{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:03:01Z","timestamp":1788818581035,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"INAIL (National Institute for Industrial Accidents and Workers\u2019 Compensation) Research","award":["BRIC 2022 ID 52"],"award-info":[{"award-number":["BRIC 2022 ID 52"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Foundries represent complex exposure scenarios where metals, particulate matter, and combustion by-products coexist, posing potential cumulative biological effects. Urinary metabolic profiles from 64 foundry workers and 78 residents living in surrounding areas were investigated using multivariate statistical modeling. Differences in urinary metabolite patterns were observed between the two groups, including lower levels of several amino acids (e.g., valine, alanine, tyrosine, and tryptophan) and tricarboxylic acid intermediates (e.g., citrate and succinate), together with higher levels of selected branched-chain amino acid catabolites (e.g., 3-hydroxyisobutyrate and erythro-2,3-dihydroxybutyrate) in workers. Variations in gut microbiota-related metabolites, such as phenylacetylglycine and p-cresol sulphate, were also detected. Based on these metabolic patterns, potential molecular mechanisms related to energy metabolism, oxidative stress and host\u2013microbiome interaction are discussed as interpretative hypotheses. The comparison between workers and residents was interpreted, taking into account differences in demographic and lifestyle characteristics between groups. Overall, the results indicate that occupational exposure in foundries is associated with measurable differences in urinary metabolic profiles, demonstrating that the applied NMR-based metabolomic strategy is capable of capturing early biological effects and supporting its potential as a non-invasive and holistic biomonitoring tool for evaluating the health impact of complex occupational exposures.<\/jats:p>","DOI":"10.3390\/jox16010014","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:26:36Z","timestamp":1768465596000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Urinary Metabolomics as a Window into Occupational Exposure: The Case of Foundry Workers"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1242-3954","authenticated-orcid":false,"given":"Michele","family":"De Rosa","sequence":"first","affiliation":[{"name":"Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"NMR-Based Metabolomics Laboratory, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-0140","authenticated-orcid":false,"given":"Silvia","family":"Canepari","sequence":"additional","affiliation":[{"name":"Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-6046","authenticated-orcid":false,"given":"Giovanna","family":"Tranfo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Epidemiology, Environmental and Occupational Hygiene (INAIL), Via Fontana Candida 1, 00078 Monte Porzio Catone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia","family":"Giampaoli","sequence":"additional","affiliation":[{"name":"NMR-Based Metabolomics Laboratory, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4471-8107","authenticated-orcid":false,"given":"Adriano","family":"Patriarca","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"NMR-Based Metabolomics Laboratory, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Smolinska","sequence":"additional","affiliation":[{"name":"Faculty of Health, Medicine and Life Sciences, Pharmacology and Toxicology, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands"},{"name":"Nutrition and Translational Research in Metabolism (NUTRIM), School of Nutrition & Translational Research in Metabolism, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-1117","authenticated-orcid":false,"given":"Federico","family":"Marini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"NMR-Based Metabolomics Laboratory, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-5722","authenticated-orcid":false,"given":"Lorenzo","family":"Massimi","sequence":"additional","affiliation":[{"name":"Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1982-2712","authenticated-orcid":false,"given":"Fabio","family":"Sciubba","sequence":"additional","affiliation":[{"name":"NMR-Based Metabolomics Laboratory, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"Interdepartmental Center of Applied Sciences for the Protection of the Environment and Cultural Heritage (CIABC), Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9061-7159","authenticated-orcid":false,"given":"Mariangela","family":"Spagnoli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Epidemiology, Environmental and Occupational Hygiene (INAIL), Via Fontana Candida 1, 00078 Monte Porzio Catone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.spc.2024.03.005","article-title":"A Sustainability Assessment of the Foundry Production Process in Italy","volume":"46","author":"Monteleone","year":"2024","journal-title":"Sustain. Prod. Consum."},{"key":"ref_2","unstructured":"(2025, September 30). Assofond-2023. Available online: https:\/\/www.assofond.it\/en\/magazine-2023."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e12913","DOI":"10.1016\/j.heliyon.2023.e12913","article-title":"Comparison of the Chemical Health Risk Assessment of Exposure to Metal Fumes for the Furnace Operator of a Foundry Industry Using Quantitative and Semi-Quantitative Methods","volume":"9","author":"Zeverdegani","year":"2023","journal-title":"Heliyon"},{"key":"ref_4","unstructured":"Wilbur, S., Abadin, H., Fay, M., Yu, D., Tencza, B., Ingerman, L., Klotzbach, J., and James, S. (2012). Health Effects. Toxicological Profile for Chromium, Agency for Toxic Substances and Disease Registry (US)."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105048","DOI":"10.1016\/j.yrtph.2021.105048","article-title":"Occupational Exposure to Hexavalent Chromium. Part I. Hazard Assessment of Non-Cancer Health Effects","volume":"126","author":"Hessel","year":"2021","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1515\/reveh.2011.012","article-title":"Exploring the Molecular Mechanisms of Nickel-Induced Genotoxicity and Carcinogenicity: A Literature Review","volume":"26","author":"Cameron","year":"2011","journal-title":"Rev. Environ. Health"},{"key":"ref_7","first-page":"67","article-title":"Nickel Carcinogenesis","volume":"533","author":"Kasprzak","year":"2003","journal-title":"Mutat. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Peres, T.V., Schettinger, M.R.C., Chen, P., Carvalho, F., Avila, D.S., Bowman, A.B., and Aschner, M. (2016). Manganese-Induced Neurotoxicity: A Review of Its Behavioral Consequences and Neuroprotective Strategies. BMC Pharmacol. Toxicol., 17.","DOI":"10.1186\/s40360-016-0099-0"},{"key":"ref_9","unstructured":"Williams, M., Todd, G.D., Roney, N., Crawford, J., Coles, C., McClure, P.R., Garey, J.D., Zaccaria, K., and Citra, M. (2012). Toxicological Profile for Manganese, Agency for Toxic Substances and Disease Registry (US). Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bbamcr.2016.12.002","article-title":"Iron Mediated Toxicity and Programmed Cell Death: A Review and a Re-Examination of Existing Paradigms","volume":"1864","author":"Eid","year":"2017","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2478\/intox-2014-0009","article-title":"Toxicity, Mechanism and Health Effects of Some Heavy Metals","volume":"7","author":"Jaishankar","year":"2014","journal-title":"Interdiscip. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13059-017-1215-1","article-title":"Multi-Omics Approaches to Disease","volume":"18","author":"Hasin","year":"2017","journal-title":"Genome Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s12967-025-06446-x","article-title":"Algorithms and Tools for Data-Driven Omics Integration to Achieve Multilayer Biological Insights: A Narrative Review","volume":"23","author":"Morabito","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_14","first-page":"3","article-title":"\u201cOmics\u201d in Pharmaceutical Research: Overview, Applications, Challenges, and Future Perspectives","volume":"13","author":"Yan","year":"2015","journal-title":"Chin. J. Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1038\/nprot.2007.376","article-title":"Metabolic Profiling, Metabolomic and Metabonomic Procedures for NMR Spectroscopy of Urine, Plasma, Serum and Tissue Extracts","volume":"2","author":"Beckonert","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"De Rosa, M., Giampaoli, O., Patriarca, A., Marini, F., Pietroiusti, A., Ippoliti, L., Paolino, A., Militello, A., Fetoni, A.R., and Sisto, R. (2025). Urinary Metabolomics of Plastic Manufacturing Workers: A Pilot Study. J. Xenobiotics, 15.","DOI":"10.3390\/jox15020039"},{"key":"ref_17","unstructured":"(2024, December 04). BMRB\u2014Biological Magnetic Resonance Bank. Available online: https:\/\/bmrb.io\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The Human Metabolome Database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jmr.2009.11.012","article-title":"iCoShift: A Versatile Tool for the Rapid Alignment of 1D NMR Spectra","volume":"202","author":"Savorani","year":"2010","journal-title":"J. Magn. Reson."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1021\/ac7025964","article-title":"NMR-Based Characterization of Metabolic Alterations in Hypertension Using an Adaptive, Intelligent Binning Algorithm","volume":"80","author":"Sinnaeve","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1021\/ac051632c","article-title":"Probabilistic Quotient Normalization as Robust Method to Account for Dilution of Complex Biological Mixtures. Application in 1H NMR Metabonomics","volume":"78","author":"Dieterle","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"167513","DOI":"10.1016\/j.scitotenv.2023.167513","article-title":"Metabolome Analysis to Investigate the Effect of Heavy Metal Exposure and Chemoprevention Agents on Toxic Injury Caused by a Multi-Heavy Metal Mixture in Rats","volume":"906","author":"Zhou","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124673","DOI":"10.1016\/j.envpol.2024.124673","article-title":"Metabolic Signatures of Population Exposure to Metal Mixtures: A Metabolome-Wide Association Study","volume":"360","author":"Wu","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3390\/toxics3010020","article-title":"Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms","volume":"3","author":"Rubino","year":"2015","journal-title":"Toxics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00204-024-03903-2","article-title":"Heavy Metals: Toxicity and Human Health Effects","volume":"99","author":"Jomova","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117926","DOI":"10.1016\/j.envres.2023.117926","article-title":"Sub-Lethal Impacts of Lead Poisoning on Blood Biochemistry, Immune Function and Delta-Aminolevulinic Acid Dehydratase (\u03b4-ALAD) Activity in Cape (Gyps coprotheres) and White-Backed (G. africanus) Vulture Chicks","volume":"245","author":"Naidoo","year":"2024","journal-title":"Environ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.bbrc.2008.05.052","article-title":"Heavy Metal Ions Are Potent Inhibitors of Protein Folding","volume":"372","author":"Sharma","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Koyama, H., Kamogashira, T., and Yamasoba, T. (2024). Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies. Antioxidants, 13.","DOI":"10.3390\/antiox13010076"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Miyazaki, I., and Asanuma, M. (2023). Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson\u2019s Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12040894"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1039\/C8MT00165K","article-title":"Metallothionein Diversity and Distribution in the Tree of Life: A Multifunctional Protein","volume":"10","author":"Ziller","year":"2018","journal-title":"Metallomics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153136","DOI":"10.1016\/j.tox.2022.153136","article-title":"Heavy Metals Induced Mitochondrial Dysfunction in Animals: Molecular Mechanism of Toxicity","volume":"469","author":"Sun","year":"2022","journal-title":"Toxicology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuropharm.2016.03.013","article-title":"Kynurenine Pathway Metabolites and Enzymes Involved in Redox Reactions","volume":"112","author":"Pineda","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_33","first-page":"501","article-title":"Heavy Metal Induced Oxidative Stress & Its Possible Reversal by Chelation Therapy","volume":"128","author":"Flora","year":"2008","journal-title":"Indian J. Med. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.freeradbiomed.2004.03.010","article-title":"Cadmium Inhibits the Electron Transfer Chain and Induces Reactive Oxygen Species","volume":"36","author":"Wang","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA Cycle Metabolites Control Physiology and Disease","volume":"11","author":"Chandel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"16003","DOI":"10.1038\/npjbiofilms.2016.3","article-title":"The Gut Microbiota: A Major Player in the Toxicity of Environmental Pollutants?","volume":"2","author":"Claus","year":"2016","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41577-019-0198-4","article-title":"The Intestinal Microbiota Fuelling Metabolic Inflammation","volume":"20","author":"Tilg","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.envint.2019.02.048","article-title":"Heavy Metal Exposure Causes Changes in the Metabolic Health-Associated Gut Microbiome and Metabolites","volume":"126","author":"Li","year":"2019","journal-title":"Environ. Int."},{"key":"ref_39","first-page":"e230015","article-title":"Effects of Heavy Metals on Gut Barrier Integrity and Gut Microbiota","volume":"2","author":"Ghosh","year":"2024","journal-title":"Microbiota Host"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Anchidin-Norocel, L., Iatcu, O.C., Lobiuc, A., and Covasa, M. (2025). Heavy Metal\u2013Gut Microbiota Interactions: Probiotics Modulation and Biosensors Detection. Biosensors, 15.","DOI":"10.3390\/bios15030188"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Breton, J., Massart, S., Vandamme, P., De Brandt, E., Pot, B., and Folign\u00e9, B. (2013). Ecotoxicology inside the Gut: Impact of Heavy Metals on the Mouse Microbiome. BMC Pharmacol. Toxicol., 14.","DOI":"10.1186\/2050-6511-14-62"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"118854","DOI":"10.1016\/j.ecoenv.2025.118854","article-title":"Xenobiotic-Induced Liver Injury: Molecular Mechanisms and Disease Progression","volume":"303","author":"Wang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109388","DOI":"10.1016\/j.envint.2025.109388","article-title":"Unveiling the Hidden Impact of Long-Term Metal-Rich Volcanic Pollution on Male Reproductive Functions Using Isotope Metallomics","volume":"198","author":"Moreira","year":"2025","journal-title":"Environ. Int."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Fritsche, K., Zikov\u00e1-Kloas, A., Marx-Stoelting, P., and Braeuning, A. (2023). Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032686"}],"container-title":["Journal of Xenobiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4713\/16\/1\/14\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:31:10Z","timestamp":1768473070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4713\/16\/1\/14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jox16010014"],"URL":"https:\/\/doi.org\/10.3390\/jox16010014","relation":{},"ISSN":["2039-4713"],"issn-type":[{"value":"2039-4713","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]}}}