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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:
weight of evidence
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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
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.