For definition of Groups, see Preamble Evaluation.
VOL.: 71 (1999) (p. 947)
Chem. Abstr. Name: 1,2-Dimethylhydrazine
5.1 Exposure data
1,2-Dimethylhydrazine is believed to be used only as a laboratory chemical. No information on potential human exposure is available.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
1,2-Dimethylhydrazine was studied for carcinogenicity in many experiments in rats and mice, mainly by subcutaneous, infrequently by oral and rarely by other routes of administration.
Whatever the route of administration, 1,2-dimethylhydrazine, if given at an appropriate dosage, produced in mice and rats a high incidence of adenomas and adenocarcinomas of the colon and, to a lesser extent, of the small bowel. When given with drinking water or by gavage at low single doses, it produced a high incidence of vascular tumours.
In some experiments in rats, it produced ear duct papillomas and carcinomas, hepatocarcinomas, kidney adenomas, carcinomas and fibrosarcomas. When given to rats at very high single doses, it produced high incidences of nephroblastomas.
In some strains of mice, it produced a high incidence of hormone-dependent angiosarcomas of the kidney capsule (males only), uterine sarcomas or vascular tumours and tumour-like lesions of the ovary.
5.4 Other relevant data
1,2-Dimethylhydrazine is readily absorbed. It can be N-demethylated, yielding formaldehyde, and can be oxidized through several steps to yield methylazoxymethanol. It binds covalently to protein, DNA and RNA in many mammalian tissues. The colon of rats is a target organ for 1,2-dimethylhydrazine toxicity, where it can produce aberrant crypts. In developmental studies, it is embryo- and feto-toxic in rats.
1,2-Dimethylhydrazine formed DNA adducts and induced gene mutations, DNA breaks and micronuclei in vitro and in vivo in rodents. In vitro it formed DNA adducts and induced unscheduled DNA synthesis and gene mutations in mammalian cells. Conflicting evidence has been obtained for its genotoxicity in bacteria.
Although the activating pathway has not been clarified in detail, there is good evidence that human tissues, cells and subcellular preparations can activate 1,2-dimethylhydrazine in a similar manner to the corresponding rodent models.
1,2-Dimethylhydrazine requires bioactivation to become mutagenic and alkylates DNA in several species in vivo. It is not genotoxic in bacteria, but it is mutagenic for various endpoints in virtually all somatic test systems examined in vitro and in vivo.
No epidemiological data relevant to the carcinogenicity of 1,2-dimethylhydrazine were available.
There is sufficient evidence in experimental animals for the carcinogenicity of 1,2-dimethylhydrazine.
1,2-Dimethylhydrazine is probably carcinogenic to humans (Group 2A).
In making the overall evaluation, the Working Group took into account that 1,2-dimethylhydrazine is consistently mutagenic in a wide range of test systems and gives rise to a similar pattern of DNA damage in human and animal tissues in vitro.Previous evaluations: Vol. 4 (1974); Suppl. 7 (1987) (p. 62)
See Also: Toxicological Abbreviations