March of Dimes Foundation
Office of Government Affairs
1401 K Street, NW Suite 900A
Washington, DC 20005
Telephone (202) 659-1800
Fax (202) 296-2964
marchofdimes.org
nacersano.org
September 30, 2015
SUBMITTED VIA ELECTRONIC TRANSMISSION
Stephen Ostroff, M.D.
Acting Commissioner
U.S. Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993
Docket No. FDA-2015-N-1514-0001
Dear Commissioner Ostroff,
The March of Dimes, a unique collaboration of scientists, clinicians, parents, members of the business
community, and other volunteers affiliated with 51 chapters representing every state, the District of
Columbia, and Puerto Rico, appreciates this opportunity to comment on the advanced notice of the
proposed rulemaking (ANPRM) on “Nicotine Exposure Warnings and Child-Resistant Packaging for Liquid
Nicotine, Nicotine-Containing ELiquid(s), and Other Tobacco Products” (FDA-2015-N-1514-0001). As an
organization committed to the health and wellbeing of women, infants, children, and families, the
March of Dimes commends the Food and Drug Administration (FDA) for its commitment to develop the
most appropriate, science-based regulatory policy regarding liquid nicotine and other tobacco products.
We urge the FDA to require both graphic warning labels and child-resistant packaging for liquid nicotine
and other tobacco products, and to ensure that warnings sufficiently express the dangers of exposure to
women who are or could become pregnant, as a means to protect these vulnerable populations.
PART A: Nicotine Exposure Warnings
The Need for Warning Text on Liquid Nicotine
The proven danger of nicotine, especially to pregnant women, warrants a requirement of warning text
on liquid nicotine packaging and, to the extent practicable, cartridges. Liquid nicotine, used in electronic
cigarettes (e-cigarettes), is addictive, prompting symptoms of irritability, depression, restlessness, and,
upon withdrawal, anxiety.i Furthermore, researchers have discovered that e-cigarettes deliver high
doses of nanoparticles, which can cause inflammation and subsequent illnesses such as asthma, stroke,
heart disease, and diabetes.ii Studies also show that the solvents found in liquid nicotine can transform
into carbonyls, which can be carcinogenic.iii According to medical professionals, ingestion of, or even
mere skin exposure to, small amounts of nicotine (potentially as low as one teaspoon), can lead to
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serious toxicity or even death.iv Symptoms of toxic exposure include: rapid heartbeat, elevated blood
pressure, nausea, vomiting, diarrhea, dizziness, confusion, seizures (which could prompt coma or death),
low blood pressure, and low heartrate. Beyond the general risks of liquid nicotine (those that affect the
population as a whole), there are also serious harms that specifically threaten pregnant women and
children.
Exposure to nicotine in utero poses serious consequences for fetal development. The effects of prenatal
exposure to nicotine on autonomic functioning has been researched in several different species,
including humans. These investigations have revealed that detrimental health effects can occur largely
due to inadequate respiratory adjustment.v Nicotine interacts with receptors in both the lungs and
brain, resulting in decreased respiratory activity in response to stress, as well as abnormalities in
neurodevelopment.vi When examining the direct effect of nicotine on the developing fetal brain,
researchers have discovered that nicotine can induce abnormalities in cell proliferation and
differentiation, resulting in brain cell damage.vii With these risks in mind, health researchers warn that
no amount of nicotine is known to be safe during pregnancy.viii The specificity of this risk warrants a
labeling requirement similar to that required under the Alcoholic Beverage Labeling Act (P.L. 100-690)
that informs pregnant women of the risks these products pose and advises them not to ingest or inhale
liquid nicotine or other tobacco products.
Beyond both the general consequences of nicotine use and exposure, and those specific to pregnant
women, one of the most dangerous aspects of liquid nicotine exposure stems from the risk of poisoning,
especially to infants and children. In 2014, the Centers for Disease Control and Prevention (CDC) cited an
increase in the number of calls involving e-cigarettes reported to poison control centers across the
nation.ix This surge is demonstrated in the fact that, between September of 2010 and February of 2014,
calls related to e-cigarettes received by poison control centers increased from an average of one per
month to 215 per month in the United States.x The calls reflected nearly 4,000 exposures (via ingestion,
inhalation, skin or eye absorption) to liquid nicotine in 2014, nearly twice as many calls as were reported
in 2013.xi According to the American Association of Poison Control Centers, as of August 31st 2015, there
were 2,209 cases of exposure to e-cigarettes and liquid nicotine reported to poison centers this year
alone.xii This number is alarmingly high in comparison to the 271 cases reported in all of 2011, and
confirms the increasing trend seen in the 3,783 cases reported for 2014. More than half of the calls
regarding poisonings involved children under the age of five years old.xiii In one survey, all but two of the
25 cases reported over a two month span this year in Oklahoma involved children under the age of
five.xiv Data also shows an increase in hospital visits dealing with liquid nicotine exposure, with vomiting,
nausea, diarrhea, confusion, agitation, and eye irritation listed as the most common symptoms.xv,xvi,xvii
Included in this increase in hospital visits is the case of a two-year-old in Oklahoma City, who drank a
small bottle of liquid nicotine and was rushed to the emergency room, and a toddler from upstate New
York who died last December after swallowing liquid nicotine.xviii,xix,xx These stories confirm the toxicity
and health risks of liquid nicotine, a substance so potent that only a teaspoon of highly diluted e-liquids
can kill a small child.xxi
Given the health consequences of liquid nicotine, warning labels are imperative to reduce the dangers
posed by these products. One of the largest risks posed by e-liquids is that these products are marketed
in ways that hide risk and can prove attractive to youth. The bright colors and sweet flavors (including
cherry, bubble gum, and chocolate) risk making such products attractive to youths.xxii Furthermore,
advertising may suggest to adults that these products are a safer alternative to cigarettes, and the lack
3
of public awareness of the risks posed by liquid nicotine could misinform parents, leaving children at an
increased risk of accidental exposure. A study published last year found that placing either the warning
labels currently used for smokeless tobacco (“Warning: This product is not a safe alternative to
cigarettes”) or a graphic warning label on e-cigarette advertisements produced a significant increase in
the perception of harm.xxiii Based on the current research, March of Dimes recommends nicotine
exposure warning labels on liquid nicotine, in order to protect the health of both parent and child.
Further, the warnings should disclose the risks of these products specifically to pregnant women.
The Need for Warning Text on Other Tobacco Products
Tobacco products other than liquid nicotine, most notably novel tobacco products, share many of the
same risks presented by liquid nicotine products, therefore justifying a requirement to include warnings
on these products as well. Novel tobacco products (often addressed as “other tobacco products” or
OTPs) include dissolvables, which are flavored, smoke-free tobacco products that appear much like
candy, and dissolve in the user’s month.xxiv This category of products also includes finely ground flavored
tobacco (such as strips, sticks, and orbs), snuff (tobacco presented in a teabag-like pouch placed
between the lips and gums), and “cigarillos” or little cigars.xxv Though OTPs are sometimes marketed as
safer than traditional tobacco products, current research shows that there is no known safe level of
tobacco use, and that novel tobacco products can also lead to oral cancer, gum disease, nicotine
addiction, and increased cardiovascular disease.xxvi These novel tobacco products, as is often the case
with liquid nicotine, come in a variety of sweet flavorings that could be appealing to children.
Studies show that dissolvables pose a risk for the unintentional poisoning of children, given their
resemblance to candy or mints.xxvii For Orbs, a finely ground flavored tobacco product shaped like small
hard candies and produced by R.J. Reynolds Tobacco Company, there has been at least one case of
ingestion by a 3-year-old in Oregon.xxviii In addition, two cases of mild poisonings among toddlers were
reported for snus (flavored oral tobacco products that are sold without any child-warning labels).xxix
Beyond the direct health risks and potential for poisoning of these novel tobacco products, health
professionals also warn that these products could lead to tobacco initiation among children.xxx In a study
conducted by the Virginia Foundation for Healthy Youth, 39% of minors believed that Camel Orbs were
not tobacco products, but mints or gum, leading 28% of the minors in the study to say they would try
this product based on the packaging.xxxi Given the ambiguous presentation and harmful effects of novel
tobacco products, warning labels are especially important to protect the health of children. Therefore,
March of Dimes strongly encourages the FDA to require nicotine exposure warnings on all novel tobacco
products. These warnings should also disclose the specific risks these products pose to women who are
or may become pregnant.
Issues Addressed by Warning Labels
The March of Dimes recommends that the FDA mandate warnings labels on both liquid nicotine and
other tobacco products that include the risks to both pregnant women and children. Studies on the
effects of nicotine during pregnancy have found that women using smokeless tobacco (such as liquid
nicotine and novel tobacco products) give birth earlier than women not using these products.xxxii In fact,
4
the research showed that these tobacco products increased the risk of preterm birth by a factor of 1.4
for the women involved in the study.xxxiii Furthermore, studies have found that pre-eclampsia, a
potentially fatal complication of pregnancy, is more common in snuff users.xxxiv Smokeless tobacco has
also been shown to result in low birth weight among babies born to mothers using these products
during pregnancy.xxxv Based on research regarding these negative effects of nicotine exposure on both
mothers and infants, health professions have concluded that there is no known amount of nicotine
considered safe during pregnancy.xxxvi Therefore, warning labels that specifically address the risk of liquid
nicotine and other tobacco products to pregnant women are critical to protect the health of mothers
and babies.
Children are another vulnerable population that should be specifically considered in developing warning
labels for liquid nicotine and novel tobacco products. Liquid nicotine and novel tobacco products pose a
serious health risk to children. In one study, one in three teenagers (younger than 18) mistook a
smokeless tobacco product for candy or gum.xxxvii Even if youth do recognize that these products contain
tobacco, they may still perceive these products as less harmful, given the lack of public awareness and
available information about the potential harms of these products. Therefore, warning labels serve an
important role in ensuring children know the risks these products pose for their health. In addition,
these products pose life-threatening risks to youth through the risk of accidental poisoning. Given the
potential harm of liquid nicotine to children, the American Association of Poison Control Centers
recommends keeping e-cigarettes and liquid nicotine out of the reach of children.xxxviii One step in
ensuring children do not have access to these, and other tobacco products, is the implementation of
warning labels that focus on the risk to children and advice adults to “keep out of the reach of children.”
March of Dimes supports requiring such labels on all liquid nicotine and other tobacco products.
Beyond labels addressing the risk to pregnancy and children, FDA should focus on the harmful effects of
skin exposure to concentrated nicotine. The American Association of Poison Control Centers advises that
consumers take precaution in protecting their skin when handling products containing liquid nicotine.xxxix
Skin exposure to liquid nicotine can have serious health consequences. In one case in Kentucky, a
woman was rushed to the hospital with cardiac symptoms after her e-cigarette broke on her and the
liquid nicotine was absorbed through her skin.xl Thus, warning labels should include information
regarding the appropriate handling and disposal of such products, and the need to avoid skin exposure.
For the protection of vulnerable populations like pregnant women and children, March of Dimes urges
FDA to require that labeling include information regarding actions that should be taken in the case of an
accidental exposure to liquid nicotine or other tobacco products. This information is fundamental in
promoting quick treatment for those involved in accidental exposure, poisonings, or overdoses. The
American Association of Poison Control Centers recommends that those exposed to liquid nicotine call
the local poison control center immediately.xli Therefore, warning labels on liquid nicotine and other
tobacco products should include this recommendation, and instructions on how to access treatment in
the case of potential poisoning. In addition, by encouraging those involved in accidental exposures to
contact the poison control centers, more accurate data can be obtained regarding the rate of nicotine
poisonings and the overall public health risk of these products. The current data does not provide the
most accurate information, given that not all who have an incident call the poison control centers. Thus,
FDA regulation that requires information about what to do in the case of an accidental exposure to
liquid nicotine or other tobacco products would be an important step in ensuring both public health and
better health data about liquid nicotine and other tobacco products in the future.
5
Communicating the Dangers Associated with Nicotine Exposure
Liquid nicotine and OTPs have been proven to be harmful, especially to pregnant women and children.
Nicotine, including in its liquid form, is addictive; it can cause inflammation of the lungs resulting in
subsequent illnesses such as asthma, stroke, heart disease, diabetes, and cancer. Unfortunately, many
children may not read, or be able to read, warning label text, much less understand them and then
make a reasoned judgment. Therefore, in addition to the recommendation that the FDA mandate
warnings that include both the risks to pregnant women and children, and the harmful effects of skin
exposure to nicotine, the March of Dimes also recommends that the FDA mandate graphic pictorial
warning labels on liquid nicotine products and OTPs.
With respect to traditional tobacco products such as cigarettes, graphic health warning labels are
arguably the most cost-effective tool for educating smokers and non-smokers about the health risks of
tobacco use. According to the 2009 International Tobacco Control (ITC) Warning Report, health
warnings on cigarette packages are among the most prominent sources of information about the harms
of smoking and tobacco use. More smokers report getting information about the risks of smoking from
packages than from any other source except television. xlii Therefore, warning labels serve as an effective
platform for informing smokers about the health hazards of smoking, encouraging smokers to quit, and
preventing nonsmokers from starting to smoke. The effectiveness of graphic pictorial warning labels is
supported by various studies conducted in countries that have instituted pictorial warning
requirements. For example, after large pictorial warnings were introduced in Canada in 2000, 91% of
smokers surveyed reported that they read the warning labels and were able to demonstrate a thorough
knowledge of its content.xliii
Furthermore, at follow-up, smokers who read and discussed the warning labels in greater depth stated
that they were significantly more likely to either quit, attempt to quit, or reduce their smoking.xliv In
Brazil, 73% of smokers approved the introduction of graphic pictorial warnings, 54% reported that being
exposed to the warnings changed their opinion of the health consequences of smoking, and 67% of
people surveyed said that the warnings made them want to quit smoking.xlv Brazil instituted a second
round of warning labels in 2004. A study evaluating the effectiveness of both sets of warning labels
determined that the most graphic and threatening warning labels increased intentions to avoid
smoking.xlvi Finally, in Singapore, a Health Promotion Board survey conducted after the government
introduced its first pictorial warning labels in 2004, reported that 28% of smokers surveyed reported
smoking fewer cigarettes because of the warnings, 14% of smokers said that they made sure to avoid
smoking in front of children, and 12% of smokers said that they made sure to avoid smoking in front of
pregnant women.xlvii Furthermore, graphic pictorial warnings are especially impactful because they are
able to clearly communicate the harms to youth and to those with low literacy levels.xlviii Based on the
data, it is apparent that the use of graphic elements in health warning labels is effective in deterring
tobacco use, encouraging users to quit or reduce use, and preventing non-tobacco users from starting.
The issue of unclear graphic pictorial elements is not uncommon in countries where pictorial warnings
are required on tobacco products. In a study conducted by Oswal et. al. looking at the effectiveness of
current tobacco pictorial warnings in India, focus group discussions and field surveys were used to
determine which graphic elements and/or colors were most effective in communicating the dangers
associated with tobacco. Participants of the focus group discussions were divided into four groups: low
6
socio-income, professionals and high education, youth (college students), and women. The majority of
the focus group responded that is was better to have pictures, rather than just text. Many also
responded that the type of picture displayed on packages was vital. The results of the survey and focus
group discussions revealed that the most effective images were both clear and colored. Participants
stated that graphic elements should include a picture of the human body, which can be easily
understood even by a layman. In addition, if body parts are displayed on tobacco packages, many
suggested that there should also be text labeling the body part and what diseased condition is being
displayed, in order to optimize the effectiveness of the warning label.xlix
To maximize the chances that the graphic element will elicit the desired response, it is important that
the labels alter perceptions of severity and susceptibility, but do not elicit a defensive response. Based
on current research with traditional tobacco products, and knowledge of the harmful effects of nicotine
exposure for liquid nicotine and OTPs, March of Dimes recommends clear and colored graphic elements
be displayed on these products. Images have been successful in Brazil in informing smokers about the
health hazards of smoking, encouraging smokers to quit, and preventing nonsmokers from starting to
smoke, and may have a similar effect in conjunction with the use of liquid nicotine and OTPs.l
In addition to effective graphic elements, research indicates that the use of color, as opposed to black
and white, affects the overall noticeability of pictorial elements of health warnings and messages. In the
study conducted by Oswal et. al., participants suggested red text, as red is not only representative of
danger, but is also a bold and therefore noticeable color.li March of Dimes recommends that warning
labels should require full color, rather than black and white, for pictorial elements of health warnings
and messages. In addition, warning labels should have contrasting colors for the background and the
text in order to enhance noticeability and maximize the legibility of text-based elements of health
warnings and messages.
In addition to emotionally strong graphics, strongly worded health warnings are effective in
communicating the dangers associated with tobacco products. The results of a survey conducted in the
EU in 2008 revealed that 61% and 56% of respective Romanian and British participants recognized that
health warnings on tobacco packs were more effective when they included both pictures and text,
rather than text alone. In the study conducted by Oswal et. al., which looked at the effectiveness of
current tobacco pictorial warnings in India, participants stated that a combination of text and picture
was necessary for health warning labels.lii In addition, researchers found that 50% of subjects
remembered the text-only warning label, while 83% correctly recalled the label that contained a graphic
image. The quicker smokers looked at the large text in the graphic warning, as well as the longer they
viewed the graphic image, the better their recall ability. This research indicates that drawing attention
to the warning label can improve how a smoker recalls the warning label information, improving the
chances they will take the information about smoking risks to heart.liii In order to enhance the
effectiveness of graphic health warning labels, March of Dimes recommends that the FDA require a
combination of text, color, and graphic elements on health warning labels for liquid nicotine and other
novel tobacco products.
7
Different Nicotine Exposure Warnings for Different Packaging Types
Warnings should be required on all nicotine products to ensure that potential users have access to
information about health risks, which will help reduce the misperception that only cigarettes (and not
other tobacco and liquid nicotine products) cause harm. Because the advent of liquid nicotine products
such as e-cigarettes and novel tobacco products is relatively recent, there is little regulation on these
products and the public may not be fully aware of the products’ potential harmful effects. Options to
overcome these challenges include: requiring warnings on individual products, especially if products are
sold in loose packaging or in bundles without outer packaging; requiring minimum package sizes, if
packages are too small to implement the required warnings practicably; allowing warnings to be printed
on permanent or nonremovable stickers applied to the product or its packaging, if it is impractical to
print the warning directly on the product or packaging; and requiring pictorial warning signs at all places
where tobacco products are sold, and on any permitted advertising or promotion for tobacco products.
Tobacco products not sold in traditional commercial packaging, or served and purchased in devices
other than the original packaging, should not be exempt from warnings. Plain packaging could be a
deterrent to child use of novel tobacco products such as tobacco “mints” which are packaged in
containers similar to breath mints. Australia became the first country to require plain (or generic)
packaging of all tobacco products, such that brand logos and colors have been banned and replaced with
a drab brown background and identical fonts noting only the brand and product type.liv This law also
increased the size of graphic health warnings, to cover 75% of the front, and 90% of the back, of packs.
Furthermore, additional text warnings and the national quit-line number must appear on package sides,
and misleading product descriptors such as “light” and “mild” are prohibited.
Logistics of Nicotine Exposure Warnings
The World Health Organization (WHO) has provided guidelines for the implementation of Article 11 of
the WHO Framework Convention on Tobacco Control, which encourages parties to implement effective
packaging and labeling measures within a period of three years after entry. Research indicates that
health warnings and messages are more visible at the top of the package rather than the bottom. In
addition, health warnings and messages should be positioned on the front and the back, or on all main
faces, rather than just on one side, in order to ensure that health warnings and messages are highly
visible. In Egypt and other countries, tobacco companies are marketing double packages that open up to
reveal additional main faces that do not carry health warnings. Requiring warnings on “all main faces”,
rather than just on the front and back, or on one side of the packaging could improve the impact of the
warnings. In addition, it is important to make sure that warnings are placed in such a way that the
normal opening of the package does not permanently damage or conceal the text or image of the health
warning.
While best practice in health warning labels may vary (for example, the most effective image or warning
in one country might not be the most effective in another country), two objective benchmarks are the
required size and location of pictorial warnings. Larger warnings are more effective than smaller
warnings because they are more noticeable. Smokers are more likely to recall larger warnings than
smaller ones, and even tend to equate the size of the warning with the magnitude of the risk of tobacco
use. One study showed that larger messages are also perceived as more credible. Recent studies in
8
Canada show that increasing the size of the health warning from the current size of 50% of the main
pack faces, to up to 100%, would have a greater add-on impact. The studies also showed that, for both
adults and young people, there are substantial incremental impacts in increasing the percentage from
75% to 90%, and from 90% to 100%.liv The WHO Framework Convention recommends that warnings
occupy 50% or more of the principal display area of a tobacco product package and requires that they
occupy no less than 30%.lvi
In addition to large warnings, using multiple warnings will make the messages more relevant to a variety
of priority audiences and will help prevent wear-out of the messages. Multiple messages should be
required to be rotated on packaging during a single time period to ensure variety and to ensure that
manufacturers cannot choose warnings they think will be less effective (for example, placing pregnancy
warnings on brands with a mostly male market share). Sets of health messages should be regularly
refreshed (every two to three years) to retain novelty. Some countries – Australia, Brazil, Chile,
Singapore, Thailand and Uruguay – have now implemented multiple rounds of pictorial warnings.lv
Based on the guidelines provided by the World Health Organization’s Framework Convention on
Tobacco Control and the best practices of several countries that have implemented graphic warning
labels, March of Dimes recommends that the FDA require graphic health warning labels on liquid
nicotine and other novel tobacco products to be positioned on the top of the package on all main faces.
In addition, to maximize the effectiveness of warning labels, they should take up 50% or more of all
main faces of product packaging, and should rotate and vary over time.
PART B: Child-Resistant Packaging
Need for Child-Resistant Packaging for Liquid Nicotine and Other Novel Tobacco Products.
Liquid nicotine, the key ingredient in e-cigarettes, is extracted from tobacco and infused with flavors,
colors, and chemicals. Nicotine in high concentrations, either when ingested or with skin exposure, can
result in serious or fatal poisoning. Since the tragic death of a one-year-old boy in Fort Plain, New York,
who accidently ingested liquid nicotine, the need for child-resistant packaging has become evident.lvi
The bright colors and packaging used to make products that closely resemble candy often appeal to
children, placing them at higher risk of completely preventable harm.
American Academy of Pediatrics (AAP) President Dr. James M. Perrin supported this argument, saying
that “Because liquid nicotine comes in a variety of bright colors and in flavors appealing to children such
as cotton candy and gummy bear, it is no surprise that these products have found their way into the
hands of children.”lvii Typically, during a single session, an electronic cigarette delivers a systemic dose of
approximately 1mg of nicotine, consistent with the amount of nicotine delivered to the body by
traditional cigarette smoking. However, the liquid used in an e-cigarette is mixed with highly
concentrated nicotine solution. Generally, in e-cigarettes, the highest nicotine concentration mixed in eliquids is 32mg/ml, but some refill solutions can be purchased on the Internet with concentrations as
high as 100mg/ml. Nicotine in these high concentrations, either ingested or by skin exposure, can result
in serious or fatal poisonings. At these concentrations, a small 15 ml dropper bottle of liquid nicotine
could be enough to kill four toddlers.lviii
9
Similar to liquid nicotine, many novel tobacco products come in packaging that appeals to children and
adolescents because they are flavored and packaged like candy or breath mints. As a result these
products can be easily misidentified by toddlers and young children, and accidentally ingested. These
dangers are especially pronounced in infants and young children. Many, if not all, cases of accidental
nicotine poisoning are preventable with adequate child-resistant packaging. Therefore, March of Dimes
recommends that FDA require child-resistant packaging for liquid nicotine and other novel tobacco
products.
Mitigation of Exposure Risks for Liquid Nicotine and Other Tobacco Products
Child-resistant packaging for liquid nicotine and other tobacco products can mitigate oral, dermal, and
ocular exposure risks. CDC officials have acknowledged publicly the need for measures to avoid the
increasing possibility of unintended death from nicotine poisoning.lix The toxicity of nicotine is such that
ingestion by an adult of amounts as small as one teaspoon has the potential for symptoms such as rapid
heartbeat, elevated blood pressure, nausea, vomiting, diarrhea, dizziness, confusion, seizures, low blood
pressure, low heart rate, coma, or even death.lx Children are at an especially high risk of unintentional
nicotine poisoning.
The current ease of access to liquid nicotine containers explains the increasing rate of nicotine exposure
calls to poison control centers, given that 51% of these calls involve children ages 0 to 5.lxi Policymakers
assert that child-resistant packaging could be an effective way to reduce the number of liquid nicotine
poisonings, especially among young children.lxii It is worth noting that some representatives from the
tobacco industry support efforts to require child-resistant packaging, acknowledging the need to protect
children from these products.lxiii March of Dimes recommends that FDA mandate child-resistant
packaging for all liquid nicotine and OTPs.
Beyond the exposure risks of oral ingestion, child-resistant packaging requirements could also mitigate
both dermal and ocular exposure risks. Unlike other tobacco products, liquid nicotine presents the
danger of dermal exposure, a risk that can be especially pronounced among young children, and which
could be largely mitigated by the introduction of child-resistant packaging. Furthermore, ocular
exposure to nicotine may cause similar symptoms of irritation seen in dermal exposure. Thus, childresistant packaging requirements could decrease the risks of unintended oral ingestion poisoning, as
well as dermal and ocular risks posed by exposure to liquid nicotine and other tobacco products.
PART C: OTHER ACTIONS AND CONSIDERATIONS
The Need for Both Warning Labels and Child-Resistant Packaging
March of Dimes strongly encourages the FDA to require both nicotine exposure warnings and childresistant packaging for liquid nicotine and other tobacco products, including, but not limited to, novel
tobacco products. Specifically, warning labels would prove effective in targeting the adult population,
especially women who are or may become pregnant. While warning labels alone aid in the protection of
children by informing parents of potential risk to both themselves and their children, the additional
component of child-resistant packaging is needed to protect young children and infants. March of Dimes
10
urges the FDA to require both warning labels and child-resistant packaging for all liquid nicotine and
OTPs.
Additional Measures
March of Dimes recommends that FDA regulate the sale and availability of flavors that may appeal to
children for liquid nicotine and other tobacco products, including novel tobacco products. The currently
unregulated market for the flavorings of these products leaves young children at risk of unintentional
poisoning, and leaves older children at risk of tobacco initiation and nicotine addiction. The sweet
flavorings of liquid nicotine, such as cherry, chocolate, and bubble gum, may encourage children to use
or ingest these products, leaving children vulnerable to poisoning and the associated health
consequences of toxic nicotine.lxiv Furthermore, as these flavors mask the harsh, toxic properties of
other tobacco products, youth may be more inclined to use, and continue using, these nicotine
products, thereby increasing the likelihood of tobacco initiation and, later, a nicotine addiction.lxv In
September of 2009, the FDA issued a ban on cigarettes containing certain characterizing flavors,
including strawberry, grape, orange, clove, cinnamon, pineapple, vanilla, coconut, licorice, cocoa,
chocolate, cherry, or coffee.lxvi The FDA implemented this ban as a means to reduce smoking in America,
acknowledging that flavored products serve as an avenue for youth to become addicted to tobacco.lxvii
Similar actions should be taken for flavoring in liquid nicotine and other tobacco products, such as novel
tobacco products. This additional measure would help further reduce the risk to children.
The March of Dimes appreciates the opportunity to comment on this ANPRM. If we may provide further
information or answer questions, please contact James Gelfand at [email protected] or (202)
659-1800.
Sincerely,
Dr. Jennifer L. Howse
President
11
i
National Center for Biotechnology Information. PubChem Compound Database; CID=89594,
https://pubchem.ncbi.nlm.nih.gov/compound/89594 (accessed Sept. 30, 2015).
ii
Glantz, S. “E-Cigarettes, A Scientific Review.” Contemporary Reviews in Cardiovascular Medicine. 2014;129:19721986. http://circ.ahajournals.org/content/129/19/1972.full (accessed Sept 30, 2015).
iii
Ibid.
iv
The National Institute for Occupational Safety & Health, Centers for Disease Control and Prevention. “Nicotine:
Systemic Agent.” http://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750028.html (accessed Sept 30,
2015).
v
Wickström, R. “Effects of Nicotine During Pregnancy: Human and Experimental Evidence.” Curr Neuropharmacol.
2007 Sep; 5(3): 213–222. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656811/ (accessed Sept 30, 2015).
vi
Ibid.
vii
Ibid.
viii
Suter, M et al. “Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy?” Birth Defects Res
A Clin Mol Teratol. 2015 Mar;103(3):186-95. http://www.ncbi.nlm.nih.gov/pubmed/25366492 (accessed Sept 30,
2015).
ix
Dennis, B. “FDA Weighs Warning Labels, Child-Resistant Packaging After Surge in Liquid Nicotine Poisonings,”
June 30, 2015. Washington Post. http://www.washingtonpost.com/news/to-your-health/wp/2015/06/30/fdaweighs-warning-labels-child-resistant-packaging-after-surge-in-liquid-nicotine-poisonings/ (accessed Sept 30,
2015).
x
Ibid.
xi
Ibid.
xii
American Association of Poison Control Centers. E-Cigarette Devices and Liquid Nicotine.
http://www.aapcc.org/alerts/e-cigarettes/ (accessed Sept 30, 2015).
xiii
Chatham-Stephens, K et al. “Notes from the Field: Calls to Poison Centers for Exposures to Electronic Cigarettes
— United States, September 2010–February 2014,” April 4, 2014. Centers for Disease Control and Prevention,
Morbidity and Mortality Weekly Report (MMWR).
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6313a4.htm (accessed Sept 30, 2015).
xiv
Richtel, M. “Selling a Poison by the Barrel: Liquid Nicotine for E-Cigarettes.” The New York Times. March 23,
2014. http://www.nytimes.com/2014/03/24/business/selling-a-poison-by-the-barrel-liquid-nicotine-for-ecigarettes.html (accessed Sept 30, 2015).
xv
American Association of Poison Control Centers. E-Cigarette Devices and Liquid Nicotine.
http://www.aapcc.org/alerts/e-cigarettes/ (accessed Sept 30, 2015).
xvi
Chatham-Stephens, K et al. “Notes from the Field: Calls to Poison Centers for Exposures to Electronic Cigarettes
— United States, September 2010–February 2014,” April 4, 2014. Centers for Disease Control and Prevention,
Morbidity and Mortality Weekly Report (MMWR).
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6313a4.htm (accessed Sept 30, 2015).
xvii
“Nicotine Exposure Warnings and Child-Resistant Packaging for Liquid Nicotine, Nicotine-Containing ELiquid(s),
and Other Tobacco Products; Request for Comments,” ANPRM. Federal Register Vol. 80, No. 126. Wednesday, July
1, 2015. Pages 3755-37559. http://www.regulations.gov/contentStreamer?documentId=FDA-2015-N-15140001&disposition=attachment&contentType=pdf (accessed Sept 30, 2015).
xviii
Richtel, M. “Selling a Poison by the Barrel: Liquid Nicotine for E-Cigarettes.” The New York Times. March 23,
2014. http://www.nytimes.com/2014/03/24/business/selling-a-poison-by-the-barrel-liquid-nicotine-for-ecigarettes.html (accessed Sept 30, 2015).
xix
“Nicotine Exposure Warnings and Child-Resistant Packaging for Liquid Nicotine, Nicotine-Containing ELiquid(s),
and Other Tobacco Products; Request for Comments,” ANPRM. Federal Register Vol. 80, No. 126. Wednesday, July
1, 2015. Pages 3755-37559. http://www.regulations.gov/contentStreamer?documentId=FDA-2015-N-15140001&disposition=attachment&contentType=pdf (accessed Sept 30, 2015).
12
xx
Mohney, G. “First Child’s Death from Liquid Nicotine Reported as “Vaping” Gains Popularity.” ABC News.
December 12, 2014. http://abcnews.go.com/Health/childs-death-liquid-nicotine-reported-vaping-gainspopularity/story?id=27563788 (accessed Sept. 30, 2015).
xxi
Richtel, M. “Selling a Poison by the Barrel: Liquid Nicotine for E-Cigarettes.” The New York Times. March 23,
2014. http://www.nytimes.com/2014/03/24/business/selling-a-poison-by-the-barrel-liquid-nicotine-for-ecigarettes.html (accessed Sept 30, 2015).
xxii
Ibid.
xxiii
Popova, L and Ling, P. “Nonsmokers’ responses to new warning labels on smokeless tobacco and electronic
cigarettes: an experimental study,” September 25, 2014. BMC Public Health.
http://www.biomedcentral.com/1471-2458/14/997 (accessed Sept. 30, 2015).
xxiv
“Novel Non-Cigarette Tobacco Products: An Overview of Regulatory Options,” 2011. Tobacco Control Legal
Consortium. http://publichealthlawcenter.org/sites/default/files/resources/tclc-fs-novelotps-2011.pdf (accessed
Sept. 30, 2015).
xxv
Ibid.
xxvi
Ibid.
xxvii
Ibid.
xxviii
Connolly, G et al. “Unintentional Child Poisonings through Ingestion of Conventional and Novel Tobacco
Products,” Pediatrics. April 19, 2010. http://pediatrics.aappublications.org/content/early/2010/04/19/peds.20092835.full.pdf+html (accessed Sept. 30, 2015).
xxix
Ibid.
xxx
Freiberg, M. “Options for State and Local Governments to Regulate Non-Cigarette Tobacco Products,” 2012.
Annals of Health Law, Vol. 21, Issue 2, Winter 2012.
http://lawecommons.luc.edu/cgi/viewcontent.cgi?article=1006&context=annals (accessed Sept. 30, 2015).
xxxi
Virginia Foundation for Healthy Youth. 2010 Annual Report.
http://leg2.state.va.us/dls/h&sdocs.nsf/By+Year/RD832011/$file/RD83.pdf (accessed Sept. 30, 2015).
xxxii
Wickström, R. “Effects of Nicotine During Pregnancy: Human and Experimental Evidence, 2007.” Current
Neuropharmacology. Available online at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656811/ (accessed Sept
30, 2015).
xxxiii
Ibid.
xxxiv
Ibid.
xxxv
Ibid.
xxxvi
Suter, M et al. “Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy?” Birth Defects
Res A Clin Mol Teratol. 2015 Mar;103(3):186-95. http://www.ncbi.nlm.nih.gov/pubmed/25366492 (accessed Sept
30, 2015).
xxxvii
Virginia Foundation for Healthy Youth. 2010 Annual Report.
http://leg2.state.va.us/dls/h&sdocs.nsf/By+Year/RD832011/$file/RD83.pdf (accessed Sept. 30, 2015).
xxxviii
American Association of Poison Control Centers. E-Cigarette Devices and Liquid Nicotine.
http://www.aapcc.org/alerts/e-cigarettes/ (accessed Sept. 30, 2015).
xxxix
Ibid.
xl
Richtel, M. “Selling a Poison by the Barrel: Liquid Nicotine for E-Cigarettes,” The New York Times. March 23, 2014.
http://www.nytimes.com/2014/03/24/business/selling-a-poison-by-the-barrel-liquid-nicotine-for-ecigarettes.html (accessed Sept 30, 2015).
xli
American Association of Poison Control Centers. E-Cigarette Devices and Liquid Nicotine.
http://www.aapcc.org/alerts/e-cigarettes/ (accessed Sept 30, 2015).
xlii
Hammond, D et al. “Effectiveness of Cigarette Warning Labels in Informing Smokers About Risks of Smoking:
Findings from the international Tobacco Control (ITC) Four Country Survey.” Tobacco Control. 2006;15(Suppl
III):iii19-iii25. http://cdrwww.who.int/fctc/treaty_instruments/ArtElevenHammondOne.pdf (accessed September
30, 2015).
xliii
Hammond, D et al. “Impact of the Graphic Canadian Warning Labels on Adult Smoking Behavior. Tob Control.
2003;12(4):391-395 http://www.who.int/fctc/guidelines/ArtElevenHammondFourteen.pdf?ua=1 (accessed
September 30, 2015).
13
xliv
Fong, G et al. The impact of pictures on the effectiveness of tobacco warnings. Bulletin of the World Health
Organization. 2009;87:640-643. http://www.who.int/bulletin/volumes/87/8/09-069575/en/ (accessed September
30, 2015).
xlv
Nascimento, B et al. “Avoidance of Smoking: The Impact of Warning Labels in Brazil.” Tobacco Control.
2008;17(6):405-409. http://tobaccocontrol.bmj.com/content/17/6/405.abstract (accesssed September 30, 2015).
xlvi
Costa e Silva, V. Presentation to EU Commission on enforcement of health warnings in Brazil. Brussels, 2002.
xlvii
Health Promotion Board – Singapore. Graphic Health Warnings on Tobacco Packaging Inspire Smokers to Quit
the Habit. 2004.
xlviii
Fong, G et al. The impact of pictures on the effectiveness of tobacco warnings. Bulletin of the World Health
Organization. 2009;87:640-643. http://www.who.int/bulletin/volumes/87/8/09-069575/en/ (accessed September
30, 2015).
xlix
Oswal, K et al. “Are Current Tobacco Pictorial Warnings in India Effective?” Asian Pacific Journal of Cancer
Prevention. 2011;12(1):121-124. http://www.tobaccolabels.ca/wp/wp-content/uploads/2013/12/India-2011-Arecurrent-tobacco-pictorial-warnings-in-India-effective-Asian-Pacific-J-Cancer-Prev-Oswal-et-al.pdf (accessed
September 30, 2015).
l
American Association of Poison Control Centers. E-Cigarette Devices and Liquid Nicotine.
http://www.aapcc.org/alerts/e-cigarettes/ (accessed September 30, 2015).
li
Oswal, K et al. “Are Current Tobacco Pictorial Warnings in India Effective?” Asian Pacific Journal of Cancer
Prevention. 2011;12(1):121-124. http://www.tobaccolabels.ca/wp/wp-content/uploads/2013/12/India-2011-Arecurrent-tobacco-pictorial-warnings-in-India-effective-Asian-Pacific-J-Cancer-Prev-Oswal-et-al.pdf (accessed
September 30, 2015).
lii
Ibid.
liii
Strasser, A et al. “Graphic Warning Labels in Cigarette Advertisements.” American Journal of Preventive
Medicine. July 2012, Volume 43, Issue 1, Pages 41–47. http://www.ajpmonline.org/article/S0749-3797(12)002073/abstract (accessed September 30, 2015).
liv
Wakefield, M et al. “Australian adult smokers’ responses to plain packaging with larger graphic health warnings
1 year after implementation: results from a national cross-sectional tracking survey.” Tobacco Control,
2015;24:ii17–ii25. http://tobaccocontrol.bmj.com/content/24/Suppl_2/ii17.full.pdf+html (accessed September 30,
2015).
lv
Fong, G et al. The impact of pictures on the effectiveness of tobacco warnings. Bulletin of the World Health
Organization. 2009;87:640-643. http://www.who.int/bulletin/volumes/87/8/09-069575/en/ (accessed September
30, 2015).
lvi
Searcey, D. "Attorney General Faults Liquid Nicotine Retailers for Improper Packaging." New York Times. June 23,
2015. http://www.nytimes.com/2015/06/24/business/attorney-general-faults-liquid-nicotine-retailers-forimproper-packaging.html (accessed September 30, 2015).
lvii
Perrin, James M. AAP Statement on Legislation to Require Child-Proof Packaging for Liquid Nicotine. July 7, 2014.
https://www.aap.org/en-us/about-the-aap/aap-press-room/pages/LiquidNicotinePoisoningPreventionBill.aspx
(accessed September 30, 2015).
lviii
California Poison Control System, University of California at San Francisco. Comments filed on Docket No. FDA2014-N-0189, Child resistant packaging of electronic cigarette devices and refill liquid containers containing
nicotine to prevent childhood. June 27, 2014. https://tobacco.ucsf.edu/child-resistant-packaging-electroniccigarette-devices-and-refill-liquid-containers-containing-nicot (accessed September 30, 2015).
lix
Reinberg, S. “Liquid Nicotine in E-Cigarettes Rising Cause of Poisonings: CDC.” HealthDay, April 3, 2014.
http://www.webmd.com/smoking-cessation/news/20140403/nicotine-in-e-cigarettes-a-growing-public-healththreat-cdc-says?page=3 (accessed September 30, 2015).
lx
Centers for Disease Control and Prevention. Case Definition: Nicotine Poisoning.
http://www.bt.cdc.gov/agent/nicotine/casedef.asp (accessed September 30, 2015).
lxi
Chatham-Stephens, K et al. “Notes from the Field: Calls to Poison Centers for Exposures to Electronic Cigarettes
— United States, September 2010–February 2014,” April 4, 2014. Centers for Disease Control and Prevention,
Morbidity and Mortality Weekly Report (MMWR).
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6313a4.htm (accessed Sept 30, 2015).
14
lxii
Tobacco Control Legal Consortium. Policy Approaches to Prevent Liquid Nicotine Poisonings. Available online at:
http://publichealthlawcenter.org/sites/default/files/resources/tclc-fs-e-liquid-nicotine-poisonings-2015.pdf.
lxiii
Ibid.
lxiv
U.S. Food and Drug Administration. Guidance for Industry and FDA Staff: General Questions and Answers on the
Ban of Cigarettes that Contain Certain Characterizing Flavors (Edition 2), December 23, 2009. Available online at:
http://www.fda.gov/downloads/TobaccoProducts/Labeling/ProductsIngredientsComponents/FlavoredTobacco/UC
M195420.pdf.
lxv
World Health Organization. WHO Technical Report Series: The Scientific Basis of Tobacco Product Regulation,
2008. Available online at:
http://www.who.int/tobacco/global_interaction/tobreg/publications/9789241209519.pdf?ua=1.
lxvi
U.S. Food and Drug Administration. Flavored Tobacco. Available online at:
http://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/FlavoredTobacco/default.htm
lxvii
U.S. Food and Drug Administration. Guidance for Industry and FDA Staff: General Questions and Answers on the
Ban of Cigarettes that Contain Certain Characterizing Flavors (Edition 2), December 23, 2009. Available online at:
http://www.fda.gov/downloads/TobaccoProducts/Labeling/ProductsIngredientsComponents/FlavoredTobacco/UC
M195420.pdf.