To date, few in-depth studies on the in vivo behavior of PAMAM dendrimers have been carried out. This could be in part due to the diverse behavior of PAMAMs depending on surface modification (see below), which make characterization of their in vivo properties largely case-dependent. Nonetheless, the fate and transport of unmodified PAMAM dendrimers is an important case study as any biological applications could involve unmodified PAMAM as a metabolic byproduct. In the only major systematic study of in vivo PAMAM behavior, injections of high levels of bare PAMAMs over extended periods of time in mice showed no evidence of toxicity up through G5 PAMAM, and for G3-G7 PAMAM, low immunogenicity was observed. These systemic-level observations seem to align with the observation that PAMAM dendrimers are not extremely cytotoxic overall; however, more in-depth studies of the pharmacokinetics and biodistribution of PAMAM are required before a move toward in vivo applications can be made.