ISOPROPANOL 13-WEEK VAPOR INHALATION STUDY IN RATS AND MICE WITH NEUROTOXICITY EVALUATION IN RATS

This study was conducted to evaluate the possible subchronic toxicity as well as neurobehavioral effects of isopropanol, a widely used indus trial and commercial solvent. Five groups, each containing 10 Fischer 344 rats/sex and 10 CD-1 mice/sex, were exposed for 6 hr/day, 5 days/w eek, for 13 weeks to isopropanel vapor at concentrations of 0 (control ), 100, 500, 1500, or 5000 ppm. An additional 15 rats/sex were assigne d to the 0, 500, 1500, and 5000 ppm groups for assessment of neurobeha vioral function. No exposure-related mortalities occurred during the s tudy. The narcotic effects of isopropanol were noted only during expos ures at 1500 and 5000 ppm. These signs, noted during exposures, were t ypically absent following exposures. The only clinical signs observed following exposures included swollen periocular tissue, perinasal encr ustation, and ataxia for rats of the 5000 ppm group. Neurobehavioral e valuations indicated no changes in any of the parameters of the functi onal observational battery; however, increased motor activity for fema le rats in the 5000 ppm group was noted at Weeks 9 and 13. Decreases i n body weight and body weight gain were observed for rats of the 5000 ppm group at the end of the first week of exposure. During the remaini ng weeks, increases in body weight and/or body weight gain were observ ed for rats of the 1500 and 5000 ppm groups. No exposure-related effec ts on body weight were noted for male mice; however, increased body we ight and body weight gain were observed for female mice of the 5000 pp m group. Increases or decreases in food and water consumption generall y corresponded to changes in body weight and body weight gain. Various changes in clinical pathology parameters were observed for rats and f emale mice of the 5000 ppm group. The only organ weight effect noted w as an increased relative liver weight in both sexes of rats and female mice of the 5000 ppm group. At necropsy, there were no gross lesions determined to be exposure related. Furthermore, the only microscopic c hange observed was hyaline droplets within the kidneys of all male rat s (including controls). The size and frequency of the hyaline droplets were increased for the isopropanol exposure groups compared to the co ntrol group. These differences were not clearly concentration related, although this microscopic change was most pronounced in the high-conc entration group. Neuropathologic examination revealed no exposure-rela ted lesions in the central or peripheral nervous system of exposed rat s. Thus, repeated exposures to isopropanol for 13 weeks produced toxic effects only at the highest concentration and a kidney change in male rats of unknown biological significance. (C) 1994 Society of Toxicolo gy.