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EC number: - | 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:
- From 20/11/2015 to 08/02/2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-compliant study performed according to an internationally-recognized guideline.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
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:
- no
- 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)
- Remarks:
- 2015-06-04
Test material
- Details on test material:
- Name: 1-phosphonobutane-1,2,3,4-tetracarboxylate and 2-phosphonosuccinate sodium salts
Constituent 1
Test animals / tissue source
- Details on test animals or tissues and environmental conditions:
- Chicken head collection and transport:
Strain of chicken: ROSS 308
Source: TARAVIS Ltd. (Address: H-9600 Sárvár, Rábasömjéni út. 129., Hungary)
Chicken heads were collected after slaughter in a commercial abattoir from chickens (approximately 7 weeks old and 2.1 kg) which are used for human consumption. Heads were collected by a slaughter house technician and heads transported to CiToxLAB Hungary Ltd. at ambient temperature at the earliest convenience.
After collection, the heads were inspected for appropriate quality and wrapped with tissue paper moistened with physiological saline, then placed in a in a lockable plastic box (4-5 heads per box). The heads were transported to CiToxLAB Hungary Ltd. and processed within approximately 2 hours after collection.
Eyes selection
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.
Preparation of eyes
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.
Eyes examination and acclimatization time
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) while 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 dripping from a stainless steel tube, at a rate of approximately 3-4 drops/minute or 0.1 to 0.15 mL/minute. The door of the chamber was closed except for manipulations and examinations, to maintain temperature and humidity.
The appropriate number of eyes was selected and placed in the superfusion apparatus. After that, the eyes were examined again with the slit lamp microscope to ensure that they were in good condition. The focus was adjusted to clearly see 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 it was 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.
Identification
The eyes were identified by chamber number, marked on the door of the chamber
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: physiological saline 0.9%
- Amount / concentration applied:
- After the zero reference measurements, the eye (in its retainer) was removed from the chamber, held in a horizontal position and the test item was applied onto the centre of the cornea, taking care not to damage or touch the cornea.
A volume of 30 µL of test item was applied to the entire surface of the cornea attempting to cover the cornea surface uniformly with the test substance. - Duration of treatment / exposure:
- The time of application: 10 secondes
- Observation period (in vivo):
- The control eyes 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 approximately ±5 minutes were considered acceptable.
Corneal thickness and corneal opacity were measured at all time points. Fluorescein retention was measured on two occasions, at baseline (t=0) and approximately 30 minutes after the post-treatment rinse. Haag-Streit BP 900 slit-lamp microscope was used for the measurements - Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): The time of application was observed, then after an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with 20 mL physiological saline at ambient temperature, taking care not to damage the cornea but attempting to remove all residual test item (or controls), if possible. The eye was returned to the chamber after rinsing. The time while the eye was out of the chamber was limited to the minimum.
SCORING SYSTEM: The endpoints evaluated are corneal opacity, swelling, fluorescein retention, and morphological effects (e.g., pitting or loosening of the epithelium).
Results from corneal opacity, swelling, and fluorescein retention are 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 substance
Positive Control
Name: Benzalkonium chloride solution, 50% in water
Batch number: SZBC2960V
CAS Number: 63449-41-2
Expiry date: 25 March 2018
Manufacturer: Sigma-Aldrich Co.
Storage condition: Room temperature
This material was diluted with distilled water (Supplier: Teva Co., Lot number: 6820914, Expiry date: 30 September 2017) to achieve the final concentration of 5% (w/v). The treatment solution was prepared immediately before the experiment.
Negative Control
Name: Physiological saline (0.9% (w/v) NaCl solution)
Batch number: 51642Y05-1
Manufacturer: B. Braun Pharmaceuticals SA
Expiry date: 31 March 2018
Storage conditions: Room temperature
Quality: Sterile
Fluorescein retention test
Name: Fluorescein, 10% (w/v) solution
Batch number: 13221042
Manufacturer: Delpharm Huningue SAS
Expiry date: 30 April 2016
Storage conditions: Room temperature
This material was mixed with physiological saline (Supplier: B. Braun Pharmaceuticals SA, Lot No: 51642Y05-1, Expiry Date: 31 March 2018) to achieve the final concentration of 2% (w/v). The resulted solution was stored at room temperature (Dispensary code: S43090, Expiry date: 02 January 2016).
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- other: Corneal swelling
- Basis:
- mean
- Time point:
- other: 75 min
- Score:
- 0
- Irritation parameter:
- other: Corneal Swelling
- Basis:
- mean
- Time point:
- other: 240 min
- Score:
- ca. 0
- Irritation parameter:
- cornea opacity score
- Remarks:
- Opacity
- Basis:
- mean
- Score:
- 0.17
- Irritation parameter:
- other: Fluorescein retention
- Basis:
- mean
- Score:
- 0
Any other information on results incl. tables
Test item
Observation |
Value |
ICE Class |
Mean maximum corneal swelling at up to 75 min |
0.0% |
I |
Mean maximum corneal swelling at up to 240 min |
-0.5% |
I |
Mean maximum corneal opacity |
0.17 |
I |
Mean fluorescein retention |
0.00 |
I |
Other Observations |
None |
|
Overall ICE Class |
3xI |
Based on thesein vitroeye irritation assays in isolated chicken eyes with 1-phosphonobutane-1,2,3,4-tetracarboxylate and 2-phosphonosuccinate sodium salts (EC number: 942-790-8), the test item was not irritant (No Category), UN GHS Classification: Not classified
Positive Control
Observation |
Value |
ICE Class |
Mean maximum corneal swelling at up to 75 min |
10.5% |
II |
Mean maximum corneal swelling at up to 240 min |
25.7% |
III |
Mean maximum corneal opacity |
4.00 |
IV |
Mean fluorescein retention |
3.00 |
IV |
Other Observations |
Loosening of epithelium was observed in two eyes at 75 minutes and in one eye at 180 minutes after the post-treatment rinse. |
|
Overall ICE Class |
1xIII 2xIV |
The positive control (5% (w/v) Benzalkonium chloride solution)was classified as severely irritating,UNGHS Classification: Category 1.
Negative Control
Observation |
Value |
ICE Class |
Mean maximum corneal swelling at up to 75 min |
0.0% |
I |
Mean maximum corneal swelling at up to 240 min |
0.0% |
I |
Mean maximum corneal opacity |
0.00 |
I |
Mean fluorescein retention |
0.00 |
I |
Other Observations |
None |
|
Overall ICE Class |
3xI |
The negative control (Physiological saline)was classified as non-irritating, UN GHS Classification:Non-classified.
Validity of the test
The results from all eyes used met the quality control standards. The negative control and positive control results were within historical control data. The experiment was considered to be valid.
Historical Control data (updated on 24 September 2015):
Negative Control: Physiological Saline
Observation |
Min. Value |
Max. Value |
Maximum corneal swelling at up to 75 min |
-3.2 % |
3.4 % |
Maximum corneal swelling at up to 240 min |
-4.8 % |
3.4 % |
Maximum corneal opacity change |
0.00 |
0.50 |
Fluorescein retention |
0.00 |
0.50 |
Number of studies |
200 |
Positive Control: 5% (w/v)Benzalkonium chloride soultion
Observation |
Min. Value |
Max. Value |
Maximum corneal swelling at up to 75 min |
-8.5 % |
27.0 % |
Maximum corneal swelling at up to 240 min |
-10.7 % |
34.8 % |
Maximum corneal opacity change |
2.50 |
4.00 |
Fluorescein retention |
1.50 |
3.00 |
Number of studies |
108 |
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: OECD GHS
- Conclusions:
- Based on these in vitro eye irritation assays in isolated chicken eyes with 1-phosphonobutane-1,2,3,4-tetracarboxylate and 2-phosphonosuccinate sodium salts (EC number: 942-790-8), the test item was not irritant (No Category), UN GHS Classification: Not classified
- Executive summary:
In vitro eye irritation test in isolated Chichen Eyes with 1-phosphonobutane-1,2,3,4-tetracarboxylate and 2-phosphonosuccinate sodium salts was realised according to the OECD 438 guideline and under GLP conditions.
1-phosphonobutane-1,2,3,4-tetracarboxylate and 2-phosphonosuccinate sodium salts was a colourless to yellow aqueous solution with a purity of 97.1%. 30µL of the substance was applied on top isolated eyes for an exposure period of 10 seconds and the surface of the cornea was rinsed thoroughly with 20 mL of physiological saline at ambiant temperature.
No signs of irritation with the test item were describe during the test.
Negative and positive controls were within the historical data.
The test item was not classified according to UN GHS classification.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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