Comparative analysis of Rapid Equilibrium Dialysis (RED) and solid phase micro-extraction (SPME) methods for In Vitro-In Vivo extrapolation of environmental chemicals.

ABSTRACT: In vitro to in vivo extrapolation (IVIVE) is a critical component of the efforts to prioritize and assess environmental chemicals using high-throughput in vitro assays. The plasma unbound fraction (F_ub) is a key toxicokinetic parameter in IVIVE, and is usually measured via the Rapid Equilibrium Dialysis (RED) assay widely used for pharmaceuticals. However, pharmaceuticals have a narrower range of physicochemical properties than environmental chemicals. Motivated by the observation that high LogK_OW compounds appeared to have disproportionately low F_ub measurements using RED, we added a protein-free control in order to verify equilibration to 100% unbound in the absence of proteins. We found that many high LogK_OW non-pharmaceuticals fail to equilib

SUBMITTER: Ferguson KC 

PROVIDER: S-EPMC6717004 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature