FDA GRAS Proposed Rule
What is the FDA's new GRAS proposed rule?
FDA's proposed rule "Substances Generally Recognized as Safe" (Docket FDA-2025-N-3262, RIN 0910-AJ02, FR Doc. 2026-16296) was published on 11 August 2026. It would make GRAS notification mandatory. Today anyone who concludes a food substance is GRAS may tell FDA but does not have to. Under the proposal, anyone putting a substance into interstate commerce on a GRAS basis would have to send FDA a GRAS notice explaining why, unless an exception applies. It covers human and animal food, both direct ingredients and indirect substances such as those from packaging. It amends 21 CFR parts 170 and 570.
Approach: I read the official Federal Register text of the proposed rule. The FDA Federal Register dataset I hold can only be searched by document number, so I found that number through official web sources.
Background. FDA says the HHS Secretary directed it on 10 March 2025 to explore ending the route by which firms market self-determined GRAS uses without telling FDA. It ties the proposal to the Make America Healthy Again initiative.
Key provisions
- Mandatory notice (§ 170.205(a)). Anyone introducing a substance under the GRAS provision of FD&C Act section 201(s) must notify FDA of the basis for the GRAS conclusion. For uses that meet the food-contact substance definition, a food contact notification is an alternative route.
- No premarket approval. This stays a notification scheme. If a use has not been notified, FDA would treat that as a factor when it prioritises substances for post-market review.
- When no notice is needed (§ 170.205(b)):
- An existing "no questions" letter already covers the use.
- The use is listed or affirmed as GRAS in parts 182, 184 or 186.
- The use is GRAS under § 170.30(d) or (i)(1).
- FDA has reviewed the use through an established process for spotting unapproved additives, and the public outcome does not call for a GRAS notice.
- The use has a threshold-of-regulation exemption.
- An effective food contact notification covers the use, and the substance comes from the manufacturer or supplier named in it.
- The use is covered by a streamlined submission that appears on FDA's public list.
- Extra exceptions for animal food (§ 570.205(b)(5)-(6)):
- Uses that went through an FDA animal food ingredient consultation (such as AFIC) where FDA's public summary raises no concerns.
- Ingredients listed in, and used in line with, the 2024 AAFCO Official Publication, Chapter 6, where FDA has not publicly raised a GRAS concern.
- Streamlined submission for substances already on the market (new Subpart F, § 170.305). This is a one-time option for substances already sold under the GRAS provision before the final rule's effective date.
- Content: submitter, substance, conditions of use, and evidence the substance was in interstate commerce before that date.
- Deadline: one year after the effective date. Submissions go through the Centralized Online Submission Module (CVM by email for animal food).
- Not allowed for uses that got an insufficient-basis letter or an FDA "not GRAS" determination.
- What FDA does with them: it posts them on a public list. A posting does not mean FDA has reviewed GRAS status. FDA can still require a full GRAS notice or a food additive petition.
- Changes to the review procedure (§ 170.265):
- Initial filing evaluation within 45 days.
- The 180-day response time can be extended by 90 days, up to twice.
- If FDA ceases evaluating a notice, the notification requirement is not met.
- FDA may send questions after issuing a no-questions letter, and may update or rescind such letters (§ 170.38(c)).
- Transparency:
- Notice data are open to public disclosure from the date FDA receives the notice (§ 170.275).
- Notifiers must explain how a GRAS conclusion holds if it relies on non-public safety data claimed as confidential (§ 170.250(e)).
- Notices must be filed electronically, and foreign-language material needs an English translation.
- Other changes:
- Threshold of regulation (§ 170.39) is widened to cover human food uses and food-contact substances generally, with the 0.025 µg/kg bw/day dietary threshold.
- § 170.285 on GRAS affirmation petitions is revoked.
Timing
- Comments: due 120 days after publication, which works out to 9 December 2026.
- Effective date: 60 days after the final rule is published.
- Compliance date: 18 months after the effective date for §§ 170.205 and 570.205.
- Alternatives: FDA specifically asks for comments on less burdensome options, such as allowing streamlined submissions for all GRAS substances.
Costs. OIRA has classed the rule as economically significant. FDA estimates the present value of costs at about $89.6 million (range $34.9M to $210.0M, 3% discount rate over 10 years, 2024 dollars). Annualised, that is about $10.5 million at 3% or $11.7 million at 7%. It expects about 98 more firms a year to file GRAS notices.
Does it change the threshold of regulation exemption?
Yes. The proposal rewrites the threshold of regulation (TOR) exemption in 21 CFR 170.39 in four ways. It widens the exemption from food-contact articles to any substance used in food, direct or indirect. A TOR exemption would also excuse the use from the new mandatory GRAS notice. The 0.5 ppb dietary-concentration trigger would become a body-weight-based intake of 0.025 µg/kg bw/day. Finally, several procedural paragraphs are cut or modernised.
Approach: The FDA Federal Register document in the datasets (FR Doc. 2026-16296, published 11 August 2026) [1] holds only the rule's first page. So I read the preamble (section V.D) and the amended regulatory text in the official Federal Register PDF.
1. Scope widened from packaging to all food uses
- The section's new title would be "Threshold of regulation for substances used in food or as a food-contact substance." Today it covers substances in food-contact articles that migrate into food.
- Under amended § 170.39(a), a substance used in food or as a food-contact substance would be exempt "from regulation as a food additive or from the GRAS notification requirement under § 170.205" if it meets the criteria. FDA says this applies whether the substance enters food directly or indirectly.
- Current § 170.39(a)(3) would be deleted. It requires that the substance have no technical effect in the food. FDA calls that test packaging-specific and at odds with the wider scope. Old (a)(4) becomes (a)(3).
2. Link to mandatory GRAS notification
- A granted TOR exemption is one of the exceptions to the notice requirement (§ 170.205(b)(5)).
- FDA says a substance meeting the TOR criteria may also be GRAS. Where an intended use is GRAS and meets the criteria, FDA recommends that industry use the TOR route.
- References to the GRAS notification requirement would run through § 170.39(b), (c) and (e). A request could seek exemption from food additive regulation or from the notice requirement.
- Under the revised revocation paragraph, if FDA withdraws an exemption, continued use would need one of three things: a food additive regulation, an effective food contact notification, or a GRAS notice.
3. Updated exposure and cancer-risk criteria
| Criterion | Current § 170.39 | Proposed |
|---|---|---|
| Dietary exposure, (a)(2)(i) | At or below 0.5 ppb in the diet, which equals 1.5 µg/person/day based on 1,500 g solid plus 1,500 g liquid food | At or below 0.025 µg/kg bw/day |
| Carcinogenic impurity, (a)(1) | No impurity with a TD50 below 6.25 mg/kg bw/day | Lifetime cancer risk no greater than 1 in 1 million at 0.025 µg/kg bw/day in the diet, calculated from a TD50 "or another approach" based on chronic feeding studies. Where several TD50s exist, the lowest appropriate one is used. |
| Regulated direct additive, (a)(2)(ii) | (unchanged in substance) | Exposure at or below 1% of the ADI |
FDA's reasons:
- The per-kg intake evens out exposure across subpopulations with different body weights and food intakes.
- A TD50 of 6.25 mg/kg bw/day equals a cancer risk below 1 in 1 million at the new threshold, so the level of protection is unchanged.
The requirement for no significant adverse environmental impact stays, as (a)(3).
4. Procedural changes
- (c): Requests no longer have to be filed in triplicate. They must state whether they rely on the 0.025 µg/kg bw/day threshold or the 1%-of-ADI route.
- (d): Requests must be filed electronically through the Centralized Online Submission Module (COSM). A paper waiver is available from the Office of Pre-market Additive Safety.
- (e): FDA's response no longer has to be "by letter." FDA will keep a "publicly available" list of exempted uses, without trade names, instead of a list on display at the Dockets Management Staff.
- (f): The petition-for-reconsideration paragraph is removed. Reconsideration stays available under the general rule in § 10.33.
- (h): The guidance-availability paragraph is removed. Old (g), revocation on significant new information, becomes (f).
Animal food: The part 570 amendments contain no TOR provision, and the animal food exceptions in § 570.205(b) do not list a TOR exemption.
Sources: Federal Register PDF, FR Doc. 2026-16296. The preamble is section V.D, PDF pp. 47-52; the regulatory text of § 170.39 is pp. 116-120, and § 170.205(b) is pp. 122-123.
When are comments due?
Comments on FDA's GRAS proposed rule (Docket No. FDA-2025-N-3262) are due by 9 December 2026. Electronic or written comments on the proposed rule must be submitted by that date. Comments on the Paperwork Reduction Act information collection are also due by 9 December 2026 [1].
Approach: I read the DATES and ADDRESSES sections of the proposed rule in the FDA Federal Register record (91 FR 51834, 11 August 2026).
How and when to file [1]
- Electronic: regulations.gov accepts comments until 11:59 p.m. Eastern Time on 9 December 2026. FDA states that late comments will not be considered.
- Paper (mail, hand delivery or courier): these count as on time if received on or before 9 December 2026. Send them to Dockets Management Staff (HFA-305), FDA, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
- Docket number: every submission must cite Docket No. FDA-2025-N-3262, "Substances Generally Recognized as Safe."
- Confidential information: this can only go in by paper. Send two copies: one marked "THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION" and one redacted copy for public posting.
- Information collection comments: these can also go to OMB's Office of Information and Regulatory Affairs via reginfo.gov. The collection is titled "Substances Generally Recognized as Safe: Notification Procedure."
As of today (11 October 2026), there are just under two months left in the comment period.