ToxSci Advance Access published online on July 14, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh217
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Reproductive Toxicology Division, MD #72, RTP, NC 27711
* To whom correspondence should be addressed. E-mail: klinefelter.gary{at}epa.gov.
Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in which offspring were exposed from gestation day (GD) 15 through adulthood revealed significant delays in preputial separation and vaginal opening, dose-related decreases in the fertility of cauda epididymal sperm, and dose-related diminutions in the sperm membrane protein SP22. Subsequent studies consisted of groups in which exposure ceased on postnatal day 21 (PND21) vs adulthood. For each exposure, animals were evaluated after puberty (PND56) as well as at adulthood (PND120). Exposure to 4, 40, or 400 ppm DBA from GD15 through PND21 failed to result in any significant reproductive alterations. By contrast, continuous exposure until adulthood resulted in dose-related alterations consistent with those observed in the dose-finding study. Preputial separation and vaginal opening were delayed 4 and 3 days in males and females exposed to 400ppm (76.3 mg/kg) DBA. This was associated with increased responsiveness of both the testis and ovary to hCG ex vivo; hCG-stimulated testosterone production by testicular parenchyma on PND56 was increased at 4ppm (0.6 mg/kg) DBA and higher. Finally, the quality of proximal cauda epididymal sperm was compromised by continous exposure to DBA. The sperm membrane proteome was compromised in a dose related manner with SP22 and one of its charged variants diminished at 40 ppm (3.6 mg/kg) DBA and higher. As more sensitive endpoints are evaluated, lower effect levels can be attributed to haloacid exposure. We are now extending our evaluations to epidemiology studies designed to evaluate sperm quality in men exposed to varying levels of disinfection by-products.
Accepted July 1, 2004
Reproductive and Developmental Toxicology
Continuous Exposure to Dibromoacetic Acid Delays Pubertal Development and Compromises Sperm Quality in the Rat
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