Biologically based dose-response model for liver tumors induced by trichloroethylene.
The existing extensive laboratory data on trichloroethylene (TCE) and its two metabolites, dichloroacetic (DCA) and trichloroacetic (TCA), are used to explore the relationship among these three compounds. Under the hypothesis that these compounds induce liver tumors in mice through promotion of preexisting initiated cells, it is demonstrated that DCA alone could be responsible for all the response of carcinomas in liver of B6CF(1) mice. The focus of this paper is on how a plausible biological assumption could impact on low-dose risk estimates, rather than on the risk estimate per se. The findings suggest that low-dose risk estimates to humans would be overestimated unless the different background rates between mice and humans are properly accounted for.
Chen
C W
CW
National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC 20460, USA. chen.chao@epa.gov
D000818:Animals; D002274:Carcinogens, Environmental / Q000009:adverse effects*; D003999:Dichloroacetic Acid / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D051379:Mice; D008954:Models, Biological; D018570:Risk Assessment; D014238:Trichloroacetic Acid / Q000009:adverse effects; D014241:Trichloroethylene / Q000009:adverse effects*
D002274:Carcinogens, Environmental; D014241:Trichloroethylene; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid