Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 22 October 1997 and 04 November 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to OECD/EU guidelines under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Identity: 97-204-01
Commercial name: Montaverdi
Appearance: Clear colourless liquid
Storage conditions: Room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain, obtained from Charles River UK Ltd., Margate, Kent, England.
They were in the weight range of 2. 6 to 3.6 kg and approximately 11 to 16 weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment.
The rabbits were selected without conscious bias for the study. They were housed individually in stainless steel cages with perforated floors in Building R14 Room 5.
A standard laboratory diet STANRAB (P) SQC Rabbit Diet and drinking water were provided ad libitum.
The batch of diet used for the study was analysed for nutrients, contaminants and micro-organisms.
Results of routine physical and chemical examination of drinking water as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd as quarterly summaries.
Animal room temperature was maintained at 13 to 25. 5 °C and relative humidity at 25 - 73%. These environmental parameters were recorded daily. Air exchange was maintained at approximately 19 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.
Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This number was unique within the Huntingdon Life Sciences Acute Toxicology Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study schedule number, animal number and initials of the Study Director and Home Office licensee.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5.ml amount of the test substance
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TREATMENT PROCEDURE
Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
A 0.5.ml amount of the test substance was applied under a 25 mm by 25 mm gauze pad, to one intact skin site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.
At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (37°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal: 2446 Female
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: score 1 at end of study period
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal: 2447 Female
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal: 2448 Female
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: score 1 at end of study period
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal: 2446 Female
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal: 2447 Female
Time point:
other: 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal 2448 Female
Time point:
other: 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Well-defined erythema with slight oedema was seen in all animals. Desquamation of the stratum corneum (characterised by dryness/sloughing) was seen in one rabbit on Days 8 and 9. The dermal reactions gradually ameliorated and had resolved in one rabbit by Day 10. However very slight erythema persisted in the remaining two rabbits at study termination on Day 14.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Table 1                      Dermal reactions

 

Rabbit no. & sex

E = Erythema

O = Oedema

Day

1*

2

3

4

5

6

7

8

9

10

11

12

13

14

2446 Female

E

1

2

2

2

2

2

2

2a

1a

1

1

1

1

1

O

0

2

2

1

2

2

2

2

1

0

0

0

0

0

2447 Female

E

1

1

2

2

2

2

2

2

1

0

 

 

 

 

O

1

1

2

1

2

2

2

2

0

0

 

 

 

 

2448 Female

E

1

1

2

2

2

2

2

2

2

2

2

2

2

1

O

0

1

2

1

2

2

2

1

1

1

1

1

1

0

 

*          Approximately 60 minutes after removal of the dressing

a         Desquamation of the stratum corneum (Characterised by dryness and sloughing)

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single semi-occlusive application of Montaverdi to intact rabbit skin for four hours elicited well-defined dermal irritation. Slight dermal reactions were noted in two animals at the end of the 14 day observation period, however these were only minimal in nature and not considered sufficient to classify the substance as category 2 skin irritant or R38.
Executive summary:

A study was performed to assess the skin irritation potential of Montaverdi to the rabbit. The method followed was that described in:

EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (skin irritation) and OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion". Adopted: 17 July 1992. Three rabbits were each administered a single dermal dose of 0. 5 ml of the test substance and observed for up to 14 days. A single semi-occlusive application of Montaverdi to intact rabbit skin for four hours elicited persistent welldefined dermal irritation. Reactions had resolved in one animal by Day 10 but slight erythema was noted in the remaining two rabbits at study termination on Day 14. The effects seen in 2 of the animals for the 14 day observation period were only minimal in nature and therefore classification as a category 2 irritant is not warranted.