{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T03:25:42Z","timestamp":1768706742888,"version":"3.49.0"},"reference-count":115,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2019\/33B\/NZ7\/01441"],"award-info":[{"award-number":["2019\/33B\/NZ7\/01441"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Exposure to hexavalent chromium Cr(VI) may occur in several occupational activities, placing workers in many industries at risk for potential related health outcomes. Untargeted metabolomics was applied to investigate changes in metabolic pathways in response to Cr(VI) exposure. We obtained our data from a study population of 220 male workers with exposure to Cr(VI) and 102 male controls from Belgium, Finland, Poland, Portugal and the Netherlands within the HBM4EU Chromates Study. Urinary metabolite profiles were determined using liquid chromatography mass spectrometry, and differences between post-shift exposed workers and controls were analyzed using principal component analysis. Based on the first two principal components, we observed clustering by industrial chromate application, such as welding, chrome plating, and surface treatment, distinct from controls and not explained by smoking status or alcohol use. The changes in the abundancy of excreted metabolites observed in workers reflect fatty acid and monoamine neurotransmitter metabolism, oxidative modifications of amino acid residues, the excessive formation of abnormal amino acid metabolites and changes in steroid and thyrotropin-releasing hormones. The observed responses could also have resulted from work-related factors other than Cr(VI). Further targeted metabolomics studies are needed to better understand the observed modifications and further explore the suitability of urinary metabolites as early indicators of adverse effects associated with exposure to Cr(VI).<\/jats:p>","DOI":"10.3390\/metabo12040362","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T01:03:01Z","timestamp":1650330181000},"page":"362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["HBM4EU Chromates Study: Urinary Metabolomics Study of Workers Exposed to Hexavalent Chromium"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2905-4005","authenticated-orcid":false,"given":"Lucyna","family":"Koz\u0142owska","sequence":"first","affiliation":[{"name":"Laboratory of Human Metabolism Research, Department of Dietetics, Warsaw University of Life Sciences, 02776 Warsaw, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8150-4985","authenticated-orcid":false,"given":"Tiina","family":"Santonen","sequence":"additional","affiliation":[{"name":"Finnish Institute of Occupational Health, 00250 Helsinki, Finland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9350-3816","authenticated-orcid":false,"given":"Radu Corneliu","family":"Duca","sequence":"additional","affiliation":[{"name":"Labotoire National de Sant\u00e9 (LNS), Unit Environmental Hygiene and Human Biological Monitoring, Department of Health Protection, 3555 Dudelange, Luxembourg"},{"name":"Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven (University of Leuven), 3000 Leuven, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4764-8835","authenticated-orcid":false,"given":"Lode","family":"Godderis","sequence":"additional","affiliation":[{"name":"Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven (University of Leuven), 3000 Leuven, Belgium"},{"name":"IDEWE, External Service for Prevention and Protection at Work, 3001 Heverlee, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-6873","authenticated-orcid":false,"given":"Karolina","family":"Jagiello","sequence":"additional","affiliation":[{"name":"QSAR Laboratory Ltd., 80172 Gdansk, Poland"},{"name":"Laboratory of Environmental Chemoinfomatics, Department of Environmental Chemistry and Radiochemistry, Faculty of Chemistry, University of Gdansk, 80308 Gdansk, Poland"}]},{"given":"Beata","family":"Janasik","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Monitoring, Nofer Institute of Occupational Medicine, 91348 Lodz, Poland"}]},{"given":"An","family":"Van Nieuwenhuyse","sequence":"additional","affiliation":[{"name":"Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven (University of Leuven), 3000 Leuven, Belgium"},{"name":"Laboratoire National de Sant\u00e9 (LNS), Department of Health Protection, 3555 Dudelange, Luxembourg"}]},{"given":"Katrien","family":"Poels","sequence":"additional","affiliation":[{"name":"Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven (University of Leuven), 3000 Leuven, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-8339","authenticated-orcid":false,"given":"Tomasz","family":"Puzyn","sequence":"additional","affiliation":[{"name":"QSAR Laboratory Ltd., 80172 Gdansk, Poland"},{"name":"Laboratory of Environmental Chemoinfomatics, Department of Environmental Chemistry and Radiochemistry, Faculty of Chemistry, University of Gdansk, 80308 Gdansk, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8546-2161","authenticated-orcid":false,"given":"Paul T. J.","family":"Scheepers","sequence":"additional","affiliation":[{"name":"Radboud Institute for Health Sciences, Radboudumc, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}]},{"given":"Monika","family":"Sijko","sequence":"additional","affiliation":[{"name":"Laboratory of Human Metabolism Research, Department of Dietetics, Warsaw University of Life Sciences, 02776 Warsaw, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6060-0716","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Silva","sequence":"additional","affiliation":[{"name":"Human Genetics Department, National Institute of Health Dr. Ricardo Jorge (INSA), Toxicogenomics and Human Health (ToxOmics), NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3288-4309","authenticated-orcid":false,"given":"Anita","family":"Sosnowska","sequence":"additional","affiliation":[{"name":"QSAR Laboratory Ltd., 80172 Gdansk, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-8760","authenticated-orcid":false,"given":"Susana","family":"Viegas","sequence":"additional","affiliation":[{"name":"Public Health Research Centre, NOVA National School of Public Health, Universidade NOVA de Lisbon, 1600-560 Lisbon, Portugal"},{"name":"Comprehensive Health Research Center (CHRC), 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-5126","authenticated-orcid":false,"given":"Jelle","family":"Verdonck","sequence":"additional","affiliation":[{"name":"Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven (University of Leuven), 3000 Leuven, Belgium"}]},{"given":"Wojciech","family":"W\u0105sowicz","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Monitoring, Nofer Institute of Occupational Medicine, 91348 Lodz, Poland"}]},{"name":"on behalf of HBM4EU Chromates Study Team","sequence":"additional","affiliation":[]},{"name":"on behalf of Statistical Team","sequence":"additional","affiliation":[]}],"member":"1968","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"ref_1","unstructured":"National Institute for Occupational Safety and Health (NIOSH) (2013). Occupational Exposure to Hexavalent Chromium, U.S. Department of Health and Human Services (DHHS), NIOSH."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Clarkson, T.W., Friberg, L., Nordberg, G.F., and Sager, P.R. (1988). Chromium. Biological Monitoring of Toxic Metals, Springer US.","DOI":"10.1007\/978-1-4613-0961-1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"126729","DOI":"10.1016\/j.jtemb.2021.126729","article-title":"Hexavalent Chromium: Regulation and Health Effects","volume":"65","author":"Alvarez","year":"2021","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_4","unstructured":"International Agency for Research on Cancer (IARC) (1990). Evaluation of Carcinogenic Risks to Humans. Chromium, Nickel and Welding, IRAC."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.freeradbiomed.2006.10.055","article-title":"Reduction of Hexavalent Chromium by Human Cytochrome B5: Generation of Hydroxyl Radical and Superoxide","volume":"42","author":"Borthiry","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_6","first-page":"1","article-title":"Imbalance of Oxidative and Reductive Species Involved in Chromium(VI)-Induced Toxic Effects","volume":"3","author":"Hu","year":"2017","journal-title":"ROS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mrfmmm.2003.09.006","article-title":"Complexities of Chromium Carcinogenesis: Role of Cellular Response, Repair and Recovery Mechanisms","volume":"533","year":"2003","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev-pharmtox-010818-021031","article-title":"Metals and Mechanisms of Carcinogenesis","volume":"59","author":"Chen","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s12011-021-02743-w","article-title":"Examining the Potential Formation of Ternary Chromium-Histidine-DNA Complexes and Implications for Their Carcinogenicity","volume":"200","author":"Lankford","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_10","unstructured":"Agency for Toxic Substances and Disease Registry (ATSDR) (2000). Toxicological Profile for Chromium, Department of Health and Human Services, Public Health Service."},{"key":"ref_11","unstructured":"International Agency for Research on Cancer (IARC) (2012). Arsenic, Metals, Fibres, and Dust, Volume 100 C, a Review of Human Carcinogens, IRAC."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1080\/00039896.1983.10545822","article-title":"Chrome Plating: Symptoms, Findings in the Upper Airways, and Effects on Lung Function","volume":"38","author":"Lindberg","year":"1983","journal-title":"Arch. Environ. Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1191\/096032701682693062","article-title":"Mechanisms of Chromium Toxicity, Carcinogenicity and Allergenicity: Review of the Literature from 1985 to 2000","volume":"20","author":"Dayan","year":"2001","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0003-4878(01)00004-7","article-title":"Effect of Cr(VI) Exposure on Sperm Quality: Human and Animal Studies","volume":"45","author":"Li","year":"2001","journal-title":"Ann. Occup. Hyg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1600-0536.1988.tb02889.x","article-title":"Irritant Contact Dermatitis and Chrome-Passivated Metal","volume":"19","author":"Bruynzeel","year":"1988","journal-title":"Contact Dermat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1136\/pgmj.54.632.414","article-title":"Intravascular Haemolysis and Acute Renal Failure Following Potassium Dichromate Poisoning","volume":"54","author":"Sharma","year":"1978","journal-title":"Postgrad. Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"505","DOI":"10.5271\/sjweh.2388","article-title":"Urinary Excretion of Proteins in Chromeplaters, Exchromeplaters and Referents","volume":"9","author":"Lindberg","year":"1983","journal-title":"Scand. J. Work Environ. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ijheh.2017.01.007","article-title":"Human Biomonitoring as a Tool to Support Chemicals Regulation in the European Union","volume":"220","author":"Ganzleben","year":"2017","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111984","DOI":"10.1016\/j.envres.2021.111984","article-title":"HBM4EU Chromates Study\u2014Overall Results and Recommendations for the Biomonitoring of Occupational Exposure to Hexavalent Chromium","volume":"204","author":"Santonen","year":"2022","journal-title":"Environ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110998","DOI":"10.1016\/j.envres.2021.110998","article-title":"Biomarkers of Effect as Determined in Human Biomonitoring Studies on Hexavalent Chromium and Cadmium in the Period 2008\u20132020","volume":"197","author":"Ventura","year":"2021","journal-title":"Environ. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/bph.12906","article-title":"Dopamine Receptors\u2014IUPHAR Review 13: Dopamine Receptors","volume":"172","author":"Beaulieu","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112458","DOI":"10.1016\/j.biopha.2021.112458","article-title":"Dopamine, a Co-Regulatory Component, Bridges the Central Nervous System and the Immune System","volume":"145","author":"Li","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1179\/1476830513Y.0000000108","article-title":"Environment, Dysbiosis, Immunity and Sex-Specific Susceptibility: A Translational Hypothesis for Regressive Autism Pathogenesis","volume":"18","author":"Mezzelani","year":"2015","journal-title":"Nutr. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"471","DOI":"10.31887\/DCNS.2010.12.4\/ycharnay","article-title":"Brain Serotonergic Circuitries","volume":"12","author":"Charnay","year":"2010","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1124\/pr.59.2.1","article-title":"Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase","volume":"59","author":"Marchitti","year":"2007","journal-title":"Pharmacol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.chemosphere.2017.04.112","article-title":"Multiple Metal Exposures and Their Correlation with Monoamine Neurotransmitter Metabolism in Chinese Electroplating Workers","volume":"182","author":"Wu","year":"2017","journal-title":"Chemosphere"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jtemb.2019.03.009","article-title":"A Urinary Metabolomics Study of a Polish Subpopulation Environmentally Exposed to Arsenic","volume":"54","author":"Janasik","year":"2019","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kiehn, J.T., Faltraco, F., Palm, D., Thome, J., and Oster, H. (2019). Circadian Clocks in the Regulation of Neurotransmitter Systems. Pharmacopsychiatry.","DOI":"10.1055\/a-1027-7055"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-3-319-60492-3_24","article-title":"Should an Artificial Window Substitute a Natural One?","volume":"Volume 607","author":"Ahram","year":"2018","journal-title":"Advances in Usability and User Experience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nature01096","article-title":"Production and Detection of Cold Antihydrogen Atoms","volume":"419","author":"Amoretti","year":"2002","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/S0891-5849(02)00809-2","article-title":"Oxidative DNA and Protein Damage in Metal-Induced Toxicity and Carcinogenesis","volume":"32","author":"Kasprzak","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1146\/annurev.bi.62.070193.004053","article-title":"Oxidation of Free Amino Acids and Amino Acid Residues in Proteins B by Radiolysis and by Metal-Catalyzed Reactions","volume":"62","author":"Stadtman","year":"1993","journal-title":"Annu. Rev. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1086\/500563","article-title":"Mutations in ACY1, the Gene Encoding Aminoacylase 1, Cause a Novel Inborn Error of Metabolism","volume":"78","author":"Sass","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tanaka, H., Sirich, T.L., Plummer, N.S., Weaver, D.S., and Meyer, T.W. (2015). An Enlarged Profile of Uremic Solutes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135657"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1750-1172-4-28","article-title":"Novel Mutation Causing Mild, Atypical Fumarylacetoacetase Deficiency (Tyrosinemia Type I): A Case Report","volume":"4","author":"Cassiman","year":"2009","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.3748\/wjg.v25.i34.5134","article-title":"Effect of Tong Xie Yao Fang on Endogenous Metabolites in Urine of Irritable Bowel Syndrome Model Rats","volume":"25","author":"Zhao","year":"2019","journal-title":"WJG"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1006\/bbrc.1999.1970","article-title":"Novel Priming Compounds of Cystathionine Metabolites on Superoxide Generation in Human Neutrophils","volume":"269","author":"Kodama","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1056\/NEJM199009063231006","article-title":"Leukotrienes and Other Products of the 5-Lipoxygenase Pathway: Biochemistry and Relation to Pathobiology in Human Diseases","volume":"323","author":"Epstein","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.molmed.2008.08.005","article-title":"Arachidonic-Acid-Derived Eicosanoids: Roles in Biology and Immunopathology","volume":"14","author":"Harizi","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/med.21251","article-title":"Eicosanoids and Their Drugs in Cardiovascular Diseases: Focus on Atherosclerosis and Stroke","volume":"33","author":"Capra","year":"2013","journal-title":"Med. Res. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrc2809","article-title":"Eicosanoids and Cancer","volume":"10","author":"Wang","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.resinv.2019.08.003","article-title":"Current State and Future Prospect of the Therapeutic Strategy Targeting Cysteinyl Leukotriene Metabolism in Asthma","volume":"57","author":"Yamamoto","year":"2019","journal-title":"Respir. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1093\/occmed\/kqs111","article-title":"An Outbreak of Occupational Asthma Due to Chromium and Cobalt","volume":"62","author":"Walters","year":"2012","journal-title":"Occup. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhong, X., de C\u00e1ssia da Silveira e S\u00e1, R., and Zhong, C. (2017). Mitochondrial Biogenesis in Response to Chromium (VI) Toxicity in Human Liver Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091877"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.2174\/1871530319666191205122249","article-title":"Nickel and Oxidative Stress: Cell Signaling Mechanisms and Protective Role of Vitamin C","volume":"20","author":"Das","year":"2020","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.mito.2018.02.009","article-title":"Mitochondrial \u03b2-Oxidation of Saturated Fatty Acids in Humans","volume":"46","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1159\/000358672","article-title":"Role of Mitochondrial Electron Transport Chain Dysfunction in Cr(VI)-Induced Cytotoxicity in L-02 Hepatocytes","volume":"33","author":"Xiao","year":"2014","journal-title":"Cell Physiol. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/jbt.21595","article-title":"Curcumin Attenuates Cr(VI)-Induced Ascites and Changes in the Activity of Aconitase and F(1)F(0) ATPase and the ATP Content in Rat Liver Mitochondria","volume":"28","author":"Zazueta","year":"2014","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0009-8981(72)90512-8","article-title":"The Identification and Metabolic Origin of 2-Furoylglycine and 2,5-Furandicarboxylic Acid in Human Urine","volume":"41","author":"Pettersen","year":"1972","journal-title":"Clin. Chim. Acta"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1152\/physrev.00030.2013","article-title":"Thyroid Hormone Regulation of Metabolism","volume":"94","author":"Mullur","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/S0196-9781(01)00429-6","article-title":"Regulation of TRH and TRH-Related Peptides in Rat Brain by Thyroid and Steroid Hormones","volume":"22","author":"Pekary","year":"2001","journal-title":"Peptides"},{"key":"ref_52","first-page":"540","article-title":"The Human Thyrotropin-Releasing Hormone Gene Is Regulated by Thyroid Hormone through Two Distinct Classes of Negative Thyroid Hormone Response Elements","volume":"9","author":"Hollenberg","year":"1995","journal-title":"Mol. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1210\/endo.136.2.7835305","article-title":"Gonadal Steroids Regulate Rat Anterior Pituitary Levels of TSH-Releasing Hormone- and Pyroglutamyl-Glutamyl-Proline Amide-like Immunoreactivity","volume":"136","author":"Akinsanya","year":"1995","journal-title":"Endocrinology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1749-6632.1989.tb46634.x","article-title":"TRH-Catecholamine Interactions in Brain and Spinal Cord","volume":"553","author":"Bennett","year":"1989","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.addr.2007.01.001","article-title":"Chronobiology in the Endocrine System","volume":"59","author":"Haus","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_56","first-page":"99","article-title":"Effects of TRH on Central Nervous System Function","volume":"68","author":"Breese","year":"1981","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_57","first-page":"1355","article-title":"Histopathological and biochemical changes in rat thyroid following acute exposure to hexavalent chromium","volume":"25","author":"Mahmood","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ecoenv.2018.09.100","article-title":"Endocrine Disruption, Oxidative Stress and Lipometabolic Disturbance of Bufo Gargarizans Embryos Exposed to Hexavalent Chromium","volume":"166","author":"Li","year":"2018","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.envres.2018.07.039","article-title":"Exposure to Environment Chemicals and Its Possible Role in Endocrine Disruption of Children from a Rural Area","volume":"167","author":"Nascimento","year":"2018","journal-title":"Environ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"144227","DOI":"10.1016\/j.scitotenv.2020.144227","article-title":"Association of Exposure to Polycyclic Aromatic Hydrocarbons and Heavy Metals with Thyroid Hormones in General Adult Population and Potential Mechanisms","volume":"762","author":"Kim","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1111\/j.1464-410X.2011.10116.x","article-title":"A Dual Physiological Character for Cerebral Mechanisms of Sexuality and Cognition: Common Somatic Peripheral Afferents","volume":"108","author":"Motofei","year":"2011","journal-title":"BJU Int."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Henderson, B.E., Ponder, B.A.J., and Ross, R.K. (2003). Hormones, Genes, and Cancer, Oxford University Press.","DOI":"10.1093\/oso\/9780195135763.001.0001"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0960-0760(03)00383-2","article-title":"Epitestosterone","volume":"87","year":"2003","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1530\/rep.1.00067","article-title":"Microcanalization in the Epididymis to Overcome Ductal Obstruction Caused by Chronic Exposure to Chromium\u2014A Study in the Mature Bonnet Monkey (Macaca radiata Geoffroy)","volume":"128","author":"Aruldhas","year":"2004","journal-title":"Reproduction"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1093\/humrep\/dei148","article-title":"Chronic Chromium Exposure-Induced Changes in Testicular Histoarchitecture Are Associated with Oxidative Stress: Study in a Non-Human Primate (Macaca radiata Geoffroy)","volume":"20","author":"Aruldhas","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.fertnstert.2006.03.025","article-title":"In Vivo Spermatotoxic Effect of Chromium as Reflected in the Epididymal Epithelial Principal Cells, Basal Cells, and Intraepithelial Macrophages of a Nonhuman Primate (Macaca radiata Geoffroy)","volume":"86","author":"Aruldhas","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.taap.2006.03.004","article-title":"Reproductive Toxicity of Chromium in Adult Bonnet Monkeys (Macaca radiata Geoffrey). Reversible Oxidative Stress in the Semen","volume":"215","author":"Subramanian","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Chambers, P.L., Preziosi, P., and Chambers, C.M. (1984). Accumulation of Toxic Metals in Male Reproduction Organs. Disease, Metabolism and Reproduction in the Toxic Response to Drugs and Other Chemicals, Springer Berlin Heidelberg. Archives of Toxicology.","DOI":"10.1007\/978-3-642-69132-4"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1385\/BTER:74:1:41","article-title":"Rats Retain Chromium in Tissues Following Chronic Ingestion of Drinking Water Containing Hexavalent Chromium","volume":"74","author":"Sutherland","year":"2000","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_70","first-page":"15","article-title":"Impact of gestational and lactational exposure to hexavalent chromium on steroidogenic compartment of post-natal rat testis","volume":"15","author":"Sekar","year":"2011","journal-title":"J. Endocrinol. Reprod."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.reprotox.2021.01.014","article-title":"Prenatal Exposure to Hexavalent Chromium Disrupts Testicular Steroidogenic Pathway in Peripubertal F1 Rats","volume":"101","author":"Navin","year":"2021","journal-title":"Reprod. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10061","DOI":"10.1074\/jbc.M117.789800","article-title":"The Mitochondrial Outer Membrane Protein MitoNEET Is a Redox Enzyme Catalyzing Electron Transfer from FMNH2 to Oxygen or Ubiquinone","volume":"29","author":"Wang","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mito.2007.03.005","article-title":"Coenzyme Q10\u2014Its Role as a Prooxidant in the Formation of Superoxide Anion\/Hydrogen Peroxide and the Regulation of the Metabolome","volume":"7","author":"Linnane","year":"2007","journal-title":"Mitochondrion"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s12033-007-0052-y","article-title":"Bioenergetic and Antioxidant Properties of Coenzyme Q10: Recent Developments","volume":"37","author":"Littarru","year":"2007","journal-title":"Mol. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/07315724.2001.10719063","article-title":"Biochemical Functions of Coenzyme Q10","volume":"20","author":"Crane","year":"2001","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1258\/000456303321610493","article-title":"Ubiquinone: Cholesterol\u2019s Reclusive Cousin","volume":"40","author":"Hargreaves","year":"2003","journal-title":"Ann. Clin. Biochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/NDS.S112119","article-title":"Potential Role of Coenzyme Q10 in Health and Disease Conditions","volume":"10","author":"Rodick","year":"2018","journal-title":"Nutr. Diet. Suppl."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Hargreaves, I., Heaton, R.A., and Mantle, D. (2020). Disorders of Human Coenzyme Q10 Metabolism: An Overview. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186695"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1080\/10408398.2018.1442316","article-title":"Coenzyme Q10: From Bench to Clinic in Aging Diseases, a Translational Review","volume":"59","author":"Villalba","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.fct.2010.04.006","article-title":"Effect of Lead Toxicity on Coenzyme Q Levels in Rat Tissues","volume":"48","author":"Abdallah","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"461","DOI":"10.13075\/ijomeh.1896.01706","article-title":"Can the Effects of Chromium Compounds Exposure be Modulated by Vitamins and Microelements?","volume":"34","author":"Sijko","year":"2021","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/jat.1077","article-title":"Protective Effect of Vitamin B6 in Chromium-Induced Oxidative Stress in Liver","volume":"25","author":"Anand","year":"2005","journal-title":"J. Appl. Toxicol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1207\/s15327914nc5502_14","article-title":"Intracellular Levels of S-Adenosylhomocysteine but Not Homocysteine Are Highly Correlated to the Expression of Nm23-H1 and the Level of 5-Methyldeoxycytidine in Human Hepatoma Cells with Different Invasion Activities","volume":"55","author":"Yang","year":"2006","journal-title":"Nutr. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/nar\/gkl1156","article-title":"Characterization of in Vitro and in Vivo Hypomethylating Effects of Decitabine in Acute Myeloid Leukemia by a Rapid, Specific and Sensitive LC-MS\/MS Method","volume":"35","author":"Liu","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1002\/bmc.689","article-title":"Direct Determination of Nucleosides in the Urine of Patients with Breast Cancer Using Column-Switching Liquid Chromatography-Tandem Mass Spectrometry","volume":"20","author":"Cho","year":"2006","journal-title":"Biomed. Chromatogr."},{"key":"ref_86","first-page":"453","article-title":"1,7-Dimethylguanosine Formation in TRNA Enzymatic Methylation","volume":"58","author":"Kanduc","year":"1982","journal-title":"Boll. Soc. Ital. Biol. Sper."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1046\/j.1523-1755.1998.00944.x","article-title":"RNA Metabolism in Uremic Patients: Accumulation of Modified Ribonucleosides in Uremic Serum. Technical Note","volume":"53","author":"Niwa","year":"1998","journal-title":"Kidney Int."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1158\/0008-5472.CAN-14-0109","article-title":"Noninvasive Urinary Metabolomic Profiling Identifies Diagnostic and Prognostic Markers in Lung Cancer","volume":"74","author":"Patterson","year":"2014","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00258449","article-title":"Melanin Synthesis and the Action of L-Dopa and 3,4-Dihydroxybenzylamine in Human Melanoma Cells","volume":"23","author":"Kable","year":"1989","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S0006-8993(97)00922-0","article-title":"Dimethoxyphenylethylamine and Tetrahydropapaverine Are Toxic to the Nigrostriatal System","volume":"773","author":"Koshimura","year":"1997","journal-title":"Brain Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0006-8993(97)00093-0","article-title":"Neurotoxic Effects of Papaverine, Tetrahydropapaverine and Dimethoxyphenylethylamine on Dopaminergic Neurons in Ventral Mesencephalic-Striatal Co-Culture","volume":"754","author":"Goto","year":"1997","journal-title":"Brain Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0005-2728(98)00034-6","article-title":"Complex I Inhibitors as Insecticides and Acaricides","volume":"1364","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/15216540152845939","article-title":"Complex I and Parkinson\u2019s Disease","volume":"52","author":"Greenamyre","year":"2001","journal-title":"IUBMB Life"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature24661","article-title":"A Gut Bacterial Pathway Metabolizes Aromatic Amino Acids into Nine Circulating Metabolites","volume":"551","author":"Dodd","year":"2017","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1139\/m80-074","article-title":"Production of Indole-3-Propanoic Acid and 3-(p-Hydroxyphenyl)Propanoic Acid by Clostridium Sporogenes: A Convenient Thin-Layer Chromatography Detection System","volume":"26","author":"Jellet","year":"1980","journal-title":"Can. J. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/1097-4644(20010601)81:3<507::AID-JCB1064>3.0.CO;2-M","article-title":"Indole-3-Propionic Acid, a Melatonin-Related Molecule, Protects Hepatic Microsomal Membranes from Iron-Induced Oxidative Damage: Relevance to Cancer Reduction","volume":"81","author":"Karbownik","year":"2001","journal-title":"J. Cell. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3389\/fimmu.2020.00157","article-title":"Host and Microbial Tryptophan Metabolic Profiling in Multiple Sclerosis","volume":"11","author":"Gaetani","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1002\/jimd.12090","article-title":"Argininosuccinate Neurotoxicity and Prevention by Creatine in Argininosuccinate Lyase Deficiency: An in Vitro Study in Rat Three-dimensional Organotypic Brain Cell Cultures","volume":"42","author":"Hertig","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1038\/s41467-018-05972-1","article-title":"Argininosuccinic Aciduria Fosters Neuronal Nitrosative Stress Reversed by Asl Gene Transfer","volume":"9","author":"Baruteau","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/gim.2011.1","article-title":"Argininosuccinate Lyase Deficiency","volume":"14","author":"Nagamani","year":"2012","journal-title":"Genet. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s12035-019-01825-0","article-title":"Free Radical Scavengers Prevent Argininosuccinic Acid-Induced Oxidative Stress in the Brain of Developing Rats: A New Adjuvant Therapy for Argininosuccinate Lyase Deficiency?","volume":"57","author":"Seminotti","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1021\/tx200465e","article-title":"Metabolomic Characterization of Laborers Exposed to Welding Fumes","volume":"25","author":"Kuo","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"108583","DOI":"10.1016\/j.envres.2019.108583","article-title":"Setting up a Collaborative European Human Biological Monitoring Study on Occupational Exposure to Hexavalent Chromium","volume":"177","author":"Santonen","year":"2019","journal-title":"Environ. Res."},{"key":"ref_104","unstructured":"World Health Organization (WHO) (1996). Biological Monitoring of Chemical Exposure in the Workplace, WHO."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"113740","DOI":"10.1016\/j.ijheh.2021.113740","article-title":"The European Human Biomonitoring Platform\u2014Design and Implementation of a Laboratory Quality Assurance\/Quality Control (QA\/QC) Programme for Selected Priority Chemicals","volume":"234","author":"Mol","year":"2021","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6511","DOI":"10.1039\/D0AN01319F","article-title":"Assessment of Human Plasma and Urine Sample Preparation for Reproducible and High-Throughput UHPLC-MS Clinical Metabolic Phenotyping","volume":"145","author":"Southam","year":"2020","journal-title":"Analyst"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/nar\/gkx1089","article-title":"HMDB 4.0: The Human Metabolome Database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed Minimum Reporting Standards for Chemical Analysis: Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11124","DOI":"10.1021\/acs.analchem.8b03065","article-title":"MetaboGroup S: A Group Entropy-Based Web Platform for Evaluating Normalization Methods in Blood Metabolomics Data from Maintenance Hemodialysis Patients","volume":"90","author":"Wang","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1039\/c3np20111b","article-title":"A Global Approach to Analysis and Interpretation of Metabolic Data for Plant Natural Product Discovery","volume":"30","author":"Hur","year":"2013","journal-title":"Nat. Prod. Rep."},{"key":"ref_111","unstructured":"Zuba, D., and Parczewski, A. (2008). Chemometria w Analityce, Instytut Ekspertyz Sadowych."},{"key":"ref_112","unstructured":"Jolliffe, I.T. (2002). Principal Component Analysis, Springer. [2nd ed.]."},{"key":"ref_113","first-page":"731","article-title":"SVD-based principal component analysis of geochemical data","volume":"3","author":"Praus","year":"2005","journal-title":"Cent. Eur. J. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/wics.101","article-title":"Principal component analysis","volume":"2","author":"Abdi","year":"2010","journal-title":"Wiley Interdiscip. Rev. Comput. Stat."},{"key":"ref_115","unstructured":"Mazerski, J. (2000). Podstawy Chemometrii, Wydawnictwo Politechniki Gda\u0144skiej."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/4\/362\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:56:01Z","timestamp":1760136961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/4\/362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,18]]},"references-count":115,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["metabo12040362"],"URL":"https:\/\/doi.org\/10.3390\/metabo12040362","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,18]]}}}