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Diss Factsheets
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EC number: 950-112-7 | CAS number: 347377-00-8
- 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
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation / corrosion, other
- Remarks:
- QSAR result
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- October 14th, 2019
- Reliability:
- 1 (reliable without restriction)
- 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
iSafeRabbit models for skin and eye irritation by KREATiS
2. MODEL (incl. version number)
iSafeRat skin irritation/corrosion prediction model v1.0
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC=CC=CC(=O)OCC(CC)(COC(=O)C=CC=CC)COC(=O)C=CC=CC
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
see documents under 'Attached justification' below
5. APPLICABILITY DOMAIN
see documents under 'Attached justification' below
6. ADEQUACY OF THE RESULT
If the substance falls within the applicability domain of the model, the result is expected to be reliable.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- not applicable
- Principles of method if other than guideline:
- The model determines whether the applied dose of a chemical substance causes cytotoxicity, and thereby be responsible for the induction of erythema and/or oedema. The dose applied and the physico-chemical properties of the test substance are the input data to a series of algorithms to determine the substance concentration in the viable epidermis and to establish if this concentration reaches a cytotoxic concentration for the keratinocytes. These concentrations are plotted against the logarithm of subcooled water solubility of the substance (Log SCLS). As shown in the figure 1, the plot is subdivided into corrosive, irritant and non-irritant zones. The substance will fall into one of these zones, thereby allowing a classification.
The parameters given in Table 1 were provided as the input data into a skin absorption model, which was based on the existing SkinPerm model (4). The Kreatis model was adapted for the experimental conditions indicated in the OECD guideline 404 (exposure period, applied dose, semi-occlusive dressing). This model provides the amount of substance which passes through the stratum corneum and that permeates into the viable epidermis. The output of this model was then used to determine the cell burden value (CB) which informs whether the substance was able to cause any cytotoxicity, therefore leading to dermal irritation or corrosion. This cell burden value is plotted against the (Log SCLS) of the substance and depending on its position on the plot (already subdivided into corrosive, irritant and non-irritant zones), it will be classified for skin irritation/corrosion. - GLP compliance:
- no
- Remarks:
- Not applicable/QSAR models
Test material
- Reference substance name:
- 2,4-Hexadienoic acid, 1,1’-[2-ethyl-2-[[(1-oxo-2,4-hexadien-1-yl)oxy]methyl]-1,3-propanediyl] ester
- EC Number:
- 950-112-7
- Cas Number:
- 347377-00-8
- Molecular formula:
- C24H32O6
- IUPAC Name:
- 2,4-Hexadienoic acid, 1,1’-[2-ethyl-2-[[(1-oxo-2,4-hexadien-1-yl)oxy]methyl]-1,3-propanediyl] ester
- Test material form:
- solid
- Details on test material:
- Physical state: solid
Constituent 1
Test animals
- Species:
- other: iSafeRat® Skin irritation/corrosion prediction model v2.0 was trained using data from studies performed using rabbits only. Therefore, the model mimics exposure of the rabbit skin to the test substance.
- Strain:
- other:
- Remarks:
- Rabbit (See study report)
Test system
- Type of coverage:
- other: iSafeRat® Skin irritation/corrosion prediction model v1.0 was trained using data from studies performed with a semi-occlusive patch only. Data from occlusive coverage was only included when the outcome was not-irritant to skin.
- Preparation of test site:
- other:
- Remarks:
- iSafeRat® Skin irritation/corrosion prediction model v1.0 was trained using data from studies using shaved rabbits only. Therefore, the model mimics exposure over shaved rabbit skin.
- Vehicle:
- other:
- Remarks:
- iSafeRat® Skin irritation/corrosion prediction model v1.0 was trained using data from studies performed using neat substances only. Therefore, the model mimics studies performed with the unchanged test substance (no vehicle).
- Controls:
- not required
- Amount / concentration applied:
- iSafeRat® Skin irritation/corrosion prediction model v1.0 calculations use 500 mg of test substance as the amount applied
- Duration of treatment / exposure:
- iSafeRat® Skin irritation/corrosion prediction model v1.0 mimics a 4 h exposure period
- Observation period:
- not applicable
- Number of animals:
- not applicable
- Details on study design:
- WORKING PRINCIPLE OF THE MODEL:
The model determines whether the applied dose of a chemical substance causes cytotoxicity, and thereby responsible for the induction of erythema and/or oedema. The dose applied and the physico-chemical properties of the test substance are the input data to a series of algorithms to determine the substance concentration in the viable epidermis and to establish if this concentration reaches a cytotoxic concentration for the keratinocytes. These concentrations are plotted against the logarithm of subcooled water solubility of the substances (Log SCLS). As shown in the figure 1 (see study report), the plot is subdivided into corrosive, irritant and non-irritant zones. The substance will fall into one of these zones, thereby allowing a classification.
The parameters given in Table 1(see study report) were provided as the input data into a skin absorption model, which was based on the existing SkinPerm model. The Kreatis model was adapted for the experimental conditions indicated in the OECD guideline 404 (exposure period, applied dose, semi-occlusive dressing). This model provides the amount of substance which passes through the stratum corneum and that permeates into the viable epidermis. The output of this model was then used to determine the cell burden value (CB) which informs whether the substance was able to cause any cytotoxicity, therefore leading to dermal irritation or corrosion. This cell burden value is plotted against the (Log SCLS) of the substance and depending on its position on the plot (already subdivided into corrosive, irritant and non-irritant zones), it will be classified for skin irritation/corrosion.
SCORING SYSTEM:
iSafeRat® Skin irritation/corrosion prediction model v1.0 was trained using data from studies that used the Draize scoring method. From these studies the substances were validated as Category 1, Category 2 and No category chemicals according to GHS/CLP classification criteria.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- erythema score
- Remarks:
- Not applicable/QSAR model
- Basis:
- other:
- Time point:
- other:
- Score:
- < 2.3
- Reversibility:
- other: Not applicable/QSAR model
- Remarks on result:
- other: iSafeRat skin irritation/corrosion model was trained with substances not-irritant to skin according to a Draize score for erythema < 2.3, assuring reversibility of effects if present.
- Irritation parameter:
- edema score
- Remarks:
- Not applicable/QSAR model
- Basis:
- other:
- Time point:
- other:
- Score:
- < 2.3
- Reversibility:
- other: Not applicable/QSAR model
- Remarks on result:
- other: iSafeRat skin irritation/corrosion model was trained with substances not-irritant to skin according to a Draize score for edema < 2.3, assuring reversibility of effects if present.
Any other information on results incl. tables
Results for iSafeRat® skin irritation/corrosion v1.0: The test substance Trimethylolpropane Trisorbate, an ester, is located within a non-irritant output region of the model (see Figure 1 in study report), in which 22 out of 22 fully validated substances are non-irritant. Furthermore, the ester of the training set which is closest to the test substance is non-irritant with a higher cell burden value and higher SCLS than the test substance. Therefore, Trimethylolpropane Trisorbate is concluded to be non-irritant to skin.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Trimethylolpropane Trisorbate is classified non-irritant to skin according to Regulation (EC) No. 1272/2008 (CLP) and to GHS. The test substance falls within the applicability domain of the model and was hence reliably predicted for its acute skin irritation/corrosion potential. Therefore, this endpoint prediction can be considered reliable without restrictions (Klimisch score K1).
- Executive summary:
The acute skin irritation/corrosion potential of Trimethylolpropane Trisorbate was predicted using the iSafeRat® skin irritation/corrosion v1.0 local model for esters. This QSAR model has been validated to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and predicts the skin irritation/corrosion potential that would be expected when testing the substance under experimental conditions in a laboratory study following the Guideline for Testing of Chemicals No. 404, "Acute Dermal Irritation/Corrosion" (1), referenced as Method B.4 of Commission Regulation No. 440/2008 (2).
Trimethylolpropane Trisorbate is predicted to be non-irritant to skin according to Regulation (EC) No. 1272/2008 (CLP) and to GHS. The test substance falls within the applicability domain of the model and was hence reliably predicted for its acute skin irritation/corrosion potential. Therefore, this endpoint prediction can be considered reliable without restrictions (Klimisch score K1).
This study is considered as acceptable and satisfies the requirement for acute skin irritation/corrosion endpoint.
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.
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