Registration Dossier

Administrative data

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
Cross-reference
Reason / purpose:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tungsten Oxide (WO3)
- Supplier: Sponsor
- Physical state: Yellow to greenish powder
- Analytical purity: 99.88%
- Purity test date: 2002-05-28
- Stability under test conditions: 5 years
- Storage condition of test material: Room temperature
- pH: 6.1 (aqu. suspension, 100 g/L)
- Solubility in water: < 10 mg/L WO3
- Melting point: Ca. 1473 degrees C

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

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.