Inhaled aerosol dosimetry: Research-related needs and recommendations

Inhaled aerosols whether beneficial or harmful express their effects depending on the amount initially deposited in the body (i.e. the deposition dose), with clearance mechanisms including dissolution, mucociliary transport and translocation then determining retained dose in the respiratory tract. The many regions of the respiratory tract differ in their shapes, cellular makeups, defenses, and pathologies. As a result, predicting, measuring, and simulating initial deposition doses and subsequent events for deposited particles, vapors and gases presents formidable challenges. Interest in supplementing and in some cases replacing laboratory animals in inhalation studies with in vitro cellular exposures, challenges researchers with both designing exposure systems and defining the internal doses to exposed cells. Addressing these challenges requires the cooperation and collaboration of many specialists that do not normally meet at discipline-specific conferences. To address that historical limitation, research related to the dosimetry of inhaled aerosols has been addressed at a series of three issue oriented international conferences. This paper addresses the research-related needs and recommendations from the third, October 2019 conference held in Irvine, CA, USA. Conference participants were invited to submit suggestions related to research. This paper includes those suggestions plus some offered by e-mail after the conference. Over 40 submitted suggestions are organized into several categories. Sample suggestions include; 1. research-related activities should address an identified health related problem; 2. in vitro aerosol systems require development in order to have better-defined doses to cells and to represent actual in vivo exposures; 3. additional knowledge on respiratory tract anatomy is needed for several species and for the variations within humans and other species; 4. dosimetric models should be expanded in scope, and should improve their usability by non-modelers; and 5. there is value in introducing newcomers to the field of inhaled aerosols. Collaborations among several disciplines are emphasized in order to advance inhaled dosimetry models and their applications to laboratory and real-life inhalation exposures. The suggestions reported here are a snapshot in time from experts from a variety of disciplines. The categories represent the major topic areas discussed at the meeting, but within each area the recommendations are not prioritized. As such, they do not carry the approval of any research institutions, research funding agencies, private entities, or regulatory agencies. The authors are solely responsible for the contents of this paper.