Dose metric considerations in in vitro assays to improve quantitative in vitro–in vivo dose extrapolations

摘要: Challenges to improve toxicological risk assessment meet the demands of EU chemical's legislation, REACH, and 7th Amendment Cosmetics Directive have accelerated development non-animal based methods. Unfortunately, uncertainties remain surrounding power alternative methods such as in vitro assays predict vivo dose-response relationships, which impedes their use regulatory toxicology. One issue reviewed here, is lack a well-defined dose metric for concentration-effect relationships obtained from cell assays. Traditionally, nominal concentration has been used define relationships. However, chemicals may differentially non-specifically bind medium constituents, well plate plastic cells. They also evaporate, degrade or be metabolized over exposure period at different rates. Studies shown that these processes reduce bioavailable biologically effective test levels far below concentration. This subsequently hampers interpretation data compare true toxic potency chemicals. Therefore, this review discusses number metrics dependency on assay setup. Recommendations are given when consider instead concentrations, order effect variability between