Inhalation Toxicity of Methylglutaronitrile in Rats

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2003-01, Vol.26 (2), p.99-115
• Main Authors: Kelly, D. P., Frame, S. R., Malley, L. A., Everds, N. E., Kennedy, G. L.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Animals; Atmosphere Exposure Chambers; Biological and medical sciences; Blood Cell Count; Body Weight - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Dose-Response Relationship, Drug; Female; Glutarates - administration & dosage; Glutarates - toxicity; Male; Medical sciences; Methemoglobin - analysis; Motor Activity - drug effects; Nervous System - drug effects; Nitriles - administration & dosage; Nitriles - toxicity; No-Observed-Adverse-Effect Level; Organ Size - drug effects; Rats; Sex Factors; Toxicity Tests, Acute; Toxicity Tests, Chronic; Toxicology; Various organic compounds
• ISSN: 0148-0545; 1525-6014
• DOI: 10.1081/DCT-120020405

Abstract Methylglutaronitrile (MGN) is a high-boiling (263°C) solvent intermediate used in the fiber industry. Twenty male rats per group were exposed nose-only to condensation aerosol vapor concentrations of approximately either 5, 25, or 200 mg m3 of MGN for 6 h day, 5 days week over a 4-week period. Ten rats group were sacrificed one day after the final exposure and the remaining rats after a four-week recovery period. No effects were observed in clinical observations during the exposure period, but body-weight depression was observed in the 200 mg m3 group. The 200 mg m3 group showed minimal decreases in red blood cell count, hemoglobin, and hematocrit values accompanied by increases in reticulocytes. There were no other effects observed in clinical or pathologic evaluations in the study. A neurobehavioral battery of tests (including grip strength, functional observational battery, and motor activity tests) given at the end of the exposure and recovery periods showed no MGN effects. During the 4-week recovery, body weights in the 200 mg m3 group returned to normal and the hematologic findings in all groups were normal. Based on the above findings of body weight depression at 200 mg m3, the no-observed-adverse-effect level (NOAEL) for this study was considered to be 25 mg m3.