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UNITED STATES OF AMERICA
DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
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CENTER FOR TOBACCO PRODUCTS
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ELECTRONIC CIGARETTES AND THE PUBLIC HEALTH: A PUBLIC WORKSHOP
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June 2, 2015 8:00 a.m.
The Marriott Inn and Conference Center
Chesapeake Ballroom Salons A&B University of Maryland University College (UMUC)
3501 University Blvd. East Hyattsville, MD 20783
FDA:
CAROLYN DRESLER, M.D., M.P.A. Associate Director for Medical and Health Sciences Workshop Moderator Center for Tobacco Products JEANNIE LIMPERT, M.D. Medical Officer Office of Science Center for Tobacco Products
This transcript has not been edited or corrected, but appears as received from the commercial transcribing service.
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PUBLIC COMMENT SPEAKERS KEVIN ALTMAN CITMA BILL GODSHALL Smokefree Pennsylvania ALI A. ROSTAMI, Ph.D., ASME Fellow ALCS Research Development & Engineering Altria Client Services SCOTT BALLIN Health Policy Consultant ANDREW COLLINS Imperial Tobacco SVEN-ERIC JORDT Duke University School of Medicine CHRISTOPHER WEBBER Free to Vape GREGORY CONLEY American Vaping Association ERICA HALLER-STEVENSON National Association of County and City Health Officials MARK GREENWOLD Campaign for Tobacco-Free Kids JAMES XU Avail Vapor
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EXHALED E-CIGARETTE AEROSOLS: EVALUATION OF CONSTITUENTS AND EXPOSURE ANDREW PERSILY, M.A., Ph.D. National Institute of Standards and Technology JONATHAN THORNBURG, Ph.D. Research Triangle Institute MOHAMADI SARKAR, M.Pharm., Ph.D. Altria Client Services JOHN D. PRITCHARD Imperial Tobacco Limited, UK FRANCIS (BUD) J. OFFERMANN, PE, CIH Indoor Environmental Engineering MACIEJ GONIEWICZ, Ph.D., Pharm.D. Roswell Park Cancer Institute HEALTH EFFECTS OF SECONDARY AND TERTIARY E-CIGARETTE EXPOSURES NEAL L. BENOWITZ, M.D. University of California, San Francisco DONALD GRAFF, Pharm.D. Celerion J. MICHAEL COLLACO, M.D., M.B.A., M.P.H. Johns Hopkins Medicine JEANNIE LIMPERT, M.D. FDA Center for Tobacco Products KEVIN CHATHAM-STEPHENS, M.D. Centers for Disease Control and Prevention DIANE M. ASHTON, M.D., M.P.H. March of Dimes Foundation National Office CARL PHILLIPS, Ph.D. Consumer Advocates for Smoke-free Alternatives Association
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M E E T I N G
(8:01 a.m.)
DR. LIMPERT: Welcome back to Day 2 of our third workshop
on e-cigarettes.
I am Dr. Jeannie Limpert from the Center for Tobacco
Products, Office of Science.
Yesterday we addressed population health issues associated
with the use of these products. This morning we will first
hold a public comment session. Each presenter will be limited
to a 3-minute presentation. As mentioned yesterday, if the
public comment session ends early, we will move on to the rest
of the agenda. This may mean that we will run ahead of
schedule today.
After the public comment session, we will have two
sessions consisting of a series of presentations followed by
clarifying questions and panel discussions. The first session
will focus on the evaluation and constituents of exhaled
e-cigarette aerosols, and the afternoon session will focus on
the health effects of e-cigarettes in nonusers. Dr. Carolyn
Dresler from CTP Office of Science will again be our moderator.
Similar to yesterday, our presenters have been asked to keep
their presentations within the time period allotted, and a
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timer will be used in order to stay on schedule.
We will have two 15-minute breaks, an hour for lunch, and
end the day at approximately 3:30.
Similar to yesterday, if you have a clarifying question or
a question for the panel, if you are here on site, please write
your question on one of the cards provided, using legible
handwriting, and give the card to one of our volunteers. If
you are participating by webcast, you can e-mail your questions
to [email protected]. Please write on the card
whether the question is clarifying and, if so, for which
speaker or whether the question is for the panel. We will try
to get to all the questions but may not be able to do so due to
time limitations. We will try to combine related questions to
avoid duplication.
The workshop is being recorded. The transcript and
webcast recordings will be posted on our website when they
become available.
I would like to remind you of a few things from yesterday.
The purpose of this workshop, and the two previous
workshops, is to gather scientific information about this novel
category of tobacco products. This workshop is not intended to
inform the Agency's proposed deeming rule. We are not looking
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for advice or consensus but are interested in an open exchange
and discussion of scientific information.
We request that all workshop participants be considerate
and respectful of all other participants, the information being
presented, and the opinions expressed by others.
We request that you refrain from use of all tobacco
products, including e-cigarettes and other electronic nicotine
delivery systems, during the meeting.
The restrooms can be found outside this room, in both
directions down the hallway.
For lunch, a deli buffet will be available for purchase in
Patuxent Room 2, and the cost of the buffet is $14.
Please note that for any media inquiries, Michael
Felberbaum is our press contact, and he's standing in the back
of the room.
I would now like to turn the podium over to our moderator
for the workshop, Dr. Carolyn Dresler.
DR. DRESLER: Thank you. And good morning. All right,
let's start.
Everybody see the green, yellow, red? So green you're
okay to go, yellow, be thinking about wrapping it up, and this
is where I stand up, okay? And then if I walk towards you,
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you're done, okay? But you also have a timer here, and it says
the amount of time that you have.
So could we please have the first speaker?
(Off microphone comment.)
DR. DRESLER: Okay.
MR. ALTMAN: That will be Number 2 on your scorecard, but
Number 1 in your heart, okay?
(Laughter.)
MR. ALTMAN: My name's Kevin Altman. I work with a lot of
people at already regulated companies, through tobacco,
smokeless, and roll your own, but I'm also working now with a
lot of e-companies. Our role through CITMA is to help people
understand how FDA involves and works with their company so
they can comply with all the regulations that are coming.
So I'm not a scientist, so excuse me for my ignorance, for
most of you that have much more advanced degrees than I, but I
want to make two points today. If you watched yesterday, you
could see there's a wide array of science on these products, a
wide array. You can also see a lot of bias that creeps into
that science because you're all talking about the same product.
Yet some people say oh, this is awful, and some people say this
is the best thing since sliced bread. That's confusing to a
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non-scientist, and it's certainly confusing to the public.
So what I think is appropriate is that the stakeholders on
all sides, be they antis, the non-antis, the pros, the
industry, the FDA -- these groups need to come together, see if
there's a way to formulate studies where the same questions are
asked to the various groups you want to ask so you get good
science. Not looking for a particular outcome, but what does
the science really tell us, because the FDA's objection and
goal is to see what the health effect is on the population as a
whole.
I looked at something yesterday. If we heard "ever use"
one time, we heard it 100 times. I don't understand how
somebody who uses something once in 30 days is a user. I'll
give you a prime example. I like ice cream. At the hotel last
week, Chunky Monkey was the only thing they had. Ben and
Jerry's. Never had it. Will never have it again. I'm not a
user, but I had it one time. And that's a live example.
So I would just ask that the groups that are going to be
informing this science -- and we have FDA, I think, doing 50
studies, somewhere in the neighborhood, I hear, of 50
studies -- we need to make sure those studies are coordinated,
and the questions and the answers are tailored to the right
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group of people. We don't want to talk to young people, as an
industry. It's not something we think is appropriate, but we
understand that's something that has to be done.
But we have to get away from the way we used to think
about doing scientific studies under cigarettes because these
products are totally different than cigarettes. So if we run
under that same model, we're probably not going to get the
right answers.
So I'd ask that anyone in the room that's going to be
involved in this process going forward, make sure you work
together to come up with a study, survey, whatever you want to
call it, that gets us the right science, because the science is
what has to take us where we go. This is an ever-changing
environment we live in, and it's not like traditional tobacco
products, because they haven't changed in 20 years. These
products change daily. The way people use these products
changes daily. And it's important to keep that in mind and
maybe go back now and look at, okay, what did we ask in the
past? And what I hear from some people is, well, if we do
that, Kevin, and we make these changes, we have no way to
compare it. It's okay that we can't compare something to last
year or 2 years ago, because what's important is what are we
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doing going forward?
Thank you.
(Applause.)
DR. DRESLER: Okay. So the request is -- and I know there
are some empty chairs and there are some travel issues, et
cetera. So as the next speaker comes up, if you could come to
the next speaker chair, because that will make sure that your
correct name is up there. So that will help a lot. So, for
example, Bill is coming up to the front, and the next speaker
would move over to the next speaker chair, over there. That
helps the process. So we'll see. Kindly.
MR. GODSHALL: I'm Bill Godshall, Founder and Executive
Director of Smokefree Pennsylvania. Since 1990 we've
successfully campaigned to ban smoking in work places, stop
cigarette marketing to youth, increase tax rates on cigarettes,
and require the FDA to impose a regulation requiring graphic
warnings on all cigarette packs, something FDA doesn't deem
important.
In 2010 we filed an amicus brief with other public health
advocates opposing the FDA's e-cigarette import ban with the
D.C. Court of Appeals, which upheld Judge Richard Leon's 2010
ruling striking down FDA's ban as unlawful.
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Since 2011 we've opposed the FDA's proposed deeming
regulation because it would ban more than 99.9% of all nicotine
vapor products currently on the market, protect cigarettes,
increase smoking, threaten the lives of several million vapers
and tens of millions of smokers, and create a huge black market
of totally unregulated vapor products.
For disclosure, neither Smokefree Pennsylvania nor I have
ever received any funding from any tobacco, drug, or vapor
product company, nor from any government agency whose policy is
to ban vapor products, which is also a clear conflict of
interest.
The scientific and empirical evidence consistently finds
that nicotine vapor products are 99%, plus or minus 1%, less
hazardous than cigarettes, have never been known to be
associated with any disease, and pose no known risk to
nonusers. Nicotine vapor products have already replaced 3
billion packs of cigarettes, and more than 99% of all nicotine
vapor products are consumed by smokers or by ex-smokers who
switched to vapor products, which are more effective and pose
fewer risks than FDA-approved and hawked smoking cessation
drugs.
Adult and teen surveys consistently find that ex-smokers
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account for more than 90% of past 30-day e-cigarette users. It
appears that more than 99% of daily vapers are smokers or ex-
smokers who have switched to vaping. But the Department of
Health and Human Services has refused to conduct or fund any
surveys that inquire about daily vaping or even if nicotine was
vaped, which has only served to bury the truth.
Two recent surveys found that 3 and 4 million U.S. smokers
respectively are no longer smokers because they switched to
vapor products. Thus, it is mathematically impossible for
vapor products to harm overall public health, even if every
nonsmoker in America began daily vaping. And yet there's no
evidence that vapor products have created daily dependence in
any nonsmoker anywhere in the world, nor is there any evidence
that vaping has served as a gateway to cigarette smoking for
anyone.
But since 2009 the FDA and the CDC have made many false
and misleading fear-mongering claims to confuse, scare, and
lobby to ban these lifesaving products under the deceitful
guise of protecting children and public health.
Dozens of DHHS funding recipients have also misrepresented
evidence on the scientific -- to scare the public on the
scientific evidence, to scare the public and the lobby to ban
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vapor products and/or vaping, including most presenters and
panelists FDA invited to speak at these three so-called public
workshops on e-cigarettes. The FDA should stop protecting
cigarettes and start protecting public health and telling the
truth.
(Applause.)
DR. DRESLER: Next speaker, please.
(Off microphone comment.)
DR. DRESLER: No, I don't think so. This isn't Greg.
(Off microphone comment.)
DR. DRESLER: We'll let him go. We'll get his right, but
we'll still get to you in a few minutes. Okay.
DR. ROSTAMI: Good morning. Thank you for the
opportunity. My name is Ali Rostami. I am an associate
principal scientist at Altria Client Services, and I'm speaking
on behalf of Nu Mark, which develops and markets e-vapor
products.
FDA is interested in gathering scientific information on
questions related to health effects of e-cigarettes on
nonusers. Some of these questions are what chemicals are
delivered to nonusers; how aerosol properties impact exposure;
how far aerosol can travel; what is the aerosol level in
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different space settings?
Running multiple experiments in a study to account for all
combinations of these variables is challenging. As a result,
we're using a parallel approach. We're using computational
modeling tools to simulate multiple scenarios. These models
will be validated by the experimental data that my colleague,
Dr. Sarkar, will talk in the next session.
The models are based on physical and thermodynamic
interactions between air, vapor, and particles, as shown in
this diagram. Exhaled aerosol is released into the room. It
mixes with the room and the ventilation air. It dilutes and
some of the volatiles evaporate. Over time, some of the
aerosol is carried out by ventilation air, some inhaled by
occupants, some remains airborne indoor, and some deposits on
the surface. These processes can be represented mathematically
by a set of equations, including conservation of mass,
vapor/liquid partitioning, mixing and dilution, as well as air
flow and species transport.
The model takes in the measure of the aerosol exhaled,
exhaled aerosol properties, space size, air change rate as
inputs and delivers the full components on the right as
outputs. The most relevant to the secondhand and thirdhand
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exposure are also indicated in this diagram.
To summarize, we developed computational models using
principles similar to those referenced by EPA for indoor air
quality analysis.
We are validating models using data from controlled
studies that my colleague Dr. Sarkar will talk about.
We'll apply models to address types of questions listed
earlier, and we will run simulations for multiple scenarios.
We intend to submit the work for publication, and we will
improve the models as additional data become available.
Thank you.
(Applause.)
MR. BALLIN: Good morning, everybody. I'm Scott Ballin,
and I've been involved in tobacco and nicotine policy related
issues for 40 years. Many things have happened over that 40-
year period, and many things will continue to evolve in the
coming months and years. As this is the last workshop before
the deeming regulations are issued, I wanted to make some
general comments.
Much of the discussion with respect to the impact on the
use of ENDS on the population is focused on, and presented
from, the standpoint of concerns about unintended consequences.
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Will such products keep people from quitting? Will they
encourage new users? Will they result in dual use? Will they
entice children and adolescents to use the products? The
answers to those questions depends on how we decide to move
forward.
And while using models and other tools are helpful in
trying to evaluate population effects, I think we all know that
this is a dynamically changing environment. I don't think
anyone, for example, could have predicted that the ENDS
marketplace would have developed as rapidly as it has. And
everyone seems to concur that innovation and technology are
going to continue to impact that marketplace.
It doesn't take an expert to recognize that we are dealing
with a very different environment, one that's going to require
new thinking and new processes in working together, which is
why I have on many occasions commended Director Zeller, as well
as the Agency, for speaking about the need for more rational
and comprehensive tobacco policy that is based on the continuum
of risk.
In addition to the questions I have mentioned, I think
there's an overarching, equally important question that needs
to be asked. What are the unintended consequences of not
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making science-based, lower-risk, regulated alternative
products available to the users of cigarettes?
This year 5.3 million people will die globally from the
use of the deadly cigarette. In this country, over 400,000
will die prematurely from using the combustible cigarette. The
devastating effects on the cigarette -- on the population
should be a paramount consideration in whatever is considered
and discussed, whether it be ENDS or other lower-risk,
noncombustible products such as snus, lozenges, dissolvable
gums, or even NRT.
It really is time to seize the opportunity to establish a
regulatory structure that meets the rapidly changing
environment, and I encourage the Agency to make that the
primary priority.
And, lastly, let me reiterate, because there was a lot of
discussion on children yesterday and adolescents. I think the
majority of people do agree that all stakeholders need to be
involved in ensuring that all tobacco, nicotine, and
alternative products, including ENDS, should not be purchased
or possessed or used by children and adolescents. Dealing with
that issue head-on, on both the individual and the public
population, I have suggested that there should be a national
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summit to discuss those issues and to work cooperatively to
achieve those objectives.
Thank you very much.
(Applause.)
DR. DRESLER: Andrew Collins.
DR. COLLINS: All right. Good morning, everybody. My
name is Andrew Collins, and I currently work for Imperial
Tobacco, within the product science department. I'll be
presenting to you some data we ran from a consumer survey
looking at e-vapor products. What I'll be doing is
specifically looking at how the consumers and the response to
that survey reported that EVP, or e-vapor products, affected
their tobacco use.
So our survey encompassed a little over 2,100 different
adults in seven different markets, shown up here. Top-level
demographics -- there we go. Sorry. It's an online survey of
weekly vapers who were vaping for at least a month. There we
go.
So top-level demographics show that the entire cohort,
about 72% of them, are dualists. So that is to say they smoke
and use EVP products simultaneously. Twenty-four percent are
quitters. So these are people who used to smoke cigarettes but
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have since quit since starting using their EVP products. And
3% are defined as newcomers. So these are people who self-
perceive as coming from a non-smoking background. But in order
to actually qualify for the survey, there had to be some degree
of smoking background there, even if it was just one cigarette.
So this graph illustrates the percentage of people who are
dualists versus those who are exclusive EVP users. Here we can
see that for heavy user classes, over 100 puffs per day, we
have 29% of people who are actually quitters. And if we
compare that to -- if the slide works. It's not working,
sorry, the forward. Oh, there we go. It did, and it's taking
its time, by the looks of it. Let's go back. So there we go.
If we compare that to the medium and light users, we can see
that the contrast is actually quite stark, particularly when we
contrast the heavy users to the light users.
So what about those who still smoke? How does EVP affect
their tobacco consumption? Well, broadly speaking, two-thirds
of people do actually report cutting down on their cigarette
consumption. So, for everybody -- so this is all the dualists
-- we see a mean loss of about five cigarettes per day compared
to levels before they started smoking. So that's a little over
27%.
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The story gets a little more interesting if we compare
that and once again stratifying to heavy, medium, and light
users. So here we can see that the heavy users showed the
biggest loss in tobacco consumption, averaging about eight
cigarettes less per day compared to levels before they started
smoking. So that's about a 38% reduction.
So, in summary, heavy users of EVP were found to be far
more likely to be quitters than those who use EVP less
frequently. For those who still smoked, we see that the
majority actually successfully cut down on their tobacco
consumption, with heavy users showing the biggest reductions.
This clearly demonstrates EVP's potential as a tool to
help users reduce their tobacco consumption. Any future
regulations on this topic should be proportional in order to
realize this opportunity and give people the chance to cut down
on their tobacco consumption with effective devices.
Thank you very much for your time. If you have any
questions, I'll be happy to answer them if you come find me
later on.
(Applause.)
DR. JORDT: Okay, my name is Sven-Eric Jordt. I am an
Associate Professor in the Department of Anesthesiology of Duke
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University School of Medicine. My expertise is in the biology
of chemical irritant receptors. In 2004 we discovered a key
receptor for toxic aldehydes, and we also linked chemical
irritation to asthma, and recently we published on mechanisms
through which menthol facilitates smoking initiation. And we
are funded by NIH.
So I'm here to voice a scientific concern about the
content of highly reactive aldehydes that are flavors in the
e-liquids, specifically unsaturated aldehydes such as
cinnamaldehyde, carvone, or damascenone. So these are
contained in some of the popular flavors, but also at very high
concentrations in some flavors sold by boutique vendors online.
This is just one example. We tested a wide range of different
products.
You can see here that this Atomic Cinnacide flavor, sold
by the company Tasty Vapor, has concentrations of more than 7%
at the 24 mg/mL nicotine solution, 13% of a reactive
unsaturated aldehyde. You can also see that the consistency
among the different flavors offered is very low. So the "no
nicotine" flavor has 7%, and the nicotine has 13%. And this
again changes depending on when this is purchased.
So reactive aldehydes are obviously acute irritants.
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There is a concern about these effects. But what I also wanted
to mention, they are known as allergens. So it's known in
studies in the '90s and from flavor industry workers that these
workers can develop contact allergies against cinnamaldehyde.
Also, in the actual -- in bakeries, this has been found. These
compounds can induce contact stomatitis. This is an allergic
condition of the mouth. Carvone has been showing the same.
So I just wanted to stress that these aldehyde flavors
don't only have acute effects, but they can also cause
allergies.
And I would like to advise FDA to regulate aldehyde-
flavoring contents, especially at these boutique vendors, and
support further research that can study the potential allergic
effects of these compounds.
Thank you very much.
(Applause.)
MR. WEBBER: Good morning. My name is Chris Webber. I
started smoking at age 15 and smoked for 10 years. Two years
ago I discovered vaping and put down cigarettes immediately.
Currently I'm also the assistant director of Free to Vape.
We're a national nonprofit organization representing tens of
thousands of vapers who successfully replaced their tobacco
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with vapor products.
Now, regardless of what side of the debate you're on, we
all share a common goal, which is ending the mortality or
morbidity associated with tobacco use. With close to a half a
million deaths a year attributed to smoking cigarettes and not
a single death ever attributed to vaping, it should be clear
that combustible tobacco is the enemy, not vapor devices.
We heard quite a bit yesterday about youth initiation of
vapor devices. But what we have not heard much about is the
continued rate of youth smoking initiation, which until the
emergence of vapor devices remained stuck at about 20%.
Now, the current generation grew up in a tobacco-control
utopia. They've never been exposed to cigarette ads. Taxes
make it exorbitantly expensive. And youth are routinely and
explicitly told about the health risks. The fact remains,
however, one in five youths still pick up a cigarette and light
it. And this tells us one thing very clearly. The existing
methods of tobacco control simply do not work.
The definition of insanity is to repeat the same action
for 20 years and expect a different result. Unfortunately, it
would seem like many tobacco control professionals in this room
are advocating doing just that. Twenty years of failure and
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millions of lives lost should tell us that we need vapor device
regulation based in reality, not fantasy. Though one could
argue a completely nicotine-free society is the ideal outcome
we should work towards, the magnitude of the tobacco control
movement over the past 2 decades, coupled with its continued
failure to stem or eliminate youth smoking initiation,
demonstrates one thing very clearly: a nicotine-free society is
simply not realistic or achievable. The reality is, in a free
society, youth will rebel, youth will experiment, youth will
make poor choices simply because they're told not to.
Unfortunately 20 years of data indicate that despite all of our
best efforts -- and I know we have all been trying really
hard -- one of those poor decisions is going to be starting
tobacco use.
Now, I'm by no means advocating for youth adoption of
vapor devices, and obviously all the age restrictions that
we're currently employing should continue to be employed. But
I am suggesting that we must accept the simple reality that
there's going to be a percentage of youth that will always
rebel and choose to inhale and exhale substances other than air
to do so.
Therefore, we must also accept that vapor -- we must also
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accept that youth initiation of vapor devices isn't always
necessarily a public health cost, because that has to be
weighed against the probability of that individual youth
rebelling with tobacco instead.
If we really want to create a society free from the death
and destruction of tobacco, we have to accept that youth
rebellion is a fact, and that while inhaling vapor may pose a
slight risk over breathing pure air -- and again we saw, in the
last workshop, it's a pretty small risk, you know, 95%, 99%
less harmful -- we have to agree that it's better than smoking.
And in the past 20 years, you know -- and this is my
generation. We grew up in a system designed to prevent us from
smoking, and I still did. I prefer that the youth don't smoke.
And that's it. Thank you.
(Applause.)
MR. CONLEY: Good morning. My name is Gregory Conley, and
I am the president of the American Vaping Association, a
nonprofit that advocates for small- and medium-sized businesses
in the vapor market. In August I will be celebrating 5 years
as a nonsmoker.
Ever since the first surveys on vapor product usage were
released years back, fair-minded researchers and advocates have
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been trying to communicate that better survey methods are
necessary to truly understand how adults and teens are using
and experimenting with vapor products. I was extremely pleased
to see that our calls have been vindicated, as several of
yesterday's presentations acknowledged the need for more
thorough and detailed data collection, especially on details
like days of the month usage and nicotine versus non-nicotine
usage.
On the other hand, regrettably, many of yesterday's
presenters were clearly guided more by ideology and less by
science and reality than others. For example, first, a
panelist assumed that until regulations are in place, one
cannot assume that vaping is any safer than smoking, as if the
absence of scientific -- as if the absence of regulation
somehow cancels out the clear body of scientific evidence on
the topic.
Second, on the marketing panel, not one speaker could
admit that if restrictions led to less adult smokers using
vapor products, such a regulation could be bad for public
health. That's not balanced.
Third, upon hearing that many doctors were truthfully
informing adult smokers that vaping was a good way to quit or
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substantially reduce their smoking, one panelist gleefully
began plotting ways to reverse that by misinforming doctors of
the relative risk of smoking versus vaping.
Fourth, panelists pushed for flavor bans without even
pausing to consider whether such restrictions could harm public
health by discouraging quitting, while another panelist felt
the need to disclose "I'm not pro harm reduction," as if that
wasn't already clear.
Fifth, panelists endorse campaigns that seek to
unethically scare smokers away from switching to vaping by
highlighting scary-sounding chemicals found in vapor, even if
those levels are far below those allowed in inhalable
medications.
To cap it off, the day ended with a panel where not a
single person was willing to state that it would be a bad
thing, and that it is a bad thing, for smokers to grossly
overestimate the risk of vapor products versus smoking.
I will close by proposing this. Instead of having
speakers declare their financial conflicts of interests, it may
be more useful for future participants at these meetings to
start off by answering the question: Are vapor products less
hazardous than smoking? After all, not knowing the truth about
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relative risk, or being unwilling to tell the truth about
relative risk, is a much bigger conflict than any financial
interest ever could be.
Thank you.
(Applause.)
MS. HALLER-STEVENSON: Good morning. I'm commenting on
behalf of the National Association of County and City Health
Officials, also called NACCHO. Thank you for calling attention
to these important issues.
NACCHO is the voice of over 2,800 local health departments
across the country. During this workshop, we are learning a
lot about research data regarding use of e-cigarettes, products
that are used by adults and youth, the related health effects,
and consumer protections about the products. I'm going to tell
you how local communities are grappling with the surge in use
of e-cigarette products and their availability and what that
means for the public's health.
In the absence of overarching laws and product regulation,
local health departments are establishing policies regarding
e-cigarettes in their own communities to create environments
that make it easier for people to be healthy and safe. Over
350 communities and three states have established e-cigarette
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use restrictions to align with their existing smoke-free air
laws. Communities are also beginning to create minimum-age-of-
sale laws for e-cigarettes to reduce youth access to the
products. There is a demand from communities to minimize the
risk to the public.
The availability of scientific information regarding the
safety and potential risks to users and bystanders related to
e-cigarettes is increasing. The area of concern for the
public's health is that there is a risk involved with the use
of e-cigarettes and that the risks should be -- there is a risk
that should be mitigated.
Generally speaking, the position of the public health
sector is not to outlaw e-cigarettes. It is to protect the
public's health. E-cigarette users should know what the
products contain, and the associated risks, through consistent
and accurate product and warning labels.
Nonusers should not be exposed to e-cigarette aerosols in
public venues, in order to limit harm. Youth access to
e-cigarettes, as many of us have already agreed to, should be
restricted to the remarkable -- due to the remarkable increased
use of the products. And child-resistant packaging should be
in place for the e-liquids to prevent the escalating child
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poisonings, as reported to poison control centers across the
country.
We cannot leave local communities to manage this emerging
public health issue alone. We need to create an environment
that supports informed e-cigarette users and protects youth and
nonusers. We have an opportunity to reduce the potential for
harm much earlier than we did related to the increase and
popular use of combustible tobacco products. Don't make this a
50-year path.
Thank you for your attention and for the opportunity to
comment on this important issue.
(Applause.)
MR. GREENWOLD: I'm Mark Greenwold, senior consultant with
the Campaign for Tobacco-Free Kids.
In order for e-cigarettes to play a constructive role in
reducing tobacco-related disease, FDA must act promptly to
subject them to regulation. The unregulated market for
e-cigarettes has permitted e-cigarette manufacturers to target
adolescents in their advertising and marketing, and led
millions of young people to experiment with this addictive
product. Regardless of the potential e-cigarettes may have to
help adults quit smoking, exposing our kids to addictive
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products is too high a price to pay. FDA's first and
overriding priority should be the protection of our youth.
Nicotine is not a harmless substance, especially to kids.
Besides being highly addictive, it interferes with brain
development in adolescents. Kids who use e-cigarettes not only
risk addiction, they also jeopardize their mental development.
Increased e-cigarette usage among kids is no accident. It
is the inevitable result of federal regulatory paralysis that's
done nothing to prevent or even discourage e-cigarette
companies from marketing to kids.
FDA should take the following steps:
First, it should promulgate the deeming rule as soon as
possible. When it sets a target date, it should actually meet
it.
Second, it should immediately apply to e-cigarettes all
the provisions of the 2010 rule on marketing to youth.
Third, it should prohibit the sale of e-cigarettes in
remote transactions, including Internet sales.
Fourth, it should prohibit kid-friendly flavors in
e-cigarettes. To the extent there may be tradeoffs between
maximizing the range of conceivable flavors in order to appeal
to adult smokers and potentially addicting kids to nicotine,
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those tradeoffs should be resolved in favor of preventing kids
from becoming addicted.
Fifth, FDA should adopt rules requiring e-cigarettes to
meet high standards of purity and strict product
specifications, and prohibit the sale of e-cigarettes unless
they're manufactured according to good manufacturing practices.
Sixth, FDA should immediately require child-resistant
packaging of e-cigarettes.
None of these steps would prevent e-cigarettes from
playing a constructive role in promoting adult cessation. The
current unregulated market does nothing to facilitate this
goal. Instead, it rewards the most irresponsible companies who
focus their marketing on young people.
Establishment of a strong regulatory framework is the most
effective way to enable e-cigarettes to help smokers quit while
minimizing the risk of adverse population-wide effects.
(Applause.)
MR. XU: Good morning, everyone. My name is James Xu,
President of Avail Vapor.
In response to FDA's questionnaire, Avail Vapor conducted
a survey last month with 45 retail stores. With the help of
other online websites, we were able to receive 8,500 responses
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within 2 weeks. The complete report is available online at
availvapor.com. And here are some of the key findings.
If you look at the male-to-female ratio, that's about 2:1.
Our largest age group is 30 to 39, closely followed by 20 to 29
and 40 to 49; 85.2% of our respondents have reported that
vaping has helped them to quit smoking. An additional 13.06%
were able to reduce their tobacco use; 69.05% of all
respondents have reported that they're able to quit tobacco use
within 1 month or less. And 96% consider e-cig a much
healthier choice than a tobacco product.
It's not a required field for people to fill out other
comments, but 20% of our surveyors decided to leave their
comments and tell us their personal experience.
Just like we see every day in our stores, most of the
beginners, when they're coming to start vaping, they start with
traditional tobacco and the menthol flavor. Very quickly they
move on to other different flavors.
When we asked them to pick two top choices of the
e-liquid, the number one, by far, is fruity followed by dessert
and savory. And if you look at the traditional tobacco and the
menthol, they are among the least favorite by adult vapers.
And combined, it is about 86% of the users, that they switch
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their flavor at least once every week.
Safe manufacturing is extremely important to all users,
and purchasing habit, mostly online and the specialty stores;
convenience store is only less than 2%. For the e-liquid it's
only 1.4%. And very few of them started vaping without being a
traditional tobacco user.
Thank you. You can find the entire survey result on our
website, availvapor.com. Thank you.
(Applause.)
DR. DRESLER: Do we have anyone else who's -- no? No.
Okay. Then we will move on to our first session.
So the first session after the public comment session is
on Exhaled E-Cigarette Aerosols: Evaluation of Constituents and
Exposure. And our first speaker is Dr. Andrew Persily from the
National Institute of Standards and Technology, speaking on
Relating Airborne Contaminant Emissions to Occupant Exposure.
DR. PERSILY: Good morning. Thanks very much. A pleasure
to be here.
As you can see from the title, you won't see the term
e-cigarettes in there, and I'm not here to talk about that
technology or product specifically. I'm really here to talk
more about indoor air quality in general.
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I am a mechanical engineer at the National Institute of
Standards and Technology, which is an agency of the federal
government up the road a bit, where I've been doing research on
indoor air pollution for a number of years, where we try to
understand if you have a contaminant source, what aspects of
the building and the building systems impact contaminant
concentrations and subsequently human exposure, and how we can
reduce that exposure by different strategies and ideally, you
know, strategies that are effective and don't consume a lot of
energy.
As part of this work, I've also been involved in the
development of voluntary industry consensus standards for
ventilating buildings, and those ventilation rates are based on
contaminant sources that may be a factor.
So, in terms of disclosure and conflict of interest, I
have received a salary from this for 33 years, and I'm still
interested. And some days I'm conflicted, but we aren't doing
any research related to this, again, to e-cigarettes, in
particular.
Okay. So I'm really talking about, you know, if you have
a contaminant source in a building or outside, what concepts
and approaches are used to predict indoor contaminant levels
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and then subsequent human exposure. So, in some ways, this is
less about the user of the e-cigarette than the other building
occupants.
And so when we -- you know, first we think about the
source. What's emitting the contaminant that we care about?
What is the emission rate?
The transport mechanisms. Where does this contaminant go?
How is it removed? Does it stick to surfaces and so on? I
didn't mean to do that, but that's okay.
So, you know, you start with a building and that building
has air coming in. And for many contaminants, you know, that
you have -- that exist in the outdoor air, right? So if you're
trying to understand the indoor contaminant, you better make
sure you understand what's going on outside because you're
bringing air into the building. So that's an important
concept.
Yeah, okay. There you go. And then you have a
contaminant source in the building. There are lots of them.
Very different properties. Some emit one contaminant only, but
that's rare. Most of them can emit a lot of contaminants or a
variety of contaminants at different rates. So that's the next
step in the process.
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And there you go. And then you get the concentration in
the space, which will vary in time and location. And there are
a lot of important details, you know, that we could get into.
And then, finally, you have the people. And while they
all look the same in this sketch, they're all very different in
terms of age and breathing rate. And preexisting health
conditions are an important factor. Do they have asthma or
some other issue which, you know, relates the exposure they
experience to the health risk or comfort situation that they
may realize?
So those are kind of some of the fundamental concepts.
And I'm just going to kind of go through contaminant sources to
emissions, the concentration to exposure, in very general
terms, hopefully providing some useful context for some of the
discussions you're having.
Oh, there we go. So, first, airborne contaminant sources.
There's a whole host of materials and activities in buildings
that emit contaminants. And that's just a fact of life. You
know, if you're going to be inside, which we do -- 90% of our
time is spent indoors unfortunately, and there are things
inside that you need to do. You know, you need chairs, right?
You know, you do want to sit occasionally. So there are
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building materials. And I don't know if these were purchased
from Lumber Liquidators or not --
(Laughter.)
DR. PERSILY: -- but building materials emit chemicals.
The outdoor air can be a pretty important source of indoor
contaminants. And I will note that outdoor air is regulated in
this country by the EPA, and that's a big issue. EPA doesn't
have the regulatory authority for indoor air, but there are
certain agencies that have regulatory authority for specific
types of products.
And then combustion or other activities. This is a very
safe candle because it's not lit. Okay, light it, and it will
produce particulates and all sorts of other chemicals that
might not be as safe.
So, you know, you need to understand the contaminant
sources and the contaminants that might be emitted by those
sources and whether it's a constant source or it's impacted by
temperature or it's impacted by what the occupants do.
And then you're interested in the contaminant emission
rates, and people measure those in environmental chambers.
Here's just kind of a diagram. I'm having trouble with this.
There it is. You know, where you put a source. It might be a
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floor covering or something. It could be just about anything.
Here's a picture of some actual chambers, and you put the
source in there. You put some -- it better be clean air,
right? And then you measure the concentration coming out and
you can back out the emission rate.
But for some contaminants, you know, they will stick to
the surfaces, and it really complicates the calculations. You
need to understand the contaminant and its properties. You can
estimate emission rates from buildings, you know, put the
source in the building and measure the concentration. But
that's tough. I mean, the advantage is it's reality. The
disadvantage is, is that real buildings are complicated and
there are all sorts of things happening.
In general, you know, there's a lot of variability in the
contaminants released, the temporal patterns in those releases,
temperature effects, and a whole host of other issues.
But, you know, these emission rates then get you to the
concentrations, and the concentrations you can get from indoor
air quality modeling. We heard some discussions and that's
kind of what this is. Take a real building and turn it into a
computer model. There are a lot of building features that
impact the concentrations that exist in the buildings: the
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size, the ventilation rate, surface properties, a whole host of
other things, and then the emission rates I've talked about.
And then, finally, you have the concentration and then you
start to talk about exposure. You know, how many people are in
the space? You know, when are they in the space? What is
their age or activity level? And then I mentioned preexisting
health conditions already. And this is the input to the risk
assessment. So, you know, we're talking about the people in
the space exposed to contaminants emitted from various sources.
And we saw an earlier version of this in the comment
session before. But this is just a contaminant -- a very
simplified contaminant mass balance equation that we use to
understand the relationship between contaminant sources,
building ventilation rate, loss mechanisms in the space, and
then generation. I'm not going to go into this in much detail,
but I figured I should show one equation to be true to my
engineering roots.
I will make one point here. Under contaminant
concentration, you know, for different sources, there are lots
of contaminants you might be interested in, and in general,
each contaminant is a different measurement approach, and you
really need to understand the measurement technique you're
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using to get reliable data.
So whenever, for example, I see the concentrations were
not detectable, my first question is, well, what is your
detection limit? You know, because if you have sensitive-
enough equipment, you will detect it -- you know you will
detect it. It may be at a level that you don't care about from
a health or comfort perspective, but you know, keep that in
mind when you read papers and you see "not detectable." Go see
if they said what the detection limit is. And if they didn't
tell you, there's kind of a gap there to keep in mind.
So, you know, I'm talking about indoor exposure to a wide
range of contaminants, but indoor exposure takes place in
buildings, and there are no typical buildings.
You can oversimplify and say there are two types,
residential and commercial. There are about 100 million
dwellings in the United States, you know, and I wouldn't say
every one is different, but there's a lot of variation in age
and size and height and number of occupants and how it's built
and how it's heated and cooled.
And the Department of Energy has this great database where
you can learn all about the residential building stock in the
U.S. I have a link on a later slide.
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What's important to understand is that most residential
buildings are ventilated by leakage. You know, there are leaks
in the walls, and the wind blows and the air comes in. They
are not intentionally ventilated. There's a tiny, tiny
fraction in this country, and it's becoming more common, that
are ventilated intentionally. So most of them are ventilated
by accident.
There are about 5.5 million commercial buildings in the
U.S. that include offices, schools, retail spaces, healthcare,
restaurants, and so on. Again, a lot of variation. DOE has a
database on commercial buildings if you want to look at the
types, because if you're going to relate a source to exposure,
you've got to look at the building. You know, you've got to
understand the building features as well. And in most
commercial buildings, there is a mechanical system that's
designed and installed to bring outdoor air. It might not
function very well and it might not be maintained very well,
but it's there, at least on the plans.
I don't know what I did. There we go. So I talked about
buildings. The other key factor is ventilation. It's not the
most important thing, but it's pretty darn important, and
that's kind of where I've done my research all these years, is
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how much outdoor air is brought into the building? And there
are a lot of factors that influence the ventilation rate of the
building: how it's laid out, how it's built, the air tightness
of the walls, what systems you have in there to heat and cool
and move the air, how it's operated. And that's not just the
operation of the system, but are there operable windows, you
know, because that's going to have a big impact on the
ventilation rate. And how well the system is maintained.
That's a huge issue because you can have a very good system
design, but if it's not maintained, it's not going to perform
very well. And then, finally, weather conditions impact
leakage rates and how the system operates.
You know, a ventilation rate is not a constant number. In
residences, anyway, it's common to see the ventilation vary by
a factor of five to one, just due to weather alone. And so you
need to keep that in mind. When I see somebody in a paper
report a ventilation rate with no information on the conditions
under which that ventilation rate was measured, I don't know
anything, you know, because was it a windy, cold day? Was it a
calm, mild day? Was the system on or was the system off? So a
single ventilation rate without any associated information
isn't very informative.
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Similarly, and maybe more important, you know, an airborne
contaminant concentration measurement in a building without a
ventilation rate is really hard to interpret. You know, was
the ventilation system on? Was it moving five air changes an
hour? Was it moving, you know, 0.25 air changes an hour?
Without that ventilation rate, you really can't interpret the
concentration, and you can't compare it to contaminant
concentrations in other buildings. So that's an important
point to appreciate. You know, you need to understand what's
going on in the building, what's going on with ventilation to
interpret indoor contaminant concentrations.
These are just some -- I mean, these slides would be
available, right? So this is a link to that residential
building survey database, the commercial. The census folks do
an interesting housing survey periodically.
And the EPA Exposure Factors Handbook, if you're not
familiar with it and you're getting into risk assessment, you
need to take a look at it. Well, it used to be a great big
book. Now it's a great big webpage, and it's all sorts of
information that is used to relate exposure to risk. You know,
it has ventilation rate data, and it has building data. You
can look up how many pounds of carrots a 7-year-old girl eats a
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year and things like that, you know, if you're talking about
ingestion exposure.
Some other resources. ASHRAE is the engineering society
that writes ventilation standards in this country. I was
involved in that organization for a long time. Those are
voluntary standards. If they're adopted by a local
jurisdiction, they have the force of law. But these are
standards on how much ventilation air is required in a
building.
There's ASTM standards for measuring contaminant
concentrations and ventilation rates, and a few papers that
we've published on ventilation and infiltration in buildings
that may be of interest if you're pursuing that angle, and an
indoor air quality model, called CONTAM, that we've developed,
that is in the public domain.
So closing thoughts. The bottom line: You know, in order
to understand airborne contaminant sources, you need to look at
the contaminants. You know, not just the one that you happen
to have a device on your shelf that you can measure, but all
the contaminants that may be relevant; you know, the
contaminant measurement accuracy and the limits of detection
that I mentioned; how the source emission rates vary over time;
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the effects of the environment. A good example is temperature.
And I guess I mentioned measurement already. Hopefully the
point got across that the building in which the contaminant
exists and the systems in that building are really important to
understand exposure.
The good news is we have a lot of knowledge and tools and
data, you know, to support estimating human exposure to
airborne contaminant sources. And I mean, that's the good
news. So if you're going to do that kind of work, you need to
take advantage of this knowledge, these tools, and this data to
do it right.
And I believe that's it. It should end with the bottom
line, right? So we did. Thanks very much.
(Applause.)
DR. DRESLER: Okay, our next speaker is Dr. Jonathan
Thornburg from the Research Triangle Institute, speaking on
Methods of Personal Level Measurements of Secondhand Exposure
to Electronic Cigarette Emissions.
Jonathan.
DR. THORNBURG: Thank you. And thank you, Andy; your
excellent presentation made it much easier for me to give mine,
by providing all of that background information.
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So I'm the Director of Exposure and Aerosol Technology at
RTI International. As disclosures, I do not have any financial
interests. I do not receive, and my research program does not
receive, any funding from the government or from industry on
electronic -- related to electronic cigarettes. I did have
some disclosures up there on the slide.
Essentially, if you're going to do your own secondhand
exposure research, it's up to you to pick the types of devices
and measurement methods you want to use, no matter whether
you're in government, industry, academia, or a citizen
scientist. My goal today is to just present the facts.
Before jumping into the background, it occurred to me this
morning that I should probably give some background of why we
might -- you should be collecting secondhand exposure data at
the personal level or at the stationary level, and I think
there are two important reasons.
One, we know there's a lot of research going on, and we're
looking at the health effects. And I think there will be some
talks this afternoon about the health effects from electronic
cigarette emissions and secondhand exposure. Well, if you're
looking at the health effects, you know, a big part of that is
looking at the biomarkers that are produced when you're exposed
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to these chemical contaminants. Well, to do those types of
studies, you need -- you typically do that in an exposure
chamber, and you need to understand what the person is actually
breathing to make that relationship between what's in the air
that they're breathing and what happens inside their body.
Second, there was a lot of discussion yesterday about
longitudinal observational studies, you know, about usage
behaviors and such, or randomized controlled trials. Well, the
same types of studies are conducted when you're looking at
secondhand exposures. But to do that right, you need to
understand what the people are breathing.
As Dr. Persily said, there is the -- the air in our
environment is very complex, and there are lot of the same
contaminants in the outdoor air that might be contained in the
electronic cigarette emissions that lead to secondhand
exposure.
So that means you have to be able to apportion, you have
to do the source apportionment. Where did that exposure to
that contaminant originate? Was it from an electronic
cigarette, or was it from another source, like a candle burning
or a combustion byproduct from your automobile?
So moving on, so some background information here. I
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presented this slide in my first talk I gave in the December
workshop, just to clarify that the electronic cigarette
emissions generate a mixture of vapor and aerosols, where the
vapors are gas that is formed by the boiling or evaporation of
the liquid. And the vapor can contain a lot of different
contaminants: aldehydes, nicotine, and non-polar organics. The
aerosol is a solid or liquid particle suspended in the gas, and
it's usually reported in sizes such as micrometers.
I also want to point out, during my talk I will frequently
switch the terminology between aerosol and particle, but
they're both synonyms.
I also need to point out that there are several organic
species in electronic cigarettes as well as other sources that
are semi-volatiles, that is, they exist in both the gas phase
and in the particle phase.
So today's presentation will focus on the methods to
measure secondhand exposure to electronic cigarette emissions.
These are all based on scientifically proven approaches used to
investigate exposures to outdoor air pollution, formaldehyde
from building products, combustion sources, you know, many
different sources.
So I'll be talking about the methods for collecting, the
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devices you can actually use, the different approaches, whether
you use stationary measurements or personal-level measurements.
And for all of these approaches, I'll be talking about the pros
and cons.
And I'll talk about cost in some places. And I sort of
arbitrarily picked an $8,000 per device threshold to be defined
as a con.
I will not be talking about using biomarkers of exposure
or toxicology or physiological responses as a means for
assessing secondhand exposure.
So aerosol measurements. There are many different ways
available to collect aerosol measurements. So these are the
measurements of the particles in the air. One common approach
is -- anyways, the single-stage filter. So that's a common
device that's been commercially available for a long time.
Very easy to use, portable, and not very expensive. You
collect the particles on a filter. So it's very easy to take
it back to the laboratory, weigh the filter on a balance, and
then you can also analyze that filter to understand what metals
were in the air or what organic species were in the particles.
Some of the disadvantages. It's a one-shot sample. It
doesn't provide any time-resolved data. If someone wears that
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device for 24 hours, you don't know when their exposure
occurred during that 24 hours.
For electronic cigarette emissions, we know that there are
a lot of semi-volatiles in organic particles emitted,
especially initially upon exhalation by the user. As those
particles collect on the filter, they could evaporate, so you
can actually get some significant evaporative losses and you
would actually underestimate someone's exposure.
No size data. That means that you don't know the sizes
because you don't know how many particles or how much of the
mass is less than 100 nm or greater than 100 nm or greater than
500 nm.
Another big con with this device is the need for a pump.
The picture just shows the device itself, you know, that you'd
wear up here on your chest. There is a whole separate pump
that runs -- that you need to run from the inlet that you have
to wear in a waist pack. So the whole device would be rather
bulky.
You also have a similar device, a cascade system. It
collects on a filter. The big advantage for this one is it
provides size distribution data. Most of these types of
cascade systems are only used for stationary. But there is one
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device that was developed by the University of Southern
California that is commercially available that you can wear --
actually wear as a personal monitor.
Moving on down to the particle counters. We're getting
more into some of the time-resolved data now with the particle
counter and the nephelometer. You know, these are actually
electronic devices that provide real-time data, so you actually
get the time interval so you know when the exposures occurred.
And for the particle counter, you actually get the exposures as
a function of particle size.
The issue with the particle counter is the cost.
Obviously, with more data, the actual cost for the instrument
is a lot more expensive.
Another issue is that these are basically stationary
instruments. You know, these are 8, 10 pounds, and you
wouldn't be able to wear one for an extended period of time.
That being said, the University of Cincinnati is developing a
personal prototype that hopefully should be available in a few
years.
Then there's the nephelometer. It's the same type of
thing, but no size data.
And then you have these new devices called the -- which we
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have as the dual system. It collects with a filter and
provides the nephelometer data. And that's the RTI MicroPEM.
And I just happen to have one in my pocket, measuring my
personal exposure during my talk today.
Moving on to organic gases. Many different methods. You
can select the collection media based on what you're trying to
sample for. So you have the DNPH. That's a type of sorbent
media for aldehydes; activated carbon for PAHs and alkanes;
usually a filter and some sort of XAD or polyurethane foam for
semi-volatile organics; sodium bisulfite, specifically for
nicotine. And there are actually new devices coming out called
auto GC-MS units or VOCs.
All of these devices, except the auto GC-MS, you know --
well, actually the first two -- I'm sorry. The first two can
be run in passive mode or active mode. So passive mode means
it's just the little badges you see there in the pictures that
you actually clip onto your shirt. Or you can run in active
mode, which means you actually have to put it in a pump,
connect it to a pump. But those pumps are usually very large,
so they're only useful in a stationary mode.
The sodium bisulfite system for nicotine. It has been
used quite frequently historically, but there's a lot of recent
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data becoming available that is questioning its suitability for
measuring secondhand exposure to nicotine due to sampling
artifacts.
So for stationary measurements, basically you're taking
these instruments and you're putting them in a room and leaving
it at one place for an extended period of time. It can be an
exposure chamber or an occupied building.
I want to point out, one of the big cons with stationary
measurements is the exposure misclassification. That means,
just because it's stationary, it doesn't mean it's actually
measuring what someone is breathing. So if we had a stationary
system on the other side of the room, but I'm up here and
there's a strong -- and someone was vaping right next to me,
that system would not be detecting what I was actually
breathing.
Personal exposure assessment obviously is a more accurate
way to measure what someone is breathing. You know, that's
where you actually have to go out and recruit participants to
wear the aerosol and gas samplers for both either an exposure
study -- exposure chamber study or an observational study. As
I said, it's the most accurate assessment. You're actually
getting -- reducing exposure misclassification due to they are
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actually wearing devices.
But also if you design the system to be low burden,
especially like this middle system, where it's very lightweight
and very easy to wear, you can actually get people to wear the
devices for like up to 90% of the time they're awake.
But, again, these types of studies are rather expensive,
and also they require human studies research approval.
You can also do a combination of both, which is probably
the most representative exposure assessment. It actually
allows you to do some source apportionment, so identifying
where the exposures occurred, whether it's inside your home or
outside your home or in your car or at work or whatever. But,
again, these types of devices -- because you're doing both the
personal and the stationary type of monitoring, cost becomes an
issue.
So I did a quick survey -- not quick. I did a survey of
the literature looking for electronic cigarette exposure
studies, secondhand exposure studies, and I found two that have
been published in the literature.
One was Schripp et al. from 2013, very anecdotal, kind of
more of a proof of concept, you know, trying to see if there
was any exposure by putting one volunteer in a chamber where
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they just sequentially smoked -- used three types of e-liquids
in an electronic cigarette and one cigarette, conventional
cigarette.
As Andy said, it gets into the types of -- they did not
select the most appropriate experimental design, whether it's
the amount of e-cigarette emissions they generated or the
devices they used to measure the exposure. They only used six
puffs in a very large chamber, and they sampled for 15 minutes.
Their real-time formaldehyde detector, this AL4021, was not
meant for low levels of exposure assessment, so a lot of their
data was with a low detection limit. The good news about their
data is that their aerosol size distribution that they measured
does agree with several other studies that have been published
since.
The second study was Schober et al. from 2014. Here's a
summary of kind of what they did. This is a German study.
They did it in an office building with volunteers who had 2
hours of exposure over 5 different days. Their goal was, I
think, to determine if a potential exposure exists. Yes, it
does, in my opinion, based on their results. However, the
study was very underpowered and did not control for potential
exposure to other sources. That really limited their ability
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to attribute the air concentrations and the biomarkers they
found on their participants to the electronic cigarette
emissions.
Finally, one of our own studies at RTI that has not been
published, kind of looking at the spatial temporal distribution
of the secondhand exposures to electronic cigarette emissions.
This is a very anecdotal study, sort of a very low-budget, one-
shot deal just showing that secondhand exposures are very
transient, usually lasting less than 10 seconds, and that there
are also large spatial gradient concentrations within the room.
So basically, in conclusion, when you're designing a
secondhand exposure study, you know, what you want to do and
the type of instrumentation you use depends on what you want to
prove. Is it proof of concept? Does an exposure occur? Are
you looking at method development studies maybe looking at
biomarkers, for example? Fate and transport types of studies.
Exposure characterization looking at the different levels. Or
you go all the way and do a population-representative exposure
assessment.
A very important point is the last bullet -- and I'll
finish on that -- is that when you're designing and then trying
to propose an exposure assessment study, it's very important to
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consider the cost per data point. You can design a study and
propose something for $100,000, but you have to convince the
funding agency that if you can double that budget to $200,000,
you could probably get 10 times as much data.
Thank you.
(Applause.)
DR. DRESLER: Thank you. Good luck with that persuasion.
(Laughter.)
DR. DRESLER: Our next speaker is Dr. Mohamadi Sarkar from
Altria Client Services. So this is looking at ALCS Controlled
Clinical Study to Evaluate Constituents Released When E-vapor
Products are Used.
DR. SARKAR: Well, I'm happy to be here. I want to thank
the organizing committee and CTP for inviting me to participate
in this workshop.
As Dr. Dresler pointed out, my name is Mohamadi Sarkar.
I'm from Altria Client Services, speaking on behalf of Nu Mark,
which is an Altria company that develops and markets innovative
tobacco products, including e-vapor products for adult tobacco
consumers.
What I'm going to do today is share with you results of
studies that we have conducted to address many of the questions
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that FDA has posed for this specific session.
In a recent review, Dr. Chang, one of the FDA scientists,
did a nice job of summarizing the state of the science on
passive vaping and acknowledged that there's a paucity of data
on this topic. Dr. Chang also stated that a study addressing
and measuring levels of constituents during e-cigarette use
under different conditions would be highly informative,
particularly if the study was done with a range of e-vapor
products that are currently available. And we agree with that.
So what we have done is we have identified three main
questions that need to be answered. They are, what are the
levels of the constituents in a room where such products are
used? The second question is, what is exposure to nonusers?
And the third one, and probably the most important one, is that
if there is indeed measurable exposure, what is the potential
for harm to nonusers?
We've gone about trying to address this using a very
systematic approach. We started by constantly reviewing and
monitoring the published literature, but we've also generated
our own data. We've done three studies: two pilot studies and
one controlled study. Today I'm going to give you an overview
of the pilot studies and describe the controlled clinical study
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in greater detail.
As you heard from Dr. Rostami, my colleague at Altria, we
are also in the process of developing a computational model to
predict air levels under different use conditions. And then
ultimately what needs to be done, as the previous speaker
pointed out, that one needs to do a risk assessment by
integrating all the available evidence to determine the
potential for harm to nonusers. Today I'm going to just talk
about the studies that we have conducted and share the results
of the studies.
So the pilot studies that we ran were done with the
objective to evaluate the major chemical constituents in a room
where e-cigarettes were used. The second study was done to
replicate the first study. These studies were conducted in a
room which was compliant with the applicable U.S. building
codes and were conducted by our industrial hygienist in the
environmental safety group of the company, primarily to
determine the potential workplace exposure to the staff.
So we measured a number of these constituents using
sampling and analytical methodologies that have been
established by NIOSH for workplace air contaminants.
In this study, adult consumer participants were in the
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room evaluating various prototype e-cigarettes. The study was
set up in such a way that the participants were asked to take
six puffs. There were six 1-hour rating sessions over a
duration of 12 hours, and we conducted the air sampling over
the 12-hour duration for 4 consecutive days. The participants
were asked to take the six puffs, fill in a ballot, and then
move to the next sample. And depending on the number of
participants and the number of products tested, there was a
range of puffs from 200 to about 1,300 puffs per day. We also
conducted background measurements before and after the 4-day
period.
The total sample size for the first study was 183
panelists, and the second study, 165 panelists. The
participants were seated in the perimeter of the room, as you
can see in the schematic.
So what did we find? The results showed that the levels
of the constituents that we measured using the NIOSH analytical
method -- and as the previous speaker pointed out, it's
important to remember the analytical detection limits. So at
the detection limits of the NIOSH methods, these levels were
below the detection limit.
We also measured formaldehyde and that was found -- the
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levels of formaldehyde, which was measured under a similar
method, were within the background range.
So the overall conclusions from these two pilot studies
were that these measured chemical constituents were several-
fold below the current limits. Arguably, although the levels
were below the detection limit, even if we used the detection
limit as the maximum limit, these levels were several-fold
below the threshold.
And we have presented the results at many scientific
conferences, and the details are available at our science
website. We've also written this up as a manuscript and
submitted it to the Journal of Occupational and Environmental
Hygiene for publication.
So now let me talk to you in greater detail about this
third study, which I'm describing as the controlled clinical
study. This study had two objectives. The first objective was
to evaluate the exhaled breath, room air, and surface levels of
selected constituents following the use of various types of
e-vapor products as well as conventional cigarettes under
controlled and ad-lib conditions. The second objective, as my
colleague pointed out, was to generate input parameters for the
computational model.
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This was an open-label, single-center, observational
study. We targeted to recruit 40 participants that were
healthy adult males and females who were either e-vapor users,
tank users, or conventional cigarette smokers.
In this study, we tested four products. The first product
was a MarkTen Classic e-cigarette. The second was a prototype
GreenSmoke e-cigarette. The third were tanks where the
subjects were asked to bring their own e-liquids. And the
fourth group was of conventional cigarette smokers where they
smoked their own cigarettes.
And as I mentioned, we conducted three investigations:
exhaled breath, room air levels, and surface samples. Due to
the time limits, I'm just going to focus on the last two
endpoints.
So let me just describe a little bit about the background
of the study. This study was done in collaboration with a CRO,
Inflamax Research, which specializes in respiratory research.
And the reason we partnered with this CRO was that they have
this unique chamber, as you can see in the schematic, that is
being designed to do allergen research where they actually
release allergens in the room and the therapeutic agents for
the allergens are tested in this room. And these have been
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submitted and approved for FDA -- in clinical studies.
Now, this chamber is unique in the sense that it allows
you to constantly monitor the temperature, the humidity, and
the airflow in the chamber. Also, it has its own dedicated
HVAC system, as you can see from the lines leading into the
room, and this dedicated HVAC allows for accurate control and
precise control of the inflow and the outflow of the air from
the room.
Now, Inflamax set up this room at a site in North
Carolina, and they validated this chamber, as well as the
sampling of the room air was done through Enthalpy, which
specializes in air emission measurements. I don't know whether
you can see this, but there are some airflow monitors that were
set in the room. They were custom designed by the scientists
at Enthalpy.
This slide shows you kind of a bird's eye view of the
room. And the point I want to make from this slide is that we
set up four sampling manifolds for the air measurements, and
four surface sample measurements were taken at different
locations within the room. We also took one inflow air
measurement.
Now, remember I told you that we had four groups in the
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study, the MarkTen, GreenSmoke, tanks, and conventional
cigarettes. I'm going to use the MarkTen just as an
illustrative example to walk you through the sequence of events
that were taking place during the study.
So, on Day 1, after an air purge and taking background
measurements, we brought the participants in and took baseline
measurements without them using any product. These were
baseline measurements of the subjects in the room.
On Day 2, after additional background measurements, we
brought the participants in and asked them to use the product,
which was MarkTen in this case, under controlled use
conditions, which was they took 10 puffs, each a 5-second
duration every 30 minutes for a period of 4 hours. So a total
of 80 puffs were generated per participant. Now, the 5-second
duration was based on a topography study that we had published
previously, and that kind of represents the maximum use
condition.
After background measurements, we actually allowed the
participants to use the products under ad-lib conditions for a
period of 4 hours and to the same kind of -- the same
measurements.
On Days 3 and 4, we carried out similar measurements for
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the GreenSmoke prototype. On Day 5, we took the tank
measurements. Now, for the tank measurements, we only did the
ad-lib measurements and not the controlled use. And on Day 6,
we did the conventional cigarettes, once again under only ad-
lib conditions.
We collected several measurements of different
constituents, including nicotine, propylene glycol, and
glycerin, as well as about 15 carbonyls, including formaldehyde
and acrolein, and 12 volatile organics as well as trace metals.
Now, due to the time limits, I'm going to only be focusing
on the selected constituents of interest for today's
presentation.
So let me just show you the results. I want to first
orient you to the slide. On the y-axis you're looking at the
room air levels of nicotine -- this first slide is on
nicotine -- and on the x-axis the four different groups.
And I want to highlight one point that was made by the
previous speaker. The detection limit that you see on this
slide is set at 0.26. Now, this is much lower than the
detection limit of the previous study. Remember I told you
that in the two previous studies we didn't see any detectable
levels of nicotine in the room. Because that method was based
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on the NIOSH method, the detection limit for that was 15 µg/m3.
And because we wanted to generate data for the computational
model, we really pushed the sensitivity of the method, and if
you really stretch it and if you look hard enough, you will
find it, as was pointed out by Dr. Persily.
And you can see, from the results of the study, which is
showing the baseline controlled use and ad-lib use, that there
were no baseline measurements of nicotine because people are
not exhaling nicotine when they don't use the product. And
with the MarkTen, the levels were slightly above detection
limit, and low levels of nicotine were observed for the other
e-vapor products. On the contrary, the levels of nicotine with
cigarettes were about tenfold higher in the room.
So what do these levels mean? Just as a point of
reference and putting some context around these levels, if you
compare the nicotine levels in the room for the e-vapor
products against the permissible limit set by OSHA, these
levels were several-fold below that threshold.
This next slide is for propylene glycol, once again set up
the same way. The y-axis is the room air levels, and the
various groups are shown on the x-axis. Now, in this case we
measured -- we were able to detect baseline levels of propylene
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glycol, and you see a lot of variability between the groups.
Now, this is interesting because this suggests that we exhale
propylene glycol even without using any product. That's not
surprising because propylene glycol is a common food additive,
and it's found in many household products.
Interestingly, the levels of propylene glycol from the
e-vapor products were reflective of the proportion of propylene
glycol in the different products, with the tanks having the
highest level.
Once again trying to contextualize the results, now OSHA
does not have a permissible exposure limit for propylene
glycol, but there is a consensus limit based on the American
Industrial Hygiene Association set at about 10 mg/m3. And you
can see that these levels are several-fold below that threshold
limit.
This next slide is on glycerol. Once again we are set up
the same way. The y-axis is the room air levels, and the
different groups are shown in the x-axis. And if you try to
compare the baseline controlled use and ad-lib use for the
e-vapor products, similar to what we saw with propylene glycol,
the levels are proportionate with the levels that you would see
in the products, and the tanks having the highest levels.
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There were no measurements in the cigarettes, probably because
it gets combusted, and if you compare with the OSHA limits,
several-fold below for the e-vapor products.
The next series of slides I'm going to show you are
formaldehyde. And, once again, referring back to Dr. Persily,
that formaldehyde is omnipresent, if you look at the levels or
the 6-day duration of the study, you see a lot of variability.
But, nevertheless, measurable formaldehyde levels were
found in the room without any people present in the room. And
note the variability then on some data points on Day 2 are
higher than the others.
Now, if you superimpose the results for the different
usage period, whether it was under controlled use or ad-lib
use, they were all within the background levels. And just to
compare it against the cigarette, you see that it was
significantly above the background. And that was one of the
main reasons we had used the cigarette group, was to include it
as a reference to demonstrate the sensitivity of our detection
methods.
And if you then contextualize the levels of the e-vapor
products against OSHA limits, they were several-fold below the
threshold set by OSHA.
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Now, the last set of results that I want to show you are
for the surface sample. Just a reminder that we had four
different stations where we measured the surface levels of the
constituents.
And this is the result for nicotine. We were able to see
slightly above detection limits on two of the surface samples.
Now, I can't sit here and tell you whether these are real or
whether they are artifacts of experimental collection
techniques. But, nevertheless, 22 of the 24 samples were below
detection limit over the duration of the study, including the
ones for cigarettes.
So, in conclusion, what we can say based on the three
studies that we have conducted under the study conditions and
with the products tested, the room air levels of the
constituents were several-fold below the threshold set for the
exposure limit.
And based on the results of the surface sample analysis,
the evidence suggests that the thirdhand exposure of non-
exposures [sic] to nicotine is unlikely.
Now, you know, we saw that we were able to see measurable
levels for the different constituents if you truly stretch the
analytical limits. Now, how does that translate into actual
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exposure to nonusers? Well, I think that based on the
biological variability and the other sources of exposure, I
don't know whether we would be able to differentiate that.
But, nevertheless, further research would be needed to
definitively determine the exposure of these constituents in
nonusers under different conditions. And then, of course, the
risk assessment needs to be done to evaluate the potential for
harm with this level of exposure.
And that's about where I end. Thank you very much for
your attention, and I'll be ready and happy to answer any
questions.
(Applause.)
DR. DRESLER: Okay, we will take some clarifying questions
from your cards. If you can write on your cards and pass those
to the sides, we'll spend a few minutes with clarifying
questions and then a break, and then we'll continue with this
session with further speakers. Thank you.
Dr. Persily -- Dr. Sarkar. I'm sorry, this is for
Dr. Sarkar. Dr. Persily stated that it is important to
understand building ventilation when studying airborne
emissions. Did you measure ventilation in the pilot studies
and the controlled clinical study?
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DR. SARKAR: Yes. So, in the pilot study, as I said, it
was conducted in a commercial building, and we did measure the
airflow exchange rates. And in the controlled clinical study,
of course, since we were able to measure this in a very precise
way -- because remember I told you that there was a dedicated
HVAC in it where the inflow and outflow could be measured. So
yes, we did measure that.
DR. DRESLER: Okay. You must have explained it so well,
guys.
(Off microphone comment.)
DR. DRESLER: Oh, they're writing. Okay.
UNIDENTIFIED SPEAKER: Yeah, we're still writing legibly.
DR. DRESLER: Oh, legibly. Yes, please, that will be very
kind.
(Off microphone comment.)
DR. DRESLER: Okay.
Considering the recent concern about nanoparticle
generation in e-cigs -- I'm going to guess that that's e-cigs
-- how do we measure and assess this risk? So considering the
recent concern about nanoparticle generation in e-cigs, how do
we measure and assess this risk? So nanoparticles.
UNIDENTIFIED SPEAKER: Is that directed to someone?
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DR. DRESLER: I'm sorry?
UNIDENTIFIED SPEAKER: Is that directed to someone?
DR. DRESLER: No.
UNIDENTIFIED SPEAKER: It's a panel question. Save it for
a panel.
DR. DRESLER: Oh, save it for a panel. Okay. You guys
are off, so you have a few minutes to think about that one,
okay?
Dr. Persily, how does formaldehyde release from furniture
compare to e-cigarettes? So formaldehyde measured that's in
the room at baseline anyway. So how does the release from
furniture compare to e-cigarettes?
DR. PERSILY: For me?
DR. DRESLER: Yeah. I'm sorry, I was looking at him.
Sorry about that.
DR. PERSILY: I mean, that's a really good question, but
you know, I don't really have an answer. You know, the amount
of formaldehyde emitted by the piece of furniture depends on
what it's made of and its history and the temperature and the
environment. And whether that's higher, lower, or the same as
an e-cigarette is just -- you know, there are too many
variables to just give a simple answer to that. So I'll give a
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short but not simple answer.
DR. DRESLER: Okay. Maybe it will come out more in the
panel, too.
Dr. Sarkar, this one is for you. Can you please provide
details about your study participants? Were they e-cig users?
If so, what type? Conventional product users?
DR. SARKAR: So, you know, we're going to present these
results at an upcoming TSRC meeting, and we're going to publish
this. So the details of the study --
DR. DRESLER: What's a TSRC meeting?
DR. SARKAR: The Tobacco Science Research Conference
meeting.
But, generally, if you remember the slide that I showed,
we targeted 40 participants. Twenty of them were regular
e-cigarette users. They had used e-cigarettes in the past 30
days. Ten of them were tank users, and 10 of them were
conventional cigarette users.
DR. DRESLER: Thank you. You used a 30-minute interval.
Did you mean 30-second interval? Again, Dr. Sarkar, this is
for you. Thirty-minute interval or a 30-second interval?
(Off microphone comment.)
DR. DRESLER: Yeah, I don't know either.
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DR. SARKAR: So the controlled puffing conditions were set
where the participants were asked to take 10 puffs, each a 5-
second duration, and these 10 puffs were repeated every 30
minutes over a period of 4 hours.
DR. DRESLER: Oh, the next one is for you too.
Formaldehyde data from aerosol from electronic cigarettes was
interesting, but were there any chemicals of concern that you
saw above background levels? So you presented data, I think,
you had at the top, right? That's the information that you
presented. It was nicotine and formaldehyde and --
DR. SARKAR: Propylene glycol.
DR. DRESLER: Thank you. So did you find anything else
interesting?
DR. SARKAR: So there were lots of constituents that we
measured, and I don't have the data with me in front of me.
But, generally, most of these constituents were below detection
limit when the e-vapor products were used, and of course a lot
of them were above detection limit when cigarettes were used,
which was the purpose of including the cigarette as a reference
group. There were occasional sporadic measurements for acetone
at slightly above levels. That's what I remember. But, once
again, I think it's worthwhile to wait for the publication.
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Once we write this up and publish it, you can get all the
details in the publication.
DR. DRESLER: Okay. I'm sorry, don't sit down.
(Laughter.)
DR. DRESLER: Are you ready for this longer one? Okay.
And -- okay. Do you really think -- so that's always something
when it starts out that way. Do you really think occupational
exposure guidelines are appropriate for assessing the exposure
to nonusers in an office space? IAQ -- do you know what IAQ is
as an initial?
DR. SARKAR: Indoor air quality.
DR. DRESLER: Oh, thank you. That's very good. All
right, indoor air quality researchers typically use 190 of --
1% of occupational exposure guidelines. Your ACGIH guideline
for propylene glycol exceeded 300 µg/m2, which is three times
1% of what is in the guideline.
DR. SARKAR: I was going to say, maybe we should save that
for the panel.
DR. DRESLER: Do you want to? That sounds good.
(Off microphone comment.)
DR. DRESLER: Okay, that sounds good.
All right. Yeah. And this one I'm going to save for the
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panel too. I think that's a good one for the panel.
So break time. Okay, so 15 minutes. So let's make it 17
minutes and come back at 10 o'clock, okay?
Thank you.
(Off the record at 9:44 a.m.)
(On the record at 10:02 a.m.)
DR. DRESLER: Shall we gather back together, please?
Okay, welcome back.
We're going to continue on with this first session that is
on Exhaled E-Cigarette Aerosols: Evaluation of Constituents and
Exposure. And our next speaker is John Pritchard from Imperial
Tobacco from the UK, speaking on the Assessment of Indoor Air
after E-cigarette Use: Modelled and Experimental Findings.
MR. PRITCHARD: Thank you very much. Okay, good morning.
I'm John Pritchard from Imperial Tobacco Limited, UK, and I
thank the FDA for this opportunity to talk here today. My
presentation is entitled Assessment of Indoor Air after E-
cigarette Use: Modelled and Experimental Findings.
Okay. So let me begin by stating that the work we
conducted was supported by Imperial Tobacco Limited, UK. By
way of reference, Imperial Tobacco Limited, through its wholly
owned subsidiary Fontem Ventures, manufactures and sells a
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range of e-vapor products, that is, e-cigarettes, in the UK and
elsewhere in Europe.
And I'll use the term e-vapor products, or EVPs, through
the talk, since the product category is broader than simply
e-cigarettes. And today I'll cover some of our work in this
area.
We acknowledge and are extremely grateful for the input
provided by the independent external laboratories who helped
design and conduct the experimental work that we undertook, as
well as the contribution of our coworkers at Imperial Tobacco.
Okay. So today I'll provide a brief context for this
talk, give an overview of our mathematical model, which was
developed to evaluate constituents in ambient air following
e-vapor product use. With regards to the experimental data,
we've conducted studies which directly assess the source of
e-vapor product emissions into ambient air, that is, the
exhaled air immediately after EVP use. I will also present an
indoor air quality assessment made in a small office space
before, during, and after EVP use. And nicotine has been the
focus of some discussion on the topic of potential secondhand
exposure. And I'll report early findings from a study in this
area and relate this to potentially thirdhand or tertiary
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exposures following EVP use. And, finally, I'll give a
summary.
So context for the talk today. It's been reported by
Action on Smoking Health UK last year that as many as 2.1
million British adults currently use e-cigarettes and e-vapor
products. In a report last week, this has increased to 2.6
million consumers. Two-fifths are ex-smokers; three-fifths
report using both EVP and cigarettes.
With increasing prevalence of e-cigarettes, there's a
growing discussion amongst public health organizations and the
scientific community as to whether the aerosol exhaled from
such products has implications for the air breathed by
bystanders through so-called passive vaping, akin to that which
has been reported for environmental tobacco smoke from
combusted tobacco products. Given the recent emergence of
EVPs, the scientific research in this area is burgeoning. And,
to date, a range of approaches have been applied to assess
different products using different methodologies and under
different study designs and conditions, and as a result, it can
be difficult to compare results of the studies that have been
undertaken.
It has been reported that the common components of
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e-liquids -- so nicotine, propylene glycol, glycerol -- may be
released into the air during the use of e-cigarettes, as well
as compounds including carbonyls, polycyclic aromatic
hydrocarbons, and trace metals. And to investigate the topic
we've taken two approaches, mathematical modeling and
experimental studies.
So mathematical models have been widely used to
investigate a range of potential exposures in the workplace or
public spaces. And, furthermore, it's a flexible approach
allowing investigation of the effect of different parameters,
different scenarios, or environmental conditions. We developed
and published a mathematical model to explore the potential
levels of nicotine from a bystander perspective in an office
environment. The full details, such as the formula applied,
are available through the QR code or at this reference given
here. And I'm going to give an overview of the key points of
interest.
So model output: single puff profile. The model may be
used to predict indoor air concentrations of chemical
constituents based on successive steps or puff phases. So
following exhalation of a single puff, a profile of nicotine
concentration in ambient air at the bystander position can be
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derived from the model shown here.
So, in Phase 1, the e-cigarette user takes a single puff
and inhales the nicotine-containing aerosol, and then the user
exhales this into the indoor air, and this is dispersed in all
directions. And here the bystander is not yet exposed to the
aerosol.
In Phase 2, the bystander's peak exposure to exhaled
nicotine in the air is observed, corresponding to the time the
exhaled aerosol reaches the position of the bystander and
dispersion of the exhaled vapor in the indoor air is not yet
complete.
In Phase 3, there is a reduction in the concentration of
nicotine at the position of the bystander due to dispersion,
dilution of aerosol in the air, and any potential surface
deposition. And it is assumed that air extraction starts when
80% of the room volume is filled with the exhaled aerosol.
In Phase 4, mixing of the exhaled aerosol in the ambient
air is complete, and the concentration of nicotine is reduced
by the air extraction and any further surface deposition. And
there is a further reduction in the concentration of nicotine
at the bystander position.
That's a single puff profile. Let's consider repeat
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product use.
So here we can illustrate the flexibility of the model
approach in the scenario described. Two employees are working
in the same office. One is an e-cigarette user and makes one
puff every 5 minutes, inhaling 60 µg of nicotine per puff and
exhaling 30 µg of nicotine per puff. So a 50% retention rate
there.
The room size: 50 m3. The air exchange is 1.33 air
changes an hour. And that generates movement to convection,
which makes an exhaled puff fill the room in around 5 minutes.
The other employee is not an e-cigarette user. They're
seated 2 m from their colleague and spend 8 hours at work
together. And here's a 1-hour lunch break as well. As you can
see, in the computer simulation that's running in the
background here, there's an increase in the ambient
concentration following successive exhalations over the morning
period, and the maximum concentration is reached when the
exhaled aerosol emission rate and the air extraction rate are
equal.
And what we see then is a rapid decrease in the room
during the lunch break and an increase with recommencement of
vaping in the afternoon. And in this scenario, the maximum
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concentration of nicotine in the ambient air over the working
day is 1.8 µg/m3. And by way of context, the UK 8-hour
workplace exposure limit, as well, is at 500 µg/m3.
Okay. Great. I'd like to show an additional capability
within the model. So what you can also do is to consider the
contribution of each of the parameters on the level of nicotine
in indoor ambient air, and therefore potential bystander
exposure.
So here we examined the collective effect of varying --
all of the five parameters concurrently over an 8-hour working
day in the scenario we gave in the previous slide. And the
dataset was generated by assigning each parameter a value of
low, medium, and high, which resulted in 243 unique modeled
scenarios at 3 to the 5, which collectively predicts the range
of average nicotine concentrations in ambient air over 8 hours
in the workplace.
And in reviewing the data, perhaps unsurprisingly, the
most important model parameter identified here was found to be
the quantity of nicotine exhaled. Therefore, it is essential
that precise measurements are made regarding the quantity of
nicotine exhaled or retained by the e-cigarette user, when
determining potential bystander exposure in exhaled e-cigarette
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aerosol.
The second approach we took was an experimental one, and I
will now present some of our work in this area.
Okay. We have conducted studies that consider EVP at
source, that is, the exhaled air, and also the potential impact
of e-vapor products on indoor air quality. The details of the
indoor air quality study are published in an open-access
journal and are available through the reference given here, or
for those with technology at hand, the QR code.
Okay. So I'd just like to show this here. Let's look at
the exhalation at source. And this row was presented at the
SRNT meeting here in the U.S. earlier this year. And here we
investigated, in real time, directly exhaled air following a
single puff on an e-vapor product, and we also considered
conventional products by way of comparisons.
The technique here, proton-transfer-reaction mass spec,
has been previously used for exhaled air analysis in other
industries and other settings. It has the advantage that no
sample preparation is required, and measurements can be made on
a per-puff basis. And this gives a clear snapshot and reviews
the technique published elsewhere.
What we see here are mass spectra comparing exhaled air
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analysis following a single puff from a conventional cigarette
and an e-cigarette. And it's clear that the aerosols are not
equivalent, with the data showing how complex the combustion
aerosol for a cigarette is when compared with the aerosol
generated from heating a simple liquid phase.
And this study considers the initial exhalation without
dilution. Well, then, the ambient air impact from successive
puffs were indeed the effects from multiple users in a typical
indoor space.
So, as noted earlier, there are several studies that
report different findings within EVP aerosols, and using these
publications, we looked at the chemicals highlighted in these
reports and conducted a comprehensive screening under a
realistic scenario in a small office space. Findings are
reported against relevant exposure values and were published,
including UK workplace exposure limits. And to replicate a
real-life scenario, we conducted an assessment of indoor air
quality before, during, and after e-vapor product use.
The study was conducted in an independent, accredited
laboratory in the UK, with expertise in indoor air quality
assessment. A small unoccupied office was available at the
laboratory for this study, which was furnished for a typical
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business meeting and fitted with a range of sampling and
monitoring equipment, with samples collected in an adjacent
room.
The schematic illustrates the office space and sampling
arrangement where five individuals were seated in the office
space, arranged around the table. Three participants were
experienced e-vapor product users and two were nonusers.
The volume of the room was 38 m3 with a measured air
exchange of 0.8 air changes per hour. For context, the UK
Chartered Institution of Building Services Engineers state that
such a space should have at least one air change per hour. So
the findings from this study were likely to represent an
overestimate.
Doors and windows remained closed for the duration of the
study, and there was no entry or egress from the room by
participants. And there was no mechanical ventilation or
recourse to cooling, and the sampling schedule was as follows.
Okay. In conducting such a study, it's essential to
establish adequate baseline data. To that end, measurements
were taken of the unoccupied office and also once the office
was occupied by the participants, but before product use. The
product used in this study was a closed-system disposable
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product containing 16 mg of nicotine in a propylene glycol and
glycerol base, which is a common product confirmation in the
UK.
And I'll present the key findings from the chemical
analyses. Further details are given in the publication.
So the first two chemicals that we'll go through are
propylene glycol and glycerol, principal components of
e-liquid. And as expected, PG, or propylene glycol, increased
with vaping and dropped at the end of the vaping period. For
glycerol, which was also expected to show similar changes over
the study phases, the method was not as sensitive as
anticipated. Nonetheless, in both cases, measured levels were
substantially lower than the UK workplace exposure limit.
So carbonyls. Carbonyls have been reported in the ambient
air following e-vapor product use, and it's been reported that
a potential source of these compounds is the heating process of
propylene glycol. Formaldehyde changes across the different
measuring periods remained substantially lower than the indoor
air quality guidelines established by the World Health
Organization in all measurements. And this is consistent with
other data in the literature shown on the right.
Similarly, for acetaldehyde, we saw changes across the
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different measuring periods. And as with formaldehyde, these
remained substantially lower than the European Union indoor air
quality guidelines. And, again, this is consistent with other
data in the literature.
Okay, so other chemicals. A further part of the screen
loss considered other chemicals. We saw no measurable increase
of any of the U.S. EPA Priority 16 polycyclic aromatic
hydrocarbons. By way of context, the LOD there is of less than
1.25 µg/m3 compared to the U.S. OSHA PEL of 200 µg/m3.
So, for metals, air samples were taken on filter
assemblies and analyzed for the U.S. EPA Method 29 metals plus
aluminum and phosphorus. We did not identify any increase in
metals or metal particles in any of the air samples taken, and
all samples were below the respective UK workplace exposure
limits, where established.
Acrolein has been reported as a substantial breakdown
product from the heating of glycerol, and in our work there was
no measurable increase of acrolein, which corroborates other
findings in the literature.
With regard to tobacco-specific nitrosamines, there was no
measurable increase in any of the samples.
Okay. So nicotine is present in most e-liquids, and in
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our study there's no measurable increase in the airborne
concentrations of nicotine with vaping.
Several studies have looked for the presence in ambient
air using different experimental approaches, and where
detected, this has been at levels below the UK workplace
exposure limit. The low level measured in this study and
elsewhere is of interest and may be attributable to the high
retention rate of nicotine by the user, which has previously
been reported following inhalation for tobacco smoke. And
further e-vapor product research in this area will be
informative for us in seeking to explore this further. And
we've also conducted nicotine retention investigations.
So here we show a novel approach to determine nicotine
retention, and this recent work is in preparation. By
determining the quantity of nicotine inhaled and the quantity
of nicotine exhaled, retention rate can be determined. And
it's well known, as I said, that nicotine is retained with high
efficiency with conventional combusted tobacco products and
other nicotine-containing aerosols, up to 99% in cigarettes.
And here we found the nicotine retention used in a closed-
system product to be around 98%. And this high retention may
account for the low measured levels in our air quality study
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and other studies and shows the importance of not relying on
smoking machines when looking at potential bystander exposure.
And with this mind, let's now consider potential tertiary
exposure from exhaled e-vapor aerosol. Okay. So I think we're
going to hear a little bit more on this later on, so just very
briefly here.
So the main point here is the impact that different
methodologies and experimental designs could have in the
evaluation of potential thirdhand exposure. So we can see
here, on the one hand, machine-generated aerosol, a chamber
study where necessarily, as a machine, there won't be
retention. There's 100% emission.
And then we have -- in our evaluation of thirdhand
exposure in a study on the different materials, we can see the
presence of nicotine. Compare this with the real-world study
using vapors in their own homes, high nicotine retention. And
then a really good question of thirdhand exposure. There's no
significant difference between the homes of those that do not
smoke and do not vape compared with those that use electronic
cigarettes.
Okay. So, in summary, our model offers -- it went ahead
again. Okay. This is very sensitive. Okay, I think we're
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there. Our model offers a flexible approach to explore
potential bystander exposure under different conditions and
scenarios. Model outputs are comparable with the published
experimental data.
And inside the model, the quantity of nicotine exhaled is
an important factor, and therefore precise measurements need to
be made when looking at this area. And the experimental data
indicates high retention.
And inside our study, any additional chemicals in the
ambient air from exhaled EVP aerosol are unlikely to present an
air quality issue when compared with regulatory standards, and
a clear need for further research in this area to support the
development of appropriate product standards and other science-
based regulatory measures.
And from the currently available literature, thirdhand
exposures in real life are unlikely to be an issue for
bystanders, and more research in this area will be informative.
Thank you all for your attention this morning. Thank you.
(Applause.)
DR. DRESLER: Okay, our next speaker is Francis (Bud)
Offermann, who is from Indoor Environmental Engineering, and he
will be speaking on Chemical Emissions from E-cigarettes:
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Direct and Indirect Passive Exposures.
MR. OFFERMANN: Thank you. Well, I want to thank you for
granting my request to come and share our research here. I
thank Dr. Persily for letting me sleep in his basement last
night.
(Laughter.)
MR. OFFERMANN: I'm going to talk a little bit about a
study I did. Or, actually, used Maciej Goniewicz's data, but I
have some new data to share with you.
Indoor Air is a conference that happens every 3 years. It
was in Hong Kong last summer, and I was amazed that there
wasn't a single paper on e-cigarettes there. So I told the
conference coordinator, I said, I know it's only a month away,
but I'm going to put together a paper on a hazard assessment,
both direct exposure and indirect exposure to chemicals emitted
by e-cigarettes. So the right one is the front one.
Okay. So we're looking at the chemical emission rates
through the literature for direct exposure for the e-cigarette
user and the indirect passive exposure.
All right. So I used Maciej Goniewicz's data at the time
that I did this. And, boy, the field is really evolving fast,
right? So back last summer, this was deemed the best, largest
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study of chemical emissions from e-cigarettes. Eleven
chemicals were measured. He used 150 puffs. They were 1.8-
second 70 mL puffs. He did carbonyl compounds. We, at least,
analyzed the data from his carbonyl emissions, volatile
organics, tobacco-specific nitrosamines, and heavy metals.
So let's look at what we've got here. And I am going to
share a little extra data here. As you can see, the big guys
on this are the propylene glycol, right? And that is a big
issue. And I think we need to talk more about not carcinogens
all the time, but the immense amount of oil of nano-sized
droplets filled with flavorings and stuff that go deep into the
lungs. That's the big one. Nicotine, not surprisingly, is the
next biggest item. And then there are these aldehydes, and
there's been a lot of talk about the carbonyl formations,
formaldehyde and aldehydes from thermal oxidation in the
e-cigarette.
For formaldehyde, the Goniewicz study had a maximum of
56.1 µg in this 150-puff sample. We kind of know now,
recently, that most of the formaldehyde, more than two-thirds
of the formaldehyde, is not in the particle phase, which the
sampler that was used in this study was designed to catch
mostly the vapor phase. So two-thirds is in the particle
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phase.
We developed a sampler and did QA/QC on recovery and
stuff, using DNPH on silica gel, but with a very fine mesh
size. And we were worried about if you put so much oil into
that DNPH sampler, could we get good analytical recovery? And
we did. We got 99%. And in our study, just for comparison,
our median was 200 µg for 150 puffs, and our maximum was 2,233.
Oh, I'm sorry. I'm sorry, 555 µg for formaldehyde and 1122
maximum.
For acetaldehyde, the maximum in the Goniewicz study was
13.6, and we had a median of 200 and a maximum of 2,223.
So one of my conclusions is that a lot of people are
measuring the formaldehyde emissions with techniques that
under-measure it. And I also think the same thing applies to
nicotine, and we'll get on to that.
So these are the players, these are some of the big
contaminants. Of course, I think we need more research on what
the real usage per day is. I used Etter's data, self-reported.
I think we can do better than self-reported. Dr. Goniewicz has
an excellent study that's going to come out. I will use that.
But for now I'm using 175 puffs per day. Dr. Farsalinos says
600 puffs per day is average. I don't know. But I used 175
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for direct.
Indirect exposure. We had -- this is worst case -- a
small space, 0.3 air changes an hour, one user and one nonuser.
For the cancer health effects, we're using the OEHHA
CRELs. Non-cancer effects -- I mean, for the cancer effects,
we're using the OEHHA NSRLs. So, for formaldehyde, it's 40 µg
a day. For the non-cancer effects, we're using the OEHHA
chronic reference exposure levels, the CRELs.
For the nicotine and propylene glycol -- and we talked
about detection limits and occupational standards. We
certainly think there's no place for occupational standards
really in assessing exposure to nonusers, like in an office
space. That's just not right. We used 1% of the PELs when we
didn't have a CREL.
And I will note that if you take compounds, 13 compounds
that have CRELs and have OEHHA and have PELs of exposure
guidelines, it's about 1% of the exposure guideline is the
CREL. So, indeed, you know, when we have children and
sensitive people, we need to have lower exposure guidelines
than occupational guidelines.
Now, what I'm going to show you in the next thing is
hazard quotients. It's easier because you don't have to look
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at the number and then look at the guideline for exposure. It
boils it into one thing. A hazard quotient is the exposure in
micrograms per cubic meter divided by the exposure guideline.
So here we are for the direct. This is the person that's
smoking or vaping. Or, really, it's not vapor, right?
Aerosolizing. The big one, of course, is -- the biggies are
propylene glycol, hazard quotient 967; nicotine 222; diacetyl
butter flavorant -- so we heard talk earlier today about the
flavorants -- 2,720. I mean, these hazard quotients are off
the charts. Formaldehyde, 1.6. But, of course, if you take
the formaldehyde measurements that we're measuring, 32.2. This
is for the user.
Now, if we go to the passive exposure, the primary things
are propylene glycol, hazard quotient 23; nicotine 5.4. And if
you look at the last speakers, the gentleman from Imperial and
the gentleman from Altria, if you use 1% of the OSHA
guidelines, their measurements show there's an issue for the
passive exposures for propylene glycol. And then diacetyl, of
course, the butter flavorant, at 63. So those are the -- and
there's no -- these were all that we saw over here. The blues
are cancer. The CRELs or hazard quotients exceed the cancer
guideline. And the red ones are the non-cancer.
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For the nonuser in the office space -- worst case -- we're
not really seeing hazard quotients for the cancer-causing
compounds so much. It's the propylene glycol.
I think the aldehyde emissions from Goniewicz -- but not
just Goniewicz, but other people that are using DNPH on silica
gel -- you can see the aerosol go right through the sampler,
and we know that most of the formaldehyde is dissolved in the
liquid aerosol droplets.
Also, I think we're all using a smaller number of puffs.
I used Maciej's data. He was using 150 puffs. I believe he's
using less puffs now. But we wonder about how much oil, if you
put in that much oil into a sampler, how effective it can be.
The aldehyde emissions are believed to be, of course,
primarily from the result of oxidation of glycols and -- let's
see if I can get to here -- we think that the formaldehyde
emissions reported by others are about a factor of three low.
We were wondering why our samples had so much higher emissions,
and I think I know now.
The DNPH for the tobacco industry that's using CORESTA
methods within impingers, the aerosol goes right through these
impingers. It's going to underreport. And measurements by
Giese collected the particles first and then the vapor onto
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DNPH, and his measurements were very, very, very low. Again,
most of the formaldehyde -- and I didn't think myself,
formaldehyde is extremely volatile. Who would think it would
be in the particle phase? But it is.
All right, nitrosamines. I won't talk too much about
that. When they do find themselves in e-cigarettes, of course
the nicotine is extracted from tobacco, and there's some
carryover.
Regulation. FDA, we need some regulation. I mean,
literally, there are people mixing stuff up in their bathtubs.
This industry needs to be regulated.
Flavorants. Again, I speak to the FDA. You're being
abused or misused when they cite "generally recognized as safe
by the FDA." That's for ingestion, right? So inhaling these
things and then for the companies to say the FDA approved it, I
think that's not right.
The propylene glycol. This would be the amount of
propylene glycol. And, remember, these are nano-sized drops,
right? So this liquid propylene glycol, nano-sized drops with
nicotine flavorants and formaldehyde that goes deep into your
lungs for the average user in 1 year.
So I know there's a lot of attention to the carcinogens,
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but the immense amount of oil, all for the purpose of just
emulating that tobacco-smoking experience, if you really want
to make a true-sensation nicotine delivery device, I don't
think trying to emulate the tobacco experience is the way to
go, and I think this is a big issue.
Conclusions. E-cigarettes, they do emit many harmful
chemicals. The industry, I think, has backed down a little
bit, but not long ago it was it's just harmless water vapor.
Some of these are carcinogenic, such as formaldehyde, the
metals, and the nitrosamines that are carried over from the
nicotine extraction.
In addition to posing health risks to the users, the
emissions of glycol and nicotine from e-cigarettes pose a
significant health risk to nonusers. So I think we need to
think about those things. And the emissions of formaldehyde
and nicotine need to be examined for both the particulate phase
and the gas phase.
If you really want to know this and you go back to what we
did as researchers on tobacco, on combustion cigarettes, we
used denuders to determine precisely what the phase
distribution is of these chemicals, and that's what I've
suggested to CDC and FDA is that this research get under way.
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E-cigarettes need to be regulated in the same manner as
tobacco smoking. Dr. Persily talked about ASHRAE, the American
Society of Heating, Refrigerating, and Air-Conditioning
Engineers, and they have now adopted into their ventilation
standards, which are the model for the country, no e-cigarette
usage. The ventilation rates are not adequate to protect
people in offices when you have e-cigarette use. So that's
good.
Consumers should be warned, right, that while the health
risks associated with e-cigarettes are probably less harm
reduction -- probably, maybe, we hope -- this is an epi study,
I guess, going on. We'll see. That's a lot of oil. I'm not
sure, but I'm sure it's less. There remain, of course,
substantial health risks associated with the use of
e-cigarettes. It probably is less than combustion cigarettes.
So that's all I have to say. Thank you very much.
(Applause.)
DR. DRESLER: Yeah, we can get those afterwards.
MR. OFFERMANN: Yeah.
DR. DRESLER: Thank you. Unless you want to drink them,
Maciej.
(Laughter.)
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DR. DRESLER: Okay, our next speaker is Dr. Goniewicz from
Roswell Park Cancer Institute, and he will be speaking on
Nicotine Residues in Houses of Electronic Cigarette Users,
Tobacco Smokers and Non-Smokers.
Maciej.
DR. GONIEWICZ: Thank you so much. Thank you for the
invitation.
This is my disclosure. And I want to add that I'm not an
employee of FDA, even though I'm speaking third time on the
third workshop on electronic cigarettes. But thank you so much
for the invitation. It's a glad pleasure and honor to be here.
So we heard yesterday that some of the marketing
strategies for the electronic cigarettes -- from the electronic
cigarette industry -- are actually targeting of the use of the
electronic cigarettes in indoor spaces, whether it's a bar,
it's a home. But you can find some of the advertising
materials showing the message that this product is safe to be
used indoor and can be used indoor. And actually some of the
owners of the bars and clubs encourage using electronic
cigarettes.
And just a little story. I was offered the electronic
cigarettes in one of the bars in Washington, D.C., to try. I
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didn't do it, but I was approached by one of the companies.
So there are some controversies whether we should allow
using electronic cigarettes in indoor air. However, there is a
risk associated with being passively exposed to vapors from --
to aerosols emitted from electronic cigarettes or not. And I
think we try to contribute to this research and try to answer
some of the urgent questions.
When you look at the users, when you look at the smokers,
whether they support the indoor ban on electronic cigarettes, I
only found one study published in the literature, and this is
the study of the almost 300 current or former smokers, and it
was a survey, cross-sectional survey. And what they found is
that the support for indoor bans varied by product type. So
even though the majority of the samples were smokers, they
strongly supported a restriction on cigarette smoking in homes
and workplaces.
But, in contrast, participants were significantly less
supportive of complete or even partial restriction of
electronic cigarette use in either home or workplace settings.
Minority of smokers and former smokers endorse at least
partial indoor ban on electronic cigarette use. And there was
some predictors for being supportive for the ban. So being
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younger, single, and with the lower income, participants were
less supportive of complete bans of both products, electronic
and tobacco cigarettes.
So just a simple model of the secondhand smoke and the
secondhand aerosol, why they are different, what you might
expect that the differences in exposure.
So the secondhand smoke emitted from tobacco cigarettes is
a byproduct of active smoking. So there is the sidestream
smoke, which is a very significant contributor to the
environmental tobacco smoke, and this is the smoke that's
emitted between puffs. So when the smoker is not puffing on
tobacco cigarette, the cigarette is still burning, and there is
smoke emitted from the tobacco cigarettes. We call this
sidestream smoke. There are some compounds. There is some
smoke diffused through the cigarette wrapper, and there is
exhaled mainstream smoke and the smoke escaping through the
cigarette mouthpiece.
And when we compare this with the electronic cigarettes,
we actually eliminated the first two components of the
sidestream vapor, sidestream aerosols. So there was no
sidestream smoke because, when the user is not operating the
electronic cigarette, nothing is emitted from the device, or
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maybe negligible fraction. We should not see compounds
diffused through the cigarette's wrapper.
But when we look closely at the user of the electronic
cigarette, we can see that some of the aerosol is exhaled. And
depending on the product, depending on the user, depending on
the product characteristic composition, we see some variations
in the amount of the aerosol that is exhaled by the user. So I
think the users and the product will be the first very
important variables that will affect the secondhand exposure to
any chemicals from electronic cigarettes.
And when we look at the very simple model, you know, of
what's going on with any chemical that is present in the
electronic cigarette -- and let's take nicotine. What's going
on with the nicotine? So if we have nicotine in the vapor and
part of the vapor is exhaling, if the nicotine is not
effectively absorbed in the lungs, is retained in the lungs --
we saw some data showing that it is. It can be absorbed. And
the nicotine that e-vapers puffed showed that at least some of
the devices are very effective in delivering nicotine. But,
again, if we have the device that does not really provide the
nicotine doses to the users, then part of the nicotine will be
exhaled with the aerosol.
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So we will have the nicotine in indoor air where we will
be able to detect the chemical in the indoor air. And then we
will have a lot of dynamics going on in the air. So we might
observe the deposition of the chemicals on the surfaces.
And the first study that we conducted was to find out
whether the nicotine can be released from electronic cigarettes
and can be found in indoor air. So we recruited the dual
users. We were looking for the people who are using electronic
cigarettes but also continue to smoke tobacco cigarettes. And
we asked them to come to our lab and sit in an exposure
chamber.
First, we took background measurements, and we wanted to
make sure that nothing is there because the exposure chambers
are used for many experiments, so we want to make sure that we
don't have any background levels. And then we asked them to
use electronic cigarettes, twice in the first hour, ad-lib as
they want, but we ask them to use it twice and then smoke two
regular cigarettes. We did not control for the product. We
asked them to bring their own brands and use it as they want.
We used the standard methods.
This study is published. You can look at all the
specifications of the method and validation and the limit of
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quantitations.
So this is what we found looking at the particulates and
the droplets. So there was some emission from electronic
cigarettes. The instruments that we used in the study, that
you heard in the previous presentation, were able to detect
some droplets of the aerosol emitted from the electronic
cigarettes. It was much higher, the really high concentration
of the particulates emitted from tobacco cigarettes.
When we look at the nicotine levels in the air in this
study, we concluded that the electronic cigarettes can be a
source of emission of the nicotine in indoor air, and we found
that the emission is approximately 10 times lower. But, again,
it will depend on the user and the product.
There was a concern about the thirdhand exposure. So
what's going on with the aerosol that is emitted from the
electronic cigarette, is exhaled by the user? What's going on,
whether it's ventilated and is evacuated from the room or it
can be deposited on the surfaces? And then the concept of the
thirdhand exposure. The study with the tobacco cigarette came
out, so we decided to look at what's going on with the vapor
released from the electronic cigarettes.
And why we should bother about nicotine exposure, the
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thirdhand exposure from nicotine? And I think there's really
-- the nicotine per se has the effect, and we know that there
is some dermal absorption and this may happen. And there is
also some evidence suggesting that nicotine, when deposited on
the surfaces, can undergo further chemical reactions, and then
potentially harmful substances can be formed from this
deposited nicotine.
This is the study found in laboratory conditions. We
don't really understand right now what is the health risk
associated with being exposed to the thirdhand nicotine or the
chemicals formed from the nicotine. I think the diffusion
study will answer this question.
So the first study that you already seen, we just released
the vapor in the exposure chamber. We wanted to make sure that
the vapor can stick, or it was the question that explored in
the study whether the vapor can stick to the surfaces and we
can find and detect the nicotine on the surfaces. And we
simply released the vapor in an exposure chamber. We wait a
little bit and we wipe the surfaces, different surfaces, in
exposure chamber, and we were able to see some increase of the
nicotine levels deposited on the surfaces.
So with this very simple experiment, we concluded that
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there might be the danger of the thirdhand exposure to nicotine
with electronic cigarettes, and especially with the floor. The
products that we used in the study, we think that there was
some kind of the droplets of aerosols were actually deposited
on the floor, and that's why we found significantly higher
levels of the nicotine deposited on the floor.
But then we decided to confirm the study with real-life
conditions. And it was a very small study, the pilot study,
but I think this is the first of this kind. We went to the
houses of the electronic cigarette users. We were looking for
long-term user, so the people who are using the product for a
long time. And we also went to smoker houses, and we went to
the nonsmokers and nonusers of electronic cigarettes because we
want to have this control, the negative and the positive
control, in our study.
I want to mention, this is the first study, the pilot
study, but here are the results. We found that nicotine levels
deposited on the surfaces in the houses of electronic cigarette
users are actually the same as what we found in the nonsmokers
and nonusers of electronic cigarettes, and they were
significantly lower than found in the smokers' houses.
So is there any potential that the nicotine either
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deposited on the surfaces or present in the indoor air can be
absorbed by the nonusers? So the people who are living with
the users of electronic cigarettes or the children of the users
at home. And I found one study that is already published,
showing the levels of the biomarker of exposure to nicotine,
which is cotinine, and this study suggested that the nicotine
from electronic cigarettes can be absorbed by nonusers.
So just the conclusions from our studies and the other
studies that I presented.
Electronic cigarettes are not a source of many volatile
toxicants in indoor air. This is the comparator with tobacco
cigarettes. I didn't mention the formaldehyde and other
carbonyls in my presentation, as it was discussed previously.
I think that we need to continue research and look for the
other chemicals.
We have these other ingredients added to electronic
cigarettes, like flavorings, and we don't really know whether
these flavorings are exhaled and in what amount and what's
going on with the aromatic aldehydes and the other chemicals.
Electronic cigarettes are a secondhand exposure to
nicotine, but to much lower extent than tobacco cigarettes. I
think all the studies that were presented today showed similar
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findings. So you see some increase in the nicotine from the
background is low, but it is, and it's much lower than from
tobacco cigarettes. So using electronic cigarettes indoors
significantly reduced secondhand and thirdhand exposure to
nicotine compared to smoking tobacco cigarettes.
And we need research to evaluate long-term effects of
passive exposure to vapor from electronic cigarettes, including
using the products to reduce harmful tobacco smoke exposure to
others or to get around a smoke-free policy.
And I want to thank you for your attention.
(Applause.)
DR. DRESLER: Could I ask the panelists to come up,
please? Okay.
And for our transcriber, first sitting is Dr. Goniewicz,
followed by Dr. Offermann, Persily, Pritchard, Sarkar, and
Thornburg, okay?
All right. So everybody's writing their questions down
and passing them to the inside, please.
Clarifying question. The study on formaldehyde published
in the New England Journal said that no formaldehyde was
detected when used as intended, as designed. Did you consider
this? Wouldn't this show your testing machines are not
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calibrated to mimic human use, as shown by your outlier results
similarly suggest? And that's for Bud Offermann.
MR. OFFERMANN: No. We did 28 brands now, flavors of
e-cigarettes. Only a couple of them were variable to each.
All of them, every single one of them produced aldehydes,
including formaldehyde. Our techniques are robust, sound.
Unlike some of the other studies I've seen, we did a lot of
quality assurance/quality control on the sampler. I believe
the higher emissions that we're seeing in formaldehyde are as a
result of -- most of the formaldehyde is actually in the
particulate phase. So I think that's it.
When we did the variable voltage tests, there were
criticisms in the New England Journal article about that it was
run at too high a voltage and it gave a burned taste; a dry
puff was the criticism. I think that's a good criticism.
Fortunately, that criticism was raised before we did our
variable voltage test. So we had taste tests done to determine
at what voltage we started getting dry puff, and we conducted
our tests below that voltage.
So I believe in our measurements, and I believe we have
found that most of the formaldehyde is in the particle phase
and that research going forward needs to collect both the
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particle phase and the gas phase. And that's also true for
nicotine.
DR. DRESLER: Okay, anybody else? Would you like to?
DR. SARKAR: I just want to add a clarifying comment. And
Dr. Offermann made this comment a couple of times about the
robustness of the methods in other publications. I'm sure
you're not referring to ours because, as far as our methods, we
considered that methods that they had employed were all
validated.
So the data that I showed from the first two studies were
NIOSH methods that were validated and had the appropriate
standards and controls, as well as the analytical methods that
we used for the controlled clinical study were also validated.
DR. DRESLER: So how does someone correctly and most
accurately explain to the average person -- and I'm going to
say, to the average person and then to the scientists -- the
difference between vapor or aerosol? So we keep hearing the
words "vapor," but they're aerosols. So which is
scientifically the correct terms to use publicly and then when
talking to scientists? That's for everyone.
MR. OFFERMANN: Okay. They had a nice definition, one of
the speakers earlier today. Vapor is a gas. And primarily
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what we're dealing here with is aerosol, which is a combination
of gas and suspended particles, and these particles are liquid
droplets.
So I think it has a lot of appeal to say vaping, but in
truth, what people are doing are aerosolizing. So the correct
terminology is aerosol, but I think the public has adopted
vaping. So I don't know if we're going to get away from that.
MR. PRITCHARD: Okay. Yeah, I was pleased to see earlier
that one of the presenters has started to explore definitions
and criteria, because as we heard yesterday afternoon, there
was even the term "smoke" being invoked, and we've seen "fog"
appearing elsewhere, you know, a clear reference to theatrical
smoke, similar terminology. So, again, I would agree, there is
a popular or general term, but I think for us, as we would sit
here today, it would be an aerosol at the technical level.
DR. DRESLER: Anyone else?
DR. SARKAR: I'll just put my two cents. I think that I'd
agreed that scientifically aerosol is the right terminology,
but vaping seems to have the right kind of ring to it, and that
has stuck. But if you're talking in a scientific context,
probably aerosol is the appropriate term.
DR. DRESLER: Okay. I think, you know, this goes to how
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do we educate the public about what they're doing? Since we're
interested in good education to the public, how do we explain
that to them too, that it's actually an aerosol that they're
vaping?
Dr. Offermann, how did you come up with the 1% of OSHA?
MR. OFFERMANN: A good question. Let me just preface that
the 1% -- I think I mentioned that doing something less than
the occupational guideline when you're talking about young
children, women, whatever, the general public, it should be
something less. So what we did is we took the 15 or so
compounds that have both OSHA PELs and have OEHHA CRELs, which
are nonindustrial levels, and we looked at those, and the
average is 1%. It hovers around that. So that's how we
arrived at using 1%.
DR. DRESLER: Okay. And if you think this follows on, can
you please explain in detail the various governmental and other
standards or baselines for chemical exposure for us nonexperts?
So maybe that's for everyone. So whose standard are we going
to use? You picked 1%. NIOSH? How will we decide what we use
as standards or baselines for chemical exposure?
MR. OFFERMANN: I'll just kick it off and then pass it on
down, because I've been critical of studies that invoke the
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occupational exposure guidelines.
First of all, occupational exposure guidelines are not
protective OSHA guidelines. At those levels we're anticipating
having injury and stuff, so we would want to use something not
even approaching that. And when we're working with people that
are going to be exposed for more than 8 hours a day, perhaps in
a home or whatever, or have sensitive people like infants and
pregnant women, we want to use something less. The OEHHA
guidelines from California are designed with that protection
factor in place. If you don't have an OEHHA guideline, you
might look at the ratio of OEHHA to PELs, which is about 1%.
DR. DRESLER: What's PEL?
MR. OFFERMANN: Permissible exposure guideline, the OSHA.
And so we would use 1%, which is what I used and other
researchers in the indoor air quality field use.
DR. DRESLER: Dr. Persily.
DR. PERSILY: Let me just add to that a little bit. It's
really important to distinguish between standards and
guidelines. I mean, standards are formal declarations of what
is or isn't acceptable. We have standards for occupational
exposures out of OSHA, which, as Bud noted, has been -- you
know, is clear. If you look at the indoor air quality field,
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those are not appropriate for nonindustrial environments,
schools, homes, nonindustrial workplaces.
We mentioned the ASHRAE Standard 62.1, the ventilation and
indoor air quality standard. It is a very good explanation of
what those occupational standards are good for and that they
really don't apply to indoor environments. So that's an
accepted -- I hate to use the word "fact," but it's an accepted
principle in the indoor air quality field.
So we have occupational standards. We have outdoor air
quality standards issued by EPA. And then everything else is
kind of a guideline. And that's fine. You know, it's
important, when you look at a guideline, is it an indoor air
quality guideline for nonindustrial environments? And if it
is, then it's relevant. And so you need to keep that in mind
because of the differences in the population and the goals of
those guidelines and standards.
DR. DRESLER: Anyone else?
MR. PRITCHARD: Okay, if I could just kind of separate
some of this slightly. When we were presenting the data for
formaldehyde and acetaldehyde, that was not a workplace
exposure. That wasn't the UK WEL, because for those there are
general guidances available, and the guidance set for WHO, at
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their level. There's more detail in the paper. But
essentially the level set by WHO, they state that this value is
sufficient to prevent long-term health effects, including
cancer. And this is based on two distinct risk assessment
models.
So I think, you know, when we're having this debate, we
need to be clear. As you say, there are the workplaces, the
industrial, and there are guidelines which apply differently in
different ways. Okay, so that's just a point there.
And as we were presenting, for us, it was for context
because so often in making communications -- you know, there's
a graph for what does that level mean? What does it mean? How
does that relate to something else which has been established?
So there's a point there as well.
On the ASHRAE standard, I note that being referenced as
sort of -- as a matter of fact. But in there it also calls --
you know, default minimum ventilation is 0.78, and yet we see,
in the data presented, a value of 0.3 was used for air changes
per hour. So I think, you know, there needs to be care
exercised there.
DR. DRESLER: And you're saying it's complicated?
MR. PRITCHARD: I'm saying it's complicated, indeed.
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Certainly for some of the workplace exposure limits, there are,
I think -- from my recollection, there are about eight or nine
different regulations, for example, around PG standards for
that. And they're all coming from the same source data. I
believe it's Schober et al., which is the sort of lead paper in
that area. And yet there are different risk assessment tools
used by different regulatory authorities, all ostensibly trying
to achieve the same endpoints. There's a question there. Why
the big difference? And there are different models applied.
DR. DRESLER: Okay.
MR. PRITCHARD: And just one final point. I believe that
in making a conversion, I would, from a toxicological
perspective, question dividing something by 100 just as a
matter of course. I recall that was common practice over 10,
over 10, you know, division conversions. But I believe that
what is standard practice for risk assessment is more
sophisticated than divide by 100 using such things as DNELs and
so on and so forth. And this is common inside the European
discussion on chemical risk assessment.
DR. DRESLER: Dr. Goniewicz.
DR. GONIEWICZ: Yeah, I want to add one thing. I'm not
using the occupational standards in my research to understand
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the risk of the electronic cigarettes. And the reason is, you
know, if you are taking the chemicals from tobacco smoke --
from tobacco smoke -- and you do the same modeling and the same
prediction, what would be the level in the indoor air, most of
the chemicals will be below limits of occupational exposure.
But we all know how dangerous is secondhand tobacco smoke, and
the people are getting sick from being exposed to secondhand
tobacco smoke.
The second point is that the exposure is the function of
the concentration and the time you are exposed. And when we
are considering the electronic cigarette, the passive exposure
to electronic cigarettes, we need to consider the scenario that
there was a person, for example, living with the users in the
same home and being exposed for 10 years to certain chemicals.
And, finally, we need to remember the effect of being
exposed to either tobacco smoke or secondhand vapor is a
cumulative function of being exposed to all the chemicals,
propylene glycol, glycerin, nicotine, and the other chemicals.
When we are taking just one standard, we are just talking about
one chemical, that you are exposed to one chemical. Tobacco
smoke is like thousands of chemicals. With electronic
cigarette vapor, maybe 100 maximum. But it will be the
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cumulative effect, and I think it's too early to make any
conclusion about the health effects and health consequences
just based on the comparing of the concentration with the work
standards.
DR. DRESLER: Dr. Sarkar.
DR. SARKAR: I just wanted to remind everybody that -- and
as you said, Dr. Dresler, it's not simple; it's complicated.
But also it's not something that we can sit here and answer. I
think it goes back to the point that I made in my presentation,
that what you need is to look at all the available evidence and
integrate it all into a risk assessment and the likelihood of
harm to the nonusers. It's not only just comparing the levels
in the air to some exposure limits set by OSHA. I used that
just as a point of reference to contextualize, but I think what
we need to do is do a full assessment of the potential for
harm.
As Maciej pointed out, you know, what is the cumulative
exposure and what is the likelihood of harm to the nonuser in
making this determination? It should be based on science and
evidence, and the appropriate regulatory body should be
involved in making that determination.
DR. DRESLER: A quick question for Bud. It says, on your
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y-axis of your graphs, I didn't see any units. Was it
micrograms per day or micrograms per meter cubed?
MR. OFFERMANN: That's good. Okay. Well, there were two
graphs. They were the hazard quotients you might remember I
spoke of, which is it's dimensionless. There's no dimension to
it. It's a hazard quotient. So it's just like the ratio of
the exposure.
Let's say the exposure is 100 µg/m3, and let's say the
guideline for exposure is 50 µg/m3. One hundred divided by 50
is 2. The hazard quotient is 2. Hazard quotients over 1
indicate a health risk.
And as Dr. Goniewicz stated, you really need to
cumulatively do what they call the hazard index, and you add up
the hazard quotients for those chemicals that target the same
organ, like the lungs. So I didn't do that in mine, but we
would actually add them up, and that gives you a higher risk
assessment.
DR. DRESLER: Okay, for the panel. Given that there are
hundreds of different e-cigarettes, including the great variety
of nicotine concentrations, voltage, design, device design, et
cetera, is it really appropriate to generalize any study to the
e-cig category? What do we do with all of this being done on
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one, two, three products and there's, what, 450 in the U.S.?
MR. OFFERMANN: Well, I think that's a good question.
We've done 28 brand flavors. They all make formaldehyde but
some make 500 times more, and even within brands. And if you
look at the researchers' data from all of us around this table,
even within the same brand, the same e-cigarette, there's a lot
of variation. The vaporization process, the mass transfer is a
chaotic process. So they don't precisely deliver the same
thing every time. So the point is well taken. You wouldn't
want to generalize from one. I'm generalizing from 28 brands,
but that's a good point.
DR. GONIEWICZ: I agree. We always try to use as many
brands as we can in our research and make a conclusion based on
the variability of the products. I don't know what would be
the optimum approach here. I think we need to decide, for the
product testing, on some kind of standard method that we will
use for all products for the regulatory purposes. I don't know
if this is the best approach for the risk assessment. Maybe
not. But I cannot imagine that we will have standards for the
Product A and standards for the Product B just to evaluate what
is the risk, what is the nicotine delivery, what is the
performance of the products? It will be very challenging for
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you or FDA to test each product with a different standard
method. I cannot foresee it.
DR. THORNBURG: In respect to secondhand exposures, you
know, to get to the question, you know, you're asking for sort
of a representative observational exposure study where you're
not really -- with a sufficient sample size where you don't
have to control for the type of e-cig being used. So that
actually could turn into a very large study.
But I think an advantage of that type of study -- and this
gets into the representativeness of exposures and some of the
earlier discussion. You know, we live in a complex
environment, and there are a lot of chemicals in the e-cig
emissions, but there are also a lot of other chemicals in the
air, and it's trying to apportion, you know, where is someone's
exposure and dose coming from? Is it actually coming from the
e-cig, secondhand exposure to the e-cig emissions, or is it
coming from some other source?
DR. DRESLER: So Dr. Sarkar and then --
DR. SARKAR: Go ahead.
DR. DRESLER: No, it's all right, Dr. Sarkar. Go ahead.
DR. SARKAR: Yeah. You know, I just want to bring us back
to the discussion that we were having on modeling. Perhaps one
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of the approaches could be that if we had a model that was good
enough to simulate the different types of conditions in the
products -- and that would be one way of addressing. Clearly,
it would be very difficult to test all 3,000 or so different
e-vapor products that are on the market, but maybe modeling
will be an approach.
MR. PRITCHARD: Just to follow on from that. I see some
value in that, but it would need to be some kind of a tiered
approaches that are essentially through product standards or by
the development of an appropriate model that you could screen
for different products essentially. And just from a practical
level, testing all 3,000 different iterations of all different
products out there would be a significant challenge for any
regulator and indeed the manufacturers.
So I see, while there is a role in modeling, as we've
seen, there are different approaches you can take just within
the models, you know, like compare ours with that taken by Bud
here.
So, yeah, I think probably a tiered approach screening and
then moving forward with those products. And, you know, you've
got to have some analytical thing. There are clear differences
between some of the experimental techniques, using machine
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based, than we actually see in the real world.
DR. PERSILY: I just wanted to -- oh, excuse me -- point
out that, you know, variability in sources and product types is
a fact of life in the risk assessment field, and people have
been doing risk assessments for years and decades, a
combination of modeling, field studies. And there's probably
no perfect risk assessment, but there are sound techniques and
approaches that are well established, that whoever does this
for this particular class of products or any class of products
you just have to deal with. But you're not making it up from
the beginning.
DR. DRESLER: I have one ton of questions. Okay, so based
on the scientific evidence, what is the most important factors
that raise health concerns relative to the secondary and
tertiary exposures? Okay, so what are those most important
factors? For example, is it the toxicity of the chemicals or
is it the size concentration of the aerosol particles? Which
is it? How do you weigh them?
MR. OFFERMANN: Well, there's a saying, that it's dose
that makes the poison. So every chemical has a certain
toxicity to it, but the e-cigarettes put off a lot of
chemicals. Some of them are more toxic than others. But it
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also puts out different amounts of them. For instance,
propylene glycol, generally recognized as safe for ingestion by
FDA. In my mind, not particularly good to breathe in, but not
exceptionally toxic. But there's just so much of it that is
produced. So you have to weigh both the amount that you're
exposed to and then what the specific toxicity is.
DR. THORNBURG: Yeah, it's a combination of all of the
factors. It's how toxic the chemical is, whether the chemicals
in the particle are gas phase. If it's a particle, how big is
that particle? And then you get into the user characteristics,
you know, like what's your total exposure? You know, not just
the time of exposure, but how much do you actually breathe in
during that time you're being exposed? There are a lot of
different factors that determine whether or not something is
dangerous or not to the public.
DR. DRESLER: Well, would you list out the top four? What
are the top four? Or top two or top one? How do you start
ranking them? How do you start saying what to look at? You're
writing a guideline. How do you make recommendations?
MR. OFFERMANN: Well, the hazard quotient is considered to
be, from a toxicological standpoint, the thing that rolls
everything in, the concentration, the toxicity. And so from a
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hazard quotient for the passive exposed person, it's the
propylene glycol and the nicotine. Those are the top two,
propylene glycol by the far the biggest and then nicotine
second.
DR. DRESLER: Okay.
MR. PRITCHARD: I think there's actually a step before all
of that, and it's the product or device level. We've heard
reports of different compounds, for example, or elements.
There are reports of some metals in the literature, and that
then raises a concern. Yet, in our own work or elsewhere, that
hasn't been seen. And, indeed, on the product level there are
things that can be engineered out such that those wouldn't be
seen, as well as just measuring the end of the product, so to
speak, on the emission side. I don't think it's just about
that. I think there's a role for device quality standards
there also. But, again, I would agree with the gentleman on
the end. You know, it's really integration of all of those
different issues.
DR. DRESLER: Okay. Some of the studies on flavorings
have shown that they can be harmful when inhaled. What are the
best approaches to evaluating the exposure to and potential
toxicity of flavorings in aerosol by exposed bystanders?
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DR. GONIEWICZ: I think there are some standard methods to
evaluate the toxicity of inhalation of substances. We can
start with the cell line experiments, so when we take cell
lines and expose to the vapor or smoke or aerosol. Then animal
studies. They are not perfect, but they provide some
information on the toxicity of the aerosol. And I think this
is the good beginning. We need the data on some of the
compounds that are used as the flavorings.
Right now, even if something is approved as the GRAS
compound for food, when we eat it, when we ingest it, it does
not necessarily mean that this compound will be safe for
inhaling. The acetaldehyde is one of the best examples. It is
GRAS approved, but it is very dangerously retained for the
inhalation. Some of the flavorings, like benzaldehyde, have
been shown to be toxic when inhaled, but they are completely
safe when we eat them.
So I think this step-by-step approach -- I don't think
there's one good method to test this, but there are well-
established methods to test for the toxicity, inhalation
toxicity.
DR. DRESLER: Okay. And this was for bystanders. So the
second- or thirdhand exposure, the same thing?
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DR. GONIEWICZ: It's the same.
DR. DRESLER: Okay, okay.
MR. PRITCHARD: I would agree with that. There are a
number of different approaches that can be taken. So there are
some cell line studies.
But, again, to my earlier point. I think there's a role
around the sort of feedstock for the devices. I was discussing
with one of the panelists earlier. They had some data which
showed the wide variation between flavors being used, and by
that I mean the absolute purity of them and the consistency of
that. So there's a role there in making an assessment on the
emission. If you've got wide-ranging product variability, then
you assess on one level, and it's fine. The product is
entirely inconsistent, unreliable, low-quality control, and
then, you know, that level doesn't achieve the aim there. So
there's a role there.
On the theme of the FEMA GRAS point that's been made a
number of times, now, when I hear that, I have to reflect that
from my own experience, with my own organization, we have a
team of experienced professional toxicologists with probably
combined experience running into the decades, and they're
making their assessment for our products, their product
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stewardship. It isn't simply a case of, well, does it have
FEMA GRAS? Well, that's fine. Any level goes. That is not
how any responsible manufacturer conducts their business.
DR. DRESLER: Anyone else?
DR. SARKAR: I just want to add to some of the stuff that
Dr. Goniewicz was saying. Let's not forget that these are not
new chemical entities, so there is probably a lot of published
information on these products already existing. It may not be
for the inhalation route, but maybe for other routes. And if
there are no data available for an inhalation route, then maybe
some preliminary studies where you can assess the breakdown of
the product and what are the levels of the products even before
you start testing them in cell lines or animal studies. Put
some context around what's the actual emission and what the
levels that you test in the test system would be important to
consider.
DR. DRESLER: So this is a do-you-agree question. When
companies are measuring impacts on nonsmokers, shouldn't we use
the alternative as clean air and not cigarettes or from
tobacco? So the comparator is to cigarettes. Are cigarettes
the correct comparator when you use clean air?
DR. GONIEWICZ: I think we should use both. This is my
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answer.
MR. OFFERMANN: Yeah. When you're going into the harm
reduction argument, I guess you certainly would want to look at
them compared to cigarettes. But if you want to look for
passive exposure to a non-cigarette smoker, we would be looking
to the clean air, I think.
DR. THORNBURG: I agree with everyone. Just a good study
would measure the background air concentrations before you
actually did exposures to electronic cigarettes or conventional
tobacco. So when you do those background measurements, your
goal is to make the air as clean as possible.
MR. PRITCHARD: I would go back to the point made by the
last gentleman. In making our study, you know, we were very
minded to the background control, and we're incredibly glad
that we did because what we found was the significant
contribution from personal care products. So things like
cyclohexenes coming up from that. So I think that the
background, the framing of it is absolutely essential. So I
was a surprised. I didn't think I put many hair care products
on that morning, but obviously I had.
(Laughter.)
DR. PERSILY: I just wanted to point out that the
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background level is a not a fixed constant. It's going to vary
from day to day and environment. And if it's a contaminant
from outside, you know, those outdoor contaminant levels can
vary quite a bit. So, you know, it's important to compare it
to the background, but you need to really establish your
background level as relevant to your measurements.
DR. SARKAR: I just want to set the record straight. In
our study, we used a cigarette as a reference, but not as a
reference to compare against but mainly to test the sensitivity
of our method. And as far as, you know, what's the right
comparator, I guess, you know, the background and the
likelihood of exposure from other sources should definitely be
considered. You know, if you really want clean air, you need
to live in the mountains.
DR. GONIEWICZ: If I can just --
DR. DRESLER: I do, I do.
DR. GONIEWICZ: -- add one thing. I think for us, the
scientists, it's more easy because it depends on what's the
question we ask. So if we ask the question of whether
electronic cigarettes can contribute to the secondhand
pollution of the indoor, so then our comparator will be the
indoor air. If we are asking, you know, what's the reduction
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in risk comparing to smoking or being passively exposed to
tobacco smoke, then the comparator will be tobacco smoke. But
I think let's go complex and let's use both comparators in our
studies. It will provide us with the complex answers.
DR. DRESLER: Okay. So what should the public perceive
when one study shows that no formaldehyde is created when the
product is used as intended, and other researchers claim the
polar opposite? So we did have presentations today that showed
that some results showed one direction and some showed the
other.
MR. OFFERMANN: Well, I think we're right.
(Laughter.)
MR. OFFERMANN: Well, we did spend a lot of effort on -- I
realize the other gentleman used NIOSH-approved techniques and
stuff. But I think when you apply these techniques to, like,
e-cigarettes, it's almost incumbent to do some recovery tests
and blank tests and these types of things. We did so much of
that that I'm very confident that although our measurements are
much higher than others, I think there's a good explanation for
it.
In fact, in studies now where we collected formaldehyde
both from the particulate fraction and separately from the gas
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fraction, we're seeing most of it -- two-thirds of it is in the
particulate phase. And most of the other researchers, to date,
are using samplers that primarily collect just the gas phase.
So I think there's a logical explanation for it, and so I trust
my measurements.
DR. SARKAR: Well -- go ahead.
MR. PRITCHARD: To Bud's point, then. He's very confident
in his data, and what I note in his publication, the NSRLs --
so the cancer reference and then the CREL levels that are
coming out for formaldehyde -- you know, notwithstanding
questions I have on some parts of the model, the hazard
quotient is coming up 0.04. And then on the indirect exposure,
they're 0.009, which is clear water below the level of 1. So,
you know, if that's right, read that.
MR. OFFERMANN: I want to agree here, that even with --
well, even with the very much higher emissions of formaldehyde
that we're seeing from e-cigarettes, I think that that
particular chemical, formaldehyde, is not likely to exceed the
hazard quotient. I agree. I think it approaches the hazard
quotient, but it doesn't. So I guess I agree with you. On the
other hand, the direct exposure to the user to these aldehydes
is very high.
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MR. PRITCHARD: Just on that last point -- and I note in
the model that, for the direct exposure, there's 100% retention
assumption, and for the bystander it's 100% inhalation of that.
So I think, you know, in looking at those levels of the hazard
quotient, direct, of 1.64, I think that's with 100% retention
assumed, and is that established?
MR. OFFERMANN: Yeah, a good question. I don't know why I
wrote that in the paper, 100% absorption for the direct user,
because it doesn't come into it. We're talking about exposure,
not dose. And so the exposure has nothing to do with
retention, how much. Although I would say that formaldehyde,
at least in the vapor phases, it's got a high retention factor,
but it doesn't play into the picture of the exposure hazard
assessment because we're talking exposure, not dose.
DR. DRESLER: Dr. Sarkar.
DR. SARKAR: I don't want to get into a debate about who's
right or who's wrong, but I think the important thing to
remember is that formaldehyde and a lot of these other emission
chemicals, it's a complicated story, right? And what we did
was if you look at what's the recommended method by a
regulatory body -- you know, NIOSH has a recommended method,
and we use that method, and we see that even with our sensitive
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methods, you see formaldehyde background levels.
As it was pointed out by one of the other speakers, this
is omnipresent, and you find it everywhere. So formaldehyde is
kind of a touchy subject anyway, to begin with. But it's also
present from a lot of other sources, and you'd find this in
ambient air.
DR. DRESLER: I think that's one of the things, is how
complex it is and controversial. So how do we move forward in
this?
So this is for the panel, but also Dr. Offermann. And
some formaldehyde -- you expressed a concern about formaldehyde
in particulate phase. For e-cigs, the particulates evaporate
rapidly in secondhand aerosols. Given the small mass of
particles in the aerosol, why are you concerned about
collection of aldehydes on DNPH? So why the concern? You're
saying they're in particles, but they evaporate quickly.
MR. OFFERMANN: Well, right. Well, I would debate that
they evaporate "quickly." Certainly we see people exhale the
particulate phase. The propylene glycol has a pretty low vapor
pressure, but the particles are small, so they do evaporate.
But okay, what's the point, though?
The formaldehyde, a lot of it's in the particulate phase.
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The particulate liquid phase, propylene glycol or glycerol,
evaporates along with the flavorants and the formaldehyde. And
so it changes from the particle phase to the gas phase. It
doesn't exist in the atmosphere. So the fact that there's a
phase transfer from particle to gas phase, I don't think is
relevant. It's still in the air.
DR. DRESLER: So let's change a little bit away from
formaldehyde. The particulate distribution for e-cigarettes is
smaller than for conventional cigarettes, and users exhale
ultra-fine particles. Do these ultra-fine particles remain in
the air longer than conventional cigarette particles and
potentially result in increased exposure for the nonuser?
MR. PRITCHARD: As I recall it, the aerosols have very
distinct properties, you know, on the physical side. I mean,
you saw data that we had on the mass spectrum. My
recollection, the longevity, as it were, of the aerosol, I
believe, has been reported in the literature: about 11 seconds
compared to around 20 minutes for cigarettes, cigarette smoke.
So I think, you know, immediately we're talking of very
different entities here, the rapid evaporation essentially of
the droplets, you know, back into the ambient air.
DR. DRESLER: Dr. Sarkar.
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DR. SARKAR: If you remember, I presented the overview of
the two pilot studies that we conducted in the room. We had
measured total suspended particles in that study, and it was
remarkable that the levels just drop as soon as the product use
was completed. So, you know, the longevity of the aerosol in
the room was very, very brief. And the results of that
particular graph that I'm talking about is in the publication
that we have on our science website.
DR. THORNBURG: Yeah, I disagree with you slightly on
that. It depends on the types of instrumentation you're using
to measure the aerosol size distribution in a room. Some of
the work we've done at RTI -- and Battelle Memorial Institute
has done similar work using a scanning mobility particle sizer,
which is something that can measure particles smaller than 100
nm. You're getting down into the 10 to 20 to 50 nm size
ranges. Those aerosol particles generated by the electronic
cigarettes do stay in the air for an extended period of time,
and they don't evaporate.
DR. DRESLER: Okay. So could these particles be
potentially moved more deeply into the lungs, into the alveoli
of the nonuser, due to the smaller size distribution?
DR. THORNBURG: So those very small particles typically
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would not penetrate to the deepest part of the lungs because
they're so small. Their diffusion rate is so quick, they would
deposit higher up in your respiratory tract.
DR. DRESLER: Okay. Actually, I thought they were
exhaled. When they get small enough, aren't they exhaled
out --
DR. THORNBURG: And they can also be exhaled too.
DR. DRESLER: Yeah. Anybody else?
DR. GONIEWICZ: I have a question, actually. Can they get
bigger in terms of agglomeration with the bigger particles?
DR. THORNBURG: Yes, they can also -- inside the lungs
they will. These particles will also absorb water, and they
will grow in size as well.
DR. DRESLER: Okay. Dr. Goniewicz, if nicotine was
detected in homes of non-cigarette and non-e-cigarette users,
where did it come from?
DR. GONIEWICZ: There are a few studies showing the same
pattern, that in some houses of the nonusers, nonsmokers, the
nicotine can be detected. First of all, this is the function
of the method that we used. So if you go with the very
sensitive method, you are able to detect low levels of the
nicotine. There might be some carryover effects. So if
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someone smoked in the house many years ago, we are still able
to detect the nicotine deposited on the surfaces. There is
some evidence showing that nicotine can actually penetrate in
the walls.
DR. DRESLER: Um-hum.
DR. GONIEWICZ: And there is some evidence suggesting that
even when there is no smoker present in the room, the nicotine
is slowly released from the surfaces. So this is quite a
dynamic process, and it does not stop immediately after smoking
ends.
DR. DRESLER: And I'm wondering too, for the public. So
nicotine is quite a sticky chemical too. You have to be quite
careful in the laboratory when measuring nicotine also.
DR. GONIEWICZ: Yes, there are studies showing that it's
actually really difficult to remove nicotine from the surfaces.
DR. DRESLER: Right. Anybody else?
(No response.)
DR. DRESLER: Dr. Sarkar, what do we know about harm from
PG or VG above a set limit? What do we know about the harm
from a set limit? It doesn't give me what the set limit is.
And the second part is you distinguished e-vapor from tank
systems. Please describe the difference.
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DR. SARKAR: So let me start with the last question first.
What we had done was, in the study that we had conducted, we
had asked the participants to bring their own e-liquids, and in
order to just standardize the conditions, we had used one
commercial version of a tank. And, of course, I think
everybody in the audience probably knows the difference between
the tanks having, you know, e-liquids versus -- the two e-vapor
products that we tested were cartridge-based systems.
Now, as far as your first question about the harm from PG
or glycerin, yeah, what we had done was compared it to the OSHA
limit as just a reference point. I think that in order to
assess the potential for harm from any of these constituents,
you'd have to take into consideration all the available
evidence, including the actual level of exposure in the
nonusers as well as the likelihood of the breakdown and all the
potential literature that's out there on the specific
constituents to make an assessment. So that's, you know, a
more broader, complicated risk assessment question.
DR. DRESLER: Okay. Anybody else want to -- no. Okay, as
e-cigarettes are proposed as substitutes for combusted
cigarettes, isn't it essential to compare e-cigarette emissions
to those from cigarettes, as some of the data presented? So
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this goes back to the question, I think. You said do both.
DR. GONIEWICZ: Yes. I think it depends on the question
that we ask. So if we are talking, for example, about a smoker
and we are proposing this harm reduction approach to
substituting tobacco cigarettes with electronic cigarettes --
and today, at the session, we are discussing secondhand
exposure and all the data we've heard today suggesting that
this harm reduction approach may be also -- may also affect
nonsmokers.
So if we have a smoker at home exposing their family
members to the tobacco smoke, and this smoker will switch to
electronic cigarettes and will not smoke anymore a conventional
cigarette, then the harm reduction will be also -- will also
affect the members of the family.
If we are taking about introducing electronic cigarettes
to indoor air, clean, protected spaces, then again the data
showing that something is released, something is coming out
from the device, from the aerosol exhaled, then the answer
would be electronic cigarettes can contribute to the secondhand
exposure to the contamination in the indoor air. And then the
answer would be different.
DR. DRESLER: So I'm going to follow up on that because
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sometimes these questions are coming from different people. So
this will be interesting after what you just said.
Speaking of background air quality, can the panelists give
a rule-of-thumb estimate for air constituents in the room we're
in now? Would any e-vapor used in this room make any
significant impact otherwise?
MR. OFFERMANN: So one puff or --
DR. DRESLER: No, let's say someone's having an
e-cigarette in the center of the room.
MR. OFFERMANN: One person with an e-cigarette?
DR. DRESLER: Okay, fine. Three. One, three. I'll give
you any of those.
MR. OFFERMANN: Well, I guess my point is it depends on --
you know, I think Andy's presentation about looking at how much
source there is -- so how many people are vaping and then the
size of the room. And then if we assume that this place meets
code on ventilation, I suppose that one e-vaper in the middle
of the room there, probably it wouldn't have a significant
impact on concentrations here, I would probably guess.
DR. DRESLER: Okay.
DR. THORNBURG: Just a caveat. It depends on where you're
sitting. Obviously, if you're sitting in the middle of the
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room --
DR. DRESLER: Yeah, right. So the caveat. So dose, we
have a dose, how close you are.
DR. THORNBURG: Correct.
DR. DRESLER: Is it ventilated? So some depends.
DR. SARKAR: What's the type of the product? Is it a
tank?
DR. DRESLER: What type?
DR. SARKAR: Yeah.
DR. DRESLER: Okay.
DR. GONIEWICZ: Again, maybe a little bit from the public
health perspective. You know, this same debate we might have
had here maybe 50 years ago. It doesn't really matter whether
it's one smoker or half of you are smoking tobacco cigarettes
right now, what would be the risk?
I don't know if this is the right debate. You know, if we
go with these nuances, the question is whether electronic
cigarettes should be allowed in the indoor spaces. And if the
electronic cigarettes become more and more popular, probably
more and more, we will have more and more users here sitting
and vaping. And then the question is whether we want to be
exposed to the secondhand vapor.
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I think all the factors affects. That's true. The amount
of the aerosol exhaled from the devices is a primary factor
here, the ventilation, the density. I think there are too many
variables.
MR. OFFERMANN: I think that's right. So if we have this
kind of unusual thing where one person way over there is
vaping, and is that a significant thing, I say no. But the
reason I did my passive exposure with, you know, 0.3 air
changes an hour, which, you know, if you don't have mechanical
ventilation and you have open windows and it's cold and it's
closed -- and I did a worst case, right?
So I'm kind of checking the fences, and if all the
chemicals that I evaluated came back with very low hazard
quotients, I'd be like, well, maybe there really isn't a
passive exposure issue here. But as you saw from my
presentation, that clearly was not the case. With the worst-
case assessment, hazard quotients were over 20. So that, I
think, frames the debate on should we allow e-cigarette use
indoors. And I think the answer is clearly no.
DR. DRESLER: Dr. Persily.
DR. PERSILY: I just wanted to comment on the 0.3 air
changes an hour is really not a low rate for a home. You know,
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for residences, the building -- the ventilation standards are
in the 0.2 to 0.3 air changes an hour range. For office
buildings, it really depends on the type of space, whether it's
a conference room or an office or, you know, a big office or a
classroom. You know, the air change rates can cover quite a
range.
And there's an important distinction to be made between
what the standards say and what occurs in actual buildings.
You know, just because you write -- put a ventilation
requirement in a standard, in a building code doesn't mean it's
actually going to happen in a real building. If you want to do
these things and think about worst cases or best cases, you
want to look at the standards. But you also want to look at
the ventilation measurements that have actually been made in
homes and commercial buildings and use those numbers. But back
where I was, 0.3 is not low for a house.
DR. DRESLER: You know, sort of following up on this, one
last question, I guess. So when you're talking about those
standards and the commercial standards and the standards in a
home, do those take into account the contamination over the
long term or is that -- you know, we heard before that we're
measuring at a single point. But when you're looking at those
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standards, is that for exposure over the long term?
DR. PERSILY: The standards are based on really all the
science that's available to the committee, which is limited,
okay, and a lot of it is based on practical experience. They
aren't based on, you know, strong episodic sources. You're not
going to control a strong episodic source with ventilation.
You know, you're going to control that with source control or
exhaust or something. So, you know, they don't -- they're not
really -- the ventilation standards don't really use a risk
assessment, you know, public health model to things.
DR. DRESLER: Okay.
DR. GONIEWICZ: One thing. In a risk assessment, if we
are going this road, I think we also need to consider who is
exposed to the potential secondhand vapor, and we should also
include what we called here, I think, in some presentations,
the sensitive population. So we might have the person with
asthma. We might have a pregnant woman. And so we need to
consider all these variables. So my reaction on the secondhand
exposure will be different than the other one, the other
person. And I think this is also the complex problem, and I
think that most of the occupational standards consider the
healthy subject being exposed.
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DR. PERSILY: Most of the occupational standards are based
on very, very old data for healthy white males, you know, which
I guess is not the population at large, and it is intended to
protect them from these -- Bud can probably -- he knows the
language better than I -- but from severe impairment on the
job. They're not intended for the general population of
sensitive individuals and children and people with asthma.
MR. OFFERMANN: Yeah, it's even worse than that. I mean,
it is a compromise between labor, industry, and government.
And these are not at all protective at the occupational level.
The healthy adult worker that is only exposed 40 hours a week,
half of them are expected to be impacted adversely. So we
don't start worrying, in industrial hygiene, when we're
approaching the PEL. We take action well below that. And what
we're suggesting for nonindustrial is like 1%. But even if it
was industrial, if we were at a third or a half of the PEL, we
would be in a respiratory program.
DR. DRESLER: Dr. Sarkar.
DR. SARKAR: I just want to make a comment. This was in
response to one of the previous questions. I think that
clearly this is a charged issue, and you know, there are a lot
of opinions. But at the end of the day, I think what we need
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to do is just rely on the scientific evidence and get a bunch
of experts together in a room -- no pun intended -- and just
have the regulations that are based on evidence and science.
DR. DRESLER: What a great way to end up the panel. So
thank you. Thank you very much to the speakers and to the
panel. This was a difficult topic. Thank you very much.
(Applause.)
DR. DRESLER: Okay. So we are going to do lunch. So we
are going to come back 1 hour later at a quarter to 1:00.
Okay, thank you very much.
(Whereupon, at 11:56 a.m., a lunch recess was taken.)
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A F T E R N O O N S E S S I O N
(12:46 p.m.)
DR. DRESLER: So welcome back for the afternoon session.
A heads-up. They were thinking they were going to march on
through, and probably not with that break. If anybody
disagrees with that -- I'm not seeing any disagreement with
that. So we'll go with clarifying questions and the panel
discussion.
We'll start out with the first session. The session is on
Health Effects of Secondary and Tertiary E-cigarette Exposures.
Our first speaker is Dr. Neal Benowitz from the University of
California in San Francisco. He will be speaking on Biomarkers
of Exposure to Secondhand Tobacco Smoke and Electronic
Cigarette Emissions: Implications for Predicting Adverse Health
Consequences.
And the other thing too. Because he needs to leave, so if
people will be doing their questions and write those and get
them over to the side so we'll ask them during the clarifying
questions. So clarifying and hard questions for Dr. Benowitz,
okay?
DR. BENOWITZ: Thank you, Carolyn.
So what I've tried to do in this presentation is to
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address the issues of what we know about passive smoke exposure
and disease, and what we know about the extent of exposure to
electronic cigarette emissions, and what we might be concerned
about for disease risk. The bottom line, as I'm sure you all
know, is that we don't know what the disease risks are from
secondhand e-cigarette emissions at this time.
Okay, so my disclosures. I have been a consultant to
pharmaceutical companies that market smoking cessation
medications, and I have in the past been a paid expert in
litigation against tobacco companies.
So if you look at sort of a toxicant exposure/disease risk
model, this is what you might see. There is an exposure. We
heard this morning about air levels of toxicants. I'll be
talking about biomarkers of exposure, internal dose. And then
there are early biological effects in which there are also some
biomarkers; subclinical health effects, there may be some
biomarkers for that; and then clinical disease.
We really don't have anything yet for passive exposure to
electronic cigarette emissions for early biological effects or
subclinical effects. So I'll talk -- use some of the data we
heard this morning about air exposure and talk about biomarkers
and what we might be concerned about.
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So an overview of my talk. I want to start talking about
secondhand smoke because that's sort of a gold standard for
positive control for disease. We know it causes disease, and
we'll talk about how it does that and what biomarkers we have
of exposure. We'll then talk about the constituents of
cigarette smoke versus electronic cigarette emissions, the
biomarker studies that have been done for secondhand
e-cigarette emissions, and challenges for assessing biomarkers
and concerns for disease risk.
So if we start with just secondhand smoke, these are the
numbers of diseases that have been well established to be
related to secondhand smoke, and they really come into four
categories. There are respiratory infections, cancer,
cardiovascular disease, and reproductive hazards. So it's
clear that secondhand emissions to tobacco smoke constituents
can cause disease.
If we look at tobacco smoke, this is just a small number
of the many toxicants. There are thousands of toxicants in
tobacco smoke. Many of those are carcinogens or reactive
compounds that are involved in causing inflammatory responses.
The ones here that are -- aside from nicotine and minor
alkaloids, virtually all the rest of them are products of
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combustion. And so the big issue is how much of the disease
risk from secondhand smoke is from combustion products versus
the things that might be found in electronic cigarette
emissions.
If we look at electronic cigarettes, we see nicotine,
which is common with tobacco. We certainly heard about
propylene glycol and glycerin. Tobacco-derived nitrosamines,
which are carcinogenic. Some products have them in low levels,
levels much lower than those of cigarettes and secondhand
tobacco smoke.
Particulates still remain a concern. We heard a little
bit this morning about particulates. We heard the question
about metals. And I would just get back to the issue that the
particulate nature may depend on the product and the metals in
the products. It's very difficult to generalize about
e-cigarette emissions when product design influences the
emissions.
Volatile organic compounds are clearly of concern.
Flavorants you heard a little bit about. Cinnamaldehyde should
also be on this list, too, this morning. I thought those data
were very interesting. And then some of the e-cigarettes,
especially the early ones, had a number of different
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contaminants. But there are no combustion products.
So Maciej talked about, on the panel, when you look at
individual constituents, it's hard to assess overall risk
because you're really looking at a combination of things. At
least with e-cigarette emissions, the combination is much
smaller than the secondhand tobacco smoke, where we have
hundreds or thousands of potential toxicants interacting with
one another.
So some comments about what happens to the constituents of
tobacco smoke in the air. So here's a cartoon showing
generation of gases, which include formaldehyde -- I guess it's
also in the particles, as you heard before -- carbon monoxide,
benzene, nitrogen oxides, butadiene, acrolein, et cetera. And
then particles which when they're first generated contain
nicotine and then nicotine rapidly leaves the particles. I
suspect that's true for electronic cigarette particles as well,
because nicotine is extremely volatile. The particles are
alkaline, and some nicotine probably leaves the e-cigarette
particles quickly as well, and there are no data about how fast
and what the partition is.
An important issue is what happens to smoke in a room.
And this is a very important study that was published by Brett
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Singer from Lawrence Berkeley Laboratory in California, and
this was a study done in a chamber that resembled a room. So
it had carpets, it had curtains, it had fabrics.
And he basically looked at the constituents of secondhand
smoke over 2 hours, and this shows what was left 2 hours later.
So you can see some things, like isoprene, acrolein, and
benzene, are mostly still in the air. This is the percentage
of what was present 2 hours ago, so 80% or more. If you look
at nicotine, less than 1% is left.
So nicotine is basically leaving the particles, leaving
the secondhand emissions, and it's going into the room, it's
going into the carpets and the walls and the surfaces. That's
an issue because we know nicotine does go into the environment,
and it stays there and also builds up. So with regular
exposure, nicotine levels build up for months or years.
Another thing about this is that most of the data we have
on secondhand smoke, in terms of biomarkers and disease risk,
relates for cotinine and disease risk. But you can see, if
you're looking at the nicotine levels, which would be the
cotinine exposure, versus another toxicant -- say you look at
benzene, but it could be nitrosamines -- because nicotine
levels drop quickly, nicotine exposure underestimates exposure
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to other toxicants.
And so a study that we did with -- Maciej, I think, was
involved with this as well. We looked at the NNAL, which is a
nitrosamine biomarker to cotinine ratio in people who are
active smokers versus secondhand smokers, and the ratio was
much, much higher in secondhand smokers because nicotine levels
are -- their nicotine exposure is relatively low. So
secondhand smoke gets enriched with other toxicants, so
nicotine underestimates exposure. But still, that's the best
biomarker we have, disease risk from secondhand smoke.
Thirdhand smoke you heard about before. This is really
the residual smoke that remains on the surfaces and dust after
the tobacco has been smoked. You heard again from Maciej that
secondary pollutants can be generated.
Here's also a slide he showed, which basically shows that
with nitrogen oxides and water, you generate HONO, which is
reactive, you know, reacts with nicotine, and generates
nitrosamines on surfaces, including NNA, which is not present
in tobacco smoke. So actually some unique nitrosamines present
in the environment that are markers are thirdhand smoke
exposures.
We've actually been trying to measure this in people, and
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we've not been able to measure it yet. Either levels are low,
or we don't have adequate sensitivity, but we're still trying
to get a sense of what the systemic exposure is from thirdhand
smoke toxicants. But clearly this is a concern with
e-cigarette emissions if there is a lot of cigarettes and a lot
of nicotine exhaled.
So if you look at the toxicants that the World Health
Organization study group for tobacco regulation has identified
as key toxicants for tobacco smoke, and presumably for
secondhand smoke as well -- so it's nitrosamines,
benzo(a)pyrene, other PAHs, carbon monoxide, and then
acetaldehyde, benzene, butadiene, acrylonitrile,
crotonaldehyde.
For e-cigarettes there, in general, is little
nitrosamines, although some products have them; pHs are low;
carbon monoxide is not. The aldehydes clearly are a concern
for e-cigarettes and disease risk.
So let me just talk a little bit about what kind of
biomarker studies you can use for secondhand smoke exposure and
what's the best we can do.
So I'll show you data from a study that we did in San
Francisco, a very sort of semi-real life study. A parked
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automobile in a parking lot with the windows open, variable
degrees. A smoker sitting in the front seat. A nonsmoker in
the back seat. The smoker smokes three cigarettes, one every
20 minutes, in the front seat, and then the nonsmoker gets
submitted to our research ward for 24 hours and we get
biomarkers. So I think this is the most controlled sort of
situation. And we looked at exchange rates and air levels and
whatnot, but I'll just show you the biomarkers.
So the first is cotinine. So you can see that -- and in
terms of the intensity of exposure, the nonsmokers did not find
the secondhand smoke exposure very irritating. So it was not
high enough to be really irritating to the nonsmoker. You can
see, though, there's a very strong cotinine signal, a very
clear effect. The levels are pretty low. We're talking about
an increase from 0.05 to 0.15 ng/mL, where smokers got a level
of 200. So you can see this sort of sensitivity that you need
to measure cotinine levels from secondhand smoke exposure.
Urine cotinine levels are shown here. These levels are
about five times higher because concentrations are higher in
urine. So there are ways that you can look at that as well.
Here is urine NNAL, which again the only two really
specific biomarkers we have for tobacco smoke exposure are
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nicotine and metabolites like cotinine and tobacco
nitrosamines. And you can see a very strong signal for NNAL.
Cotinine is the one biomarker that has been related to
disease risk and for secondhand smoke. NNAL certainly is
thought to play a role, but it's not been directly associated,
and it's not likely to be useful for electronic cigarettes.
The aldehydes, which you've heard a lot about. There are
a number of aldehydes that are measured in -- that are
generated by cigarette smoking and some presumably by
e-cigarette use. These are the ones that are thought to be
toxicants. And a hazard index analysis of these suggests that
these VOCs are actually responsible for the biggest percentage
of cardiovascular and pulmonary disease of all the constituents
of tobacco smoke and a major contribution to cancer as well.
And these can be measured in the urine as mercapturic acid
metabolites.
And so in our car study you can see acrylonitrile, a
carcinogen. Levels increased twofold looking at urine
mercapturic acid metabolites. Benzene causes leukemia and
increases 50%. Butadiene, a carcinogen, also increases as
well.
So, in a carefully controlled situation, you can measure
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exposure to VOCs, even with secondhand smoke exposure, but you
can also see that there's a background level. So these things
are not as specific for tobacco smoke. And as you heard this
morning, there can be quite a lot of variability in the
environment. So whether you could measure something like this
from secondhand exposure to e-cigarette emissions, it's
doubtful.
So, again, to restate what Maciej said this morning,
cigarette smoke -- secondhand cigarette smoke is a combination
of exhaled mainstream smoke and sidestream smoke, and 75% of
the cigarette ends up in sidestream smoke. So most of what
you're exposed to is from sidestream smoke generation. An
electronic cigarette is really exhaled mainstream smoke only.
And I think there have been a number of passive
e-cigarette emission exposure studies that have tried to use
direct emissions, and those would be not appropriate. If
you're going to look at secondhand exposure, we really need to
look at what gets emitted by the smoker -- not a smoker, but
e-cigarette user, because it's not the same thing.
And I'll show you again -- okay, before I get to that, the
question is, well, how much gets exhaled by the user? And it
really depends on the user and how you're using it and why
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you're using it.
So here is an adolescent girl who's playing with smoke.
So she's taking it in and blowing it out, and she's generating
a lot of aerosol. There's probably a lot of nicotine in this
aerosol.
You know, in our lab we do studies a little bit like you
heard this morning from Dr. Pritchard, where we have people use
e-cigarette devices and they use it in a standardized protocol,
so like 15 puffs. And then we have them exhale into a trap
system where we trap nicotine, you know, as well as propylene
glycol and glycerin, in a series of traps and making sure that
we get all of it because the third trap has got nothing. And
then we can measure what we collect in the traps and compare it
to what they're using. So I'll just show data for nicotine.
Here's data from 10 users. We estimate the dose exposure
by how much e-liquid gets used from the device. We measure the
device weight before and afterwards, and that gives us an
effective dose of nicotine. And so we figure out how much
nicotine gets delivered in milligrams, and then we measure what
gets exhaled. So we trap what gets exhaled and figure out what
gets retained. So, in our study, by and large, we find that
more than 95% gets retained by most people, but not everybody.
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One person only retained 55%.
So if we're saying this is the source of secondhand
exposure of electronic cigarette aerosol, it really depends on
the user and how they're using, probably what the device is,
and whether they're blowing smoke rings or whether they're
using it to get nicotine. Our people were all pretty solid
electronic cigarette users who were taking in a fair amount of
nicotine.
So I think it is hard to generalize about secondhand
exposure to nicotine because it depends on who's using it and
how they're using it and what device is being used.
Here's some data from Schober's paper. You heard about
this, this morning. I just show this to emphasize the fact
that propylene glycol and glycerin seem to be and should be
present in the environment. Although I should also say I
haven't shown the data now, but people retain 70% to 80% of
propylene glycol and glycerin as well. There's also high
retention of that, and most likely formaldehyde as well. So a
lot of the materials from electronic cigarettes get retained.
This study did not find significant increases in
formaldehyde, acetaldehyde, acrolein, and benzene. PM2.5
obviously gets as well.
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Here's something from Maciej's paper. He also showed that
this morning, suggesting nicotine levels are about 10% in the
air when people are using e-cigarettes compared to regular
cigarettes and higher than background. And PM2.5 was sevenfold
higher. So I think the concerns, at least here, are what are
potential effects of nicotine and what are the effects of
PM2.5?
On the one study, the Ballbe study, which you heard about
again this morning from Maciej -- it's sort of summarized here.
This was a small study. So these were looking at nonsmokers
who lived either with cigarette smokers, e-cigarette users, or
nonusers, the controls. There are only five e-cigarette homes,
so the sample size is small.
What he found looking at air nicotine levels, there's
about a fivefold difference in air nicotine levels where
e-cigarettes were used compared to regular cigarettes. There
was a twofold difference in cotinine, so a much smaller level.
But this is the only biomarker study, so it shows that there
certainly can be some nicotine exposure. Why there's a
discrepancy between air levels and saliva levels, I don't know.
There could be exposure outside the home, which is common in
Spain.
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So it does suggest, if we saw this kind of an effect for
secondhand smoke, we'd say this is consistent with a risk of
cardiovascular disease, at least, you know, and maybe cancer.
However, for secondhand smoke, nicotine is a marker for the
other thousands of toxicants rather than nicotine being a
toxicant itself. And so whether nicotine predicts other
toxicant exposure here is hard to know. So that's one of the
things we have to deal with.
So the challenges in assessing secondhand smoke exposure,
in terms of systemic exposure, the exposure levels are low.
Nicotine is the only specific biomarker, and it underestimates
exposure to other toxicants in general. For e-cigarettes,
there's also the complication that people use different amounts
of nicotine and different e-cigarettes. For tobacco, most
cigarettes contain about 10 mg of nicotine, so nicotine is
pretty consistent. So it's a challenge using that.
Other toxicants of concern, like aldehydes, are
endogenous. So there are natural levels and there are other
environmental sources.
So let me just get -- I'll just go on. So the concerns
for disease risk, so far as I can see from what -- we see
nicotine. Certainly there is potential low-level exposure, not
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likely to have cardiovascular effects.
There are some very interesting data looking at effects of
secondhand tobacco smoke and nicotinic receptors, showing
nicotine can actually activate brain receptors at even
secondhand smoke levels. So there is the possibility that
nicotine could have effects even at low levels.
The particles are clearly there. They're present in lower
concentrations in secondhand smoke. We know that particles
convey cardiovascular risk from cigarette smoke and
carbonaceous particles. We don't know what the risk is of
particles per se from electronic cigarettes.
Carbonyls, if they are present -- and we saw conflicting
data about these -- certainly there is concern for pulmonary
inflammation and asthma.
Propylene glycol. I think there are certainly some animal
studies that show that propylene glycol can cause a pulmonary
inflammatory response, and I think there are concerns, you
know, for both of these in terms of asthma.
And, finally, what's not here are the flavorants. And I
think the data we heard this morning suggesting that there
might be -- 15% of the e-liquid might be a flavorant. So we
need to also look at what the potential presence in the
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environment is of flavorants.
So thank you for your attention.
(Applause.)
DR. DRESLER: We'll do questions after, okay?
Okay, our next speaker is Dr. Donald Graff from Celerion,
discussing on Assessing Second-Hand E-cigarette Aerosol
Exposure using 13C3-labeled Propylene Glycol.
DR. GRAFF: All right, thank you, FDA, for inviting me
here today to speak.
In the way of confidentiality -- not confidentiality,
conflict of interest. Sorry. My general counsel said
something about confidentiality, so that's where that came
from. As a contract research organization, we have performed
services for various companies who are evaluating electronic
cigarettes as well as other tobacco products, but also pharma
companies who are evaluating nicotine replacement therapy
products as well. But the data that I'm going to show you from
the study today was funded solely by Celerion.
Okay. So if we consider the centuries-old adage that it's
the dose that makes the poison, we really need to have an
understanding of not only what e-cigarette chemicals are in the
aerosols, and we did -- there was a fantastic discussion
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earlier today about those -- but we also need to have an
understanding in what amounts bystanders are exposed to, and
have some understanding of what amounts that are in the body at
the site of action, where they can elicit some sort of
physiological response if we're really looking to be able to
establish a cause-and-effect relationship here.
Okay. So at the most basic level of the secondhand
exposure debate, here we have two friends. Friend 1 here is a
vaper. And I'm going to use the term vaper today because --
well, mostly out of habit, but secondly, aerosolizer just
doesn't quite roll off the tongue as well. So Friend 1 here is
a vaper, Friend 2 is not, and when they get together, Friend 2
suggests that Friend 1's e-cigarette is making him sick. But
as Friend 1 questions here, how can we be sure?
And so it sounds like a very simple problem to answer, but
it's really quite complex, as we saw earlier today. Nicotine
and a lot of the other solvents, components of the e-liquids,
are everywhere in the environment. You can get them from food.
You can get them from cosmetics and a variety of other sources.
So what would be useful is if we are able to come up with a way
to establish what actually comes from the e-cigarette as
opposed to some of these other sources. And so the solution
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that we've come up with in the current study was to replace the
solvent -- and in this case, propylene glycol -- with one made
of stable isotopes and then use mass spectroscopy in order to
distinguish the constituents that came from the e-cigarette and
from potential other sources.
So in this case what we've done is Friend 1's e-cigarette
has been loaded with carbon-13 labeled propylene glycol, and as
the only source of carbon-13 labeled propylene glycol probably
that this guy has ever come into contact with, anything that
shows up in this guy's blood likely or definitely came from the
electronic cigarette of his friend.
Okay, just a little bit of chemistry here so that you have
an understanding of what's going on. So the atomic mass of
propylene glycol when we use carbon-12 is 76. And so when we
replace the carbons with carbon-13, we increase the atomic mass
by three, and the mass spec is able to differentiate between
these two.
And so building on something -- some other discussions
that were going on this morning. In addition to other benefits
of using a stable isotope, what we hope to be able to establish
is, is methods that can utilize this labeled propylene glycol
in order to track thermal and metabolic degradation products
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from propylene glycol, so, for example, formaldehyde and
acetaldehyde. Eventually we hope to be able to use this method
for that as well. I'll get to that later.
Okay. So the study that we performed is a small pilot
study, proof-of-concept study, where we took three vapers or we
enrolled three vapers and three non-vapers. The vapers self-
reported a 6-month product use history, daily product use for
30 days prior to the test visit. So they were experienced in
using vaping products. For the non-vapers, we asked that they
had no nicotine product use for 14 days prior to the test visit
and then limited their -- avoided environmental exposure to
nicotine for 48 hours prior to the test visit. We got a very
sensitive nicotine assay, so we wanted to get to have a long
enough washout period for those subjects.
All right. So, in terms of the study design, all six of
these subjects were confined to the test room. It was about
21.5 m3 in size. So we put them in the room about a half hour
before product administration, and they remained in the room
for 2 hours after.
And so at 8 o'clock we asked the vapers to begin using the
product, and we used a controlled administration in this case.
We asked them to take 30 puffs -- 30 3-second puffs at 30-
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second intervals, so about a 15-minute exposure. Kind of short
over that period of time. And then we -- there we go. We drew
blood before exposure and then for 8 hours after exposure.
And at noon, 4 hours after the exposure, we fed the
subjects a meal containing foods that were known to have
propylene glycol in them. So we gave them a Big Mac, a side
salad with 3 ounces of Kraft fat-free ranch dressing, two
chocolate fudge Pop Tarts, and an A&W root beer.
(Laughter.)
DR. GRAFF: So not exactly the lunch of champions, but
you'll see in a minute, it served the purpose for our study.
Actually, it sounds like my college meals that I used to have.
Okay. So for the device that we used, we used the kGo
bottom-feeder tank that we purchased from GNS Vapor there in
Lincoln, Nebraska. For the nicotine solution, we acquired the
pure nicotine from Nicobrand and the carbon-heavy propylene
glycol from Aptochem and then created our own solution. So we
made up a 1.8% nicotine solution and 98.2% propylene glycol
solution. And, of course, this is not a solution that you're
ever going to find in any commercial -- or likely to find in
any commercially available e-liquid.
But that wasn't our purpose here. What we wanted to do
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was to try to maximize the amount of exposure that the vapers
and the non-vapers would have. I actually wanted a higher
concentration of nicotine, but people who use these products
said there's no way. I wanted 5%, but they weren't going to --
that wasn't going to happen.
Okay. So the estimated exposure and the estimated dose to
propylene glycol and nicotine in the vaping subjects. So you
can see here Subjects 1 and 3 had a very similar -- acquired a
very similar dose of both propylene glycol and nicotine. And
the way we did this is we basically took the weight of the
product after, from the weight of the product before, and then
multiplied it by the concentration.
Subject 2, on the other hand, had a much lower exposure.
It was very evident that this guy was having some difficulty
activating the product during the exposure period. I think it
might have had something to do with the viscosity of the
solution, but I'm not 100% sure of that.
And so in terms of nicotine, which is kind of the known
quantity here, we were looking at about just over 4 mg for
Subjects 1 and 3 and then just over 1.5 for Subject 2.
All right. So for the nicotine plasma concentrations,
again, this is the known quantity. Based on the doses that we
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saw, pretty much the peaks that we expected to see, so ranging
from about 7.5 to just under 25 ng/mL. Then, of course, it
dissipated or was eliminated over the remaining 8 hours. And
so that's the vapers.
So the non-vapers, Subjects 4 and 6, we didn't see any
measurable concentrations at our limit of quantitation of 0.2.
Subject 5. Subject 5 had baseline concentrations. So he
came in prior to the exposure with concentrations of about 0.35
ng/mL, and he kind of hovered there for about 2 hours, and then
it went to not measurable. So, you know, this guy, can we 100%
definitively say that he didn't receive any nicotine from the
exposure? Well, no. If we had been able to label the nicotine
in this case, then we could have said that. We wanted to and
we tried, but we couldn't get the nicotine synthesized in time.
But we didn't really see a bump during the exposure either. So
the likelihood of this guy being very different than the other
two is slim, I think.
All right. So unlabeled propylene glycol here. Four of
the subjects had measurable concentrations coming in. I
thought all six would, but not the case. The concentrations
decreased over time to the point where we administered the
meal. And, of course, after that they increased again, and the
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remaining two subjects had measurable concentrations after
that.
So what you can see from this is that, you know, we had
various rates and various extensive propylene glycol
absorption, and so we really have to be careful. And this is a
very good example of why you need to be careful when you're
designing a clinical study to evaluate something that's
ubiquitous in the environment and separating that from your
intervention.
All right. So the 13C3-labeled propylene glycol plasma
concentrations in the vaping subjects. Again, based on the
very high amount of propylene glycol in the solution that we
used, we see peak concentrations in the neighborhood of 2,000
to about 4,000 and then decreasing over time to 8 hours -- to
about 100 to right around 700. And notice that there wasn't a
bump after the meal. So that just kind of speaks to the
specificity of the method that we used in this case.
All right. So back to our two friends here. What's the
verdict? Does this guy -- can his friend -- can Friend 2 here
blame Friend 1 for his whatever it is that he's feeling?
In the three vaping subjects, we found no quantifiable
concentrations at a limit of quantitation of 5 ng/mL. And if
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you think back to the concentrations that we saw in the vapers,
these are orders of magnitude lower -- the limit of
quantitation there is orders of magnitude lower than both the
peak and the trough concentrations that the vapers actually
experienced.
However, if we wanted to -- so that's the limit of
quantitation. Now, with the mass spec we can detect lower
concentrations, and our limit of detection in this case is 0.2
ng. So were we able to -- we can't really quantitate it that
low, but were we able to detect it? And so the answer is yes.
So we were able to detect peak levels at about 1 ng/mL, again,
thousands of times less than the peaks that we saw in the
vaping subjects.
Okay. And so back to the dose makes the poison. In terms
of adverse events, none were reported by the non-vapers.
Again, there were only three, but we had nothing reported by
the non-vapers.
Subject 1, on the other hand, who was a vaper, vomited
about 7 minutes following completion of product use, and upon
questioning, we found out that he hadn't eaten most of the day
prior due to his work schedule and hadn't eaten prior to coming
in that morning. So almost 4.5 mg of nicotine over a 15-minute
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period, it's really no surprise that he had an upset tummy
there.
Okay. And so our conclusions. Again, with the very
specific conditions of our study, non-vapers in close proximity
to the vapers using a highly concentrated propylene glycol
solution experienced very little uptake of 13C3-labeled
propylene glycol during a relatively short exposure period and
reported no adverse events.
And so we believe that stable labeling can be a powerful
tool for testing direct and secondhand exposure to e-cigarette
components, allowing scientists to differentiate exposure from
other sources such as food.
And, finally, the data generated from these kinds of
studies evaluating e-cigarettes that include labeled e-liquid
components may help regulators make informed, science-based
decisions about these products in their efforts to protect the
public health.
And so I'd just like to acknowledge the staff here.
Dr. Michael Gartner, who was the principal investigator on the
study; Stephanie Grone and Holly Lehman, who are basically the
study managers and operationally and logistically made the
study go forward; the bioanalytical staff led by Kirk Newland,
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who was the bioanalytical principal investigator; and then Ray
Farmen, our vice president of bioanalytical sciences, who
basically paid for this study.
That's it.
(Applause.)
DR. DRESLER: Okay, our next speaker, Dr. Collaco -- I
hope I said that correctly -- from Johns Hopkins School of
Medicine. Impact of E-cigarettes on Lung Growth and Behavior
in a Mouse Model.
DR. COLLACO: Thank you. My name is Mike Collaco. I am a
pediatric pulmonologist at Johns Hopkins. I want to thank the
organizers for the opportunity to present some of our data
today. I'm actually presenting on behalf of the principal
investigator, Dr. McGrath-Morrow, who's unfortunately in an NIH
meeting today.
This is where the particular research that you're going to
see has been funded by.
So briefly I'm going to discuss the background and our
study aims; walk you through our mouse model; demonstrate some
of the effects that we've seen on lung growth with e-cigarettes
in our mouse model; demonstrate some of the effects on adult
mouse behavior from prenatal/neonatal exposure; and also
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discuss some future research directions that we're considering.
So as pediatric pulmonologists, Sharon and I are very
interested to know whether there are any adverse consequences
to e-cigarette exposure on the very young, particularly since
that's a critical time for organ development, both prenatally
and in early childhood.
And small children may be exposed to a variety of
constituents from e-cigarettes through multiple routes,
including inhalation, dermal absorption, breast milk, and
possibly thirdhand through contaminated surfaces.
So we have two studies that I'm going to present today.
One has already been published in PLOS ONE, the pulmonary
study. The other is under review.
In our pulmonary study, we wanted to see whether
e-cigarette exposure in early life affects lung growth, using
the mouse model. And in the behavioral study, we wanted to see
if early e-cigarette exposure affects adult mouse behavior,
again in the model.
There we go. So one of our first questions is, you know,
could nonusers of e-cigarettes be exposed potentially to
emissions? This is a study -- it's a theoretical model using a
particle sampler, and they're basically predicting where
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particles might deposit, you know, from an aerosol. And we can
certainly debate the percentages of where we think particles
are ending up, but you know, a substantial fraction of them may
be exhaled by certain e-cigarette users.
Perhaps more telling is this data, which you've heard
referred to twice today. It is a study on a very small number
of individuals, nonusers. The researchers in this study
recruited subjects from households where no exposure took
place, households where e-cigarettes were used, and households
where conventional cigarettes were used. There were no dual-
use households in this particular study.
And, you know, although the salivary cotinine levels are
less, slightly, in the e-cigarette exposure than the
conventional cigarette exposure -- cotinine is again a
metabolite of nicotine -- they're very much similar in urinary
cotinine, and statistically, they're no different, suggesting
at least in this small sample that nicotine is absorbed by
secondhand means.
So this is our mouse model. In the foreground, where the
red arrows are, are the chambers where the e-cigarettes are.
The emissions are drawn in through the pump that you see in the
mid part of the picture and then transmitted via the tubing
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that you can see in the background to the chambers where the
mice are. The mice are exposed 20 minutes per day, either once
or twice a day, depending on the protocol.
Another question is, you know, does a pump generate
similar emissions to a human e-cigarette user? Again, it
probably varies by e-cigarette user. But at least there's one
study that suggests at least the nicotine air concentration and
the aerosol particle concentration are roughly comparable.
So we have three arms in our studies. One is a group of
mice that aren't exposed to any products whatsoever. The
second is a group of mice that are exposed only to the 0%
nicotine-containing e-cigarettes, so that is, they are exposed
to the carrier agent, in which our case is propylene glycol.
And there may or may not be other compounds present there. All
of the e-cigarettes that we used in our study have no
flavoring. And then the third group is either exposed again,
depending on the protocol, either to 1.8% or 2.4% nicotine.
For the purposes of our model, although we know that there
are certainly other compounds present in e-cigarettes, we
assume that they were at low enough concentrations that we did
not think that they affected the mice, but again this is an
assumption.
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The next question then is, you know, in this model, what
are the mice actually being exposed to? Is it something
that's, you know, real life or not? You know, I'm sure you've
all heard about the saccharine studies where mice were exposed
to thousands of levels of -- you know, times the levels that
humans would be exposed to and develop cancer. So we did some
back-of-the-envelope calculations, which you see here, and
based on a previous study by Etter, human e-cigarette users may
inhale up to 24 mg of nicotine per day. In our mouse model,
2.5 mg per mouse entered the chamber. I don't know, obviously,
if all of that was inhaled. I would suspect not, but that
would be the maximum dose.
To confirm this, we looked at plasma cotinine levels in
the mice to get an idea of what type of exposure it is. In our
mouse study data in our pulmonary study, the mice had levels of
62 ng/mL. In the behavioral study it was 23. If you look at
human data from the literature, in adult conventional cigarette
smokers, the levels of plasma cotinine, again a biomarker for
nicotine, are 122.
For secondhand exposure for the type that we're trying to
get at, which is very young children, there are a couple of
studies which have measured newborn levels of plasma nicotine,
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which range from 31 to 76. So, as you can see, our levels are
probably more akin to secondhand exposure in newborns.
So our pulmonary study. The aim is to determine whether
e-cigarette exposure in early life affects lung growth. We
know from conventional cigarette studies that maternal smoking
during pregnancy causes adverse effects on lung function
throughout childhood that can be measured on lung function
testing. We also know that exposure to secondhand smoke during
childhood also causes adverse effects on lung function. And
it's, you know, obviously at this point unknown whether
e-cigarettes have the same effect on infants and children.
So the timing of our exposure in our study. So this is a
timeline for lung development in humans and in mice. E in the
mice column refers to prenatal embryonic days, and PN refers to
postnatal days after birth. In our study, mice were exposed on
Postnatal Days 1 through 9, which corresponds in people to late
fetal development, third trimester, into perhaps infancy.
So before we show you the lung growth data, I just wanted
to bring this slide up because I think it is interesting data.
This is the growth for the mice body weights on the vertical
axis, and on the horizontal axis is days, Day 1 through Day 10.
The white bar represents the mean for room air-exposed
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mice. The light gray is the 0% nicotine, and the dark gray is
the 1.8% nicotine. And what we saw was, with time, the mice
that were exposed to both the 0% as well as the 1.8% weighed
less than the room air mice by about 11 to 12 -- I'm sorry, 11%
to 13%, as you can see on the slide, which suggests, even in
mice that aren't exposed to nicotine-containing e-cigarettes,
that there may be effects on growth.
So this is a slide for lung growth, and I want you to
concentrate on the pictures rather than on the graphs, for
starters. So on the far left -- these are all sample sections
of lung tissue from the mice. The picture on the left is a
sample from mice exposed to room air, representative, and this
represents fairly normal lung architecture. And this is not
that dissimilar to human lung tissue. You have air spaces.
The air spaces allow oxygen to be taken in and carbon dioxide
to be expelled.
And then, as you move across from 0% nicotine to 1.8, you
can start to see some changes in the lung architecture. The
spaces are much bigger, larger. And that's what the graphs
above show. They're measuring something called mean linear
intercept, which is just the measure of how much distance there
is across that air space.
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So what does that mean? So if you have larger air spaces
like this, you have less surface area in your lungs. And the
lung is all about gas exchange. You need surface area to
exchange gas. So if you have a reduced surface area, as you do
in the 1.8% nicotine-exposed mice, that implies that your gas
exchange isn't as efficient.
And those of you who have, perhaps, a medical background
or have looked at lung tissue samples before may have seen
similar sorts of findings in human lung tissue in people with
lung disease, particularly with emphysema or COPD, and they too
have decreased surface area in their lungs. And if you have
decreased surface area, this usually leads to shortness of
breath and/or exercise limitations.
So these studies suggest, at least in mice, that exposure
to e-cigarettes in early life does result in some durable
changes in lung architecture that may have consequences.
The second study I'm going to talk to you today is our
mouse behavioral study. This is currently still under review.
The purpose of the study was to determine whether e-cigarette
exposure in early life affects adult behavior, using a mouse
model. The rationale for this particular study was that ADHD
has been associated with fetal exposure to maternal
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conventional cigarette smoking during pregnancy, and it's
obviously unknown whether e-cigarettes have any such effects.
So mouse brain development does not exactly follow the
same timeline as human brain development. The exposure that we
exposed the mice to in this particular study was the pregnant
mice were exposed from Embryonic Days 15 through 19, and then
the baby mice were exposed from days -- postnatally from 1 to
14, roughly corresponding to the second or third trimester
exposure for humans, as you can see in the graphic above.
Male mice underwent behavioral testing at 3 months of age.
Mice typically become adults somewhere between 28 and 36 days
of life. So at 3 months of age, these are clearly adult mice.
Why only in the male mice? Unfortunately it's another form of
gender bias. There are only validated behavioral standards for
male mice at this time.
The behavioral test, which I'll walk you through in the
subsequent slides, that we performed are standard behavioral
tests for mice, including an open field test, an elevated zero
maze test, rotarod, and light-dark box test, which measure sort
of different parameters of mouse activity.
The open field test is when mice are placed in an open
field chamber and allowed to move freely. The mice that were
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exposed to 2.4% -- we used 2.4% nicotine e-cigarettes in this
particular study -- traveled longer distances, as indicated by
the bar graph on the left, and demonstrated increased rearing
behavior, which is sort of standing on their hind legs. These
are sometimes taken in mouse behavioral studies to represent,
potentially, hyperactivity. We did not see these similar
behaviors in the 0% nicotine-exposed mice, again suggesting
that this is a function of the nicotine exposure.
The zero maze -- I'm sorry, the elevated zero maze test is
when a mouse is placed in a quadrant maze that has open and
closed sections, and typically researchers measure the time in
open sections as a measure of anxiety. We did not see any
differences between the three groups in that. The mice who
were in the -- also were measured for a number of head dips,
which is a measure of exploration. And the 2.4% nicotine-
exposed mice did experience more head dips, which suggests
again, from the mouse behavioral literature, that it may be
associated with less timid behavior and more impulsivity.
The other tests that we did, the rotarod test, where a
mouse is placed on a rotating rod, and it requires locomotion
to avoid falls, we did not see any differences.
We also did not see any differences with a light-dark box
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test, where a mouse is allowed to move freely between lighted
and dark box components as a measure of anxiety.
So, to summarize these results, nicotine exposure via
e-cigarettes with prenatal and early postnatal life in mice is
associated with behavioral changes in later life that appear to
be durable, an increase in what might be considered
hyperactivity or risk-taking behaviors, but no change in
anxiety-related behaviors.
Does this have any relevance to human data for nicotine
exposure? As I said previously, there have been several human
studies that have reported exposure associations between
prenatal nicotine exposure and behavioral changes during
childhood, including ADHD and oppositional defiant disorder.
There is less solid data for whether there's an association
between NRT and ADHD.
Lastly, I just wanted to touch base on this subject of
thirdhand e-cigarette exposure. As has been presented in data
earlier today, nicotine is readily detectable on surfaces of
lab equipment as well as indoor surfaces of e-cigarette users.
Obviously, we cannot exclude the possibility in our study that
mice in our study also absorbed nicotine through thirdhand
routes, but that may also be a possibility.
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So, in conclusion, you know, I think this mouse data
presents some interesting findings that early exposure to
e-cigarettes, at least in mice, does cause changes in lung
growth as well as behavior. You can debate as to what the
specifics of those behavioral changes are, or what they mean on
those tests, but there's clear -- you know, I think our data is
fairly clear that there are at least some behavioral changes
associated with e-cigarette exposure in early life in mice.
We need, obviously, more research to determine the effects
of e-cigarettes on lung function, susceptibility to infections,
whether there are gender differences with e-cigarette exposure
in the extremely young, and obviously human studies are needed
to confirm our research in mice.
Thank you.
(Applause.)
DR. DRESLER: Okay. So we're going to do clarifying
questions now, and if you have any hard questions for
Dr. Benowitz before he leaves, I'll take those too.
So this one is for you, Dr. Benowitz. Considering ENDS do
not contain smoke or combustion, nicotine as a biomarker is not
applicable -- considering ENDS do not contain smoke or
combustion, nicotine as a biomarker is not applicable nor
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comparable to actual cigarette smoke. It is not a good measure
of harm or risk to people. For example, it has been shown that
nicotine is the same in vapers' homes and nonsmokers' homes.
Thus, as a biomarker, it tells us nothing of the constituents
found in vapor exposure. Don't we need new measures developed
for vapor products, considering some vapor products don't
contain nicotine?
DR. BENOWITZ: Yes, that would be a great idea. The
things we would like to have markers for, say, aldehydes,
formaldehyde, acetaldehyde, are difficult. They're endogenous
compounds. I know that there's some work trying to look at
potential adducts of formaldehyde, but we don't really have any
other specific markers.
I certainly agree that nicotine does not say the same
thing with e-cigarette use than it says for cigarette use. And
for cigarettes, nicotine is really a marker for everything
else. For e-cigarettes, it is not that. On the other hand, I
think if a nonuser wants to be nicotine free, they're entitled
to be nicotine free. So even though I don't know what the
disease caused by low-level nicotine might be, I think that
still, you know, a nicotine-free world is desirable.
DR. DRESLER: Wait. So don't sit down. Here's another
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one for you. What constituents in tobacco smoke are of most
concern for cardiovascular health?
DR. BENOWITZ: So, for cardiovascular health, there's
pretty solid evidence that the combustion products are the
things that are responsible for most of the inflammatory
response, the prothrombotic response, the endothelial
dysfunction response.
Nicotine plays a role mostly in the hemodynamic effects,
which means that heart rate goes up, blood pressure goes up,
cardiac output goes up. Those are things that can potentially
cause problems if you already have cardiovascular disease, but
it probably doesn't play a role in the causing of
cardiovascular disease, sort of an aggravator. So I think it's
mostly the combustion products.
You know, for secondhand smoke there is one concern. We
know that secondhand smoke exposure can trigger acute
cardiovascular events. So you can have a myocardial infarction
or sudden death with acute secondhand smoke exposure if you're
not a smoker. We don't think that that's nicotine related, but
nicotine could play some role, and that's something that I
think needs to be thought about.
DR. DRESLER: Thank you.
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Dr. Collaco. So I want to thank you for looking at those
gender differences because I was going to ask Dr. Graff why you
did only men. Just saying. No, just saying. I have to do
that to represent the women, though. I appreciate that it was
a small n. But no, the question, sir, was for you.
If nicotine NRT is not associated with ADHD, would not
that be similarly expected with ENDS? So NRT is not associated
with ADHD.
DR. COLLACO: I think it probably has to do again with the
exposure, how much, how often, when, you know, during
pregnancy, during early childhood. So I think there are a lot
of variables there that still need to be sorted out. And,
again, it's hard for me to comment, you know, exactly the role
of NRT since we didn't have an NRT arm in our study.
DR. DRESLER: Okay, I have a few more for you. So, in the
mouse model, you were testing exclusively developing lungs in
mice and not that of grown adult mice. Does the study provide
any information on the effect on full-grown and developed lungs
in humans? And it would be likely to be smoking and
replacement with ENDS. So what would your studies predict for
adults, could you say?
DR. COLLACO: We actually can't say earlier, so I wouldn't
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feel confident saying something definitive on that. And,
unfortunately, at least in human studies, this may take
decades, you know, for durable or permanent changes to occur.
DR. DRESLER: Okay. A few more for you, okay? How clear
is the mice behavior literature at seeing anxiety behavior?
For example -- and I can tell you guys tried to help me with
this. For example -- can you read what that word is?
DR. COLLACO: Control.
DR. DRESLER: For example, control mouse --
DR. COLLACO: Drops?
DR. DRESLER: Head drops. Okay, control mouse head drops
and standing, can it be just greater curiosity?
DR. COLLACO: It's a good question. I think these tests
have been standardized over decades with the behavioral
literature, and they've been used for a variety of purposes,
and certainly, you know, with other drug exposures in the past,
such as alcohol, methamphetamines, et cetera. Yes. You know,
there is definitely some speculation on my part, from
interpreting mouse behavior to interpreting human behavior.
But I think what you see in the mice studies is that there
is a behavioral change. That's clear. What you interpret that
behavioral change to be is up for debate, but there is a
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behavioral change suggesting that, at least in early life,
these things may not necessarily be benign.
DR. DRESLER: Okay. And I think this one is going to
follow on, on this. Isn't greater activity in open field and
maze movement in the light-dark test often taken as an
indication of lower anxiety? Why did you interpret it as ADHD?
DR. COLLACO: Again, you know, I think these tests are
objective in terms of what they're measuring, subject in terms
of their interpretation. Based on the fact that, you know, the
other anxiety tests did not differ between any of the control
groups or the nicotine or 0% nicotine-exposed mice, we tended
to think that our results are related to more activity levels
or hyperactivity.
DR. DRESLER: Okay, thank you. Let me go to Dr. Graff.
Yeah, sit up front, though, because I know I have another one
for you.
So, Dr. Graff, you measured blood PG levels. Lung
concentrations could be much higher. What can you say about
the pulmonary risk of PG from secondhand emissions?
DR. GRAFF: So based on our study, I can't say anything
about it. But the good thing is, is that using a method -- a
labeled propylene glycol like we have, we certainly could use
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that to assess what the concentrations are at the site within
the lung. But from our study, we really can't say anything
about that.
DR. DRESLER: Okay. In the mouse model of lung toxicity,
the PG alone caused increased air space. So was it the
nicotine or was it the PG?
DR. COLLACO: That's a very good question. We did several
different trials or repeated trials. In one trial, we did see
a difference between room air and 0% nicotine in terms of the
air space. In the second trial, it was not statistically
significant. So being conservative, when we did report it to
the journal, we said that we did not see a difference.
DR. DRESLER: So here's another one for -- if nicotine has
been reported to be used to relieve negative mood anxiety in
schizophrenics, could you comment on why such changes in mouse
anxiety behavior were not seen?
DR. COLLACO: Yeah, I'm not sure I can speculate on the
role of nicotine and schizophrenics related to our mice study,
unfortunately.
DR. DRESLER: Okay. Dr. Benowitz, I'm going to ask you
this one. So since I know that you're going to have to leave,
we may come back to this question for some of the others too.
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So what about in pregnant women that are exposed to this
aerosol? We kind of touched on this in the earlier session.
What is the best way to better understand potential adverse
health outcomes of e-cigarettes in the pregnant women, and
especially on the impact on the fetus?
DR. BENOWITZ: Well, certainly for active exposure. And I
think the study that you just heard, in the mice, raises real
concerns that if the mother is using e-cigarettes during
pregnancy, it certainly could have adverse effects. So I
think, to me, that's pretty clear.
Secondhand emissions, it's not so clear. I think there
could be some nicotine levels. What those levels mean, you
know, it's hard to say. We do have studies with NRT during
pregnancy, where at least NRT compared to cigarette smoking
appears to be less harmful. The levels from e-cigarettes are
certainly going to be lower than levels from secondhand --
levels from secondhand e-cigarette emissions are certainly
going to be lower than NRT levels.
So I would guess that you probably are not going to see
adverse effects, but there are some effects of nicotine that
occur at incredibly low concentrations that we don't
understand. So I would say probably not, but not definitely
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not.
DR. DRESLER: Okay, all right. Any other questions
because Dr. Benowitz is going to have to leave?
(No response.)
DR. DRESLER: So okay, thank you. And we'll come back for
more panel questions after the next two speakers.
So the next speaker is Dr. Jeannie Limpert. She's from
the FDA Center for Tobacco Products. She's going to be
speaking on Electronic Nicotine Delivery Systems: Nonuser
Adverse Experiences Reported to FDA/CTP.
DR. LIMPERT: Good afternoon. My name is Jeannie Limpert,
and I'm a medical officer with FDA/CTP Office of Science. I
don't have any financial conflicts -- financial disclosures or
conflicts of interest. I look forward to providing a brief
summary of the adverse experiences related to e-cigarettes and
other electronic nicotine delivery systems, or ENDS, in
nonusers that have been reported to CTP.
I will first provide a brief overview of the process for
reporting an adverse experience to CTP. CTP receives voluntary
reports of adverse experiences involving tobacco products from
consumers, healthcare professionals, and members of the public.
Reports are received via the Safety Reporting Portal, MedWatch,
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mail, and e-mail. And voluntary reports have described adverse
experiences not only in users but also in nonusers.
In January of 2014, CTP launched a web-based reporting
system called the Safety Reporting Portal, featuring tobacco
product-specific queries to streamline the incoming
information. The portal can be accessed via the FDA website or
directly via the web address noted here on the bottom of this
slide.
The goal of the Safety Reporting Portal is to identify
previously undetected health concerns and take appropriate
action to prevent further adverse experiences and to educate
consumers about health risks. Reports submitted are reviewed,
evaluated, and where appropriate, issues are addressed to
ensure the protection of the public health.
Reports may be about tobacco products currently regulated
by CTP as well as those that are not currently under CTP
jurisdiction, such as ENDS products.
This is a screenshot of the first page of the tobacco
product-specific Safety Reporting Portal, and the portal takes
reporters through screens designed to gather information both
about the tobacco product and the issue of concern.
So I will now move on to review the voluntary adverse
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experiences associated with ENDS, reported to CTP, in nonusers.
This graph depicts the number of adverse experience reports
related to ENDS, broken down by whether the report identified
an adverse experience in a user or nonuser. So for each year,
the number of reports in dark red and on the left represent
users, and the number of reports in pink and to the right
represent nonusers.
So, as you can see, while the number of reports -- while
the overall number of reports is small, the number of reports
that we received have increased, including the number of
reports in nonusers.
The highest number of nonuser reports are related to
passive exposure to exhaled aerosols. We've also received
reports of device malfunction, choking, dermal exposure, and
e-liquid ingestion.
So as per the previous slide, the highest number of
nonuser reports are related to exhaled aerosols, and reports
have described symptoms, including dizziness, eye irritation,
headache, nausea, racing and irregular heartbeat, chest
discomfort, respiratory complaints, and sore throat. And
respiratory complaints were the most frequently reported
symptoms. And some examples of the types of respiratory
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complaints received include asthma exacerbation, difficulty
breathing, pneumonia, and coughing.
Of note, reporters frequently reported more than one
symptom or adverse experience. These exposures were typically
in indoor spaces such as apartments and homes or public
settings such as offices or restaurants. Some reports included
information about recurrent adverse experiences after repeat
exposure, symptoms in more than one person, medical attention
and treatment received, and history of underlying conditions.
Other exposure reports have included four reports of burns
due to device overheating and device explosion and two reports
of death. The first was an infant who died after choking on an
e-liquid cartridge, and the second report was a toddler who
ingested e-liquid containing nicotine and died. We also
received one report of lip cheilitis, or local inflammation,
that developed after the reporter had kissed someone who had
used an e-cigarette.
So these reports provide important information about
potential health risks. However, interpretation of these
reports has important limitations. Reporting adverse
experiences to CTP is voluntary. So reports received likely
underestimate the true number and types of adverse experiences
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associated with these products. Data cannot be used to
calculate incidence or to estimate risk, and experiences
reported may not have a causal relationship to product
exposure.
Additionally, the launch of the Safety Reporting Portal in
2014 may have affected trends in reporting and content.
So, in conclusion, although small in number, adverse
experiences associated with ENDS have been reported in
nonusers. Most commonly, these reports are associated with
passive exposure to aerosols and most commonly identify
symptoms consistent with respiratory tract irritation. Some
symptoms may suggest nicotine exposure and potential toxicity
and suggest that passive aerosol exposure is not completely
innocuous.
Adverse experience reports also include injuries related
to device explosion and overheating, and deaths from accidental
exposure in children have been reported.
Thank you.
(Applause.)
DR. DRESLER: Okay, our next speaker is Dr. Kevin Chatham-
Stephens from the Centers for Disease Control and Prevention,
and he'll be presenting on Calls to U.S. Poison Centers
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Involving Exposure to Electronic Cigarettes.
DR. CHATHAM-STEPHENS: Thank you for the opportunity to
discuss our projects.
So I think there have been several descriptions of the
rising incidence of e-cigarette use, so I'm just going to fast-
forward through these slides.
Given the increasing use of these relatively new devices,
there have been questions regarding the safety of e-cigarettes
and e-liquid. So who is being exposed and how are they being
exposed? And are the exposures leading to health effects?
So some of the acute health effects that may occur
following nicotine exposure include vomiting, headache,
agitation, seizures, and death. Many of these questions were
raised when, in December 2014, the media reported that a
1-year-old child died after ingesting e-liquid.
Given the questions regarding the safety of e-cigarettes
and e-liquid, we sought to quantify calls to U.S. poison
centers reporting exposures to e-cigarettes and e-liquid and
describe the associated acute adverse health effects.
There are currently 55 poison centers in the United
States. When someone calls a poison center, poison center
staff collect standardized information, including information
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about the exposed person, the substance or medication to which
the person was exposed, and any resulting symptoms. These data
are actually uploaded within minutes to the National Poison
Data System, or NPDS, which serves as a national data
repository and surveillance system for poisonings. Each
substance or medication has a unique code in NPDS.
The code for e-cigarettes was released in 2010. So we
searched NPDS from September 2010 through December 2014 for
calls involving e-cigarettes or e-liquid. We combined those
calls and refer to those calls in this presentation as
e-cigarette calls. And to provide a comparison to a
conventional established product with known toxicity, we also
searched for calls involving conventional tobacco cigarettes.
We excluded calls involving multiple exposures, such as to
ethanol and e-cigarettes.
We quantified the number of calls involving e-cigarettes
or e-liquid and conventional tobacco cigarettes. We also
compared e-cigarettes to conventional tobacco cigarettes by age
of the exposed person, using chi-square tests, considering a
p-value of less than 0.05 significant.
In NPDS, health effect severity is categorized as minor,
such as a transient cough; moderate, such as vomiting causing
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dehydration; major, such as respiratory failure or death.
In NPDS, we are unable to tell whether exposures in adults
result from direct use of e-cigarettes or from secondhand
exposures, such as through secondhand aerosol. Since this
particular session focuses on potential health effects in
nonusers of e-cigarettes, I'll present the total number of
calls for all ages and then focus on the effects in children
under the age of 11 years, assuming that these individuals are
not directly using e-cigarettes.
So during the study period, poison centers received 5,970
human exposure calls involving e-cigarettes or e-liquid. And
of these, 163 were excluded for involving exposure to multiple
substances, leaving a total of 5,807 e-cigarette calls.
Poison centers received 21,106 human exposure calls
involving conventional tobacco cigarettes. And of these, 751
were excluded for involving multiple exposures, leaving a total
of 20,355 human conventional tobacco cigarette calls.
Annual e-cigarette calls increased from 238 in 2011 to
3,692 in 2014, which represents a greater than 1,400% increase.
Monthly e-cigarette calls increased from 1 in September
2010 to a peak of 401 in April 2014, followed by a decline to
295 in December 2014, while conventional tobacco cigarette
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calls ranged from 302 to 514 per month.
Here I show the age groups for e-cigarettes and
conventional tobacco cigarettes; 58% of e-cigarette exposures
occurred among the 0- to 5-year age group, and 35% of exposures
occurred among the greater than or equal to 20-year age group,
while 95% of conventional tobacco cigarette exposures occurred
among the 0- to 5-year age group.
So, for the remainder of the presentation, I'll focus on
the 3,449 calls involving children younger than 11 years of age
who were exposed to either an e-cigarette or e-liquid. Just
over half of the e-cigarette calls involved males.
In terms of the location of calls, 17% of e-cigarette
calls came from the healthcare facility. For the 2,713 calls
that originated outside of a healthcare facility, the majority
of e-cigarette calls (69%) were managed on site. An additional
30% of e-cigarette calls were referred to a healthcare facility
or already en route to a healthcare facility.
The most common route of exposure for e-cigarette calls
was ingestion at 80%, followed by multiple routes of exposure
at 10%, inhalation/nasal exposure at 4%, skin exposure also at
4%, and eye exposure at 2%.
To determine the medical outcome, poison center staff must
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collect sufficient information about the exposure, route, and
health effect. Of the 3,449 e-cigarette calls, sufficient
information was available for 69%. And of these calls with
sufficient information, 37% of e-cigarette calls reported an
adverse health effect. And of the calls reporting an adverse
health effect, 92% were categorized as a minor effect, 7% as a
moderate effect, 0.3% as a major effect, and there was one
death reported to U.S. poison centers.
For the e-cigarette calls reporting a health effect, the
eight most common effects were vomiting, drowsiness, eye
irritation, nausea, cough, tachycardia, agitation, and red eye.
This analysis is subject to several limitations. Because
reporting to poison centers is voluntary, we likely
underestimate the total number of e-cigarette and conventional
tobacco cigarette exposures. And, in fact, the Institute of
Medicine estimates that less than half of all poisonings are
reported to poison centers.
The type of e-cigarette device involved in each exposure
was also unknown, which may limit our ability to generalize the
results of this analysis, given the variety of devices that are
available and the rapidly changing e-cigarette market. We also
have limited data on the concentration of the e-liquid involved
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in each of these exposures.
As I mentioned earlier, in NPDS, we are unable to
differentiate primary exposures from secondary exposures. So
this analysis likely misses adults who experience secondhand
exposures.
In addition, almost one-third of the e-cigarette calls did
not have outcome data. And the lack of data on monthly
e-cigarette use meant that we were unable to calculate rates of
adverse health effects.
To conclude, annual e-cigarette calls increased by greater
than 1,400% from 2011 through 2014, with 60% of the calls
involving children less than 11 years of age. Most of the
health effects commonly reported in the e-cigarette calls were
consistent with nicotine exposure. And the majority of
e-cigarette calls resulted in minor adverse health effects.
Given the overall increase in e-cigarette calls to U.S.
poison centers and predictions of e-cigarette use continuing to
increase, healthcare providers and the public should be aware
of the potential for acute adverse health effects from
e-cigarettes.
Developing strategies to monitor and prevent adverse
health effects from these novel devices is critical. Some
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strategies may include CDC continuing to use NPDS for
surveillance of e-cigarette calls; manufacturers evaluating the
potential use of child-resistant containers for e-liquid;
manufacturers considering implementation of clear, standardized
labeling for e-cigarettes and e-liquid; and public health
messaging to e-cigarette users regarding safe handling of
e-liquid as well as appropriate storage of the devices and
e-liquid around children.
I would like to thank our collaborators at CDC, including
the Office on Smoking and Health, and FDA as well as the
AAPCC/local poison centers. Thank you.
(Applause.)
DR. DRESLER: So could we have the presenters come up to
the front, and we'll go for clarifying questions and other --
so please send your questions over. Yes, sir, it's coming.
Diane Ashton. Diane Ashton, are you coming over here or
is it going to be down there? Wherever you would like.
Okay. And for our transcriber, Dr. Chatham-Steffens --
Stephens, Steffens. Okay. Dr. Graff, Dr. -- oh boy, Collaso.
I know I haven't got this pronunciation; Collaso?
(Off microphone comment.)
DR. DRESLER: Colloso. Okay, thank you. Dr. Phillips and
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Diane Ashton, right? Dr. Ashton. Yes, thank you.
Okay. So could we have, please -- so the last two, could
you please say where you're from and your declaration of
interests, please?
DR. PHILLIPS: Sure. I'm Carl V. Phillips. My research
is focused on tobacco harm reduction for 15 years, first as a
professor and now with CASAA. I'm here under the auspices of
CASAA, which represents its 60,000 members and other consumers
and would-be consumers of low-risk tobacco products. I would
say this is not a conflict of interest because consumers are
the one group whose interest is to understand, without spin or
hype, the real health effects of the products.
I wanted to note that this marks the first time that any
public meeting in the history of CTP, that a representative of
the primary stakeholder, the consumers, has been given a seat
at the table, which appears to be a small step in the right
direction, though since I'm here in my role as a scientific
expert rather than consumer advocate, it's not clear whether it
should really count.
In terms of my personal funding outside of CASAA, at one
time or another I received research grants or consulting
contracts from most everyone with a financial interest in this
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matter. That includes companies that sell e-cigarettes. It
also includes those that benefit from the sale of competing
products, pharmaceuticals, smokeless tobaccos, and cigarettes.
In particular, I received funding from those who profit the
most from the sale of cigarettes, which of course is the
government of the United States and other jurisdictions as well
as those who manufacture those products.
DR. DRESLER: So your declaration of interest, please,
Dr. Ashton.
DR. ASHTON: I am an obstetrician-gynecologist. I'm the
Deputy Medical Director at the March of Dimes, Vice President
for Health Equity, and I too am, I guess, representing the
consumer interest.
The mission of the March of Dimes is to improve the health
of babies by preventing birth defects, prematurity, and infant
mortality. And one of our earliest interventions when we began
our prematurity campaign in 2003 was smoking cessation and the
impact of tobacco on preterm birth and adverse birth outcomes.
So we definitely have an interest in the use of e-cigarettes
and potential for adverse outcomes.
DR. DRESLER: Okay. All right, the first question is for
you, Dr. Graff. If glycerin is added, would it be more or less
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likely to see bystander absorption due to the variation of
particle size or viscosity of the carrier liquid? So if
glycerin is added.
DR. GRAFF: That's a great question, and I don't think
that I have an answer for it. I do know that, you know, the
composition of our liquid that we used in our study is
obviously not standard, and so there could be a lot of
different characteristics upon heating, that when you add
glycerol, you could see something completely different.
DR. DRESLER: Okay. Even though e-cigarette aerosols
appear to be less toxic than secondhand smoke, how can we be
sure they don't pose any additional risk to bystanders,
especially children? So what evaluations should be conducted?
So, in this area looking at bystanders such as children,
infants, what evaluations should be conducted?
DR. COLLACO: Well, I think there's -- you know, obviously
there are a lot of ethical issues about researching children.
I mean, I don't think I know any parents who would voluntarily
expose their child to e-cigarettes as part of a research study.
So sometimes, you know, we're left with either modeling through
animal models or other types of studies to get at secondhand
exposure effects or, you know, retrospective studies,
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observational studies of the health effects of e-cigarettes in
children. And to the best of my knowledge, there aren't any
large-scale studies of that sort that have been started yet.
DR. GRAFF: So I think when you talk about a prospective
clinical trial, then yes, you're not going to find any parents
who are not consumers that are going to, you know, expose their
children. However, if you look at some of the work that EPA
has done with pesticides and some of the natural exposures in
epidemiological-type studies, something like that might provide
some of that information. It's just a matter of who's willing
to do that, perform those studies.
DR. DRESLER: Anyone else?
DR. PHILLIPS: One important point that's getting lost
here in terms of the importance of this information is that
supposedly a ban of e-cigarettes is not actually on the table,
and that means that from a policy and regulatory perspective,
we're talking about whether we're going to be imposing exposure
bans in adult venues, like bars and offices, whereas the
exposures to children are mostly in the home. And so, yes, it
would be tremendously useful to be able to advise consumers as
to whether they're causing harm for their children. But from a
regulatory perspective, it's not one of the relevant questions.
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DR. ASHTON: I think there is also the question of
exposure in pregnant women. And, anecdotally, looking at blogs
on the Internet, you do understand that there are pregnant
women who do use e-cigarettes and may not be aware of what
their potential for adverse outcomes are. I think there may be
an opportunity in that population to be able to at least gather
some information about what possible birth outcomes these women
are experiencing, not in a randomized clinical trial. But at
least there would be the opportunity for some information.
DR. DRESLER: Dr. Chatham-Stephens, in poison center
calls, do you differentiate between adverse events of the
device or the liquid?
DR. CHATHAM-STEPHENS: So currently there are two
different codes that we use to differentiate, or the American
Academy of -- American Association of Poison Control Centers
uses for e-cigarettes, and there's one code for e-cigarettes
and one code for the e-liquid. And so up until this point, all
of our analyses have looked at those two codes combined,
because we have some concern regarding the accuracy of those
codes differentiating between exposure to the e-liquid itself
versus the actual device. And it's something that we talked
about with our colleagues, moving forward and starting to look
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at that and see if there is any difference in terms of health
effects surrounding exposure or anything like that.
DR. DRESLER: Okay, and this sort of follows up with this.
Since e-liquid is a liquid and tobacco cigarettes are solid, is
this a good comparison for poisoning for ingestion? So
wouldn't a product like laundry detergent pods be more
applicable for a similar type of vector? A liquid's path can
be oral and through the skin, and tobacco cigarettes have no
path through the epidermis but could cause choking.
DR. CHATHAM-STEPHENS: So, yes, I think at the beginning
of the project we spent quite a bit of time trying to figure
out (1) should we have a comparison group, and (2) what would
be the optimal comparison group? And we talked about several
different things, including laundry pods. Our group was the
group that authored the MMWR a couple of years ago on laundry
pod poisonings.
So I think the reason why we chose to go with the
comparison to conventional tobacco cigarettes was the fact
that, at that point, there was a lot of talk of individuals
switching from conventional tobacco cigarettes to e-cigarettes,
and we thought that they are products that are relatively used
similarly. And so we thought, at that point, that the best
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comparison was conventional tobacco cigarettes, but it's
definitely something that we're continuing to reevaluate.
DR. DRESLER: Okay. Dr. Ashton, this is a question about
the March of Dimes, and what is the official stance of the
March of Dimes related to e-cigs, and perhaps compare that with
what you do for cigarettes or something.
DR. ASHTON: Well, our official stance in terms of tobacco
is that there is no known safe level for women during
pregnancy, and we would certainly extrapolate that same opinion
to be used with e-cigarettes.
DR. DRESLER: Okay. Dr. Chatham-Stephens, taking into
account the number of people who smoke cigarettes versus those
who use e-cigarettes, how do the numbers of calls to the poison
center compare; i.e., there are more smokers than people who
use e-cigarettes? So can you account for that, and how do the
numbers look?
DR. CHATHAM-STEPHENS: Sure. So one of the graphs that I
showed had the number of calls involving e-cigarettes or
e-liquid, and you saw that dramatic increase and then the
slight decline as well. And then the following slide was the
chart showing the conventional tobacco cigarette calls. And at
one point the number of e-cigarette calls actually surpassed
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the number of conventional tobacco cigarette calls, which I
think we were all quite surprised by.
You know, from our standpoint, it's been difficult to find
numbers that you can cite in a medical journal, but some of the
numbers that we found for overall sales was tobacco sales were
about $80 billion, and e-cigarettes sales were about
$2 billion. So there's quite a discrepancy between the sales.
And then what we saw in our findings was that the e-cigarette
calls were actually approximating the tobacco cigarette calls.
DR. DRESLER: So there's a whole bunch more people who
smoke cigarettes than there are e-cigarettes, but about an
equal number --
DR. CHATHAM-STEPHENS: Correct. If you look, there's
still a greater number of tobacco cigarette calls, but the
e-cigarette calls were approaching and surpassed it for 1 month
before tapering off a little bit.
DR. DRESLER: Okay. And the next question has to do with
that the last two speakers showed graphs that showed a drop-off
and compared it to the increased rates per annum, but in 2014
it started to look like there was dip down. What would you
attribute that dip down in adverse events to be?
DR. CHATHAM-STEPHENS: We're not quite sure. So it could
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be that users are becoming more accustomed to e-cigarettes and
they're just not calling poison centers as frequently because
they aren't having as many acute health effects. It could be
some other factor.
We do know that there's some seasonality in all calls to
poison centers. So calls to poison centers are more common
during the summer months, and then they seem to taper off a
little bit in the winter months and then pick back up. So
there is that seasonality effect, and so we stopped looking at
calls through December of last year. So one of the things that
we're hoping to do is update the analysis once we're able to
and see if that seasonality effect continues.
DR. DRESLER: Okay. Yes.
DR. PHILLIPS: I could suggest that within the consumer
community, there was a dramatic increase in awareness about the
possible risks of exposures. And, of course, this is an easily
preventable exposure, through simple physical distance.
There's also been a gratifyingly higher percentage of e-liquid
that's sold in child-resistant containers.
DR. DRESLER: Do you know what percentage that is that are
sold in child-resistant versus other?
DR. PHILLIPS: No, I really don't know what the percentage
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is, but almost all responsible dealers are now going to all
child-resistant. And a lot of that has changed over the last
year and a half or so. So we would have expected to see that
drop-off, just like we did.
DR. DRESLER: Okay. And this question goes to overall,
for poison centers. Actually, I'm forgetting that number,
3,449. Do you remember that? Okay. So what share of total
calls to the poison centers do the 3,449 represent? So I think
the question is what proportion of poisons overall are from
that?
DR. Chatham-Stephens: So each year there are millions of
calls to U.S. poison centers. I believe it's somewhere around
two million, give or take. So if you look at any individual
substance or medication, they account for a very small
proportion. I can't do that math off the top of my head, but
it would be 3,449 divided by all the calls to U.S. poison
centers, so about a couple million.
DR. DRESLER: Okay, all right. So this question goes to
child-resistant packaging, but it seems like additional
measures are needed to adequately protect children. What else
could be done to mitigate the risk of these accidental
poisonings?
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DR. PHILLIPS: Well, I mean, just to repeat what I pointed
out earlier, it's a relatively simple technology to keep that
from happening: child-proof containers and keep out of the
reach of children, exactly what you would do with a bottle of
Tylenol. And, you know, it's useful to have that message out
there, and it's unfortunate that it isn't completely obvious to
everybody even without having the message out there. But
there's just a lot of success in getting it out there. I mean,
obviously nobody wants it to happen, and it's easy to avoid.
DR. DRESLER: So this is a question that -- are any
government agencies working on a rule to require child-
resistant packaging for liquid, like nicotine?
DR. PHILLIPS: Well, there's a bill in Congress right now
that would do it as a one-off regulation at that level. Other
than that, I'm not aware of anything. Individual states have
made some moves, too.
DR. DRESLER: Anybody else?
(No response.)
DR. DRESLER: Dr. Chatham-Stephens, were you able to
ascertain whether the liquids versus devices involved in
incidents as marketed were child resistant? So do you have any
information on your reports of those ingestions, whether they
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were packaged in child-resistant packaging?
DR. CHATHAM-STEPHENS: We do not. So, in NPDS, the
primary purpose behind the AAPCC poison centers is just to
serve as a clinical resource for parents and providers
regarding poisonings. And so we kind of piggyback off of that
for a public health surveillance factor. So right now there
isn't any way to discern whether or not that packaging is child
resistant in NPDS.
DR. DRESLER: Are you planning on doing that, capturing
it?
DR. CHATHAM-STEPHENS: I'm not aware of any proposed
changes, but I would have to touch base with AAPCC.
DR. DRESLER: Okay, all right. So this one is for
Dr. Limpert. Were adverse event reports made by healthcare
professionals, and does the database collect information on
specific products?
DR. LIMPERT: So, for the first question, anyone can
submit a report to the Safety Reporting Portal. The majority
were from consumers, but I know of at least one that was from a
healthcare professional.
And then in terms of specific products, currently in the
dropdown, it's the products that are regulated by CTP, but
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there's an "Other" category where people can report any tobacco
product, and there are plans to add more in the future.
DR. DRESLER: Okay. Then, do you want to address what was
the -- because this is a question about how are you getting the
information about the awareness of the adverse event portal?
Do you want to talk about the rollout and the information that
was shared about the rollout of AE? Is there going to be
information shared about the AE? How do people find out about
the AE profile portal?
DR. LIMPERT: So we've done some presentations about the
Safety Reporting Portal. We haven't done like a PSA about it.
So we hope to kind of raise awareness through these
presentations.
DR. DRESLER: Okay, good. All right, thank you.
Dr. Chatham-Stephens, can you please provide more details
about the three serious cases and the one death case?
DR. CHATHAM-STEPHENS: So, in terms of the death, I think
most -- we didn't gather any additional information from NPDS
than what was portrayed in the media, and that is a 1-year-old
child with ingestion of the e-liquid. So we don't have any
details in NPDS regarding the specifics of the circumstances of
how the child got exposed to it and what else is going on at
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that point.
And then, for the other three, there were three major
effects, and from my recollection, it was a combination of
respiratory effects. As I mentioned, respiratory failure was
one of the defining criteria for major effects. So if I recall
correctly, it's a combination of respiratory effects and then
neurological effects as well.
DR. DRESLER: Okay. For the panel, how can the risk
associated with involuntary exposure to these products be
communicated to the public? How do we let the public know?
DR. PHILLIPS: Well, the question assumes that there's a
risk from the involuntary exposure, and you know, based on the
numbers that we saw from all the credible presenters today, it
doesn't appear that there's any serious risk. The numbers are
in the order of three orders of magnitude lower than the
exposure to the vapors themselves, and we haven't seen much of
a problem there. We aren't entirely sure that there is one,
although certainly we have to keep in mind that there might be.
So, you know, what's to communicate?
I mean, we saw the information yesterday about marketing
and propaganda and so forth that showed that people
overwhelmingly overestimate the risks from the exposure. So I
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suppose, if anything, we need to be communicating to people
that there's far less risk than they might think there is.
DR. DRESLER: I'm going to ask you to go ahead, because
you said the credible ones. So who are the credible ones or
who were the non-credible ones?
(Laughter.)
DR. PHILLIPS: The majority of the presentations, in
keeping with the rest of the science that's out there that
looked at actual measures of environmental exposure, found that
they were trivial. They found that, you know, the nicotine was
being retained by the vapor, the propylene glycol was being
retained by the vapor and so forth, just as we would expect and
just as everything has pointed to already.
There was one exception, but it's a good general rule that
if you think you've discovered something that lots of smart
people are working on who have missed it for a very long time,
there's a 1% chance you're an outstanding genius and a 99%
chance you're from San Francisco.
(Laughter.)
DR. DRESLER: Or we could think of Sir Richard Doll in the
1950s, right? He was that outstanding genius.
Yeah, Dr. Ashton.
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DR. ASHTON: I think there's a lot that's still unknown.
We don't know what long-term exposure is. We still are looking
for questions about what the exact secondhand and thirdhand
exposure is, because these residues, at least these thirdhand
residues, are thought to accumulate over time. And we
certainly don't know what the impacts are as far as fetal
effects, what the thresholds are as far as maternal effects
during pregnancy.
So there are a lot of unknowns, and I think it behooves us
to at least let the consumers know that there are a lot of
unknowns, and if they have the opportunity to avoid exposure,
that we would certainly encourage them to do that. And
hopefully, you know, there will be more research and more
confirmatory research where we're finding consistent results
and we will have more information to be able to counsel
patients more appropriately. But until then I think there's
still a lot that's unknown.
DR. PHILLIPS: Actually, I'd like to clarify my previous
answer and respond to that, because, yes, I was talking about
all the circumstances in the world except pregnancy, and there
is definitely a legitimate concern there that we should be
paying more attention to, you know, either for humans or larval
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mice.
DR. DRESLER: Dr. Collaco.
DR. COLLACO: Yeah, I think it's not just also for
pregnant women, but there's also, you know, a variety of
vulnerable populations out there, you know, where the effects
may be more substantial than for the average otherwise healthy
e-cigarette consumer that we don't know the effects on. And
these vulnerable populations may have, you know, durable
changes to a variety of end organs that we don't know yet, and
that may take some time to develop. Just because we don't see
anything over the 5- or 6-year lifespan of e-cigarettes in the
United States so far, as in terms of long-term health
consequences, doesn't mean they don't exist.
DR. DRESLER: Dr. Graff.
DR. GRAFF: So I guess my opinion on this is that it's an
individual's choice. And so just as use of the products is an
individual's choice, some people are going to take a more
conservative approach to their position on whether or not they
want to be present where these products are used.
And so, on the one hand, you don't want to, you know, use
scare tactics and make something -- make it sound like
something is there that's not. But, at the same time, you
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know, how do you convey that, well, we don't know? We don't
know enough at this point, and we need to continue to evaluate,
and it might take a long time before -- you know, the 5 years
that they've been on the market perhaps isn't long enough.
But, again, I do go back to it's a personal choice, and
you know, if people want to use the products, great. If they
don't want to be in the presence of people who use -- involved
where the products are being used, you know, that's their
personal choice.
DR. CHATHAM-STEPHENS: So just a follow-up point. So as
pediatricians, we often provide anticipatory guidance to our
families on creating a safe and healthy home, and part of that
is simply having our parents be aware of potentially dangerous
substances that are in the house, and that ranges from anything
like their prescription medications to gasoline for the lawn
mower to pesticides for their backyards.
So I think from our standpoint, a very simple thing is
just for parents to be aware that if they do have e-cigarettes
or e-liquid in the house, that it could potentially be
dangerous to infants and young children.
DR. DRESLER: Okay.
DR. Phillips: Just to pick up on some of that. You know,
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there's this chorus of "we don't know." On my live blog, they
had turned it into a drinking game. But we actually know quite
a lot more than is being implied because, as was pointed out by
a couple of speakers -- Dr. Sarkar, I think -- these are not
novel exposures. We know about the exposure to nicotine
ex-smoke from lots of people who have used smokeless tobacco
for a very long time. We know about exposures to humectants.
We know about exposures to most of these constituents from
plenty of studies of other products.
And so to pretend that we are completely ignorant about
all of that and that we have to only study the exposure to this
one particular product means that we never know anything. I
mean, by that logic, we don't know that smoking in the 21st
century is bad for you. I mean, we have a lot of evidence that
it was bad for you in the 20th century, but we don't have that
evidence about the 21st century yet. Oh, but we can
extrapolate from what we already know, and we need to do that.
That's what science does, it tries to make the best use of the
available information, not to throw up our hands and say we
don't have the perfect information, so we don't know anything.
DR. DRESLER: So I think that's a good segue into the next
question. So we know from secondhand smoke laws that not only
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did that protect the nonusers, but it also impacted initiation
in youth, that they were less likely to start smoking if they
were in an environment with secondhand smoke laws. So how does
this exposure now to e-cigarettes and their use impact
initiation, especially in youth and nonsmokers, and does it
renormalize tobacco use?
DR. GRAFF: I think somebody mentioned yesterday, in one
of the presentations, there was a question like this, and the
expectation, I think, is probably going to be just based on
logic and human nature that kids are going to do what their
parents do. And so it wouldn't surprise me a bit, and I think
the speaker yesterday -- and I've forgotten who it was -- said
pretty much the same thing. You know, if you see your parents
smoking, history tells us that your kids are going to smoke.
If your parents are using these products, I would assume that
there's a pretty good likelihood that the kids will as well.
DR. DRESLER: Anyone else? The pediatricians not going
near that?
DR. COLLACO: You know what we're going to say on that.
DR. DRESLER: Maybe they don't.
DR. COLLACO: Well, I think -- you know, I think everyone
in the room would agree that youth not initiating these
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products is a good idea. You know, I don't think anyone would
disagree with that. And certainly there is a debate about how
best to achieve that, but at the end of the day, I think we
share that goal. You know, as a pediatrician, I think at least
my primary intervention is counseling in the office. But, you
know, certainly there are other avenues for getting that
message out.
DR. DRESLER: Okay.
DR. PHILLIPS: Just on the renormalizing trope, because we
hear that all the time, but it's very difficult to understand
how ostentatiously not smoking, which is what vapers are doing,
can tend to convince people that smoking would be a good idea.
DR. DRESLER: Smoking e-cigarettes?
DR. PHILLIPS: Yeah. So vaping is very obviously not
smoking. Ninety-nine percent of those who are doing it did it
to quit smoking, and that's a signal that smoking is not a good
idea and you should try to avoid it, rather than a signal that
smoking is normal.
DR. DRESLER: So why are the youth rates going up so much?
DR. PHILLIPS: Youth rates of smoking are not going up.
DR. DRESLER: No, for e-cigarette use. No, it's the issue
of renormalizing inhalation of a nicotine delivery device.
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DR. PHILLIPS: Well, that's a different question than the
usual claim, and the way you phrased your question --
DR. DRESLER: That's what they meant, though, it's
renormalizing. So that was what -- because the issue is, is
that e-cigarette use in kids is going up. And so would that
normalize inhalation of a cigarette or e-cigarette?
DR. PHILLIPS: Well, to some extent. Of course, those
numbers are exaggerated also. We heard plenty about people
finally coming around and recognizing that ever tried is not
used. Tried in the last 30 days is not current use. So we
have grossly exaggerated numbers there. But, of course, it is
increasing exactly as you would expect for any normal -- for
any novel product.
I mean, the fact is that a substantial portion of the
human population likes the effects of nicotine. A substantial
but fortunately much smaller portion of kids are going to go
out and use some drug, whatever it is. If it's this one, it's
almost certainly better than whatever their second choice was
going to be for them.
And the reality is that -- you know, I make no secret of
my predictions in this. You know, I predict that in 2050, half
the population is going to be using nicotine again, like they
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once were, because they can be using it in forms that are very
low risk, and they will know that they are very low risk as
opposed to the misinformation that's widespread today. In
fact, we don't know if the risk is positive at all from this.
There are certainly benefits too.
And so, yeah, we have a new normal. It's like the normal
of coffee drinking or the unfortunate normal of cigarette
smoking 50 years ago. What's left out of that worry is why
that's a bad thing.
DR. DRESLER: Dr. Ashton, what is the March of Dimes
recommendation for breastfeeding and nicotine or e-cigarette
use?
DR. ASHTON: That's a good question. I mean, I can't say
that we have a firm policy, but at least as far as good medical
advice, we know that nicotine is transmitted through breast
milk, and we would sincerely recommend that mothers do not
smoke and breastfeed. The American College of Obstetricians
and Gynecologists very clearly recommend that we take active
measures to counsel women and work with pregnant women on
behavioral modification. We know that pregnancy is a time
where there is a high motivation to quit smoking among mothers,
and we certainly try and take advantage of that.
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So at this point we would, you know, recommend that women
undergo behavioral modification to stop smoking during
pregnancy and especially be cognizant that it is being
transmitted in their breast milk.
DR. DRESLER: Okay. So the question came up about choice,
personal choice. So personal choice is not relevant in
secondhand and thirdhand exposure. Please comment on how to
minimize risk exposures to others' risk of nicotine. So, in
those who are -- it's not a choice in second- and thirdhand.
Please comment on minimizing the risk. This was in response to
you.
DR. GRAFF: Yeah.
DR. DRESLER: No, you go ahead and address it, even though
it said not for you because you're --
DR. GRAFF: Okay.
DR. DRESLER: -- the one who brought it up. But you can
go ahead. Go ahead.
DR. GRAFF: So I think it is a personal choice, and I go
back to I'm from Lincoln, Nebraska, and for a number of years
in my college days and maybe post-college days, you know, there
were certain establishments that didn't allow smoking. And so
I chose those establishments if I didn't want to be around
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smokers. So it's the same thing here. I think a lot of the
laws these days are sort of bringing electronic cigarette use
into the indoor smoking regulations, and so I do think that
it's a personal choice.
DR. DRESLER: So is that limiting? Because this does get
into the choice argument, and I think that's why the person is
suggesting not going, too, because it does limit the choices of
people who want to go into that establishment but can't because
they have asthma. So you couldn't go --
DR. GRAFF: Well, I suppose, yes.
DR. DRESLER: Yeah.
DR. GRAFF: Yes.
DR. DRESLER: Okay.
DR. GRAFF: Yeah.
DR. DRESLER: I think that's probably what they were going
to.
Anybody else want to address that?
(No response.)
DR. DRESLER: No? Okay.
With nicotine addiction often characterized in research as
more difficult to quit than heroin, why would we want 50% of
the population addicted to nicotine?
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DR. PHILLIPS: Well, it's not a matter of what we want;
it's a matter of what individuals want for themselves. But the
premise of the question is a little sketchy because there's
very little evidence that nicotine ex-smoke causes this thing
that sometimes gets called addiction.
You know, incidentally, by NIDA's definition, which is the
only official government definition of addiction I'm aware of,
smoking isn't addictive. It doesn't fit their description but
take as the vague definition of addiction that which is
experienced by smokers.
There is no evidence that e-cigarette users or users of
other low-risk products have the same experience. NRT is
officially non-addictive. It's a nicotine delivery system.
Most people who switch from smoking to vaping, people who
thought, oh, I can never quit smoking and, you know, believed
that that was their feeling switched to vaping and find in 6
months they can take it or leave it. Usually they keep taking
it because they like it. It's a choice. There's not a single
case study reported of anyone reporting saying I have become
addicted using e-cigarettes as a never smoker.
So the assumption that this experience, call it addiction,
which isn't really a very good term, or whatever you want, this
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experience of smokers translates to these other products
appears to be wrong.
DR. DRESLER: So e-cigarettes are not addicting?
DR. PHILLIPS: Well, again, by NIDA's definition, neither
are cigarettes. It's a very fuzzy term. What I would say is
that that which is experienced by cigarette smokers, and it
sometimes gets called addiction, does not seem to be present,
certainly not to the same extent and potentially not at all
among exclusive users of e-cigarettes.
DR. DRESLER: Anybody else want to address whether
e-cigarettes or nicotine or smoking is addictive?
DR. GRAFF: I'm pretty sure that nicotine is addictive.
(Laughter.)
DR. DRESLER: Okay, I noticed -- this is for Dr. Chatham-
Stephens. I noticed high rates of calls to poison centers from
a group of nonusers about 20 years old. What kind of adverse
events were reported in this age group and what routes of
exposure? So, in the people that were nonusers over 20, what
were those adverse events and routes of exposure?
DR. CHATHAM-STEPHENS: Sure, just to clarify. So when I
showed all the ages, that was the entire cohort or the entire
group of calls to poison centers, so that didn't exclude
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adults. So when I showed that table with individuals over 20
years, those were adults who reported some health effect from
e-cigarettes, and it could have been users or nonusers. We
can't tell for sure in NPDS.
What we do know is that, not surprisingly, the majority of
calls for the 0- to 5-year age group were mostly ingestion.
And as you get up into the older age groups, then you find that
the proportion of individuals reporting an ingestion exposure
decrease and the inhalation/nasal exposure increases.
DR. DRESLER: Okay.
DR. CHATHAM-STEPHENS: Which is not surprising given the
exposures.
DR. DRESLER: Okay. Are there any other questions?
Questions? No?
(No response.)
DR. DRESLER: Any other questions from the panelists to
the other panelists? No?
(No response.)
DR. DRESLER: Well, very good. Thank you so very much for
the presentations and for all of the panelists. Thank you.
(Applause.)
DR. DRESLER: Thank you for sticking it out through the
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second day and staying on. And we conclude our series of
e-cigarettes. Thank you.
(Whereupon, at 2:44 p.m., the meeting was concluded.)
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C E R T I F I C A T E
This is to certify that the attached proceedings in the
matter of:
ELECTRONIC CIGARETTES AND THE PUBLIC HEALTH:
A PUBLIC WORKSHOP
June 2, 2015
Hyattsville, Maryland
were held as herein appears, and that this is the original
transcription thereof for the files of the Food and Drug
Administration, Center for Tobacco Products.
_______________________
CATHY BELKA
Official Reporter