{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T04:12:37Z","timestamp":1791691957316,"version":"4.3.4"},"reference-count":79,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/120030\/2016"],"award-info":[{"award-number":["SFRH\/BD\/120030\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["IF\/00265\/2015"],"award-info":[{"award-number":["IF\/00265\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/Multi\/04378\/2019"],"award-info":[{"award-number":["UID\/Multi\/04378\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish Cancer- and Allergy fund (Cancer- och Allergifonden)","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>The last decade witnessed extraordinary advances in \u201comics\u201d methods, particularly transcriptomics, proteomics and metabolomics, enabling toxicologists to integrate toxicokinetics and toxicodynamics with mechanistic insights on the mode-of-action of noxious chemicals, single or combined. The toxicology of mixtures is, nonetheless, a most challenging enterprise, especially for environmental toxicologists and ecotoxicologists, who invariably deal with chemical mixtures, many of which contain unknowns. Despite costs and demanding computations, the systems toxicology framework, of which \u201comics\u201d is a major component, endeavors extracting adverse outcome pathways for complex mixtures. Still, the interplay between the multiple components of gene expression and cell metabolism tends to be overlooked. As an example, the proteome allocates DNA methyltransferases whose altered transcription or loss of function by action of chemicals can have a global impact on gene expression in the cell. On the other hand, chemical insult can produce reactive metabolites and radicals that can intercalate or bind to DNA as well as to enzymes and structural proteins, compromising their activity. These examples illustrate the importance of exploring multiple \u201comes\u201d and the purpose of \u201comics\u201d and multi-\u201comics\u201d for building truly predictive models of hazard and risk. Here we will review the state-of-the-art of toxicogenomics highlighting successes, shortcomings and perspectives for next-generation environmental toxicologists.<\/jats:p>","DOI":"10.3390\/ijerph16234718","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T03:55:51Z","timestamp":1574826951000},"page":"4718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["The State-of-the Art of Environmental Toxicogenomics: Challenges and Perspectives of \u201cOmics\u201d Approaches Directed to Toxicant Mixtures"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3182-884X","authenticated-orcid":false,"given":"Carla","family":"Martins","sequence":"first","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Departamento de Ci\u00eancias da Vida, Faculdade de Ci\u00eancias e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"},{"name":"Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-4293","authenticated-orcid":false,"given":"Kristian","family":"Dreij","sequence":"additional","affiliation":[{"name":"Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-3522","authenticated-orcid":false,"given":"Pedro M.","family":"Costa","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Departamento de Ci\u00eancias da Vida, Faculdade de Ci\u00eancias e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10408449509089885","article-title":"Minamata disease: Methylmercury poisoning in Japan caused by environmental pollution","volume":"25","author":"Harada","year":"1995","journal-title":"Crit. 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