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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
30 November 1982 - 2 March 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented guideline study with minor deviations to current OECD guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
early first ampling, 50 instead of 100 cells/animal analysed
Qualifier:
according to
Guideline:
other: OECD Guideline 422, Final Draft November 1982
Deviations:
no
GLP compliance:
not specified
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
colorless, clear liquid
Purity: 99.8%
Molecular weight: 90.1 g/mol

Test animals

Species:
hamster
Strain:
other: Han: Chinese
Sex:
male/female
Details on test animals and environmental conditions:
-Body weight
males: 20-34 g
females: 21-31 g
- Housing: single in Makrolon type-1 cages with wire mesh tops and softwood bedding
- Room temperature: 22 +/- 2°C
- Humidity: 55 +/- 10%
- 12 hours light/12 hours dark
- Acclimatisation period: 5 days
- Diet: Hamster-Diät Altromin 7010 ad libitum
- Water: Community tap-water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Water
Details on exposure:
All animals were treated with 2000 Ethylene glycol dimethyl ether mg/kg bw by a single oral application. In parallel animals of the negative control group received water (vehicle) and animals of the positive control group were treated with 100 mg endoxan/kg bw i.p. 4, 24 and 48 hours after the application all animals received a Colcemid injection and were killed after a further 2 hours by using CO2.
Duration of treatment / exposure:
1 single application
Frequency of treatment:
1 single application
Post exposure period:
6, 26 and 50 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
2000 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
5 per sex, dose and termination point
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (Endoxan) 100 mg/kg bw i.p.

Examinations

Tissues and cell types examined:
Bone marrow cells:
50 metaphase spreads were scored per animal for completeness and aberration of chromosomes.
Details of tissue and slide preparation:
4, 24 and 48 hours after the application of Ethylene glycol dimethyl ether all animals received a Colcemid injection and were killed after a further 2 hours by using CO2 and the adhering muscle and epiphysis of one femur were removed. The marrow "plug" was removed with a syringe and aspirated into 2 mL of Hanks´balanced salt solution (BSS) in a test tube and capped. The specimens were centrifuged at 1,500 rpm for 5 min, decanted and 2 mL of hypotonic 0.5% KCl solution was added with gentle agitation to resuspend the cells. Following centrifugation for 5 min at 1,500 rpm, the supernatant was decanted and the remaining cells resuspended. 4 mL 1% Sodium citrate solution were added and the resulting cell suspension was incubated at 37°C for 20 minutes. After centrifugation (1,500 rpm, 5 minutes) the supernatant was decanted and 2 mL of fixative (3:1 absolute Ethanol:glacial acetic acid) was added. The cells were resuspended in the fixative with gentle agitation, capped and placed at 4°C fovernight. The fllowing day the specimens were again centrifuged, decanted, prepared fixative was added and the cells were resuspended. 2-3 drops of the suspension were allowed to drop onto a clean, dry slide. The slides were dried at roomtemperature. The slides were stained using Giemsa solution for 10 min, rinsed in acetone, 1:1 bidestilled water, and placed in fresh xylene. Suitable metaphase spreads that were countable were examined.
Evaluation criteria:
No data
Statistics:
No data

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
yes
Additional information on results:
Toxicity:
All animals survived. There were no clinical signs.

Chromosome Aberration Study Results:
Ethylene glycol dimethyl ether did not produce detectable significant aberration of the bone marrow metaphase chromosomes of hamsters when administered orally at 2000 mg/kg.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Ethylene glycol dimethyl ether did not produce detectable significant aberrations of the bone marrow metaphase chromosomes of hamsters when administered orally at 2000 mg/kg.
Executive summary:

Triethylene glycol dimethyl ether and Ethylene glycol dimethyl ether, which is tested in vivo for its genotoxic potential, belong to the glycol ether family. These substances have been demonstrated to be very similar in structure, physical/chemical properties and the toxicological profile. Due to the fact that Ethylene glycol dimethyl ether and Triethylene glycol dimethyl ether have nearly the same chemical structure (especialy with reference to the functional groups):

1. Triethylene glycol dimethyl ether:H3C-O-CH2-CH2-O -CH2-CH2-O-CH2-CH2-O-CH3

2. Ethylene glycol dimethyl ether:H3C-O-CH2-CH2-O-CH3

the same mode of interaction with bio-macromolecules, living cells and tissue and metabolic pathway is expected. Therefore, a read-across from Triethylene glycol dimethyl ether to data obtained with Ethylene glycol dimethyl ether is scientifically justified.

Ethylene glycol dimethyl ether was tested in the chromosome aberration test in hamsters. The test item was diluted with water and dosed at 2000 mg/kg bodyweight to male and female hamsters. According to the test procedure the animals were killed 6, 26 and 50 hours after administration.

Cyclophosphamide was used as positive control substance and administered intraperitoneally at a dose of 100 mg/kg bodyweight.

The chromosomal abnormalities observed in the positive controls were significantly higher than the solvent control or Ethylene glycol dimethyl ether. Ethylene glycol dimethyl ether did not produce a detectable significant aberration of the bone marrow metaphase chromosomes of hamsters.