Utility of In Vitro Bioactivity as a Lower Bound Estimate of In Vivo Adverse Effect Levels and in Risk-Based Prioritization

A Case Study

Use of high-throughput, in vitro bioactivity data in setting a point-of-departure (POD) has the potential to accelerate the pace of human health safety evaluation by informing screening-level assessments. The primary objective of this work was to compare PODs based on high-throughput predictions of bioactivity, exposure predictions, and traditional hazard information for 448 chemicals. PODs derived from new approach methodologies (NAMs) were obtained for this comparison using the 50th (PODNAM, 50) and the 95th (PODNAM, 95) percentile credible interval estimates for the steady-state plasma concentration used in in vitro to in vivo extrapolation of administered equivalent doses. Of the 448 substances, 89% had a PODNAM, that was less than the traditional POD (PODtraditional) value.

PAUL FRIEDMAN Katie;  GAGNE Matthew;  LOO Lit-Hsin;  KARAMERTZANIS Panagiotis;  NETZEVA Tatiana;  SOBANSKI Tomasz;  FRANZOSA Jill;  RICHARD Ann;  LOUGEE Ryan;  GISSI Andrea;  JOEY LEE Jia-Ying;  ANGRISH Michelle M.;  DORNE Jean-Lou;  FOSTER Stiven;  RAFFAELE Kathleen;  BAHADORI Tina;  GWINN Maureen R.;  LAMBERT Jason;  WHELAN Maurice;  RASENBERG Mike;  BARTON-MACLAREN Tara;  THOMAS Russel; 

2022-01-28

OXFORD UNIV PRESS

JRC117500

1096-6080 (online),   

https://academic.oup.com/toxsci/article/173/1/202/5571376,    https://publications.jrc.ec.europa.eu/repository/handle/JRC117500,   

10.1093/toxsci/kfz201 (online),