α-tocopherol

Basic toxicokinetics

Administrative data

Endpoint:

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles; pre-GLP study, please refer to IUCLID section 13 for read across justification.

Data source

Reference

Reference Type:

publication

Title:

Distribution and Metabolism of Two Orally Administered Esters of Tocopherol.

Author:

Gallo-Torres HE et al

Year:

1971

Bibliographic source:

Lipids 6 (5): 318-325

Materials and methods

Objective of study:

toxicokinetics

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-
l',2'-3H2-acetate

GLP compliance:

no

Remarks:

pre-GLP study

Test material

Test material information

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:

231-710-0

EC Name:

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

Cas Number:

7695-91-2

IUPAC Name:

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

Constituent 2

Reference substance name:

D,L-alpha-tocopheryl acetate

IUPAC Name:

D,L-alpha-tocopheryl acetate

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

Radiolabelling:

yes

Remarks:

³H

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- 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

ENVIRONMENTAL CONDITIONS: no data

No further data.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

ethanol

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

Remarks:

Doses / Concentrations:
50 µCi/animal

No. of animals per sex per dose / concentration:

10

Control animals:

no

Positive control reference chemical:

none

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.

Statistics:

no data

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

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.