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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
The Freund´s Complete Adjuvant Test and the Open Epicutaneous Test. A complementary test procedure for realistic assessment of allergenic potential.
Author:
G. Klecak
Year:
1985
Bibliographic source:
Curr Probl Dermatol 14 pg 152-71

Materials and methods

Principles of method if other than guideline:
The open epicutaneous test represents an animal bioassay conducted with guinea pigs and designated to generate quantitative data. The generation of skin sensitization data includes a 3 step way. In the pretesting phase the primary irritating treshold concentration of the test substance is determined. The induction phase consists of a 3-week period of daily open applications. The final determination wheter sensitization has occured or not takes place in the final challenge phase.
GLP compliance:
no
Type of study:
open epicutaneous test
Justification for non-LLNA method:
A reliable test method (open epicutaneous test) was already performed in 1985 to fulfill the data requirements of this endpoint.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 300-450 g

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, open
Vehicle:
other: not specified
Concentration / amount:
3 phases:
Irritation: 0.025 mL of each test concentration
Induction: 21 x 0.1 mL in the concentrations (if possible) 100, 30, 10, 3, 1 and 0.3 %
Challenge: 0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations (no data)
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: not specified
Concentration / amount:
3 phases:
Irritation: 0.025 mL of each test concentration
Induction: 21 x 0.1 mL in the concentrations (if possible) 100, 30, 10, 3, 1 and 0.3 %
Challenge: 0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations (no data)
No. of animals per dose:
5-7 groups of 6-8 males and females
Details on study design:
RANGE FINDING TESTS: 1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group. A single application of 0.025 mL of each test concentration (e.g. 100, 30,10 and 3%) is simultaneously performed on one of the areas measuring 2cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. The minimal irritating and the maximal nonirritating concentrations are determined by an all-or-none criterion. The minimal irritating concentralion is defined as the lowest one causing skin irritation. The maximal nonirritating concentration is defined as the highest one not causing macroscopic skin reactions in any of the animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21 applications
- Exposure period: For 3 weeks
- Test groups: 5-7 groups of 6-8 animals
- Site: on an area of 8 cm2 on the clipped flank skin
- Frequency of applications: daily
- Duration: 3 weeks
- Concentrations: if possible 100, 30, 10, 3, 1 and 0.3 %

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 21 and 35
- Test groups: Both the test and the control group
- Site: on the contralateral flank
- Concentration: 0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations (no data)
- Evaluation (hr after challenge): 24, 48 and 72 h
Challenge controls:
no data
Positive control substance(s):
not specified

Results and discussion

Positive control results:
no data

In vivo (non-LLNA)

Results
Key result
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

The test substance was found to have no sensitizing effect on the skin.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In the Open Epicutaneous Test the test substance did not induce skin reactions indicating a sensitising potential.
Executive summary:

The skin sensitizing potential of the test item was tested in the open epicutaneous test with guinea pigs. The test was conducted on groups of 6 -8 male and female animals weighting 300 -450 grams. Daily applications were made for 3 weeks to a clipped 8 cm2 area on the flank of each guinea pig. The test sites were not covered and the reactions were read 24 hours after each application. A total of 21 applications of 0.1 mL test material in an unspecified vehicle were made for 21 days. The 10 controls were either left untreated or treated with 0.1 mL of the vehicle for 21 days. At the challenge phase, both the test and control animals were treated at some lower primary non-irritating concentrations. On the basis of these resulst, the test substance was considered to be non sensitising. This result is supported by results of skin sensitization tests on humans, as described in this publication.