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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6-hour exposure 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; actual test report not available for review but sufficient data were provided to determine classification. 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 Basic Toxicity Summary Report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Method is an in vivo study using groups of four male rats exposed (whole body) to an atmosphere containing the test material for a period of six hours. After termination of exposure, the animals were observed for mortality and adverse clinical signs for a period of 14 days. Body weights were measured prior to exposure and at termination of the 2-week observation period. No gross pathology was performed at study termination.
GLP compliance:
no
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method using a 6-hour inhalation exposure period.
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:
Weight Range at Study Initiation: 181-233 grams

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
Rats were exposed (whole-body) to target vapor concentrations of 800, 1600, 3200, or 6400 ppm of the test material for 6 hours. The test material was vaporized, diluted with ambient (room temperature) air, then directed to a 20-liter glass bell jar for exposure, and monitored by infrared spectroscopy. Actual mean vapor concentrations achieved were 802, 1603, 3207, and 5878 ppm.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Atmosphere concentrations monitored by infrared spectroscopy.
Duration of exposure:
6 h
Concentrations:
Mean vapor concentrations achieved were 802, 1603, 3207, and 5878 ppm.
No. of animals per sex per dose:
4 males/dose concentration
Control animals:
not specified
Details on study design:
Groups of four male rats (strain not available) with a weight range of 181-233 grams were exposed (whole-body) to target vapor concentrations of 800, 1600, 3200, or 6400 ppm of the test material for 6 hours. The test material was vaporized, diluted with ambient (room temperature) air, then directed to a 20-liter glass bell jar for exposure, and monitored by infrared spectroscopy. Actual mean vapor concentrations achieved were 802, 1603, 3207, and 5878 ppm. During and subsequent to exposure, the animals were observed for mortality and adverse clinical signs for a period of 14 days. Body weights were measured prior to exposure and at termination of the 2-week observation period. No gross pathology was performed at study termination.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
> 3 207 - < 5 875 ppm
95% CL:
> 1 903 - < 3 805
Exp. duration:
6 h
Remarks on result:
other: Based on mortality, the calculated LC50 (6-hr) was approximately 3813 ppm (17806 mg/m3).
Mortality:
All rats in the 5878 ppm concentration group died within 2.5 hours after the start of exposure. One of four rats in the 3207 ppm concentration group died just prior to termination of the 6-hour exposure.
Clinical signs:
other: At the 5878 ppm concentration level, eye irritation and narcosis were observed for all animals prior to death during the exposure period. Within 2 hours of the start of exposure, all animals exposed to a concentration of 3207 ppm displayed signs of eye ir
Body weight:
Although the three surviving rats in the 3207 ppm group lost weight (3-13 grams) between Day 0 and Day 3, subsequent weight gain was normal. All other rats gained weight normally over the 14-day study.
Gross pathology:
Not performed

Any other information on results incl. tables

An LC50 (6-hr) of 3813 ppm is equivalent to an LC50 (4-hr) of approximately 5000 ppm.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under conditions used in this study, methyl isoamyl ketone was lethal by the inhalation route to all male rats exposed to a concentration of 5878 ppm for 2.5 hours. Since only one of four male rats died at a concentration of 3207 ppm, the LC50 (6-hr) in male rats was >3207 ppm but <5878 ppm. The calculated LC50 (6-hr) was approximately 3813 ppm which is equivalent to an LC50 (4-hr) of approximately 5000 ppm.

Based on a calculated inhalation LC50 (6-hr) value of 3813 ppm (equivalent to a 4-hr LC50 of approximately 5000 ppm), methyl isoamyl ketone is classified as Category IV for classification and labeling for acute lethality by the inhalation route under GHS.

Methyl isoamyl ketone currently carries an R20 Risk Phrase (Harmful if Inhaled) under Annex 1 of the European Union Dangerous Substances Directive.
Executive summary:

In an acute inhalation toxicity study, groups of four male rats were exposed (whole body) to methyl isoamyl ketone at vapor concentrations of 802, 1603, 3207, and 5878 ppm for a period of 6 hours. All rats in the 5878 ppm group and one of four rats in the 3207 ppm group died during the exposure period. At the 5878 ppm concentration level, eye irritation and narcosis were noted for all animals prior to death. Within 2 hours of exposure, all animals exposed to a concentration of 3207 ppm displayed signs of eye irritation, unresponsiveness, and impaired gait. By 4-5 hours of exposure, these rats were narcotized with depressed respiration. The three remaining rats at this concentration level recovered fully following cessation of exposure. At the 1603 ppm concentration level, abnormal signs were limited to sluggish responses after 6 hours of exposure. In the 802 ppm group, animals appeared alert during exposure, though immediately after exposure, animals appeared a bit sluggish. Although the three surviving rats in the 3207 ppm group lost weight (3-13 grams) between Day 0 and Day 3, subsequent weight gain was normal. All other rats gained weight normally over the 14-day study. The LC50 was calculated to be 3813 ppm for a 6-hour exposure. Methyl isoamyl ketone was toxic to rats at high airborne concentrations and caused reversible effects on the central nervous system.