Multiscale Modeling Identifies Cardiovascular Risks from Common Chemical Exposures
Researchers applied a multiscale computational modeling workflow to assess cardiovascular toxicity risk for 859 chemicals, identifying 17 substances where estimated human exposure exceeds in vitro-derived bioactive doses by more than 100-fold. The study combined high-throughput screening data from over 300 assays with physiologically based pharmacokinetic models and real-world exposure estimates, covering personal care product ingredients, flame retardants, pesticides, herbicides, pharmaceuticals, and industrial byproducts. The findings suggest that current animal-based toxicology studies may underestimate cardiovascular risk for the vast majority of chemicals tested, and offer a scalable, human-biology-based alternative for regulatory risk assessment.
A new study published on bioRxiv presents an integrative, multiscale framework for identifying chemicals that pose cardiovascular risks at human-relevant exposure levels, without relying primarily on animal testing. The researchers used physiologically based pharmacokinetic (PBPK) models to translate bioactive concentrations from more than 300 high-throughput screening assays into human equivalent administered doses for 859 substances. These doses were then compared against real-world human exposure estimates and traditional animal-study points of departure to generate risk predictions. Seventeen chemicals were flagged as high concern, with a bioactivity exposure ratio indicating that typical human exposures exceed the in vitro bioactive threshold by more than 100-fold. Notably, the in vitro cardiovascular assays proved more risk-protective than animal studies for 96.4% of the chemicals assessed, raising questions about the adequacy of conventional toxicological methods. Chemicals of concern were found to preferentially target endothelial cell signaling and nuclear hormone receptors, both critical to cardiovascular function. The study also incorporated geospatial analysis to estimate population-level risk, positioning the framework as a tool for evidence-based regulatory and public health decision-making.
What's missing
As a preprint, this study has not yet undergone formal peer review, and its findings should be interpreted with caution. The framework does not yet account for mixture effects or cumulative exposures to multiple cardiovascular-active chemicals simultaneously.
What different sources said
- bioRxivCenter
Multiscale Modeling Identifies Cardiovascular Risk from Common Chemical Exposures
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