title: Why toxic equivalency factors are not suitable for perfluoroalkyl chemicals.
abstract: The pervasive nature of perfluoroalkyl chemicals in the environment has generated considerable interest for developing new strategies for risk assessment. In experimental animal models, exposure to perfluoroalkyl chemicals can cause developmental toxicity and hepatotoxicity. Peroxisome proliferator-activated receptor-α (PPARα) is required to mediate some but not all of these effects. Since PPARα has a role in mediating some of these effects, and there is some overlap in the type of toxicities elicited by perfluoroalkyl chemicals, it has been suggested that a scaling system analogous to the toxic equivalency factor (TEF) system used for polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and polychlorinated biphenyls (PCB) could be used for perfluoroalkyl chemicals. However, evidence suggests that perfluoroalkyl chemicals can activate/interfere with other receptors, and there is reason to suggest the possibility of species differences in the response mediated by different receptors as well as qualitative differences in toxicities elicited by perfluoroalkyl chemicals. These differences and other data gaps preclude the development of a TEF approach for perfluoroalkyl chemicals.
authors.affiliation: Department of Veterinary and Biomedical Sciences and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University , University Park, PA 16802, United States. jmp21@psu.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Peters
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D000090702:Constitutive Androstane Receptor; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods; D013045:Species Specificity; D013501:Surface-Active Agents / Q000633:toxicity*
chemical_list: D000090702:Constitutive Androstane Receptor; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D006845:Hydrocarbons, Fluorinated; D047492:Peroxisome Proliferator-Activated Receptors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013501:Surface-Active Agents