Evaluation of global literature for definition of dose-response relationship for hexachlorobenzene toxicity

Numerous research groups have generated data that can be collated to define the hexachlorobenzene (HCB) dose-response relationship for subchronic/chronic target-organ toxicity, oncogenicity and reproductive toxicity. Subchronic toxicity studies in rats are typified by Kuiper-Goodman et al. (1977) and Mollenhauer et al. (1975) in which the lowest-observed-effect-level was 0.25-2.0 mg/kg per day and the no-observed-effect-level was 0.05-0.5 mg/kg per day. In the pig, den Tonkelaar et al. (1978) defined the subchronic lowest-observed-effect-level and the no-observed-effect-level as 0.5 and 0.05 mg/kg per day, respectively. In a 12-month dog study by Gralla et al. (1977) the lowest-observed-effect-level was 10 mg/kg per day and the no-observed-effect-level was 1 mg/kg per day. Rozman et al. (1978) reported a no-observed-effect-level of 0.033 mg/kg per day in a study of 18 months' duration in the monkey. Oncogenic assessment of HCB has been carried out in studies using the hamster (Cabral et al., 1977), the mouse (Cabral et al., 1979) and the rat (Arnold et al., 1978; Smith & Cabral, 1980), with responses obtained at doses of approximately 2-4 up to greater than 24 mg/kg per day, but no response at doses of approximately 0.4-0.8 up to 6 mg/kg per day. Reproductive toxicity studies of HCB have used the cat (Hansen et al., 1979a), the pig (Hansen et al., 1979b) and the rat (Grant et al., 1977), obtaining no-observed-effect-levels of 1.0, greater than 0.025-0.5 and 1-2 mg/kg per day respectively, for the three species. Overall, the substantial amount of toxicity data from these studies can be collated into a cohesive pattern that defines the dose-response relationship for HCB toxicity.