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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
Eye irritation
Administrative data
- Endpoint:
- eye irritation, other
- 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 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- not applicable
- Principles of method if other than guideline:
- The model determines whether the instilled dose of a chemical substance causes cytotoxicity, and thereby responsible for the induction of corneal opacity and/or conjunctival redness. The dose applied and the physico-chemical properties of the test substance are the input data for a series of algorithms to determine the substance concentration in the eye tissue and to establish if this concentration reaches a cytotoxic concentration. This concentration is plotted against the subcooled water solubility of the substance, 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 an eye tissue absorption model which was based on the existing SkinPerm model on the basis that the eye tissue of the eye shares the same permeation properties as the viable epithelium of the skin, i.e., under the conditions required to reach cell burst associated to irritation/corrosion. KREATiS eye irritation/corrosion prediction model was adapted to account for the experimental conditions indicated in the OECD guideline 405 (applied dose) and to account for the physiological differences between the eye and the skin (eye tissue thickness, rabbit eye tear volume and reflex tearing rate). This model, provides the amount of substance which permeates through the eye tissue (comprising the epithelium, the stroma and the endothelium layers) and which is therefore accumulated in the eye tissue. The output of this model is then used to determine the cell burden (CB) value which informs whether the substance is able to cause cytoxicity, therefore leading to eye irritation or corrosion. This cell burden value (mol/kg) is plotted against the subcooled liquid water solubility (SCLS) of the substance and depending on the position of the substance on the plot (already subdivided into corrosive, irritant and non-irritant zones), it will be classified for eye 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 / tissue source
- Species:
- other: iSafeRat® Eye irritation/corrosion prediction model v1.0 was trained using data from studies performed using rabbits only. Therefore, the model mimics exposure of rabbit eyes to the test substance.
- Strain:
- other:
- Remarks:
- Rabbit (See study report)
Test system
- Vehicle:
- other:
- Remarks:
- iSafeRat® Eye 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® Eye irritation/corrosion prediction model v1.0 calculations use 100 mg of test substance as the amount applied
- Duration of treatment / exposure:
- iSafeRat® Eye irritation/corrosion prediction model v1.0 used data from studies that were performed without washing out the test substance or for which the substance was washed out with water or saline 24 h after instillation of the substance.
- Observation period (in vivo):
- Not applicable
- Duration of post- treatment incubation (in vitro):
- Not applicable
- Number of animals or in vitro replicates:
- Not applicable
- Details on study design:
- WORKING PRINCIPLE OF THE MODEL:
The model determines whether the instilled dose of a chemical substance causes cytotoxicity, and thereby responsible for the induction of corneal opacity and/or conjunctival redness. The dose applied and the physico-chemical properties of the test substance are the input data for a series of algorithms to determine the substance concentration in the eye tissue and to establish if this concentration reaches a cytotoxic concentration. This concentration is plotted against the subcooled water solubility of the substance, 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 an eye tissue absorption model which was inspired from the existing SkinPerm model (2) on the basis that the eye tissue of the eye shares the same permeation properties as the viable epithelium of the skin, i.e., under the conditions required to reach cell burst associated to irritation/corrosion. KREATiS eye irritation/corrosion prediction model was adapted to account for the experimental conditions indicated in the OECD guideline 405 (applied dose) and to account for the physiological differences between the eye and the skin (eye tissue thickness, rabbit eye tear volume and reflex tearing rate). This model, provides the amount of substance which permeates through the eye tissue (comprising the epithelium, the stroma and the endothelium layers) and which is therefore accumulated in the eye tissue. The output of this model is then used to determine the cell burden (CB) value which informs whether the substance is able to cause cytoxicity, therefore leading to eye irritation or corrosion. This cell burden value (mol/kg) is plotted against the subcooled liquid water solubility (SCLS) of the substance and depending on the position of the substance on the plot (already subdivided into corrosive, irritant and non-irritant zones), it will be classified for eye irritation/corrosion.
SCORING SYSTEM:
iSafeRat® Eye 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. Therefore, the model allows to predict the GHS/CLP classification criteria for eye irritation.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Remarks:
- Not applicable/QSAR
- Basis:
- other:
- Time point:
- other:
- Score:
- < 1
- Reversibility:
- other: not applicable
- Remarks on result:
- other: iSafeRat eye irritation/corrosion model was trained with substances not-irritant to eyes according to a Draize score for corneal opacity < 1, assuring reversibility of effects if present.
- Irritation parameter:
- iris score
- Remarks:
- Not applicable/QSAR model
- Basis:
- other:
- Time point:
- other:
- Score:
- < 1
- Reversibility:
- other: Not applicable/QSAR model
- Remarks on result:
- other: iSafeRat eye irritation/corrosion model was trained with substances not-irritant to eyes according to a Draize score for iris < 1, assuring reversibility of effects if present.
- Irritation parameter:
- conjunctivae score
- Remarks:
- Not applicable/QSAR model
- Basis:
- other:
- Time point:
- other:
- Score:
- < 2
- Reversibility:
- other: Not applicable/QSAR model
- Remarks on result:
- other: iSafeRat eye irritation/corrosion model was trained with substances not-irritant to eyes according to a Draize score for conjuctival redness < 2, assuring reversibility of effects if present.
- Irritation parameter:
- chemosis score
- Remarks:
- Not applicable/QSAR model
- Basis:
- other:
- Time point:
- other:
- Score:
- < 2
- Reversibility:
- other: not applicable/QSAR model
- Remarks on result:
- other: iSafeRat eye irritation/corrosion model was trained with substances not-irritant to eyes according to a Draize score for chemosis < 2, assuring reversibility of effects if present.
Any other information on results incl. tables
Results foriSafeRat® eye irritation/corrosion v1.0: In the eye irritation/corrosion model’s graph (Figure 1), the test substance Trimethylolpropane Trisorbate, an ester, is located within a non-irritant region (See Figure 1 in study report) in which 20 out of 20 fully validated substances are non-irritant (coloured green). Furthermore, the ester of the training set which is closest to the test substance is non-irritant with a higher cell burden value than the test substance.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Trimethylolpropane Trisorbate is classified as non-irritant to eyes 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 eye irritation/corrosion potential. Therefore, this endpoint prediction can be considered reliable without restrictions (Klimisch score K1).
- Executive summary:
The acute eye irritation/corrosion potential of the Trimethylolpropane Trisorbate was predicted using the iSafeRat® eye irritation/corrosion v2.0 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 eye 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. 405, "Acute Eye Irritation/Corrosion" (1), referenced as Method B.5 of Commission Regulation No. 440/2008.
Trimethylolpropane Trisorbate is predicted as non-irritant to eyes 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 eye 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 eye 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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