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Perfluorooctanoic Acid (PFOA): Studies of Human & Animal Toxicity

Perfluorooctanoic Acid (PFOA): Studies of Human & Animal Toxicity. John L. Cicmanec, DVM, MS, ACLAM, U.S. EPA And DeeAnn Staats, PhD DEP West Virginia. What is PFOA (C-8)?. Ammonium Perfluorooctanoate Like hydrocarbons but with all Hydrogen atoms replaced with Fluorine

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Perfluorooctanoic Acid (PFOA): Studies of Human & Animal Toxicity

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  1. Perfluorooctanoic Acid (PFOA): Studies of Human & Animal Toxicity John L. Cicmanec, DVM, MS, ACLAM, U.S. EPA And DeeAnn Staats, PhD DEP West Virginia

  2. What is PFOA (C-8)? • Ammonium Perfluorooctanoate • Like hydrocarbons but with all Hydrogen atoms replaced with Fluorine • Compounds are very stable • They repel both water and oils and reduce surface tension dramatically • Over 100 thousand pounds produced each year, captured on-site with resin in water

  3. Focus of Occupational Studies • Liver function • Pancreatic function • The endocrine system • Lipid metabolism

  4. “Possible” Endocrine- Related Findings in Workers Increased Cholecystokinin levels in 2 workers Elevated Estrogen levels in 4 workers-correlation with body fat index ratios Worker blood levels – 0-114 ppm (mean – 5 ppm)

  5. Little Hocking Wellfield

  6. Biopersistence (94 days) Biodegradation 13% at 28 d. Sediment adsorption Fish toxicity LC50 Mammalian LD50 Acute Oral toxicity 3 species Inhalation LC50 2 species Dermal LD50 Eye Irritation 2-year Feeding Study Repeated Dermal Dose Developmental toxicity Metabolic studies Cholestyramine resin Placental transfer Respirator evaluation Glove permeation Synopsis of Testing (PFOA)

  7. Quantitative Non-cancer Risk Assessment Critical Studies • Critical Effects • Supporting Data • Uncertainty Factors • Derive RfD/RfC (Reference Dose) »Calculate Screening Values (water, soil & air)

  8. The Principal Animal Studies Used for RfD Determination StudyCritical Adverse Effect Palazzolo, 1993 increased liver weight 90-day rat study & histopathology York, 2002 increased liver weights 2-generation reproductive & histopathology 3M, 1983 ovarian stromal hyperplasia; 2-year rat study hepatic megalocytosis Butenhoff, 2002 increased liver weight 26-week monkey study decreased T-3 & T-4 levels*

  9. Critical Effect Level for Animal Studies • Palazzolo,1993 0.47 mg/kg-day • York,2002 1.0 mg/kg-day • 3M, 1983 1.6 mg/kg-day • Butenhoff, 2002 3 mg/kg-day

  10. Uncertainty Factors FACTOR EXTRAPOLATION H 10 Average Human to Sensitive Human A 10 Animal to Human S 10 Short Term to Long Term Exposure L 10 LOAEL to NOAEL D 10 Minimum to Complete Database A value of 1, 3, or 10 can be used in each category

  11. PFOA Screening Levels • Water – 150 micrograms/Liter(ppb) Soil – 240 milligrams/kilogram (ppm) • Air – 1 microgram/cubic meter (ppb)

  12. Animal Carcinogenicity Studies for PFOA Riker Labs (1993) found treatment-related increases in Leydig cell adenomas* and mammary gland fibroadenomas in rats Biegel, et al. (2001) found treatment-related tumors in the liver*, Leydig cells* and pancreas* * Causative mechanism involves peroxisome proliferation in rats; this mechanism may not be significant in humans

  13. Significant Differences in PFOA Metabolism for Humans & Rats • There is a marked gender difference in serum & tissue half-lives for rats; females much shorter than males-in humans it is about equal • Peroxisome proliferation is much more significant for rats than humans

  14. Risk Characterization Describe the scientific data base Describe the exposure scenario List key assumptions that were made Describe how the process wasperformed, including calculations Describe other approachesand conflicting data Uncertainty vs variability

  15. PFOS Doses-30,150,750 ųg/kg-da 750 ųg/kg- low T3, low body weight, increased liver weight Two of six males died in the high dose group Blood levels- 67-83 ppm monkeys; 0.028 ppm humans PFOA Doses - 3, 10, 30/20 mg/kg One death in 3 mg/kg-day group & 2 deaths in 30/20 mg/kg-day Adverse effect- increased liver weight 3 mg/kg-day Blood level – 10 ppm Comparison of Monkey study Results

  16. Comparison of Experimental Monkey Blood Levels to Environmental Human Exposure Levels • 26-week Monkey study resulted in blood concentrations of 10 ppm • Occupational human exposure levels – 0 to 114 ppm (mean 5 ppm) • Environmental human exposure levels 0 to 40 parts per billion

  17. Summary • The results of animal studies and environmental monitoring indicate that PFOA is not presently an environmental health threat • Although some endocrine effects have been observed, they are not the critical adverse effect

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