Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
yes (incl. QA statement)
Type of assay:
mammalian cell gene mutation assay
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
S9 microsomal fraction from male rats which has been induced with phenobarbital/beta-naphthoflavone.
Test concentrations with justification for top dose:
0, 25, 50, 100, 200, 300, 400, 450, 500 - Expt 1 (-S9)
0, 50, 100, 200, 300, 400, 450, 500, 550 - Expt 1 (+S9)
0, 6.25, 12.5, 25, 50, 100, 150, 200, 250 - Expt 2 (-S9)
0, 50, 100, 200, 300, 350, 400, 450, 500 - Expt 2 (+S9)
The purity of the test item was 94.8% and was therefore accounted for when formulating the dosing solutions in the preliminary toxicity and mutagenicity tests.
Vehicle / solvent:
DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
ethylmethanesulphonate
Evaluation criteria:
For a test item to demonstrate a mutagenic response it must produce a statistically significant increase in the induced mutant frequency (IMF) over the concurrent vehicle mutant frequency value. Following discussions at an International Workshop on Genotoxicity Test Procedures in Plymouth, UK, 2002 (Moore et al 2003) it was felt that the IMF must exceed some value based on the global background MF for each method (agar or microwell). This Global Evaluation Factor (GEF) value was set following a further meeting of the International Workshop in Aberdeen, Scotland, 2003 (Moore et al 2006) at 126 x 10-6 for the microwell method. Therefore, any test item dose level that has a mutation frequency value that is greater than the corresponding vehicle control by the GEF of 126 x 10-6 and demonstrates a positive linear trend will be considered positive. However, if a test item produces a modest increase in mutant frequency, which
only marginally exceeds the GEF value and is not reproducible or part of a dose-related response, then it may be considered to have no toxicological significance. Conversely, when a test item induces modest reproducible increases in the mutation frequencies that do not exceed the GEF value then scientific judgement will be applied. If the reproducible responses are significantly dose-related and include increases in the absolute numbers of mutant colonies then they may be considered to be toxicologically significant.
Statistics:
The experimental data was analysed using a dedicated computer program, Mutant 240C by York Electronic Research, which follows the statistical guidelines recommended by the UKEMS (Robinson W D et al, 1989).
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

The substance was considered to be non-mutagenic to mouse lymphoma cells in vitro.

Additional information

The substance gave negative results in a reliable in vitro bacterial mutation assay, a reliable in vitro cytogenetics assay and a reliable in vitro gene mutation assay.


Justification for selection of genetic toxicity endpoint
All of the available in vitro studies were negative so no study has been selected.

Short description of key information:
The substance gave negative results in three different in vitro gentoxicity assays.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The substance gave negative results in three in vitro gentoxicity assays and therefore there is no requirement for classification.