Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2001-01-19 to 2001-02-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

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

Test material

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival (UK) Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.0 to 3.5kg
- Fasting period before study: no
- Housing: individually in suspended metal cages.
- Diet: ad libitum
- Water : ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From: To:

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: each animal served as its own control
Amount / concentration applied:
TEST MATERIAL
- Amount applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
4 hour exposure period
Observation period:
60 min, 24, 48, 72 hrs and 7d, 14d after removal the patch.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: 2.5x2.5 cm
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual material was removed by gentle swabbing of the skin with cotton wool soaked in 74% Industrial Methylated Spirits
- Time after start of exposure: 4 hours after the start of exposure.

SCORING SYSTEM: according to OECD guideline 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
other: Small areas of dermal necrosis where the surgical adhesive tape was in contact with the skin were noted after patch removal. At the end of the 14-day observation period, these small areas showed reduced fur growth
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
- 1 hour after the removal of the dressing, well defined erythema and oedema (score of 2) were noted in animal n°1. Small areas of green coloured dermal necrosis where the surgical adhesive tape was in contact with the skin was also noted. Animals n°2 and 3 showed very slight erythema (score 1) and very slight (score 1) or no oedema.
- Well defined erythema and oedema (score of 2) was noted at the 24, 48 and 72-hour examinations in animal n°1. In addition, small hardened dark brown coloured scabs developed where the dermal necrosis were previously noted. Well defined or slight erythema (score 2 or 1) together with slight oedema (score 1) were observed at the 24, 48 and 72 hour examinations in animals n°2 and 3.
- The treated skin sites of animals n°2 and 3 appeared normal at the 7-day obervation. In animal n°1, desquamation and further reduced fur growth were observed where the scabs were previously noted at the 14-day observation.

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The authors of the study concluded that the test material was a moderate irritant to the rabbit skin as they do not consider the dermal necrosis noted in animal n°1 as an effect of the test material.
However, considering the very alkaline pH of the test material (pH = 12), the registrant considers that it cannot be definitely ruled out that dermal necrosis are not attributed to the test material.
Therefore, the registrant classifies the test material as corrosive category 1 C according to the criteria laid down in CLP (Reg 1272/2008/EC).
Executive summary:

The potential of the test material to induce skin irritation was assessed in 3 rabbits according to OECD guideline 404 in compliance with Good laboratory Practices.

A single dose of 0.5 ml of the test material was applied to the skin of the rabbits under a semi-occlusive dressing for a 4-hour exposure period. Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing and then on days 7 and 14,in order to observe their reversibility. The mean values of the scores for erythema and oedema were calculated for each animal.

The mean scores over 24, 48 and 72 hours for individual animals were 2.0, 2.0, and 1.3 for erythema and 2.0, 1.0, and 0.7 for oedema.

One hour after the removal of the dressing, well defined erythema and oedema (score of 2) were noted in animal n°1. Small areas of green coloured dermal necrosis where the surgical adhesive tape was in contact with the skin was also noted. Animals n°2 and 3 showed very slight erythema (score 1) and very slight (score 1) or no oedema. At the 24, 48 and 72 -hour examinations, well defined erythema and oedema (score of 2) were noted in animal n°1. In addition, small hardened dark brown coloured scabs developed where the dermal necrosis were previously noted. Well defined or slight erythema (score 2 or 1) together with slight oedema (score 1) were observed in animals the two other animals.

Skin reactions were fully reversible within 7 days in animals n°2 and 3. In animal n°1, desquamation and further reduced fur growth were observed where the scabs were previously noted at the 14-day observation.

The authors of the study concluded that the test material was a moderate irritant to the rabbit skin as they do not consider the dermal necrosis noted in animal n°1 as an effect of the test material.

However, considering the very alkaline pH of the test material (pH = 12), the registrant considers that it cannot be definitely ruled out that dermal necrosis are not attributed to the test material. Therefore, the registrant classifies the test material as corrosive category 1 C according to the criteria laid down in CLP (Reg 1272/2008/EC).