Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
genetic toxicity in vitro, other
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 and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE

OASIS TIMES 2.27.19

2. MODEL (incl. version number)

Ames mutagenicity v.12.12

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

CCC(C)(O)C=C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
see attached QMRF

5. APPLICABILITY DOMAIN
see attached QPRF


Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: REACH guidance on QSARs R.6, 2008

Test material

Constituent 1
Chemical structure
Reference substance name:
3-methylpent-1-en-3-ol
EC Number:
213-044-2
EC Name:
3-methylpent-1-en-3-ol
Cas Number:
918-85-4
Molecular formula:
C6H12O
IUPAC Name:
3-methylpent-1-en-3-ol
Details on test material:
- Name of test material (as cited in study report): 3-methyl-1-Penten-3-ol

Results and discussion

Test results
Key result
Species / strain:
other: QSAR calculation
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)

Any other information on results incl. tables

Prediction of Bacterial mutagenicity. Mutagenicity of chemicals, we have combined the alerting group approach with a pattern recognition type of model to delineate reactivity of chemicals toward DNA within a given interaction mechanism. The explicit generation of metabolites allowed the DNA reactivity model to be applied not only to parent chemicals but also their stable metabolites.

The applicability domain consists of the following sub-domain layers:

1.General parametric requirements. The variations of molecular parameters that may affect the quality of the measured endpoint significantly are included here (such as molecular weight, ect.). The domain of general parametric includes the range of variation of hydrophobicity (log Kow) and molecular weight (MW) of chemicals in training set.

2.Structural domain. The structural component of the model is based on the structural similarity between chemicals in the training set which were correctly predicted by the model. The structural neighborhood of atom-centered fragments is used to determine this similarity. The training chemicals in chromosomal aberration (CA) were split into two subsets: correct and incorrect chemicals. These two subsets of chemicals were used to extract characteristics that determine the structural space of correct and incorrect chemicals. Extracted characteristics were split into two categories: unique characteristics of correct and incorrect chemicals. The structural characteristics of a target chemical can belong to the following four categories:

-Unique characteristics of correct chemicals

-Unique characteristics of incorrect chemicals

The distribution of structural characteristics of the target chemical and accepted thresholds is used as a criterion to determine how well the target is respsented in the structural space of correctly predicted chemicals. The accepted domain thresholds Mutagenicity are as follows:

- Correct = 100%

- Incorrect = 0%

3.Domain of simulated metabolism(Active metabolite reliability) Metabolism component - the reliability of simulated metabolism (metabolites, pathways and maps) is taken into account in assessing the reliability of predictions.

In order to belong to the model domain a target structure must meet the requirementsof all the domain layers.

The registrant considers the prediction as valid because this model was validated with more than 2000 substances. The general mutagenicity model was found to have 82% sensitivity, 89% specificity and 88% concordance for training set chemicals (Serafimova et al., Chem.Res.Toxicol. 2007, 20, 662 -676).

The QSAR program calculated no genotoxic potential of the test substance. The substance is in domain of the system.

Applicant's summary and conclusion