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Genetic toxicity in vitro

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
Study period:
from November to December 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions; the applied strains of bacteria may not detect certain oxidising mutagens, cross-linking agents
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
- TA 102 or E.coli WP2 strains are not included; only one experiment (direct plate incorporation procedure) was performed
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Target gene:
Histidine gene locus
Species / strain:
other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98
Additional strain characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced male Wistar rat liver S9 mix
Test concentrations with justification for top dose:
100, 250, 500, 1000, 2500, 5000 µg/plate








Vehicle:
phosphate buffer ((pH 7.4, 0.1 M)
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
benzo(a)pyrene
cyclophosphamide
other: anthracen-2-amine
Species / strain:
other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no, but tested up to limit concentrations
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

None of the five tester strains showed increased reversion to prototrophy in assays with ZK 156454 at 6 concentrations tested between 0.1 and 5.0 mg/plate, either in the absence or presence of S9 mix. Generally, growth inhibition of the background lawn was not observed. There were no precipitates in the agar. Negative controls and positive controls with known mutagens produced the expected numbers of revertant colonies.

Executive summary:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 in the presence and absence of S9 mix according to OECD TG 471. Evidence of mutagenic activity was not seen up to the maximum recommended dose level of 5000 µg/plate. No substantial increases in revertant colony numbers of any of the five tester strains were observed at any dose level in the presence and absence of metabolic activation. Therefore, the test substance was considered to be non-mutagenic in the Salmonella typhimurium reverse mutation assay.

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

Additional information

Additional information from genetic toxicity in vitro:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 in the presence and absence of S9 mix according to OECD TG 471. Evidence of mutagenic activity was not seen up to the maximum recommended dose level of 5000 µg/plate. No substantial increases in revertant colony numbers of any of the five tester strains were observed at any dose level in the presence and absence of metabolic activation. Therefore, the test substance was considered to be non-mutagenic in the Salmonella typhimurium reverse mutation assay.


Justification for selection of genetic toxicity endpoint
Only one study available

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC, Annex VI, or Regulation (EC) No. 1272/2008 (CLP), Annex I, is not warranted.