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Administrative data

Description of key information

Acute oral studies with rats and mice are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: As this study was pre-GLP, detail in the report is lacking but the study was conducted in a state-of-the-art facility to the standards of the time.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
The study guideline was equivlaent to the OECD 401 study.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Animals were given a single oral dose of the test article.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 1 600 - < 3 200 mg/kg bw
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: US CPSC / US OSHA
Conclusions:
The LD50 of the study was given as 1600-3200 mg/kg.
Executive summary:

Groups of rats were treated with methyl propyl ketone by oral gavage. The reported LD50 was 1600 -3200 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 600 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in a GLP facility using OECD guidelines
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
The test item was contained in a glass syringe located on an infusion pump thus providing a constant supply of test item into the air stream. Immediately after the injection site, the air supply was ducted, via suitable tubing and a conical flask, through a water bath, maintained at approximately 50°C, to ensure complete vaporization. Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the test item. The cylindrical exposure chamber had a volume of approximately 30 liters (dimensions: 28 cm diameter x 50 cm high). The concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump. The extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system.
Homogeneity of the test atmosphere within the chamber was not specifically determined during this study. Chambers of the same design (ADG Developments Ltd, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animals’ breathing zone with a wide variety of test items (Green J D et al, 1984). Prior to the start of the study, test item atmospheres were generated within the exposure chamber.
During this characterization period test item input rates were varied in an attempt to achieve the required atmospheric conditions.

On the day of exposure each rat was acclimatized (for approximately 2 hours) to a tapered polycarbonate restraining tube. During the exposure, each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere. Following an appropriate equilibration period a single group of six rats (three males and three females) was exposed to an atmosphere of the test item for a period of four hours. A target concentration of 20 mg/L was used for the exposure. As the mean achieved concentration was 128% of target and no deaths occurred, no further levels were required.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
25.5 mg/l
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
6 rats, (3 per sex per dose) were exposed to a single atmosphere of 25.5 mg/l of methyl n-propyl ketone for 4 hours, followed by a 14-day observation period.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 25.5 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
None
Clinical signs:
Common abnormalities noted during the study included increased respiratory rate, ataxia, hunched posture, pilo-erection and wet fur. There were occasional instances of prostration, an isolated occurrence of splayed gait was also noted. Animals recovered to appear normal on Day 6 post-exposure.
Body weight:
All animals exhibited body weight losses on the first day post-exposure. Reasonable bodyweight gains were noted for all animals during the remainder of the recovery period.
Gross pathology:
One male animal exhibited dark patches on the lungs at necropsy
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 25.5 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of methyl propyl ketone, CAS# 107-87-9, in the RccHanTM : WIST strain rat, was greater than 25.5 mg/L .
Executive summary:

A study was performed to assess the acute inhalation toxicity of the test item. The method used was designed to be compatible with that described in the OECD Guidelines for Testing of Chemicals (2009) No. 436 “Acute Inhalation Toxicity – Acute Toxic Class Method”. A group of six RccHan™ : WIST strain rats (three males and three females) was exposed to a vapor atmosphere. The animals were exposed for four hours using a nose only exposure system,followed by a fourteen day observation period. The mean achieved atmosphere concentration was 25.5 mg/l. Common abnormalities noted during the study included increased respiratory rate, ataxia, hunched posture, pilo-erection and wet fur. There were occasional instances of prostration, an isolated occurrence of splayed gait was also noted. Animals recovered to appear normal on Day 6 post-exposure. All animals exhibited body weight losses on the first day post-exposure. Reasonable bodyweight gains were noted for all animals during the remainder of the recovery period. One male animal exhibited dark patches on the lungs at necropsy. No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 25.5 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of methyl propyl ketone in the rat was greater than 25.5 mg/L.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
25 500 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A study was performed to assess the acute inhalation toxicity of the test item. The method used was designed to be compatible with that described in the OECD Guidelines for Testing of Chemicals (2009) No. 436 “Acute Inhalation Toxicity – Acute Toxic Class Method”. A group of six RccHan™ : WIST strain rats (three males and three females) was exposed to a vapor atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period. The mean achieved atmosphere concentration was 25.5 mg/l. Common abnormalities noted during the study included increased respiratory rate, ataxia, hunched posture, pilo-erection and wet fur. There were occasional instances of prostration, an isolated occurrence of splayed gait was also noted. Animals recovered to appear normal on Day 6 post-exposure. All animals exhibited body weight losses on the first day post-exposure. Reasonable bodyweight gains were noted for all animals during the remainder of the recovery period. One male animal exhibited dark patches on the lungs at necropsy. No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 25.5 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of methyl propyl ketone in the rat was greater than 25.5 mg/L (Globally Harmonized Classification System –unclassified).

In a pair of acute oral toxicity studies, the LD50 was 1600 -3200 mg/kg for rats and 1600 mg/kg for mice. These studies were pre-GLP and not well documented, but were done in a state of the art facility to the standards of the time.

Acute dermal toxicity testing was not conducted as the test article is volatile.


Justification for selection of acute toxicity – dermal endpoint
Based on Annex VIII, this test was waived as the test article is volatile.

Justification for classification or non-classification

Acute oral toxicity testing supports an acute 4 classification