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Matching target dose to target organ
Desmond I Bannon1, Marc A Williams1
1Toxicology Directorate, Health Effects Division, U.S. Army Public Health Center, Edgewood, MD, USA.
Abstract:
In vitro assays have become a mainstay of modern approaches to toxicology with the promise of replacing or reducing the number of in vivo tests required to establish benchmark doses, as well as increasing mechanistic understanding. However, matching target dose to target organ is an often overlooked aspect of in vitro assays, and the calibration of in vitro exposure against in vivo benchmark doses is often ignored, inadvertently or otherwise. An example of this was recently published in Environmental Health Perspectives by Wagner et al (2016), where neural stems cells were used to model the molecular toxicity of lead. On closer examination of the in vitro work, the doses used in media reflected in vivo lead doses that would be at the highest end of lead toxicity, perhaps even lethal. Here we discuss the doses used and suggest more realistic doses for future work with stem cells or other neuronal cell lines.
Insights
This study highlights the critical need to match in vitro toxicology assay doses to relevant in vivo exposures. Using realistic doses in neural stem cell models is crucial for accurate lead toxicity assessments.
Area of Science:
- Toxicology
- Cell Biology
- Neuroscience
Background:
- In vitro assays are vital for toxicology, aiming to reduce animal testing and enhance mechanistic insights.
- A key challenge is aligning in vitro doses with in vivo target organ exposures and benchmark doses.
Purpose of the Study:
- To critically evaluate the dose selection in a recent in vitro study modeling lead neurotoxicity.
- To propose more physiologically relevant doses for future in vitro studies using neural stem cells.
Main Methods:
- Review and analysis of dosing concentrations used in in vitro neural stem cell cultures.
- Comparison of in vitro doses with established in vivo lead toxicity data.
Main Results:
- The doses employed in the referenced in vitro study represent the upper, potentially lethal, range of in vivo lead exposure.
- A significant discrepancy exists between the tested in vitro doses and realistic in vivo lead exposure levels.
Conclusions:
- Accurate dose calibration is essential for the validity and predictive power of in vitro toxicology assays.
- Future research should utilize more relevant and realistic doses to improve the modeling of lead toxicity in neural stem cells.
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