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

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given, comparable to guidelines, but no replication of the test

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

no replication of the test

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Deviations:

yes

Remarks:

no replication of the test

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

261-853-4

EC Name:

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

Cas Number:

59673-82-4

Molecular formula:

C15H12Cl2N2O3

IUPAC Name:

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

Details on test material:

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

Method

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 100, TA 1535, TA 1537, TA 1538, TA 98 and E.coli WP2uvrA

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:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Na-azide (TA 100, TA 1535), 9-Aminoacridine (TA1537), 2-Nitrofluorene (TA98, TA 1538), N-Methyl-N'-nitro-N-nitrosoguanidine (WP2uvrA)

Remarks:

without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Benzo[a]pyrene (all strains), 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, no replication of the test

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

Evaluation criteria:

positive: significant increase in the number of revertant colonies or dose dependent increased in the number of revertant colonies
negative: no significant increase in the number of revertant colonies and no dose dependent increased in the number of revertant colonies

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 100, TA 1535, TA 1537, TA 1538, TA 98 and E.coli WP2uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

except for slight cytotoxicity for TA 100 at the higest dose level tested

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

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

ADDITIONAL INFORMATION ON CYTOTOXICITY:
no cytotoxicity observed for up to 5000 µg/plate for most of the bacterial strains; the test item was slightly toxic for TA 100 at 5000 µg/plate as indicated by an incomplete bacterial lawn.

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, TA 1537 and TA 1538, as well as in Escherichia coli WP2uvrA 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.