Notice2026-07910

Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List Additions and Request for Comments

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Published
April 23, 2026

Issuing agencies

Health and Human Services DepartmentFood and Drug Administration

Abstract

The Food and Drug Administration (FDA, the Agency, or we) is adding constituents to the list of harmful and potentially harmful constituents (HPHCs) in tobacco products and tobacco smoke (the established HPHC list) as required by the Federal Food, Drug, and Cosmetic Act (the FD&C Act).

Full Text

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<title>Federal Register, Volume 91 Issue 78 (Thursday, April 23, 2026)</title>
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[Federal Register Volume 91, Number 78 (Thursday, April 23, 2026)]
[Notices]
[Pages 21824-21829]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-07910]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2026-N-2642]


Harmful and Potentially Harmful Constituents in Tobacco Products 
and Tobacco Smoke; Established List Additions and Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; established list additions and request for comments.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
adding constituents to the list of harmful and potentially harmful 
constituents (HPHCs) in tobacco products and tobacco smoke (the 
established HPHC list) as required by the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act).

DATES: Either electronic or written comments on the notice must be 
submitted by May 26, 2026.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until

[[Page 21825]]

11:59 p.m. Eastern Time at the end of May 26, 2026. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are received on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
    <bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
    <bullet> If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
    <bullet> Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    <bullet> For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2026-N-2642 for ``Harmful and Potentially Harmful Constituents in 
Tobacco Products and Tobacco Smoke; Established List Additions and 
Request for Comments.'' Received comments, those filed in a timely 
manner (see ADDRESSES), will be placed in the docket and, except for 
those submitted as ``Confidential Submissions,'' publicly viewable at 
<a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between 
9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
    <bullet> Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: Anna Julia Adams or Matthew Brenner, 
Center for Tobacco Products, Food and Drug Administration, Document 
Control Center, Bldg. 71, Rm. G335, 10903 New Hampshire Ave., Silver 
Spring, MD 20993-0002; 1-877-287-1373, <a href="/cdn-cgi/l/email-protection#db988f8b89bebcaeb7baafb2b4b5a89bbdbfbaf5b3b3a8f5bcb4ad"><span class="__cf_email__" data-cfemail="cd8e999d9fa8aab8a1acb9a4a2a3be8daba9ace3a5a5bee3aaa2bb">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Introduction

    The Family Smoking Prevention and Tobacco Control Act (Pub. L. 111-
31), enacted on June 22, 2009, amended the FD&C Act by, among other 
things, adding a new chapter (chapter IX) granting FDA the authority to 
regulate the manufacture, marketing, and distribution of tobacco 
products to protect the public health. Cigarettes, cigarette tobacco, 
roll-your-own (RYO) tobacco, and smokeless tobacco were immediately 
subject to chapter IX.
    For other types of tobacco products, the statute authorizes FDA to 
issue regulations ``deeming'' them to be subject to chapter IX. FDA 
published a final rule on May 10, 2016, deeming all products that meet 
the statutory definition of ``tobacco product'' set forth in section 
201(rr) of the FD&C Act (21 U.S.C. 321(rr)), including components and 
parts, but excluding accessories of deemed products, to be subject to 
chapter IX of the FD&C Act.\1\
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    \1\ See ``Deeming Tobacco Products To Be Subject to the Federal 
Food, Drug, and Cosmetic Act, as Amended by the Family Smoking 
Prevention and Tobacco Control Act,'' 81 FR 28974 (May 10, 2016), 
codified at 21 CFR part 1100. On August 9, 2023, the U.S. District 
Court for the District of Columbia issued an order vacating FDA's 
rule deeming tobacco products to be subject to FDA's tobacco product 
authorities ``insofar as it applies to premium cigars.'' Cigar Ass'n 
of Am. v. FDA, No. 16-cv-01460, 2023 WL 5094869, at *6 (D.D.C. Aug. 
9, 2023), affirmed in part, reversed in part, and remanded, 132 
F.4th 535 (D.C. Cir. 2025).
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    Section 904(e) of the FD&C Act (21 U.S.C. 387d(e)) requires FDA to 
establish, and periodically revise as appropriate, ``a list of harmful 
and potentially harmful constituents, including smoke constituents, to 
health in each tobacco product by brand and by quantity in each brand 
and subbrand.''
    In 2011, FDA provided guidance that discussed the meaning of 
``harmful and potentially harmful constituent'' in the context of the 
HPHC list requirement (76 FR 5387, January 31, 2011).\2\ In 2012, after 
considering comments solicited from the public, as well as scientific 
and other information, FDA developed a list of 93 constituents in 
tobacco products and tobacco smoke that are believed to be harmful or 
potentially harmful to health (the HPHC established list).\3\
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    \2\ FDA revised the 2011 Guidance that discusses the meaning of 
HPHC in the context of the HPHC list requirement in August 2016. 
``Harmful and Potentially Harmful Constituents'' in Tobacco Products 
as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic 
Act available at <a href="https://www.fda.gov/media/80109/download">https://www.fda.gov/media/80109/download</a>.
    \3\ ``Harmful and Potentially Harmful Constituents in Tobacco 
Products and Tobacco Smoke; Established List,'' 77 FR 20034 (April 
3, 2012).
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    In August 2016, FDA extended its authority under the Deeming Rule 
to all products, including components and parts (but excluding 
accessories of deemed products) that met the statutory definition of 
tobacco product, including electronic nicotine delivery systems (ENDS). 
Therefore, consistent with section 904(e) of the FD&C Act, the Agency 
considered revising the HPHC established list to reflect the current 
range of tobacco products now subject to the Agency's tobacco product

[[Page 21826]]

authorities as well as the Agency's growing scientific expertise with 
respect to all tobacco products. In 2019, the Agency requested comments 
on whether 19 additional constituents should be added to the HPHC 
established list. The Agency has considered comments solicited from the 
public, as well as scientific and other information, and has added 
tobacco product constituents to the established HPHC list that FDA 
currently believes are harmful or potentially harmful to health based 
on scientific evidence. FDA is adding 18 new constituents to the 
established list consistent with the requirement in section 904(e) of 
the FD&C Act to periodically revise, as appropriate, the established 
HPHC list (Table 1). In this document, we are also finalizing the 
addition of a new criterion for whether a constituent should be added 
to the list and seeking comments on the proposed addition of three new 
constituents to the list.

II. Background

    FDA first established the HPHC list on April 3, 2012 (77 FR 20034) 
(the April 2012 notice).\4\ The list currently contains 93 HPHCs. The 
April 2012 notice describes the history of the HPHC established list, 
and for additional background, we refer readers to that notice and the 
notice FDA published in the Federal Register on August 12, 2011 (76 FR 
50226) (the August 2011 notice), in which we solicited public comment, 
including scientific and other information, concerning the HPHCs in 
tobacco products and tobacco smoke, such as constituents that should be 
included on the HPHC established list, and the criteria used in 
determining whether a constituent is harmful or potentially harmful 
such that it should be included on the HPHC list.\5\
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    \4\ ``Harmful and Potentially Harmful Constituents in Tobacco 
Products and Tobacco Smoke; Established List,'' 77 FR 20034 (April 
3, 2012).
    \5\ ``Harmful and Potentially Harmful Constituents in Tobacco 
Products and Tobacco Smoke; Request for Comments,'' 76 FR 50226 
(August 12, 2011).
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    Further, on August 5, 2019 (84 FR 38032) (the August 2019 notice), 
FDA published a request for comments on 19 additional constituents 
proposed to be added to the established list to reflect the current 
range of tobacco products subject to the Agency's tobacco product 
authorities as well as the Agency's growing scientific expertise with 
respect to all tobacco products. The August 2019 notice mentions FDA's 
application of existing criteria to deemed tobacco products to propose 
the addition of glycidol and ethylene glycol. Glycidol is a thermal 
byproduct of glycerol and a common component in e-liquids. Ethylene 
glycol, which has also been identified in e-liquids, adversely affects 
reproduction and development. The notice also stated that FDA would 
tentatively apply one additional criterion regarding whether a 
constituent should be included on the HPHC list: constituents 
identified by the National Institute for Occupational Safety and Health 
(NIOSH) as having adverse respiratory effects. The notice also proposed 
diethylene glycol (DEG) be added to the list due to it being a 
potential contaminant in either glycerol or propylene glycol. If 
ingested, DEG can cause kidney failure, neurological damage, and death.
    When determining whether a constituent should be included on the 
established HPHC list, FDA considers whether there is evidence that the 
constituent meets established criteria, such as determinations from 
third-party scientific and public health organizations like NIOSH, the 
Environmental Protection Agency (EPA) or the Agency for Toxic 
Substances and Disease Registry (ATSDR). As part of the Centers for 
Disease Control and Prevention, NIOSH is the Federal agency responsible 
for conducting research and making science-based recommendations to 
prevent work-related illness and injuries, including those related to 
human health hazards and respiratory disease from inhalation exposures 
to toxicants. FDA has now finalized its previously tentative conclusion 
that constituents identified by NIOSH as respiratory toxicants will be 
an additional criterion that will be applied for determining whether a 
constituent should be included on the HPHC established list. The 
previously established criteria for determining whether a constituent 
should be included on the established HPHC list includes constituents 
identified by the EPA or ATSDR as having adverse respiratory or cardiac 
effects. Considering information from NIOSH in this regard is 
consistent with FDA's current practice of looking to other recognized, 
government experts such as EPA or ATSDR for their ability to identify 
constituents as having adverse respiratory or cardiac effects. As 
indicated by the original criteria (the April 2012 notice), FDA has 
previously considered this information from NIOSH when determining 
whether a constituent is harmful or potentially harmful by including 
constituents identified by NIOSH as a potential occupational carcinogen 
as a current criterion.
    After review and consideration of the relevant comments received 
from the August 2019 notice, FDA is adding 18 of the 19 proposed 
constituents to the HPHC list. Although FDA proposed that ethyl 
acetoacetate be added to the list, based on it having been tentatively 
identified as a respiratory toxicant, FDA has determined that there is 
insufficient information to warrant its inclusion on the list at this 
time. FDA's determination is based on the fact that ethyl acetoacetate 
does not meet any of the criteria for adding constituents to the HPHC 
list, including that NIOSH has not identified it as having adverse 
respiratory effects. This determination may be revised, consistent with 
the directive in section 904(e) of the FD&C Act that FDA periodically 
revise the established list as appropriate. The list of the 
constituents added to the established HPHC list is in Table 1.\6\
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    \6\ See Appendix A for complete HPHC established list.

  Table 1--List of the Additional Chemicals and Chemical Compounds Identified by FDA as Harmful and Potentially
                           Harmful Constituents in Tobacco Products and Tobacco Smoke
----------------------------------------------------------------------------------------------------------------
                                                  Carcinogen (CA), respiratory toxicant (RT), reproductive or
                 Constituent                         developmental toxicant (RDT), poisonous chemical (PC)
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Acetic Acid.................................  RT
Acetoin (also known as 3-hydroxy-2-butanone)  RT
Acetyl Propionyl (also known as 2,3-          RT
 pentanedione).
Benzyl Acetate..............................  RT
Butyraldehyde...............................  RT
Diacetyl....................................  RT
Diethylene Glycol...........................  PC

[[Page 21827]]

 
Ethyl Acetate...............................  RT
Ethylene Glycol.............................  RT, RDT
Furfural....................................  RT
Glycerol....................................  RT
Glycidol....................................  CA
Isoamyl Acetate.............................  RT
Isobutyl Acetate............................  RT
Methyl Acetate..............................  RT
n-Butanol...................................  RT
Propionic Acid..............................  RT
Propylene Glycol............................  RT
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III. Request for Comments and Information

    Based on the August 2019 notice, FDA received several comments that 
suggested adding constituents to the established HPHC list beyond those 
proposed in the notice. FDA has statutory authority under section 
904(e) of the FD&C Act and intends to continue to revise the 
established HPHC list as additional criteria are defined and additional 
scientific information becomes available. As a result of comments to 
the August 2019 notice, FDA is proposing to add three additional 
constituents to the established list and requests comments on the three 
proposed additions: pulegone, furfuryl alcohol, and methyl eugenol. 
These constituents are often added to e-liquid formulations as flavors, 
but may also be present in other tobacco products, such as cigarettes 
and smokeless tobacco. FDA has tentatively concluded that these three 
constituents meet the criteria used in determining whether a 
constituent is harmful or potentially harmful and should be included on 
the HPHC established list, unless other scientific information obtained 
by or submitted to the Agency shows that the constituent is not, in 
fact, harmful or potentially harmful.

IV. Identification of HPHCs Is an Ongoing Effort

    FDA continues to review relevant science to determine whether to 
add additional constituents to the list. That a constituent has not 
been so identified by FDA or other entities could be because it does 
not currently meet established criteria, it has not been adequately 
studied, or it has not yet been systematically reviewed. Consistent 
with the obligations under section 904(e) of the FD&C Act, FDA intends 
to continue: (1) our efforts to review other disease outcomes to assess 
whether additional chemicals or chemical compounds in tobacco products 
or tobacco smoke, including chemicals or chemical compounds in the 
emissions from the range of tobacco products now deemed to be subject 
to chapter IX of the FD&C Act, are harmful or potentially harmful 
constituents that contribute to the risk of other diseases; (2) our 
consideration of whether additional or different criteria should be 
selected to help identify other classes of harmful or potentially 
harmful chemicals and chemical compounds for inclusion on the HPHC 
established list and whether individual constituents should be added; 
and (3) our efforts to review new information to determine if it would 
be appropriate to remove one or more of the constituents that appear on 
the HPHC established list, or to add additional constituents to the 
list.

      Appendix A--Established List of the Chemicals and Chemical Compounds Identified by FDA as Harmful and
                     Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke
----------------------------------------------------------------------------------------------------------------
                                                  Carcinogen (CA), respiratory toxicant (RT), cardiovascular
                                                 toxicant (CT), reproductive or developmental toxicant (RDT),
                 Constituent                      addictive (AD), poisonous chemical (PC), banned in food (in
                                                                  smokeless tobacco products)
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Acetaldehyde................................  CA, RT, AD
Acetamide...................................  CA
Acetic Acid.................................  RT
Acetoin (also known as 3-hydroxy-2-butanone)  RT
Acetone.....................................  RT
Acetyl Propionyl (also known as 2,3-          RT
 pentanedione).
Acrolein....................................  RT, CT
Acrylamide..................................  CA
Acrylonitrile...............................  CA, RT
Aflatoxin B1................................  CA
4-Aminobiphenyl.............................  CA
1-Aminonaphthalene..........................  CA
2-Aminonaphthalene..........................  CA
Ammonia.....................................  RT
Anabasine...................................  AD
o-Anisidine.................................  CA
Arsenic.....................................  CA, CT, RDT

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A-[alpha]-C (2-Amino-9H-pyrido[2,3-b]indole)  CA
Benz[a]anthracene...........................  CA, CT
Benz[j]aceanthrylene........................  CA
Benzene.....................................  CA, CT, RDT
Benzo[b]fluoranthene........................  CA, CT
Benzo[k]fluoranthene........................  CA, CT
Benzo[b]furan...............................  CA
Benzo[a]pyrene..............................  CA
Benzo[c]phenanthrene........................  CA
Benzyl Acetate..............................  RT
Beryllium...................................  CA
1,3-Butadiene...............................  CA, RT, RDT
Butyraldehyde...............................  RT
Cadmium.....................................  CA, RT, RDT
Caffeic acid................................  CA
Carbon monoxide.............................  RDT
Catechol....................................  CA
Chlorinated dioxins/furans..................  CA, RDT
Chromium....................................  CA, RT, RDT
Chrysene....................................  CA, CT
Cobalt......................................  CA, CT
Coumarin....................................  Banned in food
Cresols (o-, m-, and p-cresol)..............  CA, RT
Crotonaldehyde..............................  CA
Cyclopenta[c,d]pyrene.......................  CA
Diacetyl....................................  RT
Dibenz[a,h]anthracene.......................  CA
Dibenzo[a,e]pyrene..........................  CA
Dibenzo[a,h]pyrene..........................  CA
Dibenzo[a,i]pyrene..........................  CA
Dibenzo[a,l]pyrene..........................  CA
Diethylene Glycol...........................  PC
2,6-Dimethylaniline.........................  CA
Ethyl Acetate...............................  RT
Ethyl carbamate (urethane)..................  CA, RDT
Ethylbenzene................................  CA
Ethylene Glycol.............................  RT, RDT
Ethylene oxide..............................  CA, RT, RDT
Formaldehyde................................  CA, RT
Furan.......................................  CA
Furfural....................................  RT
Glu-P-1 (2-Amino-6-methyldipyrido[1,2-        CA
 a:3',2'-d]imidazole).
Glu-P-2 (2-Aminodipyrido[1,2-a:3',2'-         CA
 d]imidazole).
Glycerol....................................  RT
Glycidol....................................  CA
Hydrazine...................................  CA, RT
Hydrogen cyanide............................  RT, CT
Indeno[1,2,3-cd]pyrene......................  CA
IQ (2-Amino-3-methylimidazo[4,5-f]quinoline)  CA
Isoamyl Acetate.............................  RT
Isobutyl Acetate............................  RT
Isoprene....................................  CA
Lead........................................  CA, CT, RDT
MeA-[alpha]-C (2-Amino-3-methyl)-9H-          CA
 pyrido[2,3-b]indole).
Mercury.....................................  CA, RDT
Methyl Acetate..............................  RT
Methyl Ethyl Ketone.........................  RT
5-Methylchrysene............................  CA
4-(Methylnitrosamino)-1-(3-pyridyl)-1-        CA
 butanone (NNK).
Naphthalene.................................  CA, RT
n-Butanol...................................  RT
Nickel......................................  CA, RT
Nicotine....................................  RDT, AD
Nitrobenzene................................  CA, RT, RDT
Nitromethane................................  CA
2-Nitropropane..............................  CA

[[Page 21829]]

 
N-Nitrosodiethanolamine (NDELA).............  CA
N-Nitrosodiethylamine.......................  CA
N-Nitrosodimethylamine (NDMA)...............  CA
N-Nitrosomethylethylamine...................  CA
N-Nitrosomorpholine (NMOR)..................  CA
N-Nitrosonornicotine (NNN)..................  CA
N-Nitrosopiperidine (NPIP)..................  CA
N-Nitrosopyrrolidine (NPYR).................  CA
N-Nitrososarcosine (NSAR)...................  CA
Nornicotine.................................  AD
Phenol......................................  RT, CT
PhIP (2-Amino-1-methyl-6-phenylimidazo[4,5-   CA
 b]pyridine).
Polonium-210................................  CA
Propionic Acid..............................  RT
Propionaldehyde.............................  RT, CT
Propylene Glycol............................  RT
Propylene oxide.............................  CA, RT
Quinoline...................................  CA
Selenium....................................  RT
Styrene.....................................  CA
o-Toluidine.................................  CA
Toluene.....................................  RT, RDT
Trp-P-1 (3-Amino-1,4-dimethyl-5H-pyrido[4,3-  CA
 b]indole).
Trp-P-2 (1-Methyl-3-amino-5H-pyrido[4,3-      CA
 b]indole ).
Uranium-235.................................  CA, RT
Uranium-238.................................  CA, RT
Vinyl acetate...............................  CA, RT
Vinyl chloride..............................  CA
----------------------------------------------------------------------------------------------------------------


Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-07910 Filed 4-22-26; 8:45 am]
BILLING CODE 4164-01-P


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