This chapter describes different theories relevant to understanding the behavior, fate, and effects of manufactured nanomaterials (NMs). It discusses the identification of key physicochemical properties that are relevant for characterizing and understanding the behavior of NMs. The chapter also describes regulatory information requirements for NMs, with a special focus on Registration, Authorisation and Restriction of Chemicals, as well as the scientific and technical basis for understanding their behavior. It focuses on the scientific basis of NM behavior, since the understanding is important in the development and application of standard and alternative approaches to animal testing. The transport of NMs in fluids follows Brownian diffusion, a random and chaotic motion of particles resulting in collisions between the particles and the fluid molecules surrounding them. NMs can reach the gastrointestinal tract via intake of food or water, or accidental ingestion, or following inhalation and clearance by the mucociliary escalator.