Methyl 4-[[(2,5-dichlorophenyl)amino]carbonyl]-2-nitrobenzoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 471), with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Test not performed with the strains E. coli WP2 uvrA, or E. coli WP2 uvrA (pKM101), or S. typhimurium TA102

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EU Method B.14 (Mutagenicity -Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

83929-47-7

IUPAC Name:

83929-47-7

Constituent 2

Reference substance name:

Methyl 4-[[(2,5-dichlorophenyl)amino]carbonyl]-2-nitrobenzoate

EC Number:

281-339-3

EC Name:

Methyl 4-[[(2,5-dichlorophenyl)amino]carbonyl]-2-nitrobenzoate

Cas Number:

83929-47-9

Molecular formula:

C15H10Cl2N2O5

IUPAC Name:

methyl 4-[(2,5-dichlorophenyl)carbamoyl]-2-nitrobenzoate

Details on test material:

- Name of test material (as cited in study report): Nitro-MMT-2,5-dichloranilid TTR

Method

Species / strain

Species / strain / cell type:

other: S. typhimuriumTA 98, TA 100, TA 1535, TA 1537

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9 mix

Test concentrations with justification for top dose:

0, 4, 20, 100, 500, 2500, 5000 µg/plate

Vehicle / solvent:

- Vehicle used: DMSO

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sodium-azide (TA 100, TA 1535), 9-Aminoacridine (TA1537), 2-Nitrofluorene (TA98)

Remarks:

without metabolic activation

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene (all strains)

Remarks:

with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation
INCUBATION TIME: 48-72 h
NUMBER OF REPLICATIONS: 3 plates per concentration per test, two independent tests

OTHER: Animals (for rat liver S9) were pretreated with Aroclor 1254 as inducer of several drug metabolizing enzymes.

Evaluation criteria:

- at least a 2-fold increase in the mean number of revertants per plate of at least one of the tester strains over the mean number of revertants per plate of the appropriate vehicle control at complete bacterial background lawn

or

- a dose related increase in the mean number of revertants per plate or at least one of the tester strains over the mean number of revertants per plate of the appropriate vehicle control in at least two to three concentrations of the test compound at complete bacterial background lawn

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 98, TA 100, TA 1535, TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

- Precipitation: visible at concentrations of 500 µg/plate and above

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- dose-related toxicity at concentration of 2500 µg/plate and above in the presence of metabolic activation with the tester strains TA 100 and TA 1537
- without metabolic activation toxicity was observed at concentration of 500 µg/plate and above (TA 1537, TA 98) and 2500 µg/plate and above (TA 100, TA 1535)

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The test item did not exert mutagenic activity in the reverse bacterial mutation assay (plate incorporation) with or without metabolic activation (induced rat liver S9) under the conditions tested.

Executive summary:

Mutagenic activity of the test item was investigated in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 with and without metabolic activation (induced rat liver S9) at concentrations of 4, 20, 100, 500, 2500 and 5000 µg/plate.

The test item did not reveal any mutagenic activity under the conditions tested (plate incorporation assay). The appropriate reference substances showed distinct positive mutagenic effects.