Altria Group, Inc. · NYSE:MO
Altria — Technical Presentation (September 2019)
14 slides from Altria's technical presentation, Sep 17, 2019
Slide 1: Preclinical Testing of Flavors in E-vapor Products, Part 1
Preclinical Testing of Flavors in E- vapor Products, Part 1: Selection of Representative Flavor Mixtures for Toxicological Evaluations using a Structural Grouping Approach Kimberly Ehman Tobacco Science Research Conference September 17, 2019 Kimberly Ehman l Regulatory Affairs l Altria Client Servic
Slide 2: Overview of Session
Overview of Session ▪ Part 1: Selection of Representative Flavor Mixtures Using a Structural Grouping Approach (Kim Ehman) ▪ Part 2: Preparation and Stability Characterization of Representative Flavor Mixtures (Cameron Smith) ▪ Part 3: In Vitro Cytotoxicity and Genotoxicity of Representative Flavor
Slide 3: Preclinical Testing of Flavors in E-vapor Products: Overview
Preclinical Testing of Flavors in E-vapor Products: Overview Preclinical Application In-vitro Flavors 200-300 Flavors In-vivo exposure Kimberly Ehman l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final
Slide 4: Approach Rationale
Approach Rationale ▪ Evaluate structural similarities to develop a representative test formulation for preclinical toxicity testing ▪ Limitations in toxicological review and testing: - Food grade and GRAS (Generally Recognized as Safe) for use in food - Ingredient-specific inhalation data ▪ Not alwa
Slide 5: Overview of Flavor Selection Approach
Overview of Flavor Selection Approach Kimberly Ehman l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 5
Slide 6: Overview of Flavor Selection Approach
Overview of Flavor Selection Approach Kimberly Ehman l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 6
Slide 7: Structural Groupings (EC Reg No. 1565/2000)
Structural Groupings (EC Reg No. 1565/2000) Our approach: • Instead of 1 representative for Group 1 and 1 representative for Group 2, the groups were combined and 5 representatives were selected to better represent the broad category Kimberly Ehman l Regulatory Affairs l Altria Client Services l TSR
Slide 8: Example of Structural Groupings
Example of Structural Groupings Group Representative Flavor EC Groups: Group 1 (straight-chain) and Group 2 (branched-chain) 1 Acetal Acetals 1-2a Isobutyraldehyde Aldehydes 1-2b Isoamyl alcohol Alcohols 1-2c 2-Methylbutyric acid Acids 1-2d Ethyl 2-methylbutyrate Esters Flavors within a given chemic
Slide 9: Overview of Flavor Selection Approach
Overview of Flavor Selection Approach Kimberly Ehman l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 9
Slide 10: Toxicological Review for Each Flavor
Toxicological Review for Each Flavor ▪ Conducted comprehensive literature search for each flavor - Selected reliable experimental studies, for example: ▪ Acute toxicity ▪ Repeated dose toxicity ▪ In vitro and in vivo genotoxicity ▪ Developmental/reproductive toxicity ▪ Irritation/sensitization ▪ Car
Slide 11: Selection of Flavor Group Representative
Selection of Flavor Group Representative ▪ Considered both experimental and predicted data - Gaps in experimental data created difficultly for comparison among compounds within a group - Predicted data provided a consistent comparison ▪ “Worst-case” could be approximate ▪ Endpoints were assigned a n
Slide 12: Attributes for Selection of Flavor Group Representative
Attributes for Selection of Flavor Group Representative Example: Aliphatic and Aromatic Hydrocarbons Chronic Avg. Final LD50 DevTox ToxPi™ Irritation Name LOAEL group group rank rank ranka rank rank rank rank Experimental Predicted Predicted Predicted Predicted Alpha-pinene 1 2.5 4 1 2 2.1 1 Beta-ca
Slide 13: Summary
Summary ▪ Approach creates a representative mixture for preclinical testing to support >200 flavors - Reduces time needed to generate data on a large number of individual flavors - Reduces animal testing - Supports read-across strategies for inclusion of future flavors ▪ Limitations of approach - Us
Slide 14: Acknowledgements
Acknowledgements Altria Client Services, Richmond, Virginia, USA Timothy B. Langston Ashutosh Kumar K. Monica Lee PMI R&D, Neuchâtel, Switzerland Davide Sciuscio Patrick Vanscheeuwijck Julia Hoeng Kimberly Ehman l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 14
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