An inhalation study was conducted to investigate the toxicokinetics and mechanism(s) of carbon disulfide (CS2) neurotoxicity in rats. The objectives of the toxicokinetic studies were to determine the systemic availability, evaluate dose proportionality, and establish basic pharmacokinetic parameters for CS2 in rats. The objectives of the neurotoxicity study were to characterize the progression of CS2 neurotoxicity and dose-repose relationships, identify biomarkers of CS2 exposure; determine the molecular mechanism(s) of CS2 peripheral neuropathy, characterize the morphology of neurotoxic lesions and correlate the neurobehavioural studies and electrophysiology with biomarkers of exposure and neuropathology. Rats were exposed to 4 exposure concentrations of CS2 gas 6 hours/day, 5 days/week for 2, 3, 8, or 13 weeks. At each time point, blood was analyzed for CS2, urinary metabolites were measured, neurobehavioural and electrophysiological tests were conducted to monitor development of neurotoxicity, and brain, spinal cord and nerve tissues collected for histopathology/electron microscopy and measurement of biomarkers. Analysis of data is in progress. An update of the neurotoxicity study was presented to the NTP Board of Scientific Counselors in June 1995.
