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Key value for chemical safety assessment

Additional information

In a reverse gene mutation assay in bacteria, performed according to the OECD Guideline 471 and in compliance with GLP, Silatrizole (encoded "G4375") did not induce an increase in the number of revertants in Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and in Escherichia Coli (WP2 and WP2 uvrA) either by the direct incorporation method and pre-incubation method and in the presence or in the absence of metabolic activation. Positive controls showed distinct increase of induced revertant colonies. Silatrizole was considered as not mutagenic in these strains.

In an in vitro mammalian cell mutation assay performed according to the OECD test guideline 476 and in compliance with GLP,Silatrizole did not induce any toxicologically significant or dose-related increases in the mutant frequency at the HPRT locus inChinese hamster ovary cells (CHO) cells at any dose level, either in the presence or absence of metabolic activation, in both experiments. Silatrizole was considered as not mutagenic in these strains.

In an in vitro chromosome aberrations study, performed according to the OECD No.473 guideline and in compliance with GLP, Silatrizole did not induce structural chromosome aberrations as determined by the chromosome aberration test in V79 cells (Chinese hamster cell line) in vitro. Therefore, Silatrizole is considered to be non-clastogenic in this test with and without S9 mix, when tested up to the highest required concentration.

In an in vivo bone marrow micronucleus assay performed according to OECD test guideline 474 and in compliance with GLP, Silatrizole did not induce any increase in the number of micronucleated polychromatic erythrocytes in the bone marrow of mice dosed once at doses up 2000 mg/kg bw. Silatrizole was therefore considered non-clastogenic in this test.

All the tests performed are complementary and provide evidence that the registered substance has no genotoxicology concerns, investigating gene mutation both in bacteria and mammals and mammalian chromosome aberration both in vitro and in vivo.


Justification for selection of genetic toxicity endpoint
No study was selected since all in vitro and vivo studies performed on the substance were negative and of good quality.

Short description of key information:
- Ames Test (OECD 471, GLP, K, V1): non mutagenic up to 5000.0 µg/plate in Salmonella typhimurium (TA 1535, TA 1537, TA 98, TA 100) and Escherichia Coli (WP2 and WP2 uvrA)
- HPRT Mammalian cell Gene Mutation Test (OECD 476, GLP, K, V1): non mutagenic up to cytotoxic concentrations.
- V79 Chromosome aberration test (OECD 473, GLP, K, V1): non clastogenic up to cytotoxic or precipitating concentrations.
- In vivo Mouse Micronucleus Test (OECD 471, GLP, K, V1): non clastogenic up to 2000 mg/kg bw (oral route)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

As Silatrizole was negative in an in vitro Ames assay in bacteria and in an in vitro Mammalian Cell Gene Mutation test, it is not classified as mutagenic according to the CLP Regulation (EC) N°1272/2008.

As Silatrizole was not clastogenic in an in vitro chromosome aberration test and in an in vivo bone marrow micronucleus assay, it is not classified as clastogenic according to the CLP Regulation (EC) N°1272/2008.