ACUTE AND SUBCHRONIC INHALATION NEUROTOXICITY OF PHOSPHINE IN THE RAT

Abstract

Phosphine is a highly toxic gas used as a grain fumigant, as a dopant in semiconductor manufacturing, and in the production of organophosphines. To evaluate potential acute neurotoxic effects, 11 male and 11 female CD rats per group were exposed via wholebody inhalation for 4 h to mean concentrations of 0, 21, 28, or 40 ppm phosphine. A functional observational battery (FOB) consisting of quantitative and qualitative neurobehavioral parameters and motor activity was evaluated pretest, at the time of peak effect postexposure, approximately 1 h, and at 7 and 14 days postexposure. Six rats per sex per group were evaluated for neuropathologic effects 14 days postexposure. Exposure to phosphine did not alter FOB evaluations. A phosphine-related decrease in horizontal activity, vertical activity, total distance, and stereotypy was observed in the 21, 28, and 40 ppm phosphine exposure groups when compared to the control group on day 1, but not 7 or 14 days later. No phosphine-related neuropathologic changes were found. To evaluate potential subchronic neurotoxicity, 4 groups of 16 male and 16 female CD rats were exposed 6 h/day, 5 days/ wk, for 13 wk to either 0, 0.3, 1, or 3 ppm phosphine. In the 0 and 3 ppm groups an additional 6 rats per sex per group were used for a 2-wk recovery study. FOB and motor activity evaluations were conducted prior to study initiation and during wk 4, 8, and 13 of exposure. Following 13 wk of exposure, 6 rats per sex per group were randomly selected for neuropathology evaluation, as were the additional 6 rats per sex in the 0 and 3 ppm groups after 2 wk of recovery. There were no phosphine-related changes seen in the FOB, motor activity, or neuropathologic evaluations. Under the conditions of this subchronic inhalation study, exposure to 0.3, 1, or 3 ppm phosphine was not neurotoxic.