An integrated exposome risk prioritization strategy for disease-specific substance priority listing: Preeclampsia as a proof-of-concept

<p>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, <i>in vitro</i> cytotoxicity, metabolism-disruption, and <i>in silico</i> 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.</p>