BREW – Plenary Meeting May 2004 ‘Risk taxonomy and risk assessment of biotechnological processes for bulk chemicals and intermediates’ Ries de Visser (PRI – Wageningen UR) Partners: PRI, UCM, ATO, Dupont

Area covered by BREW – WP4 Risk Assessment Biotechnology GMO / LMO Bulk Chemical Production

Taxonomy of Risks Terminology & definitions Generic approach Hazard identification: Generic Routes of Production Inventory of knowledge (gaps) about risks Sources – Adv. Committees (e.g. UK: ACER; NL: COGEM; International: OECD) Generic tool for cases: Decision tree

Terminology & definitions Natural Sciences: Impact = Effect x Chance (neutral) Risk = Hazard (negative effect) x Chance [Benefit = Positive effect x Chance] Social Sciences: Perceived Risk = Impact x Weighing factor-Actors (negative)

Risk assessment – Choices Generic framework Hazard identification Chemistry, Biotechnology, Ecology, ….. NOT: Social sciences, Economics, …. Risk taxonomy NOT: Risk management Risk communication Case (s)

Hazard identification Generic Biological Route block diagram

Hazard identification Generic Chemical Route block diagram

Hazard identification - Generic Hazards Present Chemical toxicity (inhalation, skin irritant, ingestion) Thermal Pressurized Vessels Flammable Materials Explosive Long-term (systemic) toxicity Biological Allergenics Dust: respiratory irritant, allergenic, flammable / explosive Ergonomics Warehouse issues Structural Noise

Hazard identification – Generic & Examples

Hazard identification Generic Biological Route

Hazard identification Generic Chemical Route

Options for Bulk Chemical Production Processing Chemical Biotechnological Hybrid? Inputs Fossil-based Bio-based, may (not) involve biotechnology

Optional Production Processes

Selection of the information required Risk Assessment 1. General methodology (e.g. Vlek, Van der Sluijs; not management, etc.) 2. BREW-specific methodology, for biotechnology & bulk chemical production; generic, taxonomy; identification tools (e.g. Edler ea) Chemical processes (good reference; Hill, Scheringer ea., Wenning ea.) Biotechnological processes, with/ without GMO/LMO Enzymatic Fermenter Field crops (e.g. Koivisto et al.; Hill et al.) Hybrid processes and/or inputs? Sources: Experts Literature (on GMO/LMO: in its infancy) (Inter)National Biosafety Boards; Cartagena Protocol on Biosafety;

Risk taxonomies in the literature Direct/indirect effects of GMO’s (Hails 2002) Natural Science / Public Perception (e.g. Slovic 2002, Vlek 1996) Non-GM ‘baseline’ / GM Field Crop – Comparisons (e.g. PRI’s Amylopectin potato &‘Agrogen’ scenario studies; long-term field studies: Farm Scale Evaluations UK)

Decision tree YES Risk 1 Stop or redirect development NO Risk 2 Risk 3 Continue Risk 5

Decision trees: examples (enzymatic, fermenter, field crops) A. Risks at Gene/construct level Is transgene expression stable during development of the GM? If no then STOP further development Are any genes present that are coding for products like allergens or toxins which are harmful to people and/or animals? If ‘yes’ then STOP other questions: metabolic side-effects; antibiotic resistance present? B. Risks at Organism level C. Risks at Ecosystem level

Risk assessments - CASES Tools: generic approach, decision trees Risk prioritizing: ‘Need to know’ or ‘Nice to know’? Case proposed: starch crops (maize, wheat, potato) or sugar crops (sugar cane, sugar beet) ~starch value chain ~range of important platform chemicals (glucose  organic acids, PLA) ~much knowledge available Output: Matrices

Decision trees: examples (enzymatic, fermenter, field crops) C. Risks at Ecosystem level Main: Super weeds, running wild, outcrossing, biodiversity Is production of the GM crop possible in many places, such that isolated areas might be used? Can negative effects on (agro-)biodiversity be expected which differ from the case of production of non-GMO’s? Are negative effects known or expected on non-target and/or protected plant or animal species? Or on: food webs, soil flora & fauna, soil quality, greenhouse gas emissions?

Decision trees: examples (enzymatic, fermenter, field crops) B. Risks at Organism level Are the wildtype and/or wild relatives of the GM organism indigenous in NL and/or EU? Cases: oilseed rape, sugar beet, Non-cases: maize Is outcrossing of the GMO possible with a wild relative? (sub-questions on occurrence of flowering, pollen dispersal, pollination of non-GMO; are the hybrid seeds formed viable and fertile?) Others, e.g. re: overwintering parts, Horizontal Gene Transfer, parts or ingredients used for feed or food?

STARCH VALUE CHAIN FOR CHEMICALS CRD/BB/Starch Value Chain for Chemicals - 10/03 Renewable Raw Materials (maize, wheat, potatoe, …) Vegetable Proteins Proteins based plastics Starch Glucose Sorbitol Isosorbide PU Ascorbic acid PTT Propane Diol Other polyols (mainly for food markets today) Maltitol Mannitol Xylitol Arabitol Erythritol… Cyclodextrines Modified Starches Organic acids Erythorbic acid + salts Oxalic acid + salts Lactic acid + salts Succinic acid Fumaric acid Glucuronic acid Arabinonic acid Itaconic acid Citric acid + salts Lactate esters PLA Malic acid Glucaric acid Thermoplastic starches Polyhydroxyalcanoates Alkylpolyglucoside Alkylmethylglucamide Methylglucosideesters Glucamine Sorbitan esters Dibenzylidenesorbitol and der. Polyesterpolyols Isosorbide esters Dimethyl isosorbide Polyethylene Isosorbide Modified Terephtalate Thermo setting resins PEIT Current bulk productions Productions on large pilote scale Productions to be evaluated Gluconic acid + salts C = chemical process B = biotechnological process C B B + C Ethanol C2 chemistry… ETBE, fuel 2 cetogulonic acid

Acetic Ethanol Biomass Acid Ethylene PVAc EVA VAM PVOH Ethyl acetate Capacity 8.2 mtpa Output 6.5 mtpa Capacity >35 mtpa Output 29.4 mtpa Acetic Acid Biomass Ethanol Sugars Starch Ligno-Cellulose PVAc + co-polymers Ethylene Capacity 110 mtpa Output 94 mtpa Output ~ 2.3 mtpa EVA Output 0.3 mtpa VAM PVOH Ethanol to acetaldehyde was not considered as it is not part of the Acetyls value chain but is relevant C2 bulk chemical than could be accessed from bio ethanol. Information sources: TECNON 1999 report SRI public reports Directory of Chemical Producers (DCP) European Chemical News (ECN) Chemical News 21/08/02 BP estimates Capacity 4.8 mtpa Output 4.1 mtpa Output 1.3 mtpa Ethyl acetate EVOH Output ~ 1 mtpa Output 0.1 mtpa Platform green chemical 2nd derivative green chemical 3rd derivative green chemical

Risk assessment systematics

WP4 Workplan rough assessments- starting points Risks only (benefits in other WP’s) Sources of risks: legal supervision boards, stakeholders and literature Taxonomy, form: decision trees of questions [YES/NO] Three catagories of production systems Enzymatic systems (indoor; no living organisms present; leakage; prions?) Fermentor systems (indoor; bioreactors, living organisms, may evolve, adapt, and/or escape) Crop systems (outdoor; free-living organisms; dispersal, gene flow). One case, i.e. one bulk chemical, per production system category One biotechnological type per case: GM compared to non-GM Separate the effects of GMO’s (scientific method) from the stakeholder perceptions of these effects.