Public Health
Consequences of
E-Cigarettes

Committee on the Review of the Health Effects of
Electronic Nicotine Delivery Systems

Kathleen Stratton, Leslie Y. Kwan, and David L. Eaton, Editors

Board on Population Health and Public Health Practice

Health and Medicine Division

A Consensus Study Report of

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

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This activity was supported by Contract No. HHSF223201610054C between the National Academy of Sciences and the U.S. Department of Health and Human Services: Food and Drug Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-46834-3
International Standard Book Number-10: 0-309-46834-5
Digital Object Identifier: https://doi.org/10.17226/24952
Library of Congress Control Number: 2018932760

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Public health consequences of e-cigarettes. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24952.

COMMITTEE ON THE REVIEW OF THE HEALTH EFFECTS OF ELECTRONIC NICOTINE DELIVERY SYSTEMS

DAVID L. EATON (Chair), Dean and Vice Provost, Graduate School, University of Washington

ANTHONY J. ALBERG, Professor and Chair, Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina

MACIEJ GONIEWICZ, Associate Professor of Oncology, Roswell Park Comprehensive Cancer Center

ADAM LEVENTHAL, Director, USC Health, Emotion, & Addiction Laboratory, Professor of Preventive Medicine and Psychology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California

JOSÉ E. MANAUTOU, Professor of Pharmacology & Toxicology, Interim Head, Department of Pharmaceutical Sciences, University of Connecticut

SHARON McGRATH-MORROW, Professor, Department of Pediatrics, Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine

DAVID MENDEZ, Associate Professor, Health Management and Policy, University of Michigan

RICHARD MIECH, Research Professor, Department of Youth and Social Issues, University of Michigan

ANA NAVAS-ACIEN, Professor, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University

KENT E. PINKERTON, Professor and Director, Center for Health and the Environment, Department of Anatomy, Physiology, and Cell Biology, University of California, Davis

NANCY A. RIGOTTI, Professor of Medicine, Harvard Medical School; Director, Tobacco Research and Treatment Center; Associate Chief, Division of General Internal Medicine, Massachusetts General Hospital

DAVID A. SAVITZ, Professor of Epidemiology, School of Public Health, Professor of Obstetrics and Gynecology and Pediatrics, Warren Alpert Medical School, Brown University

GIDEON St.HELEN, Assistant Professor of Medicine, Division of Clinical Pharmacology, Department of Medicine, University of California, San Francisco

Study Staff

KATHLEEN STRATTON, Study Director

LESLIE Y. KWAN, Associate Program Officer

AIMEE MEAD, Research Associate (from July 2017)

ALEXIS WOJTOWICZ, Senior Program Assistant

JORGE MENDOZA-TORRES, Senior Research Librarian

REBECCA MORGAN, Senior Research Librarian

DORIS ROMERO, Financial Associate (until March 2017)

MISRAK DABI, Financial Associate (from April 2017)

HOPE HARE, Administrative Assistant

ROSE MARIE MARTINEZ, Senior Director, Board on Population Health and Public Health Practice

Christine Mirzayan Science and Technology Policy Graduate Fellow

ANDREW MERLUZZI, Ph.D. Candidate at the University of Wisconsin–Madison (until April 2017)

Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

RAFAEL MEZA, University of Michigan

MEIR STAMPFER, Harvard Medical School and Harvard T.H. Chan School of Public Health

THOMAS A. WILLS, University of Hawaii Cancer Center

JUDITH T. ZELIKOFF, New York University School of Medicine

SHU-HONG ZHU, University of California, San Diego

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by ERIC B. LARSON, Kaiser Permanente Washington Health Research Institute, and HUDA AKIL, University of Michigan. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Preface

On May 10, 2016, the Food and Drug Administration (FDA) issued a rule to extend regulatory authority to all tobacco products, including e-cigarettes, that meet the statutory definition of a tobacco product. This so-called “Deeming Regulation” allows FDA to regulate the manufacturing, distribution, and marketing of tobacco products such as e-cigarettes and includes automatic provisions such as youth access restrictions on sales. Although various forms of battery-powered “electronic nicotine delivery systems” (ENDS) devices have existed for more than a decade, their popularity, especially among youth, has increased in the past 5 years, although most recent data show a slight decline. In contrast to combustible tobacco cigarettes, e-cigarettes do not “burn,” and do not contain most of the estimated 7,000 chemical constituents present in tobacco smoke. Thus, it is generally believed that e-cigarettes are “safer” than combustible tobacco cigarettes, yet exposures to nicotine and a variety of other potentially harmful constituents do occur. Harm might also occur if youth who begin their “tobacco” use with e-cigarettes then transition to combustible tobacco cigarettes or if adult cigarette smokers use e-cigarettes to supplement their smoking, rather than quitting combustible tobacco cigarettes completely.

In order to inform the public about the consequences of e-cigarettes and in support of future FDA and congressional action, a thorough and objective analysis of the state of scientific evidence relating to e-cigarettes and public health is needed. To that end, the ENDS Committee was established in December 2016 under the National Academies of Sciences, Engineering, and Medicine, with an ambitious timeline to complete a

review of the science that can inform the understanding of public health risks and benefits of e-cigarettes. What are the short- and long-term health risks of regular use of e-cigarettes? What variables of the numerous types of devices and use patterns are important determinants of risk? Are e-cigarettes an effective means to quit smoking combustible tobacco cigarettes? Are e-cigarettes an “initiation pathway” of youth to smoking combustible tobacco cigarettes? These are just some of the important questions addressed by the committee in this report. Where feasible, the committee applied the most important attributes of systematic review methodology to the scientific literature to establish the strength of evidence surrounding the health risks (e.g., direct harmful effects, initiation of smoking) and benefits (e.g., smoking cessation) associated with e-cigarette use. Although the use of these products is relatively new, the committee identified more than 800 peer-reviewed scientific studies in this report. Based on this review, the committee has provided a summary of the current state of knowledge about the health risks and benefits of e-cigarette use, and has provided a series of research recommendations.

I am deeply gratified by the remarkable hard work and insights provided by my fellow committee members and indebted to the tireless and thoughtful work of the National Academies staff that so ably kept us on task throughout the duration of this study.

David L. Eaton, Chair
Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems

Contents

SUMMARY

SUMMARY ANNEX

1 INTRODUCTION

Statement of Task

A Note on Terminology: What Are E-Cigarettes?

The Rapid Rise of E-Cigarette Use in the United States

Potential Public Health Risks and Benefits of E-Cigarettes

Regulatory Background

Outline of the Report

References

2 COMMITTEE APPROACH

Literature Search

Literature Review and Quality Assessment

Approach to Assessing Causality

Conclusions

References

SECTION I: E-CIGARETTE DEVICES, CONSTITUENTS, AND EXPOSURES

3 E-CIGARETTE DEVICES, USES, AND EXPOSURES

Characteristics of E-Cigarette Devices

E-Cigarette Use

Exposure to Aerosols and Particulates

Secondhand Exposure to E-Cigarette Aerosol

References

4 NICOTINE

Concentration of Nicotine in Commercial E-Cigarettes

Nicotine Concentration in E-Cigarette Emissions

pH of E-Liquids

Nicotine Salts

Toxicology and Modes of Action

Exposure to Nicotine and Nicotine Derivatives from E-Cigarettes

Relationship Between E-Cigarette Topography and Nicotine Exposure

Synthesis

References

5 TOXICOLOGY OF E-CIGARETTE CONSTITUENTS

Humectants (Delivery Solvents)

Flavorings

Carbonyl Compounds

Minor Tobacco Alkaloids

Tobacco-Specific Nitrosamines

Free Radicals and Reactive Oxygen Species

Other Toxicants

Synthesis

Metals

References

6 RESEARCH NEEDS: E-CIGARETTE DEVICES, CONSTITUENTS, AND EXPOSURES

Addressing Gaps in Substantive Knowledge

Improving Research Methods and Quality

Reference

SECTION II: EFFECTS OF E-CIGARETTES ON HEALTH

7 MODES OF ACTION

Endothelial Cell Dysfunction

Oxidative Stress

Conclusions

References

8 DEPENDENCE AND ABUSE LIABILITY

Characterization of Disease Endpoints and Intermediate Outcomes

Optimal Study Design

Questions Addressed by the Literature

Epidemiology

Human Laboratory Studies

Conclusions

References

9 CARDIOVASCULAR DISEASE

Characterization of Disease Endpoints and Intermediate Outcomes

Human Evidence from Studies of Cardiovascular Effects

Conclusions

References

10 CANCERS

Characterization of Disease Endpoints and Intermediate Outcomes

Optimal Study Design

Epidemiology

Case Reports and Other Clinical Studies

In Vivo Animal Studies

Studies of Effects of Major Components of E-Cigarettes on Cancer Outcomes

Vulnerable/Susceptible Populations

Synthesis

References

11 RESPIRATORY DISEASES

Characterization of Disease Endpoints and Intermediate Outcomes

Optimal Study Design

Questions Addressed by the Literature

Clinical and Epidemiological Studies in Humans

In Vivo Animal Studies and In Vitro Mechanistic Studies

Synthesis and Conclusions

Vulnerable/Susceptible Populations

References

12 ORAL DISEASES

Characterization of Disease Endpoints and Intermediate Outcomes

Optimal Study Design

Questions Addressed by the Literature

Studies in Humans (Clinical and Epidemiological)

In Vitro Studies

Synthesis

References

13 DEVELOPMENTAL AND REPRODUCTIVE EFFECTS

Characterization of Disease Endpoints and Intermediate Outcomes

Optimal Study Design

Questions Addressed by the Literature

Epidemiology

Case Reports and Other Clinical Studies

In Vivo Animal and In Vitro/Mechanistic Studies

Studies on Combustible Tobacco and Nicotine

Synthesis

References

14 INJURIES AND POISONINGS

Burns and Explosions

Intentional and Unintentional Exposure to E-Liquid

References

15 RESEARCH NEEDS: EFFECTS OF E-CIGARETTES ON HEALTH

Addressing Gaps in Substantive Knowledge

Improving Research Methods and Quality

Reference

SECTION III: PUBLIC HEALTH IMPLICATIONS OF E-CIGARETTES

16 COMBUSTIBLE TOBACCO CIGARETTE SMOKING AMONG YOUTH AND YOUNG ADULTS

Conceptual Framework: Patterns of Use Among Youth and Young Adults

Evidence Review: Levels of Evidence Available

Evidence Review: Methods

Evidence Review: Results

Synthesis

References

17 SMOKING CESSATION AMONG ADULTS

Conceptual Framework: Patterns of E-Cigarette Use Among Established Smokers

Evidence Review: Levels of Evidence Available

Evidence Review: Methods

Evidence Review: Results

Synthesis

Conclusions

References

18 HARM REDUCTION

Evidence Review: Levels of Evidence Available

Evidence Review: Methods

Evidence Review: Results

References

19 MODELING OF E-CIGARETTE USE

Model

Modeling Assumptions

Simulation Scenarios

Results

Summary

References

20 RESEARCH NEEDS: PUBLIC HEALTH IMPLICATIONS OF E-CIGARETTES

Addressing Gaps in Substantive Knowledge

Improving Research Methods and Quality

Reference

21 CONCLUDING OBSERVATIONS

References

APPENDIXES

A Questions from the Center for Tobacco Products of the Food and Drug Administration Submitted for the Committee’s Consideration

B Search Strategy and Quality Assessment

C Glossary of Terms Related to E-Cigarettes

D Cytotoxicity Tables

E Public Meeting Agenda

F Committee Biosketches

Boxes, Figures, and Tables

BOXES

S-1 Statement of Task

S-2 Levels of Evidence Framework for Conclusions

S-3 Research Needs: E-Cigarette Devices, Constituents, and Exposures

S-4 Research Needs: Effects of E-Cigarettes on Human Health

S-5 Research Recommendations: Public Health Implications of E-Cigarettes

1-1 Statement of Task

1-2 Major Provisions of the Food and Drug Administration Deeming Tobacco Products to Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act

2-1 Levels of Evidence Framework for Conclusions

8-1 Criteria for Tobacco Use Disorder from the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th Edition

B-1A Search Strategy for E-Cigarettes in Human Populations

B-1B Search Strategy for E-Cigarettes in In Vivo Animal Populations

B-1C Search Strategy for E-Cigarettes in In Vitro Populations

B-1D Search Syntax for E-Cigarettes with No Population Limits, Excluding Results from Earlier Searches (Boxes B-1A, B-1B, B-1C)

B-1E Search Syntax for E-Cigarettes and Dermal and Ingestion Exposure

B-1F Search Syntax for E-Cigarettes with No Limit on Population or Publication, Excluding Results from Prior Searches (Boxes B-1A, B-1B, B-1C, B-1D, B-1E)

B-2 Inclusion Criteria for the Literature Review on the Health Effects of E-Cigarettes

B-3 Search Syntax for E-Cigarettes and Dependence

B-4 Search Syntax for E-Cigarettes and Combustible Tobacco Cigarette Smoking Initiation

B-5 Search Syntax for Systematic Reviews and Meta-Analyses on E-Cigarettes and Combustible Tobacco Cigarette Smoking Cessation

B-6 Search Syntax for Original Studies on E-Cigarettes and Smoking Cessation

B-7 Search Syntax for E-Cigarettes and Combustible Tobacco Cigarette Smoking Reduction

FIGURES

2-1 General and simplified conceptual framework of potential causal pathways by which e-cigarettes could affect health

3-1 First-, second-, and third-generation e-cigarette devices

3-2 Mass frequency and cumulative mass distributions derived from impactor particle size distribution measurement of e-cigarette 1

3-3 Temporal evolution of the number/size distribution of inhaled combustible tobacco cigarette smoke particles (panel A) and e-cigarette droplets (panel B) during puffing, mouth-hold (MH), inhalation, and exhalation, based on the same initial size distribution

3-4 Photograph taken during a cloud competition at about 2 pm at a vaping convention, April 2016, Maryland

3-5 Event room PM_2.5 concentrations before, during, and after an e-cigarette convention

3-6 Real-time changes of PM₁₀, CO₂, and TVOC concentrations during a vaping convention in Maryland

3-7 Estimated disability-adjusted life-years (DALYs) lost due to exposure to secondhand e-cigarette aerosol

4-1 Nicotine metabolic pathways

5-1 Postulated pathways and by-products formed during thermal dehydration of propylene glycol and glycerol

5-2 Effects of nicotine solvent and battery output voltage on levels of carbonyl compounds released from e-cigarettes (µg/15 puffs; n = 3; puff duration = 1.8 seconds, puff volume = 70 ml, puff intervals = 17 seconds)

5-3 Scanning electron microscopy and energy-dispersive X-ray spectroscopy analysis of disposable e-cigarette/e-hookah wires and joints

5-4 Distribution of metal concentrations within and across brands of disposable e-cigalike devices

7-1 Publications by year on e-cigarettes and in vitro systems

7-2 Endothelial cell dysfunction by tobacco smoke

7-3 Proposed signaling cascade triggered by nicotine that partially overlaps with that used by combustible tobacco cigarette smoke extracts to disrupt the endothelial cell barriers and cell proliferation

7-4 Publications by year on e-cigarettes and oxidative stress

7-5 Principal component analysis of top 2,000 genes by median absolute deviation

7-6 Changes in glutathione status and generation of reactive oxygen species

8-1 Distribution of tobacco dependence among each tobacco product use group in the Population Assessment on Tobacco and Health Study Wave 1

8-2 Dependence score as a function of nicotine concentration

8-3 Subjective reward responses for the nicotine e-cigarette and the placebo (non-nicotine) e-cigarette

8-4 Interactions between time and condition (Hydro e-cigarette, NPRO e-cigarette, own-brand combustible tobacco cigarette, and sham [unlit combustible tobacco cigarette]) for subjective effects

9-1 Conceptual framework of plausible pathways, including mechanisms and intermediate outcomes, by which exposure to e-cigarettes influences cardiovascular disease

9-2 Endothelial progenitor cells (EPCs) during e-cigarette inhalation and control

10-1 Conceptual framework of plausible pathways, including mechanisms and intermediate outcomes, by which exposure to e-cigarettes influences cancer outcomes

11-1 Conceptual framework of plausible pathways, including mechanisms and intermediate outcomes, by which exposure to e-cigarettes influences respiratory disease

III-I Smoking transitions between e-cigarette use, combustible tobacco cigarette smoking, and non-use

16-1 Conceptual framework for transition from e-cigarette use to combustible tobacco cigarette use initiation and progression

16-2 Meta-analysis of adjusted odds of current (past 30-day) combustible tobacco cigarette smoking at follow-up among non-current combustible tobacco cigarette smokers at baseline and current e-cigarette users at baseline compared with non-current e-cigarette users at baseline

16-3 Past 30-day use of e-cigarettes and combustible tobacco cigarettes among high school and middle school students in the 2011–2016 National Youth Tobacco Survey

17-1 Conceptual framework of smoking cessation and e-cigarette use

18-1 Changes in select carcinogen levels over 2 weeks of electronic cigarette use among 20 smokers (mean ± SD)

18-2 Urinary metabolite levels for selected toxins and carcinogens, by group

18-3 Forced expiratory volume (FEV1) at the four time points of assessment for all 18 patients

18-4 Changes in diastolic blood pressure from baseline, follow-up 1 (6 ± 1 month) and follow-up 2 (12 ± 2 months) separately for e-cigarette users (exclusive and dual) and exclusive combustible tobacco cigarette smokers

18-5 Changes in the number of chronic obstructive pulmonary disease exacerbations from baseline, at follow-up visit 1 (12 ± 1.5 months) and visit 2 (24 ± 2.5 months) separately for e-cigarette users and controls

18-6 Comparison of indoor air nicotine (left) and aerosol particle (right) concentrations released from e-cigarette with background values and combustible tobacco cigarette smoking

TABLES

1-1 Percentage of High School and Middle School Students Who Have Ever Used E-Cigarettes; National Youth Tobacco Survey (NYTS) 2011–2016

1-2 Summary of the Key Events in the History of E-Cigarette Regulation

3-1 Summary of E-Cigarette Puffing Topography Studies

3-2 Particle Size Distribution Parameters Determined from Cascade Impactor Analysis

4-1 Pharmacokinetic Parameters of (S)-Nicotine and (3´R,5´S)-Trans-3´-Hydroxycotinine After Intravenous Administration

4-2 Summary of Clinical Studies Examining Nicotine Exposure from E-Cigarette Use

5-1 Dose Limits of Commonly Used Drugs to Avoid Propylene Glycol Intoxication Based on a Maximum Amount of PG Equal to 69 g/day

5-2 Plasma Pharmacokinetics of Propylene Glycol Given as a 4-Hour Intravenous Infusion

5-3 Acute Lethal Dose (LD₅₀) of Propylene Glycol in Rats, Mice, Guinea Pigs, and Rabbits

5-4 Overview of Common Flavorings and Their Inhalation Toxicity

5-5 Summary of Experimental Studies Determining Carbonyl Compounds in E-Cigarette Aerosols

5-6 Volatile Compounds Detected in E-Cigarette Aerosol

8-1 Epidemiological Studies on E-Cigarettes and Dependence

8-2 Laboratory/Experimental Studies on Dependence and Abuse Liability

8-3 Tobacco Dependence Instruments and Questions Included, Examined in Response Models, and Retained on a Final Common Tobacco Dependence Instrument in the Population Assessment on Tobacco and Health Study Wave 1

8-4 Product Liking for Vuse Solo E-Cigarettes with Different Nicotine Concentrations Compared with Usual Brand Combustible Tobacco Cigarette and Nicotine Gum

9-1 Clinical Studies of Short-Term Effects of E-Cigarette Use on Cardiovascular Endpoints

9-2 Epidemiological Studies on Chronic E-Cigarette Use and Cardiovascular Endpoints

10-1 In Vitro Mutagenicity/DNA Damage Assessment of E-Cigarette Liquids and Aerosols

10-2 Comparison of Formaldehyde and Acrolein Levels in Smoke from One Combustible Tobacco Cigarette and in Aerosol from 15 Puffs of an E-Cigarette

10-3 Formaldehyde and Acrolein Levels Generated from Five E-Cigarette Devices at Different Power Levels

10-4 Occurrence of Tumors in Female Sprague-Dawley Rats Exposed to Nicotine for Up to 24 Months and Controls

11-1 Clinical and Epidemiological Studies in Humans

16-1 INITIATION: Summary of Prospective Cohort Studies of the Association Between Ever Use of E-Cigarettes (Versus Never Use) and Subsequent Risk of Ever Smoking of Combustible Tobacco Cigarettes Among Youth/Young Adults Who Were Non-Smokers at Baseline

16-2 PROGRESSION: Summary of Prospective Cohort Studies of the Association Between E-Cigarette Use and Subsequent Risk of Recent Smoking/Heavier Smoking of Combustible Tobacco Cigarettes Among Youth/Young Adults

16-3 DOSE–RESPONSE: Summary of Prospective Cohort Studies of the Association Between E-Cigarette Use Frequency and Subsequent Risk of Smoking of Combustible Tobacco Cigarettes Among Youth/Young Adults

16-4 Meta-Analysis of Unadjusted and Adjusted Odds of Ever Smoking Combustible Tobacco Cigarettes Among Combustible Tobacco Cigarette–Never Smokers at Baseline and E-Cigarette–Ever Users at Baseline Compared with E-Cigarette–Never Users at Baseline

17-1 Systematic Reviews of E-Cigarettes and Smoking Cessation Identified by Literature Search

17-2 Characteristics of Three Randomized Controlled Trials Testing the Efficacy of E-Cigarettes for Smoking Cessation

17-3 Selected Systematic Reviews: Part 1

17-4 Selected Systematic Reviews: Part 2

18-1 Comparison of Toxicant Levels Among Combustible Tobacco Cigarette Smoke and E-Cigarette Aerosol

18-2 Comparison of In Vitro Studies That Compared Toxicity of E-Cigarettes and Combustible Tobacco Cigarettes

18-3 Comparison of Animal Studies That Compared Toxicity of E-Cigarettes and Combustible Tobacco Cigarettes

19-1 Summary of Simulation Runs Considered by the Committee

19-2 Model-Estimated Life-Years Lost During 2015–2050 Due to E-Cigarettes

19-3 Model-Estimated Life-Years Lost During 2015–2070 Due to E-Cigarettes

19-4 Model-Estimated Life-Years Lost During 2015–2050 Due to E-Cigarettes

19-5 Model-Estimated Life-Years Lost During 2015–2070 Due to E-Cigarettes

19-6 Model-Estimated Life-Years Lost During 2015–2050 Due to E-Cigarettes

19-7 Model-Estimated Life-Years Lost During 2015–2070 Due to E-Cigarettes

19-8 Model-Estimated Life-Years Lost During 2015–2050 Due to E-Cigarettes

19-9 Model-Estimated Life-Years Lost During 2015–2070 Due to E-Cigarettes

D-1 Summary of Exposure, Comparison, and Control Conditions and Cell or Tissue Type Used in In Vitro Studies of E-Cigarettes Assessing Cytotoxicity

D-2 Summary of Test Agents, Cell or Tissue Type Used, and Assays Employed in In Vitro Studies of E-Cigarettes Assessing Cytotoxicity

D-3 Summary of Results from In Vitro Studies of E-Cigarettes Assessing Cytotoxicity

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