module c

Biosafety Resourceanalysis risk Book module

Resource Bookc

BiosafetyRome, 2011 the U Organization of Food and Agriculture analysis risk Andrea Sonnino Kakoli Ghosh Oliver Brandenberg Alessandra Sensi nited Nations ii List of contributors

This module has been prepared based on the lectures and contributions of:

Bassam Al-Safadi Desiree M. Hautea Plant Biotechnology Division Institute of Plant Breeding Atomic Energy Commission University of the Philippines Damascus, Syria Los Baños, Philippines

Nelson Onzere Amugune Samuel Kiboi Department of Botany University of Nairobi University of Nairobi Nairobi, Kenya Nairobi, Kenya Leticia Pastor Chirino Esther Argote Pelegrino Departamento de Autorizaciones Departamento Desarrollo Académico Centro Nacional de Seguridad Biológica Instituto Superior de Tecnologías La Habana, Cuba y Ciencias Aplicadas Ministerio de Ciencias Tecnologías Alessandra Sensi y Medio Ambiente Research and Extension Branch La Habana, Cuba Food and Agriculture Organization of the United Nations (FAO) Rodrigo Artunduaga Rome, Italy Agricultural BioTech (present address: Regulatory Network-ABTR EuropeAid Co-operation Office, Unit A.3 Vancouver, Canada Centralised Operations for Europe, the Mediterranean and the Middle East Oliver Brandenberg Brussels, Belgium) Research and Extension Branch Food and Agriculture Organization of Sandra Sharry the United Nations (FAO) Universidad Nacional de La Plata Rome, Italy La Plata, Argentina (present address: Institute of Medical Virology, Andrea Sonnino University of Zürich, Research and Extension Branch Zürich, Switzerland) Food and Agriculture Organization of the United Nations (FAO) Kakoli Ghosh Rome, Italy Plant Protection and Production Division Food and Agriculture Organization of Fred Tairo the United Nations (FAO) Mikocheni Agricultural Research Institute (MARI) Rome, Italy Dar-es-Salaam, United Republic of Tanzania

iii iv The riskanalysis process:riskmana chapter 4 The riskanalysis process:riskassessment chapter 3 The riskanalysis process:b chapter 2 Biological risks:b chapter 1 LIST OFABBREVi LIST OFCONRIBUTORS 4.2 4.1 3.2 3.1 Keysteps 2.4 2.3 2.2 2.1 1.3 1.2 1.1 Risk management andsoci The keystpsinrisk management Informati Key stepsinrisk assessme nt Concepts andiss ues inrisk analy sis The meth Principles ofrisk analy sis: genralaspcts Components ofRisk Analysis Bi Classificati Bi ological ag ents andrisk groups ological risks odology ofrisk assessme nt andrisk management on requirements forrisk assessment TIONS on fbi asic conceptsandlassifia ological ag ents asic concepts o-econ gement omic considerati tion contents ons :

module c 11 24 38 46 41 29 25 16 15 14 12 iii vi 1 5 4 1 chapter 5 The risk analysis process: risk communication 49 5.1 When to communicate about risk 53 5.2 Applying risk communication principles in risk analysis 53 5.3 Facilitating public engagement in the risk analysis process 55

Annex 1 management of risks in facilities 59 A Causes of accidents in laboratories for biological containment 59 B oTHer risks in facilities: chemical, physical and psycho-physiological 61

Annex 2 Principles and methodologies for the environmental risk assessment 69 A Objective 69 b General Principles 70 c Methodology 70 d Conclusions on the potential environmental impact FRom the release or the placing on the market of GMOs 73

References 76 useful reading 79

v module c risk analysis Resource Book Resource iosafety b

LIST OF ABBREViATIONS

ABS Access and benefit-sharing IUCN International Union for AIA Advanced Informed Agreement Conservation of Nature ASEAN Association of Southeast LMO Living modified organism Asian Nations NGO Non-governmental organization BCH Biosafety Clearing-House OECD Organisation for Economic CBD Convention on Biological Diversity Co‑operation and Development Codex Codex Alimentarius OIE Office International des Epizooties COP-MOP Conference of the Parties serving PGRFA Plant Genetic Resources for as the meeting of the Parties Food and Agriculture to the Protocol PRA Pest Risk Analysis CPB Cartagena Protocol on Biosafety SPM Sanitary and Phytosanitary Measures CPM Commission on Phytosanitary Measures SPS Sanitary and Phytosanitary DNA Deoxyribonucleic acid Agreement EC European Commission TBT Technical Barriers to Trade EIA Environmental Impact Assessment TRIPS Agreement on Trade-related Aspects EU European Union of Intellectual Property Rights FAO Food and Agriculture Organization of UN United Nations the United Nations UNECE United Nations Economic Commission FFP Food, or feed or for processing for Europe GATT General Agreement on Tariffs and Trade UNEP United Nations Environment Programme GDP Good Development Principles UNIDO United Nations Industrial GMO Genetically modified organism Development Organization IP Identity preservation UPOV International Union for the IPPC International Plant Protection Protection of New Varieties of Plants Convention USDA United States Department of ISPM International Standard for Agriculture Phytosanitary Measures WHO World Health Organization ITPGRFA International Treaty on Plant Genetic World Trade Organization Resources for Food and Agriculture WTO

vi chapter 1

Biological risks: basic concepts and classification

Biosafety To prevent, manage, minimize or eliminate hazards to human health and security and to protect the 1.1 Biological risks environment from biological agents and organisms used in The objective of a biosafety system is to prevent, manage, minimize or eliminate research and trade. hazards to human health and security and to protect the environment from biological Biological agentS agents and organisms used in research and trade. The following terminologies Living organisms, or materials derived associated with biological risks are defined or described: from them, which can potentially cause diseases in, or harm Biological agents - living organisms, or materials derived from them, which can to, humans or the potentially cause diseases in, or harm to, humans or the environment. environment.

Hazard Hazard – a hazard can be described in general terms as “a situation in which particular A situation in which particular circumstances represent a danger”, that is, the potential for an adverse occurrence. circumstances One example is a threat to the quality of life of an individual or a group. represent a danger.

1 biological materials humans, animals or that present arisk, Biological risk The riskassociated adverse event ata agent ororganism Infectious agents of the occurrence the magnitude of is the probability specific time and or potential risk, with abiological other organisms. to the health of damage caused. the consequent of aparticular Biological or hazardous module hazards 2 biosafety Resource Book c Table 1.1 An overview of biological hazards ispresented inTable 1.1: Biological hazards are numerous and diverse. organisms/particles, starting from asmall amount of initially released material. agents havethe abilitytoreproduce and togiveriselarge numbers of infectious indirectly through damage tothe environment. U animals orotherorganisms.The riskcanbemanifested directly through infection, or biological materialsthatpresentarisk,orpotentialtothehealthof humans, Biological hazards, orbiohazards - risk analysis combination of twofactors: the probability and the consequence of anadverse property and the environment under specificconditions. The riskistherefore a potential for a hazard having adverse consequences on human existence and health, Biological risks -The riskassociated withahazard canbeconsidered asthe Adapted from:FA alien species Invasive in relation tofood “Biosafety” plants andanimals relation to “Biosafety” in quarantine Plant health Plant health Animal health Z Food safety oonoses | Definitions of hazard asapplicabletodifferent biosecuritysectors O , 2007. whose introduction and/or spread threatens biodiversity An invasivealien species outside itsnatural pastorpresent distribution product that couldhaveanadverseeffectonhuman health A recombinant DNAorganism directly affecting orremaining inafood of biological diversity, taking into account alsoriskstohuman health is likely tohaveadverseeffectsonthe conservation and sustainable use genetic material obtained through the useof modern biotechnology that A living modified organism (LMO) thatpossessesanovel combination of being officially controlled and not yetpresent there, orpresent butnot widely distributedand A pestof potential economic importance tothe area endangered thereby injurious toplants orplant products Any species, strain orbiotype of plant, animal orpathogenic agent animal health Any pathogenic agent thatcouldproduce adverseconsequences on domestic animals and humans A biological agent thatcanbetransmitted naturally betweenwildor the potential tocauseanadversehealth effect A biological, chemical orphysical agent in,orcondition of, food with arethoseinfectiousagentsorhazardous nlike chemical hazards, infectious » » or human-caused: Biological riskscanbeclassifiedinto twobroad categories: naturally occurring It canbeexpressed asfollows: RISK=likelihood xconsequence of adverseeffects. be applied toallclassesof risk.Riskisameasure of the probability and severity any consequent damage done. such as exposure to the hazard, the frequency of exposure and the severity of the magnitude of the consequent damage caused, depending onvarious factors probability of the occurrence of aparticular adverseevent ataspecifictime and occurrence. Thus the riskassociated withabiological agent ororganism isthe (2) (1) Human-caused orrelatedbiologicalrisks, which canbefurther classifiedinto: (6) (5) (4) (3) (2) (1) Naturally occurringbiologicalrisks include

selection, mutation and modern biotechnology. biotechnological riskssuch asproducts of traditional cross-breeding and through warfare orterrorism; and deliberately induced riskssuch asthe useof harmful biological agents invasive alien species (plants, animals and micro-organisms). parasitic infection outbreaks inhumans; ochratoxin ); toxins arising from certainmolds and fungi (deoxynivalenol, aflatoxins, disease tohumans via direct contact, vectorsorwater/foodstuffs; spreading of azoonosis, i.e. infectedanimal populations conveying the Ebola, Lassafever); naturally emerging pathogens attributedtodeforestation (monkeypox, pneumonia, fluepidemic); the emergence of antibiotic resistant bacterial infections (tuberculosis, Biological risks:b M any aspects of risk analysis are generic and can asic conceptsandlassifia : tion

of anincident. consequence occurrence x Likelihood of Risk chapter 1 3 module 4 biosafety Resource Book c and material is required to assure appropriate handling and minimize potential risks. occur. Therefore, detailed knowledge about the classification of biological agents could become contaminated ifanaccidental escapeof biological agents were to infection, bycontaining pathogenic micro-organisms. M materials orfoods and feeds. Such materials canpotentially represent sources of direct services are among those thatteach,research, produce and control biological The personnel of research institutions, biomedical firms and veterinary quarantine of such agents, using appropriate techniques, needs tobemade available. associated withand the characteristics of the agents. Education insafehandling harmful biological agent must bemade aware of the potential dangers thatare infectious biological agents, genetically modified material orany other potentially of the risks associated with genetically modified organisms. Those in contact with biotechnology and the advances ingenetic engineering require detailed analyses spreading pathogenic agents inthe environment. Furthermore, the growing field of incidence of diseasescontracted bypeopleand becauseof the possibledanger of The need toclassifybiological agents according totheir riskarisesfrom the high 1.2 Adapted from:FA measures canbetaken: According tothe hazard and the associated risk,hazard-based and risk-based risk analysis level of protection thatislikely tobeachieved. Risk-based –Acontrol measure thatisbasedonquantitative and verifiableinformation onthe level of protection thatislikely toresult. level of hazard control thatislikely tobeachieved butlacking quantitative knowledge of the Hazard based–Acontrol measure thatisbasedonquantified and verifiableinformation on the W orking definitinsforhazard-b

Classifica O , 2007. tion ofblogcala ased andrisk-b ased controlmeasures oreover, the environment gents The World Health » » » a biological risk.These are: There are three waysthatbring workers into contact withmaterials thatmay pose if they escapefrom the laboratory. the risksthey posetolaboratory workers who handle them, and tothe community biotechnology raised awareness about the hazards of infectious micro-organisms and since the beginning of the twentieth century. However, the advent of modern multicellular parasites. Laboratory acquired infectionsLAI) havebeendocumented ( include the fullrange of micro-organisms: bacteria, viruses, fungi, protozoa and Biological agents are typically used in research or biomedical laboratories, and to human health and the environment uponaccidental or intentional release. One waytoclassifybiologicalrisks isbasedonthe riskposedby biological agents 1.3 classification for laboratories, aimed at defining the appropriate containment levels

or animal and plant materials orpeople, inthe workplace orelsewhere. Exposure whichisnotaresultof work–unintentional contact withanimals materials, such ashypodermic needles orsewage treatment plants. fluids and excreta, and handling materials that may becontaminated bythese include farming, refuse collection, sewage treatment, handling human body because biologicalagentsarepresentascontaminants-areas and activities Exposure whichdoesnotresultfromtheworkitselfbutisincidental toit, experimental work. plants and materials thatoriginate from animals and plants aspartof the materials usedfor genetic modification and intentional contact withanimals, isolation, identification and culture of micro-organisms orcells, including microbiology laboratories, greenhouses and animal houses. Activities include Exposure asaresultof workingwithbiologicalagents–areas of workinclude Biological a Biological risks:b Organization (WH gents andriskgroup O , 2004) has recommended an agent asic conceptsandlassifia risk group mainly mainly tion

treatment. measures and of preventive availability transmission, of mode as pathogenicity, on factors such defined, based agents were for biological Four riskgroups Risk groups environment. health orthe danger tohuman may represent a agents that to biological The contact Exposure intentional release. accidental or environment upon health and the agents tohuman posed bybiological Based onthe risk classifia Biological risk chapter 1 5 tion module 6 biosafety Resource Book c » » » » agents include: Other considerations thatmay betaken into account inclassifying biological » » » » not get infected, basedonriskcriteria/factors described below: required toprotect peopleworking withbiological agents and ensuring they do risk analysis drink, saliva),direct contact (cuts, bites, injection). Nature androuteof transmission–inhalation (dust, aerosol), ingestion (food, of apathogen, the greater the likelihood of infection. Number/concentration of pathogens– the higher the number and concentration conditions. Ability of the organism to survive – dormancy or resting period during unfavourable severe infections withno availabletreatment. exotic agents posehigher riskstohuman health becausethey may causemore Origin/source –indigenous (native, local)orexotic (foreign, alien) origin; consideration the possibilityof emergence of resistant strains. exposure vaccination, antibiotics, and chemotherapeutic agents, taking into Availability of effectivetreatment-includes passiveimmunization and post- or animal products. of peopleoranimals; and controlling the importation of infectedanimals the control of animal pathogen reservoirs orarthropod vectors;the movement by vaccination orantisera; sanitarymeasures, e.g. food and waterhygiene; Availability of effectivepreventivemeasures-these may include: prophylaxis presence of appropriate vectorsand standards of environmental hygiene. existing levelsof immunity, density and movement of the host population, Mode of transmissionandhostrangeof theagent–these are influenced by allergenicity, and modulation of physiological activity. infectivity. Diseasescausedbyproducts of abiological agent include toxicity, based onfactors such asthe severityof the diseaseitcauses, itsvirulence and Pathogenicity of theagentoritsproduct-inherent risksof apathogen are indicated above. genetically modifiedagentsinto aparticular riskgroup using the same criteria Adapted from:BML,2007. The Table 1.2 The four resulting WH classifications and criteria. Risk Group IV Risk Group II Risk Group I Risk Group III Classification Risk Group National Instituteof Health, USA (NIH, | Riskgroup classification of biologicalagents usually available. therapeutic interventions are not disease for which preventive or cause serious orlethalhuman Agents that are likely to available. therapeutic interventions may be disease for which preventive or with serious orlethalhuman Agents thatare associated often available or therapeutic interventions are serious and for which preventive human diseasewhich israrely Agents thatare associated with humans with diseaseinhealthy adult Agents thatare not associated Molecules, 2002 Involving RecombinantDNA NIH GuidelinesFor Research Biological risks:b M any countries haveadopted the WH O and NIHriskgroups are presented belowinTable 1.2: asic conceptsandlassifia (High individual and community risk.) preventive measures are not usually available. directly orindirectly. Effectivetreatment and transmitted from one individual toanother, or animal diseaseand thatcanbereadily A pathogen thatusually causesserious human (High individual risk;lowcommunity risk.) measures are available. another. Effectivetreatment and preventive spread from one infectedindividual to or animal diseasebutdoes not ordinarily A pathogen thatusually causesserious human (M are availableand the riskof spread islimited. effective treatment and preventive measures exposures may causeserious infection, but livestock, orthe environment. Laboratory to laboratory workers, the community, disease butisunlikely tobeaserious hazard A pathogen thatcancausehuman oranimal (No orlowindividual and community risk.) human diseaseoranimal disease. A micro-organism thatisunlikely tocause 3rd Edition2004 Laboratory BiosafetyManual World HealthOrganization 2002) oderate individual risk; lowcommunity risk.) established aclassification of O and NIHriskgroup tion

represent. danger they to the potential groups, according GMOs into four risk Classicication of classifia GMO chapter 1 7 tion dangerous biological a animals/ plants gents affecting agents, riskgroups for classification pathogens have of animal/plant pathogens and been defined. Biological As for human module potentially 8 biosafety Resource Book

c Table 1.3 following scheme (Table 1.3): U risk analysis l » that biological agents thataffectanimals beclassifiedinto four riskgroups: group withinthe International Veterinary Biosafety Working Group recommended biosafety procedures, butisnot strictly applicable toanimals. Instead, The classification of the WH 1.3.1 in thatcountry basedonthe above-mentioned criteria and considerations. each country draw upitsownclassification byriskgroup of the agents encountered disagreements exist inallocating agents toaparticular riskgroup. WH The four-risk group classification of biological agents iswidely recognized but Group Hazard sing the above criteria of classification, hazard groups can be summarized in the 1 4 3 2 for animal health and for which transmission ispoor. ow risk animal pathogens: Agents that cause diseases of minor importance

affect animals Classification of biologicalagentsthat human disease U for humans Pathogenicity human disease Causes severe human disease Can causesevere human disease Can cause nlikely tocause | Hazard group classification O isusedinthe initial stages of establishing laboratory possibly serious Intermediate to workers Serious Hazard Likely/ Low Spread tothe community M U U ay spread Likely nlikely nlikely Effective prophylaxis U U

sually available sually available or treatment U O recommends Available navailable a working » » » The factors affecting development of adiseaseinclude: of micro-organisms causing plant diseases(Kuenzi etal.,1987). biosafety of the same federation, and they proposed anew systemfor classification classification in1985, which was then revised in1992by the working group on The the classification. Because some of these agents canaffecthuman health they are included in therefore the development of criteria for biosafety procedures in plant facilities. for the environment resulting from handling of biological agents, facilitating In the caseof plants, the classification enables the definition of the risks 1.3.2 » » » m means of dissemination: water, air, soilorvectors; cultural practices and chemical application); resistance of the pathogen toenvironmental conditions (humidity, temperature, inoculum density; high morbidity and mortality. that causeserious diseases, are highly transmissible and are associated with transmissible withinthe animal population. It also includes micro-organisms includes pathogenic agents that cause serious diseases and which can be highly Very high riskanimal pathogens: There isadual definition for thisgroup. It diseases withahigh levelof morbidity and occasional mortality. High riskanimal pathogens: Agents thatcauseserious, easilytransmissible of transmission withacertainlevelof morbidity, butseldom cause mortality. E uropean Federation of Biotechnology ( oderate riskanimal pathogens: Agents thatcausediseaseswithamoderate risk affect plants Classification of biological agentsthat Biological risks:b asic conceptsandlassifia E FB) developed the first system of

tion

chapter 1 9 module 10

biosafety Resource Book c the host-vector relationship and the resultant GMO employed depending onthe riskassociated withthe selecteddonor, the recipient, For genetically modified organisms (GMOs), the four-risk group classification is » » » The classification proposed bythe working group was: » » » risk analysis

from national bodies. of these isgenerally prohibited. Work withthem generally requires authorization Class 3.Micro-organisms included onquarantine lists. Importation and handling plants and forests. Work withsuch pathogens issubjecttonational regulations. Class 2.Micro-organisms thatcauseimportant diseaseoutbreaks incrops, ornamental measures tobeworked with,except good laboratory practices (GLP). They generally include indigenous species and do not require special biosafety Class 1.Micro-organisms thatcan cause diseases in plants of minor importance. virulence of the pathogen. spatial relationship betweensusceptiblehosts and pathogens; presence of susceptiblehosts; . chapter 2

The risk analysis process: basic concepts

Risk analysis can be broadly defined as an integrated process consisting of three Risk analysis An integrated major components: risk assessment, risk management and risk communication. The process to analyse individual components are distinct, but are linked to achieve a well-functioning risk and form the risk analysis process that forms the basis for decision-making on any operation or basis for further decision-making. dealing of GMOs (Australian Government, 2005).

In the case of biosafety, risk analysis involves a scientific process to estimate the risks to human life and health, as well as the impact on the environment, associated with the use of a particular GMO or its products. The prevention, reduction or elimination of these risks requires methods of risk management that are normally implemented as actions conforming to particular regulations. Risk assessment and risk management have to be implemented along with risk communication, which involves all interested parties and allows for an iterative process of risk analyses.

Risk assessment is important in the process of risk analysis given that if a particular risk is not identified, the steps taken to reduce it cannot be formulated in the risk management process. Risk assessment relies on a solid scientific base. Each case has to be dealt with individually and a separate evaluation has to be undertaken for each phase of obtaining, researching, testing, producing and releasing into

11 identified bythe risk Risk mana concerned withrisk. opinions concerning various stakeholders Risk assessment assessment process risk and risk-related levels of riskposed then selecting and implementing the communica whether the risks as appropriate to control measures identify ahazard are minimizedor and manageable, ensure thatrisks estimates of the with evaluating process usedto information and are acceptable science-driven The process of qualitative or factors among Is concerned by ahazard. quantitative module exchange of of exchange and obtain controlled. A rigorous gement tion 12 Risk

biosafety Resource Book

c strengthens the overall process of riskanalysis byhelping todefine the issuesand stakeholders concerned withrisk(Codex Alimentarius Commission, 2003). information and opinions concerning riskand risk-related factors among various risk assessment and riskmanagement processes. Risk communicationisrecognized asthe third component thatunderpins the of riskmanagement and other considerations ispresented inChapter4. risks are minimizedorcontrolled. Amore detailed discussion onthe methodology then selecting and implementing the control measures asappropriate to ensure that the risks identified by the risk assessment process are acceptable and manageable, other risk considerations. Risk management is concerned with evaluating whether risk analysis. It isprimarily supportedbyriskassessment butisalsosupportedby Risk management is the second and discussion of riskassessment ispresented inChapter 3. estimation, (3)consequence evaluation; and (4)riskestimation. Amore detailed four steps:(1)hazard analysis (identification and characterization), (2)likelihood adverse effectsonhuman health and the environment. quantitative estimates of the levelsof riskposedby ahazard, including possible rigorous science-driven process usedtoidentify ahazard and obtainqualitative or Risk assessmentisthe firstand the scientificcomponentof riskanalysis. 2.1 be extrapolated tothe large scale. difficulties. M this sense, evaluation of possible impacts over the long term presents many very high, since this can result in a vast range of effects and interactions. In analysis process applied to a large variety of genes and gene combinations is the environment of GMO risk analysis

Componets ofRiskAnalysis oreover, the results of riskassessments from small-scale testscannot s on a large or small scale. The complexity of the risk decision-making component It isthe process of exchange of It typically consists of of the process of It isa It It countries and across regulatory institutions. this separation israrely clear-cutand variation initsimplementation exists among and risk managers, and to minimize any conflict of interest. In practice, however, assessment, to avoid confusion over the functions to be performed by risk assessors management. The reasons are: tomaintain the scientific integrity of the risk Risk analysis applied inthe broad sense separates the riskassessment from risk Adapted from:FA Figure 2.1 is depicted inFigure 2.1: The interplay betweenriskassessment, riskmanagement and riskcommunication processes of riskcommunication are presented inChapter5. risk assessment and riskmanagement (FA providing the linkand the feedbackmechanism thatinforms the twoprocesses of | O Genericcomponentsof riskanalysis , 2007. risk assessment scientific advice risk communica The riskanalysis process:b O , 1999).The principles, structures and tion risk management decision basedon policy and values scientific inputs, asic concepts

chapter 2 13 have beendefined assure reliability risk analysis Principles of that need tobe of the obtained General aspects of riskanalysis maintained to module results. 14

biosafety Resource Book

c comparators and well-established baseline information. parental organisms, withinthe context of the intended use. Thisrequires appropriate considered inthe context of the risksposedbythe non-modified recipients or Comparative (e.g. presence of wildrelatives, non-target species, endangered species, etc.). (e.g. laboratory, field, market) in nature and levelof detail, depending onthe GMO concerned, itsintended use for eachcase, the riskassessment methodology and required information may vary Case bycase-Riskshould beassessedonacase-by-casebasis. Thismeans that regard tothe interests involved. selected on the basis of their expertise, experience, and their independence with conduct the risk assessment. confidentiality. Thisprinciple also refers tothe selection of experts who will accessible toallinterested parties, whilerespecting legitimate concerns topreserve should befullydocumented inatransparent manner. Documentation should be Open, transparentanddocumented–Allaspectsof the process of riskanalysis scientific scrutiny and peer review. used should beappropriate and data generated of high quality towithstand reproducible, withtestablenull hypothesis, qualitative and/or quantitative. M application of science and scientific methods, i.e. rigorous and systematic, Science-based environment share many similarities. These include: general principles inassessing risksposedbyGMO s tohuman health and the While regulatory frameworks for riskanalysis varyamong countries, the underlying 2.2 risk analysis

Principles ofriskanalysis: generalaspects - Risks should be compared with background risks, i.e. risks are – Riskshould beassessedusing information obtained through and the likely potential of the receiving environment E xperts responsible for risk assessment should be ethods

likelihood estimation -Anevaluation of the likelihood of these adverseeffects » » followed are enumerated below. Protocol onBiosafety (CBD,2000)isagood exemplary guide and the stepstypically of GMOsexists and they share many similarities. Annex III8of the Cartagena General guidance onthe methodologyof riskassessmentandmanagement 2.3 should beensured inallaspectsand stages of the process of riskanalysis. organizations. Effectivecommunication and consultation withallinterested parties into account expert advice of, and guidelines developed by, relevant international It should draw information from a wide range of credible sources and could also take management of food- ororganism-related riskstohuman health and the environment. components of riskanalysis should beapplied within anoverarching framework for Inclusive –The process of riskanalysis should beall-encompassing. The three relative tonew information. newly generated scientific data. Conclusions and assumptions should be examined Iterative assess the risk,and manage and communicate the risks. key stepsare: establishthe purpose, scopeand boundaries of the riskassessment, Systematic -The riskanalysis should follow astructured, step-by-stepapproach. The

potential receiving environment tothe living modified organism. being realized, taking into account the leveland kind of exposure of the likely environment, taking alsointo account riskstohuman health. adverse effectsonbiological diversity inthe likely potential receiving characteristics associated withthe living modified organism that may have Hazard analysis -Anidentification of any novel genotypic and phenotypic - Risks should be evaluated and reviewed as appropriate in the light of risk mana The methodologyofriskassessmentand gement The riskanalysis process:b : keystep asic concepts

risk management. estimation, and estimation, risk consequence estimation, likelihood hazard analysis, process include: Key stepsof the risk analysis Methodology of chapter 2 15

comparing itwith its non-modified Evaluating the potential risks Familiarity counterpart. of aGMO by module 16

biosafety Resource Book c 2.4 Chapters 3and 4). of riskassessment and riskmanagement are presented inlaterchapters(see indicated above vary across countries. It should benoted thatthe levelof details and sequence of some of the steps » » » risk analysis of familiarity, effectivemethods cande devised toavoid ormanage the risks using already availableinformation onthe attributes of the organism. Because The concept of familiarity provides awaytorecognize the potential risksby and experience of itssafeuse. sufficient information availableaboutthe organism’s attributes, and along history GMOs todate havebeendeveloped from organisms thatare “familiar” i.e. there is history of safeuseof the organism that is subjected to genetic modification. Risk assessment of GMOs requires information onthe identity, characteristics and 2.4.1 better understanding of the process of riskanalysis. These include: There are anumber of concepts and issuesthatare veryimportant ingaining a

strategies tomanage these risks, including monitoring. are acceptableormanageable, including, where necessary, identification of Risk management –Arecommendation astowhether ornot the overall risks identified adverseeffectsbeing realized. organism basedonthe evaluation of the likelihood and consequences of the Risk estimation -Anestimation of the riskposedbythe living modified adverse effectsberealized. Consequence evaluation - An evaluation of the consequences should these

The conceptof familiarity Concepts andissueinriskanalysis M ore detailed discussions of the methodology M ost ost agricultural orenvironmental effect? marker gene orDNAsequence thatwillhaveno is the plant modified onlybythe addition of a equivalent toaproduct of aclassical method? is the genetically modified plant phenotypically classical genetic methods? is the genetically modified plant a product of Figure 2.2 following illustration (Persley etal.,1993): An example of afamiliarity testfor genetically modified plants isshown inthe evaluating and managing risks. of familiarity isnot ariskassessment initself,but ausefultoolfor identifying, the gene usedingenetic modification isavailable. allergenicity of aGMO ifknowledge and historyof safeuseof the origin/source of presence of wild compatible relatives. Likewise, it is possible to identify the potential organism (e.g. presence of traits thatare associated withinvasiveness) and the invasiveness of aGMcrop basedonknowledge of the biology of the non-modified to acceptablelevels. Forexample, itispossibletodetermine the potential for regard asnot f | Afamiliarity assessmentframework no no no amiliar The riskanalysis process:b yes yes yes In thiscontext, the concept regard asf asic concepts amiliar

chapter 2 17 established history their conventional that GMOs canbe components and/ organism/variety Convetinal safety basedon counterp of the GMO or products for compared with equiv Subst which there is experience of The principle that havean counterparts common use module of safeuse. A related alence antial as food. 18 art , its

biosafety Resource Book c section3.10–Principles: Codex AlimentariusCommissionPrinciplesandGuidelineson Foods Derived annex III5–RiskA Cartagena Protocol onBiosafety(CBD,2000) The relevant texts (initalics) are asfollows: Biosafety, and in food safety assessment bythe Codex Alimentarius Commission. the principles for environmental risk assessment by the Cartagena Protocol on Internationally, the concept of substantial equivalence isrecognized asone of levels of safety, butrelative levelsof safety. counterpart. The concept of substantial equivalence does not establishabsolute GMO is“as safeas”orpresents any new orgreater risksthanitsconventional between the GMO and its conventional counterpart to be able to determine if the similarities and differences (including intended changes and unintended changes) use (Codex Alimentarius Commission, 2003).The concept isusedtoidentify the with their conventional counterparts that have an established history of safe Substantial equivalence isbasedonthe principle thatGMOs canbecompared concept of familiarity is used together with the concept of substantial equivalence . In assessing the risksposedbyGMOs tohuman health and the environment, the 2.4.2 risk analysis from Biotechnology(Codex AlimentariusCommission,2004), potential receiving environment. risks posedbythenon-modifiedrecipientsorparentalorganismsin likely the useof modern biotechnology, shouldbeconsideredinthecontext of the detectable novel combinations of replicable genetic material obtained through processed materials that are of living modified organism origin, containing Risks associatedwithlivingmodifiedorganismsorproducts thereof, namely,

The conceptof substantialequivalence ssessment subjective, inconsistent and pseudo-scientific (Millstone etal.1999). concept of substantial equivalence inriskassessment hasbeencriticized as As afinal note, inaddition tothe limitations mentioned above, the use of the » » » are illustrated inthe three casespresented below. of sufficient scientific information relevant to the riskassessment. These points application islimitedbythe choice of anappropriate comparator and availability and to focus on the identified differences that may require further testing. Its starting It should benoted thatthe concept of substantial equivalence isconsidered a concept of substantial equivalence cannot beapplied. in biotechnology, these kinds of GMOs willbeproduced. Inthese cases, the of these GMOs. Nevertheless, it is conceivable that with future developments Up tonow, and probably for the near future, there havebeenfewexamples GMOs thatarenotsubstantiallyequivalenttotheconventional counterpart. the endogenous traits, orproduce new traits inthe host organism. the intended effect of the genetic modification that may, or may not, change on the defined differences. Typically, the defined differences will result from for defineddifferencesneed further safetyassessment which should focus only GMOs thataresubstantiallyequivalenttotheconventionalcounterpartexcept safety considerations other thanthose for the counterpart are necessary. counterparts are regarded asbeing “as safeas”their counterpart. No further GMOs that are shown to be substantially equivalent to the conventional characterized todetermine itsrelevance tohuman health. is identified bythe safetyassessment, the riskassociated withitshould be differences. Ifanew oraltered hazard, nutritional orother safetyconcern and itsconventionalcounterpartfocusing ondeterminationof similaritiesand include acomparisonbetweenthefood derivedfrommodernbiotechnology Risk assessment includes asafetyassessment (…)The safetyassessment should point for the safetyassessment tostructure the safetyassessment procedure, The riskanalysis process:b asic concepts However,

chapter 2 19 effective measures precautionary threats of serious postponing cost- “Where there are damage, lackof not beusedas certainty shall environmental or irreversible degradation.” full scientific a reason for module appro to prevent a 20 The ch biosafety Resource Book

c » » Rio Declaration inconducting riskanalysis. There are anumber of important points tokeep inmind aboutPrinciple 15of the Principle 15of theRioDeclaration onEnvironment andDevelopment 2.4.3 to framing the riskassessment process. of substantial equivalence remains the most practical approach currently available despite its limitations and criticisms, there is wide recognition that the concept risk analysis measures indicates that costs canbeconsidered when applying the approach. preventive measures to protect the environment; and use of “cost-effective” scientific uncertainty (i.e. source or form of doubt) should not prohibit using The precautionary approach in the context of Principle 15 explains the idea that approach” isviewed assoftening of the “precautionary principle”. cost-effective inapplying the approach. Inview of these, the “precautionary allows other costs(e.g. social oreconomic) tobeconsidered inorder tobe capability, which alaworprinciple willnot allow. Furthermore, Principle 15 discrimination between countries in applying the approach based on their Because itisan“approach” and not a“principle”, Principle 15allowsfor cases but normally does not have the same force as alaw (Recuerda, 2008). is compulsoryorlegallybinding whilethe former may bebinding insome from the legal connotation of the term“precautionary principle”. The latter The term“precautionary approach” isspecificallyusedtodifferentiate it environmental degradation.” not beusedasareason for postponing cost-effectivemeasures toprevent threats of serious orirreversible damage, lackof fullscientific certainty shall widely applied byStatesaccording totheir capabilities. Where there are “In order toprotect the environment, the precautionary approach shallbe (UNCED, 1992)statesthat:

The precautionary approach » are enumerated below: are fivedifferent types of uncertainty thatcanbeapplied toriskanalysis, which (Hayes, 2001). analysis, including risk assessment, riskmanagement and riskcommunication U 2.4.4 activities withlimitations, when appropriate. preventive measures are built in their risk management design to allow certain evidence when making decisions. Inconformity withthe precautionary approach, of riskanalysis. M on thresholds of riskand degree of scientific uncertainty allowedinthe process precautionary approach vary across countries because they differ intheir opinions on the precautionary approach. The interpretation and implementation of the in their regulatory systems and have established risk assessment mechanisms based M » » »

ncertainty is an inherent property of risk and is present in all aspects of risk any countries haveadopted the same phrasing of Principle 15of the Rio Declaration epistemic and precaution. damage ishigh, decision-makers willactfrom the perspectivesof prudence important application of the precautionary approach. Where risksfor irreversible Finally, Principle 15refers topotentially irreversible harmtobethe most Principle 15identifies the triggers topropose aprecautionary approach. (linguistic uncertainty), models, figures, pictures or symbols (such as those used descriptive experiments, and byapplying more powerfulstatistical analyses and GLP. unreliable data. Epistemic uncertainty couldbereduced bydesigning more rigorous from animal models to humans), and incomplete, ambiguous, contested or common examples are statistical errors, useof surrogate data (e.g. extrapolation Uncertainty

- uncertainty of knowledge, its acquisition and validation. The most - uncertainty of descriptions thatmay beinthe form of words Simply defined, uncertainty isa form of source of doubt. There any regulatory approaches recognize the imperfect nature of The riskanalysis process:b asic concepts

communication. and risk risk management risk assessment, analysis, including all aspectsof risk and present in property of risk An inherent Uncert chapter 2 21 ainty module 22

biosafety Resource Book c » There are anumber of waystoaddress uncertainty inriskanalysis of GMOs: » » » risk analysis to acquire greater knowledge increase almost exponentially with each demand question. However, itmust berecognized thatthe effort and resources required there isuncertainty, more experiments may berequired inorder toanswer the Request orobtainfurther information onthe specificissues of concern. Where used tocoverthistypeof uncertainty. data. Inriskmanagement, safetyfactors and other protective measures are that itcannot bereduced bymore effort, such as more data ormore accurate example, from genetic difference. or indeterminacy of athing, quality orprocess. Randomness canarise, for intrinsic in the system. generating more information aboutthe various components and relationships conditions cannot beperfectlyspecified. Complexity couldbe reduced by a deterministic systemcanhaveunpredictable outcomes becausethe initial inability toestablishthe completecausalpathwaysinasystem.Consequently, (e.g. the atmosphere). Complexity and incomplete knowledge contribute tothe dynamic systems such as acell,anorganism, the ecosystem,orphysical systems entropic (complexity) is through effectivecommunication strategies. arbitrariness, doubt, orchangeability. One waytoreduce cognitiveuncertainty uncertainty canbeviewed asguesswork,speculation, wishfulthinking, cognitive definitions and providing clearparameters, scopeand boundaries. Descriptive uncertainty couldbereduced byusing accurate and consistent of harm,magnitude of aharmfuloutcome and tothe overall estimate of risk. words. Forexample, the word “low” may beambiguously applied to likelihood measurements and inconsistent and incomplete definition and application of in formal logic, geometry and mathematics). - uncertainty that expresses the inherent randomness, variability (including bias, perception and sensory uncertainty) -cognitive - uncertainty thatisassociated withthe complex nature of A critical feature of intrinsic uncertainty U sually associated with qualitative is Box 2.1 » » » » » Risk assessment the elementsofriskanalysis Examples ofuncert u u u evaluating whatthe consequences of the occurrence wouldbe. focus is less on determining the likelihood of an occurrence, but rather on information, the “worstcase”scenario approach canbeapplied, where the In cases where further experimentation may not provide the necessary in the receiving environment. Implement appropriate risk management strategies and/or monitor the GMO (e.g. no valid protocol) orpractically (e.g. unaffordable cost)possible. for greater precision or detail. In many instances, these may not be technically consequences; of hazards, likelihood and process, including assessment within the riskassessment over long time periods; processes, orlandscape changes other biological entities and of the GMO environment-specific performance properties of the introduced genes, knowledge of biochemical the GMO terminology, useof related terms due toinsufficient explanations of in qualitative riskassessments ncertainty of the calculations ncertainty inthe nature of ncertainty indescriptions used , such asthe lackof , itsinteraction with ainty within The riskanalysis process:b Risk communication Adapted from:Australian Government, 2005. » » » Risk management u conflicting values. of incomplete knowledge and Decision-making inthe presence effectiveness; protective measures against their Balancing the sufficiency of different contexts. the useof the same termin that are not fullycongruent or traditions, morals, valuesand beliefs. in knowledge, language, culture, effectiveness due todifference

ncertainty of communication

asic concepts

chapter 2 23 chapter 3

The risk analysis process: risk assessment

Components of Risk assessment is the core of biosafety because it represents the basis for making risk assessment decisions on the protection of the environment and human health in the case of (1) hazard analysis (hazard identification uncertain scientific backgrounds. To guarantee its integrity and objectivity, risk and characterization), assessment has to be separated from risk management. (2) likelihood estimation, (3) consequence Risk assessment is a science-based process consisting of four steps: (1) hazard evaluation; and (4) risk estimation. analysis (hazard identification and characterization), (2) likelihood estimation, (3) consequence evaluation; and (4) risk estimation, all of which are described below.

A generally accepted methodology for biotechnology risk assessment has been outlined in several easily accessible documents including the UNEP International Technical Guidelines for Safety in Biotechnology (UNEP, 1995), the EC Directive 2001/18/EEC, and Annex III 8 (a-d) of the Cartagena Protocol on Biosafey (CBD, 2000). In this section, the latter is used as a guide to enumerate the steps typically

24 the respective measureable properties. has occurred. Table 3.1summarizes examples of potential biological harms and the measurable properties of the hazard inorder toaccurately assessthatharm exposure betweenahazard and anadverseoutcome. It alsoinvolvesidentifying Hazard analysis alsoinvolves establishing the causallinkand pathwayorroute of evidence) toexperimental data (strong evidence). analysis. Evidentiary supportcouldrange from unsubstantiated statements (weak up). A checklist and the inductive approach appear to be the status quo of hazard Approaches tohazard analysis may beinductive (top down) ordeductive (bottom analysis, hierarchical holographic model (HHM),SWO expert consultation, fault and event trees. Quantitative techniques include HAZOP (Hayes hazard. Quantitative and qualitative techniquesare usedinhazard identification evaluate, inqualitative and quantitative terms, the nature of the identified intrinsic agent (e.g. GMO orGMfoods) tocauseharm.Hazard characterization aims to Hazard identification investigates the intrinsic or“built-in”potential of the biological taking alsointo account riskstohuman health (CPB, Annex III8(a)). adverse effectsonbiological diversityinthe likely potential receiving environment, phenotypic characteristics associated with the living modified organism that may have Hazard analysis canbedefined asan identification of any novel genotypic and 3.1.1 3.1 and the FA primarily from the RiskAnalysis Framework of the Australian Government (2005) environment. The additional information tohelp explain eachstepwasabstracted followed inriskassessment whether for food products ororganisms released into the kEystepinriskassessment

et al,2001).Qualitative techniquesinclude checklist, brainstorming, Hazard analysis, identificationandcharacterization O Biosecurity Toolkit (2007). The riskanalysis process:RISKASSESSMENT T analysis, Delphianalysis, etc.

environment. potential receiving diversity inthe likely effects onbiological may haveadverse organism that the living modified associated with characteristics and phenotypic any novel genotypic An identification of chara and identfca Hazard analysis, chapter 3 25

cteriza tion tion the living modified potential receiving An evaluation of kind of exposure realized, taking environment to the likelihood Likelihood effects being the leveland estima into account of the likely module of adverse organism. tion 26

biosafety Resource Book

c the riskfinding isqualitative onthe basis of aweight of evidence analysis. is possibleincertainriskcalculations, such asnon-target risks, butmore frequently which something willhappen innature cannot alwaysbemeasured orpredicted. It Here the term “estimation” is chosen because exact numbers of the frequency with term outcome ismore accurately assessedthanalong-term outcome. accuracy of prediction isdirectly proportional totime of occurrence, i.e. ashort- It isimportant toremember thatlikelihood estimation isapredictive process. The zero toone, where zero isanimpossibleoutcome and one isacertainoutcome). measure of frequency (the number of occurrences perunittime) and probability (from Likelihood isthe probability thatthe harmwilloccur. It isexpressed asa relative Annex III8(b)). likely potential receiving environment tothe living modified organism (CPB, effects being realized, taking into account the level and kind of exposure of the Likelihood estimation canbedefined asanevaluation of the likelihood of adverse 3.1.2 Table 3.1 risk analysis Human toxicity and allergenicity Creation of new viruses Loss of biodiversity and extinction of species altered bio/geo-chemical cycles Habitat modification - Toxicity of aGMO tonon-target organisms invasion of aGMO Increased fitness, increased persistence, Hazard likelihood estimation | Examples of potentialharmsandtheirmeasurable properties age of morbidity abnormalities; mortality; frequency and Biological, physiological and physical Occurrence, number, severity, host range Diversity indices; species richness of floods, fire; pollutant concentration Carbon, nitrogen, phosphorus flux;frequency species richness M traits for weediness and invasiveness Occurrence and biological properties – Measurement A ortality; survival;population morbidity, ttributes » » Descriptors of consequence assessment: » » » » » following criteria should betaken into consideration: the significance and impact of the adverse outcome if the hazard occurs. The be realized (CPB,Annex III8(c)).Consequence evaluation involvescharacterizing Consequence evaluation isanevaluation of the consequences should adverseeffects 3.1.3 abiotic attributes. and the characteristics of the receiving environment, including its biotic and harm will occur are the survival, reproduction and persistence rates of the GMO For GMOs, the most important factors thatcontribute tothe likelihood that » » » » Likelihood assessment may bequalitatively described asfollows: Minor -slight injurytosome peoplewho may require medical treatment; medical aid; minimal or no degradation of the environment; Marginal -minimal orno injuryexcept toafewindividuals who may require (e.g. GMO). background risk–that may occurinthe absence of the stressor cumulation and reversibility; temporal extent –duration and frequency; organism (individual, population, community, ecosystem); spatial extent –geographical (local,national, global); severity –number, magnitude, scale; rare circumstances Highly unlikely Unlikely -couldoccurinsome circumstances Likely -couldoccurinmany circumstances Highly likely -isexpected tooccurinmost circumstances

Consequence evaluation

(negligible or effectively zero) - may occur only in very The riskanalysis process:RISKASSESSMENT

,

effects berealized. should adverse the consequences An evaluation of ev Consequnce chapter 3 27 alua tion

the living modified Risk estima and consequences on the evaluation the riskposedby An estimation of of the likelihood of the identified organism based adverse effects being realized. module tion 28

biosafety Resource Book c » » » » » » Descriptors of riskestimate: corresponding riskmanagement treatments orcontrol measures. 3.1). identified hazard tocome upwiththe riskestimate matrix shown below(Figure Risk estimation combines the information onlikelihood and consequence of the adverse effectsbeing realized (CPB,Annex III8(d)). based onthe evaluation of the likelihood and consequences of the identified Risk estimation isanestimation of the riskposedby the living modified organism 3.1.4 risk analysis not readily reversible. ecosystems, communities may result indeath; Major limited severity; disruption tobiological communities thatiswidespread butreversible orof Intermediate -injurytosome peoplewho require significant medical treatment; and spaceornumber of individuals/populations affected; disruption tobiological communities thatisreversible and limitedintime and effective. High - riskis unacceptable unlessactions for mitigation are highly feasible that need tobedemonstrated aseffective; Moderate - risk is of marked concern that will necessitate actions for mitigation practices; Low -riskisminimal, butmay invoke actions for mitigation beyond normal for mitigation; Negligible -riskisinsubstantial and there isno present need toinvoke actions As ageneral rule, riskswithmoderate and high estimates willinvoke the riskestimation - Severe injurytosome peoplewho may require hospitalization or extensive biological and physical disruption of whole or anentire species thatpersistsovertime oris hazard andtheresulting risklevel classification Figure 3.1 Adapted from:Australian Government, 2005. (Konig etal.,2002). Biosafety. points enumerated aboveobtained from Annex 9 of the Cartagena Protocol on Risk assessment for the release of G 3.2 » » » » » » depending onthe dealing of GMOs, couldbetaken into consideration: Finally, inconducting the stepsoutlined above, the following characteristics, severity informa the receiving environment. the intended use(e.g. the scaleof the activity-fieldtrial orcommercial use); available methods for detection and identification of the GMO; the resulting GMO; transformation system; inserted genes, sequences and related information about the donor(s) and the recipient, host orparental organisms; negligible moderate critical catastophic | A more detailed discussion of the various points ispresented below Thecombinationsbetween severity andprobability of a tion requiremesforiskassssme t IV III II I The riskanalysis process:RISKASSESSMENT frequent extremely high A MO s typically takes into consideration the likely B medium high low prob risk level occasional ability C seldom D unlikely E

chapter 3 29 Informa use, compositional Includes identity, the recipent history of safe analysis, etc. performance, distribution, or p module org geographic agronomic tion anism arent 30

biosafety Resource Book

c species. These documents provide excellent sources of relevant information on (1) biological attributesand (2)compositional characteristics for certaincrop The OECDhasbeencompiling consensus documents (OECD,2009)onthe be the focus of further assessments. information tohelp planthe riskassessment strategy, e.g. identifying whatshould receiving environments. data when comparing the GMO withitsnon-modified counterpart under different of the natural variation of the traits inthe recipient isessential ininterpreting with itsnon-modified counterpart, i.e. itservesasa reference point. recipient organism guide the choice of testparameters for comparisonof the GMO are introduced through genetic modification methods. The characteristics of the The recipient orparent organism refers tothe organism into which the genes » » » » outset include: The typeof information onthe parent crop thatshould begathered atthe 3.2.1 risk analysis relatives; information bothfrom the literature and from analytical data. biologically active substances associated withparent and sexually compatible Compositional analysis –key nutrients, toxins, allergens, antinutrients, information onpreparation, processing, and cooking. allergenic characteristics orintolerances; importance inthe diet, including History of safeuse–any known nutritional, antinutritional, toxicological, and centre of diversity. Geographical distribution/sourceororigin–area of cultivation, centre of origin proximate composition and key nutrients and anti-nutrients. race/isolate, common name, and sexually compatiblewildrelatives); chemical the completename, family name, genus, species, subspecies, cultivar/breed/ Identity, phenotypicandagronomicperformance – taxonomic identity (including information ontherecipient orparent organism The history of safeuseof the parent canprovide additional Knowledge

» » » » » The information required includes: 3.2.2 has beenacceptedbybiosafety regulatory authorities insome countries. the parent orrecipient crop. Information from these OECDconsensus documents recombinant DNAand the host genome. Characterization of insertionsite–information onthe junction of the inserted transgene insertion overfiveor more generations. discussion), absence of vector backbone; and verification of the stability of to host genomic D insertion sites, copynumber of the introduced DNA,ends of inserts adjacent Characterization of introducedDNA–includes information onthe number of DNA orother plasmid DNAorvectorsequences. includes proof of absence of contaminating sequences of bacterial chromosomal that strain; for direct transformation methods, such as the particle gun, it information requirement includes donor strain and any plasmid contained in Transgene delivery process transferred, and nucleotide sequence information. restriction sites;proof of absence of vectorfragments not intended to be coding sequences, promoters and termination signals, vectormaps withrelevant elements usedtoconstruct and amplifythe transformation vector, including Description of vector DNA used inthe transformation. to the donor; and, where possible, function of any recombinant DNAsequences potential toxicity, allergenicity orpathogenicity, historyof useand exposure Description of donor(s)–includes classification and taxonomy, evidence of information ontheinsertedgenesandsequences the transformation system and related information aboutthedonor(s)and NA; a genomic library of each transformed plant line (under The riskanalysis process:RISKASSESSMENT – includes information on the source of all genetic – For Agrobacterium -mediated transformation the

insertion site. DNA and the of the inserted characterization of the vector, description the donor, description of Includes sequnce genes and on theinserted Informa chapter 3 31 tion

module 32

biosafety Resource Book c of riskanalysis. market release. Thisispartof the “case-by-case” and “step-by-step”approach to afullcharacterization asrequired for large-scale fieldtrials orcommercial/ to confined fieldtrials, more detailedcharacterization is requested, leading strict containment measures (see Section 2). When the activity has moved on Hence, the riskassessment isconducted onthatbasisand riskismanaged by that the entire construct may havebeenintegrated into the recipient organism. when fullmolecular characterization hasnot yetbeenconducted, itcanbeassumed For example, in the early stages of research and development of the GM product, Finally, the level of detail required should depend on the nature of the dealing. included inthe riskassessment. are transferred toanorganism inaddition tothe functional genes need tobe in abacterium.To conclude, allregulatory regions and other sequences that replication of the gene in the – unlikely – event that it is taken up and recovered plant cell,butwill a gene witha prokaryotic origin of replication (ori)willnot beexpressed ina of unintended effects due to the presence of these D process, such asselectablemarker genes. The underlying reason isthe possibility they are the “genes of interest” orgenes thathave“travelled along” inthe genes With regard tothe characteristics of the introduced DNA,allinserted functional gene products, thus limiting the chance of transferring transfer vectorDNA. vector withtransfer function and contain arecognition sitefor the transfer-mediating (Gelvin, 2000).The vectorwiththe recombinant DNAmay beseparate from the Agrobacterium, the riskof transfer of random DNAtothe plant isrelatively small With regard tothe transformation method, ithasbeenargued thatinusing risk analysis are, inprinciple, relevant tothe riskassessment, regardless of whether be considered inthe risk assessment becauseitmay facilitate NA sequences. For example, » » process. The information required for the gene products is: (metabolite) gene products. Hence, both are relevant to the risk assessment to the recipient organism are translated into primary (protein) and secondary With certainexceptions, like anti-sense DNA,allinserted functional genes transferred 3.2.3 diet. However, almost all allergens are proteins. With regard to toxicity, safety concerns toxic when consumed orally as they are largely part of a standard human and animal perspective of food/feed safety, itiswidely recognized thatproteins are not generally of risk assessment, particularly for GMOs thatwillbeusedasfood/feed. From the Toxicity andallergenicity of the gene products are the primary concerns and focus » » Mode of action/specificity- changes inthe levelsof substances detected during compositional analysis. or macronutrients (e.g. Vitamin A in Golden Rice), and significant unexpected protein levelsinvarious host tissues),changes inlevelsof inherent crop micro catalysed reactions (ifthe gene product isanenzyme), expression levels(recombinant glycosylation and phosphorylation), immuno-equivalence, activityand specificity of weight, amino acid sequence, Structure, identityandcharacterization–Forproteins, thisincludes the molecular allergenic proteins, and/or allergenicity of the recombinant protein itself. Allergenicity –changes inthe characteristics orlevelsof expression of endogenous information onstructure and function and toxicity testsare required. of previous toxicity testing programmes; for novel proteins/metabolites, Toxicity –information ondocumented exposure and historyof safeuse;results amino acids of allplants and micro-organisms). the herbicide glyphosate butdoes not affectthe biosynthesis of the aromatic or substance specificity(e.g. the CP4EPSPSenzyme thatconferstolerance to pathways thatcouldbeaffectedbythe enzyme’s presence oraltered levels toxic tocertaininsects butnot humans), overview of allrelevant metabolic information onthegeneproducts; recombinant proteins and/ormetabolites The riskanalysis process:RISKASSESSMENT

mechanism of action (e.g. Bt-proteins which are post-translational modification (e.g. levelof

used asfood/feed. GMOs thatwillbe particularly for of riskassessment, concerns and focus The primary allerginicity allerginicity, etc. of action, toxicity, of proteins, mode characterization Includes products on thegee Informa T chapter 3 o 33 xicity and tion

agronomic analysis, Informa Includes identity, the resul safety analysis. compositional analysis, and module tion ting GMO 34

biosafety Resource Book

c commercial releases of identical GMOs invarious locations. also be obtained from the Biosafety Clearing House for information on field and existing food composition, chemical analyses, and toxicology tests. Datacan for planned commercial growing. Other major sources of data are databases on under adiversityof environmental conditions representative of those typical chambers, greenhouses and/or earlier fieldtrials. Field trials are usually undertaken Data aboutthe resulting G MO are availablefrom growing the GMO ingrowth Sources of data toenable detailed comparisoncancome from avariety of sources. (3) safetyanalysis (animal studies). The information from these analyses isobtained (2) compositional analysis and (1) identity, phenotypic and agronomic analysis; Information requirement for the resulting GMO includes: 3.2.4 altered the allergenic properties of the product derived from the GMO? cross-reactive withIgE antibodies raised byknown allergens?; (b)Has transformation allergenic source orknown allergen? Is itabletoinduce denovosensitization?; Is it the following key considerations: regard to allergenicity, the amount of new data required should take into account of proteins thathaveno historyof adverseeffectsonhumans and animals. With exposure. proteins/metabolites that are routinely used by humans and animals, and history of the light of existing information on the protein/metabolite prevalence, similarity to and the amount of new data thatwillberequired should becarefully considered in risk analysis animal feeding studies. compositional and nutritional values, and dietary subchronic responses in any indicative differences in test parameters, such as agronomic performance, in comparisonwiththe non-GM counterpart. These analyses focus ondetecting information ontheresulting GMO Safety concerns and new data requirements should belowerinthe case (a) Is the recombinant protein derived from an the market. Development inthe areas of detection and testing are being pursued be adequate for the safety assessment of the GMOs that are currently available on ease of use, specificity, sensitivity, costs, etc. Existing methods have proven to Each of these methods has its own advantages and disadvantages in terms of targets, » » » Toxicology testmethods include: » » » » Protein-based testing methods include: » » » » used include: Examples of currently availableDNA-based GMO detection methods widely resulting GMO are crucial forMO G analysis. and testmethods focusing onthe inserted DNA,the resulting proteins and the gene products, and the resulting GMO generate information onthe characteristics of the inserted DNAsequences, the of a G and characterization. Invarious stages of research, development and release GMO Detectionandidentificationmethodsare important inhazard identification acute animal toxicity studies chronic toxicity, carcinogenicity and reproduction studies in vivoand invitrotestsystems Protein chips Lateral flowstrips ELISA Western blot DNA chips Quantitative real-time PCR Qualitative PCR Southern blot MO , molecular characterization and toxicological tests are conducted to The riskanalysis process:RISKASSESSMENT . Thismeans thatdetection, identification

in M described indetail characterization; identification and for hazard Highly important methods identfca and GMO detection chapter 3 35 odule A.

tion

This may include the intended use ofaGMO Informa rela a wide range range wide a of activities, module commercial research to large-scale from basic ting to release. tion 36

biosafety Resource Book

c (b) conduct experiments withGMOs; (c)breed GMOs; (d) propagate G MO applications. These include: (a)make, develop, produce ormanufacture GMOs; The intended useof aG MO possiblyencompasses awide range of activities and 3.2.5 refer toM For amore detailed discussion onDNAand protein detection techniques, please of modern biotechnology. to improve existing techniquesand address the safetyof next generation products risk analysis labelling ormonitoring. is, inprinciple, unrestricted except for specificproduct-use conditions, such as whereas after placing the GMO on the market for commercial production, its use that withfieldtrials the GMO involvedisstillunder various degrees of control, release. The major distinction betweencommercial release and fieldtrials is irrespective of scaleand availability of confinement measures and commercial of GMOs. Inmany regulatory systems, thismeans any trial conducted inthe field Release into the environment, inthisdocument, refers tonon-contained usage environment (CPBdefinition). that effectivelylimittheir contact with,and their impacton,the external which involvesliving modified organisms thatare controlled byspecific measures any operation undertaken within a facility, installation or other physical structure, (1) contained use; and (2) release into the environment. Contained use means These activities and applications canbeclassified into two categories: product; and (f)grow, raise orculture GMOs, possiblyonanindustrial scale. (e) investigate the useof GMOs inthe courseof development ormanufacture of a information relating totheintendeduseof aGMO odule 1:Agricultural Biotechnology.

s;

European Community (EC)legislation, isprovided asanadditional guideline. to betaken into consideration for the riskassessment of GMOs, extracted from case-by-case basisfor eachindividual GMO case. InAnnex 4,asummary of points and the likely receiving environment, riskassessment hastobeperformed ona GMO isdifferent concerning itsdesign, purpose, biology of the parent organism process, thatneeds tointegrate avariety of data and considerations. Since every Taken together, itshould beclearthatriskassessment isacomplex, science-driven » » » » of the trial, taking into consideration the following relevant characteristics: For fieldtrials, the information requirement includes the specific physical location 8. 7. 6. 5. doesthe GMO posehazards tolocalfauna orflora? 4. doesthe GMO havenew weedcharacteristics? 3. doesthe GMO havealtered resistance toinsects orpathogens? 2. 1. questions for specificapplications tobeassessed: When releasing genetically modified plants into the environment, there are relevant The characteristics of the receiving environment are crucial for the riskassessment. 3.2.6 doesthe GMO havenew weedcharacteristics thatcouldmake itsuccessful presence of sexually compatiblewildrelatives. presence of sexually compatiblecrops; organism (e.g. climate, soilconditions); specific environmental factors influencing survival and distribution of the environment for release; comparison betweenthe normal growing environment withthe proposed outside of the managed ecosystems? Can the new trait impartincreased competitiveness toweedy relatives? Are cross-hybridizing relatives present inthe same area? Is there potential for negative impactonnatural (non-managed) ecosystems? Is there potential for negative impactonmanaged ecosystems? information onthereceiving environment The riskanalysis process:RISKASSESSMENT

assessment. crucial for the risk environment are of the receiving The characteristics enviromet the receiving Informa chapter 3 37 tion

chapter 4

The risk analysis process: risk management

Risk Risk management is the second and the decision-making component of the process management of risk analysis. Risk management is defined as “the process of weighing policy The process of weighing policy alternatives to mitigate risks in the light of risk assessment, and, if required, selecting alternatives to and implementing appropriate control options, including regulatory measures” (FAO/ mitigate risks in the light of risk WHO, 1995). Its objective is to determine which risks require management and how assessment, and, if these risks can be effectively managed or controlled so that the goal of ensuring required, selecting and implementing adequate protection for people and the environment is attained. appropriate control options, including regulatory The management of risk is basically founded on: measures. » Understanding and identification of risks and adverse conditions associated with work, which are determined in the risk assessment process. The principal objective of the evaluation is to know which management measures and controls are to be applied to the identified risks. If a risk is not identified, one cannot develop risk management procedures. » The development and implementation of technical and organizational measures that correspond with the determined risks. » The type of organism released (transgenic, non-transgenic, exotic).

The risk management framework is depicted in Figure 4.1:

38 depicted inFigure 4.2: between riskmanagers, scientists and riskassessors and other stakeholders is control measures are properly implemented and complied with.The relations risk management decisions and hasthe overall responsibility for ensuring that is the competent authority having jurisdictional powerthatmakes the final Although other stakeholders participate inriskanalysis, atanational levelit » » » As such, the measures to develop couldbethose for: » » The fundamental objective of theriskmanagementprocess isto: Adapted from:FA Figure 4.1 substitution of risks. reduction of risks; elimination of risks; avoid orreduce exposure tothe identified risk factors. assessment; eliminate, reduce orsubstitutethe riskfactors identified inthe risk M onitoring and | review O Componentsof ageneric risk managementframework , 2007. The riskanalysis process:riskmana Implementation Preliminary risk management management of control measures activities Identification and selection management management options of risk gement

risk factors. the identified reduce exposure to and avoid or risk assessment; identified inthe the riskfactors or substitute Eliminate, reduce mana of risk Objective chapter 4 39 gement

module 40

biosafety Resource Book c management process Figure 4.2 risk analysis » » » The preliminary riskmanagement activities canindicate that: Adapted from:FA Functional role of industry and other stakeholders Functional role of scientists and riskassessors Functional role of riskmanagers Risk Assessment evaluation canbegin. information onrisksand the required biosafety measures, and the formal risk The case is straightforward or there already exists adequate experience and request more information. The availableinformation isnot adequate and it is therefore necessary to be authorized toevaluate the risks. The availableinformation issufficient and the competent authority cantherefore | Roleof theriskmanagerin application of thegenericrisk O , 2007. M and review onitoring Implementation Preliminary risk management management of control activities measures risk management and selection of Identification options Implementation by stakeholders Risk Profiling a consideration of appropriate riskmanagement strategies. In this step, decisions are made on whether the identified risk is manageable, i.e. 4.1.1 Risk management isastep-by-stepprocess which consists of: 4.1 between riskassessment and riskmanagement. the riskassessment process, itisimportant tokeep the conceptual separation There isageneral consensus that,inorder tomaintain the scientific integrity of of GMOs. Thisadds apolitical component tothe riskmanagement process. other interested parties concerned withrisks, inthe final decision onany dealing other inputs, e.g. socio-economic considerations (if allowed by the regulation) from manager ordesignated national competent authorities totake into consideration assessment process butmay consider risksinawider context. Thisallowsthe risk In any case, riskmanagement isprimarily supportedbythe results of the risk Specific measures depend onthe type of organism. engineering measures, including control techniquesand organizational measures. before their useand release into the environment according totechnical and procedures are those applicable toallorganisms (transgenic ornon-transgenic) of different measures, contributing tomore complex management. The general Risk management measures are various; they canbesimpleoracombination be addressed. and objectivelyformulate the scopeof the riskevaluation and the questions to If the riskevaluation iscommissioned, the competent authority should clearly

riskevaluation The keystepinriskmana The riskanalysis process:riskmana gement gement

strategies. risk management of appropriate a consideration manageable, i.e. identified riskis whether the made on decisions are In thisstep, Risk ev actions. appropriate implementing mitigation, and evaluation, risk Include risk mana in risk Key step chapter 4 41 gement alua tion Risk mitg to reduce oravoid options and plans Determines the module the risks. a tion 42

biosafety Resource Book c 4.1.2 is lessclearinthisstep. In practice, the functional separation betweenriskmanagement and riskassessment Risk evaluation servesasthe vitallinkbetweenriskassessment and riskmanagement. for management. risks withestimates of high ormoderate wouldgenerally invoke arequirement “yes”, then ariskmanagement strategy isdefined inthe next step.For example, the identified risks require specificrisk management measures. If the answer is the identified riskis manageable oracceptable. The question toaddress iswhether deemed tobe“negligible” or“marginal”, the risk evaluation considers whether cases where, onthe basisof the riskestimation step,the risksinvolvedare not risk estimate. Riskevaluation startsfrom the result of the riskestimation step.In The rigorous scientific process of the riskassessment implementation ends in a risk analysis » Depending onthe case, riskmitigation measures oroptions may include: may alsobeareason torevisit and possiblyrevise ariskassessment. new data, derived for instance from aconfined, “risk managed” field experiment, reason why riskassessment isoften calledan“iterative process”. Availability of reduce the likelihood orthe consequence of potential adverse effects.. Thisis one assessment to determine whether the proposed riskmanagement strategies sufficiently has beendefined, the riskassessment “loopsback”tothe earlier stepsinthe risk plans to reduce or avoid the risks. For cases where a risk management strategy This step is central to the risk management process. by removal of flowers, use of isolation distances or border rows, temporal of biological material. Forgenetically modified plants: reproductive isolation 2), as well as the conditions for use, handling, storage, transport and disposal specifying the appropriate containment facilities and BSLs(pleaseseeChapter riskmitigation It determines the options and

Box 4.1 » » » » Post labelling andmonitorin g techniques to allfoodstuffs. not onlyapplytoGMOs, itapplies increase costs. Traceability does monitoring techniquesand can is possiblethrough labelling and necessary recall materials. This to control quality and when production and distribution chains, commercialization, along the products inallthe phasesof follow the organisms ortheir Traceability isthe capacityto in the caseof transgenic foods. the caseof GMOs and particularly the element of traceability in Risk management caninclude labelling (voluntary ormandatory) GMO detection (for details, M please see monitoring and surveillance submission of contingency oremergency plans » » » size orduration of anapplication canbeconsidered and evaluated in: isolation, special design features such asmale sterility, and reduction of the Commercial-scale tests(under fieldproduction conditions) Semi-commercial tests(contained) Controlled fieldtrials (isolatedfrom other cultivatedareas) -commercializa The riskanalysis process:riskmana tion riskmana » » » » these include: commercialization are concerned, As far asthe objectives of post- odule 1) specific products. Preservation of the identity of labelling. Assisting control through and the environment. perceived risktohuman health Recalling products ifthere isa the environment. effects onhuman health and Following the long-term gement through

gement

chapter 4 43 licence required for Selecting and process thatwill implementing decision-making rejection, of the to authorization and issuance, or ultimately lead options and module any dealing a of G of The final ctions MO 44

s. biosafety Resource Book

c a political process. of unacceptable risks. This stepmakes the riskmanagement process essentially the need toprotect human health and the environment from the adverse effects Decision-makers need to balance the individual rights of different stakeholders with have conflicting interests. wider acceptance of the decision. These stakeholders havediverseviews and may (e.g. riskperceptions) from various stakeholders toinspire confidence and achieve risk issues (e.g. socio-economic considerations) and other risk-related factors and inthisstep,the riskmanagement process may take into account other non- assessment. However, several factors govern decisions aboutthe release of aGMO Final decisions are based primarily on the results of the scientific process of risk licence conditions. of GMOs. The riskmitigation measures identified are included aspart of the authorization and issuance, orrejection, of the licence required for any dealing This step refers to the final decision-making process that will ultimately lead to 4.1.3 management measures. under waytostandardize and harmonize the guidelines onthese various risk how these riskmanagement measures are designed and implemented. Efforts are are stillno internationally agreed guidelines, except for containment, onexactly M planning arepresentedinModuleD. Detailed information onall aspectsof monitoring,surveillanceandemergency risk analysis any countries haveputuptheir ownguidelines for dealings onGMOs butthere selectingandimplementingthemostappropriate options andactions

the environment ortohuman health. based, inpart,onadetermination thatthey do not poseanunacceptable risk to related areas. Decisions regarding the useof thistechnology and itsproducts are meeting national goals and objectivesinfood production, food security, trade and agricultural research and development and the potential role of biotechnology in products made from them. Such decisions take into account national policies for Countries individually decide whether todevelop, deploy, oruseGMOs and the Adapted from:Traynor etal.,2002. Figure 4.3 are summarized inthe following figure: and food safety and responsibilities under international agreements. These factors input, public concerns and opinions, existing policies inagriculture, the environment, Typically, decision-making incorporates, whether formally orinformally, stakeholder stakeh ethical issues nati policies olders’ | input Factors influencingnationalGMOdecision-making onal n on-safety issues The riskanalysis process:riskmana safety assessment na decision making tional impacts on trade agreements internati opini public considerati econ social and on onal omic ons gement

chapter 4 45 Socio-economc considera might betaken during the risk considerations management management into account module process. tions Such 46

biosafety Resource Book

c considerations indecisions onGMOs, itmust bedone ina manner thatis condition thatwhen countries decide totake into account socio-economic but onlythose where GMOs directly impactbiodiversity. It alsospecifiesthe The definition implies that not allsocio-economic considerations canbeincluded, considerations indecision-making onrisksposedbyGMOs tothe environment. of Article 26defines the limitsand conditions when applying socio-economic economic considerations inmaking decisions withregard toGMOs. Paragraph 1 It isclearinArticle 26of the CPBthatcountries may take into account socio- indigenous andlocalcommunities. of biologicaldiversity, especiallywithregardtothevalueof biologicaldiversityto the impactof livingmodifiedorganismsontheconservationandsustainableuse with their international obligations, socio-economic considerations arising from domestic measuresimplementingtheProtocol,maytake intoaccount,consistent 1. TheParties, inreachingadecisiononimportunderthisProtocolorits that: Article 26of the Cartagena Protocol onBiosafety, inparticular paragraph 1states on Biological D iversity; and (b)the Codex Alimentarius (international food code). environment. These are: (a)the Cartagena Protocol onBiosafety of the Convention in decision-making withregard topotential risksof GMOs topeopleand the two relevant international documents which address socio-economic considerations Socio-economic considerations coverawide range of issuesand concerns. There are 4.2 force, biosafety assessments willbecome partof international trade agreements. for the safetransfer, handling and useof living modified organisms thatisalready in With the Cartagena Protocol onBiosafety, alegallybinding international protocol risk analysis riskmana socio-economc considera gement and

tions » These include: to socio-economic considerations. to inthe Second Statement of Principles outlines the points and criteria relevant (Codex, 2003) and the Criteria for the Consideration of the O Appendix IVof the Codex Working Principles for RiskAnalysis onhuman health Principles for RiskAnalysis.” general decisionsof theCodex AlimentariusCommissionaswelltheCodex Working where relevant,takingintoaccountotherlegitimatefactors inaccordancewiththe be proportionaltotherisk,basedonoutcomeof theriskassessmentand, “Risk management measures for foods derived from modern biotechnology should modern biotechnology (2003),which statesthat: considerations include Section 3.16of Codex Alimentarius for foods derived from Codex principles onriskmanagement particularly relevant tosocio-economic may betaken into account indecisions on GMO Codex Alimentarius guidance documents alsostate thatsocio-economic considerations World Trade Organization (WT consistent withother international obligations, which includes treaties of the (For details, pleaserefer toM WT referred tospecificallyinthe Sanitaryand Phytosanitary Agreement (SPS) of the are not legally binding to national legislations. However, Codex principles are O , which isalegallybinding international treaty signed bymany countries. » » the promotion of fair practices infood trade basedonthe following criteria: other legitimate factors relevant for the health protection of consumers and for other factors which canbeacceptedonaworldwide basis, oronaregional basis other factors should not affect the scientific basis of riskanalysis The riskanalysis process:riskmana odule E). O).

s.

U nlike the CPB, Codex principles ther Factors Referred gement

chapter 4 47 module 48

biosafety Resource Book c that haveformally included abenefit assessment withintheir regulatory structure. factor” like economic risk-benefit analysis, there are no biosafety regulatory systems process. analysis and incorporating socio-economic considerations into the decision-making definitions and scopes of socio-economic considerations and methodologies for considerations ingeneral terms. To date, there are stillno internationally agreed As can be noted in the above, the existing guidance documents treat socio-economic » » The riskmanagement process should: risk analysis paying particular attention tothe circumstances of developing countries consider the economic consequences and feasibilityof riskmanagement options, disadvantages take into account anassessment of their potential advantages and » » » other factors should not create unjustifiedbarriers totrade and concerns related toeconomic interests and trade issues other factors should consider the feasibilityof riskmanagement options specific other factors should be determined onacasebybasis Even atthe national leveland for whatmay beconsidered a“legitimate chapter 5

The risk analysis process: Risk Communication

Risk communication is “the interactive exchange of information and opinions Risk throughout the risk analysis process concerning hazards and risks, risk-related communication The interactive factors and risk perceptions among risk assessors, risk managers, consumers, industry, exchange of the academic community and other interested parties, including the explanation information and opinions of risk assessment findings and the basis of risk management decisions” (Codex throughout the Alimentarius Commission, 2003). risk analysis process concerning hazards and Risk communication in this sense is also addressed in Article 23 of the Cartagena risks, risk-related factors and risk Protocol on Biosafety on public awareness and public participation which perceptions among states that: risk assessors, risk managers, 1. The Parties shall: (a) Promote and facilitate public awareness, education and consumers, participation concerning the safe transfer, handling and use of living modified industry, the academic organisms in relation to the conservation and sustainable use of biological community and diversity, taking also into account risks to human health. In doing so, the Parties other interested parties. shall cooperate, as appropriate, with other States and international bodies; (b) Endeavour to ensure that public awareness and education encompass access to information on living modified organisms identified in accordance with this Protocol that may be imported.

49 module 50

biosafety Resource Book c can understand the information of the riskwithout becoming emotionally involved. is the presentation of a dealt witheffectively. Goodcommunication isthe key. GoodRiskCommunication Risk does not havetoturninto acrisisifitcanbeidentified, planned for, and to achieve the desired outcomes. assessors, riskmanagers and other interested parties concerned withrisksinorder concerned with risk; and (2) to promote interactive communication between risk understanding onallaspectsof the riskanalysis process byallinterested parties Therefore, the main goals of risk communication are: (1) to improve knowledge and can control bythemselves, ordissuading peoplefrom risky, antisocial behaviour. mandatory regulations, informing and advising peopleaboutriskswhich they Communication isalsoavitalpartof implementing decisions -whether explaining deciding how risksshould bemanaged. all interested parties, not onlyriskassessorsand risk managers, toparticipate in Risk communication isessential inmaking decisions (ILGRA,1999).It enables groups and individuals concerned withrisk. interested parties like government, industry, academia, consumers, public interest communication involvesnot onlyriskassessorsand riskmanagers, butalsoother phases of riskassessment and riskmanagement. It isalsorecognized thatrisk There iswide agreement thateffectiveriskcommunication isessential atall 3. 2. risk analysis to theBiosafetyClearing-House. Each Party shallendeavortoinform itspublicaboutthemeansof publicaccess while respectingconfidentialinformation inaccordancewithArticle21. organisms andshallmake the resultsof suchdecisionsavailabletothepublic, consult thepublicindecision-makingprocessregardinglivingmodified The Parties shall,inaccordance withtheirrespective lawsandregulations, scientific assessment of risk in such a way that the public

smootherimplementation » earlydiscussions withstakeholders and the public canhelp toinform responsible » leadtobetterdecisionsabouthow tohandlerisks » risk more effectively: Good communicationwiththe public canalsohelp responsible agencies tohandle » » » » » Good riskcommunication must: A key feature of riskmanagement, and of policy-making, isthe need todeal with have aknock-on effectonothers. This canbeparticularly important where action taken totackleariskcould authorities tospotaspectsof ariskthatmight otherwise havegone unnoticed. account of awide range of views and experience. It canalsohelp responsible stakeholders and the public inriskdecisions canhelp ensure thatdecisions take associated withnew technologies, such asGMOs. Engaging awide range of It can be particularly valuable where there are public concerns about risks to take earlyaction toaddress those concerns, before they turninto crises. authorities of potential areas of public concern earlyon.Thiscanenable them Preventing crises management of acertainrisk. may contribute to formulating well-suited and adequate decisions about the Considering and integrating awide number of public and stakeholders’ opinions skills, and participatory opportunities. analyze the conditions needed for the public toacquire relevant information, their questions and concerns; understand the public’s concern withregard toriskissues, and acknowledge address issuesof credibility and trust; programmes; explain the uncertainty ranges, knowledge gaps, and ongoing research understandable terms; translate the scientific findings and probabilistic risk assessment into The riskanalysis process:riskcommunica tion

build trustetc. prevent crises, in betterdecisions, of ways, e.g. result process inavariety entire riskanalysis will profit the with the public communication Good communica Good chapter 5 51

tion module 52

biosafety Resource Book c » » » » » » » » » Also, effectiveriskcommunication canhelp responsible agencies to: overtime, communication withstakeholders canhelp toreduce suspicion, » » risk analysis build afoundation for dialogue and shared problem solving before operations begin. develop agood reputation withregulators and the public; build relationships based ontrustand respect; improve dialogue and reduce tension betweencommunities and companies; community members; increase the effectiveness of riskmanagement decisions byinvolving concerned respond topublic concerns and misinformation; anticipate community responses tothe intended activities; understand the multi-dimensionality of risk; explain technical risksmore effectively; and withthe public interest inmind. for themselves thatdecisions havebeenmade onthe bestavailableevidence can help bybringing people“inside the tent”, and byenabling them tosee and buildtrustinthe information government provides. Opencommunication Building trust reduce the riskof scares. in turn help to foster a climate of greater empowerment and reassurance, and to make informed judgments onhow tohandle risksbythemselves. Thiscan to make realistic assessments of the risksthey face and, where appropriate, Providing clearand accurate information aboutthe nature of riskscanhelp people Empowering andreassuring thepublic risks, particularly where these require the public totake action. and bitterness lateron.Thiscanmake iteasier toimplement measures toaddress reflect public values and can reduce the scope for misunderstanding, disagreement at anearlystage indecisions aboutriskscanhelp ensure thatdecisions better different and often conflicting perspectives. Engaging stakeholders and the public The joint FA 5.2 management processes. in explaining the results and the procedures of the risk assessment and risk common language that will be clearly understood by all parties is needed active participation of stakeholders and other interested parties. Finding a addition tothe scientific inputinthe evaluation of arisk.Thisshould involve of riskmanagement options, the riskmanagers may need toconsider factors in issues of concern and reduce potential points of conflict. During the selection opinions of interested parties aboutthe potential hazards canhelp define the conflicts and achieve desired outcomes. Inhazard identification, the views and measures –require effectiveriskcommunication tohelp buildtrust,reduce processes; two key steps – hazard identification and selection of risk management analysis process. It isembedded into the riskassessment and riskmanagement It iswidely acknowledged thatriskcommunication isanintegral partof the risk 5.1 » to riskassessment and risk management processes, are illustrated below: and strategies for effective risk communication (FA to food standards and safetymatters identified the elements, principles, barriers aPPlyin g riskcommunica Know the audience opinions, concerns and feelings. general public. It isimportant tolistenand understand their motivations, may include riskassessors, riskmanagers, government, interest groups and the be done through surveys, interviews and focus groups. and the processes used. U delivery of credible information onthe risksidentified, the decisions made, in riskanalysis When to communica O/WH O expert consultation onthe application of riskcommunication . In the risk analysis process, the different types of audience The riskanalysis process:riskcommunica nderstanding the audience’s perception of riskcan These are important inthe development and te aboutrisk tion princles O , 1999). The principles, applied

tion

identified. have been communication for effectiverisk and strategies principles, barriers Several elements, princiles communica Risk chapter 5 53 tion module 54

biosafety Resource Book c » » » » risk analysis for the outcome. Since science must bethe primary basisfor decision-making, and the media. Eachhasaspecific role toplay, buthavejoint responsibility process. These include riskassessors, riskmanagers, other interested parties Share responsibility: adds tothe credibility of asource. in delivery and up-to-date information toaddress current issuesand problems the riskissues, trustworthy, competent, committed and consistent. Timeliness should beperceived asgenuinely concerned withthe views and opinions on likely receive higher acceptance. To becredible, the source of information assessments byregulatory bodies of many countries onaparticular GMO will sources lend more credibility tothe riskassessment. Resultsof safety information from acompany consultant. Consistent messages from multiple Commission onfood safetyassessments willmore likely beacceptedthan will likely be accepted. For example, information from the Codex Alimentarius in question, and other interested parties. Information from acredible source information are riskassessors, riskmanagers, applicants of the technologies Be a credible source of information. has tobeimproved bytraining and experience. early aspossible. Communication expertise of riskmanagers and riskassessors communication expertise. Risk communication experts have to be involved as audience. Developing credible information and delivering iteffectivelyrequires enormous amounts of information which is of interest to a wide-ranging Establish expertise incommunication. formulate their decision. risk managers can clearly and fully understand the risks and consequently assessment, including the assumptions and subjectivejudgments, sothat with GMOs. These experts must beabletoexplain clearlythe results of their closely withthe riskmanagers inarriving atthe final decision onany dealing the riskanalysis process intheir capacityasriskassessors. They workvery Involve thescientific experts. There are multiple actorsinvolvedinthe riskanalysis Scientific experts are primarily involvedin

In the risk analysis process, the sources of The riskanalysis process generates » » » GMOs topeopleand the environment isincreasingly being recognized. Thistrend is The need toengage the public indecision-making processes concerning the safetyof better understanding of and increased levelof acceptance inthe decisions made. interactive dialogue may not change their individual positions, butmay leadtoa on all aspects of the risk analysis process. E views and interests of the regulators, other interested parties and the general public improving the understanding of riskissues, butalsoatdealing withconflicting Risk communication not onlyaims atinforming and educating the public, i.e. 5.3

concern should beavoided. associated withthe technology. step, the riskmanager may examine the riskinthe context of the benefits target audience make upitsmind. Forexample, inthe decision-making by emphasizing the information aboutthe riskthat isrelevant tohelp the Put theriskinperspective. Inthe process of riskanalysis, thiscanbedone information (ifallowedbyregulation). examination byinterested parties, butgiving due regard toconfidentiality of of risk assessment and risk management must be accessible and available for outcomes, the process must be transparent. This means the process and results Assure transparency. decisions made inthe riskmanagement process. “facts” from “values” in reporting the results of the risk assessment and Differentiate between science and value judgment.: the resulting riskmanagement decisions. principles and data supporting the riskassessment and the policies underlying all parties involvedinthe communication process should know the basic Fa the riskanalysis process cilit a ting publicen The riskanalysis process:riskcommunica For the public to accept the risk analysis process and its Risk comparisons thatunderestimate the ngaging all parties in a responsive and a gement in It is essential to separate

tion eng public Fa the decisions made. of acceptance in and increased level understanding lead toabetter dialogue may and interactive in aresponsive Engaging allparties chapter 5 55 cilit a gement

a ting

module 56

biosafety Resource Book c opportunities for public comment. openness aboutthe purpose, location and design of biosafety trials; (4)ensuring openness about applications for biosafety review and commercialization; (3) ensuring of public concern (rather thanassuming whatpeopleneed toknow); (2)ensuring trials. The kinds of processes thatthen may beused include: (1)engaging withareas reporting, public scrutiny and accountability; (4)location and design of biosafety about?); (2)roles, duties and powersof responsible agencies; (3)mechanisms of (1) identification of riskissues(what do citizens know, whatare they concerned of the riskanalysis process, some of the choices identified are: making process in the implementation of regulatory frameworks. choices regarding the point atwhich the public couldbeinvolvedinthe decision- The Institute for Development StudiesDS, 2003)alsoconsidered (I some of the implementation and evaluation strategy. options, developing criteria for selecting those options and providing inputtothe whenever practical and reasonable, should beinvolvedinidentifying management decision alternatives byriskmanagers. It wassuggested thatinterested parties, management step, specifically in the identification and weighting of policy and process where public inputmay beconsidered. The most important isthe risk food standards and safety matters (FA The joint FA risk analysis process. guidelines astothe extent and manner public inputcanbeintegrated into the in the approval of GMproducts. public engagement isneeded are riskassessment and riskmanagement, particularly Forum (Ruane and Sonnino, 2005).The decision-making processes identified where clearly presented inthe results and background documents of the FA risk analysis O/WH O expert consultation onapplication of riskcommunication to However, there are stillno internationally agreed

O , 1999)identified stepsinthe riskanalysis O Biotechnology In the context Box 5.1 » analysis processes, include the following: in communication withthe public and establishing adialogue onrisksand risk perception of risk,and which therefore need tobeconsidered when engaging highly subjectiveand context-dependent. Factors thatmay influence the public public comments. Furthermore, itshould benoted thatthe perception of riskis with routine opportunities for public comment and obligations torespond to accessible and widely advertised and public registers of applications under review, The kinds of toolswhich may beconsidered include stakeholder forums thatare » » » » » » stakeholder groups in identifyingrelevant Questions thatwillassist eng stronger fearsthansomething seenaslessdreadful. d angered ifnot included? who reasonably might be decisions before? in being involvedinsimilar who hasexpressed interest risk situations before? who hasbeeninvolvedinsimilar expertise thatmight be helpful? who hasinformation and risk management decision? who might beaffected by the applicable regulatory process? are officially involvedinthe which branches of government(s) read. a gement ofs Hazards thatprovoke arisk thatisperceived asdreadful tend toevoke The riskanalysis process:riskcommunica akeholders » » n » » » » » » » meeting techni to engagestakeholders Example of tactics on-meeting techni hotlines and toll-free numbers interviews scientific meetings stakeholder groups in inclusion of non-scientific workshops focus groups question and answer sessions briefings public meetings public hearings ques ques tion

chapter 5 57 module 58

biosafety Resource Book c and stages of development of eachcountry. to take into account the different situations, sociological differences, capabilities work everywhere. Appropriate forms of public participation and consultation need and awareness-raising. What works in some places or in some circumstances will not the concerns are similar, there isno “one sizefitsall” formula for public participation As afinal note, IDSemphasizedthatpublic participation is highly contextual. » » » » » » » » risk analysis more they willbeafraid. are responsible for exposure tothe riskorcommunication aboutthe risk,the Trust. there isno perceived benefit, the riskseems larger. of a vaccination are perceived to outweigh the risk of the side effects); if behaviour or choice, the risk associated with it seems smaller (e.g. the benefits Risk-benefits trade-off. When peopleperceive abenefit from acertain often irrelevant topeopleand anineffective form of riskcommunication. they know couldbeavictim -thishelps explain why statistical probability is Personal exposure. Any riskseems larger ifanindividual thinksthey orsomeone that risk. A risk toadults. Children. that isimposed. Choice. even when facts show thatthe former present greater risks. as less wonying than human-made risks (e.g. anthropogenic sources of radiation) Natural if ithadbeendecided byaprocess overwhich the individual hadno control. the process determining the riskfaced, thatriskusually seems smaller than Control. wareness. Research hasshown thatthe lesspeopletrustthe institutions that or human made. Natural risks(e.g. sunradiation) are usually perceived A riskthatanindividual chooses usually seems lessriskythanarisk When anindividual feelsasthough she/he hassome control over Risks tochildren are generally perceived asworsethanthe same Greater awareness of a risk increases conscious concern about While While annex 1

management of risks in facilities

A Causes of accidents in laboratories for biological containment

Most accidents in containment facilities occur due to inadequately trained staff, Accidents Most accidents poor handling, negligence and lack of adherence to norms of prevention and in containment protection. For such reasons, national and international organizations, such as facilities occur due the WHO, have developed technical guides on general and specific methods that to inadequately trained staff, should be taken into consideration in facilities dealing with pathogenic agents. poor handling, negligence and lack of adherence The probability of accidents occurring when working with pathogens is directly to norms of related to the type of work being done, but is generally much lower in facilities prevention and protection. in which the personnel are better trained. Training on the following topics should be provided: » nature of dangerous agents, substances and products that exist in the laboratory; » work procedures, the means of containment and safety and the means for individual protection; » use and operation of equipment; » means for disinfection and sterilization; » what to do in the case of emergencies.

59 subjective factors Generally, causes technical factors of accidents can be grouped into (personnel). a module Causes of (equipment ccidents etc.) and 60

biosafety Resource Book

c » » » The causesof contamination canalsobegrouped by: » » can begrouped according tothe factors thatcausethem: maintained equipment and facilities. Independent of their diversenature, accidents own safetyand not applying correct containment procedures becauseof badly can becausedbypersonnel obviating inconvenient procedures designed for their fail or where safety practices and procedures are not followed. Such situations Accidents result from circumstances where containment measures and equipment » » factors should beconsidered: situation. To guarantee safetyatworkwithpathogens orGMOs, twoimportant for adequate containment and protection for each typeof laboratory and for each assessment of the potential riskhasbeendeveloped tofurnishnorms and methods The risk analysis psychological conditions. Human causes, associated withcapacity, training and discipline, aswell safety procedures. operation of securitysystems, failure toadhere toGLPand factors concerning Technical causes, associated with methods of protection, equipment functioning, the lackof asecurityprocedure. Organizational causes, associated withsupervising and overseeing workor tiredness and other uncontrolled actions. observe technical procedures, poorcontrol overprocesses, lackof attention, Subjective factors, related to poor use of equipment and methods, failure to methods and systems of protection, containment and biosafety. Technical factors normally associated with badly functioning equipment, out the workunder safeconditions. are involvedinthe laboratory processes and who are important incarrying The subjective factors, in terms of the people who, in one form or another, terms of guaranteeing containment and safety. The objective or technical factors regarding the facility and its equipment, in causes of accidentsincontainment facilities are diverse. Therefore, an characteristics of achemical substance onitslabel. Internationally established norms and regulations exist onthe need to specifythe appropriate means for their handling. properties, soastobeableidentify possibledangers and determine the most When using chemicals itisimportant tohaveaccurate information ontheir B.1 B must beinstituted. In this respect, regular medical monitoring of personnel and adequate prophylaxis to transmissible infections must beconsidered, including pregnancy orlactation. taken into account inassessing risk.Allconditions thatmight predispose personnel The stateof health of the personnel isone of the most important factors tobe experience inworking withthe samples. at level 3and 4, it is necessary to have in-depth training in biosafety and specific general experience innecessary techniques. However, from level2,and particularly When working atBSL1,itissufficient toknow the GLPof the laboratory and have materials being handled, represent main factors inthe prevention of accidents. of prevention and protection, and specificwork experience withthe biological of exposed personnel are important. The general levelof training inmeasures Training and experience, stateof health, prophylaxis and medical monitoring humans, animals and plants. jeopardize safetyand result inliberation of biological material dangerous to of entrance of non-authorized personnel orlaxsecurityduring transport can of the biological agents should alsobetaken into consideration. The possibility Inherent riskfactors associated withsecurityatthe facilities and during transport

Chemical risks O and psycho-physiological ther risksinf a cilities: chemal,physial mana gement ofrisksinf a cilities

chemical agents. by the useof Risks posed Chemical risk annex 1 61 module 62

biosafety Resource Book c M organic solvents and the danger of explosion from inflammable gasesand peroxides. Potential problems arising from mismanagement include electrostatic combustion of dangerous, but is easily managed with adequate preparation and knowledge. The handling of solvents and gases, aswellordinary chemicals, ispotentially » » » » Chemical substances thatcausecellularchanges inanorganism canbegrouped into: » » » » » » the danger they represent canbeclassifiedaccordingly: The physico-chemical properties and toxicity of chemical substances interms of Classification of chemical compounds risk analysis any of the chemical substances incurrent useinfacilities cancausedangerous compounds and they must bestored and handled withcare. and explode orbecome extremely toxic. These are termed incompatible chemical that do not represent a high risk, butothers that can provoke violent reactions Other: Among those substances deemed to have achemical risk there are some the foetus. Teratogen: Chemicals thatproduce birthdefects following malformation of tar, phenols and sulphur. carcinogens. Among those usedinlaboratories are xylol,benzine, benzedine, in animals and humans. M Carcinogen: Chemical agents whose adverseeffectsare promotion of tumours acids and mustard gases. composition of the basesof DNA,such as5-bromouracil, 2-aminopurine, nitric Mutagen: Compounds orsubstances thatproduce chemical changes inthe noxious. combustible; inflammable and extremely inflammable; irritant; corrosive; toxic and verytoxic; any of the substances thatcausemutations are also Box B.1 in Box B.1: Safety principles and risksassociated withchemical substances are summarized of their properties. reactions, such asfires, and havetobestored carefully withfullunderstanding » » » substances Principles of safetyfor chemical S » » » » » » » afety princilesforhandlingchemalsubt donot pipettebymouth. donot smoke, eator keep food u minimizevapourproduction by donot tasteorsmell chemicals. mind yourpersonal safetyby in laboratories. instructions. according tomanufacturers’ Store inventilated places not leaving containers open. secure containers. Transport the substances in protection. using recommended means of Pay attention when handling. sources of information. Read the labelsand other to capture toxic emissions. se ventilated fume cupboards mana gement ofrisksinf chemical substances General precautions for handling substances Risks linked withchemical » » » » » » » » » » u Poisoning. donot workwearing contact environment. Contamination of the Fires and explosions. Illnesses and changes inhealth. equipment is. Know where the emergency Know the emergency procedures. lenses. incidents. Inform aboutallaccidents and Recognize symptoms of exposure. protective glasses. se glovesand ances a cilities

annex 1 63 module 64

biosafety Resource Book c

Box B.2 provided inBox B.2: A summary of facility design and storage and handling of chemical substances is health and the capacitytowork. effects, manifested as biological changes that disturb normal functions and impair effects, while prolonged exposure to lower concentrations can result in chronic effect. Short exposure tohigh concentrations of asubstance canresult inacute The form (liquid, solid, gaseous)of the chemical substance greatly influences its risk analysis » » » » should putinplace General methodsthefacilities Fa » » »

showers tocopewithemergencies. Install emergency high‑pressure for emergency cases. install supplementary ventilation to avoid build-upof vapour, Ventilation should besufficient electricity. Protect the networks for gasand Place twodoors inopposition. with lotsof water. Clean splashes immediately and mucous membranes. Avoid contact withskin,eyes Work inaflowchamber. cility designforwork with chemcalsubst » » » » » Storing chemicalsubstances » » m m donot smoke, eatordrink inflammable products separate. Keep inflammable and non- storage near the areas of work. a well-ventilated placetoavoid Install anauxiliary storeroom in Place sinksnear toworking areas. of danger.of Take note of the symbolsfor level in laboratories. procedures inplace. aintain products in groups ake sure there are emergency ances » » » areas of afacility and accidents canbedifferent innature: Physical risks, posing aconsiderable danger topersonnel, are tobefound inall B.2 » » »

accidents are rare but when they occurcanbefatal. when precautions are not taken and protective equipment is not used. Such risk of electrical discharge and severe burns when handling isincorrect or overloading. Infacilities withovens, incubators, autoclavesetc., there isthe gases). Among the causes are faulty electric cables, bad connections and for particular reactive chemicals inthe laboratory (inflammable vapoursand Electrical: Includes the possibilityof shock, fire and the source of ignition and lowtemperatures can causehypothermia (coldrooms, liquid nitrogen). Thermal: Among others, high temperatures cancauseburns (ovens, autoclaves) that needs tobehandled withspecificattention. objects withpotential energy, such asgascylinders etc., represent equipment and objectsare badlylocated. M inadequately cleaned, there isinadequate illumination, movement is obstructed Mechanical: M

bottom shelves. Keep heavy containers onthe Keep sunlight out. containers. Keep substances intheir original together. substances are not brought making sure thatincompatible corrosives, toxic oxidants etc., according todanger posed, Physical risks echanical accidents most often occurwhen storerooms are mana otors, centrifuges, compressors and other gement ofrisksinf » » » oxidizing agents (ethyl ether, special storage. and activepoisons require Carcinogens, inflammables than sixmonths. must not bestored for more isopropyl ether), once opened, substances atthe lowestlevels. Keep the most reactive a cilities

radiation and fire. thermal, electrical, e.g. mechanical, and forces, physical factors All risksrelated to Physical risks annex 1 65 module 66

biosafety Resource Book c be regularly maintained and checked. bromochlorodifluoromethane (Halon 1211,BCF) extinguishers). Equipment should fire extinguishers (including water, carbondioxide, carbonated ice, foam and in strategic areas incorridors and rooms and should include hoses, buckets and Equipment for fighting fires should besituated nearto the doors of the facility, » » » » » » » » According toWH the refrigerator. explosion-proof and itis important thatthe wiring of the thermostat isoutside It is important that refrigerators are of the domestic type, they should be » » risk analysis explosive and inflammable chemicals stored in regular refrigerators. lack of care inhandling inflammable materials; poor handling of phosphorus; naked flames; equipment thatisplugged inwhen not necessary; gas pipesand electric cablesthatare toolong; poor maintenance of the electrical system; consequences of adding equipment tothe circuit; electrical overload; installing new equipment without considering the and explosive materials. electrical wires, incorrect positioning of equipment and handling of inflammable Fire: Causedbyvarious sources of heat, faulty electrical equipment, defective reduction inbone marrow, cataracts, immunological defects and death. of radiation can be burns to the skin, cancer, alterations to the blood system, important, such asUVlight and lasers. Consequences of exposure tohigh levels and electron microscopes. Other sources of non-ionizing radiation canbe the most serious risk and its sources are radioactive isotopes, X Radiation: Ionizing radiation (alpha,beta,gamma, X-rays, neutrons) ispotentially O , the most common causesof fire in facilities are: -ray equipment attached riskoriginate from human error. large proportion of the problems thatcanariseduring aprocess withaparticular of the staff,intellectual capacity, training, working atmosphere and conditions. A to aptitudes and capacities tocarryoutthe work,physical and psychological state considerably increase the riskassociated withother factors. The risksare related An additional risk group is composed of human and environmental factors that can B.3 4 3 2 1 Table B.2 |How toextinguish fires In Table B.2 common typesof fire and control methods are given: system thatallowsrapid response. It isveryimportant toinstall smoke detectors and alarms aspartof adetection electrical conductor Type Violent reactions withwater, generating hydrogen and producing explosive mixtures withair Incompatible withwater, withwhich itcancausefire Can beusedbutlesseffective A D B C

solids ingeneral Wood, textiles, paperand Combustible material Electrical equipment materials M grease etc.) (petrol, acetone, with lowcombustion points Inflammable liquids orsolids environmental conditions Psycho-physiological and etals and combustible Water No No No Yes mana 4 3 2 gement ofrisksinf Foam No No Yes Yes

4 3 Extinguisher Yes No Yes Yes CO 4 1 2 Chemical Yes dusts Yes Yes Yes 1 a cilities Special agents Yes Yes Yes No 1 1

annex 1 67 module 68

biosafety Resource Book c terms of health damage, pollution and economic losses. ultimately use of safetyequipment. originate from human error, and depend onthe levelof training, such asinthe A large percentage of problems thatcanariseinaprocess withadetermined risk illumination. tasks inarange of facilities, including temperature, humidity, ventilation and Environmental conditions havetobetaken into account when carrying out » » conduct; » » » Such influencing factors canbe: risk analysis psycho-social stress. intellectual capacityand jobtraining; psychological state; physiological state; result inserious consequences for personnel and the environment in Errors and accidents caused byuntrained personnel can annex 2

Principles and methodologies for the environmental risk assessment

The following information regarding the establishment of an environmental risk assessment was extracted from legislation of the European Community (EC, 2001). Further guidance literature providing detailed explanations concerning the individual steps of the ERA has been prepared and is available online (EFSA, 2006a,b). Further, the requirements for information that must be submitted when handing in an application for a GMO release prove useful in determining the individual points that must be investigated in the ERA (see EC, 2001, Annex III). Connor et al. (2003) have also provided an interesting paper, critically investigating the ERA procedure and general risk perception and discussing major areas of environmental concerns associated with GM crops. The information provided here might serve as guidelines for the establishment of individual country environmental risk assessment procedures and relevant legislation.

A Objective

The objective of an ERA is, on a case by case basis, to identify and evaluate potential adverse effects of the GMO, either direct or indirect, immediate or delayed, on human health and the environment which the deliberate release or

69 module 70

biosafety Resource Book c » » » » should befollowed when performing the ERA: In accordance with the precautionary principle, the following general principles B appropriate methods tobeused. a view toidentifying ifthere isaneed for riskmanagement and, ifso,the most the placing onthe market of GMOs may have. The ERAshould be conducted with risk analysis » » and scientific details regarding characteristics of: Depending onthe case, the ERAhastotake into account the relevant technical C.1 C Methodology

environment becomes becomes environment If new information on the GMO and its effects on human health or the i.a., GMOs already inthe environment; intended useand the potential receiving environment, taking into account, information may varydepending onthe typeof the GMOs concerned, their The ERAshould becarried outonacasebybasis, meaning thatthe required based onavailablescientific and technical data; The ERAshould becarried outinascientifically sound and transparent manner organism from which itisderived and itsuseunder corresponding situations; cause adverse effects should be compared to those presented by the non-modified Identified characteristics of the GMO and itsusewhich havethe potential to and relevant The genetic modification(s), beitinclusion or deletion of genetic material, The recipient orparental organism(s); is aneed for amending the riskmanagement accordingly. to: (I) determine whether the risk has changed; (II) determine whether there Genral Principls Characteristics of GMOsandreleases information onthe vector and the donor;

available, the ERAmay need to bereaddressed inorder Principles andmethodoogforthenviromet » » effectsonthe dynamics of populations of species inthe receiving environment » » diseasetohumans including allergenic ortoxic effects; » case tocase, and may include: basis thatitisunlikely tooccur. Potential adverseeffectsof GMOs willvaryfrom modification. It isimportant not todiscount any potential adverseeffectonthe identifying the particular potential adverseeffectsarising from the genetic organism under corresponding conditions of the release orusewillassistin A comparisonof the characteristics of the GMO(s) withthose of the non-modified in adverseeffectsonhuman health orthe environment should beidentified. Any characteristics of the GMOs linked tothe genetic modification that may result 1. Identification of characteristics whichmaycauseadverse effects: In drawing conclusions for the ERAthe following points should beaddressed: C.2 and their interaction with similarenvironments canassistthe ERA. Information from releases of similarorganisms and organisms withsimilartraits » » » » diseasetoanimals and plants including toxic, and insome case, allergenic effects; stepsintheERA used inhuman orveterinary medicine; treatments, for example by transfer of genes conferring resistance to antibiotics Compromising prophylactic ortherapeutic medical, veterinary, orplant protection diseases and/or creating new reservoirs orvectors; Altered susceptibilitytopathogens facilitating the dissemination of infectious and the genetic diversityof eachof these populations; The interaction betweenthese. The potential receiving environment; and The intended release oruseincluding itsscale; The GMO ; al riskassessment

annex 2 71 module 72

biosafety Resource Book c such occurrence. of the adverseeffectoccurring withthe magnitude of the consequences of any potential tocauseadverseeffects. Thiscanbedone bycombining the likelihood the environment posed by each characteristic of the G An estimation should be made asfar aspossibleof the risktohuman health orto 4. Estimationof theriskposedby eachidentifiedcharacteristic of theGMO(s) be released, and the manner of the release. are the characteristics of the environment into which the GMO(s) isintended to M adverse effect 3. Evaluation of thelikelihood of theoccurrence of eachidentifiedpotential which the GMO(s) is(are) intended tobereleased and the manner of the release. magnitude of the consequences islikely tobeinfluenced bythe environment into evaluated. This evaluation should assume that such an adverse effect will occur. The The magnitude of the consequences of eachpotential adverseeffectshould be 2. Evaluation of thepotentialconsequencesof eachadverse effect,ifitoccurs » » » » » include: Adverse effectsmay occurdirectly orindirectly through mechanisms which may effectsonbiogeochemistry (biogeochemical cycles),particularly carbonand » risk analysis

ajor factors in evaluating the likelihood or probability of adverse effects occurring Changes inmanagement, including, where applicable, inagricultural practices. Interactions withother organisms, Phenotypic and genetic instability, organism whether genetically modified or not, The transfer of the inserted genetic material to other organisms, or the same The spread of the GMO(s) inthe environment, nitrogen recycling through changes insoildecomposition of organic material. MO identified as having the Principles andmethodoogforthenviromet 4. 3. 2. any riskmanagement strategies which are proposed. 1. D.1 the placing onthe market of GMOs: drawing conclusions onthe potential environmental impactfrom the release or D2 should beincluded, as appropriate, innotifications withaview toassisting in outlined insections Band C,information onthe points listedinsections D1or O D An evaluation of the overall risk of the G 6. Determinationof theoverall riskof theGMO(s) manage them, and ariskmanagement strategy should bedefined. The riskassessment may identify risksthatrequire management and how bestto or marketing of GMO(s) 5. Applicationof management strategies for risks from thedeliberate release n the basis of an E

l inthecaseof GMOsother than higherplants indirect interactions between the GMO and target organisms (ifapplicable). Potential immediate and/or delayed environmental impactof the direct and those species. release of the GMO and any selectiveadvantage ordisadvantage conferred to Potential for gene transfer toother species under conditions of the proposed of thisbecoming realized under the conditions of the proposed release(s). Any selectiveadvantage ordisadvantage conferred tothe GMO and the likelihood under the conditions of the proposed release(s). ikelihood of the G imp Conclusins thepote ntial evirome the marketofGMOs a ct fromtheelasopla RA carried out in accordance with the principles and methodology MO to become persistent and invasive in natural habitats MO (s) should bemade taking into account al riskassessment cing on al

annex 2 73 module 74

biosafety Resource Book c 9. 8. 7. 6. 5. risk analysis 3. 2. 1. D.2 5. 4.

likelihood of the GMHPbecoming more persistent thanthe recipient orparental

inthecaseof geneticallymodified higherplants: are different from those usedfor non-GMOs. of the specifictechniquesused for the management of the GMO where these Possible immediate and/or delayed, direct and indirect environmental impacts and non-target organisms inthe vicinity of the GMO release(s). resulting from potential direct and indirect interactions of the GMO and target Possible immediate and/or delayed effectsonbiogeochemical processes derived from it,ifitisintended tobeusedasanimal feed. for the feed/food chainresulting from consumption of the GMO and any product Possible immediate and/or delayed effects onanimal health and consequences with, coming into contact withorinthe vicinity of the GMO release(s). potential direct and indirect interactions of the GMO and persons working Possible immediate and/or delayed effectsonhuman health resulting from parasites and pathogens. impact onpopulation levels of competitors, prey, hosts, symbionts, predators, indirect interactions betweenthe GMO withnon-target organisms, including Potential immediate and/or delayed environmental impactof the direct and species under conditions of planting the G Potential for gene transfer tothe same orother sexually compatibleplant Any selectiveadvantage or disadvantage conferred tothe GMHP. plants inagricultural habitats ormore invasiveinnatural habitats. and indirect interactions of the GMHPwithnon-target organisms (alsotaking Possible immediate and/or delayed environmental impact resulting from direct predators, parasitoids, and pathogens (ifapplicable). and indirect interactions betweenthe GMHPand target organisms, such as Potential immediate and/or delayed environmental impactresulting from direct or disadvantage conferred tothose plant species. M HP and any selective advantage Principles andmethodoogforthenviromet 9. 8. 7. 6.

the GMHPwhere these are different from those usedfor non-GMHPs. of the specificcultivation, management and harvesting techniquesused for Possible immediate and/or delayed, direct and indirect environmental impacts and non-target organisms inthe vicinity of the GMO release(s). resulting from potential direct and indirect interactions of the GMO and target Possible immediate and/or delayed effectsonbiogeochemical processes products derived from it, ifitisintended tobeusedasanimal feed. for the feed/food chainresulting from consumption of the GMO and any Possible immediate and/or delayed effects onanimal health and consequences with, coming into contact withorinthe vicinity of the GMHPrelease(s). potential direct and indirect interactions of the GMHPand persons working Possible immediate and/or delayed effectsonhuman health resulting from parasites and pathogens. on population levelsof competitors, herbivores, symbionts (where applicable), into account organisms which interact withtarget organisms), including impact al riskassessment

annex 2 75 module 76

biosafety Resource Book c F EFSA (European Food SafetyA EFSA (European Food EC (Councilof theEuropean Communities),2001:Directive 2001/18/ECof the European EC (European Commission). Directive 2001/18/EEC.Available at: Conner AJ,Glare TR,Nap JP, 2003:The release of genetically modified crops into the Codex AlimentariusCommission. 2004.FoodsDerivedfrom Biotechnology.J Codex AlimentariusCommission. 2003.Reportof the Twenty-Sixth Session. Rome. 30 CBD (Convention of Biological Diversity). 2000.Cartagena Protocol on Biosafety to the BMBL (BiosafetyinMicrobiological andBiomedicalLaboratories) 2007.5thEdition. A REFEENCES risk analysis A ustralian Government. 2005.The RiskAnalysis Framework. Department of Health and O. 1999.TheApplicationof RiskCommunicationtoFoodStandardsandSafety Matters. Report Paper 70. of europa.eu/en/scdocs/scdoc/374.htm Organisms (GMO). E FSAJ intended for food and feedusebythe Scientific Panel onGenetically M assessment of genetically modified microorganisms and their derived products online athttp://www.efsa.europa.eu/en/scdocs/scdoc/99.htm Panel onGenetically M assessment of genetically modified plants and derived food and feedbythe Scientific eu/LexUriServ/LexUriServ.do?uri=OJ:L:2001:106:0001:0038:EN:PDF 90/220/EEC. the environment of genetically modified organisms and repealing Council Directive Parliament and of the Council of 12M http://ec.europa.eu/environment/biotechnology/legislation.htm 19-46. Available online at http://www.inai.org.ar/ogm/The%20relese...... part%202.pdf environment. Part II: Overview of ecological risk assessment. The Plant J http://www.fao.org/docrep/007/y5819e/y5819e00.htm WH fao.org/docrep/006/y4800e/y4800e0o.htm#bm24 Programme, Foodand Agriculture Organization, Rome. Available at: http://www. in the Framework of the Codex Alimentarius. J June -7July2003.Appendix IV. Working Principles for RiskAnalysis for Application Convention of Biological Diversity. Available at:http://www.cbd.int Convention onBiological Diversity:text and annexes. M http://www.cdc.gov/OD/OHS/biosfty/bmbl5/BMBL_5th_Edition.pdf Disease Control and Prevention and National Institutes of Health. Available at: Washington. U.S.Department of Health and Human Services. Centers for Ageing, Office of the Gene Technology Regulator.

J O Food oint FA Available at:ftp://ftp.fao.org/docrep/fao/005/x1271e/x1271e00.pdf O/WH Standards Programme CODEXAlimentarius Commission. Available at: OJ L106,17.4.2001,p.1–39.Available onlineathttp://eurlex.europa. O Expert Consultation. Rome 2-6 February 1998.Food and Nutrition Safety odified Organisms (GMO). EFSAJ ournal 374,1-115.Available online athttp://www.efsa. A uthority), 2006b:Guidance document for the risk uthority), 2006a: Guidance document for the risk arch 2001onthe deliberate release into oint FA ournal 99,1-100.Available ontreal. Secretariat onthe O/WH O FoodStandards ournal 33, ournal 33, oint FA odified O/

REFERENCES

FAO. 2007. FAO Biosecurity Toolkit. Rome. Available at:http://www.fao.org/docrep/010/ a1140e/a1140e00.HTM FAO/WHO. 1995. Application of risk analysis to food standards issues. Report of the Joint FAO/WHO Expert Consultation. Geneva, 13-17 March. WHO, Geneva. Gelvin, S.B. 2000. Agrobacterium and plant genes involved in T-DNA transfer and integration. Annual Review of Plant Physiology and Plant Molecular Biology. 51: 223-256. Hayes, K. 2001. Environmental Risk Assessment for GMs. CSIRO Marine Division and Biodiversity Sector. Available at: apec.biotec.or.th/pdf/KeithHayes.pdf IDS (Institute for Development Studies). 2003. Public Participation and the Cartagena Protocol for Biosafety. A review for DfID and UNEF-GEF, Institute for Development Studies (IDS). By D. Glover, J. Keeley, P. Newell, R. McGee. Brighton. Institute for Development Studies. ILGRA (Interdepartmental Liaison Group on Risk Assessment). 1999. Risk Communication, A Guide to Regulatory Practice. Health and Safety Executive, Risk Assessment Policy Unit. London. ISO (International Organization for Standardization). ISO/IEC 17025. 2005. General requirements for the competence of testing and calibration laboratories. Konig, A., Cockburn, A., Crevel, R,W., Debruyne, E., Graftstroem, R., Hammerling, U., Kimberg, I., Knudsen, I., Kuiper, H.A., Peijnenburg, A.A., Penninks, A.H., Poulsen, M., Schauzu, M. & Wal, J.M. 2004. Assessment of the Safety of Foods Derived from genetically Modified (GM) Crops. Food and Chemical Toxicology. 42: 1047-1088. Küenzi, M., Archer, L., Assi, F., Brunius. G., Chmiel, A., Collins, C.H., Deak, T., Donikian, R., Financsek, I., Fogarty, L.M., Frommer, W., Hamp, S., Houwink, E.H., Hovland, J., Lagast, H., Mahler, J.L., Sargeant, K., Tuijnenburg Muijs, G., Vranch, S.P., Oostendorp J.G. & Treur, A. 1987. The WP Safety in Biotechnology of the European Federation Biotechnology, Safe Biotechnology - 2. The classification of micro-organisms causing diseases in plants. Appl. Microbiol. Biotechnol. 27: 105. Millstone, E., Brunner, E. & Mayer, S. 1999. Beyond ‘substantial equivalence’, Nature. 401: 525–526 NIH (National Institute of Health). 2002. Guidelines For Research Involving Recombinant DNA Molecules. Available at: http://oba.od.nih.gov/rdna/nih_guidelines_oba.html OECD (Organization for Economic Co-operation and Development). 2009. Consensus Documents for the Work on Harmonisation of Regulatory Oversight in Biotechnology. Available at: http://www.oecd.org/document/51/0,3343, en_2649_34387_1889395_1_1_1_1,00.html OECD (Organization for Economic Cooperation and Development). Good Laboratory Practices, published by the OECD’s Environment Directorate, revised in 1998, document ENV/MC/CHEM(98)17. http://www.oecd.org/document/63/0,3343, en_2649_34381_2346175_1_1_1_1,00.html Persley, G.J., Giddings, L.V. & Juma, C. 1993. Biosafety, The safe application of biotechnology in agriculture and the environment. ISNAR Research Report 5. Recuerda, M.A. 2008. Dangerous Interpretations of the Precautionary Principle and the Foundational Values of European Union Food Law: Risk versus Risk. J. Food L. & Poly. 4(1).

77 module 78

biosafety Resource Book c Ruane, J.&Sonnino,2006.Resultsfrom the FA risk analysis UNCED (United Traynor, P.L., Frederick, R.J&K Traynor, P., A WHO (World HealthOrganization). 2004.Laboratory Biosafety M UNEP(UnitedNationsEnvironment Programme). 1995.UNEPInternational Technical Dialogue onSelectedIssues. FA Declaration onEnvironment andDevelopment. Rio de J U Biotechnology: AWorkbook for Technical Training. EastLansing. Michigan State Available at:http://www. isb.vt.edu/cfdocs/greenhouse_manual.cfm Research withTransgenic Plants and Microbes. Guidelines for SafetyinBiotechnology. niversity. dair, D.&IrwinR.2001.APractical Guide toContainment Greenhouse Nations Conference on Environment and Development). 1992. Rio och, M.2002.Biosafety &RiskAssessment inAgricultural O Research and Technology Paper 11.FAO O Biotechnology Forum:Background and aneiro. anual. 3 rd Edition. Geneva. . Rome. . USEFUL READINGS

Andersen, M.C., Megan, E. & Northcott, J. 2004. Risk analysis and management decisions for biological control agents: perspectives from theoretical ecology. Available at: http://www.usda.gov/oce/reports/risk/AndersenBioControlReport.pdf ASTHO (Association of State and Territorial Health Officials). 2002. Communication In Risk Situations. Responding To The Communication Challenges Posed By Bioterrorism And Emerging Infectious Diseases. Available at: http://www.astho.org/pubs/astho%20risk%20communication%20e-workbook.Htm Belgian Biosafety Server. 2006. International classification schemes for micro-organisms based on their biological risks. Available at: http://www.biosafety.be/RA/Class/ ClassINT.html Biological Agents: Managing the Risks in Laboratories and Healthcare Premises. 2005. Advisory Committee on Dangerous Pathogens. Department of Health and Department of Environment, Food and Public Affairs. United Kingdom. Available at: www.hse.gov.uk/aboutus/meetings/committees/acdp/050208/acdp88p6.pdf Caucheteux, D. & Mathot, P. 2005. Biological Risk Assessment: An Explanation Meant for Safety Advisors in Belgium. Applied Biosafety. 10(1): 10-29. Available at: http://www.absa.org/abj/abj/051001caucheteux.pdf Cellini, F., Chesson, A., Colquhoun, I., Constable, A., Davies, H.V., Engel, K.H., Gatehouse, A.M., Kärenlampi, S., Kok, E.J., Leguay,J-J., Lehesranta, S., Noteborn, H.P., Pedersen, J. & Smith, M.. 2004. Unintended effects and their detection in genetically modified plants. Food and Chemical Toxicology. 42: 1089-1125. Available at: http:// www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6P-4C004D33&_user=10&_ rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_ urlVersion=0&_userid=10&md5=02997d8e5098161ab4f9a0ccf3bb81c9\ Chassy, B.M. 2002. Food Safety Evaluation of Crops Produced through Biotechnology. Journal of the American College of Nutrition. 21( 3): 166S-173S. Published by the American College of Nutrition. Chen, M., Zhao, J-Z., Collins, H.L., Earle, E.D., Cao, J. & Shelton, A.M. 2008. A Critical Assessment of the Effects of Bt Transgenic Plants on Parasitoids. PLoS ONE 3(5) e2284. Available at: http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0002284 Consulting and Audit Canada for Emergency Preparedness Canada. 1995. Managing Biological Risk with an emphasis on risks associated with biotechnology. Available at: http://www.dsp-psd.pwgsc.gc.ca/Collection/D82-54-1995E.pdf EC (European Commission). Guidance Document for the Risk Assessment of Genetically Modified Plants and Derived Food and Feed. 2003. Prepared for the Scientific Steering Committee by the Joint Working Group on Novel Foods and GMOs Composed of members of the Scientific Committee on Plants, Food and Animal Nutrition. Available at: http://www.ec.europa.eu/food/fs/sc/ssc/out327_en.pdf

79 module 80

biosafety Resource Book c Halsey, M.E.2006.Integrated Confinement System for GeneticallyEngineeredPlants. OECD (Organization for Economic Cooperation and Development).Overview An of the Nuffield CouncilonBioethics. 2004.The U National Research Council.Improving RiskCommunication: Free Executive Summary. Hancock, J.F. Gupta, K., Fox, A.2003.GLPregulations vs. ISO 17025requirements: how do they differ?Accred Qual Fischhoff, B. 1995.RiskPerception and Communication U Falck-Z risk analysis Meek, S.&K Lemaux, P.G. 2008. GeneticallyEngineered Plants and Foods:AScientist’s Analysis of the Lehrer, S.B. Potential Health Risksof Genetically M Jaffe, G.2008.Establishing National Biosafety RegulatorySystems. Key Outstanding Program for Biosafety Systems. St.Louis, at: www.apcoab.org/documents/bs_pub.pdf and Agriculture Organization of theU Asia-Pacific Consortium on Agricultural Biotechnology, New Delhi,and FA Countries. Asia-Pacific Association of Agricultural Research Institutions Bangkok; Transgenic Plants. Available at:http://www.oecd.org/dataoecd/7/55/39018232.pdf Workshop: Beyond the BlueBook–Framework for Risk/Safety Assessment of Countries: AFollow-upDiscussion Paper. London. Biosafety and WT of Article 26.1?Paper presented at12 biosafenet/M http://www.sds.hss.cmu.edu/media/pdfs/fischhoff/FischhoffU Society for RiskAnalysis. RiskAnalysis. 15(2).Society for RiskAnalysis. Available at: edu/nap-cgi/execsumm.cgi?record_id=1189 Committee onRiskPerception and Communication. Available at:http://www.nap. Regulation of GMOs.M Science Center. Available at:http://www.ifpri.org/pbs/pdf/pbsbriefhalsey.pdf Assur. 8:303. Zepeda_Ravello_14_giugno(1).pdf 14 Biotechnology: Creative annualreviews.org/doi/abs/10.1146/annurev.arplant.58.032806.103840 Issues (Part I). http://www.cgiar.org/biotech/rep0100/Lehrer.pdf be Assessed and Brief No. 12.Available at:www.ifpri.org/pbs/pdf/pbsbrief12.pdf Issues U epeda, J.2008.Socio-economic Considerations, the Cartagena Protocol for June 2008. Available at: http://www.economia.uniroma2.it/icabr/Public//File/ arihaloo, J.L&Khetarpal,R2008.Biosafety Regulations of Asia-Pacific eese, P. 2006.Putting Theory Into Practice –Applying RiskAnalysis tothe 2003. A Framework for Assessing the Risk of Transgenic Crops. nder the Cartagena Protocol for Biosafety. Program for Biosafety System, eek.pdf Annu. Rev. Plant Biol. 59: 771-812. Available at: http://arjournals. O: Whatare the issuesand whatisatstake for developing countries Minimized? Agricultural Biotechnology and the Poor. Available at: elbourne, Australia. Available at:www.gmo-safety.eu/pdf/ Destruction, Adoption or Irrelevance. Ravello, Italy. 12- th se of Genetically M nited Nations), Rome. P.108 +i-x.Available ICARB Conference: The Future of Agricultural Missouri, odified Organisms: How CanAllergens nplugged: Twenty Y U SA. Donald Danforth Plant odified Crops inDeveloping nplugged.pd BioScience. 53(.5). ears of Process. O (Food useful readings

OECD (Organization for Economic Cooperation and Development.). 2001. Communicate Risk. Meeting of Senior Officials from Centers of Government on RiskM anagement, Reykjavik, 22-23 October 2001. OECD. Peterson, G., Cunningham, S., Deutsch, L., Erickson, J., Quinlan, A., Raez-Luna, E., Troell, R., Woodbury, P. & Zen, S. 2000. The Risks and Benefits of Genetically Modified Crops: A Multidisciplinary Perspective. Conservation Ecology. Available at: http://www.consecol.org/vol4/iss1/art13/ Rationalizing and Harmonizing Plant Biotechnology Regulations in Southeast Asia: A Learning Forum. 4-7 March 2008, Miracle Grand Convention Hotel, Bangkok, Thailand. Note: contains several powerpoint presentations on status of biosafety regulation of various SEAsian countries, and lectures on environmental risk assessment, plant biotechnology. Available at: http://www.searca.org/web/training/courses/2008/ march_c/index.html Reeves, C. 2007. Managing outrage and crises: Dealing with Risk by Understanding your Audience. Guelph Food Technology Center News, reprint. Number 49. Risk Communication Manual. 2005. Capacity Building in Biosafety of GM Crops in Asia. FAO (Food and Agriculture Organization of the United Nations). Bangkok. GCP/ RAS/185/JPN. Document No. 1.2005. Risk Communication Tool. 2003. Electronic Resource and Preservation Network. Available at: http://www.erpanet.org/guidance/docs/ERPANETRiskTool.pdf Romeis, J., Bartsch, D., Bigler, F., Candolfi, M.P., Gielkens, M.M.C., Hartley, S.E., Hellmich, R.L., Huesing, J.E., Jepson, P.C., Layton, R., Quemada, H., Raybould, A., Rose, R.I., Schiemann, J., Sears, M.K., Shelton, A.M., Sweet, J., Vaituzis, Z. & Wolt., J.D. 2008. Assessment of Risk of Insect-Resistant Transgenic Crops to Non- Target Arthropods. Nature Biotechnology. 26(2). Ruane, J. & Zimmermann, M. 2001. Agricultural Biotechnology for Developing Countries: Results of an Electronic Forum. FAO Research and Technology Paper 8. FAO. Rome. Spok, A.,, Hofer, H., Lehner, P., Valenta, R., Stim, S., & Gaugitsch, H. 2004. Risk Assessment of GMO Products in the European Union. Toxicity Assessment, Allerginicity Assessment and Substantial Equivalence in Practice and Proposal for Improvement and Standardization. Umweltbandesamt GmBH Wein, Vienna, Austria. Available at: http://www.umweltbundesamt.at/fileadmin/site/publikationen/BE253.pdf Torgersen, H. 2004. The Real and Perceived Risks of Genetically Modified Organisms. Europe Molecular Biology Organization Reports. Special Issue Vol. 5, 2005, pp. 817- 821. Available at: http://www.oeaw.ac.at/ita/ebene5/HT_1243.pdf WB (World Bank). 2003. Biosafety Regulation: A Review of International Approaches. WB Agriculture and Rural Development Department. Wolt, J.D. & Peterson, R.K.D. 2000. Agricultural Biotechnology and Societal Decision- Making: The Role of Risk Analysis. AgBioForum. 3(1): 39-46. Available at: http:// www.agbioforum.org/v3n1/v3n1a06-wolt.pdf

81 Design and layout: Pietro Bartoleschi and Arianna Guida (Studio Bartoleschi) Cover illustrations elaborated from “l’Encyclopédie Diderot et d’Alembert” Printed in Italy on ecological paper, Forest Stewardship Council (FSC) certified, May 2011 Biosafety Resource Book interest tomost countries. since these are of immediate assessment of GMcrops and environmental risk on crop biotechnology communication. It focuses management and risk of riskassessment, risk principles, and methodologies on biological risks, concepts, provides basic information Risk analysis Module c [email protected] or contact www.fao.org/biotech please consult For additional information