4-amino-2,5-dimethoxy-N-methylbenzenesulphonamide

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:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well performed OECD study with GLP

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:

4-amino-2,5-dimethoxy-N-methylbenzenesulphonamide

EC Number:

256-435-3

EC Name:

4-amino-2,5-dimethoxy-N-methylbenzenesulphonamide

Cas Number:

49701-24-8

Molecular formula:

C9H14N2O4S

IUPAC Name:

4-amino-2,5-dimethoxy-N-methylbenzene-1-sulfonamide

Details on test material:

Purity: 99.5 %

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:

rat S9 mix

Test concentrations with justification for top dose:

50, 160,500, 1600 and 5000 IJg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

sodium azide

other: 9-aminoacridine hydrochloride hydrat, 1-methyl-3-nitro-1-nitrosoguadine, 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.

Statistics:

not mandatory for Ames test

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:

negative

Cytotoxicity / choice of top concentrations:

not determined

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):
other: negativ with and without metabolic activation

The results lead to the conclusion that 4-Amino-2,5-dimethoxy-N-methylbenzolsulfonamid is not mutagenic in these bacterial test systems either in the absence or in the presence of an exogenous metabolizing system.

Executive summary:

4-Amino-2,5-dimethoxy-N-methylbenzolsulfonamid 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, each in the absence and in the presence of an Aroclor-induced metabolizing system derived from a rat liver homogenate. For both studies, the compound was suspended in DMSO, and each bacterial strain was exposed to 5 dose levels. Concentrations for both studies were 50, 160, 500, 1600 and 5000 µg/plate. 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 mutagenicity experiment toxicity was only observed without metabolic activation at the concentration of 500 µg/plate in the strain TA 1537 and at concentrations of 1600 µg/plate and above in the tester strain TA 98. In the presence of metabolic activation the test compound proved to be not toxic to the bacterial strains. In the preincubation test toxicity was observed without metabolic activation in a dose range of 50 µg/plate and above but only in the tester strain TA 98. In the presence of metabolic activation the test compound proved to be toxic to the bacterial strain TA 1537 at a concentration of 1600 µg/plate. Mutagenicity: In the absence and in the presence of the metabolic activation system 4-Amino-2,5-dimethoxy-N-methylbenzolsulfonamid did not result in relevant increases in the number of revertants in any of the bacterial strains.