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Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice. I. Systemic toxicity.

Lynch DW; Moorman WJ; Burg JR; Phipps FC; Lewis TR; Khan A; Lewis DM; Chandler FW; Kimbrough RD; Spira TJ
J Toxicol Environ Health 1985 Jan; 15(6):823-833
The effect of subchronic inhalation exposure to isobutyl-nitrite (542563) on body weight, selected organ weights, hematology, gross pathology, and histopathology was evaluated in mice. BALB/c-mice of both sexes underwent inhalation exposure to isobutyl-nitrite at concentrations of 0, 20, 50, or 300 parts per million (ppm) 6.5 hours a day, 5 days a week, for up to 18 weeks. Fifteen male and female animals each from the 0 and 20ppm exposure groups were sacrificed after week 13. The same numbers of mice from the 50ppm group were sacrificed following 3, 7, and 13 weeks of exposure. Fifteen male and female mice from the 300ppm group were sacrificed following exposure weeks 13 and 18. Individual body weights were recorded weekly for both test and control animals. The hematological indices evaluated included red blood cell, white blood cell, and differential cell counts, with hemoglobin and methemoglobin measurements being made at the time of the week 13 sacrifices. A complete necropsy was performed on all animals that died or were sacrificed. Most of the changes observed occurred in mice exposed to isobutyl-nitrite at a concentration of 300ppm and included decreased thymus weights in females, decreased liver weights and white blood cell counts in males and focal hyperplasia, together with vacuolization of the epithelium lining bronchi and lung bronchioles, in animals of both sexes. In addition, elevated methemoglobin concentrations were detected in mice of both sexes undergoing isobutyl-nitrite exposures at concentrations of 50 and 300ppm. The authors conclude that the major toxic effects associated with the inhalation exposure of mice to isobutyl-nitrite at concentrations of up to 300ppm for a period of 18 weeks are mild tissue injury, restricted to the lungs, and methemoglobinemia. It is recommended that additional research be carried out relative to the pulmonary toxicity of inhaled isobutyl-nitrite and aliphatic nitrites in general.
NIOSH-Author; Lung-irritants; Air-sampling; Pulmonary-function; Respiration; Lung; Pulmonary-clearance; Pulmonary-congestion; Toxic-effects; Laboratory-animals; Lung-cells; Inhalants
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Journal Article
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Journal of Toxicology and Environmental Health
Page last reviewed: May 11, 2023
Content source: National Institute for Occupational Safety and Health Education and Information Division