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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
single dose followed by 14-day observation period
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted prior to introduction of Good Laboratory Practices; data from a summary report; number of animals similar to that used in current guideline studies; actual test report not available for review but raw data were reviewed for this entry. Study was conducted by an internal Eastman Kodak Company method developed prior to established guidelines. The results of this study are valid for classification insofar as the conditions of exposure are at least as stringent as modern guidelines. Dose range sufficient to determine actual LD50 value for classification purposes.

Data source

Reference
Reference Type:
other: Eastman Kodak Company Summary Report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Four groups of four male rats (age and weights not provided) were administered a single dose of the test material at dose levels of 1000, 2000, 4000, or 8000 mg/kg bw by oral gavage and observed for a period of two weeks. The rats were observed for adverse clinical signs and mortality. Body weights were collected prior to dosing and at termination of the observation period. Gross pathology was performed at study termination.
GLP compliance:
no
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method.
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
-Name of test material as cited in study report: Methyl isoamyl ketone
-Appearance: liquid
-Melting Point: -74 °C
-Boiling Point: 145 °C at 760 mm Hg
-Solubility: 0.5% in water at 20 °C
-Purity: 98%
-Impurities: 2% MIBK, 10-20 ppm HOMME
-Shipped to testing laboratory: May 16, 1978
-Source of test material: Tennesse Eastman Company (Eastman Chemical Company)
-Storage conditions: room temperature and humidity

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Each animal received a single dose of the test material by oral gavage.
Doses:
1000, 2000, 4000, or 8000 mg/kg bw
No. of animals per sex per dose:
4 males/dose level
Control animals:
no
Details on study design:
Four groups of four male rats (age and weights not provided) were administered a single dose of the test material at dose levels of 1000, 2000, 4000, or 8000 mg/kg bw by oral gavage and observed for a period of two weeks. The rats were observed for adverse clinical signs and mortality. Body weights were collected prior to dosing and at termination of the observation period.
Statistics:
The LD50 estimate was determined by the geometric mean of the top two dose levels.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
5 657 mg/kg bw
Remarks on result:
other: The two highest dose levels (4000 and 8000 mg/kg bw) used in this study were higher than that used for a limit dose in present-day guideline studies.
Mortality:
No mortality was noted in the 1000, 2000, or 4000 mg/kg bw dose groups. All rats assigned to the 8000 mg/kg bw dose group died within one day of dosing.
Clinical signs:
No abnormal clinical signs were evident in the 1000 and 2000 mg/kg bw dose groups. At the 4000 and/or 8000 mg/kg bw dose levels, clinical signs of toxicity included weakness, ataxia, tremors, and prostration. All rats assigned to the 4000 mg/kg bw dose level recovered and survived to study termination. No other clinical abnormalities were reported during the study.
Body weight:
All surviving rats gained weight during the 14-day observation period.
Gross pathology:
Not reported

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under conditions used in this study, methyl isoamyl ketone was not acutely toxic by the oral route in male rats. The oral LD50 in male rats was 5657 mg/kg bw.

Based on an acute oral LD50 value between 4000 and 8000 mg/kg bw (geometric mean of 5657 mg/kg bw) in male rats, methyl isoamyl ketone is not classified for acute lethality by the oral route under GHS.
Executive summary:

In an acute oral toxicity study, four groups of four male rats were administered a single dose of methyl isoamyl ketone by gavage at dose levels of 1000, 2000, 4000, or 8000 mg/kg bw and observed for mortality and adverse clinical signs for a period of 14 days. No mortality was noted in the 1000, 2000, or 4000 mg/kg bw dose groups. All rats assigned to the 8000 mg/kg bw dose group died within one day of dosing. No abnormal clinical signs were evident in the 1000 and 2000 mg/kg bw dose groups. At the 4000 and/or 8000 mg/kg bw dose levels, clinical signs of toxicity included weakness, ataxia, tremors, and prostration. All rats assigned to the 4000 mg/kg bw dose level recovered. All surviving rats gained weight during the 14-day observation period. The oral LD50 in male rats administered methyl isoamyl ketone is considered to between 4000 and 8000 mg/kg bw, with a geometric mean of 5657 mg/kg bw. Ingestion of large amounts may cause effects on the central nervous system.