Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2nd November to 7th November 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The material was valuated in rabbits according to OECD (No. 404, 24th April 2002) and EC (2004/73/EEC, B.4, 29th April 2004) guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The test item was applied on the posterior left flank for animal Nos. 34 and 36 (application for 4 hours) instead of the posterior right flank.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The test item was applied on the posterior left flank for animal Nos. 34 and 36 (application for 4 hours) instead of the posterior right flank.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Beige powder

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Sex, species, strain: male New Zealand White rabbits.
Reason for this choice: species generally accepted by regulatory authorities for this type of study.
Breeder: CEGAV, Saint Mars d'Egrenne, France.
Number: three animals were used, as recommended by the international guidelines.
Age/weight: on the day of treatment, the animals were 2 to 4 months old and had a mean body weight ± standard deviation of 2.5 ± 0.1 kg.
Acclimation: at least 5 days before the beginning of the study.
Identification: individual metal ear tag.

The conditions in the animal room were set as follows:
• temperature: 18 ± 3°C
• relative humidity: 30 to 70%
• light/dark cycle: 12 h/12 h
• ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these
daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular
intervals.
The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
Each cage was equipped with a food container and a water bottle.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
500mg
Duration of treatment / exposure:
The duration of exposure was 3 minutes, 1 hour and 4 hours.
Observation period:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.
Since there was persistent irritation reactions at 72 hours, the observation period was extended up to their complete reversibility (day 5).
Number of animals:
3
Details on study design:
As possible irritant effects were anticipated, the test item was first evaluated on a single animal (No. 34). The duration of exposure was 3 minutes, 1 hour and 4 hours.
Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals (Nos. 36 and 37).
Doses of 500 mg of the test item in its original form were placed on a dry gauze pad, which was then applied to the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) and the posterior right or left flank (application for 4 hours) of the animals.
The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.
The untreated skin served as control.
After removal of the dressing, any residual test item was wiped off by means of a moistened cotton pad.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 3 minutes
Score:
0
Max. score:
0
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 3 minutes
Score:
0
Max. score:
0
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hour
Score:
1
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 hour
Score:
0
Max. score:
0
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 4 houor
Score:
0
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4 hour
Score:
0
Max. score:
1
Reversibility:
no data

Any other information on results incl. tables

After a 3-minute exposure (one animal):

No cutaneous reactions were observed.

After a 1-hour exposure (one animal): A very slight erythema (grade 1) was noted from day 2 up to day 4.

After a 4-hour exposure (three animals): A very slight erythema (grade 1) was observed in 2/3 animals on day 1 only. No other cutaneous reactions were recorded.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the test item is slightly irritant when applied topically to rabbits. However according to the classification criteria
laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative
provisions relating to the classification, packaging and labeling of dangerous substances, the test item should not be classified as irritating to the
skin.
Executive summary:

Under the experimental conditions, the test item is slightly irritant when applied topically to rabbits. However according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labeling of dangerous substances, the test item should not be classified as irritating to the skin.