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Assessment of reproductive effects on complex mixtures of disinfection by-products in a multigenerational rat bioassay of drinking water concentrates
Citation:
NAROTSKY, M. G., E. S. HUNTER, G. R. KLINEFELTER, J. M. GOLDMAN, L. F. STRADER, J. G. PRESSMAN, R. J. MILTNER, T. F. SPETH, S. D. RICHARDSON, L. K. TEUSCHLER, G. E. RICE, AND J. E. SIMMONS. Assessment of reproductive effects on complex mixtures of disinfection by-products in a multigenerational rat bioassay of drinking water concentrates. Presented at Teratology, Monterey, CA, June 28 - July 02, 2008.
Impact/Purpose:
Presentation @ Annual Meeting of the Teratology Society
Description:
To address concerns raised by epidemiology studies, we conducted a multigenerational reproductive toxicity study in rats using a “whole” mixture of drinking water disinfection by-products (DBPs). Raw water was concentrated ~130 fold, chlorinated, and provided as drinking water to Sprague-Dawley rats; controls received purified water. A custom-designed water-delivery system minimized headspace and maintained the water in a chilled, dark environment. Timed-pregnant females (P0 generation) were exposed from gestation day 2 until weaning of the F1 litters. Litters were culled to eight pups on postnatal day (PD) 6. Two blocks of P0 females (40 control, 60 treated per block) were maintained through PD 6 of the F1 generation. Litter examinations on PD 0, 6, and 21 revealed no treatment effects on pre- or postnatal survival, or pup weight. Anogenital distance, examined on PD 0 in 12 randomly selected litters per group, was unaffected. Examination of eye opening and nipple retention on PD 13 also revealed no treatment effects. At weaning, two females and two to four males were maintained at least through puberty in their respective treatment groups. Females were examined for vaginal opening (VO) and males were examined for preputial separation as indicators of puberty. Onset of puberty was unaffected in males. Serum and testicular levels of testosterone (T) were also unaffected in pubertal males on PD 55. In females, puberty was significantly, albeit slightly, delayed; the mean ± SE day of VO was 34.1 ± 0.3 and 34.9 ± 0.3 for controls and treated females, respectively. Serum progesterone and estradiol levels on the day of VO, however, were unaffected. Estrous cycles, examined for 3 weeks prior to breeding, showed no treatment effect. Treatment had no effect on fertility. F2 litters, examined on PD 0 and 6, showed no effects on pre- or postnatal survival, or pup weight. At necropsy of bred F1 rats (≥ PND 90), organ weights of reproductive tissues were comparable between groups, as were levels of male serum T and female hypothalamic catecholamines. Thus, thorough examination of potential effects of a concentrated mixture of DBPs on reproduction revealed a slight, but significant, delay in puberty for F1 females.