Evaluation of subchronic neurotoxicity of n-butyl acetate vapor

n-Butyl acetate, a common industrial solvent, was selected by the US EPA as a chemical of concern for neurotoxicity as part of the Multisubstance Rule for the Testing of Neurotoxicity. The neurotoxic potential of n-butyl acet ate was investigated in Sprague-Dawley rats using a functional observationa l battery, motor activity, neurohistopathology, and schedule-controlled ope rant behavior (SCOB) as indicators of neurotoxicity. Animals were exposed t o concentrations of 0, 500, 1500, or 3000 ppm of n-butyl acetate for 6 hour s per day for 65 exposures over 14 weeks. Functional observational battery and motor activity values for ad libitum-fed male and female rats were meas ured during Weeks -1, 4, 8, and 13. SCOB testing of food-restricted animals , using a multiple fixed ratio/fixed interval schedule, was conducted daily prior to each exposure to maintain the operant behavior; the data from Wee ks -1, 4, 8, and 13 were evaluated for evidence of neurotoxicity. Transient signs of sedation and hypoactivity were observed only during exposure to t he 1500 and 3000 ppm concentrations. The only signs of systemic toxicity we re reduced body weights for the 3000 ppm ad libitum-fed groups and occasion ally for the female 1500 ppm ad libitum-fed group. No evidence of neurotoxi city was seen during the functional observational battery examinations. Mot or activity for the 3000 ppm male group was significantly (p less than or e qual to 0.05) higher than for the control group only during Week 4. No sign ificant differences were observed among groups for Weeks 8 and 13. No signi ficant differences in motor activity values were observed for female rats. No significant differences were seen in operant behavior at any test vapor concentration. Microscopic evaluations of sections from the brain, spinal c ord (cervical and lumbar regions), dorsal and ventral spinal roots, dorsal root ganglia, sciatic nerve, and tibial nerve of animals in the control and 3000 ppm groups did not indicate any treatment-related effects. ln conclus ion, there was no evidence of cumulative neurotoxicity based on the functio nal observational battery, motor activity, neurohistopathology, and schedul e-controlled operant behavior endpoints. The data presented here are releva nt to the neurotoxicity risk assessment of n-butanol due to the rapid hydro lysis of n-butyl acetate in vivo. (C) 1998 Intox Press, Inc.