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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 guidelineopen allclose all
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
Qualifier:
according to guideline
Guideline:
EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
Deviations:
not specified
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

Constituent 1
Reference substance name:
83929-47-7
IUPAC Name:
83929-47-7
Constituent 2
Chemical structure
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
Controlsopen allclose all
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
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.