Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-12-13 - 2011-12-16
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:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification:
Description: yellow slightly viscous liquid
Batch number:
Purity : not supplied
Date received : 24 November 2011
Expiry date : 01 December 2012
Storage conditions: room temperature in the dark

The integrity of supplied data relating to the identity, purity and stability of the test item is the responsibility of the Sponsor.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.32 to 2.99 kg
- Housing: individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum. 2930 Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL


Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: an elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: directly after the patch removal

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Erythema/Eschar Formation
Basis:
animal: 71461 male
Time point:
other: Score at 0, 1, 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 48 hours
Irritation parameter:
other: Erythema/Eschar Formation
Basis:
animal: 71462 Male
Time point:
other: Score at 0, 1, 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
other: Erythema/Eschar Formation
Basis:
animal: 71463 male
Time point:
other: Score at 0, 1, 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 48 hours
Irritation parameter:
other: Oedema Formation
Basis:
animal: 71461 male
Time point:
other: Score at 0, 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No evidence of skin irritation
Irritation parameter:
other: Oedema Formation
Basis:
animal: 71462 male
Time point:
other: Score at 0, 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No evidence of skin irritation
Irritation parameter:
other: Oedema Formation
Basis:
animal: 71463 male
Time point:
other: Score at 0, 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No evidence of skin irritation
Irritant / corrosive response data:
The individual scores for erythema/eschar and oedema are reported.
Very slight erythema was noted at all treated skin sites at the 24 hour observation and persisted at one treated skin site at the 48 hour observation.
Two treated skin sites appeared normal at the 48 hour observation and the remaining treated skin site appeared normal at the 72 hour observation.
Other effects:
Individual bodyweights and bodyweight changes are reported.
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Interpretation of Results

Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme

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 item. The test item 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.46‑59:

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 item is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

Table 1. IndividualSkin Reactions

Skin Reaction

Observation Time
(following patch removal)

Individual Scores – Rabbit Number and Sex

Total

71461Male

71462Male

71463Male

Erythema/Eschar Formation

Immediately

0

0

0

(0 )

1 Hour

0

0

0

( 0 )

24 Hours

1

1

1

3

48 Hours

0

1

0

( 1 )

72 Hours

0

0

0

0

Oedema Formation

Immediately

0

0

0

( 0 )

1 Hour

0

0

0

( 0 )

24 Hours

0

0

0

0

48 Hours

0

0

0

( 0 )

72 Hours

0

0

0

0

Sum of 24 and 72‑HourReadings(S): 3

Primary Irritation Index (S/6): 3/6 = 0.5

Classification: MILD IRRITANT


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

Table 2. Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 3

71461Male

2.38

2.41

0.03

71462Male

2.32

2.37

0.05

71463Male

2.99

3.05

0.06


Applicant's summary and conclusion

Interpretation of results:
other: mild irritant
Remarks:
Criteria used for interpretation of results: other: Draize classification scheme
Conclusions:
The test item produced a primary irritation index of 0.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

Results. A single 4‑Hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight erythema. Two treated skin sites appeared normal at the 48‑Hour observation and one treated skin site appeared normal at the 72‑Hour observation.

Conclusion. The test item produced a primary irritation index of 0.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.