10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Aerosol Dosimetry and Extrapolation between Species
MICHAEL OLDHAM, Altria Client Services LLC
Abstract Number: 1710 Working Group: Bioaerosols
Abstract Aerosol dosimetry is a critical link between exposure to inhaled particulate matter and potential toxicity. Aerosol dosimetry can also be used as a tool for extrapolation of results between species for inhaled material. Viable aerosols can present unique aerosol dosimetry challenges/opportunities when used in in-vitro and in-vivo studies. Similar aerosol dosimetry challenges/opportunities exist when extrapolation between species is done for viable aerosols.
The goals of in vitro dosimetry studies have evolved from simply knowing the exposure concentration in the culture, to determining the cell exposure concentrations, as well as the cell surface dose that causes the response. Now, the goal is to determine the internal cell dose that results in the response, and even to determine the dose at the receptor inside the cell. Recent use of 3D human tissue constructs combined with air-liquid-interface (ALI) in-vitro exposure systems has enabled direct aerosol exposure similar to what occurs in the respiratory system. Coupling the 3D human tissue constructs, ALI exposure methods, aerosol dosimetry measurements with 21st century “omic” techniques are providing new insight to disease processes.
Well defined aerosol dosimetry (spatial and temporal) is essential to obtain the most insight from in-vivo studies regardless of the exposure method (whole body, nose-only, individual mask, nasal cannula, etc.). Aerosol dosimetry for in-vivo studies has evolved from measuring exposure concentration to measuring biomarkers of exposure and/or biomarkers of potential harm and correlating those measurements with predictions of doses delivered to specific locations within the respiratory tract. Combining measurements of biomarkers of exposure and/or potential harm with location specific tissue dose predictions has shown in some cases that dose rate is more important than the total delivered dose.
Use of aerosol dosimetry for species extrapolation is complicated by some of the inherent species differences and by the lack of specific information regarding those potential differences. Important species differences include particulate inhalability, respiratory tract anatomy, physiology, and the anatomical variability of the respiratory tract anatomy. For example, recent use of aerosol dosimetry in two types of mice demonstrated that respiratory tissue sensitivity to inhaled methacholine is 50% of previously measured values.
Aerosol dosimetry for viable aerosols is a multi-factorial process that not only requires knowledge of the physical/chemical aerosol properties and their potency, but also the physical/chemical properties of the exposure environments (in-vitro setup, in-vivo setup, species specific respiratory tract anatomy and physiology). Continued development of and consistent use of appropriate aerosol dosimetry techniques can facilitate better extrapolation of in-vitro to in-vivo results and extrapolation between species for inhaled material.