In vitro versus in vivo exposure to combustion emissions

Defining the key components of a potentially hazardous aerosol mixture, whether at the level of source contributions or specific physical or chemical constituents, is a challenging but important problem. From the economic, efficiency, and ethical points of view, in vitro techniques have considerable appeal for these types of studies. However, no in vitro technique will ever have the complexity of the whole animal or person. Even for lung-specific endpoints, inhalation of aerosol mixtures by a living animal has the potential to induce systemic effects such as recruitment of inflammatory cells and neurogenic effects that can secondarily affect the lung, as well as local respiratory system responses such as cytokine production, oxidant stress, and cell death. Recent studies also demonstrate the potential for the inhaled materials to cause diverse systemic effects, which are not easily modeled in vitro. To evaluate the effects of aerosol toxicants on lung cells, various in vitro testing techniques have been developed. These methods differ in the cell types used (human or other, primary cells or transformed cell lines, epithelial or other), the exposure method (suspension of collected materials, exposure of conventional cultures to aerosols, or air-liquid interface exposures), and the toxicological endpoints assessed (cell viability, cytokine production, oxidant stress, cell type-specific function). Because these studies may have implications for regulatory decisions, it is critical that any in vitro screening process of comparative toxicology be validated by comparisons with the effects in animal models, and where possible, by controlled human exposures. This article discusses relevant parallels and discrepancies between exposures of cells and living animals.