Risk and Our Use of PesticidesComparison of data from different countries reveals wide differences in the rates of many types of cancer. This leads to the hope that each major type of cancer may be largely avoidable, as is the case for cancers due to the use of tobacco, which constitute 30% of the cancer deaths in the United States and the United Kingdom. Despite numerous suggestions to the contrary, there is no convincing evidence of any generalized increase in either the US or UK cancer rates other than what could plausibly be ascribed to the delayed effects of previous increases in tobacco usage. Thus, whether or not any recent changes in life-style or pollution in industrialized countries will substantially affect future cancer risks remain to be seen. That is, important determinants of current risks remain to be discovered among long established aspects of our way of life. Epidemiologic studies have indicated that dietary practices are the most promising areas to explore. Such studies suggest that a general increase in the consumption of fiber-rich cereals, vegetables, and fruits and a decrease in the consumption of fat-rich products and excessive alcohol would be prudent. This is still, however, a lack of definitive evidence about the dietary components that are critical for humans and about their mechanisms of action. Laboratory studies of natural foodstuffs and cooked food are beginning to uncover an extraordinary variety of mutagens and possible carcinogens and anticarcinogens. Plant, in general, synthesize toxic chemicals in large amounts, apparently as a primary defense against the hordes of bacterial, fungal, insect and other animal predators. Plants that humans ingest do not represent exceptions to this rule. The variety of the toxic chemicals that plants make are so numerous that chemists have made careers of characterizing them for over 100 years. New plant chemicals are still being discovered. Toxicological studies have, however, been conducted on only a small percentage of natural plant products. Let me give you some examples. 1. Safrole, estragole, methyleugenol and related compounds are present in many edible plants. Safrole, estragole, methyleugenol are carcinogens in rodents, and several of their metabolites are mutagens. Oil of sassafras, which has been used in natural sarsaparilla root beer, is about 75% safrole. Black pepper contains small amounts of safrole and large amounts (close to 10% by weight) of the closely related compound, piperine. Extracts of black pepper cause tumors in mice at a variety of sites at a dose of extract equivalent to 4 mg of dried pepper per day for a three month period. Humans ingest, on average, over 140 mg per day. Capsaicin, the pungent material in hot pepper is a mutagen and there is preliminary evidence for its being a carcinogen. 2. Most hydrazines that have been tested are carcinogens and/or mutagens. Large amounts of carcinogenic hydrazines are present in edible mushrooms. The widely eaten False Morel contains 11 hydrazines, three of which are known carcinogens. One of these hydrazines, N-methyl-N-formyl hydrazine is present at a concentration of 50 mg per 100 gms of mushroom and causes lung tumors in mice at the extremely low dietary level of 20 µg per mouse per day. The most common commercial mushroom, Agaricus bisporus, contains about 300 mg of agaritine per 100 gm of mushroom as well as smaller amounts of other related carcinogens. Agaritine is not appreciably destroyed by cooking and when eaten, is distributed in tissues where it is converted to a diazonium derivative which is a very potent carcinogen (a single dose of 400 µg/gm of body weight gives 30% of treated mice stomach tumors). 3. Linear furocoumarins such as psoralen derivatives are potent light activated carcinogens and mutagens are wide spread in plants of the Umbelliferae family (celery, parsnips) and the Moraceae family (figs). The level in celery (about 100 µg/100 gm) can increase about 100-fold if the celery is stressed or diseased. Celery pickers and handlers commonly develop skin rashes on their arms when exposed to diseased celery. Oil of Bergamot, a citrus oil, is very rich in psoralen and was used as an ingredient in a leading sun tan lotion in France. Psoralens, when activated by sunlight, damage DNA and induce tanning more rapidly than the UV component of sunlight, which is also a carcinogen. 4. The potato glycoalkaloids solanine and chaconine are strong cholinesterase inhibitors and possible teratogens and are present in amounts of about 15 mg/200 gm of potato. When potatoes are diseased, bruised or exposed to sunlight, these and other glycoalkaloids reach levels that can be lethal to humans. Plants typically respond to damage by making more and often different toxic chemicals as a defense against fungi and insects. The different cultivars of potatoes vary in the concentrations of toxic glycoalkloids that they produce. One cultivar, bred for insect resistance, was withdrawn from use because its potential toxicity to humans (>40 mg/200 gm of potato) was simply too great. 5. Quercetin and several similar flavenoids are found to be mutagens in several short-term test systems. Flavenoids are extremely common (daily levels close to 1 gm) in the human diet. 6. Quinones and their phenol precursors are widespread in the human diet. Quinones are quite toxic and can react with DNA. A number of dietary quinones and phenols have been shown to be mutagens. Mutagenic anthraquinone derivatives are found in plants such as rhubarb and certain molds. Many dietary phenols can spontaneously autooxidize to quinones (catechol derivatives such as the caffeic acid component of chlorogenic acid, for example, is present at levels of about 250 mg per cup of coffee). The amounts of these phenols in human urine and in our diets is also appreciable. Catechol, for example, is excreted in urine at levels of about 10 mg/day and appears to be derived mainly from the metabolism of plant substances. Catechol is a potent promoter of carcinogenesis, an inducer of DNA damage, and a likely active metabolite of the carcinogen, benzene, and is also a toxic agent found in tobacco smoke. 7. Theobromine, a relative of caffeine, has been shown to be mutagenic in a number of tests. It potentiates DNA damage (as does caffeine) by various carcinogens in human cells. It also causes testicular atrophy and spermatogenic cell abnormalities in rats. Cocoa powder is about 2% theobromine and therefore humans may consume hundreds of milligrams of theobromine a day from chocolate. Theobromine is also present in tea. 8. Pyrrolizidine alkaloids are carcinogenic, mutagenic and teratogenic and present in thousands of plant species, often at levels greater than 1% by weight. Some of these plants are ingested by humans, particularly as herbs and herbal teas and sometimes in honey. Pyrrolizidine alkaloid poisonings in humans cause lung and liver lesions and are commonly misdiagnosed. Comfrey, a herb that is widely used for tea, is carcinogenic. 9. The broad bean (fava bean), a common food of the Mediterranean region and California, contains the toxins vicine and convicine at a level of about 2% of its dry weight. Pythagoras forbade his followers to eat broad beans, presumably because he was one of the millions of Mediterranean people with a deficiency of glucose-6-phosphate dehydrogenase. This deficiency results in a low glutathione level in blood cells, which offers increased resistance to malaria. The low glutathione level also results in a marked increase in sensitivity to the toxins mentioned earlier that are found in fava beans. Sensitive individuals who ingest fava beans develop a severe hemolytic anemia. 10. Allyl isothiocyanate is a major flavor ingredient in oil of mustard and horseradish and is also one of the main toxins of mustard seeds. This compound has been shown to cause aberrant chromosomes in hamster cells when used at quite low concentrations. It is also a known carcinogen in rats. 11. Gossypol is a major toxin in cottonseed and accounts for about 1% of cottonseed dry weight. Gossypol causes pathological changes in rat and human testes, abnormal sperm and male sterility. Genetic damage has been observed in embryos sired by gossypol-treated male rats. Gossypol appears to be a carcinogen as well. Crude, unrefined cottonseed oil contains considerable amounts of gossypol (100-750 mg/100 ml). Thus, human consumption may be appreciable in countries where crude cottonseed oil is used extensively for cooking (Egypt). Gossypol is being tested as a male contraceptive in over 10,000 people in China as it is inexpensive and causes sterility during its use. Plant breeders have developed "glandless" cotton, a new strain that synthesizes low levels of gossypol, but seeds from this strain are much more susceptible to attack by the fungus Aspergillis flavus, which produces the potent carcinogen, aflatoxin. 13. The phorbol esters present in the Euphorbiaceae are found in plants used as folk remedies and herbal teas. These are potent promoters of carcinogens and may have been a cause of nasopharyngeal cancer in China and esophageal cancer in Curacao. 14. Alfalfa sprouts contain canavanine, a highly toxic arginine analog that is incorporated into protein in place of arginine. Canavanine, which occurs in alfalfa sprouts at about 1.5% of their dry weight, appears to be the active agent in causing the severe lupus erythematosus-like syndrome seen when monkeys are fed alfalfa sprouts. Lupus in man is characterized by a defect in the immune system, i.e., autoimmunity, antinuclear antibodies, chromosome breaks and various other types of pathologies. The human dietary intake of nature's pesticides is likely to be several grams per day... probably at least 10,000 times higher than the dietary intake of any man-made pesticides. The burnt and browned material from heating protein during cooking is highly mutagenic. The browning reaction products from the caramelization of sugars, of the reaction of amino acids and sugars during cooking (i.e., the brown material on bread crusts and toast) contain a large variety of DNA damaging agents and presumptive carcinogens. The risk from inhaled cigarette smoke can be one reference standard: an average life shortening of about 8 years for a two pack a day smoker. The amount of burnt material inhaled from severely polluted city air, on the other hand, is relatively small: it would be necessary to breathe smogy Los Angeles air (111 µg/cubic meter total particulates; 31 µg/cubic meter soluble organic matter) for 1 to 2 weeks to equal the soluble organic matter of the particulates or the mutagenicity from one cigarette (20 mg tar). Epidemiologic studies have not shown significant risks from city air pollution alone. Air in the houses of smokers is considerably more polluted than city air outside. Coffee, which contains a considerable amount of burnt material, is mutagenic. One cup of coffee also contains about 250 mg of the natural mutagen chlorogenic acid which is also an antinitrosating agent (anticancer agent), about 100 mg of caffeine which inhibits DNA repair and can increase tumor yields. There is preliminary evidence that heavy coffee drinking is associated with cancer of the ovary, bladder, pancreas and the large bowel. What you end up with is that nature is not very benign. There are a number of mutagens and carcinogens in every meal. Nature's pesticide's are present at parts per hundred and parts per thousand while man-made pesticides are present at parts per million or parts per billion. We are eating more than 10,000 times the amount of nature's pesticides than man's pesticides. Tobacco smoking is without doubt, a major and well-understood risk, causing about 30% of the cancer deaths and 25% of the fatal heart attacks in the U.S. We subsidize the growing of tobacco in the U.S. Risks from carcinogens are not linear with time. For example, among regular cigarette smokers, the excess annual lung cancer incidence is approximately proportional to the 4th power of the duration of smoking. Excessive alcohol consumption is another large risk. Certain other exposures might turn out to be important in some people. For instance, certain drugs, where consumption can reach hundreds of mgs/day; certain cosmetics; and certain occupational exposures. It is sometimes said that pollution is being neglected is the U.S. Consider
for a moment that the budget for the Environmental Protection Agency is
essentially the same as the budget for the National Cancer Institute.
Consider also, that in spite of the "risks" I have noted, the overall trend in life expectancy in the U.S. is continuing steadily upward. You might be interested in what people perceive as risk. The following table illustrates risks as perceived and ordered from 1 to 30 by four groups of people. Do you agree with the experts or with the League of Women Voters? You might also be interested in our relative exposures to various "chemicals." Examine the following table. Finally, take a look at this last table. You might also be interested in " of mice and men." Return to the Syllabus Page.
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