Registration Dossier

Administrative data

Description of key information

No acute toxicity data are available for tungsten dioxide. However, in an acute oral toxicity study conducted in rats and according to OECD 423, the LD50 was reported to be >2000 mg/kg for tungsten trioxide. Moreover, in an acute inhalation toxicity study conducted in rats and according to OECD 403, the LC50 was reported to be >5.36 mg/L for tungsten trioxide. These data are used for read-across to tungsten dioxide. An acute dermal toxicity study was available on sodium tungstate, which will be used for read-across. The acute dermal LD50 for sodium tungstate was determined to be > 2000 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2002-07-02 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 423, limit test. 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 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.
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
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)IGS BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River WIGA
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 166-167 g (females), 195-201 (males)
- Fasting period before study: Yes; the feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
- Diet: Altromin 1324 forte, gamma irradiated with 25 kGy60Co, ad libitum.
- Water: Tap water from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22.2 C
- Humidity (%): Average of 64.7%
- Air changes (per hr): 12/hr
- Photoperiod (hrs dark / hrs light): 12 dark/12 light (6 am to 6 pm)

IN-LIFE DATES: From: 2002-07-02 To: 2002-07-17
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
DOSE VOLUME APPLIED: 10 mL /kg body weight

DOSAGE PREPARATION: Doses of 2000 mg/kg body weight were prepared as suspensions in deionised water. Suspensions were prepared freshly before administration and were administered within 5 minutes after the preparation.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As requested by the sponsor
Doses:
2000 mg/kg body weight (in two steps)
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Clinical observations- 0-0.5, 0.5-1, 1-2, 2-4, and 4-6 hours after administration and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
- Body weights- before administration, day 7, and day 14 post administration. Bodyweight gain was calculated for each week of the study, i.e. between 0 and 7 days post administration and 7 and 14 days post administration.
- Necropsy of survivors performed: Yes
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No toxic effects were present after a single dose of 2000 mg/kg of the test substance.
Mortality:
None
Clinical signs:
All animals were normal during the whole observation period.
Body weight:
All animals gained weight in both weeks post administration.
Gross pathology:
All animals were normal at the necropsy, 14 days post administration.
Other findings:
There was no significant sex difference in the response to the test substance at 2000 mg/kg body weight.
Interpretation of results:
GHS criteria not met
Conclusions:
A test according to OECD 423 was conducted to determine the acute oral toxicity of tungsten trioxide to 8 week old male and female rats (starin Crl:CD(SD)IGS BR). 3 male and 3 female fasted rats were given a single oral dose of tungsten trioxide of 2000 mg/kg bw in water. The substance was administered in two steps. Animals were subsequently observed for 14 days. No toxic effects were present after a single dose of 2000 mg/kg of the test substance, LD50 > 2000 mg/kg bw. Thus, ist can be concluded that tungsten trioxide is practically nontoxic to male and female rats.
Executive summary:

No acute oral toxicity data of sufficient quality are available for tungsten dioxide (target substance). However, acute oral toxicity data are available for sodium tungstate (source substance), which will be used for reading across. Due to lower water solubility and lower toxicity for the target substance compared to the source substance, the resulting read across from the source substance to the target substance is appropriate as a conservative estimate of potential toxicity for this endpoint. In addition, read across is appropriate because the classification and labelling is more protective for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, lower for the source substance. 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
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant. 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.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2002-08-21 to 2002-11-28
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 403, "Acute Inhalation Toxicity". 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 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.
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 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)IGS BR, Sprague Dawley, SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River WIGA, Germany
- Age at study initiation: Approximately 9 weeks at time of administration
- Weight at study initiation: 305-336g (males), 207-225g (females)
- Housing: Housed singly in Makrolon cages type III (39 cm x 23 cm x 18 cm)
- Diet: Altromin 1324 forte, gamma irradiated with 25 kGy 60Co - ad libitum (withheld during the exposure)
- Water: Tap water from an automated watering system - ad libitum (withheld during the exposure)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target of 22 degree C
- Humidity (%): Target of 50%
- Air changes (per hr): 12/hour
- Photoperiod (hrs dark / hrs light): 12 dark/12 light (6 am to 6 pm)

IN-LIFE DATES: From: 2002-08-21 To: 2002-09-25
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: TSE, Technical & Scientific Equipment- article no. 504101. It consisted of a two chamber system. The apparatus was 30 cm in diameter and 27 cm in height, resulting in a total volume of 19 litres.
- Exposure chamber volume: 19 L
- Method of holding animals in test chamber: Trapped in outer chamber with opening to exposure chamber
- Source and rate of air: Obtained from a central pressure pump, 1836 L air/dust per hour
- System of generating particulates/aerosols: RBG 1000 dust generator
- Method of particle size determination: Cascade impactor (Berner-Impaktor Type LP14/0,06/2)
- Temperature, humidity, pressure in air chamber: 21-23 degree C, 12.7 to 16.0 %, approx. 3 bar.

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric analysis- dust was collected 9 times during the exposure period in plastic pipette-tips filled with cotton wool, which were inserted into the inhalation facility through a separate hole between two inhalation tubes.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 64% of the mass was in the fraction with a diameter of less than 5 micrometers, the size distribution did not exactly follow a log-normal distribution but had an additional fraction of particles larger that 16 micrometers.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD=3.7 micrometers, GSD= 2.3


Analytical verification of test atmosphere concentrations:
yes
Remarks:
4.47- 5.87 mg/L (detected 9 times)
Duration of exposure:
ca. 4 h
Concentrations:
- Mean concentration= 5.36 mg/L
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations- 1, 2, 3, 4, 5, and 6 hours after the start of the exposure, and then at least once a day for a total of 2 weeks.
- Body weight:
Individual- before administration, day 7, day 14, and post mortem
Body weight gain was calculated for each week of the study, 0 and 7 days post administration, 7 and 14 days post administration.
- Necropsy of survivors performed: Yes; in attempt to identify the target organs
Statistics:
no data
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.36 mg/L air
Exp. duration:
4 h
Mortality:
- All animals survived until the end of the study.
Clinical signs:
- Immediately after exposure the fur at the head of all animals was stained yellow (due to sedimentation of the test substance).
- Three animals showed chromodacryorrhoea for a short time after the exposure. This is a sign of general malaise and may be caused by the restraint in the inhalation tubes.
- One hour after the exposure all animals were normal and stayed so for the rest of the 14-day observation period.
Body weight:
- The mean body weights at the end of the exposure were 319 g for males and 216 g for females. The mean body weight gain in the first week after the exposure was 47 g for males and 16 g for females. In the second week males gained 43 g, females 14 g.
- No animal lost weight during the study.
Gross pathology:
- Nothing abnormal was seen in any of the animals.
Other findings:
- Other observations: No sex differences can be established from the results of this study.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute inhalation toxicity study according to OECD 403, 5 male and 5 female young adult rats (Crl:CD(SD)IGS BR, Sprague Dawley, SPF ) were exposed by inhalation route to tungsten trioxide (99.88 %) for 4 hours (nose only) to tungsten trioxide at a single mean concentration of 5.36 mg/L.  Animals then were observed for 14 days. Three animals showed chromodacryorrhoea for a short time after the exposure. This is a sign of general malaise and may be caused by the restraint in the inhalation tubes. One hour after the exposure all animals were normal and stayed so for the rest of the 14-day observation period. The LC50 for male and female rats was determined to be > 5.36 mg/L air. Thus, tungsten trioxide is considered practically nontoxic.
Executive summary:

As no data on the acute inhalation toxicity of tungsten dioxide are available tungsten trioxide results are used in a read-across approach. 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 substance tungsten trioxide, 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
5 360 mg/m³
Quality of whole database:
The study is GLP compliant. 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.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1998-03-09 to 1999-06-24
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 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.
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 Oxide
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 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd,Bicester, Oxon, England
- Age at study initiation: 8 to 11 wks
- Weight at study initiation: 235 to 300 g
- Housing: Individually in metal cages with wire mesh floors.
- Diet: ad libitum - Special Diet Services RM1(E) SQC expanded pellet.
- Water: ad libitum
- Acclimation period: 18 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22.5 C
- Humidity (%): 29 to 50%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: March 9, 1998 To: March 23, 1998
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10%
- Type of wrap if used: Porous gauze with a non-irritating dressing covered by a waterproof dressing encircled firmly around the trunk of the animal.


REMOVAL OF TEST SUBSTANCE
- Washing: with warm water and blotted dry with absorbent paper.
- Time after start of exposure:24 hrs


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- Constant volume or concentration used: yes
-Test material was applied by spreading it evenly over the prepared skin.
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bodyweight, single dose.
Maximum practical concentration of 250% w/v in distilled water and administered at a dose volume of 0.8 mL/kg bodyweight.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at lest twice daily for mortalities through 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
-Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation.
-Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
-Macroscopic pathology: All animals were subjected to a macroscopic examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded and macroscopic abnormalities were preserved.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths and no evidence of a systemic response in any animal throughout the study.
Clinical signs:
Slight erythema only was observed in three rats following removal of the dressings on Day 2 which was still evident in two animals on Day 3 before resolving in all instances by Day 4. No dermal irritation was seen in the remaining seven animals.
Body weight:
A slightly low bodyweight gain was evident in one female on Day 8 and Day 15. All other rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed at study termination on Day 15.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study according to OECD 402, 5 male and 5 femaleyoung adult Sprague-Dawley rats were dermally exposed to sodium tungstate dehydrate (99,9 %) tungsten trioxide in water for 24 hours to 10 % (body surface area)at a single dose of 2000 mg/kg bw (limit test). Animals then were observed for 14 days. There were no deaths and no evidence of a systemic response in any animal throughout the study. Slight erythema only was observed in three rats following removal of the dressings on Day 2 which was still evident in two animals on Day 3 before resolving in all instances by Day 4. No dermal irritation was seen in the remaining seven animals. No macroscopic abnormalities were observed for animals killed at study termination on Day 15. The acute lethal dose (LD50) was determined to be greater than 2000 mg/kg bw for male and female Sprague-Dawley rats. Thus, tungsten trioxide is considered to be practically nontoxic.

There were no deaths and no evidence of a systemic response in any animal throughout the study following a single dermal application of the test substance to rats at a dose level of 2000 mg/kg-bw. The acute lethal dose was determined to be greater than 2000 mg/kg bw.
Executive summary:

As no data on the acute dermal toxicity of tungsten dioxide are available sodium tungstate dihydrate results are used in a read-across approach. 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 substance sodium tungstate dihydrate, 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant. 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.

Additional information

No acute toxicity data are available for tungsten dioxide (target substance). However, acute dermal toxicity data are available for sodium tungstate (source substance) and acute oral and inhalative toxicity data are available for tungsten trioxide (source substance). These data were used for read-across.

Due to similar physico-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 (tungsten trioxide and sodium tungstate), 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.

Justification for selection of acute toxicity – oral endpoint

Only one study is available.

Justification for selection of acute toxicity – inhalation endpoint

GLP Guideline study

Justification for selection of acute toxicity – dermal endpoint

GLP Guideline study

Justification for classification or non-classification

Acute toxicity studies with tungsten trioxide of sufficient quality and tested in accordance with standard methodology showed that in rats the acute oral LD50 was greater than 2000 mg/kg and the acute inhalation LC50 was greater than 5.36 mg/L/4h. These data are used for read-across to tungsten dioxide. The cut-off oral LD50 value for classification is 2000 mg/kg, and the cut-off inhalation LC50 value for classification is 5.0 mg/L/4 hr for dusts and mists. Therefore, no classification is required for the acute oral and acute inhalation toxicity endpoints for tungsten dioxide. An acute dermal toxicity study was not available for tungsten dioxide. However, the acute dermal LD50 for sodium tungstate was >2000 mg/kg, which will be used for read-across. The cut-off LD50 value for acute dermal toxicity classification is 2000 mg/kg. Therefore, no classification is required for tungsten dioxide based on available data.