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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-guideline study; concentration of diethyl ether not measured nor quantified (likely ca. 60%); period of exposure not recorded; concentration of oxygen in the exposure chamber not measured - based on the design, displacement of oxygen likely).

Data source

Reference
Reference Type:
publication
Title:
Neonatal inhalatory anesthetic exposure: reproductive changes in male rats
Author:
Arena, A.C., Pereira, O.C.M.
Year:
2002
Bibliographic source:
Comparative Biochemistry and Physiology Part C, 2002, 133, 633-640

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Neonatal male rats were exposed to a single massive dose of diethyl ether inducing anesthesia (as determined by loss of reflexes). Pups were returned to own mothers until 21st day of lactation, upon which males were separated and housed collectively. At 75d sexual behaviour was followed. At 90d a subgroup were sacrificed for organ-weight determination. After reaching maturity the male rats were mated, and on the 21st day of pregnancy the females were sacrificed and examined. Body weight, organ weight, testosterone levels, fertility, quantity of spermatozoa, and sexual behaviour were endpoints examined.
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No information on the test material was reported.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: virgin female Wistar rats mated within own colony
- Age at study initiation: immediately after birth

ENVIRONMENTAL CONDITIONS
- Temperature: 25°C
- Humidity: 55%
- Photoperiod (hrs dark / hrs light): 12h / 12h

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: closed glass container containing cotton wool saturated with diethyl ether
- Method of holding animals in test chamber: not specified
- Source and rate of air: none
- Method of conditioning air: none
- Temperature, humidity, pressure in air chamber: not specified
- Air flow rate: none
- Air change rate: none

TEST ATMOSPHERE
- Brief description of analytical method used: none
Details on mating procedure:
- M/F ratio per cage: 1:5
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
No information on the duration.
Frequency of treatment:
Single exposure.
Doses / concentrations
Remarks:
Doses / Concentrations:

Basis:
no data
No. of animals per sex per dose:
Not reported.
Control animals:
yes

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not examined
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
effects observed, treatment-related
Reproductive performance:
effects observed, treatment-related

Details on results (P0)

A reduction was observed in the wet weight of the seminal vesicale free of secretion in the diethyl ether exposed group. No other changes in body or organ weights was seen in the adult males. No change in testosterone levels was observed. 26% reduction in pregnancy rate was observed compared to controls. A significant reduction in spermatids and spermatozoa was seen.

Effect levels (P0)

Dose descriptor:
NOAEC
Basis for effect level:
other: Only a single dose was used
Remarks on result:
not determinable
Remarks:
no NOAEC identified Generation not specified (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

None delivered.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

20% of male rats exposed to diethyl ether did not present male sexual behaviour.

Applicant's summary and conclusion

Conclusions:
The study is considered to be not reliable due to the uncontrolled manner of exposure to diethyl ether. It cannot be ruled out that the effects observed are the result of hypoxia on the developing animal, either due to the anesthesia itself, or physical displacement of oxygen from the "exposure chamber" by the heavier diethyl ether vapour.
The concentrations used are not relevant to human exposure (at least ca. 60% based on saturated vapour pressure).
Similar effects on sexual development in rats have been seen due to other environmental stressors (immobilisation, cold, anesthesia, electric shock), as noted by the authors.