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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:
1986-11-10 to 1986-11-24
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP accreditated laboratory. Result negative but no independet repeats followed.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Tin (II) methanesulfonate
- Physical state: white powder
- Storage condition of test material: at room temperature, light protected

Method

Target gene:
not applicable
Species / strain
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9-mix (rat-liver homogenate (Aroclor induced); lot umber 07415; protein content - 35.7 mg/mL)
Test concentrations with justification for top dose:
Preliminary toxicity determination: 0, 19, 39, 78, 156, 312, 625, 1250, 2500 and 5000 µg/plate
Experiment 1: 0, 8, 40, 200, 1000 and 5000 µg/plate (with and without metabolic activation)
Experiment 2: 0, 61.7, 185, 555, 1666 and 5000 µg/plate (with and without metabolic activation)
Vehicle:
- Vehicle(s)/solvent(s) used: A. dest.
50 mg of tin (II) methanesulfonate was dissolved in 1 mL A. dest.
Controlsopen allclose all
Negative controls:
no
Solvent controls:
yes
Remarks:
A. dest.
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
Positive control: without metabolic activation; 0.25 µg/plate for strains TA 100 and TA 1535
Negative controls:
no
Solvent controls:
yes
Remarks:
A. dest.
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
Positive control: without metabolic activation; 5 µg/plate for strain TA 98
Negative controls:
no
Solvent controls:
yes
Remarks:
A. dest.
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Positive control: without metabolic activation; 50 µg/plate for strains TA 1537
Negative controls:
no
Solvent controls:
yes
Remarks:
A. dest.
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene
Remarks:
Positive control: with metabolic activation; 2.00 µg/plate for strains TA 1535 and TA 1537; 0.25 µg/plate for strains TA 100 and TA 98
Details on test system and conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 72 hours

NUMBER OF REPLICATIONS: 3

NUMBER OF CELLS EVALUATED:
The number of his+ revertants was counted and recorded.

PRELIMINARY TOXICITY DETERMINATION:
To know from which concentration on a compound shows toxicity for the tester strains, before mutagenicity testing, the survival, spontaneous reversion and the inhibition of the background lawn of auxotrophic cells of one of the strains (TA 100) is determined at different concentrations of the compound.
Bacterial cells are exposed to different concentrations of the compound and after incubation the background lawn and the number of spontaneous revertants are examined.
Parallel appropriate (10^-6) dilutions of the cells are plated on NB agar plates and the influence of the compound over the survival of the cells is determined.
Evaluation criteria:
A compound will be considered to be mutagenic if the following criteria are fullfilled: if the his+ revertants of the solvent control lie in the normal range, at least for one strain a dose response effect must exist and the greatest increase of the revertant colonies has to be two times higher than the solvent control. The result has to be reproducible.

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:
no, but tested up to limit concentrations
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: TA100, TA1535, TA98, TA1537
Additional information on results:
PRELIMINARY TOXICITY DETERMINATION:
The test compound did not show toxicity up to a concentration of 5000 µg per plate.
Therefore the mutagenicity experiments were performed in a concentration range from 8 µg to 5000 µg (1. experiment) resp. 61.7 µg to 5000 µg (2.experiment) per plate.

MUTAGENICITY EXPERIMENTS:
The controls without mutagen showed a normal number of revertants
The positive controls demonstrated the sensibility of the indicator strains and the activity of the metabolising system. The sterility controls of top agar, S9-mix and test compound showed no growth.
The results of the mutagenicity experiments with the test compound tin (II) methanesulfonate indicate, that in the tested concentration range with and without metabolic activation no significant increase of his+ revertants over the spontaneous values could be detected with the tester strains TA100, TA1535, TA98 and TA1537.

Please also refer for results to the field "Attached background material" below.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

It is concluded that tin (II) methanesulfonate showed no evidence of mutagenic activity in this bacterial system under the test conditions employed.