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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
reference to other study
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Later 1979 study determined actual exposure concentrations were 8-fold lower than the reported calculated nominal concentrations
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
- 99+% purity
- Test material ID: pilot plant material, Lot: R-624-20
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
- Weight at study initiation: ~250 g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
For both exposure levels (10,820 and 5,960 ppm), six male Sprague-Dawley rats weighing approximately 250 g were exposed in a 19 liter glass exposure chamber to vapors generated by bubbling air through the liquid test material which was maintained at room temperature. The exposure concentrations given are nominal concentrations, i.e., calculated from the weight of material used and the airflow through the chamber. For the high exposure level, air was bubbled through the test material at the rate of 1 liter per minute for 7 hours and delivered undiluted to the chamber.

For the lower exposure level air was bubbled through the test material at the rate of 0.5 liters per minute and a stream of filtered air was added downstream at the rate of 0.5 liters per minute prior to entry into the exposure chamber. This exposure was also of 7 hours duration. A single control group of five male rats was maintained under ambient conditions.
Duration of exposure:
7 h
Concentrations:
10,820 and 5,960 ppm
No. of animals per sex per dose:
6 males/dose
Control animals:
yes
Details on study design:
During exposure the rats were observed for signs of toxicity such as eye and nasal irritation and respiratory distress. Body weights were taken twice a week for two weeks. At the end of this period gross pathologic examinations were carried out on all of these animals.
Statistics:
compared to controls by Analysis of Variance and Dunnett's test, p<0.05
Mortality:
The results found ETOX lethal for 5 of 6 rats at a nominal concentration of 10,820 ppm for 7 hours.
ETOX was not lethal for any of 6 rats at a nominal concentration of 5,960 ppm for 7 hours.
Gross pathology:
no pathologic changes when presented
Other findings:
Determination of cholinesterase activity - The six rats exposed to 10,660 ppm for this determination reacted the same as those described in the high level exposure. They all slept deeply for most of the exposure, were breathing more deeply at the end of exposure, and were nervous when removed from the chamber. There were no statistically significant deviations in plasma or red cell cholinesterase when compared to control values.
Interpretation of results:
GHS criteria not met
Executive summary:

Analysis during the 1979 study of the ETOX exposure chamber by infrared spectrophotometry revealed a major discrepancy between the analytical and nominal concentrations. Since the 1979 study carefully duplicated the test system of the 1977 study it was concluded that the actual exposure concentrations in the 1977 study were appreciably lower or approximately 750 and 1,330 ppm ETOX, 8-fold lower than the reported calculated nominal concentrations of 5,960 and 10,820 ppm ETOX, respectively.

There were no statistically significant deviations in plasma or red cell cholinesterase when compared to control values in the present study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethyl-2-oxazoline
EC Number:
233-912-4
EC Name:
2-ethyl-2-oxazoline
Cas Number:
10431-98-8
Molecular formula:
C5H9NO
IUPAC Name:
2-ethyl-2-oxazoline
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
- Exposure chamber volume: 19 liter glass chamber
- System of generating particulates/aerosols: The ETOX atmosphere was generated by bubbling air through liquid ETOX at room temperature (~23°C) at a rate of 0. 5 liters per minute for 7 hours, while filtered air at a rate of 0.5 liters/minute was mixed with the vapor airstream prior to entry into the exposure chamber.

Analytical Verification:
The analytical concentration of ETOX in the exposure· chamber as determined by infrared spectrophotometry using a Miran I infrared spectrophotometer equipped with a variable pathlength gas cell. The wavelength used for the analysis was 9.9µ. Chamber air analysis was performed by attaching a Saran gas sampling bag to the exhaust port of the chamber, collecting 8 liters of the exhausted chamber atmosphere, and diluting it with 32 liters of filtered air to acquire sufficient volume to pump through the gas cell of the infrared spectrophotometer for analysis. Standards were made using 100 liter Saran gas sampling bags connected to a glass U-tube for evaporation of ETOX prior to entry into the bag. The U-tube was gently heated with an air gun to improve evaporation of the test material. The nominal concentration of ETOX vapor in the chamber was calculated from the weight of material used and the total airflow through the chamber.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
7 h
Concentrations:
Nominal 5,960 ppm (20.5 mg/l)
No. of animals per sex per dose:
5 control animals
6 treatment animals
Control animals:
yes
Details on study design:
During and after exposure the rats were observed for signs of toxicity, such as eye and nasal irritation and respiratory distress. Body weights were taken prior to exposure and 3 times a week for 2 weeks after exposure. At the end of this period gross pathologic examinations were performed on all rats.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
> 20.5 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
7 h
Remarks on result:
other: 5068 ppm
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 635 ppm
Based on:
test mat.
95% CL:
> 578 - < 692
Exp. duration:
7 h
Remarks on result:
other: time weighted analytical concentration
Mortality:
No mortality
Clinical signs:
other: Throughout most of the 7 hour exposure to ETOX the rats' extremities (ears, paws, scrotal sacs, and tails) were pinker than those of the control rats, their respiration was labored, and their reaction to sound was diminished (anesthetic symptom). Upon rem
Body weight:
After an initial body weight decrease, the ETOX exposed rats gained weight in a manner comparable to the controls.
Gross pathology:
Upon gross pathologic examination 1 of 5 control rats and 5 of 6 ETOX exposed rats were described as having pale kidneys but were otherwise normal.

Any other information on results incl. tables

The control chamber atmosphere was analyzed by infrared spectroscopy to determine whether ammonia from the rats' urine would interfere with the infrared analysis for ETOX. No significant interference was found.

The nominal concentration of ETOX in the exposure chamber was calculated as 5,068 ppm (20.5 mg/L), while the time weighted analytical concentration was found to be 635±57 ppm. This marked difference was attributed to the adherence of ETOX to the walls of the chamber and to its affinity for the water produced by condensation from expired air and from urination in the small 19 liter exposure chamber.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Male rats were exposed to 635 ppm (measured concentration) ETOX vapour via whole body exposure. No mortality was reported. No toxicologically significant gross pathological findings were reported. The 7-hour LC50 is >635 ppm.