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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:
Start: 1999-12-13 End: 2000-01-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
In vivo test performed in 1999-2000.

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(2-{2,4-dihydroxy-5-[2-(4-hydroxyphenyl)propan-2-yl]phenyl}propan-2-yl)phenyl 6-(-lambda5-diazynylidene)-5-oxo-5,6-dihydronaphthalene-1-sulfonate
Molecular formula:
C34H30N2O7S
IUPAC Name:
4-(2-{2,4-dihydroxy-5-[2-(4-hydroxyphenyl)propan-2-yl]phenyl}propan-2-yl)phenyl 6-(-lambda5-diazynylidene)-5-oxo-5,6-dihydronaphthalene-1-sulfonate
Constituent 2
Chemical structure
Reference substance name:
4-[2-(2,4-dihydroxy-5-{2-[4-({[6-(-lambda5-diazynylidene)-5-oxo-5,6-dihydronaphthalen-1-yl]sulfonyl}oxy)phenyl]propan-2-yl}phenyl)propan-2-yl]phenyl 6-(-lambda5-diazynylidene)-5-oxo-5,6-dihydronaphthalene-1-sulfonate
Molecular formula:
C44H34N4O10S2
IUPAC Name:
4-[2-(2,4-dihydroxy-5-{2-[4-({[6-(-lambda5-diazynylidene)-5-oxo-5,6-dihydronaphthalen-1-yl]sulfonyl}oxy)phenyl]propan-2-yl}phenyl)propan-2-yl]phenyl 6-(-lambda5-diazynylidene)-5-oxo-5,6-dihydronaphthalene-1-sulfonate
Test material form:
solid
Details on test material:
Batch PW-9F-29

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 5 weeks
- Weight at study initiation:
- control animals: 359 - 393 gram
- test animals: 334 - 412 gram
- Housing: group housing of 5 animals per labelled metalcage with wire-mesh Íloors
- Diet: ad libitum, standard guinea pig diet, including ascorbic acid (1000 mg/kg); (Charles River Breeding and Maintenance Diet Íor Guinea Pigs, Altromin, Lage, Germany).
- Water: ad libitum, tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
polyethylene glycol
Concentration / amount:
10 %w/w
Day(s)/duration:
Day 1
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
50 %w/w
Day(s)/duration:
48h
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
50 %w/w
Day(s)/duration:
24h
No. of animals per dose:
treatment: 10
control: 5
Details on study design:
RANGE FINDING TESTS:
Based on the results of the preliminary irritation study, the test substance concentrations selected for the main study were a 10% concentration for the intradermal induction and a 50% concentration for the epidermal induction exposure.
No signs of irritation were observed to the highest test substance concentration epidermally tested. Therefore, the test site of all animals was treated with 10% SDS approximately 24 hours before the epidermal induction in the main study, to provoke a mild inflammatory reaction.
A 50% test substance concentration was selected for the challenge phase.
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamic aldehyde

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% w/w
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 %w/w
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 % w/w
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 % w/w
No. with + reactions:
0
Total no. in group:
5
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10 %w/w
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Not concurrent test
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10 % w/w
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Not cioncurrent test

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
There was no evidence that the test substance had caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in the challenge phase. This result indicates a sensitization rate of 0 per cent.
Executive summary:

Test substance concentrations selected for the main study were based on the results of a preliminary study. ln the main study, ten experimental animals were intradermally injected with a 10% concentration and epidermally exposed to a 50% concentration. Five control animals were similarly treated, but with vehicle alone (polyethylene glycol). Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all anímals were challenged with a 50% test substance concentration and the vehicle.

There was no evidence that the test substance had caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in the challenge phase. This result indicates a sensitization rate of 0 per cent.