1,2-Dimethylhydrazine: MAK Value Documentation, addendum - Translation of the German version from 2021

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has re-evaluated the occupational exposure limit value (maximum concentration at the workplace, MAK value) of 1,2-dimethylhydrazine [540-73-8] considering all toxicological end points. Relevant studies were identified from a literature search. Chronic and subchronic exposure induced adverse effects on the liver, heart and kidneys of mice and the liver and bile ducts of mini-pigs and guinea pigs. In dogs, 1,2-dimethylhydrazine caused adverse effects on the liver. The critical effect of 1,2-dimethylhydrazine is its carcinogenic potential. In carcinogenicity studies, 1,2-dimethylhydrazine induced various intestinal and vascular tumours such as haemangiosarcomas in addition to lung tumours in rodents after oral and intraperitoneal application. Particularly noteworthy is the high incidence of colon carcinomas in rats, which was observed both after acute and chronic application. Additionally, tumours of the digestive system were caused in hamsters and monkeys after subcutaneous or intramuscular injection. On the basis of the carcinogenic effects induced in several animal species, 1,2-dimethylhydrazine remains classified in Carcinogen Category 2. It is not possible to derive a MAK value. Enzymatic activation of 1,2-dimethylhydrazine leads to highly reactive metabolites, such as the well-known procarcinogen methylazoxymethanol, which are able to methylate DNA. The substance is clastogenic and mutagenic in somatic cells in vitro and in vivo. Additionally, in mouse testes, 1,2-dimethylhydrazine was found to inhibit DNA synthesis after oral application and to methylate DNA after subcutaneous application. Therefore, the substance has been classified in Germ Cell Mutagenicity Category 3 A. Although no valid studies considering the dermal absorption of 1,2-dimethylhydrazine are available, the "H" designation has been retained because of the low dermal LD₅₀ values in animals and the potential for genotoxic effects after dermal application. Although no studies considering the sensitizing potential of 1,2-dimethylhydrazine are available, the "Sh" designation has been retained because of its structural similarity with the known contact allergen hydrazine.