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WEAPONS-GRADE ANTHRAX: DETERMINING THE ID-50 (INHALATION) IN RHESUS MONKEYS USING A BIOLOGICALLY-BASED MODEL FOR USE IN HUMAN RISK ASSESSMENT
Citation:
Cicmanec*, J L. WEAPONS-GRADE ANTHRAX: DETERMINING THE ID-50 (INHALATION) IN RHESUS MONKEYS USING A BIOLOGICALLY-BASED MODEL FOR USE IN HUMAN RISK ASSESSMENT. Presented at EPA/ORD/DOD 2004 Toxicology and Risk Assessment Conference, West Chester, OH, April 26 - 28, 2004.
Impact/Purpose:
To inform the public.
Description:
One of the significant discoveries following the bioterrorist attacks of October 2001 was that a modified form of Bacillus anthracis (Ames strain) was the causative agent. Physical alteration of the inoculum had occurred; the electrostatic charge had been altered and the resulting spores were 1 to 3 microns in diameter. Eight separate inhalation studies have been identified in which non-human primates were used for inhalation exposure to B. anthracis to determine the Infectious Dose50 (Druett 1953, Henderson, 1949, Estep 2003, etc.) Depending on the spore particle size and strain used, these values ranged from 4000 to 682,000 spores. Although some studies used spores that were one micron in diameter, conventional spore preparations will aggregate so that many of the inhaled particles will often range from four to twelve microns. The primary advantage that is gained through the use of spores with an altered electrostatic charge is that particles do not clump and essentially all of the inoculum can be deposited directly in the lungs. In order to adjust for the amount of the conventional inoculum in the non-human primate studies that was deposited in nasal passages, pharynx, and tracheobronchial regions, a methodology that has been developed for chemical particulate inhalation exposure (using the MMAD and sigma g) has been used as a model. Conveniently, cadmium chloride and radio-labeled polystyrene microspheres share the same target cell, alveolar macrophages, as anthrax spores. Through the use of ranking the dose response of these two surrogates and zones of deposition in the respiratory tract, similar dosage adjustments can be made for anthrax spores of various particle sizes. Use of this model enables us to predict that the ID50 for the modified form of anthrax is at least 15 to 500 times lower than for conventional spores. (This presentation does not represent USEPA policy).