Bismuth trinitrate

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:

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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Bismuth oxide salicylate

EC Number:

238-953-1

EC Name:

Bismuth oxide salicylate

Cas Number:

14882-18-9

IUPAC Name:

2-hydroxy-4H-1,3,2-benzodioxabismin-4-one

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.

Controls

Controls 1

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

Controls 2

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)

Controls 3

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

Controls 4

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.