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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-10-12 to 1995-11-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The GPMT is an accepted method for hazard identification of skin sensitising substances as recommended in "ECHA guidance R.7a: Endpoint specific guidance".
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre d´Elevage Lebeau, 78950 Gambais, France
- Age at study initiation: approx. 3 month
- Weight at study initiation: 314 +/- 13 g (males), 315 +/-20 g (females)
- Housing: individually
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 30-70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Induction: intradermal application of 10% (w/w) of the test substance in paraffin oil; topical application of the undiluted test substance
Challenge: topical application of 10% (w/w) of the test substance in paraffin oil on right flank, 50% (w/w) of the test substance in paraffin oil on left flank
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Induction: intradermal application of 10% (w/w) of the test substance in paraffin oil; topical application of the undiluted test substance
Challenge: topical application of 10% (w/w) of the test substance in paraffin oil on right flank, 50% (w/w) of the test substance in paraffin oil on left flank
No. of animals per dose:
20 (10 males and 10 females)
Details on study design:
RANGE FINDING TESTS:
- a preliminary test was conducted in order to determine the concentrations to be tested in the main study
- by intradermal route: 0.1 ml of the test substance at different concentrations at the dorsal region between the shoulders; evaluation after 24, 48 hours and six days after injection
- by cutaneous route: 0.5 ml of different concentration of the test substance were applied to a gauze pad (4cm²); occlusive dressing; exposure 24 h; evaluation after 24 and 48 hours after removal of the dressings;
- criteria for dose selection: concentration should be well tolerated systemically and locally; intradermal injections should cause moderate irritant effect; topical application for the induction should cause at most weak or moderate skin reaction; topical application for the challenge should should be the highest concentration which does not cause an irritant effect

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: intradermal route: on day one injection of 0.1 ml; cutanous route: on day 8 topical application of test substance for 48 h
- Test groups: yes (induction with test substance)
- Control group: yes (induction with vehicle)
- Site: dorsal region between the shoulders
- Frequency of applications: intradermal and cutanous route
- Duration: 10 days
- Concentrations: induction: intradermal injection 10 % (w/w) of the test substance in paraffin oil; topical application: 99.0% undiluted test substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 22
- Exposure period: 1 day (24 h)
- Test groups: yes (challenge with 50% (w/w) and 10% (w/w) of the test substance)
- Control group: yes (challenge with 50% (w/w) and 10% (w/w) of the test substance)
- Site: left and right flank
- Concentrations: topical application: 50% (w/w) of the test substance in paraffin oil on the left flank and 10% (w/w) of the test substance in paraffin oil on the right flank
- Evaluation (hr after challenge): 24 and 48 h after
Challenge controls:
no
Positive control substance(s):
yes
Remarks:
2,4-dinitro chlorobenzene
Positive control results:
2,4-Dinitro chlorobenzene in a concentration of 1% (w/w) induced positive skin sensitization reactions in 100% of the guinea pigs.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 % (w/w)
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% (w/w)
No. with + reactions:
11
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10% (w/w)
No. with + reactions:
5
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10% (w/w)
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% (w/w)
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% (w/w)
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% (w/w)
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:
negative control
Dose level:
10% (w/w)
No. with + reactions:
1
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:
1% (w/w) 2,4-dinitro chlorobenzene
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1% (w/w) 2,4-dinitro chlorobenzene
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions a cutaneous reactions attributable to the sensitization potential of the test substance were observed in 6 of 20 guinea-pigs when the test substance was applied at 50% (w/w). The test substance did not show sensitization effect at 10% (w/w).
Executive summary:

The potential of Luperox 219 (Di-3,5,5 -Trimethylhexanoyl)peroxide) in the vehicle paraffin oil to induce delayed contact hypersensitivity was evaluated in guinea-pigs according the maximization method of Magnusson and Kligman and the OECD guideline 406. Thirty guinea-pigs were allocated in 2 groups: a control group, consisting of five males and five females and a treated group consisting of 10 males and 10 females. No clinical signs and no deaths were noted during the study. Cutanous reactions attributable to the sensitization potential of the test substance were observed in 6 of 20 guinea-pigs when the test substance was applied at 50% (w/w). The test substance did not show a sensitization effect at 10% (w/w).

The sensitivity of the guinea-pig was checked in a recent study with a positive sensitizer (2,4 -dinitro chlorobenzene).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Cutaneous reactions attributable to the sensitization potential of the test substance were observed in 6 of 20 animals in a Guinea Pig Maximisation Test when the test item was applied at a concentration of 50 % (w/w). No sensitization effect was observed at 10 % (w/w).


Migrated from Short description of key information:
OECD 406 (CIT, 1996)

Justification for selection of skin sensitisation endpoint:
GLP guideline study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Cutaneous reactions attributable to the sensitization potential of the test substance were observed in 6 of 20 guinea pigs when the test substance was applied at 50 % (w/w). The test item is considered to be a skin sensitizer of medium hazard (Skin Sens 1B).