Abstract A step-wise or ‘tiered’ approach has been used as a rational procedure to conduct environmental risk assessments in many disciplines. The Technical Advisory Group (TAG) of EuropaBio’s Plant Biotechnology Unit (PBU) proposes that the tiered approach also be recognized as the recommended approach to evaluate the environmental safety of GM crops, in particular for potential risks to non-target organisms (NTO). The tiered process allows the ‘case-by-case’ assessment of potential risks of a GM crop to NTO and provides for a logical progression of NTO studies of increasing complexity and refinement where necessary. The tiered approach also allows the practical organization of data generation and enables rational, science-based decision-making by both registrants and regulators. Introduction GM plants may or may not pose risks to non-target organisms (NTO) in the environment. Risks vary considerably depending on the crop, the GM trait and/or the scope of use, therefore a ‘case-by-case’ approach to risk assessment is needed. Assessment of potential risks to NTO is a challenging scientific task and a rapidly developing area of regulation. Applying general principles of environmental risk assessment, the current European legislation (Directive 2001/18/EC, Annex II) provides some guidance, but the specifics are subject to interpretation by notifiers and regulators. The challenge is to develop a scientifically sound approach to assessing risks to NTO, compatible with legislative requirements. To that effect, the TAG of EuropaBio’s PBU proposes the use of a step-wise risk assessment scheme of increasing complexity and refinement, known as the ‘tiered approach’. The purpose of this poster is to provide a basis for discussion among regulators, notifiers and experts in the field of environmental risk assessment. Assessing the safety of genetically modified plants for non-target organisms Technical Advisory Group (TAG) of EuropaBio’s Plant Biotechnology Unit (PBU) ( Practical considerations on the methodology to test NTO Which species to test? NTO that are potentially at risk from the use of GM crops will vary depending on the crop and the inserted GM trait. Hence, appropriate test species should be selected on a case-by-case basis. Environmental risk assessment guidelines for GM plants already exist in other countries such as USA and Canada. In accordance with these, the TAG recommends a list of NTO groups, from which selected test species can be chosen: - Mammals - A bird - A fish - Freshwater invertebrates - Arthropods: predators, parasitoids, pollinators - Soil organisms In most cases, it will be necessary to select a limited number of species for testing. These should be relevant to the GM plant under assessment and either represent a functional group of NTO with a similar route of exposure (Figure 2) and/or be representative of the taxon to which they belong. In order to obtain meaningful results, the species should be amenable to testing in the laboratory. Ideally, validated tests should already be available or tests that can be readily adapted and validated should be established. The tests should be conducted in manner that exposes the organism to the test substance by the same route that it would be in the field (oral, contact,…). Which test substance to use? There is a range of test substances that can be used in regulatory laboratory tests for GM plants: plant material (e.g. leaves, pollen or roots), purified protein, protein expressed in a microbial system, etc. The choice of test substance should be based on the testing strategy that the assessor has decided upon and the aims of a particular test. However, it can also be influenced by the feasibility of obtaining sufficient test material to administer the desired test protein concentrations in the various NTO studies. The Tiered approach to risk assessment for NTO Tiered approach to hazard and exposure assessment According to the classical risk assessment paradigm: Risk= f (Hazard, Exposure) One of the most important steps in every evaluation of potential risk is the clear definition of the scope of the risk assessment. The risk assessment often is an iterative process where the conclusion from a given tier allows to conclude the assessment or indicates that further data are necessary and, if so, which options for refinement may be considered. A schematic presentation of the tiered approach for NTO is given in Figure 1. Tiered testing strategies Tier 0 is a problem formulation step which focuses the risk assessment and ensures conclusions relevant to risk-based decision making. If no risks are conceivable, then the risk assessment can stop there. However, if risks have been identified or cannot be ruled out with reasonable certainty (expert judgment), then the evaluation is pursued and the risk assessment is refined stepwise at higher tiers. If tests on NTO are considered necessary, a suitable testing strategy must be formulated. Relevant representative testing species can then be tested under worst-case conditions (meaning conditions that allow the consideration of high levels of exposure that would not normally occur in the field or high level doses that allow compensation for potential uncertainty in the risk assessment). If the risks under worst-case conditions are considered low or acceptable, then the risk assessment can stop there. The purpose of higher tier tests, where necessary, is to further reduce uncertainty in the risk characterization and/or, by generating additional data, to replace conservative lower-tier assumptions with confirmatory or more realistic estimates. Evaluating risk, concluding the testing The risk to NTO is evaluated at every decision point marked with an asterisk (*) in Figure 1 by consideration of the hazard and exposure data (quantitative or qualitative) available at the respective tier. In the view of the TAG this means that, depending on the case, a satisfactory risk conclusion can be reached on the basis of already available data, or through additional data generated according to the tiered testing programme, or using a combination of both.