2-ethyl-2-oxazoline

Acute Toxicity: inhalation

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

Test material information

Constituent 1

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-4,5-dihydro-1,3-oxazole

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 levels

Effect levels 1

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

Effect levels 2

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.