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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
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with OECD 471 methods, meets generally accepted scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1988

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Method

Target gene:
Salmonella typhimurium
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 97
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1535
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 mix from rats
Test concentrations with justification for top dose:
For strains TA97, TA98 and TA100: 0; 10; 33; 100; 333; 500; 667; 1000 and 2000 µg/plateFor strain: TA1535: 0; 10; 33; 100; 333; 500; 1000 and 2000 µg/plate
Vehicle / solvent:
No data
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:
TA100 an TA1535 without S9 mix
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamine (NPD)
Remarks:
TA98 without S9 mix
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA97 without S9 mix
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Anthramine
Remarks:
TA98, TA100, TA102, TA1535, TA1537 and WP2 uvrA with S9 mix
Details on test system and experimental conditions:
Cells and study compound or solvent (dimethyl sulfoxide) were incubated in the absence of exogenous metabolic activation (-S9J or with Aroclor 1254-induced S9 from male Syrian hamster liver or male Sprague Dawley rat liver. High dose was limited by toxicity or solubility but did not exceed 10 mg/plate; 0 llg/plate dose is the solvent control.
Evaluation criteria:
A test article is considered as positive if either a significant dose-related increase in the number of revertants or a significant and reproducible increase for at least one test concentration is induced.A test article producing neither a significant dose-related increase in the number of revertants nor a significant and reproducible positive response at any one of the test points is considered non-mutagenic in this system.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: TA98
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):positiveThe tested substance was mutagenic in Salmonella typhimurium strains TA97, TA98, and TA100 when tested in a preincubation protocol in the presence and absence of Aroclor 1254-induced male Sprague Dawley rat or Syrian hamster liver S9; these three strains, which are deficient in DNA excision repair capabilities, demonstrate enhanced error-prone repair of damaged DNA (Appendix E, Table E1). No increase in revertant colonies was observed in strain TA1535, which lacks both error-prone DNA repair and excision repair capabilities.
Executive summary:

The tested substance was mutagenic in Salmonella typhimurium strains TA97, TA98, and TA100 when tested in a preincubation protocol in the

presence and absence of Aroclor 1254-induced male Sprague Dawley rat or Syrian hamster liver S9; these three strains, which are deficient in DNA

excision repair capabilities, demonstrate enhanced error-prone repair of damaged DNA (Appendix E, Table E1). No increase in revertant colonies was

observed in strain TA1535, which lacks both error-prone DNA repair and excision repair capabilities.