1. Review of Ingredients Added to Cigarettes
Overview
Kara Lewis, Ph.D.
Staff Scientist
What I’d like to do is to provide an overview of the review of ingredients added to cigarettes.
The next speaker, Paula Nixon, will describe the second phase of the project : Scientific criteria, in more detail.
Please hold any questions until after both talks are done.

2. Introduction
Epidemiology shows that cigarette smoking associates with premature human mortality
Effect of added ingredients is unknown
A number of epidemiological studies have shown an association between cigarette smoking and premature human mortality.
Whether ingredients that are added to cigarettes contribute to the premature mortality associated with cigarette smoking is unknown

3. Definition of Added Ingredient
A substance other than tobacco that is added
to a cigarette
A cigarette is defined as tobacco wrapped in paper.
An added ingredient is a substance other than tobacco that is added to the cigarette
We are starting with ingredients currently added to cigarettes.
These were disclosed in the 599 list and include flavorants, casings and humectants.

4. LSRO Approach Assess relative risk of adverse health effects
Our approach to assessing the contribution of added ingredients to premature mortality is based on relative risk.

5. Relative Risk Risk (+) ingredient Risk (-) ingredient
Absolute risk is defined as an increased probability of an adverse outcome due to exposure to a defined substance.
To calculate relative risk, the absolute risk of one substance is divided by the absolute risk of another.
Manufacturers can make experimental cigarettes that are similar except for the presence and absence of a particular ingredient
We will compare the relative risk of adverse health effects from smoking similar cigarettes with and without the added ingredient.
If no difference in absolute risk exists between two substances, the relative risk would be 1.0.

6. LSRO approach Expert Panel
Robert Orth, Ph.D.
Apis Discoveries, LLC.
Resha M. Putzrath, Ph.D., D.A.B.T. (Retired)
Georgetown Risk Group
 Emanuel Rubin, M.D.
Department of Pathology, Anatomy, and Cell Biology
Thomas Jefferson University
James L. Schardein, M.Sc., F.A.T.S.
Independent consultant
Thomas J. Slaga, Ph.D.
AMC Cancer Research Center and
Center for Causation and Prevention
Carroll E. Cross, M.D.
Division of Pulmonary and Critical Care Medicine
University of California, School of Medicine
Shayne C. Gad, Ph.D., D.A.B.T.
Gad Consulting Services
Donald E. Gardner, Ph.D., F.A.T.S.
Inhalation Toxicology Associates
Louis D. Homer, M.D., Ph.D.
Holladay Park Medical Center
Rudolph J. Jaeger, Ph.D., D.A.B.T.
Environmental Medicine, Inc.
We began by assembling an advisory committee with relevant, diverse backgrounds from fields such as pulmonary medicine, toxicology, and pathology.
To date, LSRO staff and the advisory committee have :
met 11 times to discuss structure and content of the report, reviewed over 3,000 publications, and received 21 scientific presentations

7. LSRO Approach Convened 11 times to date
Reviewed more than 3000 publications
Worldwide literature
Clinical studies
Government reports
Books
Received 21 scientific presentations

8. Project Structure Phase I: Determination of Feasibility
Phase II: Development of Scientific Criteria
Phase III: Reviews of Individual Ingredients
The project has been organized into 3 phases:
Phase I: Determination of Feasibility
Phase II: Development of Scientific Criteria to apply to review of added ingredients
Phase III: Reviews of Individual Ingredients

9. Phase I - Feasibility Determined whether testing ingredients
added to cigarettes is feasible
Reviewed published literature covering
Smoke chemistry and physics
Exposure
Adverse health effects
Issues and methods in testing
The ojective of phase I of the review was to determine whether testing ingredients added to cigarettes is feasible.
We reviewed published literature covering:
Smoke chemistry and physics
Smoker’s exposure to cigarette smoke
Adverse health effects associated with smoking cigarettes
Issues and methods in testing

10. Phase I - Conclusions Testing is feasible and worthwhile.
Publication of the Phase I report is imminent.
Based on the review of the literature, LSRO has concluded that testing is feasible and worthwhile.
The Phase I report will be available later in the year

11. Phase II – Scientific Criteria
Framework to guide the process of testing ingredients added to cigarettes
Development of Scientific Criteria- Phase II of the project is currently underway.
In Phase II of the report, we are developing a Framework to guide the process of testing ingredients added to cigarettes.
Our objective is to provide sufficient information so that adequate data is supplied for review

12. Phase III - Reviews of Individual Ingredients
Use the criteria developed in Phase II
Process:
Literature review
Data analysis
Use criteria developed in Phase II of the project to conduct case-by case reviews of ingredients.
Process is likely to involve
Literature review
Data analysis

13. Summary Compare cigarettes with and without added ingredients
This approach is feasible
Phase II is underway
In summary, we will be com
and will be discussed in more detail
By Paula Nixon