Document YjR7wydJnbe7o8xYLKb9yv12n

HONEYWELL ADVANCED LIMITED ERNST & YOUNG, RIVERVIEW HOUSE HARVEY'S QUAY LIMERICK LIMERICK V94R3DE IRELAND Comparison of Toxicological Activity and Mode of Action of Trifluoroacetic Acid (TFA) with Longer-chain Polyfluorinated Compounds (PFAS) through State-of-art ToxProfiler Assay Numerous PFAS substances falling within the scope of the PFAS Restriction Proposal1 (i.e., OECD PFAS definition) do not share similar physicochemical, toxicological and ecotoxicological properties, hazards, and exposure (and consequently, do not pose equivalent risks, if any) which can be predicted by virtue of a simple structural similarity (-CF2- or CF3- moiety). According to the most recent UNEP EEAP 2022 Assessment Report2 and most international experts, "all PFAS should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner" and that "it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS". Contrary to what the Dossier Submitters indicate in the PFAS Restriction Proposal, there is a range of PFAS substances, including various fluorinated gases, that are not bioaccumulative (B), not toxic (T), not (v-)persistent (not P/vP) and do not degrade to vP substances (incl. trifluoroacetic acid - TFA) in amounts leading to their risk characterisation as non-threshold substances with properties similar to PBT/vPvB substances.With respect to the above-mentioned UNEP EEAP 2022 Assessment Report statement, the same would apply to the inclusion of TFA, with a two-carbon chain and a single CF3 group, in a class (i.e., grouping) with longer chain PFAS (e.g., PFOS). In this respect, the above Report concludes at pages 278 and 279 that "Trifluoroacetic acid has biological properties that differ significantly from the longer chain polyfluoroalkyl substances (PFAS) and inclusion of TFA in this larger group of chemicals for regulation would be inconsistent with the risk assessment of TFA". In addition to the abundant public scientific evidence on the non-toxicity of fluorinated gases (C2-C3 carbon range) and of their degradation product TFA (C2)3 compelling new scientific data have been generated using ToxProfiler4, a unique human-based reporter assay that provides an extensive quantitative toxicological profile of novel chemicals and drugs. The assay contains seven fluorescent reporter genes to visualize the major cellular stress response pathways responsible for cellular/organ toxicity. During the past Society of Toxicologists (SOT) Annual Conference in March 20235 (Annex I to this submission), solid results were presented regarding the toxicological activity profiling and potency ranking of per- and polyfluoroalkyl substances (PFAS). The ToxProfiler data clearly demonstrated that PFAS with longer carbon chains are more potent than PFAS with shorter carbon lengths. 1 On 22 March 2023, ECHA published the PFAS REACH Annex XV Restriction Report (PFAS Restriction Proposal) in the Registry of restriction intentions until outcome and started the 1st Annex XV report consultation with a final deadline for comments on 25 September 2023. 2 Environmental Effects of Stratospheric Ozone Depletion, UV Radiation, and Interactions with Climate Change, UNEP EEAP 2022 Assessment Report. 3 See also Honeywell submissions on legal aspects of the PFAS Restriction Proposal - reference number: bb6e00b6-571b-467a-ae79-7b046c6c9ab4 and on objective TFA assessment - reference number: 76bb3d12- 2101-4390-82cf-3498b47e8015), 4 https://toxys.com/toxprofiler/ 5 SOT 62nd Annual Meeting and ToxExpo, Nashville, Tennessee (USA), March 19-23, 2023. HONEYWELL ADVANCED LIMITED ERNST & YOUNG, RIVERVIEW HOUSE HARVEY'S QUAY LIMERICK LIMERICK V94R3DE IRELAND A new study from September 20236 (Annex II to this submission - Toxys project code 23063) evaluated the toxicological activity and potency of a wide PFAS series, i.e., C2-C10, comprising TFA (C2). The study demonstrated not only the repeatability and the consistency of the ToxProfiler assay, but the data also irrefutably underlined that toxicological activity is observed only with PFAS having a carbon chain length of C4 or higher. The new study clearly states that overall TFA was found to be non-toxic and did not trigger any of the 7 major toxicological pathways. A clear correlation was found between stress pathway activation and the carbon length of the tested PFAS. It was proved that C2/C3 molecules unequivocally do not trigger toxicological events in the ToxProfiler assay. To summarize, short-chain polyfluorinated (<C4) compounds do no exhibit toxicological activity, and hence it is demonstrated that TFA has biological properties that differ significantly from the longer-chain polyfluoroalkyl substances (PFAS). Therefore, the inclusion of TFA, and the precursor fluorinated gases it degrades from, into the larger group of PFAS chemicals for REACH restriction purposes is not scientifically and legally justified. This submission should be read in conjunction with the following two linked earlier Honeywell submissions: 76bb3d12-2101-4390-82cf-3498b47e8015 and 145ab85b-73c2-49d7-81a65e2141b7d372 ***END*** 6 Commissioned by Honeywell