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Comprehensive Assessment of a Chlorinated Drinking Water Concentrate in a Rat Multigenerational Reproductive Toxicity Study##
Narotsky, M., G. Klinefelter, J. Goldman, D. Best, Anthony McDonald, L. Strader, J. Suarez, A. Murr, I. Thillainadarajah, E. Sidney Hunter, S. Richardson, T. Speth, R. Miltner, J. Pressman, L. Teuschler, G. Rice, V. C. Moser, R. Luebke, AND Jane Ellen Simmons. Comprehensive Assessment of a Chlorinated Drinking Water Concentrate in a Rat Multigenerational Reproductive Toxicity Study##. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 47(18):10653-59, (2013).
Some epidemiological studies report associations between drinking water disinfection by-products (DBPs) and adverse reproductive and developmental effects, e.g., low birth weight, spontaneous abortion, stillbirth, and birth defects. To address concerns raised by these studies, we evaluated an environmentally relevant “whole” mixture of DBPs (i.e., including unidentified DBPs and realistic proportions of known DBPs at low-toxicity concentrations) in a multigenerational rat bioassay. Source water was collected from a drinking water utility, concentrated 136 fold, chlorinated, and provided as the sole source of drinking water to Sprague-Dawley rats. Timed-pregnant females (P0 generation) were exposed during gestation and lactation. Weanlings (F1 generation) were maintained in their respective treatment groups and bred to produce an F2 generation. Large sample sizes enhanced statistical power, particularly for pup weight. No adverse effects were observed for most endpoints, including pup weight, prenatal loss, pregnancy rate, gestation length, onset of puberty in males, hormone levels, estrous cycles, immunological endpoints, and most neurobehavioral endpoints. Significant, albeit slight, effects included delayed puberty for F1 females, reduced caput epidydimal sperm counts in F1 adult males, and increased incidences of thyroid follicular cell hypertrophy in adult females. These findings highlight areas for future research whereas the largely negative findings, particularly for pup weight and prenatal loss, ease concerns raised by some epidemiological studies.
This research investigates the reproductive/developmental effects of environmentally realistic complex mixtures of drinking water disinfection by-products in a multigenerational study with rats, addressing uncertainties in findings from epidemiological studies.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
TOXICOLOGY ASSESSMENT DIVISION
ENDOCRINE TOXICOLOGY BRANCH