Diethyl ether

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information from peer reviewed reference.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1986

Reference 2

Reference Type:

publication

Title:

Health effects assessment for ethyl ether

Author:

U.S. Environmental Protection Agency

Year:

1987

Bibliographic source:

Health effects assessment for ethyl ether, U.S. Environmental Protection Agency, 1987, EPA/600/8-88/039

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: no information available

Principles of method if other than guideline:

Study conducted by reputable testing laboratory for the U.S. EPA. Likely to be an early guideline study.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diethyl ether

EC Number:

200-467-2

EC Name:

Diethyl ether

Cas Number:

60-29-7

Molecular formula:

C4H10O

IUPAC Name:

diethyl ether

Details on test material:

No information on the test material is available.

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Daily gavage

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

2 000 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

3 500 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

30 animals per sex per dose

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

Data collected from the study included body weight and organ weight changes, consumption of food, ophthalmological examinations, biochemical, clinical and gross morphology changes, and target organ histopathology.

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

Sacrifice and pathology:

An interim sacrifice was performed after 6 weeks of dosing. 10 rats per sex were used and the remaining allowed to continue until the end of the study.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY
Mortality observed at 3500 mg/kg bw. 15/60 rats (6 male and 9 female) died.
Mortality observed at 2000 mg/kg bw. 4/60 rats (2 male and 2 female) died.
Light anesthesia was observed at 2000 mg/kg bw and especially so at 3500 mg/kg bw.

BODY WEIGHT AND WEIGHT GAIN
Body weight loss was observed at 3500 mg/kg bw in both sexes.
Only males showed significant loss at 2000 mg/kg bw.

FOOD CONSUMPTION
Decreased food intake was observed at 3500 mg/kg bw in males.

OPHTHALMOSCOPIC EXAMINATION
Ophthalmoscopic examination at sacrifice revealed retinal atrophy 2 male rats at 3500 mg/kg bw, 2 female rats at 2000 mg/kg bw, and in one female rat exposed at 500 mg/kg bw.

HAEMATOLOGY
At 3500 mg/kg bw exposure males had significant decreases in hemoglobin and hematocrit values and a slight increase in red blood cell count. Females showed no treatment related effects at 500 or 2000 mg/kg bw exposure.

CLINICAL CHEMISTRY
At 3500 mg/kg bw, SGPT and serum cholesterol levels were significantly increased in males, and SGOT levels were elevated in females. At 2000mg/kg bw transient increase of cholesterol in females was seen. Females showed no other treatment related effects at 500 or 2000 mg/kg bw exposure.

URINALYSIS
Females showed no treatment related effects at 500 or 2000 mg/kg bw exposure.

ORGAN WEIGHTS
The relative weights of brain, kidneys and testes/epididymides were increased in males at 3500 mg/kg bw, however, the significant reduction in body weight observed in this group makes interpretation difficult. Increase in relative liver weight was observed in females at 2000 mg/kg bw exposure. Females showed no other treatment related effects at 500 or 2000 mg/kg bw exposure.

GROSS PATHOLOGY
Necroscopy of 2000 and 3500 mg/kg bw exposed animals showed lung and liver discolouration and distention and discolouration of the stomach.

HISTOPATHOLOGY
No effects related to diethyl ether exposure were observed in target organ histopathology.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: significant body weigh depression

2

Dose descriptor:

LOAEL

Effect level:

2 000 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: significant body weigh depression

Target system / organ toxicity

Critical effects observed:

not specified