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Toxicological information

Repeated dose toxicity: other routes

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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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Referenceopen allclose all

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 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.