Estimating safe doses of perfluorooctane sulfonate (PFOS): an international collaboration

Many government agencies and expert groups have estimated a safe dose (aka a "reference dose," [RfD]) for perfluorooctane sulfonate (PFOS). Notably, these agencies have derived safe doses that vary over at least 600-fold range. The range is larger still if one includes the U.S. Environmental Protection Agency (USEPA) current science-policy position under the Safe Drinking Water Act, which is that the only safe dose of PFOS is zero. This wide range in safe dose-estimates is surprising, since PFOS is a relatively well-studied, and ubiquitous, chemical. The Steering Committee of the Alliance for Risk Assessment (ARA) called for health-scientists interested in attempting to understand and, if possible, narrow this range of estimates. An advisory committee of eight scientists from four countries was selected from nominations received, and a subsequent invitation to scientists internationally led to the formation of three teams comprised of 24 scientists from nine countries. Each team independently reviewed toxicologic and epidemiologic data, and developed PFOS safe dose-estimates. All three teams concluded that currently available epidemiologic data could not form a reliable basis for PFOS safe dose-assessments. In contrast, results of bioassays of PFOS in laboratory monkeys and rats did provide usable bases from which serum-concentration-based "points of departure" were derived. After applying several, necessarily imprecise, uncertainty factors, the three groups derived PFOS safe dose-estimates that ranged, narrowly, from 20 to 100 nanograms (ng) of PFOS/kg body weight/day. In contrast, USEPA's current (United States Environmental Protection Agency (USEPA) (2024) Human health toxicity assessment for perfluorooctane sulfonic acid (PFOS) and Related Salts. EPA Document No. 815R24007.) estimate of the safe dose is 0.1 ng of PFOS/kg-day.