2-ethoxynaphthalene-1-carbonyl chloride

Genetic toxicity: in vitro

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

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

Test material information

Constituent 1

Reference substance name:

Diethyl fumarate

EC Number:

210-819-7

EC Name:

Diethyl fumarate

Cas Number:

623-91-6

Molecular formula:

C8H12O4

IUPAC Name:

1,4-diethyl (2E)-but-2-enedioate

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 / cell type:

bacteria, other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type 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 / solvent:

Vehicle
- Vehicle(s)/solvent(s) used: Acetone

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle 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 experimental 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:

bacteria, other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

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.

Remarks on result:

other: No mutagenic effect were observed

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.