Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 Feb - 02 Apr 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
Type of study:
Buehler test
Justification for non-LLNA method:
The test was done before LLNA as first-choice method for in-vivo testing was set into force.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 8 - 12 weeks
- Weight at study initiation: 338 - 426 g
- Housing: singly or in pairs in solid-floor polypropylene cages, bedding woodflakes
- Diet: Guinea Pig FD1 Diet (Special Services Limited, Witham, UK) ad libitum
- Water: mains tap water, ad libitum, analysis was performed
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
Day 0 - 14
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol/diethylphtalate 1:1
Concentration / amount:
50% (v/v) and 100%
Day(s)/duration:
Day 28
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 (controls), 20 (test groups)
Details on study design:
RANGE FINDING TESTS:
The concentrations of test material to be used at each stage of the main study were determined by sighting tests in which groups of guinea pigs were treated with various concentrations of test material. 4 animals were used: 2 animals for the topical induction and 2 for the topical challenge.
For the topical induction 2 animals were treated with 4 concentrations of the test item (10%, 25%, 50% and 100%). Applications were made to the clipped flanks under occlusive conditions for 6 h. The highest concentration of the test item producing only minimal dermal irritation was selected for the topical induction stage of the main study.
For the topical challenge 2 animals were treated with 2 concentrations of the test item (50% and 100%). Previously, the animals had been treated identically to the control animals of the main study an Days 0, 7 and 14. Applications were made to the clipped flanks under occlusive conditions for 6 h. The highest concentration of the test item which produced no evidence of dermal irritation, and 50% of the maximum non-irritant concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: undiluted test substance
- Control group: a blank patch was applied
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14
- Concentrations: 100%, under occlusive conditions

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 28
- Exposure period: 6 h
- Test groups: test substance and test substance in ethanol/diethylphthalate 1:1
- Control group: test substance and test substance in ethanol/diethylphthalate 1:1
- Site: right flank (100% test substance) and a separate skin site on the right flank (50% test substance)
- Concentrations: 50% and 100%
- Evaluation (hr after challenge): 24 and 48 h after patch removal
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole, topical induction and challenge: 50% in acetone/Peg 400 (70:30)

Results and discussion

Positive control results:
A reliability test with 2-mercaptobenzothiazole (50% in acetone/Peg 400 (70:30)) was performed not more than 6 months previously (Feb 1999) using the same animal supplier. The incidence of sensitisation was 55% (11 out of 20 animals).

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; Challenge: 50% and 100%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 100%; challenge: 50% and 100%
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge: 50% and 100%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 100%; challenge: 50% and 100%
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
other: not specified
Hours after challenge:
24
Group:
positive control
Dose level:
50% in induction and challenge
No. with + reactions:
11
Total no. in group:
20

Any other information on results incl. tables

Bodyweight gains of animals in the test group, between Day 0 and Day 30, were comparable to those observed in the control group animals over the same period.

No skin reactions were noted at the topical induction sites of test or control group animals at the 1, 8 or 15-day observations.

No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-hour observations.

Applicant's summary and conclusion

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 Buehler test the test substance revealed no sensitising properties.