Registration Dossier

Toxicological information

Endpoint summary

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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion
Endpoint conclusion:
no study available

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Genetic toxicity: In vitro

A registration dossier shall contain information on the human health hazard assessment (regulation 1907/2006, Art.10). However, it is considered that the information requirements for tall oil as laid down in annex VII to IX can be fulfilled by adaptation of the standard testing regime according to Annex XI, points 1.2. and 1.3. as presented in the following:

According to Regulation (EC) No 1907/2006 Annex V substances obtained from natural sources and not modified such as vegetable fats and oils as well as fatty acids from C6 to C24 and their potassium, sodium, calcium and magnesium salts are excluded from the obligation to register.

The substance subjected to registration is a mixture of different saturated and unsaturated C16 -C18 fatty acids. Based on this, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

Based on in vitro data the HERA document on fatty acid salts (2002) reported that “fatty acids are negative in in vitro bacterial systems used in the Ames test (BIBRA, 1988; BIBRA, 1996). In addition, saturated fatty acids up to and including C12, and the unsaturated acid C18:1, have shown inhibition of the mutagenic activity of N-nitrosodialkylamines on Eschericha coli (Negishi et al. 1984). Also, fatty acids from C12 up to C19 have shown anticlastogenic effects in the chromosome aberration test (Renner, 1986)” (HERA, 2002).

“Stearic acid (C18) was tested for mutagenicity using the Ames test with Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538. Spot tests were performed using 50 mg/ml stearic acid suspensions in distilled water (50 μg/plate) with and without microsomal activation from hepatic S9 fractions from rats induced with Aroclor 1254 (50 μl/plate). Stearic acid had no mutagenic activity over background in the strains tested with and without metabolic activation (CIR, 1987)” (HERA, 2002).

“A solution of 99.9% pure oleic acid (C18) was tested in the Ames test using Salmonella typhimurium strains TA98, TA100 and TA1535. It was tested at concentrations of 1, 5, 10, 50, 100, 500, 1000 and 5000 μg/plate with and without metabolic activation and produced negative results (IUCLID, 2000e). In the Escherichia coli reverse mutation assay using E. coli strain WP2uvrA, concentrations of 1, 5, 10, 50, 100, 500 1,000 and 5,000 ug/plate, with and without activation, a solution of 99.9% pure oleic acid also produced negative results. It has also produced negative results in Saccharomyces cerevisiae and in DNA and damage repair assays using Bacillus subtilis (BIBRA, 1986; IUCLID, 2000e). Fatty acids, C18-22 produced negative results with and without metabolic activation in the Ames test at concentrations ranging between 4-1250 μg/plate using Salmonella typhimurium (IUCLID, 2000g)” (HERA, 2002).

The EFSA NDA Panel reported in their re-evaluation of fatty acids (E570) as a food additive, that “in the study by Shimuzu et al. (1985), stearic acid (60% purity) was assessed for its mutagenicity in a bacterial reverse mutation assay using S. Typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and E. coli WP2uvrA. The pre-incubation test was performed in the presence and absence of metabolic activation (liver S9 from polychlorinated biphenyl induced male rats) at concentrations of 1–1,000 µg/plate (seven concentrations) including negative, vehicle and positive control. The test substance did not induce an increase in revertants colonies compared to the concurrent negative control” (EFSA ANS Panel, 2017).

Overall, it was considered by the EFSA Panel as well as HERA that the available data did not raise a concern for genotoxicity of fatty acids and their salts.

Additionally, the Austrian assessment report for octanoic acid in accordance with regulation (EU) no 528/2012 concerning the making available on the market and use of biocidal products stated:

“The absence of genotoxicity is supported by the evaluation of bacterial mutation tests, in vitro chromosomal aberration tests with the CHO cell line and in vitro gene mutation tests with mouse lymphoma cells and a respective total weight of evidence discussion. Each of the three assays are available for Decanoic acid as well as Octanoic acid.” [Assessment report for octanoic acid; 2013]

In conclusion, the conduct of any further mutagenicity studies would not contribute any new information and is therefore not considered to be required.

 

References

Assessment report for octanoic acid (2013): Evaluation of active substances, Regulation (EU) n°528/2012 concerning the making available on the market and use of biocidal products, Standing Committee on Biocidal Products, Austria.

BIBRA (1986) Toxicity Profile. Oleic acid. The British Industrial Biological Research Association. Surrey, UK.

BIBRA (1988) Toxicity Profile. n-Octanoic acid and its sodium and potassium salts. The British Industrial Biological Research Association. Surrey, UK.

BIBRA (1996) Toxicity Profile. n-Decanoic acid (and its sodium and potassium salts). The British Industrial Biological Research Association. Surrey, UK.

CIR (1987) Final report of the safety assessment for oleic acid, lauric acid, palmitic acid, myristic acid, stearic acid. Prepared by the Expert Panel of the Cosmetic Ingredient Review, Washington D.C.

EFSA ANS Panel (EFSA Panel on Food Additives and Nutrient Sources added to Food), Mortensen A, Aguilar F, Crebelli R, Di Domenico A, Dusemund B, Frutos MJ, Galtier P, Gott D, Gundert-Remy U, Leblanc J-C, Lindtner O, Moldeus P, Mosesso P, Parent-Massin D, Oskarsson A, Stankovic I, Waalkens-Berendsen I, Woutersen RA, Wright M, Younes M, Boon P, Chrysafidis D, G€urtler R, Tobback P, Gergelova P, Rincon AM and Lambre C, 2017. Scientific Opinion on the re-evaluation of fatty acids (E 570) as a food additive. EFSA Journal 2017;15(5):4785, 48 pp.

Human & Environmental Risk Assessment (HERA) on ingredients of European household cleaning products- Fatty Acid Salts, Draft for Public Comment, June 2002

IUCLID (2000e) IUCLID Dataset on Fatty acids, rape oil. Creation Date 19 February 2000. European Chemical Bureau, Ispra, Italy.

IUCLID (2000g) IUCLID Dataset on Fatty acids, C18-22. Creation Date 19 February 2000. European Chemical Bureau, Ispra, Italy.

Negishi, T. and Hayatsu, H. (1984) Inhibitory effect of saturated fatty acids on the mutagenicity of N-nitrosodimethylamine. Mutation Research 135: 87-96.

Renner, H.W. (1986) The anticlastogenic potential of fatty acid methyl esters. Mutation Research 172: 265-269.

Justification for classification or non-classification