Registration Dossier

Administrative data

Description of key information

No irritation data are available for tungsten dioxide; however, data are available for WO3, which were used for read-across. In a skin irritation study conducted on rabbits and according to OECD 404, WO3 was deemed to be not irritating. In an eye irritation study conducted on rabbits and according to OECD 405, WO3 was deemed to be not irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2002-06-24 to 2002-08-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The reliability of this study for the substance tested is a K1, but in application of read-across to a different substance ECHA’s guidance specifies that the score can be a maximum of K2. Due to similar water solubility, in vitro bioaccessibility in synthetic sweat fluid simulating dermal exposure, and available toxicity data for the target (TBO) and source (WO3) substances, the resulting toxicity potential would also be expected to be similar so read across is appropriate between these substances. In addition, read across is appropriate for this endpoint because the classification and labeling is the same for the source and target substances, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, sufficiently similar or more conservative for the target substance. For more details refer to the attached description of the read across approach.
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Tungsten trioxide
Target: Tungsten Dioxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 1 in CSR
4. DATA MATRIX: See Annex 1 in CSR
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, D-97633
- Weight at study initiation: 1.8-2.0 kg
- Housing: Animals were housed singly in metal wire cages, type KK 016R
- Diet: Altromin 2023 diet for rabbits - ad libitum. Hay briquettes were offered additionally as a dietary supplement.
- Water: Tap water from an automatic watering system - ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 19.6 degree C
- Humidity (%): Average of 70.3%
- Air changes (per hr): 12/hr
- Photoperiod (hrs dark / hrs light): 12 dark/12 light (6 am to 6 pm)

IN-LIFE DATES: From: 2004-06-24 To: 2004-06-28
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: deionised water
Controls:
other: surrounding untreated skin
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/ 2.5 cm X 2.5 cm patch

VEHICLE
- Amount(s) applied (volume or weight with unit): 1.0 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm X 2.5 cm on the clipped dorsal areas of the trunk of the rabbits.
- Type of wrap if used: cellulose patches and self adhesive non woven, hypoallergenic fabric

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off with wet Kleenex tissues after 4 hour exposure period, if necessary.

SCORING SYSTEM: Erythema/Eschar and Oedema

- The skin was examined using a cold light source KL 1500 electronic
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
All areas to be treated with the test substance and all control areas were normal before the application and at each observation time.
Other effects:
No general toxic effects were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
All areas to be treated with the test substance and all control areas were normal before the application and at each observation time. The mean scores for three of the animals at 24, 48 and 72 hrs. post application were 0.0 when observing for Erythema/Eschar and Oedema.
Executive summary:

No skin irritation data of sufficient quality are available for tungsten dioxide (target substance).  However, skin irritation data are available for tungsten trioxide (source substance), which will be used for read across. Due to similar water solubility, in vitro bioaccessibility in synthetic alveolar, lysosomal, and interstitial fluids simulating inhalation exposure, and available toxicity data for the target and source substances, the resulting toxicity potential would also be expected to be similar, so read-across is appropriate between these substances. In addition, read-across is appropriate for this endpoint because the classification and labeling is the same for the source and target substances, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, sufficiently similar. For more details, refer to the read-across category approach included in the Category section of this IUCLID submission and/or as an Annex in the CSR.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2002-07-01 to 2002-08-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented, scientifically sound study that was conducted in accordance with GLP and OECD Guideline 405. The reliability of this study for the substance tested is a K1, but in application of read-across to a different substance, ECHA's guidance specifies that the score can be a maximum of a K2.
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Tungsten Trioxide
Target: Tungsten Dioxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 1 in CSR
4. DATA MATRIX: See Annex 1 in CSR
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga
- Weight at study initiation: 2.1-2.2 kg
- Housing: Individual caging in metal wire cages (79 cm x 59 cm bottom area, 38 cm height, with a wooden rest shelf, 15 cm x 59 cm)
- Diet (e.g. ad libitum): Altromin 2023 diet for rabbits, ad libitum. Hay- briquettes were offered additionally as a dietary supplement.
- Water (e.g. ad libitum): Tap water from an automatic water system, ad libitum
- Acclimation period: 5 days (one animal), 12 days (two other animals)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 19.4 C
- Humidity (%): average of 66.7%
- Air changes (per hr): 12/hr
- Photoperiod (hrs dark / hrs light): 12 dark/12 light (6 am to 6 pm)

IN-LIFE DATES: From: 2002-07-01 To: 2002-07-12
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eyes remained untreated and served as a control
Amount / concentration applied:
The approximate equivalent of 0.1 mL (~100 mg) of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent a loss of test substance.

Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 females
Details on study design:
SCORING SYSTEM: Scoring scheme for ocular lesions- examined the whole eye, the corneae, irises, and conjunctivae

TOOL USED TO ASSESS SCORE: otoscope lamp
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Both the untreated eyes and the eyes treated with the test substance, for all three animals, were normal at each observation point.
Other effects:
No general toxic effects of the test substance were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The administration of 100 mg of the test substance to the eyes of female rabbits, resulted in no signs of eye irritation. According to the Directive 2001/59/EC, the test substance is not "irritating to eyes."
Executive summary:

No eye irritation data are available for tungsten dioxide (target substance). However, eye irritation data are available for tungsten trioxide (source substance), which were used for read-across.

Due to similar physical-chemical properties, similar or lower transformation/dissolution results and similar or lower in vitro bioaccessibility in synthetic body fluids for tungsten dioxide (the target substance) than the source substances, the resulting toxicity potential would also be expected to be similar or lower, so read-across is appropriate. Therefore, the dose descriptors are expected to be sufficiently similar or higher for the target substance, and read-across to the source chemical is adequately protective. For more details refer to the attached description of the read-across approach.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No skin and eye irritation data of sufficient quality are available for tungsten dioxide (target substance).  However, skin and eye irritation data are available for tungsten trioxide (source substance), which will be used for read across. Due to similar water solubility, in vitro bioaccessibility in synthetic alveolar, lysosomal, and interstitial fluids simulating inhalation exposure, and available toxicity data for the target and source substances, the resulting toxicity potential would also be expected to be similar, so read-across is appropriate between these substances. In addition, read-across is appropriate for this endpoint because the classification and labeling is the same for the source and target substances, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, sufficiently similar. For more details, refer to the read-across category approach included in the Category section of this IUCLID submission and/or as an Annex in the CSR.

Justification for classification or non-classification

No irritation data are available for tungsten dioxide; however, data on WO3 were used for read-across. Skin and eye irritation studies of sufficient quality and tested in accordance with standard methodology indicated that WO3, and tungsten dioxide through read-across, was not irritating to skin or eye. Therefore, no classification is required for the skin and eye irritation endpoints based on the available data from read-across.