Inhalation Toxicity of Phosphine in the Rat: Acute, Subchronic, and Developmental

Abstract

Lethality is the primary hazard of phosphine exposures. All phosphine-related effects seen at sublethal exposure levels were relatively small and completely reversible either during the exposure or during a recovery period. Acutely, phosphine exposures were lethal to female Fischer 344 rats at a cumulative concentration-time product of about 180 ppm-hr if the concentration were greater than 5–7 ppm. For daily 6-hr exposures, the median lethal times were 3 days at 10 ppm and 4 days at 7.5 ppm. Thirteen daily 6-hr exposures to 5 ppm were not lethal. Decreased erythrocytes, lung congestion, and increased kidney weights with coagulative necrosis of the tubular epithelium in the outer cortex were seen in the 10 ppm rats only. The effects were more severe in females than in males. Subchronic exposures to 0.37, 1, or 3.1 ppm of phosphine were conducted. Ten animals per sex per group were sacrificed after 4 and 13 weeks of exposure and 4 weeks of recovery. These exposure produced a dose-related decrease in body weight gain at 1 and 3 ppm. Food consumption was decreased at 1 and 3 ppm and transiently in the 0.37 ppm group. Five percent decreases in erythrocytes, hemoglobin, and hematocrit were seen in the 3 ppm group after 13 weeks of exposure. All effects seen in the subchronic study were completely reversible either during the 13-week exposure or the 4-week recovery period. Exposure of pregnant CD^R rats (24 per group) to 0.03, 0.33, 2.8, or 4.9 ppm of phosphine for 6 hr/day over the days 6–15 gestation interval was not maternally or developmentally toxic.