title: Cumulative effects of antiandrogenic chemical mixtures and their relevance to human health risk assessment.
abstract: Toxicological studies of defined chemical mixtures assist human health risk assessment by establishing how chemicals interact with one another to induce an effect. This paper reviews how antiandrogenic chemical mixtures can alter reproductive tract development in rats with a focus on the reproductive toxicant phthalates. The reviewed studies compare observed mixture data to mathematical mixture model predictions based on dose addition or response addition to determine how the individual chemicals in a mixture interact (e.g., additive, greater, or less than additive). Phthalate mixtures were observed to act in a dose additive manner based on the relative potency of the individual phthalates to suppress fetal testosterone production. Similar dose additive effects have been reported for mixtures of phthalates with antiandrogenic pesticides of differing mechanisms of action. Overall, data from these phthalate experiments in rats can be used in conjunction with human biomonitoring data to determine individual hazard indices, and recent cumulative risk assessments in humans indicate an excess risk to antiandrogenic chemical mixtures that include phthalates only or phthalates in combination with other antiandrogenic chemicals.
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), PO Box 12233, Mail Drop K2-04, Research Triangle Park, NC 27709-2233, USA. Electronic address: howdeshellkl@niehs.nih.gov.
authors.forename: Kembra L
authors.initials: KL
authors.lastname: Howdeshell
authors.affiliation: National Center for Environmental Assessment (NCEA), National Health and Environmental Effects Research Laboratories (NHEERL), Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Hotchkiss
authors.affiliation: Toxicology Assessment Division, National Health and Environmental Effects Research Laboratories (NHEERL), Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: L Earl
authors.initials: LE
authors.lastname: Gray
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D004347:Drug Interactions; D006801:Humans; D008954:Models, Biological; D018570:Risk Assessment
chemical_list: D000726:Androgen Antagonists
keywords: Antiandrogens; Cumulative risk assessment; Male reproductive tract development; Mixtures; Pesticides; Phthalates