Altria Group, Inc. · NYSE:MO

Altria — Technical Presentation (September 2018)

28 slides from Altria's technical presentation, Sep 18, 2018

  1. Slide 1: Structure-Activity Relationships of Propylene Glycol, Glycerin, and Select Analogs

    Structure-Activity Relationships of Propylene Glycol, Glycerin, and Select Analogs for Carbonyl Thermal Degradation Products Melvin, M.S.; Ballentine, R.M.; Gardner, W.P.; McKinney, W.J.; Smith, D.C.; Pithawalla, Y.B.; Wagner, K.A. Altria Client Services l Matt Melvin l September 18, 2018 l Final l

  2. Slide 2: Thermal Degradation of eLiquids

    Thermal Degradation of eLiquids Propylene Glycol Heat Glycerin Nicotine Flavor Systems  Propylene glycol (PG) and Glycerine (GLY) can thermally degrade upon heating - Formaldehyde, Acetaldehyde, Acrolein1,2,3 Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 2

  3. Slide 3: Carbonyls in E-Cigarettes

    Carbonyls in E-Cigarettes  Geiss et al. and Gillman et al. demonstrated that carbonyl formation increased with temperature1,4  US FDA PMTA Draft Guidance for ENDS Products recommends reporting four carbonyls in e-liquid and aerosol5 Altria Client Services l Matt Melvin l September 18, 2018 l Final

  4. Slide 4: Objectives and Approach

    Objectives and Approach  Determine the formation pathways of formaldehyde, acetaldehyde, acrolein, and crotonaldehyde: 1. Identify source of degradation products using 13C3-labeled PG and GLY 2. Determine the role of 3-hydroxypropanal (3-HPA) as an intermediate during the thermal degradation of e-l

  5. Slide 5: Microwave Model System

    Microwave Model System  Model microwave system used to generate target carbonyls CEM Discovery SP Hybrid - Previously used to identify diacetyl and acetyl propionyl formation pathways6  Microwave system evaluated for equivalent yields to e-cigarette - Sample = 50% PG : 50% GLY + 2.5 % nicotine (w/

  6. Slide 6: Analyte Yield Comparison

    Analyte Yield Comparison 140 puffs using 55 ml Puff Volume, 5 sec Puff Duration, 30 sec Puff Period; Square Wave 30 Liquid Analyte Amount (µg /g) 25 Microwave Aerosol 20 15 10 5 0 Formaldehyde Acetaldehyde Acrolien Crotonaldehyde was not detected Altria Client Services l Matt Melvin l September 18,

  7. Slide 7: Identify Source of Degradation Products Using 13C-labeled PG and GLY

    Identify Source of Degradation Products Using 13C-labeled PG and GLY Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 7

  8. Slide 8: Carbon-13 Labeled PG and GLY

    Carbon-13 Labeled PG and GLY  Samples: - 50% 13C3-PG : 50% GLY + 2.5% nicotine (w/w) - 50% PG : 50% 13C3-GLY + 2.5% nicotine (w/w) Microwave DNPH UPLC-UV- Isotope Heating* Derivatization MS/MS Distribution *500 mg of sample heated to 180 °C and held for 3 min  Labeled products directly traceable t

  9. Slide 9: Product Distribution Using 13C3-PG

    Product Distribution Using 13C3-PG 50% 13C3-PG : 50% GLY + 2.5 % Nicotine (w/w) 30 100% 13C-PG 93.2% 94.0% Percentage of Total Analyte 26.1 90% GLY 25 Concentration (µg / g) 80% 74.9% 70% 20 60% 15 50% 40% 10 25.1% 30% 4.7 20% 5 6.8% 6.0% 0.7 10% 13C 13C 13C 0 0% Crotonaldehyde was not detected Altr

  10. Slide 10: Product Distribution using 13C3-GLY

    Product Distribution using 13C3-GLY 50% PG : 50% 13C3-GLY + 2.5 % Nicotine (w/w) 100% PG 95.3% 13C-GLY 87.6% 90% Percentage of Total 80% 77.3% 70% Analyte 60% 50% 40% 30% 22.7% 20% 12.4% 13C 10% 13C 13C 4.7% 0% Formaldehyde Acetaldehyde Acrolein Crotonaldehyde was not detected Altria Client Services

  11. Slide 11: Summary: 13C-Labeling Studies

    Summary: 13C-Labeling Studies  Formaldehyde was predominantly formed from GLY  Acetaldehyde and acrolein were predominantly formed from PG  Crotonaldehyde was not detected Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 11

  12. Slide 12: Determine the Role of 3-hydroxypropanal (3-HPA) as an Intermediate

    Determine the Role of 3-hydroxypropanal (3-HPA) as an Intermediate During the Thermal Degradation of e-Liquids Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 12

  13. Slide 13: 3-Hydroxypropanal Background

    3-Hydroxypropanal Background  Researchers proposed formaldehyde and acetaldehyde are produced from the retro-aldol condensation of 3-hydroxypropanal (3-HPA)4,7 Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 13

  14. Slide 14: 3-HPA Fortification Studies

    3-HPA Fortification Studies 500 mg e-liquid 50% PG : 50% GLY + 2.5 % nicotine (w/w) Fortify samples with 3-HPA at 3 levels (300, 700, 1500 µg) Microwave Heating: 180 °C for 3 min DNPH Derivatization UPLC-UV-MS/MS Analysis Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018

  15. Slide 15: Results: 3-HPA Fortification

    Results: 3-HPA Fortification (N=3) 50% PG : 50% GLY + 2.5 % Nicotine (w/w) Formaldehyde Acetaldehyde Acrolein 600 Analyte Amount (µg / g) 500 400 300 200 100 0 Unfortified 350 700 1400 3-HPA Fortification (µg) Acrolein Yield ~ 30% Altria Client Services l Matt Melvin l September 18, 2018 l Final l T

  16. Slide 16: Summary: 3-Hydroxypropanal (3-HPA)

    Summary: 3-Hydroxypropanal (3-HPA)  Unfortified e-liquids - 3-HPA, acrolein, and crotonaldehyde were not detected  E-liquids fortified with 3-HPA - Crotonaldehyde was not detected - No increase in formaldehyde and acetaldehyde - 3-HPA converted to acrolein with ~30 % yield  The retro-aldol conden

  17. Slide 17: Suggested Formation Pathways in Aerosol

    Suggested Formation Pathways in Aerosol 3-HPA was not detected  Formaldehyde from Glycerin  Acetaldehyde from Propylene Glycol  Acetaldehyde from Propylene Glycol Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 17

  18. Slide 18: Determine Key Reaction Centers Using Rationally Selected Derivatives of PG and GLY

    Determine Key Reaction Centers Using Rationally Selected Derivatives of PG and GLY Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 18

  19. Slide 19: Experimental: Evaluation of Derivatives

    Experimental: Evaluation of Derivatives  Derivatives: - Methoxy derivatives selected to reduce autoxidation efficiency - Methyl derivatives selected to reduce dehydration efficiency  Samples: - 50% PG : 50% GLY-Deriv + 2.5 % nicotine (w/w) -> Formaldehyde - 50% PG-Deriv : 50% GLY + 2.5 % nicotine

  20. Slide 20: GLY Derivatives: Formaldehyde

    GLY Derivatives: Formaldehyde Methoxy Derivatives Methyl Derivatives Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 20

  21. Slide 21: Formaldehyde: GLY Derivatives

    Formaldehyde: GLY Derivatives Results support proposed mechanism 50 Methoxy Derivatives Formaldehyde (µg / g) Methyl Derivatives 40 30 20 10 0 Control Control D E G F H N O P R Q Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 21

  22. Slide 22: PG Derivatives: Acetaldehyde and Acrolein

    PG Derivatives: Acetaldehyde and Acrolein Methoxy Derivatives Methyl Derivatives Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 22

  23. Slide 23: Acetaldehyde: PG Derivatives

    Acetaldehyde: PG Derivatives Results do not support proposed mechanism Methoxy Derivatives Methyl Derivatives Acetaldehyde (µg / g) 40 30 20 10 0 Control Control A B C I M J K L Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 23

  24. Slide 24: Acrolein: PG Derivatives

    Acrolein: PG Derivatives Results support proposed mechanism Methoxy Derivatives 0.40 Methyl Derivatives Acrolein (µg / g) 0.30 0.20 0.10 0.00 Control Control A B C I M J K L Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 24

  25. Slide 25: Summary: Methoxy and Methyl Derivatives

    Summary: Methoxy and Methyl Derivatives  Formaldehyde: GLY Derivatives - Substitution reduced formaldehyde generation - Consistent with proposed pathway  Acetaldehyde: PG Derivatives - Substitution increased acetaldehyde production - Not consistent with proposed pathway - Under further investigati

  26. Slide 26: Conclusions

    Conclusions  Formaldehyde derived primarily from glycerin  Acetaldehyde and acrolein derived primarily from propylene glycol  3-hydroxypropanal pathway has negligible contribution to formaldehyde and acetaldehyde generation  Proposed pathways for formaldehyde and acrolein are consistent with exp

  27. Slide 27: References

    References: 1. Geiss, O., Bianchi, I., and Barrero-Moreno, J. (2016) Correlation of volatile carbonyl yields emitted by e-cigarettes with the temperature of the heating coil and the perceived sensorial quality of the generated vapours. Int J Hyg Environ Health 219, 268-277. 2. Farsalinos, K. E., and

  28. Slide 28: Further data and details: www.altria.com/ALCS-Science

     Further data and details: www.altria.com/ALCS-Science Altria Client Services l Matt Melvin l September 18, 2018 l Final l TSRC 2018 #87 l 28

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