Carcinogens, Delaney Clause

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. 

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. 

Until 1994 the EPA regulated pesticides proposed for use on food crops under certain sections of the Food, Drug, and Cosmetics Act. Carcinogenic pesticides were subject to the Delaney clause, and were thus prohibited. The use of a non-carcinogenic pesticide was allowed if its manufacturer provided data sufficient to establish an RfD, and information on expected food residue levels sufficient to document that the RfD would not be exceeded when people consumed food containing residues of the pesticide. The tool for determining compliance with this criterion is called a tolerance, and it is expressed as the maximum amount of a pesticide that can be present in a given amount of food, if the RfD is not to be exceeded. 

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... 

Finally it should be noted that prior to the FQPA in 1996, the Delaney clause prohibited the establishment of tolerances or maximum allowable levels for food additives if it has been shown to induce cancer in human or animal. This is an important change in regulations because pesticide residues were considered as food additives. Because of the FQPA, pesticide residues are no longer regarded as food additives, and there is no prohibition against setting tolerances for carcinogens. 

Minutes, EMS Council Meeting (October 17,1972), EMS, Mailing Papers. The Delaney Clause, passed in 1958 as part of an amendment to the Food and Drug Act, banned food additives that tested positive in human or animal carcinogenicity tests. Chu to de Serres (October 24,1975), RRS, MS 1261, Box 1, Folder 18. 

Delaney Clause prohibited any carcinogenic additive in food, regardless of its potency, and was an early example of the application of a precautionary measure, even though the implications of the clause have been downplayed since then. 

A unified safety standard for raw and processed foods This amends the Delaney clause in the FFDCA. Under the Delaney clause, a chemical that causes cancer in experimental animals (regardless of dose) shall not be allowed in processed food. Under the FQPA, pesticide residues shown to cause cancer in humans or animals are allowed on food if the EPA determines that the tolerance is safe, meaning that there is a reasonable certainty that no harm will result from exposure to the pesticide. This amendment is necessary mainly because of improved analytical capabilities. Under the Delaney clause, a carcinogen pesticide would be given a zero tolerance in processed food. However, zero tolerance caused many problems. As the analytical sensitivity increased, concentrations that were zero by old methods became measurable. A unified safety standard eliminates longstanding problems posed by multiple standards for pesticides in raw and processed foods. 

As noted above, the FFDCA tasks FDA with determining whether a food contact notification has demonstrated the safety of the proposed use. The food additive Delaney clause of the FFDCA states that no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of food additives, to induce cancer in man or animal... . Therefore, demonstration of carcinogenicity in any animal species is deemed sufficient to prohibit approval as a food additive. 

As discussed above, the Delaney clause applies to substances proposed for use as food additives, but does not apply to individual constituents of a food additive. Examples of constituents would include residual monomers or catalysts. The constituents policy, subjected to judicial review in Scott v. FDA, 728 F. 2d 322 (6th cir. 1984), states that FDA may consider the potential risks of constituent exposure under the general safety standards set forth in FFDCA. The notification process places the responsibility upon the notifier for addressing the carcinogenic risk of constituent exposure from a proposed use of a food additive. FDA recommends that notifiers include in their food contact notification a safety narrative that addresses the safety of each carcinogenic constituent at any exposure (in addition to the recommendations listed in Table 7.1). This narrative should include an estimate of the potential human cancer risk from the constituent due to the proposed use of the food contact material (FDA, 2002). 

Weissburger, J.H. Human protection against non-genotoxic carcinogens in the us without the delaney clause. Exp. Toxic. Pathol. 1996, 48, 201-208. 

The lake of erythrosine (ED C red 3), for example, has been delisted (see Section 16) in the USA since 1990, following studies in rats that suggested that it was carcinogenic. This delisting was as a result of the Delaney Clause, which restricts the use of any color shown to induce cancer in humans or animals in any amount. However, erythrosine was not regarded as being an immediate hazard to health and products containing it were permitted to be used until supplies were exhausted. ... 

Finally, the scheme has generally not been considered, even by its proponents, appropriate to apply to carcinogens. This view may stem from the legal stricture (which exists in the United States in the form of the Delaney clause of the Food, Drug and Cosmetic Act) that no ADI can be established for a carcinogenic additive, in which case no safety assessment scheme is needed. On the other hand, it may stem from a scientific view that the mode of action of carcinogens is such... 

The USP discourages the internal use of comfrey because of studies showing hepatotoxicity and carcinogenicity, and no studies have shown the benefit of taking comfrey orally (USP, 1998). The Delaney Clause of the Food, Drug and Cosmetic Act establishes no tolerance for carcinogens in foods. Even so, comfrey is considered a dietary supplement, and can be sold if labeled as such. 

Much of this regulatory zeal was driven by the Delaney Clause, which amended the Food, Drug and Cosmetic Act of 1938. This clause forbids the addition of any amount of animal carcinogen to the food supply. This was originally based on our belief at the time that even one molecule of a carcinogen could cause cancer in humans. This concept was largely influenced by theories of radiation-induced cancer. Thresholds were not allowed. As we discussed, this is no longer considered valid since the processes of absorption, distribution, elimination, metabolism and cellular defense, and repair mechanisms make this possibility far less than remote. However, the United States... 

For regulatory purposes, mycotoxins are considered contaminants, whereas fungicides and pesticides are considered indirect food additives. Under the Delaney Clause of the Federal Food Drug and Cosmetic Act, no residue of any food additive that has been demonstrated to be a carcinogen is... 

EPA establishes raw agricultural commodity (RAC) and food additive tolerances for pesticides on food. Carcinogenic pesticides may be registered and tolerances may be set for the raw agricultural commodity if the levels are safe however, if the concentration of a pesticide on food increases when it is processed, a food additive tolerance is required. The Delaney clause of FFDCA does not allow a food additive tolerance to be set, even if EPA believes it is safe, if the compound has been shown to induce cancer in man or animal. A narrow interpretation of the Delaney clause has prevented registration of new products in circumstances where the upper-bound risks were estimated to be much less than one in a million. 

The regulation of carcinogenic pesticides on foods depends upon how EPA interprets and applies FIFRA, FFDCA Sections 408 and 409, and especially the Delaney clause in the FFDCA. Pesticide registrations are granted or denied under the FIFRA risk-benefit standard. However, food use pesticides cannot be registered, unless a tolerance or an exemption from a tolerance for the RAC was also granted under Section 408 of the FFDCA. 

EPA felt no significant human health risk was posed from this use. Even though Aliette would replace other much more clearly carcinogenic fungicides, however, the presence of Aliette on the processed food would have required a food additive (409) tolerance. The Delaney clause in Section 409 prevented establishing a 409 tolerance, because Aliette had been shown to Induce tumors in animals. This strict drafting and interpretation of FFDCA Section 409 prevented the use of a beneficial and less risky product. 

If the changes are Implemented in the Delaney clause then the door could be opened to the registration of a number of new products. The products favorably affected by changes in the policy would be those that are positive in animal carcinogenicity studies, but are either of very low potency, or caused tumors considered less relevant to human risk. The Delaney clause would not increase the chances of registering a product that appeared to pose a significant risk by dietary exposure. 

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