1. Agrifood Nanotechnology:Agrifood Nanotechnology: Upstream Assessment of Risk andUpstream Assessment of Risk and OversightOversight

2. OutlineOutline Introduction to Nanotechnology & AgrifoodIntroduction to Nanotechnology & Agrifood ApplicationsApplications Risk and Oversight IssuesRisk and Oversight Issues Research on Nano OversightResearch on Nano Oversight DiscussionDiscussion 3. Nanotechnology: What is it?Nanotechnology: What is it? Small, Diverse, Conglomerate of ExistingSmall, Diverse, Conglomerate of Existing Fields (enabling technology)Fields (enabling technology) Unified by 3 criteriaUnified by 3 criteria 1) research and development at the atomic,1) research and development at the atomic, molecularmolecular scale of approximately 1 - 100of approximately 1 - 100 nm range (1 billionth of a meter)nm range (1 billionth of a meter) 2)creating and using structures, devices2)creating and using structures, devices and systems that haveand systems that have novel propertiesnovel properties because of their small size, andbecause of their small size, and 3) ability to3) ability to control or manipulatecontrol or manipulate on theon the atomic scale.atomic scale. Creation of nanomaterials by Top Down orCreation of nanomaterials by Top Down or Bottom Up approachesBottom Up approaches 4. Assembling NanomaterialsAssembling Nanomaterials Bottom up or top downBottom up or top down Use biology (DNA)self assembly/chemical synthesis Use tools (Atomic force microscopy) Use electron beams/ light/chemistry (lithography) Use electricity (electrospray) 5. State of NanotechnologyState of Nanotechnology 2000 National2000 National Nanotechnology InitiativeNanotechnology Initiative (NNI), $270 M for R&D(NNI), $270 M for R&D Unusual, multidisciplinaryUnusual, multidisciplinary Not really mission-basedNot really mission-based 2008 NNI continues, $1.4 B2008 NNI continues, $1.4 B for R&D, including 4% of NNIfor R&D, including 4% of NNI budget devoted to socialbudget devoted to social and ethical implicationsand ethical implications Congressional hearings onCongressional hearings on need for more EHS andneed for more EHS and societal work (2008)societal work (2008) Despite this funding, noDespite this funding, no coordinated U.S.coordinated U.S. governance or oversightgovernance or oversight policy for nanotechnologypolicy for nanotechnology Time for independent studyTime for independent study of oversight models forof oversight models for nanotechnologynanotechnology More talk and acceptance ofMore talk and acceptance of the need for publicthe need for public participation and dialogueparticipation and dialogue early and oftenearly and often 6. NNI organizationNNI organization White House/OSTPCongress PCASTOMB Nanoscale Science, Engineering and Technology Subcommittee Independent Agencies CPSC, EPA, FDA, ITIC, NASA, NIH, NIOSH, NIST, NRC, NSF, OMB, PTO Departments DHS, DHHS, DOC, DOD, DOE, DOJ, DOS, DOT. DOTreas, USDA Nano Health and Environ. Impacts (NEHI) Nano Innovation and Industry Liaison (NIIL) Global Issues In Nanotechnology (GIN) Nano Public Engagement Group (NPEG) Congress PCASTOMB Nanoscale Science, Engineering and Technology Subcommittee Independent Agencies CPSC, EPA, FDA, ITIC, NASA, NIH, NIOSH, NIST, NRC, NSF, OMB, PTO Departments DHS, DHHS, DOC, DOD, DOE, DOJ, DOS, DOT. DOTreas, USDA Nano Health and Environ. Impacts (NEHI) Nano Innovation and Industry Liaison (NIIL) Global Issues In Nanotechnology (GIN) Nano Public Engagement Group (NPEG) National Nanotechnology Coordinating Office (NNCO) Courtesy of N. Savage, EPA 7. NNI historical budgetNNI historical budget 8. NNI recent BudgetNNI recent Budget 9. Anticipatory GovernanceAnticipatory Governance Near Medium Long EHS: Health/environmental risk Technology funding, development, incentives Worker Safety Large Societal changes Social/Ethical Human rights Norms, standards Science, Risk, SocietyScience, Risk, Society 10. Parallels to Ag BiotechnologyParallels to Ag Biotechnology Oversight Policy ChallengesOversight Policy Challenges Applications diverseApplications diverse Agencies and laws broad and diverseAgencies and laws broad and diverse Product not process issuesProduct not process issues Wait and see, using existing laws is theWait and see, using existing laws is the current approachcurrent approach Perils of moving too fast and over promisingPerils of moving too fast and over promising Distribution of risks and benefits of firstDistribution of risks and benefits of first generation productsgeneration products 11. Has agricultural biotechnology suffered? www.isb.vt.edu Some companies abandoning pharmaceutical production in food cropsSome companies abandoning pharmaceutical production in food crops Down swing in approvalsDown swing in approvals Lost trade to EU and other countries with labeling policiesLost trade to EU and other countries with labeling policies Lack of approval of GE animals in U.S.Lack of approval of GE animals in U.S. Has the public suffered as a result? Fewer potential Benefits?Has the public suffered as a result? Fewer potential Benefits? 12. Kuzma, JNR 2007 Selected Categories of Nanotechnology Applied to Food and Agriculture Smart and precision ag Agriculture Bio-Energy or Products Single molecule detection to determine enzyme/substrate interactions (e.g. cellulases in production of ethanol). Materials from biomass Agrochemical Delivery Delivery of pesticides, fertilizers, and other agrichemicals more efficiently (e.g. only when needed or for better absorption). Animal Production Delivery of growth hormone in a controlled fashion. Identity preservation and tracking. Animal or Plant Health Detect animal pathogens, such as foot and mouth disease virus. Detect plant pathogens early. Animal Medicine Deliver animal vaccines. Plant Production Delivery of DNA to plants towards certain tissues (i.e. targeted genetic engineering). Food Sensing Detect chemicals or foodborne pathogens; biodegradable sensors for temperature, moisture history, etc. Safety Selectively bind and remove chemicals or pathogens. Packaging Prevent or respond to spoilage. Sensing features for contaminants or pathogens. Healthy Food Better availability and dispersion of nutrients, nutraceuticals, or additives. 13. Agrifood Nano-Products on MarketAgrifood Nano-Products on Market Glycerin micelles to remove pesticides Micelles for functional food (phytosterols) Geohumus Soil wetting agent PrimoMAXX Syngenta (plant growth regulator) Several dietary supplements Traceability of food and feed FoodExpert-ID DNA chipbioMrieux Nanobarcodes , Nanoplex Technologies, USA Project on Emerging Nanotechnologies consumer inventory www.nanotechproject.org Storage of food with Ag antimicrobialStorage of food with Ag antimicrobial Cocoa delivery with little sugarCocoa delivery with little sugar Cooking Oil Quality--nanoceramicCooking Oil Quality--nanoceramic Nanoclay barriers to ONanoclay barriers to O22 and COand CO22 Omega-3 bakery productsOmega-3 bakery products Lycopene BASFLycopene BASF 14. Agrichemicals in developmentAgrichemicals in development FOE 2008 15. ConvergenceConvergence Nano-Geo-(Bio)-Info technologyNano-Geo-(Bio)-Info technology Berry et al. 2008 16. Stages of NanoStages of Nano 2001 2005 2010 2020 Systems of Nanosystems Robotics 3D networks Guided assemblers Molecular Nanosystems Molecules by design Evolutionary systems Passive Nanostructures Coatings, polymers,ceramic s Active Nanostructures Transistors Targeted drugs Adaptive structures Quantum/classical physics interface Self-directed, emergent behaviors Nano-Bio Interface Adapted from M. Roco NSF Drexler Rice University 2001 2005 2010 2020 Agrifood applicatinos currently in passive to early active stage 17. Emerging products for trackingEmerging products for tracking FoodExpert-ID DNA chipbioMrieux, France 80,000 oligonucleotide probes synthesized onto a glass surface using photolithography. specific vertebrate cytochrome b genes identification of animal species in sample Traceability of food and feed Nanobarcodes , Nanoplex Technologies, USA Supply chain tracking 18. Special Features of NanoparticlesSpecial Features of Nanoparticles A double-edged swordA double-edged sword Promise Pitfalls Increased surface area Increased reactivity? Increased bioavailability and targeted to certain tissues Increased toxicity? Lower doses effective Lower doses toxic? Penetration ability for remediation Impair subsurface ecosystems Skin, membrane penetration may speed onset of action Toxicity through nontraditional routes of administration? 19. Percent of Neutrophils in BAL 24 hrs after Instillation of TiO2 in Rats 0 500 1000 1500 2000 0 10 20 30 40 50 ultrafine TiO2 (~20nm) fine TiO2 (~250nm) saline Correlation with Particle Mass Particle Mass, g %Neutrophils J. Finkelstein, presentation 2005 20. Implications Side: Unique Challenges?Implications Side: Unique Challenges? Distribution in soils, water, airDistribution in soils, water, air Transport, transformation and fateTransport, transformation and fate ReactivityReactivity Unique challenges?Unique challenges? Impacts on human health--ToxicologyImpacts on human health--Toxicology Exposure--Inhalation, ingestion,Exposure--Inhalation, ingestion, contactcontact Dose-ResponseDose-Response Bioaccumulation,Bioaccumulation, biotransformation, bioavailabilitybiotransformation, bioavailability Impacts on ecosystems and particularImpacts on ecosystems and particular speciesspecies Either direct (toxicity)Either direct (toxicity) Indirect (changes local conditionsIndirect (changes local conditions or prey)or prey) Royal Society 2004 Fullerene Toxicity studies 21. Risk analysisRisk analysis Many being developedMany being developed (Morgan, Risk Analysis 2005) BUT..Little to no data to fill boxes Data on product safety not in public domain --Conflict of interest, transparency and intellectual property rights About 1% to 5% of NNI budget goes to Environmental Health & Safety Research Frameworks developing 22. Gaps in Oversight?Gaps in Oversight? CPSC EPA OSHA FDA USDA TODAY 2006 2010 No pre-market testing Pre-market testing possible Pre-market testing required Lack of guidance Chemicals/Particles Manufacturing Devices Drugs/biologics Agricultural products Food Cosmetics Consumer Products Adapted from E. Michelson,WWIC 23. Oversight CharacteristicsOversight Characteristics Complex mixture of laws andComplex mixture of laws and featuresfeatures Some technology based,Some technology based, others command and controlothers command and control Mixed burden of proof inMixed burden of proof in existing regulationsexisting regulations Some medium based, someSome medium based, some intent based, someintent based, some manufacturing & use basedmanufacturing & use based Existing regulations arguablyExisting regulations arguably have adequate authority tohave adequate authority to regulate nanotechnology if soregulate nanotechnology if so desireddesired (American Bar Association 2006)(American Bar Association 2006) Current resources inadequateCurrent resources inadequate for existing regulatory structuresfor existing regulatory structures to oversee nanotechnologyto oversee nanotechnology Current statutes orCurrent statutes or interpretation of them paralyzeinterpretation of them paralyze regulatory agencies (TSCA andregulatory agencies (TSCA and burden of proof)burden of proof) Nano version of existingNano version of existing products does not triggerproducts does not trigger regulationregulation New law best solutionNew law best solution (Davies 2006)(Davies 2006) 24. Coordinated Framework for the Regulation ofCoordinated Framework for the Regulation of Biotechnology Products circa 1986Biotechnology Products circa 1986 AgencyAgency JurisdictionJurisdiction LawsLaws US Dept. ofUS Dept. of Agriculture (USDA)Agriculture (USDA) Plant pests, plants,Plant pests, plants, veterinary biologicsveterinary biologics Federal Plant Pest ActFederal Plant Pest Act (FPPA)1957(FPPA)1957 Food and DrugFood and Drug AdministrationAdministration (FDA)(FDA) Food, feed, food additives,Food, feed, food additives, vet. Drugs, human drugs,vet. Drugs, human drugs, medical devicesmedical devices Federal Food, Drug andFederal Food, Drug and Cosmetic Act (FFDCA)--Cosmetic Act (FFDCA)-- 19581958 EnvironmentalEnvironmental Protection AgencyProtection Agency (EPA)(EPA) Microbial and plantMicrobial and plant pesticides; novel microbespesticides; novel microbes Federal Insecticide,Federal Insecticide, Fungicide, andFungicide, and Rodenticide Act (FIFRA)--Rodenticide Act (FIFRA)-- 1947; Toxic Substances1947; Toxic Substances Control Act (TSCA)--1976Control Act (TSCA)--1976 No new risks, no new laws needed, product not process 25. Coordinated Framework ProposalCoordinated Framework Proposal Kuzma ELR 2006 4 arguments for coordinated oversight of nano4 arguments for coordinated oversight of nano Regulation is an important part of governance for emerging technologicalRegulation is an important part of governance for emerging technological applications and productsapplications and products New laws and institutions are not necessary in the near term, much canNew laws and institutions are not necessary in the near term, much can be done for nanotechnologypolitical will is main barrierbe done for nanotechnologypolitical will is main barrier Coordinated framework for regulation of nano products is possible basedCoordinated framework for regulation of nano products is possible based on existing statuteson existing statutes Law is based on policy can be interpreted broadly. There is precendentLaw is based on policy can be interpreted broadly. There is precendent for doing so.for doing so. 26. PossiblePossible FrameworkFramework Kuzma ELR 2006Kuzma ELR 2006 Several roles forSeveral roles for USDAUSDA 27. Oversight ProgramsOversight Programs Industry Standards and Guidelines ICON, ANSI, ISO, IRGC, Foresight Institute IRGCindustry reportcant regulate, too much uncertainty and little data ED and DuPont partnership Risk Framework 2007 EPA Nanoscale Voluntary Program under TSCA implemented 2008 EPA decision to regulate nano-silver emitted from washing machines as pesticide under FIFRA2007 REACH EUIs nano captured? 28. Risk Assessment of EngineeredRisk Assessment of Engineered NanomaterialsNanomaterials Helland et al, EST 42:640 (2008)Helland et al, EST 42:640 (2008) 40 German and Swiss companies working with NMs40 German and Swiss companies working with NMs 65% do not perform any risk assessment of their NMs65% do not perform any risk assessment of their NMs 45% no toxicity tests45% no toxicity tests Participation in the UKs voluntary program is minimal (DEFRAParticipation in the UKs voluntary program is minimal (DEFRA 2006)2006) U.S. voluntary systemas of May 2008U.S. voluntary systemas of May 2008 DuPont and Office ZPI, while 10 other companies haveDuPont and Office ZPI, while 10 other companies have committed to reporting.committed to reporting. 29. Public InterfacePublic Interface Focal Groups & ConsensusFocal Groups & Consensus ConferencesConferences Studies indicate little knowledge butStudies indicate little knowledge but general support forgeneral support for nanotechnologypublic seesnanotechnologypublic sees benefits.benefits. However,However, labeling, mandatorylabeling, mandatory safety testing and bettersafety testing and better access to informationaccess to information aboutabout which nanotechnologies arewhich nanotechnologies are being publicly funded arebeing publicly funded are important to publicimportant to public Hart Res. Assoc. 2007 30. What Do People Care About withWhat Do People Care About with Regard to Risk?Regard to Risk? People do not care only aboutPeople do not care only about the number of deaths andthe number of deaths and injuries.injuries. They also care aboutThey also care about - EquityEquity - ControllabilityControllability - Voluntary or involuntary exposureVoluntary or involuntary exposure - Time Frame: Immediate or delayedTime Frame: Immediate or delayed - Intergenerational effectsIntergenerational effects - Nature and extent of KnowledgeNature and extent of Knowledge - (multiple works of social psychologists,(multiple works of social psychologists, P. Slovic, Decision Research, and B.P. Slovic, Decision Research, and B. Fischoff, CMU)Fischoff, CMU) Unknown Dread Auto Exhaust DNA Technology Radioactive Waste Bicycles Home Swimming Pools PVC Coal Mining Antibiotics Slovicet al, 1980 Unknown Dread Auto Exhaust DNA Technology Radioactive Waste Bicycles Home Swimming Pools PVC Coal Mining Antibiotics Slovicet al, 1980 31. Siegrist, et al 2007 Food packaging outside Better accepted than food particles inside Public views dependent onPublic views dependent on productproduct && trusttrust 32. Looming regulatory policy questionsLooming regulatory policy questions 1) Should benefits be considered in the regulatory process?1) Should benefits be considered in the regulatory process? Most agencies do not have authority to do soMost agencies do not have authority to do so Harm from NOT approving new technologies?Harm from NOT approving new technologies? Delicate balanceassuring safety and public confidence and allowing technology toDelicate balanceassuring safety and public confidence and allowing technology to flourish and do good in societyflourish and do good in society 2) How much weight should be placed on potential, but not demonstrated,2) How much weight should be placed on potential, but not demonstrated, risks?risks? Cultural differencesEU vs. US on GEOsCultural differencesEU vs. US on GEOs 3) Who should be engaged in setting boundaries and standards?3) Who should be engaged in setting boundaries and standards? Who should be involved in setting acceptable levels of risk?Who should be involved in setting acceptable levels of risk? What risk information is available and generated by independent sources?What risk information is available and generated by independent sources? Should the public be engaged?Should the public be engaged? 4) What about other factors (e.g. social, cultural, and ethical) should they be4) What about other factors (e.g. social, cultural, and ethical) should they be considered in oversight processes? If so, how?considered in oversight processes? If so, how? 33. Social & Ethical IssuesSocial & Ethical Issues Utilitarian, Intrinsic, Structural,Utilitarian, Intrinsic, Structural, Rights-basedRights-based Distribution of risks and benefits?Distribution of risks and benefits? (GEOs parallels)(GEOs parallels) How far should we go with humanHow far should we go with human enhancement? (NBIC, Roco 2005)enhancement? (NBIC, Roco 2005) Technology have and have-nots?Technology have and have-nots? IPR and ownership impacts?IPR and ownership impacts? Technology drawing attention awayTechnology drawing attention away from more sustainable low-techfrom more sustainable low-tech solutions?solutions? Privacy issues with surveillance &Privacy issues with surveillance & detection?detection? Held together by principles ofHeld together by principles of justice, equity and fairnessjustice, equity and fairness Not a distinct separation betweenNot a distinct separation between risk or technical issues and otherrisk or technical issues and other onesones Power relationships within safetyPower relationships within safety evaluationsevaluations (Lewenstein 2005; Kuzma in(Lewenstein 2005; Kuzma in press, Nanoethics)press, Nanoethics) 34. Comprehensive Study of Oversight PolicyComprehensive Study of Oversight Policy Scientists Technology Developers Risk Assessors Regulatory Policy Makers Practical S&T Policy Wonks Regulatory Assessors (CBA focused) Social Scientists S&T Studies Political Scientists Public Policy Analysts Historians And Philosophers of Science Lawyers Academic Legal Studies Other Fields? Input? Social Psychology Who is thinking about oversight in a comprehensive way? Ethicists Communication Experts Economists 35. Two ApproachesTwo Approaches Top-Down & Botton UpTop-Down & Botton Up Anticipatory Oversight PolicyAnticipatory Oversight Policy Agrifood nano Lessons from GEOs Oversight 36. Why Agrifood Nanotechnology?Why Agrifood Nanotechnology? Little information about R&D, safety,Little information about R&D, safety, and products in the public domainand products in the public domain (CBI, IPR)(CBI, IPR) Overlapping or missing jurisdiction forOverlapping or missing jurisdiction for products (e.g. premarket testing)products (e.g. premarket testing) Food and humans have a specialFood and humans have a special relationship tied to necessity, culture,relationship tied to necessity, culture, and environment.and environment. Distribution of risks and benefits areDistribution of risks and benefits are often different than for medicaloften different than for medical applicationsapplications Need for transparency in productNeed for transparency in product review and oversight processreview and oversight process Need for regulatory clarity and holisticNeed for regulatory clarity and holistic approaches to convergence productsapproaches to convergence products EU vs. US position on GEOs in foodEU vs. US position on GEOs in food and agriculture (internationaland agriculture (international harmonization)harmonization) Initially, few benefits to those who boreInitially, few benefits to those who bore any potential riskany potential risk Need for public information andNeed for public information and dialogue early and oftendialogue early and often Holds promise for moreHolds promise for more sustainablesustainable and safer methods of food and fiber productionand safer methods of food and fiber production Lots of potential applications, a few on the market, but currently, little attention to oversight issuesLots of potential applications, a few on the market, but currently, little attention to oversight issues Potential Challenges: Lessons (AgBiotech) : Time for independent study of oversight models for agrifood nanotechnologyTime for independent study of oversight models for agrifood nanotechnology 37. Bottom Up MethodsBottom Up Methods Agrifood Nanotechnology OversightAgrifood Nanotechnology Oversight Phase 1*: Start with individual productsPhase 1*: Start with individual products Inventory, survey, and assessment ofInventory, survey, and assessment of research and development inresearch and development in nanotechnology as applied to food,nanotechnology as applied to food, agriculture, and agroecosystemsagriculture, and agroecosystems Phase 2:* Select individual productsPhase 2:* Select individual products Selection of case studies andSelection of case studies and qualitative risk/benefit issuequalitative risk/benefit issue identificationidentification Phase 3: Assess individual products,Phase 3: Assess individual products, extrapolate upextrapolate up Analysis of regulatory or non-regulatoryAnalysis of regulatory or non-regulatory governance systems for agrifoodgovernance systems for agrifood applicationsapplications ** Research TopicsResearch Topics Research TechniquesResearch Techniques Estimated time to commercializationEstimated time to commercialization Part of food or product supply chainPart of food or product supply chain Endpoints of exposureEndpoints of exposure Qualitative risk/benefit rankingQualitative risk/benefit ranking 38. Methodology for inventoryMethodology for inventory Public databases and websitesPublic databases and websites Nano and food or agriculture as search termsNano and food or agriculture as search terms USDA-CRIS, PTO, EPA, NIH, DOE, DOD, DHS, NSFUSDA-CRIS, PTO, EPA, NIH, DOE, DOD, DHS, NSF 2000-Fall 20052000-Fall 2005 Adjusted USDA categories for research, techniques, and topics asAdjusted USDA categories for research, techniques, and topics as specified in 2003 report,specified in 2003 report, Nanoscale Science and Engineering forNanoscale Science and Engineering for Agriculture and Food Systems.Agriculture and Food Systems. Own criteria for other categories, such as type of research, time toOwn criteria for other categories, such as type of research, time to commercialization, qualitative risk/benefit ranking, exposurecommercialization, qualitative risk/benefit ranking, exposure endpoints, sectors in the food supply continuumendpoints, sectors in the food supply continuum 160 projects were found160 projects were found 121 entries were sent to PIs121 entries were sent to PIs for reviewreview 39. Agrifood Nanotechnology InventoryAgrifood Nanotechnology Inventory LimitationsLimitations Not focused on industrial or consumer productsNot focused on industrial or consumer products Stopped searches in Dec. 2005needs updating on a regular basisStopped searches in Dec. 2005needs updating on a regular basis Publicly available informationPublicly available information No investigative reportingNo investigative reporting Categorization based on available information and PI knowledge/experienceCategorization based on available information and PI knowledge/experience Reviewed by PIs positively, but limited response (14%)Reviewed by PIs positively, but limited response (14%) StrengthsStrengths Good start to getting compiled information, analysis, and dialogue in publicGood start to getting compiled information, analysis, and dialogue in public domaindomain Independent analysis (e.g. PIs have no vested interest in this topic, such asIndependent analysis (e.g. PIs have no vested interest in this topic, such as stock holdings, products being developed, ties to agencies, etc,)stock holdings, products being developed, ties to agencies, etc,) 40. Techniques for Projects 41. Topics for Projects 42. USDA Research AreasUSDA Research Areas 43. Stage and Type of WorkStage and Type of Work 44. Sector of Food Supply Chain 45. Endpoints of ExposureEndpoints of Exposure Kuzma & Verhage PEN 2006 46. Risk and Benefit Qualitative RankingRisk and Benefit Qualitative Ranking 47. Mining the Database to Focus EHS research 48. Other ways to mine databaseOther ways to mine database Particles of interestParticles of interest Private vs. publicPrivate vs. public 0 20 40 60 80 100 120 140 160 Silver(4) TiO 2 (4) CNT (5) Fullerenes (2) Total 2 5 9028 15 20 EPA NIH USDA PTO (ind.) PTO (univ) NSF 49. Key Results of Agrifood InventoryKey Results of Agrifood Inventory Large focus on food packaging andLarge focus on food packaging and sensing for foodborne pathogenssensing for foodborne pathogens Focus on retail and consumerFocus on retail and consumer applicationsapplications More of a focus on health thanMore of a focus on health than environmental benefits. But significantenvironmental benefits. But significant proportion on environment/ag wasteproportion on environment/ag waste No high risk projects, according toNo high risk projects, according to our criteria of toxic materials underour criteria of toxic materials under widespread usewidespread use Most projects applied, and projected toMost projects applied, and projected to be commercial in 5-15 years.be commercial in 5-15 years. Database can be mined in variousDatabase can be mined in various ways to focus EHS researchways to focus EHS research 50. Bottom Up MethodsBottom Up Methods Agrifood Nanotechnology OversightAgrifood Nanotechnology Oversight Phase 1*: Start with individualPhase 1*: Start with individual productsproducts Inventory and assessment ofInventory and assessment of research and development inresearch and development in nanotechnology as applied tonanotechnology as applied to food, agriculture, andfood, agriculture, and agroecosystemsagroecosystems Phase 2:* Select individual productsPhase 2:* Select individual products Selection of case studies andSelection of case studies and qualitative risk/benefit issuequalitative risk/benefit issue identificationidentification Phase 3:* Assess individualPhase 3:* Assess individual products, extrapolate upproducts, extrapolate up Analysis of oversight systemsAnalysis of oversight systems and issues for selected agrifoodand issues for selected agrifood applicationsapplications Criteria for case selection:Criteria for case selection: Frequency of topics and techniques inFrequency of topics and techniques in databasedatabase Sector of supply chainSector of supply chain Exposure endpointsExposure endpoints Oversight relevanceOversight relevance Research Methods:Research Methods: Literature searchesToxnet, Fed Reg, etc.Literature searchesToxnet, Fed Reg, etc. Researcher inquiriesResearcher inquiries Case study comparison approachCase study comparison approach 51. Case Study #1Case Study #1 AgroecosystemEnvironmental applicationAgroecosystemEnvironmental application Using Nanotechnology to identify and characterize hydrological flowpaths inUsing Nanotechnology to identify and characterize hydrological flowpaths in agricultural landscapes (Walter, et al. Cornell University)agricultural landscapes (Walter, et al. Cornell University) Encapsulated DNA and PCR detection--use the vast diversity of DNA sequences forEncapsulated DNA and PCR detection--use the vast diversity of DNA sequences for finer resolution of flows in order to address non-point source pollutionfiner resolution of flows in order to address non-point source pollution . Photo from Quinn et al. http://www.ncl.ac.uk/wrgi/TOPCAT/TCTheory.html 52. Case Study #1Case Study #1 Risk & Oversight IssuesRisk & Oversight Issues Risk IssuesRisk Issues CapsuleCapsule Generally non-toxicGenerally non-toxic PLGA-chitosan used in drug-deliveryPLGA-chitosan used in drug-delivery Dissolve in waterDissolve in water However, not tested at large scaleHowever, not tested at large scale environmental releaseenvironmental release Fate and transport in environmentFate and transport in environment Information neededInformation needed PIs are conducting this work in phase IIPIs are conducting this work in phase II DNADNA Uptake by microbes?Uptake by microbes? Persistence and fate in environment?Persistence and fate in environment? Usually degradedUsually degraded Oversight IssuesOversight Issues Broad range of statutesBroad range of statutes TSCA, CWA, FIFRA, etc?TSCA, CWA, FIFRA, etc? Lack of certainty about convergenceLack of certainty about convergence applicationsapplications Nano-bio-environmentNano-bio-environment Detection capabilitiesDetection capabilities For large scale release?For large scale release? SocietalSocietal Public perception and concern aboutPublic perception and concern about large scale release of DNA in thelarge scale release of DNA in the environmentenvironment 53. Case Study #1Case Study #1 ConclusionsConclusions Relatively easy to find information on nature of particleRelatively easy to find information on nature of particle and researchers plans (transparent)and researchers plans (transparent) High degree of uncertainty as to regulatory system &High degree of uncertainty as to regulatory system & statutesstatutes Research needs on fate and transport of PLGA and DNAResearch needs on fate and transport of PLGA and DNA project included some of these elementsproject included some of these elements High potential for public concern in watershed areasHigh potential for public concern in watershed areas perception of DNA released into environmentperception of DNA released into environment 54. Case study 2: On-farm plant productionCase study 2: On-farm plant production Nano-and Micro-encapsulation of Agrochemicals Nano-and Micro-encapsulation of Agrochemicals SBIR Phase 1, LNK ChemsolutionsSBIR Phase 1, LNK Chemsolutions 1-Naphthalene Acetic acid (NAA, the target agrochemical) in chitosan1-Naphthalene Acetic acid (NAA, the target agrochemical) in chitosan Timed release of agrochemicals, lesser amountsTimed release of agrochemicals, lesser amounts Marie, et al. Biomolecules, 2002, Chitosan nanocapsule 55. Case Study #2Case Study #2 Risk & Oversight IssuesRisk & Oversight Issues Risk IssuesRisk Issues Capsule--chitosanCapsule--chitosan Generally non-toxicGenerally non-toxic Many toxicity studies foundMany toxicity studies found However, not tested at large scaleHowever, not tested at large scale environmental releaseenvironmental release Fate and transport in environmentFate and transport in environment Information neededInformation needed Not clear if it is being fundedNot clear if it is being funded NAAplant growth regulatorNAAplant growth regulator Toxicity studies at macro level indicateToxicity studies at macro level indicate human nasal, skin, and severe eyehuman nasal, skin, and severe eye irritantirritant Effects on animals include CNSEffects on animals include CNS depression, decreased live births, birthdepression, decreased live births, birth weight, and infant survivalweight, and infant survival Data submitted to EPA for registrationData submitted to EPA for registration Exemption for food tolerance underExemption for food tolerance under FQPAFQPA Oversight IssuesOversight Issues Clear StatuteFIFRAClear StatuteFIFRA Nano-scale formulation evoked?Nano-scale formulation evoked? Social IssuesSocial Issues Special attention and concerns relatedSpecial attention and concerns related to nano-scale formulation of commonlyto nano-scale formulation of commonly used substances?used substances? General perceptions of pesticides inGeneral perceptions of pesticides in the environmentthe environment 56. Case Study #2Case Study #2 ConclusionsConclusions Relatively easy to find information on nanoparticle as componentsRelatively easy to find information on nanoparticle as components are both already used in drugs and agricultureare both already used in drugs and agriculture High degree of uncertainty as to whether regulatory system &High degree of uncertainty as to whether regulatory system & statutes would give attention to the nano scalestatutes would give attention to the nano scale Research needs on fate and transport of chitosan (and NAA?) inResearch needs on fate and transport of chitosan (and NAA?) in environmentenvironment Research needs on health effects at nanoscaleFQPA exemption?Research needs on health effects at nanoscaleFQPA exemption? Public generally concerned about agrochemicals, but what concernsPublic generally concerned about agrochemicals, but what concerns would the nano-version trigger? (UPE)would the nano-version trigger? (UPE) 57. Case Study #3Food additivesCase Study #3Food additives Nano-and Micro-encapsulation of Food AdditivesNano-and Micro-encapsulation of Food Additives SBIR Phase 1, LNK ChemsolutionsSBIR Phase 1, LNK Chemsolutions Gum arabic/maltodextrin formulation for the shell of citral capsulesGum arabic/maltodextrin formulation for the shell of citral capsules Timed release of nutraceuticals that inhibits bacterial growth and imparts lemon flavorTimed release of nutraceuticals that inhibits bacterial growth and imparts lemon flavor Capsule restricts the diffusion of air and dissolves readilyCapsule restricts the diffusion of air and dissolves readily 58. Case Study #3Case Study #3 Risk & Oversight IssuesRisk & Oversight Issues Risk IssuesRisk Issues CapsuleCapsule GRASGRAS Only harmful when animalsOnly harmful when animals overfedno carcinogenic effectsoverfedno carcinogenic effects No nano encapuslation toxicityNo nano encapuslation toxicity studies, howeverstudies, however Fate and transport in environmentFate and transport in environment Information neededInformation needed Not clear if it is being fundedNot clear if it is being funded CitralCitral Micro encapsulated citral shown toMicro encapsulated citral shown to have negative effects for animalhave negative effects for animal feeding studiesfeeding studies Malignant lymphomaMalignant lymphoma Liver and fore-stomach damageLiver and fore-stomach damage Oversight IssuesOversight Issues Clear StatuteFFDCAClear StatuteFFDCA GRAS or food additive?GRAS or food additive? Micro-level citral GRASMicro-level citral GRAS DSHEA if not in food-supplementDSHEA if not in food-supplement Social IssuesSocial Issues Consumer knowledge of risks andConsumer knowledge of risks and benefits of encapsulated citral atbenefits of encapsulated citral at nano scalenano scale LabelingLabeling Post-market monitoringPost-market monitoring Transparency in safety processTransparency in safety process Industry does testingIndustry does testing FDA relies on industry nanoFDA relies on industry nano claimsclaims 59. Case Study #3Case Study #3 ConclusionsConclusions Relatively easy to find information on nanoparticle as componentsRelatively easy to find information on nanoparticle as components are both already used in food and dietary supplementsare both already used in food and dietary supplements High degree of uncertainty as to whether regulatory system &High degree of uncertainty as to whether regulatory system & statutes would give attention to the nano scalestatutes would give attention to the nano scale Research needs on health effects at nanoscaleis citral GRAS,Research needs on health effects at nanoscaleis citral GRAS, especially at the nanoscale?especially at the nanoscale? Pre and post market safety evaluation given citral effectsPre and post market safety evaluation given citral effects Consumer rights to knowlabeling of nano-particles in foodConsumer rights to knowlabeling of nano-particles in food 60. Case study #4biobased consumer andCase study #4biobased consumer and medical productsmedical products Cellulose Nanocrystal Composites (Simonsen, OSU)Cellulose Nanocrystal Composites (Simonsen, OSU) Stronger than steel or alumiumStronger than steel or alumium AFM image of cellulose nanocrystal film, Simonsen, http://woodscience.oregonstate.edu/faculty/simonsen/ 61. Case Study #4Case Study #4 Risk & Oversight IssuesRisk & Oversight Issues Risk IssuesRisk Issues Cellulose nanocompositesCellulose nanocomposites Diffusion out of matrix?Diffusion out of matrix? Microcrystalsno observed effectMicrocrystalsno observed effect Fate and transport in medical productFate and transport in medical product Diffusion out of filters forDiffusion out of filters for hemodialysis?hemodialysis? Blood toxicityBlood toxicity Cross blood-CNS barriers?Cross blood-CNS barriers? For non-medical productFor non-medical product Life cycle issuesLife cycle issues Environmental pros and consEnvironmental pros and cons Oversight IssuesOversight Issues Clear Statute for device useClear Statute for device use FFDCA and medical deviceFFDCA and medical device amendmentsamendments Will nano composites in devices byWill nano composites in devices by considered as new or under class I orconsidered as new or under class I or II PMN and 510k?II PMN and 510k? WHO precautionary approach toWHO precautionary approach to crystals under 5 umcrystals under 5 um Limit content of particles under thisLimit content of particles under this sizesize ADI not specifiedADI not specified Social IssuesSocial Issues Medical community informedMedical community informed about nanoscale particlesabout nanoscale particles embedded in matrix?embedded in matrix? Patients informed?Patients informed? Acceptable level of risk versusAcceptable level of risk versus medical benefit of improvedmedical benefit of improved dialysis?dialysis? 62. Case Study #4Case Study #4 ConclusionsConclusions Relatively easy to find information on nanoparticle as components used inRelatively easy to find information on nanoparticle as components used in materialsmaterials Research needs on nanocellulose diffusion out of matricesResearch needs on nanocellulose diffusion out of matrices Research needs on health effects at nanoscaleis micro and nano scaleResearch needs on health effects at nanoscaleis micro and nano scale cellulose of concern?cellulose of concern? FDA might not consider nanocellulose in devices as a novel deviceClass IFDA might not consider nanocellulose in devices as a novel deviceClass I or IIor II International harmonizationWHO taking precautionary approachInternational harmonizationWHO taking precautionary approach Patient/doctors ability to knowenough information to determine what riskPatient/doctors ability to knowenough information to determine what risk is acceptable for them vs. the medical benefitis acceptable for them vs. the medical benefit Life cycle analyses of production of nanocellulose and environmentalLife cycle analyses of production of nanocellulose and environmental benefits-risksbenefits-risks 63. Case study #5Animal production & foodCase study #5Animal production & food safetysafety Adhesin-specific Nanoparticles for removal of pathogens from livestockAdhesin-specific Nanoparticles for removal of pathogens from livestock *Latour et al. Clemson University*Latour et al. Clemson University Block bacterial colonization in guts and remove these important humanBlock bacterial colonization in guts and remove these important human pathogens on the farmpathogens on the farm . Photo from Dr. Gary E. Kaiser, http://student.ccbcmd.edu/~gkaiser/goshp.html Nanoparticles bind and block this interaction 64. Case Study #5Case Study #5 Risk & Oversight IssuesRisk & Oversight Issues Risk IssuesRisk Issues Use of polyethylene glycol for deliveryUse of polyethylene glycol for delivery PEG shown to be safePEG shown to be safe No effect on cell death and do notNo effect on cell death and do not activate immune responseactivate immune response Nano version effects not knownNano version effects not known Weigh any potential risk with benefit ofWeigh any potential risk with benefit of reduction of antibiotics important forreduction of antibiotics important for human healthhuman health Targeting moleculeTargeting molecule Mannose for E. coliMannose for E. coli Effects on other helpful gut floraEffects on other helpful gut flora On farm useOn farm use Effects on environmental floraEffects on environmental flora Animal waste streams to waterAnimal waste streams to water Oversight IssuesOversight Issues Difficult to find information on theDifficult to find information on the nanoparticlenanoparticle Intellectual property issuesIntellectual property issues Statutory authority and exercise byStatutory authority and exercise by agencies unclearagencies unclear CWA and CAFO for animalCWA and CAFO for animal waste?waste? FFDCANAD?FFDCANAD? FDA--Feed additive or GRAS?FDA--Feed additive or GRAS? Agencys Feed Safety SystemAgencys Feed Safety System USDA (VSTA)USDA (VSTA) SocialSocial Risk perceptionRisk perception Trust in ag industryTrust in ag industry Antibiotics and/or hormones inAntibiotics and/or hormones in meat?meat? 65. Case Study #5Case Study #5 ConclusionsConclusions Not very easy to find information on nanoparticles, as intellectualNot very easy to find information on nanoparticles, as intellectual property rights soughtproperty rights sought Regulatory uncertaintyconvergence-type productRegulatory uncertaintyconvergence-type product Trust and independence of communicatorsTrust and independence of communicators Benefits of antibiotic reductionhuman health benefitsBenefits of antibiotic reductionhuman health benefits Perception of antibiotics or hormones in foodPerception of antibiotics or hormones in food Research needs on environmental issues with nanoparticles inResearch needs on environmental issues with nanoparticles in animal wasteanimal waste 66. Case Study #6Food quality and safety inCase Study #6Food quality and safety in retail and consumptionretail and consumption Nanoclays in food packaging materialsbarriers to O2 and CO2Nanoclays in food packaging materialsbarriers to O2 and CO2 Silica, silicite, clay,organomontmorillonite, calcium carbonateSilica, silicite, clay,organomontmorillonite, calcium carbonate Picture from CSIRO http://www.cmit.csiro.au/brochures/tech/nanotech/ 67. Case Study #6Case Study #6 Risk & Oversight IssuesRisk & Oversight Issues Risk IssuesRisk Issues Clay nanoparticles toxicityClay nanoparticles toxicity Macro versions non-toxicMacro versions non-toxic Nano versions more reactive, and whatNano versions more reactive, and what does this mean for toxicity?does this mean for toxicity? Nanoparticle migration out of matricesNanoparticle migration out of matrices Lack of researchLack of research Migration likely lowMigration likely low When composites containWhen composites contain antimicrobials, detection molecules,antimicrobials, detection molecules, etc. there will be additional risk issuesetc. there will be additional risk issues Ag in food packagingAg in food packaging Life cycle issues with manufacturingLife cycle issues with manufacturing Oversight IssuesOversight Issues Statutory authority clearFFDCAStatutory authority clearFFDCA Food Contact SubstancesFood Contact Substances (Food additive or GRAS if there is(Food additive or GRAS if there is a substance in packaging that isa substance in packaging that is intended to migrate to food)intended to migrate to food) Most now go through NotificationMost now go through Notification Process now (FCN)Process now (FCN) Data requirements?Data requirements? Ag in packaging has gone throughAg in packaging has gone through this processthis process Social IssuesSocial Issues Transparency &TrustBPA?Transparency &TrustBPA? Many FCS with nanoparticles onMany FCS with nanoparticles on market,market, Public unaware and safety studiesPublic unaware and safety studies not availablenot available 68. Case Study #6Case Study #6 ConclusionsConclusions Many patents, and compositions of marketed products can beMany patents, and compositions of marketed products can be found, but not easily (I.e. no FDA website of nanopackagingfound, but not easily (I.e. no FDA website of nanopackaging materials and data submitted, and FCN)materials and data submitted, and FCN) Transparency and public trust/consumer knowledgeTransparency and public trust/consumer knowledge Regulatory mechanism clear, but questions as to whether FDARegulatory mechanism clear, but questions as to whether FDA would be likely to invoke the petition and threshold process forwould be likely to invoke the petition and threshold process for nanocompositesnanocomposites Research needs on environmental issues with nanoparticles duringResearch needs on environmental issues with nanoparticles during manufacturinghigh volume application (TSCA, RCRA, etc.)manufacturinghigh volume application (TSCA, RCRA, etc.) 69. UpstreamUpstream Oversight AssessmentOversight AssessmentDatabase of 160 Emerging R&D Applications of Agrifood Nanotechnology1 Selection of Case Studies Case Study Analysis Approach Identification of Risk and Oversight Policy Issues2 Kuzma, Romanchek, Kokotovich Risk Analysis, in press 70. Agrifood Future WorkAgrifood Future Work Update database and select additional casesUpdate database and select additional cases Use of case study analysis forUse of case study analysis for Expert judgment solicitationExpert judgment solicitation Upstream public engagementUpstream public engagement Discussions with decision makerDiscussions with decision maker First year USDA has included ELSI componentFirst year USDA has included ELSI component in RFPin RFP (Lindquist, Verdlitz, and Kuzma USDA proposal)(Lindquist, Verdlitz, and Kuzma USDA proposal) 71. Anticipatory GovernanceAnticipatory Governance UOA UPE--Upstream Public Engagement RTTA Upstream Oversight Assessment (guided by Integrated Oversight Assessment) Real Time Technology Assessment Integrate natural science and engineering investigations with social science and policy research from the outsetGuston and Sarewitz, ASU Identify and address regulatory and non- regulatory oversight issues associated with new technological products long before they are marketed so that system is preparedKuzma et al., UMN McNaughten, Willis, Wilsdon, Wynne, Marris, et al. 72. Top-Down Approach to Study Oversight forTop-Down Approach to Study Oversight for NanotechnologyNanotechnology Wolf, Kokolli, Kuzma, Paradise, RamachandranWolf, Kokolli, Kuzma, Paradise, Ramachandran Multiple methods criteria, disciplines, stakeholders, and experts involvedMultiple methods criteria, disciplines, stakeholders, and experts involved Rooted in historical analysis, expert elicitation, stakeholder input, and multi-Rooted in historical analysis, expert elicitation, stakeholder input, and multi- criteria decision analysiscriteria decision analysis Quantitative & Qualitative, Normative and EmpiricalQuantitative & Qualitative, Normative and Empirical Phase 1Evaluation of 6 historical oversight models, all relevant to nano-bioPhase 1Evaluation of 6 historical oversight models, all relevant to nano-bio interfaceinterface Drugs, Devices, Gene Therapy, GEOs in food and agriculture, Chemicals in theDrugs, Devices, Gene Therapy, GEOs in food and agriculture, Chemicals in the Environment, Chemicals in the WorkplaceEnvironment, Chemicals in the Workplace Phase 2Mapping lessons to nano-bioPhase 2Mapping lessons to nano-bio Phase 3Testing lessons in scenarios for specific nano-bioproductsPhase 3Testing lessons in scenarios for specific nano-bioproducts NSF-NIRT grant 2006-2010, $1.2M 73. Developing Hypotheses :Developing Hypotheses : Integrated Oversight Assessment ApproachIntegrated Oversight Assessment Approach Kuzma et al. 2008, Risk Analysis, in press How was the oversight model developed ? What are its attributes ? What are its outcomes ? How do the attributes evolve over time ? How was the oversight model developed ? What are its attributes ? What are its outcomes ? How do the attributes evolve over time ? How was the oversight model developed ? What are its attributes ? What are its outcomes ? How do the attributes evolve over time ? 74. Consensus criteriaConsensus criteria Kuzma et al. 2008, forthcoming in Risk Analysis Development: 7 criteria D1 Impetus D2 Clarity of technological subject matter D3 Legal grounding D4 Public input D5 Transparency D6 Financial resources D7 Empirical basis Attributes: 14 criteria A8 Legal grounding A9 Data requirements; A10 Post-market monitoring A11 Treatment of uncertainty A12 Empirical basis A13 Compliance and enforcement A14 Incentives A15 Treatment of Intellectual Property A16 Institutional structure A17 Flexibility A18 Capacity A19 Public input A20 Transparency A21 Conflicts of interest A22 Informed consent Consensus of >70% of experts who rated the criteria 70 or higher How important is it to consider this criterion in our oversight case studies? On a scale of 0 (least) to 100 (most), please rate the importance of each of the criteria to the oversight assessment we plan for the six models in this project. Outcomes: 5 criteria O24 Public confidence O25 Research & innovation O26 Health and Safety O27 Distributional Health Impacts O28 Environmental Impacts Step 2: Expert and Stakeholder Elicitation3 Criteria Reduced from 66 to 28 ? ? 75. GEOs Expert ElicitationGEOs Expert Elicitation 76. GeneratingGenerating HypothesesHypotheses Kuzma, Najmaie, Larson. In prep Correlation coefficients R>0.7, p