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DELAYED PREPUTIAL SEPARATION (PPS) AND SP22 MEASUREMENT IN RATS ADMINISTERED BROMOCHLOROACETIC ACID (BCA) IN DRINKING WATER
Citation:
SLOAN, C., G. R. KLINEFELTER, J. M. GOLDMAN, K. VICK, P. FAIL, AND R. TYL. DELAYED PREPUTIAL SEPARATION (PPS) AND SP22 MEASUREMENT IN RATS ADMINISTERED BROMOCHLOROACETIC ACID (BCA) IN DRINKING WATER. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
Reproductive effects of BCA were determined in a dose range finding study (DRFS) and definitive two-generational study. Adult male and female CD� (SD) rats were administered BCA in drinking water for two weeks in the DRFS (10/sex/group) and ten weeks in the definitive study (25/sex/group) before mating. Females were dosed until the weaning of their litters. The F1 post-weanlings received BCA until acquiring puberty [PPS in males, vaginal patency (VP) in females] in the DRFS, and through mating to generated F2 offspring in the definitive study. The concentrations were 0, 50, 200, 400, 600, 800 and 1000 ppm BCA ad libitum in the DRFS and 0, 30, 300, and 6000 ppm BCA in the definitive study. Age of male PPS was used to assess reproductive development. The males at > 600 ppm in both studies showed significant delay of PPS vs. the control males; At 600 ppm mean PPS delays were 2.2 days in the definitive study and 2.7 days in the DRFS; At 800 ppm, males had mean delays of 4.7 days, and those males at 1000 ppm had delays of 5.2 days. Ages at acquisition were adjusted using body weight (BW) at acquisition as a covariate. In the DRFS, F1 females at > 600 ppm had VP delays of 6.2 days; comparable delays were not seen in the definitive study. In the DRFS, the F0 females, males and F1 offspring at both weaning and puberty had dose-related decreases in BW. In the definitive study, BW was unaltered in F0 males, but was decreased in 600 ppm F0 females. The F1 males and females had decreased BW at 600 ppm at pnd 21 and as adults; the males also had decreased caudal sperm of adult F0 and F1 males as a measure of adult reproductive competence and an important biomarker of fertility. Significant decreases in SP22 were seen with increasing BCA concentrations in both F0 and F1 males in the definitive study. This work was funded by a cooperative agreement from USEPA, RTP.