Reproductive Toxicity of a Mixture of Regulated Drinking-Water Disinfection By-Products in a Multigenerational Rat Bioassay

BACKGROUND: Trihalomethanes (THMs) and haloacetic 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, F-1, and F-2 generations) from gestation day 0 of the parental generation to postnatal day (PND) 6 of the F-2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 500x, 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; body weights were reduced at 2,000x. Prenatal and postnatal survival were unaffected. F-1 pup weights were unaffected at birth but reduced at 2,000x on PND6 and at >= 1,000x on PND21. Postweaning F-1 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. F-1 estrous cycles and fertility were unaffected, and F-2 litters showed no effects on pup weight or survival. Histologically, P-0 (parental) dams had nephropathy and adrenal cortical pathology at 2,000x. CONCLUSIONS: A mixture of regulated DBPs at up to 2,000x the MCLs had no adverse effects on fertility, pregnancy maintenance, 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.