Matrix-derived combination effects influencing absorption, distribution, metabolism and excretion (ADME) of food-borne toxic compounds and implications for risk assessment

Ivonne Rietjens , Bożena Tyrakowska , Suzanne van den Berg , Ans E. M. F Soffers

Abstract

Absorption, distribution, metabolism and excretion (ADME) of food-borne toxic compounds may be influenced by other compounds or constituents present in the food. The present review presents an overview of evidence currently available on food matrix-derived combination effects influencing the ADME characteristics of food-borne toxic compounds and the possible implications for risk assessment. The results obtained indicate that interactions may occur at all levels of ADME and that the interactions may decrease but also increase the bioavailability and/or toxicity of the compounds of interest. The overview also illustrates that food matrix-derived combination effects should be considered on a case-by-case basis, taking into account especially the mode of action underlying the interactions and the dose dependency of the effects. Especially food matrix-derived combination effects that proceed by a reversible mode of action, such as for example binding to biotransformation enzymes or transport proteins, may be detected at concentrations used in in vitro assays and at dose levels used in animal bioassays but may be absent at dose levels representing realistic human intake. It is concluded that although food matrixderived combination effects may exist, their detection in in vitro assays or in animal bioassays at high dose levels may not improve risk assessment practice because interactions observed may not be maintained at low realistic levels of intake. Insight in the mode of action underlying the interactions combined with physiologically based kinetic (PBK) modelling may prove a way to obtain better insight in whether interactions detected at high dose levels will still be relevant at more realistic lower intake levels, and thus to what extent these effects should be taken into account in the risk assessment for human exposure.
Author Ivonne Rietjens - Wageningen University
Ivonne Rietjens,,
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, Bożena Tyrakowska (WT / KTiAI)
Bożena Tyrakowska,,
- Department of Technology and Instrumental Analysis
, Suzanne van den Berg - Wageningen University
Suzanne van den Berg,,
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, Ans E. M. F Soffers - Wageningen University
Ans E. M. F Soffers,,
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Journal seriesToxicology Research, ISSN 2045-452X, (A 35 pkt)
Issue year2015
Vol4
No1
Pages23-35
Publication size in sheets0.6
Keywords in Englishfood matrix effects, bioavailability, ADME
ASJC Classification3005 Toxicology; 2307 Health, Toxicology and Mutagenesis
Languageen angielski
Score (nominal)35
Score sourcejournalList
ScoreMinisterial score = 35.0, 30-12-2019, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 30-12-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2015 = 0.748; WoS Impact Factor: 2015 = 2.161 (2) - 2015=2.752 (5)
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