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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In Vitro (Mutagenic effects - bacterial): QSAR; Bacterial reverse mutation assay. Negative. Reliability = 2.

In Vitro (Clastogenic effects - mammalian): QSAR; Chromosome aberrations. Negative. Reliability = 2.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
key study
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
Reference:
Composition 0
Qualifier:
no guideline available
Principles of method if other than guideline:
Times v.2.27.19.13 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: OC1C{P-}(O)C{P-}(O)C{P-}(O)C{P+}(O)C{P-}1O
Key result
Species / strain:
S. typhimurium, other:
Metabolic activation:
with
Genotoxicity:
negative
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)
Conclusions:
Negative with metabolic activation
Executive summary:

The Times model for in vitro bacterial cell mutagenicity was used within the QSAR Toolbox. The prediction was negative with activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
key study
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
Reference:
Composition 0
Qualifier:
no guideline available
Principles of method if other than guideline:
Times v.2.27.19.13 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: OC1C{P-}(O)C{P-}(O)C{P-}(O)C{P+}(O)C{P-}1O
Key result
Species / strain:
S. typhimurium, other:
Metabolic activation:
without
Genotoxicity:
negative
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)
Conclusions:
Negative without metabolic activation
Executive summary:

The Times model for in vitro bacterial cell mutagenicity was used within the QSAR Toolbox. The prediction was negative without activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
(Q)SAR
Adequacy of study:
key study
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
Reference:
Composition 0
Qualifier:
no guideline available
Principles of method if other than guideline:
Times v.2.27.19.13 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: OC1C{P-}(O)C{P-}(O)C{P-}(O)C{P+}(O)C{P-}1O
Key result
Species / strain:
other: CHO and CHL cells
Metabolic activation:
with
Genotoxicity:
negative
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)
Conclusions:
Negative with metabolic activation
Executive summary:

The Times model for in vitro chromosome aberrations was used within the QSAR Toolbox. The prediction was negative with activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
(Q)SAR
Adequacy of study:
key study
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
Reference:
Composition 0
Qualifier:
no guideline available
Principles of method if other than guideline:
Times v.2.27.19.13 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: OC1C{P-}(O)C{P-}(O)C{P-}(O)C{P+}(O)C{P-}1O
Key result
Species / strain:
other: CHO and CHL cells
Metabolic activation:
without
Genotoxicity:
negative
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)
Conclusions:
Negative without metabolic activation
Executive summary:

The Times model for in vitro chromosome aberrations was used within the QSAR Toolbox. The prediction was negative without activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

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

Genetic toxicity in vivo

Description of key information

In Vivo (Clastogenic effects - mammalian): QSAR; in vivo mouse micronucleus study; Negative. Reliability = 2.

Link to relevant study records
Reference
Endpoint:
genetic toxicity in vivo, other
Remarks:
in vivo micronucleus QSAR
Type of information:
(Q)SAR
Adequacy of study:
key study
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
Reference:
Composition 0
Qualifier:
no guideline available
Principles of method if other than guideline:
Times v.2.27.19.13 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: OC1C{P-}(O)C{P-}(O)C{P-}(O)C{P+}(O)C{P-}1O
Key result
Genotoxicity:
negative
Remarks:
Mammalian erythrocytes and/or peripheral blood
Remarks on result:
other: no mutagenic potential (based on QSAR/QSPR prediction)
Conclusions:
Negative
Executive summary:

The Times model for in vivo micronucleus assay was used within the QSAR Toolbox. The prediction was negative. Additional supporting documentation is provided in the prediction report attached in IUCLID.

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

Additional information

Qualitative structure activity relationships (QSAR), documented in QMRF/QPRF, predict no alerts to indicate likely mutagenic potential. The test substance is expected to be non-mutagenic in Ames with or without metabolic activation, negative for chromosomal aberrations with or without activation, and negative for in vivo micronuclei.

Justification for classification or non-classification

The test substance is not predicted to have the potential to be mutagenic or clastogenic in vitro or in vivo based on assay-specific model predictions. Additionally, published data reports that the test substance is a tumour growth inhibitor (lung and liver), supporting the prediction that it is not genotoxic. Therefore, the substance does not need to be classified for mutagenicity according to EU Classification, Labelling and Packaging of substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.