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.
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA. ssafe@vetmed.tamu.edu
S H
SH
Safe
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