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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Not mutagenic or clastogenic in bacterial and/or mammalian cells in vitro.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Adequate information exists to characterise the mutagenicity of Fatty acids, tall-oil, oligomeric reaction products with maleic anhydride and rosin, calcium, magnesium, zinc salts. The available data is summarised below.

Bacterial cell mutation

In a key Guideline (OECD 471) in vitro bacterial reverse mutation Ames test (Harlan Laboratories Ltd., 2010), Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2uvrA-were treated with the test material (Fatty acids, tall-oil, oligomeric reaction products with maleic anhydride and rosin, calcium, magnesium, zinc salts; CAS# 160901-14-4) using both the Ames plate incorporation and pre-incubation methods at up to six dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolising system (10% liver S9 in standard co-factors). The dose range was determined in a preliminary toxicity assay and was 50 to 5000 µg/plate in the first experiment. The experiment was repeated on a separate day (pre-incubation method) using a similar dose range to Experiment 1, fresh cultures of the bacterial strains and fresh test material formulations. 

 

An additional dose level (15 µg/plate) was selected in Experiment 2 in order to allow for potential toxicity following the change in test methodology.

 

The vehicle (tetrahydrofuran) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.

 

The test material caused no visible reduction in the growth of the bacterial background lawn at any dose level in Experiment 1 (plate incorporation method). However, in Experiment 2 (pre-incubation method) the test material did cause a visible reduction in the growth of the bacterial background lawn at and above 1500 µg/plate for all of the strains dosed in the absence of S9 and to tester strains TA100 and TA1535 only, dosed in the presence of S9. The toxicity caused by the test material was of insufficient severity to prevent testing up to the maximum recommended dose level of 5000 µg/plate.

 

An off-white, fibrous precipitate was noted at and above 1500 µg/plate and from 500 µg/plate in Experiment 1 and Experiment 2, respectively. These observations did not prevent the scoring of revertant colonies.

 

No toxicologically significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation.

 

A small increase in revertant colony frequency for tester strain TA98 was noted, in the presence of S9, at 150 µg/plate in Experiment 2 only. However, this increase was non-reproducible in two separate experiments and the individual counts at 150 µg/plate were within the in-house historical control range for the strain. The increase was, therefore, considered to be of no biological consequence.

 

Fatty acids, tall-oil, oligomeric reaction products with maleic anhydride and rosin, calcium, magnesium, zinc salts was considered to be non-mutagenic under the conditions of this test.

Mammalian chromosomal aberrations

In a key Guideline (OECD 473) in vitro mammalian chromosome aberration test (Harlan Laboratories Ltd., 2013a), cultured mammalian cells (human lymphocytes) were exposed to the test material (Fatty acids, tall-oil, oligomeric reaction products with anhydride and rosin, calcium magnesium zinc salts; CAS# 160901-14-4).

 

Culture cells of Human Lymphocyte were exposed to three dose levels of the test material, positive control and vehicle. Four treatment conditions were used for the study; i.e. In Experiment 1, 4 hours in the presence of an induced rat liver homogenate metabolising system (S9), at a 2% final concentration with cell harvest after a 20-hour expression period and a 4 hours exposure in the absence of metabolic activation (S9) with a 20-hour expression period. In Experiment 2, the 4 hours exposure with addition of S9 was repeated (using a 1% final S9 concentration), whilst in the absence of metabolic activation the exposure time was increased to 24 hours. The result of the test showed that the test item did not induce any statistically significant increases in the frequency of cells with chromosome aberrations in either the absence or presence of a liver enzyme metabolising system in either of two separate experiments.

 

Based on the results observed, Fatty acids, tall-oil, oligomeric reaction products with anhydride and rosin, calcium magnesium zinc salts is not considered to be clastogenic to human lymphocytes in vitro.

Mammalian cell mutation

In a key Guideline (OECD 476) in vitro mammalian cell gene mutation assay (Harlan Laboratories Ltd., 2013b), the mutagenic potential of the test material (Fatty acids, tall-oil, oligomeric reaction products with maleic anhydride and rosin, calcium magnesium zinc salts; CAS# 160901-14-4) was assessed using Mouse Lymphoma L5178Y cells.

 

Two experiments were conducted. In the first experiment, the cells were treated at eight dose levels (1.25 to 80 µg/mL), with solvent and positive controls. The cells were exposed in duplicates for 4 hours in the presence and absence of metabolic activation. In the second experiment cells were treated with the test item at up to eight dose levels (1.25 to 80 µg/mL) for 4 hours (with metabolic activation) and 24 (without).

 

The results showed that Fatty acids, tall-oil, oligomeric reaction products with maleic anhydride and rosin, calcium magnesium zinc salts did not induce any toxicological significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation.


Justification for classification or non-classification

Not classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).