Getting the dose-response right is a critical component in the assessment of chemical food safety. Being able to validate dose-response model predictions in the low-dose zone would be a critical aspect of the assurances that correct decisions about food safety and security are made. The present paper examines the history of the threshold dose-response model and how it became incorporated into governmental regulatory and risk assessment activities, including those affecting chemical food safety. The present analysis reveals that the major risk assessment models used by international regulatory agencies, such as the threshold dose-response model, were never validated prior to their acceptance and use by international regulatory agencies. Furthermore, once they were tested both the threshold and linear dose-response models failed to make accurate predictions in the low-dose zone. The only model providing accurate predictions in the low dose zone was the hormetic dose-response, a model not used by regulatory agencies. The present analysis raises important new questions for the risk assessment process in general and that of chemical food security in particular.