U.S. Food and Drug Administration (FDA) Moves on Self-Affirmed Generally Recognized as Safe (GRAS) and Chemical Reviews (2025)

Table of Contents

1. 1. What U.S. Department of Health and Human Services and the U.S. Food and Drug Administration Did
2. 2. Key Terms: Generally Recognized as Safe, Self-Affirmation and Post-Market Review
3. 3. March 10, 2025: The Self-Affirmed Generally Recognized as Safe Directive
4. 4. How Generally Recognized as Safe Notification Became Voluntary
5. 5. May 15, 2025: A Systematic Post-Market Review Program
6. 6. June 18, 2025: The Proposed Ranking Method
7. 7. August 19, 2025: The Updated List of Chemicals Under Review
8. 8. What Officials Said
9. 9. What These Steps Do Not Do
10. 10. Dates and Legal Status (as of October 11, 2026)
11. 11. How the Steps Fit Earlier and Later Actions
12. 12. Primary Documents
13. Key Research Papers
14. Connections
15. Featured Videos

1. What U.S. Department of Health and Human Services and the U.S. Food and Drug Administration Did

The 2025 record is four separate announcements, none of them a rule published in the Federal Register:

• March 10, 2025 — U.S. Department of Health and Human Services press release. The U.S. Department of Health and Human Services Secretary directed the Acting U.S. Food and Drug Administration Commissioner “to take steps to explore potential rulemaking” to revise the U.S. Food and Drug Administration’s generally recognized as safe final rule and related guidance so as to eliminate the self-affirmed generally recognized as safe pathway. U.S. Department of Health and Human Services also said it would work with Congress on legislation.
• May 15, 2025 — U.S. Food and Drug Administration press release. The U.S. Food and Drug Administration announced “a stronger, more systematic review process for food chemicals already on the market,” to be rolled out over the following months in three parts: a prioritization scheme (draft for comment), a final review process, and an updated list of chemicals under review.
• June 18, 2025 — U.S. Food and Drug Administration constituent update. The U.S. Food and Drug Administration released its proposed method for ranking chemicals in food for post-market assessment and opened Docket FDA-2025-N-1733 for comments until July 18, 2025.
• August 19, 2025 — U.S. Food and Drug Administration constituent update. The U.S. Food and Drug Administration updated its public “List of Select Chemicals in the Food Supply Under U.S. Food and Drug Administration Review,” adding BHA, BHT, azodicarbonamide (ADA) and six synthetic color additives, plus a review of opiate alkaloids on poppy seeds.

A constituent update is a short notice the U.S. Food and Drug Administration’s Human Foods Program posts for industry, advocates and the public. A Federal Register docket is the public file on regulations.gov where a document, its supporting material and the public comments are posted.

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2. Key Terms: Generally Recognized as Safe, Self-Affirmation and Post-Market Review

• Food additive. Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), a substance added to food, directly or by migrating from packaging or equipment, is a “food additive” that needs U.S. Food and Drug Administration premarket review and approval, unless an exception applies. The U.S. Food and Drug Administration’s 2026 generally recognized as safe proposal traces this requirement to the Food Additives Amendment of 1958.
• Generally recognized as safe (“generally recognized as safe”). The main exception. A use of a substance is generally recognized as safe if qualified experts generally recognize it, on the basis of scientific procedures (or, for substances used in food before January 1, 1958, common use in food), as safe under its intended conditions of use. A generally recognized as safe use is not a food additive and does not need U.S. Food and Drug Administration approval. The 2026 proposal notes that it is the use of a substance, not the substance itself, that is generally recognized as safe.
• Generally recognized as safe notice. A company may send the U.S. Food and Drug Administration a notice explaining why it concluded a use is generally recognized as safe. The U.S. Food and Drug Administration reviews it and posts its response letter in a public inventory. U.S. Department of Health and Human Services described the notice program as one the U.S. Food and Drug Administration “strongly encourages” but does not require.
• Self-affirmed generally recognized as safe. U.S. Department of Health and Human Services used this term for a company concluding that a use is generally recognized as safe “without notifying the U.S. Food and Drug Administration.” The U.S. Food and Drug Administration’s regulations call it an independent conclusion of generally recognized as safe status.
• Post-market review. A fresh safety look at a chemical that is already allowed in food — a food additive, color additive, generally recognized as safe substance, food-contact substance or contaminant — in light of new information.

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3. March 10, 2025: The Self-Affirmed Generally Recognized as Safe Directive

The U.S. Department of Health and Human Services press release, titled “U.S. Department of Health and Human Services Secretary Kennedy Directs U.S. Food and Drug Administration to Explore Rulemaking to Eliminate Pathway for Companies to Self-Affirm Food Ingredients Are Safe,” states:

• The instruction. The Secretary directed the Acting U.S. Food and Drug Administration Commissioner to explore potential rulemaking to revise the agency’s “Substances Generally Recognized as Safe (GRAS) Final Rule and related guidance to eliminate the self-affirmed generally recognized as safe pathway.” U.S. Department of Health and Human Services said this would enhance the U.S. Food and Drug Administration’s oversight of generally recognized as safe ingredients and “bring transparency to American consumers.”
• The current system. “Currently, the U.S. Food and Drug Administration strongly encourages manufacturers to submit generally recognized as safe notices … but industry can self-affirm that the use of a substance is generally recognized as safe without notifying the U.S. Food and Drug Administration.”
• Program size. The U.S. Food and Drug Administration had “completed and published more than 1,000 generally recognized as safe notices” and evaluates an average of 75 notices a year. Notices, supporting data and the U.S. Food and Drug Administration’s response letters are available in a public inventory.
• What ending self-affirmation would mean. U.S. Department of Health and Human Services wrote that it “would require companies seeking to introduce new ingredients in foods to publicly notify the U.S. Food and Drug Administration of their intended use of such ingredients, along with underlying safety data, before they are introduced in the food supply.”
• Congress. U.S. Department of Health and Human Services said it was “committed to working with Congress to explore ways legislation can completely close the generally recognized as safe loophole.”

The directive was an instruction to explore a rule, not a rule. The proposal it led to was published seventeen months later (see section 10).

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4. How Generally Recognized as Safe Notification Became Voluntary

The background section of the U.S. Food and Drug Administration’s August 2026 proposed rule (91 FR 51834) sets out the history the 2025 directive was aimed at:

• 1950–1952. A House committee chaired by Representative James Delaney investigated chemicals in the food supply and reported that substances were being used “without adequate and sufficient testing of their possible long-range injurious effects.”
• 1958. Congress passed the Food Additives Amendment, requiring premarket approval of food additives, with a two-step definition that excluded generally recognized as safe uses.
• Before 1997. The U.S. Food and Drug Administration ran a generally recognized as safe affirmation process in which interested parties petitioned the agency to affirm a use as generally recognized as safe by rule. The 2026 proposal describes this framework as having “proved to be resource-intensive.”
• April 17, 1997. The U.S. Food and Drug Administration proposed replacing affirmation petitions with a voluntary notification procedure (62 FR 18938) and began an interim pilot; the first generally recognized as safe notice was filed in 1998.
• 2010. A U.S. Government Accountability Office (GAO) report noted that the U.S. Food and Drug Administration generally has no information about generally recognized as safe conclusions that are not submitted to the voluntary program.
• August 17, 2016. The U.S. Food and Drug Administration finalized the voluntary generally recognized as safe notification regulation (81 FR 54960), the “generally recognized as safe Final Rule” the 2025 directive referred to. Under it, a company “may, but is not required to,” notify the U.S. Food and Drug Administration.
• March 25, 2025. The 2026 proposal states that the U.S. Food and Drug Administration’s human foods program had filed over 1,200 generally recognized as safe notices by this date. (U.S. Department of Health and Human Services’s March 10 figure of more than 1,000 refers to notices completed and published.)

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5. May 15, 2025: A Systematic Post-Market Review Program

The U.S. Food and Drug Administration press release “U.S. Food and Drug Administration Advances Robust, Transparent Post-Market Chemical Review Program to Keep Food Supply Safe and Healthy” announced three actions “over the coming months”:

1. A “modernized, evidence-based prioritization scheme” for reviewing existing chemicals, with a draft to be released for public comment.
2. A “final, systematic post-market review process shaped by stakeholder input.”
3. An updated list of chemicals under review, “including BHT, BHA, and ADA,” and steps to expedite reviews already under way of phthalates, propylparaben and titanium dioxide.

What it replaced. The U.S. Food and Drug Administration wrote: “Until now, the U.S. Food and Drug Administration has conducted post-market reviews on a case-by-case basis, often in response to citizen petitions or new scientific evidence. This new framework will be proactive, science-based, and built for long-term impact.” A citizen petition is a formal written request from any person or group asking the U.S. Food and Drug Administration to take or change an action.

Part of a larger initiative. The release placed the program alongside the April 2025 plan to phase out petroleum-based synthetic dyes and the March 2025 generally recognized as safe directive.

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6. June 18, 2025: The Proposed Ranking Method

The June 18 constituent update and the method document posted in Docket FDA-2025-N-1733 (“Tool for the Prioritization of Food Chemicals for Post-Market Assessment”) describe how the U.S. Food and Drug Administration proposed to decide which chemicals to look at first.

• The approach. The method uses Multi-Criteria Decision Analysis (MCDA): FDA scientists score each chemical against a fixed set of criteria, and the scores are combined into one number. The higher the total, the higher the chemical’s priority. The U.S. Food and Drug Administration said the approach is similar to one the U.S. Environmental Protection Agency uses for prioritizing chemicals, adapted to exposure from food.
• Four public health criteria. Toxicity (scored across seven data types, including cancer and genetic damage, developmental and reproductive effects, nervous-system effects, other organ effects, immune effects, and build-up in the body); change in dietary exposure since the last assessment; whether the chemical is found in food intended for susceptible groups such as infants; and new scientific information that could change an earlier conclusion.
• Three “other decisional” criteria. The level of outside attention (for example from Congress or national news coverage); whether other government agencies have acted on the chemical; and whether not assessing it could cause the public to lose confidence in the safety of the food supply.
• Scoring. Each criterion is scored on a scale using the values 1, 3, 5 or 9 depending on the criterion. In the draft, criteria within each group are weighted equally, and the public health total and the other-decisional total are weighted equally against each other; the document states the method “can accommodate non-equal weights.”
• What a score means. The document states that a chemical’s score and position on the list “is not an evaluation as to whether that chemical poses a public health risk”; it is a tool for deciding where to spend agency resources.
• Development. The U.S. Food and Drug Administration says it piloted a draft tool in 2023–2024, published a discussion paper in August 2024 and held a public meeting in September 2024 before this draft.
• Next steps. Comments closed July 18, 2025. The U.S. Food and Drug Administration said it would then send the method and the comments for review by external scientific experts, in line with the Information Quality Act.

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7. August 19, 2025: The Updated List of Chemicals Under Review

The U.S. Food and Drug Administration first published its list of select chemicals under review in July 2023 and updated it in March 2024. The August 19, 2025 update added dates for when each review began and for the latest risk-management action, and links for public input where available.

New to the list:

• Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) — synthetic antioxidants used as preservatives.
• Azodicarbonamide (ADA) — a dough conditioner and flour-treatment agent.
• Six synthetic color additives: FD&C Blue No. 1, Blue No. 2, Green No. 3, Red No. 40, Yellow No. 5 and Yellow No. 6.
• Opiate alkaloids on poppy seeds.

Other changes. Lead as a food-contact substance was separated from lead as a contaminant and given its own entry. The U.S. Food and Drug Administration said it was taking steps to expedite reviews of chemicals listed earlier, such as phthalates, propylparaben and titanium dioxide, and that it intended to seek data and information from stakeholders on BHA, BHT and ADA “in the near future.”

The site’s background pages on these substances are BHA, BHT, Azodicarbonamide, Titanium Dioxide, Phthalates and Food Dyes.

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8. What Officials Said

• The U.S. Department of Health and Human Services Secretary (March 10): “For far too long, ingredient manufacturers and sponsors have exploited a loophole that has allowed new ingredients and chemicals, often with unknown safety data, to be introduced into the U.S. food supply without notification to the U.S. Food and Drug Administration or the public.”
• The Acting U.S. Food and Drug Administration Commissioner (March 10): “The U.S. Food and Drug Administration is committed to further safeguarding the food supply by ensuring the appropriate review of ingredients and substances that come into contact with food.”
• The U.S. Department of Health and Human Services Secretary (May 15): “No parent should ever worry about what’s in their child’s food.”
• The U.S. Food and Drug Administration Commissioner (May 15): “We are prioritizing our resources and leveraging gold standard science to create, for the first time, a systematic post-market review program that consumers can trust and rely on.”

The word “loophole” in public discussion of this action is the Secretary’s; the U.S. Food and Drug Administration’s regulations describe the same practice as an independent conclusion of generally recognized as safe status.

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9. What These Steps Do Not Do

• They changed nothing legally in 2025. No generally recognized as safe rule was proposed in 2025, self-affirmed generally recognized as safe remained lawful throughout the year, and no chemical was restricted or removed.
• A place on the review list is not a safety finding. The list records that the U.S. Food and Drug Administration is reviewing a chemical; it is not a conclusion that the chemical is unsafe. The ranking method states the same about a chemical’s priority score.
• The ranking method was a draft. It was released for comment and external peer review, not adopted, in 2025.
• The directive did not by itself bind the U.S. Food and Drug Administration to a result. It directed the agency to explore rulemaking; the content of any rule was left to the rulemaking process.
• They do not cover the dye phase-out. The separate April 2025 plan on petroleum-based dyes is covered on the Synthetic Dye Phase-Out Plan page.

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10. Dates and Legal Status (as of October 11, 2026)

• Self-affirmed GRAS: PROPOSED rule, open for comment. On August 11, 2026 the U.S. Food and Drug Administration published a proposed rule, “Substances Generally Recognized as Safe” (91 FR 51834, FR Doc. 2026-16296, Docket FDA-2025-N-3262), that would convert the voluntary generally recognized as safe notification program into a mandatory one. Comments close December 9, 2026. It is not in effect. Details: U.S. Food and Drug Administration Proposal to Make generally recognized as safe Notices Mandatory (2026).
• Post-market review program: framework FINAL; reviews OPEN. The review framework was finalized on May 12, 2026. The U.S. Food and Drug Administration opened a reassessment of BHA in February 2026 and of BHT and ADA in May 2026. Details: U.S. Food and Drug Administration Safety Reassessments of BHA, BHT and ADA (2026).

Timeline

• March 10, 2025 — U.S. Department of Health and Human Services directs the U.S. Food and Drug Administration to explore rulemaking to eliminate self-affirmed generally recognized as safe.
• May 15, 2025 — U.S. Food and Drug Administration announces the systematic post-market chemical review program.
• June 18, 2025 — draft ranking method released; Docket FDA-2025-N-1733 opens.
• July 18, 2025 — comment period on the ranking method closes.
• August 19, 2025 — updated list of chemicals under review.
• February 2026 — BHA reassessment opened.
• May 12, 2026 — post-market review framework finalized; BHT and ADA reassessments opened in May.
• August 11, 2026 — mandatory generally recognized as safe notification proposed rule published.
• December 9, 2026 — comment deadline on the generally recognized as safe proposal.

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11. How the Steps Fit Earlier and Later Actions

• 1958. Food Additives Amendment creates premarket approval for food additives and the generally recognized as safe exception.
• 1997 and 2016. Generally recognized as safe affirmation petitions replaced by voluntary notification, proposed in 1997 and finalized in 2016.
• July 2023 and March 2024. The U.S. Food and Drug Administration publishes, then updates, its list of select chemicals under review.
• August–September 2024. U.S. Food and Drug Administration discussion paper and public meeting on an enhanced systematic post-market assessment process.
• January 15, 2025. The U.S. Food and Drug Administration revokes Red No. 3 in food and ingested drugs under the Delaney Clause (Red No. 3 Revocation).
• March–August 2025. The four steps on this page.
• April 22, 2025. U.S. Department of Health and Human Services and the U.S. Food and Drug Administration announce a plan to phase out petroleum-based synthetic dyes (Synthetic Dye Phase-Out Plan); the August 19 list then added six synthetic dyes to the chemicals under review.
• 2026. The review framework is finalized, BHA, BHT and ADA reassessments open, and the mandatory generally recognized as safe notification rule is proposed (section 10). Later dye steps are on U.S. Food and Drug Administration Food Dye Actions in 2026.

How U.S. food-chemical rules compare with Europe’s is covered on United States vs European Union: Food Safety Regulation Compared.

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12. Primary Documents

1. U.S. Department of Health and Human Services (2025). U.S. Department of Health and Human Services Secretary Kennedy Directs U.S. Food and Drug Administration to Explore Rulemaking to Eliminate Pathway for Companies to Self-Affirm Food Ingredients Are Safe. Press release, March 10, 2025 — hhs.gov press release (archived copy)
2. U.S. Food and Drug Administration (2025). U.S. Food and Drug Administration Advances Robust, Transparent Post-Market Chemical Review Program to Keep Food Supply Safe and Healthy. Press release, May 15, 2025 — fda.gov press release
3. U.S. Food and Drug Administration (2025). U.S. Food and Drug Administration Seeks Input on a New Method for Ranking Chemicals in Food for Post-market Assessments. Human Foods Program Constituent Update, June 18, 2025. Docket No. FDA-2025-N-1733 — fda.gov constituent update
4. U.S. Food and Drug Administration (2025). Tool for the Prioritization of Food Chemicals for Post-Market Assessment (method document for public comment). Docket No. FDA-2025-N-1733 — regulations.gov PDF; public docket: regulations.gov FDA-2025-N-1733
5. U.S. Food and Drug Administration (2025). U.S. Food and Drug Administration Update on Post-market Assessment of Chemicals in the Food Supply. Human Foods Program Constituent Update, August 19, 2025 — fda.gov constituent update
6. U.S. Food and Drug Administration. List of Select Chemicals in the Food Supply Under U.S. Food and Drug Administration Review (program page) — fda.gov list
7. Food and Drug Administration, U.S. Department of Health and Human Services (2026). Substances Generally Recognized as Safe. Proposed rule. Federal Register 91:51834, August 11, 2026. Docket No. FDA-2025-N-3262 — FR Doc. 2026-16296 (official PDF, govinfo.gov)

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Key Research Papers

1. Burdock GA, Carabin IG (2004). Generally recognized as safe (GRAS): history and description. Toxicology Letters 150(1):3-18 — PubMed PMID: 15068820
2. Maffini MV, Alger HM, Olson ED, Neltner TG (2013). Looking Back to Look Forward: A Review of FDA's Food Additives Safety Assessment and Recommendations for Modernizing its Program. Comprehensive Reviews in Food Science and Food Safety 12(4):439-453 — PubMed PMID: 33412683
3. Neltner TG, Alger HM, Leonard JE, Maffini MV (2013). Data gaps in toxicity testing of chemicals allowed in food in the United States. Reproductive Toxicology 42:85-94 — PubMed PMID: 23954440
4. Neltner TG, Alger HM, O'Reilly JT, Krimsky S, Bero LA, Maffini MV (2013). Conflicts of interest in approvals of additives to food determined to be generally recognized as safe: out of balance. JAMA Internal Medicine 173(22):2032-2036 — PubMed PMID: 23925593
5. Maffini MV, Neltner TG, Vogel S (2017). We are what we eat: Regulatory gaps in the United States that put our health at risk. PLoS Biology 15(12):e2003578 — PubMed PMID: 29261673
6. Trasande L, Shaffer RM, Sathyanarayana S; Council on Environmental Health (2018). Food Additives and Child Health. Pediatrics 142(2) — PubMed PMID: 30037972
7. Matouskova K, Neltner TG, Maffini MV (2023). Out of balance: conflicts of interest persist in food chemicals determined to be generally recognized as safe. Environmental Health 22(1):59 — PubMed PMID: 37670318
8. Palmont P, Membré JM, Rivière G, Bemrah N (2023). Risk ranking of chemical hazards in foods: comparison of aggregating methods using infant formula as an example. Food Additives & Contaminants. Part A 40(2):193-201 — PubMed PMID: 36602446

The first paper describes the generally recognized as safe exception and its history; papers 2–5 and 7 examine the U.S. food-additive and generally recognized as safe systems; paper 6 is a policy statement on food additives and children; paper 8 compares methods for ranking chemical hazards in food, the kind of task the U.S. Food and Drug Administration’s 2025 ranking method addresses.

PubMed Topic Searches

1. PubMed: GRAS and food regulation
2. PubMed: U.S. food additive safety assessment
3. PubMed: risk ranking of chemical hazards in food

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Connections

• U.S. Food and Drug Administration Actions of 2025
• U.S. Food and Drug Administration and Regulation
• U.S. Food and Drug Administration Proposal to Make Generally Recognized as Safe Notices Mandatory (2026)
• U.S. Food and Drug Administration Safety Reassessments of BHA, BHT and ADA (2026)
• Synthetic Dye Phase-Out Plan (2025)
• Red No. 3 Revocation (2025)
• Ultra-Processed Foods Definition (2025)
• The Generally Recognized as Safe Loophole (News)
• Food Additives
• BHA
• BHT
• Azodicarbonamide (ADA)
• Titanium Dioxide
• Phthalates
• US vs EU Food Safety

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