Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

The test substance was tested for mutagenic potential in the Bacterial reverse mutation assay at concentrations up to 5000 µg/plate using the following strains: TA 98 and TA100. The test substance induced 4.5 and 4.0 fold increase in the number of revertant colonies in the TA 100 strain, in the absence and presence of metabolic activation, respectively.

Consequently, the test substance was assessed for its ability to induce micronuclei in immature polychromatic erythrocytes in mouse bone marrow following intraperitoneal exposure to the maximum tolerated dose of 300mg/kg. No statistically significant decreases in the PCE/NCE ratio were observed in the 24 or 48 hr test material dose groups, compared to the concurrent control groups; however there were marked reductions in the PCE/NCE ratio at both exposure times ion animals treated with 300mg/kg test material. This accompanied with the presence of clinical signs was taken to indicate that systemic absorption has occurred and exposure of the bone marrow achieved.

There were no statistically significant increases in the frequency of micronucleated PCEs in any of the test material dose groups when compared to the concurrent controls and it was concluded that the test material was considered to be non-genotoxic under the conditions of the test.

Justification for selection of genetic toxicity endpoint

OECD guideline study conducted to GLP as part of the integrated testing strategy for genetic toxicity

Short description of key information:

The results of the assay demonstrated that there were no significant increases in micronucleated PCE compared to vehicle controls at the concentrations tested.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The results of the in vivo bone marrow micronucleus test conducted in mice, demonstrated a lack of genotoxic potential with respect to there being no increases in micronucleus frequency in immature erythrocytes. On this basis there is insufficient evidence to justify a classification for germ cell mutagenicity despite the results observed in the bacterial reverse mutation screening assay.