By Timothy S. Donahue
Top Takeaways:
- Regulatory update: FDA adds 18 chemicals to HPHC list, bringing total to 111
- Industry signal: Expanded list sharpens focus for PMTA reviews, not a product ban
- Next step: Agency proposes three more additives—common in e-liquids—for public comment
The U.S. Food and Drug Administration has expanded its list of Harmful and Potentially Harmful Constituents (HPHCs), adding 18 chemicals to tobacco and nicotine products, a move that will directly shape future product reviews.
The update, published in the Federal Register, brings the total number of listed constituents to 111 and applies across product categories—including cigarettes, cigars, hookah tobacco, and e-cigarettes, as well as their smoke and aerosol. The list now includes propylene glycol and glycerol, a major ingredient in many e-liquids.
The HPHC list is a cornerstone of the FDA’s regulatory framework. It identifies chemicals “that cause or could cause harm to users or non-users of tobacco products,” serving as both a public-facing reference point and a technical roadmap for industry submissions, according to the agency.
“FDA’s updated HPHC list delivers transparency to the public and clarity for industry,” the agency said, noting that the list highlights substances with “extensive evidence of harm, or potential harm, to human health.”
The new additions include:
- Acetic Acid
- Acetoin (also known as 3-hydroxy-2-butanone)
- Acetyl Propionyl (also known as 2,3-pentanedione)
- Benzyl Acetate
- Butyraldehyde
- Diacetyl
- Diethylene Glycol
- Ethyl Acetate
- Ethylene Glycol
- Furfural
- Glycerol
- Glycidol
- Isoamyl Acetate
- Isobutyl Acetate
- Methyl Acetate
- n-Butanol
- Propionic Acid
- Propylene Glycol
For manufacturers, the implications are immediate but not prohibitive. The HPHC list does not ban ingredients. Instead, it informs the agency’s evaluation of premarket tobacco product applications (PMTAs) and, under the Federal Food, Drug, and Cosmetic Act, requires companies to report the presence and levels of listed constituents in their products.
In practical terms, the additions raise the bar for both data disclosure and risk assessment.
The 18 newly added constituents include a mix of flavoring agents, solvents, and byproducts commonly associated with both combustible and non-combustible products. Among them are diacetyl and acetyl propionyl—compounds long scrutinized for respiratory effects—as well as propylene glycol and glycerol, which are widely used in e-liquid formulations.
While the HPHC additions are not bans, nicotine product manufacturers that use them may face greater agency scrutiny. The list can also be used to deny products authorization as the agency doesn’t offer any acceptable limits, only that the ingredients may be used at some level.
Other additions include ethylene glycol, diethylene glycol, furfural, and glycidol, reflecting the agency’s broader effort to capture a wider range of potential toxicants across product types. The update follows a multi-year process.
The FDA first proposed expanding the list in 2019 and has now finalized the additions after reviewing public comments and additional scientific data. At the same time, the agency is signaling that the list is still evolving.
FDA is now proposing to add three more constituents—pulegone, furfuryl alcohol, and methyl eugenol—and is seeking public comment through May 26, 2026. These substances are commonly used as flavoring ingredients in e-liquids and may also appear in other tobacco products.
The agency is also refining how it determines which chemicals qualify for the list. The FDA confirmed it will include respiratory toxicants identified by the National Institute for Occupational Safety and Health as an additional criterion for HPHC designation, thereby expanding the scientific framework for future updates.
