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EC number: 293-297-3 | CAS number: 91053-33-7
- 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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 20-01-2015 to 21-05-2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study performed under GLP. All relevant validity criteria were met.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: The Ocular Toxicity Working Group (OTWG) of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Interagency Centre for the Evaluation of Alternative Toxicological Methods (NICEATM)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: In Vitro Techniques in Toxicology Database (INVITTOX) protocol 127. Bovine Opacity and Permeability (BCOP) Assay, 2006.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Gautheron P., Dukic M., Alix D. and Sina J.F., Bovine corneal opacity and permeability test: An in vitro assay of ocular irritancy. Fundam Appl Toxicol 18:442-449, 1992.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- inspected: March 2013 ; signature: May 2013
Test material
- Reference substance name:
- Juniper, Juniperus mexicana, ext., isomerized, acetylated
- EC Number:
- 293-297-3
- EC Name:
- Juniper, Juniperus mexicana, ext., isomerized, acetylated
- Cas Number:
- 91053-33-7
- Molecular formula:
- Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)
- IUPAC Name:
- (1S,2R,5S,7S)-2,6,6,8-tetramethyltricyclo[5.3.1.0¹,⁵]undec-8-ene; 1-[(1R,2R,5S,7R)-2,6,6,8-tetramethyltricyclo[5.3.1.0¹,⁵]undec-8-en-9-yl]ethan-1-one
- Test material form:
- liquid
- Details on test material:
- - Physical state: Liquid.
- Storage condition of test material: At room temperature protected from light.
- Other: Pale yellow
Constituent 1
Test animals / tissue source
- Species:
- other: bovine
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Recognised supplier (documented in the full study report)
- Number of animals: Not reported.
- Characteristics of donor animals (e.g. age, sex, weight): > 9 months old (typically).
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Freshly isolated bovine eyes of at least 9 month old donor cattle were collected from the abattoir. Excess tissue was removed from the excised eyes. Post-excision, the isolated eyes were stored in physiological saline in the cooled slaughter-house until transportation to the laboratory using a suitable container. The corneae were isolated on the same day after delivery of the eyes.
- Time interval prior to initiating testing: < 24 hours. Corneas were prepared for testing immediately on same day arrival.
- indication of any existing defects or lesions in ocular tissue samples: None. Only corneas free from damage utilised (e.g. presenting defects such as vascularization, pigmentation, opacity and scratches were discarded).
- Indication of any antibiotics used: None reported.
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration (if solution): undiluted - Duration of treatment / exposure:
- 10 minutes at 32 ± 1ºC.
- Duration of post- treatment incubation (in vitro):
- The holders were incubated, anterior chamber facing forward, at 32 ± 1 ºC for 120 ± 10 minutes. A post-treatment opacity reading was taken and each cornea was visually observed.
- Number of animals or in vitro replicates:
- Three (3) per test item, or negative or positive controls, respectively.
- Details on study design:
- SELECTION AND PREPARATION OF CORNEAS: All eyes were macroscopically examined before and after dissection. Only corneas free of damage were used. The isolated corneas were stored in a petri dish with cMEM (Eagle’s Minimum Essential Medium containing 1% (v/v) L-glutamine and 1% (v/v) Foetal Bovine Serum. The isolated corneas were mounted in a corneal holder (one cornea per holder) of MC2 (Clermont-Ferrand, France) 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. 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. The opacity of each cornea was read against an air filled chamber, and the initial opacity reading thus determined was recorded. Corneas that had an initial opacity reading higher than 7 were not used. Three corneas were selected at random for each treatment group.
QUALITY CHECK OF THE ISOLATED CORNEAS: The corneas were examined for defects macroscopically (e.g. presenting defects such as vascularization, pigmentation, opacity and scratches) and where necessary discarded. Additionally, only corneas with opacity < 7.0 are discarded, in accordance with the guideline.
NUMBER OF REPLICATES: 3 (Triplicate)
NEGATIVE CONTROL USED: physiological saline solution
SOLVENT CONTROL USED (if applicable): Not applicable.
POSITIVE CONTROL USED: 10% (w/v) Benzalkonium Chloride solution prepared in physiological saline.
APPLICATION DOSE AND EXPOSURE TIME: 0.75 mL and 10 minutes at 32 ± 1ºC.
TREATMENT METHOD: Closed chamber
POST-INCUBATION PERIOD: The holders were incubated, anterior chamber facing forward, at 32 ± 1 ºC for 120 ± 10 minutes. A post-treatment opacity reading was taken and each cornea was visually observed.
REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: After the incubation the solutions were removed and the epithelium was washed with MEM with phenol red (Eagle’s Minimum Essential Medium) and thereafter with cMEM. Possible pH effects of the test substance on the corneas were recorded. The medium in the posterior compartment was removed and both compartments were refilled with fresh cMEM.
- POST-EXPOSURE INCUBATION: The holders were incubated, anterior chamber facing forward, at 32 ± 1 ºC for 120 ± 10 minutes. A post-treatment opacity reading was taken and each cornea was visually observed.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Measured through light transmission through the cornea quantitatively using an opacitometer
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD490)
- Others (e.g, pertinent visual observations, histopathology): Any other pertinent visual observations would be recorded.
SCORING SYSTEM: Opacity, Permeability and In Vitro Irritancy Score (IVIS)
DECISION CRITERIA: The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:
In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value). A test item that induces an In Vitro Irritancy Score >/=55.1 is defined as an ocular corrosive or severe irritant. A test item with an IVIS = 3.0 is predicted to be not irritating to the eye (UN GHS and/or CLP Regulation (EC) 1272/2008 as amended).
Results and discussion
In vitro
Results
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- mean (n=3)
- Value:
- 1.1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Remarks:
- IVIS scores ranged from 1.0 to 1.3 after 10 minues treament
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: None. No pH effect of the test item was observed on the rinsing medium.
DEMONSTRATION OF TECHNICAL PROFICIENCY: The laboratory previously demonstrated technical proficiency of the validated method with proficiency test items (information in the public domain). Additionally, concurrent positive control and negative controls were within the current historic control range (HCD) (documented in the full study report), each meeting the validity criteria respectively.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes. 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.
- Acceptance criteria met for positive control: Yes. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 128.2 and was within the historical positive control data range.
- Range of historical values if different from the ones specified in the test guideline: The mean in vitro irritancy score of the negative control were less than the upper limits of the laboratory historical range and for the positive control (10% (w/v) Benzalkonium Chloride) at 128.2 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. The test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 1.1 after 10 minutes of treatment. Applicant assessment of the data indicates that the positive control and negative controls were within the current historic control range (HCD) (documented in the full study report), each meeting the validity criteria respectively.
Any other information on results incl. tables
Table 1 : Summary of opacity, permeability and in vitro scores
Treatment |
Mean Opacity #1 |
Mean Permeability #1 |
Mean In vitro Irritation Score #1 , 2 |
Negative Control |
0 |
0.000 |
0.0 |
Positive Control (Benzalkonium chloride) |
81.7 |
3.102 |
128.2 |
Test item |
1.0 |
0.010 |
1.1 |
#1 Calculated using the negative control mean opacity and mean permeability values
#2 Mean in vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value)
Table 2 : Opacity score
Eye |
Opacity before treatment |
Opacity after treatment |
Final opacity #1 |
Negative control corrected final opacity #2 |
Mean Opacity |
Negative Control |
|||||
1 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
|
3 |
0 |
0 |
0 |
0 |
|
Positive Control |
|||||
4 |
0 |
83 |
84 |
84 |
81.7 |
5 |
0 |
83 |
84 |
84 |
|
6 |
0 |
76 |
77 |
77 |
|
Test item |
|||||
13 |
0 |
1 |
1 |
1.0 |
1.0 |
14 |
-1 |
0 |
1 |
1.0 |
|
15 |
-1 |
0 |
1 |
1.0 |
#1 Final Opacity = Opacity after treatment – Opacity before treatment
#2 Negative control corrected Final Opacity = Final opacity – Mean final opacity negative control
Table 3 Permeability score individual values (uncorrected)
Eye |
Dilution Factor |
OD490 1 |
OD490 2 |
OD490 3 |
Average OD490 |
Final OD |
Mean Final Negative Control |
|
Negative Control |
|
|||||
1 |
1 |
0.010 |
0.011 |
0.011 |
0.011 |
0.011 |
0.008 |
2 |
1 |
0.004 |
0.004 |
0.004 |
0.004 |
0.004 |
|
3 |
1 |
0.009 |
0.007 |
0.008 |
0.008 |
0.008 |
|
|
Positive Control |
|
|||||
4 |
6 |
0.314 |
0.311 |
0.312 |
0.312 |
1.874 |
|
5 |
6 |
0.482 |
0.479 |
0.473 |
0.478 |
2.868 |
|
6 |
6 |
0.794 |
0.781 |
0.775 |
0.783 |
4.700 |
|
|
Test item |
||||||
13 |
1 |
0.022 |
0.033 |
0.024 |
0.026 |
0.026 |
|
14 |
1 |
0.009 |
0.011 |
0.012 |
0.011 |
0.011 |
|
15 |
1 |
0.013 |
0.013 |
0.018 |
0.015 |
0.015 |
Table 4 : In vitro irritancy score
Eye |
Negative control corrected final opacity |
Negative control corrected Final OD490 |
In vitro Irritancy Score #1 |
Negative Control |
|||
1 |
0.0 |
0.003 |
0.0 |
2 |
0.0 |
-0.004 |
-0.1 |
3 |
0.0 |
0.000 |
0.0 |
Positive Control |
|||
4 |
84.0 |
1.829 |
111.4 |
5 |
84.0 |
2.823 |
126.3 |
6 |
77.0 |
4.655 |
146.8 |
Test item |
|||
13 |
1.0 |
0.019 |
1.3 |
14 |
1.0 |
0.003 |
1.0 |
15 |
1.0 |
0.007 |
1.1 |
#1 In vitro irritancy score (IVIS) = opacity value + (15 x OD490 value)
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of this study, the test item is not considered to be irritant in the in vitro eye corrosion/irritation test using Bovine Corneal Opacity and Permeability model. The in vitro irritancy score (IVIS) was < 3.0 in the prediction model.
- Executive summary:
The study was performed according to OECD TG 437 and EU Method B.47 to assess the eye irritancy potential in accordance with GLP of the item in isolated bovine corneas. The purpose of this test was to evaluate the test item for its potential to induce serious eye damage/ocular irritation. In this test method, damage by the test item is assessed by quantitative measurements of changes in corneal opacity and permeability. A total of three corneas per treatment group were used. A volume of 750 microlitres of the item was placed the cornea. The negative control group received saline and the positive control group received 10% benzalkonium chloride. For each group the corneas were incubated for 10 minutes at 32 degrees C. After the incubation the solutions were removed and the corneas were washed with MEM with phenol red (Eagle’s Minimum Essential Medium) and thereafter with cMEM. Possible pH effects of the test item on the corneas were recorded. The medium in the posterior compartment was removed and both compartments were refilled with fresh cMEM. Subsequently the corneas were incubated for 120±10 minutes at 32±1°C. After the completion of the incubation period opacity determination was performed. Each cornea was inspected visually for dissimilar opacity patterns. Following the final opacity measurement, permeability of the cornea to Na-fluorescein was evaluated. 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 (10% (w/v) Benzalkonium Chloride) was 128.2 (GHS Category 1 : eye damage prediction) and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. The item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 1.1 after 10 minutes of treatment. Based on these results the item is considered to be not irritating or corrosive in the Bovine Corneal Opacity and Permeability test.
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