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Administrative data

basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
other information
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Comparable to guideline study with limitations which do not impair the overall conclusion from the data. Sufficiently detailed description of the test procedure in accordance with scientific standards (critical supporting information given, such as species tested, substance identity and dosing procedure).

Data source

Materials and methods

Test material


Test animals

Details on test animals or test system and environmental conditions:
animal weight between 25 and 45 kg

Administration / exposure

Route of administration:
other: saline
Details on exposure:
The tracheal lobe was exposed to 100 ml of saline containing 100 mg of particulates. Exposure of the tracheal lobe was carried out via bronchoscopic catheterization of the tracheal bronchus and slow infusion of the suspension in the lobe.
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Doses / Concentrations:
100 mg of particulates per animal
No. of animals per sex per dose / concentration:
Details on dosing and sampling:
The animals were studied by bronchoalveolar lavage (BAL) prior to exposure and post-exposure at months 2, 4, 6 and 8. After wedging the distal tip of the bronchoscope in the tracheal lobe bronchus, bronchoalveolar lavage was carried out by slow infusion of four 50-ml 39°C aliquots of PBS through a 50 ml syringe attached to the work channel of the bronchoscope and by gentle aspiration of the effluent. The fourth BAL syringe of effluent was retained for analysis of particles. At month 8 of the study, all sheep were sacrificed and the lungs removed from the chest cavity. The tracheal lobe was identified and tissue samples were taken for analysis.

Results and discussion

Applicant's summary and conclusion

Executive summary:

The pulmonary retention in the sheep of two morphological types of SiC (angular and fibrous) was studied. Animals were injected in the tracheal lobe with equal mass (100 mg) of particulates prepared from SiC materials taken in the field. Particles were measured by analytical transmission electron microscopy in samples of bronchoalveolar lavage fluids (BAL) obtained at months 2, 4, 6 and 8 after the injection. They were also measured in samples of lung parenchyma obtained at month 8. Measurements in BAL and in lung samples both indicated a much lower retention for fibrous than for angular SiC. The retention rate in lung parenchyma at month 8 was 30 times lower for fibrous SiC. The half-life of decrease of concentrations was 3.4 times shorter for fibrous SiC.