# Presentation: 675229

## 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**
**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**

## Focus of Occupational Studies

- Liver function
- Pancreatic function
- The endocrine system
- Lipid metabolism

##  “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)**

## Little Hocking Wellfield

## Synopsis of Testing (PFOA)

**Biopersistence (94 days)**
**Biodegradation 13% at 28 d.**
**Sediment adsorption**
**Fish toxicity   LC****50**
**Mammalian    LD****50**
**Acute Oral toxicity 3 species**
**Inhalation   LC****50   ****2 species**
**Dermal       LD****50**

**Eye Irritation**
**2-year Feeding Study**
**Repeated Dermal Dose**
**Developmental toxicity**
**Metabolic studies**
**Cholestyramine resin**
**Placental transfer**
**Respirator evaluation**
**Glove permeation**

## Quantitative Non-cancer Risk Assessment

- Critical Studies
- Critical Effects
- Supporting Data
- Uncertainty Factors
- Derive RfD/RfC (Reference Dose)
- 		»Calculate Screening Values
- 		        (water, soil & air)

## The Principal Animal Studies Used for RfD Determination

_**Study**_                                    _**Critical 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*****

## 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  **

## 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**
**       **

## PFOA Screening Levels

**Water – **
_**150 **_**micrograms/Liter(ppb)**
**Soil – **
_**240**_** milligrams/kilogram (ppm)**
**Air – **
_**1**_** microgram/cubic meter (ppb****)**

## 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

## 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**

## Risk Characterization

**Describe the scientific **_**data base**_
**Describe the **_**exposure scenario**_
**List key **_**assumptions**_** that were made**
**Describe **_**how the process was**_** **_**performed**_**, including calculations**
**Describe **_**other approaches**_** ****and conflicting data**
**Uncertainty vs variability**

## Comparison of Monkey study Results

**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 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**_

## 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**