Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline conform study

Data source

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

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK, Margate, Kent, England.
- Age and weight at study initiation: Animals used within the study were at least 6 weeks old and body weights were less than 3.5 kg.
- Housing: Individually housed in labelled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netheriands).
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charies River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BMI, Helmond, the Netheriands) was provided once a week.
- Water (e.g. ad libitum): Free access to tap-water. Certificates of quarteriy analysis were examined and retained in the NOTOX archives.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES:
Start: 25 January 2000
End : 28 January 2000

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: ethanol
Controls:
no
Amount / concentration applied:
0,5 g in 1 ml
Duration of treatment / exposure:
4h
Observation period:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.
Number of animals:
3 of one sex
Details on study design:
exposing an area of approximately 150 square centimeters (10x15 cm2)
A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
The test substance was moistened with 1 ml of the vehicle and applied to the skin of one flank, using a metalline patch* of 2x3 cm. The patch was mounted on Micropore tape', which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water and vehicle.


SCORING SYSTEM:

Erythema and eschar formation.

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) * 4

. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

Oedema formation:

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: all time points
Score:
0
Max. score:
4
Remarks on result:
other: red staining of the skin by test substance itselfs (red pigment)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: all time points
Score:
0
Max. score:
4
Irritant / corrosive response data:
No skin irritation was observed by 4 hours exposure to TKP 50048. Due to red staining of the skin by the test substance, erythema could not be scored in all animals after 1 and 24 hours. There was no evidence of a corrosive effect on the skin.
Other effects:
Light red or red staining of the treated skin by the test substance was observed during the study period. No symptoms of systemic toxicity were obsen/ed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Since no oedema was observed and since erythema grade 0 was scored after 48 and 72 hours, the substance is considered to be not irritating and not corrosive.
Executive summary:

Three rabbits were exposed to 0.5 gram of the test substance, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure. No skin irritation was observed by 4 hours exposure to TKP 50048. Due to red staining of the skin by the test substance, erythema could not be scored in all animals after 1 and 24 hours. Since no oedema was observed and since erythema grade 0 was scored after 48 and 72 hours, severe irritation is not to be expected.