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EC number: 203-203-4 | CAS number: 104-45-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The available data for this endpoint include one Ames assay, an European Food Safety Authority (EFSA) review and QSARs conducted using VEGA and ToxTree software.
Link to relevant study records
- Endpoint:
- genetic toxicity in vitro, other
- Remarks:
- in silico prediciton
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- 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 : ToxTree (Estimation of Toxic Hazard- A Decision Tree Approach)
2. MODEL: v.2.6.13
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
: O(c1ccc(cc1)CCC)C
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint:
In vitro mutagenicity (Ames test) alerts by ISS decsion tree method. A decision tree for estimating in vitro mutagenicity (Ames test). Developed by Istituto Superiore di Sanita for JRC IHCP Computational Toxicology and Modelling and IdeaConsult Ltd., (Sofia, Bulgaria)
5. APPLICABILITY DOMAIN
No details on how the substance falls within the applicability domain of the model was provided by the software.
6. ADEQUACY OF THE RESULT
No details on how the prediction fits the purpose of classification and labelling and/or risk assessment was provided by the software.
This endpoint study record is part of a weight of evidence approach comprising of QSAR predictions using ToxTree and OECDToolbox. Both data sources agree with the prediction that the test substance is a mutagen. - Qualifier:
- no guideline required
- Conclusions:
- A QSAR using ToxTree software and applying the 'In vitro mutagenicity (Ames test)' decsion tree results in ' No alerts for S. tymphimurium mutagenicity'.
- Executive summary:
A QSAR using ToxTree software and applying the 'In vitro mutagenicity (Ames test)' decsion tree results in ' No alerts for S. tymphimurium mutagenicity'.
- Endpoint:
- genetic toxicity in vitro, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- 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 limited documentation / justification
- Justification for type of information:
- 1. SOFTWARE
: VEGA QSAR MODEL Core version 1.2.4
2. MODEL: Mutagenicity (Ames test) model (CAESAR) 2.1.13
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL :O(c1ccc(cc1)CCC)C
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Mutagenicity
- Unambiguous algorithm:
- Defined domain of applicability: Compound is into the Applicability Domain of the model
- Appropriate measures of goodness-of-fit and robustness and predictivity: Good reliabilility
5. APPLICABILITY DOMAIN
- Descriptor domain: Global AD Index = 0.96
- Similarity with analogues in the training set: Strongly similar
6. ADEQUACY OF THE RESULT
The model is considered reliable.
This endpoint study record is part of a weight of evidence approach comprising of experimental data and supporting QSAR predictions using ToxTree and VEGA. Both experimental data and QSARs predict that the compound is not mutagenic. - Qualifier:
- no guideline required
- Conclusions:
- A QSAR conducted using VEGA software and applying the CAESAR model results in a 'non-mutagenic' prediction.
- Executive summary:
A QSAR conducted using VEGA software and applying the CAESAR model results in a 'non-mutagenic' prediction.
- Endpoint:
- genetic toxicity in vitro, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- 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
- Justification for type of information:
- 1. SOFTWARE
: VEGA QSAR MODEL Core version 1.2.4
2. MODEL: Mutagenicity (Ames test) model (ISS) 1.0.2
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL :O(c1ccc(cc1)CCC)C
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Mutagenicity
- Defined domain of applicability: Compound could be out of the Applicability Domain (AD)of the model
- Appropriate measures of goodness-of-fit and robustness and predictivity:Not optimal
5. APPLICABILITY DOMAIN
- Descriptor domain: Global AD Index = 0.665
- Similarity with analogues in the training set: Not adequate
6. ADEQUACY OF THE RESULT
The model is considered reliable, however, the accuracy of prediciton for similar molecules found in the data set is not adequate and the predicted compound could be out of the AD of the model.
This endpoint study record is part of a weight of evidence approach comprising of experimental data and supporting QSAR predictions using ToxTree and VEGA. Both experimental data and QSARs predict that the compound is not mutagenic. - Qualifier:
- no guideline required
- Conclusions:
- A QSAR conducted using VEGA software and applying the ISS model results in a 'non-mutagenic' prediction. However, the accuracy of prediction for similar molecules in the training set is not adequate.
- Executive summary:
A QSAR conducted using VEGA software and applying the ISS model results in a 'non-mutagenic' prediction. However, the accuracy of prediction for similar molecules in the training set is not adequate.
- Endpoint:
- genetic toxicity in vitro, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- 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
- Justification for type of information:
- 1. SOFTWARE
: VEGA QSAR MODEL Core version 1.2.4
2. MODEL: Mutagenicity (Ames test) model (KNN/ReadAcross) 1.0.0
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL :O(c1ccc(cc1)CCC)C
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Mutagenicity
- Defined domain of applicability: Compound could be out of the Applicability Domain of the model
- Appropriate measures of goodness-of-fit and robustness and predictivity: Moderate reliability
5. APPLICABILITY DOMAIN
- Descriptor domain: Global AD Index = 0.891
- Similarity with analogues in the training set: Strongly similar
6. ADEQUACY OF THE RESULT
The model is considered reliable (experimental data)
This endpoint study record is part of a weight of evidence approach comprising of experimental data and supporting QSAR predictions using ToxTree and VEGA. Both experimental data and QSARs predict that the compound is not mutagenic. - Qualifier:
- no guideline required
- Conclusions:
- A QSAR using VEGA software and applying the KNN/Read Across model results in a 'non mutagen' prediction. However, the accuracy of prediction for similar models found in the training set is not optimal.
- Executive summary:
A QSAR using VEGA software and applying the KNN/Read Across model results in a 'non mutagen' prediction. However, the accuracy of prediction for similar models found in the training set is not optimal.
- Endpoint:
- genetic toxicity in vitro, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- 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 limited documentation / justification
- Justification for type of information:
- 1. SOFTWARE: VEGA QSAR MODEL Core version 1.2.4
2. MODEL: Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:O(c1ccc(cc1)CCC)C
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Mutagenicity
- Defined domain of applicability: the predicted compound is iwithin the Applicability Domain of the model
- Appropriate measures of goodness-of-fit and robustness and predictivity: Good reliability
5. APPLICABILITY DOMAIN
- Descriptor domain:Global AD Index = 0.96
- Similarity with analogues in the training set: Strongly similar
6. ADEQUACY OF THE RESULT
The model is considered to be of good reliability; the predicted compound is within the AD of the model, the accuracy of prediction for similar molecules found in the training set is good and similar molecules found in the training set have experimental values in the training set have been found.
This endpoint study record is part of a weight of evidence approach comprising of experimental data and supporting QSAR predictions using ToxTree and VEGA. Both experimental data and QSARs predict that the compound is not mutagenic. - Qualifier:
- no guideline required
- Conclusions:
- A QSAR using the VEGA software and applying the SarPy/IRFMN model results in a 'possible non-mutagenic' prediction.
- Executive summary:
A QSAR using the VEGA software and applying the SarPy/IRFMN model results in a 'possible non-mutagenic' prediction.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Study period:
- 2011
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Remarks:
- EFSA review of available mutagenicity data; details on methodology are not reported.
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- No details reported.
- Target gene:
- No details reported
- Species / strain / cell type:
- other: Salmonella typhimurium (TA98, TA100, TA1535, TA1537, TA1538)
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Concentrations up to 750 micrograms/plate were tested (no further details reported).
- Vehicle / solvent:
- No details reported.
- Details on test system and experimental conditions:
- No details reported.
- Rationale for test conditions:
- No details reported.
- Evaluation criteria:
- No details reported.
- Statistics:
- No details reported.
- Key result
- Species / strain:
- other: TA98, TA100, TA1535, TA1537, TA1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- The test item was found to be negative in the Ames test (with or without metabolic activation). EFSA concluded that there was "no safety concern" regarding the test item, at the estimated level of intake as a flavouring substance.
- Executive summary:
This review summarises the results of an Ames assasy conducted by Wild, et al. (1989). The original data reported by Wild et al. (1989) is included in this registration as part of the weight of evidence approach.
EFSA report that the test item was found to be negative in the Ames test (with or without metabolic activation). EFSA concluded that there was "no safety concern" regarding the test item, at the estimated level of intake as a flavouring substance.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- No details reported.
- Species / strain / cell type:
- other: Salmonella typhimurium (TA 1535, TA 100, TA 1537, TA 1538, TA 98)
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Five doses of the test item were tested (up to 3.6 mg/plate) in all five tester strains with and without S9 mix. No further details on dose concentrations were reported.
- Vehicle / solvent:
- No details on the vehicle for the test item used in this study are reported. However, it is noted that If the test item was found to be soluble, then water was used as the vehicle. Otherwise dimethylsulphoxide (DMSO) was used as a solvent for test chemcials that were poorly soluble in water.
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: The Ames test was perfomed in Volger-Bonner medium according to a standard plate procedure.
DURATION
- Preincubation period:48 hours
- Exposure duration: No details reported
- Expression time (cells in growth medium):No details reported
- Selection time (if incubation with a selection agent):No details reported
- Fixation time (start of exposure up to fixation or harvest of cells):No details reported
SELECTION AGENT (mutation assays):No details reported
NUMBER OF REPLICATIONS: Each chemical was tested at least twice. No further details reported.
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED:No details reported
NUMBER OF CELLS EVALUATED: Overnight bacterial cultures had cell titres of at least 10^9 cells/ml. No further details reported.
CRITERIA FOR MICRONUCLEUS IDENTIFICATION:
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No details reported.
- Any supplementary information relevant to cytotoxicity: No details reported - Rationale for test conditions:
- No details reported
- Evaluation criteria:
- No details reported.
- Statistics:
- Statistical significance was determined according to the methods of Kastenbaum & Bowman. Test items that produced reproducible, dose-related and at least two-fold elevation of the spontaneous revertant frequency were regarded as positive. Test items producing reproducible, dose-related and significant (P <0.01) but less than two-fold elevations were classified as marginally mutagenic under the experimental conditions.
- Key result
- Species / strain:
- other: TA 1535, TA 100, TA 1357, TA 1358, TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Conclusions:
- The test item was found to be 'genetically inactive' in the Ames test. Therefore, the test item is considered to be negative for mutagenicity.
- Executive summary:
The test item was found to be 'genetically inactive' in the Ames test. Therefore, the test item is considered to be negative for mutagenicity, according to CLP criteria (EC Regulation 1272/2008).
Referenceopen allclose all
A QSAR using ToxTree software and applying the 'In vitro mutagenicity (Ames test)' decsion tree results in ' No alerts for S. tymphimurium mutagenicity'.
A QSAR conducted using VEGA software and applying the CAESAR model results in a 'non-mutagenic' prediction.
A QSAR conducted using VEGA software and applying the ISS model results in a 'non-mutagenic' prediction. However, the accuracy of prediction for similar molecules in the training set is not adequate.
A QSAR using VEGA software and applying the KNN/Read Across model results in a 'non mutagen' prediction. However, the accuracy of prediction for similar models found in the training set is not optimal.
A QSAR using the VEGA software and applying the SarPy/IRFMN model results in a 'possible non-mutagenic' prediction.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
The test item was negative for genotoxicity in the Ames test. This result is supported QSARs of the test item using VEGA and ToxTree result in an overall negative result for mutagenicity. Furthermore, a recent review by the European Food Safety Authority (EFSA) based on the available genotoxicity data for the test item, states that there is 'no safety concern' for at the current estimated level of intake.
Therefore, considering all of the available data (negative Ames assay, overall negative QSAR predictions, EFSA review), the test item is not classificable for genetic toxicity according to CLP criteria (EC Regulation 1272/2008).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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