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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from J-Check

Data source

Reference
Reference Type:
other: Collection of data
Title:
In vitro Genetic toxicity study for Dimethyl naphthalene-2,6-dicarboxylate
Author:
National Institute of Technology and Evaluation
Year:
2017
Bibliographic source:
Japan chemicals collaborative knowledge database (J-check), 2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Principles of method if other than guideline:
To evaluate the mutagenic potential of Diethyl Fumarate in Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA by Bacterial reverse mutation assay.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Details on test material
- Name of test material (as cited in study report): Diethyl Fumarate
- Molecular formula: C8H12O4
- Molecular weight: 172.20 g/mol
- Substance type: Organic
Specific details on test material used for the study:
Details on test material
- Name of test material (as cited in study report): Diethyl Fumarate
- Molecular formula: C8H12O4
- Molecular weight: 172.20 g/mol
- Substance type: Organic
- Purity; : 93.3%

Method

Target gene:
Histidine for Salmonella typhimurium and tryptophan Escherichia coli
Species / strain
Species / strain:
other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Details on mammalian cell lines (if applicable):
Not applicable
Additional strain characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
Rat liver, induced with phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose:
without metabolic activation
0, 9.375, 18.75, 37.5, 75, 150, 300µg/plate (TA100),
0, 78.13, 156.3, 312.5, 625, 1250, 2500µg/plate(TA1535, TA98, TA1537),
0, 156.3 312.5, 625, 1250, 2500, 5000µg/plate (WP2)
With metabolic activation method
0, 312.5, 625, 1250, 2500 5000 µg/plate
Vehicle:
Vehicle
- Vehicle(s)/solvent(s) used: Acetone
Controls
Negative controls:
not specified
Solvent controls:
yes
Remarks:
Acetone
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: -S9, AF-2 (TA100, WP2, TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537) +S9, 2-aminoanthracene (all strains)
Details on test system and conditions:
Details on test system and conditions
METHOD OF APPLICATION: Plate incorporation method
NUMBER OF REPLICATIONS: Duplicate

OTHER EXAMINATIONS: 3 plates per test were observed.
Rationale for test conditions:
Not specified
Evaluation criteria:
Evaluation was done considering a dose dependent increase in the number of revertants/plate.
Statistics:
Not specified

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
yes
Negative controls valid:
not specified
Positive controls valid:
yes
Remarks on result:
other: No mutagenic effect were observed
Additional information on results:
Additional information on results
ADDITIONAL INFORMATION ON CYTOTOXICITY: Toxicity was observed at a concentration of 300µg/plate without metabolic activation, and 5000
µg/plate with metabolic activation.

Applicant's summary and conclusion

Conclusions:
Diethyl Fumarate (623-91-6) was evaluated for its mutagenic potential in Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA by AMES test. The test result was considered to be negative in all strain in the presence and absence of metabolic activation S9.
Executive summary:

Genetic toxicity in vitro study was assessed for Diethyl Fumarate. For this purpose AMES test was performed according to Guidelines for Screening Mutagenicity Testing of Chemicals (Japan).The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA in the presence and absence of metabolic activation S9. The concentration of test material used in the absence of metabolic activation were 0, 9.375, 18.75, 37.5, 75, 150, 300µg/plate (TA100),0, 78.13, 156.3, 312.5, 625, 1250, 2500µg/plate(TA1535, TA98, TA1537) and 0, 156.3 312.5, 625, 1250, 2500, 5000µg/plate (WP2). While concentration used in the presence of metabolic activation were 0, 312.5, 625, 1250, 2500 5000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore Diethyl Fumarate was considered to be non mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA by AMES test. Hence the substance cannot be classified as gene mutant in vitro.