Document G6nM4YYrKZooRrQED262pxVbn
SUPPLEMENTAL DATA A Critical Review of the Application of Polymer of Low Concern
and Regulatory Criteria to Fluoropolymers
Barbara J. Henry**, Joseph P. Carlin*, Jon A. Hammerschmidtt, Robert C. Bucks, L. William Buxton*, Heidelore Fiedle0, Jennifer Seed', and Oscar Hernandez#
tW. L. Gore & Associates, Inc., Elkton, MD, 21921, USA *The Chemours Company, 1007 Market Street, Wilmington, Delaware, 19899, USA MTM Research Centre School of Science and Technology, Orebro University, Orebro Sweden 'Risk Assessment Consultant, Alexandria, VA, 22301-1603, USA #Bergeson & Campbell, Washington, DC 20037, USA
*Corresponding Author: email:
@wlgore.com; Tel.
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Contents
Glossary of Terms.................................................................................................................................... 3 PFAS & Fluoropolymers ........................................................................................................................... 4 Fluoropolymer Primer ............................................................................................................................. 6
Figure S1. Where Does PTFE Come From?........................................................................................... 6 Low MW Leachables: Ingredients used in the Manufacture of Fluoropolymers .................................... 7 Table S1: PTFE Polymerization and Post Polymerization Aids .............................................................. 7 Figure S2. Fluoropolymer Primer - PTFE Polymerization Scheme ........................................................ 9 Figure S3. Fluoropolymer Primer - PTFE Finishing Scheme................................................................ 10 Table S2: Alterative Fluoropolymer Processing Aids - Sources of Data .............................................. 11 U.S. EPA - Hazard Determination for a Polymer..................................................................................... 12 Polymers are too large to penetrate cell membranes ............................................................................ 14 Water Solubility................................................................................................................................. 14
Table S3 Solubility Table from USP 34 NF29 General Notices, Section 5.3.0, p6.............................. 14 Representative SMLs for Fluoropolymers .............................................................................................. 15
Table S4. EU Specific Migration Limits (SMLs) for Monomers in Representative Fluoropolymers (in mg monomer/kg food)................................................................................................................... 15 ISO 10993 Biocompatibility Tests........................................................................................................... 15 Additional text describing the 10993 Biocompatibility Tests. ............................................................. 15 Evaluation of PTFE in Medical Devices ................................................................................................... 16 Table S5. Biocompatibility Tests, Conditions and Acceptance Criteria Results for ePTFE patch ...... 17 Polymer of Low Concern (PLC) Assessment Criteria ............................................................................... 27 Molecular Weight (MW), Number Average Molecular Weight (Mn) and Molecular Weight Distribution (MWD) .............................................................................................................................................. 27 Figure S2. An FEP Fluoropolymer Molecular Weight Distribution - from a rheological study ......... 28 Reactive Functional Groups (RFG) and RFG Ratio to MW (FGEW)....................................................... 28 Table S6: US EPA's Chemical Categories of Concern, 2010 ............................................................. 29 PTFE Fine Powder Resin Extractable and Leachable Analytical Report for Polymer of Low Concern Concept................................................................................................................................................. 31 References ............................................................................................................................................ 55
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Glossary of Terms
TERM Biocompatible e-PTFE ETFE FEP Fluoropolymer
Fluorinated Polymer
Fluoroelastomer Fluorochemical
Fluorosurfactant
Food Contact Material (FCM)
Functional Group Equivalent Weight (FGEW) HFP Homopolymer Modified Homopolymer Oligomer PAVE PPVE PFA PTFE PVDF PVF PFPE Perfluoroalkyl acid (PFAA)
DEFINITION the ability of a material to perform with an appropriate host response in a specific application. (Williams, 1987). expanded polytetrafluoroethylene ethylene-tetrafluoroethylene co-polymer fluorinated ethylene-propylene; a co-polymer of tetrafluoroethylene (TFE) and hexafluoropropylene (HFP) a distinct subset of fluorinated polymers, namely, those made by (co)polymerization of olefinic monomers, at least one of which contains F bound to one or both of the olefinic C atoms, to form a carbon-only polymer backbone with F atoms directly attached to it, e.g., polytetrafluoroethylene (Buck et al., 2011) the broad generic term to encompass all polymers for which one or more of the monomer units contains the element F, in the backbone and/or in side chains. Fluorinated polymers may or may not be PFAS, depending on whether they contain perfluoroalkyl moieties (Buck et al., 2011) An elastic rubber-like polymer to which fluorine is bound. Fluoroelastomers are highly durable and resistant to heat, oils, solvents, fuels, and ozone. a general, nonspecific name that describes a universe of organic and inorganic substances that contain at least 1 F atom, with vastly different physical, chemical, and biological properties. Synonyms include "fluorinated substance" and "fluorinated chemicals." (Buck et al., 2011) A substance used to lower aqueous surface tension in which the hydrophobic portion contains F bound to C, often as a perfluoroalkyl moiety, often referred to as ``fluorinated surfactants'', ``fluorosurfactants,'' ``fluorinated tensides,'' or ``fluorotensides'' (Buck et al., 2011) is made with the FCS (any substance that is intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use of the substance is not intended to have any technical effect in such food) and (usually) other substances. It is often (but not necessarily) a mixture, such as an antioxidant in a polymer. The composition may be variable. (https://www.fda.gov/Food/IngredientsPackagingLabeling/Definitions/default.htm) the ratio of the molecular weight to the number of occurrences of that functional group in the molecule. It is the weight of substance that contains one formulaweight of the functional group. (40 CFR 723.250(b)) hexafluoropropylene: CF3CF=CF2 a polymer made with one monomer only polymers containing not more than 1% by weight of other fluoromonomers. (ASTM D4895 Standard Specification for Polytetrafluoroethylene (PTFE) Resin Produced From Dispersion section 1.1) a polymer molecule consisting of only a few monomer units (dimer, trimer, tetramer) (40 CFR 723.250(b)) perfluoroalkyl vinyl ether (generic name) in which the alkyl group is methyl, ethyl or propyl perfluoropropyl vinyl ether CF3CF2CF2-O-CF=CF2 perfluoroalkoxy polymer (generic name) Polytetrafluoroethylene polyvinylidene fluoride -(CF2CH2)npolyvinyl fluoride -(CFH-CH2)nA perfluoropolyether is a polymer in whose backbone -CF2-, -CF2CF2-, and possibly -CF(CF3)CF2- units are separated by O atoms (Buck et al., 2011) long-chain perfluoroalkyl acids, include perfluoroalkyl carboxylic, sulfonic, sulfinic, phosphonic, and phosphinic acids which are highly persistent
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PFAS
PFECA PFSA PFCA Polymerization processing aid (PPA)
Polymer of Low Concern (PLC) Reactive Functional Group (RFG)
Specific Migration Limit (SML) Migration Limits TFE
substances, such as PFOA or PFOS. They are released into the environment directly or are formed indirectly from the environmental degradation or metabolism of precursor substances (Buck et al., 2011) a very diverse group of per- and poly-fluoroalkyl substances including the class of polymers (fluoropolymers, perfluoropolyethers, side chain fluorinated polymers) and non-polymers (perfluoroalkyl substances for which all hydrogens on all carbon not associated with functional groups have been replaced by fluorines, and polyfluoroalkyl substances for which all hydrogens on at least one, but not all, carbon have been replaced by fluorines). (Buck et al., 2011) Per- and poly-fluoroether carboxylate perfluoroalkyl sulfonic acid: F(CF2)nSO3H perfluorocarboxylic acid: F(CF2)nCOOH A substance (e.g., catalyst, stabilizer, surfactant) added to the reactor vessel from 0.01% to 0.5% of the weight of water, depending on the rate and degree of reaction (Ebnesajjad, 2000) a polymer deemed to have insignificant environmental and human health impacts (OECD, 2009). 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. is the maximum permitted amount of substance (e.g., monomer) in food that has been determined to not pose a risk to human health
tetrafluoroethylene: CF2=CF2
PFAS & Fluoropolymers
The very broad term PFAS, per- and poly-fluoroalkyl substances, describes a very large universe of substances with very different properties. (See Buck et al., 2011.) The term "PFAS" was created in the context of focus on long-chain perfluoroalkyl acids (PFAAs, such as PFOS) and their precursors as a way to talk about substances that were relevant including alternatives, all of which have the requisite perfluoroalkyl moiety and are aliphatic. The environmental concern focus was (and is) on PFAAs and things that can turn in to them (aka precursors). The term PFC or PFCs has been erroneously used somewhat synonymously with the term PFAS. The term PFC was defined in the 1980's and codified by industry, regulators (including the U.S. EPA) and NGOs (including Greenpeace) to mean perfluorocarbons in the context of global warming and the Kyoto Protocol.
The long-chain perfluoroalkyl acids (PFAAs, such as perfluorooctanoic acid and perfluorooctane sulfonate) are highly fluorinated, small enough to be bioavailable, mobile and persistent. As such, these PFAAs and precursor substances (that may degrade to form PFAAs under normal foreseeable use and environmental conditions) are PFCs of environmental concern. Although not all PFAS are of environmental concern (e.g., PTFE fluoropolymer is highly stable, too large to be bioavailable, practically insoluble in water, and does not degrade in the environment) some PFAS are hazardous (e.g., PFOA), that is, some are highly persistent and have the potential to become widely dispersed in water, where they will remain for multiple generations.
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PFAS definition (See Buck et al., 2011.):
"PFASs are aliphatic substances containing one or more carbon atoms on which all the hydrogen substituents present in the non-fluorinated analogs from which they are notionally derived have been replaced by fluorine atoms, in such a manner that PFASs contain the perfluoroalkyl moiety CnF2n+1."
Two essential functional attributes of a PFAS substance are that it is aliphatic and has a perfluoroalkyl moiety CnF2n+1. o This means that a PFAS substance contains, at minimum, a CF3- functional group o Also, PFASs are defined as aliphatic. This means that substances with a CnF2n+1moiety bound to an aromatic ring such as is present in many drug and pesticide actives are not PFASs.
Perfluoroalkyl Substances (See Buck et al., 2011.):
"defined as aliphatic substances for which all of the hydrogen atoms attached to carbon atoms in the non-fluorinated substance from which they are notionally derived have been replaced by fluorine atoms, except those hydrogen atoms whose substitution would modify the nature of any functional groups present."
Polyfluoroalkyl Substances (See Buck et al., 2011.):
"defined here as aliphatic substances for which all hydrogen atoms attached to at least one (but not all) carbons have been replaced by fluorine atoms, in such a manner that they contain the perfluoroalkyl moiety CnF2n+1 (e.g., C8F17CH2CH2OH). Thus, while the general chemical concept of "polyfluorination" embraces compounds containing "scattered" multiple fluorine atoms (such as in CH2FCHFCHFCH2OH), as well as "grouped" ones (such as in CF3CF2CH2COOH), we consider that only those polyfluorinated substances having at least one perfluoroalkyl moiety CnF2n+1belong to the PFAS family." The key functional attribute of a PFAS substance is the perfluoroalkyl moiety CnF2n+1-. This functional group is THE critical structural element that defines a PFAS substance.
Fluoropolymers (See Buck et al., 2011.):
Fluoropolymers are a distinct class of polymeric PFAS based on their common chemical structure as well as exhibiting similar thermal, physical, chemical and biological characteristics.
"In compliance with time-honored usage within the industry, we recommend further that the term "fluoropolymers" be applied only to a distinct subset of fluorinated polymers, namely, those made by (co)polymerization of olefinic monomers, at least one of which contains F bound to one
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or both of the olefinic C atoms, to form a carbon-only polymer backbone with F atoms directly attached to it, e.g., polytetrafluoroethylene"
Fluoropolymer Primer
Fluoropolymers have been the subject of many prior reviews, books and articles (Gangal and Brothers, 2015; Ebnesajjad, 2011a; Ameduri, 2010; Drobny, 2008; Schiers, 1997). Fluoropolymers are typically synthesized via free radical polymerization methods. These fluoropolymer resins can be homopolymers like PTFE, or, copolymers like FEP, ETFE and PFA. Fluoropolymers are linear, semi-crystalline, high molecular weight polymers. Copolymers may have a monomer sequence that is either random (FEP, PFA) or alternating (ETFE). Fluoromonomers are produced from minerals (e.g., fluorospar, calcium fluoride, CaF2, also known as fluorite) and their manufacture involves the use of ozone depleting chemicals, whose use is strictly regulated by the Montreal Protocol and best available control technology is employed during their use. Figure S1. Where Does PTFE Come From?
Note: Mono-chloro di-fluoro methane (aka CHClF2 or R22) is regulated under the Montreal Protocol as an ozone depleting substance with high global warming potential.
Fluoromonomer purity is essential to achieve high molecular weight fluoropolymers. For example, one of the routes in which, the high molecular weight PTFE (for expanded PTFE) is produced requires 99.999% pure tetrafluoroethylene (TFE) monomer (gas) for polymerization.
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Very pure/deionized water is required for polymerization. Polymerization aids, ranging from 0.01% to 0.5% of the weight of water in the reactor, are used depending on the rate and degree of polymerization (Ebnesajjad, 2000). See Table S1 showing PTFE polymerization and post polymerization aids, which was assembled from patents, literature, publications and the authors' experience. Note that no PTFE manufacturer uses all of these in a PTFE polymer.
Low MW Leachables: Ingredients used in the Manufacture of Fluoropolymers
Note: Table S1 is a survey list. Not all are used in all manufacturing processes. These ingredients were disclosed in patents and publicly available literature.
Table S1: PTFE Polymerization and Post Polymerization Aids
PTFE polymerization / post polymerization aids based on PTFE patents and publicly available information (no single PTFE uses all of these)
(Note: Initiator concentration depends on rate and degree of polymerization, from 0.01 wt% to 0.5 wt% of the water.)
Function
coagulating agent
Name
Acetone
Surfactant
4,9-dioxa-3H-perfluorononanoate
Initiator
Ammonium carbonate
pH adjuster
Ammonium hydroxide
Initiator
Ammonium persulfate
Initiator
Ammonium sulfite
Initiator
Barium peroxide
Initiator
Borax
Initiator
Disuccinic peroxide
Surfactant
Ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy-) propionate
pH adjuster
Hydrochloric acid
Initiator
Hydrogen peroxide
Initiator
Lithium persulfate
Modifier, coagulating agent
methanol
pH adjuster
Nitric acid
Stabilizer
Nitrogen
Anticoagulant stabilizer
Parrafin wax
Surfactant
Perfluoro, 2-2-(methoxypropoxy)propanoic acid ammonium
Coagulation aid
Potassium nitrate
Initiator
Potassium permanganate
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Dispersant Surfactant Removes monomer inhibitor Initiator Initiator pH adjuster Initiator Initiator
Purified deionized water Ammonium, difluoro[1,1,2,2-tetrafluoro-2(pentafluoroethoxy)ethoxy] acetate
Silica gel Sodium bisulfite Sodium hydrosulfite Sodium hydroxide
Succinic acid Zinc peroxide
Concentration of leachables from fluoropolymers, particularly PTFE "fine powder" (ASTM4895-16 Type I fine powder definition) are typically very low (<1ppm). (See the analytical report starting on page 32 of this Supplemental Data). This finding can be explained by the sensitivity of the PTFE polymerization reaction to contamination, and, is due to the post polymerization processing steps aggressively exercised to wash out residuals and drive off volatiles. In order to achieve high molecular weight polymerization of TFE, all traces of telogenic hydrogen or chlorine-bearing impurities must be removed (Ebnesajjad, 2011b). Therefore, despite the use of one or more of the aids on Table S1, after the PTFE resin is washed and dried to a fine powder, the final fluoropolymer has the inherent hazard of the polymer alone, as the data presented in this article and Supplemental section verify.
To further illustrate the low concentration of leachables, some details of the responsible manufacture of fluoropolymers are provided here. Fluoropolymers, such as PTFE, may be produced from aqueous dispersions by free-radical polymerization via addition polymerization (Ebnesajjad, 2011b): the PTFE fine powder polymerization starts with 99.999% pure TFE monomer and purified/deionized water in reactor vessel. (See Figure S2.) Other polymerization aids, (e.g., initiator, catalyst, stabilizer, surfactant) are added to the reactor vessel from 0.01% to 0.5% of the weight of water, depending on the rate and degree of reaction (Ebnesajjad, 2000).
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Figure S2. Fluoropolymer Primer - PTFE Polymerization Scheme
Removal of residuals in a "finishing" step is performed on equipment with strict environmental control technology, such as thermal oxidizers, which have been demonstrated to be effective on TFE monomer (ECETOC, 2003). The result of the polymerization is an aqueous dispersion (with ~30% by weight PTFE polymer) which exits the reactor, is further diluted, pH adjusted, coagulated and dried in an oven to evaporate water and volatile residuals, leaving the pure PTFE polymer behind. (See Figure S3.)
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Figure S3. Fluoropolymer Primer - PTFE Finishing Scheme
The ASTM4895-16 standard pertains to polytetrafluoroethylene (PTFE) prepared by coagulation of a dispersion, such as described above (ASTM4895-16). To adhere to this standard, PTFE resins must be homopolymers of TFE, or, be modified homopolymers containing not more than 1 % by weight of other fluoromonomers. In addition, PTFE resins meeting this specification do not include mixtures of PTFE with additives such as colors, fillers, or plasticizers, nor do they include reprocessed or reground resin or any fabricated articles. Therefore, none of these additives are available within the PTFE polymer to leach out of the polymer and potentially affect health or the environment. Other fluoropolymer standards include: ASTM D2116-16, Standard Specification for FEP Resin Molding and Extrusion Materials and ASTM D3307, Standard Specification for Perfluoroalkoxy (PFA) Resin Molding and Extrusion Materials. 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, 2014) 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. TFE, for example, is a highly volatile gas monomer (boiling point of -76.3 C) used in the making of PTFE. TFE is listed on the National Toxicology Program's Annual Report on Carcinogens (U.S.
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Dept. of Health and Human Services, 1997). The fluoropolymer industry is well aware of TFE health and safety risks. TFE polymerization facility explosions have been documented (Reza and Christiansen, 2007). Fluoropolymer manufacturers follow documented industry best practices to ensure the safety of workers, manufacturing processes and products (Society of the Plastics Industry, 2005; Plastics Europe, 2012). These include increasing process automation, such as automatic cleaning and automation at the autoclaves, and use of localized ventilation and vacuum extraction at the end of the polymerization process (IARC, 2017). In the EU, for example, TFE must be used in a closed process with no likelihood of exposure (ECHA, 2014). Residual TFE monomer is not detected in PTFE resin by headspace GC-MS with a limit of detection of 1 ppm. (See the analytical report starting on page 32 of this Supplemental Data.) In addition, publicly available analytical data from independent industry authorities demonstrates that TFE is not detected in finished articles made from fluoropolymers at detection limits down to about 0.01ppm wt/wt (Society of the Plastics Industry, 2005).
Table S2: Alterative Fluoropolymer Processing Aids - Sources of Data
NOTE to the READER: please be aware that there are additional fluorinated alternative processing aids (see Table S1 above) commercially manufactured and used in fluoropolymer manufacturing for which there is no publicly available, citable data, such as is provided below.
Sources of Additional Details on Surfactants Used in Fluoropolymer Manufacturing
Author
Source
Surfactant Addressed
European Chemicals Agency
Gordon, Steven C.
European Chemicals Agency European Chemicals Agency
J.M. Caverly Rae, et al.
Robert A. Hoke, et al.
ANNEX XV PROPOSAL FOR A RESTRICTION - Perfluorooctanoic acid (PFOA), PFOA salts and PFOA-related substances. The German and Norwegian competent authorities, VERSION NUMBER: 1.0, DATE: 17 October 2014
Toxicological evaluation of ammonium 4,8dioxa-3,4-perfluorononanoate, a new emulsifier to replace ammoniumm perfluorooctanoate in fluoropolymer manufacturing, Regulatory Toxicology and Pharmacology 59(2011) 64-80.
https://echa.europa.eu/registration-dossier//registered-dossier/6858
https://echa.europa.eu/hr/registration-dossier//registered-dossier/4729/1 Evaluation of chronic toxicity and carcinogenicity of ammonium2,3,3,3tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague-Dawley rats. Toxicology Reports 2 (2015) 939-949. Aquatic hazard, bioaccumulation and screening risk assessment for ammonium 2,3,3,3tetrafluoro-2-(heptafluoropropoxy) - propanoate. Chemosphere 149 (2016) 336-342.
ammonium 2,3,3,3-tetrafluoro-2(heptafluoropropoxy) -propanoate; ammonium 4,8-dioxa-3,4-perfluorononanoate; ammonium difluoro[1,1,2,2-tetrafluoro-2(pentafluoroethoxy) ethoxy]acetate
ammonium 4,8-dioxa-3,4-perfluorononanoate
ammonium 4,8-dioxa-3,4-perfluorononanoate
ammonium difluoro[1,1,2,2-tetrafluoro-2(pentafluoroethoxy)ethoxy]acetate
ammonium 2,3,3,3-tetrafluoro-2(heptafluoropropoxy) -propanoate
ammonium 2,3,3,3-tetrafluoro-2(heptafluoropropoxy) -propanoate
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Shawn A. Gannon, et al.
European Chemicals Agency Yoshinori Nanba
Yoshinori Nanba
Absorption, distribution, metabolism, excretion, and kinetics of 2,3,3,3- tetrafluoro-2(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat, mouse, and cynomolgus monkey. Toxicology 340 (2016) 1- 9.
https://echa.europa.eu/hr/registration-dossier//registered-dossier/2679/1
ammonium 2,3,3,3-tetrafluoro-2(heptafluoropropoxy) -propanoate
ammonium 2,3,3,3-tetrafluoro-2(heptafluoropropoxy) -propanoate
Patent #US20150299342, Production Method for Polytetrafluoroethylene Aqueous Dispersion, Daikin Industries, LTD, October 22, 2015. Patent #US 201503222.37A1, POLYTETRAFLUOROETHYLENE AQUEOUS DISPERSION, AND POLYTETRAFLUOROETHYLENE FINE POWDER, DAIKIN INDUSTRIES, LTD., Osaka, November 12, 2015.
perfluoro[2-(2-methoxypropoxy)propanoic acid] ammonium
perfluoro[2-(2-methoxypropoxy)propanoic acid] ammonium
U.S. EPA - Hazard Determination for a Polymer
The following example is provided to show how an EPA polymer hazard determination (based on molecular weight and physicochemical properties) in combination with a low exposure potential (based on the same characteristics) leads to a "no unreasonable risk" determination for the polymer in question. For additional examples like this one, the reader is directed to U.S. EPA's web page on PMN decisions (https://www.epa.gov/reviewing-new-chemicals-undertoxic-substances-control-act-tsca/chemicals-determined-not-likely).
Example text from a PMN Determination Letter published on the website above:
TSCA Section 5(a)(3)(C) Determination for Premanufacture Notice (PMN) TSCA Section 5(a)(3) Determination: Chemical substance not likely to present an unreasonable risk (5(a)(3)(C))
Assessed Conditions of Use (intended, known, or reasonably foreseen)1: Intended use(s) (generic): Additive for plastics. Known and reasonably foreseen use(s): Adhesive and sealant chemical.
Summary: The chemical substance is not likely to present an unreasonable risk based on low human health hazard and low environmental hazard. Although EPA estimated that the new chemical substance would be very persistent, this did not indicate a likelihood that the chemical substance would present an unreasonable risk, given that the chemical substance has low potential for bioaccumulation, low human health hazard, and low environmental hazard.
Fate: Environmental fate is the determination of which environmental compartment(s) a chemical moves to, the expected residence time in the environmental compartment(s) and removal and degradation processes. Environmental fate is an important factor in determining exposure and thus in determining whether a chemical may present an unreasonable risk. EPA estimated a number of physical-chemical and
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fate properties of this new chemical substance using EPI (Estimation Programs Interface) Suite, a suite of physical/chemical property and environmental fate estimation programs (https://www.epa.gov/tsca-screening-tools/epi- uitetmestimationprogram-interface). Overall, these estimates are indicative of low potential for this chemical substance to volatilize into the air and a low potential for this chemical to migrate into ground water. Removal of the substance in wastewater treatment is likely due to sorption.
Persistence: Persistence is relevant to whether a new chemical substance is likely to present an unreasonable risk because chemicals that are not degraded in the environment at rates that prevent substantial buildup in the environment, and thus increase potential for exposure, may present a risk if the substance presents a hazard to human health or the environment. EPA estimated biodegradation half-lives of this new chemical substance using EPI (Estimation Programs Interface) Suite, a suite of physical/chemical property and environmental fate estimation programs (https://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-programinterface). These estimates indicate that the chemical substance is very persistent.
Bioaccumulation3: Bioaccumulation is relevant to whether a new chemical substance is likely to present an unreasonable risk because substances that bioaccumulate in aquatic and/or terrestrial species pose the potential for elevated exposures to humans and other organisms via food chains. EPA estimated the potential for this new chemical substance to bioaccumulate using EPI Suite (https://www.epa.gov/tscascreening-tools/epi-suitetm-estimation-program-interface). These estimates indicate that this new chemical substance has low bioaccumulation potential.
Human Health Hazard4: Human health hazard is relevant to whether a new chemical substance is likely to present an unreasonable risk because the significance of the risk is dependent upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the substance. EPA estimated the human health hazard of this chemical substance based on its estimated physical/chemical properties (which indicate that it will not be absorbed if inhaled, ingested or by dermal contact) and by comparing it to structurally analogous chemical substances for which there is information on human health hazard. There is low concern for human health hazard for the chemical substance based on physical/chemical properties of the chemical, as well as estimates of potential hazard based on analogous chemical substances/structure-activity relationships.
Environmental Hazard5: Environmental hazard is relevant to whether a new chemical substance is likely to present unreasonable risks because the significance of the risk is dependent upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the substance. EPA estimated environmental hazard of this new chemical substance using the Ecological Structure Activity Relationships (ECOSAR) Predictive Model (https://www.epa.gov/tsca-screening-tools/ecologicalstructure-activity-relationships-ecosar-predictivemodel).
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Based on these estimated hazard values from ECOSAR, EPA concludes that this chemical substance has low environmental hazard.
Potential Exposures: The exposure to a new chemical substance is potentially relevant to whether a new chemical substance is likely to present unreasonable risks because the significance of the risk is dependent upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the substance. In this case, EPA did not estimate the exposure because EPA determined that the chemical substance presents both low human health hazard and low environmental hazard. Due to low hazard, EPA believes that this chemical substance would be unlikely to present an unreasonable risk even if exposures were high.
Potentially Exposed or Susceptible Subpopulation(s): Workers are potentially exposed. Given the low hazard of this chemical substance, EPA finds that this chemical substance is not likely to present unreasonable risk to workers.
Polymers are too large to penetrate cell membranes
Molecular weight is an important predictor of biological effect because very large molecules (>1,000 - 10,000 Da) are too large to penetrate cell membranes. References that describe this:
Alberts B, Bray D, Lewis J et al., Molecular Biology of the Cell, 3rd Ed., Garland Science, NY, 1994, pp. 958, 963.
Beyer EC, Gap Junctions. Inter. Rev. Cytol. 137, p2, in Molecular Biology of Receptors and Transporters: Pumps, Transporters and Channels, Friedlander M and Mueckler M, Editors, Academic Press, Inc., San Diego, 1993.
Walmor C. De Mello, Ed., Cell-to-Cell Communication, Plenum Press, NY, 1987, p34.
Water Solubility Table S3 Solubility Table from USP 34 NF29 General Notices, Section 5.3.0, p6
Descriptive Term Very soluble Freely soluble Soluble
Sparingly soluble Slightly soluble Very slightly soluble Practically insoluble or insoluble
Parts of Solvent Required for 1 Part of Solute Less than 1 From 1 to 10
From 10 to 30 From 30 to 100 From 100 to 1,000 From 1,000 to 10,000 Greater than or equal to 10,000
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Representative SMLs for Fluoropolymers
Table S4. EU Specific Migration Limits (SMLs) for Monomers in Representative Fluoropolymers
(in mg monomer/kg food)
PTFE 0.05 mg/kg TFE
FEP 0.05 mg/kg TFE, 0.01 mg/kg HFP
ETFE None for Ethylene, 0.05 mg/kg for TFE
PFA 0.05 mg/kg for PMVE and PPVE, None for PEVE
ISO 10993 Biocompatibility Tests
Website for ISO 10993: http://www.iso.org/iso/catalogue_detail.htm?csnumber=44908 Cytotoxicity Irritation or Intracutaneous Reactivity Acute Systemic Toxicity Implantation In Vitro Genotoxicity In Vivo Genotoxicity Material Mediated Pyrogenicity Sensitization Subchronic Systemic Toxicity Hemocompatibility - Hemolysis Hemocompatibility - Complement Activation Hemocompatibility - Thrombogenicity Chronic Systemic Toxicity Carcinogenicity Reproductive/Developmental Toxicity Degradation
Additional text describing the 10993 Biocompatibility Tests.
Irritation and intracutaneous reactivity tests are performed whereby pieces of the device are extracted in polar and nonpolar solvents at 50C for 72 hours followed by subcutaneous injection of the extracts into rabbits. Signs of localized irritation or reactivity are noted in the animals after 72 hours of observation indicating the device readily leaches irritating substances.
Acute systemic toxicity is also performed where similar extractions are intravenously and/or intraperitoneally administered to mice. Signs of toxicity are observed after 72 hours post-injection, indicating if acute toxicity results from systemic administration of the device extracts. Mortality and body weight are also collected in the acute systemic toxicity test.
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The implantation study involves intramuscular placement of solid strips of the device into rabbits for 3 and 7 days. The implantation sites are then examined for any adverse reactions aside from slight inflammation and fibrosis surrounding the strips, reactions that are ubiquitously observed after short implantation durations.
To determine the compatibility of a device with circulating blood, hemocompatibility is examined with both in vitro and in vivo hemolysis (breakage of red blood cells) protocols to determine if potentially deleterious interactions with red blood cells may occur. Other hemocompatibility studies include complement activation and thrombogenicity.
To examine whether the device is a mutagen (capable of altering DNA structure), three standardized genotoxicity studies (an Ames bacterial mutagenesis assay, a mouse lymphoma assay and an in vivo micronucleus study) are performed according to OECD guidelines with extracts of the device.
Evaluation of PTFE in Medical Devices
PTFE, a representative fluoropolymer, in three physical forms (sheet, fiber, tube) was subjected to the BS EN ISO 10993-1 (Biological evaluation of medical devices - Part 1: Evaluation and testing) testing in compliance with Good Laboratory Practices (GLPs, 21 CFR, Part 58) at an accredited contract laboratory, NAMSA (Northwood, OH) in accordance with current ISO 10993 guidelines. All three physical forms of PTFE were manufactured, sterilized and packaged using methods intended for commercial product. Traceability of samples is maintained by reference numbers supplied in the associated study reports. Extraction conditions were established in each study protocol as indicated in the following data tables and were based upon the surface area of the test sample (ISO 10993-12:2009). The results of these tests are summarized in the following table.
This PTFE data was generated under Good Laboratory Practices in compliance with ISO
10993, ASTM and OECD standards.
ISO 10993-3: Bacterial Mutagenicity (Ames test)
OECD 471
ISO 10993-3: Mouse Lymphoma Assay
OECD 476
ISO 10993-3: Peripheral Mouse Micronucleus Test
OECD 474
ISO 10993-4: Hemolysis
ASTM F756
ISO 10993-4: Partial Thromboplastin Time (PTT)
ASTM F2382
ISO 10993-10: Irritation and Skin Sensitization
OECD 406
ISO 10993-11: Systemic Toxicity
OECD 408
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Table S5. Biocompatibility Tests, Conditions and Acceptance Criteria Results for ePTFE patch Page 17 of 58
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/ Note: VT6 = ePTFE tube
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Note: VT6 = ePTFE tube
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Note: VT6 = ePTFE tube
Polymer of Low Concern (PLC) Assessment Criteria
Molecular Weight (MW), Number Average Molecular Weight (Mn) and Molecular Weight Distribution (MWD) Polymers contain monomer chains of unequal length. The molecular weight of a polymer is not a single value. The polymer exists as a distribution of chain lengths and varying molecular weights. The molecular weight of a polymer must therefore be described as some average molecular weight calculated from the molecular weights of all the chains in the sample. The number average molecular weight (Mn) is the statistical average molecular weight of all the polymer chains in the sample. Mn can be predicted by polymerization mechanisms and is measured by methods that determine the number of molecules in a sample of a given weight; for example, end-group assay. If Mn is quoted for a molecular weight distribution, there are equal numbers of molecules on either side of Mn in the distribution. The OECD Expert Group on Polymers noted: "One of the most striking findings related to the number-average molecular weight (Mn) of a polymer; the lower the Mn, the higher the potential for health or ecotoxicological concern (OECD 2009, p9.)."
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Molecular Weight Distribution (MWD), aka polydispersity index, measures the heterogeneity of size of polymer molecules in a polymer. MWD is an important parameter for predicting potential biological effects of polymers because while Mn may be a large value, low MW oligomers <1,000 Da may be present which could penetrate the cell.
Figure S2. An FEP Fluoropolymer Molecular Weight Distribution - from a rheological study
Reactive Functional Groups (RFG) and RFG Ratio to MW (FGEW) Not only does the number of functional groups per polymer Mn impact the health and environmental impact of a polymer, but so does the relative hazard ("low", "moderate, " high" concern) of the functional group itself. The Deloitte report concluded that most polymer of low concern and polymer of low concern-eligible polymers are over 10,000 Da MW and are mostly inert (BIO by Deloitte 2015). Those polymers with MW>1,000 <10,000 Da with RFG of "moderate concern" should have functional group equivalent weight, FGEW >1,000 each and combined FGEW >1,000 (BIO by Deloitte 2015). Those polymers with MW > 1,000 < 10,000 Da with both "high" and "moderate" concern RFGs should have a combined FGEW >5,000; each high concern group should have a FGEW >5,000; each moderate concern group should have a FGEW >1,000 (BIO by Deloitte 2015). Similar to FGEW, the ratio of residual monomers to MW is a rough metric for whether or not the potential impact of the monomer is substantially diluted by polymeric material. This ratio is used as an indication of the degree of hazard of the polymer. The higher the percent residual monomer in the Mn, the more the polymer would be expected to behave like the monomer. As shown in the Table 1 of the main paper, for PTFE, the ratio of residual TFE monomer to PTFE molecular weight is <0.07%.
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As previously discussed, PTFE is surrounded by an envelope of fluorine atoms and has two carboxylic acid end groups per molecule. Both carboxylic acid and halogen RFG (except reactive halogen-containing benzylic or allylic halides) were concluded to be "low concern" functional groups (BIO by Deloitte 2015). See Table S6.
Table S6: US EPA's Chemical Categories of Concern, 2010
US EPA's Chemical Categories of Concern (2010 "current" list)
Acid Chlorides
Hindered Amines
Acid Dyes and Amphoteric Dyes
Imides
Acrylamides
-Naphthylamines, Sulfonated
Acrylates/Methacrylates
Lanthanides or Rare Earth Metals
Aldehydes
Neutral Organics
Aliphatic Amines
Nickel Compounds
Alkoxysilanes
Nitriles, allylic/vinyl
Aluminum Compounds
Nonionic Surfactants
Aminobenzothiazole Azo Dyes
Organotins
Anhydrides, Carboxylic Acid
Peroxides
Anilines
Persistent, Bioaccumulative, and Toxic (PBT) Chemicals
Dianilines
Phenolphthaleins
Anionic Surfactants
Phenols
Azides
Phosphates, Inorganic
Benzotriazoles
Phosphinate Esters
Benzotriazole-hindered phenols
Polyanionic Polymers (& Monomers)
Boron Compounds
Polycationic Polymers
Cationic Dyes
Polynitroaromatics
Cationic (quaternary ammonium) surfactants
Respirable, Poorly Soluble Particulates
Cobalt
Rosin
Diazoniums
Stilbene, derivatives of 4,4-bis(triazin-2-ylamino)-
Diisocyanates
Thiols
Dichlorobenzidine-based Pigments
Substituted Triazines
Dithiocarbamates
Triarylmethane Pigments/Dyes with Non-solubilizing Groups
Epoxides Esters
Vinyl Esters
Ethylene Glycol Ethers
Vinyl Sulfones
Hydrazines and Related Compounds
Soluble complexes of Zinc
Zirconium Compounds
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Note: The following is an analytical chemistry report from W.L. Gore & Associates. This report is intended to supplement the information in the main text to the complete PLC criteria table which supports the conclusion that PTFE is equivalent to a Polymer of Low Concern. This analytical report may be reported in a separate technical document for publication in an appropriate journal following peer review.
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PTFE Fine Powder Resin Extractable and Leachable Analytical Report for Polymer of Low Concern Concept
Introduction The global 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 as a Polymer of Low Concern (PLC) to health and the environment (OECD, 2009). Polymers satisfying these essential data elements were deemed to warrant reduced regulatory requirements (OECD, 2009). A recent report commissioned be European Community (EC) compiled existing polymer regulations outside the EU and proposed alternative options for EU polymer registration (BIO by Deloitte, 2015). The BIO by Deloitte report identified the eligibility criteria to be considered a Polymer of Low Concern with respect to potential for adverse impact on health and the environment.
Recent regulatory interest and pending restrictions have caused some concern that fluoropolymers, although stable and benignly persistent, would be included in these restrictions. An avenue toward protecting these valuable polymers from restriction is to demonstrate that they meet the criteria for a Polymer of Low Concern. Many of the defined criteria can be gleaned from the available literature and supplier technical reports. Not all of the necessary information is readily available and must be generated to complete the data set for the Polymer of Low Concern (PLC) assessment. A study was conducted to investigate several PLC properties of fluoropolymers of interest to W.L. Gore & Associates, Inc. The fluoropolymer investigated in this report was polytetrafluoroethylene, PTFE.
Purpose This analytical study was performed to develop and apply analytical approaches to generate the following PLC data for the fluoropolymer polytetrafluoroethylene, PTFE, with the sensitivity and selectivity needed. The specific properties that are not readily available and will be investigated in this work are:
low molecular weight leachables and extractables % oligomer residual monomers
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Materials and Methods
The selection of materials for this study was made for their relevance to Gore PTFE resins used broadly in the majority of products sold. Chromatographic techniques were performing using the most appropriate grade and purity and are identified below.
PTFE Samples:
Polytetrafluoroethylene meeting ASTM4895 Type I fine powder definition (CASRN 9002-84-0, PTFE) selected from raw material inventory by a Gore associate (Joe Carlin), from a Gore facility (Cherry Hill plant), April 2016.
Standards & Analytical chemicals:
Hexane, Honeywell Burdick and Jackson GC^2 Grade
Isopropyl alcohol (IPA), EMD Omnisolv High Purity Water, Millipore Milli-Q 18 M
FC-72, 3M Fluorinert FC-72 Electronic Liquid
Novec 7300, 3M Novec 7300 Engineered Fluid
Isopar K, Exxon-Mobil Isopar K Solvent (lot number not known)
Diethylene glycol, Sigma-Aldrich ReagentPlus, 99%
Butylated hydroxytoluene (BHT), Sigma-Aldrich, >99%
Dioctyl phthalate, Sigma-Aldrich 99%
GC/MS standard reference material (SRM): undecane, tridecane, tetradecane, pentadecane, Sigma-Aldrich >99%; 4-chlorophenol, > 98%, TCI America; 1Dodecylamine, >99%, TCI America; methyl dodecanoate, > 98%, TCI America; 1dodecanol, 99.5%, ChemService; all blended in hexane
LC/MS SRM: caffeine, ReagentPlus, Sigma-Aldrich; Carbowax PEG 600, Dow; sulforhodamine B (aka Acid Red 52), 75% dye content, Sigma-Aldrich; bromothymol blue sodium salt, Sigma-Aldrich; calibrant ion 922 = hexakis(1H,1H,3Htetrafluoropropoxy)phosphazene, calibrant ion 1522 = hexakis(1H,1H,5Hoctafluoropentoxy)phosphazene, Synquest Laboratories, all blended in 25% methanol (EMD Omnisolv LC/MS grade) and 75% aqueous 2 mM ammonium acetate (EMD HPLC grade) in 18 M water
PFC standard: perfluorobutane sulfonic acid, potassium salt, >98%, TCI America; perfluorohexanoic acid, sodium salt, Synquest Laboratories; perfluorooctanoic acid, sodium salt, 97%, Lancaster Synthesis; perfluoroctane sulfonic acid, tetraethylammonium salt, 98%, Sigma-Aldrich; perfluorononanoic acid, 97% Sigma-Aldrich, all blended in EMD Omnisolv LC/MS Grade methanol, nominally 100 ng/mL each Extractables, leachables and oligomers were measured using common extraction techniques and multiple solvents of various polarities (hexane, IPA, 55% water/45% IPA by weight).
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PTFE powder was extracted with solvents of varying polarities (hexane, IPA, and 55/45 water/IPA by volume) to recover low molecular weight extractable and leachable compounds, as well as low molecular weight oligomers. The extracts were analyzed for their detectable analytes by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) utilizing electrospray ionization in both positive and negative modes
Headspace GC/MS Method Headspace-GC/MS analysis was carried out on nominally one gram samples of the solid polymer to detect volatile species entrained in the material. The samples were heated for thirty minutes at 120C, agitated 10 seconds every two minutes, and then a one- mL sample of the headspace gas was drawn for analysis.
Volatile species, such as entrained solvents and residual monomers, are determined by headspace GC/MS analysis of the raw polymer. For example, tetrafluoroethylene (TFE) monomer is the principal component of polytetrafluoroethylene and is a gas at normal ambient conditions. As such, TFE would not be recoverable via extraction but could be detected by headspace analysis.
Headspace GC/MS Method Suitability Check The suitability of this procedure was verified by performing a replicate test with known quantities of fluorosolvents available for reference. Five-L aliquots of 0.2 mg/mL mixture of fluorinated solvents in hexane (FC-72 and Novec 7300), was added to the empty vial and also to a vial containing one gram of PTFD powder, resulting in a net spike of one g of each fluorosolvent, corresponding to a one g/g concentration in the PTFE if present. The samples were analyzed by headspace GC/MS as described above. Both the FC-72 and Novec 7300 were recovered within acceptable ranges and detected in the suitability check.
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Liquid Injection GC/MS System Suitability and Performance Checks Additional GC/MS System Suitability tests were conducted for ensuring accurate detection of analytes across the spectral range of interest and verify that the instrument was operating within normal parameters. The standard reference material (SRM) is used to check the performance of the GC inlet, column, and mass spectrometer. It is a subset of the Grob test mixture for gas chromatography. All of the compounds were detected at their expected retention times with acceptable peak shapes and with the correct mass spectra.
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The compounds in the SRM are nominally present at 10-30 g/mL and are listed below: 1. Undecane 2. 4-Chlorophenol 3. Tridecane 4. Tetradecane 5. 1-Dodecanamine 6. 1-Dodecanol 7. Pentadecane 8. Methyl dodecanoate
The response of the check standards indicate that the GC/MS system was operating within normal limits. The system suitability check is intended to verify the ability of the GC/MS system to detect analytes with very different properties and ionization efficiencies. The check standards are blends of diethylene glycol, dodecane, BHT, and bis(2-ethylhexyl)phthalate (DEHP) in hexane prepared at 0.1 ppm, 1 ppm, and 10 ppm. All of the compounds were detected at 10 ppm; diethylene glycol (DEG) was not detected at 0.1 and 1 ppm, an expected result; dodecane was
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detected in trace at 0.1 ppm while the others gave visible peaks and easily recognizable mass spectra at this level.
Extractable & Leachable Methods for GC/MS & LC/MS Analysis Extractable testing is performed to force any materials present in the polymers into the solvents through aggressive laboratory conditions. Leachable testing is performed to simulate more routine conditions experienced in the direct contact (e.g. aqueous based environments) of a material. Each of the polymers was extracted in two ways:
1. a heated ultrasonic extraction at 55 C for 3 hours 2. a leachable extraction carried out at 40 C for 72 hours in a shaking water bath. Duplicate one-gram portions of the polymers were prepared in 10 mL each of hexane, isopropyl alcohol (IPA), and 55% water / 45% IPA. GC/MS analysis was carried out on the hexane and IPA extracts and LC/MS analysis was carried out on the IPA and 55/45 water/IPA extracts.
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A standard reference material (SRM) is used to check the performance of the LC column, UVVis detector, and mass spectrometer. The test compounds were detected with appropriate peak shapes and correct mass spectra. Peaks noted with an "X" are system artifacts.
Results The quantitative results of the tests are shown in the table below. Where quantification was needed, additional analytical methods were employed (e.g. a G/MS method for Isopar K capable down to less than 0.5 g/g with the extraction conditions here was used). Details are included below in the Analysis section for reference.
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Properties of interest *% oligomer
Final PTFE Results
Concentration
PLC Criterion
Not detected
< 2% wt/wt (20,000 ppm)
^residual monomers
low molecular weight leachables & extractables
Not detected #2 ppm
No Limit Established by OECD, 2009
No Limit Established by OECD, 2009
*Polymers with potential health concern had an increased incidence of higher oligomer content that began at 5% for <1000 Da and 2% for <500 Da oligomeric content (OECD, 2009, page 24). The table lists the lower limit, 2%, which is 20,000 ppm.
^The data set used by OECD (2009) to establish the PLC criteria was insufficient to establish a universal limit for all residual monomers, though residual monomer content was established as a PLC criteria (OECD, 2009). According to U.S. EPA's Safer Choice criteria (SCP, 2015), tetrafluoroethylene is a residual of concern, which is not allowed to be present in Safer Choice recognized products at 0.01% or higher. There is no specific limit on residual monomer in the PLC criteria (OECD, 2009).
#Isopar K, an unavoidable ambient air contaminant adsorbed to the PTFE fine powder, was detected at < 2ppm.
The result of the headspace GC-MS analysis is shown in the figure below for a grade of PTFE.
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Interestingly, Isopar K was detected in the sample headspace as well as in the hexane and IPA extracts of the PTF powder. Isopar K is a well-known mineral spirit used in PTFE fine powder paste processing, not the PTFE resin manufacturing. It is used in the facility in which the resin sample was collected and is, therefore, most likely an airborne contaminant of the sample. A 2 ppm Isopar K standard was prepared and analyzed to confirm the positive identification. A 0.2 ppm standard was used to give a semi-quantitative estimate of Isopar K in the PTFE sample.
Liquid injection GC/MS results of the solvent extracts of the PTFE are shown in the figures below.
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As shown in the GC/MS analysis for IPA and hexane extractions, there is no discernable difference between the PTFE samples and the blanks except for the trace of Isopar K in the extracts. The limit of quantitation for Isopar K is estimated to be < 1.5 g/g in the PTFE by the method employed.
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LC/MS analyses of the IPA and IPA/water extracts in both negative and positive ion modes show results similar to the GC/MS analyses in that the extracts are almost indistinguishable from the blank extractions. There is an erucamide peak present in both the samples and blanks from a persistent contaminant in the LC/MS system. No other peaks were detected in the analyses.
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The IPA extracts of the PTFE were also tested for the presence of possible common fluorinated surfactants. These compounds were not detected in the extracts.
Sample ID
PTFE Extract #1 PTFE Extract #2 Blank
Extractable/Leachable Analysis of PTFE
Nominal Sample Mass, g
Headspace GC/MS analysis
Ultrasonic IPA
extraction GC/MS
1
tracea c
trace a
1
tracea c
trace a
1
< 1 ppm < 1 ppm
Ultrasonic Hexane extraction GC/MS
trace a trace a < 1 ppm
Ultrasonic Extraction 55% H2O/45% IPA ESI(+)
LC/MS
< 1 ppm
< 1 ppm < 1 ppm
Ultrasonic Extraction 55% H2O / 45% IPA
ESI(-) LC/MS < 1 ppm
< 1 ppm < 1 ppm
Ultrasonic Extraction IPA ESI(+)
LC/MS
< 1 ppm < 1 ppm < 1 ppm
Ultrasonic Extraction IPA ESI(-)
LC/MS
72 hr IPA 72 hr IPA Leachable Leachable extraction extraction ESI(+) LC/MS ESI(-) LC/MS
72 hr IPA Leachable extraction
GC/MS
< 1 ppm < 1 ppm < 1 ppm
< 1 ppm < 1 ppm < 1 ppm
< 1 ppm < 1 ppm < 1 ppm
trace a trace a < 1 ppm
72 hr Hexane Leachable extraction GC/MS
trace a trace a < 1 ppm
72 hr 55% H2O / 45% IPA Leachable extraction
ESI(+) LC/MS
72 hr 55% H2O / 45% IPA Leachable
extraction ESI() LC/MS
< 1 ppm b < 1 ppm b < 1 ppm
< 1 ppm < 1 ppm < 1 ppm
a - IK trace only from environmental contamination b - slight erucamide peak, a persistent system contaminant that was also detected in the blank. c - Hydrocarbon, fluorocarbon peaks but below identification threshold d - Hydrofluorocarbon fragmentation peaks ~MW=532 e - A trace of 7H-perfluoroheptanoic acid, 9H-perfluorononanoic acid, ~600 ppb each. f - A trace of an unidentified compound likely formula is C27H48O8 ESI(+) indicates positive ion mode acquisition ESI(-) indicates negative ion mode acquisition
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