Registration Dossier

Administrative data

Description of key information

Skin irritation: Not irritating
- RA: 10191-41-0, OECD 404, not irritating
- OECD 404, not irritating (24 h exposure time, abraded skin, occlusive dressing)
- OECD 404, not irritating (occlusive)
Eye irritation: not irritating
- OECD 405, not irritating
- OECD 405, not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
July 3, 1996 - July 18, 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to OECD Test Guideline No. 404, 1992 and under GLP , please refer to IUCLID section 13 for read across justification.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms (UK) Limited. Froxfield, Hampshire
- Housing: individually housed in grid bottomed metal cages
- Diet: ad libitum antibiotic-free rabbit diet
- Water: ad libitum mains drinking water via an automatic watering system
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17- 24
- Humidity (%): 54 - 82
- Air changes (per hr): air conditioned
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100 %
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm² (left flank, immediately caudal to the last rib)
- Type of wrap: encircling the trunk with "Elastoplast" elastic adhesive bandage


REMOVAL OF TEST SUBSTANCE
- Washing: cleansed using water
- Time after start of exposure: four hours

SCORING SYSTEM: subjective numerical according to OECD Guideline 404 (Erythema and Eschar formation / Oedema formation). Maximum possible
score: 4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: The sum of the 24 and 72 hour values for erythema and oedema (12 scores) were divided by 6 to give the primary irritation index
Irritant / corrosive response data:
There were no apparent signs of irritation at the treated skin site of the animal used for the preliminary screen throughout the 72 hour observation period.
In I of the 2 remaining animals irritation was evident from 24 hours after patch removal. Erythema appeared to increase throughout the initial observation
period and at the 72 hour observation, was noted to be moderate to severe. Barely perceptible oedema was also evident at the treated skin site of this animal 48 and 72 hours after patch removal.
In a second animal irritation was only apparent from 72 hours after patch removal, at which time both erythema and oedema were barely perceptible at the
treated skin site. In view of this delayed response, further examinations were made of the treated skin sites of these 2 animals 7 and 14 days after patch
removal.
At the examination conducted 7 days after patch removal, erythema persisted in both animals; slight oedema was only evident in 1 animal.
At the final examination conducted 14 days after patch removal, there were no apparent signs of irritation at the treated skin sites of either animal.
The Primary Irritation Index for the three animals was calculated to be 1.2.

Time after patch removal

Individual Skin Irritation Scores

Rabbit Number 39 (preliminary screen)

Rabbit Number 44

Rabbit Number 45

1 hour

Erythema

0

0

0

Oedema

0

0

0

24 hours

Erythema

0

1

0

Oedema

0

0

0

48 hours

Erythema

0

2

0

Oedema

0

1

0

72 hours

Erythema

0

3

1

Oedema

0

1

1

7 days

Erythema

-

3

1

Oedema

-

2

0

14 days

Erythema

-

0

0

Oedema

-

0

0

Interpretation of results:
slightly irritating
Remarks:
Migrated information Primary Irritation Index = 0.6 = 3.0 Criteria used for interpretation of results: not specified
Conclusions:
Under the conditions of this study, the test article, Alpha-Tocopherol as such, may be considered as a slight irritant to the skin of the albino rabbit. It is noted that the irritant response subsided completely within 2 weeks of dosing.
Executive summary:

The purpose of this study was to evaluate the degree of irritation produced by the test article, DL-a-Tocopherol, when applied to the intact skin of the albino rabbit. The procedures used were in accordance with those described in OECD Guideline for the Testing of Chemicals, No. 404 (adopted 17th July 1992).

A 0.5 ml aliquot of the test article was spread evenly over a 2.5 cm square of surgical lint and applied over a previously clipped area of the dorsal skin of 3 albino rabbits. The test article was held in contact with the skin, under a semi-occlusive patch assembly, for a 4 hour period. At the end of this period, the patches were removed and the treated skin site on each animal gently cleansed with water. Reaction to treatment, i.e. erythema and eschar as well as oedema formation was assessed 1, 24, 48 and 72 hours and, for 2 animals, also 7 and 14 days after patch removal.

There were no apparent signs of irritation at the treated skin site of the animal used in the preliminary screen throughout the 72 hour observation period.

In 1 of the 2 remaining animals, erythema appeared to increase throughout the initial observation period and at the 72 hour examination it was noted to be moderate to severe. Barely perceptible oedema was also visible 48 and 72 hours after patch removal at the treated skin site of this animal. In a second animal, irritation was evident from 72 hours after patch removal and consisted of barely perceptible erythema and oedema at the treated skin site. Signs of irritation were still evident in both animals at day 7 but subsided completely by day 14.

The Primary Irritation Index for the three animals was calculated to be 1.2.

Under the conditions of this study, the test article, DL-a-Tocopherol as such, may be considered as a slight irritant to the skin of the albino rabbit.

It can be assumed accordingly, that cutaneous exposure to DL-a-Tocopherol such as may potentially give rise to an irritant skin reaction in humans.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliable guideline study with limited information about the test item.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New York State Rabbit Development, Hartwick, N.Y.
- Weight at study initiation: 2 - 4 kg
- Housing: individually housed in wire mesh bottom cages in an environment-controlled room and quarantined for a minimum of 5 days
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
6 animals (no wash-out)
3 animals (wash-out 4s after instillation)
Observation period (in vivo):
24, 48, 72 h, 7 days
Number of animals or in vitro replicates:
6 animals (no wash-out)
3 animals (wash-out 4s after instillation)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): done in 3 animals
- Time after start of exposure: 4s after instillation

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: eyes were examined with sodium fluorescein and an ultraviolet lamp
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
None of the animals showed signs of irritation after instillation of the test item in the eye.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The test article is considered to be non-irritating to the rabbit eyes without a washout and with a washout 4 seconds after instillation.
Executive summary:

The eyes of six animals were not washed out after instillation of the test article. The eyes of 3 animals were washed out, approximately 4 seconds after instillation of the test article, by flushing with physiological saline until all visible test article was removed.

Single application of the test item in the eyes of 9 rabbits was well-tolerated (primary irritation score = 0.0).

Based on this result it can be expected that the test item is not irritating to eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

The skin irritation potential of "D-alpha-Tocopherol" was evaluated on the basis of three in-vivo tests. The key study is done with a very close homolog of the test item, "DL-alpha-Tocopherol" and both supporting studies are done with the test item itself.

Key study:

An 0.5 ml aliquot of DL-alpha-Tocopherol was applied to the intact skin of three albino rabbits. The test article was held in contact with the skin, under a semi-occlusive patch assembly, for a 4 hour period. At the end of this period, the patches were removed and the treated skin site on each animal gently cleansed with water. Reaction to treatment was assessed 1, 24, 48 and 72 hours and, for 2 animals, also 7 and 14 days after patch removal. Individual scores for edema and erythema were 0/0 (animal #1), 0.7/2 (animal #2) and 0.3/0.3 (animal #3), respectively. The test substance was slightly irritating to skin under the conditions of this study (DSM, 1996). All findings of edema and erythema were fully reversible within 7 days.

Supporting study:

An 0.5 ml aliquot of D-alpha-Tocopherol was spread evenly over a one-inch square area and applied on intact and abraded dorsal skin of 6 albino rabbits. The test article was held in contact with the skin, under a occlusive patch assembly, for a 24 hour period. At the end of this period, the patches were removed and the exposure sites were gently wipped with clean gauze to remove as much non-absorbed test article as possible. Only slight erythema and barely perceptible edema was visible at 24 h after patch removal. No edema was visible at 72h whereas slight signs of irritation were still evident in all animals at 72 h after patch removal.

The Primary Irritation Index for the six animals was calculated to be 0.92.

Under the conditions of this study, the test article may be considered as a slight irritant to the skin of the albino rabbit.

In the second supporting study an 0.5 ml aliquot of the test article was spread evenly over a one-inch square area and applied on intact and abraded dorsal skin of 6 albino rabbits. The test article was held in contact with the skin, under a occlusive patch assembly, for a 4 and 24 hour period. At the end of this period, the patches were removed and the exposure sites were gently wipped with clean gauze to remove as much non-absorbed test article as possible (24 h) or gently cleaned with a solvent (4 h).

All animals exhibited a score of 1 (slight erythema) at both the 4 and 48 hour observation periods. The mean primary irritation score is 1.17. The test article is not considered corrosive and not considered to be a primary skin irritant to the skin of rabbits.

Eye irritation:

The eye irritation potential of "D-alpha-Tocopherol" was evaluated on the basis of two in-vivo tests done with the test item.

Key Study:

An 0.1 ml aliquot of D-alpha-Tocopherol was applied to the eye of 9 albino rabbits. The eyes of six animals were not washed out after instillation of the test article. The eyes of 3 animals were washed out, approximately 4 seconds after instillation of the test article, by flushing with physiological saline until all visible test article was removed.

Single application of the test item in the eyes of 9 rabbits was well-tolerated (primary irritation score = 0.0).

Based on this result it can be expected that the test item is not irritating to eyes.

Supporting Study:

An 0.1 ml aliquot of D-alpha-Tocopherol was applied to the eye of 6 New Zealand albino rabbits. The test item was not washed out after instillation.

Single application of the test item in the eyes of 9 rabbits was well-tolerated (primary irritation score = 0.0).

Based on this result it can be expected that the test item is not irritating to eyes.

Based on the results obtained from these in-vivo tests, it is concluded that the test item is neither a skin nor an eye irritant and that therefore no classification for skin or eye irritation is needed.


Justification for selection of skin irritation / corrosion endpoint:
Most reliable guideline study which is the basis for classification.

Justification for selection of eye irritation endpoint:
Most reliable guideline study which is the basis for classification.

Justification for classification or non-classification

The available data on skin and eye irritation does not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.