Skip Navigation



ToxSci Advance Access published online on April 28, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp083
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
110/1/117    most recent
kfp083v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by de Jong, E.
Right arrow Articles by Piersma, A. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Jong, E.
Right arrow Articles by Piersma, A. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared to the in vivo potency of their parent compounds

Esther de Jong*,{dagger}, Jochem Louisse{ddagger},§,¶, Miriam Verwei{ddagger}, Bas J. Blaauboer{dagger}, Han van de Sandt{ddagger}, Ruud A. Woutersen{ddagger},§,¶, Ivonne M.C.M. Rietjens§,¶ and Aldert H. Piersma*,{dagger}

* National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands {dagger} Institute for Risk Assessment Sciences, Utrecht University, PO Box 80177, 3508 TD Utrecht, The Netherlands {ddagger} TNO Quality of Life, PO Box 360, 3700 AJ Zeist, The Netherlands § Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands TNO/WUR Centre for Innovative Toxicology

Corresponding email: Esther.de.Jong{at}rivm.nl

Received March 13, 2009; revision received April 17, 2009; accepted April 17, 2009


  Abstract

The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of chemically related compounds can define the usefulness of the assay for the chemical class tested. The aim of the present study was to evaluate the relative sensitivity of the EST for a selected series of homologous compounds and to compare the data to the relative developmental toxicity of the compounds in vivo. To this end a series of proximate developmentally toxic glycol ether alkoxy acid metabolites was tested in the EST. All glycol ether alkoxy acid metabolites tested showed a concentration-dependent inhibition of cardiomyocyte differentiation at non-cytotoxic concentrations, with methoxyacetic acid (MAA) as the most potent compound followed by ethoxyacetic acid (EAA), butoxyacetic acid (BAA) and phenoxyacetic acid (PAA), respectively. The potency ranking of the compounds in the EST corresponds with the available in vivo data. The relative differences between the potencies of the compounds appeared more pronounced in the in vivo studies than in the EST. A possible explanation for this discrepancy could be the difference in the kinetics of the compounds in vivo as compared to their in vitro kinetics. This study illustrates that the EST can be used to set priorities for developmental toxicity testing within classes of related compounds.

Key Words: embryonic stem cells; glycol ethers; alternatives to animal testing; developmental toxicology.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.