PFAS and Human Health: A Review of Current Epidemiological Evidence
Exposure pathways
Drinking water is the dominant exposure pathway in communities near PFAS-contaminated sites — typically military air bases, airports, and fluorochemical manufacturing plants where aqueous film-forming foam (AFFF) has been used. Dietary exposure (via contaminated food packaging, processed foods, and produce irrigated with contaminated water) is the dominant pathway in the general population away from point sources. PFAS are highly persistent: PFOA has a human serum half-life of approximately 3.5 years, meaning body burden accumulates with continued low-level exposure.
Thyroid effects
The most consistent epidemiological association is between serum PFOA/PFOS concentrations and subclinical thyroid dysfunction. A 2020 meta-analysis of 17 cohort studies (n = 54,000) found a pooled odds ratio of 1.32 (95% CI: 1.18–1.47) for hypothyroidism per interquartile range increase in serum PFOA. The mechanism — competitive binding to thyroid hormone transport proteins and interference with hepatic clearance of T4 — is biologically plausible and consistent across rodent and primate models.
Cholesterol and cardiovascular risk
Elevated total cholesterol and LDL-cholesterol are among the most replicated PFAS-associated outcomes, observed in both occupationally exposed workers and community cohorts. The C8 Health Project (n = 69,000 residents near DuPont's Washington Works plant) found a 4.7 mg/dL increase in total cholesterol per doubling of serum PFOA concentration. Whether this translates to elevated cardiovascular event risk is not yet established, because confounders (diet, physical activity, genetic lipid disorders) are difficult to control at the required scale.
Immune function and vaccine response
A 2012 cohort study of Faroese children (n = 513) found that PFOS and PFOA concentrations in maternal serum at gestational week 32 were associated with significantly attenuated antibody response to childhood tetanus and diphtheria vaccines, with a doubling of serum concentration associated with a roughly 50% reduction in vaccine-induced antibody titres. This finding — replicated in subsequent studies — has been explicitly referenced by the US EPA in setting the 2024 MCLs.