Nanotoxicology: in Vitro–in Vivo Dosimetry

Gangwal et al. (2011) addressed an important topic for nanotoxicology about assessing the toxicity of inhaled nano materials by recom mending relevant concentrations for in vitro toxicity testing. Their efforts to select in vitro concentrations based on reported occupational exposure levels of inhaled nano materials are, indeed, laudable. Their under lying 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 nano material-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 alveo lar 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 nano materials that is retained or accumulated on the pulmonary alveolar surface over a full working lifetime of 45 years of exposure to 1 mg/m 3 airborne concentration. Gangwal et al. then converted this 45-year accumulated surface area dose to an equivalent in vitro concentration (per square centi meter) as a selection criterion for in vitro dosing. Under " Concentrations recommended for in vitro testing, " they concluded that the long-term retained human alveo lar surface area dose equates to in vitro concentrations of 50–68 µg/mL and that These amounts for a full working lifetime lie within the range of the highest in vitro assay concentrations tested in the literature for Ag [silver nano particles] and TiO 2 [titanium dioxide nano-particles] on human, rat, and mouse cell lines. These are extraordinarily high concentrations , and unfortunately this article may be viewed as a justification for using such high in vitro dosing uncritically. Gangwal et al. (2011) did not discuss anywhere in the article the reasoning behind equating lifetime accumulated doses with doses that are given all at once as a bolus in a short-term in vitro system. The difference in dose rate alone— not considering anything else—spans many orders of magnitude. At best, these extrapolated high in vitro concentrations may be labeled as the high-end limit of an …