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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:
1995-01-03 - 1995-02-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid guinea pig maximisation test is available and therefore no in vitro test is necessary.
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone, DIBK
- Physical state: clear liquid
- Analytical purity: 95.6%
- Lot/batch No.: 02254 00010
Species:
guinea pig
Strain:
other: (Crl:(HA)BR)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Manston Road, Margate, Kent, UK.
- Age at study initiation: Males 4-8 weeks, females 3-5 weeks
- Weight at study initiation: Males 350-544g, females 246-307g
- Housing: Individually in suspended cages (25.5cm length x 50cm width x 20.7cmheight). The cages were made of stainless steel, with one solid sheet side and a wire mesh floor and front and remaining side.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17±2
- Humidity (%): 55±15
- Air changes (per hr): 25-30/h
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
10% w/v
Route:
epicutaneous, open
Vehicle:
corn oil
Concentration / amount:
10% w/v
No. of animals per dose:
20 for test material, 10 as control group
Details on study design:
RANGE FINDING TESTS: The dose-levels for each of the three stages of this study were determined by a sighting study in which groups of two or four guinea pigs were used and up to four dose-levels were tested on each group of animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 48h for topical
- Test groups: Freund's Complete Adjuvant plus corn oil in the ratio 1:1; 10% w/v preparation of the test sample in corn oil; 10% w/v preparation of the test sample in a 1:1 preparation of Freund's Complete Adjuvant plus corn oil
- Control group: Identical procedure to that used for the test animals without the test substance
- Site: Intradermal: on each side of the midline of the animals back; topical: scapular area
- Frequency of applications: Day 1 intradermal, day 7 topical
- Concentrations: Intradermal: 10%; Topical: Undiluted

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24h
- Test groups: Filter paper with test substance on shaved skin
- Control group: Filter paper with test substance on shaved skin
- Site: Right flank undiluted, left flank 30% in corn oil
- Concentrations: Undiluted and 30%
- Evaluation (hr after challenge): 48 and 72h


OTHER: The day prior to topical induction the application site was clipped and 0.5ml of a 10% w/v preparation of sodium lauryl sulphate (CTL Ref:Y00076/005, Sigma Chemical Company) in paraffin wax was applied in order to provoke a mild inflammatory response
Positive control substance(s):
yes
Remarks:
Hexylcinnamaldehyde
Positive control results:
Following challenge of previously-induced guinea pigs with undiluted hexylcinnamaldehyde, scattered mild redness or moderate diffuse redness was
seen in fourteen of the twenty test animals. The net percentage response was calculated to be 50% and hexylcinnamaldehyde was classified as a moderate skin sensitiser under the conditions of the test.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No effects.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No effects.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No effects.
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
100%
No. with + reactions:
14
Total no. in group:
20
Clinical observations:
Scattered mild to moderate diffuse redness
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 100%. No with. + reactions: 14.0. Total no. in groups: 20.0. Clinical observations: Scattered mild to moderate diffuse redness.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No effects.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 30%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No effects.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No effects.
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
100%
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
Scattered mild to moderate diffuse redness
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: positive control. Dose level: 100%. No with. + reactions: 13.0. Total no. in groups: 20.0. Clinical observations: Scattered mild to moderate diffuse redness.

Diisobutyl Ketone (DIKB) is not a skin sensitiser to guinea pig skin and has therefore not to be classified according to DSD and CLP.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Diisobutyl Ketone (DIKB) is not a skin sensitiser to guinea pig skin (0% sensitization rate). Hence, no classification is required according to DSD and CLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Two reliable studies (Klimisch rating 1 and 2) in guinea pigs are available for DIBK. Both studies report no sensitization response in any of the tested animals. In addition, an invalid study reporting some sensitization effects (2 out of 5 animals) is available. However, the low number of animals used in this study does not allow to derive any definitive conclusions and the purity of the test material was only 65%.


Migrated from Short description of key information:
A GLP-studies according to OECD guideline 406 and a GLP-study according to the footpad method are available for diisobutyl ketone.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No experimental data on respiratory sensitization is available for diisobutyl ketone. However, based on the negative results from the skin sensitization studies it can be concluded that DIBK is not expected to have any respiratory sensitization potential.


Migrated from Short description of key information:
No experimental data on respiratory sensitization is available for diisobutyl ketone.

Justification for classification or non-classification

Pure DIBK did not induce sensitization in any of the tested animals. Hence, no classification for sensitization is required according to EU criteria.