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STRAIN COMPARISON OF ENDOCRINE RESPONSE IN RATS TO BROMODICHLOROMETHANE (BDCM) DURING PREGNANCY
Citation:
Bielmeier, S. R., D S. Best, AND M G. Narotsky. STRAIN COMPARISON OF ENDOCRINE RESPONSE IN RATS TO BROMODICHLOROMETHANE (BDCM) DURING PREGNANCY. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
STRAIN COMPARISON OF ENDOCRINE RESPONSE IN RATS TO BROMODICHLOROMETHANE (BDCM) DURING PREGNANCY.
S. R. Bielmeier1, D. S. Best2 and M. G. Narotsky2
1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
2 Reproductive Toxicology Division, NHEERL, USEPA, RTP, NC, USA
Sponsor: A. Cummings
Previously, we reported that BDCM, a drinking water disinfection by-product, causes pregnancy loss, i.e. full-litter resorption (FLR) in F344 rats when treated during the luteinizing hormone (LH)-dependent period. We also found that Sprague-Dawley (SD) rats were unaffected at even higher doses. Here, we examined the effects of BDCM on serum progesterone and LH levels during pregnancy in both strains. BDCM, in 10% emulphor, was dosed by gavage on gestational days (GD) 6-10 (plug day = GD 0) at 75 mg/kg/d in the F344 rat, and 100 or 200 mg/kg/d in the SD rat. Blood samples were collected from the lateral tail vein once daily on GD 6-11; serum progesterone and LH were measured using DELFIA?. The rats were allowed to deliver and pups were examined postnatally. FLR was confirmed by staining uterine resorption sites with 10% ammonium sulfide. Unlike the F344 rats, the SD rats maintained their litters and progesterone levels; although, similar to the F344 rats, they did display decreased LH levels. F344 rats had an 88% (7/8) incidence of FLR at 75 mg/kg/d, whereas SD rats had 0% (0/10, 0/9) incidences at both 100 and 200 mg/kg/d. BDCM-treated F344 dams with FLR had reduced progesterone and LH levels on GD 10; mean ? SE LH levels were 0.07 ? 0.04 vs. 0.15 ? 0.02 ng/ml for controls. In contrast, the SD rats treated at 200 mg/kg/d did not show a decrease in serum progesterone levels on GD10; however, serum LH levels were significantly decreased from controls (0.24 ? 0.06 vs. 0.49 ? 0.06 ng/ml). Importantly, control serum LH values were significantly higher in SD than F344 rats (p<0.0001). Thus, these dramatic strain differences in baseline LH levels and susceptibility to BDCM-induced pregnancy loss exemplify the importance of strain as a consideration when assessing reproductive toxicity.
[Funded by the EPA/UNC Toxicology Research Program, Training Agreement CT827206 Curriculum in Toxicology, UNC-Chapel Hill. This abstract does not necessarily reflect EPA policy.]