Subchronic Neurotoxicity of Vaporized Diisopropyl Ether in Rats

The neurotoxicity potential of diisopropyl ether (DIPE) during subchronic exposures was evaluated in rats using a functional observational battery (FOB), automated motor activity, and neuropathology. Sprague-Dawley rats were exposed 5 dl wk for 13 weeks by inhalation to either 0, 450, 3250, or 7060 ppm DIPE. Body weights were recorded weekly and clinical observations were recorded prior to each exposure. The FOB and a measurement of motor activity were performed before the first exposure. The FOB was repeated following 2, 4, 8, and 13 weeks of exposure, and motor activity was determined following 4, 8, and 13 weeks of exposure. After completion of the final evaluations, the animals were intravascularly perfused with phosphate-buffered 5% glutaraldehyde. Microscopic examination of the brain, spinal cord, gasserian and dorsal root ganglia, and sciatic nerve was performed on six animals/ group/ sex exposed to 0 or 7060 ppm DIPE. Motor activity in a figure-eight maze and unperturbed activity in the FOB were decreased at week 4 in females exposed to 7060 ppm; activity in the FOB was also decreased in females exposed to 450 ppm at week 4. Other changes in the FOB appeared to be minor, and none were observed during microscopic examination of tissues from the nervous system. In conclusion, inhalation exposures to DIPE at concentrations as high as 7060 ppm for 13 weeks resulted in few observable effects on the nervous system.