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Description of key information

Acute Oral Toxicity: The study was carried out based on the guidelines described in: EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No.423, "Acute Oral Toxicity-Acute Toxic Class Method". Tungsten disulphide was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. The oral LD50 value of tungsten disulphide in Wistar rats was established to exceed 2000mg/kg body weight.

 

Acute Inhalation Toxicity: The acute inhalation toxicity of tungsten disulfide was studied by nose-only exposure of one group of five male and five female rats for a 4-hour period to a test atmosphere containing an aerosol of tungsten disulfide at the limit concentration of 5.25 ± 0.13 g/m3. The Mass Median Aerodynamic Diameter of the particles in the test atmosphere was measured once before and once during exposure and yielded 2.7 and 3.0 µm, respectively. The distribution of particle sizes had a geometric standard deviation of 1.9 in both instances. After exposure, the animals were kept for a 14-day observation period. Clinical signs during exposure consisted of a slightly decreased breathing rat in right animals as well as labored breathing in one animal. All animals felt cold after exposure and had a black discoloration on their heads. The overall body weight gain in males were within normal limits. Overall body weight gain in females was within normal limits during the first week of the observation period, and low during the second week of the observation period. No mortality occurred during exposure or during the 14 -day observation period. The 4-hour LC50 value of an aerosol of tungsten disulfide was larger than 5.25 g/m3 for both sexes.

 

Acute Dermal Toxicity:  No acute dermal toxicity data of sufficient quality is available for tungsten disulphide (target substance). However, acute dermal toxicity data are available for tungsten metal (source substance), which will be used for reading across. Similar water solubility and lower toxicity for the target substance compared to the source substance, the resulting read across from the source substance to the target substance is appropriate to estimate of potential toxicity for this endpoint. For more details, refer to the attached description of the read-across approach. An acute dermal toxicity study on tungsten metal (source substance) conducted according to OECD 402 reported no deaths and no evidence of a systemic response in any animal throughout the study following a single dermal application of the test substance to rats at a dose level of 2000 mg/kg-bw.  The acute lethal dose was determined to be greater than 2000 mg/kg bw.

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:
2001-11-28, 2001-12-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 16031/01
- Expiration date of the lot/batch:01 April 2002
- Purity: >98%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark
- Stability under test conditions:Stable
- Solubility and stability of the test substance in the solvent/vehicle: 1% Aq. Carboxymethyl cellulose- not indicated

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 7 weeks old
- Weight at study initiation: average of 166g for females and average of 252g for males
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing:Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 15 cm.) containing purified sawdust as bedding material
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1)
- Water (e.g. ad libitum):Free access to tap-water
- Acclimation period:at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3°C
- Humidity (%): relative humidity of 30-70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% Aq. Carboxymethyl cellulose
Doses:
single dose
No. of animals per sex per dose:
three Winstar rats of each sex at each dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,Mortality/Niability, Necropsy
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Lethargy and/or piloerection were noted among the females on day 1. One male showed lethargy on day 1. No clinical signs of systemic toxicity were noted among the other males.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of tungsten disulphide in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The study was carried out based on the guidelines described in: EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No.423, "Acute Oral Toxicity-Acute Toxic Class Method". Tungsten disulphide was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. The oral LD50 value of tungsten disulphide in Wistar rats was established to exceed 2000mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Toxicity study conducted following OECD guidelines and under good laboratory principles (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:
2002-02-07,2002-02-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
traditional method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: batch no.16031/01
- Expiration date of the lot/batch:2002-04-01
- Purity test date: >98%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in a dark dry place
- Stability under test conditions: Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: particle size distribution
- Final preparation of a solid: test material was ground with a blender

FORM AS APPLIED IN THE TEST (if different from that of starting material): test material was grounded
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes/no]: yes
- Age at study initiation: 5-6 weeks
- Weight at study initiation: mean body weight of 305 g and 192 g for male and female animals, respectively
- Housing:suspended stainless steel cages fitted with wire-mesh floor and front
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 41 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 20.0 and 24.3 °C
- Humidity (%): 70% relative humidity
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12-hour light and 12-hour dark cycle

IN-LIFE DATES: From: To:2001-08-17,2002-02-18
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
ca. 3 µm
Geometric standard deviation (GSD):
ca. 1.9
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only inhalation chamber
- Exposure chamber volume: ca.50
- Method of holding animals in test chamber:secured in plastic animal holders (Battelle), positioned radially through the outer cylinder around the central column
- Source and rate of air: air controlled by a pressure reducing valve at 0.76 bar
- Method of conditioning air:
- System of generating particulates/aerosols:
- Method of particle size determination:
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: yes/no

VEHICLE
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 min
Concentrations:
5.25 +/- 0.13 g/m3
No. of animals per sex per dose:
5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Other examinations performed: clinical signs, and body weight
Preliminary study:
Preliminary study trials were used to generate a test atmosphere with the test material and a MMAD was used to measure particle size distribution
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 5.25 other: g/m3
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during exposure or during the 14-day observation period.
Clinical signs:
other: Clinical signs during exposure consisted of a slightly decreased breathing rate, observed in eight animals, and slight laboured breathing, observed in one animal. Shortly after exposure, all animals felt cold. Black discolouration of the head was observed
Body weight:
Overall body weight gain in males was considered to be within normal limits for animals of this strain and age. Overall body weight gain in females was considered to be within normal limits during the first week of the observation period, and low during the second week of the observation period.
Gross pathology:
At necropsy, treatment-related macroscopic changes consisted of grey discolouration of the lungs in seven animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The 4-hour LC50 value of an aerosol of Tungsten disulfide was larger than 5.25 g/m3 for both sexes.
Executive summary:

The acute inhalation toxicity of tungsten disulphide was studied by nose-only exposure of one group of five male and five female rats for a 4-hour period to a test atmosphere containing an aerosol of tungsten disulphide at the limit concentration of 5.25 ± 0.13 g/m3The Mass Median Aerodynamic Diameter of the particles in the test atmosphere was measured once before and once during exposure and yielded 2.7 and 3.0µm, respectively. The distribution of particle sizes had a geometric standard deviation of 1.9 in both instances. After exposure, the animals were kept for a 14-day observation period. Clinical signs during exposure consisted of a slightly decreased breathing rat in right animals as well as labored breathing in one animal. All animls felt cold after exposure and had a black discoloration on their heads. The overall body weight gain in males were considered to be within normal limts. Overall body weight gain in females was considered to be within normal limits during the first week of the observation period, and low during the second week of the observation period.
No mortality occurred during exposure or during the 14 -day observation period.The 4-hour LC50 value of an aerosol of tugsten disulphide was larger than 5.25 g/m3   for both sexes.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5.25 mg/m³
Quality of whole database:
Toxicity study conducted following OECD guidelines and under good laboratory principles (GLP)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1998-03-24 to 1999-06-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Tungsten Metal
Target: Tungsten Disulphide


3. CATEGORY APPROACH JUSTIFICATION: See Annex 1 in CSR

4. DATA MATRIX: See Annex 1 in CSR
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
One animal was found to be above the specified weight range of 200-300 g on Day 1 prior to dosing. The deviation was not considered to have affected the integrity of the study.
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 to 11 wks
- Weight at study initiation: 235 to 304 g
- Housing: Individually in metal cages with wire mesh floors in Building R14 Rm 6
- Diet: ad libitum Special Diet Services RM1(E) SQC expanded pellet
- Water: ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 to 22
- Humidity (%): 34 to 59
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1009-03-23 To: 1998-04-07
Type of coverage:
occlusive
Vehicle:
other: 1% w/v aqueous methylcellulose
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region
- % coverage: 10%
- Type of wrap if used: The test substance was applied by spreading it evenly over the prepared skin. The treatment area (50 x 50 mm ) was covered with porous gauze held in place with a non irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressings were removed and the treated area of skin was washed with warm water to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.56 ml/kg bodyweight (200 mg/kg bodyweight)
- Concentration (if solution): 357% w/v in 1% w/v aqueous methylcellulose

VEHICLE
- Concentration (if solution): 1% w/v aqueous methylcellulose
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bodyweight.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Frequently on day 1 and then twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

One day prior to treatment, hair was removed from the dorso-lumbar region of each rat, exposing an area equivalent to approximately 10% of the total body surface area.
The test substance was applied by spreading it evenly over the prepared skin. the treatment area (approximately 50 mm x 50 mm) was covered with porous gauze held in place with a non irritating dressing, and further covered by a waterproof dressing encricled firmly around the trunk of the animal.
Treatment in this manner was performed on Day 1 (day of dosing) of the study only.
At the end of the 24 hours exposure period the dressings was carefully removed and the treated area of skin was washed with warm water (30 to 40 C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

-Bodyweights: 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.

-Macroscopic pathology: All animals were subjected to a macroscopic examination wihich consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.
Statistics:
no data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
Dermal responses were confined to a residual staining (grey) from the test substance on Day 2 only (staining did not impair dermal assessment) in all ten rats and accompanied at this time in one rat only by slight erythema (resolving by Day 3).
Body weight:
A minor bodyweight loss was evident in two female rats at Day 8 only. All remaining animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were recorded at the macroscopic examination on Day 15.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal lethal dose to rats of tungsten metal powder was demonstrated to be greater than 2000 mg/kg bodyweight.
Executive summary:

No acute dermal toxicity data of sufficient quality are available for tungsten disulphide (target substance). However, acute dermal toxicity data are available for tungsten metal (source substance), which will be used for reading across. Similar water solubility and lower toxicity for the target substance compared to the source substance, the resulting read across from the source substance to the target substance is appropriate to estimate of potential toxicity for this endpoint. For more details, refer to the attached description of the read-across approach. An acute dermal toxicity study on tungsten metal (source substance) conducted according to OECD 402 reported no deaths and no evidence of a systemic response in any animal throughout the study following a single dermal application of the test substance to rats at a dose level of 2000 mg/kg-bw.  The acute lethal dose was determined to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Toxicity study conducted following OECD guidelines and under good laboratory principles (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, and the acute inhalation LC50 was greater than 5.25 mg/L/4h for tungsten disulphide. The cutoff oral LD50 value for classification is 2000 mg/kg, and the cutoff inhalation LC50 value for classification is 5.0 mg/L/4 hr for dusts and mists. Therefore, no classification is required for the acute oral and acute inhalation toxicity endpoints for tungsten disulphide. An acute dermal toxicity study was not available for tungsten disulphide (target substance). However, the acute dermal LD50 for tungsten metal (source substance) was >2000 mg/kg, which will be used for read-across. The cutoff LD50 value for acute dermal toxicity classification is 2000 mg/kg. Therefore, no classification is required for tungsten disulphide based on the available data.