Human health impacts of PFAS exposure: A second-order meta-analysis

Lorenzo Ricolfi, Yefeng Yang, Kyle Morrison , Niki Marjerrison, Marcin W. Wojewodzic, Malgorzata Lagisz, Shinichi Nakagawa

Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals with pervasive human exposure. Numerous meta-analyses have synthesised results on the association between PFAS exposure and human health, yet findings remain fragmented and often inconsistent across compounds, outcomes, and studies. We assessed the magnitude and consistency of associations between PFAS exposure and human health outcomes by integrating evidence from 23 meta-analyses encompassing 161 primary studies. PFAS exposure was associated with a 5% increase in the odds of adverse health outcomes (overall OR = 1.05, 95% CI: 1.03–1.08) and a moderate heterogeneity (overall I² = 64%, 95% CI: 42–78%). Perfluorobutanesulfonic acid (PFBS) showed the largest and most consistent association among chemicals (OR = 1.30, I² = 38.1%), endocrine diseases showed the strongest association among health outcomes (OR = 1.11, I² = 61.7%), and pregnancy-related outcomes showed the highest consistency (OR = 1.04, I² = 35.9%). The widespread nature of PFAS exposure means even small relative risks could translate into substantial population-level burdens. These findings strengthen the evidence base for regulatory measures, highlight vulnerable health domains, and identify priority areas for further research, particularly for understudied compounds and outcomes.