title: Validation of an air-liquid interface toxicological set-up using Cu, Pd, and Ag well-characterized nanostructured aggregates and spheres.
abstract: Systems for studying the toxicity of metal aggregates on the airways are normally not suited for evaluating the effects of individual particle characteristics. This study validates a set-up for toxicological studies of metal aggregates using an air-liquid interface approach. The set-up used a spark discharge generator capable of generating aerosol metal aggregate particles and sintered near spheres. The set-up also contained an exposure chamber, The Nano Aerosol Chamber for In Vitro Toxicity (NACIVT). The system facilitates online characterization capabilities of mass mobility, mass concentration, and number size distribution to determine the exposure. By dilution, the desired exposure level was controlled. Primary and cancerous airway cells were exposed to copper (Cu), palladium (Pd), and silver (Ag) aggregates, 50-150 nm in median diameter. The aggregates were composed of primary particles <10 nm in diameter. For Cu and Pd, an exposure of sintered aerosol particles was also produced. The doses of the particles were expressed as particle numbers, masses, and surface areas. For the Cu, Pd, and Ag aerosol particles, a range of mass surface concentrations on the air-liquid interface of 0.4-10.7, 0.9-46.6, and 0.1-1.4 µg/cm2, respectively, were achieved. Viability was measured by WST-1 assay, cytokines (Il-6, Il-8, TNF-a, MCP) by Luminex technology. Statistically significant effects and dose response on cytokine expression were observed for SAEC cells after exposure to Cu, Pd, or Ag particles. Also, a positive dose response was observed for SAEC viability after Cu exposure. For A549 cells, statistically significant effects on viability were observed after exposure to Cu and Pd particles. The set-up produced a stable flow of aerosol particles with an exposure and dose expressed in terms of number, mass, and surface area. Exposure-related effects on the airway cellular models could be asserted.
authors.affiliation: Department of Design Sciences, Ergonomics and Aerosol Technology, Lund University, 221 00 Lund, Sweden.
authors.forename: C R
authors.initials: CR
authors.lastname: Svensson
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
authors.forename: S S
authors.initials: SS
authors.lastname: Ameer
authors.affiliation: Department of Physics, Solid State Physics, Lund University, 221 00 Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Ludvigsson
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Ali
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden ; Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Alhamdow
authors.affiliation: Department of Physics, Solid State Physics, Lund University, 221 00 Lund, Sweden.
authors.forename: M E
authors.initials: ME
authors.lastname: Messing
authors.affiliation: Department of Design Sciences, Ergonomics and Aerosol Technology, Lund University, 221 00 Lund, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Pagels
authors.affiliation: Department of Design Sciences, Ergonomics and Aerosol Technology, Lund University, 221 00 Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Gudmundsson
authors.affiliation: Department of Design Sciences, Ergonomics and Aerosol Technology, Lund University, 221 00 Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bohgard
authors.affiliation: Institute of Emerging Diseases and Innovative Therapies (iMETI), Division of Prions and Related Diseases (SEPIA), Atomic Energy Commission (CEA), 18 Route du Panorama, 92265 Fontenay-aux-Roses, France.
authors.forename: E
authors.initials: E
authors.lastname: Sanfins
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Kåredal
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden ; Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Broberg
authors.affiliation: Department of Design Sciences, Ergonomics and Aerosol Technology, Lund University, 221 00 Lund, Sweden ; Chemistry, Materials and Surfaces, SP Technical Research Institute of Sweden, 223 70 Lund, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Rissler
keywords: A549; Aggregates; Air–liquid interface; Cytokines; DMA-APM; Health effects; NACIVT; SAEC; Toxicity