Tobacco Research Library:
Sharing Our Science




Abuse liability of two electronic nicotine delivery systems compared with combustible cigarettes and nicotine gum from an open-label randomized crossover study

Chris Campbell, Tao Jin, Elaine K. Round, Eckhardt Schmidt, Paul Nelson, Sarah Baxter

Scientific Reports

An assessment of the likelihood of use and abuse potential for new tobacco products is an important part of tobacco product regulation in the United States and abroad. This paper reports the results of a randomized, open-label, crossover clinical study that assessed factors related to product adoption and abuse liability (AL), comparing two closed electronic nicotine delivery system (ENDS) products to combustible cigarettes and nicotine gum, high- and low-AL comparator products, respectively.


Using a Novel Connected Device for the Collection of Puffing Topography Data for the Vuse Solo Electronic Nicotine Delivery System in a Real-World Setting: Prospective Ambulatory Clinical Study

Robert Underly, Gary M Dull, Evan Nudi, Timothy Pionk, Kristen Prevette, Jeffrey Smith

JMIR Formative Research

The Product Use and Behavior instrument was developed and used to capture the use of the Vuse Solo ENDS in an ambulatory setting to best replicate real-world use behavior. This study aims to determine overall mean values for topography outcomes while also providing a definition for an ENDS use session.


Purchase Intent and Product Appeal of Velo Nicotine Pouches Among Current Tobacco Users and Nonusers of Tobacco

Robert E. Freeland, Deena R. Battista, Michael Polster, Robyn Chae, Nicole Dianno and Kimberly Frost-Pineda

Contributions to Tobacco & Nicotine Research

Oral nicotine pouches is a rapidly growing product category that potentially offers less risk than combustible tobacco products. This paper presents population-level estimates of purchase intent and product appeal for multiple Velo nicotine pouch products (including different flavors,nicotine strengths, format, and packaging) among five adult tobacco user groups (current established cigarette smokers, current established non-cigarette tobacco users,current tobacco experimenters, former tobacco users, and never ever tobacco users).


Oxidative Stress and Lung Fibrosis: Towards an Adverse Outcome Pathway

Patrudu Makena, Tatiana Kikalova, Gaddamanugu L. Prasad and Sarah A. Baxter

International Journal of Molecular Sciences

Lung fibrosis is a progressive fatal disease in which deregulated wound healing of lung epithelial cells drives progressive fibrotic changes. Persistent lung injury due to oxidative stress and chronic inflammation are central features of lung fibrosis. The objective of this manuscript is to develop an adverse outcome pathway (AOP) that serves as a framework for investigation of the mechanisms of lung fibrosis due to lung injury caused by inhaled toxicants, including cigarette smoke.


Changes in Biomarkers of Exposure and Potential Harm in Smokers Switched to Vuse Vibe or Vuse Ciro Electronic Nicotine Delivery Systems

Milly N. Kanobe, Paul R. Nelson, Buddy G. Brown, Peter Chen, Patrudu Makena, John W. Caraway, Gaddamanugu L. Prasad, Elaine K. Round


Electronic nicotine delivery systems (ENDS) have the potential to provide nicotine to tobacco consumers while reducing exposure to combustion-related toxicants. Here, we report changes in biomarkers of exposure (BoE) and biomarkers of potential harm (BoPH) in smokers who completely switched to Vuse Vibe and Vuse Ciro ENDS products, or to smoking abstinence in a randomized, controlled clinical study.


Purchase Intent and Appeal of ENDS Products among Current, Former and Never Ever Users of Tobacco Products in the U.S.

Kimberly Frost-Pineda, Robyn Chae, Nicole Dianno, Robert Freeland, Michael Polster

Contributions to Tobacco & Nicotine Research

The last decade has seen extensive research into electronic nicotine delivery systems (ENDS) such as e-cigarettes. Although some studies assess ENDS’ potential benefits, there is a paucity of studies that provide population-level estimates of purchase intent or product appeal among various tobacco user groups, or that have examined the impact of different product characteristics on those variables. This paper provides the first population estimates of both purchase intent and product appeal for various ENDS products among adult tobacco users and nonusers; information that is critical for evaluating the impact on public health.


Identification and Quantitation of Nicotine Polacrilex in Nicotine Pouches and Other Oral Nicotine Delivery Products

Serban Moldoveanu

Contributions to Tobacco & Nicotine Research

Nicotine polacrilex (CAS-No. 96055-45-7) can be used as the source of nicotine in nicotine pouches and other oral nicotine delivery products such as lozenges, tablets, and gums. Present study describes a unique procedure to identify the presence of the compound nicotine polacrilex in oral nicotine delivery products and to evaluate its level.


Part two: an unblinded, parallel, randomized study to assess nicotine pharmacokinetics of four Vuse Solo ENDS flavors in smokers

Brian M. Keyser, Kyung Soo Hong, Patricia DeLuca, Tao Jin, Bobbette A. Jones, Paul Nelson, Eckhardt Schmidt, Elaine K. Round

Scientific Reports

We report the findings from a randomized, parallel study designed to evaluate nicotine pharmacokinetics (PK) following 10 min of ad libitum use of electronic nicotine delivery system (ENDS) in four flavor variants. Subjects were randomized an investigational product (IP) and blood samples were collected for PK assessments during a test session.


Two Techniques for the Analysis of WS-3 With Potential Application to the Analysis of Other Cooling Agents

Serban Moldoveanu, Robert Bussey

Contributions to Tobacco & Nicotine Research

WS-3 (N-ethyl-p-menthane-3-carboxamide) is a compound used as a cooling agent for tobacco or nicotine products. Three other similar compounds WS-23 (N,2,3-trimethyl-2-propan-2-ylbutanamide), Evercool 180 (N-p-benzene-aceto-nitrile menthanecarboxamide), and Evercool 190 (N-(2-pyridine-2-yl)ethyl-3-p-menthancarboxamide) also have cooling properties and can be used as tobacco additives. A few previously reported methods for WS-3 analysis were rather complex, and the goal of present work was to develop a simple, rapid, and accurate procedure for simultaneous analysis of WS-3 and of the other three cooling compounds.


Biomarkers of Exposure and Potential Harm in Two Weeks of Smoking Abstinence: Changes in Biomarkers of Platelet Function, Oxidative Stress, and Inflammation

Patrudu Makena, Eric Scott, Peter Chen, Hsiao-Pin Liu, Bobbette A. Jones, Gaddamanugu L. Prasad

International Journal of Molecular Sciences

A 14-day smoking abstinence study was conducted under clinical confinement conditions and enrolled 70 subjects into younger (24–34 years, n = 33) and older (35–60 years, n = 37) age cohorts. Biomarkers of Exposure (BoE), which indicate exposure to nicotine and other toxicants, were measured at baseline, 7 and 14 days. Several BoPH including previously identified eicosanoids (leukotriene 4 (LTE4) and 2,3-dinor thromboxane 2 (2,3-d-TXB2) and others were evaluated.


Key Challenges and Recommendations for In Vitro Testing of Tobacco Products for Regulatory Applications: Consideration of Test Materials and Exposure Parameters

Martha M. Moore, Irene Abraham, Mark Ballantyne, Holger Behrsing, Xuefei Cao, Julie Clements, Marianna Gaca, Gene Gillman, Tsuneo Hashizume, Robert H. Heflich, Sara Hurtado, Kristen G. Jordan, Robert Leverette, Damian McHugh, Jacqueline Miller-Holt, Gary Phillips, Leslie Recio, Shambhu Roy, Mariano Scian, Liam Simms, Daniel J. Smart, Leon F. Stankowski, Jr, Robert Tarran, David Thorne, Elisabeth Weber, Roman Wieczorek, Kei Yoshino, and Rodger Curren

Alternatives to Laboratory Animals

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to identify, discuss and develop recommendations for optimal scientific and technical approaches for conducting in vitro assays, to assess potential toxicity within and across tobacco and various next generation nicotine and tobacco products (NGPs), including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS). Summaries of the speaker presentations and the recommendations developed by the workgroup are presented.


Partial Vapor Pressures, Activity Coefficients, Henry Volatility, and Infinite Dilution Activity Coefficients of Nicotine from Binary Mixtures with Glycerol and with 1,2-Propanediol at 298.15 K

F. Kelley St. Charles, Serban Moldoveanu

ACS Omega

The equilibrium headspace concentration of nicotine in nitrogen gas was measured by gas chromatography for binary mixtures of nicotine with glycerol and with 1,2-propanediol at temperatures near 298.15 K.


Comparison of two methods for ginsenosides quantitation

Serban Moldoveanu, Huamin Gan

Journal of Separation Science

The present study provides a comparison of two liquid chromatography–tandem mass spectrometry methods for ginsenosides analysis. As an application, the ginsenosides were measured in several types of ginseng root, several dietary supplements containing ginseng extracts, four energy drinks, and a sample of ashwagandha.


Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum

Chris Campbell, Tao Jin, Elaine K. Round, Eckhardt Schmidt, Paul Nelson, Sarah Baxter

Scientific Reports

Abuse liability (AL) of electronic nicotine delivery systems (ENDS) is relevant as the category increases in popularity as a potentially less-harmful alternative to cigarette smoking. AL assessments are important to the FDA in determining if a new product is appropriate for the protection of public health. This paper reports the results for Vuse Solo (G2 cartridge design) compared to high and low AL-comparators evaluated in an open-label, randomized crossover confinement AL study.


Part three: a randomized study to assess biomarker changes in cigarette smokers switched to Vuse Solo or Abstinence

Milly N. Kanobe, Bobbette A. Jones, Paul Nelson, Buddy G. Brown, Peter Chen, Patrudu Makena, Eckhardt Schmidt, John Darnell, John W. Caraway, G. L. Prasad, Brian Nordskog & Elaine K. Round

Scientific Reports

Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled, confinement study of BoE in smokers switched to ENDS.


Characterization of smoke and aerosol deliveries from combustible cigarettes, heated tobacco products and electronic nicotine delivery systems in the Vitrocell® Mammalian 6/48 exposure module

Brian M.Keyser, Robert Leverette, Michael Hollings, Adam Seymour, Randy A. Weidman, Carlton J. Bequette, Kristen Jordan

Toxicology Reports

The rapid development associated with Next Generation Tobacco Products (NGTP) has necessitated the development of high throughput methodologies to test their genotoxic potential in vitro when compared to conventional cigarette smoke (CS). An assessment of two Vitrocell® Mammalian 6/48 exposure modules in three independent experiments was made by comparing results from multiple dosimetric techniques applied to aerosol generated from 3R4F Kentucky Reference cigarettes, commercially available electronically heated tobacco product (eHTP) and Electronic Nicotine Delivery System (ENDS) using the Vitrocell® VC10®.


A Systematic Review and Meta-analysis of the Association between E-cigarette Use among Cigarette Smokers and Quit Attempts Made to Abstain from Cigarette Smoking

Mimi Kim, Isabella Steffensen, Red Miguel, Julien Carlone, Geoffrey Curtin

American Journal of Health Behavior

Following AMSTAR 2 and PRISMA guidelines, in this synthesis of evidence we sought to identify and characterize any associations between e-cigarette use among cigarette smokers and cigarette smoking quit attempts.


Designing Studies to Inform Tobacco Harm Reduction: Learnings From an Oral Nicotine Pouch Actual Use Pilot Study

Chris Campbell, Michael Feehan, Claudia Kanitscheider, Patrudu Makena, Jenny Cai, Sarah Baxter

JMIR Formative Research

The aim of this pilot study was to develop and test a protocol for an actual use study of a new tobacco product. The product included in this study was a commercially available oral nicotine pouch. Through the process of study design and execution, learnings were garnered to inform the design, execution, analysis, and report writing of future full-scale actual use studies with tobacco products.


Ciliary Beat Frequency: Proceedings and Recommendations from a Multi-laboratory Ring Trial Using 3-D Reconstituted Human Airway Epithelium to Model Mucociliary Clearance

Holger Behrsing, Adam Wahab, Lindsey Ukishima, Chad Grodi, Stefan Frentzel, Stephanie Johne, Shinkichi Ishikawa, Shigeaki Ito, Roman Wieczorek, Jessic Budde, Brian Keyser, Linsey Haswell, David Thorne, Emma Bishop, Damien Breheny, Xuefei Cao, Qin Qin, Vivek Patel

Alternatives to Laboratory Animals

In June 2015, the Institute for In Vitro Sciences (IIVS) held a technical workshop to evaluate the potential for standardisation of methods, including ciliary beat frequency (CBF). The applicability of a protocol suggested in the workshop was assessed in a multi-laboratory ring study. This report summarises the findings, and uses the similarities and differences identified between the laboratories to make recommendations for researchers in the absence of a validated method.


Progress in Technology of the Chromatographic Columns in HPLC (Book Chapter)

Serban C. Moldoveanu and Victor David

Analytical Liquid Chromatography - New Perspectives

Chromatographic column is an essential part of a any HPLC separation, and significant progress has been made in developing columns with better performance to provide better separation, a shorter separation time, resilience to a wider pH range of the mobile phase, longer lifetime, use of lower volumes of mobile phase, etc.


Does the Level of NNK in Tobacco and Tobacco Products Depend on the Level of Pseudooxynicotine or of Nicotine-1′-N-Oxide?

Huihua Ji and Serban C. Moldoveanu

Contributions to Tobacco and Nicotine Research

4-(N’-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potentially carcinogenic tobacco specific nitrosamine (TSNA) and an important compound in the Harmful and Potentially Harmful Constituents (HPHCs) list of U.S. Food and Drug Administration (FDA). Present study evaluated the correlation between the levels of NNK and those of PON in a variety of tobaccos and tobacco products. Since nicotine-1′-N-oxide can be involved in the formation of PON, the correlation of the levels of this compound with the levels of NNK was also evaluated.


Differential gene expression of 3D primary human airway cultures exposed to cigarette smoke and electronic nicotine delivery system (ENDS) preparations

Rachael E. Rayner, Patrudu Makena, Gang Liu, G. L. Prasad, and Estelle Cormet-Boyaka

BMC Medical Genomics

Acute exposure to cigarette smoke alters gene expression in several biological pathways such as apoptosis, immune response, tumorigenesis and stress response, among others. However, the effects of electronic nicotine delivery systems (ENDS) on early changes in gene expression is relatively unknown. The objective of this study was to evaluate the early toxicogenomic changes using a fully-differentiated primary normal human bronchial epithelial (NHBE) culture model after an acute exposure to cigarette and ENDS preparations.


Characterization of Aerosol Deliveries from Combustible Cigarettes, Heated Tobacco Products, and Electronic Nicotine Delivery Systems Using the Vitrocell Ames 48

Brian M. Keyser, Robert Leverette, Michael Hollings, Adam Seymour, Randy J. Weidman, Carlton J. Bequette, and Kristen Jordan

Applied in Vitro Toxicology

The Vitrocell® Ames 48 whole-aerosol exposure module offers a high-throughput platform for air-agar-interface exposures that mimic human exposure conditions for assessing potential mutagenic activity of a test article. The aim of this study was to characterize the Vitrocell Ames 48 exposure module for assessment of aerosolized tobacco products utilizing multiple dosimetry techniques and nicotine deposition as determined by chemical analysis.


Advantages of Ion Mobility Coupled with HPLC/UPLC (Book Chapter)

Robert Owen Bussey III

Analytical Liquid Chromatography - New Perspectives

Ion mobility is a new separation technique that can be coupled with high performance liquid chromatography (HPLC) or ultra-performance liquid chromatography (UPLC). Options ranging from descriptive data collation into instrument libraries to sensitivity enhancement for trace analysis will be explored in this chapter along with the description of different forms of ion mobility.


Ionic Liquids in Liquid Chromatography (Book Chapter)

Serban C. Moldoveanu and Victor David

Analytical Liquid Chromatography - New Perspectives

Ionic liquids (ILs) are salts of organic cations that are present in liquid state. They can be used as alternative to organic solvents for various analytical processes such as extracting solvents in sample preparation, or as mobile phase or components of the mobile phase in high performance liquid chromatography (HPLC). The chapter presents various applications of ILs in liquid chromatography.


A Single-Center Evaluation of Environmental Emissions from Electronic Cigarettes and Combustible Cigarettes

John W. Caraway, Tao Jin, Eckhardt Schmidt and Paul R. Nelson

Contributions to Tobacco and Nicotine Research

This study evaluated the differences in concentrations of volatile and particulate compounds (including formaldehyde, benzene, glycerol, propylene glycol, nicotine, and particulate matter) in secondhand vapor (SHV) after ad libitum subject vaping of cig-a-like ENDS, after-subject smoking of combustible cigarettes (CC), and after-subject non-smoking/non-vaping (blank) in an environmental test chamber.


A survey of aerosol exposure systems relative to the analysis of cytotoxicity: A Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) perspective

David Thorne, Roman Wieczorek, Toshiro Fukushima, Han-Jae Shin, Robert Leverette, Mark Ballantyne, Xiang Li, Betsy Bombick, Kei Yoshino

Toxicology Research and Application

During a Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) meeting, the in vitro toxicity testing Sub-Group (IVT SG) met to discuss the evolving field of aerosol exposure research.


Reporting and methodological quality of systematic literature reviews evaluating the associations between e-cigarette use and cigarette smoking behaviors: a systematic quality review

Mimi Kim, Lynley Pound, Isabella Steffensen, Geoffrey Curtin

Harm Reduction Journal

Several published systematic reviews have examined the potential associations between e-cigarette use and cigarette smoking, but their methodological and/or reporting quality have not yet been assessed. This systematic quality review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2 to evaluate the quality of systematic reviews investigating potential associations between e-cigarette use and cigarette smoking.


Transcriptomic Response of Primary Human Bronchial Cells to Repeated Exposures of Cigarette and ENDS Preparations

Rachael Rayner, Jack Wellmerling, Patrudu Makena, Jing Zhao, G.L. Prasad, Estelle Cormet-Boyaka

Cell Biochemistry and Biophysics

In order to assess the effect of repeated exposures of ENDS, primary normal human bronchial epithelial (NHBE) cells grown at air-liquid interface (ALI) were exposed to cigarette and ENDS preparations daily for 10 days.


Human Abuse Liability Assessment of Tobacco and Nicotine Products: Approaches for Meeting Current Regulatory Recommendations

Andrea Vansickel, Sarah Baxter-Wright, Neil Sherwood, Michael Kong, Leanne Campbell

Nicotine and Tobacco Research

Regulators, including FDA, and many public health officials and researchers consider abuse liability assessment a model which predicts the likelihood that the use of the tobacco product would result in addiction and be used repeatedly or even sporadically resulting in undesirable effects. The purpose of this review is to provide background information and practical recommendations for human abuse liability testing methods to meet tobacco regulatory needs.


Cigarette Smoke Preparations, Not Electronic Nicotine Delivery Systems (ENDS) Preparations, Induce Features of Lung Disease in a 3D Lung Repeat-Dose Model

Rachel Rayner, Patrudu Makena, G. L. Prasad, Estelle Cormet-Boyaka

American Journal of Physiology

This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in a repeat-dose exposure to evaluate and compare the effect of combustible cigarette and ENDS preparations.


Diacetyl and Other Ketones in e-Cigarette Aerosols: Some Important Sources and Contributing Factors

Kevin McAdam, Gareth Waters, Serban Moldoveanu, Jennifer Margham, Anthony Cunningham, Carl Vas, Andrew Porter, Helena Digard

Frontiers in Chemistry

We quantified direct transfer from e-liquids, examined thermal degradation of major e-liquid constituents VG, PG and 1,3 propanediol (1,3 PD) and the potential for AC, AP and DA production from sugars and flavor additives when heated in e-cigarettes.


Machine Vaping of Electronic Cigarettes – A Comparison of Puffing Regimes

Amit Gupta, Rana Tayyarah, Gene Gillman, Charles Garner, Rob Stevens

Contributions to Tobacco & Nicotine Research

Several machine-based puffing regimes for collection of e-cigarette aerosol were evaluated with the objective of recommending one regime for standardization. The study involved a comparison of several candidate regimes for which puff volume, duration, interval, profile shape, and puff number were defined and varied. Testing was conducted at four laboratories using seven e-cigarette test products.


Variation with Temperature of Phase Ratio in Reversed Phase HPLC for a Methanol/Water Mobile Phase

Andreia-Cristina Soare, Victor David, Serban Moldoveanu


A procedure based on proportionality of retention factors k on octanol/water partition coefficients log Kow for several aromatic hydrocarbon homologues was used for the measurement of Φ.


Differences in biomarkers of inflammation and immune responses in chronic smokers and moist snuff users

Quynh Tran, Subhashini Arimilli, Eric Scott, Peter Chen, G.L. Prasad


We evaluated markers related to immune regulation in smokers (SMK), moist snuff consumers (MSC) and non-tobacco consumers (NTC) to better understand the effects of chronic tobacco use.


Impact of Cigarette Versus Electronic Cigarette Aerosol Conditioned Media on Aortic Endothelial Cells in a Microfluidic Cardiovascular Model

Om Makwana, Gina A. Smith, Hannah E. Flockton, Gary P. Watters, Frazer Lowe & Damien Breheny

Scientific Reports

We have developed a functional in vitro adhesion assay using BioFlux microfluidic technology to investigate THP-1 (human acute monocytic leukaemia cell) monocyte adhesion to human aortic endothelial cells (HAECs).


Metabolomics analysis indentified reduced levels of xenobiotics, oxidative stress, and improved vitamin metabolism in smokers switched to an Electronic Nicotine Delivery Device System

Gang Liu, Chi Hen Lin, Charles Yates, G.L. Prasad

Nicotine and Tobacco Research

To investigate the biochemical effects of switching from smoking to an Electronic Nicotine Delivery Systems (ENDS), we assessed global metabolomic profiles of smokers in a 7-day confinement clinical study.


Derivatization procedures and their analytical performances for HPLC determination in bioanalysis

Victor David, Serban Moldoveanu, Toma Galaon

Biomedical Chromatography

The derivatization process is discussed according to the analytical procedure used to achieve the reaction between the reagent and the target compounds (containing hydroxyl, thiol, amino, carbonyl and carboxyl as the main functional groups involved in derivatization).


Variations of TSNA Levels in Tobaccos Upon Heating at Moderate Temperatures

Serban Moldoveanu, Marlene Adams, Frank St. Charles

Contributions to Tobacco Research

Since the increase of TSNAs in heated tobacco is still not well understood, the present study evaluated TSNA levels in six types of tobacco as a function of moderate heat exposure.


Extraction of Benzo[a]pyrene from Moist Snuff with Water or Artificial Saliva (Part 2)

Serban Moldoveanu, Andrew Harrison

Contributions to Tobacco & Nicotine Research

The present study evaluated the in vitro extraction of benzo[a]pyrene (BaP) from moist snuff into water and into artificial saliva. Nine moist snuff samples (eight being the same brands as evaluated in the previous study) were analyzed in the present study.


Assessing comprehension and perceptions of modified-risk information for snus among adult current cigarette smokers, former tobacco users, and never tobacco users

Janine Pillitteri, Saul Shiffman, Mark Sembower, Michael Polster, Geoffrey Curtin

Addictive Beaviors Reports

This study assessed comprehension and perceptions of modified-risk information regarding snus. Adult cigarette smokers, former tobacco users, and never tobacco users (N = 3,922) from a US internet panel viewed an advertisement stating that smokers who switched completely to snus could greatly reduce risk of lung cancer, respiratory disease, heart disease, and oral cancer. Respondents answered questions regarding the modified-risk information and rated perceived risks of snus relative to cigarettes and other smokeless tobacco products.


Randomized Trial to Compare Smoking Cessation Rates of Snus, With and Without Smokeless Tobacco Health-Related Information, and a Nicotine Lozenge

Paul Nelson, Peter Chen, Deena Battista, Janine Pillitteri, Saul Shiffman

Nicotine and Tobacco Research

This study compared smoking cessation rates for snus, with and without information about reduced risk relative to smoking, with a nicotine lozenge (without relative risk information).


Genotoxicity evaluation of tobacco and nicotine delivery products: Part One. Mouse Lymphoma Assay

David Thorne, Robert Leverette, Damien Breheny, Mel Lloyd, Stephen McEnaney, James Whitwell, Julie Clements, Betsy Bombick, Marianna Gaca

Food and Chemical Toxicology

The aim of this study was to assess the suitability of the MLA for genotoxicity testing with a variety of tobacco and nicotine products.


Development of a quantitative method for assessment of dose in in vitro evaluations using a VITROCELL® VC10® smoke exposure system

Brian Keyser, Robert Leverette, Kathy Fowler, Wanda Fields, Victoria Hargreaves, Lesley Reeve, Betsy Bombick

Toxicology in Vitro

The aims of this study were to investigate dosimetry during whole smoke exposure in the VITROCELL® VC10® smoking robot using quartz crystal microbalances (QCMs) and to support the use of photometers for concurrent assessment of ‘dose’ during whole smoke exposures.


Urinary leukotriene E4 and 2,3-dinor thromboxane B2 are potential biomarkers of effect in short-term tobacco switching studies

Patrudu Makena, Gang Liu, Peter Chen, Charles Yates, G.L. Prasad

Cancer Epidemiology, Biomarkers & Prevention

This study evaluated whether arachidonic acid (AA)-derived metabolites serve as short-term BoPH for predicting harm reduction in tobacco product–switching studies.


Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers

Gang Liu, Douglas Lee, Eckhardt Schmidt, G.L. Prasad

Bioinformatics and Biology Insights

In this study, we investigated the effects of tobacco consumption on additional metabolic pathways using pathway-based analysis tools. To this end, metabolic pathway enrichment analysis and topology analysis were performed through pair-wise comparisons of global metabolomic profiles of SMK, MSC, and NTC.


Optimization of Normal Human Bronchial Epithelial (NHBE) Cell 3D Cultures for in vitro Lung Model Studies

Rachael Rayner, Patrudu Makena, Gaddamanugu Prasad, Estelle Cormet-Boyaka

Scientific Reports

We evaluated the ability to expand primary NHBE cells in different culture conditions while maintaining their 3D culture characteristics such as ciliated and goblet cells, and ion channel function.


Assessing likelihood of use for snus with modified-risk information among current smokers, former tobacco users and never tobacco users

Karen Gerlach, Saul Shiffman, Deena Battista, Michael Polster, Geoffrey Curtin

Addictive Behaviors Reports

This study evaluates likelihood of snus use among tobacco users and non-users provided modified-risk information.


Combustible Cigarette and Smokeless Tobacco Product Preparations Differentially Regulate Intracellular Calcium Mobilization in HL60 Cells

Subhasshini Arimilli, Patrudu Makena, G.L. Prasad


In this study, we evaluated the effects of tobacco product preparations (TPPs), including total particulate matter (TPM) from 3R4F reference cigarettes, smokeless tobacco extract (STE) from 2S3 reference moist snuff, and nicotine alone on Ca2+ mobilization in HL60 cells.


Extraction from Moist Snuff with Artificial Saliva of Benzo[a]pyrene and Other Polycyclic Aromatic Hydrocarbons

Serban Moldoveanu, Jerry Marshall, Thomas Poole

Contributions to Tobacco & Nicotine Research

The present study evaluated in vitro extractability of various polycyclic aromatic hydrocarbons (PAHs) from moist snuff, when the extracting agent was water or artificial saliva. The extraction was performed on nine brands of moist snuff samples that are commercially available and were purchased from the market in January 2018.


Investigation of multiple whole smoke dosimetry techniques using a VITROCELL®VC10® smoke exposure system

Brian Keyser, Robert Leverette, Michael Hollings, Adam Seymour, Lesley Reeve, Wanda Fields

Toxicology Reports

The aim of this study was to investigate and compare multiple dosimetry techniques that may be employed during combustible cigarette whole smoke exposure using the Vitrocell® VC10® smoking robot.


Genotoxicity evaluation of tobacco and nicotine delivery products: Part Two. In vitro micronucleus assay

David Thorne, Robert Leverette, Damien Breheny, Mel Lloyd, Stephen McEnaney, James Whitwell, Julie Clements, Betsy Bombick, Marianna Gaca

Food and Chemical Toxicology

In this study, a variety of test matrices from tobacco and nicotine delivery products were assessed against a 3R4F Kentucky reference cigarette using the in vitro micronucleus assay.


Distinct gene expression changes in human peripheral blood mononuclear cells treated with different tobacco product preparations

Subhasshini Arimilli, Patrudu Makena, Gang Liu, G.L. Prasad

Toxicology in Vitro

To better characterize the biological effects of different categories of tobacco products, a genome-wide gene expression study was performed.


Cigarette smoke preparations, not moist snuff, impair expression of genes involved in signaling and cytolytic functions in PBMCs

Gang Liu, Subhashini Arimilli, Evan Savage, G.L. Prasad

Scientific Reports

To understand how tobacco products impact immune responses, we assessed transcriptomic profiles in peripheral blood mononuclear cells (PBMCs) pretreated with Whole Smoke-Conditioned Medium (WS-CM) or Smokeless Tobacco Extracts (STE), and stimulated with lipopolysaccharide, phorbol myristate and ionomycin (agonists).


Cigarette and ENDS preparations differentially regulate ion channels and mucociliary clearance in primary normal human bronchial 3D cultures

Rachel Rayner, Patrudu Makena, G. L. Prasad, Estelle Cormet-Boyaka

American Journal of Physiology

This study aimed to compare the effects of acute exposure of primary normal human bronchial epithelial (NHBE) 3D cultures at air-liquid interface to combustible cigarette and ENDS preparations on mucociliary function, including ion channel function, ciliary beat frequency (CBF), and airway surface liquid (ASL) height.


Inflammatory profile analysis reveals differences in cytokine expression between smokers, moist snuff users, and dual users compared to non-tobacco consumers

Judi Azevedo Sgambato, Bobbette Jones, John Caraway, G.L. Prasad


The aim of this study is to investigate the inflammatory alterations due to the use of smokeless tobacco and dual use of smokeless tobacco and cigarettes, relative to smoking. Our findings contribute a better understanding of how the use of different tobacco products contributes to inflammation.


Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum

Mitchell Stiles, Leanne Campbell, Tao Jin, Donald Graff, Reginald Fant, Jack Henningfield


We evaluated the abuse liability of three menthol-flavored Vuse Solo ECs with the same nicotine contents (14, 29, and 36 mg) in a group of EC-naïve, menthol cigarette smokers, relative to comparator products.


Global Methylation Profiles in Buccal Cells of Long-Tem Smokers and Moist Snuff Consumers

Walter Jessen, Michael Borgerding, G.L. Prasad


The aim of this study is to investigate global methylation changes in the buccal cells of smokers and smokeless tobacco users.


Nicotine pharmacokinetics of electronic cigarettes: A review of the literature

Ian Feron, Alison Eldridge, Nathan Gale, Mike McWan, Mitchell Stiles, Elaine Round

Regulatory Toxicology and Pharmacology

In this review, we provide a critical overview of the literature to describe what is known about nicotine delivery from e-cigarettes.


An LC-MS Method for the Analysis of Some Organic Acids in Tobacco Leaf, Snus, and Wet Snuff

Serban Moldoveanu, Thomas Poole, Wayne Scott

Contributions to Tobacco & Nicotine Research

The present study describes the analysis of several organic acids in tobacco and smokeless tobacco products using a liquid chromatography (LC) method with mass spectrometric (MS) detection (LC-MS). The study describes the advantages and disadvantages of the LC-MS method for the analysis of organic acids in tobacco and smokeless tobacco products.


Critical evaluation of several techniques for the analysis of phthalates and terephthalates: Application to liquids used in electronic cigarettes

Serban Moldoveanu, Ravikiran Yerabolu

Journal of Chromatography A

This study describes several original methods that were developed with the goal of measuring phthalates and terephthalates. These methods include gas chromatography/mass spectrometry (GC/MS), GC/MS/MS, liquid chromatography with UV detection (LC/UV), LC/MS, and LC/MS/MS. The study compares the advantages and disadvantages of these methods and their applicability to measuring phthalates and terephthalates in the liquids used in electronic cigarettes (e-liquids). The analytes evaluated include eight phthalates and two terephthalates.


Feeding of tobacco blend or nicotine induced weight loss associated with decreased adipocyte size and increased physical activity in male mice

Mingzia Liu, Chia-Chi Key, Allison Weckerle, Elena Boudyguina, Janet Sawyer, Abraham Gebre, Wayne Spoo, Om Makwana, John S. Parks

Food and Chemical Toxicology

Although epidemiological data and results from rodent studies support an inverse relationship between nicotine consumption and body weight, the molecular mechanisms are poorly understood. CD-1 mice were fed a basal diet or a basal diet containing low or high dose smokeless tobacco blend or high dose nicotine tartrate for 14 weeks.


The Determination of Diacetyl and Acetylpropionyl in Aerosols From Electronic Smoking Devices Using Gas Chromatography Triple Quad Mass Spectrometry

Serban Moldoveanu, Amanda Hudson, Andrew Harrison

Contributions to Tobacco & Nicotine Research

A reliable and sensitive method for the measurement of the level of diacetyl (2,3-butanedione) and acetylpropionyl (2,3-pentanedione) in the aerosol (both the particles and the suspending gas) of electronic smoking devices (e-cigarettes) has been developed. The method uses a gas chromatographic separation on a Carbowax type column with the measurement of the analytes on a triplequadrupole mass spectrometer working in positive MRM mode.


Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability

Mitchell Stiles, Leanne Campbell, Donald Graff, Bobbette Jones, Reginald Fant, Jack Henningfield


The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abuse liability comparator products (usual brand combustible cigarettes and nicotine gum, respectively) in a group of 45 EC-naïve smokers.


AKR1C1 as a Biomarker for Differentiating the Biological Effects of Combustible from Non-Combustible Tobacco Products

Sangsoon Woo, Hong Gao, David Henderson, Wolfang Zacharias, Gang Liu, Quynh Tran, G.L. Prasad


Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible ones using oral cell lines.


Characterization and Application of the VITROCELL VC1 Smoke Exposure System and 3D EpiAirway Models for Toxicological and e-Cigarette Evaluations

Wanda Fields, Anna Malone, Brian Keyser, Betsey Bombick

Applied in Vitro Toxicology

The VITROCELL VC1® smoke exposure machine is an aerosol exposure system that has been used to conduct toxicological assessments with cigarettes and e-cigarettes and can be used with the human 3D EpiAirway™ tissue model (MatTek Corporation). The goals of this study were to assess exposure parameters of the VC1, and evaluate donor-to-donor variability of three EpiAirway tissue donors with the following endpoints: viability, barrier integrity, and gene promoter/expression regulation.


Analysis of Traces of Tobacco-Specific Nitrosamines (TSNAs) in USP Grade Nicotine, E-Liquids, and Particulate Phase Generated by the Electronic Smoking Devices

Serban Moldoveanu, Jeff Zhu, Nancy Qian

Contributions to Tobacco & Nicotine Research

The present study describes the development of a liquid chromatography tandem mass spectrometry (LC-MS/MS) technique for the analysis of trace levels of four tobaccospecific nitrosamines (TSNAs): nitrosoanabasine (NAB), nitrosoanatabine (NAT), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and nitrosonornicotine (NNN). The technique can be applied for the analysis of TSNAs in USP grade nicotine.


Gene expression profiles associated with cigarette smoking and moist snuff consumption

Subhashini Arimilli, Behrouz Madahian, Peter Chen, Kristin Marano, G.L. Prasad

BMC Genomics

US epidemiological studies indicate that non-combustible tobacco products are less harmful than smoking and yet very limited biological and mechanistic information is available on the effects of these alternative tobacco products. For the first time, we characterized gene expression profiling in PBMCs from moist snuff consumers (MSC), compared with that from consumers of cigarettes (SMK) and non-tobacco consumers (NTC).


Thermodynamic and kinetic behavior of glycerol aerosol

Timothy Wright, Chen Song, Stephen Sears, Markus Petters

Aerosol Science and Technology

Glycerol and propylene glycol mixtures are common carrier solutions in electronic cigarettes. Here, we apply a temperature and relative humidity-controlled hygroscopicity/volatility tandem differential mobility analyzer system to study the growth and evaporation kinetics of glycerol aerosol over a wide range of temperature, relative humidity, and residence times.


The Activity and Enthalpy of Vaporization of Nicotine from Tobacco at Moderate Temperatures

F. Kelley St. Charles, Serban Moldoveanu

Contributions to Tobacco & Nicotine Research

The vapor pressure of nicotine has been reported for unprotonated nicotine and for nicotine-water solutions. Yet no published values exist for nicotine in any commercially relevant matrix or for protonated forms (e.g., tobacco, smoke, electronic cigarette solutions, nicotine replacement products, nicotine salts). Therefore a methodology was developed to measure nicotine activity (defined as the vapor pressure from a matrix divided by the vapor pressure of pure nicotine).


Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 1. Study design and methodology

Michael Ogden, Kristin Marano, Bobbette Jones, Mitchell Stiles


A randomized, multi-center study was conducted to assess potential improvement in health status measures, as well as changes in biomarkers of tobacco exposure and biomarkers of biological effect, in current adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) evaluated over 24 weeks. Study design, conduct and methodology are presented here along with subjects’ disposition, characteristics, compliance and safety results.


Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 2. Biomarkers of exposure

Michael Ogden, Kristin Marano, Bobbette Jones, Walter Morgan, Mitchell Stiles


A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects’ experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed.


Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 3. Biomarkers of biological effect

Michael Ogden, Kristin Marano, Bobbette Jones, Walter Morgan, Mitchell Stiles


A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) for 24 weeks was conducted.


A cross-sectional study of biomarkers of exposure and effect in smokers and moist snuff consumers

G.L. Prasad, Bobbette Jones, Peter Chen, Evan Gregg

Clinical Chemistry and Laboratory Medicine

Epidemiological data indicate the use of smokeless tobacco (ST) is associated with significantly lower risk for smoking-related diseases compared to cigarettes. Several biomarkers of exposure (BioExp) and effect (BioEff) associated with smoking and use of moist snuff (ST) were evaluated.


Toxicological evaluation of smokeless tobacco: 2-year chronic toxicity and carcinogenicity feeding study in Wistar Han rats

Eugenia Theophilus, Johnnie Hayes, Paul Ayres, Walter Morgan, Ryan Potts, Charles Garner, Dawn Fallacara, Milton Hejtmancik, Allen Singer

Experimental and Toxicologic Pathology

A comprehensive 2-year oral chronic toxicity/carcinogenicity study was conducted with smokeless tobacco using modern toxicological test methods and well-accepted standards. The study included a 1-year interim subgroup to assess toxicity at that intermediate time point.


Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

G.L. Prasad, Bobbette Jones, Eckhardt Schmidt, Peter Chen, Adam Kennedy

Journal of Metabolomics

To understand the effects of tobacco consumption, global metabolomic profiles were generated. Here, we describe metabolomic changes in oxidative stress and inflammation pathways.


Changes in Biomarkers of Exposure and Subjective Effects When Smokers Switch to Dual Use of Cigarettes and Either Snus or a Dissolvable Tobacco Product: A Summary of Three Clinical Studies

Elaine Round, Leanne Campbell, Mitchell Stiles, Mixhael Dixon, Michael Borgerding

Contributions to Tobacco & Nicotine Research

A series of ambulatory clinical studies were conducted to evaluate changes in biomarkers of tobacco exposure and subjective product ratings when adult smokers switched to dual use of cigarettes with Camel Strips (Strips), Camel Sticks (Sticks), or Camel (SNUS). In all studies, subjects smoked ad libitum for one week (baseline). In incremental stages over three subsequent weeks, subjects were instructed to reduce cigarettes per day (CPD) by at least 75% and include use of one type of smokeless tobacco product (STP).


Study of cardiovascular disease biomarkers among tobacco consumers. Part 2: biomarkers of biological effect

Brian Nordskog, Buddy Brown, Kristin Marano, Leanne Campbell, Bobbette Jones, Michael Borgerding

Inhalation Toxicoloogy

An age-stratified, cross-sectional study was conducted in the US among healthy adult male cigarette smokers, moist snuff consumers, and non-tobacco consumers to evaluate cardiovascular biomarkers of biological effect (BoBE). Physiological assessments included flow-mediated dilation, ankle-brachial index, carotid intima-media thickness and expired carbon monoxide.


Study of cardiovascular disease biomarkers among tobacco consumers. Part 1: biomarkers of exposure

Leanne Campbell, Buddy Brown, Bobbette Jones, Kristin Marano, Michael Borgerding

Inhalation Toxicoloogy

A study was conducted to evaluate biomarkers of biological effect and physiological assessments related to cardiovascular disease (CVD) among adult male cigarette smokers (SMK), moist snuff consumers (MSC) and non-consumers of tobacco (NTC). Additionally, biomarkers of tobacco and tobacco smoke exposure (BoE) were measured in spot urines and are reported here.


Study of cardiovascular disease biomarkers among tobacco consumers. Part 3: evaluation and comparison with the US National Health and Nutrition Examination Survey

Kristin Marano, Steven Kathman, Bobbette Jones, Brian Nordskog, Buddy Brown, Michael Borgerding

Inhalation Toxicoloogy

Cardiovascular disease (CVD) biomarkers of biological effect (BoBE), including hematologic biomarkers, serum lipid-related biomarkers, other serum BoBE, and one physiological biomarker, were evaluated in adult cigarette smokers (SMK), smokeless tobacco consumers (STC), and non-consumers of tobacco (NTC). Data from adult males and females in the US National Health and Nutrition Examination Survey and a single site, cross-sectional study of healthy US males were analyzed and compared.


Particle Size Distribution of E-Cigarette Aerosols and the Relationship to Cambridge Filter Pad Collection Efficiency

Steven Alderman, Chen Song, Serban Moldoveanu, Stephen Cole

Contributions to Tobacco & Nicotine Research

Described here is a study in which e-cigarette aerosols were collected on Cambridge filters with adsorbent traps placed downstream in an effort to capture any material passing through the filter. Amounts of glycerin, propylene glycol, nicotine, and water were quantified on the filter and downstream trap.


Consumption patterns and biomarkers of exposure in cigarette smokers switched to Snus, various dissolvable tobacco products, Dual use, or tobacco abstinence

George Krautter, Peter Chen, Michael Borgerding

Regulatory Toxicology and Pharmacology

The objectives of this clinical study were to evaluate changes in tobacco product use behavior and levels of selected biomarkers of exposure (BOEs) for smokers who switched to one of six conditions during clinical confinement: exclusive use of; Camel Snus, Sticks, Strips or Orbs, controlled Dual use of cigarettes and Camel Snus, or tobacco abstinence.


Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

Gloria Malpass, Subhashini Arimilli, G.L. Prasad, Allyn Howlett

Toxicology and Applied Pharmacology

Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR.


Comparison of Consumption Patterns, Biomarkers of Exposure, and Subjective Effects in Cigarette Smokers Who Switched to Dissolvable Tobacco (Camel Orbs), Dual Use, or Tobacco Abstinence

George Krautter, Michael Borgerding

Nicotine and Tobacco Research

The objectives of this trial were to investigate short-term changes in product usage, tobacco-related biomarkers of exposure, and subjective effects in smokers who switched to dissolvable tobacco (Camel Orbs) use. Participants were randomized into 1 of 4 groups (continued smoking, switched to consuming Orbs, switched to dual use of cigarettes and Orbs, and tobacco abstinent) and confined for 6 days with dietary restrictions


Combusted but not smokeless tobacco products cause DNA damage in oral cavity cells

Hong Gao, G.L. Prasad, Wolfgang Zacharias

Environmental Toxicology and Pharmacology

The aim of this work was to investigate genomic DNA damage in human oral cavity cells after exposure to different tobacco product preparations (TPPs). The oral carcinoma cell line 101A, gingival epithelial cells HGEC, and gingival fibroblasts HGF were exposed to TPM (total particulate matter from 3R4F cigarettes), ST/CAS (2S3 smokeless tobacco extract in complete artificial saliva), and NIC (nicotine).


Electronic cigarette aerosol particle size distribution measurements

Bradley Ingebrethsen, Stephen Cole, Steven Alderman

Inhalation Toxicology

The particle size distribution of aerosols produced by electronic cigarettes was measured in an undiluted state by a spectral transmission procedure and after high dilution with an electrical mobility analyzer.


Assessment of mouth-level exposure to tobacco constituents in U.S. snus consumers

John Caraway, P.X. Chen

Nicotine and Tobacco Research

The objective of this study was to evaluate the mouth-level exposure (MLE) to selected tobacco constituents from snus by adult consumers of Camel SNUS (CSNUS).


Evaluation of cytotoxicity of different tobacco product preparations

Subhashini Arimilli, Brad Damratoski, Betsy Bombick, Michael Borgerding, G.L. Prasad

Regulatory Toxicology and Pharmacology

Here, we investigated the relative biological effects of 2S3 reference ST, and whether ST elicits differential cellular/molecular responses compared to combustible tobacco product preparations (TPPs) prepared from 3R4F cigarettes. Total particulate matter (TPM) and whole smoke conditioned medium (WS-CM) were employed as combustible TPPs, while the ST extract was used as non-combustible TPP.


Differential cell-specific cytotoxic responses of oral cavity cells to tobacco preparations

Hong Gao, G.L. Prasad, Wolfgang Zacharias

Toxicology in Vitro

To examine the effects of standardized (reference) tobacco preparations on human oral cavity cells, two oral squamous cell carcinoma cell lines (101A, 101B) and normal human gingival epithelial cells (HGEC) were treated with cigarette smoke total particulate matter (TPM), smokeless tobacco extracted with complete artificial saliva (ST/CAS), or whole-smoke conditioned media (WS-CM).


Cadmium exposure and tobacco consumption: Biomarkers and risk assessment

Kristin Marano, Ziad Naufal, Steven Kathman, Joy Bodnar, Michael Borgerding, Charles Garner, Cody Wilson

Regulatory Toxicology and Pharmacology

To investigate whether cadmium has an independent role in diseases associated with tobacco consumption, epidemiology data were reviewed, biomonitoring data were analyzed, and probabilistic risk assessment (PRA) was performed.


Differential exposure biomarker levels among cigarette smokers and smokeless tobacco consumers in the National Health and Nutrition Examination Survey 1999–2008

Ziad Naufal, Kristin Marano, Steven Kathman, Cody Wilson


Using the US National Health and Nutrition Examination Survey (NHANES, 1999–2008), biomarkers of volatile organic compounds, halogenated aromatic hydrocarbons (HAHs), polycyclic aromatic hydrocarbons (PAHs), acrylamide, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and metals were evaluated.


Toxicological evaluation of smokeless tobacco: 90-Day rodent feeding studies

Eugenia Theophilus, Johnnie Hayes, Ryan Potts, Paul Ayres, Chandra Williams, Charles Garner

Experimental and Toxicologic Pathology

This manuscript presents data from 90-day toxicology studies designed to characterize the subchronic effects of a smokeless tobacco blend and an aqueous extract of that blend when administered to rodents in NTP-2000 feed. Positive control (nicotine tartrate) and treatment groups were matched for a range of nicotine levels.

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