Why We Should Close the GRAS Loophole: A Science-Backed Analysis

Executive Summary

The Generally Recognized as Safe (GRAS) provision in U.S. food safety law was originally intended as a narrow exemption for common food ingredients with established safety records. However, over time, it has evolved into what many scientists, legal experts, and public health advocates consider a significant regulatory loophole that allows potentially harmful substances to enter the food supply without adequate safety review. This comprehensive analysis presents science-backed research demonstrating why the GRAS loophole should be closed to better protect public health.

The current GRAS system suffers from fundamental flaws including inherent conflicts of interest, lack of mandatory FDA notification, outdated scientific methods, and inadequate consideration of vulnerable populations. These shortcomings have allowed substances banned in other countries to remain in the U.S. food supply, sometimes for decades after safety concerns have been identified. Through examination of the system’s history, scientific research, regulatory framework, and specific case studies, this analysis builds a compelling case for comprehensive reform of the GRAS system to ensure food additives are truly safe for consumption.

Table of Contents

1. Introduction
2. Historical Context: Evolution of the GRAS Loophole
3. Scientific Research on GRAS Safety Concerns
4. Regulatory Framework and Limitations
5. Case Studies of Problematic GRAS Substances
6. Proposed Solutions and Reforms
7. Conclusion
8. References

Introduction

In the United States, the safety of food additives is primarily regulated under the Federal Food, Drug, and Cosmetic Act (FDCA), as amended by the Food Additives Amendment of 1958. This legislation established a two-tier system for regulating substances added to food:

1. Food Additives: Substances that require pre-market approval by the FDA before they can be used in food.
2. GRAS Substances: Substances that are exempt from the pre-market approval requirement because they are “generally recognized as safe” by qualified experts.

While the GRAS provision was originally intended as a narrow exemption for common ingredients like salt, vinegar, and vegetable oil, it has expanded dramatically over time. Today, thousands of substances enter the food supply through the GRAS pathway, often without FDA review or public disclosure.

This analysis examines why the current GRAS system represents a significant public health concern and why reform is necessary to ensure that all substances added to food undergo appropriate safety evaluation.

Historical Context: Evolution of the GRAS Loophole

Origins of the GRAS Provision

The GRAS provision was established as part of the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act. Congress created this provision to exempt common food ingredients with long histories of safe use from the new requirement for pre-market approval of food additives. The exemption was intended for substances like salt, sugar, spices, vitamins, and minerals that were widely recognized as safe based on their history of use in food before 1958 or based on scientific procedures.

Expansion of the GRAS Concept

What began as a narrow exemption has expanded significantly over time:

• 1958-1969: The FDA published a list of GRAS substances based on common use in food before 1958.
• 1969-1997: The FDA initiated a comprehensive review of GRAS substances, but this process was never completed due to resource constraints.
• 1997: The FDA proposed a voluntary GRAS notification program, allowing companies to make their own GRAS determinations without FDA approval.
• 2016: The FDA finalized the GRAS notification rule, maintaining the voluntary nature of the program and allowing companies to determine the safety of their own ingredients without mandatory FDA review.

Transformation into a Regulatory Loophole

Several key developments transformed the GRAS provision from a limited exemption into what critics call a significant regulatory loophole:

1. Self-Determination: Companies can determine that their own ingredients are GRAS without any FDA review.
2. Voluntary Notification: Companies are not required to inform the FDA about their GRAS determinations.
3. Conflict of Interest: Companies often hire their own experts to make GRAS determinations, creating inherent conflicts of interest.
4. Limited Transparency: Many GRAS determinations are not publicly disclosed, limiting scientific scrutiny and public awareness.
5. Expansion to Novel Substances: The GRAS provision is now routinely applied to novel, complex substances that were never contemplated when the exemption was created.

This historical evolution has resulted in a system where potentially thousands of substances have entered the food supply without FDA review, raising significant public health concerns.

Scientific Research on GRAS Safety Concerns

Scale of the Issue

The magnitude of the GRAS loophole is substantial. According to scientific research:

• Out of more than 10,000 chemicals in the U.S. food system, at least 1,000 have completely avoided FDA scrutiny through the GRAS exemption (Neltner et al., 2013).
• A 2010 U.S. Government Accountability Office (GAO) report found that the FDA’s oversight of GRAS substances was inadequate to ensure safety.
• The Pew Charitable Trusts estimated that about 3,000 food additives have never been reviewed by the FDA for safety.

Conflicts of Interest

Research has identified significant conflicts of interest in the GRAS determination process:

• A 2023 study published in Environmental Health found that GRAS panels are populated from a very small pool of professionals, with seven panel members alone occupying almost half of all available panel positions (Maffini et al., 2023).
• The same study found that these experts often serve together on multiple panels, creating a system where the same individuals repeatedly make safety determinations.
• A 2013 study in JAMA Internal Medicine found that 100% of the GRAS determinations examined were made by experts with financial relationships to the food industry (Neltner et al., 2013).

Outdated Scientific Methods

The scientific methods used to evaluate GRAS substances have not kept pace with advances in toxicology and risk assessment:

• The FDA relies on outdated scientific assumptions, including the idea that there’s a threshold effect for non-carcinogens, which may not be valid for endocrine-disrupting chemicals (Maffini et al., 2023).
• Current testing protocols often fail to consider low-dose effects, developmental impacts, and endocrine disruption potential.
• The FDA’s guidance for chemical testing methods (the “Redbook”) has not been adequately updated to reflect major scientific advances in neurodevelopment, endocrinology, reproductive biology, and immunology.

Cumulative Effects

The current system fails to adequately consider the cumulative effects of multiple chemicals:

• Many GRAS substances have similar mechanisms of action or affect the same organ systems, yet they are evaluated individually without consideration of combined effects.
• The 1958 law actually requires consideration of cumulative effects, but this requirement has been largely ignored in practice.
• Research shows that mixtures of food chemicals can have additive or synergistic effects that are not captured by individual substance evaluations.

Vulnerable Populations at Risk

Children and other vulnerable populations face particular risks from inadequately tested food chemicals:

• Developing organisms are more susceptible to chemical exposures, yet GRAS evaluations rarely include developmental toxicity studies.
• Children consume more food per unit of body weight than adults and may be exposed to higher concentrations of food additives.
• A 2017 policy statement from the American Academy of Pediatrics expressed concern about “regulatory gaps in the current food additives regulatory process, which doesn’t adequately protect children’s health” (Trasande et al., 2018).

Contrasting Scientific Perspectives

It’s important to note that some industry-affiliated scientists have defended the current GRAS system:

• A 2016 paper in Food and Chemical Toxicology argued that the FDA’s GRAS notice process is “clearly defined, efficient, and cost-effective” with “no known public health issues following its implementation” (Hanlon et al., 2017).
• Industry representatives maintain that the GRAS process allows for innovation while maintaining safety standards.

However, independent scientific bodies have consistently raised concerns about the current system’s ability to ensure food additive safety.

Regulatory Framework and Limitations

Legal Framework of the GRAS System

The Generally Recognized as Safe (GRAS) provision was established as part of the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act (FDCA). According to the FDCA, a substance is GRAS if it meets one of two criteria:

• It has been adequately shown through scientific procedures to be safe under the conditions of its intended use
• For substances used in food before January 1, 1958, it has been shown to be safe through experience based on common use in food

Current Regulatory Process

The FDA’s current approach to GRAS substances is codified in its 2016 final rule, which established a voluntary GRAS notification process. Key aspects of this regulatory framework include:

1. Voluntary Notification: Companies can make their own GRAS determinations without notifying the FDA. If they choose to notify the FDA, the agency reviews the notice and responds with one of three outcomes:

• “FDA has no questions” (acceptance)
• “Notice does not provide a basis for a GRAS determination” (rejection)
• “At Notifier’s request, FDA ceased to evaluate the notice” (withdrawal)

1. Safety Standard: GRAS substances must meet the same safety standard as food additives – “reasonable certainty of no harm” under the conditions of intended use.
2. Public Information Requirement: For a substance to be GRAS, the scientific data supporting its safety must be publicly available, and there must be consensus among qualified experts about its safety.

Legal Challenges and Court Decisions

In 2021, the Southern District of New York upheld the FDA’s final GRAS rule against a challenge by the Center for Food Safety and the Environmental Defense Fund. The court rejected arguments that the FDA impermissibly sub-delegated its food safety duties to private manufacturers, finding that the FDA did not “abdicate its final reviewing authority” since it can bring enforcement action if it disagrees with a GRAS determination.

Key Regulatory Limitations

Despite the court’s validation of the FDA’s approach, several significant limitations in the GRAS regulatory framework have been identified:

1. Lack of Mandatory Notification

The voluntary nature of the GRAS notification process means that the FDA may be unaware of many substances being used in food. According to scientific research, at least 1,000 substances have completely avoided FDA scrutiny through the GRAS exemption.

2. Limited FDA Oversight

The FDA has limited authority to systematically collect chemical hazard and exposure information from businesses or to develop a postmarket monitoring program to track uses of chemicals. This means the agency has little information for evaluating safety or monitoring it over time.

3. Conflicts of Interest

The current system allows manufacturers to determine the safety of their own products, creating inherent conflicts of interest. Research has shown that GRAS panels are populated from a very small pool of professionals, with seven panel members alone occupying almost half of all available panel positions, and they often serve together.

4. Lack of Transparency

Many GRAS determinations are made without public disclosure, limiting transparency and preventing public scrutiny of safety assessments. The FDA’s guidance for industry on best practices for convening GRAS panels is non-binding and does not establish legally enforceable responsibilities.

5. Outdated Scientific Methods

The FDA’s guidance for chemical testing methods has not been adequately updated to reflect major scientific advances in neurodevelopment, endocrinology, reproductive biology, and immunology. This can lead to safety assessments that do not consider the latest scientific understanding of chemical risks.

6. Failure to Consider Cumulative Effects

The FDA’s approach often fails to consider the cumulative effect of multiple chemicals with similar mechanisms of action, despite this being a requirement in the original 1958 law.

International Comparisons

The U.S. GRAS system differs significantly from regulatory approaches in other jurisdictions:

1. European Union: The European Food Safety Authority (EFSA) requires pre-market authorization for all food additives, with no equivalent to the GRAS exemption. All substances must undergo rigorous safety assessment before they can be used in food.
2. Canada: Health Canada requires pre-market notification for all novel foods and food additives. While Canada has a “self-GRAS” determination process similar to the U.S., it is more limited in scope and requires notification to authorities.
3. Japan: Japan maintains a positive list of approved food additives, and any new substance requires government approval before use.

Case Studies of Problematic GRAS Substances

The following case studies illustrate how the GRAS loophole has allowed potentially harmful substances to enter and remain in the food supply, often for decades after safety concerns have been identified.

Titanium Dioxide

GRAS Status: Titanium dioxide has been used in foods since before 1958 and was formally listed as GRAS by the FDA in 1966.

Uses in Food: Used as a color additive to enhance the white appearance of foods, including candies, baked goods, coffee creamers, and sauces. According to the Environmental Working Group database, it’s listed as an ingredient in more than 1,900 products in the United States.

Safety Concerns: In 2021, the European Food Safety Authority (EFSA) concluded that titanium dioxide “can no longer be considered as safe when used as a food additive” after reviewing new scientific evidence. The EFSA panel could not rule out genotoxicity concerns (the ability of the substance to damage genetic information in cells).

Regulatory Status: Banned in foods throughout the European Union since 2022, but still permitted in the United States under the GRAS provision.

Potassium Bromate

GRAS Status: Potassium bromate was approved as a flour treatment agent before the 1958 Food Additives Amendment and has been considered GRAS since then.

Uses in Food: Used as a flour “improver” that strengthens dough, makes baked goods rise higher, and enhances texture. According to the Environmental Working Group database, it’s listed as an ingredient in more than 200 products, including packaged breads, buns, bagels, pizza dough, and other baked goods.

Safety Concerns: Classified as a potential human carcinogen by the International Agency for Research on Cancer (IARC). Animal studies have linked potassium bromate to kidney and thyroid tumors.

Regulatory Status: Banned in the European Union, United Kingdom, Canada, Brazil, China, South Korea, and many other countries, but still permitted in the United States under the GRAS provision.

Brominated Vegetable Oil (BVO)

GRAS Status: BVO was granted interim approval as a food additive in 1970, which allowed its continued use while safety studies were conducted. Despite this “interim” status lasting for decades, many manufacturers have treated it as effectively GRAS.

Uses in Food: Used as an emulsifier in citrus-flavored sodas and sports drinks to prevent flavor oils from separating and floating to the top. According to the Environmental Working Group database, it has been used in approximately 70 beverages.

Safety Concerns: Contains bromine, an element found in flame retardants. Studies in animals have linked BVO to neurological problems, thyroid damage, heart and liver problems, and behavioral, developmental, and reproductive issues.

Regulatory Status: Banned in the European Union, Japan, and many other countries, but still permitted in the United States.

Synthetic Trans Fats (Partially Hydrogenated Oils)

GRAS Status: Partially hydrogenated oils (PHOs), the primary dietary source of artificial trans fats, were considered GRAS for decades based on their long history of use.

Uses in Food: Used in thousands of processed foods to improve texture, extend shelf life, and enhance flavor stability. Common in margarine, baked goods, fried foods, and snack foods.

Safety Concerns: Conclusively linked to increased risk of heart disease, stroke, and type 2 diabetes. The CDC estimated that trans fat consumption led to approximately 20,000 heart attacks and 7,000 deaths annually in the United States.

Regulatory Status: The FDA finally revoked the GRAS status of PHOs in 2015, after decades of scientific evidence showing harm. This case illustrates how the GRAS system can allow harmful substances to remain in the food supply for decades even after evidence of harm emerges.

Red Dye No. 3 (Erythrosine)

GRAS Status: Red Dye No. 3 was approved as a color additive before the 1958 Food Additives Amendment and has been considered GRAS for food use despite being banned in cosmetics.

Uses in Food: Used as a food coloring to give a bright, cherry-red color to thousands of food products, including candies, baked goods, snacks, cereals, and sodas.

Safety Concerns: The FDA banned Red Dye No. 3 from cosmetics in 1990 after studies linked it to cancer in laboratory animals. Research has associated the dye with thyroid tumors in rats and has linked artificial food dyes to hyperactivity and other neurobehavioral effects in children.

Regulatory Status: Banned in cosmetics in the United States since 1990 and banned in foods in the European Union, but still permitted in foods in the United States under the GRAS provision.

Other Problematic GRAS Substances

Additional case studies that illustrate problems with the GRAS system include:

• Myrcene and other synthetic flavoring compounds: GRAS status revoked in 2018 after petition and legal action, despite evidence of carcinogenicity.
• Salt (Sodium Chloride): Still considered GRAS with no upper limits on use despite clear public health concerns about excessive consumption.
• Carrageenan: Maintains GRAS status despite studies linking it to gastrointestinal inflammation and digestive disorders.
• Caffeine in novel applications: GRAS status extended to new high-concentration uses without FDA review of safety at these exposure levels.

These case studies demonstrate critical flaws in the current GRAS system, including outdated safety assessments, lack of systematic review, delayed regulatory action, international discrepancies, and inadequate protection for vulnerable populations.

Proposed Solutions and Reforms

Based on the scientific research, regulatory analysis, and case studies presented, several reforms are necessary to close the GRAS loophole and better protect public health:

1. Mandatory FDA Notification and Review

• Require companies to notify the FDA of all GRAS determinations
• Establish a substantive FDA review process for all GRAS notifications
• Create a comprehensive public database of all substances added to food

2. Independent Scientific Review

• Require truly independent expert panels for safety evaluations
• Establish strict conflict of interest policies for GRAS determinations
• Create an independent scientific body to review controversial or high-risk GRAS determinations

3. Updated Testing Requirements

• Modernize testing protocols to reflect current scientific understanding
• Require evaluation of low-dose, chronic exposures
• Include developmental toxicity and endocrine disruption testing
• Consider impacts on vulnerable populations, particularly children

4. Systematic Reassessment of Existing GRAS Substances

• Prioritize review of substances with emerging safety concerns
• Establish a schedule for periodic reassessment of all GRAS substances
• Require safety data to be updated when new scientific methods become available

5. Consideration of Cumulative Effects

• Develop methods to assess cumulative effects of chemicals with similar mechanisms
• Require consideration of total dietary exposure to similar substances
• Implement aggregate exposure assessments for classes of chemicals

6. Enhanced Post-Market Monitoring

• Establish a robust system to track adverse effects from food additives
• Require manufacturers to report new safety information
• Develop biomonitoring programs to track population exposure to food chemicals

7. Legislative Reform

• Amend the Federal Food, Drug, and Cosmetic Act to close the GRAS loophole
• Provide the FDA with additional resources for food additive safety review
• Align U.S. food safety standards with more protective international approaches

8. Increased Transparency

• Require public disclosure of all safety data supporting GRAS determinations
• Establish a public comment period for new GRAS notifications
• Create a searchable public database of all substances added to food

These reforms would transform the current GRAS system from a regulatory loophole into a scientifically sound process that ensures all substances added to food are truly safe for consumption.

Conclusion

The GRAS loophole represents a significant gap in the U.S. food safety regulatory system that allows potentially harmful substances to enter the food supply without adequate safety review. The scientific evidence presented in this analysis demonstrates that the current system:

1. Permits inherent conflicts of interest in safety determinations
2. Relies on outdated scientific methods that fail to detect modern concerns
3. Does not adequately protect vulnerable populations, particularly children
4. Allows substances banned in other countries to remain in the U.S. food supply
5. Can delay regulatory action for decades even after safety concerns emerge

The case studies of problematic GRAS substances provide concrete examples of how this regulatory loophole has impacted public health, allowing substances linked to cancer, endocrine disruption, neurodevelopmental issues, and other health concerns to remain in food.

Closing the GRAS loophole through comprehensive regulatory reform is essential to ensure that all substances added to food undergo appropriate safety evaluation and truly meet the standard of “reasonable certainty of no harm.” The proposed reforms would align U.S. food safety standards with more protective approaches used internationally and fulfill the original intent of the Food Additives Amendment to ensure the safety of our food supply.

The scientific evidence is clear: the time has come to close the GRAS loophole and implement a more rigorous, transparent, and protective regulatory framework for food additives.

(This post was made possible with help from Manus AI, for research and clarity.)

References

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