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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
The test item was evaluated in an Ames Test on Salmonella typhimurium strains TA 1535, TA 100, TA, 1537, TA 98, and TA 102, performed according to OECD TG 471. The test material was considered to be non-mutagenic without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Target gene:
mutant histidine gene
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 100, TA 1537, TA 98, and TA 102
Metabolic activation:
with and without
Metabolic activation system:
S9 mix was made from the livers of male Sprague Dawley rats, which received a single intraperitoneal injection of 500 mg/kg bw Aroclor 1254, dissolved in corn oil, 5 days prior to sacrifice. The S9 mix comprised 10% S9 fraction.
Test concentrations with justification for top dose:
plate incorporation assay:
0, 50, 158, 500, 1581, 5000 µg/plate with and without S9 mix
preincubation assay:
0, 50, 158, 500, 1581, 5000 µg/tube with and without S9 mix
Repeat preincubation assay with TA102 only:
0, 800, 2200, 3600, 6000, 7400 µg/tube with S9 mix
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO for test item; deionized water for positive control Mytomycin C; DMSO (other positive controls)
- Justification for choice of solvent/vehicle: test item formed a light yellos to clear solution; stability in solvent was confirmed
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Remarks:
Na-azide (only TA 1535), nitrofurantoin (only TA 100), 4-nitro-1,2-phenylene diamine (TA 1537 and TA 98), mitomycin C (only TA 102 in plate incorporation assay), cumene hydroperoxide (only TA 102 in preincubation assay), 2-aminoanthracene
Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas for TA 1537, at least a threefold increase should be reached. For TA 102 an increase of about 100 mutants should be reached. Otherwise, the result is evaluated as negative. However, these guidelines may be overruled by good scientific judgment.
In case of questionable results, investigations should continue, possibly with modifications, until a final evaluation is possible.
Statistics:
no statistics perfomed; evaluation based on criteria mentioned above
Species / strain:
other: S. typhimurium TA 1535, TA 100, TA 1537, TA 98, and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Total bacteria counts remained unchanged and no inhibition of growth was observed in the plate incorporation test. In the preincubation the dose of 5000 µg/ml led to weak strain specific bacteriotoxic effect.
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
None of the five strains showed in the plate incorporation test a dose-related and biologically relevant increase in mutant counts over those of the negative controls with and without S9-mix. In the initial preincuation test with strain TA 102 with S9-mix an increase in revertant colonies was noted. In order to check the relevance of this result, an independent repeat experiment was performed applying higher doses o fup to and including 7400 µg/tube, in which no biologically increase in mutant counts was noted.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Executive summary:

The test item was evaluated in an Ames Test on Salmonella typhimurium strains TA 1535, TA 100, TA, 1537, TA 98, and TA 102, performed according to OECD TG 471. The test material was considered to be non-mutagenic without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Justification for selection of genetic toxicity endpoint
only one study available

Justification for classification or non-classification