FDA’s should not authorize the marketing of 20 flavored ZYN nicotine pouches with the
modified risk claim, “Using ZYN instead of cigarettes puts you at a lower risk of mouth
cancer, heart disease, lung cancer, stroke, emphysema, and chronic bronchitis”
because Swedish Match failed to provide the necessary evidence specific to ZYN
demonstrating that, as actually used by consumers, these products will benefit the health of
the population as a whole, including youth
Docket No. FDA-2025-N-0835
for “Modified Risk Tobacco Product Applications:
Applications for ZYN oral pouch products containing nicotine derived
from tobacco submitted by Swedish Match U.S.A., Inc.’’
Pamela Ling, MD, MPH; Lauren Lempert JD, MPH; Benjamin Chaffee, DDS, MPH, PhD;
Stanton A. Glantz, PhD; Bonnie Halpern-Felsher, PhD;1
Stella A. Bialous, RN, DrPH;Dorie Apollonio, PhD
University of California, San Francisco
1 Stanford University School of Medicine
January 7, 2026
Swedish Match has applied for permission to market 20 flavored ZYN nicotine pouches
(Chill, Cinnamon, Citrus, Coffee, Cool Mint, Menthol, Peppermint, Smooth, Spearmint, and
Wintergreen in two nicotine strengths – 3 mg and 6 mg) with the modified risk claim,
“Using ZYN instead of cigarettes puts you at a lower risk of mouth cancer, heart disease, lung
cancer, stroke, emphysema, and chronic bronchitis.”1 To be granted a Modified Risk Tobacco
Product (MRTP) order permitting marketing ZYN with this claim, the company must
demonstrate that the product, as actually used by consumers, will continue to both:
1) Significantly reduce harm and the risk of tobacco-related disease to individual tobacco
users; and
2) Benefit the health of the population as a whole taking into account both users of
tobacco products and persons who do not currently use tobacco products.2
Swedish Match has failed to meet this statutory burden. As detailed below, Swedish Match
failed to present scientific evidence that supports its claim that using ZYN nicotine pouches
reduces the risk of the diseases cited. In particular, the company failed to provide sufficient
1 US Food and Drug Administration. Swedish Match USA, Inc. Modified Risk Tobacco Product (MRTP)
Applications for ZYN Products. (Current as of 11/21/2025). Available: https://www.fda.gov/tobacco-
products/advertising-and-promotion/swedish-match-usa-inc-modified-risk-tobacco-product-mrtp-applications-zyn-
products
2 Family Smoking Prevention and Tobacco Control Act, section 911(g)(1), Public Law 111-31, 21 USC 387k (June
22, 2009).
1
evidence to support the claim that using ZYN will lower the risk of mouth cancer, and there is
growing evidence that using ZYN increases the risk of other negative oral health impacts.
Additionally, ZYN is not an FDA-approved nicotine replacement therapy (NRT), and Swedish
Match did not and cannot demonstrate that ZYN could be used for cessation. Nevertheless, the
aggressive marketing for ZYN nicotine pouches and the proposed MRTP marketing claims
imply, even if they do not explicitly state, that these products can be used for cessation. Taken
together, Swedish Match has failed to demonstrate that marketing ZYN nicotine pouches will
benefit the health of individuals or the health of the population as a whole.
1. Swedish Match’s sole reliance on FDA’s MRTP marketing authorization of General
Snus products is insufficient to support its MRTP application for ZYN nicotine
pouches
Swedish Match seeks to use FDA’s MRTP marketing authorization of eight General Snus
products as the central reason why FDA should grant MRTP authorization for a different
product, ZYN nicotine pouches. This reasoning is flawed on its face and is not supported by the
law, by the facts, or by previous FDA decisions. While ZYN nicotine pouches may be “similar”
to General Snus because they are used in the same manner (“held between the lip and gum for a
period of use and then discarded”) as Swedish Match argues in its MRTP application, ZYN is a
different product from General Snus. Importantly, this “similarity” does not relieve Swedish
Match of its statutory burden to provide rigorous scientific evidence specific to ZYN pouches
demonstrating why ZYN pouches (the particular products that are the subject of the current
MRTP application) significantly reduce harm and the risk of tobacco-related disease.
FDA should require specific evidence on the product under consideration and reject
arguments based on theory or analogy to different products.
The posted application materials including Modules 1-7 of the MRTP application for ZYN do
not provide the required scientific evidence necessary for scientists, researchers, or the general
public to evaluate the application because they are almost entirely redacted. Moreover, the
information that is available to the public is based entirely on the “authorized MRTPs” for a
different product -- Swedish Match General Snus -- not ZYN nicotine pouches. These data are
insufficient as a matter of law, as well as science, to support the MRTP application for ZYN
because they are not the same products.
FDA cannot assume that the Swedish Match General Snus application applies to ZYN.
First, ZYN is not snus. Swedish Match’s own study comparing ZYN to other smokeless
tobacco products and nicotine replacement therapies states the contents of both ZYN pouches
and General Snus are different.3 ZYN does not contain tobacco leaf, but contains different fillers
than snus ( “microcrystalline cellulose”, plant fibers, maltitol); unlike tobacco in snus, ZYN
contains nicotine salts or solutions and sweeteners; ZYN has different (lower) moisture content
3 Back S, Masser AE, Rutqvist LE, Lindholm J. Harmful and potentially harmful constituents (HPHCs) in two novel
nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine
replacement therapy products (NRTs). BMC Chem. 2023 Mar 3;17(1):9. doi: 10.1186/s13065-023-00918-1. PMID:
36869349; PMCID: PMC9985244.
2
than General Snus, and different nicotine delivery. Another study of nicotine pharmacokinetics
comparing ZYN to General Snus also found significant differences in nicotine extracted content,
bloodstream delivery and subjective effects in human users.4 Moreover, as we detail in another
comment, attached and incorporated by reference, unlike General Snus, ZYN pouches are
available in 20 youth-appealing flavors and nicotine strengths and are marketed to youth.
Further, the original MRTP application for eight Swedish Match General Snus smokeless
tobacco products was submitted on June 10, 2014, more than 11 years ago. 5 Studies that were
submitted more than 11 years ago (and therefore the data that were collected prior to that time,
likely collected some years before then) for General Snus are clearly not adequate to support a
current application for ZYN. Most important, while FDA did not authorize sale of ZYN until
January 2025, ZYN has been sold and used in the US since 2016, where it achieved broad use,6, 7
reaching 9.5 billion units in 2023.8, 9 This is more than enough time for the applicant, Swedish
Match, to have collected data on actual health effects of using ZYN. FDA should not
authorize any MRTP statements for ZYN until the applicant provides specific evidence on the
health effects of ZYN.
In the Decision Summary for the General Snus MRTP Order, FDA stated that although FDA’s
review found that the products would benefit the health of the population as a whole, that
determination may change over time as a function of how the product is actually used by
consumers. In particular, FDA stated at page 13 and again at page 48 of the Decision Summary,
“Although the available evidence from epidemiological studies does not demonstrate significant
youth initiation of snus products at this time, it is possible that marketing the product as a
modified risk product could change this.” 10, 11 So even relying on the General Snus MRTP
order, it is essential for FDA to consider the growing evidence that ZYN nicotine pouches, as
4 Lunell E, Fagerström K, Hughes J, Pendrill R. Pharmacokinetic Comparison of a Novel Non-tobacco-Based
Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff. Nicotine Tob
Res. 2020 Oct 8;22(10):1757-1763. doi: 10.1093/ntr/ntaa068. PMID: 32319528.
5 Modified Risk Granted Orders – Risk Modification for 8 Swedish Match General Snus Smokeless Tobacco
Products. October 22, 2019. Available: https://www.fda.gov/media/131922/download?attachment
6 Lyu JC, Ozga JE, Stanton CA, Hrywna M, Ganz O, Cornacchione Ross J, Sharma A, Ling PM. Advertising the
leading US nicotine pouch brand: a content analysis of ZYN advertisements from 2019 to 2023. Tob Control. 2025
May 7:tc-2024-059145. doi: 10.1136/tc-2024-059145. Epub ahead of print. PMID: 40335264; PMCID:
PMC12379097.
7 Duan, Z., Henriksen, L., Vallone, D., Rath, J. M., Evans, W. D., Romm, K. F., Wysota, C., & Berg, C. J. (2024).
Nicotine pouch marketing strategies in the USA: an analysis of Zyn, On! and Velo. Tob Control, 33(2), 154–163.
https://doi.org/10.1136/tc-2022-057360
8 Marynak KL, Wang X, Borowiecki M, et al. Nicotine Pouch Unit Sales in the US, 2016-2020. JAMA. Aug
10 2021;326(6):566-568. doi:10.1001/jama.2021.10366
9 Global Issues: Nicotine Pouches. Accessed September 26, 2025.
https://www.tobaccofreekids.org/what-we-do/global/nicotine-
pouches#:~:text=However%2C%20nicotine%20pouches%20contain%20either,young%20adults%20to%20e%
2Dcigarettes
10 FDA, Scientific Review of Modified Risk Tobacco Product Application (MRTPA) Under Section 911(d) of the
FD&C Act – Technical Project Lead for Eight General Snus products submitted by Swedish Match USA, Inc.
10/22/2019. Available: https://www.fda.gov/media/131923/download?attachment
11 Lindblom, Eric N. "The Tobacco Control Act's PMTA & MRTP Provisions Mean to Protect the USA from Any
New Tobacco Products That Will Not Reduce Health Harms - But FDA Isn't Cooperating." Journal of Health Care
Law and Policy, vol. 23, no. 2, 2021, pp. 121-186. HeinOnline,
https://heinonline.org/HOL/P?h=hein.journals/hclwpo23&i=124.
3
actually used and marketed, are impacting youth initiation and nicotine use, as well as
12nicotine addiction.
2. Swedish Match failed to provide sufficient evidence or long-term safety data
supporting their claim that using ZYN nicotine pouches significantly reduces the
risk of tobacco-related disease, including oral health impacts, to individual users.
As summarized above, ZYN has been sold and consumed in the United States since 2016,
which is more than enough time to collect real-world data on actual health effects. Swedish
Match has not met its statutory burden2 to demonstrate with sufficient scientific evidence that
ZYN nicotine pouches, as actually used by consumers, will significantly reduce harm and the
risk of tobacco-related disease to individual tobacco users. The applicant did not provide
sufficient long-term disease effects data specific to ZYN supporting the claim that using ZYN
nicotine pouches reduces the risk of the diseases cited. In particular, there is no evidence to
support the claim that, as actually used by consumers, using ZYN nicotine pouches will “lower
risk of mouth cancer.”
The ZYN application is theoretically supported by a toxicological safety profile, a population
health impact model (PHIM), and an oral safety study that were submitted as part of the PMTAs.
However, these are either not posted or nearly completely redacted and therefore unavailable for
public review. Moreover, they rely on the “Swedish experience” with a different product -- snus
-- which is not sufficient to support marketing ZYN with MRTP claims in the US.
For example, the ZYN MRTP application Module 213 states at page 2:
“We believe the proposed [ZYN] MRTPs meet the same requirements and health
standard for authorization of the reduced risk claim as the authorized [General Snus]
MRTPs. Due to the similarities between the proposed MRTPs and authorized MRTPs, the
scientific findings from the FDA authorization to market the authorized MRTPs with the
reduced risk claim can be extrapolated to the proposed MRTPs. More specifically, the
proposed MRTPs also contain and deliver low HPHC quantities, meet the applicable
product testing thresholds of the GOTHIATEK® standard, and demonstrate low youth
use. Therefore, we expect to observe a similar reduction in tobacco-related disease for
smokers who switch from cigarettes to the proposed [ZYN] MRTPs, as seen for smokers
who switched to the authorized [General Snus] MRTPs in Sweden.” [emphasis added]
“Beliefs” and “expectations” about a different product in a different country are not evidence
that ZYN meets the standard the FDA is mandated to follow when authorizing MRTP claims
in the Family Smoking Prevention and Tobacco Control Act.
12 Gaiha, S., Lin, C., Lempert, L., Halpern-Felsher, B. Use, marketing, and appeal of oral nicotine products among
adolescents, young adults, and adults. Addictive Behaviors. 2023 May;140:107632. PMID: 36731224. DOI:
10.1016/j.addbeh.2023.107632;
13 Swedish Match MRTP Applications for ZYN Nicotine Pouch Products —Module 2: Integrated Summary. Posted
June 17, 2025. Available: https://www.fda.gov/media/187077/download?attachment
4
Specifically, there is no legal or scientific support for the statement that “the scientific
findings from the FDA authorization to market General Snus with a reduced risk claim can be
extrapolated to the proposed ZYN MRTPs. Further, if ZYN pouches do, indeed, deliver “low
HPHC quantities” for certain constituents on and outdated list of Harmful and Potentially
Harmful Constituents (we attach an incorporate by reference another comment we submitted on
HPHCs), this does not demonstrate that ZYN products reduce actual disease risks as actually
used.
Finally, even if the applications for General Snus showed low youth use of those snus
products in 2014, that data has absolutely no bearing on how flavored ZYN nicotine products are
actually used by youth in 2026. Among high school adolescents in the US, oral nicotine pouch
use more than doubled from 1.1% to 2.4% from 2021-2024,14 and an analysis of a 2021 cohort of
California high-school adolescents and 2024 NYTS data15 showed that oral nicotine products
were the second most prevalent nicotine product, after e-cigarettes.16 Han and colleagues
analyzed data from the 2023 and 2024 Monitoring the Future survey of 10th and 12th graders.
They found that lifetime nicotine pouch use increased from 3% in 2023 to 5.4% in 2024; past 12-
month use increased from 2.4% to 4.6%, and past 30-day use increased from 1.3% to 2.6%,
respectively. These data represent a 1.8-fold increase in lifetime use, a 2.0-fold increase in past
12-month use, and a 2.1-fold increase in past 30-day use.17 Nicotine pouch use patterns are also
different: adolescents are using multiple pouches at a time, and doing so multiple times
throughout the day,18 increasing their addictive potential.19
The statement in the MRTP application that ZYN are “intended for use in the same manner
[as General Snus smokeless tobacco products] (i.e., held between the lip and gum for a period of
use and then discarded) by the same population (i.e., current 21+ adult tobacco product
consumers)”13 provides no information about disease risks of ZYN. (After all, hard candy is also
consumed by holding it between the consumer’s lip and gum. That does not make evidence on
candy’s health effects relevant to ZYN.) Obviously Swedish Match reformulated their General
Snus products for a reason; ZYN nicotine pouches are a different product that is intended for,
14 Park-Lee E, Jamal A, Cowan H, et al. Notes from the Field: E-Cigarette and Nicotine Pouch Use Among
Middle and High School Students - United States, 2024. MMWR Morb Mortal Wkly Rep. Sep 5
2024;73(35):774-778. doi:10.15585/mmwr.mm7335a3
15 Jamal A, Park-Lee E, Birdsey J, et al. Tobacco Product Use Among Middle and High School Students -
National Youth Tobacco Survey, United States, 2024. MMWR Morb Mortal Wkly Rep. Oct 17 2024;73(41):917-
924. doi:10.15585/mmwr.mm7341a2
16 Harlow AF, Vogel EA, Tackett AP, et al. Adolescent Use of Flavored Non-Tobacco Oral Nicotine
Products. Pediatrics. Sep 1 2022;150(3)doi:10.1542/peds.2022-056586
17 Han, D-H., Harlow, A.F., Miech, R.A., Bae, D., Cho, J., Dai, H.D., Sussman, S.Y., Sanchez, L.M., Meza, L., &
Leventhal, A.M. Nicotine Pouch and E-Cigarette Use and Co-Use Among US Youths in 2023 and 2024. JAMA
Network Open, 2025;8(4):e256739. doi:10.1001/jamanetworkopen.2025.6739
18 Gaiha, S., Lin, C., Lempert, L., Halpern-Felsher, B. Use, marketing, and appeal of oral nicotine products among
adolescents, young adults, and adults. Addictive Behaviors. 2023 May;140:107632. PMID: 36731224. DOI:
10.1016/j.addbeh.2023.107632.
19 For example: Mallock-Ohnesorg N, Rabenstein A, Stoll Y, et al. Small pouches, but high nicotine doses-nicotine
delivery and acute effects after use of tobacco-free nicotine pouches. Front Pharmacol. 2024;15:1392027.
doi:10.3389/fphar. 2024.1392027; Dowd AN, Thrul J, Czaplicki L, Kennedy RD, Moran MB, Spindle TR. A cross-
sectional survey on oral nicotine pouches: characterizing use-motives, topography, dependence levels, and adverse
events. Nicotine Tob Res. 2024;26(2):245-249. doi:10.1093/ntr/ntad179
5
targeted to, and popular with youth and ZYN is not only used by “current 21+ adult”
conventional cigarette users. (See attached comment focusing on youth.)
The MRTP application states at page 6:13
“The toxicological safety profile of the proposed MRTPs [ZYN] is significantly
improved compared to the authorized MRTPs [General Snus] and clinical data further
supports the reduced risk potential of the proposed MRTPs. Therefore, increased uptake
of the proposed [ZYN] MRTPs and an associated decreased cigarette usage in the U.S. is
highly likely to lead to a similar observed decline in U.S. smoking-related disease rates as
expected for the authorized MRTPs and as observed in Sweden. We submitted a
population health impact model (PHIM) as part of our PMTAs for the proposed MRTPs.
Even under the most conservative and pessimistic assumptions, the model shows uptake
of the proposed MRTPs is expected to reduce tobacco-related deaths by 600,000 by the
year 2050. Though the products have not been on the U.S. market long enough to
generate three decades of health data as in the ‘Swedish experience’ data, the PHIM data
shows what is possible in the next three decades should the proposed MRTPs be
authorized to market with the proposed reduced risk claim, allowing smokers to
accurately understand their reduced health risks if they switch completely away from
cigarettes.”
This is another theoretical statement that lacks direct empirical evidence on the disease risks
associated with ZYN. Moreover, while ZYN has not been on the market as long as snus, it has
been on the US market for 9 years, which is long enough for disease effects to begin to be
manifest.
The limited data in Module 4 (Nonclinical) appear to focus on “mutagenic or genotoxic”
effects and exposure to a limited number of HPHCs. Exposure to carcinogens does not
demonstrate actual reduced risk of cancer and fails to address the substantial cardiovascular risks
of these products, including but not limited to risk of high blood pressure, stroke and diabetes.
Again, independent scientists and researchers are not able to evaluate the PHIM data because
it was redacted and was not made available to the public. The Integrated Summary at page 1120
states:
“The toxicological safety profile of the proposed MRTPs is significantly improved
compared to the authorized MRTPs (see Module 4 of these MRTPAs) and thus, compared
to combusted cigarettes. Clinical data further support the significant improvements and
reduced risk potential of the proposed MRTPs (see Module 5 of these MRTPAs).”
20 Swedish Match MRTP Applications for ZYN Nicotine Pouch Products —Module 2: Integrated Summary. Posted
June 17, 2025. Available: https://www.fda.gov/media/187077/download?attachment
6
However, Module 421 and Module 522 provide mostly redacted, limited, and/or outdated
studies, hampering independent review.
a. The “Swedish experience” with snus is irrelevant and cannot be used to support
ZYN.
In any case, as discussed above, the “Swedish experience” for General Snus cannot be used to
demonstrate the safety profile of ZYN use in the US. In fact, FDA’s own 2016 review of the
General Snus MRTP application23 concluded that the “Swedish experience” was irrelevant.
FDA’s own conclusion was:
“The original applications were determined to contain insufficient evidence demonstrating
that the products would be used in a way that would result in a population health benefit. The
applicant proposed that, as MRTPs, its products could have a similar impact in the U.S. as
snus has had in Sweden. In particular, the applicant described a historical trend documented
in Sweden, often called the “Swedish Experience,” a grassroots movement wherein a large
proportion of smokers transitioned to exclusive snus use, bringing rates of smoking to
historically low levels and resulting in a population with a lower incidence of smoking‐
related diseases than comparable countries. Ultimately, FDA’s review of this evidence
concluded that it had limited applicability to the potential impacts of marketing the
MRTPs in the U.S. FDA pointed to the range of social and cultural differences between the
two marketing contexts—including that snus is a traditional Swedish product—limiting the
validity of extrapolating from one to the other…Thus, relying solely on the epidemiological
evidence discussed above, FDA concluded that the applicant had not demonstrated the
likelihood that consumers would use the product in a way that would benefit individual
users and population health.”
Reference to the “Swedish experience” for harm reduction is a longstanding tobacco and
nicotine industry tactic to influence policy that ignores real health harms.
Swedish Match’s application summary13 refers to “the Swedish experience” as “a decline in
tobacco-related disease (e.g., lung cancer, cardiovascular disease [CVD]) with increased uptake
of snus over time.” This framing of the “Swedish experience” has been used repeatedly by the
tobacco and nicotine industry. In 2022, the Swiss Association for Tobacco Control found that a
Swedish e-marketing group focused on promoting and selling snus and nicotine pouches
commissioned a report from a consulting company that used “industry-funded studies,
questionable experts, hidden financing and crooked reports to manipulate the “harm reduction”
debate in order to force open the EU marketing to nicotine pouches”. The Swiss Association for
Tobacco Control highlighted the weaknesses in the industry produced study that claimed that
opening the market to nicotine pouches would save up to 210,000 lives in the EU by assuming
21 Swedish Match MRTP Applications for ZYN Nicotine Pouch Products —Module 4: Nonclinical. Posted
November 21, 2025. Available: https://www.fda.gov/media/189690/download?attachment
22 Swedish Match MRTP Applications for ZYN Nicotine Pouch Products —Module 5: Clinical Individual Health
Studies. Posted November 21, 2025. Available: https://www.fda.gov/media/189691/download?attachment
23 US Food and Drug Administration. Scientific Review of Modified Risk Tobacco Product Application (MRTPA)
Under Section 911 (d) of the FD&C Act – Technical Project Lead. June 10, 2014. STN MR0000020‐22,
MR0000024‐25, MR0000027‐29. https://www.fda.gov/media/131923/download
7
Swedish policy would be effective in other contexts without considering historical or cultural
differences.24 In addition to flawed methods and assumptions that “would never stand in an
independent peer-review examination”, they noted the “study fails to mention recent and strong
evidence on the dangers of snus consumption. Snus use among men is positively associated with
increased all-cause mortality, cardiovascular mortality, with death from other causes, and
possibly with increased cancer mortality.”25
A 2024 report issued by the Public Health Agency of Sweden (PHAS report)26 found that the
scientific evidence concerning the health risks of using tobacco and nicotine products varies,
depending on how long a product has been on the market, the number of people using it, and the
amount of research available. In contrast to the long history of tobacco smoking and the strong
scientific evidence of health harms caused by smoking, this report found that the scientific
evidence is more limited for products like snus that are not used widespread globally.
Nevertheless, the report found:
“Available research suggests that use of tobacco snus may increase the risk of high blood
pressure, type 2 diabetes and death following a heart attack or stroke. Using snus during
pregnancy may increase the risk of foetal or neonatal complications. There is an absence of
scientific evidence about nicotine pouches, but all tobacco and nicotine products contain
nicotine, which is acutely toxic and highly addictive.” (PHAS report,26 p. 9)
Of particular significance, the report states:
“The absence of studies, or that the available evidence is too uncertain to determine
whether there is an association or not, does not mean that risks can be ruled out. All
tobacco and nicotine products may result in addiction and entail health risks, although
tobacco smoking is linked to especially high levels of risk.” (PHAS report,26 p. 9)
Dual- and poly-use of snus in Sweden. The Swedish Public Health Agency’s 2024 report
stated that in 2022, 19% of women and 31% of men reported using some type of tobacco or
nicotine product, either every day or occasionally, and it is common to use more than one
product. Among individuals who smoke, 18% of women and 34% of men also use snus. Among
individuals using snus, 18% of women and 15 percent of men also smoke. The report also found
that it is common to combine the use of alcohol, cannabis and nicotine products, and risky
consumption of alcohol and cannabis is more common among individuals using tobacco and
nicotine products than among those who do not use such products. (PHAS report,26 p. 19)
24 Ruggia, L. “Nicotine pouches save lives:” Just more data manipulation from the nicotine industry. Swiss
association for tobacco control. December 20, 2022. https://www.at-schweiz.ch/en/at-blog/nikotinbeutel/#sources
25 Byhamre ML, Araghi M, Alfredsson L, Bellocco R, Engström G, Eriksson M, Galanti MR, Jansson JH, Lager A,
Lundberg M, Östergren PO, Pedersen NL, Trolle Lagerros Y, Ye W, Wennberg P, Magnusson C. Swedish snus use
is associated with mortality: a pooled analysis of eight prospective studies. Int J Epidemiol. 2021 Jan 23;49(6):2041-
2050. doi: 10.1093/ije/dyaa197. PMID: 33347584; PMCID: PMC7825961.
26 Public Health Agency of Sweden, Knowledge about the harmful effects of tobacco and nicotine products; Report
on a Government assignment, 2024. Available: https://www.folkhalsomyndigheten.se/publikationer-och-
material/publikationsarkiv/k/knowledge-about-the-harmful-effects-of-tobacco-and-nicotine-products-report-on-a-
government-assignment/
8
The report also found associations between snus and tobacco smoking in non-smoking
individuals, and that over time, people who use snus more frequently start smoking tobacco than
people who do not use snus. (PHAS report,26 p. 26)
Frequently the assertion that nicotine pouches could be sold as reduced risk products is based
on assumptions that the use of nicotine pouches will be similar to the experience with snus in
Sweden. It is sometimes claimed that snus is the explanation for Sweden’s low smoking rate.
However, there is no scientific evidence for such an assertion. Snus is not a smoking cessation
product. Quite the opposite, people who use e-cigarettes or tobacco snus are more likely to start
smoking over time, compared with people who do not use e-cigarettes or snus. Young people
who use snus or e-cigarettes are more than four times more likely to also smoke cigarettes,
compared with young people in general. The increased use of snus in recent years is not driven
by former smokers switching products, but by an increase in use among new target groups such
as women and young people.27 Below, Figure 2 from the report shows the increase in snus use
among women in Sweden.
b. Swedish Match failed to demonstrate that smokers accurately understand health
risks if they “switch completely away from cigarettes,” nor have they demonstrated that
users understand what it means to “switch completely.”
Current literature suggests that users, including youth, do not understand that to get the purported
health benefits, “switching completely” means to NOT USE cigarettes at all. The predominant
27 Swedish Tobacco Policy. Key takeaways in reducing smoking and the challenges that remain. Cancerfonden,
Swedish Cancer Society. 2025. https://static-
files.cancerfonden.se/Swedish%20Tobacco%20Policy%20Publication%202025.pdf
9
pattern is dual use. Oral nicotine product use among youth is associated with use of other
tobacco products, and current use is more prevalent among Hispanics, Non-Hispanic Blacks, and
those with lower education and annual incomes.28 There is a growing body of literature showing
that using other tobacco products concurrently with conventional cigarettes does not only reduce
harm, but may in fact increase health harms. (See attached UCSF comments, incorporated by
reference, on misperceptions of ZYN MRTP claims and on IQOS MRTP renewal that provide
detailed information and references on these points.)
c. Nicotine pouches carry oral health risks
At page 8 the application states:
“…the oral safety study submitted in the original PMTAs demonstrates a significant
decrease in the number of people with, and the severity of, oral lesions upon switching from
the authorized MRTPs to the proposed MRTPs.” 13 [emphasis added]
However, the names of and actual studies that are cited to support this statement are
completely redacted.22 Therefore, independent researchers and scientists cannot verify the
scientific merit of this statement which is critical to FDA’s determination of whether to authorize
marketing ZYN pouches with modified risk claims.
Module 5-1, section 3.2, at p. 422 briefly mentions an “oral safety study” with redacted
data claiming that ZYNs “do not promote plaque acidogenesis” and that substitution of ZYN for
snus improved oral mucosal lesions, claiming these data demonstrate that ZYN’s oral health
risks are lower than snus.
These findings run counter to an existing published study reporting a higher prevalence
of oral lesions among individuals who used oral nicotine pouches than among individuals who
used other nicotine products or used no nicotine.29
Also, failure to promote plaque acidogenesis is not evidence that switching from
cigarettes to ZYN oral nicotine pouches reduces the risk of oral cancer. Plaque acidogenesis may
lead to dental caries -- a significant disease, but not one strongly linked to cigarette smoking or to
oral cancer. The lack of plaque acidogenesis suggests that the tested oral nicotine products do not
contain a large amount of fermentable carbohydrates (e.g., sugars), a finding that is not relevant
to the proposed oral cancer claim.
The redacted data are not available for review, and it is not clear what length of exposure
was used in the study. A systematic review of published data on nicotine pouches and oral
health found three studies, all of which were deemed to have a high risk of bias. There were two
cross sectional studies and one prospective experimental study, and due to problems with study
28 Patel M, Kierstead EC, Kreslake J, Schillo BA. Patterns of oral nicotine pouch use among U.S.
adolescents and young adults. Prev Med Rep. Aug 2023;34:102239. doi:10.1016/j.pmedr.2023.102239
29 Miluna-Meldere S, Vanka SA, Skadins I, Kroica J, Sperga M, Rostoka D. Oral mucosal changes caused by
nicotine pouches: case series. Diagn Pathol. 2024 Sep 19;19(1):127. doi: 10.1186/s13000-024-01549-3. Erratum in:
Diagn Pathol. 2025 Jan 28;20(1):12. doi: 10.1186/s13000-025-01606-5. PMID: 39300504; PMCID: PMC11412064.
10
design and control groups “none of the included studies could definitively determine the impact
of nicotine pouches on oral health conditions”.30 One of the studies found a significant
percentage of mucosal changes among those who used both nicotine pouches and snus,
particularly among those with longer years of use and frequent consumption of 5 to 10 pouches
per day, which were accompanied by elevated levels of inflammatory biomarkers.31 This
published data suggests that Swedish Match needs to address the issue of dual use of nicotine
pouches and snus over years of use, not only short term administrations, to be able to make
claims about reduction of oral health risks.
In their 2023 review32 of oral nicotine products’ impacts on periodontal health, Ye and
Rahman highlighted studies showing that nicotine in oral nicotine pouches interacts with host
cells and affects inflammatory responses to microbial challenges and may directly or indirectly
deteriorate periodontal tissues by activating nicotinic acetylcholine receptors, repressing
periodontal ligament fibroblasts cells, increasing cellular reactive oxygen species and
cytokines/chemokines, growth factors, breaking microbiota balance, and dysregulating
microRNAs expression. Additionally, they cited studies showing that flavorings contained in
nicotine pouches could induce microbial dysbiosis in the oral cavity and periodontium, pose
harm to periodontal innate immune responses and increase penetration of nitrosamines. Of
particular concern they found that flavored oral nicotine products increase the risk of dual- or
poly-tobacco products use among young adults, increasing detrimental effects on the
periodontium.
Industry funded studies claim to show reduced abuse liability33 and decreased gum
inflammation in nicotine pouch users compared to cigarette smokers.34 However, non-industry
funded studies have found nicotine pouch users report significant levels of nicotine addiction and
a substantial number of adverse experiences including mouth lesions (48%), upset stomach
(39%), sore mouth (37%), sore throat (21%), and nausea (9%).35 Overall, more studies without
conflicts of interest are needed to verify industry claims, and current data are insufficient to
support claims of reduced harm in nicotine pouch users.
30 Rungraungrayabkul D, Gaewkhiew P, Vichayanrat T, Shrestha B, Buajeeb W. What is the impact of nicotine
pouches on oral health: a systematic review. BMC Oral Health. 2024 Aug 3;24(1):889. doi: 10.1186/s12903-024-
04598-8. PMID: 39097712; PMCID: PMC11297755.
31 Miluna S, Melderis R, Briuka L, Skadins I, Broks R, Kroica J, Rostoka D. The Correlation of Swedish Snus,
Nicotine Pouches and Other Tobacco Products with Oral Mucosal Health and Salivary Biomarkers. Dent J (Basel).
2022 Aug 17;10(8):154. doi: 10.3390/dj10080154. PMID: 36005252; PMCID: PMC9406994.
32 Ye, Dongxia, Rahman, Irfan, Emerging Oral Nicotine Products and Periodontal Diseases, International Journal of
Dentistry, 2023, 9437475, 7 pages, 2023. https://doi.org/10.1155/2023/9437475
33 Kanobe MN, Powell CY, Patrudu M, Baxter SA, Tapia MA, Darnell J, Prevette K, Gibson AG, Ayoku SA,
Campbell L, Coffield JW, Keyser BM, Ganesh BS, Gale N, Jordan KG. Randomized crossover clinical studies to
assess abuse liability and nicotine pharmacokinetics of Velo Oral Nicotine pouches. Front Pharmacol. 2025 Mar
13;16:1547073. doi: 10.3389/fphar.2025.1547073. PMID: 40183092; PMCID: PMC11966027.
34 Liu J, Edmiston JS, Wang J, Milleman KR, Milleman JL, Yoder AL, Gogova M, Sarkar MA. Oral Health Effects
Among Adults Switching from Cigarettes to on!® Nicotine Pouches Compared to Those Who Continue Smoking.
Oral Health Prev Dent. 2025 Mar 25;23:189-201. doi: 10.3290/j.ohpd.c_1925. PMID: 40130808; PMCID:
PMC11966149.
35 Dowd AN, Thrul J, Czaplicki L, Kennedy RD, Moran MB, Spindle TR. A Cross-Sectional Survey on Oral
Nicotine Pouches: Characterizing Use-Motives, Topography, Dependence Levels, and Adverse Events. Nicotine
Tob Res. 2024 Jan 22;26(2):245-249. doi: 10.1093/ntr/ntad179. PMID: 37712111; PMCID: PMC10803111.
11
d. The published literature review cited by Swedish Match is flawed, has prominent
conflicts of interest, and makes unsupported conclusions.
In its “Individual Health Effects and Health Outcomes Lit Review”22 Swedish Match
proposes to use data on the health effects of snus to justify ZYN, which, as discussed above, is
inappropriate. In addition, the Swedish Match application cites their own (redacted) literature
review and a single published scoping review36 to justify the claim that “the reduction in toxicant
exposure translates to harm reduction potential in smokers switching to nicotine pouch
products”.22 The scoping review cited by Swedish Match has several flaws that undermine its
conclusions. The study was funded by Imperial Tobacco Company, which has a financial
conflict of interest to promote nicotine pouch use. The scoping review lacked an assessment of
study methodological quality or disclosure of conflict of interest among study authors. Most
important, the individual studies have caveats and limitations due to variations in product type,
lack of standardized approaches, differences by nicotine concentration and the presence of dual
use with cigarettes; these limitations are ignored in the review’s conclusion that nicotine pouches
“contain significantly fewer and lower levels of harmful chemicals, have a reduced toxicological
impact compared to cigarette smoke, and may convey lower health risks compared to smoking.”
The small number of studies, outcomes limited to biomarkers of exposure, and lack of data on
actual health impacts do not support these sweeping conclusions. At best, the reviewed studies
suggest nicotine pouches may reduce exposure to a limited number of HPHC, but the reduced
exposures are limited to the individual level; the population level claims are unsupported.
Furthermore, the studies do not address at all the impact of nicotine on the cardiovascular system
when assessing health impact.
A review of the literature on nicotine pouches without conflict of interest37 noted rising
appeal and prevalence of nicotine pouches, particularly among young people, and people who
use other tobacco products. Similar to other reviewers they noted efficient nicotine delivery
similar to smokeless tobacco products, and short term decreases in biomarkers of exposure to
tobacco toxicants, and consumer perceptions of decreased harm, but noted that most studies were
produced by the tobacco and nicotine industry, and that additional research is needed to verify
the results of industry funded studies. They did not find sufficient data to support MRTP
claims. They concluded, “more robust longitudinal evidence is needed to establish whether these
products can meet the public health standard, let alone modified risk standards.”
As summarized above, despite the fact that ZYN has been available and consumed in
United Stated for 9 years (since 2016), the application does not demonstrate a significant
decrease in the number of people with or the severity of oral lesions upon switching to ZYN
nicotine pouches, nor does it provide evidence that users understand that they would need to
switch completely to ZYN and not use it concurrently with other tobacco products to get the
purported health benefits. To fulfill its statutory burden and demonstrate that ZYN nicotine
36 Grandolfo E, Ogden H, Fearon IM, Malt L, Stevenson M, Weaver S, Nahde T. Tobacco-Free Nicotine Pouches
and Their Potential Contribution to Tobacco Harm Reduction: A Scoping Review. Cureus. 2024 Feb
15;16(2):e54228. doi: 10.7759/cureus.54228. PMID: 38496069; PMCID: PMC10944327.
37 Felicione NJ, Ozga JE, Eversole A, Hart JL, Tackett A, Hrywna M, Halquist M, Stanton CA. Oral Nicotine
Pouches: Rising Popularity and State of the Science. Public Health Rep. 2026 Jan-Feb;141(1):55-62. doi:
10.1177/00333549251313668. Epub 2025 Apr 28. PMID: 40293136; PMCID: PMC12037535.
12
pouches, as actually used, significantly reduce harm to individual users and to the population
as a whole, including youth and other non-users, Swedish Match was required to submit non-
clinical and clinical long-term safety data for this product as actually used in this country.
Swedish Match failed to do this, so FDA must deny MRTP authorization for ZYN nicotine
pouches.
3. Nicotine has important health harms, including cardiovascular effects
The tobacco industry tries to claim that nicotine is as harmless as caffeine,38 and that the
health harms from smoking tobacco are attributable only to the smoke and tar generated by
tobacco combustion, rather than from nicotine. However, there is extensive evidence that there
are short- and long-term health effects associated with nicotine itself, which would include
nicotine delivered in nicotine pouches, including the adverse effects of nicotine on respiratory
and cardiovascular health, cancers, brain maturation, and interfering with smoking cessation.
A comprehensive, peer-reviewed 2024 report from the World Heart Federation reviews
recent scientific evidence on nicotine and cardiovascular health.39 The report discusses health
impacts of not only combustible tobacco products, e-cigarettes, and heated tobacco products, but
also of moist/dry snuff products, including snus, and nicotine-delivering oral tobacco products,
including nicotine pouches.40 Other studies demonstrate that the regular utilization of smokeless
nicotine products confers a higher risk for diseases including cancers, Parkinson’s disease, birth
defects, oral submucosal fibrosis, periodontal diseases, cardiovascular disease, and type 2
diabetes.41, 42, 43
Dorotheo et al.39 highlight many studies showing that nicotine is associated with harmful
cardiovascular effects, including on heart rate (acute tachycardia), blood pressure (acute
hypertension), coronary vasodilator reserve (myocardial ischemia), vasoconstriction and
vasodilatation, peripheral vascular resistance, blood viscosity and platelet aggregation
(thrombosis), production and release of nitric oxide (endothelial dysfunction), total and LDL
38 Ling PM, Glantz SA. Tobacco company strategies to identify and promote the benefits of nicotine. Tob Control.
2019 May;28(3):289-296. doi: 10.1136/tobaccocontrol-2018-054300. Epub 2018 Aug 9. PMID: 30093414; PMCID:
PMC6368903.
39 Dorotheo EU, Arora M, Banerjee A, et al. Nicotine and Cardiovascular Health: When Poison is Addictive - a
WHF Policy Brief. Glob Heart. 2024;19(1):14. Published 2024 Jan 31. doi:10.5334/gh.1292
40 Shaikh SB, Newton C, Tung WC, Sun Y, Li D, Ossip D, et al. Classification, perception, and toxicity of emerging
flavored oral nicotine pouches. Int J Environ Res Public Health. 2023 Mar 3; 20(5): 4526.
DOI: https://doi.org/10.3390/ijerph20054526
41 Shaikh, S.B.; Tung, W.C.; Pang, C.; Lucas, J.; Li, D.; Rahman, I. Flavor Classification/Categorization and
Differential Toxicity of Oral Nicotine Pouches (ONPs) in Oral Gingival Epithelial Cells and Bronchial Epithelial
Cells. Toxics 2022, 10, 660.
42 Shukla, A.K.; Khaitan, T.; Gupta, P.; Naik, S.R. Smokeless Tobacco and Its Adverse Effects on Hematological
Parameters: A Cross-Sectional Study. Adv. Prev. Med. 2019, 2019, 3182946.
43 Chapman, F.; McDermott, S.; Rudd, K.; Taverner, V.; Stevenson, M.; Chaudhary, N.; Reichmann, K.; Thompson,
J.; Nahde, T.; O’Connell, G. A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic,
pharmacodynamic and safety and tolerability profiles of tobacco-free oral nicotine pouches relative to
cigarettes. Psychopharmacology 2022, 239, 2931–2943.
13
cholesterol levels (accelerated atherosclerosis), and insulin resistance (macrovascular
complications).44, 45, 46, 47, 48, 49, 50, 51, 52, 53
Of particular relevance, newer studies have found increases in cardiovascular disease
among users of snuff and have found associations between snuff and endothelial dysfunction,
decreases in diastolic heart function, and an elevated risk of fatal ischemic heart disease and
stroke.54, 55, 56, 57, 58, 59, 60
44 Benowitz NL. The role of nicotine in smoking-related cardiovascular disease. Prev Med. 1997; 26(4): 412–7.
45 Zhu BQ, Parmley WW. Hemodynamic and vascular effects of active and passive smoking. Am Heart J. 1995 Dec;
130(6): 1270–5. DOI: https://doi.org/10.1016/0002-8703(95)90154-X
46 Czernin J, Waldherr C. Cigarette smoking and coronary blood flow. Prog Cardiovasc Dis. 2003; 45(5): 395–404.
DOI: https://doi.org/10.1016/S0033-0620(03)80003-8
47 Messner B, Bernhard D. Smoking and cardiovascular disease: Mechanisms of endothelial dysfunction and early
atherogenesis. Arterioscler Thromb Vasc Biol. 2014 Mar; 34(3): 509–15.
DOI: https://doi.org/10.1161/ATVBAHA.113.300156
48 Rao ChS. The effect of chronic tobacco smoking and chewing on the lipid profile. J Clin Diagn Res;
2013. http://www.jcdr.net/article_fulltext.asp?issn=0973-
709x&year=2013&month=January&volume=7&issue=1&page=31-34&id=2663
49 Aune D, Schlesinger S, Norat T, Riboli E. Tobacco smoking and the risk of heart failure: A systematic review and
meta-analysis of prospective studies. Eur J Prev Cardiol. 2019 Feb; 26(3): 279–88.
DOI: https://doi.org/10.1177/2047487318806658
50 Chamberlain AM, Agarwal SK, Folsom AR, Duval S, Soliman EZ, Ambrose M, et al. Smoking and incidence of
atrial fibrillation: Results from the Atherosclerosis Risk in Communities (ARIC) study. Heart Rhythm. 2011 Aug;
8(8): 1160–6. DOI: https://doi.org/10.1016/j.hrthm.2011.03.038
51 D’Alessandro A, Boeckelmann I, Hammwhöner M, Goette A. Nicotine, cigarette smoking and cardiac arrhythmia:
An overview. Eur J Prev Cardiol. 2012 Jun; 19(3): 297–305. DOI: https://doi.org/10.1177/1741826711411738
52 Hom S, Chen L, Wang T, Ghebrehiwet B, Yin W, Rubenstein DA. Platelet activation, adhesion, inflammation,
and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine
concentrations. Platelets. 2016 Oct 2; 27(7): 694–702. DOI: https://doi.org/10.3109/09537104.2016.1158403
53 Ramirez JEM, Karim ZA, Alarabi AB, Hernandez KR, Taleb ZB, Rivera JO, et al. The JUUL e-cigarette elevates
the risk of thrombosis and potentiates platelet activation. J Cardiovasc Pharmacol Ther. 2020 Nov; 25(6): 578–86.
DOI: https://doi.org/10.1177/1074248420941681
54 Skaug EA, Nes B, Aspenes ST, Ellingsen Ø. Non-smoking tobacco affects endothelial function in healthy men in
one of the largest health studies ever performed: The Nord-Trøndelag Health Study in Norway; HUNT3. Schooling
CM (ed.), PLOS ONE. 2016 Aug 4; 11(8): e0160205. DOI: https://doi.org/10.1371/journal.pone.0160205
55 Janzon E, Hedblad B. Swedish snuff and incidence of cardiovascular disease. A population-based cohort
study. BMC Cardiovasc Disord. 2009 Dec; 9(1): 21. DOI: https://doi.org/10.1186/1471-2261-9-21
56 Titova OE, Baron JA, Michaëlsson K, Larsson SC. Swedish snuff (snus) and risk of cardiovascular disease and
mortality: Prospective cohort study of middle-aged and older individuals. BMC Med. 2021 Dec; 19(1): 111.
DOI: https://doi.org/10.1186/s12916-021-01979-6
57 Vidyasagaran AL, Siddiqi K, Kanaan M. Use of smokeless tobacco and risk of cardiovascular disease: A
systematic review and meta-analysis. Eur J Prev Cardiol. 2016 Dec; 23(18): 1970–81.
DOI: https://doi.org/10.1177/2047487316654026
58 Haglund B, Eliasson M, Stenbeck M, Rosen M. Is moist snuff use associated with excess risk of IHD or stroke? A
longitudinal follow-up of snuff users in Sweden. Scand J Public Health. 2007 Dec; 35(6): 618–22.
DOI: https://doi.org/10.1080/14034940701436949
59 Hajat C, Stein E, Ramstrom L, Shantikumar S, Polosa R. The health impact of smokeless tobacco products: A
systematic review. Harm Reduct J. 2021 Dec 4; 18(1): 123. DOI: https://doi.org/10.1186/s12954-021-00557-6
60 Hansson J, Galanti MR, Hergens MP, Fredlund P, Ahlbom A, Alfredsson L, et al. Snus (Swedish smokeless
tobacco) use and risk of stroke: Pooled analyses of incidence and survival. J Intern Med. 2014 Jul; 276(1): 87–95.
DOI: https://doi.org/10.1111/joim.12219
14
In December, 2025 the European Heart Journal published the first Expert Consensus paper
explicitly addressing nicotine itself as a cardiovascular toxin.61 The paper reviews how nicotine
impairs endothelial function through sympathetic activation, reactive oxygen species (ROS),
nitric oxide (NO) depletion, inflammatory signaling and BP increases. These effects are seen not
only in traditional cigarette smokers but also in users of e-cigarettes and nicotine pouches.
Nicotine increases arterial stiffness both acutely and chronically. Rodent studies demonstrate that
nicotine enhances myocardial fibrosis and hypertrophy, resulting in impaired systolic and
diastolic function. Nicotine also has powerful prothrombotic and proangiogenic effects that
stimulate endothelial cell proliferation and may contribute to plaque neovascularization and
instability as well as tumor growth.
62, 63Nicotine is toxic to developing fetuses and is a health danger for pregnant women.
Prenatal life to adolescence and into young adulthood is a sensitive period for brain plasticity,
and is an important period in terms of regulation of behavior and cognition. Preclinical and
clinical studies have shown the effect of nicotine on brain development including on maternal
smokeless tobacco use, which demonstrated that the nicotinic cholinergic receptors (nAChRs) in
the brain play critical maturational roles during adolescence.64, 65, 66 Nicotine is especially
dangerous for young people, and is highly addictive. Youth can start showing signs of nicotine
addiction quickly, even if they do not use tobacco product regularly or daily.67 Using nicotine
during adolescence can harm the parts of the brain that control attention, learning, mood,
67, 68, 69, 70depression, and impulse control, as well as lower academic performance and school-
61 Münzel T, Crea F, Rajagopalan S, Lüscher T. Nicotine and the cardiovascular system: unmasking a global public
health threat. Eur Heart J. 2025 Dec 18:ehaf1010. doi: 10.1093/eurheartj/ehaf1010. Epub ahead of print. PMID:
41406987.
62 U.S. Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A
Report of the Surgeon General. Centers for Disease Control and Prevention, U.S. Dept of Health and Human
Services; 2014.
63 U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and
Behavioral Basis for Smoking-attributable Disease. A Report of the Surgeon General. Centers for Disease Control
and Prevention, U.S. Dept of Health and Human Services; 2010.
64 Dani JA. Neuronal nicotinic acetylcholine receptor structure and function and response to nicotine.
In: International Review of Neurobiology. Elsevier; 2015. p. 3–19. DOI: https://doi.org/10.1016/bs.irn.2015.07.001
65 Castro EM, Lotfipour S, Leslie FM. Nicotine on the developing brain. Pharmacol Res. 2023 Apr; 190: 106716.
DOI: https://doi.org/10.1016/j.phrs.2023.106716
66 England LJ, Bunnell RE, Pechacek TF, Tong VT, McAfee TA. Nicotine and the developing human: A neglected
element in the electronic cigarette debate. Am J Prev Med. 2015 Aug; 49(2): 286–93.
DOI: https://doi.org/10.1016/j.amepre.2015.01.015
67 U.S. Department of Health and Human Services. E-Cigarette Use Among Youth and Young Adults. A Report of the
Surgeon General. Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2016.
68 Counotte DS, Goriounova NA, Li KW, Loos M, van der Schors RC, Schetters D, et al. Lasting synaptic changes
underlie attention deficits caused by nicotine exposure during adolescence. Nat Neurosci. 2011 Apr; 14(4): 417–9.
DOI: https://doi.org/10.1038/nn.2770
69 Iñiguez SD, Warren BL, Parise EM, Alcantara LF, Schuh B, Maffeo ML, et al. Nicotine exposure during
adolescence induces a depression-like state in adulthood. Neuropsychopharmacology. 2009 May; 34(6): 1609–24.
DOI: https://doi.org/10.1038/npp.2008.220
70 Yuan M, Cross SJ, Loughlin SE, Leslie FM. Nicotine and the adolescent brain. J Physiol. 2015;593(16):3397–
3412.
15
and substance-related risk behaviors.71, 72 Nicotine harms to brain development continues until
about age 25,67 and adolescents who use nicotine may be at increased risk for future addiction to
other drugs.70 (See attached comment on youth impacts, incorporated by reference.)
4. ZYN nicotine pouches are recreational products that have not been approved by
FDA for cessation or nicotine replacement therapy; however, marketing ZYN with the
proposed MRTP claims will likely be misunderstood by consumers to mean that ZYN
has been approved by FDA for cessation.
FDA announced73 in January 2025 that it had authorized the marketing of 20 ZYN nicotine
pouch products (10 flavors, each sold with 3 mg and 6 mg nicotine varieties) finding that the
products meet the “appropriate for the protection of public health” standard required for such
authorization. The FDA found that the products contained substantially lower amounts of
harmful constituents (HPHCs) than cigarettes and most smokeless tobacco products such as
moist snuff and snus, and therefore they pose lower risk of cancer and other serious health
conductions than those products. Further, FDA found that Swedish Match showed that these
nicotine pouch products have the potential to provide a benefit to adults who smoke cigarettes
and/or use other smokeless tobacco products that outweighs the risks of the products, including
to youth.
As discussed above, the fact that the products contain lower amounts of some HPHCs does
not demonstrate that the products are safe, as they expose users to other harmful constituents that
are not included on the outdated HPHC list. Moreover, as we discuss in a companion comment
on youth, attached and incorporated by reference, the applicants have not demonstrated that
authorizing the ZYN MRTP would “[b]enefit the health of the population as a whole taking into
account both users of tobacco products and persons who do not currently use tobacco
products,”74 as required by law.
As detailed in our companion comment on misinterpretation of MRTP claims, attached
and incorporated by reference, ZYN is being promoted, implicitly and explicitly, as useful for
helping smokers quit. Importantly, regardless of FDA’s PMTA marketing granted order,
Swedish Match has not demonstrated that ZYN nicotine pouches are safe and effective for use as
cessation products and did not apply for FDA approval (through CDER) as cessation drugs.
Unlike FDA-approved cessation products such as Transdermal nicotine patches, nicotine gums,
nicotine lozenges, nicotine sprays and inhalers, varenicline, and buproprion, ZYN nicotine
71 Chadi N, Li G, Hadland SE. Adverse school outcomes and risky sexual health behaviors among high school
students with e-cigarette and marijuana use. Subst Use Misuse. 2021 Mar 21; 56(4): 517–21.
DOI: https://doi.org/10.1080/10826084.2021.1883659
72 McCabe SE, West BT, Veliz P, Boyd CJ. E-cigarette use, cigarette smoking, dual use, and problem behaviors
among U.S. adolescents: Results from a national survey. J Adolesc Health. 2017 Aug; 61(2): 155–62.
DOI: https://doi.org/10.1016/j.jadohealth.2017.02.004
73 https://www.fda.gov/news-events/press-announcements/fda-authorizes-marketing-20-zyn-nicotine-pouch-
products-after-extensive-scientific-
review#:~:text=Today%2C%20the%20U.S.%20Food%20and,newly%20authorized%20nicotine%20pouch%20prod
ucts.
74 Family Smoking Prevention and Tobacco Control Act, section 911(g)(1), Public Law 111-31, 21 USC 387k (June
22, 2009).
16
pouches have not been shown to be safe and effective and have not been approved for
cessation.
CDC clearly stated on its website:75
• There are no safe tobacco products, including nicotine pouches. This is especially
true for youth, young adults, and women who are pregnant.
• Youth, young adults, and women who are pregnant should not use nicotine pouches.
• The FDA has not approved any nicotine pouches to help people quit smoking.
• Nicotine pouches are not an FDA-approved method for quitting smoking.”75
Conclusion:
FDA should not authorize the marketing of ZYN nicotine pouches with modified risk
claims. Swedish Match has failed to demonstrate that marketing ZYN nicotine pouches will
benefit the health of individuals or the health of the population as a whole.
Our comment provides detailed scientific evidence that:
1. The General Snus MRTP cannot be used to justify action on ZYN, which requires ZYN-
specific data.
2. The “Swedish experience” with snus is irrelevant and cannot be applied to ZYN.
3. Swedish Match failed to provide sufficient evidence or long-term safety data supporting
their claim that using ZYN nicotine pouches significantly reduces the risk of tobacco-
related disease
4. Swedish Match failed to demonstrate that smokers accurately understand health risks if
they “switch completely away from cigarettes,” nor have they demonstrated that users
understand what it means to “switch completely.”
5. Nicotine pouches carry oral health risks
6. Limited data on reduced biomarkers of exposure among ZYN users is hampered by
conflicts of interest and insufficient to justify modified risk claims.
7. Nicotine itself has substantial health harms, particularly for cardiovascular disease, that
have been ignored by Swedish Match.
8. FDA MRTP orders for ZYN are likely to be misinterpreted as authorization as a smoking
cessation product by consumers.
Taken together, Swedish Match has failed to meet its statutory burden to demonstrate
that the marketing of 20 ZYN nicotine pouches in ten flavors and two nicotine strengths with
MRTP claims will benefit the health of individuals and the health of the population as a
whole. Therefore, FDA should deny MRTP authorization for these products.
75 CDC, Smoking and Tobacco Use. Nicotine Pouches. January 31, 2025. Available:
https://www.cdc.gov/tobacco/nicotine-pouches/index.html
17
