NTP Technical Report on the Toxicity Studies of Hexachlorobenzene (CASRN 118-74-1) Administered by Gavage to Female Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats

Abstract

Despite the cessation of its production and use in many parts of the world, hexachlorobenzene (HCB) remains highly persistent in the environment, and chronic, low-dose exposure to HCB in humans continues. Its structural resemblance to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), ability to activate the aryl hydrocarbon (Ah) receptor, TCDD-like toxicities, and bioaccumulative nature suggest HCB be included in the toxic equivalency factor (TEF) methodology. Consequently, the National Toxicology Program conducted this subchronic study of HCB, including measurement of a variety of toxicological and biochemical endpoints, to allow comparison to TCDD data obtained in a previous 2-year bioassay. Groups of 10 female Sprague Dawley (Hsd:Sprague Dawley ® SD ®) rats (core study) were administered doses of 0.03, 0.1, 0.3, 1, 3, 10, or 25 mg HCB/kg body weight/day (mg/kg/day) in corn oil:acetone (99:1) by gavage, 5 days/week for 13 weeks (3 months). Elimination of HCB after repeated dosing was evaluated in a group of 10 female rats (elimination study) administered 0.03 or 25 mg/kg/day for 13 weeks (3 months) and then held without dosing until necropsy at 21 (5 rats) or 29 (5 rats) weeks. Vehicle control female rats (10 core study and 10 elimination study) were administered the corn oil:acetone vehicle only. Genotoxicity in Salmonella typhimurium was also evaluated.