Toxicological Sciences 59, 309-315 (2001)
Copyright © 2001 by the Society of Toxicology
REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY |
Pregnancy Loss in the Rat Caused by Bromodichloromethane
* Curriculum of Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and
Reproductive Toxicology Division, National Health and Environmental Effects ResearchLaboratory, Mail Drop 72, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Bromodichloromethane (BDCM), a trihalomethane, is a by-product of the chlorination of drinking water. In a recent epidemiological study, consumption of BDCM was associated with an increased risk of spontaneous abortion in pregnant women. We have previously shown that BDCM causes pregnancy loss, i.e., full-litter resorption (FLR), in the F344 rat. The mode of action was investigated, with three main findings. First, there was a dramatic difference in sensitivity between F344 and Sprague-Dawley (SD) rat strains. Following aqueous gavage treatment on gestational days (GD) 6–10, F344 rats had a 62% incidence of FLR at 75 mg/kg/day, whereas all SD rats maintained their litters. Second, the critical period encompassed the luteinizing hormone (LH)-dependent period of pregnancy. Rats treated on GD 6–10 at 75 mg/kg/day had a 75% incidence of FLR, but rats treated on GD 11–15 at 75 or 100 mg/kg/day were unaffected. Third, 24 h after a single dose, all dams with FLR had markedly reduced serum progesterone levels; however, LH levels were unaffected. The high FLR rate during the LH-dependent period, the lack of response thereafter, and the reduced progesterone levels without an associated reduction in LH levels suggests that BDCM disrupts luteal responsiveness to LH.
Key Words: bromodichloromethane; disinfection by-product; pregnancy loss; strain differences; progesterone; luteinizing hormone; corpus luteum.
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