Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 September 2003 to 08 December 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Colourless liquid
- Date received: 20 December 2002
- Storage condition of test material: Room temperature in the dark, over silica gel, under nitrogen

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
ANIMALS AND ANIMAL HUSBANDRY
- Three New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- At the start of the study the animals were in the weight range 2.0 kg to 3.5 kg and were 12 to 20 weeks old.
- After an acclimatisation period of at least 5 days each animal was given a number unique within the study, which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
- Animals were individually housed in suspended metal cages.
- Free access to mains drinking water and food (Certified Rabbit Diet (Code 5322) supplied by International Product Supplies Limited, Wellingborough, Northants, UK) was allowed throughout the study.
- 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.
- Temperature and relative humidity were set to achieve limits of 17 °C to 23 °C and 30 % to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- The rate of air exchange was at least 15 changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.
- 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.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
Four hours
Observation period:
14 days
Number of animals:
Three
Details on study design:
PREPARATION OF TEST MATERIAL
- The absorption of the test item was not determined.

MEASUREMENT OF pH
- The pH of the test material was determined prior to commencement of the study and found to be 4.7 for a 10 % w/w aqueous preparation.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: 105 (male)
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: 108 (male)
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: 111 (male)
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: 105 (male)
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: 108 (male)
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean score
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: 111 (male)
Irritant / corrosive response data:
- Individual scores for erythema/eschar and oedema are given in Table 1 (attached).
- Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal with well-defined erythema at all treated skin sites at the 24, 48 and 72 hour observations.
- Very slight to slight oedema was noted at all treated skin sites one hour after patch removal and at the 24 and 48 hour observations. Very slight oedema was noted at all treated skin sites at the 72 hour observation.
- Light brown discolouration of the epidermis was noted at all treated skin sites at the 24, 48 and 72 hour observations with loss of skin elasticity noted at all treated skin sites at the 72 hour observation.
- Crust formation, which prevented evaluation of erythema and oedema, was noted at all treated skin sites at the 7 day observation.
- All treated skin sites appeared normal at the 14 day observation.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a primary irritation index of 3.3 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for three animals calculated using data from 24, 48 and 72 hour observations were < 2.3 for erythema and edema. No corrosive effects were noted.
Executive summary:

INTRODUCTION

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the OECD Guidelines for the Testing of Chemicals No 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002) and Commission Directive 92/69/EEC Method B.4 Acute Toxicity (Skin Irritation).

RESULTS

A single 4 hour semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and very slight oedema. Other reactions were light brown discolouration of the epidermis, loss of skin elasticity and crust formation, which prevented evaluation of erythema and oedema. All treated skin sites appeared normal at the 14 day observation.

CONCLUSION

The test material produced a primary irritation index of 3.3 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for three animals calculated using data from 24, 48 and 72 hour observations were < 2.3 for erythema and edema. No corrosive effects were noted.