Hydrazine

Abstract

5.1 Exposure data: Exposure to hydrazine may occur in its production, and in the production of chemical blowing agents, agricultural chemicals and in water treatment. It has been detected at low levels in wastewater. 5.2 Human carcinogenicity data: The cancer risk of men exposed to hydrazine was investigated in two small cohort studies. In neither of these studies was an elevated risk observed for all cancers combined or for any specific cancer type. 5.3 Animal carcinogenicity data: Hydrazine was tested for carcinogenicity by oral administration to mice in several experiments, producing mammary and lung tumours. When tested by oral administration or inhalation exposure in rats, it produced lung, liver and nasal tumours and a few colon tumours. In hamsters, it produced liver tumours and thyroid adenomas following oral or inhalation exposure. 5.4 Other relevant data: Following subcutaneous administration of hydrazine to rats, maximum tissue concentrations were reached in about 30 min. Most urinary elimination was as unchanged hydrazine, with acetylhydrazine being the main metabolite but a minor elimination product. Tissue retention was longest in kidney, mainly due to the presence of acetylhydrazine. Hydrazine is metabolized and detoxified by at least three microsomal cytochrome P450 isoenzymes in rat liver (CYP2E1, CYP2B1 and CYP1A1/2), ultimately yielding molecular nitrogen. Human exposure to hydrazine has resulted in severe effects upon the central nervous system, liver and kidneys. In rats, hydrazine is hepatotoxic, causing accumulation of triglycerides, inhibition of protein synthesis and the formation of macromitochondria. Hydrazine induces gene mutations in bacteria, yeast and Drosophila and in-vivo treatment of mice, rats and Syrian hamsters results in the formation of N7-methylguanine and O6-methylguanine in liver DNA. 5.5 Evaluation: There is inadequate evidence in humans for the carcinogenicity of hydrazine. There is sufficient evidence in experimental animals for the carcinogenicity of hydrazine. Overall evaluation: Hydrazine is possibly carcinogenic to humans (Group 2B).