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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:
21 Feb - 25 Mar 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
17 July 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
according to
Guideline:
other: Japan MAFF Test Guidelines for Agricultural Chemicals (Notification No. 12-Nousan-8147)
Version / remarks:
amended 10 Dec 2002
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted prior to the current requirement in Regulation (EC) 1907/2006 to perfrom an LLNA study (OECD 429) as the preferred in vivo skin sensitisation study.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, L'Arbresle, France
- Age at study initiation: 5 - 6 weeks
- Weight at study initiation: 369.6 ± 6.6 g (controls), 379 ± 4.8 g (test group)
- Housing: two or five animals in a cage of standard size on dust-free white wood shavings
- Diet: FD1 MOD (P) SQC SDS/DIETEX (SDS Special Diets Services, Witham, UK), ad libitum
- Water: drinking water enriched with 0.02% vitamin C, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 45 - 65
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% (w/v) in water
Concentration / amount:
1%
Day(s)/duration:
single injection
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (0.5 g test substance moistened with 0.5 mL 1% carboxymethylcellulose)
Day(s)/duration:
48 h
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (0.5 g test substance moistened with 0.5 mL 1% carboxymethylcellulose)
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Range-finding study:
4

Main study:
5 (controls), 10 (test group)
Details on study design:
RANGE FINDING TESTS:
A range finding study was performed to determine the appropriate dose level of the test substance following intradermal and epicutaneous administrations. According to the results of a previous study, the maximum concentration for proposing homogeneous injectable dosing formulation of the test substance was 1% (w/v) in 1% (w/v) carboxymethylcellulose (CMC). For the selection of the topical application test substance concentrations of 25% (w/v) in 1% (w/v) carboxymethylcellulose and 100% (0.5 g test substance moistened with 0.5 mL of 1% (w/v) CMC ) were investigated. No skin lesions were observed up to and including 100% test substance concentration following topical 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:
Injection 1: a 1:1 mixture FCA/isotonic sodium chloride solution
Injection 2: 1% (w/v) test substance in 1% (w/v) CMC
Injection 3: equal amounts of 1% (w/v) test substance and FCA in isotonic sodium chloride solution
Epicutaneous: undiluted test substance (skin pre-treated with 10% SDS in vaseline)
- Control group:
Injection 1: a 1:1 mixture FCA/water
Injection 2: 1% (w/v) CMC
Injection 3: equal amounts of 1% (w/v) CMC and FCA in isotonic sodium chloride solution
Epicutaneous: 1% (w/v) CMC
- Site: retro-scapular region of the vertebral column
- Frequency of applications: on Day 1 and 9
- Duration: Days 1-9
- Concentrations: intradermal 1%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 23
- Exposure period: 24 h
- Test groups: undiluted test substance
- Control group: undiluted test substance
- Site: right lateral abdominal region
- Concentrations: 100% (0.5 g test substance moistened with 0.5 mL 1% carboxymethylcellulose)
- 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:
1-chloro-2,4-dinitrobenzene, Induction: intradermal and epicutaneous 1% in alcoholic solution, Challenge: 1% in alcoholic solution

Results and discussion

Positive control results:
The positive control substance induced positive reactions (scores 2 and 3) in 5/5 animals (100%).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction:1%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction:1%; challenge: 1%
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 1%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction:1%; challenge: 1%
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Behaviour of animals treated with test substance was normal and not different from that of the control group.

 

Mean body weight gain of animals treated with test substance was comparable to the weight gain of the control group.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the guinea pig maximisation test the test substance revealed no sensitising properties.