(741e) In vitro exposure systems for assessing the performance and safety of nano-particulate aerosols

Understanding the consequences of inhalation exposure to engineered nanoparticles (NPs) is critical due to their increasing use in aerosols, aerosol-generating processes, and subsequent environmental release. Inhalation toxicity continues to be assessed using animal models at the onset; however, the use of air-liquid interface (ALI) cell exposure has gained traction for screening lung toxicity of substances in vitro.  A driver for novel ALI techniques includes the variable interactions that particles have with exposed media.  For example, particles that enter the respiratory tract deposit in different regions dependent partially on their properties and characteristics (e.g. size: 5-30 μm particles in nasopharyngeal regions due to inertia; 1-5 μm particles will settle in tracheobronchial regions, <1 μm including NPs penetrate deeply into the alveolar regions with the potential to interact with alveolar epithelium). This talk will focus on the design of ALI cell exposure systems, including variables such as flow profiles and real-time measurements.  Studies involving ALI cell exposure for preclinical respiratory medicine testing of iron oxide nanoparticles as well as for on-site occupational exposure testing will be described.  Challenges to standardization of ALI cell exposure, such as choice in lung models, positive/negative controls, and cross-method correlation, will be discussed.  As in vitro alternatives to animal testing are continually sought, I will conclude with thoughts on the applicability of ALI cell exposure to substitute the rodent-based OECD 403 acute inhalation toxicity protocol.