Inhalation toxicity of methylglutaronitrile in rats.
Methylglutaronitrile (MGN) is a high-boiling (263 degrees 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.
Kelly
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E.I. du Pont de Nemours and Company, Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714, USA. david.p.kelly@usa.dupont.com
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Malley
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Everds
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Kennedy
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D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005977:Glutarates / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008706:Methemoglobin / Q000032:analysis*; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects; D009570:Nitriles / Q000008:administration & dosage / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012737:Sex Factors; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
D005977:Glutarates; D009570:Nitriles; C480967:methylglutaronitrile; D008706:Methemoglobin