Carcinogenicity food additives

Health and Safety Factors. The Food and Dmg Administration Hsts carrageenan as GRAS, an approved food additive in 21 CFR 172.620. Numerous tests show that carrageenan is not ulcerogenic, teratogenetic, or carcinogenic (35). 

The food additive and GRAS rules appHcable to human foods generally apply to animal food ingredients. However, the Delaney clause s prohibition against carcinogenic substances in food additives was amended to permit carcinogenic chemicals to be fed to animals if the animals are not adversely affected and no residue can be found after slaughter. 

Abbott Laboratories, which has conducted additional toxicity and carcinogenicity studies with cyclamate, a 10 1 mixture of cyclamate—saccharin, and cyclohexylamine, claimed to be unable to confirm the 1969 findings. Abbott then filed a food additive petition for cyclamate in 1973, which was denied by the FDA in 1980. In 1982, the Calorie Control Council and Abbott Laboratories filed a second food additive petition containing the results of additional safety studies (73). That petition was stiU pending as of 1996. Cyclamate is, however, allowed for use in any or all three categories, ie, food, beverage, and tabletop, in about 50 countries. Sweet n Low, known in the United States as a saccharin-based table-top sweetener, contains exclusively cyclamate in Canada. 

The function of sodium nitrite, NaN02, as a food additive is two-fold (1) it inhibits the oxidation of blood, preventing the discoloring of red meat, and (2) it prevents the growth of botulism bacteria. There is now some controversy regarding this food additive because nitrites are suspected of combining with amines under the acidic conditions of the stomach to produce carcinogenic nitrosoamines. 

In contrast, the Food Additive Amendments of 1958 to the Food, Drug and Cosmetic Act presented a different type of law, a "zero-risk" law. Under the thrust of the zero-risk law, it said "if a food additive is a carcinogen, we cannot permit any exposure since we cannot live with any such risk." Risk is the evaluation of severity of toxicity or hazardous properties... 

Some chemicals are believed to have no threshold above which toxic effects are observed. In other words, a single molecule has the potential to induce an adverse effect. The most common group of hazards in this respect are genotoxic carcinogens. Chemical carcinogens are not normally approved as food additives because an acceptable daily intake cannot be established. 

Absence of carcinogenity, genotoxicity, developmental and reproductive toxicity and of chronic toxicity effects at low exposure levels are indispensable prerequisites for food additive approvals. All substances approved in the European Union or the USA or deemed generally recognised as safe (GRAS) in the USA fulfil this requirement. 

Since food additives are subjected to the most stringent toxicological testing procedures, only a few synthetic antioxidants have been used in foods for any length of time. Antioxidants are extensively tested for the absence of carcinogenity and other toxic effects in themselves, in their oxidised forms, and in their reaction products with food constituents, for their effectiveness at low concentrations, and for the absence of the ability to impart an unpleasant flavour to the food in which they are used. 

The FDA also regulates food additives - substances, such as antioxidants, emulsifiers and non-nutritive sweeteners, that are intentionally and directly added to food to achieve some desired technical quality in the food. As noted, the Delaney clause prohibits the deliberate addition to food of any amount of a carcinogen. These additives, if they are threshold agents (not carcinogenic), can be allowed as long as the human intake does not exceed a well-documented ADI. Those who would seek approval for an additive need to supply the FDA with all of the toxicity information needed to establish a reliable ADI, and all of the product-use data that would permit the agency to assure itself that the ADI will not be exceeded when the additive is used. 

In the case of a substance like Tris, or the food additive AF-2, the combination of an extremely widespread human exposure to the chemical and a positive result in a number of short-term tests should have been sufficient evidence to stop its use, considering that alternatives were available. Yet Tris and AF-2 were not removed from the market until the results from animal cancer tests indicated that they were carcinogens. It is becoming apparent that a positive result in many of these short-term test systems is meaningful, and that the systems may not only be a complement to animal cancer testing but may also provide much additional toxicological information as well. We... 

Similarly, in order to avoid any quantitative estimate, an MOE approach has been recommended by, e.g., JECFA (the Joint FAO/WHO Expert Committee on Food Additives) and EFSA (the European Food Safety Authority) in the assessment of compounds that are both genotoxic and carcinogenic by using a benchmark dose (BMD) approach to estimate the BMDLio (benchmark dose lower limit) representing the lower bound of a 95% confidence interval on the BMD corresponding to a 10% tumor incidence (see Section 6.4). 

FA088 Soni, K. B., M. Lahiri, P. Chackradeo, S. V. Bhide, and R. Kuttan. Protective effect of food additives on aflatoxin-induced mutagenicity and hepato-carcinogenicity. Cancer Lett 1997 115(2) 129-133. 

Stoner, GD., Shimin, M.B., Kniazeff, A.J., Weisbuiger, J.H., Weisbireger, E.K. Gori, GB. (1973) Test for carcinogenicity of food additives and chemotherapeutic agents by the pulmonary tumor response in strain A mice. Cancer Res., 33, 3069-3085... 

The FDA removed saccharin from its list of approved food additives in 1972, after it caused bladder tumors in rats. The rats were fed a daily amount of saccharin equivalent to the amount in 875 bottles of diet soda (Schmeck 1972). In late 1997, the scientific advisory panel to the National Toxicology Program (NTP) considered removing saccharin from the NTP s list of suspected carcinogens at the request of NTP scientists but voted 4 to 3 to leave saccharin on the list (Stolberg 1997). 

Food Additives Act (1958) - This act included the infamous "Delaney Clause" which in effect says that substances used as food additives must be classified as human carcinogens if they lead to cancer when ingested by man or animals at any level of exposure. The additives used prior to 1958 were placed on a list and called Generally... 

Although the potentially carcinogenic nitrosamines may he present in foods, particularly cured meats, occurrence is infrequent and at low levels. USDA regulations stipulate that ascorbic acid be added to cured meats at live limes the level of nitrates and nitrites to prevent the formation of carcinogenic Af-nitroso compounds. See also Food Additives. 

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