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EC number: 700-893-3 | 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:
- August 2011 - September 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Fully Guideline- and GLP-compliant
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD-guideline 437, Bovine Corneal Opacity and Permeability Test Method (BCOP) , 7. September 2009
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- DOPO-OX-Ammonium
- IUPAC Name:
- DOPO-OX-Ammonium
- Details on test material:
- Trade name: DOPO-OX-Ammonium.
Chemical name: 9,10-dihydro-10-hydroxy-9-oxa-10-phosphaphenanthren-10-on- resp. 10-oxid-ammonium salt, corrected later to: 9,10-dihydro-10-hydroxy-9-oxa-10-phosphaphenanthren-10-oxid-ammonium salt
Article no: 21908200.
Molecular formula: C12H12NO3P.
Charge. No.:DAS-1101.
Appearance: White to slightly yellow solid.
Conditions of storage: At room temperature.
Expiry date: The sponsor guarantees stability during test period under storage conditions.
Certificate of Analysis available.
The analysis of the test substance for identity and purity is at the responsibility of the sponsor.
Constituent 1
Test animals / tissue source
- Species:
- other: in vitro system: bovine corneas
- Strain:
- other: Isolated corneas from the eyes of cows and bulls aged between 24 – 26 month and free of macroscopically visible defects.
- Details on test animals or tissues and environmental conditions:
- Isolated corneas from the eyes of cows and bulls aged between 24 - 26 month and free of macroscopically visible defects from the slaughterhouse
"Klaus Grandis", Ungerbachstraße 10, 2860 Kirchschlag, Austria were used. The study required a total of 9 corneas (3 for the test substance, 3 for
the negative control and 3 for the positive control) and additionally 3 corneas for the benchmark control.
Test system
- Vehicle:
- water
- Remarks:
- deionised water
- Controls:
- yes
- Amount / concentration applied:
- Application amount: 750µL.
Test substance: inhomogeneous suspension of 20% (w/v) in deionised water.
Positive control: Imidazole solution of 20% (w/v) in deionised water.
Negative control: deionised water.
Benchmark control: 0.9 % sodium chloride. - Duration of treatment / exposure:
- 4 hours.
- Observation period (in vivo):
- Endpoint measurement of opacity change and permeability values.
- Number of animals or in vitro replicates:
- 9 corneas (3 for the test substance, 3 for the negative and 3 for the positive control) and additionally 3 corneas for the benchmark substance.
- Details on study design:
- Fresh isolated and quality checked corneas were mounted in cornea holders and the initial opacity was determined after equilibration. 750 µL of
the test substance preparation were topically administered to 3 isolated bovine corneas to the epithelial surfaces for 4 hours and the final opacity
was measured. Then 1 ml of a fluorescein solution was added on the epithelial site and permeability was measured after 90 minutes.
Three groups of 3 corneas each served as positive, negative and benchmark controls. All control substances were administered under identical
conditions as the test substance. The following solutions served as control substances:
Negative control: sterile aqua dest.
Positive control: 20 % imidazole.
Benchmark control: 0.9 % sodium chloride.
Finally the IVIS (In Vitro Irritancy Score) was calculated as follows:
IVIS = mean opacity value + (15 x mean permeability).
The opacity and mean permeability values were corrected for background opacity and the negative control permeability values. The mean opacity
value results from subtraction of final opacity from initial opacity. A substance that induces an IVIS ≥ 55.1 is defined as ocular corrosive or severe
irritant. The positive and negative control groups were simultaneously used for other, concurrently performed studies.
Results and discussion
In vivo
Results
- Irritation parameter:
- other: IVIS (in vitro irritancy score)
- Basis:
- mean
- Time point:
- other: 4 hours
- Score:
- 39.3
- Reversibility:
- not specified
- Remarks on result:
- other: not ocular corrosive or severe irritant
- Irritant / corrosive response data:
- The IVIS of DOPO-OX-Ammonium was 39.3. Furthermore, an increase in opacity and no increase in permeability was observed.
- Other effects:
- The validity of the opacitometer is given since the measurements of the control filters were within the range of the historical data.
The validity of the cornea holder is given because the cornea holder control value Io was within the range of the historical data.
The correlation coefficient of the fluorescein dilutions was 0.995. Since the correlation coefficient was > 0.99 the linearity was given.
The mean IVIS of the corneas, treated with 20 % imidazole (PC) was 96.7, which is within the range of the historical data.
The mean opacity and the mean permeability (not corrected for negative control opacity and permeability values, but corrected for background
opacity and permeability values) of the corneas, treated with deionised water (NC) were 8.9 and -0.002 respectively.
The opacity of the negative control (8.9) slightly exceeds the upper limit of the historical data (8.5). This deviation is considered to be of no relevance for the outcome of this study since the deviation is very small in reference to a small amount of historical data (n=11) and that the test system is
biological material and high temperature during slaughter causes cell damage as in house practical experience showed.
Furthermore, the benchmark control (0.9 % NaCl) which is recommended as negative control substance by the “Draft Guidance Document in the
Supplement of Test Guidelines 437 and 438” had an IVIS (not corrected for negative control opacity and permeability values) of 0.8 which is in the
range of negative controls.
The mean IVIS of the corneas, treated with 0.9 % Sodium chloride was -8.1 (0.8 not corrected for negative control opacity and permeability values),
no historical data are available.
Any other information on results incl. tables
Results:
Opacity, permeability and IVIS values
Opacity, permeability (1 x value measured and 15 x values for IVIS calculation) and IVIS values of test substance, negative and positive controls. Individual data, means and standard deviations (SD).The mean opacity and mean permeability values of the positive control, the test substance and the benchmark substance were corrected for background and negative control opacity and permeability values. The negative control values in this table are listed not corrected for negative control opacity but for background permeability.
Substance |
Opacity |
Permeability (1x) |
Permeability (15x) |
IVIS |
|||||||
Individual |
Mean |
SD |
Individual |
Mean |
SD |
Mean |
SD |
Individual |
Mean |
SD |
|
Negative control (Aqua dest.) |
6,3 |
8,9 |
3,7 |
0,002 |
0,000 |
0,002 |
0,000 |
0,029 |
6,3 |
8,9 |
3,7 |
13,1 |
-0,001 |
13,1 |
|||||||||
7,2 |
-0,001 |
7,2 |
|||||||||
Positive control (Imidazole) |
53,8 |
54,8 |
3,0 |
2,237 |
2,792 |
0,847 |
41,882 |
12,700 |
87,3 |
96,7 |
11,1 |
52,5 |
3,767 |
109,0 |
|||||||||
58,2 |
2,373 |
93,8 |
|||||||||
Test Substance |
35,8 |
39,3 |
4,0 |
-0,003 |
-0,002 |
0,001 |
-0,032 |
0,013 |
35,7 |
39,3 |
4,0 |
43,6 |
-0,001 |
43,6 |
|||||||||
38,6 |
-0,002 |
38,6 |
|||||||||
Benchmark control |
-7,1 |
-8,1 |
0,9 |
-0,002 |
-0,003 |
0,001 |
-0,038 |
0,013 |
-7,1 |
-8,1 |
0,9 |
-8,5 |
-0,003 |
-8,6 |
|||||||||
-8,7 |
-0,002 |
-8,8 |
Opacitometer reference filter values, cornea holder control measurement, negative (NC) and positive (PC) control values
Acceptance criteria of the opacitometer via measurement of the reference filter set. The control measurement was made before determination of the initial and final opacity.
Reference filter |
Measured value LUX |
Set point range Lux |
Empty Filter holder |
1001/1001 |
997 – 1007 |
F2 (NG11) |
544/539 |
536 – 545 |
F3 (NG5) |
300/298 |
296 – 301 |
F4 (NG4) |
98/98 |
97 – 100 |
Acceptance criteria of the cornea holder via measurement of an empty cornea holder with medium.
Empty cornea holder with medium |
Measured value LUX |
Set point range Lux |
# 16 |
661 |
630 - 720 |
Measured opacity and permeability values of the negative control (NC).
NC |
Measured Opacity value |
Set point range Opacity upper limit |
Measured permeability value |
Set point range Permeability upper limit |
Aqua dest. |
8,9 +/-3,7 |
3,5 – 7,5 |
-0,002 +/-0,002 |
0,0041 +/-0,0076 |
Calculated IVIS of the positive control (PC).
PC |
Calculated IVIS |
Set point range IVIS |
20 % Imidazole |
96,7 +/-11,1 |
92,5 – 130,1 |
The historical data:
The historical data includes all generated data of this year. The historical range of the cornea holder is generated by measurement of all holders once of this year.
Acceptance criteria of the opacitometer via reference filter set.
Historical data |
Filter holder |
Filter holder |
Filter holder |
Filter holder |
Min/max values (LUX) |
997/1008 |
536/545 |
296/301 |
97/100 |
Mean (LUX) |
1002 |
540 |
298 |
98 |
+/- SD (LUX) |
5 |
5 |
2 |
2 |
n (number of measurements) |
33 |
33 |
33 |
33 |
Acceptance criteria of all 30 cornea holders with medium.
Historical data |
Empty filter holder with medium |
Range (Lux) |
630 - 720 |
Negative control historical data of the upper limits of opacity and permeability.
NC |
Opacity |
Permeability |
Min/max values (LUX) |
1,5/8,5 |
-0,005/0,021 |
Mean (LUX) |
5,5 |
0,004 |
+/- SD (LUX) |
2,0 |
0,008 |
n (number of measurements) |
11 |
11 |
Positive control historical data of the IVIS.
PC |
Historical IVIS |
Min/max values (LUX) |
100,8/127,8 |
Mean (LUX) |
111,3 |
+/- SD (LUX) |
9,4 |
2 x +/- SD (LUX) |
18,8 |
n (number of measurements) |
9 |
Applicant's summary and conclusion
- Interpretation of results:
- other: DOPO-OX-Ammonium is regarded to be not an ocular corrosive or severer irritant and needs not to be labelled as R41 (EU), Category 1 (EPA and GHS).
- Remarks:
- Criteria used for interpretation of results: other: Directive 2011/59/EC for classification.
- Conclusions:
- The IVIS of DOPO-OX-Ammonium was 39.3. Furthermore, an increase in opacity and no increase in permeability were observed.
Thus DOPO-OX-Ammonium is regarded to be not an ocular corrosive or severe irritant, according to the OECD Guideline 437 for the testing of
chemicals “Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants”.
According to the results of this study and the Directive 2001/59/EC for classification, the test substance DOPO-OX-Ammonium requires further
testing as outlined in the OECD guideline 405.
According to the results of this study and the Directive 2001/59/EC for classification, the test substance DOPO-OX-Ammonium needs not to be
labelled as R41 (EU), Category 1 (EPA and GHS). - Executive summary:
Aim:
The Bovine Corneal Opacity and Permeability Study (BCOP Test Method) was performed to reveal possible ocular corrosivity and severe irritation of DOPO-OX-Ammonium, according to the OECD Guideline 437 for the testing of chemicals “Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants”.
Method:
Fresh isolated and quality checked corneas were mounted in cornea holders and the initial opacity was determined. After equilibration 750 µL of the test substance preparation were topically administered to 3 isolated bovine corneas to the epithelial surfaces for 4 hours and the final opacity was measured. Then 1 mL of a fluorescein solution was added on the epithelial site and permeability was measured after 90 minutes.
Two groups of 3 corneas each served as positive and negative controls. Both control substances were administered under identical conditions as the test substance. The following solutions served as control substances:
- Negative control: sterile aqua dest.
- Positive control: 20 % imidazole.
Finally the IVIS (In Vitro Irritancy Score) was calculated as follows:
IVIS = mean opacity value + (15 x mean permeability).
The opacity and mean permeability values were corrected for background opacity and the negative control permeability values. The mean opacity value results from subtraction of final opacity from initial opacity. A substance that induces an IVIS ≥ 55.1 is defined as ocular corrosive or severe irritant.
Results:
The IVIS for DOPO-OX-Ammonium was 39.3.
IVIS of the negative control was 8.9 and for the positive control 96.7, thus demonstrating the validity of the experiment.
Conclusion:
According to the results of this study and the OECD Guideline 437, the test substance DOPO-OX-Ammonium considered to be not an ocular corrosive or severe irritant. For classification and labelling of DOPO-OX-Ammonium further testing as outlined in the OECD guideline 405 is required.
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