Tungsten carbide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-05-06 to 1999-05-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that followed OECD guidelines and GLP.

Cross-reference

Reason / purpose for cross-reference:

assessment report

Reference

Acute toxicity studies of sufficient quality and tested in accordance with standard methodology on tungsten carbide indicate a low potential for acute toxicity when administered through oral, inhalation, or dermal routes. No histopathological effects were reported, and the LD50s/LC50s and NOELs reported in each study were greater than the highest dose tested, > 2000 mg/kg bw, > 5.3 mg/L/4hrs, and > 2000 mg/kg bw for the oral, inhalation, and dermal routes of administration, respectively.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study conducted under OECD guidlines and under GLP

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 300 mg/m³ air

Quality of whole database:

Study conducted under OECD guidlines and under GLP

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study conducted under OECD guidelines and under GLP

Acute toxicity studies of sufficient quality and tested in accordance with standard methodology showed that the acute oral LD50 was greater than 2000 mg/kg in rats, the acute inhalation LC50 was greater than 5.3 mg/L/4hr in rats, and the acute dermal LD50 was greater than 2000 mg/kg in rats for tungsten carbide. The cutoff LD50 or LC50 values for classification are 2000 mg/kg for oral and dermal routes, and 5.0 mg/L/4hr for inhalation route. Therefore, no classification is required for the acute oral, dermal and inhalation toxicity for tungsten carbide.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Reference 2

Reference Type:

publication

Title:

SIDS Initial Assessment Report for SIAM 21 for Tungsten Carbide (12070-12-1), Washington DC,18-20 October, 2005

Author:

OECD-SIDS

Year:

2005

Bibliographic source:

UNEP Publications

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tungsten carbide

EC Number:

235-123-0

EC Name:

Tungsten carbide

Cas Number:

12070-12-1

Molecular formula:

CW

IUPAC Name:

tungsten(4+) methanetetraide

Details on test material:

- Name of tst substance: Tungsten Carbide Powder - Pure
- Physical state: Grey Powder
- Analytical purity: > 99.98%

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 weeks
- Weight at study initiation: Not advised
- Housing: In groups of 5 males and 5 females in metal cages with wire meshand were suspended on a movable rack.
- Diet: ad libitum on SDS rat and mouse diet (RM1)
- 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

IN-LIFE DATES: From: 1998-05-06 To: 1998-05-28

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 aluminium alloy.
- Exposure chamber volume: 30 litres

- Method of holding animals in test chamber: The rats were held for exposure with moulded 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 dust generator and the supply pressure was adjusted to give a flow rate of 20 litres/minute measured at the chamber and adjusted to maintain the chamber at a slight negative pressure.
- System of generating particulates/aerosols:The powder container of the WDF was advanced manually until a trace of suspended dust was seen to emerge from the WDF 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 exammination.
- Method of particle size determination: Two additional air samples were taken duriing the exposure, at a sampling rate of 2 litres per minute, using a Marple cascade impactor. The samples were taken at 90 and 220 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 Casella Type T6900 relative humidity meter. The temperature and relative humidity were recorded at the start of exposure and then at 30-minute intervals during the four-hour exposure.

The MMAD of the airborne dust was 7.3 um - as supplied. (48% were of respirable size - less than 7 um in diameter)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.3 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight,organ weights, histopathology

PROCEDURE:
The Wright Dust Feed mechanism (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 of the WDF was selected, and as a result of preliminary generation, a concentration of total particulate closest to 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 then 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 WDF 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 eposure, immediately before th 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 clear of surrounding tissue, and the weights recorded. The kidneys were weighed together.

Statistics:

In order to minimize the cumulative errors which result from repeated rounding of numbers, some of the data in this report have been calculated using unrounded data and only rounded for reporting. Consequently, any furher calculation using the data as presented will include rounding errors in the last significant figure, possibly leading to small apparent discrepancies with other data in this report.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.3 mg/L air

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

other: NOEL

Effect level:

> 5.3 mg/L air

Exp. duration:

4 h

Mortality:

There were no unscheduled deaths.

Clinical signs:

other: DURING EXPOSURE: - Residues of a black material were seen on the heads of test rats from 0.5 hours of exposure - Soiling of fur with excreta was apparent in both control test rats from 2 hours of exposure and was associated with the method of restraint us

Body weight:

Bodyweight gains of test rats were similar to control values.

Gross pathology:

There were no treatment-related macroscopic findings following the 14-day observation period.

Other findings:

Mean organ weights for test rats were similar to control values.

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.

ORGAN WEIGHTS:
Mean organ weights for test rats were similar to control values.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

There were no unscheduled deaths within 14 days following a single four-hour exposure of rats to a particulate aerosol generated from Tungsten Carbide powder - pure at a concentration in air of 5.30 mg/L. The rat inhalation NOEL and LC50 was determined to be > 5.30 mg/L.