In a program announcement in 2005, The Office of Biodefense Research, the National Heart, Lung and Blood Institute, and the National Institutes of Health expressed concern about an issue of significant public health importance: the US population's potential exposure to aerosolized, inhaled harmful chemicals possibly liberated as part of bioterrorism attacks against assembled groups of the civilian populace. The primary stated objective of the program was to encourage research about how the upper respiratory tract and lungs respond to acute exposure to highly toxic chemicals and subsequent inhalation, so that preventive strategies can be improved, antidotes devised to lessen initial irritation of mucosal surfaces, mucosal absorption minimized, and acute lung injury causing pulmonary edema counteracted.
In the context of this objective, a review of the basic and applied science of inhalation toxicology was undertaken and a research proposal developed to demonstrate the relevance of an established mouse bioassay, documented to identify and quantify the effects of inhaled agents at all three regions of the respiratory tract, by evaluating the inhalation toxicity of methyl isocyanate, an agent known to affect all three regions of the respiratory tract. Human observational methyl isocyanate exposure data from the Bhopal industrial accident are available, as are experimental animal exposure data, offering the opportunity to further establish the reproducibility and validity of the bioassay. In addition, the mouse biosassay detects effects of inhaled agents at concentrations below those at which histopathological changes occur, enabling the rapid screening of administered treatments and antidotes for effectiveness. This capacity is of fundamental importance in the development of future therapeutic agents.
With experience gained in the practical management of the experimental apparatus with the methyl isocyanate proposal, a study using the mouse bioassay to reproduce unpublished data investigating therapeutics against the inhalation toxicity of ricin would be proposed at a future date. Ricin is of outmost importance for biodefense since it is extremely potent and readily available. Furthermore, no antidote or treatment exists against this agent and the unpublished data on possible treatment should be pursued..
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06162006-153909 |
| Date | 09 August 2006 |
| Creators | Greenwood, Murray Andrew |
| Contributors | Evelyn O. Talbott, DrPH, MPH, Lawrence Keller, MS, CIH, CSP, Joseph Schwerha, MD, MPH, Yves Alarie, PhD |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06162006-153909/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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