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Toxicological information

Skin irritation / corrosion

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Alpha-Tocopherol
- Physical state: viscous liquid
- Storage condition of test material: under a nitrogen atmosphere in refrigerator

Test animals

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

Test system

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

Results and discussion

In vivo

Results
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.