9H-Carbazole-9-propanoic acid, 3-[[(4-fluorophenyl)sulfonyl]amino]-1,2,3,4-tetrahydro-, compd. with 1-butanamine (1:1), (3R)-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across, GLP study, only 4 Salmonella strains tested

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

1989

Materials and methods

Principles of method if other than guideline:

Salmonella/microsome test as described by Ames et al. (1973, 1975) and Maron and Ames (Mutation Research 113, 173-215, 1983)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

116649-85-5

Cas Number:

116649-85-5

IUPAC Name:

116649-85-5

Constituent 2

Reference substance name:

Bay U 3405

IUPAC Name:

Bay U 3405

Method

Target gene:

Histidine gene locus

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced male rat liver S9 mix

Test concentrations with justification for top dose:

First experiment: 0, 500, 1000, 2000, 4000, 8000 µg/plate (+/-S9 mix, all strains)
Second/third experiment: 0, 325, 650, 1300, 2600, 5200 µg/plate (+/- S0 mix, all strains)

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sodium azide (only TA 1535), nitrofurantoin (only TA 100), 4-nitro-1,2-phenylene diamine (TA 1537 and TA 98), 2-aminoanthracene (all strains with S9 mix).

Remarks:

The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine and cumene hydroperoxide were only used without S9 mix; the positive control 2-aminoanthracene was only used with S9 mix.

Details on test system and experimental conditions:

METHOD: Standard plate test; each concentration including the controls was tested in 4 parallel plates.

Evaluation criteria:

A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas for TA 1537 at least a threefold increase should be reached. For TA 102 an increase of about 100 mutants should be reached. Otherwise, the result is evaluated as negative. However, these criteria may be overruled by good scientific judgment. In case of questionable results, investigations should continue, possibly with modifications, until a final evaluation is possible.

Statistics:

not specified

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:

a bacteriotoxic effect at 325 µg/plate and above, however, the doses could nevertheless be used for assessment purposes

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

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

The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, and 2-aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Executive summary:

The mutagenic potential of Bay U 3405 was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 in the presence and absence of S9 mix. Bay U 3405 produced bacteriotoxic effects at 325 µg/plate and above. Nevertheless, the doses could be used for assessment purposes. No evidence of mutagenic activity was seen in the treated cultures with and without S9 -mix. Thus, the test item can be considered as non- mutagenic in the Ames Test.