{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:26:04Z","timestamp":1787217964394,"version":"build-2736575974"},"reference-count":148,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministry of Health","doi-asserted-by":"publisher","award":["PRR.AP015.165"],"award-info":[{"award-number":["PRR.AP015.165"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Human Biomonitoring (HBM) is a key tool for assessing human exposure to environmental contaminants and identifying early biological changes potentially associated with adverse health effects. However, as contaminated sites are characterized by multiple pollutants, exposure pathways and biological targets, a structured decision-support process is required to guide exposure assessment, biomarker selection, and early health-risk evaluation. This manuscript does not report biomonitoring results but describes the methodological process used to design the INSINERGIA_RT HBM study in two contaminated areas of Tuscany, Italy. The study design integrated environmental evidence, toxicological knowledge, epidemiological priorities, biomarker relevance, analytical feasibility, logistical considerations, and public health needs. Instead of proposing a universally applicable framework, the manuscript presents a structured approach that may support the design of HBM studies in similarly complex settings. Biomarkers are organized within a hierarchical model reflecting successive stages of the biological response to environmental exposure. A central feature is a mechanistic, multi-level approach encompassing upstream pathways (oxidative stress and inflammation), early markers of adverse effects and subclinical organ damage, including cardiovascular, renal, and respiratory alterations, and integrative indicators of cumulative biological responses, such as telomere length, epigenetic changes, and metabolomic profiles. Applicability is illustrated through an ongoing HBM study in Livorno and Piombino (Tuscany).<\/jats:p>","DOI":"10.3390\/toxics14070616","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:49:36Z","timestamp":1784184576000},"page":"616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Environmental Evidence to Biomarker Selection: A Structured Decision-Support Process for Human Biomonitoring Studies in Contaminated Sites"],"prefix":"10.3390","volume":"14","author":[{"given":"Elisa","family":"Bustaffa","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Aprea","sequence":"additional","affiliation":[{"name":"Southeast Wide Area Public Health Laboratory, Occupational and Environmental Toxicology Unit, Operational Headquarter of Siena, Southeast Tuscany Local Health Authority, Strada del Ruffolo 4, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Hygiene and Public Health Unit, Southern Area (Pisa-Livorno), Department of Prevention, Northwest Tuscany Local Health Authority (ATNO), Via Carlo Forlanini 26, 57025 Piombino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Benassi","sequence":"additional","affiliation":[{"name":"Regional Laboratories, Department of Padua, Regional Environmental Protection Agency Veneto, Via Ospedale Civile 24, 35121 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-8309","authenticated-orcid":false,"given":"Andrea","family":"Borghini","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2262-1102","authenticated-orcid":false,"given":"Saverio","family":"Caini","sequence":"additional","affiliation":[{"name":"S.S. Molecular and Lifestyle Epidemiology, S.C. Epidemiology of Risk Factors and Lifestyle, Institute for the Study, Prevention, and Oncology Network (ISPRO), Via Cosimo il Vecchio 2, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiuseppe","family":"Cal\u00e0","sequence":"additional","affiliation":[{"name":"Prevention Department, Azienda USL Toscana Centro, Via S. Salvi 12, 50135 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Cellai","sequence":"additional","affiliation":[{"name":"Clinical Chemical Analysis Laboratory, Department of Diagnostics, Livorno Hospital, USL Toscana Nordovest, Viale Vittorio Alfieri 36, 57124 Livorno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-1651","authenticated-orcid":false,"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6201-1843","authenticated-orcid":false,"given":"Francesco","family":"Faita","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-3952","authenticated-orcid":false,"given":"Miriam","family":"Levi","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Health Management Staff, Azienda USL Toscana Centro, Presidio San Salvi, Edificio 8 (Villa Fabbri), Via di San Salvi 12, 50135 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-3686","authenticated-orcid":false,"given":"Stefano","family":"Masi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-2690","authenticated-orcid":false,"given":"Simona","family":"Mrakic-Sposta","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology of Milan, National Research Council (IFC-CNR), Piazza dell\u2019Ospedale Maggiore 3, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-6869","authenticated-orcid":false,"given":"Katia","family":"Russo","sequence":"additional","affiliation":[{"name":"Experimental Zooprophylactic Institute of Lazio and Tuscany (IZSLT), Via Appia Nuova 1411, 00178 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7855-8253","authenticated-orcid":false,"given":"Anna","family":"Solini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular, and Critical Care Pathology, Faculty of Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0007-4731","authenticated-orcid":false,"given":"Fabrizio","family":"Minichilli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198574","DOI":"10.1155\/2014\/198574","article-title":"Industrially Contaminated Sites and Health","volume":"2014","author":"Martuzzi","year":"2014","journal-title":"J. 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