Capturing the applicability of in vitro-in silico membrane transporter data in chemical risk assessment and biomedical research

The Science of the Total Environment
Laure-Alix ClerbauxAlicia Paini

Abstract

Costs, scientific and ethical concerns related to animal tests for regulatory decision-making have stimulated the development of alternative methods. When applying alternative approaches, kinetics have been identified as a key element to consider. Membrane transporters affect the kinetic processes of absorption, distribution, metabolism and excretion (ADME) of various compounds, such as drugs or environmental chemicals. Therefore, pharmaceutical scientists have intensively studied transporters impacting drug efficacy and safety. Besides pharmacokinetics, transporters are considered as major determinant of toxicokinetics, potentially representing an essential piece of information in chemical risk assessment. To capture the applicability of transporter data for kinetic-based risk assessment in non-pharmaceutical sectors, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) created a survey with a view of identifying the improvements needed when using in vitro and in silico methods. Seventy-three participants, from different sectors and with various kinds of expertise, completed the survey. The results revealed that transporters are investigated mainly during drug development, but also for risk assessment pu...Continue Reading

Citations

Aug 1, 2019·Journal of Biochemical and Molecular Toxicology·Marc Le VéeOlivier Fardel
Nov 5, 2019·American Journal of Physiology. Renal Physiology·Stephen H Wright
Apr 3, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·K DarneyL S Lautz
Mar 5, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Susana ProençaNynke I Kramer

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Methods Mentioned

BETA
in silico methods
activated cell-sorting
in vitro methods

Software Mentioned

IVIVE
Search
Excel
TP
SimCyp
Google Chart API
PKSim
GastroPlus
Integrated Approaches to Testing and Assessment ( IATA )

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