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EC number: 701-329-9 | 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:
- 18 Jul 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
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 438 (Isolated Chicken Eye 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 June 2018
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- OGYÉI, National Institute of Pharmacy and Nutrition, Budapest, Hungary
Test material
- Reference substance name:
- Carboxylic acids, di-, C5-9
- EC Number:
- 701-329-9
- Molecular formula:
- C5di: C5H8O4 C6di: C6H10O4 C7di: C7H12O4 C8di: C8H14O4 C9di: C9H16O4
- IUPAC Name:
- Carboxylic acids, di-, C5-9
Constituent 1
Test animals / tissue source
- Species:
- chicken
- Strain:
- other: COBB 500
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 30 mg
- Duration of treatment / exposure:
- 10 sec
- Duration of post- treatment incubation (in vitro):
- not applicable
- Number of animals or in vitro replicates:
- Test and positive control item: 3 eyes each
Negative control item: 1 eye - Details on study design:
- SELECTION AND PREPARATION OF ISOLATED EYES
Chicken heads were collected after slaughter in a commercial abattoir from chickens (approximately 7 weeks old) which are used for human consumption. Heads were collected by a slaughter house technician and transported to the laboratory at ambient temperature as soon as possible. After collection, the heads were inspected for appropriate quality and wrapped with tissue paper moistened with saline, then placed in a closed plastic box. The heads were received at the laboratory and processed within 2 hours of collection.
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 2% (w/v) fluorescein solution was applied onto the cornea surface for a few seconds and subsequently rinsed off with 20 mL physiological saline. Then the fluorescein-treated cornea was examined with a 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 eyeball was carefully removed from the orbit by holding the nictitating membrane with 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.
EQUILIBRATION AND BASELINE RECORDINGS
The prepared eye was placed in a steel clamp with the cornea positioned vertically with the eye in the correct relative position (same position as in the chicken head), again avoiding too much pressure on the eye by the clamp. Because of the relatively firm sclera of the chicken eyeball, only slight pressure was needed to fix the eye properly. The clamp with the eyeball was transferred to a chamber of the superfusion apparatus. The clamp holding the eye was positioned in such a way that the entire cornea was supplied with physiological saline solution dripping from a stainless steel tube, at a rate of approximately 3-4 drops/minute or 0.1 to 0.15 mL/minutes. The door of the chamber was closed except for manipulations and examinations, to maintain temperature and humidity.
The appropriate number of eyes was selected. After being placed in the superfusion apparatus, they were examined again with the slit lamp microscope to ensure that they were in good condition. The focus was adjusted to see clearly the physiological 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, 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. If the selected eyes were appropriate for the test, acclimatization started and conducted for approximately 45 to 60 minutes. The chambers of the superfusion apparatus were at controlled temperature (32 ± 1.5°C) 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% within the -45 minute and the zero time. No significant changes in thickness (-1.6% or 1.6%) were observed in two eyes and no changes in thickness were observed in other eyes. Following the equilibration period, the fluorescein retention was measured. Baseline values were required to evaluate any potential test item related effect after treatment. All eyes were considered to be suitable for the assay.
NUMBER OF REPLICATES
Test and positive control item: 3 eyes each
Negative control item: 1 eye
NEGATIVE CONTROL USED
0.9% sodium chloride
POSITIVE CONTROL USED
30 mg powdered imidazole
APPLICATION DOSE AND EXPOSURE TIME
Test item and positive control item: 30 mg for 10 sec
Negative control item: 30 µL
OBSERVATION PERIOD
The control eyes and test eyes were evaluated pre-treatment and at approximately 30, 75, 120, 180 and 240 min after the post-treatment rinse. Minor variations within approximately ± 5 min were considered acceptable.
REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: The cornea surface was rinsed thoroughly with 20 mL physiological saline solution at ambient temperature, taking care not to damage the cornea but attempting to remove all residual test material if possible. Additional gentle rinsing with at least 3 x 20 mL saline was performed at each time point when the test item or positive control material remaining on the cornea was still observed.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: not reported
- Damage to epithelium based on fluorescein retention: not reported
- Swelling: measured with optical pachymeter on a slit-lamp microscope; slit-width setting: not reported
- Macroscopic morphological damage to the surface: not reported
SCORING SYSTEM:
- Mean corneal swelling (%)
- Mean maximum opacity score
- Mean fluorescein retention score at 30 minutes post-treatment
DECISION CRITERIA: The evaluation and decision criteria as indicated in the TG were used (see Table
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- 1
- Value:
- 4
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class IV
- Irritation parameter:
- fluorescein retention score
- Run / experiment:
- 1
- Value:
- 3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class IV
- Irritation parameter:
- percent corneal swelling
- Run / experiment:
- up to 75 min
- Value:
- 17.1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class III
- Irritation parameter:
- percent corneal swelling
- Run / experiment:
- up to 240 min
- Value:
- 17.1
- 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: Test item was stuck on all cornea surfaces after the post-treatment rinse. The cornea surfaces were cleared at 30 minutes after the post-treatment rinse. The positive control material was stuck on all cornea surfaces after the post-treatment rinse, the cornea surfaces were not cleared at 240 minutes after the post-treatment rinse. No other morphological effect was observed in the study.
DEMONSTRATION OF TECHNICAL PROFICIENCY: not reported
ACCEPTANCE OF RESULTS:
The results from all eyes used met the quality control standards. The negative control and positive control results were within the historical data range. This study was considered to be valid.
Any other information on results incl. tables
Table 1. Summary of results of test item treated eyes
Observation |
Value |
ICE Class |
Mean maximum corneal swelling at up to 75 min |
17.1% |
III |
Mean maximum corneal swelling at up to 240 min |
17.1% |
II |
Mean maximum corneal opacity |
4.00 |
IV |
Mean fluorescein retention |
3.00 |
IV |
Other Observations |
Test item was stuck on all cornea surfaces after the post-treatment rinse. The cornea surfaces were cleared at 30 minutes after the post-treatment rinse. |
|
Overall ICE Class |
1xIII 2xIV |
Table 2. Table of individual data - test item
Study Code: |
19/192-038C S |
Strain: |
COBB 500 |
||||||||||||||||||||||
Date of Exposure: |
18 July 2019 |
Test Item: |
Carboxylic Acids, di-, C4-11 |
||||||||||||||||||||||
Chamber number ↓ |
Corneal thickness (instrument units) |
Corneal opacility score |
Fluorescein retention |
||||||||||||||||||||||
Relative observation time (min) |
-45 |
0 |
C h a n g e |
30 |
change at 30 |
75 |
change at 75 |
Max change up to 75 |
120 |
change at 120 |
180 |
change at 180 |
240 |
change at 240 |
Max change up to 240 |
0 |
30 |
75 |
120 |
180 |
240 |
Max Δ Opac |
0 |
30 |
Δ Flu ret |
14 |
62 |
63 |
1.6% |
68 |
7.9% |
72 |
14.3% |
14.3% |
72 |
14.3% |
72 |
14.3% |
72 |
14.3% |
14.3% |
0 |
4 |
4 |
4 |
4 |
4 |
4.0 |
0 |
3 |
3.0 |
15 |
63 |
62 |
-1.6% |
70 |
12.9% |
74 |
19.4% |
19.4% |
74 |
19.4% |
74 |
19.4% |
74 |
19.4% |
19.4% |
0 |
4 |
4 |
4 |
4 |
4 |
4.0 |
0 |
3 |
3.0 |
16 |
62 |
62 |
0.0% |
69 |
11.3% |
73 |
17.7% |
17.7% |
73 |
17.7% |
73 |
17.7% |
73 |
17.7% |
17.7% |
0 |
4 |
4 |
4 |
4 |
4 |
4.0 |
0 |
3 |
3.0 |
Mean values: |
10.7% |
|
17.1% |
17.1% |
|
17.1% |
|
17.1% |
|
17.1% |
17.1% |
|
4.00 |
|
3.00 |
Table 3. Individual data - imidazole
Study Code: |
19/192-038CS |
Strain: |
COBB 500 |
||||||||||||||||||||||
Date of Exposure: |
18 July 2019 |
Positive Control: |
Imidazole |
||||||||||||||||||||||
Chamber number ↓ |
Corneal thickness (instrument units) |
Corneal opacity score |
Fluorescein retention |
||||||||||||||||||||||
Relative observation time (min) → |
-45 |
0 |
C h a n g e |
30 |
change at 30 |
75 |
change at 75 |
Max change up to 75 |
120 |
change at 120 |
180 |
change at 180 |
240 |
change at 240 |
Max change up to 240 |
0 |
30 |
75 |
120 |
180 |
240 |
Max Δ Opac |
0 |
30 |
Δ Flu ret |
17 |
63 |
63 |
0.0% |
66 |
4.8% |
71 |
12.7% |
12.7% |
73 |
15.9% |
78 |
23.8% |
82 |
30.2% |
30.2% |
0 |
4 |
4 |
4 |
4 |
4 |
4.0 |
0 |
3 |
3.0 |
18 |
62 |
62 |
0.0% |
67 |
8.1% |
70 |
12.9% |
12.9% |
73 |
17.7% |
77 |
24.2% |
80 |
29.0% |
29.0% |
0 |
4 |
4 |
4 |
4 |
4 |
4.0 |
0 |
3 |
3.0 |
19 |
63 |
63 |
0.0% |
67 |
6.3% |
70 |
11.1% |
11.1% |
74 |
17.5% |
79 |
25.4% |
82 |
30.2% |
30.2% |
0 |
4 |
4 |
4 |
4 |
4 |
4.0 |
0 |
3 |
3.0 |
Mean values: |
6.4% |
|
12.2% |
12.2% |
|
17.0% |
|
24.5% |
|
29.8% |
29.8% |
|
4.00 |
|
3.00 |
Table 4. Individual data - physiological saline
Study Code: |
19/192-038CS |
Strain: |
COBB 500 |
||||||||||||||||||||||
Date of Exposure: |
18 July 2019 |
Negative Control: |
Physiological saline (NaCl 0.9% w/v) |
||||||||||||||||||||||
Chamber number ↓ |
Corneal thickness (instrument units) |
Corneal opacity score |
Fluorescein retention |
||||||||||||||||||||||
Relative observation time (min) → |
-45 |
0 |
C h a n g e |
30 |
change at 30 |
75 |
change at 75 |
Max change up to 75 |
120 |
change at 120 |
180 |
change at 180 |
240 |
change at 240 |
Max change up to 240 |
0 |
30 |
75 |
120 |
180 |
240 |
Max Δ Opac |
0 |
30 |
Δ Flu ret |
20 |
63 |
63 |
0.0% |
63 |
0.0% |
63 |
0.0% |
0.0% |
63 |
0.0% |
63 |
0.0% |
63 |
0.0% |
0.0% |
0 |
0 |
0 |
0 |
0 |
0 |
0.00 |
0 |
0 |
0.00 |
5. Summary table for UN GHS classification
Criteria for “No category” (all true) |
|
3 endpoints classed as I or 2 endpoints classed as I and 1 endpoint classed as II or 1 endpoint classed as I and 2 endpoints classed as II: |
False |
No severe corneal morphological changes: |
True |
Test item was not stuck to the cornea at 240 minutes after the post- treatment rinse: |
True |
Criteria for “Category 1” (one or more true) |
|
2 or more endpoints classed as IV: |
True |
Corneal opacity = 3 at 30 min (in at least 2 eyes): |
False |
Corneal opacity = 4 at any time point (in at least 2 eyes): |
True |
Severe loosening of epithelium (in at least 1 eye): |
False |
Criteria for “No prediction can be made” (one or two true) |
|
Based on the endpoints not classifiable for No Category, or for Category 1: |
False |
Particles of test item were stuck to the cornea and could not be washed off during the study: |
False |
Applicant's summary and conclusion
- Interpretation of results:
- other: CLP/EU GHS criteria met, classified as Eye Irrit. 1 according to Regulation (EC) No 1272/2008
- Conclusions:
- Eye Irrit. 1
- Executive summary:
In this reliable and GLP-conform Isolated Chicken Eye (ICE) study according to OECD 438, exposure of chicken eyes with the test item for 10 sec, resulted in corneal swelling (both at 75 and 240 min after treatment) as well as increased corneal opacity and fluorescein retention, compared to the negative control. The test item is therefore considered as severly irritating to the eye.
The experiment met the validity criteria, therefore the study was considered to be valid.
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