8 Food Additives Tanya Louise Ditschun and Carl K. Winter CONTENTS Introduction Food Additive Functionality Food Additive Regulations Generally Recognized as Safe (GRAS) The Delaney Clause Unintentional Additives Assessment of Food Safety` Specific Food Additives Under Scrutiny Saccharin Aspartame Hydrolysis Products of Aspartame Aspartic Acid Phenylalanine Methanol Diketopiperazine Marketing of Aspartame Erythrosine (FD & C Red #3) Olestra Anectodal Reports of Health Effects Due to Olestra Effects of Olestra on Nutrient Absorption Vitamin A Vitamin E Vitamin D Vitamin K Triglycerides Dietary Phytochemicals References © 2000 by CRC Press LLC Introduction Food additives have been used for centuries in food processing practices such as smoking and salting meat. Prior to the advent of refrigeration, food grown in the summer had to be preserved for the winter; salt, sugar, and vinegar were commonly used preservatives. The pursuits of explorers such as Marco Polo were often for food additives. Additives serve many roles and common uses include maintaining product consistency and pal- atability, providing leavening or control pH, enhancing flavor, and impart- ing color. A food additive can be defined in many ways. The Codex Alimentarius Commission, which develops international regulatory guidelines for food additives, provides the following definition of a food additive: Any substance not normally consumed as a food by itself, and not normal- ly used as a typical ingredient of the food, whether or not it has nutritive value, the intentional addition of which to food for a technological (includ- ing organoleptic) purpose in the manufacture, processing, preparation, treatment, packing, packaging, transport or holding of such food results, or may reasonably be expected to result, directly or indirectly, in it or its by-products becoming a component of or otherwise affecting the charac- teristics of such food. The term does not include contaminants or sub- stances added to food for maintaining or improving nutritional qualities.1 Food Additive Functionality The functions of food additives and the mechanisms by which they work are innumerable. Over 2800 food additives are approved for use in the U.S. Table 8.1 lists properties and functions of several food additives. Food Additive Regulations Just as there are numerous ways to define food additives, there are also many ways to classify them. Additives which are “generally recognized as safe” (GRAS) need not be regulated. Other additives are subject to restricted use status and some fall under the provisions of the zero-tolerance Delaney Clause. The presence of unintentional additives also is permitted under cer- tain conditions. © 2000 by CRC Press LLC TABLE 8.1 The Properties and Functionalities of Selected Food Additives Property Function Additive Anticaking and free flow Tie up moisture in dry Salt, powdered sugar, ground agents ingredients to keep product spice blends free flowing during storage and use Antioxidants Prevent oxidation, which Butylated hydroxyanisole results in rancidity (off (BHA), butylated flavors and aromas) hydroxytoluene (BHT) Antibrowning agents Slow-browning reactions Citric acid, sulfites Antimicrobial agents Chemical preservatives used Sodium benzoate, calcium to control microbial growth propionate, sorbic acid Coloring agents Enhance product appearance Natural and synthetic dyes, such as erythrosine Curing agents Fixing meat color Nitrites Dough conditioners and Improve dough properties Phosphates, sulfates, strengtheners enzymes Fat replacers Replace fat and reduce caloric Olestra value of food Flavor enhancers Intensify flavors Monosodium glutamate Humectants Prevent drying out of semi- Propylene glycol moist foods Nonnutritive sweeteners Replace sugar and reduce Saccharin, aspartame caloric value of food Sequestrants Tie up trace minerals that Ethylenediaminetetraacetic cause color changes acid Source: Adapted from Maga, J. A., Food Additive Toxicology, Marcel Dekker, New York, 1995, 1. Generally Recognized as Safe (GRAS) This list of food additives was established in 1958 under the Food Additives Amendment to the U.S. Federal Food, Drug, and Cosmetic Act (FFDCA). According to this act, GRAS substances are … generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experi- ence based on common use in food) to be safe under the conditions of its intended use.3 GRAS additives have been classified as such through either scientific pro- cedures or their historical use in the food supply. Additives not classified as GRAS have regulated food additive status. Substances not used in food prior to the Food Additives Amendment must undergo toxicity testing to prove their safety, then must be classified as either GRAS or approved by the Food and Drug Administration (FDA) for regulated food additive status. © 2000 by CRC Press LLC The Delaney Clause According to the Delaney Clause of the 1958 amendments to the FFDCA, any food additive found to induce cancer in humans or in animals would be banned in the U.S., regardless of the level of the additive or the magnitude of the theoretical cancer risk. Many food and chemical manufacturers have pushed for a revision of the clause as it has been argued that the general terms of the FFDCA sufficiently controlled the use of hazardous additives. Furthermore, the clause could technically prohibit the addition of essential nutrients to foods, as they could cause cancer in massive doses.4 Some argued on the grounds that a zero tolerance law is scientifically impossible. Sub- stances causing cancer in animals, but not proven to be harmful to humans, also would have to be banned.5 These arguments were refuted by the Food Protection Committee of the National Academy of Sciences, who stated that “no effect” levels could be carcinogenic as the effects may be too weak to be demonstrated in feasible numbers of animals for testing, whereas carcino- genic effects may be evident in the large human population potentially exposed to additives. The committee also recognized the possibility of syner- gistic effects between diet and a person’s susceptibility to carcinogens, although these factors had not been adequately explored at the time.4 Prior to 1996, pesticides that were found to concentrate as a result of pro- cessing from raw to processed food commodities or those directly added to processed foods were also considered to be food additives and, therefore, were subject to the Delaney Clause.6,7 Subsequent legislation passed in 1996 eliminated the classification of pesticides as food additives. Unintentional Additives The remainder of additives not classified as GRAS or regulated through intentional additive use are unintentional additives. These additives are found in foods after production, processing, storage, or packaging, and include plant growth regulators and minute quantities of packaging sub- stances.5 These indirect additives are permitted in foods by law provided the processor takes every precaution to maintain good manufacturing processes and only if the quantity of the additive remains at an insignificant level. Assessment of Food Safety The safety of a food additive is determined through extensive testing in ani- mal models before FDA approves the additive. Although the regulations for animal testing are well outlined, there are no regulatory requirements for human testing. The FDA Redbook II, otherwise known as the FDA Draft Tox- icological Principles for the Safety Assessment of Direct Food Additives and © 2000 by CRC Press LLC Color Additives Used in Food, includes such guidelines for conducting human testing of food additives for safety assessment.8 For an additive to be approved, animal toxicity and metabolism studies of the additive must supply substantial information covering the following areas: 9 • Identification of hazards posed by the additive • Indication of the dose-toxicity relationship for those hazards • Estimation of the probable human consumption of such additives U.S. federal regulations outline the requirements for the FDA safety assess- ment. A determination of the NOEL (no observed effect level) or the NOAEL (no observed adverse effect level) from animal toxicity studies is essential. These are determined through chronic toxicity or lifetime exposure studies to the additive. The NOEL or NOAEL, given in terms of the weight of the addi- tive per kg body weight per day, will be used to determine the ADI (accept- able daily intake) for humans. The ADI is intended to reflect the amount ingested over an entire lifetime; it is commonly set at 1% of the NOEL or NOAEL which presumably allows for consideration of possible greater tox- icity in humans relative to experimental animals and for increased suscepti- bility to specific members of the human population.10 Specific Food Additives Under Scrutiny Saccharin Saccharin is a nondigestible sugar substitute that is 300 times sweeter than sugar.11 Diabetics and persons requiring a low caloric intake may benefit from the use of sugar substitutes. Saccharin is used in the U.S. in products such as soft drinks, tabletop sweeteners, and cosmetic products. It is available com- mercially as an acid salt, sodium salt, or calcium salt. In long-term feeding studies of 5.0 and 7.5% saccharin in the diet, rats showed an increase in uri- nary bladder tumors.12 However, more than