Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Lack of Influence of a Long-Term High or Low Vitamin E Diet on the Oxidative Damage in the Bone Marrow of Mice.
Author:
Umegaki K et al
Year:
1997
Bibliographic source:
Int J Vit Nutr Res 67: 149-154.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
Bone marrow samples at different times from week 4 to week 50. preparation and evaluation according OECD 474
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
dl-alpha-tocopheryl acetate; no further data

Test animals

Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan Clea (Tokyo, Japan)
- Age at study initiation: 4 weeks
- Weight at study initiation: ca. 18 g
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: propylene cages; no further data
- Diet: diet containing the test substance at concentrations of 0, 30, or 1000 ppm, ad libitum
- Water: tap water; ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
no data

Administration / exposure

Route of administration:
oral: feed
Vehicle:
none
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): monthly
- Mixing appropriate amounts with (Type of food): Basal VE diet and high VE diet were prepared by adding 30 mg and 1000 mg VE to 1 kg of low VE diet (Low VE diet: 50% sucrose, 20% casein, 15% cornstarch, 5% stripped corn oil, 5% cellulose, 3,5% salt mixture (AIN76), 1% vitamin mixture (without VE), 0,3% DL-methionine and 0,2% choline bitartrate.)
- Storage temperature of food: -20 degrees C
Duration of treatment / exposure:
50 weeks
interim sacrifice at 6 weeks (5 males/group)
Frequency of treatment:
continuously in the diet
Post exposure period:
none
Doses / concentrations
Remarks:
Doses / Concentrations:
ca. 0, 6, 200 mg/kg bw/d (0, 30, 1000 ppm in the diet, estimated with a conversion factor of 5)
Basis:
no data
No. of animals per sex per dose:
13 males per group
Control animals:
yes, plain diet
Positive control(s):
not included

Examinations

Tissues and cell types examined:
peripheral blood reticulcytes
Evaluation criteria:
no data
Statistics:
Statistical analysis was made using one-way analysis of variance followed by Duncan's multiple range test. P values less than 0.05 were considered significant.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not examined
Negative controls validity:
valid
Positive controls validity:
not examined

Any other information on results incl. tables

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. Corresponding to the changes in the VE, lipid peroxidation in bone marrow was higher in the low VE diet group, but was not lower in the high VE diet group. Glutathione and vitamin C in the bone marrow, which were about 100-1000 times higher than that of VE, were not different among the groups.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test substance did not induce micronuclei in peripheral blood reticulocytes of male mice after administration at concentrations of 30 and 1000 ppm in the diet.
Executive summary:

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.