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Reproductive Development in a Multi-Generational Rat Bioassay of Drinking Water Concentrates in the Four Lab Study
Citation:
Narotsky, M. G., J. G. Pressman, S. D. Richardson, AND L. K. Teuschler. Reproductive Development in a Multi-Generational Rat Bioassay of Drinking Water Concentrates in the Four Lab Study. Presented at Toxicology and Risk Assessment Conference, West Chester, OH, April 14 - 17, 2008.
Impact/Purpose:
Abstract describes effects of "whole" mixtures of disinfection byproducts in drinking water concentrates on reproductive development in a rat multigenerational reproductive toxicity study.
Description:
To address concerns raised by epidemiological 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. To minimize loss of volatile DBPs and to enhance stability, a custom-designed water-delivery system minimized headspace and maintained the water in a chilled, dark environment. Timed-pregnant females (P0 generation; 40 controls, 60 treated) were exposed from gestation day 2 until weaning of their litters (F1 generation). 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 were also unaffected in males necropsied shortly after puberty (day 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 comparable between groups. Examination of estrous cycles for 3 weeks prior to breeding showed no treatment effect. One male and one female per litter were cohabited with a non-sibling from the same treatment group during a 7-day breeding period. Treatment had no effect on mating rate, pregnancy rate, or fertility. F2 litters were examined on postnatal days 0 and 6. Although all pups died in one treated litter, this was unlikely related to treatment. Prenatal survival, postnatal survival, and pup weight were comparable between groups. At necropsy, F1 organ weights of reproductive tissues were comparable between groups, as were serum testosterone levels in males, and hypothalamic catecholamine levels in females. In summary, thorough examination of potential effects of a concentrated mixture of DBPs on reproduction revealed a slight, but significant, delay in puberty for F1 females.