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Description of key information

Skin: Primary skin irritation/corrosion study with tungsten disulphide in the rabbit (4-hour semi­occlusive application). The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, 8.4, "Acute Toxicity - Skin irritation" and OECD No.404, "Acute Dermal Irritation/Corrosion". Three rabbits were exposed to 0.5 grams of tungsten disulphide, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure. No skin irritation was caused by 4 hours exposure to tungsten disulphide. Grey staining of the treated skin by the test substance was observed on days 1, 2, 3 and/or 4, which hampered the scoring of the skin reactions on day 1, but did not hamper the scoring of the skin reactions on days 2, 3 and 4. 

Eye: The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B.5, "Acute Toxicity - Eye irritation" and OECD No.405, "Acute Eye Irritation/Corrosion". Single samples of approximately 94 mg of tungsten disulphide (a volume of approximately 0.1 ml) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation. Instillation of the test substance resulted in effects on the iris and conjunctivae. lridial irritation (grade 1) was observed in all animals and had resolved within 24 hours. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 48 hours in all animals. Grey staining of (peri) ocular tissues by the test substance was observed on day 1. Due to this staining, the eyelids, nictitating membrane and sclera could be scored partly (upper part). Remnants of the test substance were present in the eyes of two animals on days 1 and 2 and in one animal on day 1. Remnants of the test substance were present on the outside of the eyelids of two animals on days 1 and 2 and of one animal on day 1. Grey staining of the fur on the head and paws, caused by the test substance, was noted on day 1.


Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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 test date:>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:Water- Not Indicated

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The powdery test substance was moistened with water (Milli-U), immediately before application, to ensure close contact with the animal's skin.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: between 1.0 and 3.5 kg
- Housing:labelled cages with perforated floors (Scanbur, Denmark, dimensions 53.5x63x38.5 cm)
- Diet (e.g. ad libitum): Standard laboratory rabbit diet approx. 100 g. per day
- 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 (%): 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

IN-LIFE DATES: From: To:
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):0.4 ml
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

NEGATIVE CONTROL
- Amount(s) applied (volume or weight):
- Concentration (if solution):

POSITIVE CONTROL
- Amount(s) applied (volume or weight):
- Concentration (if solution):
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after exposure
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: flank
- % coverage: 150 square centimeters
- Type of wrap if used: metalline patch which was wrapped around the abdomen and secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin cleaned of residual test substance using water and ethanol
- Time after start of exposure:Four hours after the application

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
1, 24, 48 and 72 hours
SCORING SYSTEM:
- Method of calculation:
Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible} 1
Well-defined erythema 2
Moderate to severe erythema ........................................................................................•. 3
Severe erythema (beet redness}• 4
•. Where signs of necrosis or corrosion (injuries in depth} prevent erythema scoring, the maximum grade for erythema (= 4) is given.
Oedema formation:
No oedema 0
Very slight oedema (barely perceptible} 1
Slight oedema (edges of area well-defined by definite raising} 2
Moderate oedema (raised approximately 1 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure)4
Irritation parameter:
erythema score
Basis:
animal: #86, 87, 91
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal: #91
Time point:
72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
No scoring possible due to grey staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal: #86, 87, 91
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: #91
Time point:
72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
No scoring possible due to grey staining of the skin by the test substance
Interpretation of results:
study cannot be used for classification
Conclusions:
Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TUNGSTEN DISULFIDE does not have to be classified and has no obligatory labelling requirement for skin irritation.

Executive summary:

Primary skin irritation/corrosion study with TUNGSTEN DISULFIDE in the rabbit (4-hour semi­occlusive application).

 The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, 8.4, "Acute Toxicity - Skin irritation" and OECD No.404, "Acute Dermal Irritation/Corrosion".

 Three rabbits were exposed to 0.5 grams of TUNGSTEN DISULFIDE, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.

 No skin irritation was caused by 4 hours exposure to TUNGSTEN DISULFIDE.

Grey staining of the treated skin by the test substance was observed on days 1, 2, 3 and/or 4, which hampered the scoring of the skin reactions on day 1, but did not hamper the scoring of the skin reactions on days 2, 3 and 4.

 Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TUNGSTEN DISULFIDE does not have to be classified and has no obligatory labelling requirement for skin irritation.


Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks
- Weight at study initiation: between 1.0 and 3.5 kg
- Housing: Individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100 g. per day
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3°C
- Humidity (%): 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

IN-LIFE DATES: From: To:
Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):93.6 (93.4 - 93.8) mg of the test substance (a volume of approximately 0.1 ml)
Duration of treatment / exposure:
24 h
Observation period (in vivo):
1, 24, 48 and 72 hours after instillation of the test substance
Number of animals or in vitro replicates:
3 animals of one sex
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): approximately 50 ml tepid tap-water
- Time after start of exposure: 24 h

SCORING SYSTEM:
CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal lustre)..........................................O
Scattered or diffuse areas of opacity, details of iris clearly visible............................................ 1
Easily discernible translucent area, details of iris slightly obscured.......................................... 2
Nacreous area, no details of iris visible, size of pupil barely discernible.................................... 3
Opaque cornea, iris not discernible through the opacity............................................................ 4

Area of cornea involved:
No ulceration or opacity............................................................................................................O
One quarter or less but not zero................................................................................................. 1
Greater than one quarter, but less than half............................................................................... 2
Greater than half, but less than three quarters........................................................................... 3
Greater than three quarters, up to whole area.......................................................................... 4

IRIS
Normal.......................................................................................................................................... 0
Markedly deepened rugae, congestion, swelling, moderate circumcomeal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light
(sluggish reaction is positive)...................................................................................................... 1
No reaction to light, hemorrhage, gross destruction (any or all of these)...................................2

CONJUNCT/VAL IRRITAT/ON
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal.................................................................................................................. 0
Some blood vessels definitely hyperaemic (injected)................................................................. 1
Diffuse, crimson color, individual vessels not easily discernible................................................ 2
Diffuse beefy red........................................................................................................................ 3

Chemosis (refers to lids and/or nictitating membranes):
No swelling.................................................................................................................................. 0
Any swelling above normal (includes nictitating membranes).................................................... 1
Obvious swelling with partial eversion of lids............................................................................ 2
Swelling with lids about half closed........................................................................................... 3
Swelling with lids more than half closed .....................................................................................4

Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals).........0
Any amount different from normal and/or lacrimation................................................................. 1
Discharge with moistening of the lids and hairs just adjacent to lids.......................................... 2
Discharge with moistening of the lids and hairs (considerable area around the eye)................3

Where standard lighting is considered inadequate for observing minor effects, eye examinations will be performed using an ophthalmic examination lamp.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 will be used for additional control purposes.


TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animals: #98, #100, #102
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animals: #98, #100, #102
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animals: #98, #100, #102
Time point:
24/48/72 h
Score:
0.1
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Remarks:
Animals: #98, #100, #102
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
no indication of irritation

TABLE 1: INDIVIDUAL EYE IRRITATION SCORES

 

Cornea

 

Iris

 

Conjunctivae

 

Time after dosing

Opacity

Area

Fluor area(%)

 

Redness

Chemosis

Discharge

Comments

r3No 98#

 

 

 

 

 

 

 

 

 

1 hour

 

0

 

0

 

 

1

 

1

 

2

 

2

 

abce

24 hours

0

0

0

0

1

1

0

be

48 hours

0

0

 

0

0

0

0

 

72 hours

0

0

 

0

0

0

0

 

r3No 100#

 

 

 

 

 

 

 

 

 

1 hour

 

0

 

0

 

 

1

 

1

 

2

 

2

 

abce

24 hours

0

0

0

0

1

0

0

be

48 hours

0

0

 

0

0

0

0

 

72 hours

0

0

 

0

0

0

0

 

r3No 102#

 

 

 

 

 

 

 

 

 

1 hour

 

0

 

0

 

 

1

 

2

 

2

 

1

 

abce

24 hours

0

0

0

0

1

0

0

 

48 hours

0

0

 

0

0

0

0

 

72 hours

0

0

 

0

0

0

0

 

TABLE 2: MEAN VALUE EYE IRRITATION SCORES

Animal:       Corneal:              

 

opacity

 

Redness

Chemosis

 

98

 

0

 

0

 

0.3

 

0.3

100

0

0

0.3

0.0

102

0

0

0.3

0.0

Interpretation of results:
study cannot be used for classification
Conclusions:
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TUNGSTEN DISULFIDE does not have to be classified and has no obligatory labelling requirement for eye irritation
Executive summary:

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B.5, "Acute Toxicity - Eye irritation" and OECD No.405, "Acute Eye Irritation/Corrosion".

 Single samples of approximately 94 mg of TUNGSTEN DISULFIDE (a volume of approximately 0.1 ml) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

 Instillation of the test substance resulted in effects on the iris and conjunctivae.

lridial irritation (grade 1) was observed in all animals and had resolved within 24 hours. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 48 hours in all animals. Grey staining of (peri) ocular tissues by the test substance was observed on day 1. Due to this staining, the eyelids, nictitating membrane and sclera could be scored partly (upper part).

Remnants of the test substance were present in the eyes of two animals on days 1 and 2 and in one animal on day 1. Remnants of the test substance were present on the outside of the eyelids of two animals on days 1 and 2 and of one animal on day 1. Grey staining of the fur on the head and paws, caused by the test substance, was noted on day 1.

 Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TUNGSTEN DISULFIDE does not have to be classified and has no obligatory labelling requirement for eye irritation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin and eye irritation studies of sufficient quality and tested in accordance with standard methodology indicated that tungsten disulphide was not irritating to skin or eye. Therefore, no classification is required for the skin and eye irritation endpoint for tungsten disulphide.