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EC number: 228-067-3 | CAS number: 6107-56-8
- 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: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 30 April 2018 - 01 May 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
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 26 July 2013
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Calcium di(octanoate)
- EC Number:
- 228-067-3
- EC Name:
- Calcium di(octanoate)
- Cas Number:
- 6107-56-8
- Molecular formula:
- C8H16O2.1/2Ca
- IUPAC Name:
- calcium di(octanoate)
- Test material form:
- solid
- Details on test material:
- Purity: 100 %
Constituent 1
Test animals / tissue source
- Species:
- cattle
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Bovine eyes from young cattle were obtained from the slaughterhouse (Vitelco, -'s Hertogenbosch, The Netherlands), where the eyes were excised by a slaughterhouse employee as soon as possible after slaughter.
- Number of animals: Not reported
- Characteristics of donor animals (e.g. age, sex, weight): Young cattle
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Eyes were collected and transported in physiological saline in a suitable container under cooled conditions.
- Time interval prior to initiating testing: Not reported
- indication of any existing defects or lesions in ocular tissue samples: The eyes were checked 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.
- Indication of any antibiotics used: None reported
Test system
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- No workable suspension in physiological saline could be obtained, the test item was used as delivered by the sponsor and added pure on top of the corneas.
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 364.3 to 392.4 mg
- Concentration (if solution): Not applicable - Duration of treatment / exposure:
- 240 +/- 10 minutes
- Number of animals or in vitro replicates:
- 3 per treatment
- Details on study design:
- SELECTION AND PREPARATION OF CORNEAS
The isolated corneas were stored in a petri dish with cMEM (Earle’s Minimum Essential Medium (Life Technologies, Bleiswijk, The Netherlands) containing 1% (v/v) L-glutamine (Life Technologies) and 1% (v/v) Fetal Bovine Serum (Life Technologies)). The isolated corneas were mounted in a corneal holder (one cornea per holder) of BASF (Ludwigshafen, Germany) with the endothelial side against the O-ring of the posterior half of the holder. The anterior half of the holder was 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 hour at 32 ± 1°C.
QUALITY CHECK OF THE ISOLATED CORNEAS
After the incubation period, the medium was removed from both compartments and replaced with fresh cMEM. Opacity determinations were performed on each of the corneas using an opacitometer (BASF-OP3.0, BASF, Ludwigshafen, Germany). The opacity of each cornea was read against a cMEM filled chamber, and the initial opacity reading thus determined was recorded. Corneas that had an initial opacity reading higher than 7 were not used.
NUMBER OF REPLICATES
Three corneas were selected at random for each treatment group.
NEGATIVE CONTROL USED
Physiological saline (Eurovet Animal Health, Bladel, The Netherlands)
SOLVENT CONTROL USED (if applicable)
Not applicable
POSITIVE CONTROL USED
20% (w/v) Imidazole solution prepared in physiological saline
APPLICATION DOSE AND EXPOSURE TIME
The medium from the anterior compartment was removed and 750 µl of the negative control and 20% (w/v) Imidazole solution (positive control) were introduced onto the epithelium of the cornea. The test item was weighed in a bottle and applied directly on the corneas in such a way that the cornea was completely covered (364.3 to 392.4 mg).
TREATMENT METHOD: [closed chamber / open chamber] Open chamber
REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: At least three times with MEM with phenol red (Earle’s Minimum Essential Medium Life Technologies)
- POST-EXPOSURE INCUBATION:
Following the final opacity measurement, permeability of the cornea to Na-fluorescein (Sigma-Aldrich, Germany) was evaluated.
The medium of both compartments (anterior compartment first) was removed. The posterior compartment was refilled with fresh cMEM. The anterior compartment was filled with 1 mL of 5 mg Na-fluorescein/mL cMEM solution (Sigma-Aldrich Chemie GmbH, Germany). The holders were slightly rotated, with the corneas maintained in a horizontal position, to ensure uniform distribution of the sodium-fluorescein solution over the entire cornea. Corneas were incubated in a horizontal position for 90 ± 5 minutes at 32 ± 1°C.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: The opacity of a cornea was measured by the diminution of light passing through the cornea. The light was measured as illuminance (I = luminous flux per area, unit: lux) measured with the device OP-KIT)
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of a micro plate reader] (OD490)
- Others (e.g, pertinent visual observations, histopathology): None reported
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
DECISION CRITERIA: please specify if the decision criteria as indicated in the TG was used. Yes
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- Mean
- Value:
- 0.4
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- Mean
- Value:
- 0.3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- other: mean permability
- Run / experiment:
- Mean
- Value:
- 0.007
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: The corneas were clear after the 240 minutes treatment
DEMONSTRATION OF TECHNICAL PROFICIENCY: Positive and negative control criteria met
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes; the individual in vitro irritancy scores for the negative controls ranged from 2.1 to 4.1
- Acceptance criteria met for positive control: Yes, the individual positive control in vitro irritancy scores ranged from 158 to 177
- Range of historical values if different from the ones specified in the test guideline: The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (20% (w/v) Imidazole) was 165 and within two standard deviations of the current historical positive control mean. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.
Any other information on results incl. tables
Table 1: Summary of Opacity, Permeability and In Vitro Scores
Treatment | Mean Opacity | Mean Permeability | Mean in vitro irritancy Score1,2 |
Negative Control | 2.7 | 0.021 | 3.0 |
Positive Control | 121 | 2.936 | 165 |
Test item | 0.3 | 0.007 | 0.4 |
1 Calculated using the negative control mean opacity and mean permeability values for the positive control and test item.
2 In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).
Table 2: Opacity Score
Treatment | Opacity before treatment | Opacity after treatment | Final Opacity1 | Negative control corrected for Final Opacity2 | Mean Final Opacity |
Negative Control |
4.5 |
8.3 |
3.8 |
2.7 |
|
4.1 |
5.9 |
1.8 |
|||
3.8 |
6.2 |
2.5 |
|||
Positive Control |
4.4 |
123.8 |
119.4 |
117 |
121 |
5.2 |
138.1 |
132.9 |
130 |
||
3.4 |
122.6 |
119.1 |
116 |
||
Test item |
3.6 |
6.4 |
2.8 |
0.2 |
0.3 |
3.4 |
5.6 |
2.2 |
-0.4 |
||
3.2 |
7.1 |
3.9 |
1.3 |
Calculations are made without rounding off.
1 Final Opacity = Opacity after treatment – Opacity before treatment.
2 Negative control corrected Final Opacity = Final opacity – Mean final opacity negative control3
Table 3: Permeability Score Individual Values (Uncorrected)
Treatment |
Dilution Factor |
OD490 1 |
OD490 2 |
OD490 3 |
Average OD |
Final OD |
Mran final negative control |
Negative Control |
1 |
0.020 |
0.021 |
0.020 |
0.020 |
0.020 |
0.021 |
1 |
0.020 |
0.020 |
0.020 |
0.020 |
0.020 |
||
1 |
0.021 |
0.029 |
0.021 |
0.024 |
0.024 |
||
Positive Control |
6 |
0.510 |
0.508 |
0.530 |
0.516 |
3.096 |
|
6 |
0.530 |
0.540 |
0.541 |
0.537 |
3.222 |
||
6 |
0.468 |
0.476 |
0.493 |
0.479 |
2.874 |
||
Test item |
1 |
0.035 |
0.036 |
0.042 |
0.038 |
0.038 |
|
1 |
0.022 |
0.022 |
0.021 |
0.022 |
0.022 |
||
1 |
0.027 |
0.026 |
0.026 |
0.026 |
0.026 |
Calculations are made without rounding off.
Table 4: Permeability Score Individual Values (Corrected)
Treatment |
Dilution Factor |
Negative control corrected OD490 11 |
Negative control corrected OD490 21 |
Negative control corrected OD490 31 |
Negative control corrected OD490 Average |
Negative control corrected final OD490 |
Average OD |
Positive Control |
6 |
0.489 |
0.487 |
0.509 |
0.495 |
2.968 |
2.936 |
6 |
0.509 |
0.519 |
0.520 |
0.516 |
3.094 |
||
6 |
0.447 |
0.455 |
0.472 |
0.458 |
2.746 |
||
Test item |
1 |
0.014 |
0.015 |
0.021 |
0.016 |
0.016 |
0.007 |
1 |
0.001 |
0.001 |
0.000 |
0.000 |
0.000 |
||
1 |
0.006 |
0.005 |
0.005 |
0.005 |
0.005 |
Calculations are made without rounding off.
1 OD490 values corrected for the mean final negative control permeability (0.021)
Table 5: In Vitro Irritancy Score
Treatment |
Final Opacity2 |
Find OD4902 |
In vitro Irritancy Score1 |
Negative Control |
3.8 |
0.020 |
4.1 |
1.8 |
0.020 |
2.1 |
|
2.5 |
0.024 |
2.8 |
|
Positive Control |
117 |
2.968 |
161 |
130 |
3.094 |
177 |
|
121 |
2.746 |
158 |
|
Test item |
0.2 |
0.016 |
0.4 |
-0.4 |
0.000 |
-0.4 |
|
1.3 |
0.005 |
1.3 |
1 In vitro irritancy score (IVIS) = opacity value + (15 x OD490 value).
2 Positive control and test item are corrected for the negative control.
Table 6: Historical Control Data for the BCOP Studies
|
Negative Control |
Positive Control |
||
|
Opacity |
Permeability |
In vitro Irritancy Score |
In vitro Irritancy Score |
Range |
-5.4 - 5.2 |
-0.011 - 0.205 |
-5.3 - 5.4 |
86.5 - 211.4 |
Mean |
0.55 |
0.02 |
0.78 |
138.42 |
SD |
1.84 |
0.02 |
1.90 |
26.57 |
n |
166 |
166 |
166 |
166 |
SD = Standard deviation
n = Number of observations
The above mentioned historical control data range of the controls were obtained by collecting all data over the period of May 2015 to May 2018.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item induced an IVIS ≤ 3 (actual: 0.4), therefore, no classification is required for eye irritation or serious eye damage.
- Executive summary:
The eye irritation potential of the test item was investigated in an OECD 437 guideline study. The test item was applied without modification and was tested in conjunction with concurrent negative and postive controls. The test item induced a mean IVIS score of 0.4, and the negative and positive controls were within the acceptability limits and historic values. Therefore, no classification is required for eye irritation or serious eye damage.
The study is a GLP compliant guideline experimental study and is fully acceptable for assessment of this endpoint without restriction.
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