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Administrative data

Key value for chemical safety assessment

Additional information

The test substance RRR-(alpha-, beta-, gamma-, delta)-tocopherol has not been tested for toxicity to genetic material. There are a few studies available concerning genetic toxicity of close homologs of the test item. For further information please refer to the read-across justification.

Bacterial reverse mutation assay:

In a bacterial reverse mutation assay (Ames test) all-rac-alpha-Tocopheryl acetate produced negative results in 5 histidine-requiring strains (TA97, TA98, TA100, TA1535 and TA102.) of Salmonella typhimurium, both in the absence and in the presence of metabolic activation by an Arochlor 1254 -induced rat liver post-mitochondrial fraction (S-9).

DL-alpha-Tocopherol was also negative in a bacterial reverse muation assay in 2 histidine-requiring strains (TA 98, TA 100).

Cytogenetics:

RRR-alpha-tocopherol was evaluated in an in vitro mammalian chromosome aberration test according to Ishidate M Jr and Odashima S (1977), Mutat Res 48:337. The frequency of chromosomal aberrations was not significantly increased. No metabolic activation was done.

Vitamin E was tested in an in vitro cytogenetics assay. After exposure to the test article the frequency of cells with structural or numerical chromosome aberrations was not increased to a biologically relevant extent. Positive and negative controls were valid.

It is therefore concluded that vitamin E is not clastogenic or aneuploidogenic under the described experimental conditions.

Furthermore, the effect of dietary vitamin E (VE) on the bone marrow of mice was investigated. For this purpose, mice received either a low VE diet, a basal VE diet, or a high VE diet. Groups of male ICR mice were fed a diet containing the test substance at concentrations of 0, 30, or 1000 ppm (corresponding to doses of ca. 0, 6, or 200 mg/kg bw/d, respectively) for up to 50 weeks. Reticulocytes from blood samples collected at various time intervals were used for micronucleus analysis. The incidence of reticulocytes containing MNs did not increase in the low VE diet group and did not decrease in the high VE diet group when compared with the basal VE diet group. There were no statistically significant intergroup differences at each time point.

It is therefore concluded that vitamin E is not clastogenic or aneuploidogenic under the described experimental conditions.

Mammalian cell gene mutation:

A close homolog of the test item, D-gamma-tocopherol” was tested for gene mutation in mammalian cells according to Tindall KR and Stankowski LF (1989). Mutat Res 220: 241-253. The test substance had no effect on mutant frequency. A significant decrease in cloning efficiency was observed at the high concentration when compared with controls; relative cloning efficiency was approximately 85-90% (control = 100%). No metabolic activation was done.

RRR-(alpha-, beta-, gamma-, delta)-Tocopherol, is evaluated on the basis of data on close homologs. On the basis of these results, there is currently no indication of a potential for toxicity to genetic material.


Short description of key information:
In-vitro: Bacterial reverse mutation assay:
- RA: 7695-91-2, Ames test, negative
- RA: 10191-41-0, Ames test, negative
In vitro, cytogenetics:
- RA: 59-02-9, chromosome aberration, negative
- RA: vitamin E, chromosome aberration, negative
In vitro mammalian cell gene mutation:
- RA: 7616-22-0, negative
- RA, in vivo chromosome aberration, negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity does not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.