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Categories

Category name:
category PF-5056 and PF-5058

Justifications and discussions

Category definition:
See attached Category Reporting Format.
Category rationale:
This category is based on several characteristics:
A) Manufacturing process: Process steps, distillation, and purification of electrochemical fluorination (ECF) products. ECF is a process for fluorination of organic substances by application of an electrical potential in solution with hydrogen fluoride. The process may result in some rearrangement of the comparatively simple starting material (including cyclisation, ring expansion and ring contraction) and branching of alkyl groups. In contrast, other (non-ECF) synthetic routes lead to a different range of materials. For example, ring-opening polymerization (ROP) of hexafluoropropylene oxide leads to extensive branching and considerable inclusion of oxygen (one trifluoromethyl branch and one ether oxygen per HFPO unit). ROP of tetrafluorooxetane followed by treatment with elemental fluorine achieves a linear polyether, again with considerable oxygen content. Photooxidation of tetrafluoroethylene or hexafluoropropylene leads to linear (TFE) or branched (HFP) polyethers. In all cases, these alternate processes lead to polyethers with comparatively (one to three carbons) short perfluorinated alkylene units in the main chain.
B) Constituent atoms: The category consists of materials containing between five and eighteen carbon atoms. The chemical may also contain one nitrogen or oxygen atom, one nitrogen and one oxygen atom, or at most two nitrogen atoms. All heteroatoms are bonded only to carbon (i.e., no N-N, N-O, N-F or O-F bonds). The only bonds present are C-C, C-F, C-N, or, C-O. No unsaturated bonds are present. No hydrogen is present.
The carbon-fluorine bond is unique in organic chemistry. Because of the difference in the electronegativity of carbon (2.55 on Pauling scale) and fluorine (3.98 on Pauling scale), the bond is highly polar while retaining its covalent character. As a result, the bond is among the strongest chemical bonds known and is resistant to nearly all forms of chemical attack. Hydrolysis does not occur. Reaction with oxidizing agents does not occur. Chemical reduction occurs only when strong agents such as sodium metal are used. Heteroatoms (nitrogen or oxygen) which may be present in some category members do not significantly increase the reactivity of molecule. This lack of reactivity is due to two factors, one of which is steric hindrance by fluorine of the molecule backbone, and the other of which is
strong electron withdrawing by perfluoromethyl and perfluoromethylene groups. The perfluorinated amines, for example, have essentially no alkalinity and do not function as nucleophiles. No enzymatic hydrolytic, reductive or oxidative metabolic pathways for perfluorochemicals are known.
C) Physical-Chemical properties: This category is defined by volatility, vapour pressure range, boiling point, water solubility, Henry’s Law constant and octanol-water partition coefficient (see Table 2). Surface energies are very low and materials are both hydrophobic and lipophobic relative to their equivalent hydrocarbon and tend to form a third phase separate from aqueous or lipid-like phases. For comparison, physiochemical data for the corresponding hydrocarbons are included in Table 2. Because of differences in reactivity and physicochemical characteristics, extrapolation of physicochemical, environmental fate and pathways, and toxicological endpoints from hydrocarbons to perfluorinated organic chemicals is not appropriate. In addition, the members of this category degrade very slowly in the environment. In category members for which biodegradation has been examined, no biodegradation occurred. The sole known mechanism for loss in the environment is direct photolysis by short-wave (<290 nm) ultraviolet radiation. In category members for which indirect photolysis has been measured, no reaction with hydroxyl radical (*OH) or excited oxygen atoms (i.e, the O(1D) state) was observed, although some direct photolysis was observed of chemicals which have absorbance features in the range of 190-230 nm.
D) Toxicity mode of action:
When evaluating the toxicity information for the category members, the available data show no or very little biological activity. This lack of toxicity is seen despite the administration of the test substances at very high doses. In repeat dose studies on one compound, the NOAEL in a 28-day oral study is greater than 2000 mg/kg-day and the NOAEL in a 90-day inhalation study is approximately 50,000 ppm. This lack of effect can be explained by three important aspects:
1. Category members are very poorly absorbed
2. These molecules have a very low inherent toxicity
3. The molecules are not metabolized to biologically active compounds
Category members are linked by the perfluorination of the molecules and the lack of toxic effects seen in a variety of studies. The concept of a common mode of action is not relevant for this category since by definition, there is no toxicity and, therefore, no mode of action.
E) Metabolic similarities
Due to the stability of the carbon-fluorine bond, the members of this category are unable to be metabolized by aerobic organisms. Reactive oxygen species such as ∙OH or O(1D) are not sufficiently oxidizing to displace fluorine atoms from a carbon backbone. As such, normal phase I enzymes such as cytochrome P450s are unable to attack the carbon-fluorine bond. Heteroatoms such as nitrogen or oxygen, which may be present in some category members, are deactivated by the electron-withdrawing power of the perfluoroalkyl portions of the molecule and do not undergo the same reactions as would be expected in the corresponding non-fluorinated amines, ethers or morpholines. For example, the perfluorinated tertiary amine N cannot be protonated, alkylated, acylated or chemically oxidized under physiological conditions.
F) Conclusion: Therefore, read-across among category members is considered as an appropriate adaptation to the standard information requirements of Annexes VII – IX of the REACH Regulation for the target substance, applied to endpoints as noted in Tables 3, 4 and 5, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.