Subchronic inhalation neurotoxicity studies of ethyl acetate in rats.

Rats were exposed to 0, 350, 750 or 1500 ppm of ethyl acetate by inhalation for 6 h per day, 5 days per week for 13 weeks. Functional observational battery (FOB) and motor activity tests occurred on non-exposure days during weeks 4, 8 and 13, after which tissues were microscopically examined for neuropathology. A subset of rats was monitored during a 4-week recovery period. Exposure to 750 and 1500 ppm, diminished behavioral responses to unexpected auditory stimuli during the exposure session and appeared to be an acute sedative effect. There were no signs of acute intoxication 30 min after exposure sessions ended. Rats exposed to 750 and 1500 ppm had reduced body weight, body weight gain, feed consumption, and feed efficiency, which fully or partially recovered within 4 weeks. Reductions in body weight gain and feed efficiency were observed in male rats exposed to 350 ppm. The principal behavioral effect of subchronic exposure was reduced motor activity in the 1500 ppm females, an effect that was not present after the 4-week recovery period. All other FOB and motor activity parameters were unaffected, and no pathology was observed in nervous system tissues. Operant sessions were conducted in another set of male rats preconditioned to a stable operant baseline under a multiple fixed ratio-fixed interval (FR-FI) schedule of food reinforcement. FR response rate, FR post-reinforcement pause duration, and the pattern of FI responding were not affected during or after the exposure series. In contrast, within-group FI rate for the treatment groups increased over time whereas those of the controls decreased. A historical control group, however, also showed a similar pattern of increase, indicating that these changes did not clearly represent a treatment-related effect. Results from these studies indicate a LOEL of 350 ppm for systemic toxicity based on the decreased body weight gain in male rats, and a LOEL of 1500 ppm for neurotoxicity based on the transient reduction in motor activity in female rats. In conclusion, there was no evidence that subchronic exposure up to 1500 ppm ethyl acetate produced any enduring neurotoxic effects in rats.

Subchronic inhalation exposure to acetone vapor and scheduled controlled operant performance in male rats.

Groups of adult male rats (10/group) were used to assess whether subchronic inhalation exposure to 0, 1000, 2000, or 4000 ppm of acetone vapor altered schedule-controlled operant performance. Rats were exposed to acetone vapor for 6 h/day, 5 days/wk, for a 13-wk period. Extensive training prior to the exposure series established a stable baseline of lever-pressing on a multiple fixed-ratio-fixed-interval (FR 20-FI 120 s) schedule of food presentation. Operant sessions occurred prior to each daily exposure to avoid confounding the detection of enduring behavioral effects with transient acute effects. FI response rate, FI index of curvature, and FR running rate of response were not affected during or after the 13-wk exposure series. FR post-reinforcement pause duration for the control group increased during the course of the study more than that of the 2000 ppm and 4000 ppm groups, which changed only slightly relative to pretreatment baseline. Based on the performance of historical controls that had FR pause durations similar to those of acetone-treated groups, the differences in FR pause duration were probably due to drift of the concurrent control group and were not related to acetone treatment. Prolonged exposure to up to 4000 ppm acetone vapor does not appear to have enduring effects on nervous system functions that mediate the performance of a complex, learned task.