The safety of plants containing novel proteins such as the Cry1Ab/Ac protein should be addressed in two complementary steps: (1) an initial characterization and safety assessment of the protein itself and (2) the characterization and safety evaluation of the transgenic plant. This article focuses on the first step. This initial determination of the toxicological profile of the proteins is independent of the genetic modification and can be extended to any plant variety as one element of the safety assessment of any plant that contains and expresses the same protein. The safety of the Cry1Ab/Ac protein is evaluated based on an assessment of published information and on scientific studies conducted with these proteins. The safety evaluation is consistent with several recommendations provided by Authorities and International Organizations including the FAO/WHO, Codex Alimentarius and OECD.