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Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay
Citation:
Narotsky, M., G. Klinefelter, J. Goldman, A. Deangelo, D. Best, T. Mcdonald, L. Strader, A. Murr, J. Suarez, M. George, S. Hunter, AND J. Simmons. Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 123(6):564-70, (2015).
Impact/Purpose:
This paper provides a thorough assessment of in vivo reproductive and developmental toxicity of a defined mixture of nine regulated disinfection by-products (four trihalomethanes and five haloacetic acids) at environmentally realistic chemical proportions, providing insight into the potential health effects of chlorinated drinking water. Results were negative in both the F1 and F2 generations for prenatal loss and pup birth weight, endpoints of particular concern because of positive results in some epidemiology studies. Male progeny at 2000× had a small but significantly increased incidence of retained nipples and effects on sperm motility. Onset of puberty (vaginal opening in females, preputial separation in males) showed dose-related delays at 1000× and 2000×. F1 estrous cycles, breeding, and fertility were unaffected. Exposure at 500× had no adverse effects on any of the endpoints examined.
Description:
BACKGROUND:Trihalomethanes (THMs) and haloaretic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.OBJECTIVE: We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay.METHODS: Sprague-Dawley rats were exposed (parental, F1, and F2 generations) from gestation day 0 of the parental generatbn to postnatal day (PND) 6 of the F2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 50Ox, 1,000x , or 2,000x of the U.S. Environmental Protection Agency's maximum contaminant levels (MCLs).RESULTS: Maternal water consumption was reduced at ≥1,000x; bodyweights were reduced at 2,000x. Prenatal and postnatal survival were unaffected. F1 pup weights were unaffected at birth but reduced at 2,000x on PND6 and at ≥1,000x on PND21. Postweaning F1 body weights were reduced at 2,000x, and water consumption was reduced at ≥500x. Males at 2,000x had a small but significantly increased incidence of retained nipples and compromised sperm motility. Onset of puberty was delayed at 1,000x and 2,000x. F1 estrous cycles and fertility were unaffected, and F2 litters showed no effects on pup weight or survival. Histologically, PO (parental) dams had nephropathy and adrenal oortical pathology at 2,000x.CONCLUSIONS: A mixture of regulated DBPs at up to 2,000x the MCLs had no adverse effects on fertility, pregnancy maintenanre, prenatal survival, postnatal survival, or birth weights. Delayed puberty at ≥1,000x may have been secondary to reduced water consumption. Male nipple retention and compromised sperm motility at 2,000x may have been secondary to reduced body weights.
