Registration Dossier

Administrative data

Description of key information

Skin sensitisation (OECD 406): not skin sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 6 - March 16, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test performed before adoption of LLNA method.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Mistubishi Kagaku-Foods Corporation

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

FORM AS APPLIED IN THE TEST (if different from that of starting material): Solution

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre de Production Animale
- Weight at study initiation: 317-441 g
- Diet (e.g. ad libitum): Guinea pig diet, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-35
- IN-LIFE DATES: From: February 6, 2006 To: March 16, 2006
Route:
intradermal
Vehicle:
olive oil
Concentration / amount:
1.56%
Day(s)/duration:
2 injections
Route:
intradermal
Vehicle:
olive oil
Concentration / amount:
3.125% test substance and 50% Freund's Complete Adjuvant in olive oil.
Day(s)/duration:
2 injections
Route:
intradermal
Vehicle:
other: Freund's Complete Adjuvant in saline solution
Concentration / amount:
50% FCA in saline solution
Day(s)/duration:
2 injections
Route:
epicutaneous, open
Vehicle:
olive oil
Concentration / amount:
60%, pre-treatment with sodium lauryl sulfate
Day(s)/duration:
1 dose
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
30% and 60%
Day(s)/duration:
24 hrs
No. of animals per dose:
8 females, 3 males in test group
3 females, 2 males in control group
Details on study design:
RANGE FINDING TESTS: For the pre-maximum non-irritant concentration test, 2 females were injected with 0.78-25% test substance in olive oil. They were then exposed to 7.5-60% test substance in paraffin oil. No necrosis was noted after the intradermal injection. No skin reaction was noted after the topical exposure.

For the maximum non-irritant concentration test, 3 males for induced by intradermal injection with the test substance in olive oil, and then topically with the test substance in paraffin oil. After 16 days, a challenge exposure was done by topical exposure under occlusive dressing at 7.5%-60% test sustance in paraffin oil. No skin reaction was observed. Therefore, 60% was chosen as the maximum dose for the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Day 0 and Day 7
- Test groups: 1
- Control group: Yes
- Frequency of applications: One intradermal injection on Day 0, and one topical application on Day 7.
- Concentrations: 1.56% test substance intradermally, 60% test substance topically with pre-treatment with sodium laurate

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 16 days after last induction
- Exposure period: 1 day
- Test groups: 1
- Control group: Yes
- Concentrations: 30 and 60% test substance.
- Evaluation (hr after challenge): 24 and 48 hrs.
Challenge controls:
Yes
Positive control substance(s):
yes
Remarks:
Historical controls
Positive control results:
50-100% of animals were sensitized in the historical positive controls.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
11
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
11
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
60%
No. with + reactions:
0
Total no. in group:
11
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
60%
No. with + reactions:
0
Total no. in group:
11
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Key result
Group:
positive control
Remarks on result:
other: No details on results
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
The test substance is not sensitising to skin.
Executive summary:

11 guinea pigs were tested for the skin sensitization of the test substance in the GPMT. 5 animals were used as controls. The test animals were intradermally injected with 1.56% test substance, and a week later topically exposed to 60% test substance. After 16 days, a challenge exposure was done topically with 30 and 60% test substance. No reaction was observed after the challenge exposure. The test substance is not sensitizing to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The test substance was tested for its skin sensitising potential in a Guinea pig maximisation test according to OECD guideline 406 and in compliance with GLP (Richeux, 2006). 11 guinea pigs of both sexes were used for the test group; 5 animals were used as controls. Based on a range-finding test and for purpose of induction, the test animals were intradermally injected with 1.56% test substance in olive oil, and a week later topically exposed to 60% test substance after pre-treatment of the skin with SDS. After 16 days, a challenge exposure was done in test and control groups topically with 30 and 60% test substance under occlusive conditions for 24 h. No skin reaction was observed 24 or 48 hrs after the challenge exposure. Therefore, the test substance is not sensitising to skin under the conditions of this test.

 

Further, the skin sensitising potential was investigated in a Guinea pig maximisation test according to OECD guideline 406 and in compliance with GLP (Prinsen, 1997). For induction, 5 guinea pigs of each sex were exposed to 1% test substance in water intradermally, and a week later topically exposed to 30% test substance in water under occlusive conditions after pre-treatment of the skin with SDS. 3 guinea pigs of each sex were used as controls. Two weeks after the final induction exposure, the animals in both the test and control groups were exposed to 10% and 30% of the test substance topically under occlusive conditions for challenge. No skin reaction indicative of sensitization was seen 24 and 48 h after the challenge exposure. Therefore, the test substance is not sensitising to skin under the conditions of this test.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.