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Pregnancy Outcome in a Multi-Generational Rat Bioassay of Drinking Water Concentrates in the Four Lab Study
Citation:
Narotsky, M. G., E. S. Hunter, J. G. Pressman, R. J. Mitner, T. F. Speth, S. D. Richardson, L. K. Teuschler, G. E. Rice, AND J. E. Simmons. Pregnancy Outcome in a Multi-Generational Rat Bioassay of Drinking Water Concentrates in the Four Lab Study. Presented at Toxicoloy and Risk Assessment, West Chester, OH, April 14 - 17, 2008.
Impact/Purpose:
Presentation
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) were exposed from gestation day 2 until weaning of their litters (F1 generation). Litters were culled to eight pups on postnatal day (PD) 6. F1 animals were maintained in their respective treatment groups and bred to produce an F2 generation. To enhance statistical power for detecting possible effects on pup weight and prenatal loss, two blocks of animals were maintained through PD 6 of the F1 generation; each block consisted of 40 controls and 60 treated P0 females. This presentation will focus on data collected through weaning of the F1 generation. All pregnant females maintained their litters to term; no effects on gestation length were evident. Litter examinations on PD 0, 6, and 21 revealed no treatment effects on prenatal survival, postnatal survival, or pup weight. Anogenital distance, examined on PD 0 in 12 randomly selected litters per group, was unaffected by treatment. Examination of eye opening and nipple retention on PD 13 also revealed no treatment effects. Isolated incidences of unusual clinical findings (vaginal prolapse in one dam at parturition; dental malocclusion in all weanlings of one litter) were observed in the treated group, but did not appear to be treatment related.