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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; limited number of animals. 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.

Data source

Reference
Reference Type:
other: Eastman Kodak Company Summary Report
Title:
Unnamed
Year:
1964
Report date:
1964

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not specified
Principles of method if other than guideline:
Five groups of two rats each were administered single doses of 200, 400, 800, 1600, or 3200 mg/kg bw of the undiluted test substance by oral gavage and observed for a period of two weeks. Clinical observations and mortality were recorded during the study. Body weights were recorded prior to dosing and at termination of the observation period. Gross pathology was performed at study termination.
GLP compliance:
no
Remarks:
study conducted prior to GLPs
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method.
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Heptan-2-one
EC Number:
203-767-1
EC Name:
Heptan-2-one
Cas Number:
110-43-0
Molecular formula:
C7H14O
IUPAC Name:
heptan-2-one
Constituent 2
Reference substance name:
606-024-00-3
IUPAC Name:
606-024-00-3
Constituent 3
Reference substance name:
methyl amyl ketone; methyl pentyl ketone; MAK; 1-methylhexanal; butylacetone
IUPAC Name:
methyl amyl ketone; methyl pentyl ketone; MAK; 1-methylhexanal; butylacetone
Details on test material:
-Identity (according to study report): methyl n-amyl ketone (MAK)

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system 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:
200, 400, 800, 1600, 3200 mg/kg bw
No. of animals per sex per dose:
2 animals/dose (sex not specified)
Control animals:
no
Details on study design:
Two animals were assigned to each dose group (sex, age, and weights not provided). Rats were administered a single dose of the undiluted test material by oral gavage at dose levels of 200, 400, 800, 1600, or 3200 mg/kg bw. Rats were observed for a 14-day period 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.
Statistics:
no data

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 1 600 mg/kg bw
Remarks on result:
other: The highest dose level (3200 mg/kg bw) used in this study was higher than that used for a limit dose in present-day guideline studies.
Mortality:
Both animals at the highest dose level (3200 mg/kg bw) and one of two animals at 1600 mg/kg bw died 5 hours to 1 day after test substance administration. All remaining animals survived the 14-day observation period.
Clinical signs:
Clinical signs of toxicity reported in the study summary included weakness (slight to very weak), prostration, labored respiration, vasodilatation, and ataxia. Labored respiration occurred at oral doses of 800 mg/kg bw and above. No other clinical abnormalities were noted throughout the study.
Body weight:
All surviving rats gained weight over the 14-day observation period.
Gross pathology:
No findings were noted in any animal.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
In an acute oral toxicity test, the oral LD50 was approximately 1600 mg/kg bw for rats (sex not specified) administered a single dose of undiluted methyl n-amyl ketone. Abnormal clinical signs reported in the study included weakness, prostration, labored respiration, vasodilatation, and ataxia. Deaths in the 1600 and 3200 mg/kg bw dose groups occurred between 5 hours and 1 day of dose administration. All surviving animals gained weight and there were no adverse effects observed at necropsy.

Executive summary:

In an acute oral toxicity study, five groups containing two rats each were administered a single dose of undiluted methyl n-amyl ketone by oral gavage at dose levels of 200, 400, 800, 1600, or 3200 mg/kg bw. The rats were observed for mortality and adverse clinical signs for a period of 14 days. Both rats in the highest dose group (3200 mg/kg bw) and one rat in the 1600 mg/kg bw dose group died 5 hours to 1 day post dose. No other mortality was noted during the study. The oral LD50 in rats administered methyl n-amyl ketone is approximately 1600 mg/kg bw. Clinical signs of toxicity reported in the study summary included weakness (slight to very weak), prostration, labored respiration, vasodilatation, and ataxia. No other clinical abnormalities were noted throughout the study. All surviving rats gained weight over the 14-day observation period and no gross changes were observed at necropsy. Based on the results of this study, methyl n-amyl ketone is harmful by the oral route. Ingestion of large amounts may cause CNS depression (fatigue, dizziness and possible loss of concentration, with collapse, coma and death in cases of severe over-exposure).