Gordon L Klein & Wayne R Snodgrass. Cambridge World History of Food. Editor: Kenneth F Kiple & Kriemhild Conee Ornelas, Volume 2, Cambridge University Press, 2000.
The Processes Affecting Toxicity
Rather than undertaking a categoric examination of the myriad toxins in food, this essay highlights various considerations that should provide a sense of perspective in viewing toxins as a whole. It is important to realize that toxic substances must negotiate the various degradation and propulsive properties of a gastrointestinal tract in order to be absorbed and exert a harmful effect on the body. The ability of the toxin to be absorbed helps determine the amount of a substance that must be ingested before toxic effects become manifest. Moreover, the handling of ingested toxins by an immature gastrointestinal tract of a premature or term newborn infant may be different from that of the fully developed gastrointestinal tract.
Development of the tract begins during the first 12 weeks of gestation as it matures from a straight tube to one that is progressively convoluted, and the surface area for absorption increases. Over the next six months, the gut acquires a sophisticated immune system and the capacity to digest complex carbohydrates, fats, and proteins. Not all of these mechanisms, however, are fully functional until several months after birth.
The extent to which ingested substances, including food and toxins, are absorbed by the intestine is dependent on the capabilities it has developed to deal with carbohydrates, fats, proteins, water, and ions. These are highly complex issues about which varying amounts of information are understood. Nevertheless, a general concept of how absorption occurs may help put the discussion of food toxins in context.
Carbohydrates constitute the nutrients that provide the largest proportion of calories in the Western diet. Carbohydrate intake, in an adult diet, is approximately 400 grams per day. The major ingested carbohydrates are starch, sucrose (table sugar), and lactose (milk sugar) as 60 percent, 30 percent, and 10 percent, respectively, of the total digestible carbohydrates.
Starch is broken down by enzymes acting within the lumen or tube of the small intestine. The smaller molecules of sugar are digested (broken down) to molecules consisting of one to a few linked sugar molecules, and most are transported across the intestinal wall and into the blood by an energy-requiring “pump” enzyme system in the cell membrane (Van Dyke 1989).
Proteins undergo initial digestion in the stomach and are broken down further by pancreatic enzymes in the small intestinal lumen until they become either individual amino acids or small multiamino acid units called oligopeptides. The intestine has evolved separate transport mechanisms for absorption of different types of amino acids as well as oligopeptides.
Digestion of fat begins in the mouth but is primarily accomplished in the upper small intestine where bile acids from the gallbladder emulsify the fat, permitting the efficient action of the pancreatic enzyme lipase to break down the fats into free fatty acids. Because fats are poorly soluble in water, they are transported by micelles, made of bile acids and fat, to the surface of the upper small intestinal wall where they are absorbed as free fatty acids across the intestinal wall. There they enter either the blood, bound to proteins, or the lymphatic system. Many of the toxic substances in food are absorbed by the protein or fat digestion mechanism (Van Dyke 1989).
Other than the processes of digestion and absorption, intestinal factors that may affect the toxicity of substances in foods include the rapid turnover and sloughing of the intestinal epithelial cells in direct contact with toxins. Persons with intestines in which cell turnover has been slowed, as with those in developing countries suffering from protein-energy malnutrition, may be at greater risk of absorbing toxins from dietary staples.
Another factor is the motility of the gastrointestinal tract. Rapid transit, such as in diarrhea, may minimize the contact of foreign substances with the small intestine and thus reduce the opportunities for absorption (Silverman and Roy 1983). An additional consideration that has not been well studied is the presence of a variety of ingested substances in the intestinal lumen that may interfere with the ability of a toxic substance to come into contact with the intestinal absorptive surface. Thus, for example, the ingestion of phytates from various crops may interfere with the absorption of metals, such as zinc and calcium (Alpers 1989; Wallwork and Sandstead 1990).
Sometimes the ingestion of large quantities of one metal can inhibit the absorption of another. Such an inverse relationship exists between copper and zinc (Li and Vallee 1980). Furthermore, the porosity of the gastrointestinal tract is greater in young infants than in older children and adults (Silverman and Roy 1983). This allows the direct passage of intact proteins, and perhaps other substances as well, from the intestinal lumen into the blood, which could make infants more vulnerable to various toxins than older individuals.
The Concept of Bioavailability
Collectively, those factors that regulate intestinal absorption of toxic substances in foods, as well as of required nutrients, determine the bioavailability of the toxin. Although the bioavailability of many of the food toxins has not been clearly defined, it is important to consider this aspect of food toxins, because bioavailability will influence the amount of a substance that must be ingested before its toxicity becomes manifest. It is also a consideration in devising specific therapies for the ingestion of known toxins, such as the use of activated charcoal to bind a toxin in the intestinal lumen or the induction of vomiting to empty the stomach of a potential toxin.
An example of how bioavailability influences the degree to which toxic substances can produce harm is that of aluminum. Aluminum is the third most abundant element on earth and is a contaminant of many foods and medicinal products (Alfrey 1983). When it enters patients as a contaminant of solutions used for hemodialysis or intravenous feeding (total parenteral nutrition), it accumulates in bones, causing reduced bone formation and mineralization (Klein 1990). In addition, it interferes with hemoglobin synthesis, producing anemia, and in patients with kidney failure, it can accumulate in the brain causing progressive dementia and convulsions (Alfrey 1983). By contrast, oral intake of aluminum in normal individuals without damaged kidneys is well tolerated.
Excessive aluminum ingestion, as with long-term consumption of aluminum-containing antacids, may bind phosphate in the intestine and produce phosphate deficiency (Klein 1990). However, ingestion of aluminum in quantities present in normal Western diets (Alfrey 1983) or in currently manufactured infant formulas (Sedman et al. 1985) poses no threat to health so long as the kidneys function normally. The reason for this appears to be that the intestinal absorption of aluminum is very poor, probably less than 0.5 percent of intake, and the kidneys are efficient in eliminating that which is absorbed, leaving very little to accumulate in tissues (Klein 1990).Thus, oral intake of even large quantities of aluminum is not generally harmful because the bioavailability of aluminum in food is very low.
Once ingested, toxins that are absorbed are metabolized. The substances in question undergo biochemical transformation, largely in the liver, by a series of enzymes known as microsomal mixed function oxidases. Some of the reactions involving processes such as oxidation, reduction, or hydrolysis may increase or decrease the activity of the substances.
Other reactions, termed conjugation, involve coupling between the toxin and an endogenous molecule, such as a carbohydrate or an amino acid. These conjugation reactions often result in inactivation (Goodman and Gilman 1980). The fate of the particular toxin in the body will be determined by the relative rates of increased activation and inactivation. The enzymes involved in these reactions are subject to a wide range of individual variability in which genetics, age, body temperature, and nutritional status play important roles.
In general, very young children have a reduced quantity of microsomal enzymes, compared to older individuals. An increase in body temperature produces an increase in all aspects of metabolism, including microsomal enzyme activity, and protein-energy malnutrition depresses the activity of microsomal enzymes (Goodman and Gilman 1980).
The substances themselves may alter the activity of selected microsomal enzymes. Thus, such metals as aluminum, cadmium, and lead have been reported to reduce selectively some microsomal enzyme activity, although these same metals may increase the activity of some conjugating enzymes (Bidlack et al. 1987). Therefore, the variability resulting from the interaction of all the factors influencing metabolism of ingested toxins makes it extraordinarily difficult to predict the fate of any individual substance once absorbed.
It should be evident that both the bioavailability and metabolism of food toxins are very poorly understood variables, and the ensuing discussion of the nature of food toxins must be viewed in light of the highly complex response of the body to these substances, either alone or in combination.
Food toxins can be generally categorized as plant pesticides (natural and synthetic), mycotoxins, metals, and animal toxins, as well as toxins present in foods as the result of industrial contamination. Each category is considered in turn in this section.
Plant pesticides may be synthetic or natural. In recent years, synthetic pesticides have aroused public concern about possible health effects, especially carcinogenicity. Data gathered by the U.S. Food and Drug Administration (FDA) and reported by B. Ames, M. Profet, and L. Gold (1990a) showed that the average dietary intake of synthetic pesticide residues was 0.09 milligrams (mg) per person per day, compared to 1.5 grams per person per day of natural pesticides. Of the 0.09 mg, four chemicals not carcinogenic in rodents – ethylhexyl diphenyl phosphate, chloroprophan, malathion, and dicloran – constitute approximately half the intake, leaving 0.05 mg synthetics, primarily polychlorinated biphenyls (PCBs), as the only possible carcinogens consumed.
FDA monitoring for pesticides in food samples for a one-year period between 1986 and 1987 revealed that exposure of the American population to PCBs and other synthetic pesticides was consistently less than limits set by the U.S. Environmental Protection Agency (EPA), with less than 1 percent of samples containing pesticide residues exceeding the regulatory limits imposed by the FDA (Ames, Profet, and Gold 1990a).
In 1981, R. Doll and R. Peto estimated that approximately 35 percent of cancer cases could be attributed to the human diet. If true, and if synthetic pesticides account for such a small quantity of dietary intake, it is reasonable to cast suspicion, as do Ames, Profet, and Gold (1990b) and R. Beier (1990), on the natural pesticides.
These phytotoxins, as they are called, constitute a wide variety of chemical compounds produced by plants in response to injury from insects, fungi, climate, animal predators and physical damage. Although synthetic pesticide residues may be present in plants in the parts per billion range, natural pesticides may be present in plants in the parts per million or even parts per thousand range. Thus, they are present in much greater concentration than are the synthetic residues.
As an example, glucobrassicin, a polycyclic hydro-carbon, has a breakdown product called indole carbinol. Glucobrassicin is found in large quantities in vegetables, such as broccoli and Brussels sprouts. When these vegetables are chewed (cooked or raw), they release an enzyme that breaks down the glucobrassicin to indole carbinol. This substance acts biochemically in a manner similar to dioxins, some of which may be a carcinogenic synthetic residue. However, although the EPA has set an acceptable human dose limit for dioxin of 6 mg per kilogram (kg) per day, 100 mg of broccoli is estimated to contain 5 mg of indole carbinol (0.1 mg/kg/day) (Ames et al. 1990a).
Despite the large number of natural pesticides, relatively few have been tested for toxicity. Ames and colleagues (1990a, 1990b) estimate that they abound in the tens of thousands, existing in every edible vegetable and fruit to varying degrees. Yet it has also been estimated that only about 2,800 chemicals have been tested in laboratory animals, mainly rodents, for toxicity (Ames et al. 1990b).
The main categories of toxicity include (1) the potential to cause chromosome breakage in vitro, (clastogenicity); (2) the potential to cause genetic mutations (mutagenicity); (3) the potential to produce birth defects (teratogenicity); and (4) the potential to produce tumors (carcinogenicity). The vast majority of tests done using laboratory animals are carried out in rodents and at “maximum tolerated” (near-toxic) doses given chronically. B. N. Ames and colleagues (1990a) cite data showing that of 340 natural pesticides administered to rodents in conventional chronic high-dose protocols, approximately 70 percent were either carcinogens, mutagens, or both. Yet data on toxicity of these natural pesticides for humans are sparse. In addition, some of these natural pesticides (phytoalexins) have other properties that cause more acute toxicity in humans and animals without necessarily being carcinogenic.
Examples of natural chemicals that are harmful to humans include those found in a variety of Asian herbs containing pyrrolizidine alkaloids, which can be toxic to the liver. Thus, Indian herbal teas are known to cause hepatic veno-occlusive disease. Similarly, comfrey tea, made of the leaves and roots of the Japanese comfrey herb, are hepatocarcinogenic in rats, although insufficient data are available for humans. However, as much as 26 mg of pyrrolizidine alkaloids could be consumed in a cup of comfrey tea (Beier 1990).
Another instance of natural pesticides being harmful to human beings is the case of the white potato. Introduced into the Western diet as a result of the Spanish conquest of Peru, the white potato contains two major glycosteroid alkaloids, alpha solanine and alpha chaconine. Both are cholinesterase inhibitors, and thus have the potential to interfere with autonomic nervous system function.
Several outbreaks of a syndrome resembling gastroenteritis with a headache have been attributed to these alkaloids when the concentration of alpha solanine ranged from 100 to 400 micrograms per gram (mg/g) potato. Since not only the consumption of potatoes but also that of their skins (the site of peak alkaloid concentration) is increasing in restaurants, and at least one company is manufacturing a potato chip made from skins, it is possible that further outbreaks of alpha solanine poisoning will be seen. This is of special concern because these alkaloids appear to be resistant to cooking and frying. Some snack foods contain more than 7 times the safe limit of glycoalkaloids (limit of 200 mg/g potato) (Beier 1990).
Potatoes also contain nitrates with an average level of 119 mg/g fresh weight. Nitrates can react with various amine compounds to form N-nitroso compounds, which are carcinogenic and mutagenic in rodents. Potatoes supply 14 percent of the per capita ingestion of nitrates in the United States (Beier 1990).
In addition, there is epidemiological evidence suggesting that the glycoalkaloids in potatoes may be teratogenic in human beings. Attempts to breed strains more resistant to the potato blight fungus have led to an increase in the amount of natural pesticides produced by new strains of potato. L. Penrose (1957) has pointed out that Ireland has weather conducive to the growth of the blight fungus and also the world’s highest incidence of anencephaly (congenital absence of the cranial vault) and spina bifida. Other areas of the world that have developed varieties of potato more resistant to blight have undergone as much as a doubling of the frequency of anencephaly (Beier 1990).
The risk of anencephaly is not eliminated by avoiding the consumption of potato during pregnancy. That the theoretical risk remains is suggested in the report by R. Beier (1990) that solanium, the aglycone derivative of alpha solanine, is stored in the body for a long time and could possibly be released during periods of increased metabolic demand, such as pregnancy. Although evidence supporting a role of the potato glycoalkaloids in the pathogenesis of anencephaly is only circumstantial, a case can surely be made for the need to determine more definitively the relationships of these natural pesticides to human birth defects.
The example of celer y being harmful to humankind is more clearly established than that of the potato. The parsley plant group, most prominently celery, contains phytoalexins known as furanocoumarins. These are photosensitizing toxins that will cause both contact dermatitis and photodermatitis. Grocery workers subject to repeated handling of apparently healthy celery have experienced photo-dermatitis.
The problem stems from attempts to breed a more naturally pest-resistant form of the plant that have produced an elevation in its furanocoumarin content (Beier and Oertli 1983). In the epidemic of photodermatitis in grocery store workers, the linear furanocoumarin content was 14 times higher in the celery in question than in other celery varieties; psoralen, the most photosensitizing of the linear furanocoumarins, was 19 times higher than in other varieties of celery (Beier 1990).
Other evidence of harm to humans done by photosensitizing furanocoumarins are anecdotal. Psoralen ingestion followed by ultraviolet light exposure can produce cataracts in animals and humans (Lerman 1986). Severe, even fatal burns may occur in individuals ingesting psoralen and then visiting tanning parlors (Beier 1990).
These same linear furanocoumarins also are found in citrus and fig plants, which contain furanocoumarin in the peels that are used as flavorings for candies, soft drinks, and baked goods. D-limonene, a psoralen and coumarin derivative, is sold as an insecticide to control pests on household pets (Beier 1990). Fig photodermatitis is seen in fig handlers: In Turkey, 10 percent of fig handlers reportedly contract it (Beier 1990).
In addition, some crops are cultivated in developing countries because they are hardy and do not need the protection of expensive synthetic pesticides. However, they do require extensive processing to detoxify them. For example, much of the cassava root in South America and Africa contains cyanide in high concentrations and is edible only following washing, grinding, scraping, and heating (Beier 1990).Ataxia, or neuromuscular incoordination, due to chronic cyanide poisoning is prevalent in many of the areas of Africa where cassava is consumed (Cooke and Cock 1989). Similarly, in India the pest-resistant grain lathyrius sativas is grown with its seeds containing a potent neurotoxin, B-N-oxalyl-amino alanine, the cause of a crippling nervous system disorder, neurolathyrism (Jayaraman 1989).
As an alternative to plant breeding and use of synthetic pesticides, “organic” farmers claim to use only natural pesticides from one plant species against pests that attack a different species. Thus, phytoalexins, such as rotenone, employed in India as a fish poison, or pyrethrins from chrysanthemum are used. These naturally derived pesticides have not been studied in sufficient detail to determine carcinogenicity in rodents (Ames et al. 1990a, 1990b).
Inasmuch as there are so many natural pesticides in virtually all our edible produce, one might wonder how it is that we are protected against them. Given the complexities in evaluating the effects of bioavail-ability and tissue metabolism of these toxins, this becomes a very difficult question. But it does seem that what is true for rodents may not be true for humans. Thus, species differences in the bioavailability and metabolism of naturally occurring toxins may account for differences not only in the minimum ingested quantity but also in the time course necessary to produce toxicity in humans. It is possible that humans rapidly metabolize natural pesticides to nontoxic metabolites or are not so susceptible to their toxic actions as laboratory rodents.
Secondly, even within the scope of rodent testing, doses of phytoalexins lower than the maximum tolerated dose may be protective or anticarcinogenic. Examples of this include limonene, caffeic acid found in coffee bean and potatoes, and indole carbinol (Ames et al 1990a). Often, feeding rodents large quantities of cruciferous vegetables, such as broccoli, cabbage, and Brussels sprouts, before their exposure to known carcinogens, such as aflatoxin, decreases the incidence of tumors and increases the rate of survival (Ames et al. 1990b). In contrast, if the experiment is performed in reverse and rodents are given the carcinogen prior to feeding on cruciferous vegetables, the incidence of tumors is increased.
Thus, in summary, the naturally occurring phytoalexins in our foods and medicinal herbs have not been subject to the same intensive scientific scrutiny as have the synthetic pesticides. But the public’s current health concerns, the United States government recommendations that more fiber and starch be included in the American diet, and the popularity of “natural” foods and remedies sold in health-food stores combine to make mandatory an increasing amount of scientific study of the safety of such chemicals in the Western diet.
Furthermore, the continued prescription of herbal remedies without scientific basis, on the one hand, and consumption of agricultural staples high in natural pesticides by people in developing countries, on the other hand, pose both real and potential hazards of global dimensions.
Perhaps the reverse of the production of natural pesticides by plants responding to infestations and physical damage is the manufacture of toxic metabolic products by the invaders of the plants (that is, fungi). One example is the production of fungal toxins or mycotoxins. Mycotoxin poisoning was noted in ancient times in China and Egypt, and an epidemic identified by some as ergotism (one form of such poisoning) was recorded in Sparta in 430 B.C. (Beier 1990).
The mycotoxin thought to be most responsible for human disease is aflatoxin. Some others also implicated in human toxicity are ochratoxin A, trichothecenes, zearalenone, deoxynivalenol, citrinin, stergmatocytin, and ergot. These mycotoxins are relatively small molecules, with which humans most likely come in contact through contaminated foods.
The Food and Agriculture Organization of the United Nations (FAO) has estimated that 25 percent of the world’s food crops are contaminated by mycotoxins, including 10 to 50 percent of the grain crops in Africa and the Far East (Mannon and Johnson 1985).Aflatoxins are primarily found in corn, peanuts, cottonseed, and tree nuts; ergot alkaloids, in rye and wheat; ochratoxin and T-2 toxin, in a variety of grains including barley, oats, corn, soybeans, wheat, and rice; penicillic acid, in corn and dried beans; and zearlenone, in corn and wheat (Beier 1990). Of all the fungi producing mycotoxins, only aspergillus flavus and aspergillus parasiticus produce aflatoxin, which is the most highly publicized fungal toxin affecting human health (Beier 1990).
Acute aflatoxicosis in humans has been reported from Taiwan and Uganda (U.S. Council for Agricultural Science and Technology 1989).The syndrome is manifested by abdominal pain, vomiting, liver necrosis, and fatty infiltration, as well as the accumulation of fluid in the lungs (pulmonary edema).
In 1974 in western India, unseasonal rains and food scarcity were responsible in over 200 villages for the consumption of corn contaminated with aflatoxin as high as 16 parts per million. Of 994 patients examined there were 97 fatalities (mostly due to gastrointestinal bleeding). However, the presence of other mycotoxins in the corn could not be ruled out, and consequently the epidemic may have been the work of multiple mycotoxins.
This example, along with other reported cases among children in Thailand, combine to suggest a serious risk of acute aflatoxicosis in developing countries where contaminated grain is more likely to be marketed for human consumption than in developed countries. A report by the U.S. Council for Agricultural Science and Technology (1989) suggests that acute aflatoxicosis poses a low risk in Western diets due to the apparent rarity of heavily contaminated grain in the food supply.
Conversely, aflatoxin B1 has produced liver tumors in several species of experimental animals and is listed as a probable human carcinogen by the International Agency for Research on Cancer (U.S. Council for Agricultural Science and Technology 1989). Thus, there is concern about chronic low-level exposure of humans to aflatoxin despite the low risk of massive doses. The 1989 report by the U.S. Council for Agricultural Science and Technology has reviewed epidemio-logical studies from both Asia and Africa and concluded that the incidence of liver cell cancer is higher in regions where there is high chronic exposure to aflatoxin. However, there is no evidence that this correlation represents cause and effect.
In fact, a study of rural white males from different sections of the United States (Stoloff 1983) found that despite an estimated 1,000-fold difference in the intake of aflatoxin among men in different regions, the risk of death from liver cell cancer was only 6 to 10 percent higher in the most exposed population. Moreover, Chinese males living in the United States have a high incidence of liver cell carcinoma despite a low likelihood of exposure to aflatoxin (Stoloff 1983). Therefore, the risk of aflatoxin B1 to humans as a probable carcinogen is still uncertain, at least with consumption of Western diets.
In addition to the encouragement of proper harvesting, drying, and storing methods, attempts are currently being made with a variety of techniques to degrade or otherwise chemically alter aflatoxin in grains (Beier 1990). Thus, as with aflatoxins, other mycotoxins probably pose a greater threat to human health in developing countries than in the more developed countries. In the former, the scarcity of food and the increased likelihood of grain contamination combine to magnify the likelihood of human consumption of tainted food products. Nevertheless, contaminated grains that may, from time to time, enter Western markets constitute at least a theoretical risk and mandate continued vigilance by governmental regulating agencies over national food supplies.
Endogenous toxins produced by fish may be less of a public health problem than industrial contaminants entering the food chain via fish or other foods. However, ciguatoxin, saxitoxin, and tetrodotoxin are acknowledged food hazards, and mention of them should be made. Ciguatera poisoning was described as early as the 1600s in the New Hebrides (now Vanuatu), and in 1774, the British navigator Captain James Cook reported an outbreak of apparent ciguatera poisoning in New Caledonia (Hokama and Miyahara 1986).
Ciguatoxin is of low molecular weight and belongs to a class of organic compounds called polyethers. It is one of the most potent toxins known, yet associated with few fatalities because its concentration in fish flesh is very low (Tachibana et al. 1987). The toxin is synthesized by a species of flagellate called Gambierdiscus toxicus and is passed through the aquatic food chain from herbivorous to carnivorous fish and then to humans, usually by consumption of certain reef fishes encountered around islands in the Caribbean and in the Pacific (Hokama and Miyahara 1986).
The onset of toxic symptoms may begin 10 minutes to 24 hours after consumption with gastrointestinal symptoms, such as diarrhea, vomiting, and abdominal pain. Neurological symptoms are caused by ciguatoxin’s disruption of ion transport mechanisms that aid in the transmission of impulses along nerve axons (Hokama and Miyahara 1986). The symptoms include increased sensitivity to cold, which produces a painful tingling sensation, dilatation of the pupils, weakness, unsteady gait (ataxia), and abnormalities in deep tendon reflexes. With a large dose of ciguatoxin, respiratory depression may occur, and neurological symptoms can persist for months. Cardiovascular effects of ciguatoxin include abnormalities in blood pressure and heart rate, initially low, then sometimes too high, with an occasional irregular heart rhythm. These effects usually disappear within 48 to 72 hours. Of interest and concern, however, is that multiple poisonings of an individual generally increase his or her sensitivity to the toxin, resulting in more severe clinical effects with repeated ingestion.
Saxitoxin, like ciguatoxin, is produced by one or more species of flagellates (Valenti, Pasquini, and Andreucci 1979). These toxins, however, are often found in mollusks, which concentrate them. Saxitoxin is found, for the most part, in the Alaska butter clam and in mussels and scallops, especially during the warm months of the year. An epidemic of saxitoxin poisoning that occurred in Italy in October 1976 was attributable to the consumption of contaminated shellfish (Valenti et al. 1979).
Like ciguatoxin, saxitoxin is an organic compound of low molecular weight that acts as a neurotoxin by blocking the channels for sodium ion to cross the membranes of excitable nerve cells, thus blocking transmission of neuromuscular impulses. Symptoms usually appear within 30 minutes of ingestion. These include numbness around the mouth, lips, face, and extremities; a broad-based gait with neuromuscular incoordination, accompanied by nausea and vomiting and diarrhea; loss of voice; impaired swallowing; and respiratory impairment, which can lead to death within 12 hours.
A lethal dose of saxitoxin is reported to be 1 to 2 milligrams, whereas the concentration for saxitoxin in affected mollusks consumed in Italy ranged from 556 to 1479 micrograms per 100 grams pulp. Thus, there must be individual variation in the susceptibility to the effects of saxitoxin, because very large quantities of pulp are normally consumed.
Tetrodotoxin was first isolated in 1894 from the fugu (also called puffer) fish. It is found primarily in fish inhabiting the waters of Japan, China, and Polynesia and is one of the most potent toxins known. Ingestion of 2 grams of fish eggs can kill a person (Valenti et al. 1979). Female fish appear to produce greater amounts of toxin than males. Balloon fish, shellfish, toad fish, and globe fish also are known to produce tetrodotoxin. Like saxitoxin, tetrodotoxin is a rapid-acting sodium-ion channel poison that blocks neuro-muscular conduction (Valenti et al. 1979).
The onset of symptoms occurs between 10 and 50 minutes following ingestion, with vomiting, spreading numbness, voice loss, swallowing difficulty, and respiratory depression. In Japan, more than half the victims die within an hour of ingestion, and 100 percent of those that die do so within 24 hours. Those ingesting only a minimal amount of tetrodotoxin recover without residual problems (Valenti et al. 1979).
The fugu fish is considered a delicacy by the Japanese, and restaurant chefs must have a special license from the government to prepare it in such a way that tetrodotoxin is inactivated. There are some anecdotal reports in the medical literature claiming that rapid administration of anticholinesterase drugs, such as edrophonium, can immediately reverse the paralytic effects of tetrodotoxin (Torda, Sinclair, and Ulyatt 1973; Chew et al. 1984).
Food Poisoning from Microorganisms and Their Toxins
Food poisoning is, regrettably, more than an occasional public health problem, usually resulting from either unhygienic food preparation or food storage or both. Spoiled food is contaminated primarily by toxins produced by strains of clostridium and staphylococcus. Salmonella may itself contaminate certain foods, but it does not produce a toxin, according to present knowledge. The causative organism for anthrax is among a group of other microorganisms found in spoiled food. The disease results from the ingestion of contaminated undercooked meat and is manifested by bloody diarrhea, pain, and occasionally shock. Anthrax is seldom a problem in the West and is more often encountered in underdeveloped countries (American Academy of Pediatrics 1991).
Bacillus cereus, a spore-forming gram-positive rod, may be present in a variety of foods. In fried rice (where it frequently occurs) it causes vomiting, and in meat and vegetables it causes diarrhea. The spores are relatively heat resistant, and the organism can grow and produce toxins in the intestine. The course is usually mild and resolves spontaneously within 24 hours (American Academy of Pediatrics 1991).
Two forms of clostridial food poisoning are noteworthy, that originating from Clostridium botulinum (botulism) and that generated by Clostridium perfringens. Botulism is a neurological disorder produced by neurotoxins A, B, E, and F of Clostridium botulinum. The toxins create a flaccid paralysis of the muscles of swallowing and phonation, as well as double vision, blurred vision, and slurred speech. Infant botulism, which occurs primarily in those less than 6 months old, is manifested by constipation, loss of muscle tone, a weak cry, poor feeding, a diminished gag reflex, and ocular palsies.
The neurotoxins are found in improperly preserved foods, especially those that are home processed and canned (American Academy of Pediatrics 1991). Illness occurs when the neurotoxins in unheated food are consumed. Most cases of infant botulism do not have a known source for the clostridial spores. However, honey is one identified source, corn syrup another. The American Academy of Pediatrics (1991) recommends withholding honey and, perhaps, corn syrup from an infant’s diet for the first 6 months of life.
The cramping abdominal pain and watery diarrhea that develop 8 to 24 hours following ingestion of beef, poultry, gravy, and, notoriously, Mexican food usually result from a heat-labile enterotoxin produced by type A C. perfringens. The infection is generally acquired at places where food is prepared in large quantities and kept warm for long periods. Thus schools, camps, caterers, restaurants, and public markets where cooking is done would be typical sources of the infection. As in the case of infection by B. cereus, the symptoms usually resolve spontaneously within 24 hours (American Academy of Pediatrics 1991).
Caliciviruses are RNA viruses that can cause gastroenteritis-like symptoms lasting approximately four days. Outbreaks have been reported in children in institutional settings in Japan and the United Kingdom. Contaminated shellfish and cold foods are thought to be vehicles of transmission (American Academy of Pediatrics 1991).
Campylobacter jejuni, one of the most common organisms causing bloody diarrhea, has been isolated from the feces of turkeys and chickens. Transmission occurs by intake of contaminated food, including unpasteurized milk and improperly cooked poultry (American Academy of Pediatrics 1991).
Vibrio cholerae and its toxin can be acquired from ingestion of contaminated shellfish. The recent cholera epidemic in Peru and other parts of South America was originally attributable to “ceviche” (raw fish treated with lime juice) that was contaminated by V. cholerae. Adequate cooking eradicates the organism from foodstuffs.
Listeria monocytogenes is a cause of neonatal and perinatal infection. During outbreaks it has been traced to maternal intake of unpasteurized cheese or contaminated cole slaw, and milk has also been implicated.
Norwalk viruses can produce a gastroenteritis along with muscle aches, fever, and crampy abdominal pain. These RNA viruses are implicated in epidemics of gastroenteritis, and outbreaks are associated with eating contaminated shellfish and salads (American Academy of Pediatrics 1991).
Salmonellosis, or gastroenteritis produced by non-typhoid strains of salmonella, can be contracted from improperly processed meat or unpasteurized milk. Food handlers who carry salmonella are additional sources of outbreaks (American Academy of Pediatrics 1991).
Staphylococcus aureus and, occasionally, staphylococcus epidermitis can produce a variety of heat-stable enterotoxins: A, B, C1-3, D, E, and F. The enterotoxins, if present in such foods as egg and potato salads, cream-filled pastries, poultry, and ham can produce abdominal cramping pain, nausea, vomiting, and diarrhea from 30 minutes to 7 hours after ingestion. The symptoms are severe but self-limited (American Academy of Pediatrics 1991).
Yersinia enterocolitica, an infection that may mimic other gastrointestinal diseases, including Crohn’s disease (a chronic inflammatory bowel disease) and lymphoma, may be contracted by the consumption of contaminated food, especially uncooked pork and unpasteurized milk (American Academy of Pediatrics 1991).
Finally, one of the routes of transmission of toxoplasmosis, caused by a multi-organ protozoan pathogen with multiple disease manifestations, is by the consumption of poorly cooked meat. The same is true for trichinosis, caused by the nematode Trichinella spiralis. It too can cause anything from mild gastroenteritis to severe multiorgan disease and death.
Contamination of Food by Industrial Products
Industrial human-made toxins that contaminate foods include the heavy metals, such as lead, cadmium, and mercury, as well as lighter metals such as aluminum, dealt with in the section “The Concept of Bioavailability.” Other industrial contaminants include halogenated hydrocarbons used as pesticides. The following section cites several examples of these contaminants as industrial disasters, as well as potential hazards.
In the Japanese prefecture of Toyama in the Jinzu River basin, postmenopausal women became ill after eating cadmium-contaminated rice. The illness, known as “itai-itai disease” was characterized by bone pain, osteoporosis, X-ray appearance of bone thickening overlying an incomplete fracture, and kidney disease as manifested by protein and sugar in the urine. Cadmium ingestion has also been the result of leaching from cadmium-plated containers by acidic drinks, such as fruit juices. These types of containers are now prohibited by law in many parts of the United States (Klein and Snodgrass 1993).
Cadmium may be deposited in soil and water near industrial plants that utilize it in metallurgy, plastics stabilizers, nuclear reactor rods, battery plants, and semiconductors. Because cadmium concentration in the soil can be high in these areas, crops grown in such soil may have high cadmium levels (Klein and Snodgrass 1993). Such may have been the case with itai-itai disease. Cadmium can also enter the aquatic food chain, especially through plankton, mollusks, and shellfish.
Two major disasters have been reported as a result of epidemic mercury ingestion. One of these, in Japan, involved two episodes of methyl mercury ingestion as a result of waste dumping by an acetaldehyde manufacturing plant that discarded mercury into Minimata Bay. In 1956 and again in 1965, many infants of mothers from the cities surrounding the bay were born with brain malformations. They, and older individuals, developed irreversible neurological disease known in the literature as “Minimata disease.”
In Iraq, a similar set of neurological problems developed following the 1971 consumption of bread made from wheat contaminated by a mercury-containing fungicide. The neuropathies resulted from degeneration of the nervous tissue caused by the mercury. Symptoms in exposed infants included cerebral palsy, psychomotor retardation microcephaly, spastic or flaccid paralysis, visual disorders, and convulsions. In older individuals, muscle weakness and visual and hearing impairment were prominent (Klein and Snodgrass 1993).
Although there are no recent major disasters on record for lead such as those reported for cadmium and mercury, it is now recognized that ingestion of even small quantities of lead, especially by children, may result in both behavioral and learning disorders. This finding is the work primarily of H. L. Needleman and colleagues (1990). The main source of lead ingestion by children has been lead-based paint that chips off the walls in run-down inner-city housing. However, it is apparent that other sources of lead ingestion include foods. In many cases, this is because agricultural vehicles, which are not required to use unleaded gasoline, release lead-containing exhaust onto crops, and lead accumulates most prominently in green, leafy vegetables. In addition, acidic foods can leach lead from the lead solder in cans (Klein and Snodgrass 1993).
Aluminum contaminates many foods in our diet, with the average adult consuming from 2 to 5 milligrams per day (Alfrey 1983). The Joint Food and Agriculture Organization/World Health Organization Expert Committee (1989) has indicated that a provisional tolerable weekly intake is around 7 mg per kilogram body weight.
Aluminum accumulation in bone has been associated with reduced bone formation and mineralization, in some cases leading to fractures and severe skeletal pain (Alfrey 1983, Klein 1990). It has also been implicated in a progressive dementia affecting uremic patients (Alfrey 1983). As we mentioned, the intestinal absorption of dietary aluminum is very low, about 0.5 percent (Klein 1990).
In recent years, the detection of large quantities of aluminum in some infant formulas has caused concern (Sedman et al. 1985). This has prompted the American Academy of Pediatrics to caution against the use of soy-based formulas (which have a high content of aluminum) for premature infants because of their immature kidney function (American Academy of Pediatrics Committee 1986).The source of the aluminum contamination in these soy formulas is the calcium and phosphate salts added to them, as well as the soy-protein isolate itself. The calcium and phosphate salts make up the chief sources of aluminum contamination of intravenous feeding solutions in use in hospitals (Sedman et al. 1985).
There are numerous reports of halogenated, primarily chlorinated hydrocarbons contaminating the food chain, either via intake by fish or contamination of livestock feed. According to several reports, fish have been contaminated with DDT (dichlorodiphenyltrichloroethane) and other organic compounds, such as PCB (polychlorinated biphenyls), resulting in high human adipose tissue concentration of these chemicals (Kreiss et al. 1981; Ansari et al. 1986). It is also clear that these chlorinated hydrocarbons can concentrate in human breast milk to levels that may reach 20 times their concentration in cow’s milk, with large dosing of infants a potential result (Fytianos et al. 1985).
Although all of the health implications (including carcinogenicity) of these ingestions are not understood, there is a report of more than 3,000 patients who developed porphyria in southeast Turkey following ingestion of hexachlorobezene fungicide added to wheat seedlings. Many of the breast-fed infants in this exposure under 1 year of age died as a result (Cripps et al. 1984).
In Michigan in 1973-4, there was a large environmental exposure because of the erroneous mixing of approximately one ton of polybrominated biphenyls (PBBs), a commercial flame retardant, into livestock feed. By mid-1974 virtually every Michigan resident had been exposed to these polybrominated biphenyls by consuming contaminated meat, milk, eggs, and other dairy products. Approximately 300 farm family members who consumed contaminated products from their own farms were followed for study (Anderson et al. 1979; Meester 1979).
Although no specific disease was identified, many of the exposed individuals complained of fatigue, visual problems, skin rashes, reduced resistance to infection, reduced tolerance of alcoholic beverages, and reduced libido. Several individuals complained of migratory arthritis, and one patient had aplastic anemia. The amount of polybrominated biphenyls in the subcutaneous fat did not correlate with symptoms, nor was there any kind of a dose-response relationship. The potential for carcinogenicity is uncertain although animal data suggest this is a risk in high-dose, long-term exposure (Groce and Kimbrough 1984). Furthermore, G. Lambert and colleagues (1990) have found that the hepatic microsomal enzymes of individuals exposed to PBBs remain activated up to 10 years following exposures. These activated enzymes are capable of producing carcinogenic metabolites from drugs and other organic compounds.
This chapter is intended to point out the variability of human defenses against the toxic substances we ingest; to illustrate the scope of our dietary exposure to toxins and putative toxins; to suggest our relative ignorance of the potential for harm caused by the myriad chemicals we consume with our food; to indicate that the majority of these are natural and not synthetic; and to show that industrial mishaps can indeed affect our food supply.
Although the public generally has confidence in the food with which it is supplied, there is a need for further scientific study of the effects of natural chemicals on our health, as well as a need for vigilance on the part of both industry and government to ensure that our food supply is neither needlessly nor irresponsibly contaminated.
Finally, in less-developed areas of the world, where the food available for human consumption is scarce and less subject to official scrutiny, the problem of toxic ingestion is magnified and its true extent probably unknown at the present time.