The title comes from the famous line in the movie The Princess Bride, spoken by Inigo Montoya in response to Vizzini’s repeated use of the word "inconceivable." It's a clever way of pointing out that someone is misusing a word or not understanding its meaning.
It’s a humorous title for a serious and long-standing science and policy debate about the definition and classification of PFAS (per- and polyfluoroalkyl substances). The latest salvo in this debate is the recent Sigmund et al. (2025)1 commentary written by 20 scientists concerned about the definition of PFASs and a new IUPAC program2 aimed at resolving the issue. Here is a summary of the main scientific issues and regulatory approaches.
What does “PFAS” mean?
PFAS are a chemically diverse family of over 10,000 synthetic fluorinated compounds, all containing at least one carbon-fluorine (C–F) bond. This makes them highly persistent and earns them the nickname "forever chemicals." PFAS includes legacy chemicals (e.g., PFOA and PFOS), short-chain replacements, polymeric forms (such as fluoropolymers and side-chain fluorinated polymers), and many new chemical structures.
The key properties that distinguish members of this large chemical family are environmental persistence, mobility, bioaccumulation, and toxicity. Exposure potential and toxicity vary widely depending on chemical structure and use. This diversity in structural and environmental behavior is central to the debate about what is, and is not, PFAS.
Three core disagreements drive the scientific debate. First is how to measure the universe of PFAS substances. Standard laboratory tests capture only a handful of the thousands of PFAS substances. Laboratories and regulators use targeted methods for specific molecules and sum-parameter approaches (e.g., total organic fluorine or extractable organofluorine) to capture unknown and unmeasured fluorinated substances. Each measurement method has its strengths and weaknesses relative to environmental levels, exposures, and effect thresholds.
The second disagreement concerns the uncertainties in linking chemical structures to toxicity. For many new and short-chain PFAS, limited toxicology data are available; predicting hazards based on structure alone is imperfect and remains an active area of research. This uncertainty is used by some as an argument for regulating PFAS as a class precautionarily, while others advocate for using compound-by-compound evidence and assessment.
The third disagreement among scientists and policymakers concerns the importance and regulatory approach to polymeric PFAS, including side-chain fluorinated polymers (SCFPs). Unlike PFOS and PFOA, which are small perfluoroalkyl acids, SCFPs have perfluoroalkyl side chains attached to a non-fluorinated carbon backbone. Some fluorinated polymers possess unique characteristics, such as low bioavailability and diverse release profiles. Some in industry advocate for excluding certain polymeric PFAS. Scientists and regulators disagree on which substances should be excluded.
Regulatory Approaches
The science issues have a large influence – up to the point of practicality and cost - on three approaches to PFAS regulations.
Class-based regulations treat PFAS as large subgroups subject to broad restrictions or phase-outs because these substances are highly persistent, and many replacements can degrade or transform into other PFAS. Supporters say this approach helps prevent “regrettable substitution” and makes enforcement easier. The EU’s proposed PFAS restriction under REACH3 is referred to as a “generic restriction” because it applies to the entire chemical class.
Regulators in the US tend to follow a chemical-by-chemical or case-by-case approach to setting limits for the environment, consumer products, and workplaces. Historically, US regulation of PFAS has combined state-level drinking water standards for individual PFAS with, more recently, federal standards finalized by EPA in April 2024 for six specific PFAS4 (a rule still under considerable debate), along with broader environmental reporting requirements that apply to the wider PFAS class. Supporters argue that this approach is more scientifically accurate and helps avoid unnecessary burdens on PFAS uses considered to pose low risks. Some states (e.g., Maine, Minnesota, and Washington), however, appear to be moving toward a class-based approach.
Lastly, there is an “essential-use” approach, widely discussed among policymakers in the EU and US5, that aims to phase out non-essential uses while allowing essential applications, such as for certain military and critical medical purposes, through exemptions and defined transition periods. The approach promotes permitting PFAS uses considered essential for health, safety, or society’s functioning while phasing out other uses and PFAS substances.
Where the debate seems to be heading
Although it is certainly a global debate, the stark differences between the EU and US highlight the significant gap that science must bridge across the Atlantic. In the EU, ECHA and the European Commission appear to be moving toward broad subgroup restrictions under REACH, including a high-profile “universal PFAS” proposal and incremental subgroup restrictions. ECHA’s approach has generated considerable industry pushback and sparked legal and technical debates about scope and feasibility. Meanwhile, OECD and some members of the scientific community are advocating for clearer, harmonized terminology and practical, structure-based definitions to assist regulators and laboratories.
The US situation is more complicated. EPA’s 2024 US drinking-water standards for a limited set of PFAS are politically debated and might be revised in 2025. The science and environmental communities are also not well aligned. The FDA has taken steps to impose restrictions on specific uses involving food contact6. Industry and trade groups dispute the characteristics of different PFAS substances and view the EU’s class-based regulatory approach as unscientific, largely unjustified, and potentially leading to unnecessary costs and societal disruptions.
The EU is likely to pursue more extensive restrictions through phased regulations, targeting specific PFAS subgroups. This approach will not be immune to legal and technical challenges. In the US, the regulatory environment remains uncertain. The EPA has established numerical standards for a few PFAS in drinking water, but policy priorities and the implementation details will likely face litigation. The availability of viable substitutes for critical PFAS substances used in medicine adds complexities on both sides of the Atlantic.
All this to conclude that stakeholders in the EU and US sorely need objective science. This view is shared by Sigmund et al. (2025)1, Buck et al. (2011)7, Secundo et al. (2025)8, and others. Trade-offs between precaution, scientific accuracy, analytical practicality, and economic impact seem unavoidable. A hybrid approach that emphasizes rules for high-profile PFAS and enhances research to harmonize PFAS definitions and resolve debates about environmental fate, exposure, measurement methods, and toxicity may be the best course of action for now.
Supporting Literature
- Sigmund et al. (2025). https://doi.org/10.1021/acs.estlett.5c00478.
- IUPAC project n. 2024–006-3-100. https://iupac.org/project/2024-006-3-100
- ECHA (2025). https://echa.europa.eu/-/next-steps-for-pfas-restriction-proposal
- USEPA (2025). https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas
- Yu et al. (2025) https://doi.org/10.3390/toxics13040251.
- US FDA (2025). https://www.fda.gov/food/process-contaminants-food/authorized-uses-pfas-food-contact-applications
- Buck et al. (2011). https://doi.org/10.1002/ieam.258
- Secundo et al. (2025). https://doi.org/10.1002%2Fasia.202500127
