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A Brief Review of Inhalation Toxicology and the Development of a Research Proposal to Demonstrate the Relevance of an Established Mouse Bioassay to Biodefense Objectives

Greenwood, Murray Andrew (2006) A Brief Review of Inhalation Toxicology and the Development of a Research Proposal to Demonstrate the Relevance of an Established Mouse Bioassay to Biodefense Objectives. Master's Thesis, University of Pittsburgh. (Unpublished)

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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..


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Greenwood, Murray
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSchwerha, Josephschwer@pitt.eduSCHWER
Committee MemberTalbott, Evelyn O.
Committee MemberKeller, Lawrence
Committee MemberAlarie, Yves
Date: 9 August 2006
Date Type: Completion
Defense Date: 28 June 2006
Approval Date: 9 August 2006
Submission Date: 16 June 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Occupational Medicine
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: administration; animal models; biodefense; inhalation exposure; methyl isocyanate; ricin
Other ID:, etd-06162006-153909
Date Deposited: 10 Nov 2011 19:47
Last Modified: 15 Nov 2016 13:44


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