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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: Conducted similar to guideline. Purity of the test substance is not stated. Not clear if enough indicator cells were used. No GLP, because at the time of the study conduct, GLP was not compulsory.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

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
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): F76-020
- EC number: 231-867-5
- Substance type: pure active substance
- Physical state: solid

Method

Target gene:
not applicable
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
S9-mix
Test concentrations with justification for top dose:
at least six doses: 33.3, 100, 333.3, 1000, 3333.3, 10000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: 0.067M sodium phosphate buffer (pH 7)
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; strain TA 1535

Migrated to IUCLID6: 1.0 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
without metabolic activation; strains TA 1538, TA 98

Migrated to IUCLID6: 5.0 µg/plate
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; strain TA 1537

Migrated to IUCLID6: 50.0 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: AF2; 0.1 µg/plate
Remarks:
without metabolic activation; strain E.coli WP2 vurA
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-anthramine; 1.0, 2.5 or 10.0 µg/plate
Remarks:
with metabolic activation; all strains
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-anthramine; 1.0, 2.5 or 10.0 µg/plate
Remarks:
without metabolic activation; all strains
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 2 or 3 days at 37°C

NUMBER OF REPLICATIONS: The compound was tested in duplicate on all strains.

EVALUATION: The number of his+ revertant colonies is counted and recorded.

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth:
Compound F76-020 was first tested on TA 100 in a range-finding assay at 10 doses between 0.3 and 10,000 µg/plate. No mutagenicity or toxicity
was observed in this assay.

Evaluation criteria:
no data
Statistics:
not mandatory

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No mutagenicity was observed on compound F76-020 in any of the assays performed.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No toxicity was observed on compound F76-020 in any of the assays performed.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No mutagenicity was observed on compound F76-020 in any of the assays performed.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No toxicity was observed on compound F76-020 in any of the assays performed.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
No further details are given.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

For individual results see attached document.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

No mutagenicity or toxicity was observed on the test compound in any of the assays performed. According to the results of the present study, the test substance sodium thiosulphate is not mutagenic under the chosen experimental conditions.
Executive summary:

SRI International examined an FDA compound identified as F76-020. This compound was tested in the Ames Salmonella/microsome assay for induction of reverse mutation in Salmonella typhimurium strains TA1535, TA1538, TA98, and TA 100 and in Escherichia coli WP2 (uvrA} . Each assay was performed in the presence and in the absence of a rat liver homogenate metabolic activation system. Compound F76 -020 was not toxic or mutagenic in these assays. Compound F76 -020 was tested as a coded chemical. After completion of a draft of this final report and acceptance of the draft by the FDA Project Officer, the identity of the chemical was made known to SRI International: Sodium thiosulfate pentahydrate (CAS #10102 -17 -7; Mallinckrodt, Saint Louis, MO).