Toxicity of inhaled isocyanate in F344/N rats and B6C3F1 mice. I. Acute exposure and recovery studies

Journal Article · Mon Jun 01 04:00:00 EDT 1987 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.877253· OSTI ID:6061038

Bucher, J R; Gupta, B N; Adkins, B Jr; Thompson, M; Jameson, C W; Thigpen, J E; Schwetz, B A

Male and female F344/N rats and B6C3F1 mice were exposed to lethal and sublethal concentrations of methyl isocyanate by inhalation. Mortality, clinical signs, body and organ weights, and changes in clinical pathology and hematology were monitored immediately after 2-hr exposures and during the ensuing 3 months. Additional studies investigated the possible involvement of cyanide in the toxicity of methyl isocyanate. Deaths of rats and mice exposed to lethal concentrations (20 to 30 ppm) began within 15-18 hr, with males more prone to early death than females. A second wave of deaths occurred after 8 to 10 days, affecting primarily female rats and mice exposed to 20 to 30 ppm of methyl isocyanate, and male and female rats exposed to 10 ppm. Most deaths occurred during the first month following the exposures and were preceded by periods of severe respiratory distress. Body weights decreased in proportion to dose early, but then weight gain resumed in survivors at control rates. The only organ with a consistent, dose-related weight change was the lung, which was heavier throughout the studies in animals exposed to high concentrations of methyl isocyanate. Blood and brain cholinesterase were not inhibited. Studies attempting to measure cyanide in the blood of methyl isocyanate-exposed rats, and attempting to affect lethality with a cyanide antidote (sodium nitrite and sodium thiosulfate) gave negative results. The findings indicate that at these doses, methyl isocyanate inhalation causes deaths and persistent pulmonary changes, but no evidence of extrapulmonary toxicity in rodents. Cyanide does not appear to be involved in methyl isocyanate toxicity.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC
• OSTI ID: 6061038
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 72; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ANIMALS
BIOCHEMISTRY
BIOLOGICAL RECOVERY
BLOOD CHEMISTRY
BODY
BRAIN
CARBOXYLESTERASES
CENTRAL NERVOUS SYSTEM
CHEMISTRY
CHOLINESTERASE
CYANIDES
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
ESTERASES
HEMATOLOGY
HYDROLASES
INHALATION
INTAKE
ISOCYANATES
LUNGS
MAMMALS
MEDICINE
MICE
MORTALITY
NERVOUS SYSTEM
ORGANS
RATS
RECOVERY
RESPIRATORY SYSTEM
RODENTS
TOXICITY
VERTEBRATES
WEIGHT