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Toxicological information

Genetic toxicity: in vitro

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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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

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.