Registration Dossier

Administrative data

Description of key information

Acute toxicity studies of sufficient quality and tested in accordance with standard methodology on WC 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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-02-24 to 1999-06-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well documented, scientifically sound study that followed OECD Guideline 401 and GLP.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The lowest humidity recorded was 29%. This was lower than the range of 30 - 70% stated in the protocol. This deviation was not considered to have affected the integrity or validity of the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Hsd: Sprague-Dawley(CD))
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Obtained from Harlan U.K. Ltd, Bicester, Oxon, England.
- Age at study initiation: four to seven weeks or age.
- Weight at study initiation: range of 80 to 101 g.
- Fasting period before study: Access to food only was prevented overnight prior to and for approximately 4 hours after dosing.
- Housing: Rats were allocated without conscious bias to cages within the treatment group and housed in groups of five rats of the same sex in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet)
- Water: drinking water provided ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 22.5 degree C
- Humidity: 9-52%
- Air changes: Air exchange was maintained at 10 to 15 air changes per hour.
- Photoperiod: lighting controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours).


IN-LIFE DATES: From: 1998-02-24 To: 1998-03-10
Route of administration:
oral: gavage
Vehicle:
other: 1 % w/v aqueous methylcellulose
Details on oral exposure:
The test substance was formulated at a concentration of 20 % (w/v) in 1 % (w/v) aqueous methylcellulos which was administered at a volume of 10 mL/kg-bw.
Doses:
single oral gavage dose of 2000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
male/female
Dose descriptor:
other: NOEL
Effect level:
> 2 000 mg/kg bw
Mortality:
0/5 for males and females
Clinical signs:
Piloerection was observed in all rats within three minutes of dosing. This sign persisted and was accompanied on Day 2 only by ungroomed appearance (characterised by ungroomed coat) in all males. There were no other signs of reaction to treatment and recovery was complete in all animals by Day 3.
Body weight:
No changes in body weight gain were seen.
Gross pathology:
No macroscopic abnormalities at terminal kill on day 15 were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute lethal oral dose to rats of Tungsten Carbide Powder - Pure was demonstrated to be greater than 2000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study conducted under OECD guidlines and under GLP

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
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
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.
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.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
5.3 mg/m³
Quality of whole database:
Study conducted under OECD guidlines and under GLP

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-02-24 to 1999-06-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
ell documented, scientifically sound study that was conducted accordiing to GLP and OECD guideline 402.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd Bicester Oxon England
- Age at study initiation: 8-11 weeks
- Weight at study initiation: 208-255g
- Housing: Individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad lib - Special Diet Services RM1(E) SQC expanded pellet
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22.5
- Humidity (%): 29-52%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (0700 - 1900 hours)

IN-LIFE DATES: From: 1998-02-24 To: 1998-03-10
Type of coverage:
occlusive
Vehicle:
other: methylcellulose
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region
- % coverage: 10%
- Type of wrap if used: Porous gauze held in place with a non-irritating dressing covered with a waterproof dressing encircling trunk of animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Warm water (30 to 40 degrees C) to remove residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bodyweight
- Concentration (if solution): 100% w/v in 1% w/v aqueous methylcellulose
- Constant volume or concentration used: Yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 1% w/v aqueous methylcellulose
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and five females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked at least twice daily for any mortalities
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight

CLINICAL SIGNS:
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation.

BODYWEIGHT:
The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.

TERMINAL STUDIES:
-Macroscopic pathology- All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded and macroscopic abnormalities were preserved.
Statistics:
no data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
other: NOEL
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred.
Clinical signs:
No evidence of a systemic response in any animal throughout the study following a single dose application of Tungsten Carbide Powder - pure.
Body weight:
All rats achieved satisfactory weight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed at study termination on Day 15.
Other findings:
No dermal irritation was seen in any animal during the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The NOEL and acute lethal dose to rats of Tungsten Carbide Powder- Pure was demonstrated to be greater than 2000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study conducted under OECD guidlines and under GLP

Additional information

Justification for classification or non-classification

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 WC. 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 WC.