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Method to assess component contribution to toxicity of complex mixtures： Assessment of puberty acquisition in rats exposed to disinfection byproducts

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Journal of Environmental Sciences 2017年第8期29卷 311-321页

作者： Shahid Parvez Glenn E.Rice Linda K.teuschler Jane Ellen Simmons Thomas F.Speth Susan D.Richardson Richard J.Miltner E.Sidney Hunter Ⅲ Jonathan G.Pressman Lillian F.Strader Gary R.Klinefelter Jerome M.Goldman Michael G.Narotsky Indiana University Richard M. Fairbanks School of Public Health Department of Environmental Health Sciences IUPUI Campus Indianapolis IN 46202 USA National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati OH 45268 USA lincla teuschler and associates St. Petersburg FL 33707 USA National Health and Environmental Effects Research Laboratory Office of Research and Development U.S. Environmental Protection Agency Research Triangle Park NC 27711 USA National Risk Management Research Laboratory Office of Research and Development U.S. Environmental Protection Agency Cincinnati OH 45268 USA Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29208 USA

A method based on regression modeling was developed to discern the contribution of component chemicals to the toxicity of highly complex, environmentally realistic mixtures of disinfection byproducts（DBPs）. Chemical disinfection of drinking water forms DBP *** of concerns about possible reproductive and developmental toxicity, a whole mixture（WM） of DBPs produced by chlorination of a water concentrate was administered as drinking water to Sprague–Dawley（S–D） rats in a multigenerational study. Age of puberty acquisition,i.e., preputial separation（PPS） and vaginal opening（VO）, was examined in male and female offspring, respectively. When compared to controls, a slight, but statistically significant delay in puberty acquisition was observed in females but not in males. WM-induced differences in the age at puberty acquisition were compared to those reported in S–D rats administered either a defined mixture（DM） of nine regulated DBPs or individual DBPs. Regression models were developed using individual animal data on age at PPS or VO from the DM study. Puberty acquisition data reported in the WM and individual DBP studies were then compared with the DM models. The delay in puberty acquisition observed in the WM-treated female rats could not be distinguished from delays predicted by the DM regression model, suggesting that the nine regulated DBPs in the DM might account for much of the delay observed in the WM. This method is applicable to mixtures of other types of chemicals and other endpoints.

关键词： Drinking water disinfection byproducts DBP Puberty delay Four Lab Study Mixtures risk assessment

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