Developmental stage sensitivity and mode of action information for androgen agonists and antagonists.
The response from exposure to a toxic agent during development may vary depending on the dose, time of exposure and the mode of action. The mode of action and developmental stage sensitivity are established only for a limited number of chemical classes. Some aspects of developmental stage sensitivity that appear to affect the response to androgen agonists and antagonists are the levels and distribution of endogenous androgens and the androgen receptor at particular times during development. This information is summarized and discussed as it relates to two critical windows of development: the period of male reproductive tract differentiation, and the peripubertal period when male sexual maturation occurs. Developmental stage sensitivity and mode of action data for the androgen antagonist vinclozolin are reviewed. Vinclozolin acts by binding to and activating the androgen receptor and affects a number of endpoints of reproductive tract differentiation as well as pubertal maturation. Approaches to incorporating mode of action, developmental stage sensitivity, and dose/potency information into risk assessment, as well as the additional data needed for using mode of action information, both qualitatively and quantitatively, in risk assessment are discussed. These issues are also considered in the context of combining the risks of exposure to two or more chemicals with similar modes of action.
Euling
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National Center for Environmental Assessment, US Environmental Protection Agency, Washington, DC 20460, USA. euling.susan@epa.gov
Kimmel
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D000375:Aging; D000726:Androgen Antagonists / Q000633:toxicity*; D000728:Androgens / Q000819:agonists* / Q000502:physiology; D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects*; D005659:Fungicides, Industrial / Q000633:toxicity; D005865:Gestational Age; D006801:Humans; D008297:Male; D008322:Mammals; D010080:Oxazoles / Q000633:toxicity; D011944:Receptors, Androgen / Q000502:physiology
D000726:Androgen Antagonists; D000728:Androgens; D005659:Fungicides, Industrial; D010080:Oxazoles; D011944:Receptors, Androgen; C025643:vinclozolin