Details

Autor(en) / Beteiligte

• Gilbert‐Sandoval, Ixchel
• Wesseling, Sebastiaan
• Rietjens, Ivonne M. C. M.

Titel

Predicting the Acute Liver Toxicity of Aflatoxin B1 in Rats and Humans by an In Vitro–In Silico Testing Strategy

Ist Teil von

• Molecular nutrition & food research, 2020-07, Vol.64 (13), p.e2000063-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• Scope High‐level exposure to aflatoxin B1 (AFB1) is known to cause acute liver damage and fatality in animals and humans. The intakes actually causing this acute toxicity have so far been estimated based on AFB1 levels in contaminated foods or biomarkers in serum. The aim of the present study is to predict the doses causing acute liver toxicity of AFB1 in rats and humans by an in vitro–in silico testing strategy. Methods and results Physiologically based kinetic (PBK) models for AFB1 in rats and humans are developed. The models are used to translate in vitro concentration–response curves for cytotoxicity in primary rat and human hepatocytes to in vivo dose–response curves using reverse dosimetry. From these data, the dose levels at which toxicity would be expected are obtained and compared to toxic dose levels from available rat and human case studies on AFB1 toxicity. The results show that the in vitro–in silico testing strategy can predict dose levels causing acute toxicity of AFB1 in rats and human. Conclusions Quantitative in vitro in vivo extrapolation (QIVIVE) using PBK modeling‐based reverse dosimetry can predict AFB1 doses that cause acute liver toxicity in rats and human. A physiologically based kinetic (PBK) model simulating the concentration through time of aflatoxin B1 (AFB1) in blood is developed for humans and rats. By integrating a reverse dosimetry approach, oral doses corresponding to internal concentration of AFB1 are predicted. In vitro concentration–response curves for liver toxicity translated to dose–response curves are comparable with the available in vivo data.