The aim of this work is to evaluate the impact of the reduction of zinc content in Ethylene, Propylene and Diene Monomer (EPDM) elastomeric compositions. Vulcanization nanoactivators ZnO 30 (ZnO dispersed in CaCO3) and ZnO 40 (active ZnO) were used as reinforces in the elastomers, and both the properties and the cytotoxicity were investigated and compared to those of EPDM with a standard zinc oxide (sZnO) commonly used in the bus rubber profile industry. After a complete description of the physico-chemical characteristics of whole zinc oxides, the vulcanization activators were dispersed in EPDM. Although elastomers with sZnO display a cytotoxic behavior, EPDM formulations containing ZnO 30 and ZnO 40 appeared to be environmental friendly while displaying similar mechanical properties to that with sZnO composition. ZnO 30 represents the most interesting vulcanization activator to replace sZnO allowing a reduction of 77% in the zinc content without any loss of mechanical properties. Moreover, the formulations associating this nanoactivator show the lowest release of Zn2+ in water with a poor cytotoxicity in comparison to sZnO.