Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04-Mar-2003 - 09-Mar-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 guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
French Republic, Prime Minister, Interministerial Group on Chemicals (GIPC)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: white powder
-The pH of the test item at the concentration of 10% in purified water, measured at CIT, was approximately 12.
- Analytical purity: 99.8%
- Lot/batch No.: 3334
- Storage condition of test material: at room temperature, protected from humidity and under nitrogen gas.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age/weight: on the day of treatment, the animals were 2 to 4 months old and had a mean body weight ± standard deviation of 2.6 ± 0.2 kg.
- Food and water: ad libitum
- Acclimation: at least 5 days before the beginning of the study.
ENVIRONMENTAL CONDITIONS
- 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.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Doses of 500 mg of the test item were placed on a dry gauze pad which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animals. The gauze pad was used dry and not moistened with water because the pH of the test item in water is 12. The OECD Guideline No. 404 recommends to use water or another suitable vehicle (if necessary) to moisten the test item and ensure a good contact with the skin. However, as the skin of the rabbit may be sensitive to many vehicles, it was chosen not to use a moistening agent rather than a non well-tolerated vehicle (such as corn oil). Furthermore, this condition of application reflects more accurately the condition of a possible accidental exposure.
Duration of treatment / exposure:
As possible irritant effects were anticipated, the test item was evaluated on a single animal in the first instance. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank.
Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals.
Observation period:
The skin was examined approximately 1, 24, 48 and 72 hour(s) after removal of the dressing.
Since there was persistent irritation reactions at 72 hours, the observation period was extended. In the absence of complete reversibility of skin reactions on day 15, the study was ended.
Number of animals:
3

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
3-minute exposure
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 h
Score:
1
Max. score:
1
Remarks on result:
other: dryness of the skin on day 1 and 2
Irritation parameter:
edema score
Remarks:
3-minute exposure
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Remarks on result:
other: dryness of the skin on day 1 and 2
Irritation parameter:
erythema score
Remarks:
4 -hour exposure
Basis:
animal #1
Time point:
other: 24, 48, 72, 96 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
4 -hour exposure
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Remarks:
4 -hour exposure
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
4 -hour exposure
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Remarks:
4 -hour exposure
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 h
Score:
2
Max. score:
2
Remarks on result:
other: Residual test item
Irritation parameter:
edema score
Remarks:
4 -hour exposure
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 h
Score:
1
Max. score:
1
Remarks on result:
other: Residual test item

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions, the test item CaTG is irritant when applied topically to rabbits.
Executive summary:

After a 3-minute exposure (one animal), a very slight erythema (grade 1) was noted from day 1 up to day 4. Dryness of the skin was recorded on day 2 and 3 then between day 5 and day 10.

After a 4-hour exposure (three animals), a very slight or well-defined erythema (grade 1 or 2), together with a very slight oedema (grade 1) between day 2 and day 5, was noted in 1 of 3 animals from day 2 up to day 7. Dryness of the skin was recorded in the same animal from day 6 up to the end of the observation period (day 15).

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 2.0 for erythema and 0.0, 0.0 and 1.0 for oedema.