Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 216-014-7 | CAS number: 1474-02-8
- 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:
- 2005-06-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- Study performed according to INVITTOX Protocol 98 (Bovine Corneal Opacity and Permeability Assay, February 1994) and Bovine Corneal Opacity and Permeability Assay (BCO-P) SOP of Microbiological Associates Ltd., UK, April 1997 and similar to OECD guideline 437.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: INVITTOX Protocol 98 (Bovine Corneal Opacity and Permeability Assay, Feb. 1994, SOP of Microbiological Associates Ltd., UK, April 1997.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Bovine Corneal Opacity and Permeability Assay (BCO-P) SOP of Microbiological Associates Ltd., UK, Procedure Details, April 1997
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- GLP compliance:
- not specified
Test material
- Reference substance name:
- N-(1-benzylpiperidin-4-yl)-N-phenylpropionamide
- EC Number:
- 216-014-7
- EC Name:
- N-(1-benzylpiperidin-4-yl)-N-phenylpropionamide
- Cas Number:
- 1474-02-8
- Molecular formula:
- C21H26N2O
- IUPAC Name:
- N-(1-benzylpiperidin-4-yl)-N-phenylpropanamide
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Name of test material (as cited in study report): JNJ-1594164-AAA (T000424)
- Physical state: solid (powder)
- Appearance: White powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: RT000424G1A251
- Expiration date of the lot/batch: 2005-12-31
- Purity test date: no data
- Purity: 100%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5°C), light protected
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: no data
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- The test item was tested at a concentration of 20% in saline. Strong stirring with a magnetic stirrer resulted in a suspension. Until administration, the suspension was stirred with a magentic stirrer.
FORM AS APPLIED IN THE TEST (if different from that of starting material): th test item was tested at a concentration of 20% in saline.
Test animals / tissue source
- Species:
- other: bovine eyes
- Strain:
- other: not applicable
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Freshly isolated bovine eyes were collected from Abattoir Basel, Schlachthofstrasse 55, CH-4055 Basel, Switzerland. After excess tissue was removed from the excised eyes, the were stored at room temperature in Hank's balanced salt solution containing penicillin/streptomycin and then transported for further preparations. The eyes were delivered the before treatment and the isolated corneas were stored over night in a preservation medium in a regriferator.
Test system
- Vehicle:
- physiological saline
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied: 0.75 mL
- Concentration: 20% in saline
VEHICLE/NEGATIVE CONTROL
- Amount(s) applied: 0.75 mL
- Concentration: 0.9%
POSITIVE CONTROL:
- Amount(s) applied: 0.75 mL
- Concentration: 20% in saline
- Lot/batch no.: 054063/2
- Purity: >99.5% (assay) - Duration of treatment / exposure:
- 240 minutes
- Duration of post- treatment incubation (in vitro):
- After 240 minutes of treatment, opacity was measured with an opacitometer. The permeability measurement of the corneas was performed after the incubation period of about 90 minutes following the opacity measurement.
- Number of animals or in vitro replicates:
- 9 (3 per treatment group)
- Details on study design:
- SELECTION AND PREPARATION OF CORNEAS:
- All eyes were carefully examined macroscopically for defects. Those presenting defects such as vascularization, pigmentation, opacity and scratches were discarded. Each cornea was dissected from the eye using scalpel and rounded scissors. A rim of about 2-3 mm of tissue (sclera) was left for stability and handling of the isolated cornea. All corneas used in the expreiment were collected in complete minimum essential medium (cMEM) and were checked finally with a view box for defects listed above.
- Since the boven eyes were delivered in the afternoon, corneas were stored in a preservation medium over night in a refrigerator at about 4 °C. The preservation medium was composed of Medium 199 supplemented with L-glutamine, Na-bicarbonate and Taurine. Shortly before use, Dextran was added.
- Each cornea was mounted in a cornea holder with the endothelial side against the sealing ring (O-ring) of the posterior part of the holder. The cornea was gently flattened over the O-ring but stretching had to be avoided. After the anterior part of the holder was positioned on the top of the cornea and fixed in place with screws, both compartments of the holder were filled with cMEM. The posteriar compartment had to be filled first to return the cornea to its natural convex position. Care had to be taken to assure no air bubbles were present within the compartments.
- For equilibration, the corneas in the holder were incubated for about one hour at 32°C +/- 2°C in a water-bath. At the end of the incubation periode, the medium was removed from both compartments and replaced by fresh cMEM.
TREATMENT METHOD:
- Fresh cMEM was filled into the posterior compartment, while the anterior compartment has received 0.75 mL-aliquots of the test item, or negative of positive control, respectively and were evenly distributed on the surface of the corneas.
- The incubation lasted 240 minutes. During the whole experiment, cornea holders and medium were maintained in a water-bath at 32°C +/- 2°C.
REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: the test item was rinsed off from the application side by changing sMEM several times untill precipitates of the test item could be obbserved no longer.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity:
The opacitometer determined changes in the light transmission passing throught the corneas, and displayed a numerical opacity value.
The opacitometer was calibrated with a standardized opaque polyester sheet as described in the manual and the opacity of each of the corneas was determined by reading each holder placed in the photoreceptor compartment for treated cornea.
The change of opacity value of each treated cornea or positive or negative control corneas was calculated by subtracting the initial opacity reading from the post-treatment reading, for each individual cornea. The average change in opacity of the negative control corneas was calculated and this value was subtracted from from the change in opacity of each treated cornea or positive control to obtain a corrected opacity.
The mean corrected opacity value of each treatment group was then calculated from the individual corrected opacity values of the treated corneas for each treatment condition.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of spectrophotometry (OD490)
After the final opacity measurement was performed, the medium was removed from the anterior compartment and 1 mL of the fluorescein dye solution, 0.5% dissolved in Dumlbecco's phosphate-buffered saline, was placed in the anterior compartment. Corneas were incubated again in a horizontal position for about 90 minutes an a water-bath at 32°C +/- 2°C. Medium from the posterior compartment was removed with a 5 mL-syringe, well mixed and trasferred to a cuvette of 10 mm path length and the optical density was measured by photometry at 490 nm.
The corrected OD490 value of each treated cornea or positive control cornea was calculated by subtracting the average negative control value from the original permeability value for each cornea.
The mean corrected permeability values of each treatment group was calculated from the individual corrected permeability values of the treated corneas for each treatment condition.
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
- The following formula was used to determine the in vitro score:
In vitro score = opacity value + (15 x OD490 value)
DECISION CRITERIA
- Depending on the score, the test substance was classified into one of the following categories:
0-3 non eye irritant
3.1-25 mild eye irritant
25.1-55 moderate eye irritant
55.1-80 severe eye irritant
> 80.1 very severe eye irritant
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- in vitro irritation score
- Remarks:
- mean
- Run / experiment:
- 1
- Value:
- 0.5
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- SD +/- 1.2; range: -0.2 to 1.9
- Irritation parameter:
- cornea opacity score
- Remarks:
- mean
- Run / experiment:
- 1
- Value:
- 0.7
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- SD +/- 1.2; range: 0 to 2
- Irritation parameter:
- other: permeability
- Remarks:
- mean
- Run / experiment:
- 1
- Value:
- -0.008
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- SD +/- 0.003; range: -0.012 to -0.007
- Other effects / acceptance of results:
- mean in vitro irritancy score (range):
negative control: 1.3 +/- 1.2 (0.1 to 2.5)
positive control: 86.1 +/- 4.9 (82.7 to 91.7)
mean opacity scores (range):
negative control: 1.0 +/- 1.0 (0 to 2)
positive control: 58.0 +/- 2.0 (56.0 to 60.0)
mean permeability scores (range):
negative control: 0.018 +/- 0.015 (0.009 to 0.035)
positive control: 1.870 +/- 0.338 (1.586 to 2.244)
The In vitro score of the positive control (imidazole, 20%, dissolved in saline) was 86.1 +/- 4.9, proving the vailidty of the study.
Any other information on results incl. tables
Before starting the permeability test, the dye solution sodium fluorescein was checked for its quality. The dye solution is valid for use, if a dilution of the stock solution containing 10 µg/mL showed an optical density (OD490) of 1.610 to 1.910. The value found by spectroscopy was 1.693.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- As the mean in vitro irritation score was within the range 0-3, T000424 is considered to be non eye irritant.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.