Effects of inhalation exposure to hexachlorocyclopentadiene on rats and monkeys

Hexachlorocyclopentadiene (Hex or C-56) is a highly reactive intermediate used in the production of some insecticides, flame retardants, and resins. The present study was conducted to evaluate the inhalation toxicity of high-purity Hex (97.7%) in rats and monkeys to provide information on the potential hazards of accidental exposure of workers to Hex vapors. Acute, range-finding (14-d), and subchronic (90-d) inhalation studies were conducted with Sprague-Dawley rats and subchronic (90-d) inhalation studies were conducted with cynomolgus monkeys. Both acute and range-finding studies with rats showed a steep dose-response curve, and male rats were more sensitive than females. In the range-finding study with rats the threshold of toxicity for Hex was 0.11-0.5 ppm. Histopathologic examination on rats in the 0.5 ppm group revealed lesions in the olfactory and bronchiolar epithelium and inflammatory exudate in the lumens of the respiratory tract; these changes were consistent with observed impaired respiratory function, confirming the lung as the main target organ. Recovery and regression of lung lesions in rats were noted 2-3 wk after termination of exposure. In the 90-d study, inhalation of Hex vapors at concentrations up to 0.2 ppm for 6 h/d, 5 d/wk, produced no detectable physical or clinical effect and no remarkable gross or histological alterations in rats or monkeys.