Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 January 2015 to 20 January 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

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: Dark yellow viscous liquid
- Analytical purity: 100 %
- Expiration date of the lot/batch: 12 June 2016
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
ANIMALS AND ANIMAL HUSBANDRY
- Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd, Leicestershire UK.
- At the start of the study the animals weighed 2.76 or 3.39 kg and were 12 to 20 weeks old.
- After an acclimatisation period of at least 5 days, each animal was given a unique number within the study by writing with black indelible marker-pen on the inner surface of the ear and on the cage label.
- Animals were individually housed in suspended cages.
- Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories Ltd, Oxon, UK) was allowed throughout the study.
- The diet and drinking water were considered not contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Temperature and elative humidity were set to achieve limits of 17 °C to 23 °C and 30 % to 70 % respectively.
- The rate of air exchange was at least 15 changes per hour.
- Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
- 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.

Test system

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

MEASUREMENT OF pH
- The pH of a 10 % aqueous preparation of the test item was determined to be 8.62 immediately and 8.31 after 10 minutes.

PROCEDURE
- On the day before the test, two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers.
- Only animals with a healthy intact epidermis by gross observation were selected for the study.
- On the day of the test, a suitable test site was selected on the back of each rabbit.
- A quantity (0.5 mL) of the test item was applied directly to the skin under a 2.5 cm * 2.5 cm cotton guaze patch.
- The patch was secured in position with a strip of surgical adhesive tape.
- To prevent the animals interferring with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
- Four hours after application, the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Immediately following removal of the patches, and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to defined criteria (see attached scale for evaluation of skin reactions).
- If present, any other skin reactions and clinical signs of toxicity were also recorded.
- Additional observations were made on Days 7 and 14 to assess the reversibilty of the skin reactions.
- Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.


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: 74904 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: 74905 Male
Irritation parameter:
edema 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: 74904 Male
Irritation parameter:
edema 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: 74905 Male
Irritant / corrosive response data:
- Individual scores for erythema/eschar and edema are given in Table 1 (attached).
- Very slight erythema and very slight edema were noted at both treated skin sites immediately after patch removal.
- Well-defined erythema and very slight edema were noted at both treated skin sites at the 24, 48 and 72-hour observations.
- At the 7-day observation, well-defined erythema and slight edema were noted at one treated skin site with very slight erythema, slight edema and moderate desquamation at the other treated skin site.
- Both treated skin sites appeared normal at the 14-day observation.
Other effects:
BODY WEIGHT
- Individual body weights and body weight change are given in Table 2 (attached).
- Both animals showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a primary irritation index of 4.0 and was considered to be a moderate irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted. 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 below the stated limits for erythema and edema.
Executive summary:

GUIDELINE

The study was designed to be compatible with OECD Guideline for the Testing of Chemicals No 404 "Acute Dermal Irritation/Corrosion (adopted 24 April 2002) and Method B.4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No 440/2008.

INTRODUCTION

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit.

RESULTS

A single 4 -hour, semi-occluded, application of the test item to the intact skin of two rabbits produced well-defined erythema, slight edema, moderate desquamation and crust formation. Both treated skin sites appeared normal at the 14 -day observation.

CONCLUSION

The test item produced a primary irritation index of 4.0 and was considered to be a moderate irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted. 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 below the stated limits for erythema and edema.