pH. Positive results caused by high or low pH effects are considered not to be relevant for in vivo situations (ECHA 2012), and testing should be carried out at neutral pH.

Read-across justification

(a) Structural similarity: the target substance is the same as the silanol hydrolysis product of one surrogate substance, being a silicon atom with two hydroxy and two phenyl groups. The second surrogate substance produces a hydrolysis product which is a structural analogue of the target substance, being a silicon atom with three hydroxy and one phenyl group.

(b) Rapid hydrolysis of the surrogate substances: both surrogate substances hydrolyse very rapidly even at neutral pH and low temperature (relative to test and in vivo conditions).

(c) Lack of structural alerts: none of the substances has structural alerts for genotoxicity (Benigni et al, 2008).

(d) The second hydrolysis product of the surrogate substances, hydrogen chloride, is not genotoxic.

(e) Lack of effects in other silicon containing substances that form phenyl-containing silanol hydrolysis products: see Table below.

Summary of available genotoxicity data for substances in the analogue group phenylsilanes hydrolysing rapidly at pH7

CAS Number

Chemical Name

Bacterial mutagenicity

In vitro mammalian cytogenicity

In vitro mammalian mutagenicity

In vivo genotox

149-74-6

Dichloro(methyl)(phenyl)silane

Negative

LPT J (2002)

 

 

 

3027-21-2

Dimethoxy(methyl)phenylsilane

Negative

Dow Corning Corporation (1997)

 

 

Negative in micronucleus

Dow Corning Corporation (1991b)

80-10-4

Dichloro(diphenyl)silane

Negative

Bayer. (1994)

Negative

BSL Bioservice (2012)

 

 

6843-66-9

Dimethoxy(diphenyl)silane

Negative

Hüls AG (1995)

 

 

 

98-13-5

Trichloro(phenyl)silane

Negative

Dow Corning Corporation (1985)

 

Negative

Harlan (2010)

 

2996-92-1

Trimethoxy(phenyl)silane

Negative

Dow Corning Corporation (1991a)

Positive +MA

Not cytotoxic at highest dose evaluated

RCC Cytotest (2008)

 

 

780-69-8

Triethoxy(phenyl)silane

Negative

Wacker (2002)

Negative

Bioservice Scientific Laboratories (2012)

 

 

A reliable bacterial reverse mutation assay according to OECD TG 471 and GLP is available for the surrogate substance 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 the Salmonella typhimurium strains tested (Bayer 1994). An additional reliable bacterial reverse mutation assay with dichloro(diphenyl)silane is also available, in which 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 surrogate substance dichloro(diphenyl)silane has been tested according to OECD TG 473 and to GLP (BSL Bioservice, 2012). 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. This result was selected for read across because the test substance hydrolyses to the registered substance.

An in vitro mammalian cell gene mutation study on the structural analogue substance trichloro(phenyl)silane (CAS: 98-13-5) was conducted according to OECD TG 476 and to GLP (Harlan, 2010). 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, trichloro(pheny)lsilane is negative for the induction of mutations in L5178Y cells under the conditions of the test.

Bayer (1994). Diphenyldichlorosilane: Salmonella/ Microsome Test Plate Incorporation and Preincubation Method. Testing laboratory: Bayer AG, Fachberich Toxicology, Wuppertal, Germany. Report no.: 23476. Owner company: Bayer AG, Wuppertal, Germany. Study number: D01450. Report date: 1994-11-14.

 

BSL Bioservice (2012). In vitro mammalian chromosome aberration test in Chinese Hamster V79 cells with dichloro(diphenyl)silane. Testing laboratory: BSL Bioservice Scientific Laboratories GmbH, Behringstraβe 6/8, 82152 Planegg, Germany. Owner company: Reconsile consortium. Study number: 113268. Report date: 2012-01-17.

Bioservice Scientific Laboratories (2012). In Vitro Mammalian Chromosome Aberration Test in Chinese Hamster V79 Cells with Triethoxyphenylsilane. Testing laboratory: Bioservice Scientific Laboratories, Behringstrasse 6/8, Planegg, Germany. Report no.: 113655. Owner company: ReachCentrum SPRL, Avenue E. van Nieuwenhuyse 6, Brussels, Belgium. Report date: 2012-04-25.

Dow Corning Corporation (1985). Genetic Evaluation of Dow Corning Z-1216 Silane in Bacterial Reverse Mutation Assays. Testing laboratory: Dow Corning Corporation Toxicology Department. Report no.: 1985-I0005-1370. Owner company: Dow Corning. Report date: 1985-07-15. 

Dow Corning Corporation (1991a). Genetic Evaluation of Dow Corning Q1-2590 in Bacterial Reverse Mutation Assay. Testing laboratory: Dow Corning Corporation. Health and Environmental Sciences. Report no.: 1991-I0000-36093. Owner company: Dow Corning Corporation. Study number: TX-91-0400-01. Report date: 1991-02-22.

Dow Corning Corporation (1991b). A 14-day repeated dose inhalation toxicity study with Dow Corning X2-2614 in albino rats. Testing laboratory:

Dow Corning Corporation Health and Environmental Sciences, Midland, Michigan, USA. Report no.: 1991-I0000-36885. Owner company: Dow Corning Corporation. Report date: 1991-12-19.

Dow Corning Corporation (1997). Mutagenicity evaluation of phenylmethyldimethoxysilane in the Ames bacterial assay system. Report no.: 1997-I0005-0534. Report date: 1997-12-16.

 

Harlan (2010). Trichloro(phenyl)silane Mouse Lymphoma Assay. Testing laboratory: Harlan Laboratories Ltd Shardlow Business park, Shardlow, Derbyshire DE72 2GD UK. Owner company: Reconsile. Study number: Project number 2009/0005. Report date: 2010-01-29. 

Hüls AG (1995). S. typhimurium reverse mutation assay (Ames-test) with DYNASYLAN D 6010. Testing laboratory: Hüls AG, Department of Biology, D-45764 Marl, Germany. Report no.: AM-95/13. Owner company: Evonik Degussa. Study number: 95-0227-DGM. Report date: 1995-08-02.

LPT (2002.) Mutagenicity Study of Silan PM in the Salmonella Typhimurium Reverse Mutation Assay (in vitro). Testing laboratory: LPT Laboratory of Pharmacology and Toxicol KG, Redderweg 8, D-21147 Hamburg, Germany Report no.: 15425/39/02. Owner company: Wacker-Chemie GmbH. Study number: 20070820103747684. Report date: 2002-09-04

OECD (2002): SIDS Initial Assessment Report for SIAM 15, Boston, USA, 22-25 October 2002: hydrogen chloride, CAS 7647-01-0.

RCC Cytotest (2008) In vitro Chromosome Aberration Test in Chinese Hamster V79

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

Cells with Trimethoxyphenylsilane. Testing laboratory: RCC Cytotest Cell Research GmbH (RCC-CCR) In den Leppsteinswiesen 19 64380 Rossdorf Germany. Owner company: SEHSC. Study number: 11755600. Report date: 2008-07-28. 


Justification for selection of genetic toxicity endpoint
Conclusion based on the following assays: Bacterial reverse mutation assay (Ames test) (surrogate substance);
Mammalian cell gene mutation assay (surrogate substance); In vitro mammalian chromosome aberration test (surrogate substance); The selected studies on surrogate substances were conducted according to appropriate OECD protocols and in accordance with GLP.

Short 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 with the structural analogue substance dichloro(diphenyl)silane (similar to OECD TG 471) (Bayer AG, 1984).
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains: TA 98, TA 100, TA 1535, TA 1537 and E coli WPR uvrA with the structural analogue substance dichloro(diphenyl)silane (OECD TG 471) (Dow Corning Corporation 1985).

Mammalian cytogenicity (Chinese hamster lung fibroblasts V79 cell chromosome aberration assay): negative with and without metabolic activation with the structural analogue substance dichloro(diphenyl)silane (according to OECD TG 473) (BSL Bioservice, 2012).

Mammalian cell gene mutation: negative in L5178Y mouse lymphoma cells with the structural analogue substance trichloro(phenyl)silane (CAS: 98 -13 -5) (according to OECD TG 476) (Harlan, 2010).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro data for the surrogate substances, diphenylsilanediol is not classified for mutagenicity according to Regulation (EC) No. 1272/2008.