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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (OECD 406): not 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:
06 Feb - 16 Mar 2006
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
missing information on animal husbandry, test site preparation and control group treatment; test substance was not tested up to irritating dose > 60% for epicutaneous induction.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
17 July 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Commission Directive (EC) No 96/54 dated 30 July 1996
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Agence française de sécurité sanitaire des produits de santé (Afssaps), France
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was done before LLNA as first-choice method for in-vivo testing was set into force.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre de Production Animale, Olivet, France
- Weight at study initiation: 290 - 391 g
- Diet: guinea pig breeding diet, irradiated
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 53
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.39%
Day(s)/duration:
single injection
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, open
Vehicle:
physiological saline
Concentration / amount:
60%
Day(s)/duration:
48 h
Adequacy of induction:
other: non-irritant dose, but skin pre-treated with 10% SDS; dose not tested >60% in range finding test
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
7.5% and 15%
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Negative control: 3 males and 3 females
Treatment group: 2 males and 9 females
Details on study design:
RANGE FINDING TEST:
The aim of the range finding test was to find out the highest concentrations which cause mild-to-moderate skin irritation after intracutaneous and epicutaneous administration and the highest non-irritant concentration after epicutaneous administration. For the intracutaneous tolerance test 7 concentrations of the test substance ranging 0.39 - 25% (w/v) in physiological saline were injected in 2 males by intradermal route. No necrosis has been observed with the concentration of 0.39% (w/v) and therefore, this concentration was selected for the intradermal induction phase of the main study. For the epicutaneous tolerance test two males were treated with 4 concentrations of the test substance (7.5, 15, 30 and 60% w/v) in physiological saline. Applications to the skin were made under occlusive dressings for 24 hours. The test substance did not cause any irritating effects, therefore the 60% concentration was chosen for epicutaneous induction. Epicutaneous tolerance for the challenge application was tested after induction by intradermal injection with physiological saline solution and by topical application with distilled water and a 13-day rest phase. The challenge phase consists in a single topical application of the test item under occlusive dressing for 24 hours at the following concentrations: diluted at 7.5, 15, 30 and 60% (w/v) in distilled water. 24 hours after removal of the patches, a slight to moderate erythema in two animals was noted on the treated area at 60% (w/v) and in the three animals on the treated area at 30% (w/v). Therefore, 7.5 and 15% were selected for the challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: 0.39% (w/v) test substance in physiological saline
Injection 2: a 1:1 mixture (v/v) FCA/physiological saline
Injection 3: 0.78% (w/v) test substance in a 1:1 mixture (v/v) FCA/physiological saline
Epicutaneous: 60% (w/v) test substance in physiological saline
- Negative control groups: not further specified
- Site: not specified
- Frequency of applications: 7 days
- Duration: Days 0-8
- Concentrations: intradermal 0.39%, epicutaneous 60%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Days of challenge: Day 26
- Exposure period: 24 h
- Test and control groups: 7.5 and 15% (w/v) test substance in distilled water
- Site: not specified
- Concentrations: 7.5%, 15%
- Evaluation: 24 and 48 h after challenge patch removal

OTHER:
Because the test substance (60%) was non-irritating after epicutaneous administration during the preliminary study, a pretreatment of the skin with 0.5 mL 10% sodium lauryl sulphate was carried out 24 h before induction by epicutaneous administration.
Body weight was measured on Day 0 and at 48 h reading time point.
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
alpha-Hexylcinnamaldehyde
Positive control results:
The positive control is a historical background data group from three studies performed between Apr 2005 and Jan 2006. The epicutaneous administration of 12.5, 25 and 50% suspensions of a-Hexylcinnamaldehyde caused positive responses in 18 - 100% of the animals. Thus, reliability criteria for the Guinea Pig Maximisation Test is met.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Challenge: 15% (w/v)
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
skin dryness in 1/6 animals
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Challenge: 15% (w/v)
No. with + reactions:
1
Total no. in group:
11
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Challenge: 15% (w/v)
No. with + reactions:
0
Total no. in group:
6
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Challenge: 15% (w/v)
No. with + reactions:
0
Total no. in group:
11
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Challenge: 7.5% (w/v)
No. with + reactions:
0
Total no. in group:
6
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Challenge: 7.5% (w/v)
No. with + reactions:
0
Total no. in group:
11
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Challenge: 7.5% (w/v)
No. with + reactions:
0
Total no. in group:
6
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Challenge: 7.5% (w/v)
No. with + reactions:
0
Total no. in group:
11
Key result
Group:
positive control
Remarks on result:
other: historical data available

Sensitising potential assessment:

In 1/11 animals of the test group (15% w/v) a slight erythema (grade 1) was noted at 24 h reading. No other macroscopic cutaneous reactions attributable to allergy were recorded during the examination following removal of the occlusive dressing after challenge. No cutaneous intolerance reaction was recorded in animals from the negative control group.

Other Observations:

No mortality was noted during this study. A reduction in body weight gain was noted in one animal of control group. No other abnormalities in the weight gain were noted for remaining animals.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Under the conditions of the guinea pig maximisation test the test substance revealed no sensitising properties.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitising potential of the test substance was investigated in a guinea pig maximisation test (GPMT ) according to OECD Guideline 406 and in compliance with GLP (Key, Richeux, 2006c). A range finding study was performed to determine the appropriate concentration of the test substance in physiological saline following intradermal and epicutaneous administrations. Based on the results of the preliminary study, a 0.39% (w/v) solution of the test substance in physiological saline was selected for the first induction stage (intradermal) on Day 0 and a 60% (w/v) solution of the test substance was selected for the second induction stage (epicutaneous) on Day 7. Since the test substance was non-irritating after epicutaneous induction in the preliminary study, skin was pre-treated with 10% SDS 24 h before epicutaneous induction of main study. 7.5 and 15% solutions of the test substance were selected for the challenge on Day 26. In the main study, 11 animals were used to investigate the skin sensitising potential of the test substance. In addition, 6 animals served as negative control. Regularly conducted reliability checks with positive control α-Hexylcinnamaldehyde confirmed reliability of the test. In 1/10 animals slight erythema was observed 24 h after patch removal at 15 % concentration. No skin reactions at the challenge sites of the remaining test or control group animals were observed 24 and 48 h after challenge patch removal at any test concentration. One animal of control group showed dry skin 24 h after 15 % challenge. Based on the results of this GPMT, the test substance was not regarded as a skin sensitiser under the conditions of the test.

The skin sensitising potential of the test substance was investigated in a second guinea pig maximisation test (GPMT ) according to OECD Guideline 406 and in compliance with GLP (Richeux, 2006d). A range finding study was performed to determine the appropriate concentration of the test substance in physiological saline following intradermal and epicutaneous administrations. Based on the results of the preliminary study, a 3.125% (w/v) solution of the test substance in physiological saline was selected for the first induction stage (intradermal) on Day 0 and a 60% (w/v) solution of the test substance was selected for the second induction stage (epicutaneous) on Day 7. Since the test substance was non-irritating after epicutaneous induction in the range finding study, skin was pre-treated with 10% SDS 24 h before epicutaneous induction of main study. 30 and 60% solutions of the test substance were selected for the challenge on Day 26. In the main study, 10 females were used to investigate the skin sensitising potential of the test substance. In addition, 6 females served as negative control. Regularly conducted reliability checks with positive control α-Hexylcinnamaldehyde confirmed reliability of the test. No skin reactions at the challenge sites of the test or control group animals were observed 24 and 48 h after challenge patch removal at any concentration. Reactions of dry skin and depilation were observed in test and control group animals at 30 and 60%. Based on the results of this GPMT, the test substance was not regarded as a skin sensitiser under the conditions of the test.

The skin sensitising potential of the test substance was investigated in a third guinea pig maximisation test (GPMT ) according to OECD Guideline 406 and in compliance with GLP (Richeux, 2006e). A range finding study was performed to determine the appropriate concentration of the test substance in physiological saline following intradermal and epicutaneous administrations. Based on the results of the preliminary study, a 0.39% (w/v) solution of the test substance in physiological saline was selected for the first induction stage (intradermal) on Day 0 and a 60% (w/v) solution of the test substance was selected for the second induction stage (epicutaneous) on Day 7. The skin was additionally pre-treated with 10% SDS 24 h before epicutaneous induction of main study. 7.5 and 15% solutions of the test substance were selected for the challenge on Day 26. In the main study, 10 females were used to investigate the skin sensitising potential of the test substance. In addition, 6 females served as negative control. Regularly conducted reliability checks with positive control α-Hexylcinnamaldehyde confirmed reliability of the test. No skin reactions at the challenge sites of the test or control group animals were observed 24 and 48 h after challenge patch removal at any concentration. Reactions of dry skin were observed occasionally in test and control group animals at both challenge concentrations. Based on the results of this GPMT, the test substance was not regarded as a skin sensitiser under the conditions of the test.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation of the test substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.