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Arsenic Toxicokinetic Modeling and Risk Analysis: Progress, Needs and Applications
Citation:
Kenyon, E. Arsenic Toxicokinetic Modeling and Risk Analysis: Progress, Needs and Applications. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 457:152809, (2021). https://doi.org/10.1016/j.tox.2021.152809
Impact/Purpose:
This manuscript is an overview of the peer reviewed literature describing physiologically based toxicokinetic models for arsenic and their application in chemical risk assessment. This manuscript will be useful to chemical risk assessors seeking information about the current state of the science with respect to arsenic PBTK modeling and researchers seeking to make new and relevant contributions.
Description:
Arsenic (As) poses unique challenges in PBTK model development and risk analysis applications. Arsenic metabolism is complex, adequate information to attribute specific metabolites to particular adverse effects in humans is sparse, and measurement of relevant metabolites in biological media can be difficult. Multiple As PBTK models have been published and used or adapted for use in various exposure and risk analysis applications. These applications illustrate the broad utility of PBTK models for exposure and dose-response analysis, particularly for arsenic where multi-pathway, multi-route exposures and multiple toxic effects are of concern. Arsenic PBTK models have been used together with exposure reconstruction and dose-response functions to estimate risk of specific adverse health effects due to drinking water exposure and consumption of specific foodstuffs (e.g. rice, seafood), as well as to derive safe exposure levels and develop consumption advisories. Future refinements to arsenic PBTK models can enhance the confidence in such analyses. Improved estimates for methylation biotransformation parameters based on in vitro to in vivo extrapolation (IVIVE) methods and estimation of interindividual variability in key model parameters for specific toxicologically relevant metabolites are two important areas for consideration.
URLs/Downloads:
DOI: Arsenic Toxicokinetic Modeling and Risk Analysis: Progress, Needs and Applications
https://pubmed.ncbi.nlm.nih.gov/33965444/