of view are those classified herein as environmental contaminants. Included are the trace elements and organometallic compounds (e.g., arsenic, mercury, cadmium, tin, and lead), as well as a variety of organic substances [e.g., polychlorinated biphenyls (PCBs) and the halogenated hydrocarbon pesticides]. Although this category contains substances of quite diverse chemical structure, there are common characteristics in terms of behavior. The environmental contaminants tend to be stable and thus persistent in the environment, tend to bioaccumulate in the food chain, and can be biotransformed with increased toxicity. Illustrative reviews of the occurrence and the toxicity of the environmental contaminants (e.g., 46-48) indicate the importance of this class of compounds to food safety. Severity ranges over a wide spectrum of effects, depending on the duration and extent of exposure. Some of these substances (e.g., lead, mercury, and PCBs) have been shown to be of special concern in the case of the fetus, infants, and young children because of greater retention as well as susceptibility. The incidence of effects is difficult to quantitate for the environmental contaminants. By and large, incidence can be assessed only indirectly by combining what is known about toxicity with exposure data estimated by monitoring the levels found in food. Fortunately, regulatory controls in terms of permitted levels in foods appear from surveys to be helpful in minimizing human exposure, but unfortunately many consumers assume that since there is government approval, the affected foods are totally without hazard. Consistent with the spectrum of effects associated with these substances, the times of onset can vary widely from acute to long term. As noted, infants and young children are of special concern since effects induced in the short term [e.g., central nervous system (CNS) damage] can be of long-term significance. Food Hazards of Natural Origin

The tens of thousands or perhaps even hundreds of thousands of compounds naturally present in foods could in part be incorporated with those of microbial origin and in part with the environmental contaminants. However, they are treated separately in this book because of their importance and need for attention in their own right. Only a small fraction of these substances have been identified, but among the known compounds are those with significant acute and chronic toxicity.

If one were to somehow solve all the scientific and public concern problems associated with substances directly or indirectly, deliberately or accidentally added to foods, there would still remain a set of food safety questions of immense magnitude and complexity-that of the natural contaminants. These compounds include a large class of substances occurring in foods of plant origin ranging from the oxalates in spinach, through the glycoalkaloids in the white potato to the mush

The Risks From Food Hazards 9

room poisons. Also included are the trace elements and the toxicologically important mycotoxins occurring in grains and other foods susceptible to mold growth, such as the aflatoxins, ochratoxin, patulin, zearalenone, and the tricothecene toxins. Other important contaminants of natural origin include the pyrrolizidine alkaloids and paralytic shellfish poison. In addition, a large set of coumpounds produced in foods during storage, processing, or preparation, such as the nitrosamines and polynuclear aromatic hydrocarbons, are included. Two articles by Hall (30, 49) provide an excellent overview of these substances, many of which have also been reviewed by the National Academy of Sciences (46).

These contaminants of natural origin are of importance not only because of direct human consumption, but also because of secondary exposure from the edible by-products of food-producing animals. In terms of severity, this class contains acute toxicants as well as potent carcinogens. The incidence of effects associated with these constituents cannot be well quantitated, but the case of aflatoxins presents one indication of the need for concern and the possible improvements that might result from control measures (50). In accord with the wide range of potential effects, onset can vary from acute to long term.

Food and Color Additive Hazards

If public attention were the criterion, food and color additives would rank highest. However, in terms of risk, they rank below the preceding categories (31-34). This class includes a wide variety of substances— over 2000 direct additives and perhaps on the order of 10,000 indirect additives, although most of the indirect additives probably do not actually end up in finished foods. By our definition of the category, it also includes several hundred drugs used in food-producing animals.

The discrepancy between public attention and inherent hazard is in large part due to a lack of understanding of the definition of the term "additive." Contrary to popular perception, the majority of direct food additives are GRAS substances. These substances, predominantly spices and flavors, include many familiar food ingredients, some of which, like salt and certain spices, have been used for thousands of years. Review of the safety information on certain GRAS substances has revealed that about 90% present no significant hazard with normal human food uses. Most of the remaining, although requiring addditional testing to meet today's scientific standards, have not been associated with hazards to humans. The other direct additives used in foods have been approved, and their uses have been regulated by the FDA. Indirect additives, such as those used in production, processing, and packaging and that might migrate to food, are numerous but normally occur in foods, if at all, at trace levels—many at parts per billion or less. Ex

amination of severity, incidence, and onset of effects for this very large class of constituents indicates the lowest-ranking hazard.

Regardless of the risk ranking of food additives, it is consistent with sound public policy to periodically review their safety, as well as to review other factors that affect food safety, in light of rapidly advancing science and changing food consumption patterns. This review of food additives, encompassing GRAS substances, direct and indirect food additives, color additives, and drugs used in food-producing animals, is now a standard activity of the Food and Drug Administration (51).

ASSESSING THE SAFETY OF FOOD COMPONENTS

Much of the confusion about the safety of our food supply and the relative risks associated with its various aspects derives from our inability to adequately measure the safety-or, more precisely, the risk— of food components. Whether it is a microbial toxin, an essential vitamin, a natural or other environmental contaminant, or a food additive, we would like to know what risk a given exposure presents (28). In some cases there is risk evidence from direct human experience or from epidemiology studies, but in most cases we are forced to rely on animal or other laboratory tests.

Although animal tests at high dose levels-perhaps a thousand times the equivalent of normal human exposure—are treated with public skepticism, the fear of another thalidomide lurks in the back of our minds. Then, too, if animal tests are to be discounted, what are we to conclude about the many substances whose use is based on an absence of adverse effects in animal tests? Rather than dismissing animal tests (or other laboratory tests) entirely or in contrast accepting their results blindly, they should be considered in perspective. Although the regulatory decision maker or the public policymaker would like yes-no answers from the scientist, such is not always possible; more often than not the scientific answer is “"maybe."

There are many staunch defenders as well as critics of the Delaney Clause, which prohibits approval of any food or color additive, "found to induce cancer when ingested by man or animal . . . ." However, the issue is much broader than just the Delaney Clause; the FFD&C Act requires that an additive be “safe” under its conditions of use and the public expects constituents of food to be "safe" regardless of whether they are legally classified as food additives. In this context, “safe” involves not only cancer, but also any other toxic effect. However, having noted the impossibility of assuring absolute safety, the question really concerns the kinds and the levels of potential risk involved. That question, in turn, poses a host of other questions involving the chemical structure of the compound as well as its mutagenic behavior, its metabolism and biological activity, its acute toxicity, its reproductive and ter

References 11

atology effects, and in each case its dose-response characteristics. Finally, there is the question of how to extrapolate from the animal tests to humans. Obtaining sound data in each of these areas and integrating it to form a pattern that permits scientifically valid regulatory decisions is easier said than done. The Food Safety Council has proposed a decision-tree approach incorporating all these facets of toxicology and leading at several stages to a "pass," "fail," or "more testing" decision (28). Of course, a public-policy decision relative to a given food constituent may well weigh other considerations, and that possibility has generated a great deal of discussion relative to the risk-benefit concept (e.g., 52-56).

The preceding problems of safety or risk assessment are discussed in Chapter 7 with the objective of lending additional insight to the overall question of food safety. This final chapter, together with Chapters 2 through 6, should enable the reader to gain an overall perspective on food safety and thus place in proper context the continuing deluge of scientific and media reports on the safety of food constituents. The references in each chapter provide sources for the reader who is interested in pursuing these food safety topics in more depth.

REFERENCES

1. J. S. Turner, The Chemical Feast: Ralph Nader's Study Group Report on the Food and Drug Administration, Grossman, New York, 1970.

2. J. Verrett, Eating May Be Hazardous to Your Health, Simon and Schuster, New York, 1974.

3. E. M. Whalen and F. J. Stare, Panic in the Pantry, Atheneum, New York, 1973.

4. J. Hightower, Eat Your Heart Out, Crown, New York, 1975.

5. B. F. Feingold, Why Your Child Is Hyperactive, Random House, New York, 1975.

6. E. M. Whalen, Preventing Cancer, Norton, New York, 1977.

7. E. M. Whalen and F. J. Stare, Eat OK, Feel OK: Food Facts and Your Health, Christopher, North Quincy, Mass., 1978.

8. American Council on Science and Health, Cancer in the United States: Is There an Epidemic?, New York, 1978.

9. J. J. Fried, The Vitamin Conspiracy, Saturday Review Press, New York, 1975.

10. National Science Foundation, Chemicals and Health, U.S. Government Printing Office, Washington, D.C., 1966.

11. Editors, FDA Consumer, 13 (3), 2 (1979).

12. H. Tarnower and S. S. Baker, The Complete Scarsdale Medical Diet, Rawson, Wade, New York, 1979.

13. N. Pritkin and P. McGrady, Jr., The Pritkin Program for Diet and Exercise, Grossit and Dunlap, New York, 1979.

14. D. R. Reuben, Everything You Always Wanted to Know About Nutrition, Simon and Schuster, New York, 1978.

15. U.S. Senate Select Committee on Nutrition and Human Needs, Dietary Goals for the United States, U.S. Government Printing Office, Washington, D.C., 1977.

16. A. E. Harper, Am. J. Clin. Nutr., 31, 310 (1978).

17.

U.S. Senate Committee on Agriculture, Nutrition and Forestry, Food
Safety: Where Are We?, U.S. Government Printing Office, Washington,
D.C., 1979.

18. W. R. Barclay, J. Am. Med. Assoc. 242 (7), 657 (1979).

19. R. L. Hall, Chem. Technol., 3 (7), 412 (1973).

20. R. Tannahill, Food in History, Stein and Day, New York, 1973.

21. E. Corwin, FDA Consumer, 10 (9), 10 (1976).

22. W. C. Frazier, Food Microbiology, 2nd ed., McGraw-Hill, New York, 1967.

23. H. W. Wiley, An Autobiography, Bobbs-Merrill, Indianapolis, 1930. 24. O. Anderson, The Health of a Nation; Harvey Wiley and the Fight for Pure Food, Univ. Chicago Press, 1958.

25. H. Hopkins, FDA Consumer, 10 (6), 10 (1976).

26. Federal Food, Drug, and Cosmetic Act, as Amended, U.S. Government Printing Office, Washington, D.C., 1979.

27. W. W. Lowrance, Of Acceptable Risk, William Kaufmann, Los Altos, California, 1976.

28. Food Safety Council, Food Cosmet. Toxicol., 16, Suppl. 2 (1978). 29. H. R. Roberts, Fed. Proc., 37 (12), 2575 (1978).

30. R. L. Hall, “Naturally Occurring Toxicants and Food Additives: Our Perception and Management of Risks," Proceedings of Marabou Symposium on Food and Cancer, Caslon Press, Stockholm, 1978, pp. 6-20. 31. V. O. Wodicka, "Food Safety in 1973," Proceedings of Flavor and Extract Manufacturers Assoc., Washington, D.C., 1973.

32. R. L. Hall, Nutr. Today, 8 (4), 20 (1973).

33. A. M. Schmidt, Address at Food Safety-A Centenary of Progress Symposium, London, October 1975.

34. A. S. Truswell, N. G. Asp, W. P. T. James, and B. MacMahon, "Conclusions," Proceedings of Marabou Symposium on Food and Cancer, Caslon Press, Stockholm, 1978, pp. 112–113.

35. E. M. Foster, Fed. Proc., 37 (12), 2577 (1978).

36. I. C. Munro and S. M. Charbonneau, Fed. Proc., 37 (12), 2582 (1978). 37. J. V. Rodricks, Fed. Proc., 37 (12), 2587 (1978).

38. J. Doull, Fed. Proc., 37 (12), 2594 (1978).

39. National Academy of Sciences, Prevention of Microbial and Parasitic Hazards Associated with Processed Foods, Washington, D.C., 1975.

40. Staff Report, Nutr. Today, 10 (5, 6), 4 (1975).