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Administrative data

acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant near-guideline study, no restrictions, fully adequate for assessment.

Data source

Reference Type:
study report

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:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
Ethyl-t-Butyl Ether (ETBE), identification no. LF-9072, was purchased from Aldrich Chemical Company (Milwaukee, WI; Lot No. 00423HW; 99% purity). The test article was a clear, colorless liquid. It was received July 12, 1989 and was kept refrigerated (approximately 4°C).

Test animals

Crj: CD(SD)
Details on test animals or test system and environmental conditions:
Male and female CD rats, purchased from Charles River Breeding Laboratories, Inc., Portage, MI, at approximately 4 weeks of age were used in this study. Upon arrival (8/16/89), the rats were held in quarantine for approximately two weeks and examined carefully to ensure their health and suitability as test subjects.
Purina Rodent Chow 5002 (Ralston Purina Company, St. Louis, MO) and water, supplied from a reverse-osmosis purifier by an automatic watering system, were available ad libitum, except during the exposure period.
During the quarantine and the post-exposure observation periods, the rats were housed individually in suspended stainless steel cages measuring
24.0 x 17.8 x 17.6 cm. The rats were housed in nose-only exposure tubes during the exposure period. Air conditioned animal rooms were maintained at approximately 22°C and 40% relative humidity. Fluorescent lighting was provided automatically for 12 hours followed by 12 hours of darkness.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
other: filtered air
Details on inhalation exposure:
The vapour generating system comprised a U-shaped glass tube, heated to approx. 69 degrees C. ETBE was delivered into the tube at a constant rate (not specified) via 1/8 inch OD teflon tubing and a Fluid Metering Inc pump. The ETBE was completely vaporised under these conditions, and delivered to the exposure chamber (160 l, stainless steel) at 59 l/min.
The rats were placed in individual exposure tubes and inserted into a stainless steel nose-only exposure chamber (Unifab, Kalamazoo, MI).
Analytical verification of test atmosphere concentrations:
Test article concentration was measured using infra-red (IR) spectrophotometry at a wavelength of 11.7 microns. The exposure atmosphere was sampled continuously and the chamber concentration recorded approximately every 1/2 hour during the exposure.
Duration of exposure:
4 h
The test article was heated to a maximum temperature of 71°C (average = 69°C) during the exposure period. The nominal concentration was 5.99 mg/l. Infra-red (IR) analysis showed a mean actual concentration of 5.88 ± 0.077 mg/l (time-weighted average = 5.88 mg/l; minimum/maximum = 5.73/5.96 mg/l).
No. of animals per sex per dose:
Control animals:
Details on study design:
All rats were observed immediately following removal from the nose-only exposure tubes, approximately 2-1/4 hours after the exposure and at least once per day for the balance of the 14-day observation period.
All test rats were weighed prior to exposure, one week later and immediately prior to necropsy.
At the end of the 14-day observation period (9/20/89), all rats were euthanized by anesthetic overdose and subjected to a gross necropsy.
Statistical analyses were used to analyse the results: calculation of standard deviations.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 5.88 mg/L air
Exp. duration:
4 h
There were no deaths during the exposure period or during the 14 d observation period.

Clinical signs:
other: The inguinal area of all rats was soiled due to confinement in the nose-only exposure tubes. Redness around the nose/eyes and discolored facial fur were observed immediately following the exposure, however, most of the rats appeared normal the following d
Body weight:
The initial mean body weights of the male and female rats were 268 g and 179 g, respectively. All rats gained weight during the study.
Gross pathology:
Necropsy findings were within normal limits in all rats. Six rats had lung foci and/or red areas on their lungs, however, these lesions were of the type and severity commonly seen in control rats, therefore, they were deemed not to be treatment-related.

Applicant's summary and conclusion