ReviewThedevelopmentofregulationsforfoodnanotechnologyChi-FaiChau,Shiuan-HueiWuandGow-ChinYen*DepartmentofFoodScienceandBiotechnology,National Chung Hsing University, 250 Kuokuang Road,Taichung40227,Taiwan(Tel.:D886422879755;fax:D886422854378;e-mail:gcyen@nchu.edu.tw)Thepresent studyistogiveapreliminarydiscussiononthepotential applications, risks, food safety, and current regulatorysituation of nanotechnology in relation to foods, thus toprovidetheindustry, legislators, andgovernment withsomepoints,ratherthanaroadmap,thatwillneedtobeaddressedasregulationfor foodnanotechnologymovesforward. Fromthefoodindustryandpublicsafetystandpoints, somerecentfood applications of nanotechnology, safety and risk problemsof nanomaterials, routesfornanoparticlesenteringthebody,existingregulations of nanotechnologyinseveral countries,andacerticationsystemofnanoproductsarediscussed.Nanoscienceandnanotechnologyaretheunderstandingand manipulation of materials at the atomic, molecular, andmacromolecularscales. Thegreatersurfaceareapermasscompared with larger-sized particles of the same chemistryrenders nanosized particles more active biologically(Oberdorster, Oberdorster, &Oberdorster, 2005). Theseemerging technologies have shown great potential in nutra-ceuticals and functional foods for delivering bioactive com-pounds in functional foods to improve human health (Chen,Weiss,&Shahidi,2006).Amongthenanotechnologycon-sumer products to date, health and tness products form thelargest category, followed by electronics and computerscategoryaswell ashomeandgardencategory. TheUSisthe overwhelming market leader, having at least three timesmorenanoproducts onthemarket thanthoseintheEastAsiaandEurope(ElAmin,2006a).Because of the limited information on the risks of hand-ling nanomaterials, these materials of ultra-small scale havecreatedanintenseinterest intheir healthrisks. Somere-portsdiscussingthepotential risksof nanomaterialshavesurprisedthepublicbytakingastrongprecautionarytoneon health and safety risks (ETCGroup, 2005a, 2005b).Thenoninterventionof nanotechnology-basedfoodprod-ucts, namelynanofood, tocome tothe foodmarkets intheabsenceofcleardenition, publicdebate, foodsafetyassessments, andproper foodregulations mayeventuallyjeopardize the potential benets of nanotechnologies tofoodindustry. TheInstituteofFoodScienceandTechnol-ogyhas remindedthe deciencies incurrent regulationsconcerning the impact of nanotechnology on food andpackaging (IFST, 2006). Owning to the lack of informationabouttheimpactsofnanotechnologyon publicsafety,leg-islation,society,andfoodindustryaswellasthepotentialtoxicity of nanomaterials, it is probably wise to takea pre-cautionaryprinciple todeliberate the possible regulatorycontrol as a proactive approach until proven otherwise.More studies on the applications of nanotechnology infood processing and packaging, nanotoxicity, regulation,and risk-and-benet analysis are necessary to ll the know-ledgegaps, sustainthegrowthof nanofoodindustry, andavoidanyunpredictablehealthhazard. Fromthefoodin-dustryandpublicsafetystandpoints, theobjectiveof thispaper istogiveapreliminarydiscussiononthepotentialapplications,risks, food safety, and currentregulatory situ-ation of nanotechnology in relation to foods, thus to providethe industry, legislators, and government with some points,rather thanaroadmap, that will needtobeaddressedasregulationforfoodnanotechnologymovesforward.ThepotentialapplicationsofnanotechnologyinfoodindustryNanotechnologyhasbeentoutedasthenextrevolutioninmanyindustries,includingfoodprocessingandpackag-ing. Theapplicationsof nano-based technologyin foodin-dustrymayincludenanoparticulatedeliverysystems(e.g.micelles, liposomes, nanoemulsion, biopolymeric nano-particles, and cubosomes), food safety and biosecurity(e.g. nanosensors), and nanotoxicity (Chen et al., 2006;HSE,2006;IFST,2006;Maynard,2006).Worldwidesalesof nanotechnology products to the food and beverage pack-aging sector jumped fromUS$150 million in 2002 toUS$860millionin2004. Thevalueof theapplicationof * Correspondingauthor.0924-2244/$-seefrontmatter 2007ElsevierLtd.Allrightsreserved.doi:10.1016/j.tifs.2007.01.007TrendsinFoodScience&Technology18(2007)269e280nanotechnologyinfoodis expectedtosurgetoUS$20.4billionin2010(Fletcher, 2006a; Kaiser). Althoughmanyfoodscientistswouldclaimthat theindustryhavealreadyembraced nanotechnology, only limited researches in nano-technologyhavebeenperformedinfoodsandfood-relatedproducts, andtheglobal development of nanofoodsisin-deedonitsinitial stage. Infact, thefoodindustryisonlybeginningtorealizethefull potential of nanotechnology.In 2000, Kraft Foods started the rst nanotechnologylabo-ratoryanditsNanotekconsortium, involving 15univer-sities worldwideandnational researchlaboratories (ETCGroup, 2005b). In2004, it was estimatedthat there aremorethan180applicationsof nanotechnologyinvariousstagesof development infoodindustryworldwide(IFST,2006; PCAST, 2005). AsofMarch2006, arecent surveyof nanotechnology-based consumer products on the marketestimated that over 200 manufacturer-identied nanoconsumer products are currentlyavailable, andabout 59and9%of the products are categorizedas HealthandFitness (largest main category) and Food and Beverageproducts,respectively(Nanotechproject,2006).Around the world, the number of newly developed appli-cations of nanotechnology in food is growing rapidly.Sanguansri and Augustin (2006) have introduced some appli-cations of nanotechnology in the food and related industries.Some more recent examples of nanotechnology researches,nanoproducts, and applications of nanotechnology in relationto food industry (mainly from2004 to 2006) are summarizedinTable1.Itshowsthatnanotechnologyhasbeensuccess-fullybeenusedina wide range of applications suchaswater purication, cell-wall rupture, slow-release of nutraceu-ticals, micro-encapsulation, deodorization, disinfectants, anti-microbial and antifungal functions, and increase of shelflife. These applications are divided into several categories in-cludingfoodprocessing, nutraceutical delivery, packaging,and safety and sensing, in which many different typesof materials (e.g. membrane, nanocapsule, nanoemulsion,liposomal nanovesicle, nanoparticle, nanotube, nanosphere,nanoceramic material, nano-clay, or nanowire) has beenused.Safetyproblemsand potentialrisk ofnanotechnologyNanotoxicityofnonfoodmanufacturednanoparticlesNanotechnologyhas alreadyprovokedpublic concernanddebate. Nanomaterials (e.g. carbonnanotube, silver,silica, titaniumdioxide, andzincoxide)exhibitpropertiesnot found at the macro-scale and might result in unpredict-able safety problemand risk. For example, aluminumoxide, being used in dentistry because of its inertness,can spontaneously explode at nanoscale and is being testedas a potential rocket fuel (ETC Group, 2006). There is lim-itedrobust scienticevidenceabout thepotential hazardsthatmayexistortheriskstopeoplebeingexposedtothenewlydevelopedparticles, materials, anddevices. Ingen-eral, theimpact of nanoparticles onthebody(i.e. nano-toxicity) depends ontheproperties suchas particlesize,mass, chemical composition, surfaceproperties, andhowtheindividual nanoparticles aggregating together(Nel, Xia,Madler, & Li, 2006; Oberdorster, Maynard et al., 2005). Theextentto whichnanoparticlesenterhumanbodies,thesitesofpenetration,andpossibleaccumulationandtranslocationof nanoparticles in the body may also determine the potentialrisks of nanoscale materials (Oberdorster, 2001; Oberdorsteret al., 2005). For the assessment of nanotoxicity, severalcriteria may be considered: (1) exposure assessment of nano-particles; (2) toxicology of nanoparticles; (3) ability to extrap-olate nanoparticle toxicity using existing toxicologicaldatabases; (4)environmental andbiological fate, transport,persistence, and transformation of nanoparticles; and (5)recyclability and overall sustainability of nanomaterials(Dreher, 2004).In March 2006, it was reported that more than 70 peoplewere suffered fromrespiratory problems and hospitalized af-ter using the nanotechnology bathroomcleaner (ETCGroup,2006). Nanoparticlesof50and70 nmcanentercellsandlungs, respectively, while those of 30 nmcanevenpassthroughthebloodandbrainbarriers(ETCGroup, 2006).They could then translocate fromrespiratory systemto bloodcirculatory system, distributed throughout the body, and fur-ther taken up into liver, spleen, bone marrow, heart, brain, andother organs (Kreyling et al., 2002; Oberdorster et al., 2002;Oberdorster et al., 2005). ThendingsfromOberdorster,Ferin, andLehnert (1994) showedthat the inhalationofhighlyinsolubletitaniumdioxidenanoparticles(w20 nm)oflowintrinsictoxicityresultedinsignicantlyincreasedpulmonary inammatory responses. Titanium dioxide nano-particle could also penetrate through skin and even into cell,forming free radical and causing intracellular damage(Oberdorster, 2001). Someotherstudiesdemonstratedthatlong-termexposure to an environment containing carbonnanoparticles would cause pulmonary inammation and theirdiffusionfromlungtothesurroundingbloodvesselsystemwould result in furthervascular disease (Brown, Stone, Fin-dlay, MacNee & Donaldson, 2000; Nemmar et al., 2002). Itwas possible that the high dose of the aggregated nanotubesand the presence of residual metal impurities (e.g. iron, nickel)accounted for the articial toxicity (HSE, 2006; Neletal.,2006).Accordingly, ithasbeensuggestedthatnano-particles should be treated as new, potentially harmful mate-rials (IFST, 2006).ThreepossibleroutesfornanoparticlestoenterintobodyIn respect of the entry of nanoparticles into body and thetranslocationamongorgansduetotheir small size, threepossibleroutesfornanoparticlestocauseharminsidethebody include dermal exposure, inhalation, or ingestion. Be-causeof thelimitedinformationontherisksof handlingnanomaterials, astringent control onexposureshouldbeimplemented until more knowledge becomes available.For handling nanomaterials appropriately, lab safety guide-lineshavebeenprovidedbytheCommitteeonChemical270 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280Table1.Examplesaofnanotechnologyresearches,nanoproducts,andapplicationsofnanotechnologyinrelationtothefoodindustryCategory Examplesofthedifferentapplications ReferencesFoodprocessingInteractivefoodsandbeveragesgivedesiredavorsandcolors(on-demanddelivery) by the addition of nanocapsules which burst at different microwave frequenciesETCGroup,2005bTheIsraelNationalNanotechnologyInitiativeincollaborationwiththeU.S.NationalNanotechnologyInitiativehasexploredtheapplicationsofnanotechnologyinwaterpuricationandtreatmentfocusingontheareassuchasmembranesandmembraneprocesses,biofoulinganddisinfection,andcontaminantsremovalINNI,2006Developmentofnano-scaleformulationsofdifferenttraditionalherbalplantsbyreducingtheherbstonanoscalepowderoremulsionElAmin,2005bMicronizationofganodermasporetoultranepowderbytop-downapproach,resultingintheruptureofcellwallsandreleaseofpotentialactiveingredientsLiu,Wang,&Yuan,2005Fryingoilreningcatalyticdevice(madeofnanoceramicmaterial)inhibitsthermalpolymerizationoffryingoilandreduceoff-odorsOilFresh,2005Micrometreslongstiffhollownanotubesmadeofmilkproteinbyself-assemblyhavepotentialtobeusedasnovelingredientsforviscosifying,gelation,nanoencapsulation,andcontrolledreleasepurposesGraveland-Bikkera&deKruifa,2006Packaging Addingnanocompositesornanoparticles(e.g.silver,titaniumdioxide,silicondioxide,andnano-clay)intopackagingmaterialstoensurebetterprotectionoffoodsbymodifyingthepermeationbehavioroffoils,deodorizing,increasingbarrierproperties,blockingultravioletlight,improvingmechanicalandheat-resistanceproperties,anddevelopingantimicrobialandantifungalsurfacesElAmin,2005a;Fletcher,2006a;IFST,2006;Roach,2006aNylonnanocompositesprovidingbarrierstooxygenandcarbondioxideowhavebeenusedinfoodpackaging(i.e.multi-layerPETbottlesforbeerandotheralcoholicbeverages)tokeepfreshnessandblockoutsmellsSherman,2005NutraceuticaldeliveryNanotechnologyrendershydrophilicsubstancesfatsolubleandlipophilicones watersoluble,allowingnanoparticlesofsomefunctionalingredients(e.g.carotenoids,phytosterols,andantioxidants)tobedispersedinwaterorfruitdrinkstoimprovetheirbioavailabilityChenetal.,2006;IFST,2006SyntheticnanoparticlesoflycopenearedevelopedandacceptedasGRAS-afrmedbytheFDAforuseinfoodintheUSACFSAN,2005Minutemicelles(nanocapsules)areusedascarriersforessentialoils,avor,antioxidant,coenzymeQ10,and vitamins,minerals,andphytochemicalstoimprovetheirbioavailabilityElAmin,2006a;Fletcher,2006b;Pitman&Halliday,2006Encapsulatingthenanoparticlesofactiveingredients(e.g.polyphenols,minerals,andmicronutrients)toprotectthemfromoxidationandgettingtothetastereceptorsite,thustoreducetheirundesirableofftastesinthenishedapplicationHeller,2006Foodindustry applicationofliposomalnanovesiclesfortheencapsulationanddeliveryofnutrientsandfunctionalingredientssuchasproteins,enzymes,avors,andantimicrobialcompoundsWen,DeCory,Borejsza-Wysocki, & Durst, 2006Wheyproteinnanospheres(40 nm),whichareinternalizedbycellsanddegradedthereintoreleasethenutraceuticalcompounds,canbeusedascarriersfororaladministrationofnutraceuticalagentstoimprovetheirbioavailabilityChenetal.,2006SafetyandsensingProtein-coatednanocantilever,naturallyvibratingataspecicfrequency,isanewclassofultra-smallsiliconsensorsforthequickdetectionofviruses,bacteriaandotherpathogens.Whencontaminantslandonthedevices,theslightmasschangescancausethenanocantilevertovibrateatadifferentfrequency andbequicklydetectedElAmin,2006bDevelopmentofsynthetictree-shapedDNAbeingtagged withcolor-codedprobes,asananobarcodedevice,enablestheidenticationoffoodpathogensLietal.,2004Aminiatureportablemicrobiodetectorwasdevelopedusingdifferentnanowires,specicpathogenantibodies,anduorescentantibodiesforthesimultaneousdetectionoftoxins,pathogens,andchemicalsinfoodstuffsRoach,2006bSilver nanoparticleshavebeenincorporatedintodifferentproductsfrombandagestorefrigeratorsforsuppressingthespread ofbacteriaandothermicrobesNanosilver,2004aRecentexamples(butnotacompletelist)ofnanotechnologyresearchesandapplicationsinfood-relatedareas.271 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280Safetyof theAmericanChemical Society(http://membership.acs.org/c/ccs/nano.htm).DermalexposureTheimpact of nanomaterials onthebodydepends ontheir ability to penetrate through the outer protective layersandreachtheepidermisor dermis(Maynard, 2006). Theepidermis of healthy and intact skin could provide excellentprotection against nanostructured particles (Nel et al., 2006;Tsuji et al., 2006). Stratumcorneum, whichiscomposedofkeratiniseddeadcellsgluedbylipids, actsastherate-limitingbarrier (10 mm) tocutaneous absorptionof mostchemicals, watersolublemolecules, andioniccompounds(Hoet, Bruske-Hohlfeld, &Salata, 2004). The ndingsfromTinkleetal. (2003)showedthat neuorescentmi-crospheresor dextranbeads(upto1 mm), inconjunctionwith motion, might penetrate the stratumcorneumandreach the epidermis and, occasionally, the dermis. Nanopar-ticlescouldpenetrateintothedermisandthentranslocatevia lymph to regional lymph nodes (Oberdorster et al.,2005). Kreilgaard (2002) has suggested that very small tita-nium dioxide particles (w20 nm)could penetrate intoskinand interact with the immune system. Moreover, thephotogeneration of hydroxyl radicals by nanomaterials(e.g. titanium dioxide and zinc oxide) may lead to oxidativedamage in the skin (Wakeeld, Green, Lipscomb, & Flutter,2004). Asyet, thereisstill verylittleinformationonthehazards of nanomaterials to skin, and discussions onthe mechanisms of interaction and possible healthconsequencesareratherspeculative(Maynard,2006).InhalationWhile the aerodynamicdiameter of small solid materialis less than 10 mm, it can pass through nasal cavity into thelung. Particles smaller than 4 mm have greater than 50% ofprobability of penetrating to the alveolar region. The smalleristheparticulates,thedeepertheycantravelintothelung(Hoet et al., 2004). The particle size, mass, chemical compo-sition,sampletypes,andtheratesofdepositionandclear-ance of inhaled materials determine their pulmonarytoxicity or pathogenic effects (Maynard, 2006; Moolgavkaret al., 2001). It wasindicatedthat low-solubilityultraneparticlesaremoretoxicthanlargerparticlesonamassformassbasis.Becauseofthetinysize,thenanoparticlescangetdeepintothelungs.Wheninhaled,somenanoparticles(e.g. titanium dioxide, carbon tube) mayaccumulate inthelung and induce chronic diseases such as pulmonary inam-mation, pneumonia, pulmonarygranuloma, andoxidativestress (Kim et al., 2003; Nel et al., 2006). Once in the blood-stream,theparticlesmaybeabletocrossthebloodebrainbarrier. Thenanoparticlescanevenevadespecicdefensemechanismsandtranslocateoutoftherespiratorytractviadifferent pathways and mechanisms (Oberdorster et al.,2005). According to our current state of knowledge, it is stillnot possible to reachgeneric conclusions about toxicitybasedonconsiderationofsizealone;thepotentialtoxicityof eachindividual nanomaterial needstobeevaluatedona case-by-case basis (HSE, 2006).IngestionParticle size and surface area are important materialcharacteristics from a toxicological perspective. As the sur-face of villi being covered with microvilli bring overall sur-face available to nutrients to 200 m2, the safety assessmentof nanomaterials enteringthe bodythroughaningestionroute is particularly important for the food productscontainingnanomaterials. Nanoparticles candramaticallyprolongcompoundresidence time inthe gastrointestinaltract by decreasing the inuence of intestinal clearancemechanisms,increasethesurfaceavailableforinteraction,penetratedeeplyintotissuesthroughnecapillaries, andthusallowefcientdeliveryandabsorptionofcompoundsto target sites in the body (Chen, Remondetto, & Subirade,2006). Inadditiontothedirectingestionofnanomaterialsthrough food, water, cosmetics, or drugs, those clearedviathemucociliaryescalator intherespiratorytract canalsoendupinthegastrointestinal tract (Nel et al., 2006).It has been reported that particles larger than 1 mm were un-able to pass through the intestinal mucus barrier (Szentkuti,1997). In a particle translocation experiment (Jani, Halbert,Langridge, & Florence, 1990), polystyrene spheres(50 nme3 mm) were fedbygavage tofemale SpragueeDawley rats for 10 days, and the results demonstratedthat about 34and26%of nanoparticles(50and100 nm,respectively) were absorbed while particles larger than300 nmwere absent fromblood, heart or lung tissue.Fromtheobservationsofanotherstudyonlatexnanopar-ticles (Szentkuti, 1997), hydrophobic latex nanospheres(14 and 415 nm) could penetrate the mucus gel layer(30e50 mmin thickness) in 2 and 30 min, respectively.The smaller is the particle, the faster would be the penetra-tionactionacrossthemucusbarrier.Potentialhealthriskofnanotechnology-basedfoodmaterialsManyfoodsubstances or ingredients have nanostruc-turesinnatureandarepresent at micro-ornanometerinsize. Foodproteins, whichareglobular particlesbetween10sand100sofnanometers insize,aretruenanoparticles.Linear polysaccharides with one-dimensional nanostruc-tures are less than 1 nm in thickness, and starch polysaccha-rideshavingsmall 3-Dcrystallinenanostructuresareonly10s of nanometers in thickness. In the food industry,manyattemptshavebeenmadetomanufacturemicro-ornanosize food materials by the top-down (e.g. grindingdown) or bottom-up(e.g. aggregationof substances) ap-proaches.Ingeneral, physicochemicalpropertiesincludingparticle size and size distribution, agglomeration state,shape, crystal structure, chemical composition, surfacearea, surfacechemistry, surfacecharge, andporositymayall be important for understanding the toxic effects of nano-materials(Oberdorster,Maynardetal.,2005).However,it272 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280remains to be determined whether the unique physicochem-ical properties of nanomaterials will introduce new mecha-nisms of injury and result in unpredictableharmful effects.Nanotechnology opens up a whole universe of new possi-bilities for the food industry (e.g. food packaging), but the en-try of manufactured nanoparticles into food chain may resultinanaccumulationofthetoxiccontaminant infoodsandadverselyaffect humanhealth. Therearequestionsif thefoodmaterialsofnanometersized(oruptoafewmicron)shouldbecategorizedasneworunnaturalmaterialswhilecompared with their larger forms. Although the nanomateri-als might be toxic and cause harmful effects beyond the ex-pectation, research effortshavealsorevealed that the waysof making nanomaterials and processing may not necessarilyproduce products with harmful effects (Zhang et al., 2003):for instance, the toxicity of certain substance (e.g. selenium)might be signicantly reduced while its particle size was de-creasedtonanoscale.Itwasalsoreported thatpurecarbonnanotubes administered to the tracheaof mice might causedeath; whereas, doping carbon nanotubes with nitrogenreduced their toxicity and the risk of death, pavingtheway for the use of the technology in food packaging(Roach, 2006a). On the basis of a Precautionary Principle,more investigations on the toxicity of nanoparticlescontacting with food products, however, should be per-formed to dispel the doubts. In spite of the fact that most oftheexistingnanotoxicitystudiesaregenerallyfocusingonnonfood materials or consumer products, those relevant re-searchndingscanstill beuseful hintsforunderstandingthe potential toxicity of the nanotechnology-based foodmaterials.RegulationsofnanotechnologyandnanoproductsOrganizationsandresearchessupportingthedevelopmentofnanotechnologyManynanotechnologyinitiatives, commissions, orcen-ters have been launched by governments, academia, privatesectors in the United States, Europe, Japan, and some othercountries around the globe toensure rapid developmentand deployment of nanotechnology, promote economicgrowth, maintainglobal competitiveness, and improve the in-novative capability (Chen et al., 2006; ETC Group, 2005b).Some of them have also participated in proposing regulationto improve the protection of human health and the environ-ment. In Table 2, some major initiatives, centers, institutes,or government organizations are listed. These organizationsor researchcenters mainlysupportedbythegovernmentsourcesplayanessential roleinperformingorsupportingnanotechnologyresearches, includingthebasicresearcheson nanotechnology, the applications of nanotechnology,safetyassessment of nanomaterials, andthedevelopmentof regulatory control. They also provide long-termcoherenceand platforms for interdisciplinary people or experts topromote nanotechnology to the public as well as to give animpetus to the nanotechnology industry.RegulatorydevelopmentinnanotechnologyAmongthe nanotechnology-basedconsumer products,companies based in the USAhave the most products(126), followedbycompanies inAsia(42), Europe(35),and elsewhere around the world (7) (Nanotechproject,2006). In some Asian markets, some products may usethetermnanotechnology anditssmall size conceptto promote their products by claiming that the tiny ingredi-ents could be absorbed easily with novel functions, whereasmost of the products failed to prove their claims on size andfunctions with robust scientic data. In some countries (i.e.theUSA), someexistinglaws suchas notablytheToxicSubstances Control Act; the Occupational Safety andHealthAct; the Food, DrugandCosmetic Act, andthemajorenvironmentallawsmayatleastprovidesomelegalbasis for regulatingnanotechnology. CodexAlimentariusCommission, an intergovernmental agency establishedjointlybyFAOandWHO, is promotingcoordinationofall food standards work undertaken by international govern-mental and non-governmental organizations. In order toprevent regulatorygap, CodexAlimentariusCommission,participating in the development of international foodsafety regulation, should take into account the use of nano-particles and other nanoscale technologies in food andagriculture.Uptonow,thereisnointernationalregulationof nanotechnologyor nanoproducts. Onlya fewgovern-ment agencies or organizations fromdifferent countrieshave established standardand regulation to deneand reg-ulate the use of nanotechnology. The existing regulations ofnanotechnologyinseveralrepresentativecountriessuchastheUSA, UK, Japan, andmainlandChina arediscussedasfollows.The US Food and Drug Administration (FDA) is amongthe rst government agencies around the world having a def-inition of nanotechnology and nanoproducts. However, FDAhas not establishedits ownformal denition, thoughtheagency participated in the development of the NationalNanotechnologyInitiative(NNI) denitionof nanotech-nology (www.fda.gov/nanotechnology/faqs.html). Asde-scribedbytheNNI, nanotechnologyistheunderstandingandcontrolofmatteratdimensionsofroughly1e100 nm,where unique phenomena enable novel applications(www.nano.gov/html/facts/whatIsNano.html). The NNIs deni-tion of nanotechnology is (www.fda.gov/nanotechnology/faqs.html):(i) Researchandtechnologydevelopment at theatomic,molecular or macromolecular levels, in the lengthscaleofapproximately1e100 nmrange.(ii) Creating and using structures, devices and systemsthat havenovel properties andfunctions becauseoftheirsmalland/orintermediatesize.(iii) Abilitytocontrolormanipulateontheatomicscale.The denitions are relatively broad and seemto befocusing on the nonfood materials of nanotechnology.273 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280Table2.Examplesofmajorinitiatives,centers,institutes,orgovernmentorganizationssupportingthedevelopmentofnanotechnologyCountryordistrictInitiatives,centers,institutesorgovernmentorganizations LinksUSA NationalNanotechInitiative(NNI) http://www.nano.govFoodandDrugAdministration(FDA) http://www.fda.gov/nanotechnologyEnvironmentalProtectionAdministration(EPA) http://es.epa.gov/ncer/nanoCenterforNanotechnology http://www.ipt.arc.nasa.gov/index.htmlNationalScienceFoundation http://www.nsf.gov/crssprgm/nanoProjectonEmergingNanotechnologies http://www.nanotechproject.orgEuropeanUnion CommunityResearch&DevelopmentInformationService(CORDIS)http://cordis.europa.eu/nanotechnologyEuropeanNanotechnologyGateway http://www.nanoforum.orgEuropeanNanobusinessAssociation(ENA) http://www.nanoeurope.orgUK InstituteofNanotechnology(IoN) http://www.nano.org.ukTheRoyalSociety andRoyalAcademyofEngineering http://www.royalsoc.ac.uk/page.asp?id1212HealthandSafetyExecutive(HSE) http://www.hse.gov.uk/horizons/nanotech/index.htmInstituteofFoodScienceandTechnology(IFST) http://www.ifst.orgDepartmentforEnvironment,FoodandRuralAffairs(Defra)http://www.defra.gov.uk/environment/nanotech/index.htmFrance MinistryforResearchandNewTechnology http://www.nanomicro.recherche.gouv.fr/uk_index.htmlFrenchResearchNetworkinMicroandNanoTechnologies(RMNT)http://www.rmnt.org/EN/index.htmlCentreNationaldelaRechercheScientique(NationalCenterforScienticResearch)(CNRS)http://www.cnrs.fr/index.htmlGermany GermanFederalInstituteforRiskAssessment(BfR) http://www.bfr.bund.de/cd/template/index_enFederalMinistry ofEducationandResearch(BMBF) http://www.bmbf.de/en/nanotechnologie.phpItaly NationalInstituteforthePhysicsofMatter(INFM) http://www.infm.it/Associationitalianaperlaricercaindustriale(AIRI) http://www.airi.it/2005/index.phpCanada NationalInstituteforNanotechnology http://nint-innt.nrc-cnrc.gc.ca/home/index_e.htmlJapan NanotechnologyResearchersNetworkCenter(Nanonet) http://www.nanonet.go.jp/englishNationalFoodResearchInstitute(NFRI) http://www.nfri.affrc.go.jp/english/ourroles/index.htmlRIKEN http://www.rikenresearch.riken.jpJapanSocietyforthePromotionofScience(JSPS) http://www.jsps.go.jp/english/index.htmlMinistry ofEducation,Culture,Sports,ScienceandTechnology(MEXT)http://www.mext.go.jp/englishNationalInstituteofHealthSciences(NIHS) http://www.nihs.go.jp/index.htmlNationalInstituteforEnvironmentalStudies(NIES) http://www.nies.go.jp/index.htmlNationalInstituteofAdvancedIndustrialScienceandTechnology(AIST)http://www.aist.go.jp/index_en.htmlNationalInstituteforMaterialsScience(NIMS) http://www.nims.go.jp/eng/index.htmlMinistry ofEconomy,TradeandIndustries(METI) http://www.meti.go.jp/englishChina ChineseAcademyofSciences http://www.cas.ac.cn/Index/0C/Index.htmNationalCenterforNanoscienceandTechnology(NCNST) http://www.nanoctr.cn/e_index.jspKeyLaboratoryofMoleculeNanostructureandNanotechnology,ChineseAcademyofScienceshttp://www.icas.ac.cn/5_keyanxitong/stm/english/home.htmTaiwan IndustrialTechnologyResearchInstitute(ITRI) http://www.itri.org.tw/eng/research/nano/index.jspNanoTechnologyResearchCenter(NTRC) http://www.ntrc.itri.org.tw/eng/index.jspnanoMark http://www.nanomark.itri.org.tw/EngNationalNanoDeviceLaboratories(NDL) http://www.ndl.org.twNationalScienceandTechnologyProgramforNanoscienceandNanotechnologyhttp://nano-taiwan.sinica.edu.tw/newsen.aspKorea KoreanFood&DrugAdministration(KFDA) http://www.kfda.go.krNationalNanoFabCenter(NNFC) http://www.nnfc.com/index.htmlKoreaInstituteofScienceandTechnologyInformation(KISTI) http://www.kisti.re.krCenterforNanostructuredMaterialsandTechnology(CNMT) http://cnmt.kist.re.krNationalCenterforNanomaterialsTechnology(NCNT) http://www.nano.or.kr/english/index.aspAustralia CSIROManufacturingandMaterialsTechnology(CMMT) http://www.cmit.csiro.au/brochures/tech/nanotechDepartmentofIndustry,TourismandResources(ITR) http://www.industry.gov.au/nanoNanostructural Analysis Network Organisation, Major NationalResearchFacility(NANO-MNRF)http://www.nano.org.au274 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280Regardingthesizelimit(1e100 nm)asmentionedabove,it is quite likelythat newtherapeutic benets are beingderived from products that are smaller than their traditionalform but fall above the 100 nm size range limit of nanotech-nology (www.fda.gov/nanotechnology/regulation.html).Under the denition, it may even inappropriately bringanumberofstandardchemicalprocessesinfoodprocess-ing.Thus,it isstillnot clear thatthedenitionsareappro-priatefornanofoods.FDA states that it regulates products, not technologies.The regulatoryconsiderationof anapplicationinvolvingananotechnologyproduct maynot occur until well aftertheinitial development ofthat nanotechnologyaswell astheestablishment of itsstatutoryclassication. ThismayaffectthestageatwhichtheFDAbecomesengagedintheregulationof nanotechnology. FDAonlyregulatescertaincategoriesofproductsandanticipatesthatmanynanotech-nology products may span the regulatory boundaries amongdifferent agency centers within FDA and will be regulated asCombination Products by the ofce of Combination Prod-ucts (www.fda.gov/nanotechnology/faqs.html). FDAhas tra-ditionally regulated many products with particulate materialsin same size range as the cells and molecules (nano in size);hence, the existing requirements of FDA as well as the exist-ingbatteryofpharmacotoxicitytestsmaybeadequateformost nanotechnology products. Accordingly, FDAstatesthat particle size is not the issue. If new toxicological risksthat derived fromnewmaterials or manufacturing techniquesare identied, new safety tests will then be required(www.fda.gov/nanotechnology/regulation.html).Aclosecoordinationinknowledgeandpolicyamongdifferent government agencies is important for the develop-ment of a harmonized regulation on the use of nanotechnol-ogy. FDAiscollaboratingwiththeNational InstitutesofHealth, National Institute of Environmental Health Sciences(NIH/NIEHS) on nanotoxicity studies (www.fda.gov/nanotechnology/faqs.html), andis a direct contributor totheevaluationsofthetoxicityofmaterials. In2006, FDAhas formedaninternal FDANanotechnologyTaskForcefor determiningregulatoryapproachesthat encouragethecontinued development of innovative, safe and effectiveFDA-regulatedproductsthatusenanotechnologymaterials(FDA, 2006).As commissionedbythe UKGovernment, the RoyalSociety and the Royal Academy of Engineering (RS&RAE)have carried out independent studyonnanotechnologiesand reviewed the benets and problems associated withthose technologies (www.royalsoc.ac.uk/page.asp?id1212).Health and Safety Executive (HSE) has also participated inthenegotiation, agreement,andenforcementofthe regula-tions of manufacturednanoparticles (HSE, 2006). It hasbeen suggested that the regulations (available fromtheHSE) dealing with the harmful chemicals, re risk, and ex-plosion risk of materials, such as the Approved Code of Prac-tice (ACOP) under the Control of Substances Hazardous toHealthRegulations (COSHH), guidanceonCOSHHriskassessments, ACOP from the Dangerous Substances and Ex-plosive Atmosphere Regulations (DSEAR), and guidance ofprecautions against the explosion risk of combustible dusts,might beappliedfor regulatingtheuseof nanomaterials(HSE, 2004, 2006; IFST, 2006). Furthermore, it was recom-mended that chemicals in the form of nanoparticles or nano-tubes could be treated as new substances under the chemicalsafetyregulationssuchasNoticationofNewSubstances(NONS) act and also the forthcoming Registration, Evalua-tion, and Authorization Chemicals (REACH) regulationfromtheEuropeanCommission(HSE, 2006; TheRoyalSociety, 2004). The ideal goal of the REACH system beingdeveloped is to ensure that newchemicals be denied a marketin the absence of convincingsafetydata, inanother words nodata, no market. Nevertheless, whether naturally occurringsubstancesandchemicalelementsatnanoscale(forwhichtheir larger forms being already declared safe) be consideredas new chemicals or not are important to sustain the safetyof these nanomaterials under REACH (ETC Group, 2005a).AccordingtotheEuropeanInventoryofExistingCom-mercial Chemical Substances(EINECS)undertheNONSregulation, nanoscale materials could be regarded as exist-ing or new substances in relation to their ways of produc-tion(i.e. top-downandbottom-upapproaches). Top-downnanomaterials are those made by making familiar substancesatthenanoscaleandthuslesslikelytorequirenoticationunderNONS. Thereismorepotentialfornovelsubstances(i.e.nanomaterials)madebybottom-upconstructiontore-quire notication (HSE, 2006). For example, there is an entryfor titanium dioxide in EINECS database and the particlesize of a solid substance does not affect its EINECS status.Under such a circumstance, the nanoscale titanium dioxide,a top-down material, is regarded as an existing chem-icalandisnotsubjecttonoticationunderNONS.Ontheother hand,carbonfullerene, a bottom-up nanomaterial,is regardedas distinct andseparate allotrope of carbon,which is not an EINECS entry. Thus, carbon fullerenes andcarbonnanotubeswouldberegardedasnewchemicals(HSE, 2006).InJapan, thedevelopment of nanotechnologyindustryarehighlysupportedbytheJapanese governmentagenciesincludingtheMinistryofEducation, Culture, Sports, Sci-ence,and Technology(MEXT),the Ministry of Economic,Trade, and Industries (METI), the Ministry of Health, Labor,and Welfare (MHLW), and the Ministry of the Environment(MOE). MEXTis responsible for research and development,andisbuildingindustry-academia-governmentcooperativeresearchplatforms topromoteresearchanddevelopmentin nanotechnology and materials science (www.mext.go.jp/english/org/struct/029.htm). METI works for the standardi-zationoftestingmethodsforsafetyevaluationofnanopar-ticles and MHLWdevelops the evaluation methods forhealth impacts of nanomaterials (www.nanonet.go.jp/english/aboutus/index.html; www.nanonet.go.jp/english/info/policy/20060602_1.pdf). Therefore, MEXTis responsibleto perform researches on basic science for public acceptance275 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280of nanotechnology while METI, MHLW, and MOEareworking on the regulatory science. Furthermore, the Nano-technologyResearchersNetworkCenter(Nanonet), estab-lishedbyNationalInstituteforMaterialsScience(NIMS),provides informational support for the development of nano-technology (www.nims.go.jp/eng/about/whatsnims.html).In mainland China, the National Center for Nanoscienceand Technology (NCNST) was co-founded by ChineseAcademyofSciences(CAS)andMinistryofEducationinMarch 2003. The NCNST consists of several divisions suchas (1) nanoprocessing and nanodevices laboratory; (2) nano-materialsandnanostructureslaboratory;(3)nanomedicineand nanobiotechnology laboratory; (4) nanostructure charac-terization and test laboratory; and (5) coordination laboratory(NCNST, 2005). It hasestablishedapublictechnologicalplatform and engaged basic and applied researches in nano-science. In 2005, the Commission on Nanotechnology Stan-dardizationafliatedwiththeNCNST wasestablishedandresponsible for developing national standards including ter-minology, protocol, and safety requirements for particlesize measurement, nanoprocessing, nanomaterials and nano-devices, nanobiotechnology, and nanomedicines. BasedupontheexistingChinanationalstandard,thecommissiontakes part inguidingandgoverningthe assessment andaccreditation of nanoproducts, enabling the nanotechnologyindustriestoimproveproduct quality, reducehealthrisks,sustain safety, and foster new products development(NCNST, 2005).It should be noted that the safety researches of nanotech-nology and the development of nanoregulation among mostcountries arestill mainlyfocusingonthenonfoodnano-materials and aspects. As the application of nanotechnologyin food industry is growing rapidly, it is foreseeable that thesafety researches, development of regulatory standards,and public awareness and acceptance of the use of nanotech-nology inthe food industrywill alsobe coming to theforefront.CerticationsystemofnanoproductsIn2004, the Industrial TechnologyResearch InstitutewascommissionedbytheIndustrialDevelopmentBureau,Ministry of Economic Affairs of Taiwan to implement a cer-tication system for nanotechnology-based consumer prod-ucts, and hence to validate and issue the worlds rstcerticate Nano Mark for the veried nanoproducts(Nano Mark, 2005).Underthisgovernmentcerticatesys-tem, certicate is issued on the basis of promoting industri-alizationofnanotechnology,encouragingthedevelopmentof prominent andhighstandardnanoproducts, protectingthecustomers,andupgradingtheconsumersacceptabilityofnanoproducts.WiththeassistanceofanAdvisoryCom-mittee, an on-site evaluation and inspection of themanufacturing plant as well as an assessment on the criteriaincluding particle size, functional properties, processing,qualitycontrol, andrelevant safetyreports andproofs ofthe products are required. Products beingconsideredforthecerticateofNanoMark shouldatleastconformtothe following two basic requirements: (1) one of the dimen-sionsof themajor functional ingredient or component inthe product is within the length scale of approximately1e100 nmrangeand(2)thenanoproduct possessesnovelproperties or improvedfunctionalitybecauseof its smallsize(NanoMark, 2005). Until January2007, therewerethreecategoriesof nanotechnologyproductscertiedandawardedwiththeNanoMark,e.g.antimicrobialphoto-catalytic uorescent lamp, antimicrobial photocatalytictile, andphotocatalyticcoatingfor deodorizationeffects.Asyetthemainactiveingredientinatotalof42certiednanoproducts among these three categories is nanoscalephotocatalytic titanium dioxide. Up to now, all of the certi-ednanoproducts belongtononfoodcategory. Thescalelimit (1e100 nm) of the certicate systemmaypossiblyconnetheproductdevelopmentofnanofoodstoacertainextent.Besidesthegovernmental product certicatesystemasnoted above, a non-governmental association Nano Manu-factureandInspectionUnionwasestablishedin2006bydifferent domesticindustries of Taiwan(http://www.nanounion.com.tw). Unlikethenanoproduct certicatesystem,theunionis aplatformtodevelopanalytical techniques,measurement standard, inspectionprotocol, andstandardoperation procedure, and also provide services such asnanomaterialsprocessing, analysis, productinspection, in-formationexchange, andtechnical consultation. Recently,theunionisschemingoutanissuetodevelopanefcientprocess and standard inspection protocol for the productionof nepearl powder (100e500 nminsize) for whichitslargerformisacommonediblematerialinthetraditionalChinesemedicine. Theassessment criteriafor thesubmi-crosizedpearl powder includeparticlesize, heavymetal,nutritional labeling, aminoacids prole, functional prop-erty, and place of origin. The union regards the micronizedpearl powderasananoproduct. It isobviousthat thereisadiscrepancybetweenthegovernment andprivateunionintherecognition ofsizelimit forananoproduct. Perhaps,this instance canbe usedas a reference for consideringwhat the practical particle size range of the micro- or nano-sizedbiologicalorfoodproductsshouldbe.DevelopmentofregulationsfornanofoodIt is undoubted that the application of nanotechnology infoodandpackagingisgrowingrapidly. Currently, thereisstill no requirement to label food products containing nano-particles and no regulatory standard to comply with, too. Inthe marketplace, different terms such as nanofood and ultra-ne food have been used, whereas it has been difcult to ndout which merchandise could be called nano. For the ex-istingdenitionsofnanotechnologyaroundtheworld, theNNIs denition adopted by FDAis relatively explicit and re-quiresthatthelengthscaleofnanomaterialsshouldbeap-proximately within the 1e100 nmrange (www.fda.gov/nanotechnology/faqs.html). It should be noted that the276 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280denition was not primarily designated for general food pur-poses. These events remind that nomenclature is more imag-inative than regularized, and the rational particle size rangeshouldbeconsideredindeningnanofood. Todatetheconsumers fromEurope are unlikely to be aware of nanotech-nology applications in foods (IFST, 2006), and fewmanufac-turers have claimed the use of nanotechnology in themanufacture of their products or made any nanotechnologyclaims for the nished product (www.fda.gov/nanotechnol-ogy/faqs.html). Nevertheless, manymanufacturersinAsia(e.g. mainlandChina, Taiwan, andHongKong)intendtousethesetermstoemphasizethenenessof componentsfor commercial and marketingpurposes. Manyproductsclaimed to be ultrane food or nanofood in the Taiwanmarketplace, which exaggerate their physiological functionsinrelationtosmall size, werenedbythedepartment ofhealth(Taiwan)forviolationoftheexistingfoodlabelingand advertising regulations (DOH, 2006).Whiletherisksarisingfromexposuretodifferenttypesofnanoparticlesarenotyetcompletelyunderstood,theal-lowance of nanotechnology-basedfoodproducts, namelynanofood, tocometothefoodmarketsintheabsenceofclear denition, public debate, food safety assessments,and proper food regulations may eventually jeopardizethepotentialbenetsofnanotechnologiestofoodindustry.TheInstitute ofFood Science&Technologyhasremindedthedecienciesincurrent regulationsconcerningtheim-pact of nanotechnology on food and packaging (IFST,2006). For a precautionary stance, it is important to developa substantial regulatory regime that addresses the denitionand standard as well as regulates the labeling and safety as-sessment of nanoscale materials used in various food appli-cations. In Table 3, some criteria that should be consideredfor the development of the standard, denition, controlmeasure, and regulation for nanofoods are summarized.Asasteptowarddevelopingtheregulatorystandards,itisnecessarytoconsiderseveral factorssuchasparticlesizerange and measurement, processing, physicochemical prop-erties, safety, andrisksat thesametime. Inaddition, itisalsonecessarytorealizethatthetechnologymayofferdi-verse applications that will touch multiple regulatoryagencies, and also to consider whether the governmentshouldregulatetheprocessortheproduct(Jones,2006).RecommendationsAlthoughtherehavebeensomedenitionandregula-tionsfornanotechnologyinsomecountries, noregulationor policy designated for foods is available until now. In or-dertoprovidesomehintsfortheindustry,legislators, andgovernment todeliberatethepossibleregulationsspecicfor the use of nanotechnology in foods, some recommenda-tions are given in Table 4. Referring to a three-phasebottom-upprocess (Jones, 2006), theregulatorydevelop-ment process for nanofoods can be initiated by (1) theuse of the research and development database to assess ap-plications of nanotechnologytofoodandagriculture; (2)selecting particular products to assess and identify the risksandbenets; and(3) extrapolatingtoanalyzeappropriateregulatoryor non-regulatorygovernance systems for theapplicationsofnanotechnologyinfoods.Based on the current state of knowledge, the debate on thebenets and risks of applying nanotechnology in food industrywill last long. Although there are currently no conclusive dataabout the undesirable results of nanotechnology, it is probablywise to take a precautionary principle to deliberate the possibleregulatory control as a proactive approach until proven other-wise. Regulation on the use of nanotechnology in food systemsis therefore necessary for managingthe potential adverseeffects of nanotechnology and protecting the public.Furthermore,respectingthemixofpotentialharmsandbenets of nanotechnology, regulatory consideration forTable3.Differentcriterianeedtobeconsideredforthedevelop-mentofthestandard,denition,controlmeasure,andregulationfornanofoods1)Particlesizerangeandmeasurement Whatisthesizelimitfornanofoods? LookingforTrueNanoorndingAdvanceMaterialswithnovelpropertyorfunctionsatsmallsize?Which types of apparatus and measurement methods are used forparticlesizeanalysis? Should the particle size measurement be performed on the initialraw materials, intermediate materials, nal products, or materialsatanypointalongtheprocessing?2)Physicalandchemicalproperties Whether thefood materials belong toGRAS substances, naturalsubstancesbeinggenerallyconsumed,orarticialcompounds? Wouldthenanoscalefoodmaterialsbedigestedtotheirmonomers whichareabsorbedandmetabolizedinanidenticalway ascompared withtheirlargerforms? Do the nanoscale materials exist as an individual particle, twist,oragglomerate? Concerningthepropertiesofrawandnanoscalematerials,includingsolubility,waterabsorptioncapacity,texture,mass,surfacearea,andconcentration Consideringthemechanical,thermal,andpHstability ofnanoscalematerials3)Processing Nanoscalematerialsarepreparedbytop-down(milling)orbottom-up(synthesis)approaches? Owingtothehighsurfaceareaandadsorptioncapacityofnanoparticles,arethereanyresidualharmfulcompoundsleftaftertheprocessing?4)Safetyconcerns Consideringthepotentialhealthandenvironmentalimpactsofnanoscalematerialseveniftheirmacro-ormicro-sizedcounterpartshavealreadybeenapprovedtouseWhether the nanoscale materials are chemically modied or not? Whether the nanoscale materials are regarded as new substanceornot? Concerningthepotentialriskofthetoxicity,persistence,bio-accumulationandtranslocationofnanoscalematerialsinthebody Whichmethodsandtoolsareusedtomonitor andassessthesafety andtoxicityofnanoscalematerials?277 C.-F.Chauetal./TrendsinFoodScience&Technology18(2007)269e280acquiring public acceptance of the technology ought to ap-praisenot only the accuracy of public risk perceptions, butalso the legitimacy of societal and ethical concerns. Agreater sensitivity(i.e. understandingandresponsiveness)on the part of industry, science, and regulation to the publicdomain is necessary. Societal and ethical research programfor nanotechnology is therefore recommended to ensurethat societal concerns regardingthe potential unintendedconsequencesofthisnewtechnology(rangingfromnega-tive human and environmental impacts to questionable mil-itaryandsurveillanceapplications)areconsidered(Fisher,2005). In2007, theNNI hasfundedresearchprojectsforstudyingthepotential societal impactsofnanotechnologyinordertounderstandthebroadimplicationsofnanotech-nology forsociety,includingeconomic,workforceseduca-tional, ethical, and legal implications (http://www.nano.gov/html/society/home_society.html). These research ef-fortswill beuseful toavoidnegativeperceptionsof newtechnology (e.g. issue arose with genetically modiedorganisms).This review is aimed to have a preliminary discussion onthe development of regulation for nanofoods, hence to pro-videsomehints for theindustry, legislators, andgovern-ment in deliberating the possible nanoregulation inrelationtofoods. Whilemost oftheinformationprovidedby the government agencies in mainland China and Taiwanis presented in Chinese, this article would provide useful in-formation(e.g. thecerticationsystemNanoMark ofnanoproducts) for different parts of the world in developingthecerticationsystemfornanotechnologyfoodproducts.Fromaninternational marketingperspective, arestrictiveregulationmaydiscourage the innovationandmarketingof nanotechnology, leading to an impediment to the growthanddevelopmentofnanofoodindustry.Asanoversightofnanotechnologyistonurturebenecialtechnologiesratherthanstiethem,itisimportanttokeepabalancebetweentoostrict andtooloose indevelopingthestandard,denition, andregulationfor nanofoods. Furthermore, anupdatedscientic evidence of nanotoxicityinclose linkwith the newly innovative nanoproducts would be essentialforthedevelopment ofupdatedregulationsfornanofoodsto minimize the possible impacts of nanotechnology onhealth.AcknowledgementsThisstudywascarriedout withnancial support fromtheDepartmentofHealth,Taiwan.ReferencesBrown,D.M.,Stone,V.,Findlay,P.,MacNee,W.,&Donaldson,K.(2000).Increasedinammationandintracellularcalciumcausedbyultranecarbonblackisindependentoftransitionmetalsorothersolublecomponents.OccupationalandEnvironmentalMedicine,57,685e691.CFSAN. Center forFoodSafety andApplied Nutrition (2005). 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