Title
Relative embryotoxic potency of p-substituted phenols in the embryonic stem cell test (EST) and comparison to their toxic potency in vivo and in the whole embryo culture (WEC) assay
Author
Strikwold, M.
Woutersen, R.A.
Spenkelink, B.
Punt, A.
Rietjens, I.M.C.M.
Publication year
2012
Abstract
The applicability of the embryonic stem cell test (EST) as an alternative for in vivo embryotoxicity testing was evaluated for a series of five p-substituted phenols. To this purpose, the potency ranking for this class of compounds derived from the inhibition of cardiomyocyte differentiation in the EST was compared to in vivo embryotoxic potency data obtained from literature and to the potency ranking defined in the in vitro whole embryo culture (WEC) assay. From the results obtained it appears that the EST was able to identify the embryotoxic potential for p-substituted phenols, providing an identical potency ranking compared to the WEC assay. However, the EST was not able to predict an accurate ranking for the phenols compared to their potency observed in vivo. Only phenol, the least potent compound within this series, was correctly ranked. Furthermore, p-mercaptophenol was correctly identified as a relative potent congener of the phenols tested, but its ranking was distorted by p-heptyloxyphenol, of which the toxicity was overestimated in the EST. It is concluded that when attempting to explain the observed disparity in potency rankings between in vitro and in vivo embryotoxicity, the in vitro models should be combined with a kinetic model describing in vivo absorption, distribution, metabolism and excretion processes of the compounds. © 2012 Elsevier Ireland Ltd.
Subject
Life
QS - Quality & Safety
EELS - Earth, Environmental and Life Sciences
Healthy Living
Alternative toxicity testing
Developmental toxicity
Embryonic stem cell test
Embryotoxicity
Potency ranking
Substituted phenols
To reference this document use:
http://resolver.tudelft.nl/uuid:b9c97673-ab94-476d-8df8-ab2cedd3e91b
DOI
https://doi.org/10.1016/j.toxlet.2012.07.005
TNO identifier
463906
ISSN
0378-4274
Source
Toxicology Letters, 213 (2), 235-242
Document type
article