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

Abstract

BackgroundTrihalomethanes (THMs) and haloacetic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.ObjectiveWe aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay.MethodsSprague-Dawley rats were exposed (parental, F1, and F2 generations) from gestation day 0 of the parental generation to postnatal day (PND) 6 of the F2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 500×, 1,000×, or 2,000× of the U.S. Environmental Protection Agency’s maximum contaminant levels (MCLs).ResultsMaternal water consumption was reduced at ≥ 1,000×; body weights were reduced at 2,000×. Prenatal and postnatal survival were unaffected. F1 pup weights were unaffected at birth but reduced at 2,000× on PND6 and at ≥ 1,000× on PND21. Postweaning F1 body weights were reduced at 2,000×, and water consumption was reduced at ≥ 500×. Males at 2,000× had a small but significantly increased incidence of retained nipples and compromised sperm motility. Onset of puberty was delayed at 1,000× and 2,000×. F1 estrous cycles and fertility were unaffected, and F2 litters showed no effects on pup weight or survival. Histologically, P0 (parental) dams had nephropathy and adrenal cortical pathology at 2,000×.ConclusionsA mixture of regulated DBPs at up to 2,000× the MCLs had no adverse effects on fertility, pregnancy maintenance, prenatal survival, postnatal survival, or birth weights. Delayed puberty at ≥ 1,000× may have been secondary to reduced water consumption. Male nipple retention and compromised sperm motility at 2,000× may have been secondary to reduced body weights.CitationNarotsky MG, Klinefelter GR, Goldman JM, DeAngelo AB, Best DS, McDonald A, Strader LF, Murr AS, Suarez JD, George MH, Hunter ES III, Simmons JE. 2015. Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay. Environ Health Perspect 123:564–570; http://dx.doi.org/10.1289/ehp.1408579

Monohaloacetic acid drinking water disinfection by-products inhibit follicle growth and steroidogenesis in mouse ovarian antral follicles in vitro

“…57 However, a recent study evaluated the toxicity of a DBP mixture in a multigenerational bioassay in rats and observed no adverse effects on fertility, pregnancy maintenance, prenatal or postnatal survival, and birth weights. 58 Collectively, these data highlight the need for in depth studies on reproductive toxicity of DBPs and their biological mechanisms.…”

Maternal Swimming Pool Exposure during Pregnancy in Relation to Birth Outcomes and Cord Blood DNA Methylation among Private Well Users

“…Endocrine disruptors are capable of altering neural transmission and the formation of neural networks (Kajta and Wójtowicz, 2013). Animal studies, using artificial mixtures of DBPs detected in drinking water, observed endocrine disrupting effects, but these effects were not found when using trihalomethanes or haloacetic acids alone (Narotsky et al, 2015(Narotsky et al, , 2013. Thus, the driving agents of the DBP mixture toxicity and implicated mechanisms remain an active area of investigation (Plewa et al, 2017).…”

Examining Mixtures of Disinfection By-Products: Rat Study Shows No Effects on Reproduction

“…In this issue of EHP , investigators assess the reproductive toxicity of a mixture of chlorination DBPs in rats. 2 …”

“…7 Rather than setting maximum contaminant levels for individual chemicals, the agency regulates total THMs and total HAAs. 2 …”

“…The researchers reported no adverse effects on fertility, pregnancy, pup survival, or birth weight at any dose in F 1 animals, and no effects on survival or birth weight in F 2 animals. 2 This could suggest that the reproductive and developmental outcomes observed in previous studies may not be due to the regulated DBPs, says Susan Richardson, an environmental chemist and professor at the University of South Carolina, who was not involved in the study. Instead, she says, “There’s a possibility that some unregulated water disinfection by-products could be responsible for those earlier associations.”…”