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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 Aug - 14 Sep 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No data on analytical purity of test substance given. Test substance concentration used for intradermal induction (1%) did not induce mild to moderate skin irritation. No data for positive control results reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
12 May 1981
Deviations:
yes
Remarks:
No data on analytical purity of test substance given. Test substance concentration used for intradermal induction (1%) did not induce mild to moderate skin irritation.
GLP compliance:
yes
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.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white Bor: DPHW
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known: SPF
- Weight at study initiation: 300 - 412 g (males) and 315 - 369 g (females)
- Housing: 5 animals per cage in Macrolon type IV cages on LIGNOCEL
- Diet: pelleted guinea pig diet (Ssniff G-Alleindiät für Meerschweinchen, Ssniff Spezialdiäten GmbH, Soest Germany), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
peanut oil
Concentration / amount:
1%
Day(s)/duration:
on Day 0; single injection
Adequacy of induction:
other: next lower dose of concentrations causing severe erythema (2.5%)
Route:
epicutaneous, occlusive
Vehicle:
peanut oil
Concentration / amount:
100%
Day(s)/duration:
on Day 7; 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
peanut oil
Concentration / amount:
50%
Day(s)/duration:
on Day 21; 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Range-finding test: 2 males and 2 females
Main study: 10 males and 10 females for test and control group
Details on study design:
RANGE FINDING TESTS:
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 intradermal tolerance test 2 male and 2 female animals were treated intradermally with test substance concentration of 0.5, 1, 2.5 and 5% diluted in a mixture of FCA and water. Skin reactions were recorded after 48 h. Since test substance concentration of 2.5 and 5% produced local ulceration and discoloration, 1% concentration was chosen for the main study. For the epicutaneous tolerance test two animals each were treated with test substance concentrations of 25 and 50% in peanut oil or 100%, repectively. Applications were made under occlusive dressings and skin reactions were recorded after 48 h. Since the test substance caused slight to moderate erythema at a concentration of 100%, this concentration was chosen for epicutaneous induction in main study. Next lower test substance concentration of 50% causing no skin reactions was chosen for challenge of main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: 0.1 mL 1:1 mixture (w/w) FCA/water
Injection 2: 0.1 mL 1% (w/v) test substance in peanut oil
Injection 3: 0.1 mL 1% (w/v) test substance in a 1:1 mixture (v/v) FCA/water
Epicutaneous: 100% test substance
- Control group:
Intradermal (3 pairs of injections):
Injection 1: 0.1 mL 1:1 mixture (w/w) FCA/water
Injection 2: 0.1 mL peanut oil (vehicle)
Injection 3: 0.1 mL 50% mixture (w/w) arachis oil emulsified with FCA
Epicutaneous: 100% peanut oil (vehicle)
- Site: shoulder region (intradermal and epicutaneous)
- Frequency of applications: Day 1 (intradermal) and Day 8 (epicutaneous)
- Duration: Day 1 - 8
- Concentrations: intradermal: 1%; epicutaneous: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 21
- Exposure period: 24 h
- Test groups: test subsatance and vehicle
- Control group: test substance and vehicle
- Site: left flank (test substance), right flank (vehicle)
- Concentration: 50%
- Evaluation (hr after challenge): 24 and 48 h after challenge patch removal
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
The reaction to the positive control substances 2.4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) is tested periodically (last test performed in April 1991).

Results and discussion

Positive control results:
The positive control group was not carried out concurrently with this study but is tested periodically. The last test with an acceptable level of response to each of the positive control substances was performed in April 1991.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Challenge: 50%
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Challenge: 50%
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Challenge: 50%
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Challenge: 50%
No. with + reactions:
0
Total no. in group:
20
Key result
Group:
positive control
Remarks on result:
other: tested periodically, but no results given

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 guinea pig maximisation test the test substance revealed no sensitising properties.