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]

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]

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 ( printed 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]

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]

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.