[Federal Register Volume 77, Number 64 (Tuesday, April 3, 2012)]
[Notices]
[Pages 20034-20037]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-7727]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-N-0143]
Harmful and Potentially Harmful Constituents in Tobacco Products
and Tobacco Smoke; Established List
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; establishment of a list.
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SUMMARY: The Food and Drug Administration (FDA) is establishing a 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).
FOR FURTHER INFORMATION CONTACT: Carol Drew, Center for Tobacco
Products, Food and Drug Administration, 9200 Corporate Blvd.,
Rockville, MD 20850-3229, 877-287-1373.
SUPPLEMENTARY INFORMATION:
I. Introduction
On June 22, 2009, the President signed the Family Smoking
Prevention and Tobacco Control Act (Tobacco Control Act) (Pub. L. 111-
31) into law. The Tobacco Control Act amended the FD&C Act (21 U.S.C.
301 et seq.) by, among other things, adding a new chapter granting FDA
important new authority to regulate the manufacture, marketing, and
distribution of tobacco products to protect the public health. Section
904(e) of the FD&C Act (21 U.S.C. 387d(e)), as added by the Tobacco
Control Act, 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.''
The Agency has considered comments solicited from the public, as
well as scientific and other information, and has developed a list of
tobacco product constituents it currently believes are harmful or
potentially harmful to health. We are establishing this list as table 1
of this document as required by section 904(e) of the FD&C Act. In this
document, we are also providing information about related actions,
including the Agency's guidance discussing the meaning of HPHC, the
criteria the Agency used to help develop the established HPHC list, the
reasons the Agency may add or remove constituents from the established
HPHC list consistent with the directive of section 904(e), and the
addition of quantities to the list.
II. Background
On January 31, 2011, FDA announced the availability of a guidance
entitled `` `Harmful and Potentially Harmful Constituents' in Tobacco
Products as Used in Section 904(e) of the Federal Food, Drug, and
Cosmetic Act'' (76 FR 5387) (available at www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation) (HPHC final guidance). This
guidance represents the Agency's current thinking on the meaning of the
term ``harmful and potentially harmful constituent'' in the context of
implementing section 904(e) of the FD&C Act. It states: ``FDA believes
that the phrase `harmful and potentially harmful constituent' includes
any chemical or chemical compound in a tobacco product or in tobacco
smoke: (a) That is or potentially is inhaled, ingested, or absorbed
into the body; and (b) that causes or has the potential to cause direct
or indirect harm to users or non-users of tobacco products'' (HPHC
final guidance at page 2). The HPHC final guidance includes examples of
constituents that have the potential to cause direct harm and examples
of constituents that have the potential to cause indirect harm:
``Examples of constituents that have the `potential to cause direct
harm' to users or non-users of tobacco products include constituents
that are toxicants, carcinogens, and addictive chemicals and chemical
compounds. Examples of constituents that have the `potential to cause
indirect harm' to users or non-users of tobacco products include
constituents that may increase the exposure to the harmful effects of a
tobacco product constituent by: (1) Potentially facilitating initiation
of the use of tobacco products; (2) potentially impeding cessation of
the use of tobacco products; or (3) potentially increasing the
intensity of tobacco product use (e.g., frequency of use, amount
consumed, depth of inhalation). Another example of a constituent that
has the `potential to cause indirect harm' is a constituent that may
enhance the harmful effects of a tobacco product constituent'' (HPHC
final guidance at page 2).
On May 1, 2010, a subcommittee of the Tobacco Products Scientific
Advisory Committee (TPSAC),\1\ the Tobacco Product Constituents
Subcommittee (the subcommittee), was established and charged with
making preliminary recommendations to TPSAC on the HPHCs in tobacco
products and tobacco smoke. The subcommittee held public meetings on
June 8 and 9, 2010, and July 7, 2010. Prior to these meetings, FDA
solicited data, information, and/or views on HPHCs in tobacco products
and tobacco smoke from the public.\2\ At these meetings the
subcommittee:
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\1\ Information about TPSAC as well as information and
background materials on TPSAC meetings are available at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProductsScientificAdvisoryCommittee/default.htm.
\2\ See 75 FR 22147 (April 27, 2010) and 75 FR 33814 (June 15,
2010). Information submitted to the public docket for each of these
meetings is available at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProductsScientificAdvisoryCommittee/ucm222977.htm and http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProductsScientificAdvisoryCommittee/ucm222978.htm.
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Reviewed example lists of HPHCs in tobacco products and
tobacco smoke developed by other countries and organizations;
Identified criteria for selecting carcinogens, toxicants,
and addictive chemicals or chemical compounds in tobacco products and
tobacco smoke;
Identified chemicals or chemical compounds that met the
identified criteria;
Confirmed the existence of methods for measuring each
chemical or chemical compound identified; and
Identified other potentially important information or
criteria for measuring HPHCs in tobacco products or tobacco smoke, such
as smoking machine regimens to be used in measuring HPHCs.
[[Page 20035]]
The subcommittee made preliminary recommendations to TPSAC.
On August 30, 2010, TPSAC held a public meeting to deliberate on
the recommendations from the subcommittee. Prior to this meeting, FDA
published a notice in the Federal Register soliciting data,
information, and/or views from the public on the issues to be discussed
at this meeting.\3\ FDA asked what criteria TPSAC recommended the
Agency use for determining whether a constituent is a carcinogen,
toxicant, or addictive chemical or chemical compound that should be
included on the established HPHC list. As a result of its discussions,
TPSAC recommended to the Agency the following criteria for selecting
the established HPHC list:
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\3\ See 75 FR 47308 (August 5, 2010). Information submitted by
the public to the docket for this meeting is available at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProductsScientificAdvisoryCommittee/ucm232799.htm.
Constituents identified as known or probable human carcinogens
by either the International Agency for Research on Cancer (IARC), the
U.S. Environmental Protection Agency (EPA), or the National Toxicology
Program;
Constituents identified as possible human carcinogens by IARC
or EPA and/or identified by the National Institute for Occupational
Safety and Health as potential occupational carcinogens;
Constituents identified by EPA or the Agency for Toxic
Substances and Disease Registry (ATSDR) as having adverse respiratory
or cardiac effects;
Constituents identified by the California Environmental
Protection Agency as reproductive or developmental toxicants;
Constituents having, based upon a review of the peer-reviewed
literature, evidence of at least two of the following measures of abuse
liability (addiction):
[cir] Central nervous system activity;
[cir] Animal drug discrimination;
[cir] Conditioned place preference;
[cir] Animal self-administration;
[cir] Human self-administration;
[cir] Drug liking;
[cir] Signs of withdrawal; and
Constituents banned in food (for smokeless tobacco products).
On August 12, 2011, FDA published a notice in the Federal Register
(76 FR 50226) (the August 12 notice \4\) stating that the Agency had
tentatively concluded that it should consider a constituent meeting the
criteria listed in that document to be harmful or potentially harmful,
such that the constituent should be included on the HPHC list, unless
other scientific information obtained by or submitted to the Agency
shows that the constituent is not, in fact, harmful or potentially
harmful. The August 12 notice also included a list of constituents that
was developed by applying this approach to available information and
requested that interested persons submit scientific and other
information concerning the harmful and potentially harmful constituents
in tobacco products and tobacco smoke. The August 12 notice stated that
the Agency was particularly interested in comments on the following
issues: (1) The criteria FDA should use in determining whether a
constituent is harmful or potentially harmful such that it should be
included on the established HPHC list; (2) whether any chemicals or
chemical compounds not listed should be added because they are harmful
or potentially harmful, including supporting scientific or other
information; and/or (3) whether any chemicals or chemical compounds
should be removed because they are not harmful or potentially harmful,
including supporting scientific or other information.
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\4\ ``Harmful and Potentially Harmful Constituents in Tobacco
Products and Tobacco Smoke; Request for Comments,'' 76 FR 50226
(August 12, 2011).
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The Agency has considered all of the comments submitted to the
docket for the August 12 notice and has reviewed scientific and other
information submitted to support these comments. Based on the
information before it and its own knowledge and expertise, FDA
concludes that it should consider a constituent meeting the criteria
proposed in the August 12 notice to be harmful or potentially harmful,
such that it should be included on the HPHC list, unless other
scientific information obtained by or submitted to the Agency shows
that the constituent is not, in fact, harmful or potentially harmful.
Applying these criteria, and after consideration of comments and
supporting information submitted to the docket for the August 12
notice, FDA has developed the established list of harmful and
potentially harmful constituents in tobacco products and tobacco smoke
as table 1 of this document.
Three constituents included on the list we published for comment in
the August 12 notice are not included in table 1. Based on information
submitted to the docket and our review of the scientific literature, we
have determined not to include dibenz[a,h]acridine, dibenz[a,j]acridine
and 7H-dibenz[c,g]carbazole on the established HPHC list at this time
because there is not sufficient evidence that they are found in tobacco
products or tobacco smoke. This decision is based on information
presently before us, and 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.
We note that certain metals on the established HPHC list
(beryllium, cadmium, chromium, cobalt, lead, mercury, nickel, and
selenium) may exist in tobacco products and tobacco smoke in the
elemental form and/or in compounds. Both the elemental and compound
forms are harmful and/or potentially harmful under our criteria.
Identification of a metal on the established HPHC list therefore refers
to the metal regardless of whether it is found in its elemental form or
as a metal-bound compound. For example, beryllium includes both
elemental beryllium and beryllium found in beryllium compounds.
FDA recognizes that the established HPHC list may not include all
constituents that are ``harmful or potentially harmful.'' For example,
several of the criteria described in this document depend on a chemical
or chemical compound being both studied and listed by another entity,
such as constituents identified by EPA or ATSDR as having adverse
respiratory or cardiac effects. The fact that a constituent has not
been so identified by EPA or ATSDR could be because it has not been
adequately studied or has not yet been systematically reviewed by
relevant Agencies, rather than because the constituent does not have
adverse respiratory or cardiac effects. Moreover, FDA has only focused
on the five disease outcomes of cancer, cardiovascular disease,
respiratory effects, developmental or reproductive effects, and
addiction. FDA intends to review other disease outcomes to assess
whether additional chemicals or chemical compounds in tobacco products
or tobacco smoke are harmful or potentially harmful constituents that
contribute to the risk of other diseases.
In addition, the criteria FDA has selected are limited to those
that relate to carcinogens, toxicants, and addictive chemicals or
chemical compounds in tobacco products and tobacco smoke. We intend to
consider whether additional criteria should be selected to help
identify other classes of harmful or potentially harmful chemicals and
chemical compounds for inclusion on the established HPHC list, and
whether individual constituents should be added. Just as these types of
new information may lead to additions to the established HPHC list, FDA
recognizes
[[Page 20036]]
that it may become aware of new scientific information about
constituents of tobacco products that make it appropriate to remove one
or more of the constituents that appear on the list. Thus, FDA will
continue to review scientific information about tobacco product
constituents. For these reasons and consistent with the directive of
section 904(e) of the FD&C Act, FDA intends to periodically revise as
appropriate the established HPHC list.
Currently, the established HPHC list in table 1 does not contain
quantities of the HPHCs by brand and subbrand. Beginning June 22, 2012,
sections 904(a)(3) and 904(c)(1) of the FD&C Act require tobacco
product manufacturers and importers or their agents to submit a list of
constituents, including smoke constituents as applicable, identified by
FDA as harmful or potentially harmful to health in each of their
tobacco products, by brand and by quantity in each brand and subbrand.
Elsewhere in this issue of the Federal Register, FDA is publishing a
notice announcing the availability of a draft guidance for industry to
assist persons reporting to FDA the quantities of harmful and
potentially harmful constituents in tobacco products and tobacco smoke.
FDA intends to use the data and information submitted under sections
904(a)(3) and 904(c)(1) to, as directed by section 904(d)(1) of the
FD&C Act, place on public display the list of HPHCs established under
section 904(e), by brand and by quantity in each brand and subbrand, in
a format ``that is understandable and not misleading to a lay person.''
Table 1--Established List of the Chemicals and Chemical Compounds
Identified by FDA as Harmful and Potentially Harmful Constituents in
Tobacco Products and Tobacco Smoke
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Carcinogen (CA), respiratory
toxicant (RT), cardiovascular
Constituent toxicant (CT), reproductive or
developmental toxicant (RDT),
addictive (AD)
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Acetaldehyde..................... CA, RT, AD
Acetamide........................ CA
Acetone.......................... RT
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
A-[alpha]-C (2-Amino-9H- CA
pyrido[2,3-b]indole).
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
Beryllium........................ CA
1,3-Butadiene.................... CA, RT, RDT
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
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
2,6-Dimethylaniline.............. CA
Ethyl carbamate (urethane)....... CA, RDT
Ethylbenzene..................... CA
Ethylene oxide................... CA, RT, RDT
Formaldehyde..................... CA, RT
Furan............................ CA
Glu-P-1 (2-Amino-6- CA
methyldipyrido[1,2-a:3',2'-
d]imidazole).
[[Page 20037]]
Glu-P-2 (2-Aminodipyrido[1,2- CA
a:3',2'-d]imidazole).
Hydrazine........................ CA, RT
Hydrogen cyanide................. RT, CT
Indeno[1,2,3-cd]pyrene........... CA
IQ (2-Amino-3-methylimidazo[4,5- CA
f]quinoline).
Isoprene......................... CA
Lead............................. CA, CT, RDT
MeA-[alpha]-C (2-Amino-3-methyl)- CA
9H-pyrido[2,3-b]indole).
Mercury.......................... CA, RDT
Methyl ethyl ketone.............. RT
5-Methylchrysene................. CA
4-(Methylnitrosamino)-1-(3- CA
pyridyl)-1-butanone (NNK).
Naphthalene...................... CA, RT
Nickel........................... CA, RT
Nicotine......................... RDT, AD
Nitrobenzene..................... CA, RT, RDT
Nitromethane..................... CA
2-Nitropropane................... CA
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- CA
phenylimidazo[4,5-b]pyridine).
Polonium-210..................... CA
Propionaldehyde.................. RT, CT
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- CA
pyrido[4,3-b]indole).
Trp-P-2 (1-Methyl-3-amino-5H- CA
pyrido[4,3-b]indole ).
Uranium-235...................... CA, RT
Uranium-238...................... CA, RT
Vinyl acetate.................... CA, RT
Vinyl chloride................... CA
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Dated: March 23, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-7727 Filed 3-30-12; 11:15 am]
BILLING CODE 4160-01-P