Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): read-across from 3-trimethoxysilylpropyl methacrylate; negative with and without activation in all strains tested (similar to OECD TG 471) (BioReliance, 2001).
Cytogenicity in mammalian cells: read-across from 3-trimethoxysilylpropyl methacrylate; positive in Chinese hamster ovary cells (similar to OECD TG 473) (Bushy Run Research Center, 1985a).
Mutagenicity in mammalian cells: read-across from 3-trimethoxysilylpropyl methacrylate; negative with and without metabolic activation in Chinese hamster ovary cells (HGPRT gene mutation assay, similar to OECD TG 476) (Bushy Run Research Center, 1985b).

The selected studies were tested according to appropriate OECD guidelines and in compliance with GLP. The key bacterial mutagenicity study was chosen because it was the most complete, although not the most recent.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

Micronucleus assay in mouse (ip administration): Negative (similar to OECD TG 474) (Bushy Run Research Center, 1986).

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

Additional information

No measured genotoxicity data are available for the registration substance therefore reliable data are read across from a structural analogue. Read-across information is available from reliable studies for all the required in vitro endpoints. The most reliable and recent study available was chosen as key study. The results of most of the studies were in agreement. There was evidence for clastogenicity (causing chromosomal aberrations) in the presence of metabolic activation and for weak clastogenicity in the absence of metabolic activation in vitro. An in vivo micronucleus study did not support this finding, so it is concluded that the in vitro result does not reflect an ability to cause chromosome aberrations in vivo.

3-Trimethoxysilylpropyl methacrylate has been tested in a valid bacterial reverse mutation assay according to OECD TG 471 and under GLP, using Salmonella typhimurium TA98, TA100, TA1535 and TA1537 and Escherichia coli WP2uvrA (BioReliance, 2001). 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.

3-Trimethoxysilylpropyl methacrylate has been tested for ability to cause chromosome aberrations in Chinese hamster ovary cells according to a protocol that is similar to OECD 473, and in compliance with GLP (Bushy Run Research Centre, 1985c). In this study, in the absence of metabolic activation, the test substance produced a statistically significant increase in chromosome aberrations only at 0.4 mg/ml, the highest concentration tested at the 8 hour sampling period. In contrast, in the presence of metabolic activation, the test substance produced significant increases in the incidences of chromosome aberrations at both 8 and 12 hours and at several concentrations. It is concluded that the test substance is positive for clastogenicity (causing chromosome damage) under the conditions of the test. In addition, the registered substance has been tested for the induction of sister chromatid exchanges in Chinese hamster ovary cells (Bushy Run Research Centre, 1985a). No evidence for the induction of SCEs was observed.

3-Trimethyoxysilylpropyl methacrylate has been tested for mutagenicity in Chinese hamster ovary cells according to a US EPA method and under GLP (Bushy Run Research Centre, 1985a). No test substance induced increase in the number of mutations was observed. Appropriate solvent, negative (cell culture medium) and positive controls were included and gave expected results. It is concluded that 3-trimethyoxysilylpropyl methacrylate is negative for mutagenicity to mammalian cells under the conditions of the test.

3-Trimethoxysilylpropyl methacrylate has been tested in a reliable, valid in vivo mouse micronucleus assay according to a protocol that is similar to OECD TG 474 and in compliance with GLP (Bushy Run Research Centre, 1986). The test substance did not produce treatment-related or statistically significant increases in the incidence of micronuclei in the peripheral blood polychromatic erythrocytes when administered by intraperitoneal injection up to limit concentrations. A decrease in the PCE/NCE ratio at 72 hours was considered to be evidence that the test substance had reached the target tissue. Positive and vehicle controls produced appropriate responses. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.

A comet assay according to OECD 439 is currently under way with the read-across substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) following ECHA final decision number SEV-219-785-8. When available, the results of this study will be taken into consideration for the conclusions on genotoxicity for (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate.

READ ACROSS JUSTIFICATION

Read-across hypothesis and 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 silicon-containing products. The non-silicon-containing product of hydrolysis from the read-across substance is not genotoxic. Neither substance nor any of the hydrolysis products have structural alerts for genetic toxicity, therefore read across from the analogous substance with similar hydrolysis products is considered representative of the genetic toxicity of the target substance.

(1,1,3,3-Tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate hydrolyses slowly with a hydrolysis half-life of 63.1 h at pH 7, 20-25⁰C to form 3-[hydroxy(dimethyl)silyl]propyl methacrylate.

3-Trimethoxysilylpropyl methacrylate hydrolyses faster with a hydrolysis half-life of approximately 3 - 4 h at pH 7and 25°C (QSAR), to form 3-(trihydroxysilyl)propyl methacrylate and methanol.

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.

Analogue approach justification

(a) Structural similarity

(1,1,3,3-Tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate and 3-trimethoxysilylpropyl methacrylate both are silicon-containing substances that have a methacrylate ester group attached via a propyl group to the silicon atom. The registration substance is a linear siloxane with two silicon atoms connected by one oxygen atom; the Si-O bonds are subject to hydrolysis. Each silicon also has two methyl groups and one propyl methacrylate group. The read-across substance is an alkoxysilyl methacrylate which has three methoxy groups and a propyl methacrylate group attached to the silicon atom.

The silanol hydrolysis products for the registered substance is 3-[hydroxy(dimethyl)silyl]propyl methacrylate. The silanol hydrolysis product of the read-across substance is 3-(trihydroxysilyl)propyl methacrylate. The non-silicon-containing hydrolysis product of the read-across substance is methanol. The registered substance hydrolyses to silanol hydrolysis product only.

(b) Structural alerts for genotoxicity

Neither (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate nor 3-trimethoxysilylpropyl methacrylate have structural alerts for genotoxicity (Benigni et al., 2008).

(c) Consideration of the non-silanol hydrolysis product

Methanol is not expected to contribute to genotoxicity (EU RAR, 2003; OECD 2004).

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

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

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



Justification for classification or non-classification

Based on the available data for 3-(trimethoxysilylpropyl) methacrylate, the registered substance, (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate, does not require classification for genotoxicity according to Regulation (EC) No. 1272/2008.