1. 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

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

3. 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

4. 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)

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

6. Hazard identification
Generic
Biological Route block diagram

7. Hazard identification
Generic
Chemical Route block diagram

8. 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

9. Hazard identification – Generic & Examples

10. Hazard identification Generic Biological Route

11. Hazard identification Generic Chemical Route

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

13. Optional Production Processes

14. 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;

15. 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)

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

17. 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

18. 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

19. 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?

21. 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?

22. 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

23. 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

24. Risk assessment systematics

25. 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.