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EC number: 246-042-5 | CAS number: 24155-42-8
- 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:
- September 27th, 2013.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Deviations:
- yes
- Remarks:
- test item was applied dry.
- Qualifier:
- according to guideline
- Guideline:
- EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol
- EC Number:
- 246-042-5
- EC Name:
- α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol
- Cas Number:
- 24155-42-8
- Molecular formula:
- C11H10Cl2N2O
- IUPAC Name:
- 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals / tissue source
- Species:
- chicken
- Strain:
- other: ROSS 308
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: TARAVIS KFT. 9600 Sárvár, Rábasömjéni út 129. Hungary.
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): After collection, the heads were inspected for appropriate quality and wrapped with paper moistened with saline, then placed in a plastic box that can be closed (4-5 heads/box). The heads were transported to TOXI-COOP ZRT. at the earliest convenience for use approximately within 2 hours from collection. All eyes used in the assay were from the same groups of eyes collected on one specific day.
- Time interval prior to initiating testing: 2h
- indication of any existing defects or lesions in ocular tissue samples: no.
- Indication of any antibiotics used: no.
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- yes, concurrent positive control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.03 g/eye. - Duration of treatment / exposure:
- 10 seconds.
- Duration of post- treatment incubation (in vitro):
- 240 ± 5 minutes
- Number of animals or in vitro replicates:
- 3 eyes for the test item and positive control, 1 eye for the negative control.
- Details on study design:
- SELECTION AND PREPARATION OF ISOLATED EYES: After removing the head from the plastic box, it was put on soft paper. The eyelids were carefully cut away with scissors, avoiding damaging the cornea. One small drop of fluorescein solution 2 (w/v) % was applied onto the cornea surface for a few seconds and subsequently rinsed off with 20 mL isotonic saline. Then the fluorescein-treated cornea was examined with hand-held slit lamp or slit lamp microscope, with the eye in the head, to ensure that the cornea was not damaged. If the cornea was in good condition, the eyeball was carefully removed from the orbit.
The eye ball was carefully removed from the orbit by holding the nictitating membrane with a surgical forceps, while cutting the eye muscles with bent scissors. Care was taken to remove the eyeball from the orbit without cutting off the optical nerve too short. The procedure avoided pressure on the eye while removing the eyeball from the orbit, in order to prevent distortion of the cornea and subsequent corneal opacity. Once removed from the
orbit, the eye was placed onto damp paper and the nictitating membrane was cut away with other connective tissue. The prepared eyes were kept on the wet papers in a closed box so that the appropriate humidity was maintained.
The appropriate number of eyes was selected and after being placed in the superfusion apparatus, the selected eyes were examined again with the slit lamp microscope to ensure that they were in good condition. The focus was adjusted to see clearly the isotonic saline which was flowing on the cornea surface. Eyes with a high baseline fluorescein staining (i.e., > 0.5) or corneal opacity score (i.e., > 0.5) were rejected. The cornea thickness was measured using the depth measuring device on the slit lamp microscope (Haag-Streit BQ 900) with the slit-width set at 9½, equalling 0.095 nm. Any eye with cornea thickness deviating more than 10 % from the mean value for all eyes, or eyes that showed any other signs of damage, were rejected and replaced.
EQUILIBRATION AND BASELINE RECORDINGS: Acclimatization was conducted for approximately 45 to 60 minutes. The temperature of the circulating water was verified to be in the range of 32 ± 1.5 °C in all chambers during the acclimatization and treatment periods. At the end of the acclimatization period, a zero reference measurement was recorded for cornea thickness and opacity to serve as a baseline (t=0) for each individual eye. The cornea thickness of the eyes should not change by more than ±5-7 % within approximately 45 to 60 minutes before the start of application. Slight changes in thickness (-3% to 2%) were observed in the eyes, a finding considered as normal when maintaining enucleated eyes. Following the equilibration period, the fluorescein retention was measured. Baseline values were required to evaluate any potential test item related effects after treatment. The location of any minor findings was marked on the record sheet as a drawing, if applicable. If any eye was considered to be unsuitable following baseline assessment, it was discarded.
NUMBER OF REPLICATES: 3
NEGATIVE CONTROL USED: 30 µL of 9 g/L NaCl, saline (Source: REANAL, Batch: PP/2012/10937) in ultra-pure water.
POSITIVE CONTROL USED: 0.03 g Imidazole (Source: Sigma-Aldrich, Batch: SLBC7446V)
APPLICATION DOSE AND EXPOSURE TIME: 0.03 g test item, exposure 10 s.
OBSERVATION PERIOD: The control and test eyes were evaluated pre-treatment and at approximately 30, 75, 120, 180 and 240 minutes after the post-treatment rinse. Minor variations within ± 5 minutes were considered acceptable. The cornea thickness and cornea opacity were measured at all time points. Fluorescein retention was determined at baseline (t=0) and 30 minutes after the post-treatment rinse.
REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: The cornea surface was rinsed thoroughly with 20 mL saline solution at ambient temperature, while taking care not to damage the cornea but attempting to remove all the residual test item if possible. The eye in the holder was then returned to its chamber.
- Indicate any deviation from test procedure in the Guideline: The test item was stuck on the corneas at 30 minutes after the post-treatment rinse, so a gentle rinsing with additional 20 mL saline was performed. The cornea surfaces were not totally cleared, little volume of test item was stuck on the cornea surface at 240 min after the posttreatment rinse.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: qualitative assessment.
- Damage to epithelium based on fluorescein retention: qualitative assessment.
- Swelling: measured with optical pachymeter on a slit-lamp microscope; slit-width setting: 0.095 nm. Cornea thickness was measured using the depth measuring device on the slit lamp microscope (Haag-Streit BQ 900) with the slit-width set at 9½, equalling 0.095 nm.
- Macroscopic morphological damage to the surface: qualitative assessment.
SCORING SYSTEM:
- Mean corneal swelling (%):
Corneal swelling (CS) was calculated as follows: CS = [(corneal thickness at time t – corneal thickness at time t = 0)/ corneal thickness at time t = 0] x100
For the calculation of Maximum Swelling, small negative numbers for swelling (0 to -5%) following application are counted as zero. Large negative numbers (> -12 %) are probably due to erosion and indicate a severe effect (scored as class IV). Cases of values of -5 % to -12 % are evaluated on a case by case basis but in the absence of other findings do not indicate a severe effect.
- Mean maximum opacity score
0 No opacity
0.5 Very faint opacity
1 Scattered or diffuse areas; details of the iris are clearly visible
2 Easily discernible translucent areas; details of the iris are slightly obscured
3 Severe corneal opacity; no specific details of the iris are visible; size of the pupil is barely discernible
4 Complete corneal opacity; iris invisible
- Mean fluorescein retention score at 30 minutes post-treatment
0 No fluorescein retention
0.5 Very minor single cell staining
1 Single cell staining scattered throughout the treated area of the cornea
2 Focal or confluent dense single cell staining
3 Confluent large areas of the cornea retaining fluorescein
DECISION CRITERIA: as indicated in the TG.
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- fluorescein retention score
- Run / experiment:
- mean
- Value:
- 2.5
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE Class III.
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- mean max.
- Value:
- 0
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE Class I.
- Irritation parameter:
- percent corneal swelling
- Run / experiment:
- mean max. (240 min)
- Value:
- 11
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE Class II.
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: The test item was stuck on the cornea surface all test item treated eyes at 30 minutes after the post-treatment rinse. It could not be removed from cornea surface by extra rinse (20 mL/eye saline solution).
DEMONSTRATION OF TECHNICAL PROFICIENCY: yes.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes.
- Acceptance criteria met for positive control: yes.
Positive and negative control values were within the corresponding historical control data ranges (Appendix II).
- Range of historical values if different from the ones specified in the test guideline: yes.
Any other information on results incl. tables
Table 1. Summary of test item results.
Observation |
Value |
ICE Class |
Mean maximum corneal swelling at up to 75 min |
10% |
II |
Mean maximum corneal swelling at up to 240 min |
11% |
II |
Mean maximum corneal opacity |
0.0 |
I |
Mean fluorescein retention |
2.5 |
III |
Other Observations |
The test item was stuck on the cornea surface all test item treated eyes at 30 minutes after the post-treatment rinse. It cannot be removed from cornea surface by extra rinse (20 mL/eye saline solution). |
|
Overall ICE Class |
1xI, 1xII, 1xIII |
|
Conclusion |
Not a severe irritant |
Table 2. Summary of positive control (imidazole) results.
Observation |
Value |
ICE Class |
Mean maximum corneal swelling at up to 75 min |
9% |
II |
Mean maximum corneal swelling at up to 240 min |
15% |
II |
Mean maximum corneal opacity |
4.0 |
IV |
Mean fluorescein retention |
3.0 |
IV |
Other Observations |
Cornea opacity score 4 was observed in three eyes at 30 minutes after the post- treatment rinse |
|
Overall ICE Class |
1xII, 2xIV |
|
Conclusion |
Corrosive, Category 1 |
Table 3. Summary of negative control (saline) results.
Observation |
Value |
ICE Class |
Mean maximum corneal swelling at up to 75 min |
0% |
I |
Mean maximum corneal swelling at up to 240 min |
0% |
I |
Mean maximum corneal opacity |
0.0 |
I |
Mean fluorescein retention |
0.0 |
I |
Other Observations |
None. |
|
Overall ICE Class |
3xI |
|
Conclusion |
Not classified |
Applicant's summary and conclusion
- Interpretation of results:
- other: not severely irritating, based on EU criteria.
- Conclusions:
- Based on the available data (overall ICE class 1xI, 1xII, 1xIII), the test item is not a severe irritant.
- Executive summary:
An in vitro (ex vivo) study was conducted in order to determine the potential severe eye damaging effects of the test item according to the OECD guideline 438 under GLP conditions. Eyeballs were isolated from chickens killed for human consumption and after the appropriate preparation were exposed to either the test item, imidazole (positive control) or saline (negative control). Three eyeballs were used for the test item and the positive control, one for the negative control. Fluorescein retention, corneal opacity and corneal swelling were evaluated, then the results of each endpoint were assigned to ICE classes according to the guideline recomendations.
According to the overall in vitro classification, no prediction can be made since the combinations of the 3 endpoints were 1xI, 1xII, 1xIII. Based on the results, the test item is not severely irritant to the eye.
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