Document evowxrgdggO57X4z3e4OVZOGe

ANNEX III References [1] Henry, B. J.; Carlin, J. P.; Hammerschmidt, J. A.; Buck, R.C.; Buxton, L.W.; Fiedler, H.; Seed, J.; Hernandez, O. 2018. A Critical Review of the Application of Polymer of Low Concern and Regulatory Criteria to Fluoropolymers. Integrated Environmental Assessment and Management. v.14; n.3, 316-334. [2] Korzeniowski, S. H.; Buck, R. C.; Newkold, R.N., El kassmi, A.; Laganis, E.; Matsuoka, Y.; Dinelli, B.; Beauchet, S.; Adamsky, F.; Weilandt, K.; Soni, V. K.; Kapoor, D.; Gunasekar, P.; Malvasi, M.; Brinati, G.; Musio, S. 2022. A critical review of the application of polymer of low concern regulatory criteria to fluoropolymers II: Fluoroplastics and fluoroelastomers. Integrated Environmental Assessment and Management. v.00; n.00, 1-30. [3] Sales, J.; Hernndez, F.; Kappor, D.; Van den Noort, M. 2022. Fluoropolymers: The Safe Science That Society Needs. [10] Trang, B.; Li. Y.; Xue, X-S., Ateia, M.; Houk, K. N.; Dichtel, W. R. 2022. Low-temperature mineralization of perfluorocarboxylic acids. Science. v.377, 839-845. [11] Scheitlin, C. G.; Dasu, K.; Rosansky, S.; Dejarme, L. E.; Siriwardena, D.; Thorn, J.; Mullins, L.; Zaggerty, I.; Shqau, K.; Stowe, J. 2023. Application of Supercritical Water Oxidation to Effectively Destroy Per- and Polyfluoroalkyl Substances in Aqueous Matrices. ACS EST Water. v.3. 2053-2062. Integrated Environmental Assessment and Management -- Volume 14, Number 3--pp. 316-334 316 Received: 26 September 2017 Returned for Revision: 16 January 2018 Accepted: 30 January 2018 Critical Review A Critical Review of the Application of Polymer of Low Concern and Regulatory Criteria to Fluoropolymers Barbara J Henry,*t Joseph P Carlin, t Jon A Hammerschmidt, f Robert C Buck,: L Heidelore Fiedler, Jennifer Seed,// and Oscar Hernandez# tWL Gore & Associates, Elkton, Maryland, USA tChemours Company, Wilmington, Delaware, USA MTM Research Centre School of Science and Technology, Orebro University, Orebro, Sweden //Risk Assessment Consultant, Alexandria, Virginia, USA #Bergeson & Campbell, Washington, DC, USA William Buxton, I ABSTRACT Per- and polyfluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative, and biological stability. They have negligible residual monomer and oligomer content and low to no leachables. Fluoropolymers are practically insoluble in water and not subject to long-range transport. With a molecular weight well over 100 000 Da, fluoropolymers cannot cross the cell membrane. Fluoropolymers are not bioavailable or bioaccumulative, as evidenced by toxicology studies on polytetrafluoroethylene (PTFE): acute and subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation, and thrombogenicity. Clinical studies of patients receiving permanently implanted PTFE cardiovascular medical devices demonstrate no chronic toxicity or carcinogenicity and no reproductive, developmental, or endocrine toxicity. This paper brings together fluoropolymer toxicity data, human clinical data, and physical, chemical, thermal, and biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "polymers of low concern" (PLC). This review concludes that fluoropolymers are distinctly different from other polymeric and nonpolymeric PFAS and should be separated from them for hazard assessment or regulatory purposes. Grouping fluoropolymers with all classes of PFAS for "read across" or structure--activity relationship assessment is not scientifically appropriate. Integr Environ Assess Manag 2018;14:316-334. 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC) Keywords: Fluoropolymer International regulation Polytetrafluoroethylene Polymer of low concern PFAS INTRODUCTION The carbon--fluorine (C--F) bond is the strongest bond between C and another atom, instilling substances that contain a majority of C-F bonds with stability, inertness, and persistence (Banks et al. 1994). Per- and polyfluoroalkyl substances (PFAS) are a large group of highly fluorinated synthetic substances with diverse properties that have been used in a wide variety of industrial and consumer applications since the 1950s (Buck et al. 2011). Within the group are This article includes online-only Supplemental Data. * Address correspondence to (@wlgore.com Published 9 February 2018 on wileyonlinelibrary.com/journal/ieam. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. distinct substances with different properties: polymers and nonpolymers; solids, liquids, and gases; persistent and nonpersistent substances; highly reactive and inert substances; mobile and insoluble substances; and toxic and nontoxic chemicals. The PFAS are a large, diverse group of substances that, in some respects, challenge easy distinction for assessment and management. A clearer understanding of the origin of PFAS found in the environment and assessment of their properties is needed to be able to determine which classes of PFAS require management action. Perand polyfluoroalkyl substances must be assessed taking into account their differences in chemical, physical, thermal, and biological properties. A single, globally harmonized system for PFAS classification has not yet been defined, resulting in a lack of distinction between PFAS. As regulatory frameworks continue to evolve, such as the Regulation (EC) No 1907/2006 of the European Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 317 Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (RC 2006), more work is needed to distinguish classes of PFAS to ensure that regulations are appropriate in scope and proportionality. Two long-chain nonpolymer perfluoroalkyl acids (PFAAs), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) (both PFAS), found widespread in the environment and living systems, led to regulatory assessment and management efforts in several countries (Buck et al. 2011; OECD 2017; USEPA 2017a). Management actions to curtail manufacture of long-chain PFAAs, including PFOS and PFOA, and substances that may degrade to form them (also known as "precursors") have been taken (EC 2006; ECHA 2015; USEPA 2017a). Both PFOS and PFOA have been determined by regulators to be persistent, bioaccumulative, and toxic (PBT) substances (EC 2006; ECHA 2015). A current concern is the potential for certain side-chain polymer PFAS to degrade in the environment to PFOS and PFOA or lower homologues (Liu and MejiaAvendan~o 2013). In addition, PFOS (a nonpolymeric perfluoroalkyl substance) and related substances have been listed as persistent organic pollutants (POPs) under Annex B of the Stockholm Convention (UNEP 2009), and PFOA and other related substances (UNEP 2011), as well as perfluorohexane sulfonic acid (PFHxS) and related substances are being evaluated for listing (UNEP 2017a). As a result, questions about the health and environmental safety of PFAS as a group have been raised (Scheringer et al. 2014; Blum et al. 2015). These findings have prompted expanded regulatory interest and concern about PFAS as a group, spurring additional assessment and management actions. The German Environment Agency, Umweltbundesamt (UBA), published a proposal to implement new assessment criteria and procedures for identifying persistent (P), mobile (M), and toxic (T) substances under the European Union REACH chemical registration process (UBA 2017). The UBA has concluded that PM and/or PMT substances constitute "an irreversible threat to sources of drinking water and the quality of drinking water" in Germany. This has prompted the designation of PFAS substances as posing an "equivalent level of concern" under Article 57(f) of REACH and thereby has prompted the need for a new paradigm for chemical assessment and authorization. The Swedish Chemicals Agency, Kemikalieinspektionen (KEMI), announced agreement among 37 government agencies and research institutions in the European Union (EU) to expand cooperation to reduce the risks and increase the knowledge of PFAS, thereby endorsing the UBA view on the hazards posed by all PFAS substances (KEMI Swedish Chemicals Agency 2016). The KEMI announcement indicated that all perfluoralkyl substances should be considered as extremely persistent in the environment, and many are water soluble, mobile in soil, and likely to contaminate waterways and drinking water supplies. A risk assessment report prepared by KEMI is forthcoming (ChemNews 2016). The PFAS are divided into 2 primary categories: nonpolymers and polymers (Figure 1). Figure 1 shows that these 2 categories are divided into 5 classes of PFAS. The fluoropolymer class of PFAS is the focus of the present paper. The nonpolymer category includes perfluoroalkyl substances and polyfluoroalkyl substances. The polymer category includes fluoropolymers, perfluoropolyethers, and side-chain fluorinated polymers. Polymers generally have very different physical, chemical, and biological properties than do nonpolymer chemical substances of low molecular weight. Precise criteria that distinguish polymers from nonpolymers have been established (OECD 1993). There are distinct differences between the 5 classes of PFAS. For example, PFOA, in the class nonpolymer perfluoroalkyl substances, is small, mobile, and persistent; has been assessed and determined to be a PBT chemical (ECHA 2015); and is in the final stage for recommendation of listing as a POP under the Stockholm Convention (UNEP 2017b). Regulatory and industry management actions on PFOA include precursor substances that may degrade to form PFOA (USEPA 2017a). An example in the class of nonpolymer polyfluorinated substances, 8:2 fluorotelomer alcohol, is known to degrade under environmentally relevant conditions to form PFOA (Liu and Mejia-Avendan~o 2013). It is therefore a precursor substance to PFOA and subject to regulatory management (Liu and Mejia-Avendan~o 2013). Polymers derived from 8:2 fluorotelomer alcohol are examples of the side-chain fluorinated polymers class. These polymers may degrade to form PFOA and therefore are subject to regulatory management. Lastly, perfluoropolyethers class is a complex class of PFAS, which contains O linkages in the polymer backbone. In the present paper, we address fluoropolymers, a class of PFAS polymers (Figure 1). Fluoropolymers are high molecular weight solid plastics that have been studied extensively. The present paper brings together fluoropolymer toxicity data, human clinical data, and physical, chemical, thermal, and biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "polymers of low concern" (PLC) and to show that fluoropolymers are distinctly different enough from other classes of PFAS to not be grouped with them for hazard assessment or regulatory purposes. PERFORMANCE CHARACTERISTICS AND USES OF FLUOROPOLYMERS Since the discovery of polytetrafluoroethylene (PTFE) in 1938 (Plunkett 1987), the use of fluoropolymers has grown considerably to take advantage of their unique physical- chemical, thermal, and biological properties. The 4 fluoropolymers addressed in the present paper, polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), ethylene tetrafluoroethylene (ETFE), and tetrafluoroethylene copolymers with perfluoroalkyl vinyl ethers (e.g., perfluoroalkoxy polymer, PFA), accounted for approximately 70% to 75% of the world fluoropolymer consumption in 2015 (IHS 2016). The representative fluoropolymer discussed in the present paper, PTFE, made up 58% (by weight) of 2015 worldwide fluoropolymer consumption (IHS 2016). Fluoropolymers are high molecular weight plastics with unique properties attributable to the strong C-F bonds, the strongest bond between C and another atom, making Integr Environ Assess Manag 2018:316-334 wileyonlinelibrary.com/journal/ieam C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 318 Integr Environ Assess Manag 14, 2018--BJ Henry et al. Figure 1. Per- and polyfluoroalkyl substances (PFAS). them highly stable (Olabisi and Adewale 2015). Carbon atoms alone form the fluoropolymer backbone, each surrounded by an envelope of F atoms. Fluoropolymers are generally very high molecular weight (>100 000 Da); have high thermal, chemical, photochemical, oxidative, hydrolytic, and biological stability; have low flammability, neutral electrical charge, and resistance to degradation; have negligible residual monomers and low molecular weight oligomer content; have limited low molecular weight leachables; and have no reactive functional groups of concern (Gangal and Brothers 2015). The unique properties of fluoropolymers include durability, mechanical strength, inertness, thermal stability in foreseeable use conditions, and resistance to chemical, biological, and physical degradation (Hougham et al. 1999). Table 1 shows performance characteristics required in various commercial fluoropolymer applications (Gangal and Brothers 2015; Dams and Hintzer 2016). For example, medical devices are successful when they are made from "biocompatible" biomaterials, that is, the material has the ability to perform with an appropriate host response in a specific situation (Williams 1987). The inertness of PTFE allows for its acceptance into the body. Moreover, PTFE flexibility and durability deliver mechanical integrity for the device's lifetime. The microstructure of PTFE can be modified to meet specific physiological needs (e.g., porous and open structure to facilitate tissue ingrowth), enhancing its utility in medical devices. In terms of end-use function, PTFE's inertness, physical properties (Ebnesajjad 2011), and the low level of residual monomer, oligomers, and low molecular weight leachables (Supplemental Data p 32-55) meet the requirements for low levels of contaminants and particulates in manufacturing environments essential for the food and beverage, pharmaceutical, medical, and semiconductor industries (Olabisi and Adewale 2015). Manufacturing applications requiring ultrapure high efficiency particulate air (HEPA) filtration use the finely controlled microporous PTFE membranes. Other components requiring a high degree of contamination control associated with patient care (e.g., dialysis tubing) also find the properties of PTFE essential. Durability in harsh conditions makes PTFE a superior material of choice in aerospace, environmental controls, energy production and storage, and electronics, as well as in technical apparel. The thermal stability of PTFE and FEP fluoropolymers provides improved fire safety risk over other polymers when used in plenums and structural Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License C 2018 The Authors wileyonlinelibrary.com/journal/ieam Integr Environ Assess Manag 2018:316-334 Commercial application Aerospace Automotive industry Medical devices Pharmaceutical manufacture Consumer outdoor apparel Technical clothing (military, firefighters, first responders, medical personnel) Consumer electronics Wireless communications Satellite navigation systems Semiconductor industry Building construction Energy production and storage Food and beverage production Food protection and packaging Drinking water filtration Environmental protection Table 1. Fluoropolymer functionality and commercial applications Durable Mechanical strength X X X X X X Low particulation -- -- X X -- -- Resistance to chemicals X X X X Fluoropolymer characteristics Inert Functional Nontoxic, biocompatible, biological degradation resistant Friction Flexibility resistance Low dielectric constant -- X X X -- X X X X X X -- X X -- -- X X -- -- X X X -- Low leachables -- -- X X X X Stable Resistance to photolysis, oxidation, hydrolysis X X X -- -- X Stability X x X X -- X X -- X X -- X X -- X -- X X X -- -- X X -- X X X X X X -- X X -- X X -- X X X -- X X -- X X X -- X X -- X X X -- X X -- -- -- X X -- -- X X -- X -- X X -- -- -- X X X X X X X -- X X -- X X -- -- X -- X -- -- -- X X -- X -- -- -- X X X 319 Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 320 Integr Environ Assess Manag 14, 2018--BJ Henry et al. geometries in aviation and standard building construction (Olabisi and Adewale 2015). In addition, chemical resistance to acids, bases, solvents, and chemical attack, combined with its unique conformable strength, makes PTFE an ideal coating for chemical process equipment, lining for process piping, sealants for gaskets and hoses, and fabricated parts for pumps, gears, and other mechanical parts that need this extreme resistance for functionality (Olabisi and Adewale 2015). The low dielectric constant of PTFE ensures the integrity of high speed-low signal loss systems as employed in the aerospace industry for flight controls, communication, and protection from extreme cold, moisture, and altitude changes (Dams and Hintzer 2016). These are lifesaving applications that are used in satellite systems for navigation, wireless communications, in-flight navigation, and shielding from electronic interference. Civil and military aviation depends on reliable performance of these systems for long service hours with minimal maintenance down times. In addition, PTFE provides reduced friction of moving parts (e.g., cable chains), preventing particulation during automated manufacturing in cleanroom environments (Dams and Hintzer 2016). This friction reduction is also uniquely beneficial in light load bearings, gears, cams, and other mechanical machine parts as well as in weaving fibers, yarns, and greases (Dams and Hintzer 2016). ASSESSMENT OF POLYMERS History Prior to the mid-20th century, regulation of new chemical substances, mixtures, and polymers in general was very limited. National chemical inventories were created with notification requirements for new chemical substances, mixtures, and polymers. In the United States, new chemicals submitted to the US Environmental Protection Agency (USEPA) under the Toxic Substances Control Act (TSCA) (USC 1976) for addition to the US chemical inventory are reviewed for potential physical, chemical, and biological effects (environmental and mammalian), as well as for potential exposure to the environment and human populations. Over time, the USEPA regulatory scientists gained enough knowledge through the review of the thousands of data packages to develop tools to assist in the identification of physical-chemical properties, potential hazard, and potential exposure to assist in and expedite the chemical review and assessment process (Auer et al. 1990; Wagner et al. 1995; USEPA 2012; USEPA 2017b). The predictive power and reliability of these approaches were tested and refined (Wagner et al. 1995). Over time, it was recognized that many of the physical-chemical properties, such as molecular weight, limit the ability of the chemical to cross the cell membrane and therefore limit its bioavailability. Further examination of general physical- chemical properties and their relationship to hazard potential of a given chemical led to the development of general principles or criteria for the identification of chemicals, including polymers, with low hazard potential. These criteria were developed for use by USEPA for its hazard evaluation of new polymers. The USEPA made this methodology available to the public to assist submitters interested in developing low hazard polymers (USEPA 1997a). In 1984, the USEPA published the polymer exemption rule to exempt low hazard polymers from certain notification requirements under the new chemicals program (USFR 1984). The polymer exemption rule incorporated the hazard criteria as part of the criteria to determine eligibility for exemption (USEPA 1997a, 2010). The hazard criteria that support the PLC concept represent an extension of these principles and practices developed for (nonpolymeric) chemicals and rely heavily on physical- chemical properties that determine a chemical's bioavailability. In 1993, the Organisation for Economic Co-operation and Development (OECD) Expert Group on Polymers found that sufficient data existed to create a consensus document identifying the essential data elements to qualify a polymer as a PLC to human health and the environment (OECD 1993). By 2007, the OECD Expert Group on Polymers agreed that, "Polymers of low concern are those deemed to have insignificant environmental and human health impacts" (OECD 2009). Thus, there was agreement within the OECD that polymeric chemicals meeting these criteria have a low hazard potential. However, the integration of the criteria into a risk management framework may differ from country to country according to their individual regulatory mandate. In a recent report commissioned by the European Commission (EC) (BIO by Deloitte 2015), the following countries agreed on the polymer properties predictive of adverse human health and environmental hazard: Australia, Canada, China, Japan, South Korea, Philippines, New Zealand, Taiwan, and the United States. Further, the report identified the eligibility criteria to be considered a PLC with respect to potential for adverse impact on health and the environment. The report also compiled existing polymer regulations outside the EU and proposed alternative options for EU polymer registration, including defining a category of a PLC and grouping polymers into families. The PLC criteria are described in the following section. Note that there are some policy components, such as elemental composition, as well as the physical-chemical attributes, in the PLC criteria. POLYMER OF LOW CONCERN CRITERIA Here we describe each of the eligibility criteria for PLC and provide an assessment for the representative fluoropolymer PTFE. We will show that fluoropolymers, including PTFE, satisfy the widely accepted assessment criteria to be considered PLCs (Table 2) and therefore are considered to be of low hazard to human health and the environment. Polymer composition The polymer composition criterion requires structure and elemental composition of the polymer be described and identified (e.g., by Chemical Abstracts Service [CAS] number). Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 Assessment criteriaa Structure Table 2. Fluoropolymers and PLC criteria PTFE CAS 9002-84-0 ETFE CAS 25038-71-5, 68258-85-5 Fluoropolymers FEP CAS 25067-11-2 321 PFA CAS 26655-00-5, 31784-04-0 Polymer composition (must have Yes C, H, Si, S, F, Cl, Br, or I covalently bound to C) Molecular weight 389 000- 8 900 000bc (Mn > 1000 Da and oligomer content < 1%) 520 000- 45 000 000bd Molecular weight distribution 2.3i MW number average Mn (Mn and heterogeneity of MW distribution indicate if majority are >1000 or <1000 Da, which could penetrate the cell) Wt % oligomer (see Figure 2) (<5% for <1000 Da oligomers, <2% for <500 Da oligomers) Negligible Ionic character (cationic polymers associated with aquatic toxicity; polycationic with adverse human health effect) Neutral RFGsk (some highly reactive functional groups associated with adverse human health and ecotoxicology effects, e.g., acrylates, isocyanates, anhydrides, aziridines) <1 (see section Reactive functional groups and RFG ratio to MW) FGEWk (typical value) (the lower the FGEW, the more reactive the polymer and the higher the potential for health and environmental impact) >105-107 Low molecular weight leachables (MW < 1000 Da able to enter cell) <1 ppm Residual monomers (monomers have lower MW than polymers; typically more hazardous than polymers) <1 ppm Ratio of residual monomers to molecular weight (typical value) (more low MW monomer content per mole increases bioavailability and hazard potential) 10-13 to 10-15 Structural similarities to RFG of concern (increases potential risk of adverse effects) None Reference standard see also ISO 1133 (ISO 2011), ISO 12086 (ISO 2006) ASTM D 4894 (ASTM 2015a), D 4895 (ASTM 2015b) Yes -- 530 000-1 200 000ef 1.4-2.7f Negligible Neutral <1 (see section Reactive functional groups and RFG ratio to MW) >105-106 No active leachables by USP class VIl (121 C) <50 ppb 10-13 to 10-14 None ASTM D 2116 (ASTM 2016a) Yes -- 241 000- 575 000eg 1.55-2.09g Yes -- 200 000- 450 000eh 1.7j Negligible Neutral Negligible Neutral <1 (see section Reactive functional groups and RFG ratio to MW) >105 <1 (see section Reactive functional groups and RFG ratio to MW) >105 No active leachables by USP class VIl (121 C) <50 ppb No active leachables by USP class VIl (121 C) <50 ppb 10-13 10-13 None ASTM D 3159 (ASTM 2015c) None ASTM D 3307 (ASTM 2016b) (Continued ) Integr Environ Assess Manag 2018:316-334 wileyonlinelibrary.com/journal/ieam C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 322 Integr Environ Assess Manag 14, 2018--BJ Henry et al. Table 2. (Continued) PTFE Assessment criteriaa Physical-chemical properties Water solubility (per USP 2011) (water solubility <10 mg/L showed generally low health concerns; 10 mL/L to 10000 mg/ L had potential health concern) Octanol-water partition coefficient, KOW (higher KOW associated with lipophilicity and a high potential to bioaccumulate or bioconcentrate) Particle size (median mass aerodynamic diameter, MMAD, should be >5 mm) Stability Hydrolysis (breaking into Mn < 1000 Da increases hazard potential) Light (hn) (breaking into Mn < 1 000 Da increases hazard potential) Oxidation (breaking into Mn < 1000 Da increases hazard potential) Biodegradation (aerobic and anaerobic) (breaking into Mn < 1000 Da increases hazard potential) Thermal stability at normal foreseeable use maximum continuous temp (C) (breaking into Mn < 1000 Da increases hazard potential) Meets PLC criteriaa (Y/N) CAS 9002-84-0 Practically insoluble or insoluble (1 10-5 mg/L) NA 100-500 mm (powders) -- Stable Stable Stable Stable 260 Yes ETFE CAS 25038-71-5, 68258-85-5 Fluoropolymers FEP CAS 25067-11-2 Practically insoluble or insoluble Practically insoluble or insoluble NA NA 50-250 mm (powders) 2-4 mm (pellets) Stable Stable Stable Stable 150 50-250 mm (powders) 2-4 mm (pellets) Stable Stable Stable Stable 200 Yes Yes PFA CAS 26655-00-5, 31784-04-0 Practically insoluble or insoluble NA 50-250 mm (powders) 2-4 mm (pellets) Stable Stable Stable Stable 260 Yes ASTM American Society for Testing and Materials; CAS Chemical Abstracts Service; Da dalton; ETFE ethylene tetrafluoroethylene; FEP fluorinated ethylene propylene; FGEW functional group equivalent weight; ISO International Organization for Standardization; MMAD median mass aerodynamic diameter; Mn number average molecular weight; MW molecular weight; MWD molecular weight distribution; OECD Organisation for Economic Co- operation and Development; PFA perfluoroalkoxy polymer; PFPE perfluoropolyether; PLC polymer of low concern; PTFE polytetrafluoroethylene; PVDF polyvinylidene fluoride; PVF polyvinyl fluoride; RFG reactive functional groups; USEPA US Environmental Protection Agency; USP US Pharmacopeia. aSee OECD 2009 and BIO by Deloitte 2015 for details on characteristics of a "polymer of low concern." bMolecular weight is number average molecular weight. cBerry and Peterson 1951; Doban et al. 1956. dSuwa et al. 1973. eMolecular weight is weight average molecular weight. fTuminello et al. 1993. gTuminello 1989. hPutnam 1986. iChu et al. 1989. jFrick et al. 2012. kFor definition of reactive functional group; lists of low-, moderate-, and high-concern functional groups; and FGEW limits, see USEPA Polymer Exemption Guidance Manual (USEPA 1997b), BIO by Deloitte 2015 (p 191-192), and USEPA 2010. See Supplemental Data. lIn the USP<88> testing for "class VI," 2 g of the plastic (e.g., FEP, ETFE, or PFA) were extracted at 121 C in: 1) 0.9% sodium chloride solution, 2) sesame oil, NF, 3) alcohol saline, and d) polyethylene glycol. The acute systemic toxicity and intracutaneous reactivity tests were conducted with those extracts. The intramuscular implantation was conducted with the plastic. Passing these 3 tests indicates that any leachables were not released in concentrations capable of causing these adverse effects, but does not result in a quantitative concentration of leachables. (See USP 2018.) Note: The following are not addressed in this paper: PFPEs, side-chain fluorinated polymers, fluoroelastomers, PVF, and PVDF. Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 323 Molecular weight, number average molecular weight, MW distribution, and % oligomer <1000 Da The number average molecular weight (Mn) and oligomer content are the most commonly used criteria for PLC assessment. The EU assessment report (BIO by Deloitte 2015) states that the "most potential health concern polymers have a number average molecular weight, Mn, < 1000 Da and oligomer content >1%." The higher the oligomeric content, the more likely a polymer is to be a health or ecotoxicological (OECD 2009, p 9). In fact, when comparing the potential health concern of polymers with varying percent oligomer content, "...the distribution of potential health concern polymers showed an increased incidence of higher oligomer content that began at 5% for <1000 Da and 2% for <500 Da oligomeric content" (OECD 2009, p 24). Molecular weight (MW) is an important predictor of biological effect because very large molecules (>1000- 10 000 Da) are too large to penetrate cell membranes (Supplemental Data in Beyer 1993, p 14). Because large molecular weight polymers cannot enter the cell, they cannot react with "target organs," such as the reproductive system, and are not bioavailable. "Therefore, as the Mn of a polymer increases, a reduced incidence of potential health concern effects might be expected" (OECD 2009, p 20). An additional PLC consideration is the weight percent oligomers <1000 Da. Oligomers may be composed of, for example, dimers, trimmers, and tetramers, meaning they have 2-, 3-, and 4-monomer units, respectively. The EU report (BIO by Deloitte 2015) concluded that most potential health concern polymers have Mn of <1000 Da and oligomer content of >1%: "...the distribution of potential health concern polymers showed an increased incidence of higher oligomer content that began at 5% for <1000 Da and 2% for <500 Da oligomeric content" (OECD 2009, p 24). Molecular weight distribution (MWD), also known as "polydispersity index," measures the heterogeneity of size of polymer molecules in a polymer. The MWD is an important parameter for predicting potential biological effects of polymers because although Mn may be a large value, low MW oligomers <1000 Da may be present, which could penetrate the cell. Electrical charge (ionic character) Electrical charge or ionic character can be anionic, cationic, amphoteric, or nonionic. Specifically, cationic polymers have been associated with aquatic toxicity (Auer et al. 1990; USEPA 1997a). Polycationic polymers that are water soluble or dispersible are of concern due to adverse human health (inhalation) effects (NICNAS 2016). Reactive functional groups and RFG ratio to MW A "reactive functional group" (RFG) is defined as an atom or associated group of atoms in a chemical substance that is intended or can be reasonably anticipated to undergo facile chemical reaction (USFR 2012). Some highly reactive functional groups (or a high ratio of RFGs per mole) have been associated with adverse human health and ecotoxicology (e.g., acrylates, methacrylates, isocyanates, anhydrides, aziridines) (USEPA 2010). Methods have been demonstrated to identify the functional end groups on fluoropolymers (Pianca et al. 1999). The functional group equivalent weight (FGEW) is used to determine if the RFGs in a polymer are substantially diluted by polymeric material to allow the polymer to be a PLC (USEPA 1997b). The FGEW of a polymer is defined as the ratio of the Mn to the number of functional groups in the polymer. It is the weight of a polymer that contains 1 formula weight of the functional group. The FGEW is used as an indication of the degree of reactivity of the polymer; the lower the FGEW, the more reactive the polymer and the higher the potential for health and environmental impact (OECD 2009, p 10). Low MW leachables Low MW leachables are chemical molecules, either inorganic or organic, that migrate (i.e., leach) out of the polymer. These could be residual monomers or oligomers resulting from incomplete polymerization processes, surface residues, or other chemicals used in the manufacturing processes (e.g., initiators, catalysts, chain transfer agents, surfactants). Chemical analysis, by techniques such as thermal gravimetric analysis (TGA), gas chromatography mass spectrometry (GC-MS), or liquid chromatography mass spectrometry (LC-MS) are used to identify low MW leachables. Low MW leachables are critically important to the potential for a polymer to affect health and the environment, given that they may be able to migrate out of the polymer and cross cell membranes to potentially react with biomolecules. In a report to the EU (BIO by Deloitte 2015) the polymer policies for 10 countries around the world, including the EU REACH handling of polymers, were reviewed. The report concluded that "Polymers with <1% MW <1000 Da and low water extractivity are not able to cause systemic effects which are toxicologically or ecotoxicologically relevant." Monomers, by nature, are reactive. Unreacted monomer left in a polymer may migrate out of the polymer to react with biomolecules to cause potential adverse effects. Regulatory authorities (BIO by Deloitte 2015) and the OECD Expert Group on Polymers (OECD 2009) agree that the residual monomer content of a polymer is critical to determining if it qualifies to be a PLC. Particle size Particle size is also a PLC criterion. Particles that are small enough to reach the deep lung upon inhalation are often associated with adverse health effects. Therefore, to qualify as a PLC, median mass aerodynamic diameter (MMAD) of the polymer particle size should be greater than 5 mm. Structural and elemental composition In the United States, Chemical Categories of Concern are the result of the review of new chemicals by the USEPA under the TSCA (see https://www.epa.gov/reviewing-new-chemicalsunder-toxic-substances-control-act-tsca/chemical-categoriesused-review-new). New chemicals submitted to the USEPA Integr Environ Assess Manag 2018:316-334 wileyonlinelibrary.com/journal/ieam C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 324 Integr Environ Assess Manag 14, 2018--BJ Henry et al. under the TSCA for addition to the US chemical inventory are reviewed for potential chemical, physical, and biological effects (environmental and mammalian). The USEPA groups Premanufacture Notice (PMN) chemicals with shared chemical and toxicological properties into categories, enabling both PMN submitters and USEPA reviewers to benefit from the accumulated data and past decisional precedents, allowing reviews to be facilitated. The categories describe the molecular structure, boundary conditions such as MW, equivalent weight, the log of the octanol-water partition coefficient, log P, or water solubility, and standard hazard (mammalian and ecological) and (environmental) fate tests to address concerns. The categories include chemicals for which sufficient history has been accumulated so that hazard concerns and testing recommendations vary little from chemical to chemical within the category. (See Supplemental Data, p 30, for details on USEPA's chemical categories.) Elemental composition The elemental composition is a factor in the assessment of the eligibility of polymers for reduced notification requirements. The exclusion of polymers under this step is not a conclusion of hazard but a determination that the elemental composition does not fall within the parameters of the polymer set under which this rule was formulated, and consequently, these polymers would have to follow the standard notification and review process. These elemental requirements differ across jurisdictions as covered in the report to the EU on global regulatory approaches to polymer assessment (BIO by Deloitte 2015). For example, in the EU under REACH it is proposed that polymers composed from among these elements, covalently bound to C, have reduced hazard: H, N, O, Si, S, F, Cl, Br, or I (BIO by Deloitte 2015). In contrast, the USEPA Polymer Exemption Rule states that a polymer is eligible for reduced agency review when it has at least 2 of the following elements: C, H, O, N, S, or Si (USFR 1995). Water and lipid solubility and the octanol-water partition coefficient Water solubility is the extent to which a compound will dissolve in water. According to the OECD 2009 meeting of the Expert Group on Polymers, polymers with "negligible" water solubility, or those described as "hydrophobic" have been represented with a water solubility of 0.000001 mg/L (1 10-6 mg/L; assigned arbitrarily) (OECD 2009). That is equivalent to 1 ppt, a very conservative definition. Based on the data set studied, the OECD Expert Group on Polymers concluded "A higher proportion of polymers with intermediate water solubility values (10 mL/L-10 000 mg/L) displayed potential health concern. Polymers with water solubility <10 mg/L showed generally low health concerns" (OECD 2009, p 10). Although not a solubility metric, a polymer capable of absorbing its weight in water was associated with increased inhalation cancer risk in rats (OECD 2009). The octanol-water partition coefficient (KOW) is another criterion to assess chemicals and their environmental and health impact. The KOW is a physical-chemical property at equilibrium to represent the lipophilic or hydrophilic nature of a chemical, the distribution of a compound in octanol, representing the lipophilic nature, to its solubility in water, representing the aqueous nature. The higher the KOW, the more lipophilic the compound. Typically, a KOW >5000 or a log KOW >5 means high lipophilicity and, thus, a high potential to bioaccumulate or bioconcentrate. Numerous studies showed that KOW was useful for correlating structural changes of drug chemicals with the change observed in some biological, biochemical, or toxic effect (LaGrega et al. 2010). It has been found to be related to water solubility, soil or sediment adsorption coefficients, and bioconcentration factors for aquatic life. According to the Stockholm Convention, a bioconcentration factor of >5000 and a log KOW >5 is used as a criterion for bioaccumulation. Stability Stability is resistance to physical, chemical, or biological transformation. Loss of stability in the polymer breaks it down into smaller pieces, producing low MW species. As was previously described in the Polymer of Low Concern section under the Molecular weight, number average molecular weight, MW distribution, and % oligomer <1000 Da heading, molecules with Mn <1000 Da are capable of crossing cell membranes, making unstable polymers potentially hazardous to health and the environment. Abiotic stability Polymers are stable; monomers are not. Abiotic degradation may involve sunlight, water, or oxygen. Photochemical transformation is a reaction involving the radiation energy of sunlight (ultraviolet radiation) that may break a bond in a molecule to change it to another chemical entity. Hydrolytic degradation of polymers is another potential way to break the polymer bonds, creating smaller oligomers that may be bioavailable. Chemical oxidation is a reaction involving the loss of electrons from 1 atom to another. Biotic stability: aerobic, anaerobic, and in vivo Biotic stability is assessed by whether or not the polymer is degraded by microorganisms under oxygenated (aerobic) or anoxic (anaerobic) conditions; in vitro and in vivo stability studies demonstrate this. In vivo biodegradation involves the breaking of the polymer bonds by the action of bacteria, enzymes, and oxidants within the organism. Thermal stability Thermal stability of a polymer can be assessed when used as intended under normal, foreseeable use conditions or in extreme temperatures during disposal, such as by incineration. Thermal stability testing may involve Thermal Gravimetric Analysis (TGA), which determines mass loss over time and temperature of a test substance. ASSESSMENT OF FLUOROPOLYMERS ACCORDING TO PLC CRITERIA Characteristics of a PLC have been described in the preceding section. These criteria represent the combined Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 325 experience and knowledge of global regulatory authorities on factors demonstrated to be predictive of health and environmental hazards of polymers (OECD 2009; BIO by Deloitte 2015). Four fluoropolymers were assessed according to the PLC criteria. The results are summarized in Table 2, and an expanded discussion on specific criteria is provided in the remainder of this section. Polymer composition Fluoropolymers satisfy the PLC criterion of polymer composition. Polytetrafluoroethylene is a homopolymer of tetrafluoroethylene (TFE). Polytetrafluoroethylene can be a homopolymer (1 monomer) or it can be a modified homopolymer containing TFE widely and not more than 1% of another fluoromonomer (see ASTM 2015). Polytetrafluoroethylene contains only C and F having a -CF2- backbone terminated on both ends of each polymer chain with -CF3. In unique cases, based on production method and ingredients used, commercial PTFE may have end groups that contain O, H, N, or S, depending on the initiator or chain transfer agent used in polymerization (Pianca et al. 1999). Polytetrafluoroethylene meets the compositional criterion to be a PLC. Molecular weight, Mn, MWD, and % oligomer <1000 Fluoropolymers satisfy the PLC criterion of MW, Mn, MWD, and % oligomer <1000. Fluoropolymers are practically insoluble in water and all organic solvents. Therefore, standard MW methods are not applicable for fluoropolymers like PTFE and have been replaced by standardized indirect methods that use specific gravity and melt flow index to determine MW of PTFE and fluoropolymers (see Supplemental Data, p 27-28). Standard Specific Gravity (SSG) and Melt Flow Rate (MFR) are more conveniently and frequently used with fluoropolymers rather than rheological and dynamic light scattering methods (Chu et al. 1989; Starkweather and Wu 1989; Tuminello 1989; Tuminello et al. 1993). Polytetrafluoroethylene has an Mn of 500 000 to 9 000 000 Da (Berry and Peterson 1951; Doban et al. 1956; Suwa et al. 1973; Putnam 1986; Chu et al. 1989; Tuminello 1989; Tuminello et al. 1993; Frick et al. 2012). Therefore, PTFE, as a very high molecular weight polymer, cannot cross cell membranes, is not bioavailable, and cannot bioaccumulate or be toxic (see Supplemental Data, p 14). High molecular weight fluoropolymers, such as PTFE, therefore meet the PLC criterion for having MW that prevents them from entering the cells. Polytetrafluoroethylene has negligible (<<1%) oligomeric content (Starkweather and Wu 1989), as does FEP (Figure 2.) In summary, fluoropolymers are high molecular weight polymers with narrow MWD and negligible oligomer content. Reactive functional groups and RFG ratio to MW Fluoropolymers satisfy the PLC criterion of RFGs and RFG ratio to MW. Polytetrafluoroethylene most typically has a terminal -CF3 group that is not an RFG. When this is not the case, the most common terminal group is -COOH, which is Figure 2. A fluorinated ethylene propylene (FEP) fluoropolymer molecular weight distribution from a rheological study. MW molecular weight; MWD molecular weight distribution. categorized by the USEPA as a low-concern functional group. In unique cases, based on production method and ingredients used, PTFE may have end groups that may contain O, and H, N, or S, depending on the initiator or chain transfer agent used in polymerization. Fluoropolymers have a very high MW, which yields an FGEW on the order of 105 or more, well beyond the FGEW threshold of concern. Low MW leachables Fluoropolymers satisfy the PLC criterion of low MW leachables. Concentration of leachables from fluoropolymers, particularly PTFE "fine powder" (ASTM [2015] 4895-16 Type I fine powder definition), are typically very low (<1 ppm) (see Supplemental Data). This finding can be explained by the sensitivity of the PTFE polymerization reaction to contamination and is due to the postpolymerization processing steps aggressively exercised to wash out residuals and drive off volatiles. In order to achieve high MW polymerization of TFE, all traces of telogenic H- or Cl-bearing impurities must be removed (Ebnesajjad 2011; Supplemental Data). In the analysis done on PTFE (see Supplemental Data, p 32), residual TFE monomer was not detected in PTFE resin by headspace GC-MS with a limit of detection of 1 ppm. In addition, publicly available analytical data from independent industry authorities demonstrate that TFE is not detected in finished articles made from fluoropolymers at detection limits down to about 0.01 ppm wt/wt (SPI 2005). Table 3 compares the molecular weight and the 8-h time weighted average (TWA) (American Conference of Governmental Industrial Hygienists [ACGIH], threshold limit value [TLV]), for monomers used to make fluoropolymers (ACGIH 2010). The TWAs are the exposure levels to which a worker could be exposed in an 8-h shift without adverse effects. The monomers have significantly lower MW, have lower TWAs, and are reactive. Note that the fluoropolymers are high MW, have no TWAs, and are inert. Table 3 illustrates that polymers do not have the same health hazards or MWs as their monomers. Integr Environ Assess Manag 2018:316-334 wileyonlinelibrary.com/journal/ieam C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 326 Integr Environ Assess Manag 14, 2018--BJ Henry et al. Table 3. Fluoropolymer and monomer molecular weight and TLV data Substance Monomer: TFE Monomer: Ethylene Monomer: HFP Monomer: PPVE Polymer: PTFE Polymer: ETFE Polymer: FEP CAS Nr 116-14-3 74-85-1 116-15-4 1623-05-8 9002-84-0 25038-71-5, 68258-85-5 25067-11-2 Molecular weight 100 28 150 266 389 000-45 000 000 530 000-1 200 000 241 000-575 000 ACGIH TLV 8-h TWA 2 ppm 200 ppm 0.1 ppm 200 ppm (vendor limit) None None None Polymer: PFA 26655-00-5, 31784-04-0 200 000-450 000 None ACGIH American Conference of Governmental Industrial Hygienists (ACGIH 2010); CAS Chemical Abstracts Service; ETFE ethylene tetrafluoroethylene; FEP fluorinated ethylene propylene; HFP hexafluoropropene; PFA perfluoroalkoxy polymer; PPVE perfluoropropylvinyl ether; PTFE polytetrafluoroethylene; TFE tetrafluoroethylene; TLV threshold limit value; TWA time weighted average. Elemental composition Fluoropolymers meet the widely accepted elemental composition criterion (BIO by Deloitte 2015). The USEPA, in updating its Polymer Exemption Rule, which applies to new polymers only, changed some review procedures to address certain side-chain fluorinated polymers that may degrade into small, mobile, and persistent substances (USFR 2010). This has contributed to confusion regarding the assessment of fluoropolymers. The exclusion of polymers under this step is not a conclusion of hazard, but a determination that the elemental composition does not fall within the parameters of the polymer set under which this rule was formulated, and consequently, these polymers would have to follow the standard notification and review process. When USEPA updated the polymer exemption rule in 2010, the agency excluded polymers containing -CF3 or larger chains that are covalently bound to C. The agency's rationale for the change was "...because the Agency has receiving information which suggests that polymers containing PFAS (perfluoroalkyl sulfonates) or PFAC (perfluoroalkyl carboxylates) may degrade and release fluorochemical residual compounds in the environment. Once released, PFAS or PFAC are expected to persist in the environment, may bioaccumulate, and may be highly toxic..." (USFR 2006). Although USEPA recognized that PFAS and PFAC chemicals with longer C chain lengths (C7 and longer) may be of greater concern, it stated that there is insufficient evidence at this time, however, to definitively establish a lower C chain length limit to meet the "will not present an unreasonable risk" finding, which is the determination necessary to support an exemption under section 5(h)(4) of TSCA. The USEPA believes that it is possible for polymers containing these other types of perfluoroalkyl moieties to also degrade over time in the environment, thereby releasing the perfluoroalkyl moiety (USFR 2006). The updated USEPA polymer exemption definition in 2010, summarized in the Objective and Rationale section for the Final Rule, may imply that new fluoropolymers with pendant or terminal -CF3 groups, such as FEP, do not meet the polymer exemption eligibility for reduced PMN reporting (USFR 2010). However, the summary definition in USFR (2010) lacks critical context found in the preamble to the Final Rule, which elaborates the conditions that would be necessary to exclude a perfluoro chemical from the polymer exemption: The first condition is cited above, "...polymers containing PFAS (perfluoroalkyl sulfonates) or PFAC (perfluoroalkyl carboxylates)..." where the C or S atom is an integral part of the polymer molecule; and the second condition notes that, polymers containing fluorotelomers or "...perfluoroalkyl moieties that are covalently bound to either a carbon or sulfur atom where the carbon or sulfur atom is an integral part of the polymer molecule can be attached to the polymers using conventional chemical reactions." For the PFAS and PFAC as described by USEPA, the agency offers a clarification about the nature of the linkage, stating "How these materials are incorporated into the polymer is immaterial (they may be counter ions, terminal/ end capping agents, or part of the polymer backbone)" (USFR 2010). The key characteristic is the presence of a -CF3 group that is attached to, or forms part of, the polymer backbone and "this link (between the polymer backbone and the -CF3 group) is susceptible to degradation and cleavage." (USFR 2010). Thus, in USEPA's review, the presence of - CF3 group is important because it is a structural alert to consider potential degradation products. The USEPA will make a determination whether the potential degradation of the polymer in question presents an unreasonable risk to health and the environment under TSCA. As shown in Table 2, these fluoropolymers are not subject to degradation. Water and lipid solubility and the octanol-water partition coefficient Fluoropolymers, such as PTFE, are not soluble in octanol or water. Therefore, it is not possible to measure or calculate a Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 327 KOW. Because solubility in octanol is predictive of lipid solubility, PTFE cannot dissolve in cell membrane lipids to gain access to cellular contents, nor is it small enough to enter the cell due to its very high MW. Because PTFE cannot enter the cells, it is not capable of bioaccumulation or bioconcentration in aquatic life. Stability Under normal, foreseeable uses, fluoropolymers are stable. Stability is resistance to physical, chemical, or biological transformation. Loss of stability in the polymer breaks it down into smaller pieces, producing low MW species. Molecules with Mn <1000 Da are capable of crossing cell membranes, making unstable polymers potentially hazardous to health and the environment. Fluoropolymers, in general, have exceptional chemical and thermal stability; that is why they are so unique and useful. This is due to very strong C-F bonds that are stable under even extreme conditions (Gangal and Brothers 2015). Polytetrafluoroethylene is inert and chemically resistant to all solvents except molten alkali metals, chlorine trifluoride, and oxygen difluoride. Polytetrafluoroethylene, as a representative fluoropolymer, has the best chemical resistance of all currently known polymers and is insoluble in all known solvents, including water (Drobny 2006). Abiotic stability Polymers are stable; monomers are not. Photochemical transformation is a reaction involving the radiation energy of sunlight (ultraviolet radiation) that may break a bond in a molecule to change it to another chemical entity. Although PTFE will rapidly degrade in ionizing radiation (e.g., gamma radiation or high energy electron-beam radiation), it is resistant to photolysis (Drobny 2006). Photoinduced reactions with fluoropolymers do not occur. In addition, hydrolysis is a reaction involving the breaking of a bond in a molecule using water. The fluorine envelope surrounding the C backbone of PTFE is very hydrophobic. Fluoropolymers, such as PTFE, are hydrolytically stable, water resistant, and are not subject to hydrolysis catalyzed degradation (Arkles 1973). Finally, chemical oxidation is a reaction involving the loss of electrons from one atom to another. Because the C-F bond is one of the strongest known, and F is the most electronegative element, the C-F bond is thermodynamically stable, unfavorable to lose electrons (i.e., to oxidize) (Arkles 1973). Biotic stability: aerobic, anaerobic and in vivo Fluoropolymers like PTFE are biologically inert and not degraded by microorganisms under oxygenated (aerobic) or anoxic (anaerobic conditions); in vitro and in vivo studies demonstrate this. In vivo degradation involves the breaking of the polymer bonds due to bacteria and other enzymes and oxidants. For example, PTFE hernia patches explanted from patients and examined by scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, modulated differential scanning calorimetry, and optical microscope showed no degradation in vivo (King et al. 2013). Thermal stability Fluoropolymers, when used as intended under normal, foreseeable use conditions as specified in Table 2 (or "continuous processing temperature") are thermally stable (Puts et al. 2014). The fluoropolymer industry has provided significant information on appropriate use of fluoropolymers (SPI 2005). Thermal gravimetric analysis determines mass loss over time and temperature of a test substance. Polytetrafluoroethylene is one of the most thermally stable polymers. Polytetrafluoroethylene's continuous processing temperature is 260 C (SPI 2005). This means that PTFE could remain for decades at 260 C and not decompose (SPI 2005 see percent mass lost per hour at maximum continuous processing temperature). Outside of normal, foreseeable use conditions (also known as "misuse"), when fluoropolymers are held at temperatures above their recommended processing temperatures, they degrade. Upon decomposition, fluoropolymers generate volatile degradation products (SPI 2005). At 450 C, the decomposition of PTFE "only proceeds at a rate on the order of one percent per hour. It is not until considerably above the polymer first-order transition temperature (329 C) that substantial decomposition is observed" (Arkles and Bonnett 1974). As the temperatures increase above recommended processing temperatures, the rate of generation rises and may sufficiently degrade the polymer to produce hazardous gaseous byproducts and polymer (particulate) fume fever (SPI 2005). Temperature, availability of O, the physical form of the polymer article, and the residence time at elevated temperature factor into the ultimate nature of the decomposition products (SPI 2005), mainly fluoroalkenes, hydrogen fluoride, oxides of C, and lower molecular weight fluoropolymer particulates. For PTFE, TFE is the principle gaseous product observed at temperatures near 330 C. See Supplemental Data for additional information regarding overheating PTFE. PRODUCT-SPECIFIC REGULATORY REQUIREMENTS Certain product-specific regulations, such as those for medical devices and food contact for the United States and the EU, require the development of additional data beyond what is required to conduct a PLC evaluation. The following text will discuss food contact requirements for the United States and the EU, and medical device requirements. Data requirements for food, pharmaceutical, and medical device applications There are country-specific data requirements for fluoropolymer use in food, pharmaceutical, and medical device applications because the intended use of these products has the potential to directly or indirectly introduce the product into the human body. An extensive fluoropolymer data set has been developed by W.L. Gore for these uses. The clinical history of the safe implantation of more than 40 million PTFE medical devices over 40 y, extensive toxicity data, preclinical Integr Environ Assess Manag 2018:316-334 wileyonlinelibrary.com/journal/ieam C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 328 Integr Environ Assess Manag 14, 2018--BJ Henry et al. data, and chemical extractables and migration testing confirmed that fluoropolymers are not bioavailable. Although the data requirements have evolved over time for contacting food, pharmaceuticals, or use in medical devices, the data (some of which are provided in the present article, the Supplemental Data for the present paper, regulatory submissions, and product literature) confirm the conclusion that fluoropolymers are safe for these intended uses and support the conclusion that fluoropolymers should be considered PLCs. Polymer of low concern data and US and European Union food contact requirements In general, the data required to support a PLC determination are helpful, but insufficient to qualify a material for food contact use. Submissions to the US Food and Drug Administration (USFDA) to support new food contact substances require extensive data submissions, including, for example, the nature and amount of nonvolatile extractives (USFDA 2017). Fluoropolymers, however, are not new substances in applications where they come in contact with food and have longstanding acceptance by regulators. In the United States, the USFDA is responsible for regulation of materials that come in contact with food and are considered "indirect food additives," specifically polymers (USFR 2016a). Food storage or food packaging materials, such as the fluoropolymers PTFE, FEP, and PFA, are "perfluorocarbon resins" acceptable for use by application and material type, provided they meet the extractable limits specified in the regulation (USFR 2016b). Similarly, the European Food Safety Agency (EFSA) provides recommendations to the European Commission (EC) within the EU for the regulation of food contact materials, requirements for their evaluation, and authorization of acceptable uses (EC 2004). Polymer clearance is based in part upon the fact that polymers will not migrate into food due to their high molecular weight. The EU focuses on potential low molecular weight moieties, such as residual monomers and leachables, rather than on the polymer itself. The EU food contact regulation requires that monomers, other starting substances, and additives used to produce food contact polymers should be risk assessed and authorized (EU 2011). The regulation lists authorized substances that are permitted to have food contact (EU 2011). This regulation also sets the specific migration limit (SML), which is the maximum permitted amount of substance in food that has been determined not to pose a risk to human health, specifically for individual chemicals (e.g., monomer) (EU 2011). Note that these limits exist whether or not the substance is present in the food contact material (FCM). The monomers, other starting substances, and additives used to produce fluoropolymers for food contact (e.g., PTFE, FEP, and PFA) have been authorized for food contact uses. Representative SMLs for these monomers, additives, and starting substances relevant for fluoropolymers are given in the Supplemental Data (p 14). Polymer of low concern data and medical device regulatory requirements Satisfaction of the PLC criteria is insufficient to satisfy medical device requirements. Formal biocompatibility evaluations are required by the USFDA and other global regulatory authorities to support submissions for approval of medical devices and pharmaceuticals (e.g., combination products, such as drug-eluting stents or prefilled single-dose syringes). The International Organization for Standardization (ISO) 10993 Biocompatibility of Medical Devices standards describe a broad array of biocompatibility tests that require consideration for each new device or significant changes to existing devices (ISO 2009). Over the years, medical devices containing PTFE (or expanded PTFE) have been evaluated using ISO 10993 and US Pharmacopeia (USP) Class VI standards (USP 2011) and have been determined to be biocompatible in their intended uses. The ISO 10993 standards provide guidance for evaluation of the biological response to a medical device. The USFDA, as well as most international regulatory agencies, recognizes and uses ISO 10993 standards to guide safety evaluations of medical devices submitted for their approval. Requirements to demonstrate the biocompatibility of medical devices are set forth in ISO 10993-1, and regulatory authority-specific requirements (e.g., PMDA 2003; USFDA 2016). In addition, country pharmacopeial organizations also specify testing required for biological reactivity of drugs (e.g., US Pharmacopiea, EU Pharmacopiea, Japan Pharmacopiea). The ISO requirements are categorized by the nature of body contact (e.g., mucosal membrane, circulating blood, tissue, bone, dentin) and duration of contact (<24 h, 1 d 30 d, >30 d). Depending on the nature and duration of contact, requirements include cytotoxicity, irritation, sensitization, implantation, acute- subchronic-chronic systemic toxicity, material-mediated pyrogenicity, hemocompatibility (e.g., hemolysis, thrombogenicity, and complement activation), genotoxicity (in vitro and in vivo), carcinogenicity, and developmental toxicity. (See Supplemental Data p 15 for a list of ISO 10993 biocompatibility tests.) MEETING PLC CRITERIA PRECLUDES A FINDING THAT A CHEMICAL IS OF HIGH CONCERN Just as regulatory frameworks have mechanisms to identify materials of low concern such as PLCs, they also have mechanisms to identify chemicals of high concern. For example, under REACH, a mechanism exists to identify substances of very high concern (SVHCs). Having demonstrated that fluoropolymers like PTFE should be considered PLCs, we will also demonstrate that these fluoropolymers cannot be SVHCs under REACH, do not meet the PM and PMT criteria proposed by UBA, and do not meet the criteria for listing as a POP under the Stockholm Convention. Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 329 Fluoropolymers and EU REACH SVHC, CMR, PBT, vPvB, and endocrine disrupting chemical (EDC) criteria According to the European Chemicals Agency (ECHA), SVHCs are defined in Article 57 of Regulation (EC) Nr 1907/ 2006 ("the REACH Regulation") (EC 2006) and include substances that are "Carcinogenic, mutagenic or toxic to reproduction (CMR), meeting the criteria for classification in category 1 or 2 in accordance with Directive 67/548/EEC. This directive was replaced in beginning of 2009 by the new EU regulation (EC) No 1272/2008 on classification, labeling and packaging of chemical substances and mixtures, the so-called CLP Regulation. According to the new CLP Regulation these substances shall be classified as 1a or 1b." "Persistent, Bioaccumulative and Toxic (PBT) or very Persistent and very Bioaccumulative (vPvB) according to the criteria in Annex XIII of the REACH Regulation." "Identified, on a case-by-case basis, from scientific evidence as causing probable serious effects to human health or the environment of an equivalent level of concern as those above (e.g., EDCs)." Under REACH, polymer substances are not registered, but the monomers they are composed of are registered, and the registration must be supported by data submissions that are tiered on the basis of tonnage (see EC 2006, Annex VII). The REACH definition of polymer includes materials with as few as 3 repeating units. But such a small molecule would not meet common industry standard definitions for fluoropolymers (ASTM 2015). It is highly unlikely that fluoropolymers meeting the PLC criteria would exhibit the criteria of an SVHC under REACH. Fluoropolymer data developed for other regulatory needs support the predictive value of the PLC assessment criteria and demonstrate the low hazard potential of this class of PFAS. Due to their physical-chemical properties, PLCs are not bioavailable to cause toxicity or to bioaccumulate. Toxicity study data on PTFE in the Supplemental Data (p 15-27), for example, demonstrate a lack of toxicity, including genotoxicity. Although fluoropolymers are persistent, they are not bioaccumulative or toxic and therefore do not meet the PBT criteria. Fluoropolymers and German UBA-proposed PMT criteria As regulatory frameworks continue to evolve, more work is needed in the area of PFAS classification to ensure that regulations are appropriate in scope and proportionality. Although some well-known PFAS would qualify as PM or PMT substances as proposed by the UBA (2017), fluoropolymers do not possess these characteristics. Although fluoropolymers are highly stable (persistent), they do not meet the criteria to be mobile or toxic. To demonstrate this point, PTFE, a high molecular weight fluoropolymer and a member of the PFAS group, is assessed (in the last 4 paragraphs of this section) according to the proposed UBA criteria (UBA 2017). Briefly, the changes to PM and/or PMT assessment proposed by UBA address applicability, persistence, mobility, and toxicity. The UBA proposes an initial step involving assessment of the chemical composition of a substance to determine if the substance is within the applicability domain of the proposed new assessment criteria. The UBA notes that currently only identifiable organic and organometallic chemicals are considered, and purely inorganic substances or substances of unknown or variable compositions, complex reaction products, or biological material are excluded (UBA 2017). With respect to persistence, UBA proposes that the criterion for persistence be the same as in Annex XIII of REACH, which considers degradation half-lives in marine water, fresh- or estuarine water, marine sediment, and soil as part of the PBT/very persistent, very bioaccumulative (vPvB) assessment criteria; these degradation half-life criteria range from 40 to 180 d. The UBA proposes that a substance meets the persistent criterion if the degradation half-life in marine water at pH 6 to 8 and 12 C is higher than 60 d, the half-life in fresh- or estuarine water at pH 6 to 8 and 12 C is higher than 40 d, the half-life in marine sediment at pH 6 to 8 and 12 C is higher than 180 d, the half-life in fresh- or estuarine water sediment at pH 6 to 8 and 12 C is higher than 120 d, or the half-life in soil at pH 6 to 8 and 12 C is higher than 120 d. The UBA proposes that the mobility criterion for a persistent chemical should be determined on the basis of 2 considerations. First, the water solubility of a substance at pH 6 to 8 and 12 C must be greater than or equal to 150 mg/L, and the log KOC at pH 6 to 8 and 12 C must be less than or equal to 4.5. The UBA notes that the mobility criterion should be applied only to substances that have fulfilled the criterion for persistence. Lastly, with respect to toxicity, UBA proposes a 5-part test for involving data to understand if the substance is carcinogenic, germ cell mutagenic, or toxic for reproduction; if there is other evidence of chronic toxicity; and if there is evidence for effects on or via lactation. The derived no adverse effect level (DNEL) must be less than or equal to 9 mg kg-1d-1. The UBA notes that the first 2 considerations are the same criteria defined in Annex XIII of REACH as part of the PBT/vPvB assessment criteria regarding human health. The next 2 criteria specifically address concerns for drinking water exposure and are based on Regulation EC No 1272/2008 (EC 2008) and Cramer class II (Cramer et al. 1978) for substances exhibiting moderate or low biological activity, respectively. The DNEL criterion is based on Kalberlah et al. (2014). Regardless of the arguments concerning the scientific foundation and credibility of the changes proposed by UBA to REACH PM and PMT assessment criteria, the central question with respect to PTFE is whether chemical-specific assessment would lead to an outcome different from that assuming PTFE behaved similarly to other PFAS substances. Polymers, including fluoropolymers, are different from nonpolymeric chemicals and may be regulated differently. Because of these differences, it is recognized that some data requirements may not be applicable to polymers (EU 2011) For example, as we have shown, the physical-chemical criteria of PLC are predictive of lack of hazard. Integr Environ Assess Manag 2018:316-334 wileyonlinelibrary.com/journal/ieam C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 330 Integr Environ Assess Manag 14, 2018--BJ Henry et al. With respect to applicability, PTFE is not a substance currently registered under REACH because it meets the REACH definition of a polymer substance: "a molecule that contains a sequence of at least 3 monomer units, which are covalently bound to at least one other monomer unit or other reactant" (EC 2006). However, because PTFE is an identifiable organic substance, the proposed UBA framework for assessment using the proposed PMT criteria would be applicable. Further, PTFE is highly stable and persistent in the environment. It is resistant to thermal degradation, being stable for decades at temperatures up to 260 C (SPI 2005); is stable in terms of hydrolysis, oxidation, and light (Brydson 1999); and is stable in terms of anaerobic and aerobic degradation (King et al. 2013). Therefore, PTFE would fulfill the UBA's proposed persistence criterion. In contrast, PTFE is practically insoluble in water and, therefore, is not mobile in the environment. Using the descriptive solubility table for the USP (2011), the water solubility of PTFE would be classified as practically insoluble (1 10-5 mg/L or 0.01 mg/L) to very slightly soluble (1 10- 4 mg/L or 0.1 mg/L) (USP 2011). The mobility of PFTE is 1000 to 10 000 lower than UBA's proposed mobility criterion. Therefore, PTFE does not fulfill UBA's proposed mobility criterion and would not be classified as a PM or PMT substance. A similar negative finding for PTFE pertains to toxicity. The average molecular weight of PTFE is too large for the polymer to cross a cell membrane, which means it is not bioavailable or toxic. Polytetrafluoroethylene has been tested extensively in the United States and European Union to assess commercial applications for food contact and global medical device regulations (see Supplemental Data for additional details). Results demonstrate the absence of toxicity. Therefore, PTFE does not fulfill UBA's proposed toxicity criterion and would not be classified as a PM or PMT substance (Table 4). Fluoropolymers and the Stockholm Convention POP criteria In addition to country and regional regulations, there are global legally binding instruments, such as the United Nations Environment Programme-administered conventions on chemicals and waste (UNEP 2001), such as the Stockholm Convention on Persistent Organic Pollutants. The Convention aims to eliminate POPs by eliminating their production, reducing their use, or limiting their use through a cradle-tograve approach. For the listing of new chemicals into the Convention, numeric or other criteria have been set for the screening of proposed compounds. Stockholm Convention Criteria (annex D) are compared to those of the USEPA, EU REACH, and the UBA-proposed PMT (Table 4). Fluoropolymers meet the persistence criterion only, not the bioaccumulative, toxic, or mobile criteria. Fluoropolymers satisfy widely accepted criteria to be considered PLCs. Their physical-chemical properties prevent bioavailability, bioaccumulation, toxicity, and degradation. They have negligible monomer, oligomer, and leachable content and no reactive functional groups with high toxicity. These comparisons of PLC and various regulatory assessment criteria demonstrate that, in the realm of PFAS, high molecular weight fluoropolymers like PTFE have vastly different properties than do other PFAS, and therefore, they are truly a separate class of materials that must be assessed on their own merits as has been done here. They also underscore the value of a global regulatory definition of a polymer. FUTURE WORK It is important to acknowledge that the manufacture and end-of-life phases of the fluoropolymer life cycle are not the subject of the present paper. The following reflections are provided on how these may be explored in future work. Fluoropolymer manufacture includes fluoromonomers and a wide array of initiators, catalysts, et cetera, including polymer production aids, some of which are fluorosurfactants (nonpolymer PFAS) (see Supplemental Data, p 8, for more information about them). Historically, perfluorocarboxylic acids such as PFOA and perfluorononanoic acid (PFNA) were used as polymer production aids in the manufacture of fluoropolymers. They are no longer used by leading global fluoropolymer manufacturers (USEPA 2017a), who are now using alternative substances such as fluorinated polyether carboxylates (see Supplemental Data Table S2). The toxicological and environmental properties (e.g., persistence, bioavailability, and mobility) of these alternatives are very important. Future work should delve into fluoropolymer manufacture and describe the safety, health, and environmental management practices and controls employed; should describe the applicable regulations; and should assess substances used in fluoropolymer manufacture, their human health and environmental attributes, and their mass balance. At end-of-life when a fluoropolymer has fulfilled its intended use and will be disposed of, the fate of fluoropolymers should be investigated further. Although there are sufficient data to demonstrate that fluoropolymers such as PTFE do not degrade in the environment or release substances of toxicological or environmental concern (Hintzer and Schwertfeger 2014), the downstream, end-of-life process of incineration merits future work. For instance, at temperatures above 450 C, PTFE begins to degrade, releasing hazardous substances such as hydrofluoric acid. There are published studies on the incineration of fluoropolymers under normal, foreseeable municipal waste incinerator conditions targeting specific analytes (Taylor 2009). Presently, most legislation addresses the release of hydrogen fluoride (HF) as the only critical parameter; limit values are for stack emissions (e.g., EU 2000). Future work should investigate incineration under a range of relevant foreseeable use conditions to determine more comprehensively the substances formed and their amounts. Such an incineration study is underway with results to be published upon completion (W.L. Gore 2017). In addition, the practice of the open burning of fluoropolymers, or for that matter of any polymer, is unacceptable and unsafe. Responsible incineration of fluoropolymers, adhering to regulatory guidelines, at the end of their life cycle is appropriate. Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Fluoropolymers PLC--Integr Environ Assess Manag 14, 2018 331 Table 4. Comparison of United States, Stockholm Convention, EU REACH, and German Criteria Criterion United Statesa Persistence (half-life) P Water, soil, sediment > 60 d vP Water, soil, sediment > 180 d Bioaccumulation B Aquatic BCF > 1000 vB Toxicity BCF > 5000 Fish Stockholm Conventionb Water >60 d Soil, sediment >180 d Aquatic BCF or BAF > 5000 Log KOW > 5 Toxic or ecotoxic REACHc,d Marine water > 60 d Estuarine water > 40 d Fresh or estuarine sediment or soil > 120 d Marine, fresh, estuarine H2O > 60 d Marine, fresh, or estuarine sediment > 180 d Soil > 180 d BCF > 2000 BCF > 5000 Long-term aquatic NOEC or EC10 < 0.01 Low > 10 mg/L Moderate 0.1 mg/L- 10 mg/L High < 0.1 mg/L Long-range transport (potential for) (No numeric criteria) Long-range transport (potential for): Presence through monitoring or modeled data; t1/2 (air): 2 d Classified as carcinogen category 1A or 1B; mutagen 1A or 1B; reproductive toxin 1A, 1B, or 2d Specific target organ toxicity (STOT RE 1 or 2) upon repeated (chronic) exposure)d Germanyd,e Same as REACH 1) Carcinogenic, germ cell mutagenic, or toxic for reproductiond; 2) other evidence of chronic toxicityd; and 3) evidence for effects on or via lactationd. 4) DNELf 9 mg kg-1d-1 Mobility Mobility: water solubility at pH 6-8, 12 C, must be 150 mg/L, and the log KOC at pH 6-8, 12 C must be 4.5. BAF bioaccumulation factor; BCF bioconcentration factor; DNEL derived no adverse effect level; EU European Union; M mobile; P persistent; REACH Registration, Evaluation, Authorisation and Restriction of Chemicals; STOT RE specific target organ of toxicity repeat exposure; T toxic; v very. aUSEPA 1999. bUNEP 2001 cECHA 2014 dEC 2008 eUBA 2017 fBarlow 2005; Kalberlah et al. 2014. Recycling, reuse, and closed loop systems are alternative options at the end of life. Recent work has shown, on a small scale, the ability to convert fluoropolymers back to their monomers for capture (Schlipf 2014; Invertec 2017). This approach to a closed loop economy for fluoropolymers merits additional work and discussion, as does the recycling and reuse of melt-processable fluoropolymers, such as FEP. Integr Environ Assess Manag 2018:316-334 wileyonlinelibrary.com/journal/ieam C 2018 The Authors 15513793, 2018, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4035 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 332 Integr Environ Assess Manag 14, 2018--BJ Henry et al. CONCLUSIONS The present review has brought together fluoropolymer toxicity data, human clinical data, and physical-chemical characteristics, using PTFE as an example to show that fluoropolymers satisfy the widely accepted regulatory assessment criteria to be considered as PLCs. Fluoropolymers are high molecular weight, have narrow molecular weight distribution, and have negligible oligomer content and organic and inorganic leachables. Data show that fluoropolymers have thermal, chemical, photochemical, hydrolytic, and biological stability. Polytetrafluoroethylene has been extensively tested to comply with US and EU food contact and global medical device regulations (e.g., USFDA, CFDA, Korea MFDS, Japan PMDA), including ISO 10993 biocompatibility testing and preclinical animal testing. Toxicology studies on PTFE demonstrate the absence of acute or subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, in vitro and in vivo genotoxicity, hemolysis, complement activation, or thrombogenicity. The data presented demonstrate that the fluoropolymer class of PFAS is well defined, meets PLC criteria, and should be considered as distinctly different from other classes of PFAS. The grouping of all PFAS together is not supported by the scientific data. Acknowledgment--The authors would like to thank Laura Hoch and Joel Tickner of the University of MA Lowell for comments on this manuscript; Yasuhiko Matsuoka of AGC Chemicals Americas, Inc.; Mary MaloneyHuss, Greg Hannon, Paul Fisher, David Einum, Catherine Parmeter and Terry Zitzelberger of W.L. Gore for technical assistance; John Jones of W.L. Gore for chemical analyses; Terrie Stike of W.L. Gore for manuscript preparation. We would also like to thank the editors and reviewers for their comments to improve this paper. Disclaimer--BJ Henry, JP Carlin, and JA Hammerschmidt are employees of W.L. Gore, a global manufacturer of products made with fluoropolymers. RC Buck and LW Buxton are employees of The Chemours Company, a global manufacturer of fluoroproducts. O Hernandez, former Director of the Risk Assessment Division in the USEPA Office of Pollution Prevention and Toxics, is an employee of Bergeson and Campbell, a W.L. Gore contractor. J Seed, former Deputy Director of the Risk Assessment Division in the USEPA Office of Pollution Prevention and Toxics, is an independent risk assessment consultant to W.L. Gore. H Fiedler is a professor of Chemistry at the MTM Research Centre in the School of Science and Technology at O rebro University in O rebro, Sweden. Hernandez and Seed were retained and compensated by W.L. Gore & Associates, Inc., to assist in writing this paper. W.L. Gore & Associates, Inc., the Chemours Company, and the MTM Research Centre School of Science and Technology, O rebro University, O rebro, Sweden donated data and employee time to support this work. Data Accessibility--All data and information used in this manuscript have been made available in tabulated form (Tables 1-4) by the authors and are included in the paper and the Supplemental Data. SUPPLEMENTAL DATA The Supplemental Data contains descriptive and more detailed information as highlighted in the paper. Figure S1. 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Risk management profile for PFOA, (UNEP/POPS/POPRC.13/7/Add.2). Geneva (CH). [cited 2017 July 12]. http://chm.pops.int/Convention/POPsReviewCommittee/ Chemicals/tabid/243/Default.aspx [USC] US Congress. 1976. The Toxic Substance Control Act. 15 U.S.C. 26012671. Public Law 94-469. [USEPA] US Environmental Protection Agency. 1997a. Chemistry assistance manual for premanufacture notification submitters. Washington (DC). EPA 774-R-97-003. March 1997. [USEPA] US Environmental Protection Agency. 1997b. Polymer exemption guidance manual. Washington (DC). EPA-744-B-97-001. June 1997. [USEPA] US Environmental Protection Agency. 1999. Category for persistent, bioaccumulative, and toxic new chemical substances. Fed Regis 4(213). 1999 Nov 4. [USEPA] US Environmental Protection Agency. 2010. Reviewing new chemicals under the Toxic Substances Control Act (TSCA) EPA's Review Process - Chemical categories used to review new chemicals under TSCA: TSCA New Chemicals Program (NCP) Chemical Categories. 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[cited 2017 July 12]. https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocuments RegulatoryInformation/ucm081818.htm#iid2 [USFDA] US Food and Drug Administration Center for Drug Safety and Radiological Health. 2016. Use of International Standard ISO 10993-1, "Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management process" Guidance for Industry and Food and Drug Administration Staff Document. Silver Spring (MD). [cited 2017 July 12]. https://www.fda.gov/ucm/groups/fdagov-public/@fdagovmeddev-gen/documents/document/ucm348890.pdf [USFR] US Federal Register. 1984. Premanufacture Notification Exemptions for polymers; Final rule 49 FR 46066, 1984 Nov 21. FRL-2439-1. [USFR] US Federal Register. 1995. Premanufacture notification exemptions; Revisions of exemptions for polymers; Final rule. Fed Regist 60(60): 16316-16336. Environmental Protection Agency. 60 FR 16316. 1995 Mar 29. FRL-4929-8. [USFR] US Federal Register. 2006. Premanufacture notification exemption for polymers; Amendment of polymer exemption rule to exclude certain perfluorinated polymers. 40 CFR Part 723. 2006 Mar 7. Fed Reg No 06-02152. [USFR] US Federal Register. 2010. Premanufacture notification exemption for polymers; Amendment of polymer exemption rule to exclude certain perfluorinated polymers. 40 CFR Part 723. 2010 Jan 27. EPA-HQ-OPPT2002-0051; FRL-8805-5. RIN 2070-AD58. [USFR] US Federal Register. 2012. Polymers (b). 40 CFR Sect 723.250. [USFR] US Federal Register. 2016a. Indirect food additives. 21 CFR, Sect 174-178. [USFR] US Federal Register. 2016b. Perfluorocarbon resins. 21 CFR, Sect 177.1550. [USP] US Pharmacopeia 40. 2018. National Formulary 35 (USP), General Chapter 88, Biological Reactivity Tests, In Vivo. [USP] US Pharmacopeial Convention. 2011. US Pharmacopeia National Formulary 2011: USP 34 NF 29. Rockville (MD). General Notices, Section 5.3.0, p 6. Wagner PM, Nabholz JV, Kent RJ. 1995. The new chemicals process at the Environmental Protection Agency (EPA): Structure-activity relationships for hazard identification and risk assessment. Toxicol Lett 79:67-73. Williams DF. 1987. Definitions in biomaterials. Amsterdam (NL): Elsevier. 72 p. W.L. Gore. 2017. Fabrics goal for eliminating PFCs of environmental concern. [cited 2017 July 12]. https://www.gore-tex.com/pfcgoal Integr Environ Assess Manag 2018:316-334 DOI: 10.1002/ieam.4035 C 2018 The Authors Integrated Environmental Assessment and Management -- Volume 19, Number 2--pp. 326-354 326 Received: 9 March 2022 Revised: 7 June 2022 Accepted: 7 June 2022 Critical Review A critical review of the application of polymer of low concern regulatory criteria to fluoropolymers II: Fluoroplastics and fluoroelastomers Stephen H. Korzeniowski,1 Robert C Buck,2 Robin M. Newkold,2 Ahmed El kassmi,3 Evan Laganis,3 Yasuhiko Matsuoka,4 Bertrand Dinelli,5 Severine Beauchet,5 Frank Adamsky,6 Karl Weilandt,' Vijay Kumar Soni,8 Deepak Kapoor,9 Priyanga Gunasekar,9 Marco Malvasi,1 Giulio Brinati,1 and Stefana Musiol 'BeachEdge Consulting LLC, Media, Pennsylvania, USA 2The Chemours Company, Wilmington, Delaware, USA 3AGC Chemicals Americas, Exton, Pennsylvania, USA 4AGC Performance Chemicals General Division, Tokyo, Japan 5Arkema, Colombes, France 6Daikin America Inc., Decatur, Alabama, USA 'Advanced Materials Division, 3M Center, 3M Company, St. Paul, Minnesota, USA 8Gujarat Fluorochemicals Limited, Noida, Uttar Pradesh, India 9Gujarat Fluorochemicals GmbH, Regus Centre Watermark, Hamburg, Germany "'Solvay Specialty Polymers, Vie Lombardia, Bollate, (MI), Italy Abstract Fluoropolymers are a distinct class of per- and polyfluoroalkyl substances (PFAS), high molecular weight (MW) polymers with fluorine attached to their carbon-only backbone. Fluoropolymers possess a unique combination of properties and unmatched functional performance critical to the products and manufacturing processes they enable and are irreplaceable in many uses. Fluoropolymers have documented safety profiles; are thermally, biologically, and chemically stable, negligibly soluble in water, nonmobile, nonbioavailable, nonbioaccumulative, and nontoxic. Although fluoropolymers fit the PFAS structural definition, they have very different physical, chemical, environmental, and toxicological properties when compared with other PFAS. This study describes the composition, uses, performance properties, and functionalities of 14 fluoropolymers, including fluoroplastics and fluoroelastomers, and presents data to demonstrate that they satisfy the widely accepted polymer hazard assessment criteria to be considered polymers of low concern (PLC). The PLC criteria include physicochemical properties, such as molecular weight, which determine bioavailability and warn of potential hazard. Fluoropolymers are insoluble (e.g., water, octanol) solids too large to migrate into the cell membrane making them nonbioavailable, and therefore, of low concern from a human and environmental health standpoint. Further, the study results demonstrate that fluoropolymers are a distinct and different group of PFAS and should not be grouped with other PFAS for hazard assessment or regulatory purposes. When combined with an earlier publication by Henry et al., this study demonstrates that commercial fluoropolymers are available from the seven participating companies that meet the criteria to be considered PLC, which represent approximately 96% of the global commercial fluoropolymer market. Integr Environ Assess Manag 2023;19:326-354. 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). KEYWORDS: Applications, Fluoropolymers, Low concern, PFAS, Property Combinations This article contains online-only Supporting Information. Correspondence Stephen H. Korzeniowski, BeachEdge Consulting LLC, Media, PA, USA. Email: gmail.com Published 6 September 2022 on wileyonlinelibrary.com/journal/ieam. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. INTRODUCTION "Fluoropolymers are high MW polymers with fluorine atoms directly attached to their carbon-only backbone" (Ebnesajjad, 2017). The carbon-fluorine (C--F) bond is the strongest bond between carbon and another atom and imparts unique, outstanding, and beneficial properties and extraordinary functional performance to fluoropolymers (Ameduri, 2020; Ameduri & Sawada, 2017a, 2017b; Banks et al., 1994; Fluoropolymer Products Group of Plastics Europe [FPG], 2021a; Scheirs, 2007). These properties Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 327 include chemical, biological, and thermal stability, heat and chemical resistance, unique dielectric properties, and durability. Additional fluoropolymer properties include fire resistance, weather resistance, nonwetting, and nonstick. Fluoropolymers are regarded as irreplaceable in many applications because their unique combination of specific properties, which are critical to ensure optimal performance in many applications, cannot be achieved or guaranteed by alternative materials (FPG, 2021a, 2017; Henry et al., 2018; Performance Fluoropolymer Partnership of the American Chemistry Council [PFP], 2020). Per- and polyfluoroalkyl substances (PFAS), a universe of substances with widely diverse properties that have been used in industrial and consumer applications since the 1950s, include fluoropolymers as a distinct class (Buck et al., 2011; Henry et al., 2018). A single, globally harmonized definition for PFAS has not yet been agreed upon. PFAS have been defined differently based on their structure and atomic composition (Buck et al., 2021; Wallington et al., 2021). For example, the USEPA's working PFAS structure definition is "a structure that contains the unit R-CF2-CF(R)(R), where R, R, and R do not equal "H" and the carbon-carbon bond is saturated (note: branching, heteroatoms, and cyclic structures are in- cluded" (USEPA, 2021a). The European Chemicals Agency (ECHA) employed a much broader PFAS structural definition (ECHA, 2020). A recent Organisation for Economic Cooperation and Development (OECD) report, which defined PFAS as fluorinated substances that contain in their structure at least one fully fluorinated methyl or methylene carbon atom (without any H/Cl/Br/I atom attached to it), that is, with a few noted exceptions, any chemical with at least a perfluorinated methyl group (-CF3) or a perfluorinated methylene group (-CF2-; OECD, 2021). This report acknowledges that the term "PFAS" is broad, gen- eral, and nonspecific, which does not inform whether a compound presents risk or not, but only communicates that the compounds under this term share the same structural trait of having a fully fluorinated methyl or methylene carbon moiety. Further, the report highlights that, among the substances defined as PFAS, there are distinct substances with very different properties: polymers and nonpolymers; solids, liquids and gases; persis- tent and nonpersistent substances; highly reactive and inert substances; mobile and insoluble (immobile) substances; and (eco) toxic and nontoxic chemicals. In addition, the report recognizes that PFAS have diverse molecular structures (e.g., neutral, anionic, cationic, or zwitterionic; with or without aromatic rings; nonpolymers or polymers; low or high molecular weight (MW), and thus diverse physical, chemical, and biological properties (e.g., involatile or volatile; water soluble or water insoluble; reactive vs. inert; bioaccumulative or nonbioaccumulative) and as such highly recommends that such diversity be properly recognized and communicated in a clear, specific, and descriptive manner when communicating about PFAS. There is considerable media and public confusion and misunderstanding regarding PFAS, as the many different chemicals and groups are often not clearly differentiated under the broad term PFAS. Per- and polyfluoroalkyl substances, a large, diverse group of substances with vastly different properties, is too broad to allow effective, science- based assessment and regulation of chemical compounds as an entire group. This point has been raised in recent publications that suggest approaches to effectively group PFAS for regulatory assessment (American Chamber of Commerce in Europe [Amcham], 2020a; Buck et al., 2021; Bundesverband der Deutschen Industrie e.V. [BDI], 2021; Fiedler et al., 2020; Miller et al., 2020; Orgalim, 2021; Royal Society of Chemistry [RSC], 2021; Sha et al., 2019; Wallington et al., 2021). A clear understanding of the origin of PFAS found in the environment, the PFAS that are commercially relevant (Buck et al., 2021), and assessment of their properties are needed to be able to determine which classes of PFAS require management action. PFAS must be assessed based on their chemical, physical, thermal, and biological property differences and uses (Amcham, 2020a; BDI, 2021; Buck et al., 2021; RSC, 2021; Wallington et al., 2021). As regulatory frameworks, such as the EU REACH regulation, continue to evolve, more work is needed to distinguish clearly among PFAS based on their properties to assure that regulations are appropriate in scope, proportionate, and are science-based. Per- and polyfluoroalkyl substances are divided into two primary categories: nonpolymers and polymers (Buck et al., 2011). Polymeric PFAS, generally known as "fluorinated polymers," include fluoropolymers (discussed here), perfluoropolyethers (PFPE), and side-chain fluorinated polymers (SCFP; Buck et al., 2011; Henry et al., 2018 and Supporting Information: Figure 6.1). This article deals strictly with fluoropolymers. Neither PFPE nor SCFP are discussed here. The nonpolymer category includes perfluoroalkyl substances and polyfluoroalkyl substances. Certain nonpolymer PFAS substances, for example, short- and long-chain per- and polyfluoroalkyl carboxylic acids and sulfonic acids, received regulatory scrutiny recently due to their toxicity, as well as their persistence, potential to bioaccumulate, and/or mobility in the environment. Regulatory processes have been launched worldwide to address these concerns related to specific nonpolymer PFAS. These targeted regulatory measures have evolved increasingly into restrictions on the entire family of PFAS. For example, five Member States of the European Economic Area have initiated a procedure to prepare a joint restriction proposal under the EU REACH Regulation to limit the risks to human health and the environment from the manufacture and use of all substances in the PFAS family based on structure alone (ECHA, 2020). Although fluoropolymers fit the PFAS structural definition, they have vastly different physicochemical, environmental, and toxicological properties than other PFAS in addition to substantial societal benefits and importance (Fluoropolymer Products Group of Plastics Europe [FPG], 2017, 2021a). For Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 328 Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. these reasons, fluoropolymers should be considered separately and not aggregated with all other PFAS for regulatory action. Concurrently, the USEPA prepared a PFAS Strategic Roadmap laying out how it plans to evaluate and potentially regulate PFAS (USEPA, 2021a). Recognizing that there are many PFAS very diverse in their physical form, chemical structure and composition, functional characteristics, and toxicity profiles, USEPA "is conducting new research to better understand the similar and different characteristics of specific PFAS and whether and how to address groups and categories of PFAS." Fluoropolymers have documented safety profiles, are thermally, biologically, and chemically stable, negligibly soluble in water, nonmobile, nonbioavailable, nonbioaccumulative, and nontoxic (Henry et al., 2018). Some fluoropolymers have been demonstrated to meet the "polymers of low concern" (PLC) criteria, and as such do not present notable concern for human health or the environment (Henry et al., 2018). PLC criteria were developed over time within regulatory frameworks around the world as an outcome of chemical hazard assessment processes, which identified physical-chemical properties of polymers that determine polymer bioavailability and thereby report a polymer's potential hazard. For example, many of the physicochemical properties, such as MW, limit the ability of a polymer to cross the cell membrane and therefore limit its bioavailability (Kostal, 2016; Lipinski et al., 2001; USEPA, 2012). The USEPA built on this knowledge to adopt a polymer exemption rule to exempt low-hazard polymers from certain regulatory notification requirements under the Toxic Substances Control Act's (TSCA) new chemicals program (United States Federal Register [USFR], 1984). An OECD expert group on polymers reached consensus on these criteria and their respective metrics, documenting the data required for a polymer to qualify as a PLC to human health and the environment (OECD, 1993). Subsequently, an additional OECD work group concurred that PLC have "insignificant environmental health and human health impacts" (OECD, 2009). In addition, the European Commission commissioned a report (BIO by Deloitte, 2015) wherein several member countries agreed on the polymer properties predictive of adverse human health and environmental hazard. The report outlined eligibility criteria for a polymer to be considered a PLC. In 2019, the industry-led European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) developed a "Conceptual Framework for Polymer Risk Assessment" ("CF4Polymers"; ECETOC, 2019). CF4Polymers provides guiding elements to be considered in assessing potential ecological and human health hazards and risks posed by polymer substances. CF4Polymers also considers specific life-cycle stages of polymer products and their associated routes of exposure. The authors of the CF4Polymers framework support the PLC approach as a means to accomplish polymer risk assessments. They specifically support the findings of Henry et al. (2018) and state that they are "...unaware of scientific evidence to justify generally assigning fluoropolymers the same level of regulatory concern as other PFAS" (ECETOC, 2019). In 2020, the European Commission contracted a study to propose criteria for the identification of polymers requiring registration (PRR) under REACH (Wood, 2020a). The Wood report states that the authors consider that fluoropolymers meet the criteria to be considered PLC, "following the recommendations of Henry et al." Considerable debate and comment on proposals have been put forward as the process and discussion advances (American Chamber of Commerce in Europe [Amcham], 2020b; FPG, 2021a; Hafer, 2021). Four major fluoropolymers have previously been demonstrated to meet the criteria as PLC (Henry et al., 2018). This 2018 study raised interest in gathering similar data for additional commercial fluoropolymer products, both in scope and polymer type. In this study, seven global fluoropolymer manufacturers from the USA, Europe, and Asia collaborated to gather and present data for 14 additional fluoropolymers. In addition to information describing chemical composition, uses, performance properties, and functionalities of the 14 fluoropolymers, author company data for each of the PLC criteria are presented and discussed. The results demonstrate that each of the 14 commercially manufactured fluoropolymers in this study satisfy the widely accepted assessment criteria to be considered PLC and merit such designation. The study results add further evidence to demonstrate that fluoropolymers are demonstrably different and should not be grouped with other PFAS for hazard assessment or regulatory purposes. USES, PERFORMANCE PROPERTIES, AND FUNCTIONALITY OF FLUOROPLASTICS AND FLUOROELASTOMERS IN THIS STUDY The fluoropolymers described and evaluated in this study are high-performance materials used in commercial and industrial applications. Described herein are the industries and sectors (Table 1) and the performance properties and functionalities (Table 2) of the study fluoropolymers. The unparalleled combination of properties makes fluoropolymers critical materials for a broad range of applications and industrial sectors including automotive, aerospace, energy production and storage, and electronics (Table 1). Fluoropolymers are an important driver of the European Green Deal (FPG, 2021a) and UN Sustainability Development Goals (United Nations [UN], 2021), supporting smart mobility, clean energy, and sustainable industry. They are used in various components of renewable energy installations, such as hydrogen and photovoltaic panels and facilitate advanced energy storage and conversion technologies such as lithium-ion batteries (FPG, 2021a). Fluoropolymers are (i) durable, stable, and mechanically strong in harsh conditions; (ii) chemically inert, meeting the requirements for low levels of contaminants and particulates in manufacturing environments that are critical to the food and beverage, pharmaceutical, medical, and semiconductor industries; and (iii) biocompatible, nonwetting, nonstick, and highly resistant to Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 Integr Environ Assess Manag 2023:326-354 Industries End uses Transportation Automotive Aerospace Health care Pharma- ceuticals Medical devices TABLE 1 Fluoropolymer end uses and industries Chemical Consumer Oil and gas Chemical process industry (CPI) Production of goods Protection and packaging Filtration Telecommunications Electronics and semiconductors Internet and wireless communications Textiles Technical textiles Infrastructure Construction and architecture Renewable energy Energy production Hydrogen production Energy storage DOI: 10.1002/ieam.4646 Fluoroplastics PVDF homopolymer PVDF copolymer ECTFE copolymer ECTFE terpolymer PCTFE FEVE EFEP CPT THV Fluoroelastomers FEPM FKM FFKM Specialty Amorphous Ionomer 2022 The Authors Note: See also Chapter 5 in the Supporting Information. Abbreviations: CPT, chlorotrifluoroethylene-tetrafluoroethylene; ECTFE, ethylene-chlorotrifluoroethylene; EFEP, ethylene-tetrafluoroethylene-hexafluoropropylene; FEPM, trifluoroethylene-propylene copolymer; FEVE, fluoroethylene-vinyl ether; FKM, HFP-VF2 polymer and HFP-VF2-TFE polymers; FFKM, TFE-PMVE perfluoroelastomer; PCTFE, polychlorotrifluoroethylene; PVDF, polyvinylidene fluoride; THV, TFE-HFP-VF2. 329 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2022 The Authors wileyonlinelibrary.com/journal/ieam Integr Environ Assess Manag 2023:326-354 TABLE 2 Fluoropolymer properties and functionality See Supporting Information: Chapter 2 for property descriptions Mechanical strength Durable Wear resistance Low coefficient Flexibility of friction Resistance to chemicals Weatherability Inert--Stable Cryogenic properties (lower than -50 C) Fluoroplastics PVDF Homopolymer PVDF Copolymer ECTFE Copolymer ECTFE Terpolymer PCTFE FEVE EFEP CPT THV Fluoroelastomers FEPM FKM FFKM Specialty Amorphous Ionomer See Supporting Information: Chapter 2 for property descriptions Electrical insulator-- high data transmission rate Ionic conductivity Piezo-electrical properties Barrier properties Functional Nonstick properties Ultra high purity grades for clean applications Optical clarity Fluoroplastics PVDF Homopolymer PVDF Copolymer High operating temperature range High limiting oxygen index Low refractive index--used for optical effects Polymer processing additive (PPA)a (Continued ) Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. 330 FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 Integr Environ Assess Manag 2023:326-354 TABLE 2 (Continued) See Supporting Information: Chapter 2 for property descriptions Electrical insulator-- high data transmission rate Ionic conductivity Piezo-electrical properties Barrier properties Functional Nonstick properties Ultra high purity grades for clean applications Optical clarity Low refractive index--used for optical effects Polymer processing additive (PPA)a ECTFE Copolymer ECTFE Terpolymer PCTFE FEVE EFEP CPT THV Fluoroelastomers DOI: 10.1002/ieam.4646 FEPM FKM FFKM Specialty Amorphous Ionomer Note: See Chapter 5 in the Supporting Information. Abbreviations: CPT, chlorotrifluoroethylene-tetrafluoroethylene; ECTFE, ethylene-chlorotrifluoroethylene; EFEP, ethylene-tetrafluoroethylene-hexafluoropropylene; FEPM, trifluoroethylene-propylene copolymer; FEVE, fluoroethylene-vinyl ether; FKM, HFP-VF2 polymer and HFP-VF2-TFE polymers; FFKM, TFE-PMVE perfluoroelastomer; PCTFE, polychlorotrifluoroethylene; PVDF, polyvinylidene fluoride; THV, TFE-HFP-VF2. aPolymer Processing Additives (PPA): also known as Polymer Processing Aid, Extrusion Process Aids or Polymer Processing and Recycling Aids. 2022 The Authors 331 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 332 Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. temperature, fire, and weather (Table 2). Fluoropolymers are the preferred choice of material because of their unique combination of properties that are not achievable from other materials or via other functions. As a result, fluoropolymers have become a critical mainstay for our society providing vital, reliable functionality to a broad range of industrial and consumer products. Three fluoropolymer types are included in this study: fluoroplastics, fluoroelastomers, and specialty fluoroplastics. Here, we describe briefly each included in this study. Additional details about each polymer are provided in the Supporting Information: Chapter 5. Fluoroplastics The fluoroplastics included in this study are: polyvinylidene fluoride (PVDF) homopolymer, PVDF copolymer, ethylene-chlorotrifluoroethylene (ECTFE) copolymer, ECTFE terpolymer, polychlorotrifluoroethylene (PCTFE), fluoroethylene-vinyl ether (FEVE), ethylene- tetrafluoroethylene-hexafluoropropylene (EFEP) terpolymer, chlorotrifluoroethylene-tetrafluoroethylene (CPT) terpolymer, and tetrafluoroethylene, hexafluoropropylene, vinylidene fluoride (TFE-HFP-VF2 [THV]) terpolymer as well as the specialty fluoroplastics, amorphous fluoropolymers, and fluorinated ionomers. Typical monomers used in the manufacture of fluoroplastics include tetrafluoroethylene (TFE), hexafluoropropylene (HFP), vinylidene fluoride (VDF or VF2), chlorotrifluoroethylene (CTFE), vinyl fluoride (VF), trifluoroethylene (TrFE), and perfluoroalkyl vinyl ethers (PAVEs), which include trifluoromethyl trifluorovinyl ether (PMVE), pentafluoroethyl trifluorovinyl ether (PEVE), and heptafluoropropyl trifluorovinyl ether (PPVE). In some copolymers, monomers that do not contain fluorine attached to the olefinic carbons may be used. These include ethylene, propylene, perfluoroalkyl-substituted ethylenes, and others (Ebnesajjad, 2000, 2003; Grot, 2011). Fluoroelastomers The fluoroelastomers included in this study are: trifluoroethylene-propylene copolymer (FEPM), HFP-VF2 polymer and HFP-VF2-TFE polymers (FKM), and TFE- PMVE perfluoroelastomer (FFKM). Typical monomers used in the manufacture of fluoroelastomers include VDF, HFP, TFE, CTFE, PAVEs, as well as propylene, 1-hydropentafluoropropene (HPFP), and 2,3,3,3- tetrafluoropropene (HFO-1234yf; FPG, 2021a). Although fluoroelastomers are based on many of the monomers that are also used for the synthesis of fluoroplastics, they are different because of the specific composition, flexibility with subambient glass transition temperatures, as well as their elastomeric properties, resulting from the cross- linking process. Cross-linking, known as curing or vulcanizing, is a hardening process to form chemical bonds between polymer chains that gives polymers their elasticity (Amduri et al., 2001; Drobny, 2016). PVDF homo- and copolymers Polyvinylidene fluoride fluoropolymers are specified by end users across the world for their outstanding combination of properties. Because they have high temperature resistance, low permeability, and high mechanical strength, and provide chemical resistance to a wide range of aggressive chemicals, PVDF fluoropolymers are used as a contact surface for the production, storage, and transfer of corrosive fluids (chemically resistant to halogens and acids) in the chemical processing industry, oil and gas transportation, and cables industry (Arkema, 2021a; Gujarat Fluorochemicals Limited, 2018, 2022; Solvay, 2021a). The outstanding resistance to sunlight/UV exposure make PVDF suitable for architectural coatings. The outdoor aging and weathering properties of PVDF resin led to its use in long- lasting paints for coating metal sheet for the past 50 years. PVDF resins can also be used to protect thermoplastics through coextrusion or film lamination techniques to obtain antigrime and antigraffiti surfaces with exceptional weathering properties. PVDF fluoropolymers also exhibit radiation resistance, desirable burn characteristics, flame, and smoke properties, easy processing on industry-standard equipment, and easy postprocessing steps, such as welding and fabrication. PVDF is used as a binder in lithium-ion batteries as well as PVDF film for solar power panels because of its high thermal and electrochemical stability, its stability under harsh environmental conditions, and its strong adhesion properties are critical to achieving environmental goals. ECTFE (co- and terpolymers) Ethylene chlorotrifluoroethylene (ECTFE) is a semicrystalline and melt-processable fluoropolymer obtained by the copolymerization of the two monomers, ethylene and chlorotrifluoroethylene, with an essentially 1:1 alternating structure (Ebnesajjad, 2017). Due to its chemical structure, ECTFE offers a unique combination of properties including chemical resistance, high thermal rating, and very good mechanical properties (Solvay, 2021b). ECTFE terpolymer with added hexafluoroisobutylene monomer displays enhanced stress-cracking performances resulting from chain- structure modifications of the polymer. ECTFE is used widely in anticorrosion applications such as coatings or in self-supporting construction (pipes) and architectural films (Solvay, 2021c). One of the principal advantages of ECTFE fluoropolymer is the ease with which it can be processed. It is a true thermoplastic that can be handled by conventional techniques of extrusion as well as by blow, compression, injection, rotational, and transfer molding. Powder coating methods are also applicable. ECTFE embodies an exemplary trade-off among general properties, offering high chemical and mechanical resistance combined with easy processing of the resin. PCTFE Polychlorotrifluoroethylene is a homopolymer of chlorotrifluoroethylene. PCTFE is melt processable and can be Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 333 extruded or molded (Satokawa, 1990). PCTFE has outstanding mechanical properties, especially hardness, and chemical resistance compared with PTFE and PFA, although it is slightly inferior to PFA and FEP in heat resistance and chemical resistance (Daikin, 2021a; Satokawa, 1990). PCTFE has been applied widely in the semiconductor industries and aerospace industries (Curbell, 2021; Daikin, 2021a). In addition to distinguished thermal and chemical stability, it has very low moisture absorption and permeation; therefore, PCTFE is used in pharmaceutical packaging (Honeywell, 2021). FEVE Fluoroethylene-vinyl ether fluoropolymer resins are manufactured by copolymerization of fluoroethylene monomer and a vinyl ether monomer and consist of alternating fluoroethylene and alkyl vinyl ether segments (AGC Chemicals Company, 2021a; Parker & Blankenship, 2015). They were developed in 1982 as the first solvent-soluble fluoropolymers in the world (Darden & Parker, 2021; Kojima & Yamabe, 1984; Munekata, 1988; Yamabe et al., 1984). The alternating fluorinated segments provide outstanding UV stability, weather resistance, and chemical resistance, while the vinyl ether segments provide solvent compatibility and cross-linking sites (Parker & Blankenship, 2015; Scheirs, 2007). FEVE resins are used to make ultraweatherable coatings for architectural, aerospace, automotive, bridge, and industrial maintenance markets (Hoshino & Morizawa, 2017). EFEP Ethylene-tetrafluoroethylene-hexafluoropropylene is a terpolymer of ethylene, tetrafluoroethylene, and hexafluoropropylene. It was designed to have many of the properties of ETFE. It has a lower processing temperature, which allows it to be coextruded with conventional thermoplastic polymers such as polyamide, ethylene vinyl alcohol (EVOH), and modified polyethylene. EFEP can be extruded, injection molded, and blow molded, and it is used in many applications such as those identified in Supporting Information: Chapter 4.7 (Daikin, 2011a). EFEP is a melt- processable resin with good processability because of its low melting point. It also has excellent mechanical properties, provides chemical resistance, low permeability, exceptional weatherability, and good heat resistance. Other prominent features include inherent flame retardancy as well as good optical properties given that EFEP is highly transparent and has both a low dielectric constant and loss tangent. CPT Chlorotrifluoroethylene-tetrafluoroethylene is a terpolymer of chlorotrifluoroethylene, tetrafluoroethylene, and perfluoroalkyl-vinyl-ether. It is a melt-processable polymer and resin, which is readily processed because of its lower melting point. It can be melt-molded as a thermoplastic resin by extrusion, injection, and compression molding. CPT is a modified perfluoroalkoxy fluoropolymer (PFA), which utilizes chlorotrifluoroethylene to provide low permeability to PFA, and it has many outstanding properties as a hybrid polymer of PFA and PCTFE as shown below. It has demonstrated permeation resistance to organic solvent, chemicals, water vapor, and gasoline (Daikin, 2011b). CPT offers superior permeation resistance against gasoline and flexible fuel and can be part of construction meeting the LEV III requirements (US environmental protection regulations in this automotive application). CPT also has notable barrier properties against many kinds of organic solvents and strong acids, especially HF, HCl, and HNO3. This is very useful for semiconductor applications (Daikin, 2021b). In addition to the features noted above, CPT also provides heat resistance, excellent weatherability, flame retardancy, and good optical properties owing to its high transparency. THV THV fluoropolymers are a group of fluorinated thermoplastic polymers composed mainly of tetrafluoroethylene (TFE), hexafluoropropylene (HFP), and vinylidene fluoride (VDF; Domininghaus, 1998; Hintzer & Schwertfeger, 2014; Hull et al., 1997). The melting point of the different grades ranges from approximately 100 C to nearly 250 C. THV fluoropolymers are easy to process due to their broad processing windows. Different THV grades exhibit high flexibility, high transparency, bondability to fluorinated and nonfluorinated materials, and very good permeation resistance against fuels and other chemicals. The polymers are used as a barrier layer in fuel hoses, for transparent films and tubing, as matrix materials in composites, and the bonding layer in multilayer construction (Dams & Hintzer, 2017; Hull et al., 1997). The high transparency of the special film makes it an ideal adhesive film for laminated glass and the optimal protective film for surfaces. THV grades compete against other fluorothermoplastic materials for applications that require transparency and low refractive index as well as with fuel barrier materials. Commercial nonfluorinated materials cannot be used as substitutes for THV because of the unique combination of properties. Polymethylmethacrylate (PMMA) is used in conjunction with THV to provide differences in refractive index to create the total reflection needed for polymer optical fibers (Park et al., 2008). Transparent polymers, such as PMMA or polycarbonate, do not have the same chemical resistance or UV resistance to compete directly with THV. FEPM Trifluoroethylene-propylene copolymer elastomers, ASTM D1418, are high MW fluoropolymers with alternating tetrafluoroethylene and propylene segments (Kojima et al., 1977). They are also known as TFE-P copolymers. Various articles can be produced by means of compression molding, extrusion, injection molding, and calendering. FEPM elastomers are compounded and cured (cross-linked) to deliver unique and valuable properties by providing exceptional heat resistance with a continuous service temperature higher than Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 334 Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. 200 C, outstanding chemical resistance with little or no deterioration even in contact with strong acids, bases, and oxidants at high temperatures, steam resistance, and high electrical resistivity on the order of 1015-1016 /cm (bulk resistivity). Formulated FEPM components are now used worldwide in many critical industrial applications where they must function safely in harsh environments, thereby extending the life of critical components and reducing downtime and costly repairs. FEPM elastomers are used in a range of applications including thermal power plants, oil and gas industry, ocean development, chemical and nuclear plants, automotive, aerospace, heavy-duty diesel, electronics, machinery, renewable energy, food processing, and medical. Their noted heat and chemical resistance make them especially valuable in oil and gas extraction (downhole) applications, where reliability is essential to cost effective and environmentally responsible production (Hull, 1983). FEPM elastomers are also used in high-performance wire and cable applications as insulating materials with the highest heat resistance, for example, lightweight, high-voltage automotive cables and motor cables for Japanese high-speed bullet trains (AGC Chemicals Company, 2021b). Fluoroelastomers (FKM) FKM are a family of fluoroelastomer materials defined by ASTM international standard D1418 (ASTM, 2021). FKM fluoroelastomers contain vinylidene fluoride (VDF) as a monomer combined with a variety of other fluoromonomers to create a palette of polymers with properties tailored for specific uses (Dams & Hintzer, 2017; Drobny, 2016; Van Cleeff, 1997; Worm & Grootaert, 2001). Cross-linked FKM fluoroelastomers are amorphous polymers designed for demanding service applications in hostile environments characterized by broad operating temperature ranges in contact with industrial chemicals, oils, or fuels (Worm & Grootaert, 2001). FKM fluoroelastomers are used mainly in fabricated parts (e.g., o-rings, gaskets, seals) to provide barriers against a wide range of fluids under severe service conditions (Drobny, 2016). Their design allows stable extrusion and molding processes and fitting in a wide range of processing constraints, reducing the risk of failure and increasing productivity. FKM fluoroelastomers provide high temperature and aggressive fluids resistance and retention of properties over a wide and demanding range of operating use conditions (high and low temperatures) for sealing and fluid transport applications, offering far superior performance than hydrocarbon elastomers. Applications include aerospace, automotive, oil and gas, chemical processing, electrical, office equipment, food, pharmaceuticals, and consumer wearables. Additionally, uncured FKM fluoroelastomers are used as a polymer processing additive (PPA) or polymer extrusion aids in small amounts (50-2000 ppm) dispersed in polyolefins such as high-density polyethylene (HDPE) and linear low-density polyethylene (LLDPE), significantly improving their film extrusion characteristics, reducing melt fracture and die build-up, as well as increasing productivity, minimizing energy and water footprint, and enabling the extrusion of thin films (Lavalle, 2020; Shell, 2020). FFKM Perfluoroelastomers, designated by ASTM D1418 as FFKM, are a fully fluorinated class of elastomers that are typically made up of tetrafluoroethylene (TFE), a perfluoro (alkyl vinyl ether; PAVE), and a cure site monomer(s) (Ohkura & Morizawa, 2017). FFKM elastomers offer superior chemical and temperature resistance, excellent resistance to gas and liquid permeation, and resistance to weather and ozone with operating temperatures ranging from -40 C to 325 C (Drobny, 2016; Greene-Tweed, 2021a, 2021b). These polymers can also be compounded to meet the special requirements of upstream, midstream, and downstream oil and gas exploration due to their superior properties (Barnwell, 2021; Daemar, 2021). Because of these properties, FFKM elastomers are used in a wide variety of applications such as critical sealing solutions for the aerospace, pharmaceutical, medical, chemical processing, semiconductor, and oilfield industries (Atkinson, 2018; Marshall, 2017). Amorphous fluoropolymers Amorphous fluoropolymers are copolymers of TFE and specialty monomers that yield linear, high molar mass noncrystalline polymers (AGC Chemicals Company, 2021c; Gangal & Brothers, 2010; Hintzer et al., 2013; Korinek, 1994; Resnick & Buck, 1997, 1999). Amorphous fluoropolymers have the outstanding chemical and thermal stability and surface properties of semicrystalline perfluoropolymers as well as the unique properties associated with amorphous materials such as optical clarity and high gas permeability. The optical properties are outstanding, with more than 90% transmission, and thereby low dissipation, over a wide range of wavelengths (e.g., 200-2000 nm). TFE/PDD (2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole) copolymers have the lowest refractive index known for a solid organic polymer (Groh & Zimmermann, 1991). This unique combination of properties makes amorphous fluoropolymers unmatched for uses in degassing, fiber optics, photolithography, antireflective coatings, passivation and protective coatings for medical, military, and aerospace devices, as well as electronic applications (Gangal & Brothers, 2010; Hintzer et al., 2013). Fluorinated ionomers Fluorinated ionomers are copolymers of TFE and a perfluorovinylether monomer containing an ionic group, typically a sulfonic acid or carboxylic acid (Grot, 2011, 2013). Fluorinated ionomers can be extruded or cast into film and converted into ion exchange materials (IXMs). IXMs come in a variety of useful forms offering a broad range of solutions for different applications (AGC Chemicals Company, 2021d; Asahi-Kasei, 2021; Chemours, 2021a). These forms include ion exchange membranes (IEMs), dispersions, and resins. IEMs must possess the required ion transport properties for the electrochemical cell in which they reside to perform well Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 335 and work effectively. Some of these properties include high ionic conductivity, chemical resistance, high operating temperature range, low permeability, and balanced durability and performance (Chemours, 2021b). Ion exchange membranes (IEMs) stand to play a noteworthy role in today's modern world (Chemours, 2021b) and as such, are utilized in a wide range of applications and end- use industries including electrochemical processing, energy production, and hydrogen production. IEMs revolutionized the chlor-alkali industry (Grot, 2013), the manufacture of primarily caustic soda and chlorine, by eliminating the use of hazardous materials such as mercury and asbestos (Asahi-Kasei, 2021) and, in doing so, reducing energy consumption. Water electrolysis, the process of converting water into hydrogen and oxygen, relies on IEM technology. Although this process requires electricity, renewable energy sources such as solar or wind power can be utilized, allowing the potential for hydrogen to be a "clean" energy source (Science Center, 2021). Hydrogen fuel cells, some of which use a type of IEM known as a proton exchange membrane, can then convert hydrogen to electricity, a crucial technology to reach the stated target of the EU New Green Deal (EC, 2021). STUDY METHODOLOGY AND DATA Seven global fluoropolymer manufacturers (AGC Chem- icals Americas, Arkema, The Chemours Company, Daikin Industries, Gujarat Fluorochemicals Limited, Solvay Specialty Polymers, and 3M Company) participated in this study and contributed data, writing, critique, and analysis. The companies noted above are members of the US-based Performance Fluoropolymer Partnership (PFP) and/or EU-based Fluoropolymer Product Group (FPG). This study provides data on 14 fluoropolymers, building on a prior study (Henry et al., 2018). The study was chartered within two global industry groups. Participants put forward candidate fluoropolymers of notable commercial importance for the study and provided company and published data that address the PLC criteria. Thirteen PLC criteria that relate to the polymer structure and properties, including three to physicochemical properties and five to stability, set forth in BIO by Deloitte (2015) and presented in prior work on four fluoropolymers (Henry et al., 2018), are addressed in this study (Figure 1). These criteria are briefly described in Table 3 with further description provided in Supporting Information: Chapter 3 and in the prior work (Henry et al., 2018). Participants provided company and published data and a description of methods and/or public references to demonstrate the origin of the data provided. These methods and references are provided in detail in Supporting Information: Chapter 4. The PLC criteria data were compiled and are presented in Tables 4 and 5. The data assessment was done in two ways: Companies could self-assess the PLC data if they had the technical resources to do so or they could submit their PLC data to a third-party contractor for an independent technical review. The third-party consultant hired by PFP was GSI Environmental Inc. The objective was to be able to publish the references and methods behind the PLC data provided for each fluoropolymer in the study. In cases where the data and/or methods contained confidential business information, the third-party consultant independently evaluated the information supplied before it was shared in a blinded, aggregate form with the participating project companies. In several cases--FKM, PVDF, and ionomers-- several companies submitted data for the same fluoropolymer. The data were combined and are presented in Tables 4 and 5. There is no intentional company attribution for the data presented. The following describes further how the study data were generated and compiled. A third-party consulting company (GSI) was engaged to comment independently on data, methods, and references initially supplied by study participants for their respective fluoropolymers. Several study participants used this third-party consultant. Following the initial third-party assessment and assembly of the master data Tables 4 and 5 as well as the FKM data in Supporting Information: Table 4.11, a series of subsequent assessments were conducted (within PFP) FIGURE 1 OECD polymer of low concern (PLC) criteria add (C) 2021 W.L.Gore & Associates Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 336 Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. (See Supporting Information: Chapter 3 for additional details) Criterion Polymer composition Molecular weight, number average molecular weight, MW distribution, and % oligomer <1000 Da Ionic character Reactive functional groups and RFG ratio to MW Low MW leachables TABLE 3 Polymer of low concern (PLC) criteria descriptions Description The polymer composition criterion requires structure and elemental composition of the polymer be described and identified (e.g., by Chemical Abstracts Service [CAS] number). The number average molecular weight (Mn) and oligomer content are the most commonly used criteria for PLC assessment. The EU assessment report (BIO by Deloitte, 2015) states that the "most potential health concern polymers have a number average molecular weight, Mn, <1000 Da and oligomer content >1%." The higher the oligomeric content, the more likely a polymer is to be a health or ecotoxicological (OECD, 2009, p. 9). Molecular weight (MW) is an important predictor of biological effect because large molecules (>1000-10 000 Da) are too large to penetrate cell membranes (Supporting Information: in Beyer, 1993, p. 14). Because large molecular weight polymers cannot enter the cell, they cannot react with "target organs," such as the reproductive system, and are not bioavailable. "Therefore, as the Mn of a polymer increases, a reduced incidence of potential health concern effects might be expected" (OECD, 2009, p. 20). An additional PLC consideration is the weight percentage of oligomers that are <1000 Da. Oligomers may be composed of, for example, dimers, trimers, and tetramers, meaning they have 2- monomer, 3- monomer, and 4-monomer units, respectively. The EU report (BIO by Deloitte, 2015) concluded that most potential health concern polymers have Mn of <1000 Da and oligomer content of >1%: "...the distribution of potential health concern polymers exhibited an increased incidence of higher oligomer content that began at 5% for <1000 Da and 2% for <500 Da oligomeric content" (OECD, 2009, p. 24). Molecular weight distribution (MWD), also known as "polydispersity index," measures the heterogeneity of size of polymer molecules in a polymer. The MWD is an important parameter for predicting potential biological effects of polymers because, although Mn may be a large value, low MW oligomers <1000 Da may be present, which could penetrate the cell. Electrical charge or ionic character can be anionic, cationic, amphoteric, or nonionic. Specifically, cationic polymers have been associated with aquatic toxicity (Auer et al., 1990; USEPA, 1997a). A "reactive functional group" (RFG) is defined as an atom or associated group of atoms in a chemical substance that is intended or can be reasonably expected to undergo facile chemical reaction (USFR, 2012). Some highly reactive functional groups (or a high ratio of RFGs per mole) have been associated with adverse human health and ecotoxicology (e.g., acrylates, methacrylates, isocyanates, anhydrides, aziridines; USEPA, 2010). The functional group equivalent weight (FGEW) is used to determine if the RFGs in a polymer are substantially diluted by polymeric material to allow the polymer to be a PLC (USEPA, 1997). The FGEW of a polymer is defined as the ratio of the Mn to the number of functional groups in the polymer. The FGEW is used as an indication of the degree of reactivity of the polymer; the lower the FGEW, the more reactive the polymer and the greater the potential for health and environmental impact (OECD, 2009, p. 10). Low MW leachables are chemical molecules, either inorganic or organic, that migrate (i.e., leach) out of the polymer. These could be residual monomers or oligomers resulting from incomplete polymerization processes, surface residues, or other chemicals used in the manufacturing processes (e.g., initiators, catalysts, chain transfer agents, surfactants). Low MW leachables are critically important to the potential for a polymer to affect health and the environment, given that they may be able to migrate out of the polymer and cross cell membranes to potentially react with biomolecules. A report to the EU (BIO by Deloitte, 2015) concluded that "Polymers with <1% MW < 1000 Da and low water extractability are not able to cause systemic effects which are toxicologically or ecotoxicologically relevant." Monomers, by nature, are reactive. Unreacted monomers left in a polymer may migrate out of the polymer to react with biomolecules to cause potential adverse effects. Regulatory authorities (BIO by Deloitte, 2015) and the OECD Expert Group on Polymers (OECD, 2009) agree that the residual monomer content of a polymer is critical to determining if it qualifies as a PLC. (Continued ) Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 337 (See Supporting Information: Chapter 3 for additional details) Criterion Particle size Structural and elemental composition Elemental composition Water and lipid solubility and the octanol-water partition coefficient Stability Abiotic stability Biotic stability: aerobic, anaerobic, and in vivo Thermal stability TABLE 3 (Continued) Description Particle size is also a PLC criterion. Particles that are small enough to reach the deep lung upon inhalation are often associated with adverse health effects. Therefore, to qualify as a PLC, median mass aerodynamic diameter (MMAD) of the polymer particle size should be >5 m. In the US, Chemical Categories of Concern are the result of the review of new chemicals by the USEPA under the TSCA (see https://www.epa.gov/reviewing-new-chemicals-undertoxic-substances-control-act-tsca/chemical-categories-used-review-new). The categories describe the molecular structure, boundary conditions such as MW, equivalent weight, the log of the octanol-water partition coefficient, log P, or water solubility, and standard hazard (mammalian and ecological) and (environmental) fate tests to address concerns. The elemental composition is a factor in the assessment of the eligibility of polymers for reduced notification requirements. The exclusion of polymers under this step is not a conclusion of hazard but a determination that the elemental composition does not fall within the parameters of the polymer set under which this rule was formulated, and consequently, these polymers would have to follow the standard notification and review process. These elemental requirements differ across jurisdictions as covered in the report to the EU on global regulatory approaches to polymer assessment (BIO by Deloitte, 2015). For example, in the EU under REACH it is proposed that polymers composed from among these elements, covalently bound to C, have reduced hazard: H, N, O, Si, S, F, Cl, Br, or I (BIO by Deloitte, 2015). In contrast, the USEPA Polymer Exemption Rule states that a polymer is eligible for reduced agency review when it has at least two of the following elements: C, H, O, N, S, or Si (USFR, 1995). Water solubility is the extent to which a compound will dissolve in water. According to the OECD (2009) meeting of the Expert Group on Polymers, polymers with "negligible" water solubility, or those described as "hydrophobic" have been represented with a water solubility of 0.000001 mg/L (1 10-6 mg/L; assigned arbitrarily; OECD, 2009). That is equivalent to 1 ppt, a very conservative definition. Polymers with water solubility <10 mg/L showed generally low health concerns. The octanol-water partition coefficient (Kow) is another criterion to assess chemicals and their environmental and health impact. The Kow is a physical-chemical property at equilibrium to represent the lipophilic or hydrophilic nature of a chemical, the distribution of a compound in octanol, representing the lipophilic nature, to its solubility in water, representing the aqueous nature. The higher the Kow, the more lipophilic the compound. Typically, a Kow >5000 or a log Kow >5 means high lipophilicity and, thus, a high potential to bioaccumulate or bioconcentrate. According to the Stockholm Convention, a bioconcentration factor of >5000 and a log Kow >5 is used as a criterion for bioaccumulation. Stability is resistance to physical, chemical, or biological transformation. Loss of stability in the polymer breaks it down into smaller pieces, producing low MW species. As was previously described in the Polymer of Low Concern section under the molecular weight, number average molecular weight, MW distribution, and % oligomer <1000 Da heading, molecules with Mn <1000 Da are capable of crossing cell membranes, making unstable polymers potentially hazardous to health and the environment. Polymers are stable; monomers are not. Abiotic degradation may involve sunlight, water, or oxygen. Photochemical transformation is a reaction involving the radiation energy of sunlight (ultraviolet radiation) that may break a bond in a molecule to change it to another chemical entity. Hydrolytic degradation of polymers is another potential way to break the polymer bonds, creating smaller oligomers that may be bioavailable. Chemical oxidation is a reaction involving the loss of electrons from one atom to another. Biotic stability is assessed by whether the polymer is degraded by microorganisms under oxygenated (aerobic) or anoxic (anaerobic) conditions; in vitro and in vivo stability studies demonstrate this. In vivo biodegradation involves the breaking of the polymer bonds by the action of bacteria, enzymes, and oxidants within the organism. Thermal stability of a polymer can be assessed when used as intended under normal, foreseeable use conditions or in extreme temperatures during disposal, such as by incineration. Thermal stability testing may involve Thermogravimetric Analysis (TGA), which determines mass loss over time and temperature of a test substance. Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2022 The Authors wileyonlinelibrary.com/journal/ieam Integr Environ Assess Manag 2023:326-354 Supporting Information Data: Chapter PLC assessment criteriona Structure Polymer composition (must have C, H, Si, S, F, Cl, Br, or I covalently bound to carbon) Molecular weight (Mn)b (Mn >1000 Da and oligomer content <1%) Molecular weight distribution Mwc number average Mn Wt% oligomer (<5% for <1000 Da oligomers, <2% for <500 Da oligomers) Ionic character Reactive functional groups (RFGs)d and functional group equivalent weight (FGEW) Low molecular weight leachables Residual monomers Ratio of residual monomers to molecular weight (typical value) Structural similarities to RFG of concern Reference standard Fluoroplastics 4.1 PVDF Polyvinylidene fluoride CAS 24937-79-9 -(CF2-CH2)n- Yes 70 000-300 000 2-3 Negligible Neutral None and N/A No active leachables by USP class VI (121 C) <50 ppb ~10-12-~10-13 None ASTM D3222-18a TABLE 4 Fluoroplastics and PLC criteria 4.2 PVDF-HFP copolymer Vinylidene fluoride, hexafluoropropene copolymer CAS 9011-17-0 -(CF2-CH2)n-[CF(CF3) -CF2]m- Yes 4.3 ECTFE Ethylene, chlorotrifluoroethylene copolymer CAS 25101-45-5 -(CF2-CFCl-CH2-CH2)n- Yes 80 000-300 000 Mn >50 000 2-3 Negligible 1.1 Negligible Neutral None and N/A Neutral None and N/A No active leachables by USP class VI (121 C) <50 ppb ~10-12-~10-14 No active leachables by USP class VI (121 C) <50 ppb ~10-13 None ASTM D5575-18 None ASTM D3275-81 4.4 ECTFE Ethylene, chlorotrifluorethylene, hexafluoroisobutylene terpolymer CAS 54302-04-04 -(C4H2F6)n-(C2H4)m-(C2ClF3)i- Yes Mn >50 000 1.7 Negligible Neutral None and N/A No active leachables by USP class VI (121 C) <50 ppb ~10-13 None ASTM D3275-81 4.5 PCTFE Polychlorotrifluoroethylene CAS 9002-83-9 -(CF2-CFCl)n- Yes 70 000-400 000 average based on grade type 3 Negligible Neutral None and N/A Negligible <0.1 wt% <10-5 None (Continued ) Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. 338 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2022 The Authors DOI: 10.1002/ieam.4646 Integr Environ Assess Manag 2023:326-354 Supporting Information Data: Chapter Physical-chemical properties Water solubility and octanol/ water partition coefficient, Kow Particle size (median mass aerodynamic diameter, MMAD, should be >5 m) Stability Hydrolysis, light (h), Oxidation, biodegradation (aerobic and anaerobic) Thermal stability at normal foreseeable use maximum continuous temp. (C) Meets aPLC criteria (Yes or No) Fluorinated polymerization aid (PA) used? (Yes or No) Recommended processing/ application (use) temperature (TC) Supporting Information Data: Chapter PLC assessment criteriona Fluoroplastics 4.1 PVDF Insoluble/practically insoluble and N/A Powders: 5-300 m pellets: 2-4 mm Stable 150 C Yes No Processing: 200 C- 250 C Use max temp: 150 C Fluoroplastics 4.6 FEVE Fluoroethylene-vinyl ether copolymer cbi TABLE 4 (Continued) 4.2 PVDF-HFP copolymer 4.3 ECTFE 4.4 ECTFE Insoluble/practically insoluble and N/A Powders: 5-300 m pellets: 2-4 mm Insoluble/practically insoluble and N/A D50%: 50-70 m (typical) Insoluble/practically insoluble and N/A D50%: 50-70 m (typical) 4.5 PCTFE Insoluble/practically insoluble and N/A Pellet: 2-4 m, flake: 0.54 mm powder: 5-300 micron Stable Stable Stable Stable 150 C 150 C 150 C 120 C Yes Yes Yes No No No Processing: 180 C- 250 C Use max temp: 100 C-140 C depending on HFP content Processing: 250 C-280 C Use max. Temp: 150 C Processing: 250 C-280 C Use max. Temp: 150 C Yes No Molding: 230 C -330 C and Use Max same as above at 120 C 4.7 EFEP 1-Propene, 1,1,2,3,3,3- hexafluoro-, polymer with ethylene and 1,1,2,2- tetrafluoroethylene 35560-16-8 4.8 CPT 1,1,1,2,2,3,3-Heptafluoro-3- [(trifluoroethenyl)oxy]propane polymer with chlorotrifluoroethylene and tetrafluoroethylene 116018-07-6 4.9 THV 1-Propene,1,1,2,3,3,3- hexafluoro-polymer with 1,1- difluoroethylene and tetrafluoroethylene 25190-89-0 (Continued ) 339 FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2022 The Authors wileyonlinelibrary.com/journal/ieam Integr Environ Assess Manag 2023:326-354 Supporting Information Data: Chapter Structure Polymer composition (must have C, H, Si, S, F, Cl, Br, or I covalently bound to carbon) Molecular weight (Mn)b (Mn >1000 Da and oligomer content <1%) Molecular weight distribution Mwc number average Mn Wt% oligomer (<5% for <1000 Da oligomers, <2% for <500 Da oligomers) Ionic character Reactive functional groups (RFGs)d and functional group equivalent weight (FGEW) Low molecular weight leachables Residual monomers Ratio of residual monomers to molecular weight (typical value) Structural similarities to RFG of concern Reference standard Fluoroplastics 4.6 FEVE cbi Yes 7000-46 000 2.0-4.0 Mn <1000 range of <3.5% and Mn <500 is <0.7% Neutral None and N/A Negligible; cross- linked as final product 0.12%-1.43% non- fluorinated 10-7-10-8 None TABLE 4 (Continued) 4.7 EFEP -(CH2-CH2)n-(CF2-CF2)m-[CF2- CF(CF3)]l- Yes 4.8 CPT -(CF2-CF2)n-(CFCl-CF2)m-[CF2- CF(ORf)]l- Yes 4.9 THV -(CF2CH2)x-(CF2-CF-CF3)y- (CF2-CF2)z Yes 130 000 4 Negligible; <0.1 wt% oligomer content Neutral None and N/A 200 000-300 000 2-5 Negligible; <0.1 wt% oligomer content Neutral None and N/A 131 000 1.8 wt.% <1000: None Neutral None and N/A Negligible Negligible <10-5 None ASTM D7472 Negligible Negligible <10-5 None ASTM D7471 No active leachables by USP class VI (121 C) None detected ~10-13 None (Continued ) Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. 340 FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 Integr Environ Assess Manag 2023:326-354 Supporting Information Data: Chapter Physical-chemical properties Water solubility and octanol/ water partition coefficient, Kow Particle size (median mass aerodynamic diameter, MMAD, should be >5 m) Stability Hydrolysis, light (h), oxidation, biodegradation (aerobic and anaerobic) Thermal stability at normal foreseeable use maximum continuous temp. (C) Meets aPLC criteria (Yes or No) Fluorinated polymerization aid (PA) used? (Yes or No) Recommended processing/ application (use) temperature (TC) Fluoroplastics 4.6 FEVE Insoluble/practically insoluble and N/A Solution or flake 150 nm for emulsion Stable 220 C Yes No 180 C-200 C 4.7 EFEP TABLE 4 (Continued) 4.8 CPT Insoluble/practically insoluble and N/A 2-4 mm (pellets) Insoluble/practically insoluble and N/A 2-4 mm (pellets) 4.9 THV Insoluble/practically insoluble and N/A Pellets ~400-750 m Stable 130 C; low melting point 160 C-190 C and high decomposiiton temperature of 357 C-380 C Yes No Molding temperature: 200 C-280 C; Use max as noted above Stable 200 C; low melting point 239 C-251 C and high decomposition temperature of >400 C Yes No Molding temperature: 310 C-330 C; Use max as noted above Stable Continuous use is expected ~room T. (<100 C as host resin melts at 120 C); No expected degradation; fluoropolymer degrades >350 C by TGA Yes Yes and No Melt processing: <350 C Application: <100 C (in LLDPE) DOI: 10.1002/ieam.4646 Abbreviations: ECTFE, ethylene-chlorotrifluoroethylene; HFP, hexafluoropropylene; PCTFE, polychlorotrifluoroethylene; PLC, polymer of low concern; PVDF, polyvinylidene fluoride. aSee OECD (2009) and BIO by Deloitte (2015) for details on characteristics of a "Polymer of Low Concern" and Supporting Information: Chapter 3. bMolecular Weight is number average molecular weight which is defined as the total weight of the polymer divided by the total number of molecules. It is the mole fraction of molecules in a polymer sample. cMolecular weight is weight average molecular weight which is determined by summing the weights of all the chians and then dividing by the total number of chains. It is the weight fraction of molecules in a polymer sample. dFor definition of reactive functional group, lists of low-, moderate-, and high-concern functional groups and FGEW limits, see USEPA polymer exemption guidance manual, BIO by Deloitte (2015, pp. 191-192), and USEPA (2010). See Supporting Information. 2022 The Authors 341 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2022 The Authors wileyonlinelibrary.com/journal/ieam Integr Environ Assess Manag 2023:326-354 Supporting Information Data: Chapter PLC assessment criteriona Structure Polymer composition (must have C, H, Si, S, F, Cl, Br, or I covalently bound to carbon) Molecular weightb (Mn >1000 Da and oligomer content <1%) Molecular weight distribution Mwc number average Mn Wt% oligomer (Figure MWD) (<5% for <1000 Da oligomers, <2% for <500 Da oligomers) Ionic character Reactive functional groups (RFGs)d Functional group equivalent weight (FGEW; typical value) TABLE 5 Fluoroelastomers and specialty fluoroplastics--PLC criteria Specialty fluoroplastics 4.13 Amorphous 4.14 Ionomer Fluoroelastomers 4.10 FEPM 4.11 FKM Perfluoro(alkenyl vinyl) ether polymer Sodium or potassium salts of perfluorosulfonic acid/TFE copolymer or perfluorocarboxylic acid/TFE copolymer Tetrafluoroethylene- propylene copolymer 1-Propene,1,1,2,3,3,3- hexafluoro-polymer with 1,1-difluoroethylene copolymer and terpolymers 37626-13-4 9002-84-0, 1314-23-4, 409-21-2, 111173- 25-2 27029-05-6 9011-17-0, 26425-79-6, 25190- 89-0 See Supporting Information See Supporting Information See Supporting Information Supporting Information Yes Yes Yes Yes 4.12 FFKM Tetrafluoroethylene- trifluoromethyl trifluorovinyl ether copolymer 26425-79-6 -(CF2CF2)x -[CF2-CF (OCF3)]y-(Cure Site Monomer)z Yes 150 000-300 000 1.4-2.5 Negligible >100 000 1.0-2.4 Negligible Various grades vary between 146 000-275 000 Various grades give various ratios from 1.4 to 3.3 <0.01% 30 000-340 000 1.2-2.4 Negligible to <1% 10 000-1 000 000 1.2-3.5 Negligible Neutral None and N/A >105 Neutral None and N/A >105 Neutral None and N/A >105 Neutral None and N/A >104-105 Neutral None and N/A >104 (Continued ) Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. 342 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2022 The Authors DOI: 10.1002/ieam.4646 Integr Environ Assess Manag 2023:326-354 Supporting Information Data: Chapter Low molecular weight leachables Residual monomers Ratio of residual monomers to molecular weight (typical value) Structural similarities to RFG of concern Reference standard Physical-chemical properties Water solubility and octanol/ water partition coefficient, Kow Particle size (median mass aerodynamic diameter, aerodynamic diameter, MMAD, should be >5m) Stability Hydrolysis, light (h), oxidation, biodegradation (aerobic and anaerobic) Specialty fluoroplastics 4.13 Amorphous <1 ppm <1 ppm >10-5 4.14 Ionomer <1 ppm <1 ppm >10-5 TABLE 5 (Continued) Fluoroelastomers 4.10 FEPM No active leachables No residual monomers Only cross-linking agent at <1 ppm 10-11-10-12 None None None Insoluble/practically insoluble and N/A Solution, sheet or pellets Stable Insoluble/practically insoluble and N/A (1) Aqueous dispersion casting (as a film) followed by annealing or (2) Melt extrusion as a membrane (reinforced) Stable Insoluble/practically insoluble and N/A Sheet or crumb Stable 4.11 FKM <0.4 ppm to <1 ppm <50 ppt to <5 ppm >10-10-10-13 None ASTM D 1418 Insoluble/practically insoluble and N/A Sheet or block; powders 300-350 m stability increased/enhanced when cross-linked Stable 4.12 FFKM No active leachables <50 ppb 0.25 ppt as Mn = 105 (for representative FKM) None Insoluble/practically insoluble and N/A Sheet or block; or "crumb" Stable (Continued ) 343 FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 344 Integr Environ Assess Manag 2023:326-354 TABLE 5 (Continued) Supporting Information Data: Chapter Specialty fluoroplastics 4.13 Amorphous 4.14 Ionomer Fluoroelastomers 4.10 FEPM 4.11 FKM 4.12 FFKM Thermal stability at normal foreseeable use maximum continuous Temp (C) >250 C Meetsa PLC criteria (Yes or No) Yes Sulfonic acid polymer: maximum operating temperature of 175 C under anhydrous conditions, 220 C -240 C in aqueous systems carboxylic acid polymer: use below 120 C Yes 200 C Yes 180 C Yes 200 C-300 C Yes wileyonlinelibrary.com/journal/ieam Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. Fluorinated polymerization aid (PA) used? (Yes or No) Recommended processing/ application (use) temperature (TC) Yes and No <280 C Yes and No Sulfonic acid polymer: maximum operating temperature of 175 C under anhydrous conditions, 220 C-240 C in aqueous systems carboxylic acid polymer: use below 120 C No -60 C-204 C (AFLAS Technical Document) Yes and No Melt processing: <300 C 160 C-320 C (cross- linking temperature) Yes and No 160 C-320 C (cross-linking temperature) Abbreviations: FEPM, trifluoroethylene-propylene copolymer; FKM, HFP-VF2 polymer and HFP-VF2-TFE polymers; FFKM, TFE-PMVE perfluoroelastomer; PLC, polymer of low concern. aSee OECD (2009) and BIO by Deloitte (2015) for details on characteristics of a "Polymer of Low Concern." bMolecular weight is number average molecular weight. cMolecular weight is weight average molecular weight. dFor definition of reactive functional group, lists of low-, moderate-, and high-concern functional groups and FGEW limits, see USEPA polymer exemption guidance manual, BIO by Deloitte (2015, pp. 191-192), and USEPA (2010). See Supporting Information. 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 345 until all data cells in the tables cited above were backed up with a narrative, a testing method, and/or references where publicly available. Where several companies have provided data on the same fluoropolymers, the table data presented provide a multicompany compilation and assessment along with appropriate methods and references. Individual companies supplying data are identified as authors, but there is no direct attribution regarding which company supplied which data for this study. PLC ASSESSMENT RESULTS This study was conducted on commercial fluoropolymer products using the PLC criteria to characterize their potential hazard. Figure 1 illustrates the PLC criteria used (BIO by Deloitte, 2015; Henry et al., 2018). The pictured criteria encompass structure, physicochemical property, and stability criteria evaluated in the study. Data informing structure criteria, MW, Mn, and MW distribution (MWD), physicochemical property criteria, water and lipid solubility and Kow, and stability criteria are presented in Tables 4 and 5. The study also gathered structural data on (a) residual monomers, (b) ratio of residual monomers to MW, (c) structural similarities to reactive functional groups (RFGs) of concern, and (d) thermal stability at normal foreseeable maximum continuous use temperatures. Brief descriptions of PLC criteria are provided in Table 3 with additional details, including references for each criterion in Supporting Information: Chapter 3. An additional data point gathered was whether the fluoropolymer(s) presented utilized a fluorinated polymerization aid (PA) during manufacture. The study results are presented in Tables 4 and 5 and summarized below. Polymer composition: Each of the fluoroplastics, specialty fluoroplastics, and fluoroelastomers assessed in this study met the criterion of polymer composition whereby either fluorine (F) and/or chlorine (Cl) must be covalently bound to the carbon-only polymer backbone. MW and MWD: All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the criteria for MW (Mn >1000 Da) and MWD (1-3). The data demonstrate the fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study are high-MW solid polymers with fairly narrow MWD and negligible to low wt% oligomer content. The MW for fluoroplastics in Table 4 and specialty fluoroplastics in Table 5 ranged from 50 000 to 300 000, and the MWD ranged from approximately 1.4 to 3. We note that FEVE was measured in its uncured state and that, upon curing, its MW increased significantly. The MW and MWD were determined in a variety of ways depending on the fluoropolymer and its solubility (or insolubility) in various solvents. The MW and MWD data for fluoroelastomers and specialty fluoroplastics in the study are presented in Table 5. The MW and MWD varied because of the various grades of fluoroelastomers ranging from 100 000 to 250 000 with some less than (down to 10 000) and greater than (up to 500 000). MWD was on the order of 1.4 to 3.5. Fluoroelastomer MW is lower for uncured fluoroelastomer versus cured fluoroelastomer. Cured fluoroelastomer is the form used in many formed-use applications (e.g., gaskets and o-rings). The methods and references for MW and MWD data are presented in the Supporting Information: Chapter 4 with the specific chapter noted in Tables 4 and 5. Methods included size exclusion chromatography (SEC), gel permeation chromatography (GPC) along with osmotic pressure, and parallel plate rheometry methods. Weight % oligomer: The criteria for wt% oligomer are less than 5% oligomer content for Mn less than 1000 Da, and less than 2% oligomer content for Mn less than 500 Da (BIO by Deloitte, 2015; Henry et al., 2018; see also the Supporting Information). All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the wt% oligomer criteria. Many polymers in the study were reported as "negligible" for oligomers based on analyses conducted. Polymers in the study not cited as negligible have reported numerical data presented in Tables 4 and 5. In addition to SEC and GPC, analytical methods employed included a weight loss upon heating method and the FDA 21 CFR 177.1380 method. The methods and references for wt% oligomer are presented in the Supporting Information: Chapter 4 with the specific chapter noted in Tables 4 and 5. Ionic character: The fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study are neutral polymers, either containing no ionic groups or may contain anionic at the terminus of their high MW polymer chains as noted in the prior study of fluoropolymers (Henry et al., 2018). Notably different are fluorinated ionomers, which have neutralized (salts) sulfonic acid or carboxylic acid groups pendant to the polymer backbone and as such are neutral and not ionically charged in their polymeric solid form and are low in toxicity and not dermally irritating on skin contact (USEPA, 1997). None of the evaluated polymers in the study have cationic nature. The methods and references for ionic character are presented in the Supporting Information: Chapter 4 with the specific subchapter noted in Tables 4 and 5. RFG, functional group equivalent weight (FGEW) and structural similarities to RFG of concern: All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the RFG and FGEW criteria. The polymers in this study do not contain the reactive functional groups set forth in the PLC criteria (e.g., acrylates, alkoxysilanes, amines, aziridines, carbodiimides, and so forth; see Supporting Information: Chapter 3). Given that the polymers in this study have no RFGs, the FGEW values in Tables 4 and 5 are very large numbers (such as >104-105) or the value given is not applicable due to the lack of RFGs altogether. Even the polymers with some functional groups present (e.g., fluorinated ionomers) are not reactive. For example, the FEVE polymerization process leads by design to a polymer with neutral and/or anionic end groups. FEVE resins do contain a small amount of hydroxyl and carboxyl functional groups. These functional groups are classified as low concern RFG Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 346 Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. by the USEPA (1997) and OECD (2009). There are no RFG structural similarities across the polymers in this study. Low MW leachables (MW < 1000 Da): All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the low MW leachable PLC criteria, which has been widely discussed (see Supporting Information: Chapter 3 for references). Many of the study polymers report no active leachables, whereas the rest cite values less than 1 ppm (Tables 4 and 5). For FEVE, it is reported that some nonfluorinated polymer PA may well remain in the uncured polymer resin. The methods and references for low MW leachables are presented in the Supporting Information: Chapter 4 with the specific chapter noted in Tables 4 and 5. The data presented in Tables 4 and 5 were determined for each of the respective polymers in this study using techniques such SEC and GPC as the predominant analytical methods along with the use of USP Class VI testing. Additional methods included 21 CFR 177.2600 (USCFR, 2022) and the USEPA's toxicity characteristic leaching procedure (TCLP; SW-846 Test Method 1311; USEPA, 1992). Residual monomers and ratio of residual monomers to typical MW: PLC criteria of equal interest to the low MW leachables are the residual monomers and the ratio of residual monomers to typical MW (see Supporting Information: Chapter 3 for references). All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the residual monomers and ratio of residual monomers to typical MW PLC criteria. The study data presented in Tables 4 and 5 show the polymers in this study have residual monomers ranging from less than 50 ppb for several fluoropolymers and up to less than 0.1% for PCTFE based on the methods utilized. Fluoroelastomers in this study have residual monomers ranging from less than 50 ppb up to less than 5 ppm. Residual monomers were determined in several ways including dynamic and static headspace gas chromatography/mass spectrometry (GC/MS) at 150 C. The monomers used in most cases have very low boiling points and are thus readily volatilized (and captured or destroyed) during polymer manufacture processing and drying steps. The methods and references for residual monomer determination are presented in the Supporting Information: Chapter 4 with the specific chapter noted in Tables 4 and 5. Given the very low residual monomer levels reported, the ratio of residual monomers to polymer MW range from 10-11 to 10-13 for the study polymers. Water solubility and octanol/water partition coefficient (Kow): The fluoroplastics, specialty fluoroplastics, and fluoroelastomers in this study are solids that are hydro- and oleophobic, practically insoluble in both water and n- octanol. Therefore, a Kow cannot be computed and is not applicable to these substances. It is worth noting that the practical lack of solubility in water (<10 mg/L) and n-octanol indicate the inability for the study fluoropolymers to actively or passively cross cell membranes. This does mean there is no indication that these polymers can bioaccumulate or bioconcentrate in biota (Henry et al., 2018 and this study). The methods and references for solubility are presented in the Supporting Information: Chapter 4 with the specific chapter noted in Tables 4 and 5. Particle size: To meet the PLC assessment criteria for particle size, a powder must be 5 m or greater in size (median mass aerodynamic diameter [MMAD]). All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the particle size PLC criterion. As shown in Tables 4 and 5, the fluoroelastomers in this study are provided in sheets, blocks, pellets, or "crumb," and the fluoroplastics and specialty fluoropolymers in this study are provided in the form of powders, pellets, sheets, flake, or in dispersions. References and additional information regarding the form of the study polymers is provided in the Supporting Information: Chapter 4. Stability: All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the PLC criteria for hydrolysis, light stability, oxidative stability, and aerobic and anaerobic biodegradability (e.g., breakdown into species with Mn <1000 Da). Public literature has abundant thermal, chemical, and biological stability data for the polymers in this study as stability is a hallmark property for these polymers (Ebnesajjad, 2017). For biodegradation, the assessments were largely made based on property data of the study polymers demonstrating they are in- soluble and stable in environmental media and thus are not expected to be bioavailable and therefore not bio- degrade. Additionally, published literature reports (Drobny, 2016; Ebnesajjad, 2017; Grot, 2013; Henry et al., 2018; Polymer Industry Association [PIA], 2019) that the study polymers are stable at foreseeable maximum continuous use temper- atures presented in Tables 4 and 5. All polymers, including fluoropolymers can degrade when misused or when heated above their recommended use temperatures (Fluoropol- ymer Products Group of Plastics Europe [FPG], 2012; PIA, 2019). Of course, users are expected to follow guidance for use provided by manufacturers. Hence, the recom- mended temperatures for reasonably foreseeable use for the study substances are presented in Tables 4 and 5. Ref- erences and additional information regarding the stability of the study polymers is provided in the Supporting In- formation: Chapter 4. Fluorinated PA: If a fluorinated PA was used in the manu- facture of the polymer, it was reported for each fluoropolymer in this study. Nine of the 14 fluoropolymers in the study were reported not to have used a fluorinated PA in their manufacture. It is industry practice to use fluorinated PAs when it is necessary to obtain specific end-use property or performance requirements generally related to very high-polymer MWs (see also Supporting Information: Chapter 7). For five study polymers, THV, FKM, FFKM, fluorinated ionomers, and amorphous fluoropolymers, a response of "Yes and No" was provided indicating that for some polymer grades a fluorinated PA is used, but not for others. See Supporting In- formation: Chapter 4 for additional information. Results summary: This study examined three fluoroelas- tomers, nine fluoroplastics, and two specialty fluoroplastics: Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 347 ionomers and amorphous. Data for each were gathered from the author companies and assessed by the PLC criteria applicable to the polymer itself "in use" (BIO by Deloitte, 2015; Henry et al., 2018; OECD, 2009). All fluoroplastics, specialty fluoroplastics, and fluoroelastomers in the study met the PLC criteria based on the data presented in Tables 4 and 5 with additional details provided describing methods and references in the Supporting Information: Chapter 4. Including the four fluoroplastics in the prior study (Henry et al., 2018), data for 18 fluoropolymers have been provided for PLC assessment. These polymers have a wide range of compositions and structures and represent most of the global commercial fluoropolymer market (see additional text in the Discussion). These 18 fluoropolymers represent the major fluoropolymers manufactured and are used worldwide in innumerable critical end-use products and applications. Tables 1 and 2 highlight examples of the end- use markets as well as critical functionality and benefits these polymers provide. Each of the assessed polymers in this study are insoluble in both water and n-octanol, and thus Kow is not applicable. This lack of solubility in water and octanol confirms that fluoropolymers are not mobile in the environment and are not bioaccumulative and not able to bioconcentrate. The stability studies reported here on each of the study fluoropolymers reveal their stability in terms of light, hydrolysis, heat, oxidation, and biodegradation. When coupled with the lack of solubility, these fluoropolymers are most often characterized as relatively inert materials in the environment. Like any other chemical material or product, it is important to follow the fluoropolymer manufacturer's recommended use and temperature conditions. Tables 4 and 5 describe these recommendations for each fluoropolymer. As reported, the physical forms of the fluoropolymers are largely pellets, blocks, crumb, sheets, some powders (all with MMAD >5 m). The solid fluoropolymers are not nanoparticles, and concerns related to nanoparticles do not apply during normal product use. Due to the properties described above for the assessed fluoropolymers--large molecules with no water solubility--the fluoropolymers are biologically inert without the practical ability to cross cell membranes. During the evaluation of the study fluoropolymers, there was a conscious focus on several core PLC parameters: MW, low MW leachables, % oligomers, and residual monomers, which are direct outcomes related to fluoropolymer manufacturing. In addition to what is reported here in Tables 4 and 5 for the fluoropolymers themselves, industry efforts to manage emissions during manufacturing are discussed below. DISCUSSION Fluoropolymers have substantial, unique societal value: Fluoropolymers possess a remarkable combination of properties and functional characteristics, as shown in Tables 1 and 2, that make them valued materials of choice in a broad range of industries and applications critical to life and a sustainable environment in the 21st century. Their unparalleled combination of properties and performance characteristics deliver functionality to a wide variety of products and systems critical to achieving important societal goals (Amcham, 2020c; FPG, 2021a; Wood, 2020b). They are strategically important to innovation in vital sectors of the global economy requiring high-speed, high-volume data transmission, miniaturization, or operations in extreme temperatures. Moreover, they are crucial to achieving im- portant societal goals such as decarbonization, renewable energies, and/or competitiveness in the digital transition (FPG, 2021a). Fluoropolymers are indispensable for critical applications in the chemical, electronic, semiconductor, healthcare, and transport sectors and the deployment of 5G networks (FPG, 2021a). For many critical applications, fluoropolymers are the material of choice because alternatives are unable to provide the full complement of performance and functionality required. As such, there are currently no viable commercial alternatives to fluoropolymers in virtually every critical application in which they are used (FPG, 2021a, 2017; PFP, 2020). Commercial fluoropolymers in this study meet the PLC criteria: Widely used by regulators, PLC criteria have been established around the world and documented by OECD expert groups as an appropriate hazard assessment meth- odology for polymers in-use and can effectively identify low risk fluoropolymers to help prioritize regulatory action (BIO by Deloitte, 2015; OECD, 1993, 2009). Here, we present PLC data, for hazard assessment, that define a group of fluoropolymers' "in-use" properties. PLC is not a comprehensive life-cycle assessment tool. Full life-cycle assess- ments consider all phases of product "life" including creation (manufacturing) and end-of-life (disposal). Information on manufacture and end-of-life is provided later in this study. Recently, polymers have been under increased regulatory scrutiny. In 2019, the industry-led European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) developed a Conceptual Framework for Polymer Risk Assess- ment ("CF4Polymers"; ECETOC, 2019). CF4Polymers provides guiding elements to be considered in assessing potential ecological and human health hazards and risks posed by polymer substances. CF4Polymers also considers specific life-cycle stages of polymer products and their associated routes of exposure. The authors of the CF4Polymers framework support the PLC approach as a means to accomplish polymer risk assessment. They specifically support the findings of Henry et al. (2018) and state that they are "unaware of scientific evidence to justify generally assigning fluoropolymers the same level of regulatory concern as other PFAS" (ECETOC, 2019). In 2020, the European Commission contracted a study to propose criteria to identify PRR under REACH (Wood, 2020a). The report states that the authors consider fluoropolymers meeting the criteria to be considered PLC, "following the recom- mendations of Henry et al. (2018)." The properties and characteristics of fluoropolymers are anchored in the strength of the carbon-fluorine bond, which Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 348 Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. render them highly stable (thermally, chemically, and biologically), inert, and durable--long lasting in use--under exacting and high-performance conditions. Physical, chemical, thermal, and biological stability are important criteria for a polymer to be considered a PLC. The data presented in Tables 4 and 5 demonstrate that commercial fluoropolymers from the author companies meet the criteria to be considered PLC. The PLC criteria for physicochemical properties reflect the state of the polymers in this study, solids, as well as their inertness and stability. None of the fluoropolymers assessed in this study were soluble in water or octanol. They are biologically inert, insoluble in water and octanol, and not expected to move in or between environmental media. Fluoropolymers are also twice as dense as water. These properties and water insolubility mean fluoropolymers are not mobile in the environment and therefore would not be expected to be found in sources of drinking water. Fluoropolymers are neither bioavailable nor bioaccumulative. These solid polymers cannot be absorbed through a cell membrane via passive or active transport and do not bind or interact with the cell surface (see also Supporting Information: Chapter 8). In addition, whereas aquatic and mammalian toxicology studies of fluoropolymers may be desirable for some, they are technically difficult for insoluble, solid, high-MW polymers. The OECD test guidelines reiterate this in many cases. This is confirmed for example in REACH Annex VII guidance, which repeatedly states toxicity is unlikely to occur "if a substance is highly insoluble in water or the substance is unlikely to cross biological membranes" (see Supporting Information: Chapter 9). Finally, structure criteria including MW, MWD, residual monomer(s), oligomers, and other synthesis by-products, as represented by low MW extractables and leachables have been determined for the fluoropolymers presented and meet values established for the PLC criteria and regulated uses (e.g., USP). The concentrations in the fluoropolymer that have been evaluated are extremely low, reflective of effective manufacturing processes that minimize these compounds complemented by capture and/or destruction systems for such materials. For additional information, see the section below discussing responsible manufacturing. This study and prior work (Henry et al., 2018) provide a guide for other global fluoropolymer manufacturers to gather and present data on additional commercial fluoropolymers to determine if they too meet the PLC criteria. Fluoropolymer stability, aka persistence, is not an intrinsic hazard: Fluoropolymers are stable, inert, solid materials. Fluoropolymers resist degradation by acids, bases, oxidants, reductants, photolytic processes, microbes, and metabolic processes; for this reason, they are thermally, chemically, and biologically highly inert. Fluoropolymer stability was presented in the introduction and is further considered in the Supporting Information: Chapters 4 and 5. Fluoropolymers are not expected to degrade under environmental conditions or normal use and processing conditions (Wood, 2020a). They are stable and remarkably durable and are therefore persistent. However, persistence alone does not imply that there is a present or future risk to human health or the environment (Rdel et al., 2020). Persistence itself is not an intrinsic hazard, as it does not in itself imply or inform the potential for an adverse effect (aka toxicity). There is no language in REACH supporting the notion that persistence alone justifies risk-management measures. REACH has regulated persistence in combination with other properties that do inform potential hazards. In fact, REACH combines persistence with bioaccumulation and toxicity (or "very persistent" with "very bioaccumulative/very mobile" vPvB/ vPvM) to justify designation as a substance of very high concern (SVHC) and consideration of potential risk- management measures for uses associated with unacceptable risk. Therefore, persistence on its own does not justify the need for specific risk-management measures. Fluoropolymers themselves are persistent, but they are not bioaccumulative, not mobile, and not toxic and therefore not SVHCs from a regulatory perspective (Ruwona and Henry, 2021). PFAS grouping and segmentation--Scope of regulatory measures: The OECD definition of PFAS is based only on chemical structure (OECD, 2021). It describes a universe of fluorinated organic substances with vastly different physical, chemical, and biological properties, including polymers and nonpolymers; solids, liquids, and gases; highly reactive and inert substances; soluble and insoluble substances; and volatile and involatile substances and is too broad to allow effective, science-based assessment and regulation of chemical compounds as an entire group (Amcham 2020a; BDI, 2021; Buck et al., 2021; Orgalim, 2021; Wallington et al., 2021). A 2021 OECD report states: "it is highly recommended that such diversity be properly recognized and communicated in a clear, specific and descriptive manner" and "the term `PFASs' does not inform whether a compound is harmful or not, but only communicates that the compounds under this term share the same trait for having a fully fluorinated methyl or methylene aliphatic carbon moiety" (OECD, 2021). In this context, the available property data (Tables 4 and 5) reveal that fluoropolymers have distinctly different properties from nonpolymeric PFAS and from SCFPs that have a polymeric backbone that does not contain C-F bonds directly attached to it. The perfluoroalkyl moiety in SCFPs is found in a side-chain connected via a functional group to the polymer backbone and "can potentially lead to the formation of nonpolymer PFAS as a result of degradation" (Fluoropolymer Products Group of Plastics Europe [FPG], 2021b; Wood, 2020a; see Supporting Information: Chapter 6). Segmentation that clearly differentiates the broad PFAS family according to their properties, rather than using a structure-based classification alone (OECD, 2021), is needed for a scientifically sound, risk-based regulatory approach. Regulating all PFAS as one homogenous group (ECHA, 2020) absent consideration of their properties, particularly when the properties are so demonstrably different, neglects basic scientific consideration of these properties, which are the foundation of substance differentiation. The USEPA does not consider all PFAS to have Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 349 similar risk profiles and therefore they are following a categorical grouping approach based on information about similarities in structure, physicochemical properties, and existing test data on the toxicity of PFAS (USEPA, 2021b). Therefore, segmentation based on properties should be conducted before performing any grouping-based risk assessment, placing stable, nonhazardous fluoropolymers that meet the criteria to be considered PLC in a separate category (see also Supporting Information: Chapter 6). Fluoropolymer market perspective: The commercial fluoropolymer global market sales have been reported to be approximately 230 000 MT (Dams & Hintzer, 2017). Given the expected fluoropolymer market growth, ranging from approximately 4%-5% to 7%-8% (Allied Market Research [AMR], 2022; Future Market Insights [FMI], 2022; FPG, 2021a; Globe Newswire, 2021), a pro forma market table was created for 2021 using a 5% growth rate. Adding ionomers as well as updated amorphous market information (company data) to the above, the total commercial fluoropolymer market sales is estimated to be approximately 330 000 MT in 2021 (see Supporting Information: Chapter 10). Four fluoropolymers: PTFE, FEP, PFA, and ETFE, were the focus of the first fluoropolymer PLC paper (Henry et al., 2018) and account for approximately 64% of fluoropolymers sold globally in 2021 (pro forma basis). The sales volume of these four fluoropolymers is represented by the first four bars in Figure 10.1 in Supporting Information: Chapter 10. This study discusses 14 fluoropolymers representing an additional 32% (pro forma basis) of the global fluoropolymer market. Therefore, this study, in combination with Henry et al. (2018), presents PLC data from the cited manufacturers of commercial fluoropolymers representing approximately 96% of the global commercial fluoropolymer market that meet the criteria to be considered PLC. The projected 2021 sales volume of the major types of commercial fluoropolymers covered in this study (PVDF, FKM, FEPM, amorphous, ionomers, THV, ECTFE, PCTFE, and FFKM, EFEP, CTP, and FEVE) are also represented in Figure 10.1 in Supporting Information: Chapter 10. As noted, estimated market volumes were provided for the sum of FEPM, CPT, EFEP, and FEVE as well as a small "others" category. The fluoropolymer polyvinyl fluoride (PVF) was not covered by these two papers but is also shown in Figure 10.1 in Supporting Information: Chapter 10. Other fluorinated polymers, perfluoropolyethers, and SCFPs are not addressed in this study (see Supporting Information: Chapter 6). FLUOROPOLYMER LIFE-CYCLE CONSIDERATIONS This study focuses on the properties of the 14 selected commercial fluoropolymers themselves in-use providing data that demonstrate they meet the criteria to be considered PLC. Additionally, the life-cycle stages of fluoropolymer creation (manufacturing) and disposal at the end of industrial or consumer use (end-of-life) are important to consider. The primary focus in these life-cycle stages is generally nonpolymer PFAS from the manufacturing process or fluoropolymer degradation in end-of-life disposal (ECHA, 2020; FPG, 2021a; Guelfo et al., 2021; Lohmann et al., 2020). The long-established life-cycle assessment approach to environmental protection and risk management first considers the extent of emissions, their toxicity, and their exposure potential (Guinee et al., 2011). When emissions are sufficiently large in scope, toxicity, and exposure potential, emission- management methods are then considered, including process input changes and emission controls to reduce or eliminate the risk of the emissions. Fluoropolymer manufacturing and disposal life-cycle stages were discussed in the paper that first presented fluoropolymer PLC data (Henry et al., 2018). Here we provide an update and current perspective. Responsible manufacturing: As corroborated by the data presented here and in prior work (Henry et al., 2018), a large volume percentage and number of commercial fluoropolymers are manufactured that meet the criteria to be con- sidered PLC. Emissions from fluoropolymer manufacture are a key product life-cycle focus. The main focus during the manufacturing phase is not directly related to fluoropolymers but from emissions. Emissions of concern may include nonpolymer PFAS such as fluorinated PAs, unreacted monomers, oligomers, or other unintended by-products formed during manufacturing. It is important to note that, although some high-MW fluoropolymers require use of a fluorinated PA in manufacturing (see also Supporting Information: Chapter 10), it has been reported that at least 50% of commercial fluoropolymers are made without one (Pro-K Fluoropolymer Group, 2021). Recently, a group of fluoropolymer member companies of FPG voluntarily committed to responsible manufacturing principles through the commissioning of a Regulatory Management Option Analysis, developed by independent con- sulting firm Chemservices (FPG, 2021a). Member companies of this group are working on individual projects and joint projects at the trade association level with third-party experts. Specifically, companies have committed to continuously improving and/or developing the best available techniques in the manufacturing process, managing environmental emis- sions, developing R&D programs for the advancement of technologies allowing for the replacement of nonpolymer PFAS PAs and/or working with downstream users to increase the recyclability and reuse of its products in line with the objectives of circular economy (FPG, 2021a). Implementation of this voluntary industry initiative to address concerns relating to fluoropolymers will strengthen already ongoing efforts performed by the fluoropolymer industry promoting responsible manufacturing practices. In addition, member compa- nies are committed to working with EU authorities to establish and implement technical actions to guarantee adequate control of the risks derived from the manufacture and use of fluoropolymers to mitigate such risks wherever possible. This will be done following transparency principles and agree- ments to monitor progress. For example, important emission reduction has been demonstrated by major fluoropolymer manufacturers including fluorinated PA recovery for reuse, 99% removal of fluorinated PA in wastewater treatment, and Integr Environ Assess Manag 2023:326-354 DOI: 10.1002/ieam.4646 2022 The Authors 15513793, 2023, 2, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.4646 by CochraneAustria, Wiley Online Library on [13/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 350 Integr Environ Assess Manag 19, 2023--KORZENIOWSKI ET AL. 99.99% capture and destruction efficiency of gaseous emissions routed to a thermal oxidizer (Chemours, 2021c), as well as 99-99.9 plant emission reductions (Daikin, 2021c, 2022). Four other companies have reported replacement of fluorinated PAs with nonfluorinated PAs (Arkema, 2008, 2021b; Chemours, 2022; Gujarat Fluorochemicals Limited, 2022; Solvay, 2022). These are substantial efforts toward mitigating emissions associated with fluoropolymer manufacturing being worked on by fluoropolymer manufacturers. This study and the prior study (Henry et al., 2018) provide a guide for other global fluoropolymer manufacturers to gather and present data on their commercial fluoropolymers in-use demonstrating that they meet the PLC criteria. End-of-use: At the end of industrial or consumer use, fluoropolymers may be disposed via the following routes: landfill, incineration (e.g., waste-to-energy [WTE] facilities), or reuse/ recycling. There is considerable data demonstrating that fluoropolymers such as PTFE do not degrade in the environment or release substances of toxicological or environmental con- cern (FPG, 2021a; Hintzer & Schwertfeger, 2014). FPG member companies are working with the industry and end users on this subject and are engaged in a research project aimed at identifying conditions required for proper disposal (incineration) of fluoropolymers (FPG, 2021a). Fluoropolymers are chemically, thermally, and biologically stable (Henry et al., 2018; this study) and therefore are not expected to transform to dispersive nonpolymeric PFAS when disposed of in a landfill. A recent study presented results from OECD guideline biodegradation studies demonstrating that PTFE is stable and does not degrade under environmentally relevant conditions (Ruwona and Henry, 2021). Further, fluoropolymers that meet the criteria to be considered PLC, such as those in this study and prior work (Henry et al., 2018), have negligible leachables, unreacted monomers, and oligomers most likely destroyed in fluoropolymer use processing and would therefore not be expected to significantly contribute to landfill leachate (Ruwona and Henry, 2021). Available data reveal that fluoropolymers are mineralized (i.e., all C-F bonds broken, hydrofluoric acid generated, and scrubbed to calcium fluoride) under commercial WTE incineration operating conditions (Aleksandrov et al., 2019; Bakker et al., 2021; DEC, 2021; Giraud et al., 2021a, 2021b). In recent pilot scale studies representative of full-scale WTE facilities, the most common form of end-of-life destruction conducted on PTFE found that combustion converted the fluorine into controllable hydrogen fluoride gas and that, of the 31 PFAS studied, no fluorine-containing products of incomplete combustion were produced above background levels (Aleksandrov et al., 2019). Further, a recent study in- vestigating the presence of PFAS in waste incinerator flue gas stated: "based on a literature review, RIVM expects that most of the PFASs will largely degrade during the incineration process and then be removed when the flue gases are cleaned. The remaining PFASs are expected to be removed during the recovery of the carbon dioxide" (Bakker et al., 2021). The RIVM report affirmed that PTFE is the most stable fluorine-containing polymer. For PTFE, the RIVM report concluded that complete thermal decomposition is achieved at a temperature of approximately 800 C. It was therefore assumed that other fluorine-containing polymers also thermally decompose completely at a temperature of 800 C. Temperatures at the pyrolysis front and the combustion front in the waste-burning bed range from 900 C to 1100 C (As- thana et al., 2006; Mnard et al., 2006), which is well above 800 C, the temperature at which the complete thermal de- composition of PTFE is achieved (Bakker et al., 2021). Studies for additional fluoropolymers and those with additional pilot and/or full-scale fluoropolymer studies would contribute to this body of data and further affirm their results. The PFP and FPG currently have joint projects working on these potential contributions. Recycling of fluoropolymer products and articles containing fluoropolymers is difficult because separation of the fluoropolymer from the end products is not always possible (FPG, 2021a; Hintzer & Schwertfeger, 2014; Pro-K Fluoropolymer Group, 2018). This is because fluoropolymers are used predominantly in small components of larger finished articles involving a wide variety of materials. There are several options to recycle fluoropolymer products. In primary recycling, solid fluoropolymer waste is ground and later fed back into the manufacturing cycle of some fluoropolymer products. Recycled fluoropolymers may be used in high-end applications when correctly collected, cleaned, and re- processed. In secondary recycling, solid fluoropolymer waste is ground, followed by degradation to approximately 1% of the original degree of polymerization by using electron beams, gamma rays, or thermomechanical degradation. The recovered material can be used in the manufacturing of new fluoropolymer products. Lastly, in tertiary recycling or upcycling, solid fluoropolymer is ground, then decomposed into the starting monomers at temperatures higher than 600 C (pyrolysis) to obtain the same chemical components from which the fluoropolymer was manufactured; monomers, such as tetrafluoroethylene, are purified by distillation, and can then be reused to manufacture new fluoropolymer (3M, 2021; Schlipf & Schwalm, 2014). For the primary and secondary schemes, recycling treatments can be undertaken by the manufacturers of fluoropolymers themselves (onsite), or at a larger scale, mainly by specialist recycling companies. The upcycling needs to be colocated to a fluoropolymer manufacturing plant that can use tetrafluoroethylene. Primary and secondary recycling is limited because of the presence of fillers, colorants, and other materials in the composition of their final articles. Further, recycling might not work for all end-of-life components, as they are used pre- dominantly in small components of larger finished articles involving a wide variety of materials. Therefore, collecting and dismantling for recycling might not be feasible for all products (FPG, 2021a; Hintzer & Schwertfeger, 2014; Pro-K Fluoropolymer Group, 2018). However, it should be noted that upcy- cling treatment is applicable to some articles containing fluoropolymers, such as pipe liners in chemical plants, as well as other plant components such as pumps, tank liners, seals, hoses, compensators, and many other fluoropolymer Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors 513793, 2023, 2, Downloaded from hitps://setac.onlinelibrary.wiley.com/doi/10.1002Aeam.4646 by CochraneAustria, Wiley Online Library on FLUOROPOLYMERS--Integr Environ Assess Manag 19, 2023 351 mia-puv-sunapuntalaiptckeirmauttuoirsduq) suompuop pun suual am gag components and systems. These are the products for which the high quantities of fluoropolymers are used offering significant recycling potential. SUMMARY This study has described the composition, uses, perform- ance properties, and functionalities of 14 commercially available fluoropolymers, including fluoroplastics and fluoroelastomers. Fluoropolymers are the preferred material of choice because of their unique combination of properties, which are not achievable from other materials or via other functions. As a result, fluoropolymers have become a critical mainstay for society and are useful to modern living, as they provide vital, reliable functionality to a broad range of industrial and consumer products. Further, the study has presented data demonstrating the subject fluoropolymers satisfy the widely accepted polymer hazard assessment criteria to be considered PLC. The data presented demonstrate the fluoropolymers in the study are thermally, biologically, and chemically stable, negligibly soluble in water, nonmobile, nonbioavailable, nonbioaccumulative, and nontoxic, and contain low levels of impurities. These results further demonstrate that the fluoropolymer class should be considered distinctly different and should not be grouped with other PFAS for hazard assessment or regulatory purposes. When combined with earlier work (Henry et al., 2018), the study demonstrates that commercial fluoropolymers are available that meet the criteria to be considered PLC, which represent approximately 96% of the global fluoropolymer market. Lastly, emissions from fluoropolymer manufacture and disposal at end-of-use are a product life-cycle focus. Emissions may include nonpolymer PFAS such as fluorinated PAs, unreacted monomers, oligomers, or other unintended byproducts formed during manufacturing. Fluoropolymer manufacturers recently committed voluntarily to responsible manufacturing principles by continuously improving and/or developing the best available techniques in the manufacturing process, managing environmental emissions, developing R&D programs for the advancement of technologies allowing for the replacement of fluorinated PAs, and/or increasing recyclability and reusing fluoropolymers in line with the objectives of circular economy. ACKNOWLEDGMENT The authors thank GSI Environmental for assisting with this study as well as the many colleagues, including Thomas Labour, Florence Churlaud, Catherine Savary, and Betsy Edhlund who provided valuable knowledge to accomplish the study, and all the reviewers for providing valuable comments on this manuscript. There are no funders to report for this submission. CONFLICT OF INTEREST The authors are employed by companies that commercially manufacture fluoropolymers. SHK is an independent fluorotechnology consultant working on behalf of AGC Chemicals Americas Inc. and principal of BeachEdge Consulting LLC. DATA AVAILABILITY STATEMENT Data gathered for this paper is presented in the paper itself and the Supporting Information: Data file provided. Addi- tional data are available upon request from the corresponding author Stephen Korzeniowski I @gmail.com). SUPPORTING INFORMATION The Supplement contains a glossary of terms as well as additional information on the study of fluoropolymers properties and functionalities, polymer of low concern (PLC) background and criteria, references and methods for the PLC data for the study of fluoropolymers, benefits, features and alternatives assessment for the study of fluoropolymers, the differences between fluoropolymers and side-chain fluorinated polymers, fluoropolymer bioavailability and toxicity studies, fluoropolymer global market information, fluoropolymer socioeconomic analyses and risk-management options analysis (RMOA). ORCID Robert C. Buck 4 http://orcid.org/0000-0002-2604-8905 REFERENCES 3M. (2021). Up-cycling. Closing the loop. https://multimedia.3m.com/mws/ media/907323O/up-cycling-fluoropolymers-brochure.pdf?fn=Up-Cycling_ Brochure_EN.pdf AGC Chemicals Company. (2021a). 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(2022). 21 CFR 177.2600 Rubber articles intended for repeated use. https://www.ecfr.gov/current/title-21/ chapter-I/subchapter-B/part-177/subpart-C/section-177.2600 USEPA. (1992). TCLP toxicity characteristic leaching procedure (SW-846 Test Method 131). https://www.epa.gov/sites/default/files/2015-12/documents/ 1311.pdf USEPA. (1997). Polymer exemption guidance manual (EPA-744-B-97-001). June. USEPA. (2010). Reviewing new chemicals under the Toxic Substances Control Act (TSCA) EPA's Review Process - Chemical categories used to review new chemicals under TSCA: TSCA New Chemicals Program (NCP) Chemical Categories. Washington (DC): USEPA Office of Pollution Prevention and Toxics. [cited 2017 July 12]. http://www.epa.gov/oppt/ newchems/pubs/npcchemicalcategories.pdf USEPA. (2012). Sustainable futures/P2 framework manual. https://www.epa. gov/sustainable-futures/sustainable-futures-p2-framework-manual USEPA. (2021a). PFAS strategic roadmap: EPA's commitments to action 2021--2024. https://www.epa.gov/system/files/documents/2021-10/pfasroadmap_final-508.pdf USEPA. (2021b). PFAS national testing strategy. https://www.epa.gov/ assessing-and-managing-chemicals-under-tsca/national-pfas-testingstrategy#:%7E:text=To%20protect%20human%20health%20and,PFAS %20chemicals%20to%20inform%20future United States Federal Register (USFR). (1984). Premanufacture notification for polymers (Final Rule 49 FR 46066, 1984 Nov 21. FR-2439-1). United States Federal Register (USFR). (1995). Premanufacture notification exemptions; Revisions of exemptions for polymers (Final rule 60 FR 16316. 1995 Mar 29. FRL-4929-8). Fed Regist 60(60), 16316-16336. Environmental Protection Agency. United States Federal Register (USFR). (2012). Polymers (b). 40 CFR Sect 723.250. Van Cleeff, A. (1997). Fluoroelastomers. In J. Schiers (Ed.), Modern fluoropolymers (pp. 507-614). John Wiley & Sons. Wallington, T. J., Andersen, M. P. S., & Nielsen, O. J. (2021). The case for a more precise definition of regulated PFAS. Environmental Science: Processes & Impacts, 23(12), 1834-1838. https://doi.org/10.1039/D1EM00296A Worm, A. T., & Grootaert, W. (2001). Fluorocarbon elastomers. Encyclopedia of Polymer Science & Engineering. Wiley. https://doi.org/10.1002/ 0471440264.pst137 Yamabe, M., Higaki, H., & Kojima, G. (1984). New fluoropolymer coatings. In G. D. Parfitt & A. V. Pastis (Eds.), Organic coatings science and technology (Vol. 7, pp. 25-39). Marcel Dekker. Integr Environ Assess Manag 2023:326-354 wileyonlinelibrary.com/journal/ieam 2022 The Authors ICRL 112022 1 Fluoropolymers: The Safe Science That Society Needs Jaime Sales, Francisco Hernandez, Deepak Kapoor and Marcel van den Noort* Fluoropolymers are high value chemicals that provide a wide variety of properties in key industrial sectors. These chemicals are indispensable to guarantee the adequate functioning of modern society, with key contributions in safety, decarbonization, and high-tech development. Due to their chemical composition and structure,fluoropolymers match the definition of the PFAS group of substances. However, such definition was originally not intended for regulatory purposes. Indeed, this group of substances is currently under heavy pressure due to thefact that some other chemicals in the group have led to environmental concerns in the past. However, fluoropolymers show clearly differentiated propertiesfrom other PFAS, and the vast majority of these polymers have been identified as matching the definition of Polymer of Low Concern. Fluoropolymers are not expected to degrade during normal use or at their end of life, and the main concerns related to their manufacture are being successfully addressed by industry, with innovative developments in both safer designs and improvement of abatement techniques to control emissions. I. Introduction For several years, per-and polyfluoroalkyl substances (PFAS) have been on the radar of regulators, scientists, non-governmental organizations, and consumers globally, because some chemicals pertaining to this very wide group of substances have been found to be persistent, bioaccumulative, and toxic to human health and the environment. For some of these substances, this concern is justified and their (eco)toxic effects are well known. This is the case, for example, with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), for which regulatory controls have been implemented in major economic regions where they were used extensively. Regulators in these countries are now concerned about other PFAS substances where data on (eco) toxicity is not available and hence they could a potential risk in the future specially because they are likely to be persistent owing to strong C-F bond. However, the broad group of * Jaime Sales, Regulatory Advisors Chemservice Iberia S.L., Castellon, Spain. Francisco Hernandez, Regulatory Advisors Chemservice Iberia S.L., Castellon, Spain. Deepak Kapoor, Gujarat Fluorochemicals GmbH, Regus Centre Watermark, Hamburg, Germany. Marcel van den Noort, Gujarat Fluorochemicals GmbH, Regus Centre Watermark, Hamburg, Germany. For correspondence <=achemservice-group.com>. PFAS also includes groups of substances - which exhibit clearly differentiated properties compared to other substances in the PFAS group, particularly related to their expected impact on humans and the environment, degradation potential to PFAS of concern and specific applications of use. One of such unique group is fluoropolymers. This paper highlights the differences that can be established between fluoropolymers and other substances in the PFAS group and provides arguments to justify that these chemicals should be regulated separately from other PFAS. Fluoropolymers are high molecular weight substances structurally characterised by having fluorine atoms directly attached to their carbon-only backbone. This differentiates fluoropolymers from other substances typically included in the PFAS group of chemicals. In fact, they can also be further differentiated from other polymeric fluorinated substances, such as side-chain fluorinated polymers (SCFPs) or perfluoropolyethers (PFPEs). The main fluoropolymers meet criteria to be identified as Polymers of Low Concern (PLC) as developed by the Organisation for Economic Co-operation and Development (OECD). Existing scientific data demonstrates that, because of their unique set of properties, such as negligible solubility in water or high molecular weight, fluoropolymers cannot enter 2 ICRL 1|2022 or accumulate in the human tissue, and they cannot degrade into other PFAS under intended conditions of use or under ambient environmental conditions. Therefore, it is considered that fluoropolymers do not pose a significant risk to water quality, human health, or the environment. Finally, potential indirect situations that may generate concerns related to PFAS emissions, such as the need to use fluorinated polymerisation aids in the fluoropolymer manufacturing process, are being addressed by industry, with significant progress made over the last years. Furthermore, the End-of-Life (EOL) phases of applications related to fluoropolymers are not expected to be of concern. However, since fluoropolymers meet the OECD definition of PFAS, they are included in the scope of the restriction proposal that 5 Competent Authorities from Member States of the European Economic Area have announced on the broad PFAS group of chemicals under the REACH Regulation1. Therefore, fluoropolymers could face market restrictions in Europe if their differentiated properties are not clearly highlighted in the restriction proposal. This could even lead to a ban on the uses of these high value materials in different applications in which they are used. This paper argues for an exemption of the Fluoropolymer group from the PFAS restriction proposal. II. Societal Importance of Fluoropolymer Applications Fluoropolymers are used in a wide variety of highly critical applications due to their valuable properties, mainly by industrial actors.2 In the case that the use of fluoropolymers would be banned in Europe, a number of critical sectors would be significantly impacted, which could result in severe damage to the European society. The list below covers just a selection of examples of industries that could be damaged because of this. - Renewable Energy: fluoropolymers are key com- ponents in solar panels and wind turbines, where they protect against weather impacts of equipment exposed to e.g., rain and environmental contaminants. In photovoltaic cells, fluoropolymers improve electrical insulation. Furthermore, these materials are critical and absolutely necessary for optimal performance of lithium-ion batteries and hydrogen fuel cells. Without fluoropolymers, these devices will not work efficiently, and the goals of the European Green Deal would be seriously compromised. - Semiconductors: fluoropolymers provide properties that are essential in this use, such as resistance to harsh chemicals that need to be used in the manufacturing process while providing an environment completely free of impurities. No fluoropolymers available will mean that the semiconductor industry will not be able to produce the high-tech microchips that allow for the development of modern (and reduced in size yet powerful) devices such as mobile phones, laptops and many other hightech equipment. - Chemical process industry: due to their unmatched properties in terms of resistance to chemical attack and optimum performance under wide variations of temperature, fluoropolymers are the only available set of products on the market that allow for adequate performance of many chemical processes. While other materials could be used for handling chemical streams, these would need continued maintenance and replacement and what is worse, they would significantly increase the risk of failure and accidents, leading to higher probability of operators and the environment being unexpectedly exposed to highly hazardous chemicals. Fluoropolymers can be found in all kinds of tubing and industrial equipment, as well as joints and gaskets to secure operation and containment of chemicals. - Transport: fluoropolymers contribute to both fuel efficiency (as key components in combustion engines) and safety, playing a key role in systems such as brakes in cars or wing flaps in aircrafts. They are also the best option available (due to their high resistance but also high flexibility) to protect electrical cables in aircrafts, where high reliability of such cables, which can be exposed to thermal as well as chemical pressure, is fundamental. - Food and water treatment: wherever high purity is required, fluoropolymers play an irreplaceable role. These materials are present in water filtration systems (which avoids the need to use chem- 1 Regulation (EC) No 1907/2006 2 Fluro Council, `Understanding FluoroTechnology' (2017) <https://fischerpaperproducts.com/wp-content/uploads/2017/02/Understanding-Fluorotechnology-FluoroCouncil.pdf> accessed 24 October 2022. ICRL 1|2022 3 icals for water treatment) and also in food processing systems to guarantee adequate sanitary conditions and avoid contamination which could otherwise reach consumers. - Pharmaceutical and medical devices: medical implants that are intended to be used in the human body (catheters, implants) due to their biological compatibility and inertness. Certainly, materials that are used for this purpose are not toxic for human health and, due to their high durability, can last for many years in the body without replacement. Furthermore, the production of medicines and vaccines by the pharma industry require as well ultra purity conditions which can only be achieved with equipment based on fluoropolymer materials. III. Fluoropolymers Inside the Broad PFAS Group PFAS are a group of 4,730 different highly fluorinated synthetic (man-made) substances3, both polymeric and non-polymeric, although other sources increase the number to approximately 9,000 chemi- 3 OECD, `Toward a new comprehensive global database of per- and polyfluoroalkyl substances (PFASs)' (2018) Series on Risk Management, 39. 4 The National Institute for Occupational Safety and Health (NIOSH), `Per- and polyfluoroalkyl substances (PFAS)' (2022) <https://www.cdc.gov/niosh/topics/pfas/default.html> accessed 24 October 2022. 5 OECD, `Reconciling Terminology of the Universe of Per- and Polyfluoroalkyl Substances: Recommendations and Practical Guidance' (2021) Series on Risk Management, 61. 6 Ibid. 7 J k Anderson et al, `Grouping of PFAS for human health risk assessment: Findings from an independent panel of experts' (2022) Regulatory Toxicology and Phamacology, 134. 8 Interstate Technology Regulatory Council (ITRC), `Naming Conventions and Physical and Chemical Properties of Per- and Polyfluoroalkyl Substances' (2020) <https://pfas-1.itrcweb.org/fact_sheets_page/PFAS_Fact_Sheet_Naming_Conventions_April2020.pdf> accessed 24 October 2022. 9 IUPAC, `What are polymers? International Union of Pure and Applied Chemistry' (2022) <https://iupac.org/polymer-edu/whatare-polymers/> accessed 24 July 2022. 10 Plastics Europe, `Fluoropolymers vs. Side chain fluorinated polymers' (2022) <https://fluoropolymers.plasticseurope.org/application/files/3516/3913/1778/Fluorpolymers_vs._side_chain_fluorinated_polymers_final.pdf> accessed 24 July 2022. 11 (n 3). 12 R C Buck et al, `Identification and classification of commercially relevant per- and poly-fluoroalkyl substances (PFAS)' (2021) Integrated Environmental Assessment and Management 17, 1045-1055. cals.4 They are grouped together in accordance with a common definition based on chemical structure5: "PFASs are defined as fluorinated substances that contain at least one fully fluorinated methyl or methylene carbon atom (without any H/Cl/Br/I atom attached to it), i.e., with a few noted exceptions, any chemical with at least a perfluorinated methyl group (-CF3) or a perfluorinated methylene group (-CF2-) is a PFAS." It should be noted that such definition was origi- nally not intended to be used for regulatory purposes.6 This has been highlighted recently in a publica- tion by an independent panel of experts on the top- ic, which generally concluded that all PFAS should not be grouped together for the purpose of assessing human health risks, and that the definition of appro- priate subgroups can only be defined on a case-bycase manner.7 Due to the large number of chemicals pertaining to this group, and the wide variability of composition and properties, PFAS can be divided in different fam- ilies. A summary of the structure of the PFAS group is displayed in Figure 1.8 As seen in Figure 1, fluoropolymers are part of the PFAS group by definition. However, they are differ- ent to other PFAS due to their polymeric nature. A polymer is defined as a molecule of high relative mol- ecular mass (macromolecule), the structure of which essentially comprises the multiple repetitions of units derived from molecules of low relative molecular mass, known as monomers.9 In the case of flu- oropolymers, this macromolecule is a long chain (backbone) of thousands of connected carbon atoms to which fluorine atoms are bound.10 For this reason, this family of synthetic polymers can be easily dif- ferentiated from the non-polymeric PFAS, which are also based on chains of carbon atoms, but which are much shorter than those of polymers (chain length between 2 and 13 carbon atoms). According to the bibliography, out of the 4,730 substances included in the PFAS category,11 only 256 are commercially relevant.12 In the case of fluoropoly- mers, only 38 substances are currently available on the market, out of the 267 compounds that are cur- rently identified. This means that commercial fluo- ropolymers only represent 0.8% of the PFAS uni- verse, but they represent 14.8% of the PFAS with com- mercial relevance. This is a good illustration of how important fluoropolymers are in modern society, due to the unique properties of these materials and their superior performance in many applications. 4 ICRL 1|2022 Figure 1: Structure of families in the PFAS Group IV. Fluoropolymers are Non-Toxic, Polymers of Low Concern Existing scientific data demonstrates that, because of their unique characteristics such as the negligible solubility in water or the high molecular weight, fluoropolymers cannot enter or accumulate in the human bloodstream. Therefore, fluoropolymers are do not pose a significant risk to human health, or the environment.13 This allows to conclude that fluoropolymers meet the criteria to be identified as PLC. While the PLC criteria are not completely agreed worldwide, basic consensus exists around the following:14 - High molecular weight, based on the Number-av- erage molecular weight (Mn): an Mn of 1,000 Da is a generally accepted Mn range for a PLC. - Content of low molecular weight, oligomeric species (no common levels accorded among global regulations). - Presence (or absence) of specific reactive functional groups (RFGs) in the polymer: these are functional groups that are known to be associated with toxicity of polymers and include cationic species that are known to result in aquatic environmental toxicity. - Solubility (in water and other solvents): polymers with water solubilities <10 mg/L showed generally low health concern. - Other criteria: stability of the polymer, chemical class (or polymer class), residual monomer content and human health hazard classification. In order to establish if fluoropolymers meet these conditions, research was originally conducted on a set of 4 specific polymers: polytetrafluoroethylene (PTFE), ethylene- tetrafluoroethylene copolymer (ETFE), tetrafluoroethylene-hexafluoropropylene copolymer (FEP), and tetrafluoroethylene-perfluoroalkyl trifluorovinyl ethers copolymer (PFA). The evaluation of these fluoropolymers15 shows that they satisfy the widely accepted assessment criteria to be considered PLCs. All of them are high molecular weight polymers, stable against hydrolysis, light, oxidation, and biodegradation, and thermally stable in the range of 150 C to 260 C. 13 B J Henry et al, `A Critical Review of the Application of Polymer of Low Concern and Regulatory Criteria to Fluoropolymers' (2018) 14 Integrated Environmental Assessment and Management 3, 316-334. S H Korzeniowski et al, `Critical Review of the Application of Polymer of Low Concern Regulatory Criteria to Fluoropolymers II: Fluoroplastics and Fluoroelastomers' (2022) Integrated Environmental Assessment and Management. 14 OECD, `Data analysis of the identification of correlations between polymer characteristics and potential for health or ecotoxicological concern' (2009) <http://www.oecd.org/chemicalsafety/riskassessment/42081261.pdf> accessed 24 July 2022; Deloitte, `Technical assistance related to the review of REACH with regard to the registration requirements on polymers' (2015) Final report prepared for the European Commission (DG ENV), in collaboration with PIEP. 15 (n 13). ICRL 1|2022 5 Also, they are practically or completely insoluble in water and not soluble in octanol. As solubility in octanol is predictive of lipid solubility, it can be expected that fluoropolymers do not dissolve in cell membrane lipids to gain access to cellular contents. Because these fluoropolymers cannot enter the cells, they are not capable of bioaccumulation or bioconcentration in aquatic life. More recent research has expanded these conclusions to cover 14 additional fluoropolymers.16 The new data confirms the same conclusions as originally established by Henry et al. in 2018, for the original set of 4 fluoropolymers; it is confirmed that all the fluoropolymers evaluated (covering approximately 96% of the global fluoropolymer market) fulfill the PLC criteria, and can therefore be expected to be negligibly soluble, not mobile, not bioavailable, not bioaccumulative, and not toxic. V. Fluoropolymers are Different From Other Polymeric PFAS As discussed in Section II, fluoropolymers can be clearly differentiated from short-chain or long-chain non-polymeric PFAS. But fluoropolymers are also different from the other families of polymeric PFAS, such as SCFPs or PFPEs, on the basis of their nature, structure, uses, and applications, as well as from the point of view of safety and expected environmental impacts. Attending to the structure of the macromolecules, the polymeric PFAS can be grouped in the following three main categories:17 16 (n 12). 17 European Commission, `Scientific and technical support for the development of criteria to identify and group polymers for Registration/Evaluation under REACH and their impact assessment' (2020). 18 (n 13). 19 H Fiedler, `A critical review of a recommended analytical and classification approach for organic fluorinated compounds with an emphasis on per- and polyfluoroalkyl substances' (2020) 17 Integrated Environmental Assessment and Management 2, 331-351. 20 J Glge J, `An overview of the uses of per- and polyfluoroalkyl substances (PFAS)' (2020) Environmental Science: Processes & Impacts 22, 2345; S Banerjee, `Poly(fluoroacrylate)s with tunable surface hydrophobicity via radical copolymerization of 2,2,2trifluoroethyl -fluoroacrylate and 2-(trifluoromethyl)acrylic acid' (2017) Polymer Chemistry 8, 1978. 21 (n 20) Glge et al; (n 2). 22 (n 19). - Fluoropolymers: have a carbon polymer backbone with fluorine atoms directly attached to carbon atoms in the backbone.18 - PFPEs: have a polyether polymer backbone, in which repeating monomer contains a carbon-oxygen bond, with fluorine atoms directly attached to carbon atoms in the backbone. - SCFPs: have a carbon polymer backbone with fluorinated side chains directly attached to carbon atoms in the backbone. In this case, fluorine atoms are not directly attached to carbon atoms in the backbone. In the final structure, the fluorinated side chains are attached to the polymer backbone by a spacer moiety and a linking group.19 The different groups of polymeric PFAS based on their structure are displayed in Figure 2 (Wahlstrm et al., 2021). These differences in the structure of the polymeric PFAS have consequences in their properties. Fluoropolymers are solid materials known for exhibiting material properties (i.e., intrinsic to the material), whereas SCFPs, marketed as liquids, greases, or dispersions in water, have surface properties, which means that they act in direct contact with products to which they are applied. This fact has implications in the downstream uses of these materials. For example, fluoropolymers are not used in firefighting foams, which is a classical application of SCFPs. In general, while fluoropolymers are used mainly in industrial applications, such as chemical processing industries, renewable energy, telecommunications, electronics and semiconductors, automotive and aerospace, food and water processing, architecture and building, and medical devices,20 SCFPs are typically used in consumer applications, such as surface protectors to provide water, oil, and stain repellence to textiles, apparel, leather, carpets, nonwovens, and paper, and soil release properties.21 In relation to PFPEs, while these are mainly used as lubricants in specific industrial sectors, certain consumer applications related to surface protection are also relevant.22 Finally, fluoropolymers are substantially different from the other polymeric PFAS in terms of potential emissions due to degradation into small PFAS molecules during intended use or under environmental conditions and, for this reason, they have no environmental impact. Fluoropolymers have a high molecular weight, little to no water solubility and volatility, therefore they are not expected to degrade to low- 6 ICRL 1|2022 Figure 2: Types of Polymeric PFAS Based on Their Structure er molecular weight PFAS.23 Also, they are not expected to lead to the formation of long-chain PFAS as a result of degradation.24 PFPEs exhibit a similar behaviour to fluoropolymers,25 because the repeating units of the PFPEs contain only 2 or 3 perfluorinated carbon atoms per oxygen atom, and their degradation cannot lead to the formation of longchain PFAS.26 However, the linking group in the structure of the SCFPs can be susceptible to cleavage, depending on the structure of each material, resulting in loss of the fluoroalkyl side chain. Thus, SCFPs can ultimately be a source of perfluoroalkyl acids (PFAAs), such as PFOA, PFOS, perfluorobutanoic acid (PFBA), perfluorohexane sulfonic acid (PFHxS), or perfluorohexane carboxylic acid (PFHxA), unless there is stability data to prove otherwise. This means that, under environmental conditions, SCFPs can degrade to these non-polymer PFAS, which are well known due to their negative effects on the environment. VI. Use of PFAS as Polymerisation Aids in the Production of Fluoropolymers The main concerns that have been typically flagged in relation to fluoropolymers are not based on these materials as such, but on the use of other PFAS substances in the manufacturing process of fluoropolymers. Under certain conditions, the use of short-chain PFAS as polymerisation aids (surfactants) is neces- sary to achieve the final fluoropolymer substance. This may result in emissions of PFAS from the fluoropolymer manufacturing process. In addition, residuals of these fluorinated surfactants may be carried over with the final fluoropolymer substance down the supply chain, which may also result in additional PFAS emissions from fluoropolymer products during the life cycle. The production process can also involve the generation of unintended fluorinated oligomers or lower molecule polymers during the process. All the above items of concern have been raised by researchers (Lohmann et al., 2020) and regulators. The fluoropolymer industry is committed to addressing these issues, and improvements in the fluoropolymer manufacturing process continue to be investigated. Furthermore, the fluoropolymer industry in Europe, via the Fluoropolymer Products Group (FPG) of Plastics Europe, recently commissioned a Regulatory Management Option Analysis (RMOA) on fluoropolymers. The objective of the RMOA was to evaluate the possible Regulatory Management Options (RMOs) that could be applicable to fluoropolymers, and to identify the most appropriate one in terms of 23 Ibid; The Danish Environment Protection Agency, `Survey of PFOS, PFOA and other perfluoroalkyl and polyfluoroalkyl substances' (2013) Environmental Project No 1475. 24 (n 17). 25 (n 17); (n 19). 26 (n 12). ICRL 1|2022 7 different parameters, such as effectiveness and proportionality. As a conclusion of this RMOA (Plastics Europe, 2022),27 the fluoropolymer industry in Europe has established a commitment to make efforts to address the existing concerns related to the use of fluorinated polymerisation aids (FPAs) in the manufacture of fluoropolymers, and to work on minimizing emissions of low carbon chain fluorinated byproducts. Several fluoropolymer manufacturers have recently announced important achievements in the development of manufacturing processes that do not require the use of FPAs.28 These achievements, which result in technically equivalent fluoropolymer grades with no presence of unintended fluorinated by-products, are expected to have significant impact in future trends of fluoropolymer manufacture, as they should lead towards a clear reduction of the use of such fluorinated surfactants. In this regard, it is worth mentioning that, according to IHS and Chemical Economic Handbook (CEH) reports, it is estimated that 55.2% of fluoropolymer production does not require the use of FPAs.29 The global production of fluoropolymers is estimated at approximately 320,000 tonnes per year. Table 1 shows information from sources related to total volume of the main substances in the fluoropolymer family, according to the sources. With the full implementation of these new achievements as announced by industry, it is expected that close to 83% of the global production will not require the use of short-chain PFAS. It is to be noted that the three main fluoropolymers by volume (PTFE, 27 Plastics Europe, `Regulatory Management Option Analysis for Fluoropolymers' (2022) <https://fluoropolymers.plasticseurope.org/index.php/fluoropolymers/irreplaceable-uses-1/reports-policy-documents/rmoa> accessed July 24 2022. 28 Chemours, `Chemours Announces Process Innovation with New VitonTM Fluoroelastomers Advanced Polymer Architecture (APA) Offering' (2022) <https://www.chemours.com/en/news-mediacenter/all-news/press-releases/2022/chemours-announcesprocess-innovation-with-new-viton-fluoroelastomers-advancedpolymer-architecture> accessed 24 August 2022; Solvay, `Producing new fluoropolymers without fluorosurfactants' (2022) <https://www.solvay.com/en/article/eliminating-pfas> accessed August 24 2022; GFL, `Company Announcement' 2022 <https://www.gfl.co.in/upload/pages/ebce5fed9030753d0ee651bf1f48d0a0.pdf> accessed August 24 2022. 29 IHS Markit, `Chemical Economics Handbook' (2016) <https://ihsmarkit.com/products/fluoropolymers-chemical-economics-handbook.html> accessed 24 October 2024. 30 R Dams and K Hintzer, `Industrial Aspects of Fluorinated Oligomers and Polymers, in Fluorinated Polymers' (2016) Polymer Chemistry Series Volume 2: Applications, 1-31; (n 28) Chemours. PVDF and FKM) will shortly be manufactured fully without the use of FPAs, reaching only with this three fluoropolymers almost 80% of global volume (and this number is expected to grow, with expected increased volumes for some of those polymers, such as PVDF in the electric vehicle industry). Still, industry continues to make efforts on research and development to completely remove the use of fluorinated surfactants from the manufacture of fluoropolymers. While it is difficult to anticipate a date when 100% production will be possible without the use of FPAs, key industrial players expect that within 10 years they will be at or very close to that objective. In parallel to this, it is worth highlighting that industry has also made significant progress in the development of abatement techniques that currently allow for close to or even above 99% recovery of any PFAS emissions that could be related to the manufacturing process of fluoropolymer.30 Coupled with the continued efforts to remove FPAs from the manufacturing process, it is expected that the production (and continued use) of fluoropolymers will be performed under conditions that will not generate any significant risks to human health or the environment in terms of exposure to PFAS. VII. Fluoropolymers Do Not Generate Significant Concerns During Endof-Life An additional reason of concern to regulators and researchers related to fluoropolymers is the EOL stage of products manufactured with these polymers, due to uncertainties in the fate of these persistent polymers if landfilled, or to potential generation of additional PFAS during incineration. It is relevant to note that, precisely because fluoropolymers are used in specific industrial applications, the waste phase for many of those sectors of use is already significantly regulated and therefore waste containing fluoropolymers will be adequately managed, in many cases via specific legislation (e.g., electronics). In addition to this, it needs to be taken into account that fluoropolymers have a very longlife span in their applications of use (in many cases going above 30 years). This means that the rate of generation of fluoropolymer waste is significantly lower compared to other polymers (plastics). Indeed, based on recent studies that have evaluated available 8 ICRL 1|2022 Global production of fluoropolymers and use of FPAs. Fluoropolymers Volume (tonnes) % of total volume Use of FPAs % volume that does not require the use of FPAs PTFE Total 169,759 53% PTFE Suspension 84,879.5 26.5% N 26.5% PTFE Emulsion 84,879.5 26.5% Y PVDF (Homopolymer + 51,248 16% N 16% Copolymer) FKM 35,000 10.9% FKM Copolymer 25,000 7.8% N 7.8% FKM Terpolymer 10,000 3.1% Y/N 1.6% FEP 32,030 10% Y PVF 6,406 2% Y PFA 3,203 1% Y ETFE 3,203 1% Y THV 800 0.3% Y ECTFE (Copolymer + Terpolymer) 2,200 0.3% N 0.3% PCTFE 8,600 2.7% N 2.7% Others 7,851 2.5% TOTAL 320,300 54.8% % volume that will not require the use of FPAs 26.5% 26.5% 16% 7.8% 3.1% 0.3% 2.7% 82.9% data from 2020,31 it is anticipated that less than 0.01% by weight of fluoropolymers entered relevant waste streams in Europe. This is significantly lower to other plastics that are estimated at about 4.8%. In that year, the majority of fluoropolymers waste (83.5%) was either incinerated or thermally destructed. About 13% of the waste was landfilled, in an operation that is expected to result in no significant environmental concern. Pilot studies of the most common form of EOL destruction, which is municipal incineration, of the most common fluoropolymer, which is PTFE, found that the combustion converted the fluorine into controllable hydrogen fluoride gas and that of the 31 PFAS species studied, no fluorine containing products of incomplete combustion were produced above background levels.32 31 Conversio, `Fluoropolymer waste in Europe 2020 - End-of-life (EOL) analysis of fluoropolymer applications, products and associated waste streams' (2022). 32 K Aleksandrov, `Waste incineration of Polytetrafluoroethylene (PTFE) to evaluate potential formation of per- and Poly-Fluorinated Alkyl Substances (PFAS) in flue gas' (2019) Chemosphere 226. ICRL 1|2022 9 Related to the incineration, in 2021 the National Institute for Public Health and the Environment of the Netherlands carried out a literature study to investigate presence of PFAS in waste incinerator flue gases.33 It was investigated to what extent and under what conditions PFAS, including fluoropolymers, are thermally degraded and what kind of incineration byproducts are formed. In this research, PTFE was found to be the most stable fluorine-containing polymer. For PTFE, it was concluded that complete thermal decomposition is achieved at a temperature of about 800C. It was therefore assumed that other fluorine-containing polymers also thermally decompose completely at a temperature of 800C. Temperatures at the pyrolysis front and the combustion front in the waste-burning bed range from 900 to 1100C,34 which is well above the temperature of 800C at which the complete thermal decomposition of PTFE is achieved. Landfills that receive fluoropolymers containing wastes also effectively contain any fluorinated compounds that might leach from the fluoropolymer waste through their leachate collection systems. The European landfill directive defines the different categories of waste (municipal waste, hazardous waste, non-hazardous waste, and inert waste), and it applies to all landfills, defined as waste disposal sites for the deposit of waste onto or into land. Typically, fluoropolymer waste is chemically inert. Therefore, fluoropolymers disposed in landfills are not expected to pose any threat to human health and environment. For certain applications like non-stick frying pans, industry is working on suitable labelling for proper collection and recycling of used pans. VIII. Fluoropolymers Are Used in High Value Industrial Applications Fluoropolymers are extremely stable, solid specialty materials that have unique physicochemical proper- 33 Rijksinstituut voor Volksgezondheid en Milieu, `Per- and polyfluorinated substances in waste incinerator flue gases' (2021). 34 A Asthana et al, `A 2-D mathematical model of on-grate municipal solid waste combustion' (2006) Sohn International Symposium Advanced Processing of Metals and Materials; A Asthana et al, `A 2-D mathematical model of on-grate municipal solid waste combustion' (2006) Sohn International Symposium Advanced Processing of Metals and Materials. 35 (n 20). 36 (n 2). ties which render them specialty plastics that are virtually chemically inert, non-wetting, non-stick, and highly resistant to temperature variability, fire, and weather, and exhibit low flammability. They also display features such as low coefficient of friction, dielectric strength, and flexibility. The exceptionally strength of the carbon-fluoride bond in fluoropolymers generates these high value properties.35 These properties, and particularly the joint combination of all of them in single products, make them irreplaceable in many applications, and it is commonly accepted that their unique set of properties cannot be matched by alternative materials, particularly in the wide range of operability they offer. In fact, fluoropolymers are frequently the high-cost option in many industries, being the material of choice only when other products are known to fail to provide the required combination of properties for the desired application. The industrial sectors in which fluoropolymers are typically used are chemical processing industries, transport (e.g., automotive, aerospace), electronics (semiconductors, data transmission cables, electrical cables), food and water processing, pharmaceutical, medical devices, or construction.36 In most of these applications, fluoropolymers are used when the material of choice needs to withstand very harsh conditions in relation to e.g., chemical environment, very high or very low temperatures (sometimes involving wide temperature variations), usually combined with other required properties such as high flexibility, barrier properties, biocompatibility, electric properties, or flame retardancy, to name a few. Frequently the value that fluoropolymers provide to these applications are strongly related to critical areas such as: - Safety of human health or the environment, pro- viding safe equipment required to handle harsh chemicals in many industries thus avoiding releases of hazardous materials (chemical industries, food processing, pharmaceuticals), or providing protection to a wide range of systems (data transmission, electric cables in automobiles or aircrafts, protecting passengers from failure events. - Clean water, providing efficient filtration systems for water treatment and replacing outdated and environmentally aggressive processes. - Green energy production, playing a key role in the efficient development of lithium-ion batteries or hydrogen fuel cells. 10 ICRL 1|2022 - Semiconductors, where the use of fluoropolymers is irreplaceable for the purpose of ensuring the technology that is currently required to produce modern reduced electronic devices. It is worth noting that in many cases, fluoropolymers were the innovative solution that was introduced to solve previous issues in terms of safety or performance. For example, fluoropolymer-based gaskets were implemented in the chlor/alkali process years ago, and they are still considered the Best Available Technology to replace asbestos gaskets due to obvious health concerns related to carcinogenicity potential of this material).37 Furthermore, it is relevant to highlight that in some applications, products could still be manufactured without fluoropolymers, but not at the level of technological development that modern society demands. This is the case of semiconductors, which could indeed be manufactured if fluoropolymers were not available, but under technical conditions dating back many years, impacting for example on the size of microchips. This would make it factually impossible to produce modern gadgets (e.g., laptops, mobile phones) at sizes that are typical in modern society. In summary, in the absence of fluoropolymers, many EU industrial sectors would face a technological leap backwards of 50+ years, which would force Europe to lose its technological independence in front of other regions. According to the bibliography, out of the 4,730 substances included in the PFAS category,38 only 256 are commercially relevant.39 In the case of fluoropolymers, only 38 substances are currently available on the market, out of the 267 compounds that are currently identified. This means that commercial fluoropolymers only represent 0.8% of the PFAS universe, but they represent 14.8% of the PFAS with commercial relevance. This is a good illustration of how important fluoropolymers are in modern society, due to the unique properties of these materials and their superior performance in many applications. IX. Conclusions Fluoropolymers are part of the PFAS group by OECD definition. For this reason, fluoropolymers are included in the scope of the restriction proposal that is being developed in the European Economic Area. However, because of their different chemical struc- ture and properties, they need to be considered as a separate family within the broad PFAS group, clearly distinct not only from the non-polymeric PFAS, but also from the other polymeric PFAS. These differences are relevant not only in terms of grouping but more importantly also in relation to the risk for human health and the environment that will be derived from their manufacture and use. The main differences between fluoropolymers and the other members of the large PFAS group of chemicals are the following: - Structural differences, which render them a unique and clearly differentiated family of chemicals within the broad PFAS group, both from nonpolymeric as well as from other polymeric PFAS. - Safety and environmental considerations, since they meet the PLC conditions, due to their high molecular weight and negligible solubility in different fluids, and are thus not toxic, not bioavailable, not bioaccumulative, not mobile, and have insignificant human health or environmental impacts. - Limited expected potential to degrade into small PFAS molecules during the intended use or under ambient conditions in the natural environment. - Unique combination of properties, frequently related to the enhancement of safety of workers, population and the environment, as well as to the development of green energy solutions and high technological applications. This makes fluoropolymers extremely valuable and irreplaceable in extremely demanding uses in a wide variety of industrial sectors. In parallel, industry has placed significant efforts to address the concerns that have been raised on fluoropolymers, related to the use of other PFAS as polymerisation aids in the manufacturing process that may result in emissions through the life cycle. Relevant achievements on this topic have been announced over the last months from different suppliers, as well as on the improvement of abatement techniques to control emissions. 37 Joint Research Centre, `Best Available Techniques (BAT) Reference Document for the Production of Chlor-alkali' (2014) <https://publications.jrc.ec.europa.eu/repository/handle/JRC91156> accessed 24 August 2022. 38 (n 3). 39 (n 12). ICRL 1|2022 11 The value that fluoropolymers provide to downstream applications is strongly related to critical areas such as: - Safety of human health or the environment, pro- viding safe equipment required to handle harsh chemicals in many industries thus avoiding releases of hazardous materials (chemical industries, food processing, pharmaceuticals), or providing protection to a wide range of systems (data transmission, electric cables in automobiles or aircrafts, protecting passengers from failure events. - Clean water, providing efficient filtration systems for water treatment and replacing outdated and environmentally aggressive processes. - Green energy production, playing a key role in the efficient development of lithium-ion batteries or hydrogen fuel cells. - Semiconductors, where the use of fluoropolymers is irreplaceable for the purpose of ensuring the technology that is currently required to produce modern reduced electronic devices. Based on all the data available, including recent positions expressed by different experts on the topic, it appears evident that fluoropolymers should not be grouped with other PFAS for risk assessment or regulatory purposes. If fluoropolymers are to be included in the upcoming PFAS restriction under the REACH Regulation, the most reasonable and proportionate decision would be to include a broad derogation to ensure continued use of these highly valuable, PLC materials. Such derogation could be conditioned to the continued replacement of fluorinated polymerization aids from the manufacturing process of fluoropolymers, which is ultimately the only reason for concern that could be justified for these chemicals, and not the intrinsic properties of fluoropolymers. RESEARCH DEFLUORINATION Low-temperature mineralization of perfluorocarboxylic acids Brittany Trangl t, Yuli Xiao-Song Xue4, Mohamed Ateial f, K. N. Houle*, William R. Dichtell* Per- and polyfluoroalkyl substances (PFAS) are persistent, bioaccumulative pollutants found in water resources at concentrations harmful to human health. Whereas current PFAS destruction strategies use nonselective destruction mechanisms, we found that perfluoroalkyl carboxylic acids (PFCAs) could be mineralized through a sodium hydroxide--mediated defluorination pathway. PFCA decarboxylation in polar aprotic solvents produced reactive perfluoroalkyl ion intermediates that degraded to fluoride ions (78 to -100%) within 24 hours. The carbon-containing intermediates and products were inconsistent with oft-proposed one-carbon-chain shortening mechanisms, and we instead computationally identified pathways consistent with many experiments. Degradation was also observed for branched perfluoroalkyl ether carboxylic acids and might be extended to degrade other PFAS classes as methods to activate their polar headgroups are identified. p er- and polyfluoroalkyl substances (PFAS) are anthropogenic substances containing multiple C-F bonds. PFAS are used as omniphobic surfactants in many industrial processes and products, including in poly(tetrafluoroethylene) production; as water-, oil-, and stain-resistant barriers for fabrics and food service containers; and as components of aqueous film-forming foams for fire suppression (/). As a result of their widespread global use, environmental persistence, and bioaccumulation, PFAS contamination is pervasive (2) and affects drinking water, surface waters, livestock, and agricultural products around the world (3). This persistent environmental contamination is alarming because chronic exposure to even low levels of these compounds is associated with negative health effects such as thyroid disease, liver damage, high cholesterol, reduced immune responses, low birth weights, and several cancers (4). Many of these effects have been obscured by PFAS manufacturers for decades (5). The growing focus on removing parts-perbillion to parts-per-trillion levels of PFAS contamination from drinking water supplies has produced several PFAS-removal approaches, including established adsorbents such as activated carbon and ion-exchange resins, as well as emerging materials such as cross-linked polymers (6, 7). Adsorbents or membrane-based 1Department of Chemistry, Northwestern University, Evanston, IL 60208, USA. 2Department of Chemistry, School of Science, Tianjin University, Tianjin 300354, China. 3Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA. 4Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P.R. China. *Corresponding author. Email: M@chem.ucla.edu (K.N.H.); @northwestern.edu (W.R.D.) 1-These authors contributed equally to this work. $Present address: Center for Environmental Solutions & Emergency Response, US Environmental Protection Agency, Cincinnati, OH, USA. separation processes create PFAS-contaminated solid or liquid waste streams but do not address how to degrade these persistent pollutants. PFAS destruction is a daunting task because the strong C-F bonds that give PFAS their desirable properties also make these compounds resistant to end-of-life degradation. Harsh PFAS degradation methods include incineration (8), ultrasonication (9,10), plasmabased oxidation (11), electrochemical degradation (12, 13), supercritical water oxidation (14), ultraviolet-initiated degradation using additives such as sulfite or iron (15-19), and other combinations of chemical and energy inputs (20) (table S1). Leveraging the reactivity of perfluoroalkyl species might, however, offer milder alternatives to address the PFAS contamination problem. The opportunity to degrade PFAS at high concentrations in nonaqueous solvents has recently been developed using PFAS adsorbents that can be regenerated using a simple solvent wash. This development enables the destruction of these compounds after they have been removed from water resources, which broadens suitable degradation conditions beyond dilute aqueous environments. Here, we accessed reactive perfluoroalkyl anions that are mineralized under mild conditions by decarboxylating perfluorocarboxylic acids (PFCAs), one of the largest classes of PFAS compounds, at low temperatures in dipolar aprotic solvents (Fig. 1). PFCAs of various chain lengths undergo efficient mineralization in the presence of NaOH in mixtures of water and dimethyl sulfoxide (DMSO) at mild temperatures (80 to 120C) and ambient pressure. Under these conditions, perfluorooctanoic acid (PFOA, 1) is completely degraded with >90% defluorination and minimal formation of fluorocarbon by-products. Experimental observations and density functional theory (DET) calculations offer strong evidence for degradation pathways distinct from the single-carbon-chain shortening pro- cesses proposed in prior PFAS degradation studies (11, 16, 18, 21-23). This reactivity mode is immediately promising for PFCA destruction and may prove generalizable to other PFAS classes as methods to activate their polar groups are identified. Decarboxylation and defluorination of PFCAs in polar aprotic solvent Perfluoroalkylcarbanions are easily arressed by decarboxylating PFCAs in dipolar aprotic solvents. In a solution of DMSO and H2O (8:1v/v) at 120C, PFOA decarboxylates to form perfluoro1H-heptane 2, which phase separates from solution as an oi1. 111, 73C, and 19F nuclear magnetic resonance (NMR) spectroscopy of the isolated oil confirmed the formation of the decarboxylated product in high purity (figs. 51 to S4). This decarboxylation reaction is consistent with those reported by Kong et al., who found that most carboxylic acids decarboxylate reversibly in dimethylformamide (24). Zhou et al. (25) studied the origins of this reversible carboxylation computationally and determined that the lower barrier to decarboxylation was fully induced by solvent effects from the polar aprotic solvent (figs. S45 and S58). Such reactivity has also been observed as a complication for analytical standards (26,27). We found that when the same PFOA solution in DMSO/ H2O was subjected to the decarboxylation conditions but in the presence of NaOH (30 equiv), PFOA instead degraded to a mixture of fluoride, trifluoroacetate ions, and carboncontaining by-products (Fig. 2A). Degradation also occurred in other polar aprotic solvents such as dimethylacetamide and sulfolane but did not proceed in pure water (fig. S20 and table S3). 79F NMR spectroscopy of reaction aliquots collected over 24 hours indicated that resonances corresponding to PFOA were no longer detectable within 14 hours. Unexpectedly, no resonances corresponding to perfluoroalkyl groups containing between four and seven carbons were observed. Resonances corresponding to sodium perfluoropropionate (CF3CF2CO2Na) at -81.5 and -118.2 ppm were observed just above the baseline within spectra of aliquots collected at reaction times shorter than 24 hours but were absent in spectra of later aliquots (fig. S10). The only prominent fluorine resonance in the aliquot sampled at 24 hours corresponds to sodium trifluoroacetate (CF3CO2Na, -73.6 ppm; Fig. 2B). Integration of this resonance indicated that its intensity plateaued at -4 to 24 hours, corresponding to only 7% of the F content and 9% of the C content relative to the initial PFOA concentration (Fig. 2, A and C). The resonance from CF3CO2Na ions eventually decreased in intensity and presumably degraded into fluoride, albeit much more slowly than the rate of PFOA disappearance (Fig. 2C, inset). This resonance disappeared over 300 hours, which we confirmed Trang et al., Science 377, 839-845 (2022) 19 August 2022 1 of 7 RESEARCH | RESEARCH ARTICLE Fig. 1. Overview of degradation pathways identified in this study. Heating PFCAs in polar aprotic solvents such as DMSO decarboxylates them to 1H-perfluoroalkanes. When this reaction was performed in the presence of NaOH, the PFCA mineralized to fluoride, sodium trifluoroacetate, and nonfluorinated carbon-containing products. The 1H-perfluoroalkane underwent the same degradation process at even lower temperatures. Computational studies identified the corresponding perfluoroalkenes as likely intermediates, and an authentic standard of the seven-carbon perfluoroalkene was competent for the degradation. by subjecting an authentic sample of sodium trifluoroacetate to the same reaction conditions (fig. S24). PFOA degradation is thus rapid and forms CF3CO2Na and trace CF3CF2CO2Na as the only identifiable perfluoroalkyl-containing liquid-phase by-products, each of which continues to degrade over extended reaction times. Subjecting perfluorooctane sulfonate ions to the basic decarboxylation conditions did not result in decreasing perfluoroalkyl 19F NMR integrations or fluoride formation (fig. S19 and table S3), indicating that decarboxylation to the reactive anion intermediate is the key first step of the defluorination process for PFCAs. Ion chromatography (IC) indicated that 90 6% of the fluorine atoms originating from the PFOA were recovered as fluoride ions after 24 hours of reaction at 120C (fig. S29). Control experiments showed that the fluorinated polytetrafluoroethylene reaction vessels did not contribute an appreciable amount of fluoride to fluoride recovery (table S3). Fluoride analyses performed by IC at shorter reaction times indicated that fluoride increased proportionally to the decrease in [PFOA] observed by 19F NMR spectroscopy. This high fluoride recovery indicates that most of the perfluoroalkyl fluorines were defluorinated and mineralized rather than being transformed to smaller-chain PFAS or being lost as volatile fluorocarbons. Degradation of varied PFAS and by-product analysis suggest a complex mechanism PFCAs with different chain lengths (two to nine carbons) were degraded, providing fluoride recoveries between 78% and quantitative at 24 hours for all PFCAs with four or more carbons (Fig. 2D). Although the longer-chain (C 4) PFCAs had a degradation profile similar to that of PFOA in that their perfluoro- alkyl peaks disappeared from the 19F NMR spectra (fig. S22) and CF3CO2- was formed (Fig. 2D and fig. S23), the destruction of shorterchain PFCAs (C = 2, 3) was slower and appeared to occur by different mechanisms. For trifluoroacetate (C = 2), degradation is slow (>6 days; fig. S24), likely because the instability of the CF3- anion (28) hinders decarboxylation, such that destruction occurs either more slowly or by a different mechanism. The carbanion corresponding to perfluoropropionic acid (PFPrA) (C = 3) decarboxylation is similarly unstable (28), resulting in degradation faster than trifluoroacetate but slower than the longer PFCAs (fig. S22). Although the PFPrA 19F NMR peaks disappeared completely over 3 days, fluoride recovery was lower than in other PFCAs (3.9 1.6%; Fig. 2D). PFPrA, unlike others in the series, decarboxylates to form a volatile product; in the 19F NMR for PFPrA degradation, peaks corresponding to CF3CF2H can be identified (figs. S11 and S12). Headspace gas chromatography- electron-impact mass spectrometry (MS) also detected the CF3CF2+ fragment in the gas phase of the reaction (fig. S40). This finding was corroborated by atmospheric pressure chemical ionization-MS of a liquid aliquot of the reaction that had a prominent peak corresponding to CF3CF2- (compare fig. S39 with figs. S38 and S40). It appears to be more favorable to produce volatile CF3CF2H than for the C = 3 PFCA to proceed down the destruction pathway; as discussed below, this supports our proposal that a g-carbon is necessary for the major defluorination pathway to occur. Previous PFAS degradation studies have suggested that PFCAs (or other PFAS that are PFCA precursors) degrade through a decarboxylation-hydroxylation-eliminationhydrolysis (DHEH) pathway in which each PFCA is shortened by one carbon each cycle, producing successively shorter PFCAs (11, 16, 18, 21-23). However, the nonconformal degradation of the three-carbon acid and the products observed in the 19F NMR spectra of degradation reactions of PFCAs containing four or more carbons in the present study indicated that degradation instead occurs through distinct, non-single-carbon shortening mechanisms under these conditions. The hypothesis that degradation does not occur by iterative one-carbon shortening was further supported by quantifying the carboncontaining by-products formed when PFOA was degraded for 24 hours. We examined a combination of solution 1H and 19F NMR spectroscopy and quantitative 13C NMR spectroscopy of the precipitate isolated from the reaction and dissolved in D2O. We also performed ion chromatography on the combined solution and precipitate by adding water to the reaction mixture until the precipitate redissolved. These measurements accounted for the complete carbon balance of the PFOA degradation (107 8 mol% C relative to the [PFOA]0; table S4 and fig. S30). Other than the residual CF3CO2- ions described above, which continued to degrade at longer reaction times, no other organofluorine compounds were detected. Instead, one-, two-, and three-carbon products lacking C-F bonds were identified and quantified. Formate ions were found in solution (fig. S9) and in the precipitate, corresponding to 2.5 0.3 mols formate ions/mol PFOA, as determined by combining the formate concentrations measured in the solution and precipitate by NMR spectroscopy. This amount is consistent with ion chromatography of the reaction mixture and redissolved precipitate, which provided 2.1 0.2 mols formate/mol PFOA. Formate formation and the varying amounts of formate produced by PFCAs of other chain lengths inspired a deeper mechanistic study (see below). Carbonate ions were detected exclusively in the precipitate, corresponding to 2.1 0.3 mols/mol PFOA. The most likely source of carbonate ions was from the initial decarboxylation step, along with other downstream processes that generate carbon dioxide or single-carbon products at the same oxidation state. Two-carbon products, glycolate ions (0.6 0.1 mol/mol PFOA) and oxalate ions (0.7 0.1 mol/mol PFOA), were found in the precipitate, along with three-carboncontaining tartronate ions (0.2 0.1 mol/mol PFOA). The glycolate and oxalate ions were identified by 13C NMR spectroscopy and comparison with authentic standards. Tartronate ions were identified by a combination of 13C and 1H NMR spectroscopy, which were consistent with literature reports (29) and showed the expected correlations in two-dimensional NMR experiments (figs. S31 and S32). Finally, a small amount of the PFOA carbon balance was found in an unknown product, which Trang et al., Science 377, 839-845 (2022) 19 August 2022 2 of 7 RESEARCH | RESEARCH ARTICLE Fig. 2. Overall reaction scheme, experiments monitoring PFOA and CF3CO2- concentrations over the course of the reaction, and summary of degradation products from a series of PFCAs of different lengths. (A) Heating 0.089 M PFOA in 8:1 DMSO:H2O with 30 equiv NaOH allowed 90% of the initial fluorine to be recovered as inorganic fluoride and residual trifluoroacetate with few other organofluorine by-products. Formate ions (26 mol %) and several other nonfluorinated by-products were identified (107 8 mol %). (B) 19F NMR spectra from 0 to 24 hours. Peaks corresponding to PFOA perfluoroalkyl fluorines between -115 and -126 ppm, as well as at -80 ppm, disappeared in less than 24 hours. Trifluoroacetate (-73.6 ppm) appeared and disappeared (disappearance shown in inset of panel C) more slowly over the course of the reaction. (C) Amount of PFOA (purple, solid line) and sodium trifluoroacetate (gray, dashed line) in the reaction over time. Error bars correspond to the standard deviation of three experiments. (D) Fluoride recovery was calculated as mols fluoride after reaction as detected by ion chromatography per mol fluorine in PFCA reactant. Formate/PFCA was calculated as mols formate as detected by IC after reaction per mol PFCA reactant. CF3CO2-/PFCA was determined as mols CF3CO2- as calculated from 19F NMR spectroscopy after 24 hours of reaction per mol PFCA reactant. All measurements are expressed as the average of three trials unless specified otherwise, and error is expressed as a standard deviation. All reaction times are 24 hours unless specified otherwise. "a," 286 hours, single measurement; "b," 63% 12% of PFPrA starting material degraded after 24 hours. (E) Structures of the identified carbon-containing by-products. we designated as a secondary degradation product derived from the reaction of glycolate ions with other intermediates because it was formed in greater amounts when glycolic acid was included at the beginning of the PFOA degradation reaction. Identifying and quantifying these carbon products has important implications for PFOA degradation. First, the high recovery of products with no C-F bonds, along with the high fluoride ion recovery, confirms that these conditions efficiently mineralize PFCAs. Furthermore, identifying multiple two- and three-carbon by-products further implicates mechanisms more complicated than iterative one-carbon shortening processes. PFCAs of different lengths degraded by different pathways, as indicated by the distinct patterns in their formate and CF3CO2- formation. If the chain-shortening DHEH mechanism were operative, then we would expect that resonances belonging to chain-shortened species would appear transiently in the 19F NMR spectra as longer-chain PFCAs speciated into a distribution of shorter-chain PFCAs. Instead, only 19F NMR peaks corresponding to CF3CO2- and trace amounts of CF3CF2CO2- were detected, and the following by-product patterns emerged. PFCAs containing four or fewer carbons did not produce any CF3CO2-, but all PFCAs containing more than four carbons produced roughly the same substoichiometric amount of CF3CO2-: ~0.3 equivalents of CF3CO2-/mol PFCA. PFCAs containing fewer than six carbons did not produce substantial amounts of formate (Fig. 2D), but PFCAs containing six or more carbons produced increasing amounts of formate, with C = 6 and 7 producing ~1 equivalent of formate per PFCA, C = 8 ~2 equivalents, and C = 9 ~2.5 equivalents. These observations indicate that CF3CO2- and formate production occur by distinct pathways. Experiments conducted at near-ambient temperatures showed that decarboxylation is the rate-limiting step and subsequent defluorination and chain-shortening steps can occur at near-ambient temperature, giving experimental insight into the possible mechanism. Substantial defluorination still occurred when the isolated PFOA degradation product (perfluoro-1H-heptane 2) was subjected to degradation conditions but heated to only 40C (table S3). PFCAs have historically been decarboxylated by heating PFCA salts in ethylene glycol at 190 to 230C to yield perfluoro-1Halkanes (30) or by pyrolyzing PFCA salts at 210 to 300C to yield perfluoro-1-alkenes (31), but dipolar aprotic solvent-assisted degradation enabled decarboxylation at only 80 to 120C, which can be followed by an even lower-temperature defluorination. When 2 was subjected to the basic degradation conditions, both fluoride and chain-shortened PFCAs were observed by IC and 19F NMR at short reaction times (5 min at 120C) and low temperatures (25 min at 40C), in contrast to Trang et al., Science 377, 839-845 (2022) 19 August 2022 3 of 7 RESEARCH | RESEARCH ARTICLE Fig. 3. Proposed PFCA degradation mechanism with activation energies (DG, kcal/mol) for each step as calculated at the M06-2X/6-311+G(2d,p)SMD(DMSO) level. Cycle AD shows a three-carbon shortening of the original PFCA of n carbons ("1," red, top) with one carbon lost as CO2 (converted to CO32- under basic conditions) and two carbons lost to fluoroacetic acid, which readily degrades under these reaction conditions. Pathway B shows the reaction that results from the 1,2 addition of hydroxide to the carboxyl carbon of INT6. Proposed pathways for the conversion of INT14 to INT30, along with pathways for nonfluorinated, carbon-containing by-products, are described in fig. S50. The alkene INT30 becomes protonated and proceeds through a similar pathway as pathway A. At INT35, the aldehyde analog of acid fluoride INT6, 1,2 addition to the carboxyl carbon leads to the formation of formate by elimination in pathway C, whereas 1,4 addition to the b carbon leads back to pathway D. All energies are expressed in units of kilocalories per mole. reactions starting from the carboxylated PFOA at the same conditions, in which no fluoride or short-chain PFCAs were formed at short reaction times or at low temperatures (table S3). Degradation of 2 at 40C for 48 hours showed 57% defluorination (table S3). Although the insolubility of the polyfluoroalkane standard in the DMSO and water solvent precluded accurate measurements of its concentration by NMR spectroscopy, the presence of the CF3CO2- 19F NMR peak (fig. S13) indicated that the decarboxylated material likely followed a similar degradation pathway. In this lowtemperature experiment, intermediates that were not observed in the higher-temperature experiments became evident; at around -210 ppm, a triplet with J = 48 Hz appeared, which corresponds to the fluoroacetate ion (CH2FCOO-; fig. S13). The fluoroacetate peak did not appear in the higher-temperature degradations because it degrades rapidly at those temperatures, as confirmed by the degradation of a pure standard. Temperature-dependent studies of the original PFOA degradation reaction showed that the reaction slowed slightly when the reaction was conducted at 100C (time to [PFOA] = 0 is ~100 hours compared with 16 hours for 120C; figs. S21 and S25 to S27) and slowed substantially when lowered to 80C (>290 hours; figs. S21 and S28). Therefore, significant defluorination of 2 was unexpected at 40C, suggesting that the steps after the decarboxylation were low-barrier or barrierless. These observations further indicate that degradation does not proceed by successive chain shortening through iterative decarboxylation steps. Computational studies reveal steps in defluorination mechanism with negligible barriers DFT was used to determine the mechanism of this degradation reaction. These studies predicted that decarboxylation is the rate-limiting step of the degradation and that a series of low-barrier or enthalpically barrierless reactions can lead to levels of defluorination consistent with experimental observations. DFT calculations were performed at the M06-2X/ 6-311+G(2d,p)-SMD(DMSO) level (see the supplementary materials for details) and used PFOA as the starting point for the calculations. This mechanism should also be valid for the degradation of straight-chain PFCAs of other lengths. After the initial decarboxylation of PFOA (compound 1; Fig. 3) at an activation energy of about 28 kcal/mol, calculations indicated that the resulting anion INT1 would eliminate a fluoride to become perfluoroalkene INT2 (Fig. 3 and fig. S44). Unlike previous PFCA degradation mechanisms in the literature predicting that the perfluoroalkyl fragment will hydroxylate after decarboxylation (11, 16, 18, 21-23), these computational results point to the formation of an alkene followed by an enthalpically barrierless hydroxylation of the activated electrophilic alkene. Hydroxylation of the alkyl fragment INT1, as postulated in previous studies, was calculated to have an activation energy of 29.7 kcal/mol under our study's conditions after protonation of the fragment (fig. S46), whereas formation of the alkene INT2 had a barrier of 19.5 kcal/mol, followed by a hydroxylation with no enthalpic barrier (DG = -44.3 kcal/mol). The highly exothermic nature of this alkene hydroxylation step played a leading role in driving the degradation, consistent with observations that the defluorination and chain-shortening steps of the reaction neither have high energy barriers nor lead to the formation of successively shorter PFCAs. Accordingly, when perfluoro-1-heptene 3 (INT2) was subjected to degradation conditions (table S3), it also degraded to similar products even at 40C, corroborating the computational prediction and indicating that the alkene is likely on the degradation pathway. Further, calculations also suggested that the hydroxylation is specifically favored at the terminal position, because addition on the internal side of the alkene had a barrier of 8.9 kcal/mol (fig. S47). After this alkene hydroxylation (INT4), calculations suggested that a series of low- or no-barrier reactions occurred, as shown in Fig. 3 and fig. S44. The enol can then eliminate another fluoride, forming a,b-unsaturated acyl fluoride INT6 through retro 1,4-conjugate addition. This resulting a,b-unsaturated acid fluoride INT6 has two plausible reaction pathways that are consistent with the experimental findings: a 1,4-conjugate addition that leads to CF3CO2- formation (pathway D) or a 1,2 addition (pathway B) that can lead to formate formation (pathway C), which together explain Trang et al., Science 377, 839-845 (2022) 19 August 2022 4 of 7 RESEARCH | RESEARCH ARTICLE the experimentally observed by-product distribution. Calculations indicated that neither option had enthalpic barriers and thus very low free energies of activation, indicating that both reactions occurred to some extent (fig. S48). In the enthalpically barrierless 1,4-conjugate addition (Fig. 3, pathway D, X = F) that leads to the formation of shorter PFCAs such as CF3CO2-, the hydroxide adds to the b carbon of a,b-unsaturated acyl fluoride INT6, followed by an enthalpically barrierless fluoride elimination to form 1,3-diketone compound INT8. Hydroxide again adds to this intermediate on the ketone carbonyl side to generate INT9, which is more favorable than the addition on the acyl fluoride side (fig. S49). Finally, fragmentation occurs to generate an equivalent of PFCA three carbons shorter than the initial carboxylic acid and an equivalent of fluoroacetic acid, which was observed in the experiments conducted at 40C (figs. S13 and S16). As an example, if five-carbon PFCA perfluoropentanoic acid (PFPeA) went through this cycle, it would produce an equivalent of carbon dioxide (1 carbon), an equivalent of trifluoroacetic acid (2 carbons), and an equivalent of fluoroacetic acid (2 carbons) by this pathway. However, from the experimental results, only about 0.3 equiv of CF3CO2- were produced from PFPeA (Fig. 2D), indicating the PFCA degradation does not proceed quantitatively by this process. This pathway also does not account for the substantial amounts of formate produced in reactions from longer PFCAs. Formate ion production is explained by a pathway stemming from the favorable 1,2hydroxylation product, which provides an a,b-unsaturated PFCA (pathway B). As with INT6, there are multiple possible sites for hydroxide addition to INT14, either to the a (13.6 kcal/mol) or b (12.0 kcal/mol) carbons. Possible pathways propagating from both of these processes, along with the formation of oxalate and other carbon by-products, are described in the supplementary materials (figs. S50 to S54). Although both of these pathways for the conversion of INT14 to INT30 are plausible and supported by computation, the possibility of other active mechanisms cannot be ruled out. However, both of these hydroxylations are more favorable than decarboxylating the a,b-unsaturated perfluoroacid (22.3 kcal/ mol), and both lead to the formation of perfluoroalkene anion INT30. The chain length of the alkene depends on which hydroxylation pathway the substrate follows, either four carbons shorter than the original chain (1,3 addition) or five carbons shorter than the original chain (1,4 addition). Calculations showed that perfluoroalkene anion INT30 is protonated rather than eliminating a fluoride to generate the alkyne (figs. S55 and S56). After the protonation, hydroxide adds to the alkene, much like the first postdecarboxylation step in the first proposed pathway. Likewise, a,b-unsaturated aldehyde INT35, an analog to the a,b-unsaturated acid fluoride INT6, is generated through retro-1,4 addition. At this point, the intermediate again faces a bifurcation, with opportunities for both the 1,4-conjugate addition and the 1,2 addition of the hydroxide to the a,bunsaturated aldehyde. Similar to the addition to the a,b-unsaturated acyl fluoride, both of these reactions were calculated to have no enthalpic barrier (fig. S57). Through the 1,4-conjugate addition (Fig. 3, pathway D, X = H; figs. S59 and S60), the 1,3-diketone compound generated will be attacked by hydroxide, followed by the same fragmentation as noted before. That is, a PFCA and a fluoroacetic aldehyde are formed, the latter of which can be transformed into fluoroacetic acid or be rapidly hydrolyzed. However, if INT35 undergoes 1,2 addition of hydroxide to the a,b-unsaturated aldehyde (Fig. 3, pathway C; figs. S55 and S60), the resulting aldehyde (INT36) cannot eliminate a hydride, whereas its acid fluoride counterpart INT13 can eliminate a fluoride. Instead, INT36 can eliminate the entire perfluoroalkyl chain, creating an equivalent of formate and a one-carbon-shorter alkene anion that can either exit the cycle through 1,4-conjugate addition or proceed through the cycle again to form more formate, thus giving rise to the trend of increased formate formation by PFCAs of longer chain length. Experimental support for the computationally determined mechanism Our calculations affirmed that decarboxylation is the rate-determining step of the degradation, and the calculated activation energy of ~28 kcal/mol is consistent with the experimentally determined value of 30.0 kcal/mol (see the supplementary materials, page 6 and table S2). The proposed mechanism is also supported by experimental observations of CF3CO2- and the formate distribution shown in Fig. 2D. By this mechanism, CF3CO2- was produced as a nonstoichiometric by-product, in accordance with the observation that only ~0.3 to 0.4 equivalents of CF3CO2- were formed per mol PFCA for all PFCAs with C 5. This proposed mechanism also explains why fourcarbon perfluorobutanoic acid (PFBA) did not produce CF3CO2-, whereas the five-carbon PFPeA did, because PFBA that has gone through cycle AD would create FCOO-, which will decompose spontaneously to carbon dioxide and fluoride (32) or hydrolyze from INT8 to form tartronate. This two-cycle mechanism also explains why five-carbon PFPeA produced CF3CO2- but no formate, because the carbon chain is not long enough to go through pathway C. The mechanism predicts that the amount of formate will increase as the length of the initial PFCA carbon chain increases; this was also affirmed by experimental results for PFCAs of six to nine carbons (Fig. 2D). The formation of carbonaceous by-products such as oxalate, glycolate, and tartronate is also consistent with this mechanism (figs. S50 to S54). Furthermore, when conducting reactions with protodecarboxylated perfluoro-1H-heptane 2 or perfluoro1H-hexane S1 (figs. S5 to S8) at 40C, the formation of intermediate products containing five- or four-carbon fluorous chains was observed (figs. S14 and S17), respectively, which likely correspond to INT8/INT9 (figs. S15 and S18), the intermediate with the highest activation energy (25.6 kcal/mol) in this pathway. The peaks corresponding to this intermediate disappeared as peaks corresponding to the five- and four-carbon PFCAs appeared. These PFCAs that are shortened by three carbons are the logical products of a singlepathway AD cycle from their respective starting materials. The experimental observations confirm that the computed mechanism provides a complete model to describe the observations made experimentally about this complex degradation. We also performed calculations to test proposed difluorocarbene (fig. S62), perfluoroalkyl hydroxylation (fig. S46), and a-lactone (33, 34) (fig. S61) mechanisms that had been proposed for such degradations, but these were found to have barriers too high to be compatible with the experimental conditions. Generalization of the PFCA destruction method to perfluoroalkyl ether carboxylates Branched perfluoroalkyl ether carboxylic acids, another major class of PFAS contaminants, are also mineralized by perfluoroalkyl anion intermediates. The ammonium salt of hexafluoropropylene dimer acid (ammonium perfluoro (2-methyl-3-oxahexanoate; also known as FRD902, the trade name GenX, or HFPO-DA in its acid form) is a perfluoroalkyl ether carboxylic acid that was introduced as an industrial replacement for PFOA. This compound now contaminates water sources such as the Cape Fear River, which serves as the primary drinking water source for >350,000 residents of North Carolina (35). For this compound, the decarboxylation and branched CF3 chain defluorination occurred at 40C, an even lower temperature than for the PFCAs (fig. S35). This finding is consistent with computational results indicating that the barrier for GenX decarboxylation is only 20.4 kcal/mol (fig. S63). However, because of the presence of the ether oxygen in place of the g-carbon, the structure was unable to eliminate a g-fluorine and instead formed perfluoroalkyl ether carboxylic acid intermediate 5 through hydrolysis (Fig. 4), which built up in solution and was observed by both 19F NMR and electrospray ionization MS (figs. S33, S35, and S42). Further degradation occurred at elevated temperatures (80C; Trang et al., Science 377, 839-845 (2022) 19 August 2022 5 of 7 RESEARCH | RESEARCH ARTICLE Fig. 4. Proposed mechanism for branched perfluoroalkyl ether carboxylic acid degradation. Pathway A (blue) shows the branched CF3 defluorinating in the same manner as PFCAs in Fig. 3. The lack of g-fluorines forces formation of 5 through pathway E (orange), as observed by NMR and MS. Calculations show the hydroxide-mediated SN2 that eliminates the perfluoroalkoxide tail in pathway F (purple), leading to the formation of a PFCA that is degraded according to the mechanism described in Fig. 3. All energies are expressed in units of kilocalories per mole. fig. S35). Calculations showed that the decarboxylation of this intermediate was unfavorable (figs. S65); rather, a hydroxide-mediated SN2 with a barrier of 21.9 kcal/mol occurred in which the perfluoroalkoxide tail was eliminated (fig. S66). This perfluoroalkoxide formed a carboxylic acid (DG = 21.9 kcal/mol) with the same number of carbons as the original perfluoroether tail. Because GenX contains a three-carbon tail, it produced the C3 PFCA (PFPrA), the degradation of which led to incomplete defluorination (41%; Fig. 2D) and the formation of CF3CF2H (figs. S37, S40, and S41). These observations are consistent with those of the direct degradation of PFPrA (Fig. 2D and figs. S11, S12, S39, and S40). The experimental observations showed that temperatures of 40, 80, and 120C are necessary to form intermediate 5, to form the PFCA analog, and to initiate PFCA degradation, respectively. These temperature steps correspond to the calculated energy barriers of 20.4, 21.9, and 27.7 kcal/mol, respectively (figs. S35, S63, and S64). Degradation of a longer perfluoroalkyl ether carboxylic acid with a five-carbon perfluoroalkyl tail (compound 4; figs. S34, S36, S40, and S43) proceeded by a similar mechanism as that of GenX and gave fluoride recoveries consistent with those obtained from the five-carbon PFCA PFPeA. These findings indicate that perfluoroalkyl ether carboxylates also degrade through perfluoroalkyl anion- based processes. Intermediates in the degrada- tion of 4, as observed by atmospheric pressure chemical ionization-MS (fig. S43), corroborated the proposed mechanism (Fig. 4). Conclusions The perfluorocarbon reactivity that we have described here leverages low-barrier defluorination mechanisms to mineralize PFAS at mild temperatures with high rates of defluorination and low organofluorine side-product formation. In contrast to other proposed PFAS degradation strategies, the conditions described here are specific to fluorocarbons, destroy concentrated PFCAs, give high fluoride ion recovery and low fluorinated by-product formation, and operate under relatively mild conditions with inexpensive reagents. The proposed mechanism is consistent with both computational and experimental results, provides insight into the complexity of PFAS mineralization processes, and may be operative but unrecognized in other PFAS degradation approaches. This demonstration of the reactivity of perfluoroalkyl anions, and the ability to access such intermediates efficiently from PFCAs, may inform the development of engineered PFAS degradation processes and facilitate expanding this reactivity mode to PFAS with other polar head groups. REFERENCES AND NOTES 1. A. Leeson et al., Environ. Toxicol. Chem. 40, 24-36 (2021). 2. A. M. Calafat, L.-Y. Wong, Z. Kuklenyik, J. A. Reidy, L. L. Needham, Environ. Health Perspect. 115, 1596-1602 (2007). 3. United Nations Stockholm Convention, "Perfluorooctanoic acid (PFOA), its salts and PFOA-related compounds" (UN, 2017); http://chm.pops.int/Implementation/Alternatives/ AlternativestoPOPs/ChemicalslistedinAnnexA/PFOA/tabid/ 8292/Default.aspx. 4. "C-8 Medical Monitoring Program" (GCG, 2022); http://www. c-8medicalmonitoringprogram.com/. 5. N. Rich, "Rob Bilott v. DuPont," New York Times Magazine, 17 January 2016; https://hnbpjs.blogspot.com/2016/01/robbilott-v-dupont.html. 6. A. Maimaiti et al., Chem. 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Lett. 7, 477-481 (2020). 27. C. Zhang, A. C. McElroy, H. K. Liberatore, N. L. M. Alexander, D. R. U. Knappe, Environ. Sci. Technol. 56, 6103-6112 (2022). 28. D. A. Dixon, T. Fukunaga, B. E. Smart, J. Am. Chem. Soc. 108, 4027-4031 (1986). 29. T. Chatterjee, E. Boutin, M. Robert, Dalton Trans. 49, 4257-4265 (2020). 30. J. D. LaZerte, L. J. Hals, T. S. Reid, G. H. Smith, J. Am. Chem. Soc. 75, 4525-4528 (1953). 31. R. N. Haszeldine, J. Chem. Soc.4259 (1952). 32. X. Zhang, U. Gross, K. Seppelt, Angew. Chem. Int. Ed. 34, 1858-1860 (1995). 33. M. J. Pellerite, J. Fluor. Chem. 49, 43-66 (1990). 34. Y. Ge et al., Comput. Theor. Chem. 1029, 33-40 (2014). 35. G. McGrath, "Denied by Trump EPA, NC activists hope Biden EPA will force `forever chemical' study," Fayetteville Observer, 17 January 2021; https://www.fayobserver.com/story/news/ 2021/01/27/denied-by-trump-epa-nc-activists-hope-bidenepa-force-forever-chemical-study/4265453001/. ACKNOWLEDGMENTS We thank Y. Luo at Shanghai Institute of Organic Chemistry for helpful discussions about fluorine NMR; S. Shafaie at Northwestern University's Integrated Molecular Structure Education and Research Center (IMSERC) facility for assistance with MS; and R. Sponenburg at Northwestern University's Quantitative Bio-element Imaging Center (QBIC) for ion chromatography. Funding: B.B.T. is supported by the National Science Foundation Graduate Research Fellowship Program (NSF grant DGE-1842165). K.N.H. is supported by the National Science Foundation (grant CHE-1764328) and the Saul Winstein Chair in Organic Chemistry. Ion chromatography was performed at the Northwestern University Quantitative Bio-element Imaging Center, which is generously supported by the NASA Ames Research Center (grant NNA04CC36G). This work made use of the IMSERC at Northwestern University, which has received support from the National Institutes of Health (NIH grants 1S10OD012016-01 and 1S10RR019071-01A1), the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource Trang et al., Science 377, 839-845 (2022) 19 August 2022 6 of 7 RESEARCH | RESEARCH ARTICLE (NSF grant ECCS-1542205), the State of Illinois, and the International Institute for Nanotechnology (IIN). Gas chromatography MS was performed at the REACT Core Facility at Northwestern University, which acknowledges funding from the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Catalysis Science program (DE-SC0001329) used for the purchase of the GC/MS analysis system. Author contributions: Conceptualization: B.B.T., K.N.H., W.R.D.; Data curation: L.Y.L.; Formal analysis: B.B.T., L.Y.L., M.A.; Funding acquisition: K.N.H., W.R.D.; Investigation: B.B.T., L.Y.L.; Methodology: B.B.T., L.Y.L., K.N.H., W.R.D.; Project administration: K.N.H., W.R.D.; Supervision: X.S.X., K.N.H., W.R.D.; Visualization: B.B.T., L.Y.L.; Writing - original draft: B.B.T., L.Y.L., K.N.H., W.R.D.; Writing - review & editing: B.B.T., L.Y.L., X.S.X., M.A., K.N.H., W.R.D. Competing interests: Northwestern University has filed a provisional patent (63/261,772) that describes methods to degrade PFCAs on behalf of inventors B.B.T. and W.R.D. W.R.D. is a founder and equity holder in Cyclopure, Inc., which is commercializing technologies related to PFAS detection and remediation. Cyclopure is uninvolved in the research described in this manuscript. The remaining authors declare no competing interests. Data and materials availability: All data are available in the manuscript or the supplementary materials. License information: Copyright 2022 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. https://www.science.org/ about/science-licenses-journal-article-reuse SUPPLEMENTARY MATERIALS science.org/doi/10.1126/science.abm8868 Materials and Methods Supplementary Text Figs. S1 to S66 Tables S1 to S4 Data S1 References (36-57) Submitted 19 October 2021; resubmitted 19 April 2022 Accepted 8 July 2022 10.1126/science.abm8868 Trang et al., Science 377, 839-845 (2022) 19 August 2022 7 of 7 pubs.acs.org/estwater Article Application of Supercritical Water Oxidation to Effectively Destroy Per- and Polyfluoroalkyl Substances in Aqueous Matrices Christopher G Scheitlin,* Kavitha Dasu,* Stephen Rosansky, Lindy Espina Dejarme, Dinusha Siriwardena, Jonathan Thorn, Larry Mullins, Ian Haggerty, Krenar Shqau, and Julia Stowe Cite This: ACS EST Water 2023, 3, 2053-2062 Read Online Downloaded via 186.209.45.98 on September 12, 2023 at 15:03:35 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. ACCESS Metrics & More Article Recommendations *si Supporting Information ABSTRACT: Supercritical water oxidation (SCWO) is a destruction technology to treat per- and polyfluoroalkyl substance (PFAS)-impacted groundwater, investigation-derived waste, and other aqueous matrices such as landfill leachate and aqueous film-forming foam. A SCWO system, Battelle's PFAS AnnihilatorTM, was optimized with a goal of reducing all measured PFAS to non-detect levels. Laboratory-prepared and field-collected samples with inlet PFAS concentrations up to 50 ppm were consistently destroyed to less than 70 ppt for all PFAS, when running at the determined optimal operating conditions (600 C and 3500 pounds per square inch). We investigated the correlation between temperature and flowrate of the system, finding that reactor temperatures 450 C destroy perfluorinated carboxylic acids, but temperatures of 575 C are necessary to destroy perfluorosulfonic acids. A continuous 5-log reduction in concentration of PFAS (99.999% destruction) is demonstrated for 3 h at steady-state operation. The destruction efficiency is not impacted by the addition of cocontaminants such as petroleum hydrocarbons, and volatile organic compounds. The treated effluent is largely composed of complete combustion products including carbon dioxide, water, and the corresponding anion acids; hence, the treated liquid can be released back into the environment after neutralization. KEYWORDS: supercritical water, oxidation, per- and polyfluoroalkyl substances, defluorination, AFFF, SCWO, PFAS INTRODUCTION Per- and polyfluoroalkyl substances (PFAS) are man-made fluorinated hydrocarbons used in many applications since the 1940s due to their unique physical and chemical properties including being hydrophobic and oleophobic and having a low surface tension.1 In addition, the presence of strong carbonfluorine bonds provides extremely high chemical and thermal stabilities.1,2 PFAS are widely used for commercial and industrial applications, including in aqueous film-forming foam (AFFF) for fire-training and fire-fighting operations in emergency response, manufacturing facilities for surface coatings, and mist suppressants in metal-plating operations, among others.1 Due to their extensive applicability, PFAS have been ubiquitously detected in environmental media, human serum, and biota.3-7 The bioaccumulation of these compounds has gained global attention due to potential health risks such as a decline in thyroid levels, decreased vaccine antibody response, and organ toxicity.8-18 This has led to some PFAS being listed as persistent organic pollutants (POPs) under the Stockholm Convention.19 Considering the chronic health risks associated with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), the United States Environmental Protection Agency (U.S. EPA) established a preliminary remediation goal of 70 ng/L (or parts per trillion, ppt) in December 2019 for PFOS and PFOA in groundwater that is used as a source of drinking water.16 In May 2022, the U.S. Environmental Protection Agency (EPA) announced the addition of five new PFAS to the list of regional screening levels (RSLs). These include PFOS, PFOA, perfluornonanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and hexafluoropropylene oxide dimer acid (HFPO-DA). These PFAS are in addition to perfluorobutane sulfonic acid (PFBS), which was added to the RSLs in 2014 and updated in 2021.20 Multiple U.S. states have recently published or are proposing PFAS levels for monitoring, notification, and/or cleanup at or below 70 ppt.21-23 Recently, the EPA proposed to designate PFOA and PFOS, including their salts and structural isomers, as hazardous substances under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) to Received: October 27, 2022 Revised: April 27, 2023 Accepted: April 28, 2023 Published: May 15, 2023 2023 The Authors. Published by American Chemical Society 2053 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.org/estwater Article facilitate cleanup of contaminated sites and to reduce human exposure to these chemicals.24 To meet this goal, studies have evaluated a variety of conventional and advanced technologies for PFAS removal from and/or degradation in water. Conventional remediation techniques, such as oxidation using peroxide or persulfate and bioremediation, have had limited effectiveness.25-30 Application of conventional granular activated carbon adsorption and ion exchange resin are a challenge due to differing chemical and physical properties of distinct PFAS, as shorter chain PFAS tend to break through faster which necessitates the faster change out or regeneration of the sorbents.31 Several effective PFAS treatment methods are being developed, but most have only been tested at the laboratory scale with few field applications.32 Some technologies under development include sorption using carbonbased materials (biochars and nanotubes) and/or other novel sorbents, removal by ion exchange, advanced oxidation processes (AOPs; electrochemical oxidation, photolysis, photocatalysis, activated persulfate oxidation, and ultraviolet (UV)induced oxidation), advanced reduction processes (ARPs; potassium iodide (KI) combined with UV), thermal (thermal chemical reaction, microwave hydrothermal, and incineration), chemical/electrical treatment (sonochemistry, electrical discharge plasma, and high-voltage electric discharge), and microbial treatments.28,32-43 Many of these technologies have been shown to produce short-chain PFAS as byproducts or exhibit selective destruction of only perfluorinated carboxylates (PFCAs) and partial mineralization of perfluorinated sulfonates (PFSAs).37,38,44,45 Reductive methods reported in the literature for the destruction of PFAS have been shown to follow defluorination mechanisms by the cleavage of carbon-fluoride bonds. Due to the high reduction potential of hydrated electrons (-2.9 V), reductive defluorination involving hydrated electrons has been shown to be effective for PFAS destruction.46-49 Reductive methods have been shown to be generally more efficient than oxidative methods, requiring very little energy to initiate breakage of the carbon-fluoride bond. This efficiency makes reductive methods attractive compared to energy-intensive oxidative methods such as SCWO; however, reductive methods are not consistently showing degradation of all PFAS compounds to ppt concentrations.50,51 Degradation was slow and incomplete for perfluorinated sulfonates (PFHxS and PFOS), and most of these reported methods are laboratory scale with many limitations to the fullscale application of these processes. Hydrated electrons are short lived and require anoxic conditions. The presence of oxygen and water chemistry (bicarbonates, nitrates, chloride ions, and humic acids) in environmental aqueous matrices quenches the hydrated electrons generated and hence results in suppression of PFAS destruction.46,50-52 Recent interim guidance released by the U.S. EPA for the planned research and development on destruction and disposal technologies for PFAS and PFAS-containing materials mentions supercritical water oxidation (SCWO) as one of the promising innovative technologies for the destruction of PFAS in AFFF.53 SCWO involves oxidation of aqueous organic compounds at temperatures and pressures above the critical point of water in the presence of oxygen.54,55 This technology has shown rapid and near-complete destruction of several recalcitrant organic contaminants including polychlorinated biphenyls, radioactive waste, and certain nerve agents.54,56,57 The SCWO process involves reacting the dissolved organic contaminant with an oxidant in water at a temperature and pressure above the supercritical point of water (374 C and 3205 pounds per square inch [psi]). At these conditions, the water and organics become miscible and form a uniform homogeneous mixture, which results in changes in their properties and provides a single fluid phase of a water-oxygen-organic mixture. The reaction of organic molecules with oxygen generates environmentally benign end products, such as water, carbon dioxide, and inorganic salts.58 These benefits promote SCWO as a promising technology to treat PFAS despite the unique chemical and physical properties of these compounds.44,57,59 SCWO is an energy-intensive process, which operates at high temperature and high pressure. Continuous operation under high oxidizing conditions poses challenges such as salt plugging and corrosion of the reactor construction materials. However, these challenges can be managed by taking special consideration while choosing the construction materials capable of withstanding oxidizing environments to mitigate corrosion and special reactor designs to handle the salt formation and prevent salt plugging.60 The continued development of effective technologies, such as SCWO, for the complete destruction of PFAS is critical to meet the recent U.S. EPA guidance and state regulations.53 In this study, the operating conditions and destruction performance of a SCWO continuous reactor (hereafter referred to as PFAS Annihilator) were evaluated and found to have several benefits for environmental remediation and waste management industries. The PFAS Annihilator consistently achieves near-complete destruction of PFAS, bringing the concentrations down to non-detect for most target PFAS, and consistently down to less than 70 ppt for all PFAS in under 30 s. This technology can be used to treat material contaminated with PFAS and other substances such as petroleum hydrocarbons or chlorinated solvents, which are also readily oxidized.55 Moreover, SCWO can be applied to a variety of PFAS-impacted liquids such as AFFF, landfill leachate, and investigation-derived waste (IDW) due to its non-targeted carbon-fluorine bond destruction.44,59 The treated effluent is largely composed of the products of complete combustion including carbon dioxide and water and the corresponding anion acids; hence, the treated liquid can be released back into the environment after neutraliza- tion.56 MATERIALS AND METHODS Chemicals and Reagents. Laboratory-prepared feeds were spiked with technical-grade PFOA (98% purity), and PFOS (98% purity), along with lower amounts of PFBA, PFPeA, PFHxA, PFHpA, PFDA, PFUnDA, PFDoDA, 8:2 FTS, N-MeFOSAA, N-EtFOSAA, L-PFBS, and PFBS (Synquest Laboratories [Alachua, FL], Sigma-Aldrich [St. Louis, MO] and Wellington Laboratories [Ontario, Canada]) (Table S1). Volatile organic compounds (VOCs; 1,1-dichloroethene, benzene, tetrachloroethene, toluene, and trichloroethene) (SPEX CertiPrep, Metuchen, NJ) and diesel fuel (Turkey Hill, OH) were added as co-contaminants. Final concentrations in the inlet feed were determined through PFAS, total organic carbon (TOC), and VOC analysis. The full lists of PFAS and organic compounds evaluated are shown in Tables S1 and S2, respectively, but only detected compounds are presented in the figures for visual clarity. Optima grade methanol (99.9% purity) (Sigma-Aldrich) and certified American Chemical Society grade acetone (99.5% assay) and ammonia (7 N solution in methanol) (Fisher Scientific 2054 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.org/estwater Article Figure 1. PFAS Annihilator process flow diagram showing flow paths, sample heating, reactor location, and sample cooling prior to collection of the effluent samples at the sampling port. [Pittsburgh, PA]) were used to clean the reactor between trials. Hydrogen peroxide (H2O2) from Sigma-Aldrich was used as the oxygen source, and monobasic sodium hydroxide (NaOH) from Sigma-Aldrich was added to the process to neutralize the effluent stream. Deionized (DI) water was produced in house via a two-tank deionizing system in parallel, installed, and maintained by AmeriWater (Dayton, OH). SCWO Reactor. The bench-scale PFAS Annihilator is comprised of a tubular reactor heated by an Accurate Thermal Systems (Hainesport, NJ) sand bath. A tube-in-tube heat exchanger was used to preheat the feed and recover heat after the reaction. Additional cooling of the reactor effluent was performed using a cooling drum supplied with potable water. A custom-designed gas-liquid separator was used to separate the treated aqueous effluent from the generated vapor. The feeds, oxidant, and neutralization solutions were pumped through the PFAS Annihilator utilizing Shimadzu (Columbia, MD) LC 20AP preparative pumps. Pressure was monitored throughout the system with inline Swagelok (Solon, OH) 6000 psi pressure gauges. Pressure was maintained in the system utilizing a Tescom (Elk River, MN) 4000 psi back pressure regulator. Effluent pH was measured using a Sensorex (Garden Grove, CA) TX100 inline pH meter. Temperatures were measured with inline Type K thermocouple probes (Omega, Norwalk, CT). A schematic of the PFAS Annihilator used to evaluate the destruction of PFAS is shown in Figure 1. The temperature readings were output to a BrainChild PR20 data logger (CAS Dataloggers, Chesterland, OH). Due to the high temperatures and pressure operating conditions and the generation of hydrofluoric acid, a high nickel alloy (Alloy 625) that is highly resistant to corrosion was used for all hot and pressurized components of the system. No glassware or other laboratory ware is used anywhere in the system or in the handling of samples destined for PFAS analysis to mitigate the potential for PFAS loss to glassware as is well documented.61,62 Laboratory Samples. Laboratory-prepared inlet samples were composed of PFAS, petroleum hydrocarbons, and/or VOCs prepared in DI water, followed by sonication for at least 1 h. Field Samples. Upon receipt, all field samples were analyzed for PFAS, VOCs, TOC, and anions as described in sample analysis. The TOC and PFAS concentrations were used to calculate an appropriate oxidant dosing for the field sample. The field sample detailed in this report was run through the PFAS Annihilator without any preprocessing or preparation. SCWO Operating Conditions. At the beginning of each run, the SCWO reactor was allowed to reach its equilibrium temperature (10 C) running DI water at 3500 psi (200 psi). The oxidant solution was prepared to achieve 100% excess oxygen in the system, calculated assuming complete combustion of the TOC and/or total target PFAS in the feed. Either the liquid oxidant (H2O2) or the dissolved gaseous oxygen was pumped via a secondary Shimadzu LC-20AP preparative pump into the system upstream of the reactor at 3500 psi along with the feed/sample stream. A neutralization solution (NaOH) was prepared such that an effluent pH of 5 to 7 was achieved while ensuring the neutralization flow did not exceed 7% of the total system flowrate. The feed and oxidant were introduced into the PFAS Annihilator at their specified flowrates after the system temperature stabilized. The vapor stream, primarily consisting of carbon dioxide and excess oxygen, was separated from the aqueous stream in a gas-liquid separator and sampled by C18 cartridges and impingers prior to being discharged into the laboratory hood. The liquid effluent samples were collected from the sampling port as labeled in Figure 1. After each run was completed, the system was immediately flushed with DI water and/or low-concentration oxidant. After cooling, the system was rinsed with DI water, methanol, and then again with DI water. For runs with a high concentration of PFAS or where operating conditions were not optimal for PFAS destruction, ammonia in methanol and/or acetone was also used to clean the system. Sample Analysis. All samples were analyzed for PFAS at Battelle's accredited laboratory, using isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS). Transformation byproducts formed during SCWO were analyzed using a Waters Acuity I-class UPLC Sample Manager coupled to a Quadrupole time-of-flight mass spectrometer, TripleTOF/MS 5600 (AB Sciex, Framingham, MA) at Battelle's Laboratory. The aqueous influent, effluent, and equipment blanks, and gaseous effluents (methanol extracts of 2055 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.org/estwater Article C18 cartridges and impinger) were investigated for transformation byproducts. Details of all analytical methods for PFAS are described in the Supporting Information. To characterize fluorine changes, influent and effluent samples were analyzed using 19F-nuclear magnetic resonance (NMR) spectroscopy at Battelle's Laboratory. The 19F NMR spectra were obtained with a Bruker AVANCE NEO 500 MHz NMR spectrometer equipped with a broadband observe probe with gradients in a mixture of water and deuterium oxide as the solvent. Chemical shifts were reported relative to CFCl3 (0 part per million [ppm]). Fluoride was also commercially evaluated by anion analysis using U.S. EPA Method 300. TOC and VOCs were commercially analyzed using U.S. EPA Methods 9060A and 8260C, using samples collected in volatile organic analysis vials preserved with phosphoric acid and hydrochloric acid, respectively. Data Analysis. The relative change of PFAS, fluoride, TOC, and VOCs was determined by comparing the inlet and effluent concentrations of the system. Equations for percent destruction and defluorination can be found in eqs 1 and 2. This analysis assumes that little, if any, accumulation of compounds occurred in the SCWO system for accurate representation of compound destruction/production. The reported effluent concentrations are those directly measured exiting the reactor without correcting for dilution from the addition of the oxidant or neutralization solutions. This provides an accurate representation of the reactor discharge. Since the feed sample is diluted by less than 15% when using H2O2 as the oxidant, the concentration changes reported are representative of the reactor performance and are not due to significant dilution of the feed stream. %destruction ( ) effluent concentration of PFAS ng L ( ) = inlet PFAS concentration as organofluorine ng L 100 (1) %defluorination ( ) effluent inorganic fluoride ng L ( ) = inlet PFAS concentraiton as organofluorine ng L 100 (2) To simplify the data presentation when the concentration of many PFAS are being reported, the PFAS are classified as PFCAs, PFSAs, and precursors/intermediates as defined in Table S1, and the raw concentration values of each measured PFAS compound are then tabulated in the Supporting Information. RESULTS AND DISCUSSION Using the laboratory-spiked inlet samples, the effects of oxidant type, temperature, and residence time on the SCWO destruction of PFAS were evaluated. Impact of the Oxidant Type on PFAS Destruction. Two oxidant sources, dissolved oxygen in water and H2O2, were used to provide at least 100% excess oxygen in independent tests. In the initial investigation, H2O2 provided equivalent or superior destruction of all measured PFAS, including PFCAs (PFBA, PFPeA, PFHxA, PFHpA, and PFOA) and PFSAs (PFBS, PFPeS, PFHxS, PFHpS, and PFOS) compared to dissolved oxygen as the oxidant source when operating at 3500 psi and 600 C (Figure 2). Both Figure 2. PFAS destruction with H2O2 as the oxidant is equivalent or superior to the PFAS destruction when using dissolved oxygen as the oxidant. System operating at 600 C, 3500 psi, and 50 mL/min. oxidants caused a similar 4 to 6 log reduction in the concentration of the total effluent PFAS relative to the total inlet concentration of 11.3 ppm. In both cases, only the two compounds having the highest concentrations in the inlet (PFOA and PFOS) were still present at over 100 ppt in the effluent; The other measured compounds were not detected or were detected at less than 3 ppt. H2O2 has about 1000 higher oxygen density than oxygen dissolved in water at 100 psi, dramatically reducing the required volume of oxidant added to the feed stream and reducing the combined reactor volumetric flowrate by 5. This greatly reduces the volume of water that must be heated when operating the reactor, reducing energy requirements and cost of operation. Other researchers have also observed accelerated oxidation performance with H2O2 compared to oxygen on organic contaminants.55,63 This is due to the high activation energy of O2 oxidation and the slow conversion of O2 and H2O that requires three steps to produce OH radicals as shown in eq 3 through eq 5.63 Alternatively, the decomposition of H2O2 to OH radicals is direct (eq 5).63 Due to the equivalent or improved destruction of PFAS when using H2O2 in this study and in the literature, H2O2 is used as the oxidant source for the remaining tests. CF3(CF2)nRH + O2 CF3(CF2)nR + HO2 (3) CF3(CF2)nRH + HO2 CF3(CF2)nR + H2O2 (4) H2O2 2OH (5) Impact of Residence Time and Temperature on Performance. The combination of elevated temperature and residence time provides enough energy to overcome the activation energy to cleave the carbon-fluorine bond to degrade PFAS to produce carbon dioxide (CO2) and hydrofluoric acid (HF). A generic reaction is shown in eq 6 using PFOA as an exemplar PFAS. C8HF15O2 + 7H2O2 15HF + 8CO2 (6) To determine the optimal operating conditions, influent and effluent concentrations of PFAS were measured at four flowrates in 25 C increments from 450 to 625 C. At least 85% of total PFAS were destroyed under all tested conditions. Between the operating temperatures of 450 and 525 C, the reactor operated in this 85% destruction efficiency regardless of flowrate. A similar observation was made by other 2056 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.org/estwater Article researchers studying the batch-scale reactions of PFOS, where the highest PFAS destruction was observed at 500 C, and the reaction at this temperature was independent of the residence time; therefore, it was concluded that temperature is the key parameter for PFAS destruction.44 However, the current study expanded to higher temperatures using a flow through system. This setup shows that further elevated temperatures allowed the reaction to destroy >99% of PFAS. Destruction of PFAS is inversely dependent on residence time or indirectly dependent on the reactor flowrate. At temperatures 525 C, slower flowrates show improved PFAS destruction. A slower flowrate also achieves maximum destruction at lower temperatures compared to reactions run at higher flowrates. At 550 C, the slowest tested flowrate (60 mL/min) showed an additional 1- to 2-log reduction in the effluent PFAS concentration than seen at any of the other tested flowrates (100, 140, and 190 mL/min). At 575 C, the 60 mL/min flowrate achieves the maximum PFAS destruction (about 5-6 log reduction). Increasing flowrates at this operating temperature (575 C) reduced PFAS destruction efficiency. Further increasing the temperature allowed higher flowrate streams to also achieve the maximum PFAS destruction. However, the reactor was unable to maintain a temperature of 625 C at 190 mL/min due to the energy transfer required to heat the high influent flowrate. Figure 3 Figure 3. Effect of temperature and residence time on PFAS destruction. summarizes these data. The concentration of all 24 PFAS from each of two sequential samples collected at each set of conditions is shown in Table S4. Interestingly, the nonsulfonated PFAS (PFCAs) showed complete defluorination at all temperatures and flowrates evaluated, while the sulfonated acids (PFSAs) required a higher temperature and residence time to be defluorinated. The degradation of the PFCAs makes up nearly all the destruction seen at temperatures 500 C. Estimated Reaction Kinetics. The reactor flowrates were converted to residence times to estimate the reaction kinetics for the degradation of PFAS within the reactor. The residence time at each data point shown in Figure 3 is unique because under supercritical conditions, the reaction temperature has a notable impact on density, leading to variable residence times for a consistent volumetric flowrate. The reaction rates were estimated using the PFAS compounds whose concentrations were above the limit of quantitation (LOQ) for all four tested residence times, which only included PFSAs (all PFCAs were destroyed under all test conditions). A reactor operating temperature of 575 C was used for these calculations because it shows the greatest disparity in the destruction efficiency of PFAS over the tested flowrate range. At lower or higher temperatures, the reaction is either not at all impacted by the residence time, or there is only one data point that is not at either the maximum (Ct/C0 1 10-5) or minimum (Ct/C0 1 10-1) destruction, meaning that there are not sufficient data points sampled to properly estimate the kinetics at those temperatures. Figure 4 indicates first-order reaction kinetics at 575 C and provides rate constants (k) of 0.51, 0.49, and 0.48 for PFOS, PFHxS, and PFHpS, respectively. Figure 4. Natural logarithmic ratio in the effluent PFAS concentrations at four residence times. The first-order reaction equation for PFSA destruction is shown in eq 7. Although not shown in Figure 4, shorter chain PFSAs and all PFCAs proceeded to non-detect (ND) quickly, which prevented an accurate rate calculation for those compounds (Table S4). ln(A) = ln(A0) kt (7) Steady-State Operation. To determine the startup and steady-state operation of the PFAS Annihilator, the system was operated for 3 h with effluent samples collected every 20 min. These samples were analyzed to measure the loss of target PFAS and the generation of inorganic fluoride. The concentration of PFAS in the effluent decreased by 4 orders of magnitude within 20 min of introducing the feed solution, while the effluent fluoride concentration increased dramatically. The concentration of PFAS was reduced by another order of magnitude after another 20 min of operation, while the fluoride remained at nearly the same level (Figure 5). This is expected as there is a diminishing return in total generated fluoride as the concentration of PFAS undergoes further log reductions. The large increase in fluoride concentration in the effluent suggests mineralization of PFAS by defluorination during the SCWO treatment. In addition, 19F NMR analysis of influent and steady-state effluent samples further supports this finding. There is an increase in the inorganic F peak in effluent spectra, and disappearance of organofluorines (F attached to carbons) resulting from defluorination of PFAS (Figure S1). Although 19F NMR spectra represent a qualitative analysis, disappearance of the organofluorine peaks further demonstrates the complete defluorination of PFAS. The reactor showed a slight 15 C decrease in the effluent temperature for the first 40 min of operation, which was recovered and even slightly elevated by 60 min of continuous operation. By 60 min of continuous operation, all measured parameters had reached a steady value and remained constant for the remaining 120 min of testing, suggesting about a 1-h time to steady state for the PFAS Annihilator (Figure 5). Additionally, the status of the reactor is well summarized by the temperature reading; When the reactor effluent temper- 2057 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.org/estwater Article Figure 5. Concentration of PFAS and fluoride ions in the effluent overlaid with the reactor effluent temperature. Figure 6. Measured PFCAs, PFSAs, PFAS precursors/intermediates, and co-contaminants in treatments (A) lab Sample, (B) lab sample with cocontaminants spiked at low level, (C) lab sample with co-contaminants spiked at high level, and (D) field sample. The concentrations of all PFAS compounds in the stream were less than 75 ppt after passing through the SCWO reactor. ature has re-equilibrated after the introduction of a sample, the SCWO system is operating at steady state and is achieving optimal PFAS destruction. Throughout this steady-state period, the total effluent PFAS concentration remained below 50 ppt, which is six orders of magnitude lower than the total inlet PFAS concentration of 22.8 ppm (99.9998% destruction). The most concentrated compound in the inlet (PFOA) was decreased by nearly seven orders of magnitude from 12.3 ppm to 3.83 ppt. The inlet and effluent concentrations for fluoride and for all 24 measured PFAS are provided in Table S5. Comparing the total inlet and effluent fluorine, a total of 72.6% of the total inlet fluorine (largely contained in the PFAS) is detected and quantified in the effluent as ionic fluoride. While this may indicate that some fluorine is accumulating within the reactor, the reactor was rinsed with water after testing to collect any fluorine sorbed onto the reactor surfaces. While some fluoride was detected (0.77 mg/ L), this totaled less than 0.5% of the total inlet fluorine, suggesting that the reaction byproducts are not accumulating within the reactor. The total target PFAS measured in the postrun water rinse was also low (27.0 ppt), further suggesting that undestroyed PFAS is not adhering to or building up on the reactor walls. These data suggest that neither PFAS nor the reaction product, fluorine, are accumulating within the reactor. In addition, the reactor surface residuals were collected and 2058 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.org/estwater Article analyzed via energy-dispersive spectroscopy (EDS) and X-ray diffraction (XRD) and show that there is no fluorine detected on these surfaces, further supporting the idea that PFAS are destroyed rather than accumulated or sorbed onto the reactor surfaces (Figure S2). Additional effort is underway to better understand the movement of fluorine through the reactor. Effect of Co-contaminants on PFAS Annihilation. The PFAS Annihilator has been demonstrated to greatly reduce the concentration of PFAS in laboratory-spiked samples (Figures 2, 3, 5); However, environmental samples are much more complex and can have a number of additional co-contaminants. In many of the Department of Defense (DoD) sites impacted by AFFFs due to fire-fighting or fire-training activities, it is common to find VOCs and total petroleum hydrocarbons (TPH) commingled with PFAS contamination.64 To evaluate the practicality of applying this technology to environmental remediation, a laboratory-spiked sample was prepared consisting of PFAS, TPH (low and high concentration), and VOCs (low and high concentrations). The low-concentration spiked sample was found to contain 1200 ppt of total organic contaminants, and the high-concentration spiked sample was found to contain 7,400,000 ppt of total organic contaminants. The measurable TOC concentrations are shown in the bottom row of Figure 6, and detailed data of all analytes are provided in Table S6. The results show that the destruction of PFAS is largely unaffected by the addition of organic cocontaminants when compared to the laboratory sample that was only spiked with PFAS (Figure 6A) and that the total concentration of co-contaminants also decreases (Figure 6B,C). This proves that SCWO is effective for co-contaminant treatment along with PFAS destruction. The total PFAS concentrations and the sum of PFOA and PFOS measured in the low-concentration effluent sample (Figure 6B) and the PFAS-spiked lab sample (Figure 6A) were 15.72 and 1.23 ng/ L, respectively, compared to 31.46 and 28.37 ng/L in the absence of co-contaminants. Overall, the destruction efficiency of PFCAs, PFSAs, and PFAS precursors was not affected by the presence of co-contaminants (Figure 6 and Table S6). This confirms that complexity of the feed stream does not alter the destruction efficiency of PFAS, and the results demonstrate effective destruction of co-contaminants in the PFAS-impacted IDW streams. The effluent vapor was similarly analyzed for PFAS. This analysis yielded no detectable levels of any of the 24 target PFAS, confirming that the influent compounds are being destroyed rather than escaping the system as a gas. The individually detectable co-contaminants were found to decrease to undetectable levels in both the low- and highconcentration spiked samples (Figure 6B,C), and all target organic compounds (and TOC when detected) decreased. This is an expected result as SCWO processes are not specific to breaking carbon-fluorine bonds. Carbon-carbon bonds are also expected to oxidize under the operating conditions of the PFAS Annihilator.55 Demonstration on an AFFF-Impacted IDW Sample. As a final proof of concept test, an AFFF-impacted IDW sample was run through the PFAS Annihilator. The field-collected sample with an initial total target PFAS concentration of 4.9 ppm was run directly through the SCWO reactor without any preprocessing, and a similar destruction efficiency of PFAS was achieved as the laboratory PFAS-spiked sample (Figure 6D). The resultant effluent total PFAS concentration was 10.2 ppt and the sum of PFOA and PFOS measured at 1.5 ppt showing six orders of magnitude reduction in PFAS (Table S6), demonstrating the PFAS Annihilator as a viable technology to destroy high concentrations of PFAS in AFFF-impacted IDW. Although there was a slight increase in the measured concentration of two VOCs from the influent to the effluent, both concentrations are below the method quantitation limit and may not be accurate. Another interesting finding was a decrease in dissolved fluoride as the field sample passed through the reactor (Table S6). This may be associated with the dramatic change in ion solubilities as water transitions from the sub to supercritical state. Methods to collect this precipitating material are underway and will allow further evaluation of this hypothesis. In all trials (PFAS spiked, PFAS and co-contaminants spiked, and field sample), PFCA, PFSA, and PFAS precursors/ intermediates show a similar level of destruction regardless of the complexity of the feed (Figure 6A-D). The total summation of measured PFAS concentration in the effluent sample of each of the laboratory and field samples was 75 ppt (ng/L) with no individual PFAS analyte concentration remaining higher than 70 ppt for any collected effluent sample. The influent and effluent PFAS concentrations for each of the samples presented in Figure 6 are tabulated in Table S6, which highlights the similarities in the effluent PFAS concentration that are achieved by the PFAS Annihilator from disparate inlet samples, demonstrating that the complexity of the feed stream does not alter the destruction of PFCAs, PFSAs, PFAS precursors/intermediates, or organic co-contaminants. Although no pretreatment was required for any of the tested samples and no clogging was observed in these tests, the underlying tubular reactor may be prone to clogging from samples with high concentrations of dissolved solids. The builtin pressure and flow monitors would have deviated from their steady-state operational conditions if appreciable build up were occurring. During long-term operations, processing much larger samples for weeks at a time, the potential reactor clogging could be mitigated with the use of inline devices (e.g., a supercritical salt trap65) or modified reactor designs66,67 to remove salts and other compounds that precipitate out of solution at supercritical conditions. Identification of Byproducts. Aqueous influent, effluent, and equipment blanks, and gaseous effluents (methanol extracts of C18 cartridges and impinger) were investigated for transformation byproducts using LC-qToF/MS analysis. Greater than 99% destruction of PFOA and PFOS was achieved in the effluent; hence, no longer chain PFAS were detected in the samples analyzed. Some unidentified short-chain byproducts were formed (Table S7 and Figure S3) and found to elute early on the total ion chromatography (TIC) chromatogram (Figure S3). These are very low-level findings relative to the targeted compounds, which were unquantifiable without analytical standards and were not consistently seen on every run. These data suggest that SCWO completely destroyed PFAS, instead of partial mineralization, which agrees with our previous data from the liquid effluents and reactor surfaces. Environmental Implications. The PFAS Annihilator tested here is demonstrated as a promising technology for the destruction of PFAS and other common co-contaminants typically found at AFFF-impacted fire-training sites. This research presents optimization of the reaction conditions for the complete destruction of PFAS. The oxidant type (O2 and H2O2), temperature (450-625 C), flowrate (60-190 mL/ min), and time to reach steady-state conditions were studied. 2059 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.orgiestwater Article The best operating conditions (600 C and 100 mL/min or 625 C and 140 mL/min) using H2O2 as the oxidant destroyed PFAS in laboratory-spiked solutions with initial concentrations ranging from 5 to 50 ppm to below 70 ppt levels in the resultant effluent. The optimized technology was then applied to three inlet sources (PFAS spiked with and without co-contaminants and a field sample) where it successfully reduced PFAS of different chemistries, chain lengths, and precursor presence by up to 6 orders of magnitude. These preliminary data and the impact of operational changes are valuable in upscaling SCWO systems for the destruction of PFAS in contaminated sources for environmental remediation. These data suggest that the destruction of PFAS using SCWO is independent of the oxygen source used in the reactor and that higher temperatures can be used to maintain destruction efficiency while increasing throughput. Many technologies for the treatment of PFAS-impacted IDW rely on separation techniques, which transfer PFAS from one media to another and therefore generate PFASconcentrated secondary waste streams (e.g., sorbents and ion exchange regenerated solvent concentrate, reverse osmosis reject, nanofiltration) that require further treatment or disposal. Incineration poses several challenges such as off-site transportation, concerns on the incomplete combustion of byproducts, high-energy requirements, immediate release of combustion products into the environment, and cost of operation.68 As no destruction methods are readily available for the long-term effective management of PFAS-impacted IDW and these secondary waste streams, SCWO provides an effective approach. SCWO is an energy-intensive process, but much of the expended energy can be recaptured through heat exchangers in a well-designed system. SCWO is also not appropriate for thick slurries (>50% solids) as they do not pump well through a reactor. The SCWO process demonstrated here is capable of directly processing a PFAS-impacted field sample, and the effluent can be released to the environment after confirmatory analysis. Further demonstration is on-going to prove pilot- and full-scale field deployments of the PFAS Annihilator at AFFF-impacted sites, landfill leachate, as well as the destruction of stockpiled AFFF concentrates. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsestwater.2c00548. Description of sample preparation and analytical methods; Figures of 19F NMR spectra; EDS/XRD characterization of reactor surface residual; and TIC overlay spectra; tables of listed PFAS analytes and other co-contaminants measured, their analytical methods; concentrations of PFAS and other co-contaminants measured entering and exiting the PFAS Annihilator SCWO reactor at different reactor operating temperatures and flowrates; and list of SCWO transformation byproducts and their respective fragments identified from PFOS and PFOA destruction and raw tabulated data (PDF) AUTHOR INFORMATION Corresponding Authors Christopher G Scheitlin -- Battelle Memorial Institute, Columbus, Ohio 43201, United States; orcid.org/0000- 0002-9620-6550; Email: @battelle.org Kavitha Dasu -- Battelle Memorial Institute, Columbus, Ohio 43201, United States; G orcid.org/0000-0001-8180-7217; Email:.@battelle.org Authors Stephen Rosansky -- Battelle Memorial Institute, Columbus, Ohio 43201, United States Lindy Espina Dejarme -- Battelle Memorial Institute, Columbus, Ohio 43201, United States Dinusha Siriwardena -- Battelle Memorial Institute, Columbus, Ohio 43201, United States Jonathan Thorn -- Battelle Memorial Institute, Columbus, Ohio 43201, United States Larry Mullins -- Battelle Memorial Institute, Columbus, Ohio 43201, United States Ian Haggerty -- Battelle Memorial Institute, Columbus, Ohio 43201, United States Krenar Shqau -- Battelle Memorial Institute, Columbus, Ohio 43201, United States Julia Stowe -- Formerly Battelle Memorial Institute, Columbus, Ohio 43201, United States; Present Address: AECOM, 1001 Bishop Street, Suite 1600, Honolulu, Hawaii 96813, United States (J.S.) Complete contact information is available at: https://pubs.acs.org/10.1021/acsestwater.2c00548 Author Contributions CRediT: Christopher Scheitlin data curation (equal), formal analysis (equal), investigation (equal), validation (equal), visualization (equal), writing-original draft (equal), writingreview & editing (equal); Kavitha Dasu conceptualization (equal), formal analysis (equal), methodology (equal), validation (equal), visualization (equal), writing-original draft (equal), writing-review & editing (equal); Stephen Rosansky conceptualization (equal), funding acquisition (equal), project administration (equal), visualization (equal), writing-original draft (equal); Lindy Espina Dejarme conceptualization (equal), investigation (equal), supervision (equal); Dinusha Siriwardena investigation (equal), writing-original draft (equal); Jonathon Thorn formal analysis (equal); Larry Mullins formal analysis (equal); Ian Haggerty formal analysis (equal); Krenar Shqau formal analysis (equal); Julia Stowe data curation (equal), investigation (equal), writing-original draft (equal). Funding This study was supported by Battelle Memorial Institute. Notes All authors were employees of Battelle Memorial Institute, which developed the PFAS Annihilator. The authors declare the following competing financial interest(s): All authors were employees of Battelle Memorial Institute, which developed the PFAS Annihilator(). ACKNOWLEDGMENTS We acknowledge the contribution of our colleagues at Battelle: Phil Denen and Jeff Cafmeyer for NMR analysis. 2060 https://doi.org/10.1021/acsestwater.2c00548 ACS EST Water 2023, 3, 2053-2062 ACS ES&T Water pubs.acs.org/estwater Article REFERENCES (1) Prevedouros, K.; Cousins, I. T.; Buck, R. C.; Korzeniowski, S. H. Sources, fate and transport of perfluorocarboxylates. Environ. Sci. Technol. 2006, 40, 32-44. (2) Kissa, E. Fluorinated Surfactants and Repellents, Second Edition; Taylor & Francis, 2001. (3) Dasu, K.; Xia, X.; Siriwardena, D.; Klupinski, T. P.; Seay, B. 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