Health Effects: PFAS Information for Clinicians - 2024

Pathophysiology

The pathophysiology of PFAS toxicity is an area of active research. Many studies of populations have examined possible relationships between levels of PFAS in blood and rates of harmful health effects (see section below), but research has not yet confirmed mechanisms for each health effect. Complicating this challenge is that PFAS are sometimes examined as a class and other times examined as individual compounds.

Health effects associated with PFAS

The Agency for Toxic Substances and Disease Registry (ATSDR)'s 2021 Toxicological Profile for Perfluoroalkyls provides a comprehensive review of toxicological information for 12 different PFAS. ATSDR evaluated the available epidemiological data and found that the preponderance of the evidence suggested associations between exposure to individual PFAS and certain health effects.

Additionally, ATSDR and the National Institute of Environmental Health Sciences (NIEHS) funded the National Academies of Science, Engineering, and Medicine (The National Academies or NASEM) to provide an objective review of the current evidence regarding human health effects of PFAS. In its 2022 report Guidance on PFAS Testing and Health Outcomes, NASEM categorized the strength of evidence for various health effects for PFAS as a class. In addition to the health effects listed by ATSDR, NASEM also found epidemiologically-based associations with additional health effects.

Some animal and human studies find positive associations between PFAS exposure and a much wider range of health effects. For example, they identify associations with serum uric acid concentrations, reproductive health, diabetes, kidney effects, asthma, and neurobehavioral outcomes. Results of animal studies do not always correlate with human health effects because of physiologic differences between species. Inconsistent findings among human studies and study design limitations are some reasons why other potential health effects are not identified as associated with PFAS.

Health Effects Associated with PFAS

Health Effect		ATSDR Review of Associations (PFAS Associated with Health Effects)*	NASEM Category of Association†
NASEM and ATSDR Health Effects
	Increases in cholesterol levels	Evidence of an association (PFOA, PFOS, PFNA, PFDA)	Sufficient evidence of an association
	Small decreases in birth weight (<0.7-ounce decrease per 1 ng/mL blood PFOA/PFOS increase)	Evidence of an association (PFOA, PFOS)	Sufficient evidence of an association
	Lower antibody response to vaccines in children	Evidence of an association (PFOA, PFOS, PFHxS, PFDA)	Sufficient evidence of an association
	Kidney and testicular cancer	Evidence of an association (PFOA)	Sufficient evidence for kidney cancer / Limited or suggestive evidence for testicular cancer
	Pregnancy-induced hypertension or preeclampsia	Evidence of an association (PFOA, PFOS)	Limited or suggestive evidence of an association
	Changes in liver enzymes	Evidence of an association (PFOA, PFOS, PFHxS)	Limited or suggestive evidence of an association
Additional Health Effects Considered
	Thyroid disease and dysfunction	No consistent evidence of an association	Limited or suggestive evidence of an association
	Breast cancer	No consistent evidence of an association	Limited or suggestive evidence of an association
	Ulcerative colitis	No consistent evidence of an association	Limited or suggestive evidence of an association

ATSDR and NASEM use different language to describe the strength of an association.

Many newer PFAS have properties, such as a shorter half-life, that limit the ability to use blood levels as a proxy for long-term exposure. This makes it more challenging to study whether exposure to these PFAS could cause health effects.

^*ATSDR's approach took into consideration the consistency of the findings across studies, the quality of the studies, dose-response, and plausibility. Although the data may provide evidence for an association, it does not always imply that the observed effect is biologically relevant because the magnitude of the change may be within the normal limits or not indicative of an adverse health effect. Causal relationships have not been established for these health effects.

^†NASEM reviewed associations with PFAS as a class rather than by specific PFAS.

Factors impacting the risk of health effects

The risk of health effects associated with environmental exposures, including PFAS, depends on exposure factors (e.g., dose, frequency, route, and duration), individual factors (e.g., sensitivity to exposure and chronic disease burden), and other determinants of health (e.g., access to safer water and quality healthcare).