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EC number: - | CAS number: -
- 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: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13 - 17 Nov 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
- Version / remarks:
- adopted in 2020
- Deviations:
- yes
- Remarks:
- demonstration of technical proficiency not provided
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 2,2-bis[(hexadecanoyloxy)methyl]propane-1,3-diyl dihexadecanoate
- Cas Number:
- 18641-58-2
- Molecular formula:
- C69H132O8
- IUPAC Name:
- 2,2-bis[(hexadecanoyloxy)methyl]propane-1,3-diyl dihexadecanoate
Constituent 1
Test animals / tissue source
- Species:
- cattle
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Vitelco,’s Hertogenbosch, The Netherlands
- Storage, temperature and transport conditions of ocular tissue: The isolated eyes were transported in physiological saline in a suitable container under cool conditions.
- Time interval prior to initiating testing: The eyes were collected from the slaughter house and tested the day of arrival in the laboratory
- Indication of any existing defects or lesions in ocular tissue samples: The eyes were examined for unacceptable defects, such as opacity, scratches, pigmentation and neovascularization by removing them from the physiological saline and holding them in the light. Those exhibiting defects were discarded.
Test system
- Vehicle:
- physiological saline
- Controls:
- yes, concurrent vehicle
- yes, concurrent positive control
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 750 µL
NEGATIVE CONTROL:
- Amount applied: 750 µL
POSITIVE CONTROL:
- Amount applied: 750 µL
- Concentration: 20% w/v - Duration of treatment / exposure:
- 240 ± 10 min at 32 ± 1 °C
- Duration of post- treatment incubation (in vitro):
- not applicable
- Number of animals or in vitro replicates:
- triplicates for each treatment and control groups
- Details on study design:
- SELECTION AND PREPARATION OF CORNEAS
The eyes were excised by a slaughterhouse employee as soon as possible after slaughter. The isolated corneas were stored in a petri dish containing Eagle's Minimum Essential Medium (cMEM) supplemented with 1% v/v L-glutamine and 1% fetal bovine serum. A specifically designed corneal holder was used to mount each cornea.
QUALITY CHECK OF THE ISOLATED CORNEAS
After an equilibration period, the initial opacity was determined using an opacitometer (BASF-OP3.0, Duratec GmbH, Hockenheim, Germany). Only corneas that had an initial opacity reading higher than 7 were used for the assay.
TREATMENT METHOD: Closed chamber method
The corneas were mounted in a corneal holder with the endothelial side against the O-ring of the posterior half of the chamber. The anterior chamber was then positioned on top of the cornea and tightened with screws. The compartments of the corneal holder were filled with cMEM of 32 ± 1°C. The corneas were incubated for the minimum of 1 h at 32 ± 1°C.
Following equlibration and an initial opacity reading, the test item, negative or positive control were directly applied on the corneas.
The holder was slightly rotated, with the corneas maintained in a horizontal position, to ensure uniform distribution of the solutions over the entire cornea. Corneas were incubated in a horizontal position for 240 ± 10 min at 32 ± 1°C.
REMOVAL OF TEST SUBSTANCE
After the incubation the solutions and the test item were removed and the epithelium was washed at least three times with MEM containing phenol red. Possible pH effects of the test item on the corneas were recorded. Each cornea was inspected visually for dissimilar opacity patterns. The medium in the posterior compartment was removed and both compartments were refilled with fresh cMEM and the opacity determinations were performed.
METHODS FOR MEASURED ENDPOINTS
- Corneal opacity: Corneal opacity was determined by the amount of light transmission through the cornea via an opacitometer (BASF-OP3.0, Duratec GmbH). The light was measured as illuminance (I = luminous flux per area, unit: lux).
- Corneal permeability: Sodium fluorescein was distributed over the cornea and the corneas were incubated at 90 ± 5 min at 32 ± 1 °C. The passage of sodium fluorescein dye was measured with the aid of a spectrophotometer (Tecan Infinite M200 Pro Plate Reader) at 490 nm (OD 490).
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
DECISION CRITERIA
Test substance with an IVIS > 55 was considered as severe irritant/corrosive and labelled Category 1 according to CLP/EPA/GHS.
Test substance with an IVIS ≤ 3 was regarded as non-irritant and labelled in no category.
Test substance with an IVIS > 3; ≤ 55: no prediction can be made.
Results and discussion
In vitro
Results
- Irritation parameter:
- in vitro irritation score
- Remarks:
- mean value of 3 corneae
- Run / experiment:
- 240 ± 10 min exposure
- Value:
- -2.7
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes, the negative control responses resulted in opacity and permeability values that were less than the upper limits of the laboratory historical range.
- Acceptance criteria met for positive control: Yes, the positive control resulted in an IVIS value which fell within two standard deviations of the current historical mean.
Any other information on results incl. tables
Table 1: Summary of opacity, permeability and in vitro irritancy scores
|
Mean |
Mean |
Mean In vitro |
Treatment |
|
|
|
|
Opacity |
Permeability |
Irritation Score*# |
Negative control |
3.0 |
0.006 |
3.1 |
Positive control |
151 |
1.594 |
175 |
Test item |
-3.7 |
0.070 |
-2.7 |
* Calculated using the negative control corrected mean opacity and mean permeability values for the positive control and test item. # In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value). |
Table 2: Individual opacity scores
Treatment |
Opacity before |
Opacity after |
Final Opacity§ |
Negative control |
Mean Final |
|
|||||
Negative control |
2.1 |
7.6 |
5.5 |
|
3.0 |
2.4 |
5.3 |
2.8 |
|||
2.4 |
3.0 |
0.6 |
|||
|
|||||
Positive control |
4.2 |
157.2 |
153.0 |
150 |
151 |
3.9 |
150.3 |
146.4 |
143 |
||
4.9 |
166.6 |
161.7 |
159 |
||
|
|||||
|
3.4 |
2.7 |
-0.8 |
-3.7 |
|
Test item |
3.8 |
2.3 |
-1.5 |
-4.5 |
-3.7 |
|
3.4 |
3.4 |
0.0 |
-3.0 |
|
Calculations are made without rounding off. § Final Opacity = Opacity after treatment - Opacity before treatment $ Negative control corrected Final Opacity = Final opacity - Mean final opacity negative control |
Table 3: Individual permeability scores, uncorrected
Treatment |
Dilution factor |
OD490 1 |
OD490 2 |
OD490 3 |
Average OD |
Final OD |
Mean final |
|
|||||||
Negative control |
1 |
0.008 |
0.009 |
0.009 |
0.009 |
0.009 |
0.006 |
1 |
0.012 |
0.016 |
0.015 |
0.014 |
0.014 |
||
1 |
-0.005 |
-0.003 |
-0.005 |
-0.004 |
-0.004 |
||
|
|
|
|
|
|
|
|
Positive control |
1 |
1.477 |
1.482 |
1.486 |
1.482 |
1.482 |
|
6 |
0.279 |
0.277 |
0.276 |
0.277 |
1.664 |
||
6 |
0.212 |
0.242 |
0.404 |
0.286 |
1.716 |
||
|
|
|
|
|
|
|
|
|
1 |
0.180 |
0.178 |
0.178 |
0.179 |
0.179 |
|
Test item |
1 |
0.015 |
0.011 |
0.008 |
0.011 |
0.011 |
|
|
1 |
0.038 |
0.038 |
0.037 |
0.038 |
0.038 |
|
Calculations are made without rounding off. |
Table 4: Individual permeability scores, corrected
Treatment |
Dilution factor |
Negative |
Negative |
Negative |
Negative control corrected OD490 Average |
Negative control corrected final OD490 |
Average OD |
|
|||||||
Positive control |
1 |
1.471 |
1.476 |
1.480 |
1.475 |
1.475 |
1.594 |
6 |
0.273 |
0.271 |
0.270 |
0.271 |
1.627 |
||
6 |
0.206 |
0.236 |
0.398 |
0.280 |
1.679 |
||
|
|||||||
|
1 |
0.174 |
0.172 |
0.172 |
0.172 |
0.172 |
|
Test item |
1 |
0.009 |
0.005 |
0.002 |
0.005 |
0.005 |
0.070 |
|
1 |
0.032 |
0.032 |
0.031 |
0.031 |
0.031 |
|
Calculations are made without rounding off. #OD490 values corrected for the mean final negative control permeability (0.006). |
Table 5: In Vitro Irritancy Score
Treatment |
Final Opacity# |
Final OD490# |
In vitro Irritancy |
|
|||
|
5.5 |
0.009 |
5.6 |
Negative control |
2.8 |
0.014 |
3.1 |
|
0.6 |
-0.004 |
0.5 |
|
|||
|
150 |
1.475 |
172 |
Positive control |
143 |
1.627 |
168 |
|
159 |
1.679 |
184 |
|
|||
|
-3.7 |
0.172 |
-1.1 |
Test item |
-4.5 |
0.005 |
-4.4 |
|
-3.0 |
0.031 |
-2.5 |
* In vitro irritancy score (IVIS) = opacity value + (15 x OD490 value). # Positive control and test item are corrected for the negative control. |
Table 6: Historical control data
|
Negative control |
Positive control |
||
|
Opacity |
Permeability |
In vitro Irritancy Score |
In vitro Irritancy Score |
Range |
-2.60 - 6.20 |
-0.011 - 0.081 |
-2.70 - 6.30 |
86 - 251 |
Mean |
1.16 |
0.012 |
1.35 |
150 |
SD |
1.78 |
0.012 |
1.83 |
28 |
n |
180 |
180 |
180 |
183 |
SD = Standard deviation The above mentioned historical control data range of the Controls were obtained by collecting all data over the period of Nov 2017 to Nov 2020. |
Applicant's summary and conclusion
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) 1272/2008.
- Conclusions:
- The irritation potential of the test substance was assessed in the BCOP assay. Application of the test substance to bovine corneae resulted in a calculated mean IVIS of -2.7. All validity criteria were within acceptable limits. Thus, the test substance is considered to be non-corrosive.
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