Nanotoxicology: In vitro-in vivo dosimetry

摘要

Gangwal et al. (2011) addressed an important topic for nanotoxicology about assessing the toxicity of inhaled nanomaterials by recommending relevant concentrations for in vitro toxicity testing. Their efforts to select in vitro concentrations based on reported occupational exposure levels of inhaled nanomaterials are, indeed, laudable. Their underlying conceptual approach is logical, involving a widely used and well-accepted particle dosimetry model [multiple-path particle dosimetry (MPPD)] to estimate deposited and retained mass doses in the pulmonary alveolar region of nanomaterial-exposed workers. They then expressed these doses as per-unit alveolar surface area in order to select for in vitro testing the same alveolar epithelial cell surface area doses. However, while this concept makes good sense when applying it to short-term (daily) deposited doses, it makes less sense and can be highly misleading when the same approach is used for doses that have accumulated in the alveolar region after long-term chronic inhalation exposures of humans. Thus, it is unfortunate that the authors made it a main point to estimate (although crudely and with some questionable assumptions) the dose of inhaled nanomaterials that is retained or accumulated on the pulmonary alveolar surface over a full working lifetime of 45 years of exposure to 1 mg/m3 airborne concentration.