Toxicokinetics, dose-response, and risk assessment of nanomaterials: Methodology, challenges, and future perspectives

The rapid growth of nanomaterial applications has raised safety concerns for human health. A number of studies have been conducted to assess the toxicokinetics, toxicology, dose-response, and risk assessment of different nanomaterials using in vitro and in vivo animal and human models. However, current studies cannot meet the demand for efficient assessment of toxicokinetics, dose-response relationships, or the toxicological risk arising from the rapidly increasing number of newly synthesized nanomaterials. In this article, we review the methods for conducting toxicokinetics, hazard identification, dose-response, exposure, and risk assessment studies of nanomaterials, identify the knowledge gaps, and discuss the challenges remaining. We provide the rationale behind the appropriate design of nanomaterial plasma toxicokinetic and tissue distribution studies, including caveats on the interpretation and correlation of in vitro and in vivo toxicology studies. The potential of using physiologically based pharmacokinetic (PBPK) models to extrapolate toxicokinetic and toxicity findings from in vitro to in vivo and from animals to humans is discussed, and the knowledge gaps of PBPK modeling for nanomaterials are identified. While challenges still exist, there has been progress in the toxicokinetics, hazard identification, and risk assessment of nanomaterials in the past two decades. Recent advancements in the field are highlighted with relevant examples. We also share latest guidelines as well as our perspectives on future studies needed to characterize the toxicokinetics, toxicity, and dose-response relationship in support of nanomaterial risk assessment. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.