Foods can be viewed as complex mixtures of chemicals. As noted throughout this book, many of those chemicals are nutrients needed to sustain life. However, many nonnutrients exist in foods also. Some of these nonnutrient components—food additives, food contaminants, processing-induced toxicants, and naturally occurring toxicants—may be toxic under certain circumstances of exposure but are not hazardous under typical circumstances. Food contaminants and naturally occurring toxicants are examples of chemical components that are more likely to be hazardous. Processing-induced toxicants form under certain processing conditions, especially heat treatments. Because processing treatments prolong the shelf life of foods and guard against microbial hazards, the development of processing-induced toxicants is a classic risk-versus-benefit puzzle. Among food additives, certain nutrient components of food also can be potentially toxic under certain circumstances, and several of these situations will serve as examples in this chapter. However, this occurs primarily when the nutrients are used as additives or supplements rather than as a consequence of the typical levels ingested with traditional dietary practices. In recent decades, the science of food toxicology has emerged as an approach toward understanding and assessing the risks posed by the various chemicals in food.
Food toxicology could be defined as the science that establishes the basis for judgments about the safety of foodborne chemicals (1
). The central axiom of toxicology, as set forth by Paracelsus in the 1500s, states, “Everything is poison. Only the dose makes a thing not a poison.” Thus, all chemicals in foods—whether natural or synthetic, inherent, adventitious, or added—including nutrients, are potentially toxic. Most foodborne chemicals are not hazardous under typical circumstances of exposure, because the doses ingested with traditional diets are insufficient to cause injury. The degree of risk posed by exposure to any specific foodborne chemical is determined by the dose, duration, and frequency of exposure or, in the case of allergies, the degree of sensitivity of the individual. The age-old wisdom about the benefits of eating moderate amounts of a varied diet protects most consumers from any harm. Unusual diets can sometimes result in toxic responses from chemicals that normally would be considered safe under more typical circumstances of exposure.
Acute adverse reactions to foods are those adverse reactions occurring within hours to a few days following exposure to the particular foods/foodborne chemicals. Acute foodborne intoxications usually result in the rapid onset of symptoms. However, the diagnosis of chronic foodborne intoxications is complicated because symptoms typically develop more slowly with prolonged exposure. Food-associated intoxications are caused by chemicals in food, although the chemical constituents of foods vary widely in toxicity. All consumers are susceptible to most food intoxications. This chapter focuses on the various categories of chemical components that occur in foods (food additives including nutrient additives, food contaminants both manufactured and naturally occurring,
processing-induced toxicants, and nonnutrient components that can be classified as naturally occurring toxicants). In each case, illustrative examples are presented.
Numerous chemical substances are added knowingly to foods to provide a wide variety of technical benefits, including nutrients (Table 101.1
). Several thousand food additives exist, but many are used in very small amounts. Food additives can be classified on the basis of their regulatory standing in the United States: (a) generally recognized as safe (GRAS) substances, (b) flavors and extracts, (c) direct additives, and (d) color additives. Food additives are added to foods intentionally and carefully evaluated for safety. Food additives are generally not hazardous under normal circumstances of exposure.
In the United States, GRAS substances are those food ingredients that were in common use before the latest version of the Food, Drug, and Cosmetic (FD&C) Act that was enacted in 1958. The 1958 FD&C Act required approval by the US Food and Drug Administration (FDA) of any newly developed food additives, but recognized the long history of safe use of many additives. More than 600 chemicals are on the FDA GRAS list, including sucrose, salt, butylated hydroxytoluene (BHT), and spices. Many nutrient ingredients are on the GRAS list also. Most of the common food ingredients on the GRAS list were in common use before 1958. From a legal standpoint, GRAS substances are not actually additives, but that distinction is seldom made by the consumer. Although GRAS substances were in common use before 1958, it is not necessarily true that substantial toxicologic data exist for all these substances. For example, the concerns around sodium levels in the diet and hypertension ensued long after 1958, and salt and other sodium-containing ingredients such as monosodium glutamate (MSG) were placed on the GRAS list before this scientific information became available. Reviews of the safety of the GRAS substances have been conducted since 1958, and deficiencies in our information on their toxicity have been identified and corrected in some cases. Substances, or certain uses of substances, can be removed from the GRAS list if the FDA acquires evidence of hazard to consumers.
TABLE 101.1 CATEGORIES OF FOOD ADDITIVES
Oleoresins and extracts
FD&C Yellow #5
Flavors and extracts represent a large percentage of the total number of food additives. The Flavor and Extract Manufacturers Association (FEMA) keeps a list of accepted flavors and extracts. FEMA is also responsible for evaluating the safety of the chemicals on the list. In essence, the FEMA list is a GRAS list for flavors and extracts. More than 1000 chemicals are on the FEMA list, although some of these chemicals and extracts are no longer used.
Direct food additives are the category for those new food additives that have been approved by the FDA since 1958. In reality, few approvals for new food additives have been granted in recent years. Extensive and costly safety data are required to gain FDA approval for a new food additive. Aspartame, a nonnutritive sweetener, is one of the most notable direct food additives in use in the United States (and many other countries). Aspartame was approved as a nonnutritive sweetener for certain types of uses some years ago, and the consumption of this new additive has become substantial. More recently, Olestra, a noncaloric fat replacer, was approved for certain uses such as the deep fat frying of chips. Aspartame and Olestra are examples of the types of substances for which potential usage levels are high enough to warrant the cost of acquiring the toxicologic information needed to gain food additive approval.
Color additives are regulated in a separate part of the FD&C Act. New artificial color additives must be approved by the FDA in much the same way that new food additives are approved. Some color additives have been banned since 1958 because of concerns about their possible chronic toxicity. A good example is FD&C Red #2, which is banned in the United States, although it is allowed in Canada and other countries. Conversely, FD&C Red #40 is allowed for use in the United States but banned in Canada.
The degree of hazard associated with the presence of additives in our foods is quite low for several reasons. First, the level of exposure to most food additives, especially flavoring ingredients, is generally low. Furthermore, the oral toxicity of food additives tends to be extremely low, especially for acute toxicity. Still, some concerns have arisen about the chronic toxicity of a few food additives, including saccharin, cyclamate, and others. Yet another reason for the low hazard associated with food additives is the established safety of many additives. Many food additives have been subjected to safety evaluations in laboratory animals. In these cases, the toxicity of these food additives is well known, and exposure can be limited to levels far below any dose that would be hazardous. By contrast, the toxicity of naturally occurring chemicals
in foods is often not known, and we cannot be certain that hazardous circumstances will not exist under certain conditions of exposure. Other food ingredients, particularly the GRAS substances, have long histories of safe use even if classical toxicologic evaluations in laboratory animals have not always been exhaustively performed.
The safety of some food additives has been called into question. In some cases, the questions have revolved around evidence for weak carcinogenic activity in laboratory animals. Some additives, such as FD&C Red #2 and cyclamate, have been banned as a result of such evidence. Warning labels are required for saccharin. In addition to carcinogenicity, other concerns have arisen, such as the role of sugar in dental caries and abnormal behavioral reactions, the role of MSG in asthma, the role of aspartame in headaches and other behavior and neurologic reactions, and the role of Olestra in gastrointestinal complaints. The concerns range from acute toxicity such as aspartame and headaches or MSG in asthma to chronic toxicity such as saccharin and bladder cancer or sugar in dental caries. Although a detailed discussion of all of these issues is beyond the scope of this chapter, many of these assertions have been questioned and remain controversial.
A few illustrative examples are discussed. The examples include several food additives that have caused acute illness under certain conditions of exposure. These intoxications are usually the result of either excessive consumption of the additive or ingestion by an individual who has an abnormal degree of sensitivity to the additive. Misuse of food additives by consumers, or food processors, has also created hazardous situations on occasion. Saccharin will be discussed briefly as an example of an additive where chronic toxicity concerns exist. Many other examples could be cited for chronic toxicity concerns, including cyclamate and FD&C Red #2.
Sorbitol and Hexitols
Sorbitol and various other hexitols are commonly used alternative sweeteners. Dietetic food diarrhea associated with these polyol food additives is a good example of an intoxication resulting from the excessive consumption of a food additive. The hexitols and sorbitol are widely used sweeteners in dietetic foods. The hexitols and sorbitol are especially common in noncariogenic candies and chewing gum. Although these sugar alcohols are not as easily absorbed as sugar, they are equally as caloric as sugar once absorbed. Because of their slow absorption, these sweeteners can cause an osmotic-type diarrhea if excessive amounts happen to be consumed. Several cases have been reported in which consumers were ingesting more than 20 g of these sweeteners per day (2
). The levels of hexitols and sorbitol used in foods vary, but in one case the ingestion of 12 pieces of hard candy over a short period of time provided 36 g of sorbitol and resulted in diarrhea (2
Sulfites (sodium and potassium metabisulfite, sodium and potassium bisulfite, sodium sulfite, sulfur dioxide) have been widely used as food additives for many years. Sulfites serve several important technologic functions, including as antimicrobial agent, inhibitor of enzymatic and nonenzymatic browning, and bleaching agent. Sulfite-induced asthma is well established as an example of sensitivity to a food additive that afflicts only a small percentage of the population.
Tartrazine (FD&C Yellow #5)
Tartrazine, also known as FD&C Yellow #5, is an approved artificial food color. This colorant has been widely used in foods and pharmaceuticals for many years. Tartrazine is a color additive that is associated with adverse reactions (asthma and chronic hives) in a sensitive subpopulation of consumers (4
). However, unlike the situation with sulfite-induced asthma, the association of tartrazine in the provocation of asthma and chronic urticaria is controversial. Some studies have revealed a cause-and-effect relationship, whereas other studies have not (5
). Both asthma and chronic urticaria are chronic illnesses whose symptoms tend to flare up at unpredictable times. In some of the clinical trials on tartrazine, key pharmaceutical agents have been withdrawn from the human subjects prior to the tartrazine challenges. If the study is not designed carefully, the flare-up of the asthma or urticaria in such a trial could be caused by either the administration of tartrazine or the withdrawal of the medication. The plethora of poorly designed clinical trials on tartrazine has led several groups to conclude that tartrazine may not actually provoke asthma or chronic urticaria (5
Olestra received food additive approval more recently and can be used as a fat replacer. Because Olestra is poorly absorbed and is not metabolized, it does not provide the calories that would be obtained with fat in similar products. However, the use of Olestra has been associated with acute gastrointestinal complaints, including anal leakage (7
). Only certain consumers seem to be affected, although the prevalence and seriousness of such complaints is a matter of some controversy (8
). Obviously, many consumers occasionally experience postprandial gastrointestinal maladies, which makes the association of such complaints with a particular ingredient rather challenging.
Saccharin was one of the first nonnutritive sweeteners approved for food use in the United States. High doses of saccharin have been shown to cause bladder cancer in laboratory animals (9
). However, the extrapolation of these results to humans, who typically ingest much lower
levels of the ingredient, has stimulated controversy. Thus, the carcinogenicity of saccharin to humans at typical levels of intake is, at best, uncertain, and saccharin remains on the market in the United States. Despite the uncertain relevance of the toxicologic data, warning labels remain on saccharin products indicating that saccharin is known to cause cancer in laboratory animals.