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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:
experimental study
Adequacy of study:
key study
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented publication.

Data source

Reference
Reference Type:
publication
Title:
Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals.
Author:
Zeiger, E.; et al.
Year:
1986
Bibliographic source:
Environ. Mutagen. 9, 1-109

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not specified
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Bismuth subsalicylate
- No further details are given.

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-mix
Test concentrations with justification for top dose:
The test substance was tested initially at half-log doses up to a dose that elicited toxicity.
Doses: 0, 3.3, 10, 33, 100, 333, 666 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
A maximum of 0.05 mL solvent was added to each plate.
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without metabolic activation; strains TA1535 and TA100
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
without metabolic activation; strains TA97 and TA1537)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylendiamine
Remarks:
without metabolic activation; strain TA98
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
with metabolic activation; all strains
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes at 37°C
- Expression time: The histidine-revertant (his+) colonies arising on these plates were counted following 2 days incubation at 37°C.

NUMBER OF REPLICATIONS: At least 5 doses were tested in triplicate. Experiments were repeated at least 1 week following the initial trial.

EVALUATION: The plates were hand-counted when a precipitate was present; otherwise automatic colony counters were used.

DETERMINATION OF CYTOTOXICITY
- Method: The test substance was tested initially in a toxicity assay to determine the appropriate dose range. The toxicity assay was performed by using TA 100. Toxic concentrations were those at which a decrease in the number of his+ colonies was seen or at which there was a clearing in the density of the background lawn.

No further details are given.
Evaluation criteria:
An individual trial was judged mutagenic (+) if a dose-related increase over the corresponding solvent control was seen, and it was judged weekly mutagenic (+W) if a low-level dose response was seen. A trial was considered questionable if a dose-related increase was judged insufficiently high to justify a call of "+W", if only a single dose was elevated over the control, or if a non-dose-related increase was seen.
A chemical was judged to be mutagenic, or weakly mutagenic, if it produced a reproducible, dose-related increase in his+ revertants over the corresponding solvent controls in replicate trials. A chemical was considered to be questionable if a reproducible increase of his+ revertants did not meet the criteria for either a mutagenic or weakly mutagenic, or if only single doses produced an increase in his+ revertants in repeat trials.
Statistics:
According to the guideline for a bacterial reverse mutation assay (e.g. Ames test), statistical analysis is not mandatory.

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:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
No further details are reported.
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

Bismuth subsalicylate is non mutagenic in the reverse mutation assay with Salmonella typhimurium, tested with doses up to 666µg/plate.
Executive summary:

Bismuth subsalicylate is non mutagenic in the reverse mutation assay with Salmonella typhimurium, tested with doses up to 666µg/plate.