Combining perfluoroalkane acid exposure levels for risk assessment.

Perfluoroalkane acids are present in biologic samples from >90% of people in the developed world. Because people may be exposed to multiple perfluoroalkane acids, it is reasonable to consider whether the exposure levels of these agents can be combined for risk assessment purposes. To investigate this possibility, we considered whether the literature on perfluoroalkane acids could be used to justify a scaling system analogous to the Toxic Equivalency Factor (TEF) system used for polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans. We evaluated pairs of studies performed with different perfluoroalkane acids in the same species using the same design and found that endpoints for perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorobutanesulfonate (PFBS), and perfluorodecanoic acid (PFDA) could be discordant. We evaluated pairs of rat studies of PFOS, PFOA, and PFBS performed with the same design for which dose-response curves could be modeled for the concordant endpoints, but we were unable to identify a scaling system that gave values consistently within an order of magnitude for the same compounds. Currently available data do not support the combining of exposure levels of perfluoroalkane acids for risk assessment, although re-evaluation after additional data are available is recommended.

[1]  C. Lau,et al.  Perfluorooctanoic acid induced developmental toxicity in the mouse is dependent on expression of peroxisome proliferator activated receptor-alpha. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[2]  N. Kudo,et al.  Sex hormone-regulated renal transport of perfluorooctanoic acid. , 2002, Chemico-biological interactions.

[3]  John W. Froehlich,et al.  Half-Life of Serum Elimination of Perfluorooctanesulfonate,Perfluorohexanesulfonate, and Perfluorooctanoate in Retired Fluorochemical Production Workers , 2007, Environmental health perspectives.

[4]  A. Starkov,et al.  Structural determinants of fluorochemical-induced mitochondrial dysfunction. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[5]  D. Waxman,et al.  trans-activation of PPARalpha and induction of PPARalpha target genes by perfluorooctane-based chemicals. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[6]  Safe,et al.  Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. , 1998, Environmental health perspectives.

[7]  R. G. York,et al.  Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats. , 2005, Toxicology.

[8]  R. E. Staples,et al.  The embryo-fetal toxicity and teratogenic potential of ammonium perfluorooctanoate (APFO) in the rat. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[9]  A. Calafat,et al.  Serum concentrations of 11 polyfluoroalkyl compounds in the u.s. population: data from the national health and nutrition examination survey (NHANES). , 2007, Environmental science & technology.

[10]  Jeffrey H Mandel,et al.  Serum concentrations of perfluorooctanesulfonate and other fluorochemicals in an elderly population from Seattle, Washington. , 2004, Chemosphere.

[11]  B. Abbott,et al.  Activation of Mouse and Human Peroxisome Proliferator-Activated Receptors ( , / , ) by Perfluorooctanoic Acid and Perfluorooctane Sulfonate , 2006 .

[12]  M. A. Mohd,et al.  Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. , 2004, Environmental science & technology.

[13]  A. Calafat,et al.  Perfluorochemicals in pooled serum samples from United States residents in 2001 and 2002. , 2006, Environmental science & technology.

[14]  J. V. Vanden Heuvel,et al.  Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver X receptor-beta, and retinoid X receptor-alpha. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[15]  David J. Waxman,et al.  trans-Activation of PPARα and Induction of PPARα Target Genes by Perfluorooctane-Based Chemicals , 2004 .

[16]  Gerald L Kennedy,et al.  The reproductive toxicology of ammonium perfluorooctanoate (APFO) in the rat. , 2004, Toxicology.

[17]  C. Lau,et al.  Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[18]  Andrew C. Li,et al.  PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis Published, JLR Papers in Press, October 16, 2004. DOI 10.1194/jlr.R400010-JLR200 , 2004, Journal of Lipid Research.

[19]  L S Birnbaum,et al.  Developmental toxicity of perfluorodecanoic acid in C57BL/6N mice. , 1989, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[20]  John P. Vanden Heuvel,et al.  Differential Activation of Nuclear Receptors by Perfluorinated Fatty Acid Analogs and Natural Fatty Acids: A Comparison of Human, Mouse, and Rat Peroxisome Proliferator-Activated Receptor-α, -β, and -γ, Liver X Receptor-β, and Retinoid X Receptor-α , 2006 .

[21]  G. Kennedy,et al.  Absorption, Distribution, and Excretion of Ammonium Perfluorooctanoate (APFO) After Oral Administration to Various Species , 2006, Drug and chemical toxicology.

[22]  K. Helzlsouer,et al.  Historical Comparison of Perfluorooctanesulfonate, Perfluorooctanoate, and Other Fluorochemicals in Human Blood , 2005, Environmental health perspectives.

[23]  K. Wallace,et al.  Perfluorooctanoate, perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido ethanol; peroxisome proliferation and mitochondrial biogenesis. , 2002, Toxicology letters.

[24]  C. Tohyama,et al.  The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[25]  J M Rogers,et al.  Effects of prenatal perfluorooctane sulfonate (PFOS) exposure on lung maturation in the perinatal rat. , 2005, Birth defects research. Part B, Developmental and reproductive toxicology.

[26]  Jeffrey H Mandel,et al.  Characterization of risk for general population exposure to perfluorooctanoate. , 2004, Regulatory toxicology and pharmacology : RTP.

[27]  C. Lau,et al.  Effects of perfluorooctanoic acid exposure during pregnancy in the mouse. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[28]  Jeffrey H Mandel,et al.  Perfluorooctanesulfonate and other fluorochemicals in the serum of American Red Cross adult blood donors. , 2003, Environmental health perspectives.