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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:
key study
Study period:
02 Apr - 30 Jul 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
certified by the Federal Office of Public Health, 2000
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was completed in 2001 and was the standard skin sensitisation study at the time.

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): Y-15099
- Physical state: pale yellow liquid
- Analytical purity: 99.6%
- Lot/batch No.: 18161-74
- Expiration date of the lot/batch: 2002-10-23
- Stability under test conditions: stable under storage conditions
- Storage condition of test material: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight. Store under nitrogen. Avoid contact with moisture.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Ibm: GOHI
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Füllinsdorf, Switzerland
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 316 - 396 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz). Music was played during the light period.
- Diet: Pelleted standard Provimi Kliba 3418, batch nos. 33/00 and 90/01, guinea pig breeding / maintance diet, containing Vitamin C (Provimi Kliba AG, CH-4303 Kaiseraugst), ad libitum.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): Automatically controlled light cycle of 12 hours light and 12 hours dark.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (for all induction and challenge treatments)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (for all induction and challenge treatments)
No. of animals per dose:
10 animals for the test group and 5 animals for the control group
Details on study design:
RANGE FINDING TESTS:
The 100% concentration of the test item used for the intradermal application was well-tolerated systemically, causing mild skin irritation during the pretest. Epidermal application of the undiluted substance in the pretest did not cause any skin irritation.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 pairs of intradermal injections (day 1) and 1 epidermal application (day 8) for 48 hours
- Test groups: TS and FCA
- Control group: Peanut oil and FCA
- Site: dorsal skin of the scapular region
- Duration: 48 hours for epidermal induction under occlusive dressing
- Concentrations: 100% for injections as well as for epidermal application

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: Day 22
- Exposure period: 24 hours under occlusive dressing
- Test groups: TS
- Control group: TS
- Site: 3 x 3 cm area of the left flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 hours after removal of the bandage

Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole

Results and discussion

Positive control results:
A reliability check had been performed with 2-mercaptobenzothiazole half a year before in the same laboratory, confirming the sensitivity of the used animal strain.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
None
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
None
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1% in mineral oil
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1% in mineral oil
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Based on the findings in the adjuvant sensitization test (M&K-test) in guinea pigs and in accordance to Commission Directive 96/54/EEC, Y-15099 has to be classified and labelled as an extreme skin sensitizer.
Executive summary:

In order to assess the cutaneous allergenic potential of Y-15099, the Maximization-Test was performed in 15 (10 test and 5 control) female albino guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 96/54/EEC, B.6.

The intradermal induction of sensitization in the test group was performed in the nuchal region with the undiluted test item (100%). The epidermal induction of sensitization was conducted for 48 hours under occlusive conditions with the undiluted test item one week after the intradermal induction and following pre-treatment of the test areas with 10% Sodium-Lauryl-Sulfate (SLS) 24 hours prior to application of the test item. The animals of the control group were treated with 10% SLS only.

Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the undiluted test item under occlusive dressing.

Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

No toxic symptoms were evident in the guinea pigs of the control or test group. No deaths occurred.

Eight (at the 24 -hour reading) and 9 (at the 48 -hour reading) out of 10 test animals showed discrete/patchy to moderate/confluent erythema after the challenge treatment with Y-15099 at 100%. No skin effect was observed in the control group.