© 1994 Oxford University Press
research-article |
Isopropanol 13-Week Vapor Inhalation Study in Rats and Mice with Neurotoxicity Evaluation in Rats1
*Bushy Run Research Center/Union Carbide Chemicals and Plastics Company Inc. Export, Pennsylvania 15632
BP America Inc. Cleveland, Ohio
ARCO Chemical Company, Newtown Square, Pennsylvania
Exxon Biomedical Sciences Inc. East Millstone, New Jersey
¶ Shell Oil Company, Houston, Texas
Received May 27, 1993; accepted April 28, 1994
This study was conducted to evaluate the possible subchronic toxicity as well as neurobehavioral effects of isopropanol, a widely used industrial and commercial solvent. Five groups, each containing 10 Fischer 344 rats/sex and 10 CD-I mice/sex, were exposed for 6 hr/day, 5 days/week, for 13 weeks to isopropanol vapor at concentrations of 0 (control), 100, 500, 1500, or 5000 ppm. An additional 15 rats/sex were assigned to the 0, 500, 1500, and 5000 ppm groups for assessment of neurobehavioral function. No exposure-related mortalities occurred during the study. The narcotic effects of isopropanol were noted only during exposures at 1500 and 5000 ppm. These signs, noted during exposures, were typically absent following exposures. The only clinical signs observed following exposures included swollen periocular tissue, perinasal encrustation, and ataxia for rats of the 5000 ppm group. Neurobehavioral evaluations indicated no changes in any of the parameters of the functional observational battery; however, increased motor activity for female rats in the 5000 ppm group was noted at Weeks 9 and 13. Decreases in 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 remaining weeks, increases in body weight and/or body weight gain were observed for rats of the 1500 and 5000 ppm groups. No exposure-related effects on body weight were noted for male mice; however, increased body weight and body weight gain were observed for female mice of the 5000 ppm group. Increases or decreases in food and water consumption generally corresponded to changes in body weight and body weight gain. Various changes in clinical pathology parameters were observed for rats and female mice of the 5000 ppm group. The only organ weight effect noted was an increased relative liver weight in both sexes of rats of and female mice of the 5000 ppm group. At necropsy, three were no gross lesions determined to be exposure related. Furthermore, the only microscopic change observed was hyaline droplets within the kidneys of all male rats (including controls). The size and frequency of the hyaline droplets were increased for the isopropanol exposure groups compared to the control group. These differences were not clearly concentration related, although this microscopic change was most pronouced in the high-concentration group. Neuropatholo0gic examination revealed no exposure-related lesions in the central or peripheral nervous system of exposed rats. Thus, repeated exposures to isopropanol for 13 weeks produced toxic effcts only at the highest concentration and a kidney change in male rats of unknown biological significance.