Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach.
There is considerable public, regulatory, and scientific concern regarding human exposure to endocrine-disrupting chemicals, which include compounds that directly modulate steroid hormone receptor pathways (estrogens, antiestrogens, androgens, antiandrogens) and aryl hydrocarbon receptor (AhR) agonists, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Based on quantitative structure-activity relationships for both AhR and estrogen receptor (ER) agonists, the relative potency (RP) of individual compounds relative to a standard (e.g. TCDD and 17-beta-estradiol) have been determined for several receptor-mediated responses. Therefore, the TCDD or estrogenic equivalent (TEQ or EQ, respectively) of a mixture is defined as TEQ = sigma[T(i)]xRP(i)or EQ=sigma[E(i)]xRP(i), where T(i) and E(i) are concentrations of individual AhR or ER agonists in any mixture. This approach for risk assessment of endocrine-disrupting mixtures assumes that for each endocrine response pathway, the effects of individual compounds are essentially additive. This paper will critically examine the utility of the TEQ/EQ approach for risk assessment, the validity of the assumptions used for this approach, and the problems associated with comparing low dose exposures to xeno and natural (dietary) endocrine disruptors.
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S H
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Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA. ssafe@vetmed.tamu.edu
D001667:Binding, Competitive; D004347:Drug Interactions; D004703:Endocrine System / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D015386:Hazardous Substances / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008962:Models, Theoretical; D011987:Receptors, Steroid / Q000187:drug effects; D012016:Reference Values; D018570:Risk Assessment; D013329:Structure-Activity Relationship
D012739:Gonadal Steroid Hormones; D015386:Hazardous Substances; D011987:Receptors, Steroid