Subchronic oral toxicity tissue distribution and clearance of hexachloroethane in the rat

ABSTRACTHexachloroethane (HCE) was fed to Fischer 344 rats at approximate doses of 0, 1, 15 or 62 mg/kg/day for 16 weeks. Selected tissues were assayed at termination for HCE content. Histopathological examination identified the kidney as the primary target organ with male rats more sensitive than female rats. The kidney concentration of HCE increased proportionately with dose in the males, but there were disproportionately small increases with dose in females. A group of male rats was given 62 mg/kg/day for 8 weeks to estimate tissue clearance. Clearance of HCE from fat, liver, kidney and blood occurred in an apparent first-order manner with a half-life of approximately 2.5 days. The apparent first-order elimination suggests that HCE metabolism and excretion were not saturated in rats given up to 62 mg/kg/day and suggests that, in the range of doses given, toxicity should be proportional to exposure concentration. The no-observable-effect level (NOEL) for toxicity was 1 mg/kg/day for male and female rats.