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Administrative data

Description of key information

In vitro and in vivo studies on dermal and ocular irritation have been conducted on C14, C16, C18 fatty acid lithium salts, and in vitro/in vivo eye irritation studies with calcium myristate. No classifiable irritant responses were observed relevant to calcium salts of C14-22 fatty acids.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

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 irritation 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 category. 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. Additionally, ocular irritation studies have been conducted on lithium palmitate.

Published reviews consider that the irritant/corrosivity properties of fatty acids are chain length dependent, where the lower carbon chain lengths, < C9 are corrosive, C10 – C12 are irritant, and chain lengths from C14 are not irritating (HERA 2002), referencing Briggs et al, 1976 and CIR, 1987). Key in vitro and in vivo ocular irritation studies have been conducted on the category member with the shortest chain length, calcium myristate, since that would be considered the ‘worst case’ substance for irritation based on the relationship to chain length. The in vitro study (Rabbit Eye Enucleation Test - REET) showed no evidence of severe irritation/corrosivity, and the in vivo OECD Guideline 405 study demonstrated no classifiable eye irritation. Since the fatty acid salts with longer chain lengths are considered to have proportionately lower irritation potential, this negative result can be read across to the other category members. This is also supported by read across data from ocular irritation studies on relevant lithium fatty acid salts with longer carbon chain lengths. Negative in vitro and in vivo (OECD Guideline 405) studies were conducted on lithium palmitate (C16) and fatty acids, C18 (unsaturated), lithium salts. Since the lithium cation might be expected to demonstrate higher irritation potential than the calcium cations, reading across the negative results to the latter category is validated. Further supporting evidence is shown by a negative published eye irritation study on magnesium stearate, taken from a peer-reviewed article.

 

The dermal corrosion and irritant properties of magnesium stearate to the intact and abraded skin of rabbits were evaluated in a published supporting study. A primary irritation index of 0.0 was obtained after four hours exposure under occlusive dressing. Although no information on the test methods is available in the publications, it is a peer-reviewed article and considered reliable and relevant for assessment of this endpoint. A supporting study in rabbits for skin irritation using a grease formulated with calcium 12-hydroxystearate has been conducted and the formulation was non-irritant.

 

Key in vitro skin irritation studies on lithium myristate (C14) and fatty acids C18 (unsaturated) lithium salts gave negative results. The negative results from the studies with the lithium fatty acid salts are suitable for reading across to the calcium fatty acid salts for the reasons mentioned above. Since the irritation properties of fatty acids and their salts are inversely proportional to carbon chain length, the negative results are applicable for the whole category from C14 to C22.

 

Overall, the calcium fatty acid salts of C14 to C22 fatty acids are not considered to be skin or ocular irritants.

 

References

Briggs GB, Doyle RL, Young JA (1976) Safety studies on a series of fatty acids. American Industrial Hygiene Association Journal, vol. 37, pp. 251-252

CIR (Cosmetics Ingredients Review) (1987) Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid and stearic acid. Journal of American Toxicologists, vol. 6, issue 3, pp. 321-401

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

Justification for selection of skin irritation / corrosion endpoint:
This substance is a representative fatty acid salt that can be read across to the calcium salts of C14-C22 fatty acids category

Justification for classification or non-classification

Not classified under the EU CLP Regulation. All studies were negative.