Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Fatty acids are found in all living organisms fulfilling fundamental physiological functions within the body.

Based on this role within the body, no potential of fatty acids for genotoxicity is expected as it could be demonstrated in-vitro with fatty acids C6, C8, C10, C12, C18-di and C22, as well as with fatty acids mixtures C8-18 and C12-18.

Observations of no mutagenicity is also supported by the available data of C18-di (octadecanedioic acid) (Ames Test - Wollny 2001, Chromosome Aberration Test - Hamann 2002).

These observations fit to available studies for the substance category on gene mutation in bacteria were conducted according to OECD guideline 471 and under GLP conditions with hexanoic acid and docosanoic acid, respectively (C6: Banduhn, 1991; C22: Nakajiama, 2002). In both studies bacteria strains S. typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538 were tested with the fatty acids at concentrations up to 5000 µg/plate with and without metabolic activation by rat liver S9-mix. C22 fatty acid was additionally tested with bacteria strain E. coli WP2 uvr A to detect DNA-cross linking. The test substances did not induce gene mutations in the S. typhimurium and E. coli strains. No toxicity was observed up to a concentration of 5000 µg/plate, with or without metabolic activation. The other available studies were insufficient for assessment due to limited documentation (C8: Gloxhuber and Wallat 1981; C8-18: Wallat 1982; C12-18: Sterzel and Broschard 1999; C12: Gloxhuber and Wallat 1981; C22: Gloxhuber and Wallat 1981). However, according to the authors, all these studies with fatty acids of different chain lengths gave negative results showing that fatty acids do not induce gene mutation in bacteria.

Regarding gene mutation in mammalian cells an in vitro mouse lymphoma assay was performed with decanoic acid under GLP according to OECD guideline 476 (Trenz, 2010). In two experiments, mouse lymphoma L5178Y cells were treated with decanoic acid at concentrations up to 1.54 mM with metabolic activation (phenobarbital and beta-naphtoflavone-induced rat liver S9-mix) and up to 1.18 mM without metabolic activation, respectively. Although cytotoxicity was observed, all mutant values were found to be within the range of the historical control data of the test facility, so that decanoic acid was not found to be mutagenic. In addition, colony sizing was performed for the highest concentrations used to detect potential clastogenic effects and/or chromosomal aberrations. As result, decanoic acid was not found to be clastogenic at all dose groups tested.

An in vitro mammalian chromosome aberration test was conducted with C22 fatty acid (docosanoic acid) in accordance with GLP and OECD guideline 473 and Japanese Guidelines for Screening Mutagenicity Testing of Chemicals (Nakajima, 2002). Properly maintained Chinese hamster lung (CHL) cells were treated with docosanoic acid dissolved in 1% carboxymethylcellulose sodium at concentrations of 875, 1750 and 3500 µg/mL with and without metabolic activation by S9 from Phenobarbital- and 5,6-benzoflavone-induced rat liver for 6 hours. In addition, the cells were incubated with 350, 700, 1400, 2800 µg/mL without metabolic activation for 24 hours and with 288, 575, 1150 and 2300 µg/mL without metabolic activation for 48 hours. No increase in chromosomal aberrations was found at all concentration tested.

On the basis of the results for C18 -di and the other category members it is concluded that these substances are not gentoxic.

Short description of key information:
not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification