RELATIVE POTENCY OF XENOBIOTIC ESTROGENS IN AN ACUTE IN-VIVO MAMMALIAN ASSAY

The in vivo effects of xenoestrogens are of interest in relation to th eir potential health risks and/or beneficial effects on humans and ani mals. However, the apparent in vivo potency of the examined response c an be confounded by a short half-life, and the metabolism of estrogens is very dependent on the nature of conversion and/or inactivation. To minimize such variables, we examined the estrogenic potency of a rang e of xenoestrogens in an acute in vivo assay-the stimulation of increa sed uterine vascular permeability in ovariectomized mice 4 hr after su bcutaneous administration. While estradiol (E-2) and estriol (E-3; a r elatively weak natural estrogen) readily induced vascular responses [m edian effective dose (ED50) <10(-9) mol], much higher amounts of xenoe strogens were required. Bisphenol A was about 10,000-fold less potent than E-2 and E-3, and octylphenol and nonylphenol were about 100,000-f old less potent; dioctyl phthalate, benzyl butyl phthalate, dibutyl ph thalate, and trichlorinated biphenol produced no effect. Coumestrol wa s the most active phytoestrogen, with an ED50 between 10(-6) and 10(-7 ) mol; genistein was about 10-fold less potent than coumestrol, and ne ither daidzein nor formononetin produced any marked effect, even at do ses up to 10(-5) mol. All increases in vascular permeability could be blocked by the pure antiestrogen ICI 182,780. There was no evidence th at any of the compounds could act as an antiestrogen in this assay or that they could exert synergistic effects in combination. These result s indicate that even short-term exposure to most of the xenobiotic est rogens can induce typical estrogenic effects in vivo, but their estrog enic potency is very weak even when assessed in an acute response.