Neurotoxicity evaluation of rats after subchronic inhalation exposure to isobutanol.
The subchronic neurotoxic effects of isobutanol were studied by exposing Sprague-Dawley rats to isobutanol vapor concentrations of 0, 250, 1000, and 2500 ppm for 6 hrs/day, 5 days/wk, for 3 months. A comprehensive set of neurotoxicity tests (functional observational battery, motor activity, perfusion fixation neuropathology, and schedule-controlled operant behavior) including an assessment of complex behavior dependent on learning and memory was conducted. In addition, full histopathology and blood chemistry evaluations were conducted in order to assess any potential functional/behavioral effects in the context of other possible systemic toxicities. There were no morphological or behavioral effects indicative of a specific, persistent or progressive effect of isobutanol on the nervous system at exposure concentrations up to 2500 ppm. A slight decrease in response to external stimuli was observed during exposures at all concentrations. These effects are likely transient effects of acute exposure to isobutanol.
Li
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AA
Metabolism and Safety Evaluation-Newstead Laboratory, St. Louis, MO, USA. abby.a.li@monsanto.com
Thake
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DC
Kaempfe
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TA
Branch
D K
DK
O'Donnell
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P
Speck
F L
FL
Tyler
T R
TR
Faber
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WD
Jasti
S L
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Ouellette
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R
Banton
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MI
D000280:Administration, Inhalation; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001773:Blood Cells / Q000187:drug effects*; D000440:Butanols / Q000633:toxicity*; D002746:Chlorpromazine / Q000494:pharmacology; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000440:Butanols; C040507:isobutyl alcohol; D000661:Amphetamine; D002746:Chlorpromazine