Altria Group, Inc. · NYSE:MO
Altria — 2018 CORESTA
22 slides from Altria's conference presentation, Oct 24, 2018
Slide 1: A Framework for Toxicological Risk Assessment of Combustible Tobacco Products
A Framework for Toxicological Risk Assessment of Combustible Tobacco Products in the Substantial Equivalence Pathway Kimberly Ehman, PhD, DABT October 24, 2018 Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 1
Slide 2: Objective and Overview
Objective and Overview Objective: - To provide an overview of a toxicological risk assessment approach that applies to evaluation of combustible products to demonstrate that a New Product is substantially equivalent Overview: - Types of product-specific questions that trigger risk assessment in
Slide 3: Risk = Hazard x Exposure
Risk = Hazard x Exposure Hazard ≠ Risk Need to understand exposure Source: Bayer/ECPA Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 3
Slide 4: Applicability of Risk Assessment in the Substantial Equivalence Pathway
Applicability of Risk Assessment in the Substantial Equivalence Pathway Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 4
Slide 5: Applicability of Risk Assessment in the Substantial Equivalence Pathway
Applicability of Risk Assessment in the Substantial Equivalence Pathway Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 5
Slide 6: Applicability of Risk Assessment in the Substantial Equivalence Pathway
Applicability of Risk Assessment in the Substantial Equivalence Pathway Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 6
Slide 7: Exposure Assumptions are Conservative
Exposure Assumptions are Conservative Added or Increased Ingredients or Potential Pyrolysis Product-Specific HPHCs Products • Assume 40 cigarettes/daya • Assume 40 cigarettes/daya • 14.1 cigarettes/day is current CDC estimateb • 14.1 cigarettes/day is current CDC estimateb • Assume 5 cigars/dayc • A
Slide 8: Exposure Assumptions are Conservative
Exposure Assumptions are Conservative Added or Increased Ingredients or Potential Pyrolysis Product-Specific HPHCs Products • Assume 40 cigarettes/daya • Assume 40 cigarettes/daya • 14.1 cigarettes/day is current CDC estimateb • 14.1 cigarettes/day is current CDC estimateb • Assume 5 cigars/dayc • A
Slide 9: Risk Characterization
Risk Characterization Integration of hazard assessment, dose-response data and exposure assessment to determine likelihood that an identified chemical is going to introduce risk into the exposed population Identification of acceptable daily exposures - Literature search (e.g., IRIS, NTP, ECHA, O
Slide 10: Risk Characterization – Overview of Process
Risk Characterization – Overview of Process Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 10
Slide 11: Risk Characterization – Application of Health-Based OELs
Risk Characterization – Application of Health-Based OELs Risk assessments performed by external organizations that take into account all available toxicological, medical, biological and chemical information Not based on economic or technical feasibility Specific to the inhalation route of expo
Slide 12: Risk Characterization – OELs Provide a Conservative Comparison
Risk Characterization – OELs Provide a Conservative Comparison OEL: Assume 50 wks/year Cumulative Lifetime Exposure 80,000 Smoking: Assume 40 60,000 cigarettes/day, 5 min/cigarette, 7 40,000 OEL days/wk, 52 wks/yr for 60 yrs 20,000 Cigarette 0 Smoking Potential Exposure (hours) Altria Client Service
Slide 13: TTC Overview: Two Categories
TTC Overview: Two Categories Non-genotoxic chemicals - TTCs based on frequency distributions (5th percentile) of NOEL or NOAEL divided by an uncertainty factor of 100 (Kroes et al., 2000, 2004) - Cramer Classes: Class I: 1800 µg/day Class II: 540 µg/day Class III: 90 µg/day Genotoxic chemi
Slide 14: Risk Characterization – Application of an Inhalation TTC
Risk Characterization – Application of an Inhalation TTC TTC is a risk assessment tool based on the principle of establishing a human exposure threshold below which there is a very low probability of appreciable risk to human health (Kroes et al., 2000 and 2004) 1.5 µg/day is used across regulat
Slide 15: Risk Characterization – Application of an Inhalation TTC
Risk Characterization – Application of an Inhalation TTC Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 15
Slide 16: Case Studies
Case Studies Example 1 - Multiple compounds Product-specific question related to components of an adhesive added to the New Product Applied conservative exposure assumptions Compared to TTC of 1.5 µg/day Example 2 - Propylene Oxide Product-specific question related to potential pyrolysis
Slide 17: Example 1 - Application of TTC
Example 1 - Application of TTC Specific questions related to components of an adhesive in a New Product Chemical Weight in Product Estimated Daily Exposure (mg/product) (µg/day)a Estimated Daily Exposure (µg/day) (benzyloxy)methanol 0.00002 0.16 = mg/product x 1000 µg/mg x 40 cigarettes/day x 20%
Slide 18: Product-Specific HPHC Data
Product-Specific HPHC Data aHypothetical data not representative of an actual product HPHC data are reviewed in conjunction with analytical variability information (e.g., reproducibility and repeatability for the smoke constituent), literature, and reference cigarette data to determine if values a
Slide 19: Example 2: Propylene Oxide - Application of Health-Based OEL
Example 2: Propylene Oxide - Application of Health-Based OEL Potential daily exposure to Propylene Oxide - New product (2.69 µg/cigarette x 40 cigarettes = 107.6 µg/day) - Predicate product (2.02 µg/day x 40 cigarettes = 80.8 µg/day) OEL = 4.8𝑚𝑚𝑔 3 - Equal to 48 mg/day (convert using 10 m3…
Slide 20: Considerations with Product-Specific HPHC Data
Considerations with Product-Specific HPHC Data Variability - Analytical and manufacturing - Cigar variability is expected to be even greater than cigarettes HPHC difference should not be attributed to a change in a single ingredient - Predicate Product versus New Product comparisons are not desi
Slide 21: Key Takeaways
Key Takeaways Combustible tobacco products are inherently toxic Ingredient studies in the literature demonstrate that ingredients do not significantly impact the chemical or toxicological nature of smoke Standard toxicological approaches are appropriate to evaluate product- specific questions,
Slide 22: For copies of this presentation visit the Altria's Science Website
For copies of this presentation visit the Altria’s Science Website at www.altria.com/alcs-science Altria Client Services l Kimberly Ehman l October 24, 2018 l 2018 CORESTA l 22