Expanding the weight of evidence for insecticidal protein risk assessment.
Insecticidal proteins expressed in genetically modified (GM) crops represent a sustainable and effective alternative for controlling insect and nematode pests and constitute a significant portion of the GM crop portfolio. Proteins derived from Bacillus thuringiensis (Bt) are currently the most extensively studied and widely used, particularly those belonging to the Cry class. In addition to Cry proteins, other insecticidal proteins from different classes have been developed. However, for many of these, information on their mode of action (MoA) and host receptors remains limited. Over the past two decades, the European Food Safety Authority (EFSA) has evaluated more than 70 applications for GM crops expressing 24 different insecticidal proteins. These proteins belong to various classes, and the level of available information regarding their MoA varies considerably. This review aims to summarise the evidence currently available to EFSA on the MoA of insecticidal proteins expressed in GM crops. It also seeks to identify areas where further understanding of receptor binding and protein function could support the continued development of safety assessment strategies, with the goal of reducing reliance on animal studies as part of a more refined risk assessment approach.