The estrogenic activity of benzophenone and its metabolites, benzhydrol and p-hydroxybenzophenone, were investigated in vitro by estrogen receptor (ER) competitive ligand binding assay and in vivo by uterotrophic assay in juvenile female Sprague-Dawley (SD) rats. p-Hydroxybenzophenone as well as diethylstilbestrol and bisphenol A, known xeno-estrogenic compounds, competed with fluorescein-labeled 17β-estradiol to bind human recombinant ERα in a concentration-dependent manner. Fifty percent inhibitory values (IC50) of diethylstilbestrol, bisphenol A, and p-hydroxybenzophenone were approximately 10–8, 10–5, and 5×10–5 M, respectively. However, neither the parent compound nor benzhydrol at concentrations from 10–9 to 5×10–4 M impaired the binding of 17β-estradiol to ERα. Juvenile female rats (21-days-old) were given s.c. injections of benzophenone, its metabolites, and 17β-estradiol for 3 days. Administration of p-hydroxybenzophenone (100–400 mg/kg) elicited an increase in absolute and relative uterine weights in a dose-dependent manner and 17β-estradiol (10 µg/kg) increased uterine weight approximately fourfold relative to control. The uterine response caused by both compounds was accompanied by an increase in luminal epithelial height and stromal cells in the uterus and an increase in thickness of vaginal epithelial cell layers with cornification. In contrast, benzophenone and benzhydrol at a dose of 400 mg/kg affected neither uterine weight nor histological changes of the uterus and vagina. These results indicate that p-hydroxybenzophenone, a metabolite of benzophenone, exhibits intrinsic xeno-estrogenic activity in the female reproductive tract.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
About this article
Cite this article
Nakagawa, Y., Tayama, K. Estrogenic potency of benzophenone and its metabolites in juvenile female rats. Arch Toxicol 75, 74–79 (2001). https://doi.org/10.1007/s002040100225
- Benzophenone Metabolites Uterotrophic assay Competitive binding assay Female rats