Abstract BACKGROUND Hemipteran pests pose a significant threat to global agriculture, creating a continuous need for effective and safe control strategies. Tpp78Aa, a distinctive Bacillus thuringiensis (Bt) insecticidal protein, represents a breakthrough as the first single‐component Bt protein with high efficacy against these challenging hemipteran pests. Before its application in transgenic crops, a comprehensive food safety assessment is critically required from a regulatory perspective. RESULTS This study further expanded the hemipteran‐specific insecticidal spectrum of Tpp78Aa to two additional hemipteran pests, demonstrating median lethal concentration (LC 50 ) values of 21.70 μg mL −1 for Sitobion avenae and 224.31 μg mL −1 for Nephotettix cincticeps . Importantly, the protein showed no acute toxicity to the pollinator Apis mellifera . Following internationally recognized guidelines, a comprehensive allergenicity assessment was conducted through multiple complementary approaches. Bioinformatics analysis based on sequence homology revealed no significant similarity between Tpp78Aa and any known allergens. Integrated predictions from three machine learning platforms classified Tpp78Aa as a non‐allergen. In vitro stability analysis demonstrated that Tpp78Aa was degraded and inactivated rapidly after heating at 100 °C and in simulated gastrointestinal fluids. Furthermore, Tpp78Aa exhibited no hemolytic activity against sheep or rabbit erythrocytes, and no significant cytotoxicity was observed in human cell lines 293 T, Huh7, and Caco2 after 72 h of treatment. CONCLUSION Tpp78Aa, a hemipteran‐specific insecticidal protein, poses low allergenic risk and favorable mammalian safety. The study provides crucial safety data to support further research, development, and potential application of Tpp78Aa in insect‐resistant transgenic crops for controlling hemipteran pests. This work represents an important step toward the safe and sustainable use of this protein in agriculture. © 2026 Society of Chemical Industry.
Lu et al. (Wed,) studied this question.