Estrogenic potency of benzophenone and its metabolites in juvenile female rats

The estrogenic activity of benzophenone and its metabolites, benzhydrol and p-hvdroxybenzophenone, were investigated in vitro by estrogen receptor (ER ) competitive ligand binding assay and in vivo by uterotrophic assay in juv enile female Spraeue-Dawley (SD) rats. p-Hydroxybenzophenone as well as die thylstilbestrol and bisphenol A, known xeno-estrogenic compounds, competed with fluorescein-labeled 17 beta -estradiol to bind human recombinant ER al pha in a concentration-dependent manner. Fifty percent inhibitory values (I CU) of diethylstilbestrol, bisphenol A, and p-hydroxybenzophenone were appr oximately 10(-8), 100(-5), and 5x10(-5) M, respectively. However, neither t he parent compound nor benzhydrol at concentrations from 10(-9) to 5x10(-4) M impaired the binding of 17 beta -estradiol to ER alpha. Juvenile female rats (21-days-old) were given s.c. injections of benzophenone, its metaboli tes, and 17 beta -estradiol for 3 days. Administration of p-hydroxybenzosph enone (100-100 mg/kg) elicited an increase in absolute and relative uterine weights in a dose-dependent manner and 17 beta -estradiol (10 mug/kg) incr eased uterine weight approximately fourfold relative to control. The uterin e response caused by both compounds was accompanied by an increase in lumin al epithelial height and stromal cells in the uterus and an increase in thi ckness of vaginal epithelial cell layers with cornification. In contrast. b enzophenone and benzhydrol at a dose of 400 mg/kg affected neither uterine weight nor histological changes of the uterus and vagina. These results ind icate that p-hydroxybenzophenone, a metabolite of benzophenone, exhibits in trinsic xeno-estrogenic activity in the female reproductive tract.