Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed to an acceptable method and results are report in an acceptable manner. No guideline is available for this type of study.

Data source

Reference
Reference Type:
publication
Title:
Investigation of the biodurabililty of wollastonite and xonotlite
Author:
Bellman, N., Muhle, H.
Year:
1994
Bibliographic source:
Environmental Health Perspectives, Volume 102, Suppl. 5, p191-195

Materials and methods

Objective of study:
other: elimination kinetics
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Wistar rats were exposed to the test substance via intratracheal instillation into the lungs. The distribution of the test substance in the lung was analysed by scanning electron microscopy after 2 and 14 days, 1, 3, and 6 months to determine elimination kinetics.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): wollastonite
- Substance type: calcium metasilicate (CaSiO3
- Physical state: fibers
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
intratracheal
Vehicle:
other: 0.9% NaCl
Duration and frequency of treatment / exposure:
Single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
2 mg
No. of animals per sex per dose:
5 animals
Control animals:
no
Positive control:
Positive control with high durability: UICC crocidolite

Results and discussion

Preliminary studies:
Not relevant

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not relevant
Details on distribution in tissues:
Not relevant
Details on excretion:
Not relevant

Metabolite characterisation studies

Details on metabolites:
Not relevant

Any other information on results incl. tables

2 days after intratracheal instillation, SEM analysis showed fibers in the main bronchi, on the epithelium of the distal segments of bronchiole and in alveoli. There were no large agglomerations of fibers. This indicates an even distribution of the fibers in the lungs.

After 2 days, 0.6 to 2 mg wollastonite was present in the lungs, which could be calculated from the shape and density of particles. After six months the relative mass of the test material was found to be 0.02 to 0.5% of the initial lung burden. The elimination of fibers follows first order kinetics, with half-times between 15 and 24 days.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: elimination of wollastonite from lungs is relatively fast
Under the conditions of this study, the elimination kinetics of wollastonite fibers from the lung were relatively fast, with half-times of 15 to 21 days.
Executive summary:

Wistar rats were exposed to wollastonite via intratracheal instillation into the lungs. The distribution of the test substance in the lung was analysed by scanning electron microscopy after 2 and 14 days, 1, 3, and 6 months to determine elimination kinetics.

The elimination kinetics of wollastonite fibers from the lung were relatively fast, with half-times of 15 to 21 days. For the thoracic fraction of wollastonite, the elimination from the lung was as fast as for the respirable particulate fraction. This suggests that mechanical clearance mediated by macrophages could be only of minor importance for wollastonite, for which dissolution of fibers must be the important clearance process.