Registration Dossier

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.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999
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:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.3 mg/L air
Exp. duration:
4 h
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:
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 used.

OBSERVATION PERIOD:
- Residues of a black material persisted on the heads of all test rats for at least 2 hrs immediately following exposure. This sign was no longer apparent on the day following exposure.
- Soiling of fur with excreta was evident in control and test rats immediately following exposure. Brown staining on head was also seen in a proportion of control rats immediately following exposure. These signs were associated with the method of restraint and were no longer apparent on Day 1 of the observation period.
-Incidental signs of hair loss from the body and a small abrasion on the head were evident for 1 control male and 1 test male respectively. All other rats were normal in appearance and behaviour from Day 1 of the observation period.
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.