alexa Relative potency of xenobiotic estrogens in an acute in vivo mammalian assay.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Milligan SR, Balasubramanian AV, Kalita JC

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Abstract The in vivo effects of xenoestrogens are of interest in relation to their potential health risks and/or beneficial effects on humans and animals. However, the apparent in vivo potency of the examined response can 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 range of xenoestrogens in an acute in vivo assay--the stimulation of increased uterine vascular permeability in ovariectomized mice 4 hr after subcutaneous administration. While estradiol (E 2 ) and estriol (E 3 ; a relatively weak natural estrogen) readily induced vascular responses [median effective dose (ED 50 ) <10 -9 mol], much higher amounts of xenoestrogens 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-fold less potent; dioctyl phthalate, benzyl butyl phthalate, dibutyl phthalate, and trichlorinated biphenol produced no effect. Coumestrol was the most active phytoestrogen, with an ED 50 between 10 -6 and 10 -7 mol; genistein was about 10-fold less potent than coumestrol, and neither daidzein nor formononetin produced any marked effect, even at doses up to 10 -5 mol. All increases in vascular permeability could be blocked by the pure antiestrogen ICI 182,780. There was no evidence that any of the compounds could act as an antiestrogen in this assay or that they could exert synergistic effects in combination. These results indicate that even short-term exposure to most of the xenobiotic estrogens can induce typical estrogenic effects in vivo , but their estrogenic potency is very weak even when assessed in an acute response.
This article was published in Environ Health Perspect and referenced in Pharmaceutica Analytica Acta

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