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): negative with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, and E. coli WP2 uvrA (OECD TG 471) (BioReliance, 2003).
Gene mutation (Bacterial reverse mutation assay / Ames test): positive with and without metabolic activation in Salmonella typhimurium strains TA 100 and TA 1535 strains (OECD TG 471) (Litton Bionetics, 1977).
Clastogenicity in mammalian cells: positive with and without metabolic activation in mouse lymphoma L5178Y cells (similar to EU Method B.19) (Litton Bionetics, 1979).
Mutagenicity in mammalian cells: positive with and without metabolic activation in mouse lymphoma L5178Y cells (similar to OECD 476) (Litton Bionetics, 1978a)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Additional information

2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane has been tested for mutagenicity to bacteria in a study conducted according to OECD TG 471 (1979) and in compliance with GLP, using Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, and E. coli WP2 uvrA (BioReliance, 2003). The toxicity assay and the initial mutagenicity assay were conducted using preincubation; the independent repeat assay used the plate incorporation method. Cytotoxicity was observed at concentrations from 333 to 5000 μg/plate. No test subsatnce-related increase in the number of reversions was observed with any of the strains tested both with and without metabolic activation. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Additional data are available from a study conducted according to a guideline equivalent to OECD TG 471 but not under GLP, using Salmonella typhimurium TA98, TA100, TA1535 and TA1537, TA1538 and Saccharomyces cerevisiae (Litton Bionetics, 1977). There was a positive, concentration related increase in the number of revertant colonies in TA 100 and TA 1535, with and without metabolic activation. The test substance is mutagenic in these tester strains. Appropriate positive and solvent controls were added and gave expected results. It is concluded that the test substance is positive for mutagenicity to bacteria under the conditions of the test.

The registered substance was tested in a mammalian cell gene assay according to an appropriate national standard method, but not under GLP, using mouse lymphoma L5178Y cells (Litton Bionetics, 1978). The test material produced a dose related increase in cytotoxicity and mutant frequency, both with and without metabolic activation. The mutagenic response was greater under non activated conditions. Appropriate positive and solvent controls were in place which gave expected results. It is concluded that the test substance is positive for mutagenicity to mammalian cells under the conditions of the test. 

The registered substance was tested in a mammalian sister chromatid exchange assay according to a method similar to an EU guideline, but not under GLP, using mouse lymphoma L5178Y cells (Litton Bionetics, 1979). The test material produced a statistically significant increase in sister chromatid exchange frequency, both with and without metabolic activation. Appropriate positive and solvent controls were in place which gave expected results. It is concluded that the test substance is positive for clastogenicity to mammalian cells under the conditions of the test. 

One reliability 4 study was also available. A DNA damage and repair assay/unscheduled DNA synthesis in mammalian cells in vitro (Litton Bionetics, 1978) found the test material negative in the presence and positive in the absence of metabolic activation.

In the information available for 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, there was evidence for clastogenicity (causing chromosomal aberrations) in the presence and absence of metabolic activation from a sister chromatid exchange assay conducted using mouse lymphoma L5178Y cells (Litton Bionetics, 1979) as well as for bacterial mutagenicity in vitro (Litton Bionetics, 1977) and mutagenicity to mammalian cells (Litton Bionetics, 1978a).

Based on the available in vitro data, the presence of a structural alert, and the classification for carcinogenicity, the test substance is positive for mutagenicity to somatic cells. The possibility for mutation to germ cells has been considered. The toxicokinetic assessment of the substance indicates that absorption of both parent and initial product of hydrolysis, [2‑(3,4-epoxycyclohexyl)ethyl]silanetriol, would occur following oral or inhalation exposure; following dermal exposure uptake of parent is likely, but uptake of [2‑(3,4‑epoxycyclohexyl)ethyl]silanetriol is expected to be lower. Following uptake, systemic distribution is expected so a conservative assumption has been made that exposure of germ cell tissues is possible so the substance is presumed to be a germ-cell mutagen. For the purposes of overall hazard conclusions, the substance is therefore considered to be in the “high hazard” category according to REACH Guidance Part E, Table E.3.1.


Justification for classification or non-classification

Based on the available data, 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane is classified for genetic toxicity Category 2, H341: Suspected of causing genetic defects, according to Regulation (EC) No 1272/2008.