. "4 Dosimetry Considerations." Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press, 2006.
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Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models
times the inhaled air volume per unit time ( ) has been used as a measure of the exposure dose (DE). That is,
However, this measure of dose is inadequate for several reasons. First, not all of an inhaled aerosol will actually deposit in the respiratory tract upon inhalation. Therefore the deposition fraction (FT) in the target region of the respiratory tract needs to be included. Second, the inhalability (I), which is the sampling efficiency of the entrances to the respiratory tract, also needs to be considered. This depends on the particle size of the aerosol. Third, the concentration must be defined in terms of a proper dose metric (CDM). Therefore, the deposition dose (DD) becomes
The FT and I are found by measurement under the experimental conditions, by reference to published values, or from dosimetry software (Brown and others 2005; ICRP 1995; Birchall and others 1991). The CDM, T, and can be directly measured during a study. However, is often either calculated or based on values reported in the literature. In practical applications, the protocol for an exposure system can be calibrated for a specific species such that strict adherence to the protocol will provide a reproducible dose. Great care is necessary, however, to control unwanted factors such as electrical charges on the aerosol and on surfaces (e.g., chambers, piping, and animals), as these factors can affect aerosol size distribution, airflow rates, and losses in the exposure system.
Dose is commonly reported as a median lethal dose (LD50) or median infectious dose (ID50). However, LD50 and ID50, which are indices of the potency of an agent for producing a response, are very procedure-specific. The potency of an agent can be affected by the method of delivery, the aerosol-particle-size distribution, the site of deposition in the respiratory tract, and the species under study. Therefore, defining an infectious dose for a given level of response presents a significant challenge, since the dose that causes the death (LD50) or infection (ID50) of 50 percent of the test group can be different in almost every experimental situation. This makes interpretation of a study or replication of an exposure difficult. Therefore, the Committee recommendsthat when a multiple of the LD50or ID50(e.g., 10 LD50) is used to reportdose, then sufficient additional data, including indices of viability of the