Experimental Toxicology and Ecology, BASF SE, 67056, Ludwigshafen, Germany.
Scientific Consultancy-Animal Welfare, Hallstattfeld 16, 85579, Neubiberg, Germany.
Small. 2021 Apr;17(15):e2005725. doi: 10.1002/smll.202005725. Epub 2021 Feb 15.
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.
与动物研究相比，纳米材料的效应通常在体外更高浓度下观察到。这表明体内情况与通常更简单的体外模型之间存在差异。这些差异涉及毒代动力学和内暴露（在体外和体内测试系统的靶细胞中）。通过适当的体内到体外剂量外推（IVIVE）可以最小化这种差异。这里提出了一个 IVIVE 六步程序：1）确定体内暴露；2）确定在最低观察到的不良效应浓度下的体内器官负担；3）将体内器官负担外推至体外有效剂量；4）将体外有效剂量外推至名义浓度；5）设定剂量范围以建立剂量-反应关系；6）考虑体外测试系统的不确定性和特异性。评估体外研究的结果需要仔细考虑体外和体内模型之间的差异：除了不同的终点（通常是体外的细胞反应和体内器官或生物体的不良影响）之外，纳米材料在相对简单的体外模型和更复杂的相应器官中也可能具有不同的效力。然而，IVIVE 可以减少暴露的差异。
