Hydrazine, anhydrous appears as a colorless, fuming oily liquid with an ammonia-like odor. Flash point 99°F. Explodes during distillation if traces of air are present. Toxic by inhalation and by skin absorption. Corrosive to tissue. Produces toxic oxides of nitrogen during combustion. Used as a rocket propellant and in fuel cells.
Hydrazine ... is ... acetylated very rapidly in most species. The reaction is so fast that the monoacetyl metabolite is not detected, and the excreted diacetyl metabolite accounts almost entirely for the administered dose.
(15)N-labeled hydrazine and conventional methods were used to account for approx 75% of single doses of hydrazine (1 mmol/kg). In 48 hr, about 30% appeared in urine as hydrazine and about 20% emerged as derivative that is acid-hydrolyzable to hydrazine. About 25% converted to nitrogen.
Hydrazines are likely to be more rapidly absorbed into the blood after ingestion or exposure to the skin than after inhalation. Once in the blood, they are probably carried to all the tissues of the body. Soon after exposure, the levels of hydrazines in the tissues fall since they are metabolised in several products such as acetyl-, diacetylhydrazine, pyruvate hydrazone, urea, and acyclic compound (1,4,5,6-tetrahydro-6-oxo-3-pyridazine carboxylic acid). However, these metabolites interacts with some important proteins and might be harmful to the body. Some studies showed that metabolites and unchanged hydrazine leave the body within one day.
Small amounts can also be found in the expired air. (L154, A112)
IDENTIFICATION AND USE: Hydrazine is a colorless oily liquid. It is used as an oxygen scavenger in boiler water treatment, as an electrodeless nickel coating reagent, and in rocket propellant. It is also used in a variety of other fields including pharmaceuticals, explosives, polymers and polymer additives, antioxidants, metal reductants, hydrogenation of organic groups, photography, xerography, and dyes. It has been tested as an experimental therapy. HUMAN STUDIES: Skin contact with anhydrous hydrazine leads to caustic-like burns and dissolves hair. Allergic contact dermatitis has been reported. Exposure to the eyes can produce temporary blindness. Liquid splashes to the eyes can produce corneal injury and burns. In cases of acute human poisoning, vomiting, severe irritation of the respiratory tract with the development of pulmonary edema, central nervous system depression, and hepatic and renal damage have been reported. Allergic contact dermatitis has been reported. Exposure to hydrazine increases the risk of incident lung cancers and colon cancers, based on a study in a cohort of aerospace workers. ANIMAL STUDIES: Hydrazine hydrate produced moderately severe irritation when 3 to 5 mL was applied to rabbit cornea, whereas 1 mL was much less irritating. Rabbit skin that was treated with 3 mL of anhydrous hydrazine for 1 min, followed by washing the treated area. Despite washing, mortality ensued 60 to 90 min after application. Acute toxicity has been characterized by liver damage consisting of fatty degeneration, red blood cell destruction and anemia, anorexia, weight loss, weakness, vomiting, excitability, hypoglycemia, and convulsions. Groups of dogs, monkeys, rats, and mice were exposed either 24 hr/day, 7 days/wk to 6.2 or 1 ppm, or 6 hr/day, 5 days/wk to 1 or 5 ppm hydrazine for 6 months. Mortality was seen in mice and dogs, but not in monkeys or rats. Dogs showed hematologic deficits and increased numbers of reticulocytes. Liver changes that consisted of moderate to severe fatty infiltration were marked in mice and dogs, were slight to moderate in monkeys, and were absent in the rat. Groups of rats were exposed orally during gestation to 8 mg/kg bw hydrazine. Maternal toxicity, including mortality and body weight loss, was seen, along with fetal toxicity that included reduced fetal weight and viability. Although some fetuses were pale and edematous, no major congenital malformations occurred. An increase in the number of lung tumors was observed in several strains of mice, but hydrazine did not increase the tumor yield in rats following either sc injection or intratracheal application. Hydrazine is positive in most standard assays for genetic toxicity endpoints. ECOTOXICITY STUDIES: Eggs of fathead minnows (Pimephales promelas) at the mid-cleavage stage were exposed to hydrazine for 24 or 48 hr. Embryos, exposed for 24 hr, to 0.1 mg/L, showed several defects, such as slightly or moderately subnormal heart beat, hemoglobin levels, body movement, and amount of eye pigment. Embryos exposed to a hydrazine concentration of 1.0 mg/L for 48 hr appeared to have little chance of survival. Surviving embryos showed severe deformities and larvae exhibited reduced growth.
At least two mechanisms of action have been observed. One involves the direct binding of those hydrazines with a free amino group (hydrazine and 1,1-dimethylhydrazine) to key cellular molecules. Hydrazine reacts with alpha-keto acids such as vitamin B6 to form hydrazoines compounds. By binding to keto acids and forming hydrazones, hydrazine inhibits oxygen consumption with mitochondrial substrates in vitro. A second mechanism involves the generation of reactive species such as free radical intermediates or methyldiazonium ions as a result of metabolism. (L154)
Evaluation: There is limited evidence in humans for the carcinogenicity of hydrazine. A positive association has been observed between exposure to hydrazine and cancer of the lung. There is sufficient evidence in experimental animals for the carcinogenicity of hydrazine. Hydrazine is probably carcinogenic to humans (Group 2A).
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Tumors have been induced in mice, rats and hamsters following oral, inhalation or intraperitoneal administration of hydrazine and hydrazine sulfate. Hydrazine is mutagenic in numerous assays. HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3; 已确认的动物致癌物，对人类的相关性未知。
A3; Confirmed animal carcinogen with unknown relevance to humans.
Hydrazino nitrogen (assumed to be largely unchanged hydrazine) is excreted in urine after iv or sc administration of hydrazine in dogs. 5-11% of large doses (50 mg/kg - twice the LD50) is excreted within first 4 hr and approximately 50% of 15 mg/kg dose is excreted within first 2 days after injection.
Hydrazine is rapidly absorbed and rapidly distributed to and eliminated from most tissues. It may compete to slow down the formation of glutamine and urea by combining with glutamic acid, carbamyl phosphate, or amino acid precursor of the urea cycle, as a result of which ammonia is released. In mice and rats, a part of the absorbed hydrazine is excreted unchanged and a part as labile conjugates or as acid-hydrolysable derivatives via the urine. When hydrazine is metabolized, a significant amount of nitrogen is produced, which is excreted via the lungs.
