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3,3,5-trimethylcyclohexanone did not cause bacterial reverse mutation in an Ames test according to OECD 471 (Hüls 1996). In a mammalian cell gene mutation assay (HPRT Test) according to OEDC 476, V79 cells cultured in vitro were exposed to 3,3,5-trimethylcyclohexanone, dissolved in DMSO, at concentrations of 62.5 – 1000 mg/L in the presence and absence of mammalian metabolic activation (LPT 2010). 3,3,5-Trimethylcyclohexanonee was tested up to cytotoxic concentrations (1000 mg/L). All test results were within the range of the negative controls. The positive controls did induce the appropriate response. There was no evidence of induced mutant colonies over background.
In a mammalian cell cytogenetic assay [Chromosome aberration], human lymphocyte cultures were exposed to 3,3,5-trimethylcyclohexanone (99.7%), dissolved in DMSO, at concentrations of 0 – 10 mM with and without metabolic activation (CIT 2004 a). 3,3,5-Trimethylcyclohexanone was tested up to cytotoxic concentrations. A statistically significant increase to 3-30% cells with aberrations (vs. controls) was reported at the top concentration with metabolic activation. In contrast to the other in vitro findings there was evidence of a mutagenic effect in this study. However, the increase in the frequency of cells with structural chromosome aberrations was limited to the highest concentration tested. Hence, a dose dependency could not be demonstrated. In addition a marked decrease in the mitotic index was also observed at this concentration indicating some degree of cytotoxicity.

In addition to the in vitro testing battery an in vivo micronucleus test according to OECD 474 was conducted (CIT 2004 b). 5 Swiss mice/sex/dose were treated with two i.p. injections of 3,3,5-trimethylcyclohexanone (99.6 %) at dose levels of 0, 175, 350, and 700 mg/kg bw. The maximum tolerated dose (MTD) was determined in a preliminary toxicity study. Bone marrow polychromatic erythrocytes, collected 24 hours after last treatment, were examined microscopically for micronucleated polychromatic erythrocytes (PCE). There were no clinical signs of toxicity in the 175 and 350 mg/kg group. At 700 mg/kg sedation was noted in all treated animals after 15 minutes following the first treatment. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time. Hence, 3,3,5-trimethylcyclohexanone shows no genotoxic potential under condition of this in vivo study.

The indication of a positive result reported in an in vitro chromosome aberration test (CIT 2004a) was considered not strong enough to affect the overall conclusion that 3,3,5-trimethylcyclohexanone is not genotoxic.

Short description of key information:
The mutagenic potential of 3,3,5-trimethylcyclohexanone was assessed in an Ames test according to OECD 471 (Hüls 1996), an in vitro mammalian chromosome aberration test according to OECD 473 (CIT 1004a), an in vitro mammalian cell gene mutation assay according to OECD 476 (LPT 2010) and an in vivo micronucleus assay according to OECD 474 (CIT 2004 b). The test substance is non-genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The test substance is non-genotoxic.