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HomeMy WebLinkAboutCOM 0212.010 1996-1998 =J~,tl 5[0.v~C~, DEPARTMENT OF Ht:.~.TH & HUMAN SERVICES Public Health Service 1`' o bvu~ Food and Drug Administration _ Washington DC 20204 A ri122 1997 ' ~7 APii 2'1 P(1 4 18 COUf~~i" ~ ;r: COUf~TY G% HAWAII Mr. Aaron Chung Chair, Finance Committee Hawaii County Council 25 Aupuni St Hilo, Hawaii 96720 Dear Mr. Chung: Mr. Rory Flynn, of the Hawaii Agricultural Promotional Association, asked me to write to you regarding the Food and Drug Administration (FDA) position on the safety of irradiated agricultural products. I understand that you are in the process of considering irradiation technology for agricultural products from your county and are having several meetings on the subject. I regret that I am unable to join you to answer directly any questions you may have. First, let me give you some background on FDA's role on this subject. Since 1958, sources of irradiation (such as Cobalt 60 or X-ray machines) have been prohibited from use for food processing unless FDA has found that their use is safe and has promulgated regulations prescribing safe conditions of use. The standard for safety is that there is a reasonable certainty in the minds of competent scientists that no harm will result from consumption of the food. The agency cannot lower its standard to allow for benefits and, thus, consideration of benefits is not part of the safety decision. Among the several decisions FDA has issued concerning irradiation of food, two are particularly relevant to the use of irradiation of agricultural products to meet quarantine requirements. In 1963, FDA concluded that use of irradiation was safe to control insect infestation of wheat and wheat products. In 1986, FDA concluded that treatment of any food by irradiation at doses up to 1 kiloGray (kGy) is safe for controlling arthropod pests (insects and other similar pests). While I was not at FDA in 1963, I have been directly involved in all FDA evaluations of safety of irradiated foods since 1977, either as the project manager or as the supervisor of the project manager. Thus, I can speak from direct experience on how FDA reached its 1986 decision as well as any other post-1977 decisions in this area. Let me note that I have read many accounts of FDA's actions by people who were not involved in those decisions which are contrary to what I observed at FDA at the time. lixsi'. 'I'o;... ~~.0~,,,Y~1.~~ 4' i Page 2 - Mr. Aaron Chung One possible reason for confusion may be the need for a different scientific approach for assessing the safety of a food as opposed to that used for a food ingredient under the same premarket approval authority. In a typical safety evaluation for a food ingredient, isolated amounts of a food ingredient, such as a sweetener, can be fed to animals in ?arge amounts and a "no-effect level" established at amounts hundreds of times larger than humans would consume. Large safety factors can be applied to the no-effect level to allow for uncertainty in extrapolating animal data to humans. Such a safety evaluation cannot be conducted for a whole food, irradiated or not, because animals cannot safely consume calories far in excess of their needs and too much of any single food in the diet can lead to nutritional problems. Thus, in evaluating the safety of irradiated foods, scientists looked for a showing of "wholesomeness" and radiological safety for the foods; that is, would the foods promote good health by being nutritionally adequate, toxicologically safe and microbiologically safe and would they be free of any radioactive material that could prove harmful. In the early days of research, because of a lack of knowledge about radiation's effects on food, scientists conducted studies where animals were fed as much of an irradiated food that the researcher concluded the animals could tolerate. While some of these studies were reasonably successful, and while many provided useful information, it can be said that in many of the early studies, the researchers possibly learned as much about the nutritional needs of animals as about the safety of irradiated foods. FDA found it difficult to reach a decision that irradiated foods were safe based on those animal studies alone. It became clear that a more comprehensive approach to safety evaluation was needed, using data from radiation chemistry research as well as from toxicological testing.. Chemical analysis is important because the most fundamental toxicological principle that must be considered is "the dose makes the poison". Put in other words, practically everything (including salt, or even water) is toxic at some level. The issue is whether a substance is safe as consumed. Fortunately, the 1970's saw improvements in analytical technology and a the availability of a wealth of studies on the effects of radiation on the composition of food. Therefore, in 1979, FDA established a committee to recommend the best approach to evaluate the safety of irradiated foods based on the knowledge then available. The committee, which included a chemist, a nutritionist, and three toxicologists, using information on the effects of radiation on food components and using worst case assumptions about unknown chemical changes in food that may occur at undetectable levels, concluded that there would be no safety difference between foods irradiated at doses below 1 kGy and the untreated food. They recognized that the effect of radiation on food, at the levels used to control insects, was so trivial that it would be foolish to conduct any more animal feeding studies on foods irradiated at those levels because such tests, properly conducted, would show no safety effects. r Page 3 - Mr. Aaron Chung To verify that finding, FDA established a second committee to review all the known data in the world on animals fed irradiated food, as well as other relevant toxicological data. Their main charge was to determine whether any data contradicted the findings of the first committee, focussing on data that might represent health effects related to the irradiation treatment. They were also asked to address whether the animal feeding studies available were sufficiently reliable and broad based to recommend approval for foods irradiated at higher doses than 1 kGy. In considering whether further approvals should be given, the committee disregarded all data whose reliability was suspect and did not attempt to correct shortcomings in reports by requesting additional information. This committee found that there was no evidence of toxicity caused by any irradiated food and that the data supported the findings of the first committee. Because of deficiencies in many of the study reports, they withheld judgement on additional applications of irradiation at doses above 1 kGy. Based on these two reviews, the agency approved, among other things, the use of irradiation at doses below 1 kGy to control arthropod pests. Since that time, FDA has also approved a dose three times higher to treat poultry, based on further analysis of the data. In sum, I can assure you that FDA has no reservations in saying that a food irradiated at a dose below 1 kGy is as safe as a food not so treated. I have also met, on several occasions, with food safety authorities from other countries. While policies vary, in no case has the government authority of any country concluded that any irradiated food is unsafe. I am enclosing a copy of a document developed by several countries, including the U. S., in 1988 as well as FDA testimony at a 1987 congressional hearing on this subject as further background. I hope this information is helpful to you in your deliberations. Sincerely yours, Georg Pauli, Ph.D. Director Division of Product Policy, HFS-205 Center for Food Safety and Applied Nutrition 1?ec-1~-~ .6. OE PGF_IFA~ GENt~~E 0« <1 79 70 F, 02 V j~^ -;i , 7 PPR Z 4 p~ 4 18 cot , . Document on Food Irra cation Adopted on 16 December 1988 by the FAO/IAEA/WHO/ITC-UN CTAD/GATT' International Conference on the Acceptance, Control of, and Trade In Irradiated Food Geneva, 12-16 December 1988 0 ~ ~ ~ ~ 'r , -.n- The Conference, which brought together some 250 participants, was attended by official delegations from 54 countries, comprising government officials at the senior policy-making level, experts in law, health, energy, and food, and representatives of consumer unions, as well as by representatives from 11 international organizations, Issued by the World Health Orpanaation, on behalf of all sponsoring apenUes, on 21 December 198!3 'Food end Agdcutluro Oryanlzetion o1 the Unttetl Natlonc, Inrornstlonel Atomic Eneryy Agency, World HeeRh Otgenlzetlon, and the International Treds Centre (a loin! sub-oryan o11he UnRetl Nations Conference on Trade sntl Development and the Gsnenl Aproemenl on Tanttc antl Trade) 1?65-,2-21 16: CE FUfi_IFA~ GE~~EVE Cti C« 'F .2 F.~_ ti FAO/IAEANVHO/ITC•UNCTAD/GATT International Conference on the Acceptance, Control of, and Trade In Irradiated Food Conference Document -page t iNTAGDUCTION alternative to chemical fumigation and other physical methods. 1. All governments beer a responsibility to 4. No treatment of food can be employed in ensure sufFicient supplies of safe, nutritious thelongtermunlessithastheacceptanceofthe and acceptable food to meet the needs of their consumer. In many eases, acceptance can be people.Suchsupptiesshouldbeofhighquaiity expectedbecausethepalatabi]ityoftheoriginal and should comprise a wide variety of food- food is maintained or because the choice is stuffs. Governments should also feel respon- between the treated food and no food at all Bible towards contributing to the improvement (because untreated food would be spoiled). of the global food supply. Given the choice, many consumers would 2. In no country can these objectives be Benerally prefer that food should be un- ac}tievedwithout dependence on food process- Processed if at all possible, but such an ideal is ing and preservation technology to a greater or not a practicable possibility in many cases, nor lesserdegree.Theproblemsofachievementare iaitalwaysdesirable. compounded bydiffering agro-climatic condi- 5 ~e foregoing requirements for treatment tions, levels of technology, seasonality of pro- or preservation of food are currently being ad- duction and the perishable nature of many dressed by n variety of processes, some of crops. The application of food processing tech- which such as drying and salting are of consid- nologyisthereforenecessaryfortwoimportant enable antiquity, while others such as fumiga- rcasons. One is to prolong the availability of lion, canning and freezing are of more recent seasonally produced crops and to minimize i origin. Treatment by ionizing radiation is now food losses; the other is to reduce the incidence beginning to be used to supplement existing of illness caused by food-borne pathogens. technologies for certain applications. One of Each country will have differing requirements these applications, which has potential for inthesetwoareas,buttheoveralltrendtowards i beneficialpublichealtheffects,isthereduction increasing urbanization of the world's popula- of pathogenic microorganisms in solid foods. lion results in an increasing need for processed Eood, slid for the development of appropriate 6. The Conference therefore devoted itself to processing and preservation technologies. a careful consideraton of the particular condi- 3. In the case of certain food imports, adds- lions under which food irradintton should be tional specialized treatment may be applied to allowed to play a part in ensuring the supply o1 wholesome food in association with existing satisfy quarantine requirements necessary to I andalreadywidelyusedfoodpreservationanc exclude insect pests of economic or environ- kod quarantine lrealments. In this context, the mental significance frotn the importing coup- 'Conference recognized the Codex Genera try. Lack of acceptable quarantine treatments ~ Standard for irradiated Foods and Recom can result in the loss of foreign exchange earn- mended International Code of Practice for thi logs, which in turn could affect the ability of an Operation of Radiation Facilities Used for th exporting country to provide basic food sup- Treatment of Foods. The Conference also con plies and socio-economic development for its sidered consumer attitudes, inter-governmer own population. Irradiation, as a process to tat and governmental activity, process contrc ensure that a pest is unable to become estab- and trade. lished in the importing country, can be an rsae-t. :~:c<_ F~s_IFa~. c~rr-_.~ c~~ e« z- vc F.ta FAO/IAEA~INHO/ITC-UNCTAD/GATT International Conference on the Acceptance, Control oi, and Trade In Irradlaletl Food Conference Document -papa 2 CONSUMER ATTITUDES TO ~ 10. Illness due tofood-borne microorganisms IRRADIATED FOOD ; is often difficult to trace to a particular food. Its usual incidence u often underestimated by 7. The potential for food irradiation to help Consumers. If the facts on illness resulting from maintain a safe and adequate food supply food-borne microorganisms are not under- cannot be attained unless irradiated foods are stood by consumers, they may not be able to accepted by consumers. On one level of steep- understand the potential impact of food irra- la,tce,thefinal food productmustbeofsatisfac- diction and other methods for microbial con- tory quality at a reasonable cost. On a deeper trot. level, however, a consumer who is satisfied with the food currently available should not be ] 1. As part of the control of the irrndiation expected tobeenthusiasticaboutanychangein process, Consumers nerd to be convinced that the current food production system, especially the potential accomplishments of food irradia- if that change is perceived to be significant. lion arenot negated by a misuse of technology. Although irradiation cannot reverse the effects 8. A consumer Itas a right to expect that food of spoilage, consumers need reasons for confi- available in co,n,nerce is safe and wholesome; dente that irradiation will not be used to mask that is, the food promotes health because it is deficiencies of an inferior product. Such confi- nutritimtailyadequate,microbiologicnlly safe, dencecanresultfromabetlerunderstandingof and does not contribute to toxic effects due to the capabilities and limitations of the various chemicals either produced in the food during individual uses of irradiation and knowledge processing or added to food by some other that irradiation is not beingused as a substitute means. The terminology used fur food irradla. for otherwise achievable good manufacturing lion is sometimes confused with that used to practices. Furthermore, like any other process, describe radioactive contamination. This con- food irradiation must in no way be used to lusion can best be addressed by proper infor- mislead consumers, and in this respect govern- mation. Consu,nersmay also beconeerned that meats have a major mle to play. introduction of ionizing radiation technology into food processing may lead to an increased 12. information about irradiated food prod- probability of accidents leading to environ- uctsandprocessingshouldbepresentedtocon- ,nental contaminatiot or worker hazards. sumers in an objective and clear manner on a continuous basis. The need for such infonna• 9. Although wholesomeness of the food is a tio„ is particularly Important at the time of in- necessity, it is difficult for a consumer to deter- troduction of irradiated food products when mine when the criterion of wholesomeness is consumerinterestnndcuriosityareexpectedto met. Food is a complex mixture of components be greatest. If necessary, such information and its safety and nutritional adequacy cannot should include any special instructions on be judged outside the context of the diet of handling,storageandpreparationofirradiated which it is a part. As with any other lood food at home. processing technique, the matters of safety and nutritionrelaledtofoodtrradiatlonmustcon- 73. In cases where in-adiatedfoodsare permit- tinuetobe,nonitoredinteraliathroughfurther led, consumers should be able to make their late„mlfunnlcuuperadon and research. Asnew vwn choice between in'ad,a[ea ana nonirradi- information becomes available, it should be sled food. To enable them to make this choice, considered by the authorities concerned. there mustbetlearandunambiguouslabelling. It is for individual governments to meet this .?_t-1~-_. a~C- PJP_!Fi.\ G~tL.w ~r C~~ a: 7? F.C° FAO/IAEA/WHO/ITC•UNCTAD/GATT International Conference on the Acceptance, Control of, and Trade in Irrediated Food Conference Document -page 3 need intheiroKmcountries.Internationalstan- i December 1982 in order to provide a second dards for labelling are being developed by the i opinion. In its conclusions, the Board was satis- Codex Alimentarius Commission'. Docvmen- feed that there was no rouse for concern. Food ration must be sufficient to ensure transfer of irradiationwassaidtobeanimportantaddition information through international trade so that to the methods of control of food-borne patho• national labelling requirements tan be met. gees and not to present any additional hazards to health. 14. !t is well known that the changes associ- atedwithfoodirradiationaredifficuittodetect. ]8. Following these expert meetings, the However, it is recognized that detection meth- Codex Alimentarius Commission, then repre- ods, if available, would augment standard renting 122 countries, in 1983 adopted the regulatory procedures and would thereby help Codex General Standard for Irradiated Foods assurecotuumerothatprocessorsanddistribu- and the Recommended International Code of tors are adhering to government control prose- Practice for the Operation of Radiation Facili- dures. Research on detection methodology ties UsedfortheTreatmentofFoods.Therewas should be continued. broad consensus among the representatives for this adoption, except for two countries which 15. Consumer confidence can be bolstered expressed their reservations. when there is clear evidence that the food irra- diation process is being effectively controlled 19. TheCodexGeneralStandardforthe'.abel- by aresponsible industry and a governmental ling of Prepackaged Food contains provisions regulatory process. Because the factors needed on the labelling of irradiated foods (CODEX to control the irradiation process effectively are STAN. 1-1985, section 5.2). However, as many the same everywhere, it is reasonable to expect countries have not yet taken a final position as substantial harmonization of national ap- to how the fact of irradiation should be de- proaches. dared, this section remains under review until the next session of the Codex Committee on INTER•GOVERN'1FNTe1 ~,Np Food Labelling and of the CodexAlime>>carius GOVERNMEIr fAL ACTIVI fY Commission in 1989. 16. In1960,aJoitttFAO/IAEA/WHUExpert 20. Attherequestofover6DMemberStatesto Committee on the Wholesomeness of Irradi- continue a forum of intemational cro-operation ated Food declared that the irradiation of any with emphasis on harmonization of national food up to an overall average dose of ]0 kGy regulations based on the principles of the causes no toxicological hazard and introduces Codex General Standard for Irradiated Foods no special nutritional or microbiologist prob- and its associated Code of Practice, an Interna- lems. lional Consultative Group on Food Irradiation (ICGFA was established under the aegis of 17. Some concerns about the effects of irradia- PAO, IAEA and WHO in May 1984. The main tiononmicroorganisnuinfoodhadbeenraised functions of the Group are to evaluate global earlier at a meeting of the Codex Committee on developments, provide a focal point of advice Food J iygiene in 1979. Therefore the microbio- and furnish information on foodrrzadiation as logical safety of irradiated food was further required to Member States and the Organiza- considered at a meeting of the Board of the tions.7lreCroupnowhas28membercountries International Committee on Fond Mlcrobiol- contributing either in rash or in kind to its ogy and Hygiene of the International Union of activities, which include the maintenance of Microbiologist Societies ]n Copenhagen in intemational lnventorles of food irradiation 'Codex Ceneral Standard for the Labeffing of prepackaged Food (CODEX STAN.1-1985) FAOi1AEA/WHOiITC•UNCTAD~GATT International Conference on the Acceptance, Control of, and Trade in Irradiated Food Conference Document -page 4 facilities,productclearancesandnationallegis- tionally agreed standards of radiation protec- lationsand regulations, as wel(asthe organfza- lion, including worker and public safety, trans- lion of workshops and task forces, and the port and disposal of source material and envi- preparation oftechnical guidelines for irradfa- ~ ronmental protection. lion processing of various food groups. At its fifth meeting theCroupttotedthat20countries PROCESS CONTROL ere using irradiation for processing food and food ingredients; commercial and demonstra• Z4. Facilities which ore intended to carry out tionirradiatorsfortreatfngfoodarebeingcon- irradiation of food should meet appropriate structedorareintheadvancedplanningatages standards of safety and good hygiene condi- in fourteen countries. The Secretariat of the lions for processing. Therefore, such facilities Group anticipated that some 25 countries will shouldbeoperatcKiinaccrordancewiththeprin- be applying the technology on a commercial clp]esoftheCudexGeneralStandardforlrradi- scale by 7990. ated Foods and associated Code of Practice; operational control of such facilities should be 21. The attitudes of governments towards ir• subject to inspection by competent authorities. radiation o! food range from those which have accepted and are applying the technology to 25. Facilities for irradiating food should be those which are interested and exploring it, to properly designed and constructed. Operation those which Dave decided not to permit the should be by appropriately trained personnel. technology at the present time, and to those It is necessary to have an infrastructure that which have no definite opinion. Some govern- Includes support facilities and equipment, and moots consider that there is no need for the ~ a well-established regulatory system. technology in their countries. In general, how- ever, countries which express reservations, 26. Foodintertdedfortreatmentbyinadiation such as potential misuse of the technology, should be of a quality acceptab]e for Good have not disagreed in principle on the safety of Martufactuing Practices (CMP), Hygienicprac- foodtreated inaccordance with adequate scan- cites which are needed in GMP for other proc- dards, such as the Cudex General Standard for ~ asses are also necessary in the process of irra- Irradiated Foods. diation, but irradiation should not be used as a substitute for such practices. Wherever neces- 22. To a large extent the attitude of govern- sary, pre-treatment of food such as cooling, meats is influenced by consumer acceptance. if chilling and freezing should be tarried out in there is widespread opposition among con- suchamannerastoachteveeffectivetreatment. sumers, this may be taken as a reason not to Suitable packaging materials are currently accept the method. Governments share the available for use when prepackaging is re- view that iE the sale o[ irradiated foods is per- quired to prevent recontamination after irra- mitted intheir countries, the foods would have ~ diation. to be labelled to inform consumers about the ir- radiation. Adequate regulatorytontrolisgen- ~ The effectiveness oftheirradiationproceu orally regarded as the basic responsibility of ;depends on prapet application of dose, and its governments to engender consumer confi• ~ measurement. Initial dose dLstribution meas- dence in the process. urements should be carried out to characterize the process for each product and thereafter 23. Governments share the view that all food dosin,etersshou?dbeusedroutinelytomonitor irradiation facilities should conform to interna- I correct execution of the process in accordance _ ;F:-~. GIN=~~E C~ - FAO/IAEA/WHO/ITC-UNCTAD/GATT International Conference on the Acceptance, Control ot, and Trade In Irradiated Food Conference Document -page 5 with intemationalh•acceptedprocedures.The ,I 31. Becauseofthenatureoftheprocess,v`•hich dosimetry should be traceable to national or makes it difficult at present to determine the international standards and thus provide an ctrcumstances of irradiation by examination of independent control of the process. the food, control of irradiated food has to be established through legally-based administra- 28. Simple radiationindicatorswhichcanhelp five procedures. These procedures, whether the processor in identifying the food which is the product u intended for domestic use or treated, applied to the product pack prior to export, should include on the one hand a sys- treatment,areavailableforcertaindoseranges. i tam of documentation allowing each batch of irradiated food to be identified with the itradia- 29. As with ell food processing, it is important lion facility and with the treatment given, and toapplyeffectivequalitycontroi,notonlyatthe on the other hand a system of ]abelling.Other irradiation process level but also in production, methods of control and compliance should be storage, transport and retail sales. It isalso nec- considered as technology progresses; therefore essary to identify critical control points and research on analytical methods for identifica- mrthodsformonitoringbyoperatorsandregu- tionofradiation-processedfoodintradeshould latory authorities. The regulatory personnel be encotuaged. and those responsible for food irradiation should be trained in quality control. The per- 32. The purpose of labelling need not merely sonnet responsible for controlling the plant be to inform the consumer of the fact of irradia- shouldhavepropertraininginoperationofthe tion, but may also indicate the purpose fot facilities as well as i:: handling of the foods which treatment has been given (see also para- concerned, The quality control system would graph 19). The additional use of a logo to iden- alsoinclude proper packaging suitable for the tify irradiated food should be encouraged. product and appropriate temperature rnntrol in storage and handling. Products which could 33. 1'hesystem of control should apply to bosh become infested by insects or contaminated by domestically produced and imported foods. microorganisms rater treatment should be Internationallyrecognizedstandardsofcontrol packedandste-od:nszcnaw~ythatreinfesta- whichallowadequateaccounttobetaker.~fthe lion or recontamination i-s prevented. Food needs and policies of individual countries should be handled, stored and transported wouldhelptoavoidthecreationofunnecessary according to GMP before, during and after obstacles to trade. in'adiation. 34. The harmonization of Standards and TRADE Codes of Practice for regulating irradiated food and irradiation fadlltles by public authorities, 30. Control of food in trade by public authori- and for the training of inspectors, plant opera- ties is essential, whether or not the food is tors and food control officials according to an treated by any process, toensure thatanytreat- internationally accepted and certified cumcu- ment, if applied, is done in a safe and proper lum, would also help to achieve acceptance of manner and withadequatesafeguardsagainst irradiated foodstuffs by consumers in the im- abuse.Propercontrolsarepartintlarlyrelevant porting Country. The prinriples embodied in to both national and international trade in irra- the Codex General Standard for Irradiated dialed food. Control should be exercised at all Foods and associated Code of Practice are con- stages of handling up to the point of sale to sideredtoformasuitablebasisfortheharmoni- consumen• nation of national procedures. FAO/IAEA/WNO/ITC-UNCTAD/GATT Intemational Conference on the Acceptance, Control ol, and Trade In Irradiated Food Conference Document -page 6 CONCLUSIONS ' 36.3 Govemmentsshouldensurethat,asapre- requi,ice to any processing of food by irradia- 3~. The Conference recognized that: tionorsaleofirradiatedfood,regulatoryproce- 35.] Food irradiation has the potential to re- dwesforcontrolareintroduced.Keyprinciples duce the incidence of food-borne diseases which should be incorporated are the registra- through the reduction ofpathogen contamina- ~ lion/licensing, regulation and inspection of lioft in foods, especially in solid foods. food irradiation facilities, documentation and labelling of irradiated food, training of control 35.2 Food irradiation can reduce post-lian•est officials, and employment of Good Manufac- food losses and make available a larger quan- luring Practices. city and a wider variety of foodstuffs for con- sumero. It can also bean effective quarantine i 36.4 Regulatory procedures for control of the treatment torcertain foods and thus contribute food irradiation process should be consistent to international trade. with internationally agreed principles as em- bodied in the Codex Genernl Standard for Irra- 35.3 Regulatory control by competent authori- dialed Foods and associated Code of Practice. tiesisanecessaryprerequuiteforintroduction Dosimetrytraceabletonationalorinternational oftheprocessinaccordancewiththeprinciples standardsshouldbeappliedduringtlieirradia- of the Codex General Standard for Irradiated lion process, providing a means of independ- Foods and Recommended Code of Practice far ant verification. the Operation of Radiation Facilities Used for the Treatment of Foods. Food irradiation is not 36.5 Governments should encourage reseorch tobeusedasasubstltuleforGoodManufactur- into methods of detection of irradiated food so ing Practices. that administrative control of irradiated food 35.4 Intemational trade in irradiated foods once it leaves the facility can be supplemented would be facilitated by harnionization of na- by en additional means of enforcement, thus facilitating international trade and reinforcing clonal procedures based on internationally rec- consumer confidence in the overall control ognized standards for the control of food fees- system. diation. 35.5 Acceptance of irradiated food by the con- 36.6 labelling of irradiated food for interna- sumerisavitalfactorinthesuccessfulcwnmer- clonal trade should be in line with the provi- cialization ofthe irradiation process, and infor- sions as adopted by the Codex Alimentarius Commission. oration dissemination can contribute to this acceptance. 36.7 Governments should ensure that all phases of planning and operation of food irra- RECOMMENDATIONS diation facilities are subject to a regulatory structure consistent with relevant internation- 36. The Conference recommended that: ally accepted standards For human health, 36.7 Consideration should be given to the I safety and environmental protection. application of food irradiation technology for 36.6 Governments, especially those that envis- public health benefits, especially for products age authorization of food irradiation, are en- wherethis process would seem advantageous, couraged to provide clear and adequate intor- 36.2Consideration should be given to the ap- matlonaboutfoodirradiationtothepublic.The piication of food irradiation technology where active participation of all interested parties, ltcan,inappropriatecases,reducepost-harvest including consumers, should be encouraged. losses of foods and serve as a quarantine treat- ment. B~''G~ TH~7 RPR 2`i Pil `i 18 SUBCOMMITTEE ; ~ ~wau HEALTH AND THE EN~I~I~ OF THE COMMITTEE ON ENERGY AND COMMERCE HOUSE OF REPRESENTATIVES ONE HUNDREDTH CONGRESS FIRST SESSION ON H.R. 956 A BILL TO PROHIBIT THE IMPLEMENTATION OF CERTAIPd REGULA- TIONS OF THE SECRETARY OF HEALTH AND HUMAN SERVICES AND THE SECRETARY OF AGRICULTURE RESPECTING IRRADIATED FOODS, TO AMEND THE FEDERAL FOOD, DRUG, AND COSMETIC ACT TO PRE- SCRIBE LABELS FOR IRRADIATED FOOD, AND FOR OTHER PURPOSES JUNE 19, 1987 Serial No. 100-81 Printed for the use of the Committee on Energy and Commerce U.S. GOVERNbIENT PRINTING OFFICE &363L WASHINGTON :1988 For eels h9 the guparintendmt of Documents. Congirariom! gales OAioe U$ Government Printing 019oe, Waehingtm, DC 20002 STATEMENT ~ FRANK E. YOUNG, M.D., PN.D. .sue' COMMISSIONER FOOD AND DRUG AOh1INISTRATION Mr. Chairman: s I welcome the opportunity to he here today to testify about the activities of the Food and Orug Administration (FDA) in the area of food irradiation. Background 1 1 Our involvement with irradiation technology to preserve food goes back many years. The possibility that benefits could be derived from irradiated food was explored as early as the late 1930'5. It was studied in earnest by the United States government in the 1950'5 as a potential preservative for military food rations as well as a means of eliminating microorganisms from food, controlling insects, and extending the shelf life of fruits and vegetables under the Atomic Enerqy Commission's "atoms for peace" program. Although FDA had not yet acquired the specific regulatory authority over the application of this new technology that the Agency possesses today, FDA became involved nonetheless by advocating that wholesomeness testing be conducted before any irradiated foods be marketed or otherwise routinely used. FDA's involvement in the development of food irradiation became pivotal in 1958, when the Congress mandated in effect, that food irradiation be subject to federal premarket approval. This involvement was accomplished through a change in the Federal Food, Drug, and Cosmetic A.ct to prohibit the use of a new food additive until its sponsor established the additive's safety and FDA issued a regulation - 2 - specifying its conditions of use. The definition of a food additive was drafted to specifically include sources of radiation intended for use in processing food because this use may affect the characteristics of food. Since then, FDA has approved food irradiation for five different uses: o The first was to control insects in wheat and wheat flour in 1963. o The second, in 1964, was to inhibit sprout development in whlte potatoes. + o In 1985 FDA approved a third use for food irradiation to j-'~ - ~ control the organism that causes trichinosis in pork. o The most recent approvals, which occurred simultaneously in 1986, involved two uses. These were; to slow growth and ripening and to control insects in fresh fruits and vegetables and to kill insects and control microorganisms in dry or dehydrated herbs, spices, seeds, teas and vegetable seasonings. t As I will describe later in my testimony, FDA's principal focus in evaluating each of these uses was to ensure the safety of the irradiated food. As these approvals indicate, many different technical effects can he accomplished by irradiating food. irradiation can extend a i~ rl~~ A -3- , =+r. tive product's shelf life by inhibiting the growth and ripening of fresh ~d for produce, and by reducing the number of microorganisms that spoil food. -istics Complete sterilization of food by irradiation results in a shelf-stable product similar to canned food. Pathogenic organisms, parasites, and insects found in food can he controlled by irradiation. Additionally, t irradiation can change certain physical properties, such as Aecreasing the rehydration time_of dehydrated vegetables, increasing the yield of wr in fruit juice, and tenderizing meat. Other means available for accomplishing the same purposes as the permitted uses in our food in white irradiation regulations include cooking and chemical treatments. to Nhen food is irradiated, most of the radiation passes through the food without being absorbed. It kills or sexually sterilizes any ly in Insects, and prevents fruits or vegetables from ripening too fast thereby extending shelf life. Irradiation leaves no residue in food. sects in It Aoes not make the food radioactive, nor does it pose any danger of radioactivity to consumers. Consumers are not exposed to dry or radiation through handling or ingesting irradiated food. etable The ionizing radiation useA to accomplish food irradiation can come from various sources, including gamma rays, x-rays and electron beams :us in derived from electron beam accelerators. While radioactive sources that produce gamma rays are currently the most commercially used sources in producing the desired energy levels, these other non-radioactive sources (i.e. electron beams and x-rays) can substitute s can for them quite well in many instances. Ia 83-632 0 - 88 - 2 l I~ -4 - The amount of radiation necessary to treat fonds varies depending upon the intended use. Multicell organisms are affected more readily than single cell organisms; growing organisms are affected more readily than dormant organisms. Thus, doses sufficient to slow the ripening process, inhibit sprouts and kill insects would not be enough to kill organisms such as the kind that cause trichinosis. In turn, microbes simpler than trichinella spiralis require a higher dose. Viruses, which are smaller than a biological cell, are very resistant to the effects of radiation. With a few exceptions for minor dry ingredients, food irradiation permitted by EpA involves technologically low levels of radiation. For example, the amount of radiation necessary to sterilize food is - approximately 50 times higher than the amount needed to control insects. It is true, of course, that food irradiation does require levels that are far too high to directly apply to humans, such as the levels used in chest x-rays, for example, but this fact has no bearin 9 on the safety of food for human consumption that is treated with radiation. A Spectrum of Concerns Even so, the fact that this process exposes food to ionizing radiation understandably singles it out for mare public attention and y -5- coding. concern than most"'food additives receive. And as with any e readily controversial subject, there is a broad spectrum of views. ore readily On one hand, we have heard expressions of frustration that, in the ripening most technologically advanced country in the world, the full potential ~ to kill of food irradiation is not being met, especially compared with its use microbes in other countries. Many of these concerns have been reflected in •uses, recent legislative efforts by Representative Morrison and others to to the facilitate research and development leading to commercial use as well as enhance public acceptance of food irradiation. tion At Lhe other end of the spectrum, some people have expressed the tion. For view that all of the safety issues related to food irradiation have not is been resolved. These concerns are reflected in legislative efforts by ~l Representative Bosco and others that would repeal some of FDA's ~qui re approvals of fond irradiation and require the National Academy of as the Sciences to study the risk to human health and the environment bearing presented by the irradiation of food. th I can appreciate both points of view and welcome the opportunity to address these concerns today. FDA's mission is to determine the safety of the process under specific conditions of use. In summary, I remain convinced that our on and actions in accomplishing this mission have been scientifically sound. I would characterize our approach over the years as fundamentally cautious and conservative. . - 6 - . k We are, perhaps;^situated even more toward the cautious end of the spectrum when compared with other nations. The Codex Alimentarius Commission, of the World Health Organization and Food and Agricultural Organization, based on a recommendation of its Joint FAO/IAEA/WHO Expert Committee has reviewed and assessed all data on the wholesomeness of irradiated foods, and has recommended that member nations permit the use of irradiation on food in doses up to 10 times higher than those that FDA has approved. The Regulation of Food Additives I In carrying out its responsibilities, FDA has followed the same general procedures in the development of regulations for the use of sources of radiation that it follows in the development of regulations for other food additives. Congress' decision to include irradiated I food in the food additive provisions of our statute clearly shows that j it intended FDA to be responsible for regulating the use of irradiation by requiring a rigorous review of the potential hazards associated with this food treatment process. As I stated earlier, the burden of demonstrating that a source of radiation can be used safely to irradiate foods was, as with other additives, placed on the proponents of its use. The principal procedure established for premarket approval of an additive's safe use Ii it is the filing of a food additive petition. Such a petition must the contain adequate-data to demonstrate the safety of the use. rius In addition, under the food additive provisions of the act, there cultural is a second procedure by which food additive approvals may come about. uN0 The yovernment may, on its own motion, propose to approve a particular set of conditions of use. The evidence supporting the safety of these tuber conditions of use must meet the same standard for demonstrating safety 0 times as the evidence,in a petition from industry. Generally speaking, the latter procedure is used far less frequently than the petition process. It is generally reserved for circumstances in which the Agency believes that proposing to approve a particular use will be of clear benefit to e public health or will allow the Agency to operate more efficiently. In se of the case of food irradiation, both procedures have been utilized, for ulations reasons that I will explain shortly. fated ows that The principal issue associated with the approval of an additive by radiation either procedure is, of course, safety and the quality and quantity ated with of scientific evidence needed to establish safety. As with any product or process, it is impossible to prove beyond any doubt that no halm will ever result under any conceivable circumstance. Congress of recognized this fact in 1958. In the Committee reports fran both [her Fbuses on the Food Additives Amendment, Congress said that safety requires proof of a reasonable certainty that no harm will result from safe ~~se the proposed use of any additive. ii - a {I ~l+ food Irradiat'~n and Safety Testing: Early Developments d, li Since the 1960's, when the first petition for the treatment of food with radiation sources was submitted, the Agency has been confronted I,~ with questions about what Lest procedures are appropriate to establish ~ ~ to a reasonable certainty that no harm will result from the use of I~!i radiation sources in the treatment of food. T Traditionally, high dose animal feeding studies are used to determine Lhe safety of a food additive. Such testing requires a determination of the highest "no-effect level" for the tested substance and consideration of the amount of the substance likely to be consumed. To allow for uncertainty in relating data gained from laboratory i _ animals to humans, a 100-fold safety factor is typically applied. In other words, the Agency will not approve human consumption at a level that is any higher than 1 percent of the highest level of consumption of which there was no adverse effect in animals. Initial efforts by FDA and industry to establish the safety of irradiated foods r1elied on feeding irradiated food to laboratory animals. In effect, irradiated food was to be tested as if it were a discrete chemical entity similar to a "conventional" food additive. The initial philosophy of the FDA scientists was to develop a core of wholesomeness studies on different types of foods to provide a matrix from which the safety of other foods could he deduced. This approach yielded enough data to permit the Agency in the 1960's to approve i1 1 -9 - petitions for certain specified uses of ionizing radiation for inspecting food, controlling insect infestation in wheat and wheat food flour, and inhibiting sprouting in white potatoes. rooted stablish Other early petitions did not result in regulations for a variety e of of reasons. Petitions for the use of radiation for microbial control on citrus fruit, strawberries, fish and fish products, and ham were withdrawn without prejudice because they lacked sufficient data to support the effectiveness or the safety of the process. FDA did not s a act on other petitions for irradiation of other foods because they were substance clearly incomplete. :onsumed. ~y As scientists were discovering, evaluating the safety of irradiated ~d. In foods by traditional testing methods was impractical for several j level reasons. The most significant problem was the inability to obtain the imption 100-fold safety factor. Because the irradiated food itself was considered the substance to be tested in these studies, it was impossible in most instances to feed the exaggerated amounts of food that are necessary for the purpose of traditional toxicological y testing. - were a ive. FDA found that more than half of the petitions that it was :ore of receiving on irradiation, as originally presented, did not provide matrix necessary and persuasive evidence to support the requested regulations. ~proach As a result, the Agency's Bureau of Science conducted a seminar in 1967 ,ve for government scientists and administrators interested in the I~ ~ I, -1D- La - ~f~''~ processing arfdr'4~eview of petitions involving irradiation of food. The seminar presentations were compiled into a report that was used as an ll~li aiA to evaluation. The 1967 seminar noted the need for more basic research in various disciplines to improve safety evaluation. Perhaps the low point for food irradiation occurred shortly thereafter, when in 1968 FDA revoked three regulations for irradiating bacon. This revocation reflected a culmination of FDA's concerns about the ualit of the safety data being submitted in many irradiated food Y q petitions. Nhen FDA received a petition for irradiating ham that relied heavily on reports originally submitted with respect to bacon, the Agency chose to require submission of the relevant raw data on which the original reports were based. The Agency's reevaluation resulted in FDA concluding that the safety of radiation-preserved hacon had not been sufficiently demonstrated. This conclusion, and resulting revocations, discouraged interest in food irradiation for several years. Food Irradiation and Safety Testing: An Evolution of Thought Since 1968, however, scientists have learned much about radiation chemistry of foods, and new scientific data addressing the earlier questions and problems have become available. In the late 1970's, these developments resulted in a renewed interest in irradiation as a possible safe alternative to the use of chemicals in food which in turn led FDA to review of the complex issue of irradiated foods. An ~I~ j _ 11 god. The } ar. internal FDA task force, the Bureau of Foods Irradiated Feod Committee, ~d as an was formed to evaluate the Agency's policy on irradiated foods in light Basic of the then current knowledge in toxicology and radiation chemistry and to recommend criteria for safety evaluation. The first question confronting the Committee was: what should be radiating tested? Or, more appropriately, what is the difference between an erns about irradiated food and an unirradiated food? The Committee concluded that ated food the only difference of toxicological relevance was the products fo Hoed that during the irradiation process. o bacon, " to on The Committee then asked whether all such products should be of tion concern, or whether concern should be limited to Bone smaller portion rued bacon - of these products. Working with data from the U. S. Army's Nigh Protein resulting Food Sterilization Program, the Committee found that of 65 substances eral produced by irradiation that had been identified by Army scientists, most were also found in cooked meats and in other foods. Only six substances (or about 10 percent) could not be verified in the - literature as being present in non-irradiated food, although these six tion were similar to natural food constituents. The Committee thus ~.r17er concluded that possibly up to 10 percent of all radiolytic products may 170's, be unique to irradiated food, although not enough is known about :ion as a components of nonirradiated foods at such low concentrations to which in conclude Lhat these 10 percent are indeed unique. ids. An - 1? Nonethel~~`s`, the Committee decided to assume that unique radiolytic products (URP's) are formed during food irradiation. Based on a considerable body of data on radiation chemistry of foods the Committee then deduced that at an absorbed dose of 1 "kilogray" (kGy) of radiation, about 3 parts per million in a food substance could be unique to irradiated food. Because more than 10 different URP's are likely to be formed, the concentration of any one URP would thus be less than one part per million. The Committee concluded that the chances of a single URP of unusual toxicity being formed in significant amounts at doses below 1 kGy would be negligible, especially since the i identified products presumed to be unique are chemically similar to other food components. The Committee also pointed out that its _ estimates probably overstated the total number of URP's. The Committee concluded that food irradiated at a dose not exceeding 1 kGy is safe for human consumption and that below this dose, animal feeding tests are mat necessary to establish safety. The i Committee's finding of safety applied even to a diet where a rn+R~ substantial proportion of the food was irradiated at 1 kGy. Moral feeding and other toxicity tests were recommended, however, for foods ~ irradiated above 1 kGy. The Committee further concluded that a food that comprises only a small fraction of the human diet (e .g. nutmeg) and that is irradiated at doses up to 50 kGy would necessarily contribute far fewer radiolytic i i i I+ ' - 13 - proAucts to the d~,ly diet than a food representing a significant 'olytic fraction of the diet irradiated at 1 kGy. Consequently the Committee m a also recommended that foods comprising no more than 0.01% of the daily Committee - diet and irradiated at 50 kGy or less also be considered safe for human ~f' consumption without toxicological testing. d be 'P's are As a check on the Committee's findings, FDA's Bureau of Foods :hus be established a secopd team of scientists, the Irradiated Foods Task the Group, to review all available toxicological data concerning foods ;ignificant treated with irradiation. The major objectives of this Task Group were since the to compile and summarize the toxicology data pertaining to irradiated ~lar to foods, identify any consistencies with respect to adverse findings, is look for patterns or trends in results among the studies, and summarize - the experimental results at the end of the review. They also tried to determine whether food irradiated at a dose above 1kGy could be considered safe without additional testing, as recommended by Codex this dose, Alimentarius. The review involved identifying from FDA files and from The open literature all relevant toxicology studies (over 4U0). The Task Group examined all the studies, paying special consideration to those Annuai that appeared fro raise questions about adverse effects. The Task Group `or foods concluded that studies with irradiated foods had not shown adverse toxicological effects and agreed with the previous Committee's ily a conclusion that there was an adequate margin of safety for foods -radiated irradiated below i kGy. Hence, the Task Group agreed that toxicology radiolytic tests on food irradiated at 1 kGy or below are not needed to support 3~, ( ! (1 - l4 ~i ~ i a conclusion that such foods are safe. However, this data base was not adequate to support a broad decision that foods may be irradiated safely at higher doses. Regulatory Efforts i In March of 1941, FDA announced in.the Federal Register the availability ot:the first Committee's report and invited the public to comment on it. The Agency also stated that it was considering several options, including the possible issuance of regulations on the Commissioner's initiative to permit irradiation of food at doses not exceeding 1 kGy. Such an Agency-initiated regulation would be predicated on the view that since safety had been established at Lhe 1 kGy level, a review of petition after petition for uses within that dose range would be an unnecessary burden and expense to the taxpayers. Three years later, in February 1984, FDA published a proposal for its cornerstone regulation on food irradiation. Among other things, the Agency proposed to permit the use of irradiation at levels not to exceed 1 kGy for insect disinfestation of food and for the inhibition of growth and maturation of fresh fruits and vegetables. ue designed our proposal to assure that no outstanding safety questions remained with regard to four important issues: radioactivity, radiolytic products, nutritional and microbiological concerns. I In - 15 - se was not The Agency simultaoaeusly proposed to permit the use of irradiation at 3ted higher doses as well 30 kGy for microbial disinfection of dried spices and dried vegetable seasonings. This higher dosage level was consistent with the recommendation of the Committee that foods comprising only a small fraction of the human diet could be safely irradiated at 50 kGy. Also, such foods are not sources of nutrients public to ~ and, being dry, cannot support microbial growth. i several In this case, as an additional safety factor, the Agency further noted that because spices are dry, irradiation would likely cause 'es not formation of fewer URP's than it would in a moist food. This is because most of the radiolytic products formed in food result from at the 1 reactions of the hydroxyl radical with other food components and that -water is the primary source of hydroxyl radicals in food. The Agency did lower the permitted dosage level for spices and seasonings in the proposal to 30 kGy from the 50 kGy that the Committee for felt would be safe. FDA is obligated to set a limitation on the levels hings, of use of any food additive substance so that the maximum levels are no not to higher than reasonably required to accomplish the intended technical ibition effect. In this case, 30 kGy was considered sufficient from an esigned effectiveness standpoint. rained is The final regulation for these uses was published two years later with only minor modifications. In the interim, FDA approved the use of irradiation not to exceed 1 kGy to kill trichinae in pork based on a petition that it received. f - 16 - Linaerina Mispi*Fceptions Since then, we have discovered that two common misperceptions have developed about FDA's basis for approving these uses and I am happy to have this opportunity to address them. The first is that the regulations were deficient and even illegal because they were not based on animal testing, even though the law does not mandate any specific type of test. ~ Ne can all agree that there must be sufficient testing to support the conclusion that a reasonable certainty exists that no ha nn will result from the expected use of an additive. Logically, any test that ~ would not contribute to this conclusion should not be required. FDA has not required animal testing in the past in those situations where, by chemical or other testing and sound reasoning, it could conclude i j that the use of an additive was safe without animal testing. We are satisfied that low doses and for minor uses of food irradiation, this is the case. Animal testing is simply too insensitive to show an effect from irradiation of food at low doses and, thus, would not contribute additional information to the evaluation of the safety of such uses. As it turned out, our Task Force's review of the existing toxicological data led to the second misperception that the data to support the regulations were inadequate because only five of the 4U9 studies reviewed by FDA were considered by Agency scientists to be - 1 - 17 - properly conducted"and reported. It is true that most of the reports s have were inadequate by present-day standards and could not stand alone to m happy to support safety. Nonetheless, many contained individual experimental a components which, when examined either in isolation or collectively, allowed the conclusion that consumption of foods treated with low ey were not levels of irradiation did not appear to cause adverse toxicological e any effects. Further, many of the studies were deemed useful for resolving sport ,n will certain questions. For example, if a potent toxic material were test that present at any level of toxicological significance in irradiated foods 'd. FDA ingested by test animals, some consistent toxicological signs would be ins where, manifest in the studies reviewed. However, Agency scientists saw no nclude consistent patterns or trends of adverse effects that might be Ne are attributable to exposure to food irradiated at low dose levels. on, this Thus, while the annual feeding studies were consistent with a ow an firMing that the process is safe, it should also be remembered that FDA not did not rely on any of the reports of animal feeding studies as the fety of basis for its regulations. Rather, we relied primarily on data we had on the effect of radiolytic products. Conclusion data to the 4U9 The future of food irradiation will be determined primarily by the ~o be actions of consumers and the food industry rather than by FDA. It is important to remember that FDA's responsibility in the evaluation of - 18 - I i~ food irradiat1i71P is limited to the determination of the safety of the process under specific conditions of use. FDA has no proper role as a promoter of a specific food additive or food process. The primary j responsibility for such activities remains with industry and consumers I who choose irradiated food. In addition, industry's role is to assess the feasibility of this technology and to determine its commercial potential. Our present posture is to refrain from initiating any more across-the-board rulemaking at dosage levels higher than 1 kGy and to review any petitions that may be submitted to us on a case-by-case basis. At this time, two toxicity considerations prevent the Agency from proposing a general regulation allowing doses up to 10 kGy as recommended by the Codex Alimentarius Standard. First, doses sufficiently above 1 kGy irradiation may be able to retard microbial spoilage without killing all spores of Clostridium botulinum, the pathogen/bacterium that causes hotulism. Ne mist ensure that C. botulinum cannot grow and produce a toxin that constitutes a health hazard. If irradiation kills the bacteria that cause the symptoms of spoilage, such as a spoiled odor, but fails to kill all the botulinum spores, a particularly dangerous situation could result. Rased on current knowledge, FDA is unable to prescribe generic conditions of irradiation for alt foods at all feasible doses to ensure that C. hotulinum would not develop and produce toxin without obvious spoilage. M - 19 - fety of the At dosage level"s not exceeding 1 kGy there is no such risk because food er role as a would spoil in the same manner as nonirradiated food. This is because primary a dose of 1 kGy or below helps extend shelf life by retarding ripening nd consumers or sproutiny, but is not enough to kill bacteria that cause is to assess spoilage. nmercial Second, FDA reviewed a number of animal feeding studies to determine whether foods that are irradiated at doses above 1 kGy could be considered safe without additional toxicological studies. The kGy and to A enc found this data base taken alone is not g y yet adequate to -hy-case support abroad decision that all foods may be irradiated safely at the Agency higher doses. 0 kGy as ses Finally, as with any food processing, irradiation can reduce the level of nutrients somewhat, depending on the condition. Based on our microbial earlier review, nutrient loss due to irradiation at doses below 1 kGy um, the hat C. appear to be of no dietary significance. FDA has not yet permitted a a health food that is a good source of vitamins to be irradiated at higher doses. Me believe that these should be evaluated on a case-by-case symptoms of e botulinum basis. Based on itions of that C. ous spoilage. APPENDIR A HISTORY OF FDA ACTIONS ON FOOD ,~cRADIATION i - February 19§;3; FDA approved gamma radiation preservation of canned bacon. - August 1963: FDA approved gamma radiation for control of insect infestation of wheat and wheat products. I I~ - August 1963: FDA approved electron beam radiation for the ff radiation preservation of canned bacon. - October 1964: FDA approved gamma radiation for sprout inhibition of white potatoes. - December 1964: FDA approved X-radiation for the radiation of preservation of canned bacon. - July 1966: FDA approved electron beam radiation for the control of insect infestation of wheat and wheat products. - July 1966: FDA approved labeling requirements for food treated by radiation. - October 1968: FDA rescinded the bacon regulations. September 1979: Director, Bureau of Foods established the Irradiated Food Committee to provide a total reassessment of all relevant issues applicable to irradiated foods. - March 1981: Advance Notice of Proposed Procedures for the 1,~,, Regulation of Irradiated Foods for Hwnan Consumption (ANPR) published in the Federal Register. I! - Autumn, 1981: FDA offered the opportunity for use of irradiation for insect disinfestation during the California Medfly situation based on certain conditions. However, no firm furnished evidence of meeting these conditions. - July 1983: FDA approved gamma radiation for microbial decontamination of a specific list of spices and vegetable seasonings. I - February 1984: Proposed rule published in the Federal R~e~ist~er for the use of gamma radiation for sprout inhibition an~sFieTt`- life extension of fresh fruits and vegetables, for insect disinfestation of food, and for sterilization of spices. - June 1984: FDA approved gamma radiation to control insect ~ infestation in garlic powder, onion powder, and certain dried ' spices. I 'PENDix A ~ _ April 1985: FDA expanded the specific list of dried spices and ~ vegetabl Masoning to include additional he spices, and vegetabl, easonings, and blends of these sE pings. ~ --June 1985: FDA approved gamma radiation to control insect and :.microbial infests won in certain dried enzyme preparations. 'July 1985: FDA approved gamma radiation treatment of pork to control Trichinella spiralis. act ~ } April 1986: FDA issued final rule approving ionizing radiation 1 for maturation inhibition of fresh food, insect disinfestation of k food, and sterilization of spices. The final rule included 3 labeling requirements for both retail and non-retail use, and Current Good Manufacturing Practice (CGMP) provisions. The ion ~ Agency received objections to the final rule during the objection period. February 1987: FDA denied requests for a stay of the regulation for pork (1985) ana for the general regulations (1986). ~l i by 1 ~n i ~II , ~ ~ H W~ ~ ~ Q~ Q~ ~ ~ ~ i ~,1 ~ ~ ~ ~ ~ ~ i ~ Q. Q '7 Q i ~'I ~ ~ ~ y Y S° C7 O p o~ ,E Y o 8 i ~ Y ~ 0 ~ ~ ~ O ~ ~ O ? O .X O C ~ _h C C p to Q O ~ i N C y O 'O O U U ~ U t•C ~ ~ ~Ct 7 ~j r-+ O a+ ~ ~ O U f0 ~ tq to N ~ C O N O 4 O pO_.S s~ O V1 -p U U N L .C U 4 ~ F~ cCO F~ ~ F~ FQ ~ F~ ~ ~ _m ~ ~ 4 ' _ '$~c o 4 m ~ ~ C > a 9 mmm ~ ~ C ~ ~ a ~ ~ m ~ ~ S ~ ~ t 14 m Excerpts from FDA's "Red Book" ~ CD D n ~ ~ Wrrent Standard for Oral Carcinogenicity Stuaiea in the Rodent D N j ~ 1. Study Duration: A¢imala shall ba exposed co the test t Q substance 7 Gaya per week for at least 104 consecutive veeka. Exposure periods Longer than 130 veeka are not rseussaeaded. 2. Species: The rat and mouse are the species of choice, r, although other species may be used if adequate justitieatioa 0 ~ is available to demonstrate the appropriateness of that 71 speeias. 'fhe acrain of cesc animals used shall be S ~idencified.~ In 1 O 3. Awe: Dosing of rodents shall began as soon as possible after wea¢iag and acclimation and in a¢y case before the > S animals are 6 veeka old. ~ N 4. Number of Animals a. Number ac risk: Ac least 50 animals/sex/group shall be started in the study for an aeceptabla negative study. b. Survival: Data from at least 25 animals/sex/group H - exposed far 2 yearn anall be available for evaluation ualeas compound-related toxicity occurs in'the high-dote group. Ia that event, only LO animals/sex in the high N dose group are required co have 1E-month data C D1 •C available. E o O C .5. Control Group(s): A concurrent control group is required. ~ The eo¢crol group shall be given o¢Ly the carrier vehicle U used is aaminiscering the test substance. A carrier of ~ ~ unknown careiaogeaic potential shall not be used. I¢ all other respects, the control group shall be handled and maintained in a manner identical co chat used with the cesc groups. If, when the tnat aubscanee as given, more than SX of the aiec is bai¢g replaced, then a control diet of equivalent nutritional value is needed. • 6. Dose Group(s): At least 3 dosaa shall be included is the study. Under most circumstances, the high dose shall elicit ~ signs of minimal toxicity without substantially altering the O normal life apace of the cesc species dun co effects ocher - than tumor formation. The low dose used in the study shall ¢ot induce evidence of compound-related coxicacy other than tumors. No dose level of the cesc substance shall exceed SX 0 of the total diet for aon-nutritiva additives. Nutritive additives may be fed up co 201 of chi diet proviaea chat ac does not cause a aignifieanc nutritional deficit. ~s~ W d 6 LS 7. Diet: M diet known to provida adequate nutrition for the species tested shall be used. 8. Route of Administration: The test substance shall ba administered by the oral route. She test substance shall be i administered co the.aaimals in the diet, in drinking vatar, or by stomach tube provided that all animals are treated by the name method. She doses shall ba calculated on the basis of mg of test substance pnr kg of body-weight and adjusted weekly. 9. Observations of Animals: Throughout the test period, each animal shall be observed at leas[ once daily. Animal veight,_food consumption and mortality observations shall ba reported at Least once per week. All signs of behavioral abnormalities or clinical signs of toxicity or . pharmacological effects, morbidity, and mortality, shall be recorded. 10. Hematology: She following determinations shall be made ac 12, 18, and 24 months on at Least 25 animals/sex/dose group: erythrocyte eo~~nt, total and differential leukocyte counts. tihere possible the same animal should be sampled ac each time. If changes are seen at each subsequent time period, all animals shall be studied. L1. Cross Necropsy (a) All test animals shall be subjected to complete groaa necropsy, which shall include examination of the external surface, orifices, tongue, teeth, cranial cavity, the external and cut surfaces of the brain, spinal cord, and the abdominal, thoracic, ana cervical viscera. (b) All tissues listed under Riscopachologieal Examination (sec. 12) shall be saved from all animals in the study. (c) No more than LOX of the tissues of any group shall ba Lost to autolyais, cannibalism, or management problems. 12. Niacopathologieal Examination a) All groaa lesions from all animals shall be examined microscopically. i b) She liver, kidney, and Lungs with mainscem bronchi of i all animals shall be subjected co microscopic examination. I i~ E -C:~~. c) Ia addition, cha following tissues shall ba subjected to microscopic examination in all high-nose and control 7C{ animals. be ~ ~TAdrenals Pituitary oy sis + _ borta ~ Prostate i 2 bona 4eccum 6oas Marrow Nepreaantacive Lymph Nodes _q 1 1 Erain (a least ~ lave la) Salivary Gland be 1)~- Cacum Seminal Vesiclaa Colon ~ Skeletal Museln ~a Corpus and Cervix Uteri Spinal Cord (2.levels) Duodenum Spleen r.;~ - Esophagus - Stomach and Fora Stomach Eya and Contiguous Narderian Gland Testes :e at Exorbical Lacrimal Glands thymus (if present) Call bladder (if present) Thyroid/Parachyroaa - Heart Trachea Ileum Urinary Bladder Jejunum Vagina Mammary Gland Zymbals Cland (if preaeat) Nasal Turbinacas Warias and Fallopian tubas Pancreas - Paripheral Nerve (sciatic) I£ changes era aeen is any of these cissuea, then those tissues • from all animals in cha other dose groups shall be examined. Likewise, if changes are observed in nay ciasua of an organ syacam, than cha ocher tissues of that organ system shall bn subjected co microscopic examination is all animals. Mr. WAXMAN. '1'harik you Very muc;u, ui. ~~w.g. As ~ know one of the criticisms of irradiation is that irradiated food 1. s some of its nutritional valt; n your statement you said that "nutrient loss appears to be of no aietary significance." That statement is hardly a ringing endorsement. Is there nutri- tional loss, and do you have sound scientific studies or theories to ~ support your position? Mr. Youxc. I would like to refer this to Dr. Pauli, but before doing so, make two comments. ~I i ~ First, I would like to introduce for the record an article written by Dr. Pauli which goes into great detail on this. It is entitled "Ir- i, ' j radiation of Foods-An FDA Perspective." Mr. WnxMAN. Without objection, we 11 put that in the record. i [Testimony resumes on p. 81.] C [The following information was submitted for the record:) ~ ' I 1 I ~I :irradiated ` f't?". Food Raviewalnteroational, 2(1), 79-107(1986) at you said here nutri- theories to :~hh-= but before ~ " - ae written ~;tvl= _ ititled "Ir- : vik - = record. `;,l:ar 3:~ .,IRRADIATION OF FOODS- - AN FDA PERSPECTNE GEORGE H. PAULI and CLYDE A. TAKEGUCHI Food snd Drug Administration Center for Food Safety and Applied Nutrition Division of Food and Color Additives Washington, D.C. +:'t; t:. Q i~lf;,. Abstract (i Food irradiation has been a subject of controversy since its first use as a food process. This article reviews the legislative and reg- I ulatory history of food irradiation in the United States and the role of the U.S. Food and Drug Administration, then and now. This article also discusses the status of FDA's regulations on food irradiation in the production, processing, and handling of food, as promulgated in the April I8, 1986, final rule, and re- ' views the safety, labeling, and current good manufacturing practice. )1VTRODUCTION Food irradiation is an inherently controversial issue, and the U. S. Food and Drug Administration (FDA) has long been in the middle of that controversy. 79 i Copyright ©1986 by Marcel Dekker, Inc. 8755-9129/86/0201-007953.50/0 i i gp _ PAULI AND I'AKEGUCAI f Food ..ot only essential to support life but .lso an important part of social, religious, and family traditions. Food has always been an important part of gatherings or i'Xuals that encourage friendship, reinforce traditions, or celebrate good times. The popularity of ethnic restaurants is witness to the fact that food is an important way of expressing culture as well as a source of nourishment. When most people think of culture, however, they do not think of science or new developments in technology. Food is to be enjoyed, not to be analyzed rationally; it is identified more with tradition than with new technology. It ~ should not be surprising that the same people who seek the newest develop- ments in medicine, even those not thoroughly tested, cherish the traditional arts of high cuisine and fear innovation in food technology. To complicate matters further, the technology of radiation processing evokes an emotional response in many consumers that ranges from a disquieting un- certainty to intense fear. Consumers connect the concept of radiation not only with atomic bombs and nuclear power plants, but also with medical X-rays, to which they have learned unnecessary exposure is to be avoided. The com- bination of a technology (which elicits emotional responses ranpartg from un- certainty to fear) with food and its far different emotional values produces controversy. Although some consumers may react so negatively to the mere thought of food irradiation that they will never find the process acceptable, we believe most will accept irradiated products if they are convinced that their fears are being addressed appropriately by responsible authorities. This rea,uires that in- formation be conveyed accurately to avoid the confusion and mistrust that results from contradictory messages. Unfortunately, it has been our experience that information presented in the trade press, the popular press, and even professional meetings has not been very reliable. Rumors, secondhand stories, and opinions have often been presented as fact. Both opponents and proponents of food irradiation have been sources of misinformation of valid information presented in a misleading way. As staff member of the Food and Drug Administration, we have spent much time sorting fact from fiction and explaining that irradiation of food does not neces- sarily mean that a food will have an indefinite shelf life at room temperature. In this paper, we will try to correct some of the misconceptions concerning FDA and food irradiation. We will try to explain FDA's current position, why it has developed, and how it evolved. We will not attempt to forecast the effects of economics and social values on future applications of this tech- . nology, because our experience as scientists and regulatory officials gives us no special expertise for such a task. k i i CAKEGUCHI FpA PERSPECTIVE ON IRRADIATION 81 rt of social, THE FOOD ~ ~TTIVES AMENDMENT OF 1958 " ant part of iy;. x celebrate History a that food ~urishment. To understand the development of food 'eradiation in the United States, one f science or must be aware of the impact of the Food Additives Amendment of 1958 to ~e analyzed the Federal Food, Drug, and Cosmetic Act (the Act). Unfortunately, the con- inology. It ~ ventional understanding of the philosophy behind this amendment and the st develop- ~ requirements imposed for demonstrating safety are often based on total mis- traditional understanding. Considerable energy has been spent discussing whether irradia- tlon should be treated as a process or as a food additive. A reading of the ;ing evokes l~gyclative history of the 1958 Amendment makes clear that both Congress and uieting un- the Administrative agencies were well aware that food imndiation is a process n not only and never gave any indication otherwise. They did conclude, however, that this cal X-rays, process should be demonstrated to be safe before.it is used. They implemented The corn- this conclusion by defining sources of radiation (including radioactive isotopes, from un- particle accelerators, and X-ray machines) intended for use in processing food ; produces as "food additives." _ Although this defmition may seem strange at fest, it developed after years Thought of of debate and discussion and is consistent with the definition of other "indirect we believe food additives" used in food processing. For example, a filter membrane is con- r fear; are sidered a food additive because its components might migrate to food under res that in- conditions of use. Yet there is no confusion in recognizing that filtering is a ;trust that process and that the filter is an additive (albeit not an intentional additive or ingredient). In the same way, irradiation is considered a process, and a source ited in the of radiation is an additive because its use affects the characteristics of a food. been very Likewise, a source of radiation is obviously not an ingredient. presented -`:The Food Additives Amendment resulted from years of discussion con- :n sources corning food safety. The nation was concerned with changes in the patterns of As staff food production as a result of the population shift from rural to urban areas. rush time This led to less home production of food and more consumption of processed aot noses- food with a concomitant increase in the use of chemical additives and newly iperature. developed packaging materials. Congressional hearings in the early 1950s indi- ~ncerning sated that the existing food law was obsolete in that it required no testing of tion, why additives before marketing, but prohibited the use of any additive poisonous •ecast the under certain conditions, even if it was safe under other conditions of use. this tech- The fast legislative result of this food law reform movement was the Pesti- ives us no side Amendment of 1953 (often called the Miller Pesticides Amendment, for Congressman Miller of Nebraska). Congress then turned its attention to developing a "chemical additives" or "food additives" amendment. { g2 PAULI AND TAKEGUCRI A, .e same time, food irradiation res~ nand development was growing and gaining publicity through the "Atoms for Peace" program. Commercial ' application of the technology appeared imminent. Thus it is not surptising that ' a bill submitted'by Congressman Miller in January 1956 included the following ~ defmition: - ~ ~ The term new food additive means any substance or treatment used, directly or indtrect- ' ly, in or on food for the purpose of affecting the appearance, flavor, texrure or storage property of such food, or for the purpose of otherwise altering any quantity or property ' of such food, which is not recognized among experts qualified by scientific training and experience to evaluate the safety of food, to be safe for use under the conditions of such use or intended use. The term does not include a pesticide chemical as defined in section ' 201(q) of this Act, or a food additive in use prior to January 1, 1956, which presents no reasonable probability of injury to health, or any substance approved for use in food by or under this"Act. Each new food additive shall be deemed a food, for the purposes of ~ this Act (1 Congressman Miller noted special features of this bill in Congressional hear- ings as follows: . The use of the word "treatment," and I use the word "treatment" where some of the other bills do not, in this definition it also significant. [t was included so that the new and revolutionary treatment of food, the use of neutrons, ions, and so forth, that is being i used in the treatment of meat, and things that may be used in the future, I think it ought to be included in the definition. If the ionic treatment, or the neutron treatment, or the isotope treatment of food shows that there is some need for investigation by the Depart- i ment of Health, Education and Welfaze it may be done (2). Commissioner George Larrick of the Food and Drug Administration, testify- ing before Congress in February 1956, agreed that food irradiation should be regulated under any new law that might be enacted. He stated: Experiments in preservation of foods by ionizing radiation from xaay, radioisotopes, ~ and radiation from atomic piles have now advanced to a point where they offer a distinct possibility that the processes will be adapted to commercial use. These methods, as well i as the use of radioisotopes as quality conuol measures, should not be permitted until it is ~ shown that food products will be safe. We therefore recommend that the pretesting requirements and procedures of the leg• illation be made clearly applicable not only to radioactive substances that might be intro- duced into food, either deliberately or unavoidably, but also to any changes in food, or new substances formed in food, by subjecting it to radiation from internal or external i sources. YD TAICEGUCHI jrEDA PERStECTIVE ON IRRADIATION g3 tt was growing a:9' ' • We wou,_ welcome committee consultation with rep,...,entatives of the Atomic Energy n. Commercial aiti~Commission as well as our Department, in this connection. Staff members of the Depart. surprising that twment and of the Atomic Energy Commission are prepared to cooperate in working out i the following ~ an:appropriate amen rd"'rtent for assuring the safety of food affected by radiation (3). Several bills were introduced in the next two years as Congress attempted to ectly or induect• „sort out. the specific requirements that would protect consttmea, allow the :xture or storage ~ 1:(ood industry to operate efficiently, and give the government the enforcement ttity or property ,Powers to administer any law that might be adopted. Because very little discus- tttic ttartttng and ¢ Sion was given to the food irradiation process, one must seek indirect evidence ~nditions of such :Fined in section ~ r1~s ~ to .what Congress had in mind regarding the regulation of the food irradia- hichpresents no ~ .,~i9n industry. ,ruse in food by F to Several bills introduced in 1957, including one supported by the FDA, dis- the purposes of •~cussed radioactive material intended as a source for irradiation of food in the ` •definition of "food additive" (or "chemical additive" as it was often called). One noteworthy example was a new bill submitted by Congressman Miller. •essional hear- :This bill attempted to distinguish between "intentional" food additives, such as ingredients, and "incidental" food additives, which are not intentionally added to food but that might unavoidably migrate to food from packaging material ire some of the .or. processing equipment, or that might unintentionally affect the characteris- >o that the new tics of the food. The proposed definition for an incidental additive reads as th, that is being ~fOllows: [ think it ought eatment, or the ~~=17te term "incidental food additive" means any substance intended for use in menu- , by the Depart• •L' facturing, packing, processing, ptepazing, treating, packaging, or transporting food which foreseeably results, in the course of good manufacturing practice, in its getting into the ~t''food; including any radioactive material intended for such use or as a source for the ttion, testify- ~ n'% irradiation of food (4). ~n should be ~ ~ " Although the bill was substantially different from the bill eventually enacted, it provides evidence that at least one Congressman considered a sotuce of radia- radioisotopes, lion to be an incidental additive like other food processing equipment. The offer a distinct legislative history provides no evidence that other members of Congress or the ethods, as well Administration disagreed with this characterization of a source of radiation. fitted until it is The definition of a food additive finally enacted in 1958 made no legal dis- ~ unction between "intentional" and "incidental" additives. As discussed in the res of she leg• ~ official report accompanying the legislation, both types of additives wen en- night be intro- compassed by the definition and required premazket approval by regulation. ;es in food, or Although the final law makes no distinction between types of additives, the tal or external fact that Congress was considering a source of radiation as an incidental additive is significant becatue it means that sources of radiation were to be -r, 84 PAULI AND TAYEGUCffi regu. d like other food processing equip[.. ..t, although the safety issues were ' ~ - unique because the radiation affected the characteristics of the food. This ~ example illustrates that the common complaint that the Food Additives ` Amendment r~ulation of food irradiation is a mistake because irradiation is a process and not an additive is not based on fact. Congress considered a source of irradiation to be an incidental additive used for the process of irradiation, analogous to other incidental additives used in food processing equipment. Likewise, testimony from the FDA Commissioner shows that he was well ~ aware that irradiation was a process, but that this technology must be regu- lated to assure its safety. ' The Department of Health, Education and Welfare opposed Congressman Miller's bill that distinguished between two types of additives because it estab- lished two different procedures for demonstrating safety for the two types of additives. The Department believed that the same procedures and safety standards should be used regardless of whether an additive was intentionally ' introduced into food, caused changes in the food, or migrated to food. The current definition of a food additive in the Food, Drug, and Cosmetic Act reads as follows: The term "food additive" means any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a compo- nent or otherwise affecting the characteristics of any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food; and including any source of radiation intended for any such use), if such substance is not generally recognized, among experts gtral• ified by scientific training and experience to evaluate its safety, as having been ade- quately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use; except that such term does not include- a pesticide chemical in or on a raw agricultural commodity; or (2) a pesticide chemical to the extent that it is intended for use or is used in the production, storage, or transportation of any raw agricultural commodity; or (3) a color additive; or (4) any substance used in accordance with a sanction or approval granted prior to the enactment of this paragraph pursuant to this Act, the Poultry Products Inspection Act (21 U.S.C. 451 and the following) or the Meat Inspection Act of March 4, 1907 (34 Stat. 1260), as amended and extended (21 U.S.C. 71 and the following); or (5) anew anima! drug. (5) Safety Congress recognized that the word "safety" can convey different meanings to different people. At the time the Food Additives Amendment was being s: r 1. I I 'D TAKEGUCffi ~ ;1rpA PERSPECTIVE ON IRRADIATION 85 :ty issues were -considered, __.ere was a consensus that the safety .squired of a food additive he food. This ~ -should. be safety under conditions of use. In addition to the concern that food rod Additives ~ =additives are properly tested for safety, there was agreement that the food law eradiation is a A~ then in existence was obsolete in that it prohibited any added poisonous or iered a source ~ deleterious substance to food, even if that substance was safe under conditions ~f irradiation, of use. However, several proposals were offered to clarify what was meant by g equipment. .•Saf'ety_~~ _ he was well • The .concept of safety was explained in the Senate Report on the Food Ad- nust be regu- :ditives Amendment of 1958: SYU Congressman ~r::The concept of safety used in this legislation involves the question of whether a rubstance :suss it estab- .bt, is hazazdous to the health of man or animal. Safety requves proof of a reasonable certaiu- two types of ~;aty that no harm will result from [he proposed use of any additive. It does not-and can- > and safety y+~not-require proof boyond any possible doubt that no harm will result under any con- intentionally ~•ceivablecircumstance. god. .,This was emphasized particulazly by the scientific panel which testified before the sub- nd Cosmetic committee. The scientists pointed out that it is impossible in the present state of sci- " ~entific knowledge to establish with complete certainty the absolute harmlessness of any chemical substance. r~ hich results or ~ ` Congress also described, in the statute, some of the factors that should be an g a compo• considered in determining whether a substance is safe. Section 409(c)(5) of y substance acing, treating, the Act reads as follows: atlon intended ' experts qual• [n determining, for the purpose of this section, whether a proposed use of a food ad- ~irtg been ade• ditive is safe, the Secretary shall consider among other relevant factors-(a) the prob- e rued in food - -able conrumption of the additive and of any substance formed in or on food becatue of :nce based on the use of the additive; e; except that (b) the cumulative effec[ of such additive in the diet of man or animals, taking into account any chemically or pharmacologically related substance or substances in such diet; and s used in the (c) safety factors which, in the opinion of experts qualified by scientific training and r experience to evaluate the safety of food additives, are generally recognized as appro- priate for the use of animal experimentation data. (7) d prior to the upection Act Congress also considered whether specific testing procedures should be t 4, 1907 (34 prescribed by law. Some thought that specific scientific procedures were neces- sary so that proponents of new food additives could be sure they were conduct- ing the appropriate tests. However, both the Food and Drug Administration -and members of a panel of scientists selected by the National Academy of Sci- ence advised against establishing specific procedures by statute. They empha- sized that such procedures would be cumbersome and would prevent scientists .leanings to from demonstrating safety in cheaper and more effective ways, primarily was being for two reasons. Available information on the use of some substances could ~ ~ ' 86 PAULI AND TAKEGUCHI indica that abbreviated testing was cuff. .nt, while information on other substances might point to a need for specific tests that aze not routinely need- " ed. The legislation left the decision on what testing was necessary and suf- 6cient to the discretion of scientists. L, ` Procedures for Authorizing Use of an Additive t ~ jl The burden of demonstrating that a source of radiation can be used safely to ii 1. irradiate foods was, as for other additives, placed on proponents of its use. The j' principal procedure established for premarket approval of an additive's safe use is the filing of a food additive petition with data sufficient to demonstrate ~I safety. Such a petition must provide a complete record on which to base a de- cision. An important feature of such petitions, however, is that once FDA decides that a•-petition is adequate to support a regulation prescribing safe conditions of use, the resulting regulation is applicable to everyone, not just the petitioner. The food industry argued strongly at hearings on the Food Ad- ditives Amendment that the Food and Drug Administration should not have authority to grant licenses to individual companies, and Congress agreed. Although this procedure encourages competition in the marketplace for use of additives and processes shown to be safe, it probably also discourages an individual company from committing vast resources to demonstrate safety if a competitor gets equal advantages from that effort. In a second procedure established to gain premarket approval, the govem- ment proposes a regulation establishing safe conditions of use. Such a proposal must meet the standard for demonstrating safety as a petition from industry. The public is allowed at least 30 days to comment on the proposal, and all sub- stantive comments must be considered. This procedure is used faz less frequent- ~ ly than a petition because a new regulation does not necessarily have high priority in the mission of a regulatory agency unless the regulation is deemed j of clear benefit to public health or will allow the agency to operate more ~ efficiently. Enforcement of Regulatory Authority The major purpose of the Food, Drug, and Cosmetic Act, with respect to foods, is to ensure safety and fair dealing. This is accomplished by a series of prohibitions regazding two types of actions: adulteration and misbranding. ~i 1. Adulteration. The term "adulterated food" describes food that, for a variety of reasons, cannot be sold legally in the United States. It applies to food for both humans and animals. The major provision concerning irradiated foods is section 402(a)(7), which states: I iAKEGUCAI -FDA PERSPECTIVE ON IRRAbIATION g7 ,n on other finely need- A-food shat „e deemed to be adulterated if it has _.en inten[ionally subjected to ry and suf- ~ radiation, unless the use of radiation was in conformity with a regulation or exemption in effect pursuant to section 409 (the section concerning food additives). (8) ;This provision is different from the adulteration provision for other food additives, which states that a food is adulterated if it is, or if it bears or con- twins, any unsafe food additive (i.e., a food additive not permitted for use by 'd safely to regulation). This distinction is necessary because an irradiated food would its use. The not contain the food additive, namely, the source of radiation. ~e's safe use A food that has been irradiated in conformance with the appropriate regula- emonstrate lion still may be adulterated for other reasons. For example, a food contain- ~ base a de- ing filth or decomposed substances or a food held under insanitary conditions once FDA may be considered adulterated. Irradiation is not considered a substitute for :ribing safe ~ good sanitation practiees, and irradiated filth is still considered filth. lot just the 2, Misbranding. The misbranding provisions apply primarily to a label or Food Ad- # labeling, both as to what is stated and what is not stated. The Food Additives d not have Amendment of 1958 is relatively silent on the issue of labeling with a few red. minor exceptions. .ace for use (a) A petitioner, for use of an additive, is required to submit specimens of ourages an its proposed labeling [Section 409(b)(2)(B)] .This is usually not applicable to :safety if a incidental additives, although labeling may be necessary to describe to a user how an additive is to be used in conformance with a regulation. For example, :he govern- labeling on radiation sources used for inspection in food processing plants must a proposal give adequate directions for use, including the maximum dose to be applied. n industry. This provision is applicable primarily to the user of the source of radiation. tnd all sub- (b) A food additive regulation shall not be issued if its proposed use would s frequent- promote deception of the consumer or otherwise result in misbranding as have high defined by the Act [Section 409(c)(3)(B)]. (9) is deemed Thus, in detenrtining retail labeling requirements for irradiated foods, one gate more must review the general misbranding requirements of the Act. As indicated earlier, a source of radiation is not an ingredient; therefore, the provisions for ingredient listings are not generally applicable, except, perhaps, if irradia- tion of an ingredient changes it substantively so that the name given to the un- irradiate3 ingredient is no longer valid or appropriate. respect to The primary provision concerning labeling is Section 201(n), which states: a series of tding. If an article is alleged to be misbranded because the labeling or advertising is misleading, hat, fora then in determining whether the labeling or advertising is misleading there shall be es to food taken into account (among other things) not only representations made or suggested by statement, word, design, device, or any combination thereof, but also the extent to which (7), which the labeling or advertising fails to reveal facts material in the light of such representations or material with respect to consequences which may result from the use of the article to which the labeling or advertising relates under the conditions of use prescribed in the 83-632 0 - 88 - 3 h~ ~ I 88 1 PAULI AND TAKEGUCHI labeling or advertising thereof or under such condtuons of use as are customary or usual. (1Q) _ l_~ ~ ~ Thus, an important consideration for labeling of irradiated foods is whether a consumer is likely to be misled if a label does not provide clear information ~ that such foods have been so processed. (It ,i _ 1 REGULATORY HISTORY rl Background Although the use of irradiation for preserving food was explored as early as i 1936, food irradiation research in the United States started in earnest in-the late L940s. It was only a few years later, in the eazly 1950s, that the United States government became interested in this new processing method. At that ! time the United States Army conducted a feasibility study of irradiated food and, based on organoleptic and biological tests, concluded that food irradia- ,i lion could provide a wholesome, good-tasting, economical, and shelf-stable product for field rations; reduce dependence on refrigeration; and greatly reduce food-handling costs for the military. There was also substantial civilian interest in this new technology. As part of '1 President Eisenhower's "Atoms for Peace" program, the Atomic Energy Com- ~ mission (AEC) had an early interest in food irradiation, especially at !ow doses i for insect control and shelf-life extension of fruits and vegetables as well as for control of microorganisms in food. Considering the widespread interest in food irradiation, it was not surprising that FDA was interested almost from the start. FDA's involvement in the nutritional and toxicological aspects of irradiated foods began in the eazly 1950s, when in close cooperation with the military, the U. S. Department of Agriculture (USDA), and interested parties in the pri- va~e sector, the Agency suggested wholesomeness testing for such irradiated products. As discussed earlier, the passage of the Food Additives Amendment of 1958 required a premazket safety review prior to issuance of a regulation permitting ' use of irradiated foods. The agency has followed the same general procedures in the development of regulations for the use of sources of radiation as are fol- lowed in the development of regulations for other food additives. Under the Act, the agency's primary responsibility is to determine that use of the additive is safe under the proposed conditions. Since the 1960s when the fast petition for the treatment of food with radiation sources was submitted, the agency has been confronted with the questions of what test procedures are appropriate to i .KEGUCHI I•Dp PERSPECTIVE ON [RRADiATION gg -y or usual, establish a ro,.~onable certainty of no harm for use ~f radiation sources in the treatment of food. '"Traditionally, feeding studies are used to determine the safety of a typical whether ~ E~iod additive. Such testing requires a determination of the highest "no-effect •ormation l.;;vel" for the tested substance and consideration of the amount of the sub- stance likely to be consumed (11). (To allow for uncertainty in relating data. gained from laboratory animals to humans, a 100-fold safety factor is typically applied, i.e., human consumption that is 1% of the highest consumption show- ing no effects in animals is considered safe.) (12) For substances that may become a large percentage of the diet, a 100-fold ~ safety factor is impossible and wholesomeness feeding studies are performed. } "Wholesomeness" means a determination that the substance is microbiological- early as ~ ly, nutritionally, and toxicologically safe. Wholesomeness feeding studies were st in the attempted to assess tfit: safety of many irradiated foods. United Initial efforts by FDA and industry to establish the safety of irradiated foods At that !ed to a scheme approximating traditional methods for evaluating substances :ed food added to the food supply. Because the radiation chemistry of foods was still irradia- largely unknown, and because irradiation produced many substances that were lf-stable ill-defined, FDA required animal feeding studies to demonstrate that irradiated greatly foods were safe. The initial philosophy of the FDA scientists was to develop a core of wholesomeness studies on different types of foods to provide a matrix part of from which the safety of other foods could be deduced. ,ry Com- w doses Early Petitions ~ll as for _ in food On February 15, 1963, FDA published its first regulation to provide for the restart. safe use of gamma-radiation for the processing of foods (13). The regulation adiated provided for the use of sealed sources of cobalt 60 for the radiation preserva- ~tarY, tion of canned bacon at an absorbed dose of 45-65 kGy (4.5-5.6 Mrad). In the pri- addition, the regulation required that any coatings used on the inside of the can adiated meet FDA specifications (presently regulated in 21 CFR 175.300, resinous and polymeric coatings) and that dosirnetry records be retained for FDA inspection ~f 1958 for a period of one yeaz. sitting On August 21, 1963, FDA published a regulation to provide for the use of ores in gamma-radiation sources, with maximum energy not to exceed 2.2 million +re fol- electron volts (MeV), at an absorbed dose from 0.2 to 0.5 kGy (20 to SO krad) ter the for the irradiation of wheat and wheat products to control insect infestation dditive ~ (14). etition On August 30, 1963, FDA published a regulation to provide for the safe use icy has of electron beam radiation for the preservation of canned bacon at 4S to 56 fate to kGy (4.5 to S.6 Mrad) (15). The permitted radiation source was an electron accelerator producing a beam of electrons at energy levels not to exceed 5.0 s 1 90 PAULI AND TAKEGUCpI i ' ! MeV. 1. ;egulation required that the bacon _ packed under vacuum or in an inert atmosphere. These first three actions led to three separate regulations, two for high-doss irradiation of bacon from the two types of sources and one ` P ~ for low-dose irradiation of wheat. It is interesting that the high-dose irradiation ~ • was described for "processing" of food, whereas low-dose irradiation was ' ~ ' described for "treatment" of food. The regulations did not state why the dif- ferent wording was used. ~ ~ On February 6, 1964, FDA amended the regulation for gamma-radiation for the processing of canned bacon by I) changing the heading of the regula- ~ " I tion to read• "gamma radiation for the processing and treatment of food"; 2) adding cesium 137 as a permitted source of gamma-radiation; and 3) re• i, quiring that the irradiation be conducted only "after packaging under vacuum or in an inert atmosphere" (16). On July 8, 1A64, FDA published an amendment to the irradiated wheat regulation to limit the sources of radiation to cobalt 60 and to pet~nit irradia- tion of white potatoes to inhibit sprout development at an absorbed dose from 50 to 100 Gy (5 to 10 krad) (17). On October 1 Q, 1964, FDA amended the regulation permitting gamma- ~ radiation for the treatment of wheat and potatoes by including sealed units of cesium 137 as another permitted gamma-radiation source (18). ~ On December 19, 1964, FDA published a new regulation for the use of X-radiation for the processing of food. The permitted radiation was a beam of X-rays produced by an electron beam from a particle accelerator striking a I' metal target (19). The accelerated electrons were restricted to energies no i higher than 5 MeV. Other limitations were identical to those listed in the reg- ulations permitting processing of canned bacon with gamma- and electron beam radiation. On April 21, 1965, FDA amended the regulation permitting electron beam radiation for the processing of food to provide for conditions under which electrons with energies up to 10 MeV may be safely used on canned bacon and to limit the maximum thickness of food under irradiation to 3.2 cm with single beam irradiation or 7.0 cm with cross-firing beams (20). The next day, April 22, 1965, the USDA issued a regulation requiring that an approved term, such as "Processed by Ionizing Radiation," appear on the labels of irradiated foods in conjunction with the product name (21). This was the fast explicit labeling requirement. On November 9, 1965, FDA amended the regulation permitting gamma- radiatiop for the treatment of wheat and potatoes by providing an increase in the upper limit for the dose that can be applied to potatoes from 100 Gy to 150 Gy (from 10 to 15 krad) (22). On March 4, 1966, FDA published a notice of proposed rule making in the matter of various radiations regulated by the agency (23 For radiation used i i i iAYEGUCpI fDA PERSPECTIVE ON IRRADIATION 91 um or in an in.the disi .tation of wheat, the agency cons ed the term "wheat prod- regulations, ucts" as too broad and indefinite and proposed restricting the use to "wheat ces and one and wheat flour from unirradiated wheat." The agency also proposed adding irradiation the term "high-dose" to the headings for gamma-radiation, electron beam iiation was radiation, and X-radiation for the processing of food and the term "low-dose" by the dif- to the heading for gamma-radiation for the treatment of wheat and potatoes. In addition to proposing to limit the source of radiation, the conditions of use a-radiation of the sources, and the specific food, the agency also concluded that food the regula- treated with radiation should have that fact declared on the label; where re- of food"; treatment might cause the permitted maximum dose to be exceeded, a warning and 3) re- against retreatment should be included. Therefore, the agency proposed that per vacuum for high dose irradiated food, "(To) assure safe use, the labeling of any food so processed shall bear, in addition to other information required by the Act, the ted wheat statement: `Processed by ionizing radiation."' For low-dose irradiated food, nit irradia- "the label and labeling of any market package of food so treated shall bear, in dose from addition to the other information required by the Act, the statement: `Treated with ionizing radiation-do not treat again.' In the case of bulk shipment, the g gamma- invoices or bills of lading shall bear such statement when the bulk commodity :d units of has been so treated'_'. (23). On July 13, 1966, FDA issued a regulation (24) resulting from the March 4 he use of proposal and from a February 26, 1966, proposal. The new regulation provided a beam of for the use of electron beam radiation for wheat and wheat flour from unir- striking a radiated wheat with a specific thickness and flow limitation. In response to rergies no components on the labeling proposal, the agency rejected alternative labeling n the reg- terms such as "ionizing energy" for "ionizing radiation," and the terms "steril- ron beam ized" and "pasteurized" instead of "processed" and "treated." The final regu- ' lation required the following label statements for radiation treated food: ron beam er which 1. "Treated with ionizing radiation" on retail packages of low-dose treated Bacon and foods ith single 2. "Treated with ionizing radiation-do not irradiate again" on wholesale packages and on invoices or bills of lading of bulk shipments of low-dose ring that treated foods it on the 3. The statement "Processed by ionizing radiation" for high-dose gamma- 'This was radiation, electron beam radiation, and X-radiation treated food. gamma- I The agency denied a request for a hearing in a document published on Jan- crease in ~ uary 7, 1967, because reasonable grounds were not stated for a hearing on the )0 Gy to issue of relieving irradiated foods from the labeling requirements imposed or for staying the effectiveness of the order (25). In addition, the agency amended ng in the the labeling requirements to allow for optional wording to replace the term ion used "ionizing radiation" on the labeling, such as "gamma-radiation," or "electron A - 92 - PAULI AND TAKEGUCHI Y ! radiation, or "X-radiation" (26). This amendea labeling statement became effective on March 2, 1967, and remained in effect until April 18, 1986. ' The use of matetj~ls satisfactory for holding and packaging food for irradia- - p`j lion led to § 179.45 Packaging materials for use during the irradiation of pre- packaged foods (21 CFR 179.45). This regulation resulted from several food ' ~r additive petitions to provide for packaging materials that may be safely sub- , ! t ;a jected to the radiation treatment and processing of prepackaged foods. The first listing in this regulation was issued on Mazch 12, 1965, in anticipation ~~,Il,~i of irradiated food use and was subsequently amended several times (27-30). In addition to the use of radiation to treat and process food, the agency has permitted the use of sealed sources of radiation fot inspection of food and for controlling food processing 179.21) since 1960. The maximum permitted dose allowed in § 179.21 is 0.01 kGy (1 krad). This dose is so low that it does !,j not significantly affect food. Applications of these devices or gauges include uses for checking fill of the container, for checking the presence (or absence) of foreign objects in food, and for measuring moisture content. In addition to petitions resulting in the issuance of a regulation, many early petitions did no[ result in a regulation for a variety of reasons. Petitions for the t use of radiation for microbial control on citrus (lemon and oranges) (31), ' strawberries (32), fish and fish products (33), and ham (34) were withdrawn without prejudice because of insufficient data to support the effectiveness or ; the safety of the process. FDA did not act on other petitions for irradiation of other foods because they were clearly incomplete. FDA was concerned at that time that more than half of the petitions as orig- " finally presented did not provide necessary and persuasive evidence to support the requested regulations. On May 23, 1967, FDA's Bureau of Science con- e ducted a seminar for govemment scientists and administrators interested in the processing and review of petitions involving irradiation of food. The sem- inar presentations were compiled into a report (35) that was used as an aid to those interested in submitting swell-designed petition and to facilitate agency evaluation. The report included sections from various scientific and admin- istrative groups involved in the petition evaluation process at that time. [n the introductory address, Robert S. Roe, then Associate Director for the Bureau of Science stated: S The same general procedures are followed in the development of radiation regulations as are followed in the development of regulations for other types of food additives such as preservatives, emulsifiers, anticaking agents, etc. In the case of any food additive, FDA's primary responsibility is to determine that the additive or the process to be regulated is safe and that it does accomplish the intended effect. Therefore, proposals for regulations must be supported by data adequate to establish these facts. Much of this material will cover these necessary data. 1 >-~r: EGUCHI •1Py~A PERSPECTIVE ON IRRADIATION 93 i;; became 'AK Food adr,. :matters involving radiation require co. :ration as to what test pro- ;f_ ~cedures may be appropriate as compared with other food additive matters. The require- Yr•- irradia- ?'y;e at ,ments, the procedures, and the protocol must be scientifically sound, and accurately .and appropriately applied: As in all areas involving scientific advancements and tech- of pre- ~~tpological improvement, procedures and even evaluations may be expected to change. -al food ' `te Science is not static. New information appears frequently and often calls for reevaluation ~ls s~utbe '-of test procedures and bases of interpretation. FDA always hopes to develop better me[h- ~~a;~:'Y5='ods of analysis, better test procedures, and less costly and more expeditious means of ipation :";evaluating results, in this azea and other. The questions to be answered cover a wide icy t a)s "-^-gr~'spectrum of scientific disciplines. What is the significance of radiation•induced mutations in microorganisms? What is a sound basis for extrapolation of data from one product to and for f-;~ another, from one species to another, or from one level of exposure to another? What is -trotted ;iG:_the significance of the destruction of vitamins? In fact, what are appropriate safety it does .tests? (36) ~sence) Thus, the 1967 seminar noted the need for more basic research in the various `disciplines to improve safety evaluation. This set the stage for a future reevalua- y early ~ lion as the data base grew. for the ~ (3 ] Revocation of Bacon Regulations idrawn tess or FDA received a petition for radiation-sterilized ham that relied on many of the pion of ~ same reports originally submitted in the petition for radiationsterilized bacon. i FDA's growing concern that the quality of safety data submitted in irradiated ~s orig- food petitions was often not acceptable caused it to require submission of all lpport relevant raw data on which the original reports were based. The results of that e con- reevaluation sent shock waves through the food industry and discouraged ted in interest 'in food irradiation. The agency concluded that adverse effects may sem- have been seen in the studies, although the numbers of animals used were too aid to small to be sure that such effects were caused by the irradiated food. In any gency i case, evaluation of the complete data raised doubts that the safety of radiation- dmin- ~ sterilized bacon had been demonstrated. Therefore, on August 24, 1968, FDA :n the proposed to revoke the three regulations for high-dose gamma-, electron beam, ureau r and X-radiation processing of canned bacon (37). The revocation was issued as a final rule on October 17 of that year (38). ations Agency Task Groups s such ditive, Since 1968, scientists have learned much about the radiation chemistry of to be foods, providing a basis for estimating the quantity, identity, and toxicity of posals { the radiolytic products formed by chemical changes caused by the absorbed :ch of f radiation. New scientific information addressing the eazlier questions and prob- { lems were becoming available. 94 PAULI AND TAKEGUCHI In l 979, . DA established the Bureau of Foon., irradiated Food Committee (BFIFC) to review the existing agency policy and make recommendations re- garding the establishment of those toxicologic testing requirements appro- priate for assessing the safety of irradiated foods. BFIFC's recommendation ~ focused on making the degree of testing compatible with the potential risk as indicated by the level of anticipated human exposure to radiolytic products formed. BFIFC recognized that safety assessments of irradiated food should be based on 1) projected levels of human exposure to the food; 2) estimates of I the identity, amount, and potential toxicity of new chemical constituents generated in the food by the irradiation process; and 3) stateof-the-art, sen- sitive toxicological tests. BFIFC completed its review and submitted its final report in July 1980 (39). BFIFC recognized that no single approach provided sufficient data to estimate that perceaTage of food consumption that might consist of irradiated food. Hence, in projecting human exposure to irradiated food, BFIFC used estimates of total food consumption, dietary items proposed for irradiation, and the percent of each dietary item which may be irradiated. Using a rough ~ estimate based on these factors, BFIFC suggested that as much as 40% of the ~ total diet could be irradiated, but anticipated that actual human exposure would not exceed 10% of the diet. The first question confronting the Committee was: What should be tested? Or, more appropriately, what is the difference between an irradiated food and an unirradiated food? The Committee concluded that the only difference of toxicological relevance was the products formed during the process. The Com- mittee then asked whether all production of radiolytic products should be of concern, or whether concern could be limited to some smaller portion of the radiolytic products. This led to a review of available studies that identified sub- stances formed by treating various foods with radiation. The Committee used data from the United States Army's high protein food sterilization program. Army scientists had identified some 65 substances in the volatile fraction in the headspace of irradiated canned meats. Of these, 23 were also identified in thermally sterilized control meats, and 36 were identified as being present in volatile fractions of other foods. Thus, only six substances (or about 10%) could not be verified in the literature as being present in food, although these six were similar to natural food constituents. Comparison of availablc data from model studies on volatile and nonvolatile products formed by irradiation and by heating showed that there were con- siderable similarities among the thermal and radiolytic products. Based on such considerations, the Committee judged that it was reasonable to conclude that the differences between the volatile components of irradiated and nonir- radiated food could be taken to represent the relative differences caused by irradiation. Thus, based on analysis of the volatile fraction, the Committee TAKEGUCHI fpA PERSPFCTTVE ON IRRADIATION 95 Committee ndations re- ~ concluded gnat 10% of all radiolytic products ...ay be unique to irradiated ents appro- food; although not enough is known about components of nonirradiated foods :emendation ~ at such low concentrations to prove that these 10% are indeed unique. That is ~`to say, if we knew the exact composition of all processed foods, we might also ntial risk as ~ be able to identify all the radiolytic products in nonirradiated foods. is products $ecause it is impossible to prove that there are no unique products (one 3 should be ~ ~~d need perfect knowledge), the Committee assumed that unique products stimates of i are formed. They estimated that a 1-kGy absorbed dose would produce ap- onstituents ~ proximately 30 mg of radiolytic products per kg of food (this is much higher he-art, sen- t}eare seen in the volatile products discussed above). That means that fora 1-kg ed its final food substance, about !0% of the radiolytic products (or 3 mg) could be con- sidered as possibly unique; or that a total of about 3 parts per million of that et data to food substance could be unique. The 3 mg would be composed of several dif- f irradiated ferent products that-could be formed. Recognizing that the identified products FIFC used presumed to be unique were chemically similar to other food components, the eradiation, Committee concluded that any single "unique" product of unusual toxicity ng a rough that would be formed in significant amounts at doses below 1 kGy would be ~0% of the negligible. :exposure This rationale was the basis for waiving the need for animal feeding tests because the test substances (the irradiated food) consisted of a small quantity be tested? of test material (the radiolytic products) diluted in a lazge amount of food. The i food and Committee did not want to require expensive tests with hundreds or thousands ference of of laboratory animals if such tests were incapable of providing useful informa- The Com- tion. Tests were recommended for foods irradiated above 1 kGy because of a Auld be of perceived changes that, at such doses, the concentration of radiolytic products ion of the may be sufficient to allow a meaningful verification of the above safety analysis. tified sub- The Committee further concluded that a food (e.g., nutmeg) that comprises ittee used only a small fraction of the human diet (i.e., no more than 0.01% of the diet) program. and that is irradiated at doses up to 50 kGy (5 Mrad) would necessarily con- ion in the tribute far fewer radiolytic products to the daily diet-approximately 20 times ntified in less-than a food representing a significant fraction of the diet (e.g., 10%) present in irradiated at 1 kGy (100 rad). Consequently, BFIFC recommended that foods out 10%) comprising no more than 0.01% of the daily diet and irradiated at 50 kGy ugh these (5 Mrad) or less also be considered safe for human consumption without tox- icological testing. BFIFC based this recommendation on radiation chemistry ~nvolatile and the anticipated low levels of human exposure to any possible unique radio- vere con- lyric products generated in the irradiated minor ingredient. i on such The FDA agreed with BFIFC's scientific rationale and conclusion that an Jude that adequate margin of safety could be demonstrated for irradiated foods without ed nonir- the requirement of toxicological testing and adopted its recommendations con- aused by cerning the safety of food irradiated at the proposed dosage levels (40). ~mmittee ~ ~ 96 PAULI AND TAKEGUCHI II .I ' ` Subsey,.ently, in 1981, FDA's Bureau of Foods established a second team of scientists, the Irradiated Foods Task Group, to review all available toxicological E data concerning folds treated by irradiation. The major objectives of this Task Group were to compile and summarize the toxicology data pertaining to i ~ irradiated foods, identify any consistencies with respect to adverse findings, ts!` look for patterns or trends in results among the studies, and to summarize the experimental results at the end of the review (4l j ~ The data review proceeded in three phases. In phase I, all relevant toxicology t i t, III studies were identified from FDA files and from the open literature. In phase II, 409 of these (all of the relevant available studies) were obtained in hazd i ! copy and summarized. These summaries categorized the studies as 1) "ac- IiIl,1`' cepted" if on initial examination the study appeazed to be reasonably coin- i !I ~ plete; 2) "accepted with reservation" if the testing, on initial summary review, ~ appeared acceptable but had some serious deficiencies interfering with inter- ' pretation of the data; or 3) "rejected" if there were inadequacies of the experi- mental design or data collection, or if dietary problems existed in the study i that would prevent a valid evaluation. In phase III, 69 studies that either raised questions concerning the possibility of adverse effects or appeared to support ~I( a conclusion that the irradiated food studied was safe were examined in detail and reported (41). - ~ Based on its examination of all the data, the Task Group concluded that studies with irradiated foods do not show adverse toxicological effects. How- ever, the Task Group further concluded that traditional toxicological testing of food irradiated at doses below l kGy (100 krad) cannot be expected to provide meaningful answers to toxicity questions regarding such irradiated foods. The t Task Group's reasons for this conclusion were: 1) nutritional imbalances created in the test animal fed high levels of irradiated or nonirradiated foods { would tend to mask any potential toxicological manifestations; 2) the low con- centration of any potentially toxic radiolytic products in the irradiated foods 'j would prevent significant exaggeration of the amount of radiolytic products in a test diet; and 3) such toxicological testing is currently too insensitive to measure toxicity because the concentrations of unique radiolytic products potentially present in the irradiated foods tested are simply too low. Based on its review of all studies. including those which tested food irradiated at doses a more than an order of magnitude higher than 1 Gy (100 krad), the Task Group agreed with BFIFC's conclusion that there was an adequate margin of safety for foods irradiated below I kGy (100 krad). Hence, the Task Group also i' agreed that toxicology tests on food irradiated at l kGy (100 krad) or below are not needed to support a conclusion that such foods aze safe. t h{ 1 ~KEGUCIiI EDA PERSPECTIVES OIYIRRADIAi'ION , ~d team of Agency-Initi.. Rule Making ~icological f this Task Under sections 409(bLand (d) of the Act, the Secretary may approve a food taming to a.dditive petition frotrP'~n interested person or may propose the issuance of - findings, ;e.food additive regulation upon the Secretary's own initiative. It is less com• nazize the mon for FDA, acting as the Secretary's delegate, to propose and then establish a regulation itself, than to respond to a sponsor's petition. As discussed earlier, oxicology FDA had approved several food additive petitions for the use of various sources . In phase of radiation on certain foods and food-packaging materials prior to 1981. :d in hazd On March 27, 1981. FDA published an advance notice of proposed rule s I) "ac- making (ANPR) (40) that announced the availability of the BFIFC Report ably com- (39), which outlined a course of action for assuring the safety of irradiated ry review, foods and requested comments on the overall approach towards its food ir- ~ith inter- radiation policy. he experi- After evaluation of comments received on the ANPR, FDA published a the study ~ proposed rule on February 14, 1984, that would 1) establish general pro- her raised visions for food irradiation, 2) permit the use of food irradiation at doses not ~ support exceeding 1 kGy (100 krad) for inhibiting the growth and maturation of i in detail fruits and vegetables_and for insect disinfestation of food, 3) allow irradiation to be used for microbial disinfection of certain dried spices and dried vegetable ~ded that seasonings at a dose not to exceed 30 kGy (3 Mrad), 4) eliminate the current ir- :ts. How- radiated food labeling requirements for retail labeling, and S) replace then cur- testing of rent regulations dealing with the irradiation of food with new regulations (42). o provide Based on this proposal, on April 18, 1986, FDA published final regulations gods. The to permit additional uses of ionizing radiation for the treatment of food. These ibalances regulations 1) permit manufacturers to use irradiation at doses not to exceed :ed foods 1 kGy to inhibit the growth and maturation of fresh foods and to disinfest low con- i food of arthropod pests, 2) permit manufacturers to use irradiation at doses ed foods ~ not to exceed 30 kGy to disinfect dry or dehydrated aromatic vegetable sub- products stances (minor food ingredients such as spices and herbs) of microorganisms, ~sitive to 3) require that foods that are irradiated be labeled to show this fact, both at products the wholesale and at the retail level, and 4) require that manufacturers maintain Based on process records of irradiation for a specified period and make such records at doses available for FDA inspection (41 .k Group Apart from the ongoing rule making, FDA approved a number of food ad- ~f safety ditive petitions to provide for the safe use of gamma-radiation at doses up to pup also ~ 10 kGy (1 Mrad) to control insect infestation and microbial contamination in ~r below dried herbs, spices, and vegetable seasonings (43-46) and in dry enzyme prep- arations (47). FDA also issued a Final rule in response to a petition to provide ~ 98 PAULIAND'rAKEGUCHI i for the so.e use ofgamma-radiation at doses up ~0 1 kGy (100 krad) to control Tiichinella spiralis in pork (48). These were incorporated into the April 18, 1986 final rule (4y. w ~i CURRENT STATUS ''j The April 18, 1986 final rule has significantly expanded permitted uses of food ~ ; i~ irradiation. FDA authorization for this process also affects other government agencies. In particular, the USDA's Food Safety and Inspection Service, with I ' regulatory authority over meat and meat products, revised their regulations to permit irradiation of fresh pork on January 15, 1986 (49). Likewise, USDA's Animal and Plant Health Inspection Service has regulatory authority over ; quarantine restrictions for commodities that aze imported, exported, and in- tended for domestic use. The purpose of such restrictions is to avoid the accidental introduction of exotic pests that are not found in the United States, ~ or to avoid interstate movement of pests that have been introduced in certain areas of the country. USDA must recognize the efficacy of quarantine methods for specific commodities using chemical or physical treatment methods that ~ are permitted in the U.S. before such treatment methods may be used to meet quarantine requirements. Food irradiation would 'allow another physical method as an alternative treatment. ,i Safety Testing As discussed eazlier, FDA concluded that an adequate margin of safety had been demonstrated for food irradiated at a dosage below 1 kGy without re- quiring animal feeding tests. [n addition, the agency addressed all comments raising safety concerns in the April 18, 1986, final rule. One common misperception was illustrated by a comment that had asserted that FDA's proposed regulation was illegal because it was not based on animal testing. Although recognizing that neither the Food Additives Amendment of 1958 nor its legislative history specifies the exact types of tests that must be conducted to establish safe conditions of use of an additive, the comment claimed that a recurrent theme in much of the legislative history is the need for testing in animals to establish the safety of a particular additive. ~ As discussed in the section on legislative history, there is no indication in the ~ i I ; legislative history that Congress expected every additive, whether an ingredient, i a source of irradiation, or an incidental additive, to be tested the same way; 1I nor does the Act require such testing. Such a requirement would result in an unnecessary expenditure of resources. Consistent with this view, FDA has never required the same testing regimen for all types of additives. 1 tict,uCHl ppA PERSPECTIVES ON TRRADIATIOd a control :FDA believ ,hat the testing requirement envisi 1 by Congress was that 4pril 18, g pport the conclusion chat there is a reasonable there be sufficiznt tzstin to su certainty of no harm from the expected use of the additive. The agency be- Neves that any tzst that'WOUId not contribute to this conclusion should not be required. The agency has not required animal testing in the past under those situations where, by chemical or other testing and sound reasoning, it could s of food conclude that the use of an additive was safe without animal testing. Animal 'ernment testing is too insensitive to show an effect from irradiation of food at low doses ice, with and. thus, would not contribute additional information to the evaluation of the ations to safety oC stcch uses. USDA's Nevertheless. as discussed in the section on Agency Task Groups, the agency ity over reviewed all available animal studies to determine their adequacy and to ,and in- evaluate the toxicological evidence. The agency reviewed 409 toxicity studies void the on irradiated foods -~41). Forty-f`ive of these studies dealt with subacute d States ~ toxicity. 58 with subcltronic toxicity. 126 with reproductive toxicity, 14 with ' teratology, 110 with chronic toxicity, and 102 with genetic toxicity of ir- ncertain ~ radiated foods. Only five of the 409 studies reviewed (three chronic feeding ods that studies (50-52). one reproduction study (53), and one combined chronic reproduction and teratology study (54-56) were considered by agency re- . to meet viewers to be properly conducted and reported, fully adequate by 1980 toxico- physical logical standards. and able to stand alone in the support of safety. The reports of these Civz sttcdizs indicated no adverse effects from thz irradiated foods fed to test animals. Although most of the study reports were inadequate by present-day stand- fety had ards and could not stand alone to support safety, many contained individual experimental components which. when examined either in isolation or col- :hout re- lectively, allowzd the conclusion that consumption of foods treated with low ~mments l levels of irradiation did not appear to cause adverse toxicological effects. Fur- ther. many of the studies were deemed useful for resolving certain questions. asserted For example, if a potent toxic material were present at any level of toxico- n animal logical significance in irradiated foods ingested by test animals, some con- ment of sistznt toxicological signs would be manifest in the studies reviewed. However, must be agency scientists saw no such effects that present consistent patterns or trends omment of adverse effects that might be attributable to exposure to food irradiated at need for low dose levels. >n in the j ;redient, Labeling me way; The agency has required, since 1966. that all food treated with irradiation bear llt in an on the label a statement that such food has been treated with ionizing radia- ~DA has lion. This includes required labeling of irradiated food for both retail and non- retail use. ' 4 100 PAULI AND TAKEGUCHI .44i f, For irradiated foods, FDA requues that the wuolesale label bear either the - ' statement "Treated with radiation, do not irradiate again," or the statement "Treated by irradiation, do not irradiate again," and that the retail label bear the following logo 'i t.. ~i,, along with either the statement "treated with radiation," or the statement ' "treated by irradiation." In lieu of labeling individual items of unpackaged irradiated foods, FDA allows the required logo and label to be displayed to the purchaser as a point- of-purchase counter sign or cazd or on the labeling of the bulk container. As with other processing methods, such as thermal pasteurization or steriliza- tion, irradiation can alter the characteristics of food in ways that could be im- portant to consumers. Changes in orgaroleptic properties (taste, color, smell, texture) may make the processed food more or less desirable to individual I'; consumers. These changes may well be significant to prospective purchasers of irradiated food. Thus, knowing that a food has been processed by radiation may be important to many consumers. Unless the label indicates otherwise, these consumers would be likely to assume that the food has not been processed or has been processed by traditional means. It follows that the label 'F' of a food that has been irradiated but that does not state this fact is misleading, i ; i because the label fails to inform the consumers that the food has been pro- ~ i cessed, and that it has been processed in a nontraditional fashion. FDA be- i,~ lieves that changes in food caused by the irradiation allowed under the pro- posed regulation, although of no safety concern, are sufftciently important k~ that the consumer should know that this process has been used. ~ ' ' With industry uniformly using this logo in conjunction with the wording "treated with radiation" or "treated by irradiation" and an effort to educate j j. consumers about the meaning of the logo, industry may use the logo without the accompanying terminology after April 18, 1988. FDA will assess the need for the mandatory language to accompany the logo during this two-year period. i I f i :EGUCHI I~DA PERSPECTIVES ON IRRADIATION l01 ther the atement Any extension of the wording requirement, if n~..assary, will be established bel bear ~ through notice and comment rule making. Let us review what is required on food labels. Food ingredients, including ~fbod additives that have a functional effect on food, aze required to be dis- closed on food labels. Therefore, the consumer is informed of the presence of these ingredients. Conventional food-processing methods also affect the organoleptic prop- erties of food in material ways, but in these cases the processing is either obvious to the consumer or conveyed to consumers through labeling or pack- aging. Shelf-stable canned foods have obviously been heat processed and frozen foods have obviously been frozen. Pasteurized milk is not obviously pasteur- - ized, but this fact is declared on the label. Canning, freezing, and pasteurization are, of course, well-established pro- cesses with which thi' consumer is familiar. Whether information is material under Section 201(n) of the Act depends not only on the abstract worth of the information but also on whether consumer view such information as im- tement portant and whether the omission of label information may mislead a con- sumer. The large number of consumer comments submitted to FDA requesting FDA retail labeling of foods treated with radiation attest to the significance placed r point- on such labeling by consumers. FDA has historically required the disclosure of afood-processing agent :eriliza- whenever it is material to the processing of foods. For example, the word flour ' be im- in an `ingredient statement or food name is required to be modified by the term bleached if a bleaching agent is used in processing, and modified by the ~~in'dulal term "bromated" if the flour has been bromated. These requirements~are part rsers of of the standard of identity for various flours (see 21 CFR 137.205) (57). diction There are many other instances where the fact of processing must be dis- closed. Several standards of identity require label disclosure if the product has erwise, been enriched or fortified (see 21 CFR 137.305, enriched farina) (57). Several t been standards of identity for juices require that the label indicate when the product ie label is made from a previously concentrated ingredient (see Z1 CFR 146.145, °ading, orange juice from concentrate) (57). Orange juice must also be labeled 'n pro- ~•pasteurized" when pasteurization is part of the juice's processing (see 21 JA be- CFR 146.140, pasteurized orange juice) (57). ie pro- Foods made in semblance of a traditional food must disclose the processing ~ortant difference. Potato chips made from dehydrated potatoes, onion rings made offing from minced onions, and fish sticks made from minced fish are all required to ducate disclose the material differences in processing. ~ithout FDA believes the labeling of an irradiated ingredient in a multiple ingredient e need food is a different situation, however, because this ingredient has obviously period. been processed to become part of a new food, which is unlike any of its oriB- inal ingredients. Consumers would not necessarily expect a multiple ingredient t02 PAULI AND TAKEGUCHI I'I' ~ i ~'r food to ..,e any of the characteristics of rho processed ingredient, and par- i ~ titularly its holding qualities. Therefore, the retail labeling requirement applies only to food that_has been duectly irradiated (first-generation food), not to food that merely contains an irradiated ingredient (second-generation food). Current Good Manufacturing Practice III' li i FDA has issued general regulations regarding current good manufacturing pra~- II,~~ rites (CGMP) (21 CFR Part 110) (57) as well as specific CGMP regulations for some types of food (21 CFR Part 1'13, 114, 118, 123, and 129) (57) or food additives (21 CFR 172.5, 174.5, 182.1, 184.1) (58 Such regulations are based on standard practices of responsible manufacturers in the industry. CGMP regulations for irradiated food cannot be based solely on current radiation practices-because of the lack of substantial experience with food irradiation. However, there has been extensive experience with other types of radiation processing (e.g., hospital supplies), and the industry has established standards in some cases. FDA considered both the experience and standard practices in the nonfood radiation processing industry and CGMP in the food industry in developing its regulation for irradiated food. FDA's regulation con- tains five general provisions for CGMP specific to irradiation to aid industry: 1. Any firm that treats food with ionizing radiation is no different from any other food processor. Therefore, such firms must comply with the umbrella CGMP regulations contained in Part 110 and any other regulations applicable to food handling. The provisions of Part 1 l0 specify sanitation re- quirements and controls for the facilities, the equipment, the raw materials, and the process. 2. A food should be irradiated only at the dose reasonably required and under the conditions that would accomplish the intended technical effect, and not more than the maximum dose specified by the applicable regulation for that use. 3. Packaging materials subjected to irradiation, incidental to the radiation treatment and processing of prepackaged food, should be specifically author- ized for use under such conditions. 4. Radiation treatment of food should conform to a scheduled process for food irradiation. A scheduled process is a written procedure that ensures that I~ the radiation dose range selected by the food irradiation processor is adequate under commercial processing conditions for the irradiation to achieve its in- tended technical effect on a specific product and in a specific facility. Because ~ this dose range may vary with the food irradiated and the radiation facility, j FDA believes that each processor should develop and follow a scheduled process established by qualified persons having expert knowledge in radiation- processing requirements of food and specific for that food and for that irradia- tion processor's treatment facility. i i ~f EGUCHI FDA PERSPECTIVES ON IRRADIATION lV~ nd par- } 5. A food .diction processor should maintai cords, as specified, for - applies f tt period of time that exceeds the shelf life of the irradiated food product by not to t one year, up to a maximum of three years. In addition, these records should . food). ( tie available for inspection and copying by FDA. " t `„F-"'~o THE FUTURE _ tg Prac- i ' . ons for k Industry Interest ~r food r„r.. e based Whether food irradiation will be a commercially practical alternative is dif- ficult to predict because of the complexity of the issue. Many other factors, in current addition to technical feasibility, are involved. A recent report prepared by staff h food at. USDA's Economic Research Service (59) reviews in detail the technical, ypes of public health, and economic considerations applicable to food irradiation. blished [t is important to understand that FDA's responsibility in the evaluation of andard the process is limited to the determination of the safety of the process under ,e food specific conditions of use. FDA has no proper role as a promoter of a specific ~n con- food additive or food process. The primary responsibility for such activities dustry: remains with industry. ,t from Food irradiation is a technology developed, to date, primarily at government ;th the expense. In the U. S.. this started with the United States Army and the Atomic ,lations Energy Commission granting monies for research. At present, the USDA is con- tion re- ducting some research, and the Department of Energy (formerly the AEC) is iterials, providing other funds. The future of food irradiation will be determined by the actions of con- ed and sumers and the food industry. Industry's role is to assess the feasibility of this ct, and technology and to determine its commercial potential. Food irradiation will ion for never be a panacea to solve world food problems, but there are no doubt areas where this process is technically effective, economically feasible, and provides diction certain advantages to conventional processing. We have seen considerable in- iuthor- forest in the use of radiation as an alternative to chemical fumigation of spices with ethylene oxide. :ess for es that Consumer Interest equate its in- Consumer interest in this new food process is growing. As might be expected, lecause the most active, organized consumer groups have been those opposed to the acility, process. Consumer opposition has focused on labeling and the need for more ,eduled safety information, as well as nonfood issues, such as environmental safeguards nation- for the transportation and storage of radioactive material and worker safety. irradia- Food irradiation is one of many useful technologies that may be important to maintain or even improve our food supply. It is now the role of industry to ~ t 104 PAULI AND 2'AKEGUCHI t demonstrate this to the consumer. Food irradiation is definitely a controversial technology and itas critical that the process and its potential are not oversold. ka Several recent consumer surveys (60-62) have studied opinions on issues of q~ { food irradiation. The surveys seem to indicate that, although there will be I ; r broad consumer acceptance for this new technology, there will always be a group that will not accept this technology for any reason. Consumer groups opposed to food irradiation believe that a vast majority of the consumers are ` unaware of this technology and will be opposed to its use even if they are ~II ~ informed. It seems that there will be no clear answer concerning final consumer f~'k opinions until such foods are test marketed. Accurate information presented in i0 ~~f`~ a credible manner, in conjunction with ahigh-quality food product, will be j; essential for success. Thus, the future of food irradiation now seems to be in l,, the marketplace-where the focus will be on educational programs and test { ; ! marketing. I Future Agency Action At this time two considerations prevent the agency from proposing a general f regulation allowing doses up to 10 kGy as recommended by the Codex Alimen- tarius Standard (63). First, doses above 1 kGy irradiation can significantly P retard microbial spoilage without killing all spores of Clostridium botulinum. Under some conditions C. botulinum can grow and produce a toxin that constitutes a health hazard. Although this problem is not unique tp food ir- radiation. techniques and regulations have been developed for other processing methods to ensure safety. Based on current knowledge, FDA is unable to F prescribe safe conditions of irradiation at higher doses for foods to ensure that C. botulinum organisms would not develop and produce toxin without obvious {~r spoilage. Second, FDA reviewed a number of animal feeding studies to determine whether foods that are irradiated at doses above 1 kGy (100 krad) could be considered safe without additional toxicological studies. The agency found this data base, taken alone, to be inadequate to support a broad decision that all foods may be irradiated safely at higher doses up to 10 kGy (1 Mrad). Therefore, FDA does not intend to initiate further rule making on food irradiation based on the information available at this time. The agency will, of course, continue to evaluate and respond on a case-by-case basis to all food- additive petitions involving irradiation. REFERENCES 1. H.R. 8748, section 201(s), 84th Congress, 2d Session, January 24, 1956. 2. Chemical Additives in Food: Hearings on H. R. 4475, H.R. 7605, H. R. 7606, H. R. 8748, H. R. 7607, H. R. 7764, H. R. 8271, H. R. 8275 Before the Subcomm. on Health and it ?~i.. -i AKEGUCHI EDA PERSPECTIVES ON IRRADIATION 105 >ntiOVerslal Science the House Comm. on Interstate and Fo~..an Commerce, 84th Cong., 2d ,t oversold. - Sess., 40, U. S. Government Printing Office, 1956. 3. Chemical Additives in Food: Hearings on H. R. 4475, H.R. 7605, H.R. 7606, H.R. n issues Of 8748, H.R. 7607, Hdt. 7764, H.R. 8271, H.R. 8275 Before the Subcomm, on Health ere will be ""and Science of the House Comm. on Interstate and Foreign Commerce, 84th Cong., sways be a ~ 2d Sess., 196, U. S. Government Printing Office, 1956. net groups 4. H. R. 8112, section 201(t)(I), 85th Congress, 1st Session June 13, 1957. 5. Federal Food, Drug, and Cosmetic Act, §201(s), [21 U.S.C. 321(s)], U.S. Food and SumeiS ale - Drug Administration, Wazhington, D.C., 1981. '.f they ale .i 6. S. Rept. No. 2422, "Food Additives Amendment of 1958," Committee on Labor and l COnSUmer ` t. Public Welfare, 85th Cong., 2d Sess. (1958). resented in 7. Federal Food, Drug, and Cosmetic Act, §409(c)(5) [2t U. S. C. 348(c)(5)j, U.S. Food # and Drug Administration, Washington, D.C., 1981. Ct, will be g, Federal Food, Drug, and Cosmetic Act, §402(a)(7) [21 U.S.C. 342(ax7)l. U.S. Food 7S t0 be in and Drug Administration, Wazhington, DC.. 1981. ~s and test i. 9, Federal Food, Doug, and Cosmetic Act, §409(cx3)(b) [21 U.S.C. 348(c)(3)(B)], U. S. Food and Drug Administration, Washington, D.C., 1981. 10. Federal Food, Drug, and Cosmetic Act, §201(n) [21 U.S.C. 321(n)], U.S. Food and , Drug Administration, Washington, D.C., 1981. 11. Food and Drug Administration, "Toxicological Principles for the Safety Assessment a general of Direct Food Additives and Color Additives Used in Food; 'Washington, D.C., 1982. :X Allman- l2. Code of Federal Regulations, Title 21 Section 170.22, U.S. Government Printing Office, Washington, D.C., 1985. ~nifiCantly 13, Federal Register, 28:1465, February 15, 1963. ~Otullnum. 14. Federal Register, 28:9208, August 21, 1963. toxin that 15. Federal Register, 28:9526, August 30, 1963. tq fOOd ii- 16. Federal Register, 29:1808, February 6, 1964. prOCessing 17. Federal Register, 29:8329, July 8, 1964. unable t0 l8. Federal Register, 29:14027, October l0, 1964. 19. Federal Register, 29:18056, December 19, 1964. 'Ilsure that 20. Federal Register, 30:5631, April 21, 1965. ut obvious 21. Federal Register, .30:5702, April 22, 1965. ] 22. Federal Register, 30:14102, November 9, 1965. determine 23. Federal Register, 3! :3402, March 4, 1966. COUId be 24• Federal Register, 31:9491, July 13, 1966. found this 25• Federal Register, 31:140, January 2, 1967. 26. Federal Register, 32:3442, March 2, 1967. )n that all 27. Federal Register, 30:3354, March 12, 1965. 28. Federal Register, 32:8360, June l9, 1967. On food 29. Federal Register, 32:10567, July 19, 1967, Cy will, Of 30. Federal Register, 33:4657, March l9, 1968. ~ all food- 31. Federal Register, 28:13797, December 18, 1963. 32. Federal Register, 3!:7256, May l8, 1966. 33. Federal Register, 30:11801, September I5, 1965. 34. Federal Register, 31:11241, August 25, 1966. 35. Food and Drug Administration, Bureau of Science Staff Seminar. "Preparation and Processing of Food Additive Petitions: Radiation Application to Food," Wuhington, D.C., :967. 36. Food and Drug Administration, Bureau of Science Staff Seminar, "Preparation and H. R. 8748, Processing of Food Additive Petitions: Radiation Application to Food," Washington, Health and D.C., p. 1, 1967. ii 106 PAULI AND TAKEGUCHI i 37. Federal Register, 33:12055, August 24, 1968. 38. Federal Register, 33:15416, October 17, 1968. 39. A. P. Brunetti, d, Fra[tali, W. B. Greear, D. G. Hattan, C. A. Takeguchi, and L. R. Valcovic, "Recommendations for Evaluating the Safety of Irradiated Foods." S. I Food and Drug Administration, Washington, D. C., 1980. l i i I' ~ ~ 40. Federal Register, -16:18992, :March 27, 1981. ~ 41. Federal Register, 51:13376, April I8, 1986. i ~ 42. Federal Register, 49:5714, February 14, 1984. 43. Federal Register, 48:306!3, July 5, 1983. ~ ~ 44. Federal Register, 48:46022, October I I, 1983. ~ ~ 45. Federal Register, 49:'_4988, June l9, 1984. I! ' 46. Federal Register, 50:15415, April 18, 1985. 47. Federal Register, 30:'_4190, June 10, 1985. jl~`--~ 48. Federal Register, 50:29658, July 22, 1985. 49. Federal Register,51:1769, January l5, 1986. 50. P. S. Elias, "Toxicology Studies in Rat Fed a Diet Containing I5~ Irradiated Kent ~ Mangoes," Technical Report IFIP-R-58, International Project in the Field of Food ~ Irradiation, Karlsruhe, 1981. 51. J. L. Radomski, W. B. Deichmann, B. S. Austin, and W. E. McDonald. "Chronic Toxr ~ city Studies on Irradiated Beef Stew and Evaporated Milk," Toxicol..4pp1. PharmacoL, 7, 113 (1965): ~ 52. H. W. Renner and D. Reichelt, "Zur Frage der gesundheitlichen Cnbedenkiichkeit hohen Kozentrationen von Freien Radikalen in Bestrahlin Lebensmitteln," Zen[ralbl. f[lr Veterinaermed. Reihe B, 20, 648 (1973). 53. J. R. Hickman, D. L. A. McLean, and F. J. Ley, "Rat Feeding Studies on Wheat Treat- ed with Gamma Radiation, I. Reproduction," Food Cosmet. Toxicol., 1 ~ (1964). ~ 54. B. Coquet, D. Guyot, L. Galland, X. Fouillet, and J. L. Rouand, "Etude chez la Souris ~ concernat la toxicite, !'influence Sur la reproduction. is mutagenicite et le pouvoir teratogene du riz ittadie incorpore darts la nourriture," Final ReportlFiP-R-40.[nter- ~ national Project in the Field of Food Irradiation, Karlsruhe, 1976. ~ 55. B. Coquet and G. Rondot, "Oignons Irradies: Etudes de Toxicite et de Reproduction f chez le Rat," IFREB Report in WHO Irradiated Onion Monograph, World Health Or- ganization, Geneva, 1980. i 56. B. Coquet, G. Rondot, P. Genoux, M. Lheritier, Y. Guichard, J. P. Blanc, and St. C. Mary, li' "Legumes Ittadies: Essais de Toxicite et de Reproduction Chez la Rat," Technical Re- ~ port, Summary in WHO Irradiated Legumes Monograph, World Health Organization, Geneva, 1980. 57. Code of Federal Regulations, Title 21 Pazts 100-i69, U.S. Governmen[ Printing Office, Washington, D.C., 1985. 58. Code of Federal Regulations, Title 21 Parts 170-199, U.S. Government Prinnn¢ Office, + Washington, D.C., 1985. 59. R. M. Morrison and T. Roberts, "Food Irradiation: New Perspectives on a Controversial Technology," Congress of the United States, Office of Technology Assessment, Wash- ington, D. C., 1985. 60. Wiese Research Associates Inc., "Consumer Reaction to the Irradiation Concept;' Dept. of Energy Contract No. DE-SC04-84 AC 24460, March 1984. 61. Consumer Reseazch Department, "Womens Attitudes Toward New Food Technol- ogies," AGood Housekeeping Institute Report, New York, February 1985. j 62. Brand Group, Iae., "Market Survey for Seafood;' Dept. of Commerce, National Marine Fisheries Service, Chicago, 1986. ~ 63. Secretariat of the Joint FAO/WHO Food Standards Programme, "Codex Gtneral i j Standard for irradiated Foods and Recommended International Cod: of Practice for the Operation of Radiation Facilities for the Treatment of Foods;' Codex Alimentarius I Commission, FAO/WHO, CAC/Vol. XI, Ed. 1, Rome, 1984. I r~ I i 81 Mr. YouxG. Second, I would like to point out that there are ~KEGUCHI ( _ major modifications^tif particular nutrients that occur in processes jt 'such as cooking and there are many other processes that are in- volved. We feel that, on balance, as one looks at the nutrient chazacter- and L. R. ~ ization, at these low levels there is trivial loss, but I will ask Dr. :oa5.•• L•. s. pauli to speak to the few azeas focusing on vitamins and other such nutrient compositions within foods. Mr. Wnxlvinx. Dr. Pauli. Mr. Paut.t. Yes. There is a considerable body of data. You would always expect that there is going to be some nutrient loss. If there's 1 percent, 2 percent, 5 percent nutrient loss, but random variation-random samples might vary by 10 or 15 percent in a particular nutrient-then we would say 5 percent is within the normal range, that would be of no dietary significance. We have seen nothing to indicate any concern for nutrient loss .fated Kent at the low doses, and that conclusion has been stated by every d of Food other group that has looked at it. At high doses, when you're radiating to control micro-organisms, -onic roY~- there may be some situations in which nutrient loss may be impor- 'narmacoi., tart. We have deliberately not permitted irradiation of food under such conditions, at such doses. We want to look at those on a case- enklichkeit by-case basis to be sure. ze"train. Mr. WAXMnx. Later today we're going to hear from Dr. Louria of neat treat- the University of Medicine and Dentistry of New Jersey who says (i96a~, there are new data indicating that irradiation of foods can reduce ez la Souris the nutrient value of those foods. ie pouvoit Are there new studies on this point, and if so, has FDA reviewed ao. toter- them and found any reason to reconsider FDA's current position? Mr. Youxc. Dr. Pauli. production Mr. Pouts. I am not aware of the studies to which he speaks. Heaitn or- There are continual ongoing studies. The Department of Agricul- .t. c.Nary, ture is doing some. They~re keeping us informed. The questions we :hnicai Re- always have to ask are What is the dose they re talking about? zan;zat;on, and "What would this do to a person's diet if he or she routinely ate such foods?" And I cannot speak to the specifics, but for what Ong Office, we have approved so far, we have seen nothing. Mr. YouxG. I would like to add, Mr. Chairman, that even under ing Office, the most extreme conditions of irradiation of food with individuals ntroversial who are immuno-compromised, where that constitutes a substan- ent, wash- tial portion of the diet, there has been nutritional balance; howev- er, these individuals are under a special circumstance, and the Concept," levels that we're using here are very low levels in contrast to those used to sterilize food for immuno-compromised individuals. recnnoi- Mr. WAxMAN. In your statement you said that FDA has no proper role as a promoter of a specific food additive or food process, nal Marine and that FDA's responsibility is to determine the safety of irradia- tion. Because I agree with these statements, I must wonder why General FDA initiated the rulemaking to approve the use of irradiation in- ractice for stead of waiting for a company to ask you to act. Would you ex- imentarius plain? Mr. Youxc. Yes, I would like to comment in this way and then ask Dr. Miller to provide any additional perspective. ~ '7 82 i~ l As we looked at this technology and had received petitions over ~i~ the years, we established that it would be appropriate for us to set. ~ ~ ' a level which-i we considered the floor, a level so safe that there ' ~I)f; would be not any question about using it at the 1 kilogray or 100 1, C kilorad amount of radiation. In that circumstance, we would be able to establish a level which could be the base line, and would consider petitions on a case-by- ~j' case above that level. It was a prudent approach, in my opinion, ~ because it would save resources of the taxpayer by identifying a ~ minimum level at which we would not anticipate any particular ~ I harm, and could focus on some of the needs of replacing some of the fumigants that are problems in the past. When we come to higher levels of irradiation, those would be considered on a case-by- ,i ; case basis. _ " Dr. Miller, since you were involved in this throughout its devel- opment, you might be able to add further perspective. Mr. Mitt.Ex. Thank you. ' ~ I think in order to understand the Agency's actions in this issue, you have to look back at the history of the process. FDA had been ~ involved in evaluating food irradiation for many years, in large measure because of requests from the Department of Defense to de- termine the safety of these products. Through these years, there was a continual problem of looking at the data in order to see ~ whether or nor it met our standards for determining safety. Certainly, one of the largest problems we faced concerned the evaluation of the safety of the food in contrast to a food additive. Traditionally, the Agency in studying such substances performs animal tests for those substances that are going to be present in the diet in some significant amount, at levels that area hundred- fold or more of the actual use levels in order to estimate a safety ~i factor. Well, how do you do that with the food? How do you feed a hun- dred-fold the amount of potatoes that are normally in the diet? It just can't be done. ~ We're caught in a paradoxical situation. We had a lot of studies that strongly suggested irradiated foods were safe, yet those studies simply couldn't meet the kind of criteria that we would normally use for determining safety, that is, the safety factor issue. In 1979, it also became clear that the international community ~ was going ~to issue a statement concerning the safety of irradiated foods, and we in the United States would be faced with a problem of attempting to respond to that statement due to our obligations under the Codex Alimentarius treaties. At that time, we had no wayy of doing that very well. We also recognized that we were going to be faced with other kinds of whole foods whose safety had to be evaluated. As a result of this, in 1979, we appointed the Irradiated Food Committee to try to see how we could deal with these foods in the context of our own activities. In order to get comment, we published in 1981 the results of the committee's action in the form of proposed procedures. Effectively, we were saying "This is how we'll do it if, we have to do it." In 1981, also, we were faced with urgent requests-indeed de- mands-from industry and from State governments, particularly - ~ 83 ~ .4Y lions over California Ad other places to use radix. a for the purposes of • us to set :;:dealing with the then medfly epidemic. And that, in essence, was hat there ~'t]le primary stimulus for us to move and approve a process for the ay or 100purpose of dealia~"with insect infestation. Since the Irradiated vel which "'F~ Co~lttee also considered spices, that was another area we s~' decided to deal with. a case-by- So, I think that there were lots of reasons outside the Agency for r opinion, ~~FDA to move in this area, and that's the reason why we took the itifying a actions ~ we did. particular WnxMrx. Dr. Young, on the panel following you there are a some of =:';';number of scientists who believe that your decision to approve irra- come to diction is at best premature. I'm well aware that scientific review a case-b - y ~`~mvolves judgment, and that excellent scientists can disagree. Scientists will say that the data you use is flawed. What do you its devel- - -have to say to that criticism? Mr. YovxG. In any scientific analysis there will be views on both ;his issue, ~ ~ sides of issues. We look at the weight of evidence, and have ana- had been - lY~ very carefully the studies that we could find in the literature. in large I have, and will-_submit for the record, the analysis in brief form. use to de- We can update any of the multiple studies that we have rejected irs, there for a wide variety of reasons, and we have others that we have ap- er to see proved. And we would be happy to provide followup information for the record on these. ~rned the [The following material was submitted for the record:] additive. < performs resent in hundred- • a safety ~ 'd a hun- e diet? It ~f studies ;e studies normally mmunity ~ eradiated ~ problem >hgations had no ~ ith other > a result ~ee to try our own its of the 'festively, deed de- •ticularly i' ~ ~ I` STORIES THAT WERE RETECTED ~~q1,) no dose study species reason 1 300 chronic pig abstract,no controls 2 0 review ~~7 5 500 chronic rat na control,groupsize ?i" b 0 no data I 7 O review r it 0 dose not reported 16 0 review i ~ 19 200 chronic/repro mouse/rat no data 24 1000 Ames? no data ~ ~ 26 100 repro rat no data 27 SSOU subchronic rat dl et not isocal oric 26 O no irradiated food 29 O - review 31 O review i 32 O chemistry data 36 16 chronic/repro mouse interim rep.,no data 40 O nr rat tables only 45 O dominant lethal mouse +c ontr of negative 46 5600 chronic/repro dog group size,repro con 47 5580 chronic monkey group size ~I 52 O duplicate 59 5580 chronic/repro rat inadequate study 60 5580 chronic/repro rat inadequate study '1 64 0 see WHO report bb 10000 repro rat accidental death 67 5580 chronic mouse IBT 68 400 subchronic rat/dog IBT 69 400 subchronic dog IBT i~ 70 400 subchronic rat IHT ~ 77 O review ii: 81 5000 short term chicken group size, speci es ~j 82 1000 short term rat nutrition study 83 0 no tox data 94 12 chronic/repro mouse incomplete histo 88 0 No irradiation,IBT ~ 91 3000 short term rat no tox data ~ 92 0 review ~ ~ 93 O repro rat abstr act,no data 94 O review ~ 95 600 chronic dog abstr act duplicate i ~,°I 96 5580 chronic mouse incomplete histo ' !'I 101 0 dominant lethal rat not compl ete,dose nr 103 O cytogenetic rat no data 106 4500 chronic/repro rat incomplete study 107 O no tox data SOB O no tox data I'!I 110 2000 nutrition rat not relevant '-I, i~ 112 9000 chronic/subchr on rat group size ~ 113 0 review f;~ 118 0 ~ re~ti ew 122 0 review 123 0 not relevant 124 O review 12S 400 subchronic rat abstract,no data 130 O Ames S.typhim dose nr 131 200 chYOnic/repro mouse IHT 132 200 chronic mouse IHT 9~t 134 30 bact.DNA repair E.coli no metabolic act. ` 142 600 chronic/re ro rat abstract 146 10000 nutrition rat group size,nutri tion 147 10000 reproduction rat no data 150 2500 cytot or.i city mouse fib na details i 85 , - ~ - ::~Q;132 ~ -~10 subchronic pig incomplete study ~~7 0 review ~~360 O Ames S.typhim dose nr,incomplete 160 3600 chronic rat summary,translation ~-~~160 6004 reproduction rat abstract + tables ;164 0 no original data =167 O IBT,no data "168 O reproduction rat IBT 170 O review ~C:"172 700 short term hamster diet,icompl.study " ~ '.173' 1500 short term hamster diet,incgmplete stud -'"174 15 chronic rat path report • ~r'•175 O chronic rat/mouse review, summaries ~-1'=176 1000 dominant lethal mouse no primary data ~,~y. 177 6000 shortterm/repro rat group size nr $1,,178 0 summary review ,178 0 review 179 0 review -.~)i= 180 O review I3 181 0 not relevant - ; iB2 100000 subchronic/repro rat data incomplete - 183 100000 subchronic rat data incomplete ` 184 5590 chronic/repro dqg group size 185 0 review 191 200 chronic/repro dog IBT 192 0 summary,progr.rep. 194 6000 subchronic rat group size 195 O review _ ~„196 5000 reproduction rat/mouse admin.not continuous S 198 5400 subchronic/repro mouse deficient diet " 200 6000 reproduction mouse abstract 202 5580 short term rat abstract,no data S •_~.?•-.203 5580 short term rat special study i 206 5580 short term rat special study,no con .~~r 207 5380 subchronic rat irrelevant 210 5600 nr rat no data,abstract 211 5580 rat duplicate no 100 212 5580 short term rat special study,no con ' 213 0 review 214 5580 reproduction dog review group size 215 5600 reproducti an dog yroup size 217 5580 chronic/repro dog group size 220 5380 chronic/repro rat unorganized rep art 221 0 summary,no data 222 6000 short term rat deficient diet 223 5580 special rat castrated animals ' 225 0 no tox data ! 226 5600 nr rat ab str act,no data 227 5580 short term rat inadequate diet ~ 229 0 review 232 0 summary 234 5580 oncog enicty mouse not reproducible eff 235 9300 metabolism rat mete.' _sm,no to:< da 236 10000 nutrition,chem. rat ot>: dota,chemist 237 6 nutritienc -at low radi at.dose 238 SOU ~r--c/repro rat ab str act,no data 239 S~-' short term chicken nutr.no tox data 242 O Af11L5 S.typhim no data 243 O Ames S.typhim no data 246 6000 acute/digestion dog dur ati on,group size 247 33 cytogenetic Allium bu no control data 248 O no tox data 231 30G chronic/repro rat sumarry,no data 254 0 chronic rat I$T,no dose 259 75 cytogen/dom.let. mouse no data _ 261 6 subchronic/repro rat no dose ~ - -0 ~ - - review 264 .0: _ letter to editor 267- 5580 reproduction -r•at 70Y. diet replaced 269 0" IBT,no irradiation 272 1860 chronic/repro rat vitE deficiency 273 2500 reproduction mouse insufficient data 278 O chronic mouse dose nr,mortality 279 5580 chronic/repro doq group size 282 400 short term mouse amount not specified 2B3 5000 short term rat basic diet irradiat. 284 O subchronic/repro rat dose nr i 285 6000 chronic rat no data on design j 287 0 review 288 -0 review 292 5580 subchronic rat insufficient data 293 X300 chronic/repro rat incomplete study 294 2790 subchronic rat/dog/c group siz e,controls 302 20000 short term chicken high irrad.dose 308 0 subchronic rat IHTgdose nr 316 5580 chronic rat compilation studies ~ 317 5560 chronic dog compilation 319 O nr rat abstract,no data 319 600 chronic rat preliminary report 321 5580 subchronic dog group size nr 322 0 review ~ 323 O review 325 0 - no tox data. 328 60n reproduction rat ~ fbT 339 O not relevant 345 O no tox data 347 0 review 348 0 subchronic/repro rat eadiat,dose nr 349 55 subchronic/repro rat starvation/pal atabil 351 75 mutation rat no data 355 8370 short term rat nutrition study 356 5580 short term rat insufficient data 357 5580 chronic/repro rat questionable study 358 74 chronic/repro rat questionable study ,I 359 5600 chronic/repro rat poor study 360 5380 chronic/repro rat questionable study 362 O chronic dog insufficient data 368 380 Ames S.typhim incomplete study 373 30 reproduction rat/mouse level irrad.fd nr 380 500 subchronic dog group size 383 500 chronic dog duplicat e,summary 385 O review 387 5580 general toxicity dog insufficient data 388 O chronic dog IBT,interim report 389 O review 392 5580 subchronic rat incomplete study 393 5580 chronic/repro rat breeding problems co 394 15 subchronic mouse insufficient data 39 7 l o- s »C c%..w,'c /ns~v.~e not h, Sv~,' 6:....* do (-t 87 Mr. Youxc~. Based on all of our analyses, we found that this is a ~ry conservative approach. I would say two things. First, we have .r looked at this process for over 30 years, and studied very carefully ed both high and low levels of radiation. And, second, we went Por- i ward with a level which we feel is deliberately conservative at to ~ which it would be very, very difficult to identify any radiolytic tv ~ products. It would be hard at that level to establish changes that i f i ed would be different from foods processed with methods other than diet. irradiation, or not processed with any process at all. ,Therefore, we feel that, though there may be disagreement as a" } practicing scientists for over a quarter of a century, we live with ' the disagreement. We have arrived at the best decision based on ea € 'the weight of evidence. We believe that the weight of evidence fully r suppports the FDA action. -01 s = Mr. WnxMarr. I understand that Great Britain and West Germa- ny have banned irradiated food, and that the Canadian Govern- f i es went 13 considering delaying irradiation until further studies are done. That doesn't sound to me like there's a consensus among art Western countries. Why have these countries banned irradiation? Mr. Youxc. Let me direct that question to Dr. Pauli, who has analyzed that for me. Mr. Pnuri. Great Britain and West Germany, as this country, have a law that says you cannot irradiate food unless it's permit- >umm. ted. They have not yet permitted any such irradiated food, so it's banned there as it was banned here a few years ago. Both of those countries do permit irradiation of food for hospital nr patients under certain conditions. There has been a considerable nr amount of irradiated foods for hospital patients used in Great Brit- nr Sin. Mr. Youxc. Dr. Miller. Mr. Minx. I think it's also fair to point out that the action in Canada is one which was initiated by the Parliament rather than by the scientists. atii Mr. Wnxhtnx. Initiated by the what? Mr. Mrr.~x. By the legislative body in Canada rather than by the scientists. Also, in the United Kingdom, the Government ap- 'v pointed an expert committee on food irradiation that recommended iv to the Government that they approve it. iy As in the United Kingdom, and everywhere else, there is some controversy over food irradiation, but in the end, on any scientific _ issue, it's a question of judgment and experience that has to pre- vail. There never are absolute answers to these questions. Mr. WaxMnx. Dr. Young, when you approved irradiation in 1986 you required a display of a label which contains a written state- '_t went and a logo. I understand the written statement will not be required 2 years after the approval date. I also understand. that your rationale for ending the use of the ' statement was that the consumers would have seen the logo enough in 2 years to know that it stands for irradiation. Since irra- diation isn't being used, are you going to extend the requirement of the written statement? Mr. YouxG. We put that in to be sure that consumers would be able to see it. Obviously, with irradiation not taking place in any significant amount during this period of time, we will need to re- 88 eve ite that. We put in the call i reevaluation so that we :.ou14 address those issues. Mr. Wax3sax. You put in the call for reevaluation? Mr. You1aG. In other words, we put in the regulation the fact that we would reevaluate it at the end of 2 years to be sure that we had an opportunity to see whether the need were present and if the need were present for further consumer information, we will so require it. Mr. WaxMnx. So in 1986 you put in there that it would have for ~ 2 years a written statement, but it wouldn't automatically stop, it would be something to be reevaluated? Mr. YovxG. That's right. We did not put it in as a statement we t would not be able to continue at all. I believe, having been one of the ones that felt very strongly about labeling to be sure that we had consumer information, we will evaluate it carefully, and I promise to do that. We have not had any significant irradiation, so obviously con- sumers would not be able to get used to the logo at this time. Mr. Waxnanx. It seems to me that it would be sensible to have a written statement so that consumers will be aware of what that logo means, and will be able to get the information that you wanted them to get. Mr. YouxG. Yes. Mr. WnxMnx. An irradiation facility will use dangerous radioac- tive products. The environmental and occupational hazards could be serious. Did FDA do an environmental impact statement prior to approving use of this technology? And if not, why didn't you? Mr. Youxc. We have the same type of procedures that are in- volved in irradiation for sterility for devices, irradiation of a number of other products regulated by FDA. We did not feel that this introduced any different criteria than were introduced in the past, and we felt that our periodic certification and inspection pro- cedure would be adequate to determine safety. I must also add that the Nuclear Regulatory L`omm;ccion and others have responsibilities for inspecting these sites as well, so we felt there would be adequate inspections. Mr. WaxMnrr. I thank you very much for your testimony and your answers to these questions. We may have additional questions to submit to you, and we'd like you to respond in writing for the record. ' Mr. Youxc. Thank you. We should be happy to do so. Mr. WnxNtnx. 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