Studies on the toxicity of hexachlorophene in the rat

Abstract

Acute and subacute toxic effects of hexachlorophene (HCP) were studied in Wistar rats. The ip LD50 of HCP ranged between 21.8 mg/kg in mature rats and 40.0 mg/kg in weanlings. The oral LD50 varied similarly with age from 57.6 to 87.0 mg/kg, respectively. HCP was slightly less toxic to male rats than to females. Signs of intoxication were general lethargy, posterior paralysis, increased respiration rate, hyperthermia and diarrhea. Maximum body temperatures were attained approximately 1.5 hr after ip injection. In subacute studies, HCP was fed to weanling rats at dietary concentrations from 12.5 to 400 ppm HCP for a 16-week period. Animals on the 400 ppm diet, ingesting an average of 28.9 mg HCP/kg/day, developed severe posterior paralysis during the first few days of the study, and died within 10 days. No drug related mortality was observed in the other groups. Paralysis was also observed initially in rats fed the 200 ppm HCP diet (average intake 23.6 mg/kg/day) but by the second week, these animals had apparently recovered. Rats fed diets containing 100 and 200 ppm HCP (average intake 7.73 and 14.9 mg/kg/day) developed significant histopathologic changes in the brain, characterized by extensive vacuolization and edema of the myelinated areas. Significant growth depression and reduced plasma alkaline phosphatase activities were also found at 8 and 16 weeks in rats receiving the 200 ppm diet. The minimum “no effect” intake of HCP under the conditions of this study was between 3.7 mg/kg/day and something less than 7.7 mg/kg/day.