Tungsten carbide

Repeated dose toxicity: other routes

Administrative data

Endpoint:

sub-chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Non-standard, non GLP study with no data on purity of test substance but provided sufficient details on methods and results.

Cross-reference

Cross-reference 1

Reason / purpose:

reference to same study

Cross-reference 2

Reason / purpose:

reference to other study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The delayed lung responses to single and repeated intratracheal administration of pure cobalt and hard metal powder in the rat.

Author:

Lasfargues G, Lardot C, Delos M, Lauwerys R and Lison D.

Year:

1995

Bibliographic source:

Environ Res 69, 108-121.

Reference 2

Reference Type:

secondary source

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

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Evaluation of lung effects after 4 month of intratracheal instillation of tungsten carbide.

GLP compliance:

not specified

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): tungsten carbide (WC)
- Purity: > 99.9 %
- Impurities: 0.002 % cobalt
- Median particle diameter: 2 um

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 240 g
- Diet: conventional laboratory diet
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2
- Humidity (%): 50 +/- 10%
- Photoperiod (hrs dark / hrs light): 12-hr light/dark cycle

Administration / exposure

Route of administration:

other: intratracheal

Vehicle:

other: saline

Details on exposure:

The animals were anesthetized with Hypernorm (Janssen, Beerse, Belgium, 50 uL im) and instillation was performed by the transoral route in order to avoid repetitive surgical procedures.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 months

Frequency of treatment:

monthly (4 administrations)

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 5 or 10 mg/kg body weight

No. of animals per sex per dose:

15 females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Selected to allow direct comparison with WC-Co.
- Post-exposure period: 1 month

Examinations

Observations and examinations performed and frequency:

no data

Statistics:

The data were analyzed with the aid of the Statistical Analysis Software package. Differences between treatments were evaluated using a one- or two-way ANOVA complemented by Duncan multiple comparison test. When the variances were significantly different, means of ranks were compared. Statistical significance was considered at P < 0.05.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY: No mortality or complication occurred following the repeated administration.

BIOCHEMICAL PARAMETERS: There were no increases in animals treated with WC.

CELLUAR PARAMETERS: No significant differences were detected in WC animals.

LUNG HYDROXYPROLINE CONTENT:
No significant differences were found between controls and WC animals.

HISTOPATHOLOGY:
Revealed no difference to sections of controls except for the presence of fine black particles deposited in alveolar macrophages. Trichrome staining did not reveal the presence of an excess of collagen in WC animals.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 10 other: mg/kg-bw monthly over a 4 month period

Sex:

female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No alterations of biochemical or cellular parameters or lung hydroxyproline content could be observed. Histopathology of the lung revealed no difference to sections of controls except for the presence of fine black particles deposited in alveolar macrophages.