Fatty acids, tall-oil, manganese salts

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genetic toxicity study with fatty acids, tall-oil, manganese salts is available, thus the genetic toxicity will be addressed with existing data on the individual moieties manganese and tallate.

Fatty acids, tall-oil, manganese salts is not expected to be genotoxic, since the moiety manganese has not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity. The moiety fatty acids, tall-oil is obtained from natural sources and excluded from the obligation to register.

Additional information

Read-across approach

Selected endpoints for the human health hazard assessment are addressed by read-across, using a combination of data on the metal cation and the organic acid anion. This way forward is acceptable, since metal carboxylates are shown to dissociate to the organic anion and the metal cation upon dissolution in aqueous media. No indications of complexation or masking of the metal ion through the organic acid were apparent during the water solubility and dissociation tests (please refer to the water solubility and dissociation in sections 4.8 and 4.21 of IUCLID). Once the individual transformation products of the metal carboxylate become bioavailable (i.e. in the acidic environment in the gastric passage or after phagocytosis by pulmonary macrophages), the “overall” toxicity of the dissociated metal carboxylate can be described by a combination of the toxicity of these transformation products, i.e. the metal cation and carboxylate anion according to an additivity approach.

Fatty acids, tall-oil, manganese salts is the manganese metal salt of fatty acids, tall-oil, which readily dissociates to the corresponding divalent manganese cation and tallate anions. The manganese cation and the tallate anions are considered to represent the overall toxicity of Fatty acids, tall-oil, manganese salts in a manner proportionate to the free acid and the metal (represented by one of its readily soluble salts). 

A detailed justification for the read-across approach is added as a separate document in section 13 of IUCLID.

Genetic toxicity

No genetic toxicity study with Fatty acids, tall-oil, manganese salts is available, thus the genetic toxicity will be addressed with existing data on the dissociation products as detailed in the table below.

 

Table: Summary of genetic toxicity data of Fatty acids, tall-oil, manganese salts and the individual constituents.

	Manganese sulfate (CAS# 7785-87-7)	Fatty acids, tall-oil	Fatty acids, tall-oil, manganese salts (CAS# 8030-70-4)
In vitro gene mutation in bacteria	Negative	Negative	Negative (read-across)
In vitro cytogenicity in mammalian cells or in vitro micronucleus test	Negative	Negative	Negative (read-across)
In vitro gene mutation study in mammalian cells	Negative	Negative	Negative (read-across)

 

 

Manganese

No genotoxic effects were observed in a bacterial reverse mutation assay with manganese sulphate. The in vitro mammalian chromosome aberration test and in vitro mammalian cell gene mutation test were also negative.

Additionally, manganese chloride did not produce any in vivo genotoxicity in the mammalian erythrocyte micronucleus test.

These in vivo and in vitro data suggest that manganese is not genotoxic. No classification for genetic toxicity is indicated according to the classification, labelling and packaging (CLP) regulation (EC) No 1272/2008.

 

Tallate

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 Escherichia 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.

 

Fatty acids, tall-oil, manganese salts

Fatty acids, tall-oil, manganese salts is not expected to be genotoxic, since the two moieties manganese and fatty acids, tall-oil have not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity. Further testing is not required. Thus, fatty acids, tall-oil, manganese salts is not to be classified according to regulation (EC) 1272/2008 as genetic toxicant. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

Fatty acids, tall-oil, manganese salts is not expected to be genotoxic, since the moiety manganese has not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity. The moiety fatty acids, tall-oil is obtained from natural sources and excluded from the obligation to register.

Thus, fatty acids, tall-oil, manganese salts is not to be classified according to regulation (EC) 1272/2008 as genetic toxicant.