Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Identification: methyl propyl ketone
CAS# 107-87-9
Description: Clear colorless liquid
Batch: TD11000836
Purity: 93.62 %
Expiry date: 04 January 2014
Storage conditions: Stored cold at approximately 4°C, in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

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.

Results and discussion

Effect levels
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

Applicant's summary and conclusion

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.