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Administrative data

Description of key information

Reliable skin and eye irritation studies in rabbits (OECD 404 and 405 respectively, GLP) were performed with (D,L-) alpha-tocopherol . 
(D,L-) alpha-tocopherol is slightly irritating to the skin and not irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 3, 1996 - July 18, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to OECD Test Guideline No. 404, 1992 and under GLP
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:
other: 24 and 72 hrs.
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
Study period:
September 27, 1988 - September 30, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to OECD Test Guideline No. 405, 1987 and under GLP
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Directive 84/449/EEC
Deviations:
not applicable
GLP compliance:
yes
Remarks:
Statement of Compliance
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fullinsdorf, Switzerland
- Age at study initiation:
Male: 14 weeks
Females: 15 weeks
- Weight at study initiation:
Male: 2.4 kg
Females: 2.5 kg
- Housing: Individually in stainless steel cages equipped with an automatic cleaning and drinking system
- Diet: ad libitum pelleted standard rabbit maintenance diet
- Water: ad libitum community tap water
- Acclimation period: Four days under laboratory conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 40 - 70
- Air changes (per hr): 10- 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted (100%)
Duration of treatment / exposure:
72 hours (not rinsed)
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: subjective numerical according to OECD Guideline 405 (corneal, iridic and conjunctival irritation (redness/chemosis)).

TOOL USED TO ASSESS SCORE: slit-lamp 30 SL/M and Varta Cliptrix diagnostic-lamp
Irritation parameter:
maximum mean total score (MMTS)
Remarks:
cumulative
Basis:
mean
Time point:
other: 24, 48 and 72 hrs
Score:
0
Remarks on result:
other: Not rinsed
Irritation parameter:
other: Primary irritation score (100%)
Basis:
other: calculated by totaling the individual cumulative scores at 1, 24, 48 and 72 hours and then dividing by the number of figures
Time point:
other: 1, 24, 48 and 72 hrs.
Score:
0
Remarks on result:
other: Not rinsed
Irritant / corrosive response data:
Coloration: Brown staining of the eyelashes of the treated eyes by pigment or coloring of the test article was observed in all three animals at 1 hour;
from 1 to 48 hrs., and from I to 72 hrs. after the test article application.
Corrosion: no corrosion of the cornea was observed at any of the measuring intervals.
Interpretation of results:
not irritating
Remarks:
Migrated information Primary Irritation Score = 0 = 1.2 Criteria used for interpretation of results: not specified
Conclusions:
Under the conditions of this experiment, D,L-alpha-Tocopherol was found to cause a primary irritation score of: 0.00, when applied to the rabbit eye mucosa.
Brown staining of the eyelashes of the treated eyes by pigment or coloring of the test article was observed in all three animals at 1 hour; from 1 to 48 hrs., and from 1 to 72 hrs. after the test article application.
No corrosion was observed at any of the measuring intervals.
Executive summary:

Single application of D,L-alpha-Tocopherol was well-tolerated on the rabbit eye (primary irritation score = 0.0).

Based on this result it can be expected that occasional contamination of the human eye by D,L-alpha-Tocopherol will be harmless for human health.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a skin irritation study, performed according to OECD guideline 404, 3 rabbits (3 females) were exposed to alpha-tocopherol. Erythema and edema were scored at 24, 48, and 72 hours and 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 skin irritating under the conditions of this study (DSM, 1996). All findings of edema and erythema were fully reversible within 7 days.

In an eye irritation study, performed according to OECD guideline 405, 3 rabbits (1 male, 2 females) were exposed to D,L-alpha-tocopherol. Opacity, iris, redness and swelling were scored at 24, 48, and 72 hours and the mean scores were 0.0 for all animals and time points. D,L-alpha-tocopherol was not an eye irritant under the conditions of this study (DSM, 1988 ).


Effects on skin irritation/corrosion: slightly irritating

Justification for classification or non-classification

Findings do not meet the critera for classification as skin or eye irritant according to EU classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.