1. bookVolume 61 (2010): Issue 4 (December 2010)
Journal Details
License
Format
Journal
eISSN
1848-6312
ISSN
0004-1254
First Published
26 Mar 2007
Publication timeframe
4 times per year
Languages
English
access type Open Access

Dioxins and Human Toxicity

Journal Details
License
Format
Journal
eISSN
1848-6312
ISSN
0004-1254
First Published
26 Mar 2007
Publication timeframe
4 times per year
Languages
English
Dioxins and Human Toxicity

The term dioxins usually refers to polychlorinated dibenzo-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). As 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) has the highest toxic potential, the toxic potentials of other PCDDs and PCDFs are defined in comparison with it. Human exposure to dioxins can be environmental (background), occupational, or accidental pollution. In the human body, dioxins are in part metabolised and eliminated, and the rest is stored in body fat. People vary in their capacity to eliminate TCDD, but it is also dose-dependent; the elimination rate is much faster at higher than lower levels. The liver microsomal P4501A1 enzyme oxygenates lipophilic chemicals such as dioxins. It is encoded by the CYP1A1 gene. Cytosolic aryl hydrocarbon receptor (AhR) mediates their carcinogenic action. It binds to dioxin, translocates to nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1.

Dioxins are classified as known human carcinogens, but they also cause noncancerous effects like atherosclerosis, hypertension, and diabetes. Long-term exposures to dioxins cause disruption of the nervous, immune, reproductive, and endocrine system. Short-term exposure to high levels impairs the liver function and causes chloracne. The most sensitive population to dioxin exposure are the foetuses and infants.

A large number of health effects have been documented in the scientific literature, and they all place dioxins among the most toxic chemicals known to man.

Keywords

GreenFacts, Facts on health and the environment. Scientific facts on dioxins 2004 [displayed 12 November 2010]. Available from http://www.greenfacts.org/en/dioxins/index.htmSearch in Google Scholar

McKay M. Dioxin characterization, formation and minimization during municipal solid waste (MSW) incineration: review. Chem Eng J 2002;86:343-68.10.1016/S1385-8947(01)00228-5Search in Google Scholar

Behnisch PA, Hosoe K, Sakai S. Combinatorial bio/chemical analysis of dioxin and dioxin-like compounds in waste recycling, food/feed, humans/wildlife and the environment. Environ Int 2001;27:495-519.10.1016/S0160-4120(01)00029-0Search in Google Scholar

Alcock RA, Behnisch PA, Jones KC, Hagenmaier H. Dioxinlike PCBs in the environment-human exposure and the significance of sources. Chemosphere 1998;37:1457-72.10.1016/S0045-6535(98)00136-2Search in Google Scholar

GreenFacts, Facts on health and the environment. Scientic facts on Dioxins 2004. Level 2- Details on dioxins [displayed 12 November 2010]. Available at http://www.greenfacts.org/en/dioxins/dioxins-greenfacts-level2.pdfSearch in Google Scholar

Ren Z, Zheng M. Impact of human activities on dioxins emissions at national scale. Chemosphere 2009;76:853-9.10.1016/j.chemosphere.2009.03.07019427661Search in Google Scholar

Kulkarni P, Crespo J, Afonso C. Dioxins sources and current remediation technologies - A review. Environ Int 2008;34:139-53.10.1016/j.envint.2007.07.00917826831Search in Google Scholar

Shibamoto T, Yasuhara A, Katami T. Dioxin formation from waste incineration. Rev Environ Contam Toxicol 2007;190:1-41.10.1007/978-0-387-36903-7_117432330Search in Google Scholar

Inoue K, Yasuda K, Kawamoto K. Report: Atmospheric pollutants discharged from municipal solid waste incineration and gasification-melting facilities in Japan. Waste Manag Res 2009;27:617-22.10.1177/0734242X0809653019470540Search in Google Scholar

Ni Y, Zhang H, Fan S, Zhang X, Zhang Q, Chen J. Emissions of PCDD/Fs from municipal solid waste incinerators in China. Chemosphere 2009;75:1153-8.10.1016/j.chemosphere.2009.02.05119304311Search in Google Scholar

Zhu J, Hirai Y, Sakai S, Zheng M. Potential source and emission analysis of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in China. Chemosphere 2008;73(Suppl 1):S72-7.10.1016/j.chemosphere.2007.06.09218439643Search in Google Scholar

Institute of Medicine (U. S.). Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides. Other Health Effects In: Veterans and Agent Orange: health effects of herbicides used in Vietnam. National Academies Press; 1994. p. 672-708.Search in Google Scholar

Commoner B. The political history of dioxins. Synthesis/Regeneration 7-8, 1995 [displayed 12 November 2010]. Available at http://www.greens.org/s-r/078/07-03.htmlSearch in Google Scholar

Le TN, Johansson A. Impact of chemical warfare with agent orange on women‵s reproductive lives in Vietnam: a pilot study. Reprod Health Matters 2001;18:156-64.Search in Google Scholar

Environmental Protection Agency (EPA). Times Beach Site, Missouri [displayed 12 November 2010]. Available at http://www.epa.gov/region07/cleanup/npl_files/mod980685226.pdfSearch in Google Scholar

Leistner M. The Times Beach Story. Synthesis/Regeneration 7-8, 1995 [displayed 12 November 2010]. Available at http://www.greens.org/s-r/078/07-09.htmlSearch in Google Scholar

De Marchi B, Funtowicz S, Ravetz J. Seveso: A paradoxical classic disaster. In: Mitchell JK, editor. The long road to recovery: Community response to industrial disasters. Tokyo: United Nations University Press; 1996.Search in Google Scholar

Larabeke N, Hens L, Schepens P, Covaci A, Baeyens J, Everaert K, Bernheim J, Vlietinck R, Poorters G. The Belgian PCB and dioxin incident of January-June 1999: exposure data and potential impact on health. Environ Health Perspect 2001;109:265-73.10.1289/ehp.01109265124024511333188Search in Google Scholar

Chivers CJ. A Dinner in Ukraine Made for Agatha Christie. New York Times 2004.Search in Google Scholar

Sterling B, Hanke W. Dioxin toxicity and chloracne in the Ukraine. J Drugs Dermatol 2005;4:148-50.Search in Google Scholar

Sorg O, Zennegg M, Schmid P, Fedosvuk R, Valikhnovskyi R, Gaide O, Kniazevych V, Saurat JH. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites. Lancet 2009;374:1179-85.10.1016/S0140-6736(09)60912-0Search in Google Scholar

World Health Organization (WHO). Dioxins and their effects on human health [displayed 12 November 2010]. Available at http://www.who.int/mediacentre/factsheets/fs225/en/index.htmlSearch in Google Scholar

Olson, J. R. Pharmacokinetics of dioxin and related chemicals. In Dioxins and Health. A. Schecter, ed. New York, NY: Plenum Press; 1994. p. 163-167.10.1007/978-1-4899-1462-0_6Search in Google Scholar

Pirkle JL, Wolfe WH, Patterso DG, Needham LL, Michalek JE, Miner JC, Peterson MR, Phillips DL. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam veterans of Operation Ranch Hand. J Toxicol Environ Health 1989;27:165-71.10.1080/152873989095312882733058Search in Google Scholar

Aylward LL, Brunet RC, Carrier G, Hays SM, Cushing CA, Needham LL, Patterson DG, Gerthoux PM, Brambilla P, Mocarelli P. Concentration-dependent TCDD elimination kinetics in humans: toxicokinetic modeling for moderately to highly exposed adults from Seveso, Italy, and Vienna, Austria, and impact on dose estimates for the NIOSH cohort. J Expo Anal Environ Epidemiol 2005;15:51-65.10.1038/sj.jea.750037015083163Search in Google Scholar

Emond C, Michalek JE, Birnbaum L, Devito MJ. Comparison of the use of a physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments. Environ Health Perspect 2005;113:1666-8.10.1289/ehp.8016131490216330344Search in Google Scholar

World Health Organization (WHO). Executive summary. Assessment of health risks of dioxins: re-evaluation of the Tolerable daily intake (TDI). Geneva: WHO; 1998.Search in Google Scholar

Ma Q. Induction of CYP1A1. The AhR/DRE paradigm: Transcription, receptor regulation, and expanding biological roles. Curr Drug Metab 2001;2:149-64.10.2174/138920001333860311469723Search in Google Scholar

Whitlock JP. Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol 1999;39:103-25.10.1146/annurev.pharmtox.39.1.10310331078Search in Google Scholar

Fujii-Kuriyama Y, Mimura J. Molecular mechanisms of AhR functions in the regulation of cytochrome P450 genes. Biochem Biophys Res Commun 2005;338:311-7.10.1016/j.bbrc.2005.08.16216153594Search in Google Scholar

Barouki R, Coumoul X, Fernandez-Salguero P. The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein. FEBS Lett 2007;581:3608-15.10.1016/j.febslet.2007.03.04617412325Search in Google Scholar

Hu K, Bunce NJ. Metabolism of polychlorinated dibenzo-p-dioxins and related dioxin-like compounds. J Toxicol Environ Health B Crit Rev 1999;2:183-210.10.1080/10937409928121410230393Search in Google Scholar

Hoffman EC, Reyes H, Chu FF, Sander F, Conley LH, Brooks BA, Hankinson O. Cloning of a factor required for activity of the Ah (dioxin) receptor. Science 1991;252:954-8.10.1126/science.1852076Search in Google Scholar

Okino ST, Whitlock JP. The aromatic hydrocarbon receptor, transcription, and endocrine aspects of dioxin action. Vitam Horm 2000;59:241-64.10.1016/S0083-6729(00)59009-8Search in Google Scholar

Walisser JA, Glover E, Pande K, Liss AL, Bradfield CA. Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity are mediated by different cell types. Proc Natl Acad Sci USA 2005;102:17858-63.10.1073/pnas.0504757102Search in Google Scholar

Yueh MF, Huang YH, Hiller A, Chen S, nguyen N, Tukey RH. Involvement of the xenobiotic response element (XRE) in Ah receptor-mediated induction of human UDPglucuronosyltransferase 1A. J Biol Chem 2003;278:15001-6.10.1074/jbc.M300645200Search in Google Scholar

Mimura J, Fujii-Kuriyama Y. Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta 2003;1619:263-8.10.1016/S0304-4165(02)00485-3Search in Google Scholar

Puga A, Barnes S, Dalton TP, Chang C, Knudsen ES, Maier MA. Aromatic hydrocarbon receptor interaction with the retinoblastoma protein potentiates repression of E2F-dependent transcription and cell cycle arrest. J Biol Chem 2000;275:2943-50.10.1074/jbc.275.4.294310644764Search in Google Scholar

Mandal PK. Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology. J Comp Physiol B 2005;175:221-30.10.1007/s00360-005-0483-315900503Search in Google Scholar

Kim MK, Oh S, Lee JH, Im H, Ryu YM, Oh E, Lee J, Lee E, Sul D. Evaluation of biological monitoring markers using genomic and proteomic analysis for automobile emission inspectors and waste incinerating workers exposed to polycyclic aromatic hydrocarbons or 2,3,7,8,-tetracholrodedibenzo-p-dioxins. Exp Mol Med 2004;36:396-410.10.1038/emm.2004.5215557812Search in Google Scholar

Puga A, Tomlinson CR, Xia Y. Ah receptor signals cross-talk with multiple developmental pathways. Biochem Pharmacol 2005;69:199-207.10.1016/j.bcp.2004.06.04315627472Search in Google Scholar

Poellinger L. Mechanistic aspects - the dioxin (aryl hydrocarbon) receptor. Food Addit Contam 2000;17:261-6.10.1080/02652030028333310912240Search in Google Scholar

Pelclová D, Urban P, Preiss J, Lukás E, Fenclová Z, Navrátil T, Dubská Z, Senholdová Z. Adverse health effects in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rev Environ Health 2006;21:119-38.10.1515/REVEH.2006.21.2.11916898675Search in Google Scholar

International Agency for Research on Cancer (IARC). Polychlorinated dibenzo-para-dioxins and polychlorinated dibenzofurans. IARC monographs on the evaluation of carcinogenic risks to humans, Volume 69. Geneva: IARC; 1997.Search in Google Scholar

Bertazzi PA, Bernucci I, Brambilla G, Consonni D, Pesatori A. The Seveso studies on early and long-term effects of dioxin exposure: a review. Environ Health Perspect 1998;106(Suppl 2):625-33.10.1289/ehp.9810662515333889599710Search in Google Scholar

Bertazzi PA, Zocchetti C, Guercilena S, Consonni D, Tironi A, Landi MT, Pesatori AC. Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident". Epidemiology 1997;8:646-52.10.1097/00001648-199710000-00006Search in Google Scholar

Bertazzi PA, Consonni D, Bachetti S, Rubagotti M, Baccarelli A, Zocchetti C, Pesatori AC. Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol 2001;153:1031-44.10.1093/aje/153.11.103111390319Search in Google Scholar

Zambon P, Ricci P, Bovo E, Casula A, Gattolin M, Fiore AR, Chiosi F, Guzzinati S. Sarcoma risk and dioxin emissions from incinerators and industrial plants: a population-based case-control study (Italy). Environ Health 2007;16:6-19.10.1186/1476-069X-6-19194888617634118Search in Google Scholar

Reis MF, Miguel JP, Sampaio C, Aguiar P, Melim JM, Päpke O. Determinants of dioxins and furans in blood of nonoccupationally exposed populations living near Portuguese solid waste incinerators. Chemosphere 2007;67:S224-30.10.1016/j.chemosphere.2006.05.10217240423Search in Google Scholar

Viel JF, Daniau C, Goria S, Fabre P, de Crouy-Chanel P, Sauleau EA, Empereur-Bissonnet P. Risk for non Hodgkin's lymphoma in the vicinity of French municipal solid waste incinerators. Environ Health 2008;7:51.10.1186/1476-069X-7-51258746018959776Search in Google Scholar

Nadal M, Domingo JL, García F, Schuhmacher M. Levels of PCDD/F in adipose tissue on non-occupationally exposed subjects living near a hazardous waste incinerator in Catalonia, Spain. Chemosphere 2009;74:1471-6.10.1016/j.chemosphere.2008.11.05419150731Search in Google Scholar

Schuhmacher M, Kiviranta H, Ruokojärvi P, Nadal M, Domingo JL. Concentrations of PCDD/Fs, PCBs and PBDEs in breast milk of women from Catalonia, Spain: a follow-up study. Environ Int 2009;35:607-13.10.1016/j.envint.2008.12.00319162323Search in Google Scholar

Nadal M, Perelló G, Schuhmacher M, Cid J, Domingo JL. Concentrations of PCDD/PCDFs in plasma of subjects living in the vicinity of a hazardous waste incinerator: follow-up and modeling validation. Chemosphere 2008;73:901-6.10.1016/j.chemosphere.2008.07.02118715608Search in Google Scholar

Schuhmacher M, Domingo JL. Long-term study of environmental levels of dioxins and furans in the vicinity of a municipal solid waste incinerator. Environ Int 2006;32:397-404.10.1016/j.envint.2005.09.002Search in Google Scholar

Huang HY, Jeng TY, Lin YC, Ma YC, Kuo CP, Sung FC. Serum dioxin levels in residents living in the vicinity of municipal waste incinerators in Taiwan. Inhal Toxicol 2007;19:399-403.10.1080/08958370601174842Search in Google Scholar

Domingo JL, Agramunt MC, Nadal M, Schuhmacher M, Corbella J. Health risk assessment of PCDD/PCDF exposure for the population living in the vicinity of a municipal waste incinerator. Arch Environ Contam Toxicol 2002;43:461-5.10.1007/s00244-002-1280-6Search in Google Scholar

Lee SJ, Choi SD, Jin GZ, Oh JE, Chang YS, Shin SK. Assessment of PCDD/F risk after implementation of emission reduction at a MSWI. Chemosphere 2007;68:856-63.10.1016/j.chemosphere.2007.02.036Search in Google Scholar

Flesch-Janys D, Berger J, Gurn P, Manz A, Nagel S, Waltsgott H, Dwyer JH. Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of Germany. Am J Epidemiol 1995;142:1165-75.10.1093/oxfordjournals.aje.a117575Search in Google Scholar

Ott MG, Zober A. Cause specific mortality and cancer incidence among employees exposed to 2,3,7,8-TCDD after a 1953 reactor accident. Occup Environ Med 1996;53:606-12.10.1136/oem.53.9.606Search in Google Scholar

Kogevinas M, Becher H, Benn T, Bertazzi PA, Boffetta P, Bueno-De-Mesquita HB, Coggon D, Colin D, Flesch-Janys D, Fingerhut M, Green L, Kauppinen T, Littorin M, Lynge E, Mathews JD, Neuberger M, Pearce N, Saracci R. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study. Am J Epidemiol 1997;145:1061-75.10.1093/oxfordjournals.aje.a009069Search in Google Scholar

Warner M, Eskenazi B, Mocarelli P, Gerthoux PM, Samuels S, Needham L, Patterson D, Brambilla P. Serum dioxin concentrations and breast cancer risk in the Seveso Women's Health Study. Environ Health Perspect 2002;110:625-8.10.1289/ehp.02110625Search in Google Scholar

Revich B, Aksel E, Ushakova T, Ivanova I, Zhuchenko N, Klyuev N, Brodsky B, Sotskov Y. Dioxin exposure and public health in Chapaevsk, Russia. Chemosphere 2001;43:951-66.10.1016/S0045-6535(00)00456-2Search in Google Scholar

Viel JF, Clément MC, Hägi M, Grandjean S, Challier B, Danzon A. Dioxin emissions from a municipal solid waste incinerator and risk of invasive breast cancer: a population-based case-control study with GIS-derived exposure. Int J Health Geogr 2008;7:4.10.1186/1476-072X-7-4226744718226215Search in Google Scholar

Birnbaum LS, Tuomisto J. Non-carcinogenic effects of TCDD in animals. Food Addit Contam 2000;17:275-88.10.1080/026520300283351Search in Google Scholar

Luebke RW, Chen DH, Dietert R, Yang Y, King M, Luster MI. Immunotoxicology Workgroup. The comparative immunotoxicity of five selected compounds following developmental or adult exposure. J Toxicol Environ Health B Crit Rev 2006;9:1-26.10.1080/15287390500194326Search in Google Scholar

US Environmental Protection Agency (US EPA). Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. Part III: Integrated Summary and Risk Characterization for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds Washington DC: US Environmental Protection Agency; 2000. p. 264.Search in Google Scholar

Nishijo M, Kuriwaki J, Hori E, Tawara K, Nakagawa H, Nishijo H. Effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal brain growth and motor and behavioral development in offspring rats. Toxicol Lett 2007;173:41-7.10.1016/j.toxlet.2007.06.007Search in Google Scholar

Brouwer A, Ahlborg UG, Van den Berg M, Birnbaum LS, Boersma ER, Bosveld B, Denison MS, Earl Gray L, Hagmar L, Holene E, Huisman M, Jacobson SW, Jacobson JL, Koopman-Esseboom C, Koppe JG, Kulig BM, Morse DC, Muckle G, Peterson RE, Sauer PJJ, Seegal RF, Smits-Van Prooije AE, Touwen BCL, Weisglas-Kuperus N, Winneke G. Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants. Eur J Pharmacol 1995;293:1-40.10.1016/0926-6917(95)90015-2Search in Google Scholar

World Health Organization (WHO). Hazardous chemicals: main risks to children's health. Fact Sheet EURO/02/04. Copenhagen: WHO; 2004.Search in Google Scholar

Kreuzer PE, Csanady GA, Baur C, Kessler W, Papke O, Greim H, Filser JG. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch Toxicol 1997;71:383-400.10.1007/s0020400504029195020Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo