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

Ixchel Gilbert-Sandoval*, Sebastiaan Wesseling, Ivonne M.C.M. Rietjens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2000063
JournalMolecular Nutrition and Food Research
Volume64
Issue number13
Early online date18 May 2020
DOIs
Publication statusPublished - Jul 2020

Keywords

  • acute liver toxicity
  • aflatoxin B1
  • physiologically based kinetic modeling
  • reverse dosimetry

Fingerprint

Dive into the research topics of 'Predicting the Acute Liver Toxicity of Aflatoxin B1 in Rats and Humans by an In Vitro–In Silico Testing Strategy'. Together they form a unique fingerprint.

Cite this