{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:06:41Z","timestamp":1792022801045,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Titanium dioxide is produced or imported into the EU for over one million tons\/year. The International Agency for Research on Cancer (IARC) classification is 2B, a possible inhalation carcinogen for humans. This study evaluates urinary biomarkers of oxidative stress in workers of a plant producing TiO2 pigment powder, having 0.25 \u00b5m average particle size and an ultrafine fraction, compared to unexposed subjects. Urine samples were collected from forty workers before and after the shift, from six employees of the same company and eighteen volunteers from the same geographical area. Titanium and other metals concentrations were measured by ICP-MS, while DNA, RNA, and protein oxidation products by HPLC\/MS-MS. A statistically significant increase was found for the urinary concentration of Al, Cd, Cr, Cu, Fe, Mn, Pb, Ti, and Zr, and for all biomarkers of oxidative stress in post-shift workers\u2019 urine samples. Urinary concentrations after the working shift were higher than for employees and volunteers pooled together for Cd, Mn, and Zr, and for the oxidative stress biomarkers 8-oxoGuo, 8-oxodGuo, and 3NO2Tyr. Biomonitoring studies on dose and effect biomarkers for TiO2 occupational exposure provide information useful for protecting workers\u2019 health even in conditions that comply with health and safety standards, highlighting reversible effects of chronic exposure at very low doses.<\/jats:p>","DOI":"10.3390\/ijerph17239085","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T12:24:39Z","timestamp":1607343879000},"page":"9085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant"],"prefix":"10.3390","volume":"17","author":[{"given":"Flavia","family":"Buonaurio","sequence":"first","affiliation":[{"name":"Department of Chemistry, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9633-8484","authenticated-orcid":false,"given":"Maria Luisa","family":"Astolfi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sapienza University, P.le 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 Chemistry, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-4964","authenticated-orcid":false,"given":"Marco","family":"Di Basilio","sequence":"additional","affiliation":[{"name":"Department of Technological Innovations and Safety of Plants, INAIL, Products and Anthropic Settlements, Via di Fontana Candida 1, Monte Porzio Catone, 00078 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8314-6272","authenticated-orcid":false,"given":"Rocco","family":"Gibilras","sequence":"additional","affiliation":[{"name":"Department of Technological Innovations and Safety of Plants, INAIL, Products and Anthropic Settlements, Via di Fontana Candida 1, Monte Porzio Catone, 00078 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mecchia","sequence":"additional","affiliation":[{"name":"Department for Risks Assessment and Prevention, INAIL, Central Office, Via R. Ferruzzi 40, 00143 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Papacchini","sequence":"additional","affiliation":[{"name":"Department of Technological Innovations and Safety of Plants, INAIL, Products and Anthropic Settlements, Via di Fontana Candida 1, Monte Porzio Catone, 00078 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Paci","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Via di Fontana Candida 1, Monte Porzio Catone, 00078 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Pigini","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Via di Fontana Candida 1, Monte Porzio Catone, 00078 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 Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Via di Fontana Candida 1, Monte Porzio Catone, 00078 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,5]]},"reference":[{"key":"ref_1","unstructured":"Jaskula, B.W. (2020, December 04). 2014 Minerals Yearbook. Available online: http:\/\/prd-wret.s3.amazonaws.com\/assets\/palladium\/production\/mineral-pubs\/country\/2014\/myb3-sum-2014-me-na.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1016\/0016-7037(67)90011-7","article-title":"Stability relations of some titanium-minerals (sphene, perovskite, rutile, anatase)","volume":"31","author":"Schuiling","year":"1967","journal-title":"Geochim. Cosmochim. Acta"},{"key":"ref_3","first-page":"1477","article-title":"Pressure-temperature studies of anatase, brookite, rutile, and TiO2, pt. 2","volume":"54","author":"Jamieson","year":"1969","journal-title":"Am. Mineral."},{"key":"ref_4","unstructured":"US CDC-NIOSH (2020, December 04). Current Intelligence Bulletin 63: Occupational Exposure to Titanium Dioxide, Available online: https:\/\/www.cdc.gov\/niosh\/nioshtic-2\/20038613.html."},{"key":"ref_5","unstructured":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2010). Carbon black, titanium dioxide, and talc. IARC Monogr. Eval. Carcinog. Risks Hum., 93, 1\u2013413."},{"key":"ref_6","unstructured":"(2020, July 27). Titanium dioxide. Available online: https:\/\/echa.europa.eu\/it\/registration-dossier\/-\/registered-dossier\/15560\/9."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4149\/endo_2015_02_97","article-title":"Titanium dioxide nanoparticles: Some aspects of toxicity\/focus on the development","volume":"49","author":"Rollerova","year":"2015","journal-title":"Endocr. Regul."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/jdv.15943","article-title":"Safety of titanium dioxide nanoparticles in cosmetics","volume":"33","author":"Alexis","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1743-8977-10-9","article-title":"Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration","volume":"10","author":"Cho","year":"2013","journal-title":"Part. Fibre Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"600","DOI":"10.3109\/1354750X.2016.1160432","article-title":"Increased levels of oxidative stress biomarkers in metal oxides nanomaterial-handling workers","volume":"21","author":"Liou","year":"2016","journal-title":"Biomarkers"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.aca.2018.06.081","article-title":"A novel malic acid-enhanced method for the analysis of 5-methyl-2\u2032-deoxycytidine, 5-hydroxymethyl-2\u2032-deoxycytidine, 5-methylcytidine and 5-hydroxymethylcytidine in human urine using hydrophilic interaction liquid chromatography-tandem mass spectrometry","volume":"1034","author":"Guo","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/10408347.2019.1623010","article-title":"Advancements in the Analytical quantification of nitroxidative stress biomarker 3-nitrotyrosine in biological matrices","volume":"50","author":"Bandookwala","year":"2020","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1136\/oemed-2015-103161","article-title":"Markers of oxidative damage of nucleic acids and proteins among workers exposed to TiO2 (nano) particles","volume":"73","author":"Pelclova","year":"2016","journal-title":"Occup. Environ. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tranfo, G. (2020). The growing importance of the human biomonitoring of exposure. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17113934"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"WHO (1982). Environmental health criteria 24: Titanium. Environ. Health Criteria, 22, 76.","DOI":"10.1016\/0278-6915(84)90059-0"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jtemb.2006.07.001","article-title":"Selected urinary metal reference concentrations of the Viennese population\u2013Urinary metal reference values (Vienna)","volume":"20","author":"Zeiner","year":"2006","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.scitotenv.2016.03.073","article-title":"Urinary levels of trace elements among primary school-aged children from Italy: The contribution of smoking habits of family members","volume":"557\u2013558","author":"Protano","year":"2016","journal-title":"Sci. Total Environ."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.toxlet.2014.08.019","article-title":"Determination of 61 elements in urine samples collected from a non-occupationally exposed UK adult population","volume":"231","author":"Morton","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jtemb.2019.04.003","article-title":"Possibilities of single particle\u2014ICP-MS for determining\/characterizing titanium dioxide and silver nanoparticles in human urine","volume":"54","author":"Badalova","year":"2019","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ijheh.2016.10.013","article-title":"Reference levels and relationships of nine elements in first-spot morning urine and 24-h urine from 210 Chinese children","volume":"220","author":"Zhang","year":"2017","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1289\/ehp.1307563","article-title":"Urinary metals and heart rate variability: A cross-sectional study of urban adults in Wuhan, China","volume":"123","author":"Feng","year":"2015","journal-title":"Environ. Health Perspect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.3762\/bjnano.5.192","article-title":"A reproducible number-based sizing method for pigment-grade titanium dioxide","volume":"5","author":"Theissmann","year":"2014","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_23","unstructured":"(2020, December 04). Directive 2001\/20\/Ec of the European Parliament and of the Councilof 4 April 2001. Available online: https:\/\/ec.europa.eu\/health\/sites\/health\/files\/files\/eudralex\/vol-1\/dir_2001_20\/dir_2001_20_en.pdf."},{"key":"ref_24","unstructured":"(2020, December 04). International Code of Ethics for Occupational Health Professionals. Available online: http:\/\/www.icohweb.org\/site_new\/multimedia\/core_documents\/pdf\/code_ethics_eng_2012.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/clinchem\/32.3.446","article-title":"Automated determination of urinary creatinine without sample dilution: Theory and practice","volume":"32","author":"Kroll","year":"1986","journal-title":"Clin. Chem."},{"key":"ref_26","unstructured":"American Conference of Governmental Industrial Hygienists (2016). TLVs and BEIs: Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices, ACGIH."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Protano, C., Canepari, S., Astolfi, M.L., D\u2019Onorio De Meo, S., and Vitali, M. (2018). Urinary reference ranges and exposure profile for lithium among an Italian paediatric population. Sci. Total Environ.","DOI":"10.1016\/j.scitotenv.2017.11.090"},{"key":"ref_28","unstructured":"Protano, C., Astolfi, M.L., Canepari, S., Andreoli, R., Mutti, A., Valeriani, F., Romano Spica, V., Antonucci, A., Mattei, V., and Martellucci, S. (2017). Exposure to individual and multiple carcinogenic metals during paediatric age: An experience from an Italian urban scenario. Ann. Ig."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Astolfi, M.L., Protano, C., Marconi, E., Massimi, L., Brunori, M., Piamonti, D., Migliara, G., Vitali, M., and Canepari, S. (2020). A new rapid treatment of human hair for elemental determination by inductively coupled mass spectrometry. Anal. Methods.","DOI":"10.1039\/C9AY01871A"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Andreoli, R., Manini, P., De Palma, G., Alinovi, R., Goldoni, M., Niessen, W.M.A., and Mutti, A. (2010). Quantitative determination of urinary 8-oxo-7,8-dihydro-2\u2032-deoxyguanosine, 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, and their non-oxidized forms: Daily concentration profile in healthy volunteers. Biomarkers.","DOI":"10.3109\/13547500903434501"},{"key":"ref_31","unstructured":"American Conference of Governmental Industrial Hygienists (2019). TLVs and BEIs Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, ACGIH."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bevan, R., Ashdown, L., McGough, D., Huici-Montagud, A., and Levy, L. (2017). Setting evidence-based occupational exposure limits for manganese. Neurotoxicology.","DOI":"10.1016\/j.neuro.2016.08.005"},{"key":"ref_33","first-page":"58","article-title":"Biomonitoring of the Italian population to metals: Reference values 1990\u20132009","volume":"10","author":"Alimonti","year":"2010","journal-title":"Rapp. Istisan"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, Y.-S., Kawasaki, Y., Watanabe, S., Ootsuyama, Y., Kasai, H., and Kawai, K. (2020). Diurnal and day-to-day variation of urinary oxidative stress marker 8-hydroxy-2\u2019-deoxyguanosine. J. Clin. Biochem. Nutr.","DOI":"10.3164\/jcbn.19-105"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.freeradbiomed.2010.11.009","article-title":"Reference ranges of urinary biomarkers of oxidized guanine in (2\u2032-deoxy)ribonucleotides and nucleic acids","volume":"50","author":"Andreoli","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tranfo, G., Paci, E., Carrieri, M., Marchetti, E., Sisto, R., Gherardi, M., Costabile, F., Bauleo, L., Ancona, C., and Pigini, D. (2019). Levels of urinary biomarkers of oxidatively generated damage to DNA and RNA in different groups of workers compared to general population. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16162995"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/23\/9085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:41:54Z","timestamp":1760179314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/23\/9085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,5]]},"references-count":36,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijerph17239085"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17239085","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,5]]}}}