Benzoic acid, 2-fluoro-5-(methylsulfonyl)-

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

Study period:

January 2011 - October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-fluoro-5-methanesulfonylbenzoic acid

EC Number:

689-137-0

Cas Number:

247569-56-8

Molecular formula:

C8 H7 F O4 S

IUPAC Name:

2-fluoro-5-methanesulfonylbenzoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Description White solid
Purity 99.5%
Batch number BS11020465
BMG Substance number M1204-02810-01
CAS number 247569-56-8
Date received 18 June 2012
Expiry date 21 May 2013
Storage conditions Room temperature in the dark

Method

Target gene:

Salmonella typhimurium
Strains Genotype
TA1537 his c 3076; rra-; uvra-:




Type of mutations indicated


frame shift mutations








TA98

TA1535
TA100
Escherichia coli








his D 3052; rfa-; uvrB-;R-factor his G 46; rfa-; uvra-:
his G 46; rra-; uvra-; R-factor











base-pair substitutions















Strain Genotype
WP2uvrA trp-; uvrA:















Type of mutations indicated

base-pair substitution

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

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'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The test item, 5-Methylsulfonyl-2-fluorobenzoic acid R04638493, was considered to be non-mutagenic under the conditions of this test.

Executive summary:

Introduction

The test method was designed to be compatible with the guidelines for

bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including

METI, MHLW and MAFF, the OECD Guidelines for Testing of Chemicals No.

471 "Bacterial Reverse Mutation Test", Method 813/14 of Commission Regulation (EC) number 440/2008

of 30 May 2008 and the USA, EPA (TSCA) OPPTS harmonised guidelines.

Methods

Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain

WP2uvrA were treated with the test item, 5-Methylsulfonyl-2- fluorobenzoic acid R04638493, using

both the Ames plate incorporation and pre­ incubation methods at up to six dose levels, in

triplicate, both with and without the addition of a rat liver homogenate metabolising system (10%

liver S9 in standard co­ factors). The dose range for the first experiment was determined in a

preliminary toxicity assay and was 50 to 5000 microg/plate. The experiment was repeated on a

separate day (pre-incubation method) using an amended dose range (15 to 5000 microg/plate}, fresh

cultures of the bacterial strains and fresh test item formulations.

An additional dose level and an expanded dose range were selected in Experiment 2 in order to

achieve both four non-toxic dose levels and the potential toxic limit of the test item following

the change in test methodology.

Results

The vehicle (dimethyl sulphoxide) control plates gave counts of revertant colonies

generally within the normal range. All of the positive controls used in the test induced marked

increases in the frequency of revertant colonies, both with or without metabolic activation. Thus,

the sensitivity of the assay and the efficacy of the 59-mix were validated.

In the first experiment (plate incorporation method), the test item caused no visible reduction in

the growth of the bacterial background lawns of any of the tester strains except for Salmonella

strain TA1537 which exhibited weakened lawns at 5000 microg/plate in the absence of S9-mix only. In

Experiment 2 (pre-incubation method) there was no evidence of toxicity to any tester strain at any

test item dose in either the absence or presence of S9-mix. The test item was tested up to the

maximum recommended dose level of 5000 microg/plate. No test item precipitate was observed on the plates at any of the doses

tested in either the presence or absence of S9.

No significant increases in the frequency of revertant colonies were recorded for any of the

bacterial strains, with any dose of the test item, either with or without metabolic activation or

exposure method.