Dimethyl ether

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Remarks:

other: repeated dose

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 452 (Chronic Toxicity Studies)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl ether

EC Number:

204-065-8

EC Name:

Dimethyl ether

Cas Number:

115-10-6

Molecular formula:

C2H6O

IUPAC Name:

dimethyl ether

Details on test material:

- Purity: 99.98%

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Labs, Kingston, New York
- Age at study initiation: weanling rats
- Weight at study initiation: not reported
- Fasting period before study: none
- Housing: stainless steel, wire-mesh cages. Housed 3/cage upon arrival
- Diet (e.g. ad libitum): Purina Laboratory Chow Checkers #5001 (PLCC) available ad libitum except during exposures
- Water (e.g. ad libitum): ad libitum except during exposures
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±2°C
- Humidity (%): 50%±10%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure (if applicable):

whole body

Remarks on MMAD:

Not applicable in case of a gas

Vehicle:

air

Details on exposure:

The study was designed to evaluate the potential chronic toxicity and oncogenicity of the test substance in male and female rats when exposed by inhalation. Reproductive organs were examined during histopathology examinations at 6-, 12-, 18-month, and 2-year sacrifices.

Details on mating procedure:

Animals were not mated.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Chamber atmospheres were analyzed by a GC every half hour during the 6 hour daily exposure period.
Target concentrations: 0, 0.2, 1.0, 2.5%

Duration of treatment / exposure:

2 years

Frequency of treatment:

6 hours/day, 5 days/week (excluding holidays)

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.21 other: %

Remarks:

analytical concentration

Doses / concentrations 2

Dose / conc.:

1.02 other: %

Remarks:

analytical concentration

Doses / concentrations 3

Dose / conc.:

2.47 other: %

Remarks:

analytical concentration

No. of animals per sex per dose:

100 male and 100 female per concentration group

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

Reproductive organs were examined at histopathological examinations at 6-, 12-, 18-month, and 2-year sacrifices.

Statistics:

The incidences of gross and histopathological lesions were compared to control group incidences by the Fisher's Exact test.

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEC

Effect level:

>= 2.5 other: %

Sex:

male/female

Basis for effect level:

other: No adverse effects on reproductive organs or tissues were observed at the highest concentration tested.

Results: F1 generation

Effect levels (F1)

Remarks on result:

not measured/tested

Remarks:

As no findings were noted in reproductive organs and a developmental toxicity study also did not not have a negative outcome, there is no reason to expect developmental findings if an F1 generation would have been created.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

No compound-related effects on the reproductive organs of either male or female rats were observed.  An increase in the incidence of mammary tumors (benign or malignant) was observed in female rats in the 2.5% exposure group. The incidence of mammary tumors was considered not to be compound related because the incidences of tumors in the control group were uncharacteristically low in comparison with the control groups incidence in studies previously conducted at Haskell Laboratory. See Section 7.7 for additional details regarding incidence levels and historical control data.

Applicant's summary and conclusion

Conclusions:

No adverse effects on reproductive organs or tissues at concentrations of 2.5% (highest concentration tested). The study and the conclusions fulfil the quality criteria (validity, reliability, repeatability).

Executive summary:

A 2-year inhalation study was conducted in male and female rats (see Section 7.5.3 for details on the study design). Ten rats/sex/group were sacrificed and necropsied at 6, 12, and 18 months and all rats alive at the 2-year time point. All rats underwent both gross and microscopic examinations. Reproductive organs included in the histopathological evaluation included testis, epididymis, prostate, seminal vesicles, cervix, mammary gland, ovary, uterus, and vagina. The testis was weighed.

No compound-related effects on the reproductive organs of either male or female rats were observed. An increase in the incidence of mammary tumors (benign or malignant) was observed in female rats in the 2.5% exposure group. The incidence of mammary tumors was considered not to be compound related because the incidences of tumors in the control group were uncharacteristically low in comparison with the control groups incidence in studies previously conducted at Haskell Laboratory.