An integrated exposome risk prioritization strategy for disease-specific substance priority listing: Preeclampsia as a proof-of-concept
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PUBLIC SUMMARY
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The role of environmental causes in pregnancy complications is increasingly recognized.
From exposomes to multi-omics, integrating research strategy for comprehensive chemical risk assessment.
Bisphenol A, perfluorooctanoic acid and 3-phenoxybenzoic acid are the main risk factors for PE.
Establishes chemical risk hierarchy for PE using exposure thresholds and mechanistical evidence.
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ABSTRACT
Environmental risk assessment and management policies are challenged by the ever-mounting number of chemicals, mandating effective substance priority list (SPL) for health risks. Hence, a comprehensive SPL tool considering evidence from varying levels is highly needed, particularly with disease-specific precision. Here, we constructed an integrated chemical risk ranking score (ICRRS) approach based on exposomic profiling, epidemiological analyses, in vitro cytotoxicity, metabolism-disruption, and in silico toxicity, to prioritize chemicals related to the risk of preeclampsia (PE). Using this approach, of the 99 chemicals measured, we shortlisted nine chemicals of concern that are most relevant to PE, including bisphenol A, perfluorooctanoic acid and 3-phenoxybenzoic acid, affecting up to 50% women. This multi-dimensional approach containing complementary evidence from various aspects, allowing a precision prioritization of chemicals in relation to PE risk. This model of SPL construction can be adapted for other diseases, assisting the identification of pivotal substances that should be placed under more strict regulations on production and usage for human health. -
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REFERENCES
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Gao T., Tao L., Gao C., et al. (2025). An integrated exposome risk prioritization strategy for disease-specific substance priority listing: Preeclampsia as a proof-of-concept. The Innovation Medicine 3:100136. https://doi.org/10.59717/j.xinn-med.2025.100136
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Gao T., Tao L., Gao C., et al. (2025). An integrated exposome risk prioritization strategy for disease-specific substance priority listing: Preeclampsia as a proof-of-concept. The Innovation Medicine 3:100136. https://doi.org/10.59717/j.xinn-med.2025.100136
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Figure 1.
Overview of the integrated chemical exposome risk prioritization strategy, using PE as a model disease
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Figure 2.
Exposomic profiling and epidemiological screening for chemicals in relation to elevated risks (exposure risk and human health risk) of PE in the pregnant women
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Figure 3.
In vitro cytotoxicity and metabolism disruption of screened chemicals
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Figure 4.
In silico toxicity of screened chemicals
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Figure 5.
SPL of environmental chemicals for PE using the ICRRS
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Figure 6.
Precision prioritization of chemicals considering both our PE-specific SPL and exposure risk in this study
