Registration Dossier

Administrative data

Description of key information

For acute toxicity, the key studies based on D,L-alpha-tocopherol were used:
- oral: limit study similar to OECD 401, pre-GLP (DSM, 1972)
- dermal: acute toxicity test similar to OECD 402, pre-GLP (Buser, 1980)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: according to OECD Guideline 402, non-GLP: scientifically accepted
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Albino - SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Füllinsdorf
- Weight at study initiation:
Males: 207.6 +/- 7.9 g
Females: 199.2 +/- 7.2 g
- Housing: Individually in metal cages
- Diet (e.g. ad libitum): Ad libitum, Nafag 850
- Water (e.g. ad libitum): Ad libitum, tap water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 55 +/- 5
Type of coverage:
occlusive
Vehicle:
vegetable oil
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region
- % coverage: 10% (16 cm2)
- Type of wrap if used: gauze and Pergamine paper + occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Luke warm water
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
100, 300, 1000 and 3000 mg/kg (= pure substance)
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: almost once daily
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Remarks on result:
other: Maximum dosable concentration was limited by the volume of the substance (maximum volume reached at 3000 mg/kg bw)
Mortality:
No mortalities were recorded during the observation period
Clinical signs:
Local irritations in both male and female groups relative to the doses that were applied:
- Erythema: first 24-48 hours. Inflammation: most severe stage on day 2-4 for males, on day 2-6 for females. Also first signs of abrasion (desquamation).
- Edemas: in high dose groups of females, slight skin elevations (grade 0-1 and 1) during time of severe inflammation.
Body weight:
Body weights were reduced in all groups after the initial 24 hour application period. With 3000 mg/kg weight development of females was obviously
retarded during the following 5 days reflecting the period of inflammations and edemas. In male groups this development was normal.
Gross pathology:
No abnormalities
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Substance is not classified according to EU criteria (67/548/EEG) as the LD50 >3000 mg/kg, but some effects on weight and skin have been
observed.
Executive summary:

Dl-alpha-Tocopherol, which is widely known as vitamin E has been tested in an acute dermal toxicity test (similar to OECD 402, test system: Rat).

A maximum dose of 3000 mg/kg was applied as the pure substance, which is a viscous oil . Further dosages of 1000, 300 and 100 mg/kg were mixtures of the substance with a vegetable oil. This same oil was applied in control groups.

No dermal LD50 could be achieved up to 3000 mg/kg since the mode of application was limited by the volume of the substance.

However, dl-alpha-tocopherol causes well defined to severe erythemas which are obviously dose related: this response becomes evident in all dose groups 24 - 48 hours after application and on day 3 or 4 turns into a period of abrasion. Skin irritations are more pronounced in females; here also slight edemas were recorded with high dosages. Body weights were reduced in all groups after the initial 24 hour application period. With 3000 mg/kg weight development of females was obviously retarded during the following 5 days reflecting the period of inflammations and edemas. In male groups this development was normal. Final autopsies showed no abnormalities that could be related to treatment.

Substance is considered to be slightly toxic as the LD50 >3000 mg/kg is not low enough for classification according to EU criteria as harmful, toxic or very toxic (67/548/EEG), but some effects on weight and skin have been observed (possibly irritating/corrosive).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50

Additional information

The acute toxicity of D,L-alpha-tocopherol is low. The available acute oral toxicity study in rats (DSM, 1972) was selected as the key study. The oral LD50 was > 4000 mg/kg bw in rats in a well conducted pre-GLP and OECD 401-similar study.

In an acute dermal toxicity test (similar to OECD 402) D, L- alpha-tocopherol has been tested (DSM, 1980). A dermal LD50 of >3000 mg/kg was found, since no mortality occurred. The test substance caused only slight local erythema which appeared 24 - 48 hours after application. Only few animals showed signs of local abrasion.

Justification for classification or non-classification

Based on the available acute toxicity data, classification is not needed for acute toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.