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DISRUPTION IN RAT ESTROUS CYCLICITY BY THE DRINKING WATER DISINFECTANT BY-PRODUCT DIBROMOACETIC ACID: RELATIONSHIP TO A SUPPRESSION ON ESTRADIOL METABOLISM?
Murr, A S. AND J M. Goldman. DISRUPTION IN RAT ESTROUS CYCLICITY BY THE DRINKING WATER DISINFECTANT BY-PRODUCT DIBROMOACETIC ACID: RELATIONSHIP TO A SUPPRESSION ON ESTRADIOL METABOLISM? Presented at NC Society of Toxicology, RTP, NC, March 02, 2002.
Disruption in Rat Estrous Cyclicity by the Drinking Water Disinfectant By-Product Dibromoacetic Acid: Relationship to A Suppression on Estradiol Metabolism?
Ashley S. Murr and Jerome M. Goldman, Endocrinology Branch, Reproductive Toxicology Division National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC
A number of chemicals formed by disinfection of municipal drinking water have been suspected to cause reproductive alterations in humans and test animals. One class of these chemicals, the haloacetic acids, have been reported to alter a number of rat testicular endpoints, including levels of circulating testosterone. In females of the species, dibromoacetic acid (DBA) was found to alter estrous cyclicity, inducing a predominance of persistent periods of estrus at administered (by gavage) dose levels of 90 and 270mg/kg, a finding consistent with effects seen in the present study. While in vitro treatment of preovulatory follicles suggested that a fall in progesterone may have contributed to this effect on cyclicity, follicular estradiol (E2) release was unaltered. One possibility is that the extended periods of vaginal cornification could be associated with an effect on E2 metabolism. To explore this issue, 90 day-old Sprague-Dawley females were dosed by oral gavage for 14 days with DBA (0, 30, 90, 270 mg/kg/day) while cyclicity was monitored by vaginal lavage. On day 8 of dosing animals were overiectomized and 3 days later received subcutaneous estradiol implants. Additional rats were implanted with only sesame-oil vehicle capsules. Blood was then sampled by daily tail nicks for 2 consecutive days before the animals were killed and trunk blood taken on the 14th day of DBA exposure. On the third day post E2 implant, a dose-related elevation in serum E2 was present, with the highest dose approximately 2 ? times above controls. Additional dosed rats (0 and 270mg/kg) were ovariectomized and implanted as above and during the last 4 days of DBA exposure were provided with phenobarbital (PB, 0.1%, in the drinking water) to stimulate P450-catalyzed hepatic E2 metabolism. At three days post-implant, there was no statistical difference between the 0 mg/kg DBA controls and the PB-treated/270 mg DBA group, while concurrently-treated DBA-dosed females remained elevated as before. Data suggest that alterations in estrous cyclicity following exposure to DBA could be linked to increases in circulating estradiol that are in turn due to a suppression in hepatic E2 metabolism.
(This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
REPRODUCTIVE TOXICOLOGY DIVISION