Figure 3.

Allometric scaling approaches for estimating the dose and systemic clearance of nanomaterials. A. Current methods for dose estimation of the maximum recommended starting dose (MRSD) in initial clinical trials and of the animal-equivalent dose (AED) for experimental studies (i.e., human therapeutic dose equivalent in preclinical animal models). All these approaches rely on allometric scaling either of the nanomaterial dose (mg/kg) itself or of the nanomaterial clearance (CL) using preclinical pharmacokinetic data. A default safety factor of 10 is applied in the calculation of the MRSD from the human-equivalent dose (HED). A key limitation of these approaches is the extent to which the pharmacokinetic and toxicologic parameters of the nanomaterial can be accurately predicted in humans with allometry, which for most nanomaterial types is not always guaranteed. Information in A adapted from ³⁰, ⁷¹. B. Decision tree for selecting the recommended allometric scaling method of nanomaterial CL on the basis of their clearance/elimination route. These recommendations and the additional considerations are based on the best practices for interspecies scaling of nanomaterial CL reported in literature. It is not meant as a prescriptive tool. Whether or not a particular nanomaterial type is amendable to allometric scaling will ultimately depend on the multispecies experimental data.