Parvez Shahid, Rice Glenn E, Teuschler Linda K, Simmons Jane Ellen, Speth Thomas F, Richardson Susan D, Miltner Richard J, Hunter E Sidney, Pressman Jonathan G, Strader Lillian F, Klinefelter Gary R, Goldman Jerome M, Narotsky Michael G
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.
J Environ Sci (China). 2017 Aug;58:311-321. doi: 10.1016/j.jes.2017.05.042. Epub 2017 Jun 7.
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 mixtures. Because 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.
开发了一种基于回归建模的方法，以识别成分化学物质对高度复杂、环境现实的消毒副产物（DBP）混合物毒性的贡献。饮用水的化学消毒会形成DBP混合物。由于担心可能的生殖和发育毒性，在一项多代研究中，将通过浓缩水氯化产生的DBP全混合物（WM）作为饮用水给予Sprague-Dawley（S-D）大鼠。分别检查了雄性和雌性后代青春期开始的年龄，即包皮分离（PPS）和阴道开口（VO）。与对照组相比，在雌性后代中观察到青春期开始略有延迟，但具有统计学意义，而在雄性后代中未观察到。将WM诱导的青春期开始年龄差异与给予九种受监管DBP的定义混合物（DM）或单个DBP的S-D大鼠中报告的差异进行比较。使用来自DM研究的关于PPS或VO年龄的个体动物数据建立回归模型。然后将WM和单个DBP研究中报告的青春期开始数据与DM模型进行比较。在WM处理的雌性大鼠中观察到的青春期开始延迟与DM回归模型预测的延迟无法区分，这表明DM中的九种受监管DBP可能是WM中观察到的大部分延迟的原因。该方法适用于其他类型化学物质的混合物和其他终点。
