Dose- and treatment duration-related effects of p-tert-octylphenol on female rats

We conducted a study to investigate the relation between estrogenic effects of p-tert-octylphenol (OP) and serum concentration as well as treatment du ration. Adult ovariectomized rats were given daily subcutaneous injections of OP for 2 and 14 days. 17 beta-Estradiol was also administrated at a dose of 5 mu g/kg. OP was detected in serum at doses of 25 mg/kg and above for 2 days and with multiple doses (14 days) of 12.5 mg/kg. Uterine weights and luminal epithelial height were increased although the effects were weak co mpared to 17 beta-estradiol. Estrous conversion of the vaginal smear was de tected only in 14-day-treated animals. OP-treatment for 2 days caused a dos e-related increase in proliferation of uterine luminal, glandular, and stro mal cells and vaginal epithelial cells. From the 14-day experiment, the min imum estrogenic dose level of OP was concluded to be 25 mg/kg/day and the s erum level at the dose was determined to be about 80 ng/ml. These findings demonstrated that OP exerts estrogenic activity in the female reproductive tract of ovariectomized rats only at high levels of exposure and that the e ffects are fundamentally related to serum OP levels. (C) 2000 Elsevier Scie nce Inc. All rights reserved.