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Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

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Administrative data

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
received: 26 Nov 1982
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed similar to current OECD guideline with some deviations.

Data source

Reference Type:
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
2 dose levels tested, no information on mitotic index
GLP compliance:
not specified
Type of assay:
mammalian bone marrow chromosome aberration test

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-methoxyethyl) ether
EC Number:
EC Name:
Bis(2-methoxyethyl) ether
Cas Number:
Molecular formula:
Constituent 2
Reference substance name:
Constituent 3
Reference substance name:
Details on test material:
Batch no. 21150
obtained from Aldrich Chemical Company, Wisc., USA
clear, colorless liquid

Test animals

Crj: CD(SD)
Details on test animals or test system and environmental conditions:
obtained from Charles River (U.K.)

Administration / exposure

Route of administration:
inhalation: vapour
Details on exposure:
- Atmosphere generation and analysis in animal tests:
The test atmosphere was produced by bubbling dry, oxygen-free Nitrogen through Bis(2-methoxyethyl)ether contained in a Drechsel bottle immersed in a temperature controlled water bath at 50°C. The Nitrogen/vapor mixture so generated was diluted with filtered, conditioned compressed air and passed into the rat exposure chambers. These were 1.5 m3 capacity stainless steel and glas-chambers in which individually caged rats were confined to a single tier of cage occupying 0.5 m3. The chamber was ventilated at a rate of 12 air changes per hour.
Atmospheres in the chambers were analysed by infrared spectroscopy with Miran-1A Gas Analysers. Samples of chamber air were pumped continuously through the instruments and the chamber concentrations were automatically recorded. Instrument calibration was performed by a closed-loop calibration system. Known volumes of test compound were sequentially injected into the gas analyser with a Hamilton glass microsyringe. After each injection the absorbance reading was allowed to stabilise as indicated on the chart recording.

- Exposure procedure
Rodents were exposed to Diethylene glycol dimethyl ether atmospheres for 7 h/d for either 1 or 5 days. In the positive control groups EMS (please refer to "positive controls") was administered orally to all animals. Multiple dosed rodents received 100 mg/kg bw/d for 5 days while single-dosed rats received 250 mg/kg bw.

Duration of treatment / exposure:
7 h/d
Frequency of treatment:
(a) single exposure
(b) 5 consecutive days
Post exposure period:
(a) 6, 24 or 48 h
(b) 6 h
Doses / concentrationsopen allclose all
Dose / conc.:
250 ppm (analytical)
Dose / conc.:
1 000 ppm (analytical)
No. of animals per sex per dose:
Control animals:
yes, concurrent no treatment
Positive control(s):
Ethyl methanesulfonate (EMS) orally


Tissues and cell types examined:
Cytogenetic analysis of rat bone marrow cells
Details of tissue and slide preparation:
Groups of 10 males and 10 females were exposed to the test item or filtered air either 1 or 5 days. After their last exposure period, animals were injected i.p. with 3 mg Colchicine/kg bw 2 h prior to death. The 1-day-exposed groups were killed at one of three sampling times namely, 6, 24, and 48 h after the end of exposure. The 5-day-exposed groups were killed 6 h after the end of exposure. Giemsa-stained slides were labeled with numbers not corelated with the animal numbers; therefore, all assessments of metaphases were "blind". Where possible, 50 metaphases per rat were scored.
Evaluation criteria:
no data
no data

Results and discussion

Test results
no effects
Vehicle controls validity:
Positive controls validity:
Additional information on results:
- Clinical observations on rats
Male and female rat body weight was unaffected. All multiply exposed mammals in the 1000 ppm atmosphere groups were subdued and unresponsive to audio stimuli during exposure.

- Cytogenetic analysis of rat bone marrow sells
In neither the 5-days nor the single exposure test was there any evidence for the induction of chromosomal damage. the only significant increases in aberrant cell frequency occured in low-dose groups 6 h following a single exposure to the test material. In male rats exposed to 250 ppm Bis(2-methoxyethyl)ether, there was a small increase in the frequency of the total aberrations (p < 0.05). These elevations were restricted to a single sex in each case and were not reproduced at the higher dose levels. It was concluded, therefore, that Diethylene glycol dimethyl ether was not clastogen.

Applicant's summary and conclusion

Interpretation of results: negative
Diethylene glycol dimethyl ether did not produce detectable significant aberrations of the bone marrow metaphase chromosomes of rats when inhaled at concentration up to 1000 ppm.
Executive summary:

Diethylene glycol dimethyl ether was tested in the chromosome aberration test in rats. Rodents were exposed to Diethylene glycol dimethyl ether atmospheres for 7 h/d for either 1 or 5 days. According to the test procedure the animals were killed 6, 4 and 48 hours (single exposure) or 6 h (5-day exposure) after administration.

Ethyl methanesulfonate (EMS) was used as positive control substance and administered orally.

Diethylene glycol dimethyl ether did not produce a detectable significant aberration of the bone marrow metaphase chromosomes of rats.