Natural Standard Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
Dietary supplements, Federal Food, Drug, and Cosmetic Act, FDA, FFDCA, food additives, food safety, United States Food and Drug Administration.
Generally Recognized as Safe (GRAS) is a designation created by the U.S. Food and Drug Administration (FDA) in 1958 under the Federal Food, Drug, and Cosmetic Act (FFDCA). This act defines food additives as any substances intentionally added to food and states that food additives (with some exceptions) must be reviewed and approved by the FDA.
In the 1970s, the FDA developed the GRAS affirmation petition process to update the program, but funding difficulties developed. In 1997, the FDA proposed replacing the affirmation petition process with the GRAS notification program. Since then, FDA-approved food additives have been distinguished from GRAS substances based on the availability of pertinent substantive information to the public and its broad acceptance by qualified experts.
Substances used as pesticides, ingredients of dietary supplements, color additives, new animal drugs, or substances commonly used before the instatement of the FFDCA in 1958, are not considered food additives and do not need FDA approval. A substance may be exempt from these requirements and granted GRAS status if qualified experts have recognized that the substance, under the conditions of intended uses, has been shown to be adequately safe, or if the substance does not fall under the definition of a food additive.
The FDA defines "safe" as reasonable certainty amongst competent scientists that the substance in question will not be harmful, provided it is used as intended. Demonstration of safety depends on data regarding the characteristics of the substance and the consumer population for every category in which the substance will be used in the intended quantity. A long history of use in foods may be used to corroborate this data.
The list of GRAS additives is not all-inclusive and has not been recently updated.
The FDA makes clear that a substance is granted GRAS status based on widespread acceptance of its safety by qualified experts. GRAS status is not recognized outside of the United States.
Gras Affirmation Petition Process
The GRAS affirmation petition process was developed in response to concerns about the effects of cyclamate salts (no longer added to foods). President Nixon directed the FDA to reevaluate all substances that were considered GRAS according to the original 1958 law that established GRAS. The FDA found need to reevaluate these substances using contemporary standards and new information. Thus, new GRAS regulations were created, along with a process for individuals to request evaluation of a substance.
Unfortunately, the process was lengthy and complicated. As a result, not all manufacturers chose the process, and "safe" became more of an industry standard than an FDA status. Funding difficulties created additional complications, which led to an interim policy known as the GRAS notification program, pending final ruling.
Gras Notification Program
In 1997, the FDA proposed replacing the GRAS affirmation petition process with the GRAS notification program. Although the FDA has yet to issue a final ruling on this proposal, the notification program is currently in use, while the affirmation petition process remains a part of FDA regulations.
Under the GRAS notification program, an individual may inform the FDA that a specific use of a substance has been determined to be GRAS, instead of following the petition process and waiting for FDA affirmation. A GRAS notification consists of a "GRAS exemption claim," including a description of the substance, the applicable conditions of use, and the statutory basis for GRAS status. Notification must also include information about the identity and properties of the substance, as well as a discussion of how the substance was determined to be safe. The FDA's goal is to address notifications within 180 days, but is not bound to do so.
Types of Gras Status
There are currently three types of GRAS status:
Self-affirmed: The organization that manufactures the chemical or substance has performed all of the necessary research and is prepared to defend the GRAS status of their product based on this information. This includes the formation of an expert panel to review any and all safety concerns.
FDA-pending: The organization that manufactures the chemical or substance has performed all necessary steps and has submitted this information to the FDA for GRAS approval. Manufacturers may market their products before they have been accepted for GRAS status but at their own legal risk.
No comment: The FDA has reviewed the GRAS claim and granted GRAS status.
There are currently five GRAS conclusions, defined by the FDA as follows:
1: There is no evidence in the available information on the given chemical or substance that demonstrates or leads the FDA to suspect a hazard to the public when used at current levels or levels that might reasonably be expected in the future.
2: There is no evidence in the available information on the given substance that demonstrates a hazard to the public when used at current levels and in the manner now practiced. However, more data is needed to determine whether a significant increase in consumption would constitute a dietary hazard.
3: While there is no evidence in the available information, the given substance demonstrates a hazard to the public when used at current levels in the manner now practiced, uncertainties exist, and additional studies should be conducted.
4: The evidence on the given substance is insufficient to determine that the adverse effects reported are not deleterious to the public health when used at current levels and in the manner now practiced.
5: There is insufficient data upon which to evaluate the safety of the given substance for the intended use.
GRAS status of a substance may change over time. There are currently three GRAS lists currently in use:
21 CFR Part 182: Includes substances from the original GRAS list, which the FDA created soon after the passage of the GRAS exemption amendments to the Food Additives Amendment in 1958.
21 CFR Part 184: A sub-list of substances on the original GRAS list that have been reevaluated and affirmed as safe.
21 CFR Part 186: Substances that the FDA approved for indirect food use, such as GRAS preservatives.
Gras Versus Fda-Approved Designation
FDA-approved substances are evaluated based on privately-held information. This information is sent directly from the sponsor to the FDA for evaluation, which takes about 24 months for a final ruling. Food additives may not be marketed until they have been officially approved. The FDA can also stop distribution of any food substance and any foods that contain a particular substance on the grounds that such foods are unlawful or contain an unlawful food additive.
In contrast, information used to determine GRAS status is available to the public. The safety of GRAS substances must be corroborated by the same quantity and quality of scientific evidence as an FDA-approved food additive, but GRAS status is generally based on published studies. These studies may be supported by further unpublished data, but GRAS status is reliant upon widespread awareness of this information and a general consensus among qualified experts.
Unlike in the case of food additives, manufacturers of GRAS substances may choose to market their product without FDA affirmation of safety, at their own legal risk.
Limitations With Gras
GRAS status is intended only for substances that are considered safe when ingested. It does not indicate that a substance is safe if it enters the body in another manner, such as through the skin, respiratory system, or nervous system, all of which are primary exposure pathways for many products.
Substances are granted GRAS status only on the basis of their intended uses; all other uses of these substances may or may not be harmful and require separate review. For example, a sweetener such as tagatose, which received GRAS status in foods in 2001, needed separate review to obtain GRAS status as a sweetener in toothpaste and mouthwash, and other cosmetic products.
The GRAS list may be misleading, because a substance could be GRAS even if it is not listed by the FDA. Much more scientific data has become available since enactment of the FFDCA, which has raised questions about some substances once considered safe. Many substances with questionable safety remain on the GRAS list and continue to be used in the food and fragrance industries, sometimes listed as "flavoring" on product labels.
The original GRAS list recognizes that there are many food substances, such as salt and sugar, with a historical record of safety.
The current GRAS process allows for new additives and substances to be vetted under current science standards for safety assurance. However, there are concerns that because the GRAS process is long, industry members sometimes choose to market products without GRAS status.
GRAS status does not indicate that the substance will not cause an allergic reaction.
If consumers use products containing GRAS substances in greater amounts than intended, it is possible that they may experience a number of undesired effects, including toxicity, as well as interactions with foods, herbs, dietary supplements, and medications.
GRAS status does not assure safety or clinical efficacy of any substance, including those used in herbal products and dietary supplements.
GRAS status is not comprehensive; therefore, it does not indicate that a substance that is safe in one product is safe in all circumstances. For example, a GRAS ingredient that may be safe for the general public may be unsafe in infant formula, where it is consumed in large quantities and as the mainstay of a baby's diet.
Some GRAS substances long considered safe, are currently challenged in light of new or accumulated scientific evidence. For example, in late 2007, The Center for Science in the Public Interest and the American Medical Association questioned the safety of consuming salt (which has GRAS status) in certain quantities. Additional research may be needed to further clarify GRAS status for certain substances.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Burdock GA, Carabin IG. Generally recognized as safe (GRAS): history and description. Toxicol Lett. 2004 Apr 15;150(1):3-18. View Abstract
Food and Drug Administration (FDA). www.fda.gov.
FDA Center for Food Safety and Applied Nutrition. www.cfsan.fda.gov.
Levin GV. Tagatose, the new GRAS sweetener and health product. J Med Food. 2002 Spring;5(1):23-36. View Abstract
Copyright © 2013 Natural Standard (www.naturalstandard.com)
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
March 22, 2017