MFR PAPER 1185 Nitrite Additives- Harmful or Necessary? ELINOR M. RAVESI INTRODUCTION 1971; Sen, 1972; Fazio et aI., 1973; nitrite (Epstein), 1971; Hill·, 1971; Panalaks, Iyengar, and Sen, 1973; Sander and Schweinsberg 5, 1971; Can­ The use of nitrites in the preparation Panalaks et aI., 1974), cured fishery toni, Renon, and L'Acqua, 1974; of smoke-cured fishery products and products (Ender and Ceh, 1968; Sen et Myslivy et aI., 1974). Nitrosamines processed meat products dates back to aI., 1970; Fazio, Damico, Howard, have been isolated from gastric juices 1925. Prior to that, dating back to the White, and Watts, 1971; Sen et aI., of animals fed these precursors and early beginnings of the curing process, 1972; Kawabata et aI., 1973; Gadbois et under simulated human stomach con­ nitrates, usually containing nitrite aI., 1975), in addition to other products ditions (Walters, Saxby, and Newton 6, impurities, were used. Nitrites are such as cheese (Sen, Smith, Schwing­ 1971; Lane, Rice, and Bailey, 1974). used in the curing of meats to impart hamer, and Marleau, 1969), soybean oil The presence of several amines such red color, to enhance flavor, and to (Hedler et al:, 1971), milk (Hedler and as methylamine, di- and trimethyla­ protect the product from the growth of Marquardt, 1968), alcoholic beverages mine, di- and triethylamine, N-propy­ Clostridium botulinum in case of con­ (McGlashan, Walters, and McLean, lamine, and N-butylamine has been 1968), and tobacco (Hoffman et aI., tamination or mishandling. In the 1974). They have also been found to reported in a variety of fishery curing of fishery products, the addition occur in vivo. For a variety of animals products (Gruger, 1972). Their occur­ of sodium nitrite (NaNOz) prior to tested in feeding studies, many of rence, primarily a result of bacterial smoking to inhibit the growth of C. these compounds have been shown to and enzymic action, is known to vary botuUnum, thereby preventing for­ be highly potent carcinogens (Preuss­ considerably, quantitatively and quali­ mation of its toxin, is of primary mannz, 1971; Swann and Magee, 1971; tatively, depending on such factors as importance. In recent years, the use of and Preussmann, 1974). The danger of the species and the age of the fish, as nitrites has been viewed with suspicion, these N-nitroso-compounds to human well as storage and handling con­ beings has not yet been established, as and the continued use of NaNOz in the ditions. They may also arise during food industry has become a matter of there is no direct evidence of their cooking. Freshwater species of fish of controversy. The questions arising carcinogenicity in man. Although much remains to be learned concerning the from the use of nitrites are: 1) Is their 'Epstein. S. S. 1971. In vivo studies on continued use necessary for the pro­ chemistry of these compounds, they interactions between secondary amines and are known to form in foods and in the nitrites or nitrates. Presented at the Inter­ duction of a product safe from deadly national Agency for Research on Cancer and various organs of animals under the Deutshes Krebsforshungszentrum Joint bacterial toxin? 2) Is their presence Meeting on the Analysis and Formation of responsible for the occurrence and favorable conditions of pH, time, and Nitrosamines. temperature from the reaction of • Hill, M. J. 1971. Bacterial production of formation of highly potent carcinogens nitrosamines in vitro and in vivo. Presented at in foodstuffs and/or in the bodies of the secondary and tertiary amines with the I nternational Agency for Research on Cancer and the Deutshes Krebsforshungszen­ consumers of these foodstuffs? trum Joint Meeting on the Analysis and Formation of Nitrosamines. In recent years, the occurrence of 'Hedler, L., H. Kaunitz, P. Marquardt, H. ' Sander, J., and F. Schweinsberg. 1971. trace amounts of N-nitrosamines has Fales. and R. E . Johnson. 1971. Detection of In -v ivo and in-vitro experiments on the N-nitrosocompounds by gas chromatography formation of nitrosocompounds from amines been indicated in many cured meat (nitrogen detector) in soybean oil extract. and amides and nitrate on nitrite. Presented at products (Fazio, White, and Howard, Presented at the International Agency for the International Agency for Research on Research on Cancer and the Deutshes Krebs­ Cancer and the Deutshes Krebsforshungszen­ forshungszentrum Joint Meeting on the trum Joint Meeting on the Analysis and Analysis and Formation of Nitrosamines. Formation of Nitrosamines. Elinor M. Ravesi is a research 'Preussmann, R. 1971. On the significance of • Walters, C. L., M. J. Saxby, and B. E. chemist with the Northeast Utiliza­ N -nitrosocompounds as carcinogens and on Newton. 1971. Nitrosation under simulated tion Research Center, National problems related to their chemical analysis. stomach conditions. Presented at the Inter­ Presented at the International Agency for national Agency for Research on Cancer and Marine Fisheries Service, NOAA, Research on Cancer and the Deutshes Krebs­ the Deutshes Krebsforshungszentrum Joint Emerson Avenue, P.O. Box 61 , forshungszentrum Joint Meeting on the Meeting on the Analysis and Formation of Gloucester, MA 01930. Analysis and Formation of Nitrosamines. Nitrosamines. 24 the Great Lakes region, often used in approving such uses, and establishing test animals which had been simul­ the preparation of smoked fishery safe limits referred to in the law as taneously fed nitrites and certain products, have higher amine contents "tolerance limitations." secondary amines. Malignant tumors than do marine fishes. If it is proven A significant feature of the Food were produced in rats by a dose as low that the simultaneous consumption of Additives Amendment is the Delaney as 2 ppm of diethylnitrosamine (Com­ these amines and nitrites present a real Clause which is intended to protect the mittee on Government Operations, hazard to our health, then all possible consumer from the potential hazards of 1972). To date, a "no-effect level" has steps must be taken to eliminate this ingesting carcinogenic chemicals. FDA not been established for this com­ hazard. By no means would it be is prohibited by this clause from pound. A German study (Sander and possible for us to eliminate these amine approving the use of any food additive Seif, 1969), in which nitrate and the compounds from the foods we eat. We which has been found to induce cancer secondary amine diphenylamine were can, however, to some extent, control when consumed by man or animal. fed concurrently to human volunteers, the amount of nitrite we consume-at FDA may approve a proposed use of an demonstrated that both nitrosation and least that amount which is not a additive after evaluating the data the reduction of nitrate to nitrite were naturally occurring constituent of food. submitted to it and finding that there is occurring in the human body. For­ The U.S. Food and Drug Admin­ no doubt that the proposed use would mation of nitrosamines in human istration (FDA) has issued regulations accomplish the "intended physical or gastric juices due to ingestion of on the safe use of NaN0 2 for the other technical effect," that is, the precursors has also been demonstrated preservation of smoked fishery pro­ effect the additive may have on the by other investigators (Sen, Smith, ducts. As early as 1925, the U.S. sensory or other aspects of the food. and Schwinghamer, 1969; and Magee, Department of Agriculture (USDA) The task of the FDA, in its considera­ 1971). In no instance, however, was imposed an upper limit of 200 ppm tion of whether the additive produces carcinogenesis established. residual sodium nitrite in any cured the desired effect and how much of the Nitrates and nitrites received USDA meat or fish product as it was known additive is required to produce the approval for use in the curing of meats since the early part of this century that intended effect, does not include years before passage of the Food high doses of sodium nitrite had a toxic judging whether the effect increases Additives Amendment and were, effect on humans causing methemo­ the value of the product to the therefore, exempt from its provisions globinemia, the result of nitrite com­ consumer or improves its marketa­ because of "prior sanctions." However, bining with the hemogloblin of blood. bility. Significantly, the amendment prior sanctions may be revoked and Public concern and pressure for does not delegate to the FDA the regulatory action taken against the use stronger and more effective food and authority to balance the benefits of a of nitrates and nitrites. For food other drug control laws resulted in the enact­ food additive against the risks as­ than meats, no such prior sanction ment of the Federal Food, Drug, and sociated with its use in deciding exists, and the use of nitrates and Cosmetic Act of 25 June 1938. This whether to approve the use. The FDA nitrites in such foods must be pre­ legislation increased regulatory control is expected only to consider whether cleared and approved for use by FDA. over toxic s\lbstances added to food; the additive produces the intended The Delaney Clause prohibits FDA but as the use of new food additives effect and whether it is safe for human from approving any food additive "if it mushroomed, it became apparent that consumption. is found to induce cancer when ingested this law, too, was inadequate. In 1958, In January 1971, the Intergovern­ by man or animal." Application of this as a result of a study conducted by the mental Relations Subcommittee began clause to the nitrite situation is compli­ Congressional Delaney Committee, the an investigation to determine the cated by the fact that nitrites per se Food Additives Amendment of 1958 adequacy of the protection being have not been found to produce cancer was passed.