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Acute Toxicity: inhalation

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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:
1998-5-12 to 1999-05-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Conducted similar or equivalant to OECD 403 and per GLP guidelines. 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:
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: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR
Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
however, the deviations from the protocol did not affect the objectives and integrity of the study.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium wolframate
EC Number:
236-743-4
EC Name:
Disodium wolframate
Cas Number:
13472-45-2
Molecular formula:
Na2O4W
IUPAC Name:
Disodium dioxido(dioxo)tungsten
Details on test material:
- Name of test material (as cited in study report): Sodium tungstate dihydrate
- Physical state: White crystals
- Analytical purity: High grade purity

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd Manston Rd, Margate, Kent, England.
- Age at study initiation: 7 to 8 wks
- Housing: By sex in groups of 5 in metal cages and wire mesh.
- Diet: SDS rat and mouse diet (RM1) ad libitum
- Water: tap water ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55+/- 10%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: May 6, 1998 To: May 26, 1998

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The snout-only exposure chambers used for the exposures were of cylindrical form and made of aluminium alloy. The chambers have an enclosed volume of 30 litres.

- Method of holding animals in test chamber: The rats were held for exposure in molded polycarbonate restraining tubes which were attached at evenly spaced ports in the cylindrical section of the chamber, and were designed to allow only the snout to project into the chamber. Each rat was restrained in a forward position by an adjustable foamed plastic stopper which also provided a seal for the tube.

- Source and rate of air: A supply of clean dried compressed air was connected to the WDF generator and the supply presure was adjusted to give a flow rate of 15 litres/min. measured at the generator outlet nozzle. The chamber exhaust airflow was calibrated at the point of attachment to the chamber and adjusted to maintain the chamber at a slightly negative pressure.

- Method of conditioning air: The test atmosphere was passed through an elutriation column to reduce, by sedimentation, the amount of non-respirable particulate in the test atmosphere.

- System of generating particulates/aerosols: The Wright Dust Feed mechanism (WDF), the Fast WDF was used for generation of test atmosphere. The generator was designed to produce and maintain atmospheres containing dust by suspending material scraped from the surface of a compressed powder in a stream of dry air. The concentration of dust in the air is determined by the rate at which the scraper blade is advanced into the compressed powder.

- Method of particle size determination: The Mass median aerodynamic diameter (MMAD) of the airborne dust was 5.1 um. Approximately 65% of the particles were less than 7 um in aerodynamic diameter and of a respirable size.

- Temperature, humidity, pressure in air chamber: The air temperature in the exposure chamber was measured with a thermometer and the relative humidity was measured using a Casella Type T6900 relative humidity meter. The temperature and relative humidity were recorded at the start of exposure and then at 30-min. intervals during the 4-hr exposure.


TEST ATMOSPHERE
- Brief description of analytical method used: The nominal concentration of the test substance was calculated from the total amount of sodium tungstate dihydrate dispersed by the generator and the total volume of air flowing through the exposure system during the period of generation.

- Samples taken from breathing zone: yes, in the fist instance, samples were obtained following equilibration and at approximately hourly intervals after. An addtional sample was obtained to monitor the chamber concentration following adjustment to the exposure system. Each air sample was withdrawn, at a rate of 2 litres per minute, through a pre-weighed glass fibre filter (Whatman GF/A) mounted in an open face filter holder. The filters were weighed again following sampling for gravimetric analysis of the test aerosol. The volume of air sampled was measured using a wet-type gas meter.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Two additional air samples were taken during the exposure, at a sampling rate of 2 litres per min., using a Marple cascade impactor. The samples were taken at 98 and 225 min. of exposure. The volume of air sampled was measured using a wet-type gas meter.

The amount of test material collected on the stages of the sampler was determined gravimetrically. The particle size distribution of the test atmosphere was assessed using linear regression analysis. The probit of the cumulative percentage of the total particles collected, smaller than the cut-point of each stage, was plotted against the logarithm of the cut-point of each stage.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Time weighted average: 5.01 mg/L Gravimetric concentration
No. of animals per sex per dose:
10 males and 10 females divided into 2 groups (5 males and 5 females).
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed intermittently for signs of reaction to the test substance during exposure and at least twice daily through the observation period.
- Necropsy of survivors performed: yes, At the end of the 14-day observation period, the rats were killed by intraperitoneal injection.
- Clinical signs: The clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. Clinical signs were recorded immediately post exposure and than at 1 hour and 2 hours post exposure.
-Bodyweight: All rats were weighed at least twice during the week prior to the exposure, immediately before exposure (Day 0) and weekly during the observation period.
-Food consumption: The amounts of food consumed by each cage of rats was measured from weighday to weighday throughout the study. The daily mean intakes of food for each cage were calculated from the recorded data.
-Water consumption: A visual inspection of the water bottle was conducted each day.
-Macroscopic examination: All rats were subjected to a complete macroscopic examination. The lungs, liver and kidneys were removed, and weighed.
Statistics:
no data

Results and discussion

Preliminary study:
The conditions used during Preliminary Generation Trials were selected for exposure of rats in order to generate an anticipated chamber concentration close to target (5 mg/L). Re-milling of the test substance and modification of generation conditions did not significantly reduce the particle size of the dust aerosol.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.01 mg/L air
Exp. duration:
4 h
Mortality:
There were no unscheduled deaths during the study.
The LC50 (4-hour) for sodium tungstate dihydrate was determined to be in excess of 5.01 mg/L.
Clinical signs:
other: DURING EXPOSURE Wet fur on the head and around the mouth was observed in all test rats from 1 hour of exposure. Soiling of fur with excreta was noted in both control and test rats and was associated with the method of restraint used during exposure. OBSE
Body weight:
The mean bodyweight gain of male test rats was lower than that of the controls following exposure to sodium tungstate dihydrate. The mean bodyweight gain of female test rats was similar to control values.
Gross pathology:
There was slight congestion of the lungs of 2 male and 2 female test rats. Moderate congestion of the liver was also noted in 2 male test rats.
Dark foci were seen on the lungs of 2 male test rats; this finding is not uncommon in untreated rats.
Other findings:
- Organ weights: Mean organ weights for test rats were similar to control values.
-Food consumption: There was no treatment-related effect.
-Water consumption: A visual appraisal of the water bottles indicated that the amount consumed by the test rats was similar to that of the control rats.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The rat inhalation LC50 was determined to be in excess of 5.01 mg/L.
Executive summary:

No acute inhalation toxicity data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, acute inhalation toxicity data are available on sodium tungstate (source substance), which are used for read-across. Due to similar water solubility and toxicity for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate for this endpoint. In addition, read-across is appropriate because the classification and labelling is similar for the source substance and 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 read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

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