Registration Dossier

Administrative data

Description of key information

Several GLP-studies according to or equivalent to OECD guidelines 404 and 405 are available for diisobutyl ketone.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutylketone
- Physical state: Colourless liquid
- Analytical purity: 96.1%
- Lot/batch No.: D226600037
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd, Margate
- Age at study initiation: 13-16 weeks
- Weight at study initiation: 2.39 to 2.70 kg
- Housing: Individual
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 40-80
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 10/14
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): Undiluted 96.1%


Duration of treatment / exposure:
4h
Observation period:
1, 24, 48 and 72h and 8 (7 days after dosing) and 15 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 30x20mm
- Type of wrap if used: The dose was spread uniformly over the designated area and then covered by a dense gauze patch (30 x 20 mm). This in turn was covered by a larger gauze patch (40 x 40 mm) and an open weave, elasticated adhesive bandage "Steroban" from Steroplast Ltd, Bredbury which was wrapped firmly around the torso to secure the applied dose and patch in the correct position.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, swabbed with moist cotton wool
- Time after start of exposure: 4h


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
One week after treatment, the dermal test sites showed either a marked desquamation or very slight erythema. All overt effects of the semi-occluded topical application of diisobutylketone resolved within two weeks of treatment.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the study period.

A single semi-occluded application of diisobutylketone to intact rabbit skin for four hours elicited slight erythematous and oedematous reactions and other dermal changes (superficial eschar formation, tissuring and desquamation) that resolved within two weeks of treatment. Diisobutylketone has not to be classified according to DSD and CLP.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, DIBK was concluded as not irritating to semi-occluded rabbit skin. Mean scores for erythema and edema were 1.33, 0, 0.33 and 1.0, 0, 0 for animals 1, 2 and 3, respectively.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Concentration not specified, test conditions insufficient described
GLP compliance:
no
Specific details on test material used for the study:
- Source: Solvents and Coatings Materials, South Charleston, WV
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Clear non-viscous, liquid;slightly yellow, transparent non-viscous liquid.
- Analytical purity: No data
- Lot/batch No.: 475010-135-500564
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.005, 0.01 and 0.1mL
- Concentration (if solution): As supplied


Duration of treatment / exposure:
7 days without washout
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6/volume
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: 2% fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 0.1mL
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
other: 0.1mL
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 0.1mL
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 0.1mL
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 0.01mL
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
other: 0.01mL
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
other: 0.01mL
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 0.01mL
Irritant / corrosive response data:
Scores for 0.005mL were not reported due to missing effects at 0.01mL

Diisobutyl Ketone (DIBK) showed only minor irritation in rabbit eyes after instillation of 0.1mL test material that was fully reversible within 7 days. Diisobutyl Ketone has not to be classified according to DSD and CLP. However the concentration of the received test substance had not been reported.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean scores for cornea, iris, conjunctivae and chemosis over all animals at 24, 48 and 72 hours were below 0.5. Hence, no classification according to DSD and CLP is required for diisobutyl ketone.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin: Several studies in rabbits conducted under GLP and according to OECD guideline 404 showed no or very slight irritation not meeting the criteria for classification as skin irritant. Some older non-GLP studies conducted with guinea pigs showed skin irritation effects. However, the details provided in those study reports are insufficient for proper evaluation of the data and no details on the purity of the test material is given.

Eye: two studies of acceptable quality (Klimisch 2) - conducted in rabbits - showed very slight irritation not meeting the criteria for classification.

Respiratory: in a human volunteer study (see section 7.10.5) using diisobutyl ketone vapor concentrations of 50 and 100 ppm. The higher concentration caused slight irritation of the eyes and nose initially, but the sensation decreased during the exposure. In a sensory irritation study in mice, DIBK caused a significant decrease in respiratory rate following head only vapor exposure for 15 mins

at concentrations of 184 to 351 ppm, suggesting some sensory irritation of the respiratory tract.


Effects on respiratory irritation: irritating

Justification for classification or non-classification

Skin irritation: according to EEC Council Directive 67/548/EEC (amended by Directive 83/467/EEC) and GHS/CLP the mean values for erythema and edema scores were less than 2 for all animals tested. According to annex VI and I of these directives diisobutyl ketone is not classified as skin irritant.

Eye irritation: according to the annex VI of the council directive 67/548 EEC (amended by directive 83/467 EEC) the average scores over all animals cornea opacity, iris lesions, conjunctivae and chemosis were 0 at all, respectively at 24, 48 and 72 hours. According to EU criteria no classification for eye irritancy is required.

Respiratory: diisobutyl ketone is classified as respiratory irritant R37 according to annex VI of the council directive 67/548 EEC (amended by directive 83/467 EEC) and H335 according to GHS/CLP.