Pentachlorophenol carcinogenicity: extrapolation of risk from mice to humans.
1. Pentachlorophenol (PCP) has been found to be carcinogenic in mice. The objective of this study was to extrapolate to humans the risk of cancer from data obtained in mice using information on disposition, serum 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 responsible for the carcinogenicity. In addition, the occurrence of TCHQ as a metabolite of PCP in humans is still questionable. Therefore, cancer 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 serum protein binding are taken into account is used. The method gives estimates of equivalent human doses of PCP which are up to 4 times smaller than those obtained using body surface area. For both interspecies extrapolation methods, the estimated virtually-safe doses of PCP are smaller than the average daily intakes reported in groups of subjects nonspecifically 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.
Reigner
B G
BG
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
Bois
F Y
FY
Tozer
T N
TN
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000453:epidemiology; D010416:Pentachlorophenol / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013045:Species Specificity
D001798:Blood Proteins; D002273:Carcinogens; D010416:Pentachlorophenol