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Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
his+
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
0-6666ug/plate
Vehicle / solvent:
DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 4-nitro-o-phenylenediamine & 2-aminoanthracene
Details on test system and experimental conditions:
The test substance was assayed for mutagenicity in the preincubation assay. Concurrent solvent and positive controls were tested with and without the metabolic activation systems (S9 mix [hamster and rat]). At least five dose levels were tested, with three plates per dose level.
Evaluation criteria:
-Mutagenic response: a dose-related, reproducible increase in the number of revertants over background, even if the increase was less than twofold
-Nonmutagenic response: when no increase in the number of revertants was elicited by the chemical
-Questionable response: when there was an absence of a clear-cut dose-related increase in revertants, when the dose-related increases in the number of revertants were not reproducible, or when the response was of insufficient magnitude to support a determination of mutagenicity
Statistics:
yes (not further specified)
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

Diethyl carbonate was tested negative in an Ames test with Salmonella typhimurium strains TA 100, TA 1535, TA 1537 and TA 98, with and without metabolic activation, at doses up to 6666 ug/plate.
Executive summary:

Diethyl carbonate was tested negative in an Ames test with Salmonella typhimurium strains TA 100, TA 1535, TA 1537 and TA 98, with and without metabolic activation, at doses up to 6666 ug/plate.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Concerning genotoxicity, the database for diethyl carbonate (DEC) is limited as only one negative Ames test with S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 is available. Therefore, data for dimethyl carbonate (DMC) are taken into further consideration (read across). The two compounds differ with regard to the length of their ester side chain. DEC contains two ethyl and DMC contains two methyl groups. Structural similarity can be calculated by using different models/algorithms and will then result in a percentage of similarity. Using the mathematical model “Yule” from the OECD toolbox (v 2.3) a structural similarity of 88.89% is calculated (15 out of 28 possible atom pairs match to DEC, 4 out of 6 topological torsions and 4 out of 8 atom centred fragments). Although the calculated value has only an indicative character, it confirms the high structural similarity of both compounds.

In a Comet assay with L 929 mice fibroblasts, dimethyl carbonate gave no indications for a DNA damage at concentrations of up to 150 mg/mL.

In an in vivo cytogenetic test for detection of chromosome aberrations in spermatogonial mitoses (study design comparable to OECD Guideline 483), male mice were dosed once orally with 0, 0.99, 1.99 or 3.97 g/kg bw of dimethyl carbonate. The results of this study gave no indications for an increase in chromosome aberrations.

Also the main metabolite ethanol gave no indications for a genotoxic/mutagenic potential. In the OECD SIDS for Ethanol (http://www.inchem.org/documents/sids/sids/64175.pdf) it was stated:

“The balance of evidence is that ethanol is not genotoxic. Negative results from a number of bacterial mutation assays appear to be reliable. Of the mammalian cell mutation assays a weak mutagenic effect in mouse lymphoma cells occurred only at very high ethanol concentrations. In vivo tests for chromosome aberrations in both rats and Chinese hamsters have given negative results. There is very little evidence to suggest that ethanol is genotoxic in somatic cells and it may have a very limited capacity to induce genetic changes in vivo but under very specific circumstances and at very high doses achievable in humans only by deliberate oral ingestion.”

Justification for classification or non-classification

Although the database concerning genotoxicity/mutagenicity for diethyl carbonate is limited, the read across with data from dimethyl carbonate (high structural similarity of both compounds) and also from the main metabolite ethanol is not indicating a significant genotoxic/mutagenic potential for diethyl carbonate. Therefore, no classification according to EU and GHS criteria is required.