Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-08-28 to 1990-09-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD guideline study with detailed descriptions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 12.5.1981
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Weight at study initiation: The animals were weighted immediately before application of the test substance.
- Housing: The rabbits were individually housed in stainless steel cages with flat rod bases or plastic cages with performated bases, under standardized conventional conditions.
- Nutrition: Standard diet "Ssniff K 4", approx. 100-120 g per animal/day, once per day in the morning.
- Water: tap wter, ad libitum.
- Other: healthy anilmals. The health of the animals was routinely examined for the main specific pathogens by the breeder. No vaccinations or treatment with antibiotics were performed prior to receipt of the animals or during the acclimatization phase or study period. If females were used they were nulliparous and nonpregnant.
- State of health: After the acclimatization phase, the animals were examined one day prior to the start of the study to establish that they were biologically normal. Only animals not exhibiting any alterations to skin or eyes were used.
- Acclimatization: at least 14 days
- Animal housing conditions: All the animals in this study were kept in one room. For capacity reasons rabbits treated with other test substances were also housed in the same room. Adequate separation, slear cage and individual marks, as well as appropriate organization of working procedures ensured that the test animals were not mixed up.
- Randomization: Each rabbit was randomly assigned to the respective treatment groups. Randomization was performed by means of a random number generator with varying starting conditions, using an Apple 2e, Fachbereich Toxikologie.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C
- Relative Humidity: ca. 50 %
- Air changes: ca. 10 times per hour
- Photoperiod: 12 hours artificial illumination from 6 to 18 hrs CET

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Contralateral skin area not treated with test substance served as control.
Amount / concentration applied:
500 µL
Duration of treatment / exposure:
4 hours
Observation period:
24, 48 and 72 hours after application
Number of animals:
three rabbits
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap: Test substance was applied to a hypoallergenic Hansamed-patch. A further patch was moistured with water.
- Site: The patches prepared were placed on the opposite dorso-lateral areas of the trunk of each animal and were loosley held in place with a semiocclusive dressing for the duration of the exposure period. Thus, access by the animal to the patch and resultant ingestion/inhalation of the test substance was prevented.

REMOVAL OF TEST SUBSTANCE
- Washing: The exposed skin areas were carefully washed with water without altering the existing response, or the integrity of the epidermis.
- Time after start of exposure: After an exposure period of four hours the dressing and patches were removed.

CLINICAL OBSERVATION AND SCORING SYSTEM:
Dermal irritation was scored and recorded after termination of exposure at the times 1h, 24 h, 48 h, 72, 7 d and 14 d. The degree of erythema/eschar formation and oedema formation was recorded as specified by Draize, and any serious lesions or toxic effects other than dermal irritation were also recorded.

EVALUATION OF RESULTS:
For each animal the Draize scores were recorded approx. 24, 48, and 72 hours after application were added. The total of these tree values was divided by three to give the irritation index. This index was separately calculated for erythrema/eschar formation and for oedema formation. Where three animals were used, interpretation was based on the individual indices obtained from the two most sensitive animals. Where more than three animals were used, the mean irritation index was calculated averaging the total scores of all rabbits tested. If delayed reactions occured, or where no irritation indices could be calculted (e.g. due to coloration by the test substance) other interpretation criteria were applied.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results indicate that the test substance does not have a significant irritation potential on skin. Thus, the test substance can be regarded as non irritating to the skin.
Executive summary:

The irritant/corrosive potential of the test substance was studied on the skin of the rabbit in accordance with OECD guideline 404. Whilst considering OECD Interpretation Guides results were interpreted in conjunction with the nature, intensity and reversibility of responses observed. The irritation was scored according to Draize after 1 h, 24 h, 48 h, 72 h and 7 d. All three animals showed irritation indices of 0 for both erythema and edema formation. The results indicate that the test substance does not have a significant irritation potential on skin. Thus, the test substance can be regarded as non irritating to the skin.