Benzoic acid, 2-amino-5-fluoro-, methyl ester

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: GLP- and Guideline-Study with deviations from Guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only four strains of salmonella tested

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EEC Directive 92/69, L383 A, Annex B14

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

methyl 2-amino-5-fluorobenzoate

EC Number:

608-681-1

Cas Number:

319-24-4

Molecular formula:

C8 H8 F N O2

IUPAC Name:

methyl 2-amino-5-fluorobenzoate

Test material form:

other: yellow solid

Details on test material:

Storage conditions: dark at 20 °C
PH of the test item: neutral

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

S9 Rat Liver

Test concentrations with justification for top dose:

4- 5000 µg/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: 2-Aminoanthracene

Evaluation criteria:

a) The test article 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) The test article 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 article at complete bacterialbackground lawn.
The test result must be reproducible.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

with metabilic activation toxic at >= 500 µg/plate; without activation toxic at >= 2500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

2-Amino-5-fluorbenzoesauremethyIester was tested for mutagenicity with the strains TA 100, TA 1535, TA 1537 and TA 98 of Salmonella typhimurium.

The mutagenicity studies were conducted in the absence and in the presence of a metabolizing system derived from rat liver homogenate. A dose range of 7 different doses from 0.8 microgram/plate to 5000 microgram/plate was used.

Control plates without mutagen showed that the number of spontaneous revertant colonies was simiiiar to that described in the literature. All the positive control compounds gave the expected increase in the number of revertant colonies.

Toxicity: The test compound proved to be toxic to most of the bacterial strains at a dose of 2500 microgram/plate and above in the absence of a metabolic activation system.

In the presence of a metabolic activation system toxicity was observed at a concentration of 500 microgram/plate and above.

Therefore 5000 microgram/plate was chosen as top dose level without metabolic activation and 2500 microgram/plate with metabolic activation for the mutagenicity study.

Mutagenicity: In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of a metabolic activation system, treatment of the cells with 2-Amino-5-fluorbenzoesauremethylester did not result in relevant increases in the number of revertant colonies.

Summarizing, it can be stated that 2-Amino-5-f!uorbenzoesauremethylester is not mutagenic in these bacterial test systems neither with nor without exogenous metabolic activation at the dose levels investigated.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The test item did not cause any significant increase in number of revertant colonies with any of the tester strains neither in the absence nor in the presence of S-9 Mix. No dose-dependend effect was obtained. The test was performed in two independent experiments. It is concluded that the test item is not mutagenic in these bacterial test systems neither in the absence nor in the presence of an exogenous metabolizing system.