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EC number: 232-219-4 | CAS number: 7790-75-2
- 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
Endpoint summary
Administrative data
Description of key information
Skin irritation: not irritating (OECD 439; GLP)
Eye irritation: not irritating (OECD 437; GLP)
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-03-15 to 2018-03-23
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- 2015-07-28
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed 2015-09-14
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature - Test system:
- human skin model
- Source species:
- human
- Cell type:
- other: normal, human-derived epidermal keratinocytes
- Cell source:
- other: humans
- Source strain:
- other: not applicable
- Details on animal used as source of test system:
- not applicable
- Justification for test system used:
- In an international prevalidation study performed by ECVAM, the in vitro skin irritation test using the human skin model EpiDerm™ and measurement of cell viability by dehydrogenase conversion of MTT into a blue formazan salt have turned out as a sufficiently promising predictor for skin irritancy potential.
- Vehicle:
- other: Dulbecco's phosphate buffered saline
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm™ skin model (source: MatTek Corporation, 82105 Bratislava, Slovakia)
- Tissue lot number: 25888
- Delivery date: 2018-03-20
TEMPERATURE USED FOR TEST SYSTEM
- Temperature of pre-incubation: 37 ± 1.5 °C
- Temperature used during treatment / exposure: 37 ± 1.5 °C for 35 minutes, room temperature for 25 minutes
- Temperature of post-treatment incubation: 37 ± 1.5 °C
REMOVAL OF TEST MATERIAL AND CONTROLS
After the end of the treatment interval the tissues were rinsed with PBS at least 15 times in order to remove any residual test material.
After the rinsing the inserts were submerged in PBS at least three times. Afterwards the inserts were again rinsed with PBS. The tissues were then transferred into plates with assay medium. Tissues were incubated for 23.5 hours at 37 ± 1.5 °C, 5 ± 0.5 % CO2. After incubation medium was changed (pre-warmed fresh medium). Thereafter tissues were incubated for another approx. 18 hours at 37 ± 1.5 °C, 5 ± 0.5 % CO2. The complete incubation time was about 41.5 hours.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL (300 µL/ well)
- Incubation time with MTT: 3 hours
- Extraction of Formazan: after the incubation period, the tissues were rinsed three times with PBS. The tissues were transferred into new plates containing extractant solution (isopropanol) in each well ensuring that the tissues were completely covered and the plate was sealed to inhibit the isopropanol evaporation. The formazan salt was extracted for about 2 hours while shaking at room temperature.
After the extraction period was completed, the inserts were pierced with an injection needle to allow the extract to run into the well from which the insert was taken and the insert was discarded. The 24-well plates were placed on a shaker for 15 minutes until the solution was homogeneous in colour.
Per each tissue, 3 × 200 μL aliquots of the blue formazan solution were transferred into a 96-well flat bottom microtiter plate from the 15 minute exposure. The optical density was determined with a microplate reader. Mean values were calculated from the 3 wells per tissue.
- Spectrophotometer: Versamax® Molecular Devices
- Wavelength: 570 nm
TEST FOR COLOUR INTERFERENCE
Before the test started, functional check for colour interference was performed. 25 ± 2 mg of the test item were added to deionised water. The mixture was incubated in the incubator (37 ± 1.5 °C, 5 ± 0.5 % CO2) for 60 minutes. At the end of the exposure time, the mixture was shaken and the presence and intensity of the staining (if any) was evaluated.
TEST FOR DIRECT MTT REDUCTION
The test item was evaluated for its potential to interfere with MTT assay. To test if a test item directly reduces MTT, 25 ± 2 mg of the test item were added to 1 mL of the MTT-solution (1mg/mL) and was incubated in the incubator (37 ± 1.5 °C, 5 ± 0.5% CO2) for 60 minutes. Untreated MTT medium was used as control.
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: tissues pass analysis for tissue viability
- Barrier function: tissues pass analysis for tissue functionality
- Morphology: presence of a functional stratum corneum, a viable basal cell layer, and intermediate spinous and granular layers
- Contamination: absence of bacteria, yeast, and other fungi (long term antibiotic, antimycotic free culture) as well as absence of HIV1- virus, Hepatitis B virus, and Hepatitis C virus
Please also refer to the field "Attached background material" below.
PREDICTION MODEL / DECISION CRITERIA
The mean optical density (OD) of the three negative control tissues was calculated after blank correction. This value corresponds to 100% tissue viability in the current test. For each individual tissue treated with the test item or the positive control the individual relative tissue viability is calculated according to the following formula: relative viability(%) = (mean OD test item or positive control/ mean OD of negative control) x 100
For the test item and the positive control, the mean relative viability ± standard deviation of the three individual tissues was calculated and used for classification according to the following prediction model: if the mean relative tissue viability of three individual tissues is less or equal to 50% of the negative control, the test item needs to be classified and labeled for its skin irritation potential: Category 2 – irritant, H315 according to Regulation (EC) No 1272/2008. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 ± 2 mg (~ 39 mg/cm²) of the test item, wetted with vehicle
VEHICLE
- Amount(s) applied (volume or weight with unit): 25 µL DPBS
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL DPBS
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL of a 5% Sodium dodecyl Sulfate (SDS) solution - Duration of treatment / exposure:
- 60 minutes
- Duration of post-treatment incubation (if applicable):
- about 41.5 hours
- Number of replicates:
- triplicates
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- (mean)
- Value:
- 126.5
- Vehicle controls validity:
- not examined
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- - OTHER EFFECTS:
- Colour interference with MTT: the test item did not change colour in the presence of water. An additional test with viable tissues (but without MTT addition) was not necessary to be performed.
- Direct-MTT reduction: the MTT solution did not turn blue/purple, the test item was not considered to reduce MTT and an additional test with freeze-killed tissues did not have to be performed.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: after treatment with the negative control, the absorbance values (1.876, 1.589, and 1.689 (mean: 1.718)) were well within the required acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 minutes treatment interval.
- Acceptance criteria met for positive control: treatment with the positive control induced a decrease in the relative absorbance compared with the negative control to 2.9 % (acceptability criterion: positive control is ≤ 20 %).
- Acceptance criteria met for variability between replicate measurements: the standard deviations between the three tissue percentage viability values of group (test item, the positive and negative controls) in the main test were below 18 % (threshold of the "OECD Guideline for the Testing of Chemicals 439: In vitro Skin Irritation: Reconstructed Human Epidermis Test Method”: ≤ 18%).
Please refer to the field "Any other information on results incl. tables" below - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item is not irritating to the skin.
According to the Regulation (EC) No 1272/2008 and subsequent regulations, the test item is not irritating to the skin.
Reference
Table 1: Historical data
Positive Control; OD at 570 nm after |
Negative Control OD at 570 nm |
||
MeanViability |
4.28% |
Mean Absorption |
1.66 |
Standard Deviation |
1.00 p.p. |
Standard Deviation |
0.20 |
Rel. Standard Deviation |
23.44% |
Rel. Standard Deviation |
11.96% |
Range of Viabilities |
2.24%—6.19% |
Range of Absorbance* |
1.28—2.00 |
Mean Absorption |
0.07 |
* should be 0.8—2.8 (OECD 439) |
|
Standard Deviation |
0.02 |
||
Rel. Standard Deviation |
25.96% |
||
Range of Absorbance |
0.03—0.11 |
Data of 36 sets of controls shared between 147 studies performed from January 2017 until January 2018. (p.p.—percentage points)
Table 2: Results after treatment with Calcium wolframate (CaWO4) and the controls
Treatment Group |
Tissue No. |
OD 570 nm |
OD 570 nm |
OD 570 nm |
Mean OD of 3 Wells |
Mean OD of 3 Wells blank corrected |
Mean OD of 3 tissues blank corrected |
Rel. Viability [%] Tissue |
Standard Deviation |
Mean Rel. Viability [%]** |
Blank |
|
0.039 |
0.038 |
0.038 |
0.038 |
|
|
|
|
|
Negative Control |
1 |
1.947 |
1.888 |
1.908 |
1.914 |
1.876 |
1.718 |
109.2 |
8.5 |
100.0 |
2 |
1.668 |
1.598 |
1.614 |
1.627 |
1.589 |
92.5 |
||||
3 |
1.750 |
1.717 |
1.714 |
1.727 |
1.689 |
98.3 |
||||
Positive Control |
1 |
0.089 |
0.088 |
0.088 |
0.089 |
0.050 |
0.051 |
2.9 |
0.1 |
2.9 |
2 |
0.091 |
0.088 |
0.093 |
0.091 |
0.053 |
3.1 |
||||
3 |
0.088 |
0.086 |
0.087 |
0.087 |
0.049 |
2.8 |
||||
Test Item |
1 |
2.394 |
2.347 |
2.350 |
2.363 |
2.325 |
2.173 |
135.4 |
8.5 |
126.5 |
2 |
2.120 |
2.021 |
2.071 |
2.071 |
2.033 |
118.3 |
||||
3 |
2.231 |
2.180 |
2.184 |
2.198 |
2.160 |
125.8 |
* relative viability [rounded values]: 100 x (absorbance test item/positive control/negative control)/ mean absorbance negative control
** meanrelative viabiliy [rounded values]:100 x (mean absorbance (test item/ positive control/negative control))/ (mean absorbance (negative control))
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-03-13
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability 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:
- 2017-10-09
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed 2015-09-14
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature - Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: AB Schlachthof GmbH & Co. KG, 63739 Aschaffenburg, Germany
- Characteristics of donor animals: at least 9 month old donor cattle
- Storage, temperature and transport conditions of ocular tissue: isolated eyes were stored in HBSS containing 1% (v/v) Penicillin/Streptomycin (100 units/mL penicillin and 100 µg/mL streptomycin) in the cooled slaughter-house and during transportation on the same morning to the laboratory using a Styrofoam box.
- Time interval prior to initiating testing: corneae were isolated and used on the same day after delivery of the eyes - Vehicle:
- other: 0.9% (w/v) NaCl in deionised water
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration: 20 % suspension (w/v) in vehicle
The test item was tested as a suspension in the vehicle using sonication for 10 minutes. The suspension was shaken before each application. - Duration of treatment / exposure:
- 240 minutes
- Observation period (in vivo):
- not applicable
- Duration of post- treatment incubation (in vitro):
- not required
- Number of animals or in vitro replicates:
- Number of bovine corneae per dose:
Test item: triplicates
Negative control: triplicates
Positive control: triplicates - Details on study design:
- PREPARATION OF CORNEAS
- each isolated cornea was mounted in a specially designed cornea holder according to the description given in OEDC guideline 437, which consists of anterior and posterior compartments, which interface with the epithelial and endothelial sides of the cornea, respectively. Both compartments of the holder were filled with incubation medium cMEM (MEM, supplemented with sodium bicarbonate, L-glutamine, penicillin/streptomycin and 1 % fetal calf serum).
- for equilibration, the corneae in the holder were incubated in a vertical position for about one hour at 32 ± 1 °C in a water-bath.
QUALITY CHECK OF THE ISOLATED CORNEAS
- all eyes were carefully examined macroscopically for defects before removing the cornea. Those presenting defects such as vascularization, pigmentation, opacity and scratches were discarded.
- at the end of the equilibration period of the corneae in the holder, the basal opacity was determined (t0).
- only cornea with a value of the basal opacity < 7 were used
APPLICATION DOSE AND EXPOSURE TIME
- the anterior compartment received the test item suspension or negative control or positive control at a volume of 0.75 mL each on the surface of the corneae, respectively.
- corneae were incubated in a horizontal position at 32 ± 1 °C in the water-bath (incubation time: 240 minutes).
- after exposure of the test item or control items to the corneae, they were rinsed off from the application sides with EMEM containing phenol red at least three times or more if phenol red was still discoloured (yellow or purple), or the test item was still visible.
- then corneas were finally rinsed with cMEM without phenol red.
- fresh cMEM was added into the anterior compartment and opacity was measured (t240).
- permeability of the corneae was determined.
- the corneae were observed visually. No pertinent observations were recorded.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: the opacitometer (OP_KiT opacitometer (Electro Design)) was calibrated and the opacity of each of the corneae was determined by reading each holder placed in the photoreceptor compartment for treated cornea.
Evaluation of opacity:
- the change of opacity value of each treated cornea or of the positive and negative control corneae is calculated by subtracting the initial basal opacity from the post treatment opacity reading (t240 – t0), for each individual cornea.
- the average change in opacity of the negative control corneae is calculated and this value is subtracted from the change in opacity of each treated cornea or positive control to obtain a corrected opacity.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microplate reader (Versamax® Molecular Devices)(OD490).
- after the final opacity measurement was performed, the incubation medium was removed from both chambers.The posterior chamber was filled with fresh cMEM first. Then the anterior compartment was filled with 0.5 % (w/v) sodium fluorescein solution in HBSS.
- corneae were incubated in a horizontal position for 90 ± 5 minutes in a water-bath at 32 ± 1 °C.
- incubation medium from the posterior compartment was removed, mixed and the optical density at 490 nm was determined with a microplate reader.
Evaluation permeability:
- the corrected OD490 value of each cornea treated with positive control or test item is calculated by subtracting the average negative control cornea value from the original permeability value for each cornea.
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
The following formula is used to determine the IVIS of the negative control:
IVIS = opacity value + (15 x OD490 value of permeability)
The following formula is used to determine the IVIS of the positive control and the test item:
IVIS = (opacity value – mean opacity of the negative control) + (15 x (permeability value - mean permeability of the negative control)
The mean IVIS value of each treated group (negative control, positive control and test item) is calculated from the respective individual IVIS values.
Depending on the IVIS score obtained, the test item is classified into the following category according to OECD guideline 437 (please refer to table 1 in the field "Any other information on material and methods incl. tables" below).
DECISION CRITERIA:
The test will be acceptable if:
- the positive control gives an IVIS that falls within two standard deviations of the current historical mean (updated every three months), and if
- the negative control responses result in opacity and permeability values that are less than the established upper limits for background opacity and permeability values for bovine corneae treated with the respective negative control.
- a single testing run composed of at least three corneas should be sufficient for a test chemical when the resulting classification is unequivocal. However, in cases of borderline results in the first testing run, a second testing run will be considered as well as a third one in case of discordant mean IVIS results between the first two testing runs. - Irritation parameter:
- in vitro irritation score
- Value:
- 0
- Vehicle controls validity:
- not examined
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- - after exposure to the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed (mean IVIS = 0.92).
- exposure to the positive control (10% (w/v) Benzalkonium chloride in saline) caused clear opacity and distinctive permeability of the corneae (mean IVIS = 101.17) corresponding to a classification as serious eye damaging (EU CLP/EPA/UN GHS (Cat 1)).
- relative to the negative control, the test item calcium wolframate (CaWO4) did not cause an increase of the corneal opacity or permeability.
Please refer to the field "Any other information on results incl. tables" below. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In conclusion, according to the current study and under the experimental conditions reported, calcium wolframate (CaWO4) is not categorized according to the Regulation (EC) No 1272/2008 and subsequent adaptations.
Reference
Table 1: Results after 240 Minutes Treatment Time
Test Group |
Opacity value = Difference (t240-t0) of Opacity |
Permeability at 490 nm (OD490) |
IVIS |
Mean IVIS |
Proposed in vitro Irritancy Score |
||
|
|
Mean |
|
Mean |
|
|
|
Negative Control |
0 |
0.00 |
0.070 |
0.061 |
1.05 |
0.92 |
No Category |
0 |
0.053 |
0.80 |
|||||
0 |
0.061 |
0.92 |
|||||
Positive Control |
89.00* |
0.187* |
91.80 |
101.17 |
Category 1 |
||
118.00* |
0.112* |
119.68 |
|||||
87.00* |
0.335* |
92.02 |
|||||
Calcium wolframate (CaWO4) |
-1.00* |
0.004* |
-0.95 |
0.00** |
No category |
||
-1.00* |
0.012* |
-0.83 |
|||||
-1.00* |
0.012* |
-0.83 |
* corrected values
** negative value was set to zero
Table 2: Historical Data
|
Positive Control |
Negative Control |
Mean IVIS (MV) |
117.58 |
1.31 |
Standard Deviation of IVIS (SD) |
9.25 |
0.20 |
Range of IVIS |
98.30—138.03 |
0.86—1.64 |
95 % Control limits of IVISpos (MV ± 2 x SD) |
99.09—136.08 |
|
Mean Opacity t240min |
116.18 |
0.23 |
Standard Deviation of |
14.70 |
0.20 |
Range of Opacity t240min |
82.00—187.00 |
0.00—0.67 |
Mean Permeability (OD490) |
0.09 |
0.07 |
Standard Deviation of Permeability (OD490) |
0.11 |
0.01 |
Range of Permeability (OD490) |
-0.01—0.52 |
0.06—0.09 |
Values of 59 studies with solid test items sharing 32 sets of controls, performed between January 2016 and February 2018. |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
Skin irritation:
The substance was not observed to be irritating to the skin in a reliable in vitro study according to OECD 439.
Eye irritation:
According to a OECD 437 guideline study (GLP), calcium wolframate is not serious eye damaging (CLP (Cat 1) and does not need to be categorized according to the Regulation (EC) No 1272/2008 and subsequent adaptations.
Justification for classification or non-classification
Skin irritation:
The substance does not possess a skin irritation potential based on an in vitro OECD 439 study. Calcium wolframate does not require classification for skin irritation according to Regulation (EC) No 1272/2008 and its subsequent adaptations.
Eye irritation:
According to a OECD 437 guideline study (GLP), calcium wolframate is not serious eye damaging (CLP (Cat 1) and does not need to be categorized according to the Regulation (EC) No 1272/2008 and subsequent adaptations.
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