Document Em4zxg09garJE4R5pEn0Yza4

AR226-2363 )i Detecting and Quantifying Low Levels of Fluoropolymer Polymerization Aids - A Guidance Document t Fluoropolym er M anufacturers G roup (FM G ) - T echnical W orking G roup (TW G ) - A n alytical W orking G roup (AW G ) T he Society o f the P lastics Industry, Inc. 1801 K Street, NW , Suite 600K W ashington, DC 20006-1301 S EXP000571 T h is p a g e le ft in te n tio n a lly b lan k . EXP000572 NOTE TO USERS This Guidance Document was developed b y die Fluoropolymer Manufacturers Group o f The Society o f die Plastics Industry, Inc. and is intended to provide information on general guidelines for die determination o f fluoropolymer polymerization aids in a variety o f matrices. The guidelines provided are based on the collective experience o f members o f die industry, but are not intended to be either exhaustive or inclusive o f all pertinent requirements. The information provided in this guide is offered in good faith and believed to be reliable, but is made WITHOUT WARRANTY, EXPRESSED OR IMPLIED, AS TO THE MERCHANTABILITY, FITNESS FOR A PARTICULAR USE, OR ANY OTHER MATTER. The guidelines provided and the examples included are not intended to be directed to any particular product, nor are they claimed to satisfy all current requirements o f Good Laboratory Practices. Following the Guidance Document does not guarantee compliance with any regulation or standard, safe handling, nor safe operation o f laboratory equipment Users are cautioned that the information upon which this Guidance Document is based is subjectto change, which may invalidate any or all o f the comments contained herein. This Guidance Document is not intended to provide specific advice, legal or otherwise, on particular products or processes. In designing experiments and operating equipment, users o f this Guidance Document should consult with their own legal and technical advisors, their suppliers, and other appropriate sources (including but not limited to product or package labels, technical bulletins, or sales literature) which contain information about known and reasonably foreseeable health and safety risks o f their proprietary products and processes. SPI, its members and contributors, do not assume any responsibility for the user's compliance with any applicable laws and regulations, nor for any persons relying on the information contained in this Guidance Document SPI does not endorse the proprietary products or processes o f any manufacturer or user o f fluoropolymer polymerization aids, resins or products, or any manufacturer or user o f laboratory instruments or supplies. All information about an individual manufacturer's products contained herein has been provided by those manufacturers who are solely responsible for the accuracy and completeness o f the data. Copyright 2003 The Society o f the Plastics Industry, Inc. A ll Rights Reserved SPI Literature Catalogue #: BZ-102 Determining Low Levels of Fluoropolymer Polymerization Aids - A Guidance Document Copyright 2003 The Society o f the Plastics Industry, Inc., All Rights Reserved EXP000573 T h is p a g e le ft in te n tio n a lly b lan k . EXP000574 Determining Low Levels o f Fluoropolymer Polymerization Aids A Gnidance Document 1.0 P u rp ose.............................. ................. .................................................................................. ............. j 2.0 Introduction. ......................................................................... j 3.0 Safe H and ling Inform ation......................... 3 4.0 A nalytical T echnologies. ..................................... ........................ .............................................. ^ 4 5.0 A nalysis o f PFO A in W ater........................................................... 5 6- 0 A nalysis o f Am m onium P erflnorooctanoate (A P F O l in A ir................................................ 7 7- 0 D eterm ination o f Am m onium P erflnorooctanoate (A P F O ) in B iological M atrices.... 8 8.0 S olids. ................................................................................................................................................... 9 9.0 A dditional A nalytical C onsiderations............................................ 9 10.0 R eferences. ............................................................................................................................ ....... ........ TABLE 1: G eneral T erm inology and D efinitions. .............................................................................. 2 TABLE 2: D efinition s o f Q nality A ssu ran ce (Q A) C riteria . ........................................................... 10 TA BLE 3: P h ysical and C hem ical P rop erties. . . . ..................................... .......................................... ^4 APPENDIX A : E xam ples o f F luoropolym er P olym erization A id s............................................... 12 A PPENDIX B . G eneral P hysical an d C hem ical P ro p erties...................................................13 A PPENDIX C: C om parison o f A v ailab le A nalytical T ech n iqu es for F ln orop olym ers........... 16 EXP000575 This page left intentionally blank. EXP000576 1.0 Purpose This docum ent w ill focus on the determination o f low lev els o f Fluoropolymer Polym erization A ids (FPA s) in various matrices. This docum ent is not m eant to be all-inclusive, but rather to em phasize die state o f knowledge and the difficulty o f ensuring reliable sam pling and data acquisition on these materials. Since the FPA s cover a w ide range o f chem ical structures, a successful method for one compound does n ot necessarily ensure the method w ill be as useful for another. A lso, this document w ill direct the reader to a subset o f the appropriate literature that w ill be useful in establishing analytical protocols. Table 1 w ill provide the reader w ith the term inology and definitions used in the field. 2.0 Introduction Fluoropolym er Polymerization Aids (FPA s) are used in diverse industrial applications as surfactants, dispersants, etc. The most com mon use o f FPA s is as surfactants. Fluorosurfactants are sim ilar in structure to conventional surfactants in that they have a hydrophilic part and a hydrophobic part T he difference lies in that the hydrophobic part o f the fluorosurfactant m olecule contains fluorinated carbons. The extent o f the fluorination and the position o f the fluorine atoms in th e surfactant m olecule affect die characteristics o f the flnnmgm-far-tant Consequently, the surfactants may be termed either partially or fu lly flunrinateH (aka perfluorinated). The hydrophobes o f partially fluorinated surfactants contain both fluorine and hydrogen atoms. U nlike the hydrophobes o f hydrocarbon surfactants, the partially fluorinated hydrophobe consists o f two mutually phobic parts w hich are not com patible. Consequently, partially fluorinated surfactants exhibit anom alies in m acroscopic characteristics, such as critical m icelle concentration (cm c), and in m icroscopic phenom ena as w ell. H owever, partially fluorinated surfactants have several advantages over fu lly perfluorinated surfactants. The hydrocarbon segm ent provides solubility in more com m only used solvents, low ers the m alting point o f the surfactant, reduces volatility, and decreases the acid strength o f fluorinated acid s.1 Perfluorinated surfactants are remarkably stable, having exceptional thermal and chem ical stability, w hich enables them to be used in applications that w ould be too severe for conventional hydrocarbon-based surfactants. The very strong C-F bond in a carbon chain (note: the F attached to C = 0 is not stable) is stable to acids, alkali, oxidation, and reduction, even at relatively high temperatures. It is this very stability that is the root cause o f the difficulties in the Fluorosurfactants as a class o f com pounds cover a range o f chem ical structures. L ike all surfactants, fluorosurfactants are either ionic or nonionic. Ionic surfactants can nnliVe nonionic surfactants, dissociate into ions in an aqueous medium. The hydrophilic part can belong to a negative or positive ion. Fluorosurfactants can be classified into four types: 1) anionic, where the hydrophilic part is an anion; 2) cationic, where the hydrophilic part is a cation; 3) amphoteric, w hich have at least one anionic and one cationic group, and 4) nonionic. Like their hydrocarbon counterparts, ion ic fluorosurfactants dissociate in water and form a surface-active ion w ith an oppositely charged counterion. It is the surface-active ion s o f anionic fluorosurfactants that bear the negative charge. It is the anionic fluorosurfactants that are the m ost important class o f fluorinated surfactants. They are classified based on the structure o f EXP000577 1 T able 1. G en eral T erm inology and D efinitions Fhiorinated A general, non-specific term used synonym ously w ith fluuiuelieiuical. 1 C hem ical Fluorinated Organic Polymer A general term used to describe a polym er wtucn nas a hydrocarbon 1 i^fVhrmg (polyam ide, polyester, polyurethane, etc.) to w hich is appended a 1 uorinated carbon chain, also known as a fluorinated alkyl chain; an 1 exam ple would b e a polymer such as -[CH2CH(C(0)0CH2CH2(CF2)8F )]n-__1 Fluorinated Organic Surfactant A term to describe a surface active, lo w molecular w eight (< 1000), substance w hich contains fluorinated carbons; the term fluorosurfactant is non-specific but often used synonym ously; an exam ple is 1 1 1 F luorochem ical F(CF2)6CH2CH2S 0 3`NH4+ A general, non-specific term used to describe broadly a ll chem icals containing die elem ent fluorine; sp ecifically, die term is used m ost 1 1 com m only to describe sm all (1-8 carbon length) fluorinated m olecules that 1 are m ost often used for refrigeration, as fire suppression agents and as 1 Fluoropolym er specialty solvents. 1 A general term used to describe a polym er which has fluorine attached to I the majority o f carbon atoms w hich com prise the polym er chain backbone 1 [com m on fluoropolym ers are: polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), fluorinated ethylene-propylene (FEP), I etc.]; these are typically high m olecular w eight polym ers used in high performance applications where chem ical resistance and thermal stability 1 Fluoropolym er Polym erization A id Fluorosurfactant are essential. 1 A general term u sed to describe a subset o f perfluoroalkylated substances, 1 mranhars o f a class o f com m ercially available perfluoroalkyl carboxylate I surfactants, dispersants, etc. A non-specific, general term used to describe a surface active, low m olecular w eight (<100G), substance where carbons bear fluorine in place o f hydrogen. Exam ples would include CF3(CF2);S 0 3'K+, H(CF2)7CQO 1 N H 4+, F(CF2CF2)3CH2CH2S 0 3'NH4+, CH3CH2CF2CF2CH2COO-NH4+, etc. Perfluoro- / Perfluorinated Perfluorinated Surfactant D escribes specifically a substance where a ll hydrogen atom s attached to carbon atoms are replaced w ith fluorine atoms --CFn- where n = 1 - 4. A term used to describe a surface active, low m olecular w eight (<1U00), substance where a ll carbons bear fluorine in place o f hydrogen; the term fluorosurfactant is less specific but used synonym ously; an exam ple is 1 | 1 1 Perfluoroalkylated Substance F (C F 2) 6S03-N H 4+ A general term describing a substance that bears a perfluorocarbon unit, 1 also known as a perfhiroroalkyl functional group, F(CF2),,-R, where n is an 1 integer and R is not a halogen, or hydrogen. Examples include 1 F(CF2)6CH2CH2OH, F(CF2)6S02N(CH3)CH2CH2OH, and p-F(CF2)6- C6H4OH 1 EXP000578 2 their hydrophile, w hich can be divided into four m ain categories: a) carboxylates (RfCOCTM*), b) sulfonates (RiSOsTtf1) , c) sulfeies (Ri0 S 0 3'M+) ! and d) phosphates ( ^ 0 P ( 0 ) 0 2' `M2+), where Rf is a fluorine-containing hydrophobe and M* ap inorganic or an organic cation. The predominate form used a id for w inch there is d ie m ost analytical data are the perfluorinated carboxylic acids (PFO As) and their salts. In cationic Chlorinated surfactants, the fluorinated hydrophobe is attached directly or indirectly to a protonated amino group, a quaternary am m onium group, or a heterocyclic base.1 Cationic mrfartants dissociate in water, forming a surface-active p ositively charged ion and a negatively charged counterion. Like anionic surfactants, cationic surfactants are usually affected by 1he pH o f die medium and the electrolytes. There is a general b elief that cationic surfactants adsorb on negatively charged surfaces. Amphoteric fluorinated surfactants are bifunctional com pounds having at least one cationic group, one anionic group, and are electronically neutral around their isoelectric points. Amphoteric fluorinated surfactants can function both as anionic and as cationic surfactants Ha n d in g on the pH o f the medium.2 They are com patible w ith other typ es o f surfactants and are believed to absorb on either p ositively c n egatively charged surfaces.1 Amphoteric fluorinated surfactants are used in foam stabilizers, em ulsifiers for manufacturing fluoropolymers, wetting agents, repellants for paper and textiles, fire-extinguishing agents, spreading agents on hydrocarbon surfaces, cleaning agents for degreasing m etal surfaces, and personal care products. N onionic fluorinated surfactants are soluble in an acid or an alkaline m edium . They do not dissociate into ions in water. Consequently, nonionic fluorinated surfactants are less sensitive to pH and electrolyte changes. They are not preferentially adsorbed on charged surfaces.1 Appendix A covers som e o f the structure types o f th ese m olecules. A ppendix B discusses general physical and chem ical properties. 3.0 Safe Handling Information for Fluoropotymer Polymerization Aids Read safety information prior to use, including M SD Ss, and the S ociety o f the Plastics Industry, Inc. (SPI) "Guide to Safe Handling o f Fluoropolym ers D ispersions," available either online (http://www.fluoropolvm ers.org/news/APFO safehandlingguide.pdfl or directly from SPI.3 Any information whether in an M SDS or in this guide, m ay change as results o f further studies becom e available. Consult your supplier or SPI for the m ost up-to-date inform ation. A general treatment o f physical and other properties o f FPA s m ay be found in Fluorinated Surfactants.1 The majority o f the toxicology data and health studies on FPAs have been conducted on ammonium perfluorooctanoate (APFO ). APFO is a perfluorinated chem ical; it is extremely stable, degrades slow ly, and therefore persists in the environm ent APFO can be absorbed by the body and m ay be detected in the blood stream follow ing ingestion, inhalation or <dHn contact APFO has been classified by the Am erican Conference o f G overnm ental Industrial H ygienists (ACGIH) as an animal carcinogen, but available evidence does not suggest that the agent is likely to cause cancer in humans except under uncom m on or unlikely routes or levels o f exposure.4 U se o f engineering controls, good hygienic practices and personal protection equipment (PPE) are critical in reducing exposure to FPAs. A void contact w hen handling materials containing FPAs. FPAs may be released when dispersions are heated or dried. Although solids, EXP000579 3 som e FPAs have h igh vapor pressures. It is important to clean up sp ills before they dry and allow the FPA to sublim e. Handle a ll chem icals w ith caution, including fluorosurfactants. It is the responsibility o f the individuals handling neat materials, standards, and sam ples to determine the m ost appropriate precautions to fo llo w based on available information. 4.0 Analytical Technologies The logical approach to determ ining which analytical method to use for a particular application is to define the need, determ ine which analytical technologies m ight be able to solve the problem, determ ine i f these resources are available in a tim ely fashion, and if so, proceed. Often the process is not as sim ple as it m ight seem , especially if the analyte o f interest is d iffic u lt A useful to o l to define the need is "Fitness for Purpose." Fitness for Purpose is the property o f data produced b y measurement that enables th e user o f the data to make technically correct decisions for a stated purpose.5 Fitness for Purpose refers to th e magnitude o f the uncertainty associated w ife fee measurement in relation to fe e needs o f the application area. For many applications o f perfluorinated fluoropolym er polym erization aids, it m ight be sufficient to sim ply determine fee total fluoride after com bustion w ife a fluorine ion-selective electrode. For measurements required in an industrial, regulated environm ent, it would b e necessary to have more exacting quantitative and qualitative tools w ife d efensible quality assurance as an integral part o f each step. The follow ing checklist m ight also be a useful to o l in selecting fee analytical method. What is fee purpose o f fee m easurement? What concentration o f analyte is expected? H ow w ill the material be identified? What quality assurance procedures are required? H ow w ill sam pling and transport b e accom plished? What are fee sources o f potential cross contamination? What is the m ethod specificity? Should screening be used to expedite fe e measurement process? What is the linearity and range o f fe e measurement? What is fee detection lim it (both m ethod and instrument)? What is the stability o f fee sample in fee containers and conditions from sam pling to analysis? What type o f error analysis is appropriate? What criteria are needed to reject data? (R2, blank less than fee method detection lim it (M DL), nonzero blanks) Validation Time, m oney, resources ' Have you carefully considered fee next steps ("W hat i f ' planning) after fe e data are obtained? In evaluating the overall Fitness for Purpose, consideration should be given to the resources needed to im prove fee accuracy, precision, and qualitative nature o f the analysis. Generally, the more precise, accurate, and certain, the higher the cost and greater the tim e needed. EXP000580 4 The m ost com m on fluoropolym er polym erization aid is ammonium perfluorooctanoate, APFO. Since it is the m ost com m on material in use, it is also the most studied and reported upon- h i water, APFO dissociates into its anion, perfluorooctanoate, and its cation, ammonium For analytical m easurem ents, the concentrations are usually expressed as the original a m m o n ia salt (APFO) or its parent, perfluorooctanoic ad d (PFO A). The following sections w ill highlight various aspects involved in the sam pling, sample preparation, analysis, and data reduction for PFOA. 5.0 Analysis o f PFOA in W ater 5.1 Sam pling a n d P reservation Care m ust b e used in sam pling to avoid later problem s in analysis, especially when determining perfluorooctanoic a d d (PFOA) and its salts at part per billion (ppb) levels or less. It is important that m ultiple blanks and standards are run. I f blanks show measurable quantities o f PFOA, results should be considered su sp ect To avoid contamination from sam pling equipment and containers, fluoropoiym ers should be avoided, since PFOA is often used in fluoropolymer manufacture. F ield blanks can help to identify problems in this area. It is important to ensure the sampling equipm ent being used is not subject to adsorption, absorption, or volatilization losses, and does n ot compromise the sample. Sample history should be w ell documented and contain details o f sam ple collection and transport It is important to verify hold tim es for analyses o f this type. I f not analyzed promptly, samples should b e stored at temperatures at or near zero degrees Celsius. * 5.2 P reparation Different typ es o f water have different sample preparation issues associated w ith fhgm i f the PFOA salts d issolve more readily than the free acid, it m ay be necessary to adjust solution conditions through the addition o f appropriate bases, such as ammonium hydroxide (see Appendix B ). S ince PFOA and its salts are surfactants, they tend to spread and coat sam ple containers and apparatus. Thus unnecessary changing o f the test sample container should be avoided, and spike recovery analyses should be performed to assess tire degree to w hich the analyte may b e lo st due to this phenomenon. Filtration o f the sample m ay be necessary to remove undissolved solids. This should be done only i f necessary, since analyte may be lo st due to absorption onto the filter. Polypropylene filter m edia may b e preferred for certain perfluorinated surfactants, since absorption is generally less than for other m aterials.6 In the case o f very dilute sam ples it may be necessary to preconcentrate the sam ple. This can be accom plished using preconditioned cartridges such as C187, Porapak Q, or Tenax. Recovery o f spiked blanks and sam ples should be assessed to determine the efficien cy o f analyte recovery from such cartridges. Additional sam ple preparation may be necessary depending on the analytical method chosen for the determination, 5 3 Types o f W ater !!Clean" w ater, such as drinking water, usually should not require filtration , Since the concentration o f PFO A is likely to be very low , however, it is especially important to avoid contamination during sam pling and handling. Preconcentration and pH adjustment m ay be necessary. Interference from inorganic fluoride m ay cause problems w ith a non-specific analytical method, such as total fluorine content. EXP00Q581 5 Groundwater and river water m ay or may not require filtration, depending on the source. M ost o f d ie com m ents pertaining to "clean" water also apply. There may be additional problem s created b y the presence o f biological organisms and other interfering com pounds, especially in river water. Process w ater, such as that found in fluoropolymer manufacturing facilities or in plants that use fluoropolym ers in their manufacturing processes, m ay contain relatively high concentrations o f PFO A or its salts. It is important that the tim e and place o f sam pling is carefully noted, sin ce concentrations o f PFOA may fluctuate substantially w ith tim e. Filtration may be necessary to rem ove undissolved solids, but it w ill probably be necessary to analyze any solids removed, sin ce they may contain sizeable quantities o f PFOA as a result o f sorption. Interference from other com ponents in the process stream should be considered w hen choosing an analytical technique. Each type o f water mentioned above should be considered as unique, and has its ow n set o f sampling and analytical problems. Seasonal variations m ight be significant. A gain, it is important to verify h old tim es for analyses o f this type. 5.4 A nalytical M ethods ' There are m any m ethods that may be applied to the analysis o f PFOA and its salts. Factors to be considered w hen choosing a method include cost and availability o f equipm ent, analytical skill lev el required for analysts, tim e requirements for sam ple preparation and analysis, and any trade-offs required betw een sensitivity, accuracy, and precision o f measurement. T hese considerations are summarized in Appendix C. Total fluorine content is non-specific to PFOA, but m ay be adequate for relatively high concentrations in sam ples where it is known that there are no other sources o f fluorine besides PFOA. The organic fluorine must be converted to soluble fluoride ion for m any o f the m ore common techniques, and this w ill require some type o f com bustion. It should be noted that peifluorinated com pounds, such as PFOA, axe difficult to com bust com pletely.7 A nalysis o f standards and spiked sam ples are important to ensure that com bustion is com plete. Gas chromatography with flam e ionization (FID ), electron capture (ECD), or m ass spectroscopic (M SD ) detection can be used to determine PFOA. These methods have been reported for the determ ination o f PFOA in blood plasm a and urine6'9,10, and may b e adapted to water analysis. Since the acid form cannot be chromatographed, it is necessary to first convert the carboxylic acid to an ester. Various procedures can be used for the esterification, and it is important to ensure that the esterification is complete by using spiked samples. These techniques are sem i-specific, since the retention tim es o f known standards can serve to identify the m aterials being analyzed. The low er lim it o f detection for these techniques is o f the order o f one to fiv e parts per m illion b y w eig h t They have the advantage o f using relatively inexpensive and w idely available equipm ent Nuclear m agnetic resonance (I9F-NM R) has been reported* to be applicable to PFO A analysis in water w ith a detection lim it o f 10 pg/L. It is also sem i-specific, but perfluorinated surfactants other than PFOA can interfere with the determination. The presence o f branched surfactants can lead to erroneous quantitation; care m ust be taken to account for the amount o f branching. Pre-concentration o f sam ples may be necessary, but derivatization is not. The equipment is expensive and may be available only in larger laboratories. High perform ance liquid chromatography (HPLC) has been reported to be applicable to the analysis perfluorocarboxylic acids in biological sam ples11, and may be adaptable for water analysis. Since PFO A and its salts lack chromophores, it is also necessary to derivatize the sample before analysis when using fluorescence detection. A s w ith gas chromatography, it is sem i-specific in that retention tim e o f standards can be used to identify the analyte. HPLC 6 EXP000582 equipment is only m oderately expensive and is reported to be m ore sensitive than gas chromatography.11 Liquid chromatographv/tandem mass spectrometry (LC/M S/M S) has been used to d e t e n t e PFOA in river water* and human serum.12 It is compound sp ecific and does not require derivatization o f the sample prior to analysis. It is superior to LC/M S in that it provides an additional dim ension, w hich helps to avoid false p ositives. A detection lim it o f 1 pg w as reported for water8 and 10 ng/mL for serum .12 It is likely to b e the m ost generally applicable technique, especially for trace levels, but the equipment is expensive and lik ely to be available only in larger laboratories. 5.5 A nalytical M ethod V alidation Before generating analytical data on unknown sam ples w ith any o f d ie m ethods mentioned above, it is important to ensure that the method is validated. This is esp ecially important i f a method developed for one type o f medium, e.g. human serum, is to b e adapted to another medium, e.g. water. Lab spiking should be performed to address matrix effects. Blanks are very important for low -level quantitation and m inim izing sam pling artifacts. G ood guidelines for method validation can b e found in reference 13. 6.0 Analysis o f Ammonium Perfluorooctanoate (APFO) in Air Applications o f air sampling and analyses methods to the measurement o f APFO should include method validation criteria consistent w ith appropriate regulatory guidance. Due to the potential biphasic nature o f APFO and other airborne fluorochem icals consideration o f sampling m edia is critical. M ethod developm ent should include "zero" air m easurem ents as w ell as adsorption and desorption efficiencies, and holding tim e measurements. Preferably the method should be able to discrim inate between analyte on particles versus analyte in the vapor phase There should be "real" blanks, including field blanks taken to the field and exposed to all conditions except for having the air pumped through them . Demonstration o f lab capability via analysis o f spiked sam ples and replicates and all associated quality control requirements should be documented. T his docum entation should include instrumental calibrations and written Standard Operating Procedures (SO Ps) or written lab procedures for each step from materials preparation, sam pling, analysis, documentation, reporting and deliverables, and data retention. Third party validation or review is desired. Established quality criteria including method performance should b e documented (Lim it o f Quantitation - LOQ, uncertainties, accuracy precision, specificity, calibration criteria, blank criteria, matrix or lab control spike criteria! replicates, retention-tim e w indow criteria, tuning criteria); - R$ u s ? o f ana,3fses o f sem ivolatile or non-volatile fluorochem icals in air have been lim ited. ' A recent analytical air method exists for the analysis o f APFO in workplace atmospheres. This m ethod involves LC/MS/MS analysis o f acetone extracts from OSHA V ersatile Sampler (O V S) tubes (Occupational Safety and H ealth Administration, O SH A).14 This method applies to the analysis o f "clean" ambient workplace air. Application o f the method to environmental manufacturing em issions sam pling or other air matrices w ould require source specific validation. O V S tubes were used to sim ultaneously trap fluorochem ical particulates and vapors from workplace air. A nalytical methods were developed for air sam ples collected on OVS tubes to quantitatively analyze for both total fluorine, using oxygen bomb com bustion/ion selective electrode, and for nineteen analyte specific organofluorochem icals using LC/MS GC/M S, and IC (ion chrom atography).14 A method validation study was conducted according to 7 EXP000583 the National Institute o f Occupational Safety and H ealth (NIQSH) w ith minor revisions o f the experimental design due to sp ecifics o f this particular sampling application.16 Method performance for APFO analysis was sufficient in term s o f analytical recovery, sam pler capacity, storage stability, determ ination o f lim its o f detection, and precision and b ias o f the sam ples. The method com bines OVS tube sampling w ith LC/MS analysis and is applicable for quantitation o f 0.06 - 6 pgs APFO in an OVS tube sam ple. This m ethod range corresponds to quantitation o f APFO in ambient air in the concentration range o f 0.001 - 0.1 mg/m3 w ith a 60-liter air sample. 7.0 Determination o f Ammonium Perfluorooctanoate (APFO) in Biological M atrices Analyte specific detection o f APFO in biological matrices at trace levels (parts per b illion by weight) can be accom plished using two primary analytical detection techniques/8,17, andrefewrtWn) The first technique com bines chem ical derivatizafion techniques coupled w ith gas chromatography/mass spectrometry detection. The second technique com bines biological matrix extraction w ith liquid chromatography/mass spectrometry detection. B iological matrices are highly variable and im pact analytical m ethod performance with unpredictable results. Significant differences in method performance criteria can be observed for the same analytical m ethod when it is applied to biological matrix variations o f tissu e type (e.g., liver versus sera), tissue fractions/com ponents (e.g., w hole blood versus serum), and species variation (e.g., rabbit versus rat). Food and Drug Administration (FD A ) bioanalytical method validation guidance has been recently published to ensure analytical m ethod performance criteria are defined and are consistent w ith regulatory method guidelines for data reporting.13 Some recent publications on the determination o f APFO in biological matrices show low spike recovery. L ow (i.e., <70% ) spike recovery percentages may not be appropriate for reporting to regulatory agencies. Analytical m ethod validation plans for "partial" validation o f a method that already has successfully m et all requirements o f a fu ll validation w ill differ based on the sp ecific method change that requires validation. Exam ples o f sp ecific method changes requiring "partial validation" are given as a list in the FD A guidance docum ent1 1. Transfers betw een laboratories or between analysts 2. Change in analytical m ethodology (e.g ., detection system ) 3. Change in anticoagulant in harvesting biological fluid 4. Change in matrix w ithin species (e.g., human plasm a to human urine) 5. Change in sam ple processing procedures 6. Change in species w ithin matrix (e.g., rat plasm a to m ouse plasm a) 7. Change in relevant concentration range 8. Change in instruments and/or software platforms 9. Limited sam ple volum e (e.g., pediatric.study) 10. Rare m atrices (e.g ., lim ited number of.individual samples-endangered species) 11. Selectivity in the presence o f concom itant m edications 12. Selectivity in the presence o f sp ecific m etabolites 8 EXP000584 8.0 Solids The determination o f perfluorinated carboxylic acids or their salts in solids can be accom plished directly or indirectly. A n indirect method such as the com bustion o f the material with a W ickbold7 torch for total organic fluoride, follow ed by determination w ith fluoride ionselective electrode measurement, is used to see i f a fluorinated com pound is present in the solid. O f course the indirect method cannot definitively confirm the presence o f any sp ecific fluorinated material. A direct method would probably em ploy either thermal desorption, derivatization, gas chromatography m ass spectrometry (GC/M S) or solvent extraction follow ed by liquid chromatography tandem m ass spectrometry (LC/M S/M S). The m ass spectrometric methods are sp ecific and definitive since they provide both qualitative and quantitative data. The m ass spectrum and retention tim e are the minimum data needed to identify the presence o f a material in a solid. Often w ith a com plex matrix, such as a solid, it is necessary to also characterize the solid since the extraction efficien cy o f the analyte from its matrix w ill depend on the com position o f the solid and also perhaps how long the solid has been exposed to the analyte o f interest It m ight also be necessary to perform an aging and sequestration study to determine the effect o f aging and other com ponents o f the matrix. The EPA document "Preparation o f S oil Sam pling Protocols: Sampling Techniques and Strategies"18notes that m ost o f the variance involved in soil analysis com es from the sampling and not from the laboratory analysis. W ith solids from a manufacturing process, however, more information on the com position o f the solid w ould be known so that defining the analytical task should b e somewhat less co m p lex .' I f the solid's matrix contains other fluorinated species, a determination o f the concentration and source (decom position or reaction w ith the analyte o f interest) m ight also have to be performed to ascertain the "real" concentration 9.0 Additional Analytical Considerations Fluoropolymer polym erization aids are unique in their physicochem ical properties; therefore special care m ust be taken in sam ple preparation and analysis. Com m on predictive m odels may lead to significantly erroneous results for physicochem ical properties: Since these compounds "look" lik e hydrocarbons, the temptation is to assume sim ilar characteristics for measures o f volatility, solubility, etc. This temptation must be resisted and thought given to each step in die method w ith a fu ll slate o f quality assurance (QA) com ponents incorporated into the process from sam pling through analysis and date acceptance and reduction. Method validation studies need to be conducted to ensure the m ethod is sufficient in terms o f analytical recovery, sampler capacity, storage stability, determination o f lim its o f detection, and precision and bias o f the sam p les.16 Before any data are reported, if is important that the work be review ed for quality and rigor. A good resource is "Guidance for Industry, B ioanalytical M ethod Validation."13 This document is especially useful w hen GC or LC methods are em ployed, and is especially helpful for a single laboratory initiated validation. Table 2 contains som e suggested QA components that w ill add to the defensibility o f the data. EXP000585 9 T able 2 . D efin ition s o f Q uality A ssurance (Q ) C riteria QA Criteria ! Definition Blank ' A sam ple subjected to the usual analytical or measurement process to establish a zero or baseline value. Calibration A com parison o f a measurement standard, instrument, or item w ith a standard or instrument o f higher accuracy to detect and quantify inaccuracies and to report or elim inate those inaccuracies by adjustments. Check Standard A standard prepared independently o f die calibration standards and analyzed exactly like the sam ples. Duplicate Sam ples Iw o sam ples taken from, and representative of, the sam e population and carried through all steps o f sampling and analytical procedures in an identical manner. Field B lank A blank used to provide information about contam inants that m ay be introduced during sample collection, storage, and transport Laboratory Control Spike Determines the desorption efficien cy o f the target analytes from the sampling m edia. Samples are prepared by spiking blank sam pling media, preferably from die sam e lo t o f m edia used in sample collection, w ith quantities o f target analytes commensurate w ith die range determined in samples. Laboratory Split Sam ples Two or m ore representative portions taken from the sam e sam ple and analyzed by different laboratories to estim ate interlaboratory precision or variability and the data comparability. Matrix Spik e A sample prepared by adding a known mass o f a target analyte to a specified amount o f matrix sam ple for which an independent estimate o f the target analyte concentration is available. Method B lank A blank prepared to represent d ie sample matrix as closely as possible and analyzed exactly like the calibration standards, samples, and quality control (QC) samples. R esults o f method blanks provide an estimate o f w ithin batch variability o f the blank response and an indication o f the bias introduced by the analytical procedure. Split Sam ples Two or m ore representative portions taken from one sample in the field and or in the laboratory and analyzed by different analysts or laboratories. Surrogate Spike or A nalyte A pure substance w ith properties that mimic the analyte o f interest V a lid a tio n Confirmation by examination and provision o f objective evidence that the particular requirements for a specific intended use have been fulfilled. Variance (statistical) A measure o f the dispersion o f a sample or population distribution. EXP000586 10 10.0 References 1 E. K issa, "Fluorinated Surfactants and R epellents," Surfactant Science Series, A . T. Hubbard, Ed. Volum e 97, M arcel Dekkar, Inc., N ew York, 2001. 2 B . R. Bluestein and C.L. Hilton, ed s., "Am photeric Surfactants," Surfactant Science Ser. V ol. 12, Marcel Dekker, N ew York (1982). 3 Guide to the Safe Handling o f Fluoropolym er D ispersions. Fluoropolymer Manufacturers Group, The S ociety o f the Plastics Industry, Inc., W ashington, DC, October 2001. 4 ACGIH Threshold Lim it Values fo r Chemical Substances and Physical Agents and Biological Exposure Indexes (current edition). ACGIH, 1330 Kemper M eadow Drive, Cincinnati, OH 45240-1634. 5 M . Thompson and M . Ramsey, Analyst, 120 ,2 6 1 (1995). 6 J. B elisle, D . F. H agen, Analytical Biochem istry, 19 8 0 ,1 0 1 ,3 6 9 -3 7 6 . . 7 R. W ickbold, "Quantitative Com bustion o f Fluorine Containing Organic Substances," Angew. Chem., 1 9 5 4 ,6 6 ; 173-174. 8 C. A. M oody, W . C . Kwan, J. W . M artin, D . C. Muir, S. A. Mabury, Analytical Chemistry, 2 0 0 1 ,7 3 ,2 2 0 0 -2 0 6 . 9 M . Ylinen, H. Hanhijrvi, P. Peura, O . Rm , Arch. Environ. Contain, and T oxicol., 1985, 1 4 ,7 1 3 -7 1 7 . 10 J. B elisle, D . F. H agen, Analytical Biochem istry, 1 9 7 8 ,8 7 ,5 4 5 -5 5 5 . 11 T. Ohya, N . K udo, E. Suzuki, Y . Kawashim a, J. Chromatogr. B , 1 9 9 8 ,7 2 0 ,1 -7 . 12 C. Sottani, C. M inoia, Rapid Commun. M ass Spectrom ., 2 0 0 2 ,1 6 ,6 5 0 -6 5 4 . 13 Guidance for Industry, Bioanalytical M ethod V alidation. U . S. Department o f Health and Human Services, F ood and Drug Adm inistration, Center for Drug Evaluation and Research (CDER), Center for Veterinary M edicine (CVM ), M ay 2001. 14 W.K. Reagen, et. a l, "Analytical Techniques And M ethod Validation For The Measurement o f Selected Sem i-V olatile and N on-V olatile Organofluorochemicals In Air," AIH A Journal, manuscript in preparation. 15 J.W. Martin, et. a l., "Collection o f Airborne Fluorinated Organics and A nalysis by Gas Chromatography/Chemical Ionization M ass Spectrometry," Anal. Chem. 2 0 0 2 ,7 4 , 584-590. 16 Guidelines fo r A ir Sampling and A nalytical M ethod Development and Evaluation, NIOSH Technical Report (M ay, 1995). 17 K. J. Hansen, L . A . Clemen, M . E. E llefson, and H . O. Johnson; "Compound-Specific, Quantitative Characterization o f Organic Fluorochem icals in B iological Matrices," Environmental S cien ce & Technology; 2001; 35(4); 766-770. 18 "Preparation o f S o il Sampling Protocols: Sam pling Techniques and Strategies", EPA 600/R2/128 (1992). 19 T.J. Brice, in "Fluorine Chemistry," J.H. Sim ons, ed ., V ol. I, Academic Press, N ew York (1950). 20 D. Lines and H. S utcliffe, J. Fluorine Chem ., 2 5 ,5 0 5 (1984). 21 J.D. LaZerte, L.J. H als, T.S. Reid and G.H: Sm ith, J. Am . Chem. Soc. 75 ,4 5 2 5 (1953). 22 H.G. K lein, J.N . M eussdoerffer, and H. Niederprm, M etalloberflche 2 9 ,5 5 9 (1975). 23 V . Glckner, K. Lunkwitz, and D. Preseher, Tenside 2 6 ,3 7 6 (1989). 24 N . O. Brace, J. Org. Chem. 27,4491 (1962). 25 P. M ukeijee and K . J. M ysels, Pap. Sym p., 1974 ACS Sym p. Ser. 9 ,2 3 9 (1975). 26 J. H. Hildebrand, J. M . Prausnitz, and R. L. Scott, "Regular and Related Solutions," p. 204, Van Nostrand R einhold, N ew York (1970). 27 E. A. Kauck and A . R. D iessiin, Ind. Eng. Chem. 43,2332 (1951). EXP000587 11 APPENDIX A: Examples o f Fluoropolymer Polymerization Aids Chemical Name Heptafluorobutanoic acid Nonafluoropentanoic acid Ammonium nonafluoropentanoate Undecafluorohexanoic acid Sodium undecafluorohexanoate Ammonium undecafluorohexanoate Tridecafluoroheptanoic acid Potassium tridecafluoroheptanoate Ammonium tridecafluoroheptanoate Pentadecafluorooctanoic acid Potassium pentadecafluorooctanoate Sodium pentadecafluorooctanoate Ammonium pentadecafluorooctanoate Heptadecafluorononanoic acid Sodium heptadecafluorononanoate Ammonium heptadecafluorononanoate Nonadecafluorodecanoic acid Potassium nonadecafluorodecanoate Sodium nonadecafluorodecanoate Ammonium nonadecafluorodecanoate Heneicosafluoroundecanoic acid Potassium heneicosafluoroundecanoate Sodium heneicosafluoroundecanoate Ammonium heneicosafluoroundecanoate Tricosafluorododecanoic acid Potassium tricosafluorododecanoate Sodium tricosafluorododecanoate Ammonium tricosafluorododecanoate Synonym C4 acid C5 acid C5 NH4 salt C6acid C6 N asalt C6NH4 salt 7 acid C7 K salt C7 NH4 salt C8acid C8 K salt C8 Nasate C8 NH4 sait C9acid C9 Nasate C9 NH4 salt CIO acid CIO K salt CIO Na salt CIO NH4 salt C ll acid C ll K salt C ll Na salt C ll NH4 salt C12 acid C12 K salt C12 Na salt C12 NH4 salt CAS# 375-22-4 2706-90-3 68259-11-0 307-24-4 2923-26-4 21615-47-4 375-85-9 21049-36-5 6130-43-4 335-67-1 2395-00-8 335-95-5 3825-26-1 375-95-1 21049-39-8 4149-60-4 335-76-2 51604-85-4 3830-45-3 3108-42-7 2058-94-8 30377-53-8 60871-96-7 4234-23-5 307-55-1 6060-71-5 307-67-5 3793-74-6 Formula C3F7COOH C4F9COOH C4F9COONH4 C5F11COOH C5FllCOONa C5F11COONH4 C6F13COOH C6F13COOK C6F13CONH4 C7F15COOH C7F15COOK C7F15COONa C7F15COONH4 C8F17COOH C8F17COONa C8F17COONH4 C9F19COOH C9F19COOK C9F19C(X>Na C9F19COONH4 C10F21COOH C10F21COOK C10F21COONa C10F21COONH4 C11F23COOH C l 1F23COOK C l lF23COONa C l 1F23COONH4 12 EXP000588 Appendix B: General Physical and Chemical Properties a. Thermal Stability Perfluorinated surfactants are remarkably stable; enabling them to w ithstand conditions which w ould be too severe for hydrocarbon surfactants.1,16 The C-F bond is on e o f d ie strongest known, thus providing the fluorosurfactant stability even at high temperature in the presence o f acids, allralij oxidation and reduction. It has been found that perfluoroalkanecarboxylic acids and ptrfliinmalVanftsdfnnie acids are the m ost stable fluorinated surfactants, w h ile their salts decom pose more readily w ith the cation and R f chain length apparently o f profound in flu e n c e .1,17,18 b. Chem ical Stability Perfluorinated alkanoic and alkanesulfonic acids have excellent chem ical stability towards acids, oxidants and alkali.1,18,19 Perfluorinated alkanecarboxylic acids are strong acids, sim ilar in strength to m ineral acids.20 c. M elting Points The perfluorinated carbon chains o f surfactant m olecules, as compared to their hydrocarbon analogs, are stiff and inflexible due to the rigidity o f the C-F bond.1 It is believed that this contributes to their higher m elting points, a high Krafft point w ith reduced solubility in solvents. The Rf chain length and branching o f the terminal units have been found to have a marked effect on the m elting p o in t21 The size o f the cation also has an effect on the m elting p oin t The m elting points o f perfluorooactanoates w ith inorganic cations do not increase linearly w ith increasing size o f ionic radii17. This phenom enon is believed to be due to the reduce stability o f the salt w ith increasing size o f the ion ic radii. d. Solubility The unusual properties o f the fluorine atom and the C-F bond also affect the solubilities o f the fluorinated surfactants. Perfluoroalkanes are m ore hydrophobic than their hydrocarbon analogs as shown by their solubility data.22,23 T he Rfchain and the hydrophile have an effect on the solubility o f the fluorinated surfactant1 The solubility o f perfluoroalkanoic acids decreases w ith increasing chain length. A t 25 C, C l to C6 perfluorinated alkanoic acids are m iscible in water in all proportions whereas the C8 and CIO perfluorinated alkanoic acids are only slightly soluble.24 The sam e is true for the solubility o f alkali metal salts o f perfluorinated alkanoic acids in water - i.e. it decreases w ith increasing chain length. EXP000589 13 T ab le 3: P hysical and C hem ical P roperties Perfluorobutanoic acid (a) CAS# 375-22-4 M olecular F orm ula C4HF702 M olecular W eight 214.04 B oilin g P o in t 2(FC M elting Point -19.5 C (b) Perfluorovaleric acid (a) 2706-90-3 C5HF902 264.05 127 UC (c) N/A Undecafluorohexanoic acid (a) Perfluoroheptanoic acid 307-24-4 375-85-9 C6HF1102 C7HF1302 314.06 364.06 157*0 12 - 14 *C (f) at 742 mm (d) 175-177 6C 54 C in CC14 (c) Pentadecafluorooctanoic acid (g) Ammonium Pentadecafluorooctanoate (a) Perfluorononan-1-oic acid (a) 335-67-1 C8HF1502 3825-26-1 C8HF1502H3N 375-95-1 C9HF1702 414.07 431.10 464.08 89*C at 736 mm N /A N /A 55 - 56 C 157-165 C (h) 71-77 "C Perfluoro-N-decanoic acid (a,g) Perfluoroundecanoic acid (a,g) Perfluorododecanoic acid (a,g) 335-76-2 2058-94-8 307-55-1 C10HF19O2 C11HF2102 C12HF2302 514.09 564.09 614.10 28^C at 740 mm tP C at 60 mm 245^ at 740 mm 83 - 85 UC 96 -1 0 1 UC 107 -109 "C a B eilstein Institut zur Foerderung der Chem ischen W issenschaften. Copyright 1988-2001 b Henne; Fox; J. Am er. Chem.. Soc., 7 3 ,2 3 2 3 (1953). 0 B enefce-M alouet, S , Blancou, H ., Itier, J., Commeyras, A; Synthesis, 647-648 (1991). d E. A . Kauck, and A . R. D iesslin, Ind. Eng. Chem. 4 3 ,2 3 3 2 (1951). e B rice, et.al.; J. Am er. Chem .Soc. 7 5 ,2 6 9 8 -2 7 0 2 (1953). f Rubio, S., B lancou, H ., Commeyras, A .; J. Fluorine Chem ., 99(2), 171-176 (1999). 8 Data from M SD S sheets h D . Lines and H . Sutcliffe, J. Fluorine C hem .., 25,505-512 (1984). N /A - not available EXP000590 14 Perfluorobutanoic acid (a) Perfluorovaleric acid (a) Undecafluorohexanoic acid (a) Perfluoroheptanoic acid Pentadecafluorooctanoic acid (g) Ammonium Pentadecafluorooctanoate (a) Perfhiorononan-l-oic acid (a) Perfluoro-N-decanoic acid (a,g) Perfluoroundecanojc acid (a,g) Perfluorododecanoic acid (a,g) CAS# i Density 375-22-4 1.764 g/cmi (d) 2706-90-3 1.713 g/cmJ(d) 307-24-4 1.762 g/cmJ(d) 375-85-9 1.792 g/cm1(d) 335-67-1 N/A 3825-26-1 N/A 375-95-1 N/A 335-76-2 N/A 2058-94-8 N/A 307-55-1 N/A R efractive Index 1.297 1.294 at R.T. at 589 nm (e) 1.298 at R.T. at589nm 13119 at 27*C at 589 nm N /A N /A N /A N /A N /A N /A Vapor Pressure 10 mm Hg at20C N /A N /A N /A 0.1 kPa (0.75 mm Hg) N /A N /A N /A N /A N /A W ater Solubility N /A N /A N /A N /A 3.4-9.5 g/L N /A N /A N /A N /A N /A EXP000591 15 A PPE N D IX C: C om p arison o f A vailab le A n a ly tica l T ech n iqu es fo r F lu orop olym ers1 ` I g Sensitivity Total Fluorine Low ppm lT N M R * GC/FID Low ppm Low ppm GC/MS* GC/ECD Low ppm Low ppm LC LC/MS* Low ppm ppb LC/MS/MS* Sub-ppb Strengths Non-matrix specific Versatile Specificity Readily available Specificity Sensitivity Sensitivity Specificity Minimal sample preparation Specificity Minimal sample preparation W eaknesses Non-specific Operator dependent Field strength dpendrait Non-specific Multi-step (derivatization) Multi-step (derivatization) Multi-step (derivatization) Narrow range o f linearity Radiation (Ni source) Detector dependent Possible matrix interference Cost o f Instrum entation <$20,000 USD >$100,000 USD $20,000 - 50,000 USD $50,000 100,000 USD $20,000 - 50,000 USD $20,000 - 50,000 USD $50,000 100,000 USD Timing After Samnle Prenaration and Instrument Calibration One sample per hour One sample every 8 hours Data acquisition less than 1 hour Date, acquisition less than 1 hour Date acquisition less than 1 hour Date acquisition less than 1 hour 30 minutes per sample Possible matrix >$100,000 USD 30 minutes per interference sample 1Analytical techniques should be validated for each individual fluoropolym er being analyzed for. * Technique which requires greater or significantly greater operator sk ill titan others listed here. EXP000592 16