PFAS and Human Health—Epidemiological Evidence

Abstract

Per- and polyfluoroalkyl substances (PFAS) are highly persistent industrial chemicals with widespread human exposure. Epidemiological evidence published mainly since 2020 was reviewed, prioritizing systematic reviews, meta-analyses and key original studies. The strongest and most consistent associations are observed for dyslipidaemia (higher total/low-density lipoprotein), markers of liver injury and fatty liver disease and reduced vaccine antibody responses—particularly in children. Evidence also suggests associations with hypertensive disorders, type 2 diabetes, altered thyroid function, adverse birth outcomes (lower birthweight, shorter gestation), decreased fecundability and male reproductive endpoints (reduced semen quality); however, heterogeneity and exposure misclassification remain important limitations. For cancer, the International Agency for Research on Cancer classified perfluorooctanoic acid as carcinogenic to humans (Group 1) and perfluorosulphonic acid as possibly carcinogenic (Group 2B), supported by limited human evidence (kidney and testicular cancer) and strong mechanistic evidence. Regulatory benchmarks have tightened globally, reflecting concern about health risks at low exposure levels. Priority research needs include longitudinal studies at general-population exposures, mixture/next-generation PFAS, susceptible windows and clinical significance of biomarker shifts. This review synthesizes current human evidence to inform risk assessment and public health actions. The review also highlights that most toxicological findings are derived from exposure levels several orders of magnitude higher than those in the general population, underscoring the need to clarify the clinical relevance of subtle biomarker changes at low-dose exposures.