IARC 2023: Formalizing the Cancer-PFAS Link
In October 2023, the International Agency for Research on Cancer (IARC)—the cancer research arm of the World Health Organization—published Monograph 135, classifying perfluorooctanoic acid (PFOA) as Group 1 (carcinogenic to humans) and perfluorooctane sulfonic acid (PFOS) as Group 2B (possibly carcinogenic to humans). These classifications—PFOA’s upgrade from Group 2A (probably carcinogenic) and PFOS’s first formal IARC evaluation—represent the most authoritative global scientific judgment on PFAS carcinogenicity, with significant implications for regulatory standards, litigation outcomes, and medical surveillance programs for exposed populations.
How IARC Evaluates Carcinogenicity
IARC’s classification system evaluates the “strength of evidence” for carcinogenicity across three lines: human epidemiological evidence (epidemiological studies in exposed populations); animal bioassay evidence (cancer studies in experimental animals); and mechanistic evidence (understanding of biological mechanisms by which carcinogenesis could occur). Group 1 (carcinogenic to humans) requires “sufficient evidence in humans”—consistent, strong epidemiological evidence in multiple studies. Group 2A (probably carcinogenic) requires “limited evidence in humans” with “sufficient evidence in animals.” Group 2B (possibly carcinogenic) requires either limited human evidence or strong animal evidence without adequate human data. Importantly, IARC classifications reflect strength of evidence for carcinogenicity, not estimates of actual cancer risk at environmental exposure levels—a nuance often misunderstood in public communication about IARC findings.
The Evidence Base for PFOA Group 1 Classification
IARC’s working group based the PFOA Group 1 classification primarily on: Human evidence: Consistent associations between PFOA exposure and renal cell carcinoma (kidney cancer) in the C8 Health Project and in occupational cohorts at PFOA production facilities; associations with testicular cancer in multiple cohort and case-control studies; elevated risk of breast cancer in some cohort studies. The kidney cancer evidence was considered “sufficient”—meeting the Group 1 threshold. Animal evidence: Liver cancer in rats; thyroid cancer; testicular tumors in rats at PFOA doses exceeding human environmental exposure levels but providing biological plausibility. Mechanistic evidence: PFOA binding to peroxisome proliferator-activated receptors (PPARs) driving cell proliferation; oxidative stress; immune suppression potentially contributing to reduced tumor surveillance. The combination of consistent human kidney cancer evidence, supporting animal studies, and coherent mechanistic data supported the highest classification.
PFOS Group 2B: The Uncertain Evidence
PFOS received Group 2B classification because human epidemiological evidence for specific cancers was “limited”—suggestive but not consistent across multiple independent studies. Animal studies showed pancreatic cancer in rats and liver cancer at high doses. Mechanistic evidence showed PPARA activation similar to PFOA. The IARC working group concluded that the animal and mechanistic evidence supported possible carcinogenicity but that human studies did not provide the consistent evidence needed for Group 1 or 2A. This distinction may reflect the smaller occupational PFOS cohorts studied (3M’s Decatur facility) compared to the DuPont Washington Works PFOA cohort—not necessarily a fundamental difference in cancer risk. As epidemiological follow-up of PFOS-exposed populations continues, reclassification to Group 2A or Group 1 in a future IARC monograph is considered likely by many researchers.
IARC’s 2023 PFOA Group 1 classification places PFOA in the same carcinogenicity evidence category as asbestos, tobacco smoke, and benzene—a landmark scientific judgment that provides durable foundation for the most stringent regulatory standards and strengthens the epidemiological basis for ongoing PFAS litigation.