Registration Dossier

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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1986
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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 / concentrationsopen allclose all
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Dose / conc.:
2 000 mg/kg bw/day (actual dose received)
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

open allclose all
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: significant body weigh depression
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

Applicant's summary and conclusion