Altria Group, Inc. · NYSE:MO
Altria — Juul Labs — Technical Presentation (2021)
11 slides from Altria's technical presentation, 2021
Slide 1: In Vivo Genotoxicity Testing of Aerosols Generated from Commercial JUUL ENDS Products
Presentation ST 50 Abstract ID 1951 In Vivo Genotoxicity Testing of Aerosols Generated from Commercial JUUL ENDS Products Guy Lalonde1, Sridhar Jaligama2, Amit Gupta2, Monica Lee3, Utkarsh Doshi3, Jenny Yao1, Jingjie Zhang3 1 JUUL Labs Inc., San Francisco, CA, USA 2 Battelle Memorial Institute, West
Slide 2: Background and Rationale
Presentation ST 50 Abstract ID 1951 Background and Rationale • JUUL ENDS products J1and J2 were found to be positive and equivocal, respectively, for the induction of micronucleated cells in the in vitro micronucleus (MN) assay using the TK6 cell line. • The ICHS2(R1) recommends an in vivo genotoxic
Slide 3: Outline of In Vivo Genotoxicity Study
Presentation ST 50 Abstract ID 1951 Outline of In Vivo Genotoxicity Study • Aerosols generated from J1and J2 were administered to male Sprague Dawley (SD) rats by nose-only inhalation for 4 consecutive days and up to 6 hours/ day. • Negative control group received filtered air for the same exposure
Slide 4: Experimental Design
Presentation ST 50 Abstract ID 1951 Experimental Design Nicotine Tota l Pa rticula te Ma ss Group Ta rget Exposure Number of Group Description Concentra tion in Ta rget Exposure Number Dura tion a (hr) Ma le Ra ts E-liquid (%w/ w) Concentra tion (µg/ L) 1 Filtered Air Not Applicable 6 0 5 2 J1-Low 3
Slide 5: Aerosol Characterization
Presentation ST 50 Abstract ID 1951 Aerosol Characterization Propylene Tota l Pa rticula te Ma ss (TPM) Tempora l Nicotine Glycol (PG) PSDc Exposure Concentra tions Sta bility Conc. Conc. Test Article [Group # (s)] Mea sured Mea n Ta rget % of Mea n Mea n ± SD Mea n ± SD Mea n a N a MMADc (µm) (µg/
Slide 6: Systemic Exposure: Plasma Concentrations of Nicotine, Cotinine and Propylene Glycol (PG)
Presentation ST 50 Abstract ID 1951 Systemic Exposure: Plasma Concentrations of Nicotine, Cotinine and Propylene Glycol (PG) Nicotine Cotinine PG Ta rget Exposure Ta rget Exposure Group Concentra tion (ng/ mL) (ng/ mL) (ng/ mL) Dura tion a (hr) (µg/ L) Mea n ± SD Mea n ± SD Mea n ± SD Filtered Air 0
Slide 7: Comet Assay Procedure
Presentation ST 50 Abstract ID 1951 Comet Assay Procedure • Four hours after end of dosing, 5 rats/ group were euthanized with CO2/ O2, exsanguinated and nasal, lung and liver tissues harvested. • Tissues were minced (in cold HBSS with EDTA and DMSO) to release cells and sieved through a cell strain
Slide 8: Comet Assay Results: No Evidence of DNA Damage in J1 and J2 Aerosol Treated Animals
Presentation ST 50 Abstract ID 1951 Comet Assay Results: No Evidence of DNA Damage in J1 and J2 Aerosol Treated Animals Lung Liver Na sa l Group (% Ta il DNA) (% Ta il DNA) (% Ta il DNA) Filtered Air 0.64 ± 0.25a 1.59 ± 1.08 0.92 ± 0.24 J1 (6 hr/ day) 0.81± 0.22 2.24 ± 2.39 1.17 ± 0.50 J2 (6 hr/ day
Slide 9: Micronucleus Assay Procedure
Presentation ST 50 Abstract ID 1951 Micronucleus Assay Procedure • Four hours after end of dosing, 5 rats/ group were euthanized with CO2/ O2 and femoral bone marrow was harvested and smear slides prepared. • Slides were stained with Acridine Orange for 1-2 minutes and rinsed in PBS. Slides were sco
Slide 10: Micronucleus Assay Results: No Evidence of Increased Micronucleation in J1 and J2 Aerosol Treated Animals
Presentation ST 50 Abstract ID 1951 Micronucleus Assay Results: No Evidence of Increased Micronucleation in J1 and J2 Aerosol Treated Animals Group % PCEc % MNPCEc Filtered Air 53.6 ± 1.9a 0.08 ± 0.05 J1 (6 hr/ day) 54.4 ± 3.6 0.08 ± 0.06 J2 (6 hr/ day) 55.8 ± 4.6 0.08 ± 0.02 Positive Controlb 52.7
Slide 11: Summary and Conclusion
Presentation ST 50 Abstract ID 1951 Summary and Conclusion • The inhalation exposure data demonstrated that test article exposure concentrations observed at the nose port were concordant with targeted total particulate concentrations for both J1and J2 exposure systems. • Adequate systemic exposure w