Flavor ingredient regulatory record
2,3,5,6-Tetramethylpyrazine
2,3,5,6-Tetramethylpyrazine is a pyrazine in the nutty family, FEMA GRAS under FEMA number 3237 (CAS 1124-11-4). Its odor is nutty, roasted, cocoa, earthy, peanut.
- FEMA
- 3237
- CAS
- 1124-11-4
- JECFA
- 780
- EU FL
- 14.018
- Formula
- C8H12N2
- EC
- 214-391-2
GRAS status: FEMA GRAS, publication 4. Recorded by FDA in the Substances Added to Food inventory under CAS 1124-11-4.
Structure
Identity
Also known as: Pyrazine, 2,3,5,6-tetramethyl-, Pyrazine, tetramethyl-, Tetramethylpyrazine, BS factor, Ligustrazine, Tetrapyrazine, Chuanxingzine, Ligustrazin, NSC 36080, NSC 46451, tetramethylpyrazine, ligustrazine.
Can 2,3,5,6-Tetramethylpyrazine be labeled natural?
Nature makes 2,3,5,6-Tetramethylpyrazine, which is why the US label turns on process. A natural route gives natural flavor; synthesis gives artificial 2,3,5,6-Tetramethylpyrazine, same molecule. The EU and UK follow the same logic without a middle class; Mercosur and Mexico label synthetic 2,3,5,6-Tetramethylpyrazine 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
2,3,5,6-Tetramethylpyrazine is FEMA GRAS under FEMA number 3237. 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 14.018, Annex I Part A under Regulation (EC) 1334/2008, evaluation status approved (EFSA). The UK retains the same list.
JECFA (WHO / FAO)
JECFA number 780, evaluated at the 57th meeting in 2001. No safety concern 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. 2,3,5,6-Tetramethylpyrazine appears on the EPA Toxic Substances Control Act Chemical Substance Inventory under CAS 1124-11-4, where EPA names it Pyrazine, 2,3,5,6-tetramethyl-.
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: Nutty, roasted, cocoa, earthy, peanut.
Taste: Nutty, roasted, cocoa.
Where it is used
2,3,5,6-Tetramethylpyrazine is used in nut flavors, chocolate, coffee and roasted, typically as a nutty note.
Structurally similar flavor ingredients
Flavor ingredients with a GRAS determination closest to 2,3,5,6-Tetramethylpyrazine by structure. Whether one can replace it is a sensory and regulatory call; the reformulation tool works that through.
| Material | FEMA | Similarity | Occurrence |
|---|---|---|---|
| 6,7-Dihydro-2,3-dimethyl-5H-cyclopentapyrazine | 3917 | 79% | In nature |
| 2,3-Dimethylpyrazine | 3271 | 64% | In nature |
| 2,5-Dimethylpyrazine | 3272 | 63% | In nature |
| 2,5-Diethyl-3-methylpyrazine | 3915 | 63% | In nature |
| 2,3-Diethyl-5-methylpyrazine | 3336 | 60% | In nature |
More pyrazines in this index
2,5-Diethyl-3-methylpyrazine · 2-Ethylpyrazine · 2,3-Diethyl-5-methylpyrazine · 2-Acetyl-3-ethylpyrazine · 2,3-Dimethylpyrazine · 3-Acetylpyridine
2,3,5,6-Tetramethylpyrazine FAQ
Is 2,3,5,6-Tetramethylpyrazine FEMA GRAS?
Yes. The FEMA Expert Panel lists 2,3,5,6-Tetramethylpyrazine as GRAS under FEMA number 3237. The Code of Federal Regulations lists it at 21 CFR 172.515.
What are the FEMA and CAS numbers for 2,3,5,6-Tetramethylpyrazine?
2,3,5,6-Tetramethylpyrazine is FEMA 3237, CAS 1124-11-4. Its flavor category is nutty.
How is 2,3,5,6-Tetramethylpyrazine described, and where does it show up?
Flavorists describe 2,3,5,6-Tetramethylpyrazine as nutty, roasted, cocoa, earthy, peanut. On the palate it is nutty, roasted, cocoa. It is used in nut flavors, chocolate, coffee and roasted.
What did JECFA conclude about 2,3,5,6-Tetramethylpyrazine?
JECFA evaluated 2,3,5,6-Tetramethylpyrazine at the 57th meeting in 2001 under JECFA number 780. The panel concluded: No safety concern at current levels of intake when used as a flavouring agent.
Is 2,3,5,6-Tetramethylpyrazine on the EU Union List?
Yes. FL 14.018 is the Union List entry for 2,3,5,6-Tetramethylpyrazine, annex I Part A, under Regulation 1334/2008, and the UK keeps the same list.
Does 2,3,5,6-Tetramethylpyrazine count as natural in the US and the EU?
The process decides for 2,3,5,6-Tetramethylpyrazine. It occurs in nature, so a natural-source, natural-process material is natural flavor in the US and synthetic 2,3,5,6-Tetramethylpyrazine is artificial. The EU and UK follow the same logic without a middle class; Mercosur and Mexico label synthetic 2,3,5,6-Tetramethylpyrazine identical-to-natural.
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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 2,3,5,6-TETRAMETHYLPYRAZINE under CAS 1124-11-4 and carries its FEMA number, its JECFA flavor number. 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.