View source for Generally recognized as safe

{{Short description|United States government designation for food additives}}
{{Redirect|GRAS||Gras (disambiguation)}}
{{Distinguish|Generally recognized as safe and effective}}
{{food safety}}
{{Use dmy dates|date=September 2023}}
'''Generally recognized as safe''' ('''GRAS''') is a [[United States]] [[Food and Drug Administration (United States)|Food and Drug Administration]] (FDA) designation that a chemical or substance added to food is considered safe by experts under the conditions of its intended use.<ref name="gras-how">{{cite web |title=How U.S. FDA's GRAS Notification Program Works (original January 2006; updated) |url=https://www.fda.gov/food/generally-recognized-safe-gras/how-us-fdas-gras-notification-program-works |archive-url=https://web.archive.org/web/20190926011759/https://www.fda.gov/food/generally-recognized-safe-gras/how-us-fdas-gras-notification-program-works |url-status=dead |archive-date=26 September 2019 |publisher=US Food and Drug Administration |access-date=30 January 2021 |date=9 February 2018}}</ref> An ingredient with a GRAS designation is exempted from the usual [[Federal Food, Drug, and Cosmetic Act]] (FFDCA) [[food additive]] tolerance requirements.<ref name="GRASfda">{{cite web|url=https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras|title=Generally Recognized as Safe (GRAS) |publisher=US Food and Drug Administration|date=6 September 2019 |access-date=30 January 2021}}</ref>

Some examples of substances recognized as GRAS include ascorbic acid (vitamin C), citric acid, and salt, which are all commonly used in food preservation and flavoring.<ref>{{Cite journal |last=Program |first=Human Foods |date=2024-09-06 |title=Understanding How the FDA Regulates Food Additives and GRAS Ingredients |url=https://www.fda.gov/food/food-additives-and-gras-ingredients-information-consumers/understanding-how-fda-regulates-food-additives-and-gras-ingredients#:~:text=Some%20examples%20of%20GRAS%20ingredients,the%20FDA's%20GRAS%20Notification%20Program. |journal=FDA |language=en}}</ref> The concept of food additives being "generally recognized as safe" was first described in the [[Food Additives Amendment of 1958]], and all additives introduced after this time had to be evaluated by new standards.<ref name=gras-how/><ref name=gras-history/>

==Affirmation and notification==
GRAS substances can be self-affirmed upon determination by qualified non-governmental experts, with or without FDA notification, or the FDA itself can affirm:
* ''Self-affirmation without FDA notification.'' The manufacturer of this chemical or substance had performed all necessary research, including the formation of an expert panel to review safety concerns, and is prepared to use these findings to defend its product's GRAS status. FDA is not notified.
* ''Self-affirmation with FDA notification.''<ref name="fda"/> The manufacturer has performed all the aforementioned due diligence, and submitted a GRAS notification to inform the FDA of a determination that the use of a substance is GRAS. Following evaluation, the FDA provides three possible responses: 1. FDA does not question the basis for the notifier's GRAS determination,<ref name="fda"/> 2. the notification does not provide a sufficient basis for GRAS determination, or 3. the FDA has, at the notifier's request, ceased to evaluate the GRAS notice.
* ''FDA affirmation.''<ref>{{CodeFedReg|21|170|35}}, {{CodeFedReg|21|170|38}}.</ref> Rarely, the FDA can affirm GRAS status through rulemaking on its own initiative.

For substances used in food prior to January 1, 1958, a ''[[grandfather clause]]'' allows experience based on common use in food to be used in asserting an ingredient is safe under the conditions of their intended use.<ref name="gras-history">{{cite web |title=FDA's Approach to the GRAS Provision: A History of Processes |url=https://www.fda.gov/food/generally-recognized-safe-gras/fdas-approach-gras-provision-history-processes |archive-url=https://web.archive.org/web/20190612041606/https://www.fda.gov/food/generally-recognized-safe-gras/fdas-approach-gras-provision-history-processes |url-status=dead |archive-date=12 June 2019 |publisher=US Food and Drug Administration |access-date=30 January 2021 |date=4 January 2018}}</ref>

The FDA can also explicitly withdraw the GRAS classification, as it did for [[trans fat]] in 2015.<ref>{{CodeFedReg|21|170|38}}. {{USCClause|21|348|(i)}}.</ref><ref name="Jalonik">{{cite news |last1=Jalonik |first1=Mary Clare |title=FDA tells food industry to phase out artificial trans fats |url=https://www.bostonglobe.com/business/2015/06/16/fda-tells-food-industry-phase-out-artificial-trans-fats/UAiibLOV27UY1iOWGQC4HJ/story.html |access-date=July 16, 2019 |work=Boston Globe |agency=Associated Press |date=June 16, 2015 |quote=To phase the fats out, the FDA made a preliminary determination in 2013 that partially hydrogenated oils no longer fall in the agency’s “generally recognized as safe” category, which covers thousands of additives that manufacturers can use in foods without FDA review. The agency made that decision final Tuesday, giving food companies until June 2018 to phase them out.}}</ref>

==Scientific evidence required==
For new proposals, the proponent of the GRAS exemption {{ndash}} usually a [[food manufacturing|food manufacturer]] or ingredient supplier wishing to highlight a food ingredient in its manufactured product {{ndash}} has the burden of providing rigorous scientific evidence that use of the substance in an edible [[consumer product]] is safe.<ref name=GRASfda/>

Scientific procedures for GRAS exemptions require the same quantity and quality of scientific evidence needed to obtain approval of the substance as a [[food additive]], and are ordinarily based upon published studies but may be corroborated by unpublished studies, data, and information.<ref name=GRASfda/><ref>{{CodeFedReg|21|170|30}}(b)</ref><ref>{{cite web|url=https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-summary-table-recommended-toxicological-testing-additives-used-food |archive-url=https://web.archive.org/web/20190906113326/https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-summary-table-recommended-toxicological-testing-additives-used-food |url-status=dead |archive-date=6 September 2019 |title=Guidance for Industry: Summary Table of Recommended Toxicological Testing for Additives Used in Food (June 2006, updated periodically) |publisher=US Food and Drug Administration |date=2020-09-20|access-date=2021-01-30}}</ref> FDA has not issued guidance to companies on how to document their GRAS determinations.<ref name=gao/>

==Intended use==
The substance must be shown to be "generally recognized" as safe under the conditions of its intended use.<ref name=GRASfda/> To establish GRAS, the proponent must show that there is a consensus of expert opinion that the substance is safe for its intended use.<ref name="fda"/> For existing GRAS items, new uses should not substantially exceed historical occurrence levels of the substance in the diet.<ref name=GRASfda/>

==Enforcement==
When use of a substance does not qualify for the GRAS exemption, it is subject to the premarket approval mandated by the [[Federal Food, Drug, and Cosmetic Act]]. In such circumstances, the FDA can take enforcement action to stop distribution of the food substance and foods containing it on the grounds that such foods are not deemed GRAS or contain an unlawfully added ingredient.<ref>{{cite web |url=https://www.govinfo.gov/content/pkg/FR-1997-04-17/pdf/97-9706.pdf |title=Federal Register Proposed Rules – 62 FR 18937 April 17, 1997 – Substances Generally Recognized as Safe [Docket No. 97N–0103]|publisher=Federal Register, US Department of Health and Human Services|date=17 April 1997|access-date=30 January 2021}}</ref>

An example of a non-GRAS ingredient requiring enforcement actions in the form of [[FDA warning letter]]s to 15 companies in 2019 was [[cannabidiol]],<ref name="fda-cbd">{{cite web |title=FDA warns 15 companies for illegally selling various products containing cannabidiol as agency details safety concerns |url=https://www.fda.gov/news-events/press-announcements/fda-warns-15-companies-illegally-selling-various-products-containing-cannabidiol-agency-details |archive-url=https://web.archive.org/web/20191126162834/https://www.fda.gov/news-events/press-announcements/fda-warns-15-companies-illegally-selling-various-products-containing-cannabidiol-agency-details |url-status=dead |archive-date=26 November 2019 |publisher=US Food and Drug Administration |access-date=30 January 2021 |date=25 November 2019}}</ref> which, as of 2024, had not been established with sufficient scientific evidence of safety as a GRAS ingredient.<ref name="fda-cann">{{cite web |title=FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD) |url=https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd|publisher=US Food and Drug Administration |access-date=10 August 2025 |date=16 July 2024}}</ref>

==New Dietary Ingredient process==
The separate New Dietary Ingredient (NDI) notification process is FDA's premarket system for certain ingredients in [[dietary supplement]]s defined in the [[Dietary Supplement Health and Education Act of 1994]] (DSHEA). Supplement makers have been accused of "routinely and systematically" bypassing the DSHEA NDI process by using GRAS exemptions: first adding new compounds to a food and self-certifying, with or without FDA notification, then adding them to supplements.<ref>{{cite news |last=Black |first=Jane |date=6 August 2025 |title=Kennedy’s Crusade Against Food Safety Rule Threatens Supplement Industry |url=https://www.nytimes.com/2025/08/06/well/gras-kennedy-supplements.html |work=The New York Times |access-date=10 August 2025}}</ref>

==History==
On 6 September 1958, the [[Food Additives Amendment of 1958]] was signed into law, with a list of 700 food substances that were exempt from the then-new requirement that manufacturers test food additives before the manufactured foods were marketed.<ref name=gras-how/><ref name=gras-history/> In 1960, William W. Goodrich, assistant general counsel of the FDA, emphasized that GRAS status under the amendment depended on broad expert consensus, distinguishing it from mere proof of safety, and urged treating doubtful substances as food additives requiring formal approval.<ref>{{cite journal |url=http://heinonline.org/HOL/LandingPage?collection=journals&handle=hein.journals/busl16&div=14&id=&page= |title=Safe Food Additives and Additives Generally Recognized as Safe—There is a Difference |journal=The Business Lawyer |volume=16 |issue=1 |pages=107-112 |date=November 1960 |publisher=American Bar Association |access-date=2025-08-11 |last1=Goodrich |first1=William W. |jstor=40683483}}</ref> 

In the 1970s and 1980s, the FDA engaged in a systematic reconsideration of the safety of GRAS substances, giving a timeline of GRAS policies from 1958 to 2005.<ref>{{cite web |first1=Paulette M. |last1=Gaynor |first2=Richard |last2=Bonnette |first3=Edmundo |last3=Garcia, Jr. |first4=Linda S. |last4=Kahl |first5=Luis G. |last5=Valerio, Jr. |date=4 January 2018 |title=FDA's Approach to the GRAS Provision: A History of Processes |url=https://www.fda.gov/food/generally-recognized-safe-gras/fdas-approach-gras-provision-history-processes |publisher=Food and Drug Administration|access-date=17 August 2025}}</ref> In 1971, FDA issued criteria for determining GRAS status on its own initiative, and in 1972, the GRAS affirmation petition process was created to allow individuals to initiate reviews.<ref>{{Federal Register|36|20546}}, 23 October 1971. {{Federal Register|37|25705}}, 2 December 1972.</ref><ref name=1997-federal-register/> Between 1974–1976, the FDA clarified the distinction between GRAS by scientific procedures and by common use in food before 1958.<ref name=1997-federal-register/><ref>{{Federal Register|39|34194}}, 23 September 1974{{Federal Register|41|53600}}, 7 December 1976</ref>

In 1997, the FDA replaced the "GRAS affirmation process with a [voluntary] notification procedure" for which any person or company could notify the FDA that a substance had convincing scientific evidence for GRAS status under the conditions of its intended use to unburden agency resources, encourage industry disclosure, and maintain legal safeguards.<ref name=1997-federal-register>{{Federal Register|62|18938}}, 17 April 1997. {{Federal Register|81|54960}}, 17 August 2016.</ref><ref>{{cite journal |last1=Gaynor |first1=Paulette |date=1 December 2005 |title=How U.S. FDA's GRAS Notification Program Works |url=https://www.fda.gov/food/generally-recognized-safe-gras/how-us-fdas-gras-notification-program-works |journal=Food Safety Magazine |publisher=[[Food and Drug Administration]]|access-date=10 August 2025}}</ref> Starting in 2000, [[Redbook 2000]] provides core FDA guidelines for toxicity testing of direct food additives covering GRAS under 21 CFR § 170.3, including tiered studies and ADME evaluations.<ref>{{Cite web |title=21 CFR 170.3 -- Definitions. |url=https://www.ecfr.gov/current/title-21/part-170/section-170.3 |access-date=2025-12-06 |website=www.ecfr.gov |language=en}}</ref>

==Concerns about ingredient safety==
In 2010, the [[United States Government Accountability Office]] (GAO) published a report about potential deficiencies in the GRAS review process, giving four main areas of concern:<ref name="gao">{{cite report|date=5 March 2010 |title=Food Safety: FDA Should Strengthen Its Oversight of Food Ingredients Determined to Be Generally Recognized as Safe (GRAS) |url=https://www.gao.gov/products/gao-10-246|publisher=[[United States Government Accountability Office]] |access-date=17 August 2025}}</ref>

* the GRAS oversight process does not confirm the safety of all new ingredient assessments. This potential deficiency occurs because the FDA assesses GRAS petitions only if the manufacturer voluntarily notifies the FDA. 
* the FDA has not provided guidance to companies for sufficiently documenting scientific evidence of safety in GRAS petitions. 
* there is no final FDA regulation for criteria in the voluntary notification program, challenging credibility for GRAS status, and there exists insufficient monitoring in the public market for the continued safety of GRAS substances.
* companies considering use of engineered [[nanomaterial]]s in food can use the voluntary GRAS notification process, assuming full safety without the FDA having a complete assessment. In contrast to this absence of review, nanomaterials intended for use in foods must be fully reviewed for safety in Canada and the European Union before marketing.

Despite consumer group objections that this change would soften premarket safety scrutiny on new food ingredients, including a 2017 [[lawsuit]] by [[Center for Food Safety]] against the FDA, in 2021 a [[United States district court|federal district court]] found that the FDA did not unlawfully delegate its authority over food safety, and that the rule was compliant with the Federal Food, Drug, and Cosmetic Act.<ref>{{cite court |litigants=Center for Food Safety v. Becerra |vol=565 |reporter=F. Supp. 3d |opinion=519 |pinpoint= |court=[[United States District Court for the Southern District of New York|S.D.N.Y.]] |date=30 September 2021 |url=https://storage.courtlistener.com/recap/gov.uscourts.nysd.474621/gov.uscourts.nysd.474621.100.0.pdf}}</ref><ref>{{cite web |first1=Raqiyyah |last1=Pippins |first2=Howard |last2=Sklamberg |first3=Elizabeth |last3=Trentacost |title=Federal District Court Upholds FDA’s GRAS Self-Determination Process |url=https://www.arnoldporter.com/en/perspectives/advisories/2021/10/federal-district-court-upholds-fda-gras |publisher=[[Arnold & Porter]] |access-date=22 December 2025 |language=en |date=27 October 2021}}</ref><ref name="pomeranz" />

A 2024 review of the FDA GRAS program identified several deficiencies, including the large volume of food additives needing better scrutiny, the strained resources for constant FDA surveillance, delays in enforcement action, and limited postmarket overview to ensure ingredient safety.<ref name="pomeranz">{{cite journal |vauthors=Pomeranz JL, Broad Leib EM, Mozaffarian D |title=Regulation of Added Substances in the Food Supply by the Food and Drug Administration Human Foods Program |journal=American Journal of Public Health |volume=114 |issue=10 |pages=1061–1070 |date=October 2024 |pmid=39116397 |pmc=11375365 |doi=10.2105/AJPH.2024.307755}}</ref> The review provided recommendations for improving the GRAS process, including mandatory premarket assessments with application fees, more  transparency in postmarket FDA review of GRAS substances and other additives used in food manufacturing, and additional resources to be allocated by Congress.<ref name=pomeranz/>

In contrast to the need for increased resources to support the FDA, including improvements to the GRAS system, [[2025_United_States_federal_mass_layoffs#Losses|thousands of FDA employees were fired by the Trump Administration]] in April, 2025.<ref name="cnn4-25">{{cite news |vauthors=Valencia N, Goodman B, Tirrell M, Luhby T,  Lyngaas S |title=‘It’s a bloodbath’: Massive wave of job cuts underway at US health agencies |url=https://www.cnn.com/2025/04/01/health/staff-cuts-at-federal-health-agencies-have-begun |access-date=12 November 2025 |work=CNN |date=2 April 2025}}</ref>

In May 2025, the FDA announced it was planning a systematic postmarket review of GRAS substances.<ref name="fda-may25">{{cite web|date=15 May 2025 |title=FDA Advances Robust, Transparent Post-Market Chemical Review Program to Keep Food Supply Safe and Healthy |url=https://www.fda.gov/news-events/press-announcements/fda-advances-robust-transparent-post-market-chemical-review-program-keep-food-supply-safe-and |publisher=Food and Drug Administration|access-date=17 August 2025}}</ref> The announcement indicated increased scrutiny and burden of compliance for food manufacturers to justify GRAS, and a possible reevaluation of existing GRAS notifications.<ref name=fda-may25/> A congressional rule change for the GRAS review process was also submitted in early 2025.<ref name="omb">{{cite web |title=Substances Generally Recognized as Safe |url=https://www.reginfo.gov/public/do/eAgendaViewRule?pubId=202504&RIN=0910-AJ02 |publisher=US General Services Administration, Office of Management and Budget |access-date=12 November 2025 |date=Spring 2025}}</ref>

==List of GRAS substances==
The list of GRAS notices (GRAS Notice Inventory) is updated approximately each month by the FDA.<ref name=fda/> The list of GRAS affirmations by FDA appear in [[Title 21 of the Code of Federal Regulations]]. {{as of|2025|September}} (beginning in 1998), approximately 1,240 ingredient or food substances have been filed with the [[FDA]], with dozens of applications pending.<ref name="fda">{{cite web|url=https://hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&sort=GRN_No&order=DESC&showAll=true&type=basic&search=|title=Inventory of GRAS Notices|publisher=US Food and Drug Administration|date=30 September 2025|access-date=6 November 2025}}</ref> FDA posts status of the review as either without further questions (as a position of "no objection"), pending review, or the petition is withdrawn by the applicant.<ref name="fda"/>

== See also ==
* [[Generally recognized as safe and effective]]
* [[Novel food]]
* [[Substantial equivalence]]

== References ==
{{Reflist}}

== External links ==
* [https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras GRAS webpage] of the [[Food and Drug Administration|FDA]], October, 2023
* [https://hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&sort=GRN_No&order=DESC&showAll=true&type=basic&search= GRAS Notice Inventory] of the FDA, as of September, 2025

{{DEFAULTSORT:Generally Recognized As Safe}}
[[Category:Food additives]]
[[Category:Food safety]]
[[Category:Chemical safety]]
[[Category:Food and Drug Administration]]
[[Category:Food law]]