Abstract Background The Human Exposome Project (HEP) aims to chart lifelong environmental exposures and their biological consequences, furnishing the environmental counterpart to the genomic revolution. Yet the fine‑grained, multimodal data streams that fuel exposomics—biospecimens, geolocation traces, wearable‑sensor feeds, and socio‑environmental metadata—raise privacy, justice, and governance questions that may exceed the reach of conventional bioethics. Main body Building on lessons from genomics, biobanking, digital health, and environmental‑justice research, we identify five foundational ethical domains for exposome science: (1) privacy and data sovereignty, (2) informed consent and sustained participant engagement, (3) environmental justice, (4) governance and oversight, and (5) actionability and the responsible return of results,as well as (6)the adherence to research program goals. Similar to the “values in design” construct widely used in the socio-technical field and the “ethics by design” in the artificial intelligence (AI) field, we translate these domains into operational pillars for ethics‑by‑design research practice: dynamic or tiered consent architectures; participatory governance mechanisms such as community advisory boards; embedded ethics research programs; algorithmic‑fairness protocols for artificial‑intelligence analytics; and dedicated review bodies equipped to evaluate longitudinal, sensor‑based, multi‑omics studies. Concrete recommendations include federated data stewardship to minimize re‑identification risk, Evidence‑to‑Decision frameworks that couple exposomic evidence with societal values, and transparent pathways for communicating context‑dependent findings to individuals, communities, and policymakers. Conclusions Ethical preparedness and action are a prerequisite for the scientific impact and social license of exposome research. Institutionalizing the proposed roadmap—via an international Exposome Ethics Consortium, expanded training for Institutional Review Boards, harmonized regulatory guidance, and sustained community co‑governance—will help protect privacy, promote equity, and foster public trust. Embedding systematic ethical reflection as core infrastructure will enable the Human Exposome Project to realize its promise of precision public health without replicating patterns of opaque surveillance, marginalization, or data commodification. Plain Language Summary The Human Exposome Project (HEP) represents an ambitious endeavor to characterize lifelong environmental exposures in relation to health. Yet, this vision brings profound ethical challenges: from managing massive, sensitive datasets to ensuring justice for disproportionately exposed communities. This article synthesizes foundational work on exposome ethics, outlines core ethical challenges, and proposes a proactive ethical governance model that ensures scientific integrity and social legitimacy.
Sillé et al. (Sat,) studied this question.