GRAS – FDA’s Most Widely Misunderstood Acronyms - Part 3

GRAS – One of FDA’s Most Widely Misunderstood Acronyms (Part 3)

The third installment of this series addresses the misconception that in order to be designated “GRAS,” a substance must have been extensively tested and definitively proven to be safe. Many substances have been designated GRAS for their intended use(s) based solely on knowledge of their common use in foods prior to 1958. The presumption of safety for such substances is based on the assumption that a history of safe use adequately predicts future safe use provided that the level and type of use remains essentially the same. For these substances, the absence of a safety concern in the past obviates the need for extensive testing.

Many GRAS substances do not, however, have a history of common use in foods prior to 1958 and GRAS status has been affirmed based on “scientific procedures.” In this context, “scientific procedures” refers to human, animal, analytical, and other scientific studies appropriate to establish the safety of a substance. However, even for substance affirmed to be GRAS based on scientific procedures, this does not necessarily mean that a full battery of safety studies has been completed.

Review of the safety assessments made by the Select Committee on GRAS Substances (SCOGS) in the 1970s for substances later affirmed as GRAS, shows that in many cases safety judgments were made in the absence of a complete safety study dataset. In some cases, the design of toxicity studies was not optimal (e.g., incomplete assessment of usual safety endpoints or small numbers of animals). In other cases, some types of safety studies were missing (e.g., the absence of reproduction studies). In fact, some substances were determined by SCOGS not to present a safety risk with little toxicity data on the specific substance. Safety assessments for chemicals with only very limited substance-specific safety studies may have been based on data showing common metabolites with other more fully-studied substances or on known exposures through the diet to the constituents parts of other GRAS substances (e.g., for salts). These types of arguments supporting safety are widely accepted by qualified experts and support the finding that many substances are GRAS. Ultimately, it is the weight of the available evidence that determines whether a substance is GRAS. Many GRAS substances have been extensively studied for safety and that information constitutes the basis for their GRAS determinations. However, it is important to recognize that a GRAS designation does not necessarily mean that a substance has been thoroughly tested for safety.

Posted by Carrie Rabe, Senior Consultant. For more information, please contact Carrie atcarrie.rabe@weinberggroup.com.