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Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
no data
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles; pre-GLP study.

Data source

Reference Type:
Distribution and Metabolism of Two Orally Administered Esters of Tocopherol.
Gallo-Torres HE et al
Bibliographic source:
Lipids 6 (5): 318-325

Materials and methods

Objective of study:
Principles of method if other than guideline:
distribution of total radioactivity in rat tissue lipids after oral administration of d,1-3,4-3H2-alpha-tocopheryl nicotinate and d , l -alpha-tocopheryl-
GLP compliance:
pre-GLP study

Test material

Constituent 1
Reference substance name:
3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate
EC Number:
EC Name:
3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate
Constituent 2
Reference substance name:
Reference substance 001
Details on test material:
- Name of test material (as cited in study report): d,l-α-tocopheryl acetate
- Analytical purity: > 99% (tlc, glass-fiber paper chromatography)
- Impurities (identity and concentrations): no data
No further data

- Name of test material (as cited in study report): dl-α-tocopheryl 1',2'-³H2-acetate
- Analytical purity: >99% (tlc, glass-fiber paper chromatography)
- Impurities (identity and concentrations): no data
- Radiochemical purity (if radiolabelling): >99% (liquid scintillation counting)
- Specific activity (if radiolabelling): no data
No further data

Test animals

Crj: CD(SD)
Details on test animals or test system and environmental conditions:
- Source: CD Charles River Breeding Lab., North Wilmington, Mass., USA
- Age at study initiation: no data
- Weight at study initiation: 230-250 g
- Fasting period before study: 24 hours
- Housing: no data
- Individual metabolism cages: no data
- Diet (e.g. ad libitum): Purina Lab Chow ad libitum, with exception of fasting period
- Water: 0.85% saline, ad libitum
- Acclimation period: no data


No further data.

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
Ten rats were administered a single oral dose of emulsified alpha-tocopheryl acetate. Groups of 2 rats were sacrificed at 3, 6, 12, 24, or 48 hours after dosing. No further data.
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Doses / Concentrations:
50 µCi/animal
No. of animals per sex per dose / concentration:
Control animals:
Positive control reference chemical:
Details on study design:
The distribution of Vitamin E acetate and Vitamin E nicotinate was compared. dl-3,4-3H2-alpha-tocopheryl nicotinate was administered at equimolar amounts to another group of rats.
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, plasma, adipose tissue, skeletal muscle, stomach, small intestine, large intestine, liver, heart, lungs, kidneys, spleen, adrenals ovaries, brain, pituitary, and all other visceral organs
- Time and frequency of sampling: 3, 6, 12, 24, 48 h after injection

³H-radioactivity was determined in plasma and organ tissues by paper chromatography and scintillation counting.
no data

Results and discussion

Metabolite characterisation studies

Metabolites identified:
Details on metabolites:
alpha-tocopheryl quinone

Any other information on results incl. tables

The comparison of the distribution of total radioactivity in tissue lipids demonstrated a considerable variation in the concentration of vitamin E in the organs at various time intervals. A higher total radioactivity was found in the tissues of rats dosed with alpha-tocopheryl nicotinate than after alpha-tocopheryl acetate at 12 hours after dosing, but not at most other time intervals studied. According to the authors, this finding indicated that the tissue uptake of vitamin E after oral dosage with the nicotinate was, perhaps, poorer than after dosing with the acetate. Although total radioactivity in the blood and liver of rats dosed with alpha-tocopheryl acetate varied slightly with time, there was a peak of radioactivity at 12 hours after administration of alpha-tocopheryl nicotinate. In both groups of rats, the adrenals, ovaries, adipose tissue and heart appeared to extract vitamin E from the blood for up to 48 hours postabsorptively. Metabolic products of tocopherol detected by chromatography were found in both instances.

According to the authors, this analysis revealed that, after oral dosage, both alpha-tocopheryl nicotinate and alpha-tocopheryl acetate were extensively metabolized by rat tissues. The metabolite most abundantly occurring under these conditions was alpha-tocopheryl quinone. In the adrenal glands, however, the most highly labelled compound was unesterified tocopherol, which increased with time and comprised up to 90% of the chromatographed radioactivity. The authors concluded that the adrenal tissue played an definite role in the metabolism of vitamin E.

Applicant's summary and conclusion