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EC number: 202-235-6 | CAS number: 93-28-7
- 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:
- 06 November 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- GLP study conducted according to OECD test Guideline No. 438 without any deviation.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
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 26 July 2013
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 4-allyl-2-methoxyphenyl acetate
- EC Number:
- 202-235-6
- EC Name:
- 4-allyl-2-methoxyphenyl acetate
- Cas Number:
- 93-28-7
- Molecular formula:
- C12H14O3
- IUPAC Name:
- 4-allyl-2-methoxyphenyl acetate
- Test material form:
- liquid
- Details on test material:
- - Physical state/Appearance: Colourless to pale yellow liquid, slightly viscous.
- Storage condition of test material: Room temperature in the dark
- Stability under test conditions: Stable under normal temperatures and pressure
Constituent 1
Test animals / tissue source
- Species:
- chicken
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Multiple chicken heads were supplied by XXX.
- Characteristics of donor animals (e.g. age, sex, weight): Spring chickens (Gallus Gallus e.g. Ross 308 Broiler) male or female, weighed approximately 3kg and were approximately 56 days old.
- Storage, temperature and transport conditions of ocular tissue: Heads were removed immediately after the chickens had been humanely killed at the source, for use on the same day. The time interval between collection of chicken heads and placing the eyes in the superfusion chamber following enucleation was minimized. All eyes fall within the acceptance criteria identified in the test guideline. The temperature of the chambers was at 32 ±1.5 °C.
Following slaughter, the intact chicken heads were placed into individual plastic compartments within a plastic box in order to minimize any damage to the eyes. The base of each compartment was lined with a paper towel moistened with isotonic saline. The heads were transported to the test facility at ambient temperature.
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): 30 µL of the test item was applied, as supplied, to the cornea
- Concentration (if solution): Undiluted - Duration of treatment / exposure:
- The test item was applied for 10 seconds and then rinsed from the eye using 20mL of 0.9% (w/v) sodium chloride solution (pre-warmed to approximately 32 °C).
- Number of animals or in vitro replicates:
- Test item: 3 eyes
Positive control: 3 eyes
Negative control: 2 eyes - Details on study design:
- SELECTION AND PREPARATION OF ISOLATED EYES
- Eyelids were carefully excised whilst taking care not to damage the cornea. The integrity of the cornea was measured with a drop of 2% (w/v) sodium fluorescein to the surface of the cornea and then rinsed with isotonic saline after a few seconds. The treated eyes were examined with the use of the Haag-Streit BQ 900 (Switzerland) microscope, to examine for damage to the cornea. An acceptable eye for the ICE test was one where the fluorescein retention and corneal opacity scores are =< 0.5.
- Acceptable eyes were dissected from the skull and pulled from the orbit by holding the nictitating membrane firmly with surgical forceps. The tissue behind the eye was carefully removed with bent, blunt tipped scissors. Once the eye was removed from the orbit a portion of the optic nerve remained. Other connective tissue was removed from the eye on an absorbent tray liner.
- Enucleated eyes were transferred to an appropriate clamp keeping the cornea vertical. They were then transferred to chambers within the superfusion apparatus ensuring the corneas received sufficient isotonic saline from the saline drip. The temperature of the chambers was at 32 ±1.5 °C.
- Once all eyes were placed in the superfusion apparatus, the eyes were examined again with the Haag-Streit BQ 900 to ensure the eyes had not been damaged by the dissection procedure. Corneal thickness measurements are taken with a depth measuring device no. 1 on the Haag-Streit BQ 900 slit lamp microscope at the center of each cornea.
- Eyes were replaced when: (i) the fluorescein score was > 0.5; (ii) the corneal opacity score was > 0.5; or (iii) there was any additional signs of damage, (iv) the corneal thickness measurements for individual eyes deviated more than 10% from the mean value for all eyes.
- After the approval process the eyes were incubated for 45 minutes for equilibrium purposes. Time zero measurements for corneal thickness and opacity were taken to serve as a baseline. The baseline for the fluorescein measurements were taken at dissection.
NUMBER OF REPLICATES: 2, 3 and 3 eyes for negative & positive control and test item, respectively.
NEGATIVE CONTROL USED: sodium chloride 0.9% w/v
POSITIVE CONTROL USED: 5% Benzalkonium chloride
APPLICATION DOSE AND EXPOSURE TIME
- Immediately following the zero reference measurements, each test eye (including clamp) was removed from the superfusion apparatus and placed horizontally (cornea facing upwards) into a petri dish. 0.03 mL of test item was applied to the cornea. The entire surface of the cornea was evenly covered. The test item remained in place for 10 seconds and was then rinsed from the eye using 20 mL of isotonic saline. The treated eye (including clamp) was subsequently returned to the superfusion apparatus in the original upright position.
OBSERVATION PERIOD
- Treated corneas were evaluated prior to treatment and at 30, 75, 120, 180, and 240 minutes (± 5 minutes) after the eyes had been decontaminated with the isotonic saline.
METHODS FOR MEASURED ENDPOINTS:
- All observations of the cornea and measurement of corneal thickness were performed using a HaagStreit BP900 slit-lamp microscope with depth-measuring device no. 1.
- Endpoints used during the evaluation procedure were corneal opacity, swelling, fluorescein retention and morphological effects (e.g. pitting, sloughing or roughening of the epithelium). All of the endpoints, with the exception of fluorescein retention (which is only determined at 30 minutes after test substance exposure) were determined at each of the above time points.
SCORING SYSTEM:
- Mean corneal swelling (%): Percentage corneal swelling was assessed from corneal thickness measurements. Mean percentage of corneal swelling for all test eyes was calculated for all the time points. The overall category score was determined from the highest mean score for epithelial swelling as observed at any time point.
Corneal swelling (%) = ((corneal thickness at time t - corneal thickness at time = 0) / (corneal thickness at time = 0)) x 100
- Mean maximum opacity score: Corneal opacity was calculated with the most densely opacified areas for scoring. The mean value for all test eyes was calculated for all time points. The highest mean score, as observed at any time point was given an overall category for each test item.
0: No opacity
0.5: Very faint opacity
1: Scattered or diffuse areas; details of the iris clearly visible
2: Easily discernible translucent area; 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
- Pitting, loosening (sloughing), roughening of the corneal surface, and adhering of test item are all morphological effects that can be noted on the cornea. The classification of these findings was subject to interpretation.
DECISION CRITERIA:
Results from corneal opacity, swelling, and fluorescein retention should be evaluated separately to generate an ICE class for each endpoint. The ICE classes for each endpoint are then combined to generate an Irritancy Classification for each test item.
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- 1
- Value:
- >= 0.5 - <= 2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- fluorescein retention score
- Run / experiment:
- 1
- Value:
- 0.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- percent corneal swelling
- Run / experiment:
- 1
- Value:
- >= 3.74 - <= 13.08
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- OTHER EFFECTS:
The ocular reactions observed in eyes treated with the test item were:
- maximal mean score of corneal opacity: 2.0 (180-240 min.), corresponding to the ICE class III;
- mean score of fluorescein retention: 0.7 corresponding to the ICE class II;
- maximal mean corneal swelling: 13.08% (75 min.) corresponding to the ICE class III.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The combination of the three endpoints for the negative control, physiological saline solution, was 3 x I. Therefore, the negative control is classified as "No Category", as expected.
- Acceptance criteria met for positive control: The combination of the three endpoints for the positive control, 5% Benzalkonium chloride, was 3 x IV. Therefore, the positive control is classified as "Corrosive/Severe irritant", as expected.
HISTORICAL CONTROL DATA:
In order to confirm the acceptability of the test, a comparison was made with historical control data for negative and positive controls obtained by the laboratory. The test was considered acceptable as the concurrent negative and positive controls were identified as GHS Non-Classified and GHS Category 1 respectively.
Any other information on results incl. tables
Table 7.3.2/5: Individual scores and Mean scores for corneal effects - test item
End Point |
Eye Number |
Time |
|||||
0 |
30 minutes |
75 minutes |
120 minutes |
180 minutes |
240 minutes |
||
Corneal Opacity |
3A |
0.5 |
0.5 |
1 |
2 |
2 |
2 |
6A |
0.5 |
0.5 |
2 |
2 |
2 |
2 |
|
8A |
0.5 |
0.5 |
0.5 |
1 |
2 |
2 |
|
Mean |
0.5 |
0.5 |
1.2 |
1.7 |
2.0 |
2.0 |
|
ICE Class |
III |
||||||
Fluorescein Retention |
3A |
|
1 |
|
|
|
|
6A |
|
0.5 |
|
|
|
|
|
8A |
|
0.5 |
|
|
|
|
|
Mean |
|
0.7 |
|
|
|
|
|
ICE Class |
II |
||||||
Corneal Thickness |
3A |
0.72 |
0.70 |
0.84 |
0.77 |
0.78 |
0.76 |
6A |
0.72 |
0.78 |
0.80 |
0.78 |
0.76 |
0.76 |
|
8A |
0.70 |
0.76 |
0.78 |
0.84 |
0.74 |
0.70 |
|
Mean |
0.71 |
0.75 |
0.81 |
0.80 |
0.76 |
0.74 |
|
Mean Corneal Swelling (%) |
|
4.67 |
13.08 |
11.68 |
6.54 |
3.74 |
|
ICE Class |
III |
||||||
Corneal Epithelium Condition |
3A |
N |
N |
N |
N |
N |
N |
6A |
N |
N |
N |
N |
N |
N |
|
8A |
N |
N |
N |
N |
N |
N |
|
ICE Classes Combined: |
1 x II, 2 x III |
||||||
Classification: |
No prediction can be made |
Table 7.3.2/6: Individual scores and Mean scores for Corneal Effects - positive control
End Point |
Eye Number |
Time |
|||||
0 |
30 minutes |
75 minutes |
120 minutes |
180 minutes |
240 minutes |
||
Corneal Opacity |
2A |
0.5 |
3 |
3 |
4 |
4 |
4 |
5A |
0.5 |
3 |
4 |
4 |
4 |
4 |
|
7A |
0.5 |
4 |
4 |
4 |
4 |
4 |
|
Mean |
0.5 |
3.3 |
3.7 |
4.0 |
4.0 |
4.0 |
|
ICE Class |
IV |
||||||
Fluorescein Retention |
2A |
|
3 |
|
|
|
|
5A |
|
3 |
|
|
|
|
|
7A |
|
3 |
|
|
|
|
|
Mean |
|
3.0 |
|
|
|
|
|
ICE Class |
IV |
||||||
Corneal Thickness |
2A |
0.68 |
0.80 |
0.88 |
0.84 |
0.80 |
0.82 |
5A |
0.72 |
0.83 |
0.88 |
0.92 |
0.94 |
0.94 |
|
7A |
0.72 |
0.90 |
0.90 |
0.97 |
0.90 |
0.92 |
|
Mean |
0.71 |
0.84 |
0.89 |
0.91 |
0.88 |
0.89 |
|
Mean Corneal Swelling (%) |
|
19.34 |
25.47 |
28.77 |
24.53 |
26.42 |
|
ICE Class |
III |
||||||
Corneal Epithelium Condition |
2A |
N |
N |
N |
N |
N |
N |
5A |
N |
S |
S |
S |
S |
S |
|
7A |
N |
N |
N |
N |
N |
N |
|
ICE Classes Combined: |
2 x IV, 1 x III (sloughing in 1 eye) |
||||||
Classification: |
Category 1 |
Table 7.3.2/7: Individual scores and Mean score for Corneal effects - Negative controlthe test item
End Point |
Eye Number |
Time |
|||||
0 |
30 minutes |
75 minutes |
120 minutes |
180 minutes |
240 minutes |
||
Corneal Opacity |
1A |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
4A |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
|
Mean |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
0.5 |
|
ICE Class |
I |
||||||
Fluorescein Retention |
1A |
|
0.5 |
|
|
|
|
4A |
|
0.5 |
|
|
|
|
|
Mean |
|
0.5 |
|
|
|
|
|
ICE Class |
I |
||||||
Corneal Thickness |
1A |
0.68 |
0.70 |
0.70 |
0.68 |
0.70 |
0.70 |
4A |
0.72 |
0.71 |
0.74 |
0.72 |
0.70 |
0.72 |
|
Mean |
0.70 |
0.71 |
0.72 |
0.70 |
0.70 |
0.71 |
|
Mean Corneal Swelling (%) |
|
0.71 |
2.86 |
0.00 |
0.00 |
1.43 |
|
ICE Class |
I |
||||||
Corneal Epithelium Condition |
1A |
N |
N |
N |
N |
N |
N |
4A |
N |
N |
N |
N |
N |
N |
|
ICE Classes Combined: |
3 x I |
||||||
Classification: |
No Category |
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Under the test conditions, no prediction can be made for the test substance according to the Annex VI of Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
- Executive summary:
An in vitro eye irritation study was performed according to the OECD Guideline 438 and in compliance with GLP to evaluate the possible ocular corrosive or severe irritating effects of the test item after administration on enucleated chicken eyes.
The test item was applied, as supplied, at the dose of 30 µL, to 3 enucleated chicken eyes, during 10 seconds. Then the eyes were rinsed using 20 mL of isotonic saline. Three eyes were treated in the same manner with a positive control and two eyes with a negative control. Damages by the test substance were assessed by determination of corneal swelling, opacity, and fluorescein retention at 30, 75, 120, 180 and 240 minutes post-dose.
The ocular reactions observed in eyes treated with the test item were:
- maximal mean score of corneal opacity: 2.0 (180-240 min.), corresponding to the ICE class III;
- mean score of fluorescein retention: 0.7 corresponding to the ICE class II;
- maximal mean corneal swelling: 13.08% (75 min.) corresponding to the ICE class III.
The combination of the three endpoints for the negative control, physiological saline solution, was 3 x I. Therefore, the negative control is classified as "No Category", as expected. The combination of the three endpoints for the positive control, 5% Benzalkonium chloride, was 3 x IV. Therefore, the positive control is classified as "Corrosive/Severe irritant", as expected.
Under the test conditions, no prediction can be made for the test substance according to the Annex VI of Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
This study is considered as acceptable and satisfies the requirement for in vitro eye irritation endpoint.
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