The present work was planned to study the effects of E110 (sunset yellow) as a common synthetic in Egypt and E110 (curcumin) as a natural food-drug colorants on the testis of the male mouse. The plan of work was designed to cover six parameters: histopathological, cytochemical (involving DNA and total proteins), testis weight, sperm parameters (i.e., sperm abnormalities and sperm motility), and measuring testosterone levels in blood sera. The mice were divided into three groups, ten per each. The first group remained as controls, whilst the second orally given sunset yellow-E110 (30 mg/kg b.wt/day) as SY-group and the third one E100 ‘CU-group' also gavage 37 mg/kg b.wt., both fed on their acceptable daily intake (ADI) dosages for 60 days. The results detected that SY revealed distinct alterations in the desired parameters, particularly histological changes in structure of seminiferous tubules such as vacuolation, necrosis and multinucleate cells. Whilst, the cytochemical DNA and proteinic profiles of the SY-treatment mice exhibited severe damage in the DNA and total protein configurations. However, such deteriorations in the spermatogenic epithelia were also approved with changes in the other criteria after administration with E110. From such alterations, the E110 recorded a highly significant increase (P< 0.0001) in the abnormalities of sperm morphology and motility. Moreover, the testosterone levels in sera of male mice indicated the significant differences among groups. The molecular protocol manifested SY (E110) - induced DNA polymorphic changes in confrontation with control by primer OPC07, whilst CU (E100) kept on the control pattern. In conclusion, the present study explored the possibility of using the applied six parameters to assessment and differentiate between the two food flavours indicating that E100 (CU) is more biosafe than the synthetic additive E110 (SY).