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Integrated Multidisciplinary Assessment of Environmentally Realistic Complex Mixtures of Drinking Water Disinfection ByProducts (DBPs) (The 4Lab Study)
Citation:
SIMMONS, J. E., J. E. Narotsky, M. G. Teuschler, J. G. Pressman, E. S. Hunter, E. S. Hunter, G. E. Rice, G. R. Klinefelter, J. M. Goldman, T. F. SPETH, L. F. STRADER, R. J. MILTNER, S. Parvez, A. MCDONALD, D. S. BEST, AND C. A. Dingus. Integrated Multidisciplinary Assessment of Environmentally Realistic Complex Mixtures of Drinking Water Disinfection ByProducts (DBPs) (The 4Lab Study). Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
Epidemiology studies suggest associations between human use of chlorinated water and reproductive/developmental effects (pregnancy loss, low birth weight), that are unexpected based on available single-chemical animal data
Description:
More than 600 DBPs have been identified; yet ~50% of the total organic halide from chlorination is unidentified. Epidemiology studies suggest associations between human use of chlorinated water and reproductive/developmental effects (pregnancy loss, low birth weight), that are unexpected based on available single-chemical animal data. To evaluate pup weight and prenatal loss, and other endpoints, we conducted a multigenerational reproductive/developmental assay, integrated with extensive chemical analysis. To evaluate DBPs at environmentally relevant doses and include the large unidentified fraction, methods were developed for: statistical power; concentration and chlorination ofwater concentrates; an animal water delivery system; and, risk assessment. Source water was concentrated ~130 fold by reverse osmosis, chlorinated, and provided as drinking water to Sprague-Dawley rats; controls received purified water. Timed-pregnant females (PO generation, 40 control:60 treated) were exposed from gestation day 2 until weaning of the Fllitters. Treatment of 'El animals continued throughout the study. A second block of PO females was maintained through PD 6 of the Fl generation. No treatment effects were detected for pup weight, pre-and post-natal loss, eye opening, gestation length, nipple retention, or body weight. In Fl adults, no effects were detected on organ weights, male serum testosterone or female hypothalamic catecholamine levels. Statistically significant effects were increased anogenital distance in Fl males and a slight <1 day) delay in puberty in Fl females. The delayed puberty was consistent with the dose-response of a defined mixture of 9 regulated DBPs mixed at a representative ratio. (Abstract does not reflect EPA policy.)