In October 2021, the U.S. Environmental Protection Agency (EPA) announced a PFAS Strategic Roadmap that identified research as one of three top priorities. The agency pledged to “invest in scientific research to fill gaps in understanding of PFAS, to identify which additional PFAS may pose human health and ecological risks at which exposure levels, and to develop methods to test, measure, remove, and destroy them.”

As it develops a research agenda, we hope the EPA will consider the important findings of an independent critical review of PFAS studies that was funded by the Center and published in Environmental Research.

A scientific team from the University of Rovira i Virgili in Spain examined an independently pre-selected group of nine studies—four human and five animal—most often considered by those making decisions on the use of PFAS. Below are the most salient findings of the review in terms of the EPA’s agenda:

• Most of the recent studies associating exposure to PFAS with adverse health outcomes are cross-sectional analyses, making the data insufficient to draw accurate conclusions about the association of PFAS with any specific disease.
• Future research should include types and numbers of animals, computerized randomization, and descriptions of any deviation from protocols that appear in published articles to avoid bias and strengthen the evidence from animal investigations.
• When deciding dosing levels for animals, a human-relevant dose needs to be appropriately calculated in order to further link associations with human risk assessment and set tolerable daily intake (TDI) for humans.
• With recent evidence of selected PFAS involvement in immune hazards to humans, future human studies must characterize wider immune outcomes including immune effects from early exposure during pregnancy and the possible role of various PFAS in initiating allergic and autoimmune processes, conditions for which a dose-response is hard to predict.
• More longitudinal epidemiology studies are needed with additional susceptible human endpoints. In particular, prospective vaccination studies covering more varied types of vaccines and different populations, and more studies on other human immune outcomes.

The critical review also provided solid information on the scientific quality of the nine studies. It identified many strengths, but also important limitations where more evidence is needed before policy decisions can be adequately informed.

• One such limitation was the use of a conventional approach to measure toxicity, even though people are exposed to many chemicals in their lives, especially various kinds of PFAS. These co-exposures can confound any effects that are observed.
• It is also still being debated whether different PFAS compounds should be considered as one group, or separately, when developing policies. The authors recommend a grouping strategy to identify potential health effects by groups before deciding on best policies.
• Another area that needs to be addressed in future research is that of subpopulations, and how exposure to different PFAS affect each, including children and older adults.
• To address a lack of consistency between the findings of some existing PFAS studies, the review authors suggest standardized protocols to increase confidence in future research findings. These could be set by regulatory bodies working together with scientists.
• As the need for PFAS research is considered urgent, the review authors suggest the use of advancements in computational toxicology, such as in-silico tools, to reduce the time needed for experimental studies.
• Lastly, the authors strongly recommend a shift to the use of a translational toxicology approach, which involves the integration of data from many different methods, such as pharmacokinetics, pharmacodynamics, and systems biology, among others. While this   approach can be complicated and expensive, it would provide accurate information on health and environmental harms, especially for subpopulations, and will lead to better science-based decision making that reduces panic and improves policy.

The EPA has made a strong commitment to using science-based decision making to implement the Roadmap, and to direct the safe use of PFAS in products that improve safety and lives. The agency should be commended for that, while also reminded to use the best science available.