The Use of Nanomaterial In Vivo Organ Burden Data for In Vitro Dose Setting

Effects of nanomaterials are usually observed at higher concentrations in vitro compared to animal studies. This is pointing to differences between in vivo situations and generally less complex in vitro models. These differences concern toxicodynamics and the internal exposure (at the target cells of the in vitro and in vivo test system). The latter can be minimized by appropriate in vivo to in vitro dose extrapolations (IVIVE). An IVIVE six-step procedure is proposed here: 1) determine in vivo exposure; 2) identify in vivo organ burden at lowest observed adverse effect concentration; 3) extrapolate in vivo organ burden to in vitro effective dose; 4) extrapolate in vitro effective dose to nominal concentration; 5) set dose ranges to establish dose-response relationships; and 6) consider uncertainties and specificities of in vitro test system. Assessing the results of in vitro studies needs careful consideration of discrepancies between in vitro and in vivo models: apart from different endpoints (usually cellular responses in vitro and adverse effects on organs or organisms in vivo), nanomaterials can also have a different potency in relatively simple in vitro models and the more complex corresponding organ in vivo. IVIVE can, nonetheless, reduce the differences in exposures.