Human exposure to endocrine-active chemicals: hazard assessment problems.
Industrial-derived endocrine disruptors or endocrine-active chemicals (EACs) have been identified and hypothesized to play a role in human disease. Most of the xeno-EACs which have been characterized bind to the estrogen receptor, aryl hydrocarbon receptor, or androgen receptor. Hazard and risk assessment of xeno-EACs is complicated by several factors which include the following: (i) humans are exposed to relatively high levels of natural EACs compared to xeno-EACs; (ii) very little information on the effects of metabolism, serum, and intracellular binding proteins on target cell uptake of EACs is known; (iii) humans are exposed to EAC mixtures and their interactive effects may be additive, antagonistic, or synergistic and also response- and tissue-specific; and (iv) individual EACs may be agonists/antagonists for more than one endocrine response pathway. Scientific-based hazard and risk assessment of both natural and xeno-EACs clearly requires more information on dietary intakes, target organ exposures, mechanisms of action, and interactive effects of mixtures.
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Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.
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Ramamoorthy
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Gaido
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Maness
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D000818:Animals; D001665:Binding Sites; D004703:Endocrine System / Q000187:drug effects / Q000378:metabolism*; D004781:Environmental Exposure; D006801:Humans; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment; D015262:Xenobiotics / Q000633:toxicity*
D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D015262:Xenobiotics