Twenty-week exposures to the drinking water disinfection by-product dibromoacetic acid: reproductive cyclicity and steroid concentrations in the female Sprague-Dawley rat

Elevated gavage exposures to the drinking water disinfection by-product dibromoacetic acid (DBA) have been found to disrupt estrous cyclicity in the rat and induce increases in estradiol concentrations in both cycling (day of estrus) and ovariectomized/estradiol-implanted females. The present study was designed to investigate both effects in Sprague-Dawley rats following an extended 20-week treatment with lower dosages of DBA administered in the drinking water (calculated mean intake concentrations of 5, 16, and 33 mg/kg/d). No treatment-related effects on cyclicity were present, although elevations in serum estradiol on the day of vaginal estrus were noted in regularly cycling rats when assessed at the 3rd and 11th weeks of exposure. By the 19th week, this effect was no longer present in cycling animals, but its absence was attributable to a marked increase in control estradiol concentrations, which may be associated with endocrine alterations that precede a disruption in estrous cyclicity in middle-aged females. In the 20th week, diestrous estrone levels were elevated at all dosages without effects on serum androstenedione or progesterone. Uterine and pituitary weights were unchanged at this time, although there were modest increases in liver weights at the two highest dosages. A small number of rats in persistent estrus (PE) did show a general increase in pituitary weight associated with DBA exposure, possibly reflecting an added layering of treatment on the PE-associated rise in estradiol normally seen in these females. The results indicate that increases in circulating estradiol from drinking water exposures to DBA were not linked to a premature disruption of estrous cyclicity in this moderately estrogen-sensitive rat strain.