The aims of the study are (1) to investigate the mechanism by which inhaled COS causes neurotoxicity, (2) to evaluate the potential reproductive toxicity of COS, and (3) to compare the mechanisms of COS toxicity with that of carbon disulfide (CS2), a known neurotoxin. A 4-day pilot study was performed to evaluate the range of COS exposure concentrations to be used in the 12-week study. Rats were exposed to 75, 150, 300,or 600 ppm, for 6 hr/day. After two exposures to 600 ppm, animals were hypoactive, and moved with an unsteady gait. For this reason the 600 ppm exposure was terminated. Exposure to lower concentrations for 4 days had no visible effects. A second cohort of animals was exposed to 0, 15, 300, or 600 ppm COS for 1 day and then held 2 weeks in an attempt to replicate results of a previous study reporting progressive neurotoxicity after a single exposure. The neurotoxicity did not appear to be progressive; however, brain lesions were apparent upon gross observation of tissue 2 weeks after exposure. A 12-week study was conducted to evaluate the neurotoxicity of COS. Rats were exposed for 12 weeks to 0, 200, 300, or 400 ppm COS. A functional observational battery (FOB) was conducted after 6 and 12-wks of exposure. Only minimal behavioral effects were detected in exposed rats at both time points. Brains were collected from perfused rats after 4, 8, and 12 weeks for histological evaluation, and magnetic resonance microscopy (MRM). Lesions were detected in the parietal cortex by both light microscopy and MRM. In addition, MRM detected a more consistent lesion in the posterior colliculus of rats exposed to 300 and 400 ppm COS. Brains were also collected for biochemical measurements after exposure for 4, 8, and 12 weeks. Cytochrome oxidase activity was decreased in a dose-dependent manner in the parietal cortex and the posterior colliculus after 12-weeks of exposure. Electrophysiological tests were conducted on a subgroup of rats after 12-weeks of exposure; these data are still being evaluated.
