ToxSci Advance Access published online on December 9, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj074
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1 ILSI Health and Environmental Sciences Institute, Washington, DC
* To whom correspondence should be addressed. Acute and repeat dose inhalation studies have been an important part of the safety assessment of drugs, chemicals and other products throughout the world for many years. It is known that damage to the respiratory tract can be triggered either by nonspecific irritation or by specific immune-mediated pathogenesis, and it is acknowledged that traditional inhalation studies are not designed to address fully the impact of the latter. It is also recognized that different types of immune-mediated responses can be triggered by different classes of compounds and that some immune reactions in the lung are life threatening. As such, it is important to understand as fully as possible the basis for the immune-mediated damage to the lung in order to characterize adequately the risks of individual chemicals or proteins. It is against this background that a review of the methods used to assess the potential for immune-mediated respiratory hypersensitivity was conducted. The primary objectives of this review are to discuss appropriate methods for identifying and characterizing respiratory hypersensitivity hazards and risks; and to identify key data gaps and related research needs with respect to respiratory hypersensitivity testing. The following working definition of respiratory hypersensitivity was formulated: a hypersensitivity response in the respiratory tract precipitated by a specific immune response, mediated by multiple mechanisms, including IgE antibody. Because of the importance played by various classes of compounds, the subsequent sections of this review will consider protein-specific, chemical-specific, and drug-specific aspects of respiratory hypersensitivity. Disclaimer: The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the institutions represented by the authors.
Received September 1, 2005
Accepted December 4, 2005
Review
Assessing the Potential to Induce Respiratory Hypersensitivity
Michael P. Holsapple 1 *,
David Jones 2,
Thomas T. Kawabata 3,
Ian Kimber 4,
Kathy Sarlo 5,
MaryJane K. Selgrade 6,
Jui Shah 7,
and
Michael R. Woolhiser 8
2 UK Medicines and Healthcare Products Regulatory Agency, London, UK
3 Pfizer, Inc., Groton, CT
4 Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK
5 The Procter & Gamble Company, Cincinnati, OH
6 U.S. Environmental Protection Agency, Research Triangle Park, NC
7 U.S. Food and Drug Administration, Rockville, MD; Current affiliation: Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD
8 The Dow Chemical Company, Midland, MI
Michael P. Holsapple, E-mail: mholsapple{at}ilsi.org
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