Tungsten oxide

Endpoint summary

Description of key information

In an acute oral toxicity study conducted on rats and according to OECD 423 the LD50 was reported to be >2000 mg/kg.  No acute inhalation toxicity data of sufficient quality are available for tungsten oxide.  However, acute inhalation toxicity data are available for tungsten trioxide, which are used for read-across. In the acute inhalation toxicity study conducted on rats and according to OECD 403 and EU Method B.2, the 4hr-LC50 was reported to be >5.36 mg/L for tungsten trioxide. No acute dermal toxicity data of sufficient quality are available for tungsten oxide.  However, acute dermal toxicity data are available for sodium tungstate, which are be used for read-across. In the acute dermal toxicity study conducted on rats and according to OECD 402 LD50  was reported to be >2000 mg/kg for sodium tungstate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-05-13 to 2003-07-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD Guideline 423; limit test.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: No severe toxic effects were present after a single dose of 2000 mg/kg of the test substance.

Conclusions:

No severe toxic effects of tungsten oxide were noted by signs in life and post mortem. No mortality occurred. An LD50 of > 2000 mg/kg body weight for rats was established for the test substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Well documented OECD guideline study, performed under GLP.

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:

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 alveolar, lysosomal, and interstitial fluids simulating inhalation exposure, and available toxicity data for the target (tungsten oxide) 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 on Annex 3 in the CSR.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY 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 oxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR, Sprague Dawley, SPF

Sex:

male/female

Details on test animals or test system 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 °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 °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 (nominal)

Exp. duration:

4 h

Mortality:

- All animals survived until the end of the study.

Clinical signs:

other: - 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 c

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 could be established from the results of this study.

Interpretation of results:

GHS criteria not met

Conclusions:

The inhalation exposure of rats to Tungsten Oxide (WO3) at a concentration of 5.36 mg/L only produced signs of general malaise a short time after the exposure. The animals recovered within one hour and no further adverse effects were observed. The LC50, for four hours of exposure to tungsten trioxide (WO3) for male and female rats was found to be greater than 5.36 mg/L air.

Executive summary:

No acute inhalation toxicity data of sufficient quality are available for tungsten oxide (target substance).  However, acute inhalation toxicity data are available for tungsten trioxide (source substance), which are 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 description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 360 mg/m³ air

Quality of whole database:

Well documented OECD guideline study, performed under GLP.

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 lower water solubility and lower toxicity values for the target substance (tungsten oxide) compared to the source substance (sodium tungstate), the resulting read across from the source substance to the target substance is appropriate as a conservative estimate of potential toxicity for this route of exposure. In addition, read across is appropriate because the classification and labeling is the 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, conservative for the target substance. For more details refer to the attached description of the read across approach on Annex 3 in the CSR.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY 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: Sodium tungstate
Target: Tungsten oxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

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 or test system 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.

Key result

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:

other: 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.

Gross pathology:

No macroscopic abnormalities were observed for animals killed at study termination on Day 15.

Interpretation of results:

GHS criteria not met

Conclusions:

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:

No acute dermal toxicity data of sufficient quality are available for tungsten oxide (target substance). However, acute dermal toxicity data are available for sodium tungstate (source substance), which are used for read-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 description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Well documented OECD guideline study, performed under GLP.

Additional information

No acute inhalation toxicity data of sufficient quality are available for tungsten oxide (target substance). However, acute inhalation toxicity data are available for tungsten trioxide (source substance) which are 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 description in the Category section of this IUCLID submission or Annex 3 of the CSR.

No acute dermal toxicity data of sufficient quality are available for tungsten oxide (target substance). However, acute dermal toxicity data are available for sodium tungstate (source substance), which are used for read-across. Due to lower water solubility and lower toxicity values 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 route of exposure. In addition, read-across is appropriate because the classification and labeling is the more protective for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are similar, or are expected to be, lower for the source substance. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

Justification for classification or non-classification

Acute toxicity studies on tungsten oxide of sufficient quality and tested in accordance with standard methodology show that the acute oral LD50 was greater than 2000 mg/kg in rats. No acute inhalation toxicity data of sufficient quality are available for tungsten oxide; however, the acute inhalation LC50 was greater than 5.36 mg/L/4h for tungsten trioxide, which are used for read-across. No acute dermal toxicity data of sufficient quality are available for tungsten oxide. However, acute dermal toxicity data are available for sodium tungstate, which are used for read-across. In the acute dermal toxicity study conducted on rats and according to OECD 402, LD50 was reported to be >2000 mg/kg for sodium tungstate. The CLP cutoff oral LD50, dermal LD50, and inhalation LC50 values for classification are 2000 mg/kg and 5.0 mg/L/4 hr for dusts. Therefore, no classification is warranted for acute toxicity.