Open research questions in Per- and polyfluoroalkyl substances research

What the literature leaves open

• The paper also identifies the presence of PFAS in matrix blanks, which requires blank correction. The paper mentions the need to optimize the ionization conditions for LC-MS/MS analysis.

  LC–MS/MS method of 12 per- and polyfluoroalkyl substances (PFAS) in protein-rich foods for total diet study applications · 2026 · DOI

• The paper identifies a gap in the analysis of PFAS in protein-rich foods, which is a major source of human exposure. The existing methods may not be suitable for total diet study applications. The paper develops a method to fill this gap.

  LC–MS/MS method of 12 per- and polyfluoroalkyl substances (PFAS) in protein-rich foods for total diet study applications · 2026 · DOI

• It also encountered difficulties in estimating trophic levels due to the variability in trophic-level assignment and limited sample size.

  Refining Risk Assessment of Perfluoroalkyl Acids in Freshwater Ecosystems Using Submerged Macrophytes as Baseline Organism · 2026 · DOI

• There is a lack of understanding of the presence and levels of PFAS in urban environments, particularly in biota. There is a need for more studies on the bioaccumulative potential of PFAS in the urban environment. There is a gap in understanding the sources and fate of PFAS in urban environments.

  Roadkill: An Opportunistic Strategy to Track PFAS in Venomous Snakes in a South African Urban Environment · 2026 · DOI

• There is a lack of understanding of the distribution and accumulation of PFASs in terrestrial ecosystems. The study aims to fill this gap by examining the vertical distribution of PFASs in soil and taxon-specific differences among terrestrial invertebrate species.

  Distribution of Legacy and Emerging PFASs in a Terrestrial Ecosystem Located near a Fluorochemical Manufacturing Facility · 2025 · DOI

• There is a lack of understanding of the molecular determinants of PFAS binding to estrogen receptors. Prior studies have not fully elucidated the chemical properties that affect PFAS-ER binding interactions. There is a need for a predictive approach to assess the binding interactions of structurally diverse PFAS to ERs and other nuclear receptors.

  Molecular Determinants of Per- and Polyfluoroalkyl Substances Binding to Estrogen Receptors · 2025 · DOI

• The potential cardiotoxicity of F-53B remains unclear. There is a need to assess the cardiac risk associated with PFAS at environmentally relevant doses, considering environmental exposure and gene co-interaction.

  Cardiotoxic Effect Induced by F-53B via Nitric Oxide Signalling on Parkin−/− Mice · 2025 · DOI

• The study highlights the need for careful sample preparation and data analysis to ensure accurate results.

  Non-Targeted Analysis (NTA) of Plasma and Liver from Sprague Dawley Rats Exposed to Perfluorohexanesulfonamide (PFHxSA), a Precursor to Perfluorohexane Sulfonic Acid (PFHxS) · 2025 · DOI

• The study highlights the need for toxicity testing with mixtures and a more complete assessment of dosing solution purity. The authors recognize the limitations of targeted methods in detecting biotransformation products.

  Non-Targeted Analysis (NTA) of Plasma and Liver from Sprague Dawley Rats Exposed to Perfluorohexanesulfonamide (PFHxSA), a Precursor to Perfluorohexane Sulfonic Acid (PFHxS) · 2025 · DOI

• The exact scope and scale of the PFAS class are challenging to quantify. Prior work has primarily focused on the legacy PFASs, perfluorooctanoic acid (PFOA) and perfluorosulfonic acid (PFOS). There is a need to evaluate the subchronic toxicities of other PFASs.

  Subchronic Toxicities of Four Per- and Polyfluoroalkyl Substances (PFASs) by Oral Exposure in Sprague–Dawley Rats · 2025 · DOI

• The potential toxicity of long-chain per- and polyfluoroalkyl substances (PFASs) on developing zebrafish is not well studied. There is a need to investigate the effects of perfluoroundecanoic acid (PFUnDA) on zebrafish to understand its potential environmental impacts.

  Neurotoxicity Assessment of Perfluoroundecanoic Acid (PFUnDA) in Developing Zebrafish (Danio rerio) · 2025 · DOI

• One of the challenges is the difficulty in decomposing PFASs due to their stable chemical properties and long half-life. Another challenge is the need for rigorous quality filtering pipeline to ensure data reliability in transcriptomics analysis.

  Perfluorobutane Sulfonate (PFOS) Accumulation in Tissues of Cherax quadricarinatus and Its Toxicity Mechanism · 2025 · DOI

• One of the challenges is the potential for PFASs to have immunosuppressive properties in rodents and potentially in humans. Another challenge is the need to determine the no-observed adverse effect level for immunotoxicity in male rats for each of the four PFASs tested. The study also faces the challenge of interpreting the results in the context of human exposure to PFASs.

  Immunotoxicity of Four Per- and Polyfluoroalkyl Substances Following 28-Day Oral Repeat Dosing in Rats Assessed by the Anti-Sheep Red Blood Cell IgM Response · 2025 · DOI

• There is a need to assess the immunotoxicity of PFASs in rats using a 28-day oral repeat exposure. The study aims to fill this gap by evaluating the effects of four selected PFASs on serum IgM levels and organ weights.

  Immunotoxicity of Four Per- and Polyfluoroalkyl Substances Following 28-Day Oral Repeat Dosing in Rats Assessed by the Anti-Sheep Red Blood Cell IgM Response · 2025 · DOI

• The specific effect of perfluoroalkyl substances (PFASs) on Sjogren's syndrome remains unreported. The pathogenesis of pSS is postulated to ensue upon the exposure of genetically susceptible individuals to environmental risk factors.

  The Impact of Perfluoroalkyl Substances on the Clinical Manifestations of Primary Sjögren Syndrome · 2025 · DOI

• One of the challenges is the difficulty in accessing and sampling remote environments. Another challenge is the lack of standardization in methods for detecting and analyzing PFAS in different environments. The persistence and potential harm of PFAS to the environment and human health also pose significant challenges.

  Hidden Contaminants: The Presence of Per- and Polyfluoroalkyl Substances in Remote Regions · 2025 · DOI

• There is a lack of understanding of PFAS occurrence, transport, and fate in remote environments. Prior studies have focused on urban and industrial areas, leaving a gap in knowledge about PFAS in remote regions. The review aims to fill this gap by providing a comprehensive overview of PFAS in remote environments.

  Hidden Contaminants: The Presence of Per- and Polyfluoroalkyl Substances in Remote Regions · 2025 · DOI

• There are few toxicokinetic studies on PFOS in domestic livestock raised for human food consumption. The existing models may not account for sudden changes in concentrations of PFOS in the food or exposure to PFOS precursors.

  A Daily Accumulation Model for Predicting PFOS Residues in Beef Cattle Muscle After Oral Exposure · 2025 · DOI

• Uncertainties associated with TMF and BMF estimation, - Variability in trophic-level assignment, - Limited sample size, - RTMF and RBMF are relative indicators and do not represent absolute…

  Refining Risk Assessment of Perfluoroalkyl Acids in Freshwater Ecosystems Using Submerged Macrophytes as Baseline Organism · 2026 · DOI

• Adopting a multi-stressor approach for ubiquitous aquatic contaminants such as PFAS, - Investigating the effects of PFHxS at multiple concentrations, - Examining the effects of temperature on the responses to salinity…

  Hypersalinity and environmentally relevant perfluorohexanesulfonic acid independently and interactively impair survival and development in early life stage red drum (Sciaenops ocellatus) · 2026 · DOI

• Investigate the effects of PFASs on human health, - Study the transfer of PFASs between matrices, - Examine the bioaccumulation of PFASs in different…

  Distribution of Legacy and Emerging PFASs in a Terrestrial Ecosystem Located near a Fluorochemical Manufacturing Facility · 2025 · DOI

• Experimental validation of the predicted binding affinities, - Investigation of the binding interactions of PFAS with other nuclear receptors, - Development of more accurate and generalizable QSAR…

  Molecular Determinants of Per- and Polyfluoroalkyl Substances Binding to Estrogen Receptors · 2025 · DOI

• Further research is needed to validate the DAM for other PFAS and other livestock species, - Further research is needed to account for sudden changes in concentrations of PFOS in the food, - Further research is needed to account for exposure to PFAS precursors or other unaccounted for sources…

  A Daily Accumulation Model for Predicting PFOS Residues in Beef Cattle Muscle After Oral Exposure · 2025 · DOI

• The number of fish was limited, - Not all concentrations were investigated in the real-time PCR analysis, - The study was conducted in a laboratory setting, - The study only examined the effects of PFUnDA on zebrafish…

  Neurotoxicity Assessment of Perfluoroundecanoic Acid (PFUnDA) in Developing Zebrafish (Danio rerio) · 2025 · DOI

• Further studies are needed to investigate the leaching behaviour of PFAS in different soils and environments, - The development of more accurate models for predicting PFAS leaching behaviour is necessary, - Research on the effects of other factors such as pH and ionic strength on PFAS leaching behaviour…

  Evaluation of Standardised (ISO) Leaching Tests for Assessing Leaching and Solid–Solution Partitioning of Perfluoroalkyl Substances (PFAS) in Soils · 2025 · DOI

Most-cited papers in Per- and polyfluoroalkyl substances research

• An overview of the uses of per- and polyfluoroalkyl substances (PFAS) · Environmental Science Processes & Impacts · 2020 · 2,049 citations
• Per- and polyfluoroalkyl substances in the environment · Science · 2022 · 1,986 citations
• Half-Life of Serum Elimination of Perfluorooctanesulfonate,Perfluorohexanesulfonate, and Perfluorooctanoate in Retired Fluorochemical Production Workers · Environmental Health Perspectives · 2007 · 1,897 citations
• Polyfluoroalkyl Chemicals in the U.S. Population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and Comparisons with NHANES 1999–2000 · Environmental Health Perspectives · 2007 · 1,154 citations
• Per- and polyfluoroalkyl substances in water and wastewater: A critical review of their global occurrence and distribution · The Science of The Total Environment · 2021 · 902 citations
• PFAS concentrations in soils: Background levels versus contaminated sites · The Science of The Total Environment · 2020 · 816 citations
• A review of the occurrence, transformation, and removal of poly- and perfluoroalkyl substances (PFAS) in wastewater treatment plants · Water Research · 2021 · 735 citations
• Perfluorooctanoic Acid (PFOA) Exposures and Incident Cancers among Adults Living Near a Chemical Plant · Environmental Health Perspectives · 2013 · 718 citations
• Scientific Basis for Managing PFAS as a Chemical Class · Environmental Science & Technology Letters · 2020 · 712 citations
• Per and poly-fluoroalkyl substances (PFAS) as a contaminant of emerging concern in surface water: A transboundary review of their occurrences and toxicity effects · Journal of Hazardous Materials · 2021 · 614 citations

Most recent work

• From capture to circularity: carbon-based adsorbents bridging adsorption, regeneration, and destruction pathways for sustainable PFAS remediation · Journal of Materials Chemistry A · 2026
• Microplastics as vectors of antibiotics, heavy metals, and PFAS from agricultural soils to the food chain: Sources, transport pathways, and human health implications · Journal of Hazardous Materials · 2026
• Multifaceted advances in TiO 2 -based photocatalysts for PFAS degradation: a critical review of mechanisms, modifications, and challenges · Materials Advances · 2026
• Lithium metal-mediated electrochemical reduction of per- and poly-fluoroalkyl substances · Nature Chemistry · 2026
• Combined Environmental Impacts and Toxicological Interactions of Per- and Polyfluoroalkyl Substances (PFAS) and Microplastics (MPs) · Environments · 2026
• An overview of the impact of PFAS on animals, humans, and the environment using a One Health approach · Environmental Science and Pollution Research · 2026
• Competitive adsorption of per- and polyfluoroalkyl substances (PFAS) on activated carbon: Impact of activated carbon and PFAS properties · Journal of Hazardous Materials · 2026
• Environmental geochemistry of emerging contaminants: impacts on agroecosystem function, food security, and human health · Environmental Geochemistry and Health · 2026
• Risks Associated with Dietary Exposure to Contaminants from Foods Obtained from Marine and Fresh Water, Including Aquaculture · International Journal of Environmental Research and Public Health · 2026
• Challenges and Opportunities in PFAS Waste Management for Semiconductor Manufacturing · Environmental Science & Technology · 2026

Related topics in Environmental Science