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Open research questions in Per- and polyfluoroalkyl substances research

47 unresolved questions extracted from the limitations and future-work sections of 310 Per- and polyfluoroalkyl substances research papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Current human evidence is strongest for impaired vaccine antibody responses and altered growth or metabolic trajectories in studies dominated by legacy PFAS, whereas evidence for other congeners, short-chain PFAS, ether-based alternatives, and fluorotelomer compounds remains sparse.

    Prenatal PFAS exposure and offspring health: evidence review and implications for intergenerational risk assessment · 2026 · DOI

  • Metals and per- and polyfluoroalkyl substances (PFAS) represent a significant environmental concern, yet their association with epigenetic age acceleration (EAA) remain largely understudied in marine mammals.

    Epigenetic age acceleration is associated with contaminant exposure in common dolphins (Delphinus delphis) · 2026 · DOI

  • Per- and polyfluoroalkyl substances (PFAS) are ubiquitous endocrine-disrupting pollutants that cross the placenta and affect offspring health, but the extent and timing of their transfer to placental and fetal compartments remain poorly understood.

    Tracing PFAS Transfer from Mother to the Fetoplacental Unit: Insights from Trimester-Specific Maternal Serum Profiles · 2026 · DOI

  • When long chain PFAS are sparsely and covalently attached to such templates, abrasion durability of oil repellency mark- edly exceeds that of PFAS nanoparticle composites, as meas- ured by Martindale testing.

    Breaking Free from Hazardous Forever Chemicals: Pathways to PFASFree Hydrophobic and Oleophobic Coatings · 2026 · DOI

  • Curr Opin Environ Sci Health 7:8–12 De Silva AO, Armitage JM, Bruton TA, Dassuncao C, Heiger-Ber- nays W, Hu XC, Karrman A, Kelly B, Ng C, Robuck A, Sun M, Webster TF, Sunderland EM (2021) PFAS exposure pathways for humans and wildlife: a synthesis of current knowledge and key gaps in understanding.

    Occurrence of per- and polyfluoroalkyl substances in tap drinking water in British Columbia, Canada · 2026 · DOI

  • Per- and polyfluoroalkyl substances (PFAS), environmentally persistent contaminants, have been linked to developmental abnormalities, yet their impact on core embryonic gene regulatory networks especially during MZT is not well understood.

    Environmental PFOA Exposure Alters Early Developmental Programming during the Maternal Zygotic Transition · 2026 · DOI

  • Early sustainability reporting emerged largely as a voluntary practice, driven by stakeholder and institutional pressures, legitimacy concerns, and economic considerations (Hahn and Kühnen 2013). A substantial body of literature examines the determinants of voluntary sustainability reporting and finds that firm size, industry affiliation, visibility, and stakeholder scrutiny are among the most consistent predictors of disclosure (Hahn and Kühnen 2013; Dienes et al. 2016; Arkoh et al. 2024). Firms operating in environmentally sensitive industries are more likely to engage in sustainability reporting, reflecting higher exposure to environmental risks and reputational concerns (Velte 2023). However, prior research consistently documents important limitations of voluntary reporting. Disclosures tend to be selective, qualitative, and focused on positive aspects of corporate performance, while negative impacts and controversial issues are often omitted or downplayed (Hahn and Kühnen 2013; Dienes et al. 2016). This has raised concerns about symbolic reporting and greenwashing, particularly when firms face weak regulatory oversight or when reporting frameworks provide broad discretion (e.g., Luu et al. 2025; Mateo-Márquez et al. 2022). As a result, voluntary sustainability reporting often fails to provide comparable, decision-useful information to stakeholders (Christensen et al. 2021). 2.2. The shift toward mandatory sustainability reporting In response to the shortcomings of voluntary disclosure, regulators increasingly rely on mandatory sustainability reporting regimes. There is evidence that mandatory sustainability reporting can lead to improvements in environmental and social outcomes. For example, mandatory disclosure has been associated with reductions in greenhouse gas emissions, improved workplace safety, and increased investment in sustainable practices (Delmas et al. 2010; Bennear and Olmstead 2008; Chen et al. 2018; Downar et al. 2021). Related research also shows spillover effects along supply chains and across borders, suggesting that disclosure mandates can influence behavior beyond directly regulated firms (She 2022; Kim et al. 2025). In addition, mandatory sustainability reporting is found to be value relevant. Importantly, firms with stronger sustainability performance and more credible disclosures tend to benefit from mandatory regimes, whereas firms with poor performance or low transparency may face negative market reactions (Baboukardos 2017; Grewal et al. 2019; Jouvenot and Krueger 2019; Mittelbach- -Hörmanseder et al. 2021; Vishnu Nampoothiri et al. 2024). https://mab-online.nlOlga Ihl-Deviv’e, Thomas Thijssens: PFAS disclosure practices of Dutch listed companies Maandblad voor Accountancy en Bedrijfseconomie 100(3): 101–116 103 2.3.

    PFAS disclosure practices of Dutch listed companies: An exploratory study · 2026 · DOI

  • acknowledgment. First, in both NHANES (n = 118) and the GSE27276 dataset (17 POAG, 19 controls) limit statistical power, rendering our bioinformatic predictions inherently hypothesis-generating. Second, regarding our in vitro mechanistic validation, a discrepancy exists between physiological serum levels and the supraphysiological PFOS dosages (5–20 μM) strategically employed as an accelerated model to elicit senescence within a 72-h timeframe. Furthermore, standard static cell cultures inherently fail to mimic the dynamic biomechanical environment of trabecular meshwork. Finally, the proposed PFOS-FABP4-P21 axis currently lacks validation in vivo animal models. Consequently, future exposures, investigations biomechanically active 3D culture systems, and in vivo validation are essential to fully recapitulate lifelong environmental dynamics and structural complexities. the small clinical cohorts the physiological incorporating low-dose chronic present the of These mechanistic insights suggest promising therapeutic strategies. The use of FABP4 inhibitors, such as BMS309403, could prevent PFOS from interfering with endogenous lipid transport. Furthermore, our findings imply that exogenous supplementation of unsaturated fatty acids might bypass the transport blockade to maintain membrane integrity and delay HTMC senescence (Zhang et al., 2021; Kalogerou et al., 2022).

    Perfluorooctanesulfonic acid contributes to primary open-angle glaucoma in a FABP4-Dependent manner: a novel mechanism for environmental risk of glaucoma · 2026 · DOI

  • The ever-evolving abundance and diversity of PFAS has made determining negative health effects complex, time- consuming, and resource-intensive. We pinpointed sev- eral potential solutions to better research PFAS-induced lung toxicity in future studies: [i] broaden the types of PFAS being studied to include more replacement PFAS compounds, [ii] incorporate more inhalation exposure models, [iii] enhance inter-disciplinary collaboration, [iv] incorporate dose-response study designs, [v] consider PFAS mixtures and co-exposures, and [vi] leverage next generation technologies to more efficiently test across the wide variety of PFAS and PFAS-related exposures. These disparities and our recommendations are highlighted in greater detail below. Among the 37 animal and in vitro articles identified by this review, a majority evaluated legacy (long-chain) PFAS, predominantly PFOS and PFOA; however, as man- ufacturers shift away from using legacy compounds, there is an urgent need to better characterize the toxic effects of replacement PFAS chemistries, such as short chain and chlorinated and brominated PFAS [109], in both the envi- ronment and in humans [106]. Notably, many of the new and emerging PFAS are more volatile than their longer- chain predecessors, introducing an even greater risk for inhalation exposure than observed previously. Since air- borne PFAS have been detected in common outdoor and, more recently, indoor air environments, direct exposure to the lungs is a growing concern. Only six (all in rodents) of the 37 identified articles leveraged inhalation-relevant exposure techniques. Inhalation exposures can often be more technically demanding and difficult to manage than oral, dermal, or liquid application exposures in both animal and in vitro models, creating a barrier for adopting these techniques and approaches into practice. Notably, PFAS are especially difficult to generate as an aerosol or vapor Current Allergy and Asthma Reports (2026) 26:30 1 3 and require advanced equipment and expertise to ensure exposures are conducted properly. Collaborative efforts across different disciplines – air chemists, engineers, toxi- cologists, molecular biologists, medical professionals, and bioinformaticians – can help overcome these hurdles, mak- ing inhalation PFAS studies more feasible and informative. Given the importance of understanding dose-depen- dent relationships in human health risk assessments, it was surprising that this review identified only four arti- cles (one animal and three in vitro of the 37 total stud- ies) that incorporated a dose-response approach into their designs. Future studies should be designed that allow for the mathematical derivation of BMDs/BMCs, yield- ing PODs that can be integrated into human health risk assessments. Furthermore, most studies captured in this review evaluated PFAS toxicity one-chemical-at-a-time. Because environmental monitoring studies of airborne PFAS commonly detect PFAS present as mixtures [83, 110–112], it is important to design more studies evaluat- ing the health impacts of PFAS combinations representing real-world exposure scenarios. Next-generation technolo- gies that more efficiently incorporate more in vitro/in vivo endpoints, such as -omics based screening, and the use of high-throughput in vitro screening to screen legacy PFAS, emerging PFAS, and PFAS alternatives, are now crucial towards addressing the growing number and diversity of PFAS and PFAS mixtures [36, 113].

    Current Status of Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure on Lung Cell Biology and Pulmonary Outcomes along Human Health Risk Assessment Steps · 2026 · DOI

  • The excerpt emphasizes pairing total fluorine (TF) measurements with chemical speciation methods but does not address how to systematically account for the fluorine mass-balance gap in heterogeneous environmental samples. Specific methodologies for closing the fluorine mass balance gap in complex matrices remain underdeveloped.

    The hidden fluorine: a critical review of analytical methods for unmasking PFAS and closing fluorine mass balance in environmental samples · 2026 · DOI

  • The paper calls for integrated analytical approaches combining 19F-NMR, CIC, and non-targeted MS acquisition with chemical speciation methods (XPS, solid-state 19F-NMR), but does not specify protocols for coordinating these measurements or standardized workflows. Concrete integration protocols and analytical pipelines for coupling these complementary techniques need to be developed.

    The hidden fluorine: a critical review of analytical methods for unmasking PFAS and closing fluorine mass balance in environmental samples · 2026 · DOI

  • The paper identifies that coordinated development of fluorine-retentive sample-preparation strategies is needed but does not specify optimization protocols for different matrix types. Future work should develop and validate extraction and cleanup protocols specifically optimized for high fluorine recovery in solid matrices and heterogeneous materials using CIC-guided method design.

    The hidden fluorine: a critical review of analytical methods for unmasking PFAS and closing fluorine mass balance in environmental samples · 2026 · DOI

  • to address The rapid evolution of eco-engineered nanomaterials offers significant potential the growing complexity of environmental contaminants. As pollution profiles shift toward lowconcentration, persistent, and co-occurring threats such as PFAS, pharmaceuticals, microplastics, and EDCs, the demand for nextgeneration materials that are selective, multifunctional, and resilient continues to increase. Future developments are likely to focus on ligand-gated MOFs, precision-engineered platforms, biomimetic nanostructures, and hierarchical composites (e.g., Ag–graphene–Fe hybrids). These materials combine adsorption, catalytic degradation, and antimicrobial properties within responsive architectures that adjust their activity based on environmental triggers, such as pH, redox state, or contaminant concentration, while offering opportunities to minimize secondary pollution through controlled reactivity, recoverability, and multi-cycle reuse. such as In parallel, the shift toward green and scalable synthesis is driving more sustainable material production strategies. Strategies such as mechanochemical fabrication, enzyme-assisted assembly, and biomass upcycling (from sources like coconut shells, sugarcane bagasse, and banana peels) significantly reduce the environmental footprint. Coupling these approaches with LCA ensures sustainability is embedded at the design phase, not as an afterthought, and enables early-stage evaluation of toxicity tradeoffs, scalability constraints, and material aging behavior. treatment systems, particularly AI and ML are increasingly integrated into material discovery and system optimization.

    Next-generation nanomaterials for environmental remediation: smart design, hybrid materials and sustainable use · 2026 · DOI

  • Further research is required in several areas, such as age-specific toxicological effects of PFAS, impact of various other PFAS compounds beyond perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and involvement of peroxisome proliferator-activated receptors in PFAS-induced toxicity.

    Poly- and per-fluoroalkyl substances toxicity on skeletal and cognitive well-being: a comprehensive review · 2025 · DOI

  • Despite the important roles of polyamide membranes in remediating PFASs-contaminated water, the governing factors influencing PFAS transport across these membranes remain elusive.

    Elucidating governing factors of PFAS removal by polyamide membranes using machine learning and molecular simulations · 2024 · DOI

  • Despite progress in understanding the occurrence and fate of PFAS and microplastics in aquatic ecosystems, the toxicity of PFAS mixtures and their co-occurrence with other high-concern compounds remains poorly understood, especially over organisms’ life cycles.

    Combined toxicity of perfluoroalkyl substances and microplastics on the sentinel species Daphnia magna: Implications for freshwater ecosystems · 2024 · DOI

  • PFAS are recognized internationally as recalcitrant contaminants, a subset of which are known to be mobile and toxic, but little is known about environmental impacts of bis-FASIs released during LiB manufacture, use, and disposal.

    Lithium-ion battery components are at the nexus of sustainable energy and environmental release of per- and polyfluoroalkyl substances · 2024 · DOI

  • The PDI-MOF-based sensor reported herein represents a novel approach, relying on fluorescence turn-on response, that has not yet been thoroughly investigated for detecting per- and polyfluoroalkyl substances (PFAS) until now.

    Fluorescence Turn-on Detection of Perfluorooctanoic Acid (PFOA) by Perylene Diimide-Based Metal–Organic Framework · 2024 · DOI

  • Furthermore, the nontarget approach we employed allowed for identification of novel, unsaturated products from the hydrated electron treatment of perfluorooctanesulfonate (PFOS) that warrant further investigation.

    Nontarget analysis and fluorine atom balances of transformation products from UV/sulfite degradation of perfluoroalkyl contaminants · 2023 · DOI

  • Although various thermal treatment techniques have demonstrated the potential to destruct PFAS, the fate of PFAS, removal efficacy, potential emissions, and the formation of incomplete combustion products during thermal treatment are little known.

    PFAS fate and destruction mechanisms during thermal treatment: a comprehensive review · 2021 · DOI

  • Little is known about the demographic/life-style/physiological determinants explaining the variation of serum perfluoroalkyl acid (PFAA) concentrations in children.

    Determinants of serum concentrations of perfluoroalkyl acids (PFAAs) in school children and the contribution of low-level PFAA-contaminated drinking water · 2020 · DOI

  • BACKGROUND: From 1980 to 2017, a fluorochemical manufacturing facility discharged wastewater containing poorly understood per- and polyfluoroalkyl substances (PFAS) to the Cape Fear River, the primary drinking water source for Wilmington, North Carolina, residents.

    Measurement of Novel, Drinking Water-Associated PFAS in Blood from Adults and Children in Wilmington, North Carolina · 2020 · DOI

  • Infants and young children may experience distinct exposure patterns due to mouthing behavior, yet oral exposure from textile-based products such as stuffed toys remains poorly characterized.

    Stuffed toys as a source of oral PFAS exposure: Migration into artificial saliva and exposure assessment · 2026 · DOI

  • Among females, a historically understudied group, elevated levels were observed among front-line protection; construction trades; manufacturing supervisors and operators; and specialty trade contractors.

    Occupational predictors of serum per- and polyfluoroalkyl substance concentrations in a national biomonitoring survey of adults in Canada · 2026 · DOI

  • However, the effect of PFOS on the neuroendocrine system has not been investigated thus far.

    Neuroendocrine effects of perfluorooctane sulfonate in rats. · 2003 · DOI

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47 open questions have been extracted from the limitations and future-work passages of 310 Per- and polyfluoroalkyl substances research papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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