3-methylbutanone

Acute Toxicity: oral

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to acceptable scientific standards and reviewed by Quality Assurance. Conduct of study according to all aspects of GLP was not confirmed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

no

Principles of method if other than guideline:

Three groups of five rats per sex were administered single doses of 1250, 2500, or 5000 mg/kg bw of the test substance by oral gavage and observed for a period of two weeks. Clinical observations and mortality were noted during the study. Body weights were recorded on a weekly basis. Gross pathology was performed following death of animals and on all survivors at study termination.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-2-butanone

IUPAC Name:

3-methyl-2-butanone

Constituent 2

Reference substance name:

3-methylbutanone

EC Number:

209-264-3

EC Name:

3-methylbutanone

Cas Number:

563-80-4

Molecular formula:

C5H10O

IUPAC Name:

3-methylbutan-2-one

Constituent 3

Reference substance name:

methylbutanone; methyl isopropyl ketone; MIPK

IUPAC Name:

methylbutanone; methyl isopropyl ketone; MIPK

Details on test material:

-Test substance: Methyl isopropyl ketone
-Date of manufacture: October 1987
-Source: Tennessee Eastman Company

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
-Strain: Crl:CD®(SD)BR
-Sex: Male and Female (5 of each sex/group)
-Body weight (at study initiation): Males (125-140 g), Females (130-148 g)

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:

1250, 2500, 5000 mg/kg bw

No. of animals per sex per dose:

5 rats/sex/group

Control animals:

no

Details on study design:

Three groups of five rats per sex were administered single doses of 1250, 2500, or 5000 mg/kg bw of the test substance by oral gavage and observed for a period of two weeks. Clinical observations and mortality were noted during the study. Body weights were recorded on a weekly basis. Gross pathology was performed at study termination or upon death of study animals. The dose levels were selected based on the results of two range finding studies in which doses of up to 2500 mg/kg bw did not cause mortality. Selected gross lesions were processed for microscopic evaluation.

Statistics:

no data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 078 mg/kg bw

95% CL:

2 333 - 4 061

Mortality:

One male and one female died in the 2500 mg/kg bw group by 24 hours post-dose. All animals in the 5000 mg/kg bw group died between 1.7 hours to 1 day post-dose. All remaining animals survived the 14-day observation period.

Clinical signs:

other: Abnormal clinical signs in all dose groups were observed only on the day animals were dosed. Abnormal clinical signs at the 5000 mg/kg bw dose level included ataxia and slight weakness in all animals immediately after dosing. One hour after administratio

Gross pathology:

Test substance-related changes observed at necropsy of the 5000 mg/kg bw animals which died after dosing were limited to test substance in the gastrointestinal tract (2/5 males, 3/5 females). No treatment-related changes were observed at necropsy of animals administered a dose of 2500 or 1250 mg/kg bw. All other gross lesions were considered not treatment-related.

Other findings:

Selected gross lesions were processed for microscopic evaluation. These lesions either could not be confirmed microscopically, or were identified as autolytic changes. The cause of death for animals which died after exposure to the test substance was not determined.

Any other information on results incl. tables

Two range finding studies were conducted using one animal of each sex per dose level. Dose selections of 78, 156, 312, 625, and 1250 mg/kg bw were administered as a 25% solution in corn oil. In the second study, the test substance was administered neat at dose levels of 156, 312, 625, 1250, and 2500 mg/kg bw. All animals in both studies survived the 14-day observation period. 

Applicant's summary and conclusion

Interpretation of results:

other: Classified Category V per UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS); however, there is no Category V in CLP Regulation (EC) No. 1272/2008; classified Category 3 for Specific Target Organ Toxicity – Single Exposure

Remarks:

Criteria used for interpretation of results: OECD GHS

Conclusions:

Under conditions used in this study, the single dose oral LD50 in male and female rats was calculated to be 3078 mg/kg bw (95% CL 2333-4061). Clinical signs indicating reversible effects on the central nervous system included slight to moderate weakness and ataxia.

Based on an acute oral LD50 value of 3078 mg/kg bw in rats, methyl isopropyl ketone is classified as Category V for classification and labeling for acute lethality by the oral route under the UN GHS regulations; however, there is no Category V in EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Therefore, methyl isopropyl ketone is not classified for acute lethality according to EU CLP GHS in this study. Based on clinical signs indicating reversible effects on the central nervous system, methyl isopropyl ketone is classified as Category 3 for classification and labeling under GHS for Specific Target Organ Toxicity – Single Exposure. This acute oral classification is supported by similar clinical signs and an oral LD50 of 3200 mg/kg bw in an earlier supporting study conducted in rats and mice by the same test laboratory.

Executive summary:

In an acute oral toxicity study, three groups containing five rats/sex/group were administered a single dose of methyl isopropyl ketone by oral gavage at dose levels of 1250, 2500, or 5000 mg/kg bw. The rats were observed for mortality and adverse clinical signs for a period of 14 days. All rats in the 5000 mg/kg bw dose group and one rat per sex in the 2500 mg/kg bw dose group died by 24 hours after test substance administration. No other mortality was noted during the study. The calculated oral LD50 in rats administered methyl isopropyl ketone was 3078 mg/kg bw. Clinical signs of toxicity reported in the study summary included weakness (moderate to slight), ataxia, and prostration. No other clinical abnormalities were noted throughout the study. All surviving rats gained weight over the 14-day observation period. Based on the results of this study, methyl isopropyl ketone may be harmful by the oral route. Ingestion of large amounts may cause transient CNS depression.