Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Since December 12,1988 to January 5, 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to internationally accepted testing guidelines and performed according to the GLP. Further details in the endpoint summary.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG
- Age at study initiation: males : 7 weeks females: 8 weeks
- Weight at study initiation: males: 416 - 461 g females: 409 - 459 g
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding
- Diet : Pelleted standard Kliba 342, Batch 47188 guinea pig breeding/ maintenance diet, ad libitum.
- Water: tap water , ad libitum.
- Acclimation period: One week under test conditions after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 3°C
- Humidity (%):40-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light/12 hours dark, music/tight period.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
0.1, 0.3, 0.5, 1, 3 and 5 % of the test article in petrolatum
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
0.1, 0.3, 0.5, 1, 3 and 5 % of the test article in petrolatum
No. of animals per dose:
5 x sex x dose (control)
10 x sex x dose
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE: injection
- No. of exposures: 6
- Test groups: 10 males and 10 females
- Control group: 5 males and 5 females
- Site: An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped free of hair. Three pairs of intradermal injections (0.1 ml/ site) were made at the border of a 4 x 6 cm area in the clipped region
- Concentrations: 0.1 , 0.3, 1, 3, and 5% test item in petrolatum


INDUCTION EXPOSURE: One week after the injections
- No. of exposures: 1
- Exposure period: 48 h
- Test groups: 10 males and 10 females
- Control group: 5 males and 5 females
- Site: (6 x 8 cm)
- Type of coverage: filter paper was saturated with the test article (5 % in petrolatum) and placed over the injection sites of the test animals. The patch was covered by aluminum foil and firmly secured by an elastic plaster wound round the trunk of the animal and secured with impervious adhesive tape.
- Duration: 24 hours
- Concentrations: 5% in petrolatum

B. CHALLENGE EXPOSURE: The test and control guinea-pigs were challenged two weeks after the epidermal induction application.
- No. of exposures:2
- Exposure period: approximately 24 hours later
- Test groups:10 males and 10 females
- Control group:5 males and 5 females
- Site:hair was clipped and shaved from a 5 x 5 cm area on the left and right flank of each guinea-pig.
- Type of coverage: Two patches (2 x 2 cm) of filter paper
- Concentrations:3 % in petrolatum oil
- Evaluation : 0, 24, 48 hrs

OTHER OBSERVATION:
Mortality/Viability: Once daily
Body Weights: At acclimatization start, start of application and end of test.
Symptoms (local systemic): daily
Necropsy: no
All animals were killed at the end of the test period with an intraperitoneal injection of T61 (Hoechst AG) and discarded.

Study design: in vivo (LLNA)

Statistics:
Mean values with standard deviations.
Fisher-Test (The Exact Fisher Test for comparison of the basic probability of two binominal distributions. L. Sachs, Statistische Auswertungsmethoden, GeorgThieme Verlag, Stuttgart 1971).
For calculation of p-values the 24 hour readings of the animals from the control and test article-treated groups were used.
DATA COMPILATION
The following data were recorded on data sheets and transcribed for compilation and analysis:
symptoms (local/systemic), body weights (on-line), skin reactions.

Results and discussion

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No systemic symptoms were observed.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No systemic symptoms were observed..

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test article is not a sensitizer.
Executive summary:

The purpose of this skin sensitization study was to assess the allergenic potential of the substance when administered to the skin of male and female albino guinea pigs.

For this purpose the Maximization-Test of B. Magnusson and A.M. Kligman (1969) was used. Ten animals (5 males, 5 females) were treated with the vehicle alone (petrolatum oil) and 20 animals (10 males, 10 females) were treated with the test article.

The study was conducted between December 5th and January 5th, 1989 at the RCC laboratories in 4452 Itingen/Switzerland.

If necessary prior to the first reading of the reactions, the skin was flushed with the vehicle or other solvents to clean the application site from staining produced by the test article, so that the reactions (erythema) were clearly visible at that time. Due to the unequivocal findings observed after the first challenge, no second challenge was performed.