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Description of key information

Fatty acids are an endogenous part of every living cell, and their absorption and metabolism are well established. Read across data from a related salt, fatty acids C18-(unsaturated) lithium salts, show GI tract absorption and some degree of dermal absorption. The toxicokinetic properties of the substances in the category are considered to be predictable across the category.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The substances in the category are considered to be similar on the basis that they have common structures of a calcium ion varying only by the length of the fatty acid chain and the presence of unsaturated and/or hydroxyl functional groups. As a result it is expected that the substances will have similar, predictable properties. REACH Annex V, Entry 9, groups fatty acids and their potassium, sodium, calcium and magnesium salts, including C6 to C24, predominantly even-numbered, unbranched, saturated or unsaturated aliphatic monocarboxylic acids. Provided that they are obtained from natural sources and are not chemically modified, the substances included in REACH Annex V, Entry 9 are exempt from registration, unless they are classified as dangerous (except for flammability, skin irritation or eye irritation) or they meet the criteria for PBT/vPvB substances. The metal fatty acid substances in the category are therefore not expected to be hazardous. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the toxicokinetic properties are expected to be predictable across the category.

Since REACH Annex V groups together calcium, potassium, sodium and magnesium salts of C6 to C24 fatty acids as being potentially exempt from registration, these metal cations are therefore not considered to contribute to any health hazard. On this basis, relevant published or proprietary data on any potassium, sodium or magnesium salt within the fatty acid category range of C14 to C22 can be used to read across to the calcium salts of C14-C22 fatty acid category.

Lithium salts of fatty acids are not included in REACH Annex V as being potentially exempt from registration. For these salts it is expected that the lithium cation would be the species with the potentially higher toxicity profile when compared to calcium, potassium, sodium, and magnesium cations. However, the substance fatty acids C18 (unsaturated) lithium salts contains a fatty acid anion that falls within the C14-C22 range. Experimental data for the mammalian toxicity Annex VIII endpoints have been generated on this substance and the results obtained are relevant to read across to the calcium salts of C14-C22 fatty acids either in a weight of evidence approach or as key studies due to the structural similarity and its position within the category fatty acid range. This is clearly relevant when the results from the lithium fatty acid salts are negative.

The toxicokinetics of fatty acids has been reviewed in HERA (2002) (citing other published references): Fatty acids are an endogenous part of every living cell and are an essential dietary requirement. They are absorbed, digested and transported in animals and humans. When taken up by tissues they can either be stored as triglycerides or can be oxidised via the ß-oxidation and tricarboxylic acid pathways. The ß-oxidation uses a mitochondrial enzyme complex for a series of oxidation and hydration reactions, resulting in a cleavage of acetate groups as acetyl CoA. Acetyl CoA is used mainly to provide energy but also to provide precursors for numerous biochemical reactions. Alternative minor oxidation pathways can be found in the liver and kidney (ω-oxidation and ω-1 oxidation) and in peroxisomes for ß-methyl branched fatty acids (α-oxidation). The metabolic products can then be incorporated for example into membrane phospholipids. Long chain saturated fatty acids are less readily absorbed than unsaturated or short chain acids. Several investigators have found that increasing fatty acid chain length decreased their digestibility.

As discussed in HERA (2002), the greatest skin penetration of human epidermis was with C10 and C12 soaps. For three soaps that penetrated skin (C10, 12 and 14) there was a lag time of 1 hour before measurable penetration occurred, but after this the rate of penetration steadily increased. The low penetration rates of the C16 and 18 soaps suggest that little or none of these would penetrate from a short (e.g. 15 minute) wash and rinse exposure. 

The following conclusions can be drawn on the basis of a review of available key experimental data from physico-chemical and toxicological studies on fatty acids C18-(unsaturated) lithium salts performed according to international technical guidelines and in compliance with GLP in internationally recognised contract research organisations:

·        Fatty acids C18-(unsaturated) lithium salt is absorbed via the gastrointestinal tract. This is supported by the observation of signs of systemic toxicity (i.e. hunched posture, pilo-erection, ataxia, noisy respiration, sneezing, increased salivation) at 2000 mg/kg bw, as an aqueous suspension via oral gavage in an acute oral toxicity study in female Wistar rats.

·        Fatty acids C18-(unsaturated) lithium salts is absorbed to some degree via the skin. This is supported by the observation of a dose-related, but not statistically significant, increase in stimulation index following topical application of fatty acids, C18-(unsaturated) lithium salts in an ethanol/distilled water (7:3) suspension in a local lymph node assay.

·        In addition, in the dermal combined repeat dose toxicity study with a reproduction/developmental toxicity screening study in rats, systemic effects (statistically significant decrease in body weight) were noted at the highest tested dose of 1089.75 mg/kg bw. 

No available data from these studies allows conclusions to be drawn regarding distribution, metabolism or excretion of fatty acids C18-(unsaturated) lithium salts. While this information was obtained from an assessment of a lithium fatty acid salt, it is considered relevant to the calcium fatty salts in this category based on the discussion in the third paragraph above. 

Reference

HERA (Human Health and Environmental Risk Assessment on ingredients of European household cleaning products) (2002) Fatty Acid Salts (Soap) Environmental and Human Health Risk Assessment