Presentation by George H. Pauli*
The role of the Food and Drug Administration (FDA) in determining whether foods may be irradiated in this country stems from the passage, in 1958, of the Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act).(1) In that legislation, Congress explicitly defined a source of radiation as a food additive. In a report accompanying the legislation, Congress explicitly stated: "Sources of radiation (including radioactive isotopes, particle accelerators, and X-ray machines) intended for use in processing food are included in the term ‘food additive' as defined in this legislation". The Food Additives Amendment also provides that a food is adulterated (that is, it cannot be marketed legally) if it has been intentionally irradiated, unless the irradiation is carried out in conformity with a regulation prescribing safe conditions of use. Note here that the statute does not define the form of energy - radiation - or the process - irradiation - as an additive, but the equipment used to irradiate the food. Note also that the specific and explicit adulteration provision for irradiated foods is unlike that for foods which are adulterated because they contain a food additive that is unsafe within the meaning of the Act. Clearly, no one expected a food to contain a source of radiation. I mention this arcane legislative history to highlight the common misunderstanding that the statute somehow foolishly considers irradiation to be an additive rather than a process. As mentioned above, the bill report refers to sources of radiation used to process food.
The legislative history makes clear that the Food Additives Amendment does not exempt any meat or meat food product from requirements under the Federal Meat Inspection Act of 1907. Furthermore, poultry products are also subject to the Poultry Products Inspection Act. Thus, anyone interested in irradiating meat or poultry is also subject to the regulatory authority of the Food Safety and Inspection Service of the Department of Agriculture (USDA).
Additionally, one reason for irradiating some foods is to protect U.S. agriculture from the import of exotic pests. USDA's Animal and Plant Health Inspection Service (APHIS) administers the law by quarantining certain crops from transport into the country. Quarantine requirements may often be met in a variety of ways. If irradiation is to be used for such a purpose, requirements of APHIS must be met.
In sum, irradiating a food is illegal unless it is done in accordance with a regulation authorizing such processing and with all other requirements of a variety of laws. Because my expertise is limited to the law administered by FDA, I will focus my presentation on that aspect.
Promulgation of an Authorizing Regulation
In general, a food additive regulation may be established or amended in one of two ways. In the first, FDA proposes a regulation on its own initiative. The public is given an opportunity to comment on the proposal, and all substantive comments are considered. This procedure is used relatively infrequently and usually only in special circumstances. FDA used this procedure once, in the mid-1980's, to amend the food additive regulations regarding food irradiation. It requires a substantial resource from the agency, however, and is used infrequently.
Far more commonly, the food additive regulations are amended in response to petitions filed by proponents of an additive's use. In this case, the sponsor petitioning for a regulation authorizing a new use of an additive bears the burden in demonstrating that the requested use is safe. The petitioner is responsible for assembling the data and information necessary to support a safety decision by the agency.
As with a proposed regulation published by FDA, a petition is a scientific and legal document that forms the basis for the administrative record underpinning the agency's decision. That decision must be based on a record that is explicit, complete (showing, for example, that all reasonable safety questions have been addressed), and unassailable (if a regulation is challenged, it is the agency that will go to court to defend it).
Furthermore, the administrative record must contain information adequate to demonstrate that the additive is safe under all conditions of use that would be permitted. When FDA issues an authorizing regulation, that regulation is all that is needed for anyone, not only the petitioner, to use the additive in conformance with the specified conditions of use. That is, authorization is granted generically; FDA does not approve particular products or companies, and there are no further licensing or other requirements. Therefore, the agency must determine whether any limitations are necessary to assure safe use before authorization is granted.
The issuance of an authorizing regulation also requires, of course, information to establish the safety of the petitioned use. In the case of irradiated food, consideration of wholesomeness (that is, safety for human consumption) requires that four broad areas be addressed: radiological safety, toxicological safety, microbiological safety, and nutritional adequacy.
Here the question is, will radioactivity be induced in the food?
In early work on food irradiation, sources of sufficiently high energies to induce radioactivity in foods were sometimes used. As research continued, sources whose energies are too low to induce detectable radioactivity were adopted by the international community. Therefore, this issue is of no concern when currently approved sources of radiation are used, but must be addressed if other sources are being considered.
Among the questions that have been raised in attempting to establish the toxicological safety of irradiated food are:
- Is there evidence of adverse toxicological effects that can be attributed to substances produced by irradiating the food?
- What should be tested?
- What tests provide useful information?
Answering these questions has over the years proven challenging. Toxicological safety of typical food additives has traditionally been assessed by feeding large amounts of purified substances to laboratory animals and applying a safety (or uncertainty) factor to the highest dose of a tested substance that causes no toxic effects in any species. Moreover, standards for the conduct of such studies have evolved over time. For substances like irradiated whole foods, which may become a large proportion of diet, application of a 100-fold safety factor is impossible; attempts to exaggerate the amount of irradiated food in the diet have produced adverse nutritional effects that have confounded the results of many feeding studies.
Over time, however, our knowledge of the chemical changes caused in food by radiation has grown, both qualitatively and quantitatively. Nearly two decades ago, FDA established a committee (the Bureau of Foods Irradiated Food Committee, BFIFC) to, among other things, recommend modern toxicological testing requirements appropriate for assessing the safety of irradiated foods. BFIFC considered the expected characteristics and quantities of radiolytic products, estimates of projected levels of human exposure, and sensitivity of state-of-the-art toxicity testing, and made several recommendations that have guided subsequent agency decisions.(2)
Specifically, BFIFC recommended that foods irradiated at doses of less than 1 kilogray (kGy),(a) or foods representing a very small fraction of the diet, should be exempt from requirements for toxicological testing because the types and amounts of radiolytic products would not show any toxic effects in well conducted tests and their presence in the diet did not justify such testing. For foods irradiated at higher doses that were consumed in significant amounts, the Committee recommended a testing regime.
Following the issuance of the BFIFC report, the agency established a Task Group to review the available animal feeding and mutagenicity studies. The Task Group categorized each study report according to the quality and completeness of the design and reporting. The Task Group found that the studies did not appear to show any toxicological effects caused by irradiated foods.
Because many of the studies reviewed by the Task Group were incompletely reported or of low power, and sometimes confounded by nutritional effects, the Task Group concluded that the available data were not adequate to evaluate the safety of irradiation of all foods at doses greater than 1 kGy. It recommended that the agency consider requests for authorization of irradiation at these doses of foods that are consumed in significant amounts on a case-by-case basis.(3)
Since that time, the World Health Organization issued a report of a committee that looked at the more reliable animal feeding studies collectively, rather than individually.(4) FDA followed a similar approach in its evaluation of the safety of irradiated meat.(5) Using such an approach, one can readily look for any patterns of adverse effects and none have been found.
In general, the issue of microbiological safety of irradiated foods has raised two questions:
- Can irradiation mutate microorganisms, producing more virulent pathogens?
- Will irradiation preferentially reduce the numbers of spoilage organisms, allowing pathogens to grow undetected without competition?
The first question is generally not an area of concern. There is no evidence that mutants that may be produced by irradiation are any more virulent than the parent microorganism; in fact, the opposite is more likely to be the case. Furthermore, there is no reason to suspect that evolutionary pressure would select for mutant organisms.(6) It is the second question that is of special relevance to most of the applications of irradiation that have not been already authorized by FDA, i.e., irradiation at doses that do not sterilize the food, but that are high enough to appreciably reduce the number of spoilage organisms and to alter the makeup of the residual microbial population.
In these instances, FDA needs evidence that the proposed conditions of use (dose and temperature of irradiation, for example) are adequate to achieve the intended microbiological technical effect and, most particularly, that irradiated food is not potentially less safe than nonirradiated food because of the possibility of undetected pathogen outgrowth or toxin production before spoilage is evident. This safety must be demonstrated under all realistic scenarios that may occur in commercial practice. The organism that has been of greatest interest in this regard is Clostridium botulinum, both because of its public health significance, and because the spores of this organism are among the most resistant to radiation. Other relatively radiation-resistant pathogens may also be relevant, depending on the particular food and specific proposed conditions of use.
It is worth noting that the microbiological safety question is by no means unique to irradiation but is equally applicable to any food process the reduces the number of microorganisms but which does not eliminate them entirely. Likewise, if one wanted to demonstrate safety of radiation as a method for sterilizing food, one would need to develop data analogous to that used for canning processes.
With regard to nutritional issues, the agency's concern is for nutritional effects of dietary significance. Two questions are relevant:
- Does irradiation under the proposed conditions of use result in a significant loss of any nutrient in the food?
- Is this food an important dietary source of the affected nutrient?
In general, nutrient loss depends on many factors, such as radiation dose, temperature of irradiation, food composition, and the presence or absence of oxygen. At the doses relevant to irradiation of food, losses of micronutrients, particularly vitamins, may be of concern. A petition should address the issue of possible vitamin loss under the specific proposed conditions of use. If there is evidence that any vitamin level is affected significantly under the proposed conditions, data to show that these losses are not significant with respect to the overall diet are needed.
Based on the considerations above, FDA has found irradiation of food to be safe under several conditions. Authorizing regulations have been issued both in response to petitions and at FDA's initiative. In sum, FDA has issued approvals for irradiation: of food at doses not to exceed 1 kGy to control insects and other arthropods and to inhibit maturation (e.g., ripening or sprouting) of fresh foods; of poultry at doses not to exceed 3 kGy to control foodborne pathogens; of refrigerated meat at doses not to exceed 4.5 kGy and frozen meat at doses not to exceed 7.0 kGy; of dry or dehydrated enzymes at doses not to exceed 10 kGy to control microorganisms; and of dry or dehydrated aromatic substances (e.g., spices and seasonings) at doses not to exceed 30 kGy to control microorganisms. FDA has also issued a limited regulation for high-dose sterilization of meat for NASA's space flight program (REF).
Until recently, the statute has been silent on the labeling of irradiated foods. However, under the general labeling requirements, FDA has found it necessary to inform the consumer that an irradiated food has been processed, because irradiation, like other forms of processing, can affect the characteristics of food. For situations where the processing is not obvious, such as whole foods that have been irradiated, FDA requires that the label bear the radura symbol and the phrase "treated with radiation" or "treated by irradiation." If irradiated ingredients are added to foods that have not been irradiated, no special labeling is required on retail packages because it is obvious that such foods have been processed. Special labeling is required for foods not yet in the retail market that may undergo further processing, however, to ensure that foods are not irradiated multiple times. In promulgating this regulation, FDA advised that other truthful statements, such as the reason for irradiating the food, could be added to the statement and encouraged food manufacturers to do so.
In November of 1997, Congress reopened the issue of labeling for irradiated food in two ways. First, Congress mandated that FDA could not require a label statement to use print that is larger than that required for ingredients. FDA had not mandated a type size but did require the statement to be "prominent and conspicuous." On August 17, 1998, FDA updated it's regulation to clarify that the prominence requirement did not mean larger than usual type size.
Additionally, Congress directed FDA to reconsider the label requirement and to seek public comment on possible changes. On February 17, 1999, FDA issued a notice discussing the labeling issues and inviting comments on several questions to determine whether the current requirements adequately reflect U.S. food labeling policy or whether the requirements should be changed.(7)
Irradiation can cause chemical change in packaging, as well as in food, and this can affect migration of the package components (or degradation products of those components) to food. Irradiation can cause crosslinking, which would likely reduce migration, but it also can cause decomposition to lower molecular weight entities with increased migration characteristics. Sometimes, irradiation has been used in the manufacture (or sterilization) of packaging before food is added. FDA considers this use the same as any other manufacturing process, namely, the final irradiated packaging must comply with the appropriate regulations and must not otherwise adulterate food, e.g., by releasing decomposition products that may render the food injurious. FDA believes that, as part of good manufacturing practice, manufacturers must always consider the effects of changes in their manufacturing processes and test to ensure that the final product is suitable for holding food.
Irradiation of food in a package is a special case, however, because any decomposition products that might be released during irradiation would migrate directly into the food. This is different from irradiation during the manufacture of the packaging material because, in that case, a volatile decomposition product may not be present when the food is put into the package. Therefore, FDA requires that packaging that holds food during irradiation comply with regulations (21 CFR 179.45)(b) based on appropriate testing. It is important to note, however, that these regulations have been amended only once in recent years. FDA urges packaging manufacturers and others interested in using a packaging material for holding food during irradiation to check these regulations early in their planning for commercial development either to ensure that the proposed packaging has been listed in the regulations for packaging to be used during irradiation or to submit a petition (or possibly a notification) for additional packaging materials. In brief, a petition to permit irradiation of packaging material otherwise approved for food use must show that migration from the irradiated material does not raise new issues not considered in the earlier approval. FDA would be happy to provide guidance to anyone interested in submitting such a petition or notification.
Use of a source of radiation to process or otherwise treat a food must conform to an authorizing regulation based on a demonstration of safety under the conditions of irradiation. A food that has been irradiated must be so labeled as specified by regulation although this requirement is currently under reconsideration. Finally, packaging used to hold food during irradiation must have been tested and shown to FDA's satisfaction for that use.
(a)The unit currently used for measuring absorbed radiation is the Gray (Gy), which is 1 Joule of energy absorbed per kilogram of absorbing material. Previously, the unit of absorbed radiation used was the rad, which is 100 ergs absorbed per 100 grams of absorbing material. One hundred rads equals 1 Gray.
(b)In the same November 1997 legislation discussed above, Congress also provided for a notification process, rather than a petition and promulgation of a regulation, as a lawful way of establishing the safety of new packaging. This notification process is contingent on appropriation of funds. If implemented, packaging used to hold foods need not comply with 21 CFR 179.45 if their safety is established and made lawful by testing and notification.
(2)A.P. Brunetti, V. Fratalli, W.B. Grear, D.G. Hattan, C.A. Takeguchi, and L.R. Valcovic, "Recommendations for Evaluating the Safety of Irradiated Foods", U.S. Food and Drug Administration, Washington, D.C., (1980).
(7)Federal Register, 64:7834, February 17, 1999.
*George H. Pauli, Ph.D., was a Consumer Safety Officer in the Office of Food Additive Safety; Center for Food Safety and Applied Nutrition; US Food and Drug Administration; 5100 Paint Branch Parkway; College Park, MD 20740.