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 509749
Title Integrating in vitro data and physiologically based kinetic (PBK) modelling to assess the in vivo potential developmental toxicity of a series of phenols
Author(s) Strikwold, Marije; Spenkelink, Bert; Haan, Laura H.J. de; Woutersen, Ruud A.; Punt, Ans; Rietjens, Ivonne M.C.M.
Source Archives of Toxicology 91 (2017)5. - ISSN 0340-5761 - p. 2119 - 2133.
DOI http://dx.doi.org/10.1007/s00204-016-1881-x
Department(s) Sub-department of Toxicology
RIKILT - BU Toxicology Bioassays & Novel Foods
VLAG
WIMEK
Publication type Refereed Article in a scientific journal
Publication year 2017
Keyword(s) Alternative for animal testing - Embryonic stem cell test (EST) - In vitro–in vivo extrapolation (IVIVE) - Physiologically based kinetic (PBK) modelling - Reverse dosimetry - Substituted phenols
Abstract Toxicity outcomes derived in vitro do not always reflect in vivo toxicity values, which was previously observed for a series of phenols tested in the embryonic stem cell test (EST). Translation of in vitro data to the in vivo situation is therefore an important, but still limiting step for the use of in vitro toxicity outcomes in the safety assessment of chemicals. The aim of the present study was to translate in vitro embryotoxicity data for a series of phenols to in vivo developmental toxic potency values for the rat by physiologically based kinetic (PBK) modelling-based reverse dosimetry. To this purpose, PBK models were developed for each of the phenols. The models were parameterised with in vitro-derived values defining metabolism and transport of the compounds across the intestinal and placental barrier and with in silico predictions and data from the literature. Using PBK-based reverse dosimetry, in vitro concentration–response curves from the EST were translated into in vivo dose–response curves from which points of departure (PoDs) were derived. The predicted PoDs differed less than 3.6-fold from PoDs derived from in vivo toxicity data for the phenols available in the literature. Moreover, the in vitro PBK-based reverse dosimetry approach could overcome the large disparity that was observed previously between the in vitro and the in vivo relative potency of the series of phenols. In conclusion, this study shows another proof-of-principle that the in vitro PBK approach is a promising strategy for non-animal-based safety assessment of chemicals.
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