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Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro:

Weight of evidence:

Experimental results with Sodium acetate:

In the first study, reported by Ishidate et al., 1984, a reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 was carried out with Sodium Acetate according to the method of Ames et al. (1975), but only with metabolic activation. No significant increases in the numbers of revertant colonies were detected in any S. typhimurium strains at the maximum dose tested.

In the same report, Ishidate et al. reported chromosomal aberrations tests with Sodium Acetate using a Chinese hamster fibroblast cell line, CHL. The cells were exposed to each sample at three different doses for 24 and 48 hours. No metabolic activation systems were applied. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer. The incidence of cells with aberrations (including gaps) was 0%.

Read-across from experimental results obtained with Acetic Acid:

A test within the National Toxicology Program’s mutagenicity testing program and according to GLP was reported by Zeiger et al., 1992. This test was carried out with Acetic acid using Salmonella typhimurium strains TA 98, TA 100, TA 1535, and TA 97, with and without matabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these results, the read-across approach is applied and Sodium acetate is also considered as not mutagenic under test conditions.

In the next report (by Morita et al., 1990) a cytogenetic assay was carried out with Acetic acid using Chinese hamster ovary K1 cells,

with and without metabolic activation. In the absence of S9 mix, cells were exposed for 24 h to test substance at doses of 8, 10, 12, 14, and 16 mM. In the presence of S9 mix, cells were exposed for 6 h to test substance at doses of 4, 8, 10, and 12 mM, and recultured in fresh medium for 18 h. The medium used was Ham’s F12 supplemented with 17 mM NaHCO3 and 10% fetal calf serum. Cytotoxicity was evaluated by counting surviving cells.

The relationship between the pH of the medium and the clastogenic activity was examined. In order to study the effects of neutralization of the treatment medium, two kinds of treatment media were examined. One was adjusted to pH 5.8 or pH 6.0 and the other was so adjusted and then immediately neutralized to pH 6.4 and pH 7.2 with 1 M NaOH.

Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity. Low pH did induce some artificial chromosome aberrations, but these were eliminated by neutralization of the test medium.

The read-across approach is applied and Sodium Acetate is also considered to be not clastogenic under test conditions.

Read-across from experimental results obtained with Acetic Anhydride:

In the paper reported by Seifreid et al. (2006), a L5178Y Mouse Lymphoma Cell Mutation Assay was performed with Acetic anhidride to test its mutagenic potencial. The chemical was tested with and without metabolic activation. The range of concentartions was 0.04 - 0.3 g/mL. The toxicity of test substance was also determined both with and without liver S9. The mutagenicity assay was performed according to the procedure described by Clive and Spector. Resistance to trifluorothymidine (TFT) was determined by adding TFT (final concentration, 3 µg/mL) to the cloning medium for mutant selection. Results have been evaluated under the traditional criteria (old evaluation) as well as the current international “harmonization” recommendations (new evaluation).

With old evaluation: Test substance was not mutagenic with metabolic activation, and was positive without metabolic activation (this positive result is not reliable, because full requeriments for a valid test were not met).

With new evaluation: Test substance was ambiguous with and without metabolic activation.

Based on these results, the read-across approach is applied and Sodium acetate is considered to be ambiguous on mouse lymphoma cells, with and without metabolic activation.

Read-across from experimental results obtained with Phenoxyacetic acid:

A L5178Y Mouse Lymphoma Cell Mutation Assay was performed with Phenoxyacetic acid (National Toxicology Program Database). The chemical was tested with and without metabolic activation and, in general, tested concentrations were: 62.5, 125, 250, 500, 750, 1000, 1500, and 2000 µg/mL. Phenoxyacetic acid resulted to be not mutagenic with and without metabolic activation. It was toxic to cells, but at higher concentrations than precipitating concentrations.

The read-across approach is applied and Sodium acetate is considered to be not mutagenic on mouse lymphoma cells.

Estimated results with Sodium Acetate from Danish (Q)SAR Database:

A Danish (Q)SAR prediction with the Multicase model was realized to estimate the mutagenic potencial of sodium acetate on mammalian cells (mouse lymphoma and HGRT (CHO): Chinese hamster ovary cell HGPRT forward mutation assay).

The substance sodium acetate was predicted to be not mutagenic in mammalian cells. This prediction should be used for classification and risk assessment.

Genetic toxicity in vivo:

Key studies:

Experimental results with Sodium Acetate:

The Testicular DNA-synthesis inhibition test (DSI test) was performed on male mice with Sodium Acetate. This is not a standard genotoxicity test system, but it provides evidence that acetic acid, sodium salt is not genotoxic in animals. The basis of the method is to measure 3H-thymidine incorporation. Animals receive a single oral dose by gavage at concentrations of 200, 500, and 1000 mg/kg bw of test substance. No inhibitory effect on DNA-replication was detectable in animals treated with Sodium Acetate.


Short description of key information:
Genetic toxicity in vitro:
Weight of evidence: Experimental results from studies performed with Sodium Acetate, and the analogue substances Acetic acid, Acetic anhydride and Phenoxyacetic acid. Data is provided on bacterial tests, chromosome aberration test and mammalian cell gene mutation assay.
Estimated data with Sodium Acetate from Danish (Q)SAR database.

Genetic toxicity in vivo:
Key studies: Experimental results with Sodium Acetate: The Testicular DNA-synthesis inhibition test (DSI test) was performed on male mice. No inhibitory effect on DNA-replication was detectable.

Weight of evidence: Experimental results from studies performed with Sodium Acetate, and the analogue substances Acetic acid, Acetic anhydride and Phenoxyacetic acid. Data is provided on bacterial tests, chromosome aberration test and mammalian cell gene mutation assay.
Estimated data with Sodium Acetate from Danish (Q)SAR database.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification