Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
incomplete experimental data
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
no data
Doses:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 3 200 mg/kg bw

Assessed by the result of the oral LD50 of >3200mg/kg bw in rats Diisobutyl Ketone has not to be classified, but the insufficient data allows no classification.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of DIBK in rats is greater than 3200 mg/kg. Hence, no classification for acute oral toxicity is required according to EU criteria.
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
incomplete experimental data
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl
Species:
mouse
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
no data
Doses:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 3 200 mg/kg bw

Assesses by the result of the oral LD50 of >3200mg/kg bw in mice Diisobutyl Ketone has not to be classified, but the insufficient data allows no classification.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of DIBK in mice is greater than 3200 mg/kg. Hence, no classification for acute oral toxicty is required according to EU criteria.
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Incomplete experimental data
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: no data
Duration of exposure:
6 h
Concentrations:
2.3-14.6mg/L air
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 12 days
Sex:
not specified
Dose descriptor:
LC50
Effect level:
11.5 mg/L air
Exp. duration:
6 h

The result of the LC50 of 11.5mg/L air for rats Diisobutyl Ketone allows no classification due to the insufficient data.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 of DIBK in rats was estimated to be 11500 mg/m3 after 6 hours of exposure. Hence, no classification for acute inhalation toxicity according to EU criteria is required.
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no experimental data
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
not specified
Duration of exposure:
24h
Doses:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 16 mg/kg bw

Although there was a result of the dermal LD50 of >16mg/kg bw for rats for Diisobutyl Ketone, the insufficient data allows no classification.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Although there was a result of the dermal LD50 of >16mg/kg bw for rats for Diisobutyl Ketone, the insufficient data allows no classification.
Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Incomplete experimental data
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl
Species:
guinea pig
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not specified
Duration of treatment / exposure:
24h
Observation period:
no data
Number of animals:
no data
Irritant / corrosive response data:
The test material is a strong irritant producing severe erythema, moderate edema and some scarring and eschar formation

Although the test substance shows strong skin irritating and slightly corrosive effects the lack of information allows no classification.

Conclusions:
Since erythema and edema scores were not reported and the exposure duration was not conform current guidelines, the results of this study could not be used to derive a classification for skin effects
Reason / purpose:
reference to same study
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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:
no guideline available
GLP compliance:
not specified
Type of study:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Reading:
1st reading
Group:
test group
No. with + reactions:
2
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. Group: test group. No with. + reactions: 2.0. Total no. in groups: 5.0.

20% of the tested animals showed positive reactions, but the insufficient data allows no classification.

Interpretation of results:
ambiguous
Remarks:
Migrated information
Conclusions:
20% of the tested animals showed positive reactions, but the insufficient data allows no classification.
Reason / purpose:
reference to same study
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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:
no guideline followed
Principles of method if other than guideline:
Repeated dose inhalation daily for 5 days a week for 12 exposures
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: no data
Duration of treatment / exposure:
6h, 5 days per week, for a total of 12 exposure
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
2.3 mg/L
Basis:
no data
No. of animals per sex per dose:
5
Control animals:
not specified
Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes, not further specified

HAEMATOLOGY: Yes
- How many animals: all
- Parameters checked : emoglobin concentration, hematocrit and differential white cell count

CLINICAL CHEMISTRY: Yes
- How many animals: all
- Parameters checked: glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, alkalin phosphatase, urea nitrogen and glucose

- Other examinations performed: organ weight (liver and kidney), behaviour
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, not further specified
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
HAEMATOLOGY
The total white cell count was slightly reduced as a result of a 50% reduction in the white blood cell count of two rats. Similar reductions were previously reported following inhalation exposures to ethyl n-butyl ketone and methyl n-butyl ketone (Toxicology Report No. 104733T). There were no treatment related gross or microscopic changes detected. Blood forming organs may be the site of toxic action.
Dose descriptor:
NOAEC
Effect level:
2.3 mg/L air
Sex:
not specified
Critical effects observed:
not specified

Adverse effects on the total white blood cell count were observed and the NOAEC for Diisobutyl Ketone for repeated inhalative exposure was set to 2.3mg/L air (the higest dose tested). However the results and the experimental documentation are insufficient for classification.

Conclusions:
Adverse effects on the total white blood cell count were observed and the NOAEC for Diisobutyl Ketone for repeated inhalative exposure was set to 2.3mg/L air (the higest dose tested). However the results and the experimental documentation are insufficient for classification.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
10 day repeated open application to guinea pig
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: liquid
- Analytical purity: 65%
- Impurities (identity and concentrations): 32-35% 2-heptanone-4, 6-dimethyl

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified

Administration / exposure

Type of coverage:
open
Vehicle:
not specified
Details on exposure:
TEST MATERIAL
- Concentration (if solution): no data
Duration of treatment / exposure:
10 days
No. of animals per sex per dose:
5

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

On day 1 slight to moderate erythema in 4 out of 5 animals On day 10 slight to moderate erythema in 4/5, slight edema in 5/5, eschars in 5/5. Repeated application exacerbates response. The insufficient data, especially on the concentration of the test substance, allows no classification.

Applicant's summary and conclusion

Conclusions:
The insufficient data, especially on the concentration of the test substance, allows no classification.