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Key value for chemical safety assessment

Additional information

Ames Test

 

In an in vitro bacterial reverse gene mutation assay conducted according to OECD Guideline 471 but which used a fifth strain of Salmonella typhimurium, i.e., TA 1538 rather than the currently recommended E. coli WP2 uvr (with or without pKM 101) or Salmonella strain TA 102, there was no increase in cytotoxicity or mutation frequency in any strain of Salmonella typhimurium at concentrations up to 5000 µg/plate in the presence or absence of metabolic activation. Vehicle and positive controls induced the appropriate responses. In a mammalian in vitro chromosome aberration assay conducted according to OECD Guideline 473, there was no increase in chromosome aberrations or polyploidy in Chinese Hamster Ovary cells tested at concentrations up to 1200 µg/mL in the presence and absence of metabolic activation. No dose-dependent cytotoxicity was observed in the study. Vehicle, negative and positive controls induced the appropriate responses.

In Vitro Mammalian Cytogenicity

In a mammalian cell cytogenetics assay, cultures of Chinese hamster ovary (CHO) cells were exposed to methyl n-amyl ketone (MAK) at concentrations up to 1200 µg/mL (the highest recommended concentration for this study type) with and without metabolic activation, and were analyzed for chromosomal aberrations. Solvent, negative, and positive controls were also prepared and tested. The mitotic index was used to assess cytotoxicity and select concentrations for metaphase analysis. Metaphase cells were examined for chromosomal damage. There was no evidence of induction of chromosome aberrations over background levels in methyl n-amyl ketone-treated cells. There was also no statistically significant increase in the number of polyploid metaphase cells when compared to the solvent control. All positive controls induced the appropriate response. It was concluded that methyl n-amyl ketone showed no evidence of clastogenic activity under conditions of this assay at the concentrations tested.

In Vitro Mammalian mutagenicity

The study was conducted according to a method that was designed to assess the potential mutagenicity of the test item on the thymidine kinase, TK +/-, locus of the L5178Y mouse lymphoma cell line. The method was designed to be compatible with the OECD Guidelines for Testing of Chemicals No.476 "In Vitro Mammalian Cell Gene Mutation Test", Method 817 of Commission Regulation (EC) No. 440/2008 of 30 May 2008, the US EPA OPPTS 870.5300 Guideline, and be acceptable to the Japanese METI/MHLW guidelines for testing of new chemical substances. Two independent experiments were performed. In Experiment 1, L5178Y TK+/- 3.7.2c mouse lymphoma cells (heterozygous at the thymidine kinase locus) were treated with the test item at eight dose levels, in duplicate, together with vehicle (solvent) and positive controls using 4-hour exposure groups both in the absence and presence of metabolic activation (2% S9). In Experiment 2, the cells were treated with the test item at eight dose levels using a 4-hour exposure group in the presence of metabolic activation (1% S9) and a 24-hour exposure group in the absence of metabolic activation. The dose range of test item was selected following the results of a preliminary toxicity test and for the first experiment was 31.25 to 1100 ug/ml in both the absence and presence of metabolic activation. For the second experiment the dose range was 50 to 700 ug/ml in the absence of metabolic activation, and 400 to 1100 ug/ml in the presence of metabolic activation. The maximum dose level used in the mutagenicity test was limited by test item-induced toxicity. The vehicle (solvent) controls had acceptable mutant frequency values that were within the normal range for the L5178Y cell line at the TK +/-locus. The positive control items induced marked increases in the mutant frequency indicating the satisfactory performance of the test and of the activity of the metabolising system. The test item did not induce any toxicologically significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation, in either the first or the second experiment.

 


Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The total weight-of-the-evidence available indicates that methyl n-amyl ketone is not expected to induce heritable mutations in the germ cells of humans and is not classified for mutagenicity/genotoxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Methyl n-amyl ketone is not classified for mutagenicity/genotoxicity according to Annex I of Directive 67/548/EEC.