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CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS.
Citation:
Morgan, D. L., V C. Moser, D W. Herr, AND R. C. Sills. CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Carbonyl sulfide (COS) is an intermediate in the production of pesticides and herbicides, and is a metabolite of the neurotoxicant carbon disulfide. The potential neurotoxicity of inhaled COS was investigated in F344 rats. Male rats were exposed to 0, 75, 150, 300, or 600 ppm COS for 6h/d. After 2 exposures to 600 ppm rats exhibited signs of neurotoxicity. Primary lesions included necrosis in the parietal cortex, thalamus, posterior colliculus and anterior olivary nucleus. Male and female rats were exposed to 0, 300, 400, or 500 ppm COS for 12 exposures (6h/d, 5d/w). All 10 males and 4/10 females exposed to 500 ppm were moribund. Rats exposed to 400 ppm had slight gait abnormalities, hypotonia, decreased motor activity and grip strength. Bilateral malacia of the parietal cortex was observed grossly in rats exposed to 400 and 500 ppm. Lesions at 400 and 500 ppm included necrosis in the parietal cortex and putamen, and at 500 ppm included bilateral necrosis in the retrospenial cortex, thalamus, posterior colliculus, and olivary nucleus. In a 12-week (6h/d, 5d/wk) study, male and female rats were exposed to 0, 200, 300, or 400 ppm COS. Microscopic lesions were present primarily in the parietal cortex and posterior colliculus of rats exposed to 400 ppm. Occasional areas of necrosis were present in the putamen, thalamus and anterior olivary nucleus. Decreases in brain stem auditory-evoked responses were detected in the posterior colliculus, lateral meniscus and auditory olivary nucleus in rats exposed to 400 ppm COS for 12 weeks. A concentration-related decrease in cytochrome oxidase activity was detected in the parietal cortex and posterior colliculus. Cytochrome oxidase activity was decreased at COS concentrations that did not cause detectable lesions, suggesting that brain lesions may be preceded by disruption of the mitochondrial respiratory chain by COS with a subsequent decrease in cellular ATP. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.