SEPA

Human Health Toxicity Assessment for
Perfluorooctane Sulfonic Acid (PFOS)

January 2025

EPA Doc No. 822F25002

The EPA published the final human health toxicity assessment for PFOS 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 PFOS toxicity assessment identified adverse health effects associated with PFOS 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 PFOS toxicity assessment incorporated expert scientific recommendations
received from peer review and feedback from the public comment period.

Health Effects Identified for PFOS

The EPA's systematic review of over 700 human and animal health studies demonstrated PFOS exposure elicits adverse
noncancer and cancer health effects (see table below).Consistent with EPA's Guidelines for Carcinogen Risk Assessment, the EPA
concluded that PFOS is Likely to Be Carcinogenic to Humans via the oral route of exposure.

Effects observed
in human studies

^ Vaccine
response in
children

^ Infant birth

weight
t Risk of preterm
birth

^ Gestational age

o

Cardiovascular

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

o

Liver

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

Cancer

Liver cancer in
adults

Effects observed
in animal studies

^ Immune
response
^ Toxicity on the
immune system

^ Pup survival
^ Fetal and pup
body weight

Changes in
serum lipids

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

Liver,

pancreatic, and
thyroid tumors

Toxicity Values for PFOS

Based on the effects described above, toxicity values were calculated for PFOS - 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

Combined liver
adenomas and
carcinomas

Study

Butenhoff, 2012
Thomford, 2002

Population

Female rats

Toxicity Value

39.5 (mg/kg/day)-

^ Birth weight

Reference
Dose

(see page 2) ^ gerum total cholesterol

Wikstrom, 2020

Dong, 2019

Infants

20- to 80-year-old adults

1 xio-7 mg/kg/day

-------
a rpjfc Human Health Toxicity Assessment for January 2025
OCrM PerfIuorooctane Sulfonic Acid (PFOS) epa doc no. 822F25002

The chart below demonstrates that the PFOS 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 PFOS exposure in multiple studies, populations, and geographic locations, which increases confidence in
the RfD.

	 RfD #	O POD

n	7-year-old children; Faroe Islands	»	o

ueci„asea Budtz-J0rgensen, 2018

e anus	5-year-old children; Faroe Islands	O

Vaccine	7

Response Timrnerrnan, 2021	7-12-year-old children; Greenland		O

nBrroa„H	7-year-old children; Faroe Islands			O

uecr asea Budtz-J0rgensen. 2018

ip eria	5-year-old children; Faroe Islands	(~)

Vaccine	'

Response Timmerman, 2021	7-12-year-old children; Greenland Q.	Q

Decreased Granum, 2013	3-year-old children; Norway	r\

Rubella

^acc'	Zhang, 2023	12-19-year-old children: United States	A			«	O

Response

Chu, 2020	Infants; China	O

Sagiv, 2018	Infants; United States	0	0

Starling, 2017	Infants; United States	O

Wikstrom, 2020	Infants; Sweden						"O

Darrow, 2013	Infants; United States	~	""O

Yao, 2021	Infants; China	O

Dong, 2019	20-80-year-old adults; United States

Increased

Total	Steenland, 2009	18+ year-old adults; United States

Cholesterol

Lin, 2019	25+ year-old adults; United States

m

Gallo 2012	18+ year-old female adults; United	•	o

Increased ALT	States

Nian, 2019	22+ year-old female adults; China

Cardiovascular

Liver

10-7

10-6

PFOS Concentration
(mg/kg/day)

-------