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EC number: 606-946-6 | CAS number: 221640-14-8
- 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:
- March 2014 to March 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Version / remarks:
- 26 July 2013
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- n.a.
- Molecular formula:
- n.a.
- IUPAC Name:
- n.a.
- Reference substance name:
- Carbamic acid [(1S)-,2-[(2-aminoethyl)amino]-1-[(4-ethoxyphenyl)methyl]ethyl]-,phenylmethyl ester, dihydrochloride (9Cl)
- IUPAC Name:
- Carbamic acid [(1S)-,2-[(2-aminoethyl)amino]-1-[(4-ethoxyphenyl)methyl]ethyl]-,phenylmethyl ester, dihydrochloride (9Cl)
- Reference substance name:
- benzyl[(2S)-1-[(2-aminoethyl)amino]-3-(4-ethoxyphenyl)propan-2-yl]carbamate dihydrochlorid
- EC Number:
- 606-946-6
- Cas Number:
- 221640-14-8
- Molecular formula:
- C21 H29 N3 O3 . 2 Cl H
- IUPAC Name:
- benzyl[(2S)-1-[(2-aminoethyl)amino]-3-(4-ethoxyphenyl)propan-2-yl]carbamate dihydrochlorid
- Test material form:
- solid
impurity 1
impurity 2
impurity 3
Constituent 1
Test animals / tissue source
- Species:
- cattle
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Slaughterhouse Laame, Buchenhofen 26, 42329 Wuppertal, Germany
- Number of animals: at least 5
- Characteristics of donor animals (e.g. age, sex, weight): not reported
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Transport: 1L containers with 500ml HBSS and 1% penicillin / streptomycin solution, transport of the containers in coolers on ice
- Indication of any existing defects or lesions in ocular tissue samples: Eyes were examined after delivery to the laboratory for any damage (like opacity, scratches or neovascularization) on the day of slaughter (1 day before the experiment) . Eyes without any defects were transferred into new containers with fresh HBSS solution supplemented with 1% penicillin / streptomycin solution and 1 % FBS and stored overnight at temperature (2-8°C). Eyes with defects were sorted out and disposed of.
- Selection and preparation of corneas: For the preparation of the cornea the sclera was incised with a scapel and cut by scissors. A 2-3 mm wide wide scleral edge was left around the cornea for further handling. The isolated corneas were placed with the epithelium side down into a prepared cup filled with MEM medium supplemented with 1% penicillin / streptomycin solution and 1% FBS. Each cornea was placed into a cornea holder with the endothelial side on the sealing ring of the posterior chamber. The anterior chamber was then fixed by screws on the other side. The chambers were filled with MEM medium, avoiding air bubbles. The holders were placed for at least 1hour in the incubator at 32°C (±1°C).
Selection: After 1 h, the MEM medium was aspirated and the chambers were filled with fresh MEM medium. For each cornea the reference opacity value was measured before application. The measured values were put into an Excel sheet and the mean and the standard deviation calculated. Six corneas with values within the range of mean ± standard deviation were selected for the application and assigned to the positive control group and the test item group. Three corneas with the highest freference opacity values were selected for the negative control group.
Test system
- Vehicle:
- water
- Controls:
- other: vehicle control: distilled water; positive control: imidazole (20 % w/v)
- Amount / concentration applied:
- 750 µl per cornea and chamber
test item: at 20% w/v
positive control (imidazol): at 20% w/v - Duration of treatment / exposure:
- opacity: 4 hours (test item, positive/vehicle control)
permeability: 90 minutes (sodium fluorescein sodium solution) - Number of animals or in vitro replicates:
- each treatment group (test item, positive and vehicle control): 3 corneas
- Details on study design:
- closed-chamber method was applied
NUMBER OF REPLICATES: triplicate
NEGATIVE CONTROL USED: distilled water
POSITIVE CONTROL USED: 20% (w/v) imidazole solution
APPLICATION DOSE AND EXPOSURE TIME: 20 % (w/v) in distilled water (suspension), 4 hours at 32°C
TREATMENT METHOD: closed chamber
POST-INCUBATION PERIOD: no
REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: at least three times
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: The measurements of opacity were carried out using an Opacitometer BASF OP3.0 (with integrated light meter testo 545 and Comfort 3.4 SP6 software from Testo AG, Lenzkirch). Before each measurement the opacitomcter was adjusted to about 1000 LUX and a filter calibration measurement was carried out by using 3 different filters.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD490)
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
DECISION CRITERIA: the decision criteria as indicated in the TG was used.
Results and discussion
In vitro
Results
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- mean of triplicates
- Value:
- 78.8
- Vehicle controls validity:
- not examined
- Negative controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
- Opacity = (I0/I-0.9894)/0.0251
- Opacity value = opacity after application - opacity before application
- Corrected opacity value = opacity change - mean opacity change NC
- Mean opacityvalue = mean of all corrected opacity changes per group
- OD490change = OD490value - mean blank value OD490
- Corrected OD490change = OD490change - mean OD490change NC
- Mean OD490= mean of all corrected OD490changes per group
- IVIS per cornea = corrected opacity value + (15 x corrected OD490change)
- IVIS per group = mean of IVIS values per cornea in a group
Table 1: Results after 4 hours exposure period
Treatment group |
Opacity value1 |
Permeability value2(OD490) |
In vitro irritation score (IVIS)3 |
|||
|
|
mean |
|
mean |
|
mean |
Vehicle control |
9.8 |
8.5 |
0.011 |
0.009 |
9.9 |
8.1 |
8.7 |
0.008 |
8.8 |
||||
7.0 |
0.008 |
7.2 |
||||
Positive control |
62.7* |
70.8 |
1.692 |
1.563 |
88.1 |
94.2 |
67.0* |
1.415 |
88.3 |
||||
82.6* |
1.581 |
106.3 |
||||
Z-Triamin-Dihydrochlorid |
65.9* |
78.8 |
0.006 |
0.002 |
66.0 |
78.8 |
73.4* |
0.001 |
73.4 |
||||
97.2* |
0.000 |
97.2 |
*corrected values
1The opacity values were calculated by applying the following formulae:
2The permeability values were calculated by applying the following formulae:
3Calculation of In Vitro Irritancy Score (IVIS):
Applicant's summary and conclusion
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- The test substance was investigated in the Bovine Corneal Opacity and Permeability (BCOP) test according to OECD TG 437. The in vitro test method is used to identify chemicals inducing serious eye damage. Concentrations of 0 (vehicle control) and 20 % (w/v) formulated in distilled water were tested applying the closed chamber method. The positive control (20% w/v imidazole in distilled water) showed clear opacity and distinctive permeability of the corneas. Relative to the vehicle control, the test substance did not cause increase the corneal permeability but corneal opacity occurred. The calculated mean in vitro irritation score (IVIS) was 77.8 for the test substance, compared to > 55 for classification as inducing serious eye damage.
- Executive summary:
This in vitro study was performed to assess the corneal irritation and damage potential of Z-Triamine Dihydrochloride (100% a.i.) by means of the BCOP assay using fresh bovine corneae according to OECD guideline 437, adopted 26 July 2013.
The corneae were incubated with the test substance and controls for 4 hours. After rinsing with phenol red containing medium and once with pure MEM medium, the Opacity and permeability were determined. The test was performed in triplicates. The in vitro irritancy score (IVIS) were calculated as mean opacity value + (15 x mean OD490 value); a substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant.
The test item caused an increase of the corneal opacity and permeability. The calculated mean in vitro score was 78.8.
The positive control (Imidazole) increased the opacity and permeability of the corneae (mean in vitro score 70.8) corresponding to a classification as corrosive to the eye. With the negative control (distilled water) neither an increase of opacity nor permeability of the corneae mediated by treatment could be observed (mean in vitro score 8.05).
Since the mean in vitro irritancy score of the test substance was >55.1, Z-Triamine Dihydrochloride is considered to be severely irritating/ corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in this report.
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