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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The non-GLP study was performed equivalent to an appropriate OECD guideline. 0.5% (a.i.) was used for induction although this concentration did not cause irritation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no positive controls, limited information on test animals, concentration used for epicutaneous induction did not induce irritation
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed in 1993 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods".

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: COB.LABO.LAP., Yffiniac, France
- Weight at study initiation: 301-412 g
- Housing: animals were housed individually in polypropylene cages (310x465x190)
- Diet: complete pelleted diet UAR 106 (Epinay sur Orge, France), ad libitum
- Acclimation period: at least 5 days

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: distilled water
Concentration / amount:
Intradermal Induction: 0.5% (a.i.) (v/v) in distilled water
Topical Induction: 0.5% (a.i.) (v/v) in distilled water
Day(s)/duration:
0-9
Adequacy of induction:
other: maximal not irritating concentration used for intradermal and epicutaneous induction
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: distilled water
Concentration / amount:
Topical Challenge: 0.25% and 0.5% (a.i.) (v/v) in distilled water
Day(s)/duration:
20
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 (controls), 20 (in test groups)
Details on study design:
RANGE FINDING TESTS: Yes, treatment concentrations of the main study are based on these results.

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: a 1:1 mixture (v/v) FCA/water
- Injection 2: test substance 0.5% active substance
- Injection 3: test substance 0.5% active substance in a 1:1 mixture (v/v) FCA/water
- Epicutaneous: test substance (0.5% a.i.) in distilled water
- Control group:
Intradermal (3 pairs of injections):
- Injection 1: a 1:1 mixture (v/v) FCA/water
- Injection 2: distilled water
- Injection 3: 50% vehicle (v/v) in a 1:1 mixture (v/v) FCA/water
- Epicutaneous: vehicle
- Site: dorsal level (intradermal + epicutaneous)
- Frequency of applications: intradermal on Day 0 and epicutaneous on Day 7
- Duration: Days 0-9
- Concentrations: intradermal 0.5% active substance, epicutaneous 0.5% active substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: dorso-lumbar region
- Concentrations: 0.25 and 0.5% active substance
- 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):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%, challenge: 0.25% (a.i.)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions and clinical signs were observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge: 0.5% (a.i.)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions and clinical signs were observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 0.5% (a.i.), challenge: 0.25% (a.i.)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No skin reactions and clinical signs were observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 0.5% (a.i.), challenge: 0.5% (a.i.)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No skin reactions and clinical signs were observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%, challenge: 0.25% (a.i.)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions and clinical signs were observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%, challenge: 0.5% (a.i.)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions and clinical signs were observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 0.5% (a.i.), challenge: 0.25% (a.i.)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No skin reactions and clinical signs were observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 0.5% (a.i.), challenge: 0.5% (a.i.)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No skin reactions and clinical signs were observed

Any other information on results incl. tables

No mortalities occurred and no signs of systemic toxicity were observed during the study period. Neither erythema nor edema were recorded. The mean weight gain calculated for the treated animals during the test period is not significantly different from that of the control animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified

In a GPMT conducted equivalent OECD 406 the test material was not sensitising to the skin.