3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate

Endpoint summary

Additional information

In vitro genotoxicity

DL-Alpha-Tocopheryl acetate was evaluated for mutagenic activity in the Ames test (OECD 471, GLP) in absence and in presence of metabolic activation in five Salmonella typhimurium test strains (TA1535, TA97, TA98, TA100, and TA102). The concentration ranged from 50 to 5000 μg/plate.

No increase in the number of revertant colonies was apparent. It is concluded that DL-Alpha-Tocopheryl acetate

is not mutagenic in the Ames test under the described experimental conditions (DSM ( E.Gocke), 1999).

In another Ames test no increase in the number of revertants and no toxicity was observed with Salmonella typhirium strains TA 98, TA 100, TA 1535 and TA1537, with and without S9 (rat mix). The dose levels were 20, 100, 500, 2500 and 5000 microgram/plate (BASF,1989).

 

DL-alpha-Tocopheryl acetate at concentrations between 75 and 1800 μg/ml was tested in an in vitro cytogenetics assay (OECD 473, GLP) in the absence and presence of metabolic activation. After exposure to the test article the frequency of cells with structural or numerical chromosome aberrations was not increased to a biologically relevant extent. It is concluded that DL-Alpha-Tocopheryl acetate is not clastogenic or aneuploidogenic under the described experimental conditions (DSM (A. Chetelat), 1999). No increase in frequency of chromosome aberrations was observed in a chromosome aberration test in Chinese hamster fibroblast cells (CHL), in the absence of metabolic activation. The dose levels levels of the structural analogue D,L-Alpha-Tocopherol were 0.125, 0.25 and 0.5 mg/ml (Ishidate, 1984).

 

In a gene mutation test in Chinese hamster ovary AS52 cells, a stuctural analogue (d-Gamma-Tocopherol) had no effect on mutant frequency in the absence of metabolic activation at dose levels were 2.9 and 14.6 µg/ml. A significant decrease in dosing efficiency was observed at the high concentration when compared to controls; cloning efficiency was approximately 85 -90% (control = 100%). Gamma-Tocopherol had no effect on the mutation frequency. The substance caused no gene mutation in the mammalian cell cultures (Cornwell, 2002).

 

In vivo genotoxicity

The effect of DL-Alpha-Tocopheryl acetate

on the bone marrow of mice was investigated. The 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 micronuclei did not increase in the low group and did not decrease in the high group when compared with the mid group. There were no statistically significant intergroup differences at each time point (Umegaki, 1997).

Short description of key information:
No effects were noted in
-an Ames test, OECD 471, GLP (DSM (E.Gocke), 1999)
-an in vitro chromosome aberration test in human lymphocytes, OECD 473, GLP (DSM (A.Chetelat), 1999)
- an in vitro chromosome aberration test in CHL cells, near-guideline and non-GLP with structural analogue alpha-tocopherol (Ishidate, 1984)
-an in vitro gene mutation test in CHO cells, near guideline and non-GLP with structural analogue gamma-tocopherol (Cornwell, 2002)
-an in vivo micronucleus test, similar to OECD 474, non-GLP (Umegaki, 1997).
Thus, DL-Alpha-Tocopheryl acetate is not considered to be genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 classification is not warranted.