Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 489715
Title Matrix-derived combination effects influencing absorption, distribution, metabolism and excretion (ADME) of food-borne toxic compounds: implications for risk assessment
Author(s) Rietjens, I.; Tyrakowska, B.; Berg, S.J.P.L. van den; Soffers, A.E.M.F.; Punt, A.
Source Toxicology Research 4 (2015). - ISSN 2045-452X - p. 23 - 35.
Department(s) Toxicology
Publication type Refereed Article in a scientific journal
Publication year 2015
Keyword(s) st-johns-wort - dna adduct formation - polycyclic aromatic-hydrocarbons - in-vitro - aflatoxin b-1 - oral bioavailability - gastrointestinal-tract - estragole bioactivation - efflux proteins - tea polyphenols
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 matrix-derived 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
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