NRDC report APRIL 2014 r:14-03-a Generally Recognized as Secret: Chemicals Added to Food in the United States Authors: Tom Neltner, J.D. Maricel Maffini, Ph.D. Natural Resources Defense Council Executive Summary W hen President Eisenhower signed the Food Additives Amendment of 1958, he established a regulatory program intended to restore public confidence that chemicalsa added to foods are safe. In the intervening 56 years, the basic structure of the law has changed little. However, the regulatory programs the U.S. Food and Drug Administration (FDA) established to implement the law have fallen behind over time as the agency strived to keep up with the explosion in the number and variety of chemicals in food, and to manage its huge workload with limited resources. The 1958 law exempted from the formal, extended FDA on undisclosed GRAS safety determinations. This is likely the approval process common food ingredients like vinegar tip of the iceberg—we previously published in an industry and vegetable oil that are “generally recognized as safe” journal an estimate that there have been 1,000 such secret (GRAS). It may have appeared reasonable at the time, but GRAS determinations.1 For each chemical we identified in that exemption has been stretched into a loophole that has this study, we did not find evidence that FDA had cleared swallowed the law. The exemption allows manufacturers to them. make safety determinations that the uses of their newest In addition, using the Freedom of Information Act (FOIA), chemicals in food are safe without notifying the FDA. we obtained from the FDA copies of communications The agency’s attempts to limit these undisclosed GRAS between the agency and companies who voluntarily sought determinations by asking industry to voluntarily inform agency review of their GRAS determinations. We found the FDA about their chemicals are insufficient to ensure this glimpse into the review process shows that often the the safety of our food in today’s global marketplace with agency has had serious concerns about the safety of certain a complex food supply. Furthermore, no other developed chemicals, and that companies sometimes make safety country in the world has a system like GRAS to provide decisions with little understanding of the law or the science. oversight of food ingredients. As discussed later, companies found their chemicals safe Because of the apparent frequency with which companies for use in food despite potentially serious allergic reactions, make GRAS safety determinations without telling the FDA, interactions with common drugs, or proposed uses much NRDC undertook a study to better understand companies’ greater than company-established safe doses. rationale for not participating in the agency’s volutnary On those occasions when the FDA is asked to review notification program. First, we built a list of companies a GRAS determination, the agency rejects or triggers and the chemicals they market. Then we reviewed public withdrawal of about one in five notices. Moreover, the public records, company websites, and trade journals to identify has even less information about the many substances with additives that appear to be marketed in the U.S. pursuant to GRAS determinations that are never submitted to the agency an undisclosed GRAS determination, i.e. without notification in the first place—and which may pose a much greater to the FDA. danger. It is often virtually impossible for the public to find All told, we were able to identify 275 chemicalsa from 56 out about the safety—or in many cases even the existence— companies that appear to be marketed for use in food based of these chemicals in our food. “Generally Recognized as SECRET” rather than “Generally Recognized as SAFE” is a better name for the GRAS loophole that has allowed manufacturers to sanction the use of hundreds of chemicals in food that Americans eat every day. a We use the term “chemicals” to apply to the products sold by additive manufacturers. They may be individual substances or mixtures of substances. They are sometimes referred to as substances, additives, or ingredients, which, in reality, are all chemicals or mixtures of them. They may be extracted from natural products or synthesized from other chemicals. | PAGE 2 Generally Recognized as Secret: Chemicals Added to Food in the United States “We cannot require anything, as this is a voluntary program and we don’t want to frighten anyone away. Having said that, we would typical [sic] tell any notifier that their submission would have to address the total dietary exposure from new and current uses, [h]ow else could you conclude that the uses were safe, without a notion of what total exposure is[?]”2 FDA reviewer of GRAS determination submitted by manufacturer NRDC believes that “Generally Recognized as SECRET” Cosmetic Act to address these concerns.4 The law presumed rather than “Generally Recognized as SAFE” is a better that a chemical intentionally added to food was potentially name for the GRAS loophole. A chemical additive cannot unsafe and required that no chemical be used without a “reasonable certainty in the minds of competent scientists be “generally recognized as safe” if its identity, chemical that the substance is not harmful under the intended composition, and safety determination are not publicly conditions of use.”5 Congress required food companies to file disclosed. If the FDA does not know the identity of these a “food additive petition” as the primary means by which to chemicals and does not have documentation showing that get an FDA approval of a chemical’s use in food. If the agency they are safe to use in food, it cannot do its job. did propose to approve the chemical, it would inform the In an increasingly global marketplace where many public and request comments before adopting a regulation additives and foods are imported into the United States, this allowing the use.6 The system was designed at a time when an loophole presents an unsettling situation that undermines estimated 800 chemical additives were in use, far fewer than public confidence in the safety of food and calls into question the more than 10,000 allowed today.7,8 whether the FDA is performing its duty to protect public health. “The next day, [notifier] called and asked The problem is rooted in a law adopted in 1958 when Dwight Eisenhower was president and Elvis was drafted. It whether [notifier] would have an option to is time for the FDA and Congress to fix the problems. In the withdraw the notice rather than receive meantime, consumers need to demand that their grocery a letter that the notice did not provide a stores and their favorite brands sell only those food products basis for a GRAS determination. I replied with ingredients that the FDA has found to be safe. that this was an option. On September 4, [notifier] asked whether [notifier] could still sell its [name] product if it withdrew its GRAS: HOW THE LOOPHOLE GRAS notice. Consistent with my response SWALLOWED THE LAW to her earlier question about marketing Over the last five years, there have been many news stories [name], I said yes.”9 about unsafe foods that have sickened people. There have FDA officer summarizing telephone conversations with manufacturer regarding its GRAS notice review been a few reports of acute health problems related to chemicals added to foods, such as energy drinks containing a mixture of caffeine and alcohol, or rice with excessive Determining that a chemical’s use in food is and remains amounts of the vitamin niacin. But chemicals added to safe typically involves significant professional judgment. food are more likely to be associated with health problems Rarely are these decisions clear cut; there is no bright line. that may appear after years of frequent food and beverage So who decides is critical. Congress concluded that the FDA consumption. These problems are often chronic in nature. would make all safety decisions, except in the most obvious The FDA is unlikely to detect an adverse health effect (short situations in which a chemical’s use in food was “generally recognized as safe.” This is known as the GRAS exemption. of immediate serious injury) unless companies notify it about Examples include such common food ingredients as oil the chemical and its use in food. and vinegar. When a chemical’s use was determined to be That is why Congress required that a chemical’s intentional GRAS, the FDA did not need to adopt a regulation specifically use in food be determined to be safe prior to its entering allowing its use, and the formal public notice and comment the marketplace.3 In 1958 President Eisenhower signed the rulemaking process was not required.10 In other words, the Food Additives Amendment to the Federal Food Drug and | PAGE 3 Generally Recognized as Secret: Chemicals Added to Food in the United States chemical didn’t need premarket approval by the agency, In 2010, the Government Accountability Office (GAO), the and manufacturers could use it without delay. To qualify as nonpartisan investigative arm of Congress, scrutinized the GRAS, a chemical’s safety had to be generally recognized by agency’s GRAS program and found serious shortcomings. It knowledgeable scientists, as borne out by published safety concluded that “FDA’s oversight process does not help ensure studies unless commonly and safely used before 1958.11 the safety of all new GRAS determinations” and that “FDA is However, the FDA and the food industry interpreted the not systematically ensuring the continued safety of current law as allowing manufacturers to determine that a chemical’s GRAS substances.”19 use in food was safe without notifying the agency.12 As a Given these concerns, NRDC sought to identify examples result, the identity of the chemical and the foods in which of chemicals marketed pursuant to undisclosed GRAS safety it was being used could be unknown to the public and the determinations, procure such safety determinations from agency. Since 1958, an estimated 1,000 chemicals have been companies, and examine why companies choose to forgo determined as GRAS by manufacturers and have been used even the voluntary FDA notification process. in food without any approval or review by the FDA.13 The exemption has become a loophole that has swallowed the law. CLAIMING GENERAL RECOGNITION WHILE AVOIDING THE FDA’S ATTEMPTS TO DISCLOSURE LIMIT UNDISCLOSED INDUSTRY SAFETY DECISIONS As mentioned above, some 1,000 chemicals have been determined by manufacturers to be safe for use in food without FDA review or approval. Some of them, like artificial Recognizing the problem of undisclosed safety decisions, trans fat, were self-certified by industry as safe ingredients the FDA adopted regulations in 1972 inviting manufacturers decades ago and are well known. to voluntarily submit “GRAS affirmation petitions” in a NRDC’s investigation focused on newer, less known rulemaking process that was similar to the one for food chemicals marketed as GRAS for use in food in the United additive petitions, but without statutory deadlines for States since 1997. We looked at situations in which: action.14 Companies sought FDA’s approval, it appears, n t he manufacturer opted to rely on an undisclosed because their product would be more widely accepted by GRAS determination, without using the FDA’s voluntary food manufacturers. notification process; By the early 1990s, confronted with limited resources and n t he manufacturer notified the FDA, and the agency an increasingly complicated and time-consuming formal rulemaking process, the FDA faced an overwhelming backlog subsequently rejected the company’s GRAS notice; of unresolved reviews.15 In response, the agency proposed a n t he manufacturer notified the FDA but subsequently rule in 1997 to replace the 1972 GRAS petition process with withdrew its notice from FDA review. (We will discuss the a less formal review process that did not involve adopting problems with withdrawal of notices later.) regulations for specific chemicals.16 The next year, the FDA began accepting voluntary notifications from the companies that summarized the safety evidence and issuing decision Our investigation began with a list of companies and letters.17 In some cases, these decision letters are often cited chemicals from three sources: by the companies as evidence of FDA clearance, although n t he little-known (outside of the food additives industry) the agency maintains that the letters are informal and do not web-based “GRAS Self-Determination Inventory constitute approval. This process, however, largely cuts the Database,” compiled by a consulting firm that makes GRAS public and outside experts out of meaningful participation in safety determinations for industry;20 decision making. The proposed rule has never been finalized n c  onsultants who provided company names based on their despite its wide use by industry and the FDA.18 Since 2000, almost all new chemicals have passed through the loophole experience at food industry trade shows; rather than being subjected to the food additive petition n w  ithdrawn or rejected notices in FDA’s GRAS Notice process established by Congress in 1958. Inventory.21 | PAGE 4 Generally Recognized as Secret: Chemicals Added to Food in the United States Overall, we identified 398 chemicals marketed by 163 undisclosed safety determination. If the company declined companies that appear to be marketed in the U.S. based on or did not respond to our request, we classified the GRAS GRAS determinations not reviewed by FDA.b determination as “undisclosed”. Also, if the company did not For each chemical, we sought a copy of the written provide us with a revised GRAS determination that addressed documentation of the GRAS safety determination required by the FDA’s concerns after the agency rejected the company’s FDA’s regulations (21 CFR §170.30), which companies must notice, or if the company withdrew its notice before the have completed before marketing a product as GRAS. This agency made a final decision, we considered the GRAS documentation must provide the chemical composition of determination to be undisclosed. the substance, describe how it is made, estimate how much people are likely to consume (exposure), and describe what is known about the chemical’s potential hazards. Unless “Generally Recognized as Secret” a chemical was commonly and safely used before 1958, All told, 56 companies appear to rely on undisclosed GRAS the key studies evaluating the hazards ordinarily must be safety determinations for 275 chemicals (Figure 1): published, preferably in a peer review journal but the FDA n 3  5 companies selling 57 chemicals responded to does not exclude publication on a company’s website. While identifying a key study is helpful, it is not a substitute for our inquiries, but did not provide their GRAS safety providing the full safety determination. determination (Table 1). Where a company appeared to be marketing a chemical n 2  1 companies selling 218 chemicals did not respond for use in the United States as GRAS without final FDA review, to our repeated inquiries (Table 2). NRDC contacted the company to request a copy of the Figure 1: Process to Identify and Evaluate Companies and Chemicals Identified 163 Concluded that companies and determinations by 107 398 chemicals companies for 123 chemicals Not found to be from 3 resources: undisclosed were undisclosed because: n w  ww.aibmr.com n P  roduct appears not to be (94 companies, used in food: 50 companies 134 chemicals) for 60 chemicals n C  onsultants Research n F  DA appears to have reviewed chemicals (3 companies, or approved: 54 companies 193 chemicals) for 61 chemicals n N  otices to the FDA n C  ompany provided GRAS that were withdrawn determination: 3 companies or rejected for 3 chemicals GRAS (66 companies, determination 71 chemicals) was undisclosed undisclosed GRAS determinations made by 56 companies for 275 chemicals n Provided n Offered to provide n Provided links n Initially responded n Never responded only assurances if NRDC to published studies: but no follow- to NRDC’s requests: of safety: kept confidential: 7 companies through: 21 companies 13 companies 4 companies for 7 chemicals 11 companies for 218 chemicals for 32 chemicals for 5 chemicals (Table 1) for 12 chemicals (Table 2) (Table 1) (Table 1) (Table 1) b Where chemicals had similar names but different manufacturers, we treated them as separate chemicals. | PAGE 5 Generally Recognized as Secret: Chemicals Added to Food in the United States Table 1: Companies with undisclosed GRAS determinations that responded to NRDC No. of Declined Only if Only Gave No Company Country Chemicals Requests Confidential Studies Follow-up Albion USA 2 Yes Yes Aloecorp Korea 1 Yes BASF Germany 2 Yes BioCell Technology USA 1 Yes Bioriginal Canada 1 Yes Yes Yes ChromaDex USA 1 Yes Cyvex Nutrition USA 3 Yes DSM Netherlands 8 Yes Embria Health Sciences USA 1 Yes ESM Technologies USA 1 Yes Yes Frutarom Health Israel 1 Yes Genosa Spain 1 Yes GTC Nutrition USA 1 Yes HG&H Pharmaceuticals (Pty) Ltd. South Africa 1 Yes House Wellness Foods Japan 1 Yes InterHealth Nutraceuticals USA 4 Yes Ixoreal Biomed India 1 Yes Jungbunzlauer Switzerland 1 Yes Kaneka Japan 1 Yes Yes Kemin USA 1 Yes Lonza Switzerland 1 Yes Merck Eprova AG Germany 1 Yes Yes NattoPharma Norway 1 Yes NuLiv Science USA 1 Yes Yes NutraGenesis USA 4 Yes P.L. Thomas USA 1 Yes PhenoFarm Italy 1 Yes RIBUS USA 1 Yes Sabinsa Corporation USA 5 Yes SoluBlend Technologies USA 1 Yes Yes Stepan Netherlands 1 Yes Trace Minerals Research USA 1 Yes Yes TSI Health Sciences USA 1 Yes Yes Unibar USA 1 Yes Verdure Sciences Trim USA 1 Yes Yes Totals 35 companies 57 24 4 7 11 | PAGE 6 Generally Recognized as Secret: Chemicals Added to Food in the United States The 35 companies that responded but did not provide us with their GRAS determinations fit into the following four WHY DID COMPANIES FORGO categories: FDA REVIEW? n 1  3 companies provided us only with assurances that their chemicals were safe and complied with the law. About 20 companies provided explanations for why they n 4  companies were willing to share the documentation only decided not to submit a voluntary notification to the FDA. if NRDC signed a confidentiality agreement, which we These can be distilled into the following categories: declined to do. n C  oncerns about too much FDA transparency. The most n 7  companies declined to provide the GRAS determination common concern was the FDA’s routine posting of GRAS but identified a published toxicology study that supported safety determinations to its website. These companies said their analysis without providing the additional information they were worried that easy access to information about such as exposure calculations and product composition product composition and the manufacturing process needed to evaluate the safety. would enable competitors to develop identical or similar chemicals and would simplify the competition’s own GRAS n 1  1 companies acknowledged the inquiry but did not follow determinations. through. n C  oncerns about FDA delays. Several companies claimed The remaining 107 companies selling 123 chemicals fell they did not want to wait for the FDA to make a decision, into three general categories: even though the agency explicitly allows the use and n 5  0 companies did not appear to market their chemicals marketing of a chemical while a review is under way. for use in food in the United States.c n 5  4 companies that withdrew notices to the FDA later submitted revised notices and received a final review “In other words, if a panel of experts by the agency confirming product safety. reviews data that are not publicly available n 3  companies provided NRDC with a copy of their GRAS and subsequently renders an opinion determination without requiring confidentiality. regarding safety, even if the experts are Figure 2 summarizes our findings. Of the 163 companies we reviewed, 56, or 34 percent, appear to rely on undisclosed well-recognized, the opinion does not meet GRAS determinations. the general recognition of safety for GRAS ingredients because the data were not UNDISCLOSED SAFETY Determinations: publicly available.”23 Not just U.S. Companies FDA reviewer of GRAS notice As stated earlier, no other developed country in the world has a system like GRAS for food ingredients.22 On the basis of each company’s website and communications, NRDC identified the home country of the 56 companies with undisclosed GRAS determinations. See Tables 1 and 2. Figure 3 provides the results by region. Fifty-six percent of the companies are from the United States, and 44 percent are based outside the country. This distribution is similar to what one might see at a typical food expo. c Either these chemicals appear to be used only in dietary supplements and not food, or we could not find an active website for the company or the chemical, or the chemicals appear to be marketed only overseas. | PAGE 7 Generally Recognized as Secret: Chemicals Added to Food in the United States n Desire to keep investment low. Submitting a GRAS Figure 2: Undisclosed vs. Resolved GRAS Determinations determination to FDA typically means additional work whether by company employees or a consultant doing the analysis. The agency asks many questions that must be answered. Often there are meetings with the agency. We found that almost all of the chemicals NRDC reviewed were also ingredients in dietary supplements and UNDISCLOSED 34% 66% RESOLVED served no essential purpose in food other than to attract consumers’ attention. Several companies indicated that a GRAS determination sometimes is done in connection with a test of the food market for a chemical previously used only as a dietary supplement ingredient, thus minimizing the investment in an unproven market by opting out of the FDA review process. n Wish to avoid new dietary ingredient review: The Dietary Supplement Health and Education Act of 1994 (DSHEA) requires manufacturers to notify FDA about dietary ingredients that either were not on the market before 1994 or whose use in food is not GRAS. Several dietary supplement manufacturers appear to be making a GRAS determination to avoid having to notify the FDA under both DSHEA and the Food Additives Amendment of 1958. Figure 3: Undisclosed GRAS Determinations by Company’s Region n Misunderstanding of the law: Some companies apparently did not understand the requirements for a OTHER GRAS determination. It appears that they did not realize that the determination must be written, that safety information must be drawn from published scientific 7% studies, or that “generally recognized as safe” means more than obtaining the opinion an employee or consultant. Others apparently believed that an independent panel ASIA 19% of experts was required even though the FDA states that UNITED no panel is needed.24 Finally, some companies appeared 56% STATES not to understand the difference between an efficacy study, which determines whether a chemical is effective in addressing a health problem, and a toxicology study, which evaluates whether a chemical may cause harm. The 18% EUROPE scope of most efficacy studies falls far short of an adequate toxicology study. | PAGE 8 Generally Recognized as Secret: Chemicals Added to Food in the United States FDA REVIEWS OF NOTICES The FOIA documents reveal that the FDA does carefully review the notifications and asks tough questions. The REVEALED TROUBLING RISKS agency’s reviews often raise serious safety concerns or reveal that the company’s scientific analysis is flawed or inconsistent with the law. Often the FDA tells the company As described earlier, companies may voluntarily submit that it will reject a notice if it is not voluntarily withdrawn. GRAS notices (which contain the GRAS safety determination) If rejected, food manufacturers would be more reluctant to to FDA seeking the agency’s agreement with their safety buy the product since FDA posts its rejection letter and its determination, and when they do, the agency posts these reasoning on its website. notices on its website. We reviewed the quality of the The following are examples of four withdrawn industry’s notices and identified three, still under review by GRAS notices and our summary of the back-and-forth the FDA as of September 2013 (listed as “pending” on the communications between the FDA and manufacturers. FDA site), that appeared to be poorly done. They were GRN Despite the safety concerns, these chemicals have been No. 466 for polyglycerol polyricinoleic acid by McCormick listed as an ingredient in some food products: and Co., GRN No. 471 for annatto seed extract by DeltaGold, and GRN No. 474 for Bioperine by Sabinsa Corp.25,26,27 All three Epigallocatechin-3-gallate (EGCG): had the same weaknesses: limited toxicology data, poor or A Japanese company declared this chemical to be GRAS for inadequate exposure assessment, and lack of consideration use in beverages including teas, sport drinks, and juices, of children’s exposures. For each we submitted to the FDA despite evidence it may cause leukemia in fetuses based on detailed comments on the shortcomings of the safety studies using newborn and adult human cells grown on a determinations.28 See www.nrdc.org/food/safety-loophole- dish.31 Moreover, the company did not address a short-term for-chemicals-in-food.asp. study on rats showing it affected the thyroid, testis, spleen, If the FDA rejects a GRAS notice, it explains its safety pituitary, liver, and gastrointestinal tract. The notice did concerns in a letter to the company and publishes the letter not explain potentially dangerous interactions with sodium on the agency’s website. But when a company withdraws nitrite, a common preservative, or with acetaminophen a notice and asks FDA to stop further review, the agency (the active ingredient in Tylenol® and many other over the issues a letter confirming the withdrawal without publicly counter pain-killers).32 The company withdrew the notice, explaining any of the concerns that could have prompted the resubmitted it, but withdrew that one as well.33 In response to withdrawal. The withdrawal does not prevent the company our inquiries, the company assured us it was not marketing from continuing to market the product for use in food. the product in the United States. However, two other Between 1998 and the end of February 2014, the FDA companies, DSM and Kemin, appear to market chemicals rejected 17 out of 466 notices submitted to the agency; high in EGCG in the United States pursuant to undisclosed another 32 are still pending. During that time, 80 notices were GRAS determinations (Table 1). We identified more than 25 withdrawn by the companies. For notices no longer pending, food products with EGCG as a named ingredient. one out of five were either withdrawn or rejected.29 After analyzing the poor quality of notices and the number of withdrawn notices, NRDC filed a FOIA request Gamma-amino butyric acid (GABA): for communications between the FDA and manufacturers A Japanese company declared this neurotransmitter to be for 20 GRAS notifications. We chose notices for chemicals GRAS for use in beverages, chewing gum, coffee, tea, and whose use in food we were able to document through a candy.34 It did so despite having estimated exposure well commercial database30 that provides product information in excess of what the company considered safe, relying on for more than 200,000 food products; and the notices were unpublished safety studies, providing the specifications in submitted throughout the length of the program, starting Japanese, and failing to consider existing exposures.35 The in 1998. Sixteen of these notices were withdrawn, several company told NRDC that it withdrew the notice “from a of them multiple times. Although interested primarily in business perspective” and was selling the product in the understanding what concerns raised by FDA prompted United States only as an ingredient in a dietary supplement. manufacturers to ask the agency to stop reviewing the It also indicated that it would not use the chemical in food notices, we also included two notices that the agency rejected without an FDA final review. We identified five food products and two that FDA accepted as sufficient, issuing what is with GABA as a named ingredient. These products included known as a “no questions” letter. To see the FDA’s FOIA bottled tea and nutrition bars. response, go to www.nrdc.org/food/safety-loophole-for- chemicals-in-food.asp. | PAGE 9 Generally Recognized as Secret: Chemicals Added to Food in the United States Sweet lupin protein, fiber, and flour: Table 2: Companies with undisclosed GRAS determinations An Australian firm declared these chemicals to be GRAS that did not respond to NRDC* for use in baked goods, dairy products, gelatin, meats, and No. of candy, despite concerns that the chemicals would cause Company Country Chemicals allergic reactions in those with peanut allergies.36 The ADM USA 1 FDA noted that a warning label for sweet lupin would be AHD International USA 1 insufficient to alert consumers who suffered from peanut allergies.37 The company did not respond to our inquiries and Ametis JSC Russia 1 we could not find evidence that the company was marketing Applied Food Sciences USA 2 the product in the U.S. However, sweet lupin was a listed CBC Group USA 1 ingredient in more than 20 food products, none of which Davos Life Sciences Singapore 1 appear to bear any warning to those allergic to peanuts. FutureCeuticals USA 1 Theobromine: Gencor Pacific USA 1 A U.S. firm declared it to be GRAS for use in bread, cereal, Hamari Chemicals Japan 1 beverages, chewing gum, tea, soy milk, gelatin, candy, and Hanzhong TRG Biotech China 32 yogurt and fruit smoothies, despite having an estimated consumption rate more than five times the safe consumption Horizon Science USA 1 level reported by the company’s consultant.38 In addition, the Kyowa Hakko USA 2 manufacturer did not provide convincing explanations for Laurus Labs India 1 the testicular degeneration in rats and rabbits and delayed Naturex Canada 4 bone formation in rats that were seen in animal studies of Nexira France 1 theobromine.39 The FDA was especially concerned that the product would be used in baby food.40 The company did NutraMax China 154 not respond to our inquiries. Although we don’t know the Oxis International USA 1 provider, theobromine was a named ingredient in more than Skyherb China 7 20 food products, including isotonic waters, nutrition bars, Terry Laboratories USA 1 and diet foods. Fortunately, from what we could tell, none appeared in baby food. Triarco Industries USA 2 Ventria Bioscience USA 2 Totals 21 companies 218 chemicals The evidence from these FOIA responses makes it clear: the FDA’s review adds value, and many companies’ GRAS *In each case, we confirmed that we had either a: 1) confirmation from the company’s safety determinations are seriously flawed. The agency website that the webform was accepted; or 2) valid email address from website because we did not get a notice from the company’s email server that the email had should make its concerns publicly available when companies bounced or was not deliverable. withdraw their notices. Chemicals that, at least in some instances, prompted the FDA to raise safety concerns are used as ingredients in our food supply, and consumers are unprotected from their health effects. | PAGE 10 Generally Recognized as Secret: Chemicals Added to Food in the United States MANY GRAS CHEMICALS THE SYSTEM IS BROKEN AND BEGAN AS DIETARY PLAGUED WITH CONFLICTS SUPPLEMENT INGREDIENTS OF INTEREST Most of the GRAS chemicals NRDC examined were primarily When the FDA reviewed GRAS determinations made by marketed as “active” ingredients in dietary supplements. The manufacturers, the agency found flaws with one in five, availability of the GRAS loophole allows for the expansion of based on the number of notices rejected or withdrawn prior the market for such into conventional foods with claims that to a final decision.44 These notices presumably were those they made food “better for you.” The chemicals were often in which the manufacturer’s had the most confidence, since extracts of plants or highly purified or synthetic versions of the manufacturers voluntarily submitted them for agency the biologically active chemicals in those extracts, such as scrutiny. antioxidants, which were purported to have possible health Food manufacturers are ultimately responsible for the benefits. safety of the food they make. However, in today’s highly Since the Dietary Supplement Health and Education Act of competitive global marketplace, there are strong economic 199441, when Congress created separate, less rigorous safety incentives to minimize expenditures, which may lead to standards for dietary supplements under DSHEA, there has insufficiently-justified decisions. Our understanding of the been an explosion of these products. Ingredients allowed in health effects of many of the more than 10,000 chemicals dietary supplements are not necessarily safe when used in allowed in food is far from complete, and as the number conventional food. grows over time, concerns grow as well. For example, some A product may be a natural extract or a highly purified manufacturers still consider trans fats to be GRAS despite version of one, but that does not necessarily mean it is safe. the FDA’s concluding that it causes eight deaths a day in In 2014, the FDA recognized the safety threat when it issued the United States and that if it were banned from food, guidance regarding substances added to foods, including our country would realize more than $117 billion in health beverages and dietary supplements.42 The agency stated: benefits including reduced healthcare costs over 20 years.45 “We have seen a growth in the marketplace of beverages and Here is another issue of serious concern. For years, other conventional foods that contain novel substances, companies have used their own employees or hired such as added botanical ingredients or their extracts. consultants to evaluate their chemicals’ safety and then Some of these substances have not previously been used in relied on such undisclosed safety determinations to market conventional foods and may be unapproved food additives. their products for use in food. This raises serious conflict- Other substances that have been present in the food supply of-interest concerns because a company’s financial benefit for many years are now being added to beverages and other from selling a particular product can bias its employees’ or conventional foods at levels in excess of their traditional use contractors’ judgment.46 The lack of independent review levels, or in new beverages or other conventional foods. This in GRAS determinations compromises the integrity of the trend raises questions regarding whether these new uses are process and calls into question whether it can effectively unapproved food additive uses.”43 ensure the safety of the food supply.47 The FDA has acknowledged that a company’s potential It is likely that had the FDA reviewed the undisclosed GRAS legal liability and its interest in protecting its brand are determinations, it would have found some to be unapproved insufficient to ensure that food is safe.48 In 2013 the agency food additives. said, “Because the demand for many manufactured or processed foods may not be sufficiently affected by safety considerations, incentives to invest in safety measures from farm to fork is diminished. Consequently, the market may not provide the incentives necessary for optimal food safety.”49 | PAGE 11 Generally Recognized as Secret: Chemicals Added to Food in the United States “Even in cases where consumers are aware that their illness In an increasingly global marketplace where many was contracted from a specific food,” the FDA explained, “it is additives and foods are imported into the United States, this often difficult to determine who is ultimately responsible for loophole presents an unsettling situation that undermines their illness, since the particular source of contamination is public confidence in the safety of food and calls into question not known in many circumstances.”50 It concluded that “it is whether the FDA is performing its duty to protect public unlikely that the existence of brands in the food sector creates health. Until conflicts of interest are minimized and safety the optimal level of safety for society.”51 decisions are subject to mandatory FDA review, the safety As the Institute of Medicine explained in the context of chemicals in food will depend largely on the integrity of medical safety, conflicts of interest can result in bad and competence of food manufacturers. That is not in the decisions.52 Similarly, undisclosed safety determinations public’s best interest, because manufacturers have a financial affecting the food that Americans eat may be undermining incentive that may bias their judgment about an additive’s public health. Without FDA and public scrutiny—as Congress safety. intended that there be—we cannot be confident in the safety When consumers buy dietary supplements, they make a of chemicals added to food. choice to consume chemicals that the FDA has not reviewed for safety. Indeed, under the law, consumers must be told that FDA has not reviewed the health claims made for ingredients in dietary supplements. As a result, dietary supplements CONCLUSIONS carry labels disclosing that they have not been reviewed for safety by the FDA. However, when buying food, consumers can’t make informed choices because they don’t know A chemical additive cannot be “generally recognized as which ones contain reviewed chemicals or which contain safe” if its identity, chemical composition, and safety substances not reviewed by the FDA for safety. There are no determination are not publicly disclosed. Congress never warning labels. There is no disclosure. As a consequence, they intended that almost all new food chemicals would pass may unknowingly be putting their health at risk. The current through the GRAS loophole without formal agency review processes allowing this to occur should be addressed and and approval. The law places responsibility on FDA to ensure changed to better protect the health of the American public. that food additive petitions are submitted for additives without general recognition of safety and to ensure that manufacturers’ GRAS determinations are properly made. If the FDA does not know the identity of these chemicals and does not have documentation showing that their uses in food NRDC’S RECOMMENDATIONS are safe, it cannot not do its job. The problems identified in this report are rooted in a law adopted more than a half century ago. Ultimately, Congress needs to fix these problems. Until it does, the FDA should implement the recommendations made by the GAO in 2010 including strictly limiting conflicts of interests and requiring that the FDA be informed of GRAS determinations so it can confirm that the chemical’s use in food is generally recognized as safe. The agency should also make its concerns with all notices it reviews, even those that are withdrawn, publicly available. In the meantime, consumers should demand that their grocery stores and their favorite brands sell only food products with ingredients that the FDA has found safe, and call on the FDA and Congress to make the necessary changes to better ensure that food consumed in the U.S. is safe. | PAGE 12 Generally Recognized as Secret: Chemicals Added to Food in the United States ENDNOTES 21 FDA, GRAS Notice Inventory, www.accessdata.fda.gov/ scripts/fdcc/?set=GRASNotices (accessed November 15, 2013). 1 Thomas G. Neltner et al., “Navigating the U.S. Food Additive 22 Magnuson B et al., “Review of the regulation and safety Regulatory Program,” Comprehensive Reviews in Food Science assessment of food substances in various countries and and Food Safety 10 (2011), p. 342. jurisdictions,” Food Additives & Contaminants: Part A. 2013. DOI: 10.1080/19440049.2013.795293 2 NRDC, Main FDA Response to FOIA, 2014, p. 210, www.nrdc.org/food/files/chemicals-in-food-FOIA-Main.pdf 23 NRDC, Main FDA Response to FOIA, 2014, p. 207, regarding GRN No. 257. www.nrdc.org/food/files/chemicals-in-food-FOIA-Main.pdf regarding GRN No. 257. 3 21 U.S.C. § 321(s) and § 348. 24 Kahl, p. 5. 4 Pub. L. No. 85-929, 72 Stat. 1784 (1958). 25 FDA, GRAS Notice Inventory, GRN No. 466. 5 21 C.F.R. § 170.3(i). www.accessdata.fda.gov/scripts/fdcc/?set=GRASNotices. The 6 21 U.S.C. § 348. Fred H. Degnan, FDA’s Creative Application FDA issued a “no questions” letter before the NRDC submitted of the Law, Food Drug Law Institute, 2000, p. 25. its comments. 7 Degnan, p. 22. 26 Ibid, GRN No. 471. It was pending as of February 28, 2014. 8 Neltner, “Navigating,” p. 342. 27 Ibid, GRN No. 474. It was withdrawn before the NRDC submitted its comments. 9 NRDC, GRN No. 59 FDA Response to FOIA, 2014, p. 271, www.nrdc.org/food/files/chemicals-in-food-FOIA-59.pdf. 28 NRDC, Comments on GRN No. 466, 2013, www.nrdc.org/ food/files/chemicals-in-food-GRN-466.pdf and NRDC, Comments 10 21 U.S.C. §§ 321(s), 348(a). on GRN No. 471, 2013, www.nrdc.org/food/files/chemicals-in- 11 21 C.F.R. § 170.30. Neltner, “Navigating,” p. 347. food-GRN-471.pdf and NRDC, Comments on GRN No. 474, 2013, www.nrdc.org/food/files/chemicals-in-food-GRN-474.pdf. 12 Ibid. 29 As of February 28, 2014, the FDA’s website listed 498 13 Ibid. Unlike individual food manufacturers, since 1963 the notices with 32 pending, 80 withdrawn, and 17 rejected because flavor industry has publicly identified its chemicals and their they had an insufficient basis to determine the chemical was allowed uses for those it found to be GRAS. It also submitted GRAS. 20.8% = (80+17)/(498-32)*100%. its safety documentation to the agency. See Flavor and Extract Manufacturers Association, About the FEMA GRAS Program, 30 See www.gladson.com. March 15, 2013 version www.femaflavor.org/gras (accessed March 4, 2014). 31 FDA, GRAS Notice Inventory, GRN No. 225 and NRDC, Main 14 21 C.F.R. § 170.35. FDA Response to FOIA, 2014, p. 197, www.nrdc.org/food/files/ chemicals-in-food-FOIA-Main.pdf regarding GRN No. 225. 15 Neltner, “Navigating,” p. 347; Linda S. Kahl to Docket No. FDA-1997-N-0020, Substances That Are Generally Recognized as 32 Ibid. Safe (GRAS); Experience with GRAS Notices (Nov. 4, 2010), p. 26. 33 FDA, GRAS Notice Inventory, GRN No. 259. Degnan, p. 32. 34 FDA, GRAS Notice Inventory, GRN No. 257. 16 62 Fed. Reg. 18,938, 18,939 (April 17, 1997). See also Neltner, “Navigating,” p. 360. 35 NRDC, Main FDA Response to FOIA, 2014, p. 206, www.nrdc.org/food/files/chemicals-in-food-FOIA-Main.pdf. 17 FDA, Guidance for Industry: Frequently Asked Questions About GRAS, www.fda.gov/Food/GuidanceRegulation/ 36 FDA, GRAS Notice Inventory, GRN Nos. 262, 263, and GuidanceDocumentsRegulatoryInformation/ 264 and NRDC, Main FDA Response to FOIA, 2014, p. 218, IngredientsAdditivesGRASPackaging/ucm061846.htm (accessed www.nrdc.org/food/files/chemicals-in-food-FOIA-Main.pdf. January 8, 2014). 37 Ibid. 18 In February 2014, the Center for Food Safety sued the FDA 38 FDA, GRAS Notice Inventory, GRN No. 340 and NRDC, Main to finalize the proposed rule. See Center for Food Safety, Illegal FDA Response to FOIA, 2014, p. 223, www.nrdc.org/food/files/ “Fast-Track” Puts Americans at Risk for More than Fifteen Years, chemicals-in-food-FOIA-340.pdf. www.centerforfoodsafety.org/press-releases/2924/center-for- food-safety-sues-fda-over-food-additives (accessed March 4, 39 Ibid, p. 223. 2014). 40 Ibid, p. 219. 19 Government Accountability Office, Food Safety: FDA Should 41 Pub. L. No. 103-417, 108 Stat. 4325 (1994). Strengthen Its Oversight of Food Ingredients Determined to Be 42 FDA, Guidance to Industry: Considerations Regarding Generally Recognized as Safe (GRAS), 2010, p. 8, 20, www.gao. Substances Added to Foods, Including Beverages and Dietary gov/products/GAO-10-246. Supplements, 2014. See www.fda.gov/downloads/Food/ 20 American Institute for Biosocial and Medical Research, GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ GRAS Self-determination Inventory Database, www.aibmr.com/ IngredientsAdditivesGRASPackaging/UCM381316.pdf. resources/GRAS-database.php (accessed November 15, 2013). 43 Ibid. | PAGE 13 Generally Recognized as Secret: Chemicals Added to Food in the United States 44 Neltner, “Navigating,” p. 347. See Note 28. Support for this project was provided by The Pew Charitable 45 78 FedReg 67169, November 8, 2013. Trusts. The views expressed herein are those of the author(s) and do not necessarily reflect the views of The Pew Charitable Trusts. 46 Thomas G. Neltner et al., “Conflicts of Interest in Approvals of Additives to Food Determined to be Generally Recognized as Safe: Out of Balance,” Journal of American Medical Association–Internal Medicine, August 2013, E2, DOI:10.1001/ jamainternmed.2013.10559. 47 Ibid. 48 FDA, Preliminary Regulatory Impact Analysis for the Proposed Rules for Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food, Docket No. FDA-2011-N-0920, p. 2-3. See www.fda.gov/ downloads/Food/GuidanceRegulation/FSMA/UCM334117.pdf. 49 Ibid., p. 2. 50 Ibid., p. 3. 51 Ibid. 52 Bernard Lo and Marilyn J. Field, eds., Conflict of Interest in Medical Research, Education, and Practice (Washington, D.C.: National Academies Press, 2009). Natural Resources Defense Council 40 West 20th Street New York, NY 10011 212 727-2700 Fax 212 727-1773 Beijing Chicago Los Angeles Bozeman San Francisco Washington, D.C. www.nrdc.org www.nrdc.org/policy www.facebook.com/nrdc.org www.twitter.com/nrdc PAGE 14 | Generally Recognized as Secret: Chemicals Added to Food in the United States Printed on recycled paper