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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
In vitro: - gene mutation (bacterial reversion assay/Ames test): Negative - gene mutation (mammalian cell TK+/- assay in L5178Y mouse lymphoma cells): Negative - cytogenicity (chromosomal aberration assay in human lymphocytes): Negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

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 genetic toxicity 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.

It is relevant to consider metal cations and the fatty acid anions in the review of genotoxic potential of the calcium fatty acid salts. Castor oil (C18 hydroxylated) and magnesium stearate (C18) have been tested in the Ames test with negative results, as reported in the API Robust Summaries (2008, referencing NTP 1992 and Litton Bionetics 1976, respectively).Stearic acid was tested for mutagenicity with and without S9 in the Ames test (reported in CIR 1987) and no mutagenic activity was observed. A sister chromatid exchange study on oleic acid (C18 unsaturated) was reported in the same review, using Chinese hamster V79 lung fibroblasts. The mean number of SCE’s per metaphase was similar to the control, but higher incidences of aneuploidy were apparently seen with the oleic acid cultures. However, oleic (C18 unsaturated) and lauric (C12) acids have been considered as inhibitors of mutagenicity produced by positive control substances such as N-nitrosopyrrolidine and sodium azide (CIR 1987). Additional reporting of fatty acid genetic toxicity is presented in the HERA review (HERA 2002). In this review, it is stated that fatty acids are negative in in vitro bacterial systems used in the Ames test. These included capric acid (C10), lauric acid (C12), stearic acid (C18), oleic acid (C18 unsaturated), and fatty acids C18-22. Each of these substances has been subjected to reversion tests in Escherichia coli or Salmonella typhimurium strains with and without metabolic activation.

Thus there is a significant amount of published information to indicate that fatty acids and their salts are not likely to be mutagenic, particularly in view of the significant normal human intake of fatty acids in the diet.

Key bacterial reversion assays (Ames test) have been conducted on lithium salts of fatty acids within the C14-C22 carbon chain range of the calcium fatty acid salts.The substances were lithium myristate (C14), lithium 12-hydroxystearate (C18) and lithium behenate (C22), together with fatty acids C18 (unsaturated) lithium salts. In addition, a chromosomal aberration assay and a mouse lymphoma assay have been performed on the latter lithium salt. In all cases the results were negative.

Since none of the lithium, and calcium metal cations are considered to be mutagens, the negative experimental data from the lithium fatty acid salts, can be read across to all members of the calcium fatty acid salts category.

Overall, there is no evidence of genotoxicity associated with the substances in the category.

References

American Petroleum Institute (2008) Robust Summary of Information on Grease Thickeners (Creation date: October 11, 2003. Printing date: February 20, 2009. Last update: October 20, 2008. Document date: January 11, 2005)

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, iss. 3, pp. 321-401

HERA (Human Health and Environmental Risk Assessment on ingredients of European household cleaning products) (2003) Fatty Acid Salts (Soap) Environmental and Human Health Risk Assessment

National Toxicology Program (1992) Toxicity Studies of Castor Oil in F344/N Rats and B6C3F1mice (Dosed Feed Studies)


Justification for selection of genetic toxicity 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 for genetic toxicity. Negative results in all studies conducted.

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