Document DD9rd8QaQJOYbGMZjnOooObvn

El BASF We create chemistry September 20, 2023 Response to the Public Consultation of the Restriction on the manufacture, placing on the market and use of PFAS Part 7/7: PFAS uses in analytics Our Key Messages In analytical and research laboratories, PFAS are required for multiple uses. In analytics especially PFAS solvents are indispensable. REACH already includes a general exemption for research and development, but due to higher volumes required in industrial QC analytics, the low volume limits of one ton per year will likely not be sufficient. BASF requests an explicit exemption of all PFAS used for analytical purposes or contained in analytical equipment, as a substance, mixture, or article, from the scope of the PFAS restriction. Maintaining use of PFAS in R&D and QC laboratory environment to ensure future availability of highly sensitive and reliable analytical methods to protect humans and environment. For further information please contact BASF SE, M@basf.com Page 1 of 10 El BASF We create chemistry PFAS are essential substances in analytical laboratories. They are frequently required in sample preparation before analysis can even start. If a sample cannot be dissolved in a solvent or filtered to avoid impurities, measurements cannot be conducted with common analytical techniques. The analytical methods themselves are often based on additives to transform the analyte into a measurable form. The instruments require calibrants for system calibration and many components of the analytical equipment consist or contain PFAS to ensure performance and their chemical, thermal, and electrical stability. 1. Consideration of Consistency of Analytical Activities within REACH Regulation Article 67 (1) of the REACH Regulation describes that the restriction "shall not apply to the manufacture, placing on the market or use of a substance in scientific research and development." Scientific research and development are defined by Article 3.23 as any scientific experimentation, analysis or chemical research carried out under controlled conditions in a volume of less than one ton per year. A definition of `controlled conditions' is not provided in the REACH Regulation nor in the SR&D guidance description but terms ,SR&D' may include any experimental research or analytical activities at a laboratory. BASF assumes that the PFAS restriction will also apply to PFAS uses in analytical methods for quality control and product release as well as for PFAS containing articles like consumables, lab equipment, and instrument equipment. BASF proposes to explicitly exempt all PFAS used for analytical purposes, as a substance, mixture, or article, from the scope of the PFAS restriction time-independently. A restriction of the use of PFAS in analytical activities would lead to a limitation of numerous quality measurements and analytical methods employed at manufacturing sites and analytical laboratories. Consequently, analysis of chemicals, analytics in diagnostic settings as well as chemical manufacturing would be jeopardized in the EU after entry into force of the EU PFAS restriction. 2. Necessity of PFAS in Analytical Activities 2.1 Use cases of PFAS in the Analytical Laboratory In the following Table 1 PFAS chemicals and Table 2 PFAS containing consumables as well as their uses are listed, which have been identified at BASF. They are essential for the application of validated analytical methods for quality control and product release at BASF. In the following sections, specific use cases with practical examples will be presented. For further information please contact BASF SE, l=@basf.com Page 2 of 10  BASF We create chemistry Table 1: PFAS chemicals and their uses. Substance Code Hexafluoro isopropanol HFIP CAS number 920-66-1 General use solvent, extraction agent Trifluoroacetic acid TFA 76-05-1 saodldvietinvte, 2,2,2-Trifluoroethanol TFE 75-89-8 Trifluoromethanesulfonic acid N-methyl-N(trimethylsilyl)trifluoroacetamide N,OBis(trimethylsilyl)trifluoroacetamide Trifluoroacetic acid anhydride N-methyl-bis-trifluoroacetamide N-Methyl-N-trimethylsilylheptafluorobutyramide N-tert-Butyldimethylsilyl-Nmethyltrifluoroacetamide N-methyl-N-tertbutyldimethylsilyltrifluoroacetamide N,O-Bis(trimethylsilyl)trifluoractamide Heptafluorobutyric anhydride TFMS MSTFA BSTFA TFAA MBTFA MSHFBA MTBSTFA MBDSTFA Silyl-991 HFBAA 1493-13-6 24589-78-4 25561-30-2 407-25-0 685-27-8 24589-78-4 77377-52-7 85523-00-8 10416-59-8 336-59-4 solvent, titration titration derivatizing agent Specific use - Polyamides (PA), polyethylene (PET), polybutylene terephthalate (PBT) and polyoxymethylene (POM) - all analysis in solution, e.g., NMR spectroscopy, light scattering, GPC - ion pairing agent for HPLC mobile phase - solvent for proteins - agent for derivatization, enzyme inhibitor - solvent for polar polymers, e.g., polyamides, and for proteins and enzymes - conductometric titrations titration agent silylation for gas chromatography (GC) For further information please contact BASF SE, @basf.com Page 3 of 10 0 BASF We create chemistry Substance Perfluorobutanoic acid Europium tris[3(trifluoromethylhydroxymethylene)(+)-camphorate] 2,2,2-Trifluoro-1-(9-anthryl) ethanol Trifluoroacetic acid Code PFBA TFAE TFA 4-(Trifluoromethoxy)benzoic acid ,1,1-Trifluoroacetone Perfluorotributylamine PFTBA Perfluorocerosene PFK Trifluoroacetate Trans-1,1,1,3-tetrafluoropropene Hexafluoro butene Perfluoro hexane Pentafluoro butane Perfluoro pentane Heptafluoropropane Dichlorotrifluoro ethane NT HFC245F Trans-1-chloro-3,3,3-trifluoropropene R123 Solstice LBA For further information please contact BASF SE, CAS number 375-22-4 General use additive 34788-82-4 65487-67-4 76-05-1 330-12-1 421-50-1 311-89-7 reagent reference material reference material reference material reference material reference material reference material Specific use eluent additive to ion chromatography mobile phase lanthanoid shift reagents for the determination of enantiomers in NMR mass calibration of GC-MS devices 19F solid-state NMR (pulse calibration and quantification reference). 306-83-2 reference material, blowing agent blowing agent for polyurethane foams reference material for volatile organic compounds (VOC) analysis @basf.com Page 4 of 10 0 BASF We create chemistry Table 2: PFAS in consumables and their uses. Substance Polytetrafluoerethylen (Teflon) Code PTFE General use sample preparation, demoulding agent, tools, lab equipment, apparatus Perfluoralkoxy-Polymer Polyvinylidenfluorid Polyfluoroelastomer Fluorelastomer Trifluoropropylmethylpolysiloxane Pentafluorophenylpropyl PFA PVDF Kalrez 375 Fluran F-5500-A PFP lab equipment lab equipment apparatus apparatus apparatus Specific use - fuse bodies in measuring containers (solid-state NMR) - tubes, capillaries, syringes, syringe plungers, syringe filters, mixer stirrer - Teflon tape, Teflon spray - calibration samples & reference material, reference surface - resistant insulator as sample holder for electrical measurement systems, low-loss dielectric for radio frequency devices - Apparatus (sub boiling distillations of high purity acids, vessel cleaning system), fittings, sealing rings, stirring rods, temperature sensors, gasket, grooved boot, seals - cells, sensor holders - microwave vessels (Mars, Turbowave) and lids (UClave, Turbowave, Blade) dimensional flasks, bottles, trays, tubes syringe filters gasket rings tubing column in gas chromatography (e.g., DB - 210, RTX - 200 MS) column in HPLC (e.g., ChromegaChiralTM Chiral CCO F2) For further information please contact BASF SE, @basf.com Page 5 of 10 El BASF We create chemistry 2.2 Analytical Methods for PFAS The necessity for harmonization of analytical methods for the determination of PFAS in different matrices, the availability of analytical methods and the difficulties of the thresholds given for PFAS determination in the restriction proposal are discussed in in BASF's submission Part 1/7: General remarks and proposals. To support enforcement and to ensure a level playing field for all actors in the European market harmonized analytical methods for PFAS are required. 2.3 Hexafluoro Isopropanol (HFIP) as a Solvent Hexafluoro isopropanol (HFIP) is a solvent with unique properties to dissolve polymers such as polyamides, polyethylene (PET), polybutylene terephthalate (PBT) and polyoxymethylene (POM) without degradation. Dissolution is a crucial requirement for many essential analytical techniques: Size exclusion chromatography (SEC) to determine the molecular weight distribution and oligomer contents as crucial parameters for polymers and their risk assessment. Analytical techniques that require the analyte to be dissolved such as chromatographic techniques, light scattering analysis, viscometry, NMR spectroscopy are not possible for these polymers without HFIP. Due to its essential and widespread use, banning of this essential solvent will have a detrimental effect on the data generation required for Polymer REACH. The estimated amount of HFIP used in a year is 200 kg at BASF, which is only a minor consumption considering the size of BASF. If the producer/importer has several customers with a high demand for HFIP, bottlenecks in sufficient supply may occur with a 1 t per year limit of supply. To our best knowledge, no other solvent will be able to replace HFIP; no alternatives are known. If not exempt, many polymers cannot be characterized according to the state of the art, and therefore could no longer be sold. HFIP is relevant for the safe use of products made from the above-mentioned polymers. Without it, quality control and ecotoxicological risk assessment are not possible. If analysis of certain polymers is not possible anymore, fulfilling and enforcing the upcoming requirements for the registration of polymers under Polymer REACH will not be possible. The chemical identity and the purity need to be determined which requires diverse analytical techniques. The volume of residual monomers or the amount of low molecular weight fraction (< 500 g/mol) are crucial parameters for environmental and human health risk assessment. HFIP plays an important role for the analytical fulfilment of upcoming requirements under Polymer REACH, and alternatives are not available. Due to the use under controlled conditions in the analytical laboratory, a time-unlimited exemption for the analytical use of HFIP is proposed. To support our statement, we obtained the expert and manufacturer statements provided in Annex I and II (confidential). For further information please contact BASF SE, l=@basf.com Page 6 of 10 El BASF We create chemistry 2.4 Derivatizing Agents in Gas Chromatography (GC) Derivatizing agents classified as PFAS (Table 1) are used to thermally stabilize, increase the volatility, and reduce the polarity of analytes for GC analyses. They are applicable to a broad range of substances classes. Alcohols, amines, fatty acids, or sugars would be otherwise not analyzable by GC. The most commonly used derivatizing agent is N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSFTA). Advantages of MSTFA are a complete reaction with high reaction rates, even without a catalyst and the by-product of the reaction (N-methyltrifluoroacetamide) is characterized by high volatility and short retention times. Only minor volumes in the microliter range are required to improve the peak shape in the chromatogram or to increase the sensitivity. Alternatives are available but are only applicable to very specific substances or substance classes. Not all analytes will be covered with the available alternatives. Component separation of certain analytes is not possible on commercially available systems without derivatization. Products requiring specific quantification of analytes in quality control, where no alternative analytical method is available, could not be sold on the market anymore. A high number of analytical methods rely on PFAS as derivatizing agents as they play an important role for the sensitive detection of polar chemical substance classes. Due to the use under controlled conditions in the analytical laboratory, a time-unlimited exemption for the use of PFAS as derivatizing agents is proposed. 2.5 Perfluorotributylamine (PFTBA) and Perfluorocerosene (PFK) as Calibrants for Mass Spectrometry Perfluorotributylamine (PFTBA) and perfluorocerosene (PFK, mixture of perfluorinated alkanes) are used as calibrants for mass spectrometry, which is used to identify and quantify chemical compounds in gases or liquids. During ionization in the mass spectrometer, these compounds decompose in a repeatable and well-defined pattern to form well separated fragments with specific masses over a wide mass range (57 to 614 amu) without a mass defect. Thefragments can be used to tune the mass response and accuracy of the mass spectrometer. No alternatives as a calibrant for electron impact tuning which exhibit such good stability, the right volatility, and wide range fragment masses is known and no alternative is expected to be developed soon. Furthermore, mass spectrometry is one of the essential techniques to determine CMR substances (carcinogenic, mutagenic or reprotoxic). Under entries 28 to 30 of Annex XVII of REACH, the use of CMR substances of category 1A or 1B is prohibited as substances, constituents of other substances or in mixtures, for the general public if their concentrations are equal to or greater than their specific concentration limits (SCL), or in the absence of an SCL, their generic concentration limits (GCL), under Regulation (EC) 1272/2008 `Classification, Labelling and Packaging of Substances and Mixtures (CLP Regulation, consolidated version to October 2021). The GCL is 0.1% for a carcinogenic category 1A or 1B substance, 0.1% for mutagenic category 1A or 1B and 0.3% for reprotoxic category 1A or 1B. The detection of CMR substances like Bisphenol A with mass spectrometry is essential to fulfil the requirements of the REACH regulation. For further information please contact BASF SE, M@basf.com Page 7 of 10 El BASF We create chemistry PFAS containing calibrants provide a combination of the right characteristics required for mass spectrometry calibration and no alternatives are available. Mass spectrometry is an essential technique to detect e.g., CMR substances. Due to the use under controlled conditions in the analytical laboratory, a time-unlimited exemption for the use of PFAS as calibrants is proposed. 2.6 Trifluoroacetic Acid (TFA) as Solvent and Eluent in Liquid Chromatography The applications of trifluoroacetic acid (TFA) in analytical laboratories at BASF are wide ranging. TFA is mainly used as a solvent and additive for the eluents in liquid chromatography (LC), which is also described Annex A (chapter A.3.10.1.14. PFAAs and PFAA precursors) of the Restriction Proposal. Due to its unique properties, the adequate substitution is correspondingly difficult. Examples and details are given in the following. TFA is used as a solvent and as an additive for eluents in several LC methods (-65 methods are affected within BASF). The low pKa value and high polarity of TFA leads to better chromatographic performance and resolution. The best alternative for TFA is perchloric acid (HCIO4), which is already implemented where it can fulfil the analytical requirements. For other methods no alternatives were found, as the unique properties of TFA, a strong and volatile acid, are required. When using TFA, a few microliters are sufficient, whereas the use of other, less strong acids would cause a higher dilution due to the higher volumes needed. Furthermore, the ion pair forming properties are especially utilized for the analysis of proteins. Ion pairs with the basic analytes lead to an increase of the retention, improve resolution and the peak shape. As TFA is used in quantitative pesticide analytical methods for risk assessment and post-approval control and monitoring purposes according to SANTE/2020/12830, rev. 2 (14/02/2023), development and validation of new methods avoiding TFA is a highly time-consuming process. The replacement of the original methods requires time periods of 1-6 months each for development and 3-4 months each for the validation. The submitted data on registered plant protection products have to be adapted and notifications to EFSA need to be done. Additionally, methods shall be provided according to (EU) No 284/2013. Furthermore, -10 quality control methods for determination of side components of pesticides are affected. Adaption of these methods would also require high input of time and money, without knowing, whether the substitution processes are successful. TFA as a reagent is used in 97 monographs of the European Pharmacopeia and in 218 monographs of the USP-NF. It will be applied in a similar amount as well in the Japanese Pharmacopeia. All methods would have to be adopted and validated in every company using those methods for quality control and product release. When method adaptation is necessary, the acceptance by other authorities must be ensured. Overall, the amount of TFA used within BASF for analytics is estimated to be -250 kg per year. The amount used per method and measurement is low; a few milliliters are used for each determination/application. At BASF alone -65 methods are currently performed with the use of TFA. TFA plays an important role for analytical methods in the regulatory field such as Pharmacopoeia methods and diagnostic applications. Due to the use under controlled conditions in the analytical laboratory, a time-unlimited exemption for the analytical use of TFA is proposed. For further information please contact BASF SE, Milgbasf.com Page 8 of 10 El BASF We create chemistry 3. Consumables Containing PFAS Fluoropolymers such as PTFE, PFA and others belong to the group of PFAS but are not toxic, not water soluble, not bio available, not bio accumulative and are classified as polymers of low concern (e.g. Henry et al. 2018; Korzeniowski et al, 2023). Due to their high chemical, thermal, and electrical stability PFAS are part of the laboratory equipment for sample preparation, e.g., syringe filters, and often components of analytical/measuring devices, e.g., tubes in titrators or gaskets. Examples: In mass spectrometry a high vacuum of 10-6 mbar up to 10-9 mbar depending on the type of analyzer is required for a successful analysis. Teflon (PTFE) gaskets are used to achieve a stable high vacuum within the measuring device. No alternative material is known to be able to replace Teflon as a gasket material reaching the same high vacuum in the measuring device. In syringe filters, the materials polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) are used. Both are sterilizable, inert to most organic solvents, alkalis and acids as well as biologically inert and are also characterized by a low concentration of leachables and extractables. Fluorine-free materials are not suitable for ultra-trace analysis (contamination and leaching) or are not resistant/stable against aggressive chemicals like organic solvents, hydrofluoric acid. The following comments give detailed information about the use cases. Merck (Comment no. 4448, Doc 18) submitted a detailed analysis of the advantages of fluoropolymers in the analytical equipment in comparison to fluorine-free materials. Covestro (Comment no. 6215, Doc 33) submitted a detailed overview about the uses of fluorinated polymers in industry and laboratory uses. PFAS containing articles play a crucial role in sample preparation and analytical/measuring devices. Due to the use under controlled conditions in the analytical laboratory, a time-unlimited exemption for the use of PFAS containing consumables in the analytical laboratory is proposed. To support our statement, we obtained the manufacturer statement provided in Annex III (confidential). 4. Estimated Costs For analytical purposes, PFAS are widely used in BASF as solvents or additives. They are required in a high number of analytical methods with the purpose of quality control and product release including strictly regulated analytical experiments under GxP (Good Manufacturing Practice, Good Laboratory Practice) for product manufacturing and product registration. Transforming these methods, if even possible, would cost at least 13 Mio and a great deal of manpower, as well as a lot of time since the replacement of the For further information please contact BASF SE, M@basf.com Page 9 of 10 El BASF We create chemistry original methods require a transition period (1-6 months each) and the new methods require validation (3-4 months each). It would take many years to transform the methods since they cannot be changed all at the same time. Still, not all analytical methods will be replaceable. Those products which cannot undergo quality control and product release cannot be sold on the market anymore. The amount of costs and effort is not proportional to the volumes of PFAS used in the single analytical methods. Only minor volumes far below 1 t per year are used in these methods in the BASF. This estimation does not take into account PFAS containing consumables or laboratory equipment. Changing over to other materials would require enormous efforts if those materials were even available or of comparable performance. The cost for this process cannot be predicted. The costs listed here are representative for BASF at the German sites. If the cost estimate for the method conversions is extended for European and even international areas, the costs are not predictable. 5. Conclusions An explicit exemption of all PFASs used for analytical purposes, either as a substance, mixture, or article, from the scope of the PFAS restriction would ensure the high quality and safety of products. These substances are used in R&D and QC laboratory environments, where controlled disposal of PFAS materials can be guaranteed. Therefore, there is no risk on humans or the environment by the use of PFAS in analytical methods or in analytical instruments that would justify a restriction of this use. As a final point, the use of PFAS in analytical measurements is also required to meet existing regulatory requirements for a diverse product portfolio, and are essential for future regulatory requirements, such as for polymer REACH. Thereby the use of PFAS in analytics also contributes to ensure a healthy environment. About BASF At BASF, we create chemistry for a sustainable future. We combine economic success with environmental protection and social responsibility. More than 117,000 employees in the BASF Group work on contributing to the success of our customers in nearly all sectors and almost every country in the world. Our portfolio is organized into six segments: Chemicals, Materials, Industrial Solutions, Surface Technologies, Nutrition & Care and Agricultural Solutions. BASF generated sales of 87 billion in 2022. BASF shares are traded on the stock exchange in Frankfurt (BAS) and as American Depositary Receipts (BASFY) in the U.S. Further information at www.basf.com. 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