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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Data source

Reference
Title:
Caesar hybrid model for bacterial reverse mutation (Ames test) version 2.1.13
Year:
2010
Bibliographic source:
Ferrari T, Gini G (2010) An open source multistep model to predict mutagenicity from statistical analysis and relevant structural alerts. Chemistry Central Journal , 4(Suppl 1):S2

Materials and methods

Test guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
Ferrari T, Gini G (2010) An open source multistep model to predict mutagenicity from statistical analysis and relevant structural alerts. Chemistry Central Journal , 4(Suppl 1):S2. http://www.journal.chemistrycentral.com/content/4/S1/S2

The software is and is freely available through the portal of the CAESAR project.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
C(=C\F)\C(F)(F)F

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium; strains not specified
Metabolic activation:
not specified
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
not applicable
Untreated negative controls validity:
not applicable
True negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)

Applicant's summary and conclusion

Conclusions:
Mutagenicity (Ames test) model (CAESAR) version 2.1.13 predicts the substance is NON-MUTAGENIC.
Executive summary:

The prediction of Mutagenicity (Ames test) model (CAESAR;version 2.1.13) on the target compound may be considered adequate. The main reason for the low ADI value is that the target compounds has a fragment defined by the SMILES: FC=C that is an uncommon fragment not present in the compounds of the training set of the model.

Despite the Applicability Domain tool within VEGA identifies some issues to be verified, using a weight of evidence approach combining several VEGA models and read-across, it allows to support a non mutagenic assessment for the target compound. Indeed, there is agreement between the prediction and all similar compounds containing Fluorine atoms, which are experimentally non mutagenic.