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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:
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'.

Any other information on results incl. tables

This study is read across to related substance, bismuth subsalicylate (see structure attached below).

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.