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EC number: 245-442-7 | CAS number: 23128-74-7
- 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
Description of key information
The substance was reported not sensitizing in a surveillance data base (IVDK). The substance was predicted to have no sensitization potential by the OECD toolbox and by OASIS Times. The substance was not entirely in the domain of OASIS Times. The substance was negative in a human patch test.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation, other
- Remarks:
- other: surveillance data
- Type of information:
- other: data base
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: A data base exclusively designed for surveillance of contact allergies was contacted: Information Network of Departments of Dermatology (IVDK). This database gave no evidence for a sensitization potential.
- Principles of method if other than guideline:
- A data base exclusively designed for surveillance of contact allergies was contacted: Information Network of Departments of Dermatology (IVDK)
- Type of study:
- other: surveillance data
- Parameter:
- other:
- Remarks on result:
- other: The database gave no evidence for a sensitization potential.
- Endpoint:
- skin sensitisation, other
- Remarks:
- Prediction with OECD Toolbox
- Type of information:
- calculation (if not (Q)SAR)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- accepted calculation method
- Principles of method if other than guideline:
- Prediction performed with the OECD Toolbox based on read-across data gap filling
- Parameter:
- other:
- Remarks on result:
- no indication of skin sensitisation based on QSAR/QSPR prediction
- Remarks:
- The OECD Toolbox predicts the compound to be not sensitizing
- Endpoint:
- skin sensitisation, other
- Remarks:
- QSAR analysis with OASIS TIMES
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The QSAR result meets the conditions listed in REACH (EC 1906/2006) ANNEX XI 1.3.
- Justification for type of information:
- 1. SOFTWARE
TIMES-SS 2.27.19.13
2. MODEL (incl. version number)
Skin sensitization v. 21.26 with autoxidation
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(C)(C)c1cc(CCC(=O)NCCCCCCNC(=O)CCc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
QMRF attached
5. APPLICABILITY DOMAIN
The structure falls to 88.89% within the domain of the model
6. ADEQUACY OF THE RESULT
The result (negative) is used in a weight of evidence approach in combination with a negative prediction by the OECD toolbox and based on structures with similar functional groups. - Qualifier:
- according to guideline
- Guideline:
- other: REACH guidance on QSAR R.6
- Principles of method if other than guideline:
- TIMES-SS 2.27.19.13 - Skin sensitization v. 21.26 with autoxidation (structure-toxicity and structure-metabolism relationships)
- GLP compliance:
- no
- Parameter:
- other:
- Remarks on result:
- no indication of skin sensitisation based on QSAR/QSPR prediction
Referenceopen allclose all
The database gave no evidence for a sensitization potential.
The OECD Toolbox predicts the compound to be not sensitizing
TIMES-SS model aims to encode structure toxicity and structure metabolism relationships through a number of transformations simulating skin metabolism and interaction of the generated reactive metabolites with skin proteins. The skin metabolism simulator mimics metabolism using 2D structural information. The autoxidation (abiotic oxidation) of chemicals is also accounted for. A training set of diverse chemicals was compiled and their skin sensitization potency assigned to one of three classes. These three classes were Strong, Weak or Non sensitizing. The skin sensitization model was built as a composite of the following submodels: 1. Skin metabolism Simulator: This mimics the metabolic fate of parent chemical controlled by skin enzymes and thus the potential formation of protein adducts with reactive agents. 2D structural information of parent chemicals is used to model metabolism. Metabolic pathways are generated based on a set of hierarchically ordered principal transformations including spontaneous reactions, enzyme-catalyzed Phase I and Phase II drug metabolism reactions, and reactions with protein nucleophiles. The formation of macromolecular immunogens was used to identify probable structural alerts in parent chemicals or their metabolites. 2. COREPA (COmmon Pattern Recognition approach) 3D QSARs for intrinsic reactivity of compounds having substructures associated with activity. These models depend on both the structural alert and the rate of skin sensitization. Steric effects around the active site, molecular size, shape, solubility, lipophilicity and electronic properties are taken into account. These models generally may involve combinations of molecular parameters or descriptors, which trigger (“fire”) the alerting group. A quantitative structure-activity relationship (QSAR) system for estimating skin sensitization potency has been developed which incorporates skin metabolism and considers the potential of parent chemicals and/or their activated metabolites to react with skin proteins. The autoxidation (abiotic oxidation) of chemicals is also accounted for. A training set of diverse chemicals was compiled and their skin sensitization potency assigned to one of three classes. These three classes were Strong, Weak or Non sensitizing.
The applicability domain of TIMES-SS model consists of the following layers:
1. General parametric requirements - includes ranges of variation of log KOW and MW. It specifies in the domain only those chemicals that fall in the range of variation of the MW (from 30 to 737 Da, in this study) and log Kow (from -13.2 to 15.4, in this study) defined on the bases of the correctly predicted training set chemicals. This layer of the domain is applied only on parent chemicals.
2. Structural domain - it is represented by the list of atom - centered fragments extracted from the chemicals in the training set. The training chemicals were split into two subsets: chemicals correctly predicted by the model and incorrectly predicted chemicals. These two subsets of chemicals were used to extract characteristics determining the "good" and "bad" space of the domain. Extracted characteristics were split into three categories: unique characteristics of correct and incorrect chemicals (presented only in one of the subsets) and fuzzy characteristics presented in both subsets of chemicals. The target structure is also partitioned into atom-centered fragments and when they present in the list of extracted atom-centered fragments from the training set chemicals and satisfy the accepted thresholds the chemical is categorized as belonging to the structural domain.
The default thresholds for classifying of chemicals to the structural domain of the current skin sensitization model are:
· All extracted fragments to belong to the "good" domain ("Correct" = 100%)
· All fuzzy fragments are considered as part of the "good" domain
· No fragments belonging to "bad" domain ("Incorrect" = 0%)
· No unique fragment ("Unknown" = 0%)
Structural domain is applied on parent chemicals, only.
3. Mechanistic domain - in SS model it includes:
· Interpolation space: this stage of the applicability domain of the model holds only for chemicals for which an additional COREPA model is required. It estimates the position of the target chemicals in the population density plot built in the parametric space defined by the explanatory variables of the model by making use the training set chemicals. The accepted threshold of population density in the
current study is 10%. Chemicals with values below 10% are "Out of domain". "N/A" is assigned when this type of sub-domain is not relevant to the structure and will be not accounted in the total domain. "Unknown" is referred for the cases when some parameters could not be calculated by any reason or for chemicals with equivocal predictions (not reaching the probability threshold of the COREPA model and reported in TIMES as Can't predict). The mechanistic domain is applied on the parent structures and on their metabolites.
In order to belong to the model domain a target structure must meet the requirements of all the domain layers.
The registrant considers this predication as valid because TIMES-SS was validated with 100 substances from the registrant's portfolio (Teubner et al., Regulatory Toxicology and Pharmacology 67 (2013) 468–485). All predictions that fullfilled all domain requirements were correct (Specificity 100%).
The QSAR program calculated a negative sensitization potential of the test substance. The substance is not entirely in domain of the system.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
No test on laboratory animals is available. Following a weight of evidence approach, all available information regarding the dermal sensitization potential of the chemical are taken into account. A Human Patch test has been performed showing no evidence of allergenic potential. The Human Patch test was conducted in a test facility that was found to be not reliable. The results have to be used with caution and do not fully cover the endpoint sensitization. Therefore, a search in a surveillance data base (IVDK) for contact allergies was initiated. The data search revealed that the test substance and chemically related structures have no potential for skin sensitization. In addition, the chemical was predicted to be negative by the OECD Toolbox using the read-across data gap filling approach. Furthermore, the QSAR program OASIS TIMES predicted the chemical to have no sensitizing potential. Although the chemical was not entirely in the domain of the QSAR program, this result is taken into account as well. In conclusion, the chemical is considered to be not sensitizing based on the summary of data available. This is in line with our experience with other members of this chemical family which do not show a sensitization potential.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for sensitization under Regulation (EC) No. 1272/2008.
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