Registration Dossier

Administrative data

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
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): dl-alpha-tocopherol
- Physical state: Liquid

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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

Applicant's summary and conclusion

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).