‘Risk taxonomy and risk assessment of biotechnological processes

for bulk chemicals and intermediates’

Ries de Visser (PRI – Wageningen UR)

Partners: PRI, UCM, ATO, Dupont

BREW – Plenary Meeting May 2004

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 taxonomyNOT:

• Risk management• Risk communication

Case (s)

Hazard identification

Generic Biological Route

block diagram

Generic Biological Route Block Diagram

Inputs Ingredient Storage / Prep Area

Fermentation

Separation

Purification

Product

Organic Waste(can often be used as fuel)

Waste waterSterilized biomassNonhazardous waste - membranes, resins, etc.

Air

Innoculum

Air

Hazard identification

Generic Chemical Route

block diagram

Generic Chemical Route Block Diagram

Reaction 1

Reaction 2

Reaction 3

Purification

Product

Thermal Oxidizer.Other abatement

Reactants

Air

Water

Rawmaterials

Catalysts waste water

non hazardous waste

hazardous waste, e.g. catalysts

air emissions

Waste WaterTreatment

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 &

ExamplesHazards Present

General PDO-process Class. General PDO-process Class.Chemical toxicity Cleaning agents medium raw m's, intermediates, waste Acrolein high

Thermal Steam sterilization low elevated temperatures > 400C mediumPressurized Vessels Reactors medium

Flammables raw m's, intermediates, waste Propylene, Hydrogen

high

Explosive Exothermic reactions Acrolein formation high

Long-term toxicity CMRs; Raw m's, catalysts highBiological BSL-1 organism contained, not

viablelow

Allergenics microorganism, dust low

Dust handling of solids, dryer low handling of solid ingredients low

Ergonomics handling of bulk materials medium handling of bulk materials low

Warehouse forklifts, stacking, slipping low forklifts, stacking, slipping low

Structural platforms, stairs, ladders low platforms, stairs, ladders low

Noise Chillers, compressors low Chillers, compressors low

Bio Route Hazards Chem Route Hazards Examples Examples

Hazard

identificatio

n

Generic

Biological

Route

Hazards Present

General PDO-process Class.Chemical toxicity

Cleaning agents medium

Thermal Steam sterilization low

Pressurized VesselsFlammablesExplosiveLong-term toxicityBiological BSL-1 organism contained, not

viablelow

Allergenics microorganism, dust low

Dust handling of solids, dryer low

Ergonomics handling of bulk materials medium

Warehouse forklifts, stacking, slipping low

Structural platforms, stairs, ladders low

Noise Chillers, compressors low

Bio Route Hazards Examples

Hazard

identificatio

n

Generic

Chemical

Route

Hazards Present

General PDO-process Class.

Chemical toxicity raw m's, intermediates, waste Acrolein high

Thermal elevated temperatures > 400C medium

Pressurized Vessels Reactors medium

Flammables raw m's, intermediates, wastePropylene, Hydrogen high

Explosive Exothermic reactionsAcrolein formation high

Long-term toxicity CMRs; Raw m's, catalysts high

BiologicalAllergenics

Dust handling of solid ingredients low

Ergonomics handling of bulk materials low

Warehouse forklifts, stacking, slipping low

Structural platforms, stairs, ladders low

Noise Chillers, compressors low

Chem Route Hazards

Examples

Options for Bulk Chemical

Production Processing Chemical Biotechnological Hybrid?

Inputs Fossil-based Bio-based, may (not) involve biotechnology Hybrid?

Optional Production ProcessesBulk

Chemical Production

Chemical Biotechnological

Inputs

Enzymatic Fermenter Field Crop

non-GM

Field Crop

GMO

Fossil-based X - - - -

X X - - -

X X X - -

X - X - -

Bio-based

‘Green’ - 1

-/X

X

-

-

-

‘Green’ - 2 -/X -/X X - -

‘Green’ - 3 -/X -/X -/X X -

‘Green’ - 4 -/X -/X -/X - X

Biological RISK Potential

Selection of the information

requiredRisk 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

Risk 1

Stop or redirect development

Risk 2 Risk 3

Risk 4

Risk 5Continue

YES

NO

Decision trees: examples (enzymatic, fermenter, field

crops)

2. Examples

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)

MaltitolMannitolXylitol

ArabitolErythritol…

Cyclodextrines

Modified Starches

Organic acidsErythorbic 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

B

B

B

B

BC

C

C

C

C

C

C

C

C

C

B

C

B + C

C

C

EthanolC2 chemistry…

ETBE, fuel

BB

C

C

2 cetogulonic acid

C

Biomass Ethanol AceticAcid

Ethylene

VAM

Ethyl acetate

PVAc+ co-polymers

EVA

PVOH

EVOH

Platform green chemical 2nd derivative green chemical 3rd derivative green chemical

SugarsStarchLigno-Cellulose

Capacity >35 mtpaOutput 29.4 mtpa

Capacity 110 mtpaOutput 94 mtpa

Capacity 8.2 mtpaOutput 6.5 mtpa

Capacity 4.8 mtpaOutput 4.1 mtpa

Output ~ 1 mtpa

Output 0.1 mtpa

Output 1.3 mtpa

Output 0.3 mtpa

Output ~ 2.3 mtpa

Risk assessment systematics Table: Risk assessment using decision trees based on level of

biological organization, applied to specific process cases (with/without GMO).

Risk assessment Biotechnological Decision tree

Bulk Chemical Production – CASES

(level of environmental exposure) (number of risks) A

Enzymatic

GM | non-GM

B Fermenter

GM | non-GM

C Field Crop

GM | non-GM

“Gene/construct effects”

YES

YES

YES

“Organism effects” -- YES YES

“Ecosystem effects" -- -- YES

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.