Document gaaLj22zRRa2OLj3rNd0QJJqJ

Date Division/Dept. Author 02.06.2023 EL-SC-QRGD EL Product Compliance EU PFAS IN ANALYTICAL LABORATORIES Contents SUMMARY ................................................................................................................................ 1 USES OF FLUOROPOLYMERS IN ANALYTICAL LABORATORIES ................................................. 2 USE OF NON-POLYMER PFAS IN ANALYTICAL LABORATORIES ................................................ 5 PROPERTIES AND BENEFITS OF FLUOROPOLYMERS .............................................................. 10 WASTE TREATMENT ............................................................................................................... 15 EXPOSURE AND EMMISSION .................................................................................................. 16 IMPACT OF PFAS RESTRICTION ON ANALYTICAL LAB USE ..................................................... 16 LITERATURE REFERENCES AND LINKS: ................................................................................... 17 SUMMARY According to Article 67 (1) of the REACH Regulation, restriction "shall not apply to the manufacture, placing on the market or use of a substance in scientific research and development." Thus, we expect for the upcoming PFAS restriction that the use of non-polymeric PFAS as substance or mixtures in R&D applications will be exempted and that analytical standards will fall under a time-unlimited derogation. Nevertheless, this exemption may not be valid for fluoropolymers or PFAS substances that are part of analytical equipment, so we will provide information on the beneficials and irreplaceability of fluoropolymers for the laboratory use within the following sections. In analytical laboratories, a variety of PFAS chemicals as well as instruments and equipment that consist of or contain fluoropolymers is used. As part of many analytical equipment, fluoropolymers like PTFE, PFA etc. play a central role in analytical lab applications and are used in various processes where chemical, thermal, and electrical stability is required. Replacing these equipment parts with fluorine-free alternatives would disable a vast number of analyses like HPLC, GC-MS, impurity profiling of materials in low concentrations levels especially in case of ultra-trace analyses for semiconductor applications (i.e. analytical methods enabling detection and quantification of analytes in ppm and ppb and even ppt scale), Karl-Fischer titration etc. The main reason is that none of the currently available fluorine-free materials have equal chemical stability towards chemicals which are mandatory for sample preparation or during analysis (e.g. organic solvents, concentrated acids like fluoric acid). Consequently, such routine analysis would not be conducted within EU laboratories anymore and thus quality measurements required for manufacturing standards and specifications would not be available after entry into force of the EU PFAS restriction if no derogation for PFAS used in analytical laboratories is granted. PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 1 Thus, due to the inalienability of PTFE and similar fluoropolymers in analytical laboratory equipment an unlimited derogation for using fluoropolymers in analytical lab equipment is needed. Without such derogation, most of the analytical methods would not be technically feasible anymore, leading to lack of numerous quality measurements and analytical methods employed at manufacturing sites and R&D laboratories. Consequently, without an exemption for PFAS polymers in analytical and lab equipment, analysis of many chemicals, chemical R&D activities as well as chemical manufacturing would be largely jeopardized in the EU. In the following sections the use of PFAS materials in laboratory equipment is demonstrated, with practical examples illustrated and evidence for necessity to use these materials is given by information on compatibility of PFAS polymers compared to alternative materials. Information on the waste handling is given as well. Additional comments will be submitted separately by Merck to provide also regarding other PFAS uses a better basis for an adequate regulation of PFAS materials. Merck is additionally actively contributing to industry association comments as e.g. from VCI, Cefic, SEMI, SIA and EFPIA - some comments are already submitted, others will be submitted later in course of the consultation phase. USES OF FLUOROPOLYMERS IN ANALYTICAL LABORATORIES PFAS are present both as polymeric and non-polymeric substances within an analytical laboratory. The polymeric PFAS, i.e., fluoropolymers (typically PTFE, Polytetrafluoroethylene or PFA, perfluoroalkoxy polymer) used in analytical labs are often parts of analytical equipment, their spare parts and lab ware like tubes, valves, fittings etc. Furthermore, analytical sample preparation - especially when using harsh chemicals and/or when contamination-free analyses in very low detection limits (e.g. ppb to ppt range) are in demand - depends on chemically very stable materials which is only feasible using PFAS-based materials. Based on the excellent physico-chemical properties of fluoropolymers, a huge variety of lab equipment and instruments consist of this material since fluoropolymers are known to be chemically inert, very stable, durable and compatible with a broad range of organic solvents and acidic media[1]. For example, the following standard analytical instruments contain fluoropolymers in their equipment parts: the IR spectrometer (see Picture a)) contains PTFE hoses for gas transfer and various seals in the system made of PTFE. In addition, PTFE tubes are also part of the Karl-Fischer titration instruments (see Picture b)) and there are also various parts in an ICP-MS spectrometer made of PFA or PTFE (see Picture c)), such as capillaries, caps, valves, nebulizer, solvent bottles, and the spray chamber. Especially for this technique inert, chemically stable and contamination-free equipment is indispensable to allow the analysis of samples after digestion with harsh acids (e.g. fluoric acid) and/or to achieve very low detection limits for various analytes which are required not only for analyzing semiconductor materials. Furthermore, in standard HPLC systems, the core parts of the instrument such as the injector, degasser, membranes, filters etc. are also made of PFA or PTFE (see Picture d)): (Even more information how many and which PFAS substances are used can be provided by the instruments manufacturers.) PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 2 Picture a) TGA-FTIR-Spectrometer[2] Picture b) Karl-Fischer Titration Instrument[2] PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 3 Picture c) ICP-MS instrument[2] Picture d) HPLC system[2] PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 4 An overview on the application areas and life cycle of PFAS substances and fluoropolymers employed in an analytical lab is shown in Table 1 (Fluoropolymers) and Table 2 (non-polymer PFAS substances). For all uses depicted in Table 1, up to our knowledge, there are currently no alternative PFAS-free substances and polymers available which show similar properties. USE OF NON-POLYMER PFAS IN ANALYTICAL LABORATORIES Considering the non-polymer PFAS substances in Table 2, the examples of uses and applications are not exhaustive, so there are certainly more lab-specific uses where non-polymeric PFAS substances are required and cannot be replaced. According to Article 67 (1) of the REACH Regulation, restriction "shall not apply to the manufacture, placing on the market or use of a substance in scientific research and development." However, to also reflect this use of PFAS and the non-substitutability in these applications we provide the following information on non-polymer PFAS use in analytical laboratories. In general, non-polymer PFAS substances are mostly analytical lab reagents and standards used for various R&D and QC purposes such as synthesis as well as calibration of analytical instruments or analytical method validations. Especially calibration of analytical instruments for quality control purposes requires chemically stable standard solutions for accurate calibration measurements. For example, trifluoroacetic acid (TFA) is commonly used as additive in eluents in HPLC analysis. TFA acts as an ion paring agent in reversed-phase chromatography to improve peak shape and resolution. The silica used in columns may have metal ion impurities, which can cause peak tailing and loss of resolution. An ion-pair reagent such as TFA added to the mobile phase at a concentration of approximately 0.1 % can "shield" the metal ion and help to maintain good peak shape[3]. In rare cases non PFAS chemicals are preferred: For LC-MS analysis, formic acid is favored over TFA, because it was found that TFA can suppress ionization of analyte molecules[4]. Perfluorotributylamine is also a standard PFAS lab chemical that is required for tuning in gas chromatography (GC)[5], which is very substance-specific and thus cannot be replaced by a chemically different substance. Also, any other PFAS substance that is used for calibration (internal or external standard substances) of a HPLC or similar analytical instrument. Another example where PFAS are employed is derivatization in GC-MS analysis: Some substance groups such as amino acids are often not sufficiently volatile to be analyzed via GC-MS. Therefore, chemical derivatization of such substances is required to enhance the volatile properties of the amino acid subject to GC analysis, e.g. by silylation of the amino acid[6]. A typical silylating agent is N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) which reacts efficiently with the amino group and replacing one proton with the trimethylsilyl group. The resulting derivative is then volatile and thus can be analyzed by GCMS. Furthermore, various PFAS substances like deuterated TFA or Ethyl Nonafluorobutyl Ether are used as solvents for NMR and ICP-MS analysis or in chemical synthesis where other solvents fail to dissolve specific components. Also, some particular PFAS substances may serve as analytical standard when analytical methods are developed and validated to enable analysis of these specific PFAS substances in environmental media such as water (e.g. DIN 38407-42:2011-03). PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 5 Table 1: PFAS-containing equipment in a typical analytical laboratory, source Merck Single-use Multi-use* Long-term use** Application area Polymeric PFAS (PTFE, PFA, FKM, PVDF) PTFE Septum for screwcap bottles (HPLC-Vials) Part of HPLC vials for HPLC analysis Substitution / Alternative available Reason for no alternative(s) - Rubber septum with Part of HPLC vials for HPLC analysis - PTFE coating (HPLC- Vials) Syringe filter with PTFE Synthesis and analytical sample - membrane Teflon tape PTFE and PFA capillaries in auto-samplers preparation Sealing of mixing vessels, adapter fittings, flasks etc. Part of HPLC autosampler Alternative fluorine-free materials - not available, since all non- fluorinated materials and coatings - are not suitable for ultra-trace analysis (contamination and HPLC and eluent tubes Part of HPLC equipment - leaching) or are not resistant/stable Sealings and fittings in all Equipment parts of various analytical - against aggressive chemicals like analytical instruments instruments organic solvents, hydrofluoric acid. PFA-Pipet tips Standard lab equipment for handling - chemicals PFA-dispenser Standard lab equipment for handling - chemicals PFA-Spray chamber Vaporization vessel for dissolved - chemicals PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 6 Single-use PTFE ground sockets for sealing of Karl-Fischer titrator Multi-use* Gaskets/Transfer lines in various analytical instruments Long-term use** Application area PFA-Bottles (1 L, 500 ml, 250 ml, 100 ml, 50 ml) for storage of 60 % nitric acid and 40 % hydrofluoric acid PFA digestion vessels (60 ml, 50 ml, 10 ml) (automatic) dispensers PFA-Syringes Heating block/Heating plate (coating) Auto sampler needle PFA Auto sampler racks PTFE Beakers PFA/PTFE PTFE Spatula Pressure tubes Calibrated precision glass stirrer blades 6-Way-Valves (PFA/Graphite) PTFE tubes for KarlFischer titration Storage of liquid and solid chemicals Standard lab equipment in synthesis/sample preparation Liquid chemical vessel Standard lab equipment for handling chemicals Standard lab equipment in synthesis/sample preparation Part of HPLC instrument Part of HPLC instrument Used for mixing/synthesis Standard lab equipment for handling chemicals Analytical sample purification Part of calibrated precision glass stirrer used for mixing of various solvents, acids and alkaline solutions Connection of tubes for liquid/gas transport Organic-solvent and acid-resistant liquid transfer tubes Substitution / Alternative available - Reason for no alternative(s) - - - - - - - - Parts of the Karl-Fischer titrator, no PFAS-free spare parts available since high chemical inertness required PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 7 Single-use Multi-use* PTFE/PVDF vessels PTFE/PVDF caps and sealings EVol Pipettes Tweezers Long-term use** Application area Stirring bars with PTFE coating Coatings Sealings and gaskets Stirrer glands Mixing/chemical synthesis Coating of thermostat and coated glass ware used in fluorination synthesis Evaporator for solvent removal as well as inliners in caps of glass bottles; mixing vessels Mixing of chemicals/solvents Substitution / Alternative available - - Reason for no alternative(s) High chemical inertness and durability must be ensured - - Various Spare parts used in particle - PFTE/Teflon/PFA parts measurements (sealings, cartridge filters, valves, tubes, fittings) Vessels for extraction and storage of chemicals Sealing of storage vessels and bottles Spare parts supplied by analytical equipment manufacturer, high chemical and thermal resistance must be ensured High chemical inertness and durability must be ensured Temperature sensor Teflon ring(s) Standard lab equipment for handling chemicals Standard lab equipment for handling chemicals Part of several analytical instruments (Karl-Fischer, HPLC) Parts for fitting of sublimation apparatus PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 8 Single-use Multi-use* Long-term use** Teflon spray/grease PTFE-syringe filter Viton gloves used in glove box Solvent tubes and capillaries (Tefloncoated) Filter frit Barbed hose connections Taps from lab equipment SCAT adapter and cap with screw fitting for eluents SCAT adapter for solvent canisters Press crucible seal *Multi-use = Use of material for approx. up to 5 years **Long-term use = Use of material for approx.more than 5 years Application area (Organic) solvent-resistant fitting (Organic) solvent-resistant hand protective wear Transfer of liquids/gases, part of vacuum pumps Filtration of chemical mixtures containing various solvents, acids and alkaline solutions Tube fittings between various parts in analytical equipment for transfer of gases/liquids Cutoff valves for e.g. separatory funnels, dropping funnels etc. Filter frit on eluent tubes in HPLC instruments Transfer of liquids/gases Transfer of liquids/gases Sealing/fitting of press Substitution / Alternative available - - - - Reason for no alternative(s) High chemical inertness and durability must be ensured High chemical inertness and durability must be ensured - - - High chemical inertness and durability must be ensured - - PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 9 Table 2: Non-Polymer PFAS examples - used for R&D purposes, thus exempted from PFAS Restriction according to Article 67 (1) of the REACH Regulation Single-use Trifluoroacetic acid (TFA) Perfluorotributylamine (PFTBA) Ethyl Nonafluorobutyl Ether Silylating agents N,OBis(trimethylsilyl)trifluoroacetamide (BSTFA), N-Methyl-N(trimethylsilyl)trifluoracetamide (MSTFA) Deuterated Trifluoroacetic acid Application Area Eluent additive for HPLC analysis with ion-pairing properties Calibration substance and tune solvents for mass spectrometers Solvent in product analysis for various chemical products; R&D purpose, exempted from Restriction Inerting and enhancing volatile properties of non-volatile analytes (amino acids etc.) for GC-MS analysis NMR solvent; R&D purpose, exempted from Restriction Trifluoromethanesulfonic acid anhydride Trifluoromethanesulfonic acid Heptafluorobutyric acid Pentafluoropropionic acid 1,1,1,3,3,3-Hexafluoro-2-propanol (Triflate)-Synthesis, derivatization for GC-MS analysis Synthesis, strong acid, deuteration Analytical lab standard and reagent, ion-pair reagent Analytical lab standard and reagent, ion-pair reagent Analytical lab standard Perfluoroheptanoic acid Analytical lab standard Potassium tris(pentafluoroethyl)trifluorophosphate Heptadecafluorooctanesulfonic acid potassium salt Analytical lab standard Analytical lab standard PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 10 PROPERTIES AND BENEFITS OF FLUOROPOLYMERS According to the Teflon PFTE fluoropolymer resin Handbook from DuPont[1], PTFE is chemically inert and up to the temperature of 260 C known to react with only very few chemicals, i.e., molten alkali metals, turbulent liquid, or gaseous fluorine. The reason for this degree of inertness is based on the chemical structure of PTFE, consisting of strong carbon-carbon bonds and very strong carbon-fluorine bonds with the effect that the fluorine atoms form a protective sheath around the carbon core of each molecule. Therefore, PTFE also has special properties like insolubility, low-surface adherability and friction. The chemical stability and inertness of fluoropolymers allow that most of the fluoropolymer equipment in analytical instruments is used more than once, even for longer terms like months or even years (see Table 1). Considering inertness and chemical stability, the compatibility of different polymeric materials towards protic and aprotic (organic) solvents, strong acids required in an analytical lab performing routine analyses (including 50 % hydrofluoric acid used for digestion of difficult matrices) is shown in Table 3: The compatibility of materials towards solvent is indicated as colored circles and figure: a green circle with "1" means fully compatible, fully resistant, whereas yellow and red circles represent a partially or no resistance towards the solvent. The materials with other than green circles should not be used for a proper and safe handling of the equipment and product. The blue colored materials are different Fluoropolymers; the green colored materials are "fluorine free materials". When looking at the green circles in the table below, it is evident that a use of PTFE, PFA, PVDF or FKM is required when solvents such as acetone, n-heptane, acetonitrile, or xylene that are standard organic solvents in analytical labs are employed in analysis or synthesis. For example, a routine analytical method is the Karl-Fischer Titration for quantitative water content determination in a chemical substance or mixture[7]. This analytical method is based on harsh chemical conditions by using sulfur dioxide, iodine, and pyridine in methanolic solution and is conducted frequently as standard analysis several times per week or even per day in a quality control (QC) analytical lab. As it can be seen from Table 3, PTFE withstands strong acidic media like sulfuric acid as well as methanol, whilst non-fluorinated polymers like EPDM (ethylene propylene diene rubber) or NBR (Nitrile Butadiene Rubber) would be chemically unstable under the same reaction conditions in methanol and sulfuric acid. Therefore, several Karl-Fischer Titrator equipment that are commercially available[8] consist of PTFE parts to endure these strong acidic reaction conditions. The chemical inertness and smooth surface of PTFE equipment is also a prerequisite for ultra-trace analysis which is applied - amongst others - in the quality control of semiconductor materials. Since the specification of semiconductor products must be verified by measurements even down to the ppt range, no other analytical method than ultra-trace analysis based on ICP-MS is sensitive enough to detect such low concentrations. However, since this method is highly sensitive, already very low concentrations of contaminations caused by leaching of tubes, filters etc. in the analytical apparatus can hamper and falsify the measurements. This was already reported by Beinrohr et al.[9] and could be prevented by using carefully cleaned labware made of high-purity, inert materials with negligible adsorption properties. PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 11 Table 3: Comparison of several fluoropolymers and non-fluorinated polymers regarding durability against various solvents and acids used in the Merck analytical laboratory PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 12 We have also investigated the chemical stability and leaching effects of lab ware like O-rings or tubes made of various polymeric materials against standard organic solvents. For example, standard organic solvents used in analytical laboratories for chemical synthesis, chromatography, analysis etc. dichloromethane (DCM), ethyl acetate, tetrahydrofuran (THF) and xylene. At first, we tested the chemical stability of PTFE by storing weighed and measured samples of a black PTFE gasket in DCM (S1), in ethyl acetate (S2), in tetrahydrofuran (S3) and xylene (S4) for 40 days at a temperature of 80 C in tightly sealed glass bottles. At the end of this storage period, the solvents were visually inspected for any coloration of the solvent or sample changes. As it can be seen from Picture e), no coloring or changes in any of the four samples could be observed. Picture e) Stability test result of storing PTFE at 80 C for 40 days[10] Furthermore, each sample was weighed, and its length measured directly after the end of the treatment and 12 hours later after drying the sample to determine any volume or mass changes (in total: observation time 43 days). The results are summarized in Table 4: Table 4: Results of the PTFE (black sample) treatment at 80 C with various solvents after 43 days[10] Relative mass change [%] first value: directly after treatment; second value: after 12 h sample drying Solvent DCM Ethyl acetate THF Xylene PTFE black 1.1 / 0.7 0.4 / 0.2 0.5 / 0.3 0.5 / 0.3 Except for the black PTFE sample in DCM, all other samples showed only very small mass changes in the range of 0.1 - 0.5 % which was almost completely reversible after drying of each sample. The storage solvents were also analyzed via GC FID which also showed only a minor increase in unknown impurities in the ppm range. Further details and chromatograms on these stability tests can be reviewed in the test report no. 3485[10]. We also conducted similar stability tests with lab ware made of non-fluorinated polymeric materials like Ethylene Propylene Diene (Monomer) Rubber (EPDM) and silicone. The reaction conditions were similar like the ones with PTFE described above, but with even shorter storage period (max. 96 h) and at lower temperatures (40 C). PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 13 One experiment was storing a sample of an EPDM gasket for 96 h in DCM at 40 C in a sealed glass bottle and monitoring any visual changes during and after storage. Indeed, a yellow coloration of the usually colorless DCM was observed during and after the treatment (see Picture f)) which is caused by leaching of additives or impurities from the EPDM material. Picture f) Stability test of EPDM in DCM[11] A very similar test was performed by treating a silicone tube in toluene over 96 h at 40 C with subsequent dying (see Picture g)). Picture g) Stability test of silicone in toluene[11] As it was determined by weighing and measuring after 96 h treatment and after drying, the length and weight of the silicone tube did significantly change, resulting in a swelling of the tube directly after PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 14 treatment in toluene with a relative volume change of 100 % and a relative mass change of 59 %. After drying, the tube showed a volume (-7 %) and weight (-5 %) loss which demonstrated an irreversible change of the tube. Comparable stability tests and compatibility effects have also been reported by the SIA PFAS Consortium[12], reporting similar trials of chemical compatibility of PFAS-free materials like HDPE with acids like sulfuric or nitric acids. One observation from these trials was the following, which is also very critical in terms of safety: "NonPFAS elastomers have been used as O-rings and seals, by mistake, within mechanical and chemical/gas delivery systems. In some cases, these seals failed almost immediately and caused leaks due to their incompatibility with the gases and chemistries running through the lines. This has resulted in the requirement to disassemble the system and replace the O-rings, result in >10 days of lost production time to replace and requalify the system." Another observation described by the SIA PFAS Consortium[12] was the following: "HDPE was investigated as a possible replacement for PTFE in tanks, tubing, and containers, however after 6 months it was found to start decomposing in 70 % nitric acid, which leads to chemical leakage and an increased replacement rate." Overall, it becomes obvious that fluoropolymers have superior physico-chemical properties over nonfluorinated polymeric materials in analytical equipment due to their high durability and compatibility to a broad range of temperatures and solvents, which is also a safety aspect when using such equipment and chemicals in an analytical laboratory. It must be pointed out that PFAS materials are used as described above despite their high costs compared to alternative materials - PFAS materials are by far the costliest materials for such applications - however, due to the unique properties this material is chosen. A comparison of the costs for an O-ring is shown in Table 5. Table 5: Costs for an O-ring consisting of different polymer materials Material of o-ring Costs for the o-ring [/piece] NBR 0.60 Silicon 1.50 EPDM 2.30 FKM* 4.30 Silicon mantled with FEP* 17 PTFE* 19 FFKM* 230 *PFAS WASTE TREATMENT Single-use substances such as trifluoroacetic acid (TFA) applied as HLPC eluent are collected after use as chemical waste and discarded in dedicated facilities according to national regulations[13]. The same disposal route applies to multi-use and long-term use PFAS polmyers ( fluorpolymers), but since their durability and long-life, producing limited amount of waste over their long lifetime. As it can be seen from Table 1, a lot of analytical equipment consisting of fluoropolymers is used more than once and often for several years before it is replaced, thus waste is minimized and thus volumes of PFAS-containing waste are very low. PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 15 Furthermore, the PFAS equipment waste is separately collected at its end-of-life phase and is subject to hazardous-waste incineration[13]. EXPOSURE AND EMMISSION The exposition to workers handling non-polymer PFAS is minimized by wearing protective equipment such as appropriate gloves, safety goggles, and handling the chemicals in the fume hood. Furthermore, professional lab workers are trained on a regular basis in disposal and recycling of chemical waste as well as contaminated materials and equipment parts. Especially PTFE bottles and similar storage vessels are often reused multiple times before disposal, which also minimizes chemical waste. Exposure of workers to PFAS polymers is considered as not relevant due to their high stability. Since used fluoropolymer equipment as well as PFAS chemicals are collected and discharged as chemical waste, exposure to water, soil or air due to the laboratory use is considered to be not significant. IMPACT OF PFAS RESTRICTION ON ANALYTICAL LAB USE Although lab reagents are exempted for R&D purposes from restriction under REACH, the analytical equipment consisting of fluoropolymers would not be exempted according to the current restriction proposal. Thus, R&D activities as well as quality and routine analysis would be largely jeopardized in EU with critical impact on the whole chemical industry and beyond it - considering downstream consequences and impacts on other areas using comparable or even the same analytical methods as e.g. environmental analysis. Information on the economic impact on Merck Electronics is given in a confidential attachment to the Merck Electronics submission related to PFAS use in chemical manufacturing. PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 16 LITERATURE REFERENCES AND LINKS [1] Teflon PTFE DuPont Handbook: http://www.rjchase.com/ptfe_handbook.pdf [2] Analytical equipment pictures: Merck SM analytical laboratory [3] Source AAT Bioquest: https://www.aatbio.com/resources/faq-frequently-asked- questions/Why-is-trifluoroacetic-acid-TFA-used-in-reverse-phase-chromatography-for-proteinpurification [4] Source: https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/marketing/global/documents/1 29/989/11547.pdf [5] PFTBA in GC tuning https://www.chemwifi.com/2020/02/pftba-internal-standard.html [6] Villas-Bas et al., Metabolites 2011, 1(1), 3-20; https://doi.org/10.3390/metabo1010003 [7] Original publication Karl-Fischer titration: https://onlinelibrary.wiley.com/doi/epdf/10.1002/ange.19350482605 [8] Karl-Fischer Titrators and spare parts: https://www.ysi.com/product/id-tz1798/karl-fischerptfe-tube [9] Beinrohr et. Al., Chem. Papers 43 (4) 513-517 (1989): https://chempap.org/file_access.php?file=434a513.pdf [10] Blitz T., " Bestndigkeit von PTFE-Dichtungen fr Schfer IBCs in verschiedenen Lsungsmitteln", PM-ADU Corrosion & Material testing, Merck Report No. 3485, 2011 [11] Pictures and test data: Merck EL-SC-DUC group [12] Report No. 2022-0737 Rev. 0 (pages 87ff), The Impact of a Potential PFAS Restriction on the Semiconductor Sector, SIA PFAS Consortium https://www.semiconductors.org/pfas/ [13] UBA information on waste disposal: https://www.umweltbundesamt.de/en/topics/wasteresources/waste-disposal PFAS IN ANALYTICAL LABORATORIES - MERCK ELECTRONICS 17