Perfluorooctanoic acid pfoa studies of human animal toxicity
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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 l.jpg

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

John L. Cicmanec, DVM, MS, ACLAM, U.S. EPA

And

DeeAnn Staats, PhD DEP West Virginia


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What is PFOA (C-8)? Toxicity

  • 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


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Focus of Occupational Studies Toxicity

  • Liver function

  • Pancreatic function

  • The endocrine system

  • Lipid metabolism


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“Possible” Endocrine- Related Findings in Workers Toxicity

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)



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Biopersistence (94 days) Toxicity

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)


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Quantitative Non-cancer Risk Assessment Toxicity

Critical Studies

  • Critical Effects

    • Supporting Data

      • Uncertainty Factors

        • Derive RfD/RfC (Reference Dose)

          »Calculate Screening Values

          (water, soil & air)


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The Principal Animal Studies Used for RfD Determination Toxicity

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*


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Critical Effect Level for Animal Studies Toxicity

  • 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


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Uncertainty Factors Toxicity

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


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PFOA Screening Levels Toxicity

  • Water –

    150 micrograms/Liter(ppb)

    Soil –

    240 milligrams/kilogram (ppm)

  • Air –

    1 microgram/cubic meter (ppb)


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Animal Carcinogenicity Studies for PFOA Toxicity

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


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Significant Differences in PFOA Metabolism for Humans & Rats Toxicity

  • 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


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Risk Characterization Toxicity

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


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PFOS Toxicity

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


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Comparison of ToxicityExperimental 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


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Summary Toxicity

  • 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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