Health benefit considerations for the development of fish advisory guidelines for PFOS

Perfluorooctane sulfonate (PFOS) is a persistent per-fluoroalkyl substance that bioaccumulates in freshwater fish and is increasingly driving new fish consumption advisories in the United States. Toxicity assessments have derived low PFOS reference doses that might be exceeded by fish consumption from many relatively uncontaminated waterbodies. Because PFOS cannot be readily removed from fish, and fish provide substantial nutritional health benefits, advisory programs need to consider health consequences of both PFOS-initiated toxicity and lost benefits of reduced fish intake. This narrative review synthesizes epidemiological and mechanistic evidence for benefits of fish consumption overlapping with four priority PFOS noncancer health endpoints (immune, hepatic, cardiovascular, developmental) identified by USEPA. For each endpoint, biological pathways were examined through which n-3 PUFAs may counterbalance/modulate PFOS-associated toxicity, including competitive binding at nuclear receptors, anti-inflammatory signaling, lipid regulation, and effects on fetal growth and immune function. Although quantitative data are lacking, evidence supports a risk-benefit framework for PFOS fish advisories that acknowledges potential offsets between PFOS risks and fish-consumption-associated health benefits. In addition, critical data gaps were identified, including the need for biomonitoring studies assessing PFOS and fish-derived nutrient co-exposures. Overall, this review provides scientific context for balanced public health decision-making for those individuals who rely on local fish as an accessible and health-promoting food.