Food Additive Regulations: A Chronology

The Committee for the National Institute for the Environment
1725 K Street, NW, Suite 212, Wastington, D.C. 20006-1401 (202) 530-5810
cnie@cnie.org

Donna U. Vogt
Analyst in Life Sciences
Science Policy Research Division
95-857 SPR
Updated September 13, 1995

SUMMARY

The 104th Congress is actively debating proposals to reform several aspects of the Food and Drug Administration's (FDA) process for regulating consumer products, including its approval process for food additives. In June 1995, the Food and Drug Administration (FDA) announced at a House Government Reform and Oversight Subcommittee hearing several policy shifts in its food additive pre-market approval process which will soon be implemented. FDA's Center for Food Safety and Applied Nutrition (CFSAN) has already reorganized its food center. In the next year, agency officials plan to increase the petition review staff; set timetables and goals to complete reviews for additives (depending on the degree of risk shown by the additive); and establish new approaches to petition review whereby they establish a notification procedure only for noncarcinogenic packaging substances and GRAS substances. CFSAN also intends to reduce its backlog of food additive petitions by awarding contracts to independent third-party review panels to review certain types of information contained in food additive petitions. The historical chronology, contained in this report, shows the development over time of food additive regulatory policies and how the statute, the agency, and the courts helped to define FDA's policy of "safety."

INTRODUCTION
BACKGROUND
FDA'S CONCEPT OF "SAFETY"
-- Reasonable Certainty of No Harm
-- The Delaney Clause
CURRENT DEBATE OVER FOOD ADDITIVE POLICIES
CHRONOLOGY OF REGULATIONS FOR FOOD ADDITIVES

FOOD ADDITIVE REGULATIONS: A CHRONOLOGY

INTRODUCTION

The 104th Congress is actively debating proposals to reform several aspects of the Food and Drug Administration's (FDA) process for regulating consumer products including its approval process for food additives. During two days of recent hearings on this process, concerns were raised about lag times in approval of food additive petitions, and about FDA regulations stifling innovation. (1) FDA officials responded that food additives are potentially consumed by everyone in the population, including the most vulnerable populations such as children or the elderly. Consequently food additives must be carefully tested before approved for the market because they could cause deleterious health effects. This report gives background information on food additives, discusses the current Congressional debate over food additive regulatory policy, and gives a chronology of the development of food additive regulatory policies. Over time, as this chronology shows, FDA's regulatory policies on food additives have developed through amendments to statutes, court challenges, and formal rule making with publication in the Federal Register (FR) and then in the Code of Federal Regulations (CFR).

BACKGROUND

The Federal Food, Drug and Cosmetic Act of 1938 (FFDCA) gives FDA the authority to regulate food additives. Food additives are any substance or mixture of substances other than the basic foodstuff which are present in a food as a result of any phase of processing, packaging, or storage. (2) Food additives have different functions. The food industry uses additives to maintain consistency, palatability and wholesomeness, to improve nutritional value, to control acidity or alkalinity, to enhance flavor or impart a desired color, and to keep food wholesome and appealing while in route to markets. FDA approval of a food additive is not a product license limited to a single sponsor, but is generic in that anyone can manufacture or use an additive consistent with any existing patent protection. (3)

In regulating food additives, FDA classifies the additives in four categories: prior-sanctioned substances which were approved either by FDA or the U.S. Department of Agriculture (USDA) before the passage of the 1958 Food Additives Amendments; GRAS additives (generally-recognized-as-safe) which are exempt from regulation because their extensive use has produced no known harmful effects; direct additives which are intentionally added to foods such as lemon flavoring in cookies; and indirect additives which are often trace substances that leach from packaging materials and migrate to food during processing or storage.

FDA'S CONCEPT OF "SAFETY"

The degree of health risk of a food additive is determined in FDA's pre-market testing and approval process. Manufacturers must prove in its petition for pre-market approval to FDA that its additives are safe. FDA regulates the type of food in which an additive can be used, the maximum quantity that can be used, and the information that must appear on the label about the additives Regulations known as Good Manufacturing Practices (GMP) limit the amount of food and color additives used in foods. Manufacturers use only the amount of an additive necessary to achieve the desired result.

The legislative history of the "Food Additives Amendments of 1958" interpreted what Congress meant by safety. It said that a "reasonable certainty of no harm" would be the standard. The amount of data necessary to demonstrate this safety standard to the FDA reflects the proposed conditions of use of the additive. An additive may be consumed by all citizens for all ages and in all health conditions for a lifetime. In approving petitions, FDA must ensure that the data will legally support the agency's decision and that the administrative record developed must provide the basis for defending any resulting food additive approval in court. At the same time, Congress created a separate, more stringent standard for preventing cancer-causing substances from being added to foods. It included a clause, the Delaney Clause, which banned any food additive shown to cause cancer in man or animal. It basically set up a "zero-cancer-risk" standard for food additives. Later, Congress added the same zero-cancer-risk clause for amendments governing new animal drugs, and color additives. (5)

The "reasonable certainty of no harm" standard stems from the legislative history of the Food Additives Amendment of 1958 [P.L. 85-929]. The amendments created Section 409 of the FFDCA. In the report of the House Committee on Interstate and Foreign Commerce, which amended and favorably reported H.R. 13254, the Committee stated:

In addition, FDA has incorporated this concept of safety into its color additive regulations. Under 21 CFR 70.3(i), a color additive is "safe" if "there is convincing evidence that establishes with reasonable certainty that no harm will result from the intended use of the color additive." Therefore, the general safety clause prohibits approval of a color additive if doubts about the safety of the additive for a particular use are not resolved to an acceptable level in the minds of competent scientists.

The Delaney Clause is contained in Section 409 [348(c)(3)(A)] of the FFDCA. Section 409 lays out requirements for the use of all additives in foods, including pesticide residues that could concentrate from levels in raw products in their processed form, or that are added during processing. The Delaney Clause states:

The Delaney Clause does not allow consideration of whether the cancer risk is "negligible" (extremely small), or whether there are other characteristics of the product such as benefits of product use. The Delaney Clause establishes a "zero-cancer-risk" standard for food additives, including pesticide residues. If residues of carcinogenic pesticides are found to concentrate in processed foods, the Environmental Protection Agency (EPA) cannot set a tolerance or maximum legal limit for that pesticide/food combination. Since 1958, science has developed methods to detect smaller and smaller quantities of residues. Thus, when FDA monitors processed foods with more sophisticated equipment and finds residues of carcinogenic pesticides in parts per billion, these processed foods must now be considered adulterated under the law.

Over time, as the following chronology shows, the Delaney Clause "zero-cancer-risk" provision has led to the cancellation of about eight different additives: a veterinary drug; a veterinary feed additive, a flavoring agent, saccharin; indirect food additives from packing materials; and several color additives. All these additives had substitutes available at the time except for saccharin. Consequently, there was little impact on the food supply.

CURRENT DEBATE OVER FOOD ADDITIVE POLICIES

Congress, in the process of debating proposed reforms of the Federal Government's regulatory policies, has been looking at two aspects of food additive regulations: 1) the lag time in the review of food additive petitions; and 2) changing the risk standard by which to judge the safety of food additive petitions.

The House Committee on Government Reform and Oversight, Subcommittee on Human Resources and Intergovernmental Relations, held two days of hearings (June 22 and 29, 1995) on FDA delays in reviewing food additive petitions. FDA claims that lag times in approving food additive petitions are often caused by two factors: 1) the submissions by the petitioners do not include data that adequately support a conclusion that a specific additive is safe; or 2) the FDA keeps the petition file open with the clock running rather than rejecting the petition outright to allow petitioners to add supplemental information about additional safety studies. FDA claims this approach is less adversarial than simply denying petitions. Some petitioners from the industry support this cooperative process, while others complain that they are moving their businesses overseas because of the expense incurred from waiting for FDA approval.

FDA responded to many complaints about their lag time with a proposal on June 22, 1995, to streamline the pre-market approval process by: reorganizing their food center, the Center for Food Safety and Applied Nutrition (CFSAN); increasing the food additive petition review staff through shifting personnel; setting a timetable and goals to complete reviews for additives, depending on the degree of risk shown by the additive; and establishing new approaches to petition review whereby they develop a notification procedure only for noncarcinogenic packaging substances and GRAS substances. A major policy shift was announced also at the hearing. FDA stated that within the year, it will award two separate contracts: 1) to an independent third-party scientific review group to review indirect food additive petitions (components of food packaging) for safety; and 2) to another review panel to review specific types of studies such as classical, standard toxicity studies which are routinely submitted to FDA to support food additive petitions. In both cases, the FDA will reserve for itself the final decision on whether the food additive meets the "reasonable certainty of no harm" safety definition.

During the 1980s, FDA received 655 food additive petitions, of which 141 or 22 percent were for substances added directly to foods. The rest, or 78 percent were for indirect food additives. FDA currently has 151 applications pending, almost all of which are for indirect additives. Table 1 shows FDA's actions on food additive petitions over the last five years.

TABLE 1. Direct and Indirect Food Additive Petitions Received by the Food and Drug Administration, October 1, 1989, to March 31, 1995.


Fiscal Years	Petitions Received	Petitions Approved	Petitions Withdrawn	Petitions Pending
1990	50	22	15	13
1991	50	17	7	26
1992	44	15	5	24
1993	56	12	3	41
1994	3	1	1	28
1995 (to 3/31/95)	19	0	0	19

Source: Food and Drug Administration. Attachment AB. Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations for 1996. Hearings before a Subcommittee of the Committee of Appropriations. House of Representatives. Part 6. Agricultural Programs. p.663-664.

Congress is currently considering legislation on regulatory reform as well as amendments to appropriations bills that could limit the Delaney Clause influence over food and color additives and new animal drugs policies. One bill (S. 343) contains a provision which would establish a risk standard so that: "No agency shall prohibit or refuse to approve a substance or product on the basis of safety where the substance or product presents a negligible or insignificant foreseeable risk to human health resulting from its intended use." Other bills such as H.R. 1627, the Food Quality Protection Act of 1995, would amend the FFDCA and create a new Section 408. The new section, Title [V in this bill, would establish a single negligible risk standard for pesticide residue tolerances in raw and processed foods, reforming the inconsistent provisions in these statutes that govern the use of pesticides on foods by rewriting Section 408 of the FFDCA to cover both raw and processed foods. It effectively eliminates the Delaney Clause "zero-cancer-risk" criteria from the tolerance-setting process. It would allow EPA to determine what level of risk will be adequate to protect the public health as long as the dietary risk posed to food consumers is negligible.

CHRONOLOGY OF REGULATIONS FOR FOOD ADDITIVES (6)

Over time, FDA's regulatory policies on food additives have developed through amendments to statutes, court challenges, and formal rule making with publication in the Federal Register (FR) and then in the Code of Federal Regulations (CFR). The following chronology shows this development.

1889 - At this time, the U.S. Department of Agriculture (USDA) had responsibility for regulating all foods. USDA Chief Chemist, Harvey Washington Wiley, first publishes assessment of chemical preservatives. In his annual report, Wiley acknowledges that while it "was not regarded as a wise thing to prohibit absolutely the use of preservatives in foods, it was "imperative" that any food product containing a preservative must have "this fact plainly stated on the label of the package."

1898 - The Association of Official Agricultural Chemists (made up largely of State employed chemists who ensured the purity and accurate labeling of fertilizers), establishes a committee to recommend food standards. The committee was headed by Harvey W. Wiley, Chief of the Bureau of Chemistry in the USDA.

1900 - Following a USDA report on 152 "patent preservatives" (substances called: Mrs. Price's Canning Compound, Freezine, Preservaline, etc.), Congress authorizes the Secretary of Agriculture to "investigate the character of proposed food preservatives and coloring matters to determine their relation to digestion and health and to establish principles which should guide their use."

1902 - Food standards are published and incorporated into the laws in many States. Concerns about the growing use of chemical preservatives in foods (e.g., borax, salicylic acid, formaldehyde, sodium benzoate, and sulfites) lead Congress to appropriate $5000 to Harvey Wiley to study the effects of such preservatives on health. Wiley establishes his soon infamous "Poison Squad," a group of healthy young men who agree to take the various preservatives with their meals so that the effects of graduated doses of such preservatives could be studied. As a result of these highly publicized table trials, Wiley changes his mind as to the usefulness and necessity of all preservatives and becomes a staunch opponent of their use in foods.

1904 - Secretary of Agriculture issues the first "Poison Squad" report on the preservative boric acid, and its other form, borax. In this report, Wiley argues that in setting a "safe" level of use, the public's overall exposure to such an additive should be considered in deciding whether it could be used in foods. Wiley argues that if one company was allowed to use a preserving chemical, all must be allowed to use it. This means that some consumers may be exposed to large quantities of the substance, and such exposure, Wiley felt, could eventually pose a public health problem. Eventually, of the substances studied by the Poison Squad, only benzoate of soda and sulfites were allowed continued use in the food supply. Even so, sulfite use is limited and the use of benzoate has to be indicated on the product's label. Borax, salicylic acid, and formaldehyde are ruled unacceptable for use in food.

1904 - Public support grows for passage of a Federal law governing the use of additives in foods and drugs. At the 1904 St. Louis Exposition, "pure food" proponents set up a booth next to prominent food manufacturers and display colored silks made from the dyes used by major firms in their food products. Industry giants, such as H. J. Heinz and Frederick Pabst, join in the campaign for a national food law to prevent competitors from using preservatives. They felt that safe or not, preservatives undermined confidence in all manufactured and processed foods and wanted a Federal law to limit the use of preservatives. Both men had pioneered new manufacturing processes so they could avoid the use of chemical preservatives.

1906 - USDA publishes Bulletin #13, a report on salicylic acid stating that salicylate is useful as a drug in treating rheumatism and gout, but it has no place in foods because its use in small amounts only masks its deleterious effects.

1906 - Pure Food and Drugs Act is enacted by Congress. The law recognizes the U.S. Pharmacopeia as the guide for setting standards for drugs. For example, if patented drugs contain any one of 11 ingredients deemed harmful (including morphine, opium, and alcohol) they must be declared on the label if they are present in the product. But provisions are left out of the law which would have established similar standards for foods. Opponents of food standards fear that Wiley would use the standards process to outlaw the use of preservatives. Because the law includes no scientific definition of harmfulness by which substances in foods could be judged either safe or "poisonous or deleterious," USDA parameters are established through regulations and court decisions guided both government and the food industry for the next four decades. For example, Regulation #15 specifies that from time to time the Secretary of Agriculture would determine the substances permitted or prohibited in foods as well as the principles which would guide the use of preservatives, colors, and other added products. This 1906 Act prohibits the importation of a food that is not permitted in the country exporting to the United States.

1906 - USDA begins issuing rules called "food inspection decisions (FID)." FID 39 prohibits fluorides as preservatives and Martius yellow (Naphthol yellow) as a color in macaroni and noodle products.

1907 - USDA issues the "Food Inspection Decision 76 on Dyes, Chemicals and Preservatives" (FID 76). FID 76 establishes the principle that no substances could be used which lessens the wholesomeness of a food or adds any deleterious properties to a food. Salt, sugar, wood smoke, potable distilled liquors, vinegar, and mustard are ruled "condiments" and sanctioned for use in foods. Sulphur dioxide is allowed for use in food as long as its use does not exceed 350 mg/kg. FID 76 also establishes a system of permitted food colors.

1908 - USDA issues FID 89 that permits sulfites to be used in ordinary quantities in dried fruit and molasses syrup.

1908 - USDA Bulletin #13 reports that formaldehyde is poisonous, even in small quantities, and prohibits its use in food.

1909 - USDA issues an FID that allows limited use of "benzoate of soda" (1/10 of 1%) or sodium benzoate in foods provided that the amount used is clearly stated on the food container or packaging.

1911 - FID 136 reported that the continued use of saccharin for a long time in amounts over 0.3 grams per day is liable to impair digestion. After July 1,1911, all foods containing more than this amount would be considered adulterated. FID 138 extended the effective date of this rule to January 1, 1912. It explains that saccharin would be available as a drug for use by those persons whose doctors told them to avoid sugar.

1912 - FID 147 prohibits the manufacturing or marketing of "absinthe" (an alcoholic beverage flavored with absinthe or wormwood) because it is injurious to health.

1914 - The Supreme Court rules in U.S. v. Lexington Mill & Elevator Company against USDA because the Government has not shown a connection between nitrite residues in the bleached flour and the harm to humans that the residues were alleged to cause. While the Court is sympathetic to the Bureau of Chemistry's efforts to protect the public from nitrites, it nonetheless states that the Government had to show some relationship between the nitrite residues left in the flour and the harm it is capable of producing in humans. The Court states that the mere presence of such an ingredient is not sufficient to make a food illegal. After the case is settled, bleached flour is allowed in interstate commerce as long as it does not conceal damaged flour and is clearly labeled as "bleached flour."

1917 - The Government's longstanding and much heralded case against Coca-Cola was settled when the company agreed to reduce the caffeine content of the popular beverage by one-half while adding additional flavoring from coca-leaf and cola nuts.

1919-1920 - Following an outbreak of botulism traced to processed ripe olives, FDA and the industry cooperate to solve production problems which had led to the epidemic and to achieve advances in scientific understanding and industrial quality control procedures.

1910-1920 - A species of "albino rat" is standardized as the species of choice to be used in testing the effect of substances in studies of human physiology, anatomy, and behavior.

1925 - Following two "hung jury" trials, the Government drops its efforts to force a court decision on the safety of saccharin. The Bureau of Chemistry continues to oppose the use of saccharin as a general purpose sweetener. "The government has much scientific evidence to show that saccharin is harmful to health and believes that it should not be used except as a drug under the direction of a physician.... As a drug, saccharin has its uses. In our [USDA] opinion, it has no legitimate use as a food, and is harmful to health."

1930 - Congress passes the McNary-Mapes Amendment to the 1906 law which authorized standards of quality for canned food. During the Great Depression, food quality decreased sharply as many food manufacturers sought to market low-cost foods. Part of the support for the Amendment came from the old-line preserves (jam and jelly) industry. This industry nearly disappeared when faced with competition from manufacturers who substituted pectin for fruit in their products.

1930 - The Food, Drug and Insecticide Administration becomes the Food and Drug Administration (FDA) remaining under USDA.

1937 - FDA takes steps to warn manufacturers against the continued use of Diethylene glycol, which is used as a solvent in a liquid preparation of Elixir Sulfanilamide. Diethylene glycol had killed over one hundred people. It is used in small amounts as a food additive in ice cream and other baked goods as an emulsifier or solvent.

1938 - The Federal Food, Drug, and Cosmetic Act [21 U.S.C. 321-] passed. Amidst many new provisions, this act gives FDA the power to establish legally binding standards of quality and fill-of-container for processed foods. It also provides that safe tolerances be set for unavoidable poisonous substances in food. Section 402(a)(1) set a standard for food constituents that were not added, and this became the "ordinary injurious" standard; and (2) set a "may render injurious" standard when applied to added constituents that are neither necessary nor unavoidable. Section 406 allows FDA to set tolerances "for the protection of public health" for added constituents whose use was "necessary in the production of a food" for whose occurrence was "unavoidable by good manufacturing practice" and authorized factory inspections. Under section 406(b) of the Act the Secretary was charged with promulgating regulations "providing for the listing of coal-tar colors which are harmless and suitable for use in food and for the certification of batches of such colors." This provision thus mandates color certification for colors derived from petroleum. Following hearings, regulations are issued establishing procedures for admitting new colors for certification.

1944 - Congress passes the Public Health Service Act. It covers a broad spectrum of health concerns including regulation of biological products and control of communicable diseases.

1945 - FDA promulgates regulations for standards for the fortification and mandatory wartime enrichment of bread and other foods after World War II. Enrichment marks a major nutritional milestone in American history as pellagra, scurvy, and other dietary deficiency diseases began to disappear in America as a result of fortification of foods with vitamins.

1945-1960 - The processed food industry undergoes a dramatic surge in growth, called a chemogastric revolution. Processed foods began to appear more frequently in stores. Frozen orange juice, breaded shrimp, frozen desserts, frozen dinners, are all examples of new post-war foods. All of these foods used new chemical ingredients and new packaging.

1948-50 - During this period, FDA held administrative hearings to set standards for white bread. The hearings help to resolve the controversy over the use of "polyoxyethylene monostearate" as a bread "softener" because during the hearings, the issues discussed separate food additive problems from the process of setting food standards.

1948 - Studies, conducted in England, demonstrate that nitrogen trichloride, a flour-bleaching agent, causes running fits ("canine hysteria") in dogs. Even though no direct link is established between this phenomenon as observed in dogs and any effects upon humans, the substance is voluntarily removed from the American market.

1950-1952 - Representative James J. Delaney (D-NY) serves as chairman of a House of Representatives select committee charged with examining the entire issue of chemicals in food products. At a hearing in 1950, a list of 842 chemicals used in food products, is introduced. Many of these chemicals had never undergone scientific testing. The committee's recommendation is that new pesticides, food additives, and color additives be subject to pre-market approval by the FDA.

1953 - Coumarin is voluntarily withdrawn from sale for use in foods due to its newly disclosed toxicity to humans. Its use had been increasing as a food additive. Laboratory studies revealed "impressive evidence" of the capacity of coumarin to produce serious damage to the liver of experimental animals when these animals were fed comparable amounts of coumarin that were added to human food. FDA banned its use on March 5, 1954 (19 Federal Register 1239).

1954 - Congress passes the Pesticide Residue Amendment of 1954 [P.L. No. 518, 21 U.S.C. 346a]. It becomes Section 408 of the 1938 Act. This amendment split jurisdiction over pesticides between USDA, which could register pesticides for specific uses and FDA, which is charged with setting tolerances for residues of pesticides in raw agricultural products. The burden of proof is shifted to the pesticide sponsors, whereby pesticide residues found in food would mean the food is adulterated unless a sponsor receives a tolerance or an exemption.

1956-1960 - Increased concern over the safety of certain food colors leads to the USDA taking eight color additives off their list of permitted additives. USDA officials begin questioning the "safe" use of nineteen other colors.

1958 - In the decision from Flemming v. Florida Citrus Exchange, the Supreme Court upholds the FDA's very stringent definition of "harmless" under the 1938 Act ("substances incapable of producing harm in test animals in any quantity under any conditions"). This decision generates support leading to the Color Additive Amendments of 1960.[74 Stat. 397]

1958 - Congress passes the Food Additives Amendment [P.L. 85-929, 21 U.S.C. 321(s)] which establishes section 409, the section governing food additive regulations. This section also includes the anti-cancer Delaney Clause. No definition of safety is explicitly provided in the statute. "Safe" as it is interpreted according to the legislative history and by the courts, came to mean "a reasonable certainty of no harm." Pesticides on raw agricultural products, prior-sanctioned substances, and generally-recognized-as-safe (GRAS) substances are exempted from the food additive definition. Factors used by FDA to determine "safe" food include 1) probable consumption of the substance, 2) cumulative effects in the diet, taking into account chemically or pharmacologically related substances, and 3) safety factors which in the opinion of qualified scientific experts are "generally recognized as appropriate."

1958 - A public notice entitled "Substances Generally-Recognized-as-Safe" (GRAS substances) in the Federal Register contains a list of nearly 200 substances. The ruling allows that substances, whose use is "generally recognized as safe" as based on common use in foods, are exempted from the prior-approval requirement of the Act. The exemption is only for these substances where the common use provides a basis for concluding safety. USDA and FDA did also explicitly approve several food ingredients prior to September 6, 1958, and these approvals remain as "prior-sanctioned" food ingredients, exempt from the food additive requirements. In addition to such common food ingredients as salt, pepper, sugar, vinegar, and baking powder, hundreds of substances are regarded as GRAS when used in accordance with "good manufacturing practice." The latter term implies that the substances in question are of suitable food grade and when used they remain in food in amounts no higher than necessary to accomplish their intended effects.

1959 - Cranberry Crisis. Residues of the herbicide, Aminothiazole, which is found on northeast U.S. cranberry crops, prompt the FDA to take action against the marketing of these cranberries, just three weeks before Thanksgiving of 1959. FDA laboratories and some outside laboratories work around the clock to test suspect berries before Thanksgiving. Cleared berries carry a notice that the berries were tested and cleared by FDA inspection, the first such endorsement ever carried on a food product.

1960 - Congress passes the Color Additive Amendments with the Delaney Clause. Under section 721 [379e(b)(5)(B)] of the FFDCA, the so-called "general safety clause," states that a color additive cannot be listed for a particular use unless the data presented to FDA establishes that the color is safe for that use. Although what is meant by "safe" is not explained in the general safety clause, the legislative history makes clear that this clause is to have the same meaning for color additives as for food additives: "reasonable certainty of no harm." Following these amendments, color additives already in use are placed on a provisional list and allowed to be sold provided that a sponsor had petitioned for their approval and was working on obtaining adequate safety data.

1961 - A scientific committee appointed by the Secretary of Health, Education, and Welfare finds that safrole, a natural component of sassafras, is a weak hepatic (liver) carcinogen. Immediate action is taken under authority of the Delaney Clause to stop the use of safrole and oil of sassafras in root beer, sarsaparilla and other beverages and foods.

1961 - Discovery of Aspergillus nabs mold which produces a powerful toxin, "aflatoxin," made after the outbreak of "turkey x disease" in England. Aflatoxin is one of the most powerful carcinogens known to man. It occurs and grows naturally, particularly on crops stressed by drought. More than 100 mold species that produce toxins are found growing on peanuts, corn, rice, cottonseed meal, oats, hay, barley, sorghum, cassava, millet, etc. Its discovery marks the emergence of the field of study of mycotoxins. FDA chooses to set an action level instead of a tolerance level for mycotoxins. Action levels are a level for contamination of a food below, which no court enforcement action is necessary. Section 306 of FFDCA permits FDA to establish action levels in implementing the adulteration provisions. In setting action levels, FDA assures food producers that it ordinarily will not enforce the general adulteration provisions of the Act if the quantity of harmful added substance in their food is less than the quantity specified by the action level. FDA also considers whether the added substance can injure health or if it is unavoidable.

1966 - Fair Packaging and Labeling Act is passed to combat problems with short-weighing of products, especially cereals. Each product label must: identify the product, name and place of business of manufacturer, net quantity of contents, and net quantity of a serving when the number of servings is represented.

1967 - FDA invokes the zero-cancer-risk Delaney Clause against Flectol H, a component of food packaging adhesives (32 FR 5675).

1968 - Congress passes the New Animal Drug Amendments (which becomes section 512 of the FFDCA) along with the "DES" Proviso. The proviso removes the distinction between food additives and drugs, treating substances that promoted cattle growth only as animal drugs, and permitting the HEW Secretary to revoke approval of any new drug whenever he detects "an imminent hazard to the public health." The DES Proviso allows for an exception to the Delaney Clause "zero-cancer-risk" mandate. It means that FDA is not required to bar approval of carcinogenic drugs and feed additives administered to food-producing animals if, upon examination by methods acceptable to FDA, no residue of the material is be found in the edible tissues of the animals.

1969 - Delaney Clause is invoked against 4,4'-methylenebis (2-chloroaniline), a chemical used to manufacture food packaging components. [34 FR 19073]

1969 - Cyclamate is banned as a food ingredient because tests conducted at the Food Research Laboratory, New York show that a saccharin/cyclamate mixture causes cancer in experimental laboratory mice.

1969 - White House Conference on Food, Nutrition and Health recommends systematic scientific review of generally recognized as safe (GRAS) substances. Citing the prohibition of cyclamates and a subsequent loss of public confidence in the continued food use of other previously approved substances, President Nixon directs FDA, in his consumer message, to study the safety of GRAS food ingredients and to initiate a safety review of those substances which had been listed as GRAS.

1972 - Saccharin, which had been included in FDA's original published list of GRAS substances for addition to food, is removed from the GRAS list. It is reclassified as a substance approved for interim use within prescribed limitations, pending completion of further studies. The final rule on saccharin, published in 1973, prescribes limitations on the amount of saccharin allowed per serving of food and on the purposes for which saccharin could be used in food. The restrictions are intended to limit the amount of saccharin in the American diet and to confine saccharin to uses already prevalent at the time.

1972-1976 - During this period, an average of ten direct food additive applications are received and approved by FDA.

1973 - FDA publishes "Low Acid Canned Food Processing Regulations." In response to outbreaks of botulism from spores in canned salmon and soup, regulations are enacted to ensure that low-acid canned foods have adequate heat treatment to kill the botulism spores.

1974 - Amendments to the Freedom of Information Act (FOIA originally passed in 1966), further extend the FOIA's disclosure requirements. As a result, FOIA inquiries to FDA grow from a little over 2,000 in 1974 to nearly 50,000 by 1987.

1974 - Aspartame is approved for use in dry foods and chewing gums. Because of objections raised over this approval, FDA agrees to hear objections at a public board of inquiry. In December 1975, FDA stay the approval of aspartame because of its concerns about the validity of some studies submitted on behalf of the food additive petition.

1977 - FDA compiles data and evaluates the scientific literature over several years on approximately 600 food ingredient substances in the GRAS review program. By its own estimates, FDA completes approximately 40 percent of this chore. It had hoped to do a complete review of 2,100. FDA estimates in 1977 that there are about 10,000 food packaging materials and 400 functional food additives in addition to those already under review that remain to be re-evaluated.

1977 - FDA publishes revised provisional listing regulations in the Federal Register, which require new chronic toxicity studies on 31 color additives as a condition of their continued provisional listing. FDA requires these new studies because previously submitted studies were deficient under more modern protocols. In 1982, the U.S. court of appeals upheld the FDA Commissioner's powers to extend the date by which colors are provisionally listed.

1977 - As a result of experimental data that showed saccharin to be a carcinogen in rats, FDA proposes to ban saccharin under the general safety provisions of the Food Additives Amendment and the Delaney clause. (42 FR 19996). In response, Congress passes the Saccharin Study and Labeling Act on November 23, 1977. The law imposed an 18-month moratorium on FDA's proposed saccharin ban and requires that saccharin packets and foods containing bear the warning "Use of this product may be hazardous to your health. This product contains saccharin which has been determined to cause cancer in laboratory animals." FDA regulations require that this warning also appear in retail establishments that sell products with saccharin and may be required on some vending machines as well. (7) Congress extends the moratorium on prohibition of saccharin several times (1980,1981,1983,1985,1987,1991). The current extension is scheduled to expire on May 1, 1997. Because the safety concerns about saccharin have never been resolved, narrow strictures on its use remain in place.

1979 - FDA requires that products containing FD&C Yellow #5, tartrazine, carry a notice on the label to the consumer noting that the color is present in the product. There is mounting evidence of allergic-type reactions, such as hives, to this color additive in one out of 10,000 people. (44 FR 37212).

1979 - U.S. Court of Appeals, District of Columbia Circuit decision on Monsanto Co. v. Kennedy is handed down. Monsanto had sued FDA over FDA's claim that a component of plastic bottles containing food could become part of the food and is considered, therefore, a food additive. The court holds that FDA must determine with a fair degree of confidence that a substance actually migrates into food in more than insignificant amounts before it becomes a food additive. FDA had determined that a component of the plastic would migrate into the final product at unacceptable levels. The court sides with FDA. The court also recognizes the Commissioner's authority to consider the use of such substances to be de minimis and to decline to regulate when it finds migration to be insignificant, and thus exempt from regulation. The agency then began to regulate low levels of substances migrating from food packaging into the final product as food additives.

1980 - A conference sponsored by the Nutrition Foundation concludes that there is no evidence that artificial food colorings produce hyperactivity or learning disabilities in children. The report acknowledges, however, that dietary restrictions may have a placebo effect in that adults may perceive a change in the child's behavior when diet changes are made.

1981 - The artificial sweetener aspartame, which had gained FDA approval for use in dry foods in July 1974, is re-approved by FDA after several task forces and a Public Board of Inquiry, which met in 1980, had forwarded a split recommendation on the issue. But, Commissioner Arthur Hull Hayes, in announcing its re-approval, notes that "few compounds have withstood such detailed testing and repeated close scrutiny." [46 FR 50947 (October 16, 1981)]

1981 - The food additive polydextrose, a low-calorie bulking agent, is approved. [46 FR 30080 (June 5, 1981)]

1982 - FDA publishes its first "Red Book," officially known as Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food.

1982 - FDA issues the first regulation under its "constituents policy." FDA announces that if an additive is not carcinogenic, but a contaminant of that additive is a known carcinogen, the additive itself can be approved if a risk-benefit analysis shows the risk to be negligible. This policy withstood a court challenge when FDA was sued over its approval of D&C Green #5 under this policy. The first ingredient approved under this policy is D&C Green #6.

1982 - A consensus development panel established by the National Institutes of Health (NIH) concludes that there is no scientific evidence to support the claim that additives or colorings cause hyperactivity.

1985 - Cinnamyl anthranilate, a flavor ingredient, is banned under the Delaney Clause (50 FR 42929).

1985 - FDA establishes the Adverse Reaction Monitoring System (ARMS) under which FDA does not seek out adverse reactions, but does investigate complaints from consumers, physicians, or food companies about adverse reactions to food additives. Since establishing this program, FDA has received over 6,000 complaints. More than 95 percent have been about two products: the sweetener Aspartame and sulfite preservatives. No firm evidence exists to prove that aspartame actually causes many adverse reactions.

1986 - FDA bans sulfites on raw fruits and vegetables intended to be sold or served raw to consumers and on commercially marketed fresh potatoes. FDA continues to monitor sulfite use on other foods because a small, but identifiable, segment of the population is found to develop hives, nausea, diarrhea, shortness of breath, or even fatal shock after consuming sulfites. Sulfites added as a preservative in all packaged and processed foods must now be listed on the product label.

1987 - The National Research Council publishes its study, "Regulating Pesticides in Food: The Delaney Paradox." In it, the Council recommends that EPA use one consistent, across-the-board criterion referred to as a "negligible risk standard," to regulate risk in setting pesticide residue tolerances.

1988 - FDA announces the approvals of D&C Red #8 and #9 (53 FR 26766); D&C Red #19 (53 FR 26768); and D&C Orange #17 (53 FR 26768) under a de minimis policy. The agency had proposed to consider additives which posed a lifetime cancer risk of less than one-in-a-million to be de minimis, and therefore too insignificant for regulation. FDA's attempts to extend this risk standard from constituents of food packaging to food additives themselves, however, is ruled illegal in Public Citizen v. Young. The court ruled that this policy went against the intent of the zero-cancer-risk Delaney Clause. Public Citizen had sued FDA over its approval of Red #19 and Orange #17. In 1989, the four colors listed under this de minimis policy are withdrawn.

1988 - The food additive Acesulfame potassium, an artificial sweetener, is approved. [53 FR 28379 (July 28, 1988)]

1988 - In addressing the Delaney Paradox report, EPA sets the "safe" risk level during a lifetime to be negligible or less than 1 x 10-6. [53 FR 41101 - 41123 (October 19, 1988)]

1989 - Recognition by FDA officials of "macro" food ingredients. Increasingly, these food ingredients are characterized by relatively high use levels in foods and possess significant potential to alter the nutritional parameters of the human diet. These direct additives disappear into the U.S. food supply at levels above 10 million pounds annually. That level is equivalent to a per capita intake of about one milligram per kilogram of body weight per day (1 mg/kg/bw/day) so that there is considerable human exposure. FDA decided that the classical safety evaluation may not be adequate because artificial sweeteners and fat substitutes would be ingested in large quantities relative to most conventional food additives.

1989 - The Alar Scare. Headlines in the media across the country cause concern among consumers when a national environmental group reports that children are at risk from exposure to residues of suspected cancer-causing agents like Alar or Daminozide, a growth-regulating chemical used to keep apples from falling off the tree. In part because of the public outcry and consumer boycotts, the manufacturer voluntarily withdrew its food-use registrations and the EPA revoked the tolerances for these food uses in March 1990.

1990 - Uses of FD&C Red #3, a color used since 1907 and listed as GRAS, is revoked under the Delaney Clause. [55 FR 3516].

1990 - Gellan gum is approved as a food additive. [55 FR 39614 (Sept. 28, 1990)].

1990 - FDA approves a chymosin preparation, the first bioengineered milk-clotting substance called rennin, for use in making cheese. Traditionally, it had been extracted from calves' stomachs. Rennin is currently used to produce 65 percent of U.S. cheeses.

1990 - FDA confirms the GRAS status of Simpless (registered trademark), a fat replacement made from milk or egg white protein, for use in frozen desserts.

1990 - Congress passes the Nutrition Labeling and Education Act (NLEA). Under this act, the label on almost every food product in the United States is changed. For the first time, some health claims for foods were authorized (in four categories), the food ingredient panel on labels is standardized, serving sizes are standardized, and terms such as low-fat, and light are standardized.

1991 - A blue ribbon panel, appointed by the Secretary of Health and Human Services and known as the Edwards Committee, looks at the resources and responsibilities of FDA. In its final report, the Committee admonishes the agency to "recognize that approval of useful and safe new products can be as important to the public health as preventing the marketing of harmful or ineffective products," and recommended that the agency continue to "develop a flexible range of regulatory pathways, all of which uphold current standards of safety and efficacy, but which reflect the fact that not all drugs, devices, and foods are alike." The Committee's report also predicts that "current demands and constraints on the FDA are expected to remain throughout the 90's. These include demands for improved performance, continued high quality standards, an increasing number and complexity of submissions and insufficient resource relief."

1992 - FDA publishes its biotechnology policy in the Federal Register [51 FR 23309 (1986); 57 FR 22984 (1992)] in which FDA stated that it would focus on the safety of a food and not the process by which the food was developed. Under this policy, the food products of biotechnology are to be treated no differently than ordinary food, except in cases in which the genetic engineering process adds a new substance to the food that is not GRAS, or that is significantly different in structure, function, or amount than substances found ordinarily in food. [May 29]

1993 - FDA proposes a "threshold of regulation" policy under which substances migrating to food in trivial amounts would not require a food additive regulation. Instead of submitting a food additive petition to establish a regulation allowing use of such substances, a company would submit a letter with information demonstrating why it should be exempt from regulation under the policy. The dietary threshold proposed is 0.5 parts per billion (ppb) which on a body weight (bw) basis corresponds to 25 ng/kg/bw for a 60 kg individual. Food manufacturers will not need to submit any toxicological data on the additives. FDA strongly supports this policy for situations that do not present any safety concerns because it could save considerable effort by both the Government and industry. [58 Federal Register 52719, et. seq. (Oct. 12, 1993)]

1993 - FDA announces approval of the new animal drug sometribove, a recombinant bovine somatotropin (bST) product for increasing milk production in dairy cows. The approval process generates public debate and controversy.

1994 - FDA announces a mandatory Hazard Analysis and Critical Control Point (HACCP) proposal for seafood. The preventive program will ensure a systematic approach for identifying and assessing the risks of biological, chemical, and physical hazards in seafoods.

1994 - FDA approves the Flavr Savr tomato, the first whole food produced using genetic engineering. At the same time, FDA approves an enzyme encoded by a marker gene called the kanamycin or kan (r) gene.

1994 - FDA publishes an Advanced Notice of Public Rulemaking in which it extends its previously announced HACCP initiative with seafood to all foods. Some of the critical control points include the measurement of food and color additives and indirect additives. This preventive food safety system is supposed to enable FDA as well as State and local governments to make more efficient use of existing resources to ensure safe foods. It also can be used to provide consumers with the assurance that the U.S. food supply is safe.

1995 - House Government Reform and Oversight, Subcommittee on Human Resources and Intergovernmental Relations hold hearings on the food additive process. FDA proposes several policy shifts. FDA proposes to: set up a notification system for trivial packaging noncarcinogenic contaminants and GRAS products; to eliminate environmental impact statements, and to set up a consultation process whereby developers of food biotechnology products can consult with FDA. FDA proposes to classify additive petitions into three tiers and set a timetable for action. Tier I will include petitions for indirect food additives or subsequent approvals to already approved food additives; FDA's response will take place in 90 days. Tier II will contain petitions which have more data to support their approval, and FDA wants 180 days to respond. Tier III will include petitions for approval that present difficult or novel scientific or regulatory and policy issues, or have a wide range of exposure or high exposure (macro-ingredient). These will take 360 days to respond to the petition.