You are here:
Assessment of Reproductive and Developmental Toxicity of Mixtures of Regulated Drinking Water Chlorination By-Products in a Multigenerational Rat Bioassay
Citation:
NAROTSKY, M. G., J. M. GOLDMAN, D. S. BEST, A. E. MURR, G. R. KLINEFELTER, L. F. STRADER, J. D. Saurez, J. G. PRESSMAN, R. J. MILTNER, T. F. SPETH, L. K. TEUSCHLER, G. E. RICE, S. D. RICHARDSON, T. A. MCDONALD, E. S. HUNTER, AND J. E. SIMMONS. Assessment of Reproductive and Developmental Toxicity of Mixtures of Regulated Drinking Water Chlorination By-Products in a Multigenerational Rat Bioassay. Presented at Teratology Society Annual meeting, Louisville, KY, June 26 - 30, 2010.
Impact/Purpose:
Epidemiological and animal toxicity studies have raised concerns regarding possible adverse reproductive and developmental effects of disinfection by-products (DBPs) in drinking water.
Description:
Epidemiological and animal toxicity studies have raised concerns regarding possible adverse reproductive and developmental effects of disinfection by-products (DBPs) in drinking water. To address these concerns, we provided mixtures of the regulated trihalomethanes (THMs; chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and haloacetic acids (HAAs; chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, and dibromoacetic acids) as drinking water to Sprague-Dawley rats in a multigenerational reproductive toxicity bioassay. Mixtures were prepared in 0.25% (v/v) Alkamuls® EL-620, in reverse-osmosis-purified water, at 0, 500x, 1000x, and 2000x of EPA's maximum contaminant levels (MCLs) for THMs and HAAs. Chemical proportions were based on analyses at a water utility. Timed-pregnant females (PO generation; 25 per group) were exposed from gestation day 0 until weaning of the F1 litters. Litter sizes were reduced to 10 pups on postnatal day (PD) 6. Litter examinations on PD 0, 6, 21, and 26 revealed no treatment effects on pre-or postnatal survival; however, pup weights were reduced at 2000x on PD 6-21and at ~1 OOOx on PD 26. Anogenital distance, examined on PD 0 in 15 randomly selected control and high-dose litters, was unaffected. On PD 13, eye opening was unaffected, but there was an increased incidence of retained nipples in males at 2000x. At weaning (PD 26), three females and two to four males per litter were maintained at least through puberty with continued exposure in their respective treatment groups. Both vaginal opening (VO) in females and preputial separation (PPS) in males (indicators of puberty) showed significant, dose-related delays at 1OOOx and 2000x. The mean ± SE age at PPS was 45.5 ± 0.3, 46.8 ± 0.3, 48.4 ± 0.6, and 51.2 ± 0.5 days at 0, 500x, 1000x, and 2000x, respectively. For VO, the respective values were 34.0 ± 0.4,34.9 ± 0.3,35.5 ± 0.4, and 39.8 ± 0.7. F1 estrous cycles, breeding, and fertility were unaffected and their F2 litters showed no effects on pup weight, or prenatal or neonatal survival. Thus, although exposure did not affect F1 animals' ability to reproduce, puberty was delayed for both sexes at DBP concentrations ~1 OOOx the MCLs. [This abstract does not necessarily reflect EPA policy.]