Toxicity of inhaled methyl isocyanate in F344/N rats and B6C3F1 mice. II. Repeated exposure and recovery studies

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

DOI:https://doi.org/10.1289/ehp.8772133· OSTI ID:6066120

Bucher, J R; Gupta, B N; Thompson, M; Adkins, B Jr; Schwetz, B A

F344/N rats and B6C3F1 mice were exposed to 0, 1, 3, or 6 ppm methyl isocyanate by inhalation for 6 hr on 4 consecutive days. Deaths of rats were observed following 3 ppm exposures, and mice died after exposures to 6 ppm. Deaths appeared to be related to severe respiratory distress. Survivors in high dose groups lost weight initially, then gained weight at rates equal to controls throughout a 91-day recovery period. Lung weights increased significantly in male and female rats exposed to 3 ppm, but not persistent changes in brain, kidney, thymus, spleen, liver, or testis weights were seen in either mice or rats. Blood and serum from male and female rats were taken for clinical pathology and hematology assessments on day 7 of postexposure, the day prior to the first observed deaths of these animals. No changes or only slight changes were seen in measures of serum alanine aminotransferase, sorbital dehydrogenase, alkaline phosphatase, or in blood and brain cholinesterase activities. However, serum creatine kinase increased with dose in both males and females. Blood urea nitrogen, creatinine, and methemoglobin were unchanged. No changes were seen in counts of red blood cells or platelets, or in red cell indicies. Hemoglobin concentrations and hematocrits were slightly elevated. No changes were noted in absolute leukocyte counts, but counts of segmented neutrophils increased and lymphocytes decreased. These changes are consistent with slight hemoconcentration and a stress-related leukogram, as seen in acute exposure studies. The results indicate that the respiratory system is the primary site of injury following repeated inhalations of lethal and sublethal concentrations of methyl isocyanate, and give little evidence of direct effects on nonrespiratory tissues.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC
• OSTI ID: 6066120
• Journal Information: Environ. Health Perspect.; (United States), Vol. 72
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ENZYMES
BLOOD CHEMISTRY
ISOCYANATES
INHALATION
TOXICITY
RESPIRATORY SYSTEM
PATHOLOGICAL CHANGES
ALKALINE PHOSPHATASE
AMINOTRANSFERASES
BLOOD COUNT
CHOLINESTERASE
ENZYME ACTIVITY
FEMALES
INFLAMMATION
LYMPHOCYTES
MALES
MICE
MORTALITY
NEUTROPHILS
RATS
VAPORS
WEIGHT
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLESTERASES
CONNECTIVE TISSUE CELLS
ESTERASES
FLUIDS
GASES
HYDROLASES
INTAKE
LEUKOCYTES
MAMMALS
MATERIALS
NITROGEN TRANSFERASES
PHOSPHATASES
RODENTS
SOMATIC CELLS
SYMPTOMS
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology