Flavor ingredient regulatory record
Piperazine
Piperazine is a piperazine in the earthy family, FEMA GRAS under FEMA number 4250 (CAS 110-85-0). Its odor is earthy, musty, slightly sweet, chemical.
- FEMA
- 4250
- CAS
- 110-85-0
- JECFA
- 1615
- EU FL
- 14.141
- Formula
- C4H10N2
- EC
- 203-808-3
GRAS status: FEMA GRAS, publication 22. Recorded by FDA in the Substances Added to Food inventory under CAS 110-85-0.
Structure
Identity
Also known as: Antiren, 1,4-Diazacyclohexane, Diethylenediamine, Dispermine, Hexahydropyrazine, Lumbrical, Piperazidine, Pyrazine, hexahydro-, Pyrazine hexahydride, Pipersol, 1,4-Piperazine, Wurmirazin.
Can Piperazine be labeled natural?
Since piperazine is found in nature, US labeling follows how it was obtained: natural flavor from a natural source and a natural process, artificial when piperazine is synthesized. The EU and UK grant the natural claim only to that natural route; Mercosur and Mexico call synthetic material identical-to-natural.
- United States
- Natural or artificial, by process
- European Union and UK
- Natural only from natural material
- Mercosur and Mexico
- Natural or identical-to-natural
How each market defines the classes: natural vs artificial flavor under 21 CFR 101.22.
Regulatory status, with citations
United States
Piperazine is FEMA GRAS under FEMA number 4250. It is cited in the Code of Federal Regulations at 21 CFR 172.515.
European Union and United Kingdom
Listed on the Union List of flavouring substances as FL 14.141, Annex I Part A under Regulation (EC) 1334/2008, evaluation status approved (EFSA). The UK retains the same list.
JECFA (WHO / FAO)
JECFA number 1615, evaluated at the 65th meeting in 2005. No safety concern (conditional) at current levels of intake when used as a flavouring agent.
Other US flags
Not on the California Proposition 65 list.
TSCA Inventory status
A flavor ingredient is also an industrial chemical. Piperazine appears on the EPA Toxic Substances Control Act Chemical Substance Inventory under CAS 110-85-0, where EPA names it Piperazine.
Active in US commerce
EPA designates this substance active, so no Notice of Activity Form B is required before manufacturing. What active and inactive mean.
EPA publishes no regulatory flags on this listing. What the flags mean.
From the EPA non-confidential TSCA Inventory, July 2026 release. EPA also maintains a confidential portion it does not publish. Search the Inventory by CAS number.
Odor and taste
Odor: Earthy, musty, slightly sweet, chemical.
Taste: Bitter, slightly sweet, umami.
Where it is used
Piperazine is used in beverage, savory snacks and seasoning blends, typically as a earthy note.
Structurally similar flavor ingredients
Flavor ingredients with a GRAS determination closest to Piperazine by structure. Whether one can replace it is a sensory and regulatory call; the reformulation tool works that through.
| Material | FEMA | Similarity | Occurrence |
|---|---|---|---|
| Piperidine | 2908 | 94% | In nature |
| Pyrrolidine | 3523 | 87% | In nature |
| Pyrazine | 4015 | 82% | In nature |
| 2-Methylpiperidine | 4244 | 77% | In nature |
| 2-Pyridine | 2966 | 60% | In nature |
Piperazine FAQ
Is piperazine on the FEMA GRAS list?
It is. FEMA number 4250 covers piperazine. It is also codified at 21 CFR 172.515.
What is the FEMA number for piperazine?
The FEMA number for piperazine is 4250 and its CAS registry number is 110-85-0. FEMA files it in the earthy flavor category.
Is piperazine natural or artificial?
Piperazine occurs in nature, so the label depends on the route: piperazine won from a natural source by a physical, enzymatic or microbiological process is natural flavor in the United States, and synthesized piperazine is artificial. In the EU and UK the natural claim likewise needs the natural route, while Mercosur and Mexico keep a third class, identical-to-natural, for the synthetic material.
Is piperazine approved in the EU?
Piperazine is on the EU Union List of flavouring substances as FL 14.141 (Annex I Part A) under Regulation 1334/2008.
Has JECFA evaluated piperazine?
Yes. JECFA number 1615, evaluated at the 65th meeting in 2005. Conclusion: No safety concern (conditional) at current levels of intake when used as a flavouring agent.
What is piperazine used for?
Piperazine is described as earthy, musty, slightly sweet, chemical. On the palate it is bitter, slightly sweet, umami. It shows up in beverage, savory snacks and seasoning blends.
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Sources and attribution. The identity and regulatory facts on this page are taken from the FDA Substances Added to Food inventory, a US government record, which lists this substance as PIPERAZINE under CAS 110-85-0 and carries its FEMA number, its JECFA flavor number and its 21 CFR citations. The inventory is searchable at FDA. FDA records its technical effect as flavoring agent or adjuvant.
A FEMA GRAS conclusion is reached by the Expert Panel of the Flavor and Extract Manufacturers Association of the United States, and the FEMA number names that conclusion. FEMA publishes its own entry for this substance in the FEMA Flavor Library, which is the authoritative record of what the Panel decided and is worth reading alongside this page.
Ambrose Compliance is not affiliated with, endorsed by, or sponsored by FEMA. FEMA and FEMA GRAS are used here as identifiers for a published regulatory determination, not as marks of any relationship between FEMA and Ambrose.
About this page. Facts come from the FDA Substances Added to Food inventory, the Code of Federal Regulations, the EPA TSCA Inventory, the EU Union List, JECFA and the Ambrose database, with FEMA's published determination cited where it applies; parts of the text are written by Ambrose AI, which can make mistakes. Check the cited source before relying on anything here. This is not regulatory or legal advice.