{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:26:50Z","timestamp":1792189610402,"version":"4.4.0"},"reference-count":344,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/MCTES","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"FCT\/MCTES","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"FCT\/MCTES","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility.<\/jats:p>","DOI":"10.3390\/jox15040118","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T07:54:23Z","timestamp":1752479663000},"page":"118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3674-3116","authenticated-orcid":false,"given":"Ana Filipa","family":"Sobral","sequence":"first","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences-CESPU, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-1079","authenticated-orcid":false,"given":"Andrea","family":"Cunha","sequence":"additional","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7454-9878","authenticated-orcid":false,"given":"In\u00eas","family":"Costa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-8469","authenticated-orcid":false,"given":"Mariana","family":"Silva-Carvalho","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences-CESPU, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-7548","authenticated-orcid":false,"given":"Renata","family":"Silva","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-6011","authenticated-orcid":false,"given":"Daniel Jos\u00e9","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences-CESPU, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41435-022-00192-6","article-title":"Gene-environment interactions and their impact on human health","volume":"24","author":"Virolainen","year":"2023","journal-title":"Genes. 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