Skip Navigation


ToxSci Advance Access originally published online on March 19, 2009
Toxicological Sciences 2009 109(1):59-65; doi:10.1093/toxsci/kfp056
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
109/1/59    most recent
kfp056v1
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 Rouquié, D.
Right arrow Articles by Bars, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rouquié, D.
Right arrow Articles by Bars, R.
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

Standard and Molecular NOAELs for Rat Testicular Toxicity Induced by Flutamide

David Rouquié*,1, Claire Friry-Santini*, Frédéric Schorsch**, Helen Tinwell* and Rémi Bars*

* Bayer CropScience, Department of, Research Toxicology, 06903 Sophia-Antipolis, France ** Department of, Pathology, 06903 Sophia-Antipolis, France

1 To whom correspondence should be addressed at Bayer CropScience, Research Toxicology, 355 rue Dostoïevski, 06903 Sophia-Antipolis, France. Fax: 33 (0)4 93 95 84 54. E-mail: david.rouquie{at}bayercropscience.com.

Received December 17, 2008; accepted March 4, 2009


  Abstract

An important step in the safety assessment of chemicals for humans is to determine the no observed adverse effect level (NOAEL) in toxicity studies conducted in animal models. With the increasing use of molecular tools in toxicity studies, a question often posed is how a NOAEL derived from molecular data compares to a NOAEL established using standard methods. The objective of the present study was to address this question when considering testicular toxicity. To do this, we assessed the effects of the reference antiandrogen flutamide on rat testes in a standard 28-day toxicity study using doses of 0.04–150 mg/kg/day. At necropsy, blood samples were collected for testosterone measurements. The testes were collected for histopathological assessment as well as for the evaluation of gene expression changes using quantitative PCR analyses. Results showed that increases in plasma testosterone level and Leydig cell hyperplasia were detected from 6 mg/kg/day. An alteration in the level of accumulation of a selection of genes was also detected from 6 mg/kg/day. This was the case for genes functionally associated with the testicular lesion, such as lipid metabolism and cell death/cell proliferation, as well as for genes not functionally associated with the lesion. Contrary to the misgivings, these data show that, using a standard 28-day toxicity study and a well-characterized adverse effect, the NOAEL based on transcript changes is similar to the NOAELs based on testosterone levels and histopathological examination.

Key Words: antiandrogen; flutamide; Toxicogenomics; NOAEL; dose response.


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.