PENTACHLOROPHENOL CARCINOGENICITY - EXTRAPOLATION OF RISK FROM MICE TO HUMANS

1 Pentachlorophenol (PCP) has been found to be carcinogenic in mice. T he objective of this study was to extrapolate to humans the risk of ca ncer from data obtained in mice using information on disposition, seru m protein binding and metabolism of PCP across species. 2 A review of the literature indicates that neither PCP nor a mutagenic metabolite, tetrachlorohydroquinone (TCHQ), has been specifically identified as re sponsible for the carcinogenicity. In addition, the occurrence of TCHQ as a metabolite of PCP in humans is still questionable. Therefore, ca ncer risk assessment is performed on the assumption that PCP itself is responsible for the carcinogenicity. 3 For interspecies extrapolation , a new method in which interspecies differences in clearance and seru m protein binding are taken into account is used. The method gives est imates of equivalent human doses of PCP which are up to 4 times smalle r than those obtained using body surface area. For both interspecies e xtrapolation methods, the estimated virtually-safe doses of PCP are sm aller than the average daily intakes reported in groups of subjects no nspecifically exposed to PCP. Corresponding extra risks of cancer for lifetime exposure are from 20 to 140 times greater than the acceptable extra risk (10(-6)). The results obtained with this approach indicate that PCP is a possible public health hazard.