21 CFR 172.515: Synthetic Flavoring Substances

By Ambrose Compliance · September 12, 2026 · 5 min read

Checked against the eCFR text of 21 CFR 172.515 and 21 CFR 182.60; Federal Register 83 FR 50490 and 83 FR 50503; the FEMA Flavor Ingredient Library, on 12 September 2026.

Section 172.515 lists more than 700 synthetic flavoring substances FDA approved as food additives. FDA removed six in 2018, and FEMA still lists five of them.

TL;DR

21 CFR 172.515 lists the synthetic flavoring substances FDA has approved as food additives. Paragraph (b) names more than 700 of them.
Paragraph (a) holds every one of them to the minimum quantity required for the intended effect, under good manufacturing practice. No numeric ceiling is given.
21 CFR 182.60 carries the same title but lists 21 substances that are generally recognized as safe, so they need no premarket approval.
FDA removed benzophenone, ethyl acrylate, eugenyl methyl ether, myrcene, pulegone and pyridine on October 9, 2018. The Delaney Clause forced the removal even though FDA found no public health risk under intended use.
FEMA still lists five of those six. Its library footnotes each one to say the synthetic version cannot be added to US food after October 9, 2020.

21 CFR 172.515 is the section of the US food additive regulations that lists synthetic flavoring substances and adjuvants approved for direct addition to food. Paragraph (b) names more than 700 of them in alphabetical order, from acetal through zingerone.

A synthetic flavoring substance reaches food in the United States along one of three routes. It is generally recognized as safe, it was sanctioned for the use before the 1958 Food Additives Amendment, or FDA has approved it as a food additive. Section 172.515 is the list for that third route.

The four paragraphs

The section runs to four paragraphs, and only one of them is the list.

Paragraph (a) sets the usage limit for everything below it. Synthetic flavoring substances are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice. No numeric ceiling appears here. The limit is functional, so a formulator has to be able to defend a level as the amount the flavor actually needs.

Paragraph (b) is the list. It also states how the listed substances may be combined: alone, or with flavoring substances and adjuvants that are generally recognized as safe in food, prior sanctioned for such use, or regulated by an appropriate section of Part 172. A formula is not confined to this one list.

Paragraph (c) is a single carve-out for oleomargarine. Delta-decalactone and delta-dodecalactone, used separately or in combination in oleomargarine, are held to 10 parts per million and 20 parts per million respectively, in accordance with 21 CFR 166.110.

Paragraph (d) covers an antioxidant rather than a flavor. BHA may be used as an antioxidant in flavoring substances provided it does not exceed 0.5 percent of the essential, meaning volatile, oil content of the flavoring substance.

21 CFR 182.60 is also titled "Synthetic flavoring substances and adjuvants". It is a different list under a different legal test, and it is short. It names 21 substances, among them acetaldehyde, benzaldehyde, cinnamaldehyde, ethyl butyrate, limonene, linalool and vanillin.

Those 21 are generally recognized as safe, so they need no premarket approval. The substances in 172.515 are food additives, which do. Reading either section on its own gives a partial answer about whether a synthetic flavoring substance may be used.

	21 CFR 182.60	21 CFR 172.515
Legal status	Generally recognized as safe	Approved food additive
Premarket approval	Not required	Required
Entries	21	More than 700

What FDA removed in 2018, and why

On October 9, 2018 FDA amended 172.515 to stop authorizing six synthetic flavoring substances: benzophenone, ethyl acrylate, eugenyl methyl ether, myrcene, pulegone and pyridine. The agency was partially granting a food additive petition filed by the Breast Cancer Fund, now the Breast Cancer Prevention Partners, together with the Center for Environmental Health, the Center for Food Safety, the Center for Science in the Public Interest, Consumers Union, the Environmental Defense Fund, the Environmental Working Group, Improving Kids' Environment, the Natural Resources Defense Council, WE ACT for Environmental Justice, and James Huff. Styrene came off the same day under a separate rule, because that use had been permanently and completely abandoned.

FDA's reasoning is worth reading in the agency's own words, because it is not what most summaries report. FDA stated that its scientific analysis found these substances do not pose a risk to public health under the conditions of their intended use. The petitioners then supplied data showing the additives induce cancer in laboratory animals. Section 409(c)(3)(A) of the Federal Food, Drug, and Cosmetic Act, known as the Delaney Clause, bars FDA from approving any food additive found to induce cancer in people or animals. The agency concluded that it could not as a matter of law maintain the listings.

The Delaney Clause arrived with the Food Additives Amendment of 1958 and leaves no room for a risk threshold. The DC Circuit called it extraordinarily rigid in Public Citizen v. Young, rejecting an argument that a color additive posing no more than a de minimis cancer risk should therefore be approved.

FEMA still lists five of the six

Removal from 172.515 did not remove these substances from the FEMA Flavor Ingredient Library. Benzophenone (FEMA 2134), ethyl acrylate (FEMA 2418), myrcene (FEMA 2762), pulegone (FEMA 2963) and pyridine (FEMA 2966) are all still current FEMA GRAS entries. Each one carries the same footnote in FEMA's library, stating that the synthetic version of the substance is not permitted for addition to food in the United States after October 9, 2020.

Two things follow from that footnote. The compliance date was October 9, 2020, two years after the rule took effect. And the restriction is written against the synthetic version specifically, which is why the entries remain rather than being withdrawn.

Eugenyl methyl ether is the exception among the six. It no longer appears in FEMA's current library at all.

These five entries are the clearest demonstration that a FEMA number is not an FDA approval. Anyone checking US status from the FEMA library alone would see a current GRAS entry and miss a prohibition that has been in force since 2020.

Checking a substance against both lists

Ingredient lookup

Check an ingredient

Search the corpus by name, CAS number, or Flavor and Extract Manufacturers Association (FEMA) number. Every result shows FEMA GRAS status, flavor category, and whether the ingredient is natural. No account needed.

Start typing to search the ingredient corpus.

Try vanillin, limonene, ethyl butyrate or benzaldehyde. Or open the full ingredient lookup.

Ambrose publishes a reference page for every current FEMA GRAS substance, each one showing US, EU and JECFA status together. The five substances above are at benzophenone, ethyl acrylate, myrcene, pulegone and pyridine. The broader picture of how the FEMA panel reaches a conclusion is in what FEMA GRAS means, and the labeling rules that decide what a package may call a flavor sit in 21 CFR 101.22.

Sources

21 CFR 172.515, Synthetic flavoring substances and adjuvants, eCFR
21 CFR 182.60, Synthetic flavoring substances and adjuvants, eCFR
Food Additive Regulations; Synthetic Flavoring Agents and Adjuvants, 83 FR 50490, October 9, 2018
Food Additives Permitted for Direct Addition to Food for Human Consumption; Styrene, 83 FR 50503, October 9, 2018
21 CFR 166.110, Oleomargarine, eCFR
FEMA Flavor Ingredient Library

Frequently Asked Questions

What is 21 CFR 172.515?

It is the section of the US food additive regulations that lists synthetic flavoring substances and adjuvants approved for direct addition to food. A synthetic flavoring substance that is neither generally recognized as safe nor prior sanctioned has to be approved and listed before it can go into food sold in the United States.

How many substances does 21 CFR 172.515 list?

Paragraph (b) names more than 700 substances in alphabetical order, running from acetal through zingerone. The list changes whenever FDA amends the regulation.

What is the difference between 21 CFR 172.515 and 21 CFR 182.60?

Both carry the title Synthetic flavoring substances and adjuvants, and they sit on opposite sides of the food additive definition. Section 182.60 lists 21 synthetic flavoring substances that are generally recognized as safe, so they require no premarket approval. Section 172.515 lists the substances FDA has approved as food additives, which do require it.

Which flavoring substances did FDA remove from 21 CFR 172.515?

On October 9, 2018 FDA removed benzophenone, ethyl acrylate, eugenyl methyl ether, myrcene, pulegone and pyridine. Styrene came off the same day under a separate rule, because that use had been permanently and completely abandoned.

Why did FDA remove substances it said were not a health risk?

The Delaney Clause, section 409(c)(3)(A) of the Federal Food, Drug, and Cosmetic Act, bars FDA from approving a food additive found to induce cancer in people or animals. FDA stated that the six substances did not pose a risk to public health under the conditions of their intended use, and that the animal data the petitioners supplied left the agency no legal room to keep the listings.

Can the synthetic version of myrcene still be used in US food?

No. The FEMA Flavor Ingredient Library footnotes myrcene, FEMA 2762, to state that the synthetic version of the substance is not permitted for addition to food in the United States after October 9, 2020. Benzophenone, ethyl acrylate, pulegone and pyridine carry the same footnote.

Is a FEMA GRAS number enough to use a synthetic flavoring substance in the United States?

No. A FEMA GRAS conclusion is reached by the FEMA Expert Panel, an independent body, and it is not an FDA approval. Five substances FDA removed from 172.515 in 2018 remain current entries in FEMA's library, each carrying a footnote that the synthetic version cannot be added to US food. Checking the FDA regulations alongside the FEMA entry is the only way to get the whole answer.

Ambrose Compliance LLC

Ambrose builds regulatory intelligence for flavor and fragrance development. These guides are written from primary sources, the eCFR and the Federal Register among them, and from Ambrose's own corpus of every current FEMA GRAS substance. Where a claim comes from that corpus, the piece says so.

Founded and led by Will Pemble. Corrections are welcome at [email protected].

#21 CFR #FDA #food additives #flavor regulation #FEMA GRAS

Last updated September 13, 2026