1,1-dimethylheptanethiol

Endpoint summary

Additional information

In Vitro Genetic Toxicity

In Vitro Gene Mutation in Bacteria:

One key study was identified to evaluate the in vitro gene mutation potential of 1,1-dimethylheptanethiol in bacterial cells.

In a reverse gene mutation assay in bacteria (Molinier, 1995; Klimisch score = 1), strains of S. typhimurium (TA 98, 100, 102, 1535, and 1537) were exposed to 1,1-dimethylheptanethiol in DMSO at concentrations of 3, 10, 12.5, 25, 30, 50, 100, 150, 200, 300, 500, 1500, 5000 µg/plate in the presence and absence of mammalian metabolic activation using the plate-incorporation method.

1,1-dimethylheptanethhiol was tested up to limit concentrations of 5000 µg/plate. The test material did not show mutagenic activity in this bacterial reverse mutation assay on S. typhimurium. In the preliminary toxicity test, a strong toxicity was noted with the TA 102 strain with S9 mix at doses > 100 µg/plate. No toxicity was observed with this strain in the absence of S9 mix. Moderate to marked toxicity was noted in TA 98 and TA 100 at doses > 10 µg/plate without S9 mix and at doses > 100 µg/plate with S9 mix: clearing of the bacterial lawn and/or reduction in the number of revertants. In mutagenicity tests, the test substance did not induce any significant increase in the number of revertants, with or without S9 mix, in any of the 5 strains.

In Vitro Cytogenicity in Mammalian Cells:

No key in vitro cytogenicity data are available for 1,1-dimethylheptanethiol. Several criteria justify the use of the read across approach to fill data gaps for 1,1-dimethylheptanethiol using tert-dodecanethiol as a structural analogue. 1,1-dimethylheptanethiol, like tert-dodecanethiol, is a heavy mercaptan and has similar physiochemical properties. Hence, the toxicological properties of both these substances are also expected to be similar. Key read across data from tert-dodecanethiol was therefore used to evaluate the in vitro cytogenicity potential in mammalian cells.

In a key chromosomal aberration assay (Marshall 1997; Klimisch score = 1), human lymphocytes were exposed to tert-dodecanethiol at concentrations up to 94 µg/mL, with and without metabolic activation. The study was conducted according to OECD TG 473. No effects were observed at the 20-hour sampling time. At 44 hours in the absence of S9, the number of cells with aberrations was significantly higher than in concurrent negative controls at all dose levels analyzed. The numbers of cells with aberrations observed exceeded the historical control range, but this effect was only seen in both replicates at the highest concentration tested (30.03 µg/mL) at which severe mitotic inhibition was apparent. It was concluded that tert-dodecanethiol induced chromosomal aberrations in cultured human peripheral blood lymphocytes; however, this effect was restricted to prolonged, cytotoxic treatment in the absence of S9, and is therefore, considered to be equivocal.  

In a supporting in vitro Sister Chromatid Exchange (CHO cells) assay (Pence, 1984; Klimisch score = 2), Chinese Hamster Ovary cells were exposed to five graded doses (0.5-75 µg/mL) of tert-dodecanethiol with and without metabolic activation according to OECD TG 479. There were no dose-dependent increases in the number of SCEs/chromosome. Therefore, tert-dodecanethiol was considered to be negative in this test system.

 

 

In Vitro Gene Mutation in Mammalian Cells:

No key in vitro gene mutation data are available for 1,1-dimethylheptanethiol. Several criteria justify the use of the read across approach to fill data gaps for 1,1-dimethylheptanethiol using tert-dodecanethiol as a structural analogue. 1,1-dimethylheptanethiol, like tert-dodecanethiol, is a heavy mercaptan and has similar physiochemical properties. Hence, the toxicological properties of both these substances are also expected to be similar. Key read across data from tert-dodecanethiol was therefore used to evaluate the in vitro gene mutation potential in mammalian cells.

In an in vitro Mammalian Cell Gene Mutation (mouse lymphoma) assay (Pence, 1983; Klimisch score = 2), L5178Y TK (+/-) mouse lymphoma cells were exposed to eight graded doses of tert-dodecanethiol (6.1-100 µg/mL) with and without metabolic activation according to OECD TG 476. A 2-fold increase in the induction of forward mutations at the T/K locus in L5178Y mouse lymphoma cells occurred only at the 13.5 µg/mL level with activation. The test is considered positive if the dose-related response at 2 or more test concentrations is at least 2- or 3-fold higher than the mutation frequency of solvent control. Therefore, tert-dodecanethiol was considered to be negative in this test system.

Short description of key information:
1,1-dimethylheptanethiol was not mutagenic to Salmonella typhimurium in vitro. Key read across data showed that structural analogue tert-dodecanethiol was negative in vitro in human lymphocytes and in a sister chromatid exchange assay using Chinese Hamster Ovary (CHO) cells. Tert-dodecanethiol also did not increase the induction of forward mutations in L5187Y mouse lymphoma cells at the T/K locus w hile structural analogue dodecane-1-thiol did not induce an increase in micronucleated polychromatic erythrocytes in an in vivo mouse bone marrow micronucleus assay.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

1,1-dimethylheptanethiol does not meet the criteria for classification and labelling for genetic toxicity as defined by EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.