SEPA

Human Health Toxicity Assessment for
Perfluorooctanoic Acid (PFOA)

January 2025

EPA Doc No. 822F25001

EPA published the final human health toxicity assessment for PFOA in April 2024.

A toxicity assessment summarizes the potential health effects associated with exposure to a particular chemical
and identifies the dose levels at which the health effects may occur in order to calculate toxicity values.

The PFOA toxicity assessment identified adverse health effects associated with PFOA exposure using a robust systematic review
process based on EPA peer-reviewed human health risk assessment methodology.

Systematic review is a structured and documented process for transparent literature review using explicit, pre-
speciHed scientific methods to identify, select, assess, and summarize the findings across relevant studies.

Systematic review promotes use of the best available science and reduces bias.

The EPA followed its peer-reviewed human health risk assessment methodology and applicable guidance documents for all steps of
the toxicity assessment including hazard identification, cancer classification, and toxicity value development (e.g., USEPA, 2002;
USEPA. 2005; USEPA. 2012; USEPA. 2022). The PFOA toxicity assessment incorporated expert scientific recommendations
received from peer review and feedback from the public comment period.

Health Effects Identified for PFOA

The EPA's systematic review of over 780 human and animal health studies demonstrated PFOA exposure elicits adverse
noncancer and cancer health effects (see table below). Consistent with EPA's Guidelines for Carcinogen Risk Assessment, the EPA
concluded that PFOA is Likely to Be Carcinogenic to Humans via the oral route of exposure.

Effects observed
in human studies

^Vaccine
response in
children

^ Immune
response

Effects observed
in animal studies

^ Infant birth
weight

•if Pup survival
^ Fetal and pup
body weight
Delayed
developmental
timing

¦2

3H

•vascular 1



Cardie

f Serum lipids
(total cholesterol
and LDL)
f Blood pressure
in adults

^ Serum liver
enzymes (ALT)
indicative of liver
damage in
adults

Change in
serum lipids

^ Liver cell death
and serum liver
enzymes (ALT)
indicative of liver
damage

Cancer

Kidney and
testicular cancer
in adults

Testicular,
pancreatic, and
liver tumors

Toxicity Values for PFOA

Based on the effects described above, toxicity values were calculated for PFOA - a cancer slope factor (CSF) and a reference dose
(RfD) - in line with EPA peer-reviewed human health risk assessment methodology and applicable guidance documents.

•	A CSF is an upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime exposure
to an agent. The CSF is the change in risk per unit dose.

•	A RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human
population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a
lifetime. Uncertainty in the data is accounted for by including uncertainty factors in the RfD to protect public health.

Cancer Slope
Factor

Critical Effect

Kidney cancer

^ Tetanus and diphtheria
vaccine response

Study

Population

Toxicity Value

Shearer, 2021 (supported by „ . ,. ,. . ,, _ . „ .. .
Viera. 2013: see Sec. 4.2.2 1) 55-to 74-year-old adults 0.0293 (ng/kg/day)"

Reference

Dose ^ Birth weight

(see page 2)

^ Serum total cholesterol

Budtz-J0rgensen, 2018

Wikstrom, 2020
Dong, 2019

5- to 7-year-old children

Infants	3x10-8 mg/kg/day

20- to 80-year-old adults

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a rpjfc Human Health Toxicity Assessment for January 2025
OCrM	Perfluorooctanoic Acid (PFOA)	epa doc no. 822F25001

The chart below demonstrates that the PFOA exposure level expected to cause adverse noncancer effects on the immune system,
development, the cardiovascular system, and the liver in humans (Point of Departure, POD) are similar. The chart also depicts the
selected PODs with adjustments (Uncertainty Factors, UF) to be protective of at-risk populations and account for data gaps to
derive candidate reference doses (RfD). Overall, or final, RfDs are in orange.

Effects on the immune and cardiovascular systems, development, and the liver occur at the same or approximately the
same doses of PFOA exposure in multiple studies, populations, and geographic locations, which increases confidence in
the RfD.

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