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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Butanone oxime
EC Number:
EC Name:
Butanone oxime
Cas Number:
Molecular formula:
Test material form:

Test animals

Fischer 344
Details on test animals or test system and environmental conditions:
- Source: Charles River Breeding Laboratories, Kingston, NY
- Weight at study initiation: 130-180 g
- Fasting period before study: no, except during dosing
- Housing: Individually in stainless steel cages with wire mesh front and bottom
- Diet (e.g. ad libitum): Purina Rodent Chow #5001, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

- Temperature (°C): No data, but temperature was measured at hourly intervals during all exposures.
- Humidity (%): No data, but humidity was recorded at hourly intervals during all exposures.
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
other: unchanged (no vehicle)
Details on inhalation exposure:
Test Substance Administration: MEKO was administered to the test animals as a vapor in a 225 L stainess steel and glass chamber. Liquid MEKO was metered from a syringe using a Sage Model 355 syringe pump through Teflon@ tubing to a DeVilbissa nebulizer (The DeVilbiss Company, Somerset, PA). The air source for the nebulizer was a compressed air cylinder . The air passed from the cylinder , through a Matheson regulator, a Dwyer flow meter, a Whitey valve, and a Gast pressure gauge before entering the nebulizer . The MEKO aerosol produced by the nebulizer passed through an elbow of plastic flexibl e tubing, a glass 3 neck round bottom 500 mL flask, and a glass elbow before entering the chamber. The 3 neck flask was heated in a water bath in order to vaporize the MEKO aerosol. The aerosol was passed through this circuitou s route t o maximize surface area fo r aerosol impaction.

Exposure Concentration Determination: During each test material exposure, measured volumetric samples were taken at hourly intervals and were analyzed by means of a gravimetric technique. The chamber concentration was calculated by dividing the weight of the material collected i n a charcoal tube or a Glasrock glass fiber filter paper in a Glasrock Field Monitor Cassette by the number of liters of air sampled. The charcoal tubes were used t o determine the total concentration of vapor and any aerosol present and the glass fiber filter papers were used t o determine the concentration of aerosol alone. Background room air and clean chamber charcoal tube samples were taken to determine the amount of water vapor for a correction factor in the exposure samples.

Particle Size Distribution Analysis: P article size distribution was performed hourly during test material exposures to characterize any aerosol present. This was accomplished with the use of an Andersen Cascade Impactor.
Analytical verification of test atmosphere concentrations:
Duration of exposure:
<= 4 h
0, 0.19, 1.45 and 4.83 mg/L
No. of animals per sex per dose:
5 rats/sex/dose
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made daily and body weights were recorded on days 0, 1, 4, 7, 11 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, blood collected for hematology and clinical chemistry, gross examination of organs and tissues at necropsy, organ weights (brain, lung with trachea, liver spleen, each kidney and gonads), and histopathology was conducted on all spleens and sternebrae with marrow and on the lungs of 5 rats/sex/group from control and high dose groups only.
A probit analysis program was not utilized to calculate the LC50 and its 95% confidence interval since the highest obtainable concentration produced no mortality. The results of the quantitative continuous variables such as body weight changes or organ weight changes were intercompared for the dosage groups versus the control group and for the interim sacrifice and full term sacrifice groups by the use of the following analysis o f variance (Snedecor and Cochran, 1980), and Duncan's procedure (Duncan, 1955). The latter was used, if F for analysis of variance was significantly high, to delineate which groups differed from the controls. If Bartlett's test indicated heterogeneous variance, the F max test was used f o r each group versus the control. If these individual F max test s were significant or if N1=N2, Cochran t-test (Snedcor and Cochran, 1980) or the Wilcoxon Rank Sum test were used. Contingency table type data were analyzed by Fischer's Exact Test or RXC Chi Square Test, as appropriate.
Data Collection,

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 4.83 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
No mortality was observed in any test group.
Clinical signs:
other: narcotic effects
Body weight:
Decreases in rate of body weight gain were statistically significant in females in all groups at the end of the study and were evident although not statistically significant through the end of the study in high dose males.
Gross pathology:
There were no gross necropsy observations judged to be related to MEKO administration.
Other findings:
Observations that appeared related to MEKO administration were dried material around the mouth and nose in males and females and yellow staining of the anal-genital area in females. These observations were marked in the high dose group. A strong but temporary narcotic effect occurred in both sexes in the high dose group during exposures.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
The inhalation LC50 for methyl ethyl ketoxime in rats is greater than 4.83 mg/L.