MOTOR-ACTIVITY EFFECTS IN FEMALE FISCHER-344 RATS EXPOSED TO ISOPROPANOL FOR 90 DAYS

In a previous subchronic neurotoxicity study, increases in motor activ ity were observed for female rats after 9 and 13 weeks of exposure to 5000 ppm of isopropanol vapor.(1) The present study was conducted to e valuate the reproducibility of these effects and, if reproducible, to assess the potential for reversibility following cessation of exposure . Two groups, each containing 30 female Fischer 344 rats, were exposed to concentrations of zero (control) and 5000 ppm of isopropanol vapor for 6 h per day, 5 days per week. Fifteen of the animals in the contr ol and 5000 ppm groups were exposed for 9 weeks (designated as the 9-w eek subgroup), while the other 15 animals in each group were exposed f or 13 weeks (designated as the 13-week subgroup). Motor activity was a ssessed for both subgroups prior to exposure and following 4, 7 and 9 weeks of exposure. Motor activity was also measured for rats in the 13 -week subgroup following 11 and 13 weeks of exposure, These motor acti vity measurements were made 18-20 h following the end of the last expo sure for that week. In addition, to evaluate the reversibility of moto r activity effects, measurements were made on three occasions during t he week following the final exposure for rats in both the 9-week and 1 3-week subgroups and weekly thereafter for five additional weeks for r ats in the 13-week subgroup. Increases in cumulative test session moto r activity counts were observed following 4, 7 and 9 weeks of exposure for rats in the 9-week subgroup. Increases in cumulative test session motor activity counts were also observed following 4, 7, 9, 11 and 13 weeks of exposure for rats in the 13-week subgroup. Reversibility of this effect was observed for rats in the 9-week subgroup within 2 days following the last exposure. Reversibility was also noted for rats in the 13-week subgroup but not until Study Week 15 (2 weeks following t he last exposure), Minor changes were observed in the shape of the mot or activity habituation curves for isopropanol-exposed animals in the 9-week and 13-week subgroups at ca, 50% of the measurement intervals b eginning at Study Week 4, While most of these statistical changes were observed in conjunction with increases in cumulative test session mot or activity, some were observed following time points where recovery o f the cumulative test session motor activity counts had occurred. No c hange in the shape of the motor activity habituation curve was observe d at 42 days following the last exposure, indicating that complete rec overy of motor activity effects had occurred, Thus, repeated exposure of female rats to 5000 ppm of isopropanol produced reversible increase s in motor activity. (C) 1998 John Wiley & Sons, Ltd.