Altria Group, Inc. · NYSE:MO
Altria — Technical Presentation (March 2018)
21 slides from Altria's technical presentation, Mar 15, 2018
Slide 1: In-vitro/ex-vivo exposure system dosimetry: successes and challenges
In-vitro/ex-vivo exposure system dosimetry: successes and challenges Symposium: In Vitro Test Methods to Model Local Respiratory Effects after Exposure to Pulmonary Toxicants: Not just smoke and mirrors SOT Annual Meeting March 15, 2018 Michael J. Oldham Altria Client Services l M. Oldham | Draft l
Slide 2: Conflict of Interest Disclosure
Conflict of Interest Disclosure Employee of Altria Client Services LLC Altria Client Services LLC has purchased in vitro ALI equipment from Vitrocell Systems GmbH Altria Client Services l M. Oldham | Draft l 2-28-18 2
Slide 3: Outline
Outline Goal Submerged Cultures Air-Liquid Interface – Successes Air-Liquid Interface – Challenges Air-Liquid Interface - Opportunities Altria Client Services l M. Oldham | Draft l 2-28-18 3
Slide 4: Goal
Goal Know the internal cell dose that results in the observed in- vitro/ex-vivo response? Know the cell surface dose that results in the observed in- vitro/ex-vivo response? Know the cell exposure concentration that results in the in- vitro/ex-vivo observed response? Know the intended exposu
Slide 5: Submerged Cultures - Successes
Submerged Cultures - Successes ISDD: (In-vitro Sedimentation, Diffusion Dosimetry) model by Hinderliter et al., 2010 & ISD3 Thomas et al., 2018 R = gas constant T = temperature Na = Avogadro’s # µ = media viscosity r = particle radius g = gravitational acceleration ρp = particle density ρf = fluid
Slide 6: Air-Liquid-Interface
Air-Liquid-Interface Diagram of Air-Liquid-Interface exposure system and enlarged diagram of individual exposure cell Diagrams Courtesy of Vitrocell Systems GmbH Altria Client Services l M. Oldham | Draft l 2-28-18 6
Slide 7: Air-Liquid-Interface - Successes
Air-Liquid-Interface - Successes Measurement of Particle Deposition - Know the cell surface dose that results in the observed in-vitro/ex- vivo response? For a range of solid particles 90 & 196 nm diameter solid particles – TEM using a single cell (Tippe et al., 2002) 7 non-spherical solid par
Slide 8: Air-Liquid-Interface - Successes
Air-Liquid-Interface - Successes Measurement of Particle Deposition - Know the cell surface dose that results in the observed in-vitro/ex- vivo response? Quartz crystal microbalances (QCM) - Successes - Changes in vibration frequency are correlated to amount of mass on the crystal (Sauerbrey, 19
Slide 9: Air-Liquid-Interface - Successes
Air-Liquid-Interface - Successes Measurement of Particle Deposition - Know the intended exposure concentration that results in the in- vitro/ex-vivo observed response? Photometers - Light scattering is converted to aerosol mass or particle size distribution - Refractive index of aerosol will aff
Slide 10: Air-Liquid-Interface - Successes
Air-Liquid-Interface - Successes Know the cell exposure concentration that results in the in- vitro/ex-vivo observed response? - Chemical Identification 6 cell exposure module (manufacturer not specified) – mainstream tobacco smoke (Fields et al., 2017) - TPM – trapping solution at cell level -
Slide 11: Air-Liquid-Interface - Challenges
Air-Liquid-Interface - Challenges Liquid droplet aerosols (e-vapor product aerosols) - QCM not suited for measurement - Photometers - depending on exposure flowrate, aerosol concentration exceeds capacity - Significant amount of semi-volatile constituents (Ingebrethsen et al., 2012) - Differences
Slide 12: Air-Liquid-Interface - Challenges
Air-Liquid-Interface - Challenges Temperature = 37ºC (Zavala et al., 2017) - Most publications indicate that cells are kept at 37ºC but don’t indicate the temperature of the exposure atmosphere - Difficult to raise temperature of exposure air due to small residence time in exposure system Thermo
Slide 13: Air-Liquid-Interface - Challenges
Air-Liquid-Interface - Challenges Equipment Operation - Preliminary studies yield unexpected results in a Vitrocell 24/48 system for deposition of 3.2µm monodisperse fluorescent particles Between 8,000 – 10,000 particles found on filters at the end of each row Media/phosphate buffered saline b
Slide 14: Air-Liquid-Interface - Challenges
Air-Liquid-Interface - Challenges Equipment Operation - Lagrangian approach using Fluent® CFD software for air velocity profiles – added fluid channels below transwells to simulation Altria Client Services l M. Oldham | Draft l 2-28-18 14
Slide 15: Air-Liquid-Interface - Opportunities
Air-Liquid-Interface - Opportunities Quartz crystal microbalance with dissipation (QCM-D) - Challenges - Provides novel insight into viscoelastic properties of deposited mass (liquids and vapor: Vashist & Vashist, 2011) - With specific coatings has been used to measure specific volatile organic ch
Slide 16: Air-Liquid-Interface - Opportunities
Air-Liquid-Interface - Opportunities Electrostatic precipitation - Used for decades to collect ambient airborne particulate matter - For Bipolar charged 50 – 600nm particulate, 15-35% enhancement of particle deposition is possible (Savi et al. 2008) - Gaschen et al., 2010 and de Bruijne et al., 20
Slide 17: Literature Cited
Literature Cited Adamson, J., Azzopardi, D., Errington, G., Dickens, C., McAughey, J., Gaça, M.D. Assessment of an in vitro whole cigarette smoke exposure system: The Borgwaldt RM20S 8-syringe smoking machine, Chemistry Central Journal 26;5:50, 2011, doi: 10.1186/1752-153X-5-50. Adamson, J., Hughes,
Slide 18: Literature Cited
Literature Cited Fields, W., Maione, A., Keyser, B., Bombick, B. Characterization and Application of the VITROCELL VC1 Smoke Exposure System and 3D EpiAirway Models for Toxicological and e-Cigarette Evaluations, Applied in Vitro Toxicology, 3:2017, DOI: 10.1089/aivt.2016.0035. Fujitani, Y., Sugaya,
Slide 19: Literature Cited
Literature Cited Majeed, S., Frentzel, S., Wagner, S., Kuehn, D., Leroy, P., Guy, P.A., Knorr, A., Hoeng, J., Peitsch, M.C. Charaterizaton of the Vitrocell® 24/48 in vitro aerosol exposure system using mainstream cigarette smoke, Chemistry Central Journal 8:62, 2014 Neilson, L., Mankus, C., Thorne,
Slide 20: Literature Cited
Literature Cited Thorne, D., Kilford, J., Payne, R., Adamson, J., Scott, K., Dalrymple, A., Meredith, C., Dillon, D. Characterization of a Vitrocell® VC10 in vitro smoke exposure system using dose tools and biological analysis, Chemistry Central Journal, 7:146, 2013. Thomas, D.G., Smith, J.N., Thral
Slide 21: Thank you
Thank you Altria Client Services l M. Oldham | Draft l 2-28-18 21