N-[4-(aminocarbonyl)phenyl]-4-methoxy-3-nitrobenzamide

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: well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-[4-(aminocarbonyl)phenyl]-4-methoxy-3-nitrobenzamide

EC Number:

298-790-7

EC Name:

N-[4-(aminocarbonyl)phenyl]-4-methoxy-3-nitrobenzamide

Cas Number:

93839-20-4

Molecular formula:

C15H13N3O5

IUPAC Name:

N-(4-carbamoylphenyl)-4-methoxy-3-nitrobenzamide

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9-mix

Test concentrations with justification for top dose:

First plate incorporation test: 0, 50, 160, 500, 1600 and 5000 µg/plate
Second plate incorporation test: 0, 5, 10, 25, 50, 100 and 160µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

other: N-Methyl-N-nitro-N-nitrosoguanidine, 2-aminoanthracene

Evaluation criteria:

The assay is considered valid if the following criteria are met:
- the solvent control data are within the laboratory's normal control range for the spontaneous mutant frequency
- the positive controls induced increases in the mutation frequency which were both statistically significant and within the laboratory's normal range

A test compound is classified as mutagenic if it has either of the following effects:
a) it produces 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
b) it induces a dose-related 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 in at least two to three concentrations of the test compound at complete bacterial background lawn.

If the test substance does not achieve either of the above criteria, it is considered to show no evidence of mutagenic activity in this system

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

TA 98, TA 1537, TA 100 with and without S9-mix, TA 1535 and WP2 uvrA with S9-mix

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'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

The results lead to the conclusion that the tested substance is mutagenic in these bacterial test systems with and without an exogenous metabolizing system.

Executive summary:

The substance was tested for mutagenicity with the strains TA 100, TA 1535, TA 1537 and TA 98 of Salmonella typhimurium and Escherichia coli WP2uvrA. Two independent mutagenicity studies were conducted (two plate incorporation tests), each in the absence and in the presence of a metabolizing system derived from a rat liver homogenate. The second plate incorporation test was performed only with the strains TA 100 and TA 1537 in the absence and in the presence of S9-mix. For both studies, the compound was dissolved in DMSO, and each bacterial strain was exposed to 5 dose levels, respectively 6 dose levels in the second plate incorporation test. The contentrations for the first plate incorporation test were 50, 160, 500, 1600 and 5000 µg/plate. Because of toxicity and mutagenicity in the first plate incorporation test dose levels from 5 to 160 µg/plate were chosen for the second plate incorporation test. Control plates without mutagen showed that the number of spontaneous revertant colonies was within the laboratory's historical control range. All the positive control compounds showed the expected increase in the number of revertant colonies.

Toxicity: In the first plate incorporation test toxicity was observed with and without metabolic activation at a concentration of 160 µg/plate and above. Additionally, in the absence of metabolic activation the test compound proved to be toxic to the bacterial strain TA 1537 at the concentration of 50 µg/plate. In the second plate incorporation test toxicity was observed with and without metabolic activation in a dose range of 50 to 100 µg/plate and above.

Mutagenicity: In the absence and in the presence of the metabolic activation system the test compound induced a significant and dose-dependent increase in the number of revertant colonies with the bacterial strain TA 100. At toxic doses increased numbers of revertants were obtained with S9-mix in the strains TA 1535 and WP2 uvrA, and with and without S9-mix in the tester strains TA 1537 and TA 98.