Despite decades of research on per- and polyfluoroalkyl substances (PFAS), fundamental obstacles remain to addressing worldwide contamination by these chemicals and their associated impacts on environmental quality and health. Here, we propose six urgent questions relevant to science, technology, and policy that must be tackled to address the "PFAS problem": (1) What are the global production volumes of PFAS, and where are PFAS used? (2) Where are the unknown PFAS hotspots in the environment? (3) How can we make measuring PFAS globally accessible? (4) How can we safely manage PFAS-containing waste? (5) How do we understand and describe the health effects of PFAS exposure? (6) Who pays the costs of PFAS contamination? The importance of each question and barriers to progress are briefly described, and several potential paths forward are proposed. Given the diversity of PFAS and their uses, the extreme persistence of most PFAS, the striking ongoing lack of fundamental information, and the inequity of the health and environmental impacts from PFAS contamination, there is a need for scientific and regulatory communities to work together, with cooperation from PFAS-related industries, to fill in critical data gaps and protect human health and the environment.

Chair of Ecological Systems Design Institute of Environmental Engineering ETH Zürich 8093 Zürich Switzerland

Department of Environmental Science Stockholm University SE 10691 Stockholm Sweden

Department of Pharmacology and Toxicology Brody School of Medicine East Carolina University Greenville North Carolina 27834 United States

Departments of Civil and Environmental Engineering and Environmental and Occupational Health University of Pittsburgh Pittsburgh Pennsylvania 15261 United States

European Environment Agency Kgs Nytorv 6 DK 1050 Copenhagen K Denmark

Graduate School of Oceanography University of Rhode Island Narragansett Rhode Island 02882 United States

Health and Environment Program Commonweal Bolinas California 94924 United States

Institute for Arctic and Marine Biology UiT The Arctic University of Norway N 9037 Tromsø Norway

Institute of Biogeochemistry and Pollutant Dynamics ETH Zürich 8092 Zürich Switzerland

Milieu Consulting SPRL 1060 Brussels Belgium

National Institute of Environmental Health Science and U S Public Health Service Research Triangle Park North Carolina 27709 United States

Norwegian Institute for Air Research Fram Centre N 9296 Tromsø Norway

RECETOX Masaryk University 625 00 Brno Czech Republic

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