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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro DNA damage and/or repair study
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
January 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and guideline conform study.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro)
Deviations:
no
GLP compliance:
yes
Type of assay:
DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
None

Method

Species / strain
Species / strain:
other: permanent human cell line A549
Details on mammalian cell lines (if applicable):
American Type Culture Collection Nr. CCL 185
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
1000, 300, 100, 30, 10, 3, 1, 0.3 and 0.1 µg/mL
Vehicle:
water
Controls
Negative controls:
not specified
Solvent controls:
yes
Remarks:
DMSO
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: 4-Nitroquinoline-N-oxide, Benzo(a)pyrene
Details on test system and conditions:
The cells were seeded with 4 x 10(exp)5 cells/35 mm culture dish in Dulbecco's modification of minimum medium Eagle containing 10% fetal calf serum, and replicative DNA-synthesis was inhibited by arginine starvation for two days and the addition of 10 mM hydroxyurea to the medium during the assay.
Ethylen glycol dimethyl ether was dissolved in water. 4-Nitroquinoline-N-oxide and Benzo(a)pyrene were dissolved in DMSO. All substances were further diluted in culture medium. The end-concentration of DMSO in the respective cultures was kept at 1%. The incubation with the test compounds was performed at 37°C for 3 hours in the presence of 3H-Thymidine and S9 mix where indicated. After incubation the cells were washed, lysed with SDS and the DNA was precipitated with Trichloracetic acid. 3H-Thymidine incorporation was determined by scintillation counting.

Two independent cultures in triplicate
Evaluation criteria:
A chemical is considered to have mutagenic properties, when there is a significant difference in thymidine-incorporation between treated and untreated cultures.
Statistics:
t-Test performed

Results and discussion

Test results
Species / strain:
other: permanent human cell line A549
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not determined
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
Please refer to "Attached background material"

Any other information on results incl. tables

Please refer to "Attached background material"

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

Using cell line A 549, Ethylene glycol dimethyl ether showed no induction of unscheduled DNA-synthesis in concentrations ranging from 1000 µg/mL to 0.1 µg/mL.
Executive summary:

Triethylene glycol dimethyl ether and Ethylene glycol dimethyl ether, which is tested for its gene mutation 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 examined in the UDS test according to OECD Guideline 482. Using cell line A 549, Ethylene glycol dimethyl ether showed no induction of unscheduled DNA-synthesis in concentrations ranging from 1000 µg/mL to 0.1 µg/mL.