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 duration. Adult ovariectomized rats were given daily subcutaneous injections of OP for 2 and 14 days. 17beta-Estradiol was also administrated at a dose of 5 microg/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 compared to 17beta-estradiol. Estrous conversion of the vaginal smear was detected only in 14-day-treated animals. OP-treatment for 2 days caused a dose-related increase in proliferation of uterine luminal, glandular, and stromal cells and vaginal epithelial cells. From the 14-day experiment, the minimum estrogenic dose level of OP was concluded to be 25 mg/kg/day and the serum 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 effects are fundamentally related to serum OP levels.
Katsuda
S
S
Department of Pathology, Sasaki Institute, 2-2 Kanda-Surugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.
Yoshida
M
M
Isagawa
S
S
Asagawa
Y
Y
Kuroda
H
H
Watanabe
T
T
Ando
J
J
Takahashi
M
M
Maekawa
A
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D004971:Estrus / Q000187:drug effects; D005260:Female; D007279:Injections, Subcutaneous; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010636:Phenols / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D013501:Surface-Active Agents / Q000032:analysis / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000473:pathology; D014626:Vaginal Smears
D004968:Estrogens, Non-Steroidal; D010636:Phenols; D013501:Surface-Active Agents; D004958:Estradiol; C105260:4-tert-octylphenol