Registration Dossier

Administrative data

Description of key information

No acute toxicity data are available for tungstic acid; however, data are available for WO3 and sodium tungstate, which were used for read-across. In an acute oral toxicity study conducted on rats and according to OECD 423, the LD50 was reported to be >2000 mg/kg for WO3. In an acute inhalation toxicity study conducted on rats and according to OECD 403, the LC50 was reported to be >5.36 mg/L for WO3. 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 a K2.
Justification for type of information:
Tungstic acid (WO3•H2O) is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid will be considered equivalent to WO3. For more details on the rationale, refer to the attached description of the read-across approach (see Annex 3).
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
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 or test system 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- Fasting period before study: Yes; the feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.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 ⁰C
- 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, ie between 0 and 7 days post administration and 7 and 14 days post administration.
- Necropsy of survivors performed: Yes
Statistics:
no data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
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:
No toxic effects of the test substance 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.
Executive summary:

No oral acute toxicity data are available for tungstic acid (target substance). However,oral acute toxicity data are available for tungsten trioxide (source substance), which were used for read-across. Tungstic acid (WO3•H2O) is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid will be considered equivalent to WO3. For more details on the rationale, refer to the attached description of the read-across approach.

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:
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 this 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:
Tungstic acid (WO3•H2O) is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid will be considered equivalent to WO3. For more details on the rationale, refer to the attached description of the read-across approach (Annex 3).
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
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 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 ⁰C
- 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 ⁰C, 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
Key result
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:
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 can 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, Tungsten Oxide (WO3) for male and female rats was found to be greater than 5.36 mg/L air.
Executive summary:

No acute imhalation toxicity data are available for tungstic acid (target substance). However, acute inhalation toxicity data are available for tungsten trioxide (source substance), which were used for read-across. Tungstic acid (WO3•H2O) is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid will be considered equivalent to WO3. For more details on the rationale, refer to the attached description of the read-across approach.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5.36 mg/m³
Quality of whole database:
Well documented OECD guideline study, performed under GLP.

Acute toxicity: via dermal route

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.

Additional information

No acute toxicity data are available for tungstic acid (target substance). However, acute toxicity data are available for WO3 and sodium tungstate (source substances), which were used for read-aqcross. Tungstic acid is the hydrated form of tungsten trioxide (WO3). Based on Annex V, hydrates and water free forms (anhydrous) of compounds can be regarded as the same substance for registration purposes. Therefore, tungstic acid will be considered equivalent to WO3.

Due to lower water solubility and lower toxicity values WO3 compared to the sodium tungstate, the resulting read-across 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. Refer to the read-across category approach document (Annex 3).

Justification for classification or non-classification

No acute toxicity data are available for tungstic acid. The acute oral LD50 for WO3 was >2000 mg/kg in rats and the acute inhalation 4-h LC50 was > 5.36 mg/L for WO3, which were used for read-across. The cutoff oral LD50 value for classification is 2000 mg/kg, and the cutoff inhalation LC50 value for classification is 5.0 mg/L/4 h for dusts and mists. Therefore, no classification is required for the acute oral and acute inhalation toxicity endpoints based on the available data from read-across. The acute dermal LD50 for sodium tungstate was >2000 mg/kg, which will be used for read-across. The cutoff LD50 value for acute dermal toxicity classification is 2000 mg/kg. Therefore, no classification is required for tungstic acid based on the available data from read-across.