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Additional information

Based on guideline EEC 84/449 B4, The mutagenic potential of itaconic acid as been assessed in the Salmonella thyphimurium / microsomal assay.

Strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 were used in presence and in absence of liver preparation from Aroclor 1254 induced rats (S9 mix). Itaconic acid was dissolved in water and dose levels used in the main assays were: 100, 500, 1000, 1500 and 2000 µg/plate without S9 mix and 100, 500, 1000, 2500 and 5000 µg/plate in presence of S9 mix. Two independent tests were performed.

No evidence of mutagenic activity was seen at any dose level of itaconic acid in either mutation tests and it was concluded that itaconic acid was not mutagenic in this bacterial test system.

Based on guideline OECD 476, The in vitro potential mutagenic activity of itaconic acid was investigated in V79 Chinese hamster cells using the V79 / HPRT system.

The test was performed in presence and absence of a metabolic activation system, S9 mix. Due to the acidic pH of the culture medium in the presence of the test substance, the highest selected concentration was 1500 µg/ml. The test concentrations were: 62.5, 125, 250, 500, 1000 and 1500 µg/ml.

Itaconic acid was slightly cytotoxic to the cells showing a reduced cloning efficiency without S9 mix. The cytotoxicity was not evidenced in presence of S9 mix. The mutation frequency was considered similar to that of the controls; a three fold increase of the mutation frequency was not achieved in presence or in absence of metabolic activation.

It is concluded that itaconic acid is not mutagenic in this HPRT gene mutation assay in V79 Chinese hamster cells.

Based on guideline OECD 473, The in vitro potential clastogenic activity of itaconic acid was investigated in Chinese hamster ovary (CHO) cells with and without metabolic activation.

The cells were treated with the test substance for three hours with and without S9 mix. After treatment the cells were rinsed and fresh medium was added. The cultures were then incubated until chromosome preparation, i.e. 21 hours. Because of the low pH of higher concentrations, 1500 µg/ml was the maximum tested dose. The test concentrations were: 250, 500, 1000 and 1500 µg/ml.

Whatever the concentrations itaconic acid did not show cytotoxic effect to the CHO cells as measured by mitotic index. The incidence of aberrant cells in the treated cultures was similar to that in the control cultures. The positive controls responded as expected.

It is concluded that itaconic acid did not show any clastogenic activity in CHO cells under our experimental conditions.

Based on guideline EEC 84/449 B12, a Micronucleus test was performed to assess the ability of itaconic acid to induce clastogenicity in mice bone morrow cells.

The animals received a single oral dose of 1500 mg/kg. Polychromatic erythrocytes were examined for micronuclei at the three sampling times 24, 48 and 72 hours. At the three sampling times the number of micronucleated polychromatic erythrocytes and the PE/NE ratio in mice treated with itaconic acid did not differ statistically from the concurrent negative control values.

It is concluded that itaconic acid did not show any evidence of clastogenicity in the micronucleus test in mice.

Based on guideline OECD 471, a bacterial reverse mutation test (Ames test) was performed to assess the mutagenic or promutagenic potential of the test item ITACONIC ACID in the several bacterial strains.

No cytotoxic activity was observed at a test item concentration of 50.0mg/mL.

Five test item doses ranged between 5.00 and 0.06 mg/plate were assayed. None of the concentrations

assayed for the test item showed an increase in the R value either with or without S9 metabolic activation regardless of the procedure.

No dose response for the test item ITACONIC ACID was observed in none of the tested bacterial strains.

Based on the results obtained in this study, it can be concluded that the test item does not induce point mutations or frame-shifts in the genome of the bacterial strains with or without metabolic activation regardless of the procedure.

Therefore, the test item ITACONIC ACID is considered to be NON MUTAGENIC / NON PRO-MUTAGENIC under the experimental conditions assayed.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Itaconic acid is classified as not mutagenic as there are negative results in genetic toxicity bacterial and non bacterial tests, according to the Regulation (EC) No 1272/2008.