Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 February 2006 to 10 February 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70 %
Any occasional deviations from the above targets were considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light


IN-LIFE DATES: From: 7 February 2006 To: 10 February 2006

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: moistened with distilled water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 0.5 ml of distilled water
- Concentration (if solution): N/A
Duration of treatment / exposure:
4 h
Observation period:
72 hours
Number of animals:
3 male
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm cotton gauze patch secured with surgical adhesive tape
- % coverage: NDA
- Type of wrap if used: the trunk of each rabbit was wrapped in an elasticated corset


REMOVAL OF TEST SUBSTANCE
- Washing (if done): after exposure the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: four hours after application


SCORING SYSTEM: Draize scheme

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
See table below for raw data.
Other effects:
None

Any other information on results incl. tables

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) “Dermal Toxicity” In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p. 47:

 

Primary Irritation Index                                 Classification of Irritancy

                0                                                               Non-irritant

           >0 to 2                                                           Mild irritant

           >2 to 5                                                           Moderate irritant

           >5 to 8                                                           Severe irritant

 

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test material is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

Individual skin reactions

 

Skin Reaction

Observation Time

Individual Scores – Rabbit Number and Sex

Total

24 Male

25 Male

26 Male

Erythema/Eschar Formation

1 Hour

24 Hours

48 Hours

72 Hours

0

0

0

0

0

0

0

0

0

0

0

0

(0)

0

(0)

0

Oedema Formation

1 Hour

24 Hours

48 Hours

72 Hours

0

0

0

0

0

0

0

0

0

0

0

0

(0)

0

(0)

0

Sum of 24 and 72-hour Readings (S): 0

Primary Irritation Index (S/6): 0

Classification: Non-irritant

 

(  ) = Total values not used for calculation of primary irritation index

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Driaze classification scheme. No corrosive effects were noted.
Executive summary:

In a dermal irritation study (0656/0281), male New Zealand White rabbits were dermally exposed to 0.5 g of the test material moistened with distilled water for 4 hours to a 2.5 cm x 2.5 cm area of skin.  Animals then were observed for 3 days.  Irritation was scored by the method of the Draize classification scheme.

No effects were observed. In this study, the test material is not classified as a dermal irritant.