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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-05-13 to 1999-05-28
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 generally accepted guidelines with no deviations to the protocol.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium wolframate
EC Number:
234-364-9
EC Name:
Ammonium wolframate
Cas Number:
11120-25-5
Molecular formula:
(NH4)10H2W12O42*4H2O
IUPAC Name:
Ammonium (para)tungstate
Constituent 2
Reference substance name:
Ammonium paratungstate
IUPAC Name:
Ammonium paratungstate
Details on test material:
- Name of test material (as cited in study report): Ammonium paratungstate (CAS# as cited in study: 1311-93-9)
- Physical state: White powder
- Analytical purity: At least 99.9%
- Expiration date of the lot/batch: Assumed stable for duration of the study (data not available)
- Stability under test conditions: Assumed stable
- Storage condition of test material: In the dark at room temperature (approximately 20 degrees C) and in the original container.

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: approximately 7 and 8 wks old
- Housing: Housed by sex in groups of 5 in holding cages (35 cm wide x 53 cm long x 25 cm high) made of stainless steel sheet and wire mesh and were suspended on a movable rack.
- Diet: SDS rat and mouse diet (RM1)- ad libitum
- Water: Tap water- ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12/12 (artificial light between 8 am and 8 pm daily)

IN-LIFE DATES: From: 1998-05-13 To: 1998-06-04

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 were of cylindrical form and made of aluminum alloy.

- Exposure chamber volume: 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 and the supply pressure was adjusted to give a flow rate of15 litres/minute measured at the generator outlet nozzle. The chamber exhaust was calibrated a the point of attachment to the chamber and adjusted to maintain the chamber at a slight 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 WDF was designed to produce and maintain atmospheres containing a particulate aerosol by suspending material scraped from the surface of a compressed powder in a stream of dry air. The concentration of the particulate aerosol in the air was determined by the rate at which the scraper blade is advanced into the compressed powder.

- Method of particle size determination: Two additional air samples were taken during the exposure, at a sampling rate of 2 Liters per minute, using a Marple cascade impactor. The samples were taken at 90 and 210 minutes 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.

- 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 Vaisalla HM30 series hygrometer. The temperature and humidity were recorded at the start of exposure and then at 30-min intervals during the 4-hour exposure.

TEST ATMOSPHERE
- The test substance was processed using an ultracentrifugal mill in order to produce a powder suitable for generation of a test aerosol. The test substance was initially ground using a 1000 micron sieve. The milled test substance was then reprocessed twice using a 200 micron sieve and then once using an 80 micon sieve.
- Seven samples of air were removed from the test chamber during exposure in order to determine the concentration of the test aerosol. In the first instance, samples were obtained following equilibration and at approximately hourly intervals thereafter. Additional samples were obtained to monitor the chamber concentration following adjustments to the exposure system. A time weighted average was calculated from the individual data in order to prevent undue biasing of repeat samples in the overall mean. Each air sample was withdrawn, at a rate of 2 Liters per minute, through a pre-weighed glass fibre filter (Whatman GF/A) mounted in an open face filter holder. The filters were re-weighed following sampling for gravimetric analysis of the test aerosol. The volume of air sampled was measured using a wet-type gas meter.

- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 5.1 um. Approximately 63% of the particles were less than 7 um in aerodynamics diameter and therefore of a respirable size.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target concentration: 5 mg/L
Control animals were exposed to clean air only
No. of animals per sex per dose:
10 male and 10 females; allocated to 1 of 2 groups on arrival, each 5 males and 5 males.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

OBSERVATIONS:
The rats were observed intermittently for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period.

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. During the observation period a full clinical signs check was performed daily in the morning. The rats were checked for survival later in the day.

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 bottles was conducted daily.

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

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.35 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: The time weighted average (TWA) concentration of total particulate in the chamber air was in agreement with target.
Mortality:
There were no unscheduled deaths.
Clinical signs:
other: During Exposure: There were no treatment-related findings during exposure. - Soiling of the fur with excreta was seen in test and control rats from 1 hour of exposure. This finding was associated with the method of restraint. Observation Period: Irregul
Body weight:
The mean bodyweight gain (Day 0 to 7) of test rats was lower than that of the controls following exposure to ammonium paratungstate. Mean bodyweight gain of test rats in the second week of the observation period (Day 8 to 14) was higher than the controls such that Day 14 bodyweights of the male test rats were similar to control values.
Gross pathology:
Macroscopic pathology (Day 14): There were no treatment-related findings at necropsy. A dark focus was seen on the left lung of 1 male and 1 femaletest rat and 1 female control rat.
Other findings:
Food Consumption: A small reduction in the mean food consumption of test rats was apparent following exposure (Day 1 to 7). This is considered treatment-related.

Water consumption: A visual appraisal of the water bottles indicated that the amount of water consumed by the test rats was similar to that of the control rats.

Organ weights (Day 14): Mean organ weights of test rats were similar to control values.

Any other information on results incl. tables

Chamber concentration of ammonium paratungstate:

The time weighted average (TWA) concentration of total particulate in the chamber air was 5.35 mg/L and was in agreement with target.

MMAD

The MMAD was higher than the ideal range (1 um to 4 um) at 5.1 um, for an acute inhalation study and was attributable to the nature of the sample of test substance supplied.

Chamber air temperature and relative humidity:

Temperature (degrees C)

Control- Mean 20.7 +/- 0.36

2 (Test)- Mean 20.7 +/- 0.50

Relative Humidity

Control- Mean 20 +/- 2.1

2 (Test)- Mean 39 +/- 2.7

There were no extremes of chamber air temperatures or humidity considered likely to have influenced the results of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
There were no deaths following a four-hour exposure of rats to a particulate aerosol generated from ammonium paratungstate at a concentration of 5.35 mg/L. The LC50 (4-hour) for ammonium wolframate is therefore in excess of 5.35 mg/L of air.