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B6-DOW: Improved hazard assessment of chemical sensitizers through testing of novel markers

Principal Investigator

Dr. Darrell Boverhof
1803 Building, 46C
Midland, MI 48674
The United States of America
Tel: +1 989-638-7641
Fax: +1 989-638-9305

Collaborators

Dr. Michael Woolhiser, The Dow Chemical Company, USA
Dr. Ian Kimber and Dr. Rebecca Dearman, University of Manchester, UK
Dr. Russell Thomas, The Hamner Institutes for Health Sciences, USA

Description

The specific objectives of this project are as follows:

– to provide genome-wide maps of kinetic changes in gene expression induced in draining lymph nodes following exposure of mice to a panel of selected chemicals (comprising chemicals known to cause skin sensitization or sensitization of the respiratory tract, and chemicals that are known or suspected to elicit false positive responses in the LLNA);
– use advanced bioinformatics to develop a statistical classification model capable of accurately predicting skin sensitizing chemicals based on gene expression signatures;
– examine whether changes in the expression of certain genes correlate quantitatively with skin sensitizing potency (i.e. dose response assessment), and also determine whether certain gene expression signatures permit discrimination between skin and respiratory allergens;
– test the utility of and predictive accuracy of selected genes through an evaluation of a wider set of reference chemicals;

This research proposal brings together a unique group of researchers who possess comprehensive knowledge, capability, and scientific recognition in the areas of: hazard identification and risk assessment of chemical sensitizers, conduct of the LLNA, toxicogenomic evaluations, and bioinformatic analysis.  These investigators were strategically assembled to meet the above objectives and to effectively disseminate the research findings to the scientific community.

Related Publications

Posters:

Toxicogenomic Investigation into False Positive Responses in the Local Lymph Node Assay (LLNA) by D. Adenuga, I. Kimber, R. Dearman, R. Thomas, B. B. Gollapudi, M. R. Woolhiser and D. R. Boverhof, presented at the 14th Cefic-LRI Annual Workshop 2012

Toxicogenomic Investigation into False Positive Responses in the Local Lymph Node Assay (LLNA) by D. Adenuga, I. Kimber, R. Dearman, R. Thomas, B. B. Gollapudi, M. R. Woolhiser and D. R. Boverhof

Timeline: January 2010 > December 2012

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