The Testis Project uses 3-dimensional in vitro testicular co-cultures (3D-TCS) that have been shown to capture key processes of male reproductive development in order to evaluate the potential for metals and ENMs to alter these processes. We measure the ability of ENMs to alter cellular differentiation and tissue maturation with a focus on the roles of developmental timing and genetics in influencing compound susceptibility. We also explore the role of oxidative stress and inflammation pathways in mediating ENM induced perturbation of development. Finally, we use toxicokinetic and dynamic models to integrate in vitro our findings into our AOP framework.