The toxic potency of a chemical is dictated by both what the chemical does to the body (toxicodynamics, TD) and what the body does to the chemical (toxicokinetics, TK).
In vitro toxicity assays form the basis of next-generation risk assessment, i.e., chemical safety assessment based on the 3Rs principle aiming to reduce, refine and replace animal testing.
In vitro assays are ideally placed to elucidate toxicodynamic mechanisms of a toxicant, but for their application in risk assessment, a thorough quantitative understanding of a toxicant’s toxicokinetics is required to translate
in vitro effect concentrations to reference doses in target species, including humans. Both simple, as well as more complex
in silico and
in vitro tools, are currently under development to perform these
in vitro to
in vivo extrapolations (IVIVE), yet their use in regulatory toxicology is still limited.
There are a number
in vitro and
in silico approaches to estimate the absorption, distribution, metabolism and excretion (ADME) of chemicals, as well as
in silico tools to estimate external exposure levels associated with
in vitro effect concentrations, most notably physiologically-based kinetic (PBK) models. With the advent of generic PBK models, artificial intelligence (AI)/machine learning (ML), organ-on-a-chip systems and other novel (high-throughput)
in vitro tools for TK and TD assessment, the prediction accuracy of ADME and IVIVE may further improve. However, it is essential to establish strategies for their integration in a next-generation risk assessment paradigm and evaluate their applicability domain. This Research Topic aims to gather studies describing the potential of recent advances in
in silico and
in vitro tool development for toxicokinetics assessments for use in next-generation risk assessment.
Topics to consider include, but are not limited to:
• History and current status of toxicokinetics assessment.
• Regulatory uptake of PBK modeling across sectors and regulatory bodies.
• Level of precision required for toxicokinetics predictions and other considerations for model evaluations in a regulatory setting.
• Gap analyses in PBK modeling and QIVIVE assessment in next-generation risk assessment.
• Overview of efforts to implement 3R toxicokinetics assessments.
• Specific challenges of IVIVE across chemical groups and types of toxicity.
• Specific needs to assess the kinetics and perform IVIVE of nanoparticles.
• One Health approach in kinetics assessment.
• Comparison of IVIVE approaches in ecotoxicology and pharmacology and what we can learn from each discipline.
• Chemical and biological space of generic PBK modeling tools and quantitative structure activity/property relationships (QSAR/QSPR) for ADME and PBK parameterization.
• IVIVE for organ-on-a-chip systems.
• Opportunities and challenges of integrating AI/ML approaches into TK assessments assessment/IVIVE.
Different Article Types can be submitted to the Research Topic including Original Research, Review, Mini-Review, Brief Research Report, Perspective articles, among others. You can find detailed information
here.
