Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Ames Test, in-vitro: Statistically significant, dose-related and reproducible increases in revertant colony frequency were observed in tester strains TA100 and TA1535, both with and without S9, at the upper dose levels of the test substance. The dose- responsiveness of the test substance was confirmed in the second experiment after the inclusion of an intermediate dose level. The test substance was considered to be mutagenic under the conditions of this test.

Mouse Lymphoma (Chromosome aberration test), in-vitro: The test material induced reproducible, toxicologically significant increases in the mutant frequency at the TK +/-locus in L5178Y cells in the presence of metabolic activation and is therefore considered to be mutagenic under the conditions of the test.

Micronucleus, in-vivo: No statistically significant decreases in the PCE/NCE ratio were observed in the 24 or 48-hour test material dose groups when compared to their concurrent control groups. However, small dose-related decreases in PCE/NCE ratios were observed, these and the presence of clinical signs were taken to indicate that systemic absorption had occurred. The test material was found not to produce a significant increase in the frequency of micronuclei in polychromatic erythrocytes of mice under the conditions of the test. The test material was considered to be non-genotoxic under the conditions of the test.

Short description of key information:
Three genetic toxicity studies have been performed for BMS 296796-02; 2 in-vitro studies ( Ames reverse-mutation assay and chromosome aberration (mouse lymphoma ) assay) and 1 key in-vivo study ( mouse micronucleus). All studies were assigned reliability rating of 1 (reliable without restriction). All results were considered valid. The test material was considered postive for mutagenicity in the 2 in vitro studies but was not-mutagenic in the in-vivo mouse micronuleus animal study.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The two in vitro test (Ames reverse- mutation assay and chromosome aberration test) resulted in positve mutagenic effects. However, mutagenic effects were negative or not noted in an animal experiment (micronucleus test, in vivo). The negative result in the in vivo study is more significant than the 2 positive in-vitro studies and the test material does not meet the requirements for classification as a mutagen according to EU regulations.