Maricel Maffini, consultant and Tom Neltner, Chemicals Policy Director
This blog is the fourth in our Broken GRAS series where we explore the Food and Drug Administration’s (FDA) Generally Recognized as Safe (GRAS) voluntary notification system for novel chemicals added to food, how the process works in practice, and why it is broken. Companies voluntarily submit these notices seeking a “no questions” letter from FDA that makes it easier to market the chemical to food companies.
In our latest blog we address a chemical called “COZ corn oil” developed by the Iowa-based company, Corn Oil ONE. We obtained documents from FDA revealing that the agency twice raised significant concerns about the safety of COZ corn oil with the company, which withdrew its notification without addressing the agency’s questions. As with the other examples in the series, FDA did not make its concerns public or take steps to block the chemical’s use in food.
About COZ corn oil.
The chemical is manufactured from distillers corn oil, a byproduct of ethanol production that is extracted from the mash that remains after corn is fermented into ethanol. The mash can contain antibiotics and other additives. Distillers corn oil is used in animal feed and increasingly as a feedstock for the production of biodiesel. The company said it intended COZ corn oil to be used as a substitute for edible corn oil products. We did not find evidence that it is being use in food, though we cannot rule it out.
First failed attempt.
Corn Oil ONE – then called CoPack Strategies – voluntarily notified FDA in June 2017 that it intended to use COZ corn oil as an edible corn oil because it had determined it was GRAS based on scientific procedures. FDA designated the notification as GRN 704. The company based its conclusion on two unpublished studies performed at the University of Texas A&M and South Dakota State University, as well as a four-member expert panel convened by the company. The universities were asked to compare the overall fatty acid composition and cooking properties of COZ corn oil against a commercially available (Hy-Vee brand) corn oil. The panel unanimously concluded that the intended use of COZ corn oil is GRAS.
After an initial review, FDA scientists identified major deficiencies in the company’s GRAS determination, including missing or inappropriate documentation regarding the chemical composition and manufacturing method of COZ corn oil, as well as the company’s dietary exposure estimate and safety narrative. In short, FDA said Corn Oil ONE based its GRAS conclusion on a comparison of COZ corn oil with conventional corn oil without addressing differences in raw material, manufacturing process, additives used, and potential residues between the two chemicals and how that could affect safety. FDA also raised questions about the qualifications of one of the four members of the expert panel.
By September 2017, the company asked FDA to “cease to evaluate” the notice. This is a common practice companies use to avoid having FDA reject the notice and publicly document its reasoning.
Second failed attempt
Three years later, Corn Oil ONE tried again. It hired Exponent, a consulting firm, to prepare and submit a new GRAS notice (GRN 890). This GRAS determination was based in part on the conclusion of a new three-person GRAS Panel that “critically evaluated” safety documentation prepared by Exponent.
FDA again had numerous questions that we will examine in more detail below. But they cut to the chase when they said: “Please clearly state in your own words your OVERALL CONCLUSION that the COZ corn oil (subject of this GRAS notice) is GRAS for its intended use”. [Emphasis by FDA]
Corn Oil ONE’s answer can be boiled down to: “Well, it’s corn oil.” What the company actually said was slightly more detailed. In its response to FDA, it said that “conventional corn oil has had a long history of dietary exposure with recognized health benefits via an approved qualified health claim. Conventional corn oil is generally recognized as safe (GRAS). As such, COZ corn oil, which is the same as conventional edible corn oil, is also GRAS.”
So many unanswered questions
Three months after the filing of GRN 890, FDA sent the company four pages of toxicology and chemistry questions covering a wide range of issues.
On toxicology, FDA asked Corn Oil ONE to:
- Provide details on the literature search strategy it used to compile the scientific evidence it relied on for its determination, including the timeframe for the search;
- Explain why there would not be adverse health effects from long-term consumption of COZ corn oil. FDA’s review of scientific studies indicated a number of health effects associated with consumption of corn oil, including an association with diabetes, maternal effects such as loss of pups, and other adverse effects in the kidneys, pancreas, and heart; and
- Discuss what information the company used on absorption, distribution, metabolism, and excretion of corn oil to inform its determination that COZ corn oil is safe.
On chemistry, FDA asked the company:
- Whether the processing aids and materials used were suitable for the production of edible oils;
- To provide the regulatory status of chemical additives and processing aids used in raw material production that were listed in the GRAS notice as not having “the appropriate regulatory status,” including the processing agent chlorine dioxide (FermaSure XL), which FDA rejected as an animal food ingredient in 2011;
- Whether antibiotics used to ferment the corn to make ethanol would remain in COZ corn oil and how they would be removed; and
- To provide adequate information on possible pesticide contamination or the levels of mycotoxins in COZ corn oil compared to conventional corn oil and how these contaminants would be removed.
The company answered most of the questions in an 81-page amendment to the notification, but the responses prepared by Exponent generated even more questions from FDA. In a second round, FDA sent a seven-page document with more detailed chemistry and toxicology questions with extensive footnotes and references. The questions made clear that the agency’s scientists continued to have concerns about what antibiotics were used, at what levels, where they remain in the oil, screening protocols, and more.
FDA also noted that Corn Oil ONE “did not respond to our request about the literature search” to support its toxicological findings and did not calculate human exposures from animal doses used in cited scientific publications that indicated adverse effects of corn oil in animal studies.
In response to this second round of questions, Corn Oil ONE on December 15, 2020, once again asked FDA to cease to evaluate its GRAS notice.
While we were unable to confirm that COZ corn oil is being marketed as an edible oil, under the GRAS system there is nothing stopping Corn Oil ONE from doing so if it continues to think it is generally recognized as safe. FDA’s current rules allow the company to rely on its own GRAS determination, despite questions from agency scientists.
Additives rejected by FDA or never reviewed for safety
Other questions raised by agency scientists illustrate the differences between COZ corn oil and edible corn oils. They also show how companies often rely on “secret” GRAS determinations that the FDA has never reviewed.
FDA scientists asked Corn Oil ONE to provide information about chemical additives used to make COZ corn oil that the company listed as not having “the appropriate regulatory status.”
One of the additives was PhibroBreak Corn Oil Additive added directly to the distillers corn oil. Corn Oil ONE said it had relied on a GRAS determination made by the maker of PhibroBreak. It provided FDA with a letter from Phibro Animal Health Corporation, the additive manufacturer, stating that “[a]s part of achieving full regulatory compliance, Phibro sought a rigorous safety review by an independent panel of experts” who concluded the additive was safe for use and could be “properly categorized” as GRAS. This is an example of a secret self-GRAS determination that was not reviewed by FDA.
FDA also noted the use of FermaSure XL (chlorine dioxide), a DuPont processing aid for use “in potable alcohol and fuel ethanol production with resulting distillers’ grains approved for use in animal feed.” In 2011, FDA reviewed a GRAS notification for chlorine dioxide and rejected it, concluding that “[t]he notice does not provide a sufficient basis for a determination that chlorine dioxide is GRAS under the conditions of its intended use in animal food.” FermaSure XL is currently marketed as GRAS despite FDA’s concerns.
What these notices reveal about FDA’s broken GRAS program
The interactions between FDA, Corn Oil ONE, and its consultant Exponent highlight many of the core problems with the broken GRAS system, including how the concept of “general recognition of safety” is often bent to accommodate a company’s pre-conceived ideas. It also raises questions about the quality of the GRAS determinations done by hired consultants who often fail to convince FDA scientists when notifications are voluntarily submitted.
Finally, it also shows agency scientists asking good questions to help ensure products that reach grocery shelves are safe. Unfortunately, FDA’s GRAS system fails to ensure those questions are answered and the products are not used in food.