Nitromethane

CAS RN:75-52-5

Toxicity Summary

IDENTIFICATION AND USE: Nitromethane is a colorless oily liquid. It is used as solvent for cellulosic compounds, polymers, waxes, fats; chemical synthesis; model rocket fuel; gasoline additive. HUMAN EXPOSURE AND TOXICITY: Symptoms of inhalation include cough, drowsiness, headache, nausea, sore throat, unconsciousness, and vomiting. Allergic contact hand dermatitis was documented in 4 coworkers who similarly handled an adhesive solvent containing nitromethane. All 4 cases were confirmed by patch testing and resolved after allergen avoidance. One case of human poisoning has been reported. In that case, a handyman was exposed to high concentrations of nitrocellulose and nitromethane resulting in a 67% conversion of his hemoglobin to methemoglobin and sulfhemoglobin. Treatment with hyperbaric oxygen, transfusion, peritoneal dialysis and then 6 sessions of hemodialysis resulted in recovery. Nitromethane is confirmed animal carcinogen with unknown relevance to humans. ANIMAL STUDIES: The most common signs of toxicity in acute animal studies were central nervous system (CNS) depression and slight irritation of the respiratory tract. Histopathologic changes were mainly in the liver and kidneys with the liver showing the most prominent injury, ie subcapsular damage, focal necrosis, fatty infiltration, congestion, and edema. The sulfhemoglobinemia and methemoglobinemia formation activities of similar drugs were studied in mice after administration of one or three ip doses. After administration of a single dose, nitromethane did not produce methemoglobinemia. Nitromethane produced sulfhemoglobinemia only after administration of three consecutive doses. Under the conditions of 2 yr inhalation studies conducted by NTP, there was no evidence of carcinogenic activity of nitromethane in male rats. There was clear evidence of carcinogenic activity of nitromethane in female rats based on increased incidences of mammary gland fibroadenomas and carcinomas. There was clear evidence of carcinogenic activity of nitromethane in male mice based on increased incidences of harderian gland adenomas and carcinomas. There was clear evidence of carcinogenic activity in female mice, based on increased incidences of liver neoplasms (primarily adenomas) and harderian gland adenomas and carcinomas. Increased incidences of alveolar/bronchiolar adenomas and carcinomas in male and female mice exposed to nitromethane were also considered to be related to chemical administration. Reproductive effects were investigated in female rats. No differences were found between treated and control rats in percentages of successful matings, litter size, pup mortality, birth weight, or maternal behavior. Pups were tested at 2.5 months of age in a maze-learning apparatus; the offspring of treated rats showed impaired maze learning when compared to controls. In another developmental study male rats had decreased caudal, epididymal, and testicular weights and decreased sperm counts. There was a dose-response decrease in epididymal sperm motility. Female mice showed a dose-related increase in the average estrous cycle length. Nitromethane was not mutagenic in Salmonella typhimurium strains TA 98 and TA 100 with and without activation. Nitromethane was further tested for mutagenicity of using the Salmonella assay, Drosophila melanogaster and an in vivo micronucleus test. Nitromethane was inactive in each of the three mutagenic test systems.
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