[Federal Register Volume 76, Number 156 (Friday, August 12, 2011)]
[Notices]
[Pages 50226-50230]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-20502]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-N-0271]
Harmful and Potentially Harmful Constituents in Tobacco Products
and Tobacco Smoke; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
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SUMMARY: The Food and Drug Administration (FDA) is requesting comments,
including scientific and other information, concerning the harmful and
potentially harmful constituents (HPHCs) in tobacco products and
tobacco smoke. This information will assist the Agency in establishing
a list of HPHCs in tobacco products and tobacco smoke (the HPHC list).
DATES: Submit either electronic or written comments by October 11,
2011.
ADDRESSES: Submit electronic comments to http://www.regulations.gov.
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Identify comments with the docket number found in
brackets in the heading of this document.
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. Background
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 Federal Food, Drug,
and Cosmetic Act (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 generally and to reduce tobacco
use by minors. 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.''
Section 904(e) of the FD&C Act also requires that FDA ``publish a
public notice requesting the submission by interested persons of
scientific and other information concerning the harmful and potentially
harmful constituents in tobacco products and tobacco smoke.''
The Agency has solicited scientific and other information from
interested persons and has developed a list of tobacco product
constituents it currently believes are harmful or potentially harmful
to health. Although the Agency's work to date reflects consideration of
substantial scientific and other information, we believe that
additional information from the public may be beneficial to the Agency
before it establishes the list described in section 904(e) of the FD&C
Act. We are therefore publishing the Agency's
[[Page 50227]]
current list as table 1 of this document and requesting public comment
as described in section II of this document. In this section of the
document, we are also providing information about the Agency's guidance
on HPHCs, the criteria that the Agency used to help develop the list,
and reasons the Agency might add or remove constituents.
On June 10, 2010, FDA announced the availability for public comment
of a draft guidance for industry and FDA staff entitled ``Harmful and
Potentially Harmful Constituents' in Tobacco Products as Used in
Section 904(e) of the Federal Food, Drug, and Cosmetic Act'' (75 FR
32952). FDA announced the availability of the final guidance on January
31, 2011 (76 FR 5387) (available at http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation) (HPHC final guidance). This
final 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, the Agency established a subcommittee of the
Tobacco Products Scientific Advisory Committee (TPSAC), \1\ the Tobacco
Product Constituents Subcommittee (the subcommittee), and charged the
subcommittee with making preliminary recommendations to TPSAC on 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, and at the June
meeting, presentations were made by interested persons.\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 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.
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 HPHC list. As a result of its discussions, TPSAC
recommended to the Agency the following criteria for selecting the 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.
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Constituents identified as known, likely, probably, or
possible human carcinogens by the U.S. Environmental Protection Agency
(EPA);
Constituents identified as known, probable, or possible
carcinogens by the International Agency for Research on Cancer (IARC)
including IARC Group 1 (carcinogenic to humans), IARC Group 2 (probably
carcinogenic to humans), and IARC Group 2B (possibly carcinogenic to
humans);
Constituents identified as human carcinogens or reasonably
anticipated to be human carcinogens by the National Toxicology Program
(NTP);
Constituents identified as potential occupational
carcinogens by the National Institute for Occupational Safety and
Health (NIOSH):
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 (CA EPA) 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).
FDA believes having criteria for use in determining whether a
constituent is harmful or potentially harmful will be beneficial. FDA
carefully evaluated the data, information, and views on HPHCs in
tobacco products provided by TPSAC and the public, in light of the
Agency's own knowledge and expertise, and taking into consideration its
HPHC final guidance. Based on this evaluation, FDA tentatively
concludes that it should use the criteria listed previously in this
document in determining whether a constituent should be included on the
HPHC list. Specifically, FDA has tentatively concluded that it should
consider a constituent meeting these criteria 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
[[Page 50228]]
not, in fact, harmful or potentially harmful. Applying this approach to
the criteria and the available information, FDA developed table 1 of
this document.
FDA recognizes that table 1 of this document may not include all
constituents that are ``harmful or potentially harmful.'' For example,
the criteria described previously in this document generally 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. Similarly, the criteria FDA
has tentatively 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 HPHC list, and whether individual constituents should
be added. Just as these types of new information may lead to additions
to the list, FDA recognizes 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. For these reasons, FDA will continue to review scientific
information about tobacco product constituents. FDA intends to do this
both before and after it establishes its list of HPHCs for the purpose
of section 904(e) of the FD&C Act, consistent with the directive in
section 904(e) that the Agency periodically revise the list as
appropriate.
II. Request for Comments and Information
FDA is soliciting public comment, including scientific and other
information, concerning the HPHCs in tobacco products and tobacco
smoke. We are particularly interested in comments from the public on
the following topics:
The criteria FDA should use in determining whether a
constituent is harmful or potentially harmful such that it should be
included on the HPHC list;
Whether any chemicals or chemical compounds not listed in
table 1 of this document should be added because they are harmful or
potentially harmful, including supporting scientific or other
information; and/or
Whether any of the chemicals or chemical compounds listed
in table 1 of this document should be removed because they are not
harmful or potentially harmful, including supporting scientific or
other information.
III. Submission of Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. It is no
longer necessary to send two copies of mailed comments. Identify
comments with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
Table 1--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 toxicant (CT),
Constituent 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
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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]acridine.............. CA, CT
Dibenz[a,j]acridine.............. CA
Dibenz[a,h]anthracene............ CA
Dibenzo[c,g]carbazole............ 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).
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 ).
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Uranium-235...................... CA, RT
Uranium-238...................... CA, RT
Vinyl acetate.................... CA, RT
Vinyl chloride................... CA
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Dated: August 9, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-20502 Filed 8-11-11; 8:45 am]
BILLING CODE 4160-01-P