Ecotoxicology Studies To Evaluate Adverse Impacts On Non Target Organisms

Transcription

1 Ecotoxicology Studies To Evaluate Adverse Impacts On Non Target Organisms Chad Boeckman Research Scientist-Environmental Risk Assessment DuPont Pioneer Joe Huesing, PhD Senior Biotechnology Advisor USAID

2 Outline Stakeholder input Risk ERA framework Study design Tiered testing Surrogate species Conclusions 2

3 IOBC/WPRS working group GMOs in Integrated Plant Production IOBC - International Organisation for Biological and Integrated Control of Noxious Animals and Plants. West Paelarctic Regional Section. Goals To develop harmonized methods for testing the ecological impact of GMOs for Environmental Risk Assessment (ERA); The emphasis is on land dwelling non-target arthropods (insects - NTOs); The methods must be scientifically-sound, generic, & practical; They can be adopted by a variety of countries; They can be adapted to the specific regulatory needs of individual countries. 3

4 What is a Non-Target Organism (NTO)? Non-Target Organisms (NTO) are a key part of Environmental Risk Assessments. A NTO is an animal (mainly insects), which is not the intended target of the GM Plant. An NTO can be a beneficial or a pest species. 4

5 Risk is the potential for harm to occur Risk = Function (Hazard X Exposure) Bioassay Test Toxin Expression In Plant Hazard (effects test) RISK Exposure Hazard toxic effect of a substance, e.g., Bt on an insect. Exposure contact of an animal with a substance, e.g., pollen. Risk has to be assessed based on several factors. 5

6 Environmental Risk Assessment Framework Problem Formulation Review of available information Actions Stressor characteristics Ecosystem context Understand protection goals Define harm Develop conceptual model Identify exposure pathways Identify assessment endpoints Generate risk hypotheses Determine analysis plan Analysis Data generation Risk Characterization Adapted from Carstens et al

7 ERA framework helps ensure that Protection goals are identified Relevant endpoints are assessed Analysis is appropriate for data collected Analysis is meaningful for Regulatory agency Results are relevant for safety assessment Results are useful for Regulatory decision making 7

8 Environmental Risk Assessment Problem Formulation Review of available information Actions Stressor characteristics Ecosystem context Understand protection goals Define harm Develop conceptual model Identify exposure pathways Identify assessment endpoints Generate risk hypotheses Determine analysis plan Information is gathered in early problem formulation development Trait characteristics Pest spectrum screening Insecticidal trait? Targets? Specificity? Expression Where is the protein in the plant? Concentration Stability/Agronomics Substantial equivalence Focus on introduced changes Receiving Environment Cultivation or import? Crop characteristics NTOs exposed Adapted from Carstens et al

9 Problem Formulation Environmental Risk Assessment Review of available information Actions Stressor characteristics Ecosystem context Understand protection goals Define harm Develop conceptual model Identify exposure pathways Identify assessment endpoints Generate risk hypotheses Determine analysis plan Protection goals Define entity to be protected Set by Regulatory Authority Define harm 50% growth inhibition? Identify exposure pathways Generate risk hypotheses Adapted from Carstens et al

10 Problem Formulation Environmental Risk Assessment Review of available information Actions Stressor characteristics Ecosystem context Understand protection goals Define harm Develop conceptual model Identify exposure pathways Identify assessment endpoints Generate risk hypotheses Determine analysis plan Generate science and analysis plan Is there data available? Does new data need to be generated? Follow tiered-testing approach What species make sense to test? Surrogate species Determine the route and focus Adapted from Carstens et al

11 Tiered Risk Assessment Tier Laboratory Semi-field Field Increase in realism and ecological complexity Power Evaluation of potential for adverse effects Evaluation of potential consequences of adverse effects organisms ecosystems Adapted from Romeis et al

12 Effects Tests (Hazard Determination) The Number of Species Tested is Determined by Familiarity Familiarity with the trait, e.g., Bt protein Familiarity with the crop Information level Information on hazard Information on exposure Very low Broad spectrum, mode of action unknown Expression in all plant org. and tissues many species to test (11-15) Intermediate Narrow spectrum, mode of action unknown Expression in some org. and tissues some species (6-10) Very high Narrow spectrum, mode of action known Expression organ and tissue specific few species (0-5) 12

13 Species Selection - Surrogate Concept Appropriate species serve as surrogates for ecologically and economically important NTOs Surrogacy based on: Meaning: a substitute; to stand in for Taxonomy, e.g., insect order Function, e.g., pollinators, e.g., bees Stressor and stressor MOA Developed because you can t test everything. Need relevant data at appropriate costs Need validated test system Historically started in the chemical industry. Acute (short-term) Effects Tests High Dose 7-spot Ladybird Refinement has taken place for Biotech crops. Species Test Length Surrogacy allows for data transportability. 13

14 What makes a good surrogate species? Amenable to laboratory Validated bioassay Artificial diet Relationship to target pest Relevant to crop 14

15 Study Design Considerations Specific measurement endpoints Should be related to assessment endpoints. Depends on purpose of study, e.g., acute vs. chronic. Simple life-table parameters that relate to effects in the field, e.g., mortality. Other endpoints possible, e.g., weight. Statistically valid design to address question. 15

16 Study Design Considerations Life-stage to be tested Are larval and/or adult stages exposed? Selection criteria Level of likely exposure. Sensitivity to the insecticidal compound. Amenability to testing Validated Test System. 16

17 Study Design Considerations Availability of test protocols Historically pesticide testing protocols served as starting point. Test systems must be validated. Modification needed to account for: Theoral exposure pathway. Different mode of action of insecticidal proteins. 17

18 Study Design Considerations Test validation (quality control standards) Good Laboratory Practices Assures repeatability, interpretability and quality of the study. GLP standards recommended. Principles of GLP developed w/ OECD - first published in Differs from academic studies -- need for complete study/data reconstructability! Regulators, public, and researchers need confidence in the reported data. 18

19 Higher Tier Testing Conduct Higher Tier tests only when they: Will reduce uncertainty in risk assessment. They are justified by detection of unacceptable risks at lower tiers of testing. When early tier studies are not possible. Can be performed under the conditions and rigor necessary to produce interpretable results. 19

20 Tier II Test Conducted as a result of a trigger in the Tier I test. Represents more realistic exposure scenario. Usually involves plant tissue or whole plants. Common tissues are pollen or leaves. Test Levels < 10X - usually 1X If negligible risks are established, testing stops. 20

21 Tier III Test Triggered by results of Tier I and II tests. Usually green house or field tests. Complex experimental designs. Labor intensive and expensive. If negligible risks are established, testing stops. If potential risk then mitigation/monitoring. 21

22 How Effects Data Are Used The result of the Effects Test is used to establish a No Observed Effect Concentration (NOEC). The NOEC is evaluated in the context of the Maximum Expected Environmental Concentration (EEC). If the NOEC > EEC there is little risk. If the NOEC < EEC risk must be assessed. Effects data are incorporated in the overall Risk Assessment. 22

23 Conclusion Testing for potential effects of GM products on NTO is based on a Tiered testing approach. The approach is pragmatic and science-based and starts with Problem Formulation. Tiered testing concept Test animal systems consider validated systems (GLP), surrogate animals, functional groups, and the crop. Key guidance papers include: Romeis et al. (2008). Assessment of risk of insect-resistant transgenic crops on nontarget arthropods. Nature Biotechnol. 26(2): U.S. EPA White paper on tier-based testing for the effects of proteinaceous insecticidal plant-incorporated protectants on non-target arthropods for regulatory risk assessments. R. I. Rose, ed. U.S. Environmental Protection Agency Washington, D.C. 23

24 Thank You!