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157859 
Journal Article 
Review 
Inhalation toxicity of mineral particles: Critical appraisal of endpoints and study design 
Muhle, H; Mangelsdorf, I 
2003 
Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 
140-141 
223-228 
English 
Many of the mineral particles that are of concern in regard to lung toxicity are poorly soluble particles (PSPs). They
include biopersistent mineral fibers and dusts containing crystalline silica. The preparation of well-defined test particles
of respirable size range and their characterization are an essential step that may require more time and effort than the
toxicity study itself. For toxicity studies with mineral particles, an investigation of the toxicokinetics is recommended.
Such an investigation will yield information that will help to interpret the results if dust overload conditions occur. For
mineral particles such as crystalline silica and mineral fibers, an important endpoint is their potential carcinogenicity.
The following parameters are important for the design of chronic toxicity studies, and for the prediction of severe
chronic effects: lung retention of inhaled materials for assessing the accumulation of particles, persistent inflammation
in lungs, persistent proliferation of epithelial lung cells, progressive fibrogenicity, and genotoxicity in the lung cells.
These endpoints should indicate whether the materials investigated are of concern in the health effects on exposed
humans, and in the effects of the mineral particles for which chronic studies may be required. In addition, this paper
focuses on the effects of PSPs combined with fibers, and on the strategies for investigating the potential carcinogenicity
of quartz-containing dusts. 
Poorly soluble particles; Mineral fibers; Crystalline silica; Carcinogenicity; Combined effects 
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