Bis(2-(2-methoxyethoxy)ethyl) ether

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

received: 26 Nov 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The target chemical belongs to the homologues series of glymes, where there is an incremental increase in the number of CH2CH2O units. Therefore, it can be assumed that target and other glyme members (mono-, di-, and triglyme) share the same toxic mode action.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro)

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-methoxyethyl) ether

EC Number:

203-924-4

EC Name:

Bis(2-methoxyethyl) ether

Cas Number:

111-96-6

Molecular formula:

C6H14O3

IUPAC Name:

1-methoxy-2-(2-methoxyethoxy)ethane

Constituent 2

Reference substance name:

Diglyme

IUPAC Name:

Diglyme

Constituent 3

Reference substance name:

Bis(2-methoxyethyl)ether

IUPAC Name:

Bis(2-methoxyethyl)ether

Details on test material:

- physical state: clear colourless liquid
- MW 134.18
- LogPow - 0.36
- Vapour pressure (20°C) 60 Pa
- Water solubility miscible

Method

Species / strain

Species / strain / cell type:

other: Human embryonic intestinal fibroblasts

Details on mammalian cell type (if applicable):

at passages 12 and 35
obtained from Flow Laboratories, Irvine, Scotland

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

up to 19 mg/mL

Vehicle / solvent:

no data

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

Cells were routinely cultured in Dulbecco's modification of Eagle's minimalessential medium (DMEM), 10% heat-inactivated fetal calf serum (FCS), 2 mM Glutamine, and 10 µg Gentamycin/mL. Prior to an experiment, cells were harvested, 2 mL (5x10(exp)4 cells/mL) transfered to Petri dishes containing three sterile coverslips, and incubated for 72 h. At the end of this period, the medium was replaced with 2 mL Arginine-deficient DMEM, 5% FCS. This medium was changed after 24h and incubation continued for 48h. At this stage, Hydoxyurea and 6-[3H]Thymidine were added to all dishes to give final concntrations of 2.5 mM and 10 µCi/mL, repsectively. Incubation were conducted with the test compound both in the absence and presence of S9 mix for 3h at 37°C, after which Kodak AR-10 stripping film was used to coat the fixed cultures. Giemsa-stained autoradiographs were examined and grain counts made on 50 nuclei per coverslip. Data recorded were mean nuclear grain counts and standard deviations for 150 nuclei.

Evaluation criteria:

no data

Statistics:

no data

Results and discussion

Test results

Species / strain:

other: Human embryonic intestinal fibroblasts

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

There was no indication of increased UDS in cells exposed for 3 h tp concentrations of Diethylene glycol dimethyl ether up to nearly 19 mg/mL.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Analogue approach justification (target chemical: tetraglyme; source chemical: diglyme):

a.   The target chemical belongs to the homologues series of glymes, where there is an incremental increase in the number of CH2CH2O units. Therefore, it can be assumed that target and other glyme members (mono-, di-, and triglyme) share the same toxic mode action.

b.   The findings in repeated dose toxicity studies are comparable for target and source chemicals: the target is the male reproductive organ. Further, findings in thymus and altered hematological values are indicative of altered blood system.

c.    The findings in reproductive performance are comparable: No live pubs and/or reduced number of pubs were the common finding.

d.   The findings in developmental toxicity studies are comparable: the most notable findings were paw skeletal malformations. These findings were observed also at dose levels not associated with apparent maternal toxicity

Applicant's summary and conclusion

Conclusions:

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

Based on the read-across approach using glymes as source substances, tetraglyme is considered to be not genotoxic.

Executive summary:

In absence of sufficient data to assess the genotoxicity of tetraglyme, a read across approach is proposed using other glymes as source chemicals. In the reported study, diglyme was not mutagenic in the UDS test similar to current OECD Guideline 482. Combining results of all available studies (9 in-vitro studies and 4 in-vivo studies), tetraglyme is considered to be not genotoxic.