Registration Dossier

Diss Factsheets

Administrative data

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:
15/05 to 30/06 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study conform guidelines under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
study already available
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, 33176 Borchen
- Age at study initiation: young adults
- Weight at study initiation: < 500 g
- Housing: 5 animals/macrolon IV cage
- Diet: Ssniff standard laboratory guinea pig feed ad libitum
- Water: ad libitum
- Acclimation period: > 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70%
- Air changes (per hr):15/hr
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15-05-1994 To: 30-06-1994
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
epicutaneous induction I : 50%
epicutaneous induction II : 50%
epicutaneous induction III : 25% (in view of severe skin damage observed during first and sceond induction)

epicutaneous challenge: 5%

all concentrations based on pre-tests to set irritant properties
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
epicutaneous induction I : 50%
epicutaneous induction II : 50%
epicutaneous induction III : 25% (in view of severe skin damage observed during first and sceond induction)

epicutaneous challenge: 5%

all concentrations based on pre-tests to set irritant properties
No. of animals per dose:
20 in test group and 10 controls
Details on study design:
application volume 0.4 cm3 on 4 cm2

RANGE FINDING TESTS: PIT indicating 5% as non-irritant and 50% as irritant dose

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 20 animals
- Control group: 10 anaimals
- Site: 2X2 cm on flank
- Frequency of applications: induction on day 0, 7,and 14
- Concentrations: 50% first two inductions, 25% last induction

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28
- Exposure period: 6 hours
- Test groups: 20 animals
- Control group: 10 animals
- Site: 2X2 cm on flank
- Concentrations: 5%
- Evaluation (hr after challenge): 30 and 54 hours

Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazol
Positive control results:
positive in 10/10 animals at 50%
Reading:
1st reading
Hours after challenge:
30
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 30.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
30
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 30.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
54
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
54
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Interpretation of results:
GHS criteria not met
Conclusions:
In a Buehler test the test substance did not induce sensitisation in guinea pigs.
Executive summary:

In a Buehler test in guinea pigs performed in agreement with the protocol as described in OECD 406, severe irritation (erythema and oedema with scales and callus formation) was observed after epicutaneous induction. Challenge with 5% of the test substance did not induce any skin reaction. It is concluded that the test substance does not induce sensitisation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
The test substance is negative in a Bühler test (Hüls 1994). This is confirmed by the CIT maximisation test (CIT 1994). The structural analogue diisopropyl benzene hydroperoxide was ambiguous in a Bühler test.

Justification for selection of skin sensitisation endpoint:
The key study was performed according to the guideline.

Justification for classification or non-classification

No classification for sensitization is considered necessary in view of the outcome of the studies with the test substance.