Summary
Introduction:
This article explores the use of in vitro to in vivo extrapolation (IVIVE) for exposure and health impacts of electronic cigarette (EC) flavor mixtures. The study aims to identify the key factors affecting the interpretation of IVIVE predictions, including the model type, exposure route, kinetic assumptions for the test article, and choice of in vitro assay(s) relevant to clinical outcomes.
Key Points:
* The study used EC aerosols, a complex mixture, to examine the impact of various factors on the use of IVIVE in hazard identification.
* Open-source pharmacokinetic models of varying complexity and publicly available data were employed.
* Results suggest that in vitro assay selection has a greater impact on exposure estimates than modeling approaches.
* high exposure estimates would be needed to obtain in vivo plasma levels corresponding to in vitro assay data, indicating that acute toxicity would be unlikely in typical usage scenarios.
* When mechanistic (Tox21) assays were used, the exposure estimates were much lower for the low end but wider across modeling approaches.
* Limitations and considerations for assay selection to facilitate IVIVE are discussed.
Main Message:
The study highlights the challenges and complexities in IVIVE for mixtures. While in vitro assays can provide valuable insights into the bioactivity of xenobiotic chemicals, careful consideration must be given to how data from these assays are used to quantitatively inform biological responses in vivo for risk assessment and decision making. The uncertainty surrounding the cellular dosimetry related to exposure levels in vivo requires careful evaluation of various factors, including kinetic model selection, exposure route, and assay selection.
Citation
Chang X, abedini J, Bell S, Lee KM. Exploring in vitro to in vivo extrapolation for exposure and health impacts of e-cigarette flavor mixtures. Toxicology in vitro : an international journal published in association with BIBRa. 2021;72:105090. doi:10.1016/j.tiv.2021.105090
