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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-05-19 to -1999-05-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
: filters for determining chamber concentrations were disposed of following a review of the gravimetric data. Relatve humidity of the control group was below specified levels. These were not expected to affect the integrity of the study.
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tungsten metal powder
- Other names: Wolfram
- Physical state: Grey powder
- Stability under test conditions: stable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Manston Road, Margate, Kent, England.
- Age at study initiation: Males-7wks : Females-8wk
- Housing: Housed by sex; cages (35cmx53cmx25cm) made of stainless steel sheets and wire mesh, suspended on a movable rack.
- Diet: ad libitum on SDS rat and mouse diet (RMI)
- Water:ad libitum tap water
- Acclimation period: 5 days.


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

IN-LIFE DATES: From: 1998-05-19 To: 1998-06-04

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: Diluent air supply
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cylindrical, snout-only exposure chambers made of an aluminium alloy.
- Exposure chamber volume: 30 litres
- Method of holding animals in test chamber: Restrained in moulded polycarbonate 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.
- System of generating particulates/aerosols: The particulate aerosol was generated by a Wright dust feeder (WDF), using a diluent air supply and a glass concentric jet atomiser.

TEST ATMOSPHERE
- Brief description of analytical method used: The test atmosphere was passed through an elutriation column to reduce, by sedimentation, the amount of non-respirable particulate in the atmosphere.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Eight samples of air were removed from the test chamber at various times during exposure in order to determine the concentration of the test aerosol. Each air sample was withdrawn, at a rate of 2 litres/minute, through a pre-weighed glass fibre filter.
Duration of exposure:
4 h
Concentrations:
The mean gravimetric concentration of tungsten carbide powder during the exposure period was 5.40 mg/L.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
yes
Details on study design:
The WDF was positioned on a stand at the side of the exposure chamber and the output was connected to the top inlet port of the chamber via the elutriation column. The initial speed controller setting was selected as a result of preliminary generation of a concentration of total particulate close to the target (5 mg/L).
A supply of clean dried compressed air was connected to the dust generator and the supply pressure was adjusted to give a flow rate of 10 litres/minute measured at the generator outlet nozzle. A diluent air supply, adjusted to give 10 litres/minute, was connected to the glass atomiser to provide a total air supply of 20 litres/minute. The chamber exhaust airflow was calibrated at the point of attachment to the chamber and adjusted to maintain the chamber at a slight negative pressure.
Each rat was placed into a separate restraining tube and the tubes were attached to the exposure chamber.
The powder container of the WDF was advanced manually until a trace of suspended dust was seen to emerge from the outlet. The gearing on the generator was then engaged and the generator motor switched on to start the exposure. After a 5 minute equilibration period, the exposure was timed for 4 hours. The generator was then switched off and the chamber allowed to clear before the rats were removed for examination.
Following exposure, the rats were returned to the holding cages and food and water supplies were restored. The test rats were kept in a ventilated cabinet overnight and then returned to the holding room for the remainder of the observation period.
The control group was treated similarly but exposed to air only for 4 hours. The control rats were returned to the holding room at the end of the exposure procedure.

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 then at hourly intervals during the exposure. Clinical signs were also recorded immediately following exposure and at 1 and 2 hours post exposure. During the observation period, the clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs.

BODYWEIGHT:
All rats were weighed at least twice during the week prior to exposure, immediately before the exposure (Day 0), and weekly during the observation period.

FOOD CONSUMPTION:
The amounts of food consumed by each cage of rats were 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 water bottles was conducted daily.

TERMINAL STUDIES:
At the end of the 14-day observation period, the rats were killed by intraperitoneal injection of pentobarbitone sodium and exsanguinated when clinically dead. All rats were subjected to a detailed macroscopic examination. The lungs, liver, and kidneys were removed, dissected, cleared of surrounding tissue, and the organ weights recorded. The kidneys were weighed together.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.4 mg/L air
Mortality:
There were no unscheduled deaths.
Clinical signs:
other: There were no treatment-related clinical signs seen during the exposure. There were no clinical signs indicative of an irritant or toxic effect. Soiling of the fur with excreta was noted in all control and test rats immediately following exposure. Br
Body weight:
The mean bodyweight gain of male test rats was lower than that of controls following exposure to tungsten metal powder. The mean bodyweight gain of female test rats was similar to control values.
Gross pathology:
Macroscopic pathology:
There were no treatment-related findings at necropsy. Incidental findings noted in control rats included 2 dark foci on the right posterior lobe of 1 female and a red area on the cranium of 1 male and 1 female.
Other findings:
- Organ weights: The mean lung weight was higher in the female test group rats than female control rats. No other significant differences were noted in any organ weight data.

-Food Consumption: Mean food consumption of test rats was similar to control values.

-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.

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 tungsten metal powder at a concentration of 5.40 mg/L. The LC50 ( 4-hour) is therefore in excess of 5.40 mg/L of air.