2021/09/30 by Hartwig, Andrea, MAK Commission
#Chlormethan #Chlormethyl #Entwicklungstoxizität #Fertilität #Hautresorption #Kanzerogenität #MAK value #MAK-Wert #Maximale Arbeitsplatzkonzentration #Methylchlorid #Monochlormethan #Neurotoxizität #Toxizität #carcinogenicity #chloromethane #developmental toxicity #fertility #germ cell mutagenicity #keimzellmutagene Wirkung #maximum concentration at the workplace #methyl chloride #monochloromethane #neurotoxicity #skin absorption #toxicity
paper · doi:10.34865/mb7487d6_3ad
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated methyl chloride [74-87-3], considering all toxicological end points. Critical effects are neurotoxicity and reduced fertility. The NOAEC for adverse effects on fertility in male rats after 3-month exposure was 150 ml/m. A NAEC of 100 ml/mfor reduced fertility in male rats was estimated from a 2-year study.The NOAEC for degenerations of the cerebellar granular layer is 150 ml/m in mice. Slight behavioural toxic effects were observed in humans at a concentration of 200 ml/m; neurotoxic effects developed at much higher concentrations. On the basis of neurotoxic effects in humans and reduced fertility and severe neurotoxic effects in animals, the maximum concentration at the workplace (MAK value) for methyl chloride has been lowered to 10 ml/m. As the critical effect of methyl chloride is systemic, Peak Limitation Category II is retained. The initial half-live in humans is below one hour, so an excursion factor of 1 is determined. Methyl chloride is genotoxic in vitro only at very high concentrations of 8000 ml/m and above. DNA adducts were not observed even with very high concentrations of methyl chloride. From in-vivo- and metabolism-studies it can be concluded that cytotoxic and secondary genotoxic effects are of prime importance. Thus, methyl chloride is not regarded as a germ cell mutagen. The observed kidney tumours occurred only in one species and sex (male mouse) and can be explained with a mechanism, that is of no relevance in humans. In comparison with methyl bromide and methyl iodide, carcinogenic effects of methyl chloride due to alkylating effects are not to be expected. However, a possible formation of DNA adducts cannot be completely excluded. If at all, these are only formed at concentrations far exceeding the MAK value and even then only to a very small extent, so that it is of no significance for the situation at the workplace. Methyl chloride is therefore not classified in a Carcinogen Category. There are no data on developmental neurotoxicity, therefore methyl chloride is assigned to Pregnancy Risk Group D. Skin contact is not expected to contribute significantly to systemic toxicity. There are no data on sensitization.