10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
Abstract View
Tissue-Delivered Dose – Not Exposure Concentration – Allows Conversion of Toxicological Studies into Acceptable Human Exposure Limits
OTMAR SCHMID, Helmholtz Zentrum Munchen, Comprehensive Pneumology Center
Abstract Number: 1495 Working Group: Aerosols and Health - Connecting the Dots
Abstract Inhalation toxicology studies with aerosols using animal (in vivo) or cell-based (in vitro) models of the lung are technologically challenging and typically require advanced aerosol equipment for controlled exposure conditions. In spite of these efforts, conversion of these toxicological data into regulatory relevant recommendations for safe/acceptable human exposure limits is often not possible due to fundamental flaws in aerosol dosimetry.
Frequently, estimated worst case scenarios for human exposure levels are chosen as guidance for toxicological studies and “no-response” at these exposure levels is FALSELY interpreted as indicator for “safe” materials. However, not exposure levels but tissue-/organ-delivered dose is essential for reliably risk assessment. Moreover, the susceptibility of the toxicological model (cell/animal) relative to an equivalent human response has to be assessed carefully. For instance, in vitro cell-based inflammatory responses frequently occur at much higher equivalent dose levels than observed in animal models or humans. All of these issues have to be addressed for reliable risk assessment based on toxicological studies.
In this talk, the key factors linking exposure concentration in toxicological studies to equivalent human exposure concentrations and hence acceptable exposure limits are discussed. Essentially this requires careful consideration of the relationship between exposure concentration (external dose) and tissue-delivered dose (internal dose) which includes aerosol characteristics (size, density and shape) as well as geometry of the exposure system (e.g. lung morphology, geometry of cell exposure chamber), flow conditions (or respiratory conditions) and exposure time. As an example, an overview of currently available aerosol-cell exposure systems and suitable real-time dosimetry methods are presented (e.g. Quartz Crystal Microbalance).
Finally, the most difficult aspect of deriving acceptable exposure levels from toxicological studies is the assessment of model- and response-specific susceptibility factors. This issue will be elucidated by providing typical onset doses for various models and endpoints (cell-based, animal-based, acute/chronic response). These doses will be put into perspective by comparison with real world exposure scenarios in both urban and occupational settings.
This talk highlights the pivotal role of (normalized) tissue-/lung-delivered dose, preferentially in terms of surface area, for reliable risk assessment of inhaled particles. It also highlights important implications for the design of toxicological studies and the development of aerosol technology tailored towards the needs of health-effects studies.