Generally Recognized As Safe (GRAS) is a regulatory designation under the U.S. Federal Food, Drug, and Cosmetic Act that exempts certain food substances from premarket approval by the FDA, provided there is consensus among qualified experts that the substance is safe under its intended conditions of use.
A substance can achieve GRAS status through two pathways: scientific procedures based on published safety data, or through experience based on common use.
Required evidence includes the substance’s identity and specifications, absorption and metabolism data, and depending on the level of concern, toxicology studies covering genotoxicity, acute and subchronic toxicity, reproductive toxicity, and carcinogenicity.
The safety standard for GRAS substances: reasonable certainty of no harm—is identical to that required for food additives requiring premarket approval.
Since 1997, FDA has operated a voluntary GRAS notification program where manufacturers can submit their safety determinations for agency review.
However, manufacturers are not required to notify FDA of GRAS determinations, and many substances are self-determined as GRAS without FDA awareness.
The GRAS process has faced criticism regarding conflicts of interest in expert panels and FDA’s lack of awareness about all GRAS substances in the food supply.
Current evidence indicates significant safety concerns and regulatory gaps regarding self-affirmed GRAS substances, especially those not reviewed by the FDA, with potential public health implications.
Most GRAS determinations are made by manufacturers or their consultants, often without FDA notification or independent review.
Conflicts of interest are widespread, as expert panels are frequently composed of individuals with financial ties to the manufacturer, and a small group of consultants repeatedly serve on panels, undermining the credibility and objectivity of safety assessments.
The FDA’s voluntary notification system means the agency is often unaware of which substances are in the food supply, in what quantities, or their cumulative exposure risks.
Some GRAS substances—including endocrine-disrupting chemicals and additives with limited toxicity data have been linked to adverse effects, especially in vulnerable populations like children.
The current GRAS process does not require robust testing for long-term toxicity, carcinogenicity, or endocrine disruption, and the FDA lacks authority to routinely reassess previously approved or self-affirmed GRAS chemicals.
This regulatory gap is particularly concerning given the large number of GRAS substances in the food supply and the absence of mandatory notification or post-market surveillance.
The persistence of conflicts of interest, lack of mandatory FDA review, and insufficient data requirements have led to calls for reform, including mandatory notification, independent safety review, and enhanced post-market oversight.
The safety of self-affirmed GRAS substances remains uncertain, and public health may be at risk, especially for children and other sensitive groups.