Integrating human exposome data into next-generation risk assessment: a systematic framework to infer real-life exposure levels and prioritize chemical compounds for testing

Environment International, vol. 208, pp. 110110

Abstract

• Developed a flexible framework integrating exposome data into NGRA workflows. • Combined exposome, model, toxicity, and bioactivity data for chemical prioritization. • Developed Tox and ExpTox scores to prioritize chemicals. • Exposure data substantially reshaped the chemical ranking. Exposome research and next-generation risk assessment (NGRA) share the goal of improving the human relevance of chemical safety evaluations, yet practical integration remains limited. We developed a flexible framework that combines human biomonitoring (HBM) data, exposome datasets, and exposure modeling results with chemical property, toxicity, and bioactivity information to support NGRA and chemical prioritization. The framework comprises three modules: a curated human exposome database, model-based exposure estimates, and toxicity/bioactivity data integration. Its application was demonstrated in two case studies. Case study 1 focused on organ-specific carcinogens, prioritizing candidate hepatocarcinogens. Case study 2 adopted an exposure-driven approach, highlighting compounds frequently detected in biomonitoring programs across populations. The framework generated quantitative ranges of compound concentrations in biological samples, predicted blood concentrations, and external intake values, which can be compared with in vitro toxicity benchmarks such as half-maximal activity concentration (AC50). Results show that incorporating human exposure data substantially influences chemical prioritization. This framework provides a practical pathway for embedding exposome data into NGRA workflows, thereby strengthening human-relevant risk assessments and informing future chemical safety evaluations.

Authors 6

1. Yifeng Dai corresponding

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Institute of Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584CM Utrecht, the Netherlands. Electronic address: y.dai@umcutrecht.nl

2. Bob van de Water Aachen Division of Drug Discovery and Safety Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, the Netherlands

3. Jaione Telleria
   Affiliation as printed

   MedBioinformatics Solutions SL, Rambla Cataluña, 14, 7°, 1ª, Barcelona 08007, Spain

4. Laura I. Furlong
   Affiliation as printed

   MedBioinformatics Solutions SL, Rambla Cataluña, 14, 7°, 1ª, Barcelona 08007, Spain

5. Roel C.H. Vermeulen

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Institute of Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584CM Utrecht, the Netherlands

6. Jelle J. Vlaanderen

   Utrecht University

   Affiliation as printed

   Institute of Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584CM Utrecht, the Netherlands