Premium
In silico methods for physiologically based biokinetic models describing bioactivation and detoxification of coumarin and estragole: Implications for risk assessment
Author(s) -
Rietjens Ivonne M. C. M.,
Punt Ans,
Schilter Benoît,
Scholz Gabriele,
Delatour Thierry,
van Bladeren Peter J.
Publication year - 2010
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200900211
Subject(s) - estragole , in silico , in vivo , metabolite , computational biology , pharmacology , biochemical engineering , toxicology , chemistry , biology , microbiology and biotechnology , biochemistry , chromatography , essential oil , engineering , gene
In chemical safety assessment, information on adverse effects after chronic exposure to low levels of hazardous compounds is essential for estimating human risks. Results from in vitro studies are often not directly applicable to the in vivo situation, and in vivo animal studies often have to be performed at unrealistic high levels of exposure. Physiologically based biokinetic (PBBK) modeling can be used as a platform for integrating in vitro metabolic data to predict dose‐ and species‐dependent in vivo effects on biokinetics, and can provide a method to obtain a better mechanistic basis for extrapolations of data obtained in experimental animal studies to the human situation. Recently, we have developed PBBK models for the bioactivation of the alkenylbenzene estragole to its DNA binding ultimate carcinogenic metabolite 1′‐sulfooxyestragole in both rat and human, as well as rat and human PBBK models for the bioactivation of coumarin to its hepatotoxic o‐hydroxyphenylacetaldehyde metabolite. This article presents an overview of the results obtained so far with these in silico methods for PBBK modeling, focusing on the possible implications for risk assessment, and some additional considerations and future perspectives.