Inhalation toxicity of mineral particles: critical appraisal of endpoints and study design

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.