Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response.

Introduction

Historically, we have learned that everything is toxic; it is only the dose that separates the toxic from the non-toxic. Even water is toxic if a large amount (4–5 liters) is consumed in a relatively short time (2–3 hours). The pathogenesis of water intoxication includes hyponatremia, followed by cerebral edema, seizures and death.

Like water, too much of a good thing such as the antioxidant vitamin A, can have acute toxic effects leading to hepatotoxicity or chronic high levels can have a pro-oxidant effect . Something as innocent as licorice, when consumed in large amounts may be harmful. For example, Bannister and associates reported hypokalemia leading to cardiac arrest in a 58-year-old woman who had been eating about 1.8 kg of licorice per week . This licorice intoxication (dubbed “glycyrrhizism” after glycyrrhizic acid, the active component of licorice), has an effect resembling that of aldosterone, which suppresses the renin-angiotensin-aldosterone axis, resulting in the loss of potassium. Clinically, hypokalemia with alkalosis, cardiac arrhythmias, muscular symptoms together with sodium retention and edema, and severe hypertension are observed. The syndrome may develop at a level of 100 g licorice per day but gradually abates upon withdrawal of the licorice.

Recently, public health and social agendas have become more proactive in food toxicology, such as regulating (or outright banning) trans fats or “endocrine disruptors” in foods on the basis of public safety, including a suggestion of removing the generally recognized as safe (GRAS) status for salt . These agendas lose sight of the basic principle of toxicology that “the dose makes the poison” and that demanding “safety per se” or “safe at any dose”, for all foods and ingredients is a non-starter and as a concept, was abandoned with the adoption of the Federal Food and Drug Act (FFDCA) in 1958. For their part, the regulators can limit amounts of potentially toxic substances allowed in food and in those circumstances where setting limits is not effective and public health policy makers provide the public with sufficient information (e.g., label information), where possible, to protect the consumer from reasonably foreseeable problems. Labeling requirements by the FDA provide the consumer with helpful information about content of fats, carbohydrate, protein, potential allergens, caloric value, etc., but do not provide information about toxins that may be inherent in the foods or formed during processing. Because some food toxins cannot be removed from foods and others may be created during processing or cooking, consumption of small quantities of food toxins is unavoidable. The purpose of this review is to illustrate the potential risks of these toxins when consumed at concentrations normally present in foods and the steps taken by regulators to mitigate exposure where possible.

Factors Driving the Acceptance of Certain Foods

Beyond the basic requirements of nutritional or hedonic value, the concept of exactly what constitutes food is largely culturally based; that is, the consumption of pork, shellfish, eel, “rocky mountain oysters”, cracklings, chitlin’s (chitterlings), brain, monkey, guinea pig, dog, snake, insects and arachnids, etc., may be prohibited by religious practices or a matter of personal taste and, in the case of brains (or neural tissue) at least from cattle, has recently become no longer acceptable. Interestingly, there are no fruits or vegetables on any theocratic forbidden list.

There are some personal prohibitions that are genetically driven, but may not be perceived as a “toxicity” concern. For example, a genetic variant has been described for cilantro, which is perceived by some people as having an unpleasant soapy taste or rank smell . Another, better known variant is the ability to taste phenylthiourea (also known as phenylthiocarbamide, PTU or PTC) . The ability to taste and smell certain substances may be key to evolutionary survival, as while the alkaloids of many potentially poisonous plants confer a bitter flavor, Goff and Klee have indicated that certain flavors and odors may also provide sensory cues for nutritional value of some plants . For example, the characteristic odor profile of tomato (e.g., “tomato”, “green”, or “grassy”) are derived from cis-3-hexenal, cis-3-hexenol and trans-hexenal along with visual cues, to promote repeated consumption of an enjoyable food. In the context of promoting consumption of a specific food anosmia (lack of odor perception) or “specific anosmia” (which may be genetically based), will put the individual at a competitive disadvantage in food selection. Persistent or total anosmia also represents a clear safety hazard as the individual could not detect the tell-tale signs of decay or putrefaction of unfit foods.

Naturally formed substances

β-Thujone

Thujone, a monoterpene ketone, is the primary constituent of essential oils derived from a variety of plants, including sage (Salvia officinalis), clary (Salvia sclarea), tansy (Tanacetum vulgare), wormwood (Artemisia spp. and white cedar (Thuja occidentalis L.) . Essential oils from these plants are used in herbal medicines, as flavorings in alcoholic drinks and fragrances throughout the world. Thujone is potentially toxic and the presence of alpha- or beta-thujone in food and beverages

Hypericin in St. John’s wort

St. John’s wort (Hypericum perforatum) is an herbal thought to alleviate symptoms of depression, and standardized extracts of St. John’s wort are consumed typically in tablet or capsule form. The major active antidepressive constituents in St. John’s wort are thought to be hyperforin and hypericin . The mechanism of action is not fully understood, but may involve inhibition of serotonin (5-HT) reuptake, similar to conventional antidepressive drugs. In this manner, hyperforin and hypericin taken in conjunction with other serotonin reuptake inhibitors may contribute to serotonin syndrome, a potentially life-threatening elevation of serotonin in the central nervous system.