Choosing representative NTO species for meaningful risk assessment of insect-resistant genetically modified crops based on realistic evaluation of exposure, mode of action, and specific crop tissue expression data

The general approach to non-target organism (NTO) risk assessment is to determine the acceptable safety level based on the calculated margin of exposure (MOE) based on evaluation of hazard (LC₅₀ or NOEC (no observed effect concentration)) and exposure (estimated environmental concentration, EEC).  In cases where toxicity data is warranted to better understand the hazard level to NTOs, laboratory ecotoxicology studies based on worst-case exposure scenarios are usually conducted.  In order for these NTO studies to be informative, scientifically relevant surrogate species need be chosen to best represent the target NTO species that will potentially be exposed to the cultivation of the GM crop expression the insecticidal protein trait.  The well-established EPA OPPTS 885.4340 test guideline for determining potential toxicity of microbial pesticides on NTOs has historically been adapted by regulatory agencies to assess the toxicity levels of insecticidal proteins that are expressed by GM crops on NTOs.  Although this test guideline sets a good baseline framework for what NTO species to use for toxicity testing, certain unique insecticidal protein traits will require further considerations on how to properly select representative NTO species for testing.  Here, some established key principles of surrogate species selection and additional considerations will be applied to a hypothetical GM crop example that expresses a broad-spectrum insecticidal protein that is active against multiple pest insect orders.