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EC number: 219-034-4 | CAS number: 2322-77-2
- 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
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- Endpoint summary
- Stability
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- 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
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- 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
Gene mutation (bacterial reverse mutation assay / Ames test): negative with and without metabolic activation Gürtler & Görke 1997]
QSAR predictions using Leadscope and DEREK Nexus: negative, no alerts found
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Study period:
- June 2021
- 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
DEREK Nexus 6.1
2. MODEL (incl. version number)
DEREK Nexus 6.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
n/a
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: TOX 7.6.1. Genetic toxicity in vitro
- Unambiguous algorithm: logic of argumentation. Derek Nexus makes qualitative predictions for and against toxicity through reasoning. For the endpoint of mutagenicity, predictions for toxicity decrease in confidence in the following order: certain>probable>plausible>equivocal. Predictions against toxicity increase in confidence in the following order: inactive (with unclassified and/or misclassified features)shown to correlate with predictivity [Judson et al, 2013]. Multiple data sources (e.g. toxicity data from multiple assays and mechanistic evidence) are ynthesised into the structure-activity relationships that underpins Derek Nexus predictions. An appreciation of the assay unitsapplied by alert writers when building the alert training set. However, predictions are not quantitative and, as a result, do not include units.
- Defined domain of applicability: The scopes of the structure-activity relationships describing the mutagenicity endpoint are defined by the developer to be the applicability domain for the model. Therefore, if a chemical activates
an alert describing a structure-activity for mutagenicity it can be considered to be within the applicability domain. If a compound does not activate an alert or reasoning rule then Derek makes a negative prediction. The applicability of the negative prediction to the query compounds can be determined by an expert, if required, by investigating the presence (or absence) of misclassified and/or unclassified features. The applicability domain of each alert is defined by the alert developer on the basis of the training set data and expert judgement on the
chemical and biological factors which affect the mechanism of action for each alert. For non-alerting compounds, users should determine the applicability of negative predictions by evaluating the information supplied by Derek (i.e. the presence or absence of misclassified and/or unclassified features).
- Appropriate measures of goodness-of-fit and robustness and predictivity: n/a
- Mechanistic interpretation: All alerts describing structure-activity relationships for the mutagenicity endpoint have a mechanistic basis wherever possible.
Mechanistic information is detailed in the comments associated with an alert and can include information on both the mechanism of action and biological target. The mechanistic basis of the model was developed a priori by examining the toxicological and mechanistic evidence before developing the structure-activity relationship.
5. APPLICABILITY DOMAIN
- Descriptor domain:
[1]Markush structures encoding activating and deactivating features (known as patterns in the Derek Nexus knowledge base)
[2]count of non-hydrogen atoms
[3]ClogP
[4]2D structural fragments
There is an a priori assumption that patterns and associated reasoning will be used to model toxicity within Derek Nexus. Further, experts identified that misclassified and unclassified features were useful descriptors for determining the reliability of negative predictions for non-alerting compounds.
- Similarity with analogues in the training set: Non-proprietary elements of the training set are available through the references, and illustrated by the examples, within Derek Nexus. The illustrative examples are not available, due to the proprietary nature of Derek Nexus.
6. ADEQUACY OF THE RESULT
Based on the common structure of the substance and the absence of any strucutral alert, the result is considered reliable. - Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on QSARs R.6
- Version / remarks:
- Version 3.1 July 2016
- Principles of method if other than guideline:
- - Software tool(s) used including version: DEREK Nexus 6.1
- Model(s) used: DEREK Nexus 6.1
- Model description: see field 'Attached justification'
- Justification of QSAR prediction: see field 'Attached justification' - GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 102
- Remarks:
- and E.coli tester strains
- Additional strain / cell type characteristics:
- other: The QSAR prediction is based on all tester strains recommended by the current OECD Test Gudieline
- Evaluation criteria:
- Two types of models were used to predict the mutagenic potential of the test item.
The DEREK Nexus model was used as a rule-based model which is based on the training set data and expert judgement on the chemical and biological factors which affect the mechanism of action for each alert. The second model used was the Leadscope Applier which is a statistical model using structural fragments to set an alert. If experimental data are available the prediction of the statistical model may be overruled. - Key result
- Species / strain:
- other: not applicable for in silico study
- Metabolic activation:
- not applicable
- Genotoxicity:
- negative
- Remarks:
- The test item showed no alerts for mutagenicity. Therefore D-ET-Dienone was considered to be non-mutagenic and was assigned to mutagenic impurity class 5.
- Cytotoxicity / choice of top concentrations:
- other: not applicable for in silico study
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- True negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Conclusions:
- Based on the predictions performed with the statistical QSAR model Leadscope Applier and the rule-based model DEREK Nexus D-ET-Dienone is not mutagenic in a bacterial reverse mutation assay.
- Executive summary:
In a QSAR prediction using DEREK Nexus v6.1 the potential of D-ET-DIenone to induce mutagenicity was assessed. Derek Nexus makes qualitative predictions for and against toxicity through reasoning. For the endpoint of mutagenicity, predictions for toxicity decrease in confidence in the following order: certain>probable>plausible>equivocal. Predictions against toxicity increase in confidence in the following order: inactive (with unclassified and/or misclassified features)<inactive<improbable. Likelihood levels have beenshown to correlate with predictivity [Judson et al, 2013]. Multiple data sources (e.g. toxicity data from multiple assays and mechanistic evidence) are synthesised into the structure-activity relationships that underpins Derek Nexus predictions. An appreciation of the assay units applied by alert writers when building the alert training set. However, predictions are not quantitative and, as a result, do not include units.
The query structure does not match any structural alerts or examples for (bacterial in vitro) mutagenicity in Derek. Furthermore, the query structure does not contain an unclassified feature and is consequently not predicted to be indeterminate in the bacterial in vitro (Ames) mutagenicity test. However, experimental data are available clearly reporting a negative result.
Based on these results D-ET-Dienone is considered non-mutagenic as predicted by DEREK Nexus.
This study is classified as acceptable for assessment based on methodolgy and documentation. This study satisfy the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) and the data is part of an overall assessment.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Study period:
- 2021
- 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
Leadscope model applier (v2.4)
2. MODEL (incl. version number)
Leadscope model applier (v2.4)
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 2322-77-2; Chemical name: Methoxydienone
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: QMRF 4.10. Mutagenicity OECD 471 Bacterial Reverse Mutation Test
- Unambiguous algorithm:
A new ICH M7 compliant expert alert system to predict the mutagenic potential of impurities (white paper) http://www.leadscope.com/white_papers/ICHM7-WhitePaper-0314.pdf
The logic for matching alerts is detailed in "A new ICH M7 compliant expert alert system to predict the mutagenic potential of impurities" (white paper): http://www.leadscope.com/white_papers/ICHM7-WhitePaper-0314.pdf
- Defined domain of applicability: The applicability domain is defined as having at least one chemical in a reference set with at least 30% global similarity to the test structure (using the Leadscope 27,000 chemical fragments as descriptors and the Tanimoto similarity score).
- Appropriate measures of goodness-of-fit and robustness and predictivity: Chemicals/descriptor ratio: 241 alerts for 11,528 reference chemicals (ratio = 48); Alerts are run within the Leadscope model applier that provides the capability to specify one or more compounds (using SMILES, Mol files, SD files, or copying from the clipboard), select and run the alerts, assess the applicability domain, and view the results including an explanation for any prediction (such as a full description of any matched alerts). The performance was assessed using the Hansen dataset comprised of 3,700 chemicals (47% positive).
Concordance = 83%, Sensitivity = 92%, Specificity = 70%, Positive
Predictivity = 81%, Negative Predictivity = 86% , coverage = 95% were
obtained.
- Mechanistic interpretation: Accompanying any positive prediction, any alert(s) that match the test compounds are described including a description of the mechanistic basis from the literature reference that cites the alert.
5. APPLICABILITY DOMAIN
- Descriptor domain: The applicability domain is defined as having at least one chemical in a reference set with at least 30% global similarity to the test structure (using the Leadscope 27,000 chemical fragments as descriptors and the Tanimoto similarity score).
- Structural domain: Leadscope Predictive Data Miner is a software program for systematic sub‐structural analysis of a chemical using predefined structural features stored in a template library, training set‐dependent generated structural features (scaffolds) and calculated molecular descriptors. The feature library contains approximately 27,000 pre‐defined structural features and the structural features chosen for the library are motivated by those typically found in small molecules: aromatics, heterocycles, spacer groups, simple substituents. Leadscope allows for the generation of training set‐dependent structural features (scaffold generation), and these features can be added to the pre‐defined structural features from the library and be included in the descriptor selection process.
- Mechanistic domain: The global model identifies structural features and molecular descriptors which in the model development was found to be statistically significant associated with effect. Many predictions may indicate modes of action that are obvious for persons with expert knowledge for the endpoint
- Similarity with analogues in the training set: The original data set from Kazius et al. (2005) consisted of 4337 molecular structures with corresponding Ames test data.
The structural similarity of the test compound with respect to the training set compounds was analysed and quantified in terms of Tanimoto distance, which provides a quantitative measure of structural relatedness between the test compound and each training set compound. The 25 training set compounds found to be mostly similar to the test compound.
6. ADEQUACY OF THE RESULT
As can be seen from Annex A and B of the QPRF the result is considered adequate due to the presence of almost all structural features of the parent compound which can also be found in the training/validation dataset. Furthermore the prediction substantiate the experimental result for the substance of interest. - Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on QSARs R.6
- Version / remarks:
- Version 3.1 July 2016
- Principles of method if other than guideline:
- - Software tool(s) used including version: Leadscope model applier (v3.0.2)
- Model(s) used: Leadscope model applier (v3.0.2)
- Model description: see field 'Attached justification'
- Justification of QSAR prediction: see field 'Attached justification' - GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 102
- Remarks:
- and E.coli tester strains
- Additional strain / cell type characteristics:
- other: The QSAR prediction is based on all tester strains recommended by the current OECD Test Guideline
- Evaluation criteria:
- The model used was the Leadscope Applier which is a statistical model using structural fragments to set an alert. Only descrete organic compounds can be predicted. The model searches for structural fragments and combines them with eight molecular descriptors. Thus, a probability of either a negative or positive result is calculated. If experimental data are available the prediction of the statistical model may be overruled.
- Key result
- Species / strain:
- other: not applicable for in silico study
- Metabolic activation:
- not applicable
- Genotoxicity:
- negative
- Remarks:
- The test item showed no alerts for mutagenicity. Therefore the test item was considered to be non-mutagenic.
- Cytotoxicity / choice of top concentrations:
- other: not applicable for in silico study
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- True negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Conclusions:
- Based on the predictions performed with the statistical QSAR model Leadscope Applier D-ET-Dienone is not mutagenic in a bacterial reverse mutation assay.
- Executive summary:
In a QSAR prediction using Leadscope Model Applier (v2.4) the potential of D-ET-Dienone to induce mutagenicity was assessed. Leadscope uses two parameters to guide the applicability of model domain: 1) having at least one structural feature defined in the model in addition to all the property descriptors; 2) having at least one chemical in a training neighbourhood with at least 30% global similarity to the test structure. In this case the prediction is within the applicability domain, since 4 structural features were found and 25 training compounds were identified in the model training set being structurally similar to the test compound.
The query structure does not match any structural alerts or examples for (bacterial in vitro) mutagenicity in Leadscope. Furthermore, the query structure does not contain an unclassified feature and is consequently predicted to be indeterminate in the bacterial in vitro (Ames) mutagenicity test. However, experimental data are also available clearly reporting a negative result.
Based on these results D-ET-Dienone is considered non-mutagenic as predicted by Leadscope.
This study is classified as acceptable for assessment based on methodolgy and documentation. This study satisfy the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) and the data is part of an overall assessment.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- October to December 1996
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 26 May 1983
- Deviations:
- yes
- Remarks:
- - no E. coli WP2 or S. typhimurium TA102 strain tested
- Principles of method if other than guideline:
- The current OECD TG 471 requires at least 5 test strains and the use of E. coli WP2 strains or Salmonella typhimurium TA 102 to detect certain oxidizing mutagens, cross-linking agents and hydrazines. However, the substance is not a highly reactive agent and is therefore not expected to be a cross-linking agent, has no oxidizing properties and is no hydrazine. Thus, a GLP test according to former versions of OECD TG 471 without E. coli WP2 strains or Salmonella typhimurium TA 102 is considered as sufficient to evaluate the mutagenic activity of the substance in this bacterial test system.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine gene locus
- Species / strain / cell type:
- S. typhimurium TA 1538
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1537
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1535
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 100
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 98
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254 induced male rat liver S9 mix
- Test concentrations with justification for top dose:
- 50, 100, 250, 500, 1000, 2500 µg/plate
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- benzo(a)pyrene
- cyclophosphamide
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- direct plate incorporation procedure; Each concentration, including the controls, was tested in triplicate.
NUMBER OF REPLICATIONS:
- Number of cultures per concentration (triplicate)
- Number of independent experiments: one
METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding (if applicable): 1 x E+06 dilution
- Test substance added in plate incorporation
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: A toxic effect of the substance on the background lawn of non-revertant bacteria and precipitates in the agar were examined stereomicroscopically. - Evaluation criteria:
- A positive response was considered if at least 5 mg/plate or up to a toxic dose had been tested (or the compound formed precipitates in the agar) and if the number of revertants of the test compound group compared to the number of revertants of the negative control group was reproducibly higher than 2-fold. A dose-dependent inerease in the number of revertants was also considered to indicate a mutagenic effect.
- Statistics:
- The arithmetic means of the number of mutant colonies of the 3 parallel plates in the negative control groups were compared with those of the
compound groups. - Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from 500 µg/plate onwards in strain TA98 without S9 mix and from 1000 µg/plate onwards in TA 98
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- TA100 at 2500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- TA 1535 at 2500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- TA1537 at 2500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from 1000 µg/plate onwards in TA 1538
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Data on pH: not reported
- Data on osmolality: not reported
- Precipitation and time of the determination: There were precipitates in the agar found starting from 0.25 mg/plate onwards in all strains used in the tests without and with S9 mix.
STUDY RESULTS
- Concurrent vehicle negative and positive control data
0.05 mL of the solvents were plated as negative controls. In order to check the activity of the metabolizing system and the mutability of the bacteria at least two reference mutagens were tested for each strain. Their mutagenic effect occurred either directly (9-AA, 2-NF, NaN3) or after metabolic activation (2-AA, BP, CP). Sterility controls were performed additionally. Please refer to table 1 under any other information on results incl. tables.
Ames test:
- Signs of toxicity: yes: Growth inhibition of the background lawn was observed at the highest concentration tested (2.5 mg/plate) in the strains TA1535, TA100 and TA1537, from 0.5 mg/plate onwards in strain TA98 without S9 mix and from 1.0 mg/plate onwards in the strains TA 1538 and TA98.
- Individual plate counts:
TA1535: 168, 189, 139
TA1537: 189, 200, 192
TA1538: 100, 117, 144
TA100: 165, 185, 215
TA98: 213, 242, 259
- Mean number of revertant colonies per plate and standard deviation
Please refer to table 2 under any other information on results incl. tables. - Conclusions:
- The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 in the presence and absence of S9 mix according to OECD TG 471. Evaluation of the data does not indicate that the test substance is a mutagen in the Ames Salmonella/microsome test when tested up to the precipitating and cytotoxic dose levels. Appropriate positive control chemicals induced marked increases in revertant colony numbers with all strains.
- Executive summary:
In a reverse gene mutation assay in bacteria according to OECD TG 471 (adopted 21 July, 1997), strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 of S. typhimurium were exposed to D-ET-Dienon in DMSO at concentrations of 50, 100, 250, 500, 1000, 2500 µg/plate in the presence and absence of mammalian metabolic activation using the plate incorporation method.
The test item was tested limit concentration 2500 µg/plate None of the five tester strains showed increased reversion to prototrophy at any of the concentrations tested between 50 and 2500 µg/plate, either in the absence or presence of S9 mix. The positive controls induced the appropriate responses in the corresponding strains. Growth inhibition of the background lawn was observed at the highest concentration tested (2500 µg/plate) in the strains TA1535, TA100 and TA1537, from 500 µg/plate onwards in strain TA98 without 59 mix and from 1000 µg/plate onwards in the strains TA 1538 and TA98. There were precipitates in the agar found starting from 250 µg/plate onwards in all strains used in the tests without and with S9 mix..
This study is classified as acceptable. This study satisfies the requirement for Test OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.
The test material is considered non-mutagenic under the conditions of the test.
Referenceopen allclose all
None of the five tester strains showed increased reversion to prototrophy at any of the concentrations tested between 50 and 2500 µg/plate, either in the absence or presence of S9 mix.
Growth inhibition of the background lawn was observed at the highest concentration tested (2500 µg/plate) in the strains TA1535, TA100 and TA1537, from 500 µg/plate onwards in strain TA98 without 59 mix and from 1000 µg/plate onwards in the strains TA 1538 and TA98. There were precipitates in the agar found starting from 250 µg/plate onwards in all strains used in the tests without and with S9 mix.
Table 1:
| TA1535 | TA100 | TA1537 | TA1538 | TA98 | |||||
| -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 |
DMSO | 28±5 | 17±1 | 132±1 | 115±4 | 17±3 | 13±5 | 8±1 | 22±3 | 19±4 | 45±5 |
phosphate buffer | 26±10 | 19±7 | 115±8 | 116±21 | 23±2 | 17±5 | 8±2 | 25±4 | 21±3 | 39±8 |
2-AA | 29±3 | 9±1 | 152±10 | 1081±65 | 23±3 | 82±3 | 16±5 | 991±28 | 14±4 | 936±67 |
CP | 62±7 | 393±2 |
|
|
|
|
|
|
|
|
BaP 2.5 µg |
|
| 132±6 | 633±40 |
|
|
|
| 16±3 | 203±16 |
BaP 5µg |
|
| 140±5 | 793±34 |
|
|
|
| 16±3 | 155±10 |
2-NF |
|
|
|
|
|
| 1106±69 | 440±16 | 1250±63 | 355±6 |
NaN3 | 432±23 | 103±7 | 546±27 | 169±8 |
|
|
|
|
|
|
9-AA |
|
|
|
| 990±153 | 623±196 |
|
|
|
|
Tables 2:
| TA1535 | TA100 | TA1537 | TA1538 | TA98 | |||||
| -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 |
DMSO | 28±5 | 17±1 | 132±1 | 115±4 | 17±3 | 13±5 | 8±1 | 22±3 | 19±4 | 45±5 |
phosphate buffer | 26±10 | 19±7 | 115±8 | 116±21 | 23±2 | 17±5 | 8±2 | 25±4 | 21±3 | 39±8 |
0.05 mg | 29±7 | 17±3 | 135±7 | 128±19 | 23±8 | 13±2 | 10±2 | 24±5 | 19±3 | 42±3 |
0.10 mg | 28±2 | 19±7 | 147±12 | 128±13 | 25±4 | 14±3 | 8±2 | 19±6 | 20±2 | 39±7 |
0.25 mg | 28±8 | 20±3 | 152±11 | 119±8 | 18±6 | 13±4 | 11±2 | 24±6 | 22±2 | 36±9 |
0.50 mg | 30±8 | 18±2 | 149±16 | 118±1 | 24±3 | 13±5 | 10±1 | 21±4 | 16±2 | 28±7 |
1.00 mg | 27±2 | 16±2 | 172±24 | 134±1 | 21±2 | 15±3 | 6±4 | 19±2 | 20±2 | 28±4 |
2.50 mg | 29±2 | 9±1 | 125±22 | 134±7 | 16±3 | 10±3 | 9±5 | 16±2 | 18±4 | 25±6 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In a reverse gene mutation assay in bacteria according to OECD TG 471 (adopted 21 July, 1997), strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 of S. typhimurium were exposed to D-ET-Dienon in DMSO at concentrations of 50, 100, 250, 500, 1000, 2500 µg/plate in the presence and absence of mammalian metabolic activation using the plate incorporation method.
The test item was tested limit concentration 2500 µg/plate None of the five tester strains showed increased reversion to prototrophy at any of the concentrations tested between 50 and 2500 µg/plate, either in the absence or presence of S9 mix. The positive controls induced the appropriate responses in the corresponding strains. Growth inhibition of the background lawn was observed at the highest concentration tested (2500 µg/plate) in the strains TA1535, TA100 and TA1537, from 500 µg/plate onwards in strain TA98 without 59 mix and from 1000 µg/plate onwards in the strains TA 1538 and TA98. There were precipitates in the agar found starting from 250 µg/plate onwards in all strains used in the tests without and with S9 mix..
This study is classified as acceptable. This study satisfies the requirement for Test OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.
The test material is considered non-mutagenic under the conditions of the test.
In a QSAR prediction using Leadscope Model Applier (v2.4) the potential of D-ET-Dienone to induce mutagenicity was assessed. Leadscope uses two parameters to guide the applicability of model domain: 1) having at least one structural feature defined in the model in addition to all the property descriptors; 2) having at least one chemical in a training neighbourhood with at least 30% global similarity to the test structure. In this case the prediction is within the applicability domain, since 4 structural features were found and 25 training compounds were identified in the model training set being structurally similar to the test compound.
The query structure does not match any structural alerts or examples for (bacterial in vitro) mutagenicity in Leadscope. Furthermore, the query structure does not contain an unclassified feature and is consequently predicted to be indeterminate in the bacterial in vitro (Ames) mutagenicity test. However, experimental data are also available clearly reporting a negative result.
Based on these results D-ET-Dienone is considered non-mutagenic as predicted by Leadscope.
This study is classified as acceptable for assessment based on methodolgy and documentation. This study satisfy the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) and the data is part of an overall assessment.
In a QSAR prediction using DEREK Nexus v6.1 the potential of D-ET-DIenone to induce mutagenicity was assessed. Derek Nexus makes qualitative predictions for and against toxicity through reasoning. For the endpoint of mutagenicity, predictions for toxicity decrease in confidence in the following order: certain>probable>plausible>equivocal. Predictions against toxicity increase in confidence in the following order: inactive (with unclassified and/or misclassified features)<inactive<improbable. Likelihood levels have beenshown to correlate with predictivity [Judson et al, 2013]. Multiple data sources (e.g. toxicity data from multiple assays and mechanistic evidence) are synthesised into the structure-activity relationships that underpins Derek Nexus predictions. An appreciation of the assay units applied by alert writers when building the alert training set. However, predictions are not quantitative and, as a result, do not include units.
The query structure does not match any structural alerts or examples for (bacterial in vitro) mutagenicity in Derek. Furthermore, the query structure does not contain an unclassified feature and is consequently not predicted to be indeterminate in the bacterial in vitro (Ames) mutagenicity test. However, experimental data are available clearly reporting a negative result.
Based on these results D-ET-Dienone is considered non-mutagenic as predicted by DEREK Nexus.
This study is classified as acceptable for assessment based on methodolgy and documentation. This study satisfy the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) and the data is part of an overall assessment.
Justification for classification or non-classification
Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.
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