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Dioxins Marie Sedillo, Vanessa Casias, Sarah Miller and Cristina Gomez.

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Presentation on theme: "Dioxins Marie Sedillo, Vanessa Casias, Sarah Miller and Cristina Gomez."— Presentation transcript:

1 Dioxins Marie Sedillo, Vanessa Casias, Sarah Miller and Cristina Gomez

2 Dioxins Introduction What are dioxins? What is their importance? What are the sources of dioxins? How are we exposed to dioxins? Dioxin Poisoning How much is too much? Who is susceptible? What are the effects? Mechanism of Action Interactions with AhR Clean up Why is it difficult to clean up? Viet Nam – Agent Orange Biodegradation Current and Future Challenges Conclusion Children affected by Agent Orange at the Viet Nam Friendship Village. The boy was 19 years old at the time this photo was taken. Ha Noi, Viet Nam, Photo courtesy of Sarah Miller

3 Introduction What are dioxins? What is their importance? What are the sources of dioxins? How are we exposed to dioxins?

4 What are dioxins? Part of the persistent organic pollutants chemical class. Typically, polychlorinated dibenzo para dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Environmentally and biologically persistent Lipid soluble (accumulate in fatty tissue) Highly toxic: dioxins affect multiple organ systems.

5 What is their importance? Dioxins are noted to be among the most toxic chemicals. Highly toxic to humans with many associated health effects. Due to human activity, dioxins are a new threat. ◦ Prior to industrialization, dioxins were found only in small amounts. “…all human[s] and tissues studied to date by these methods have measurable dioxins and PCDFs” (Schecter et al. 2006). ◦ “these methods” refers to current detection technology used by dioxin laboratories worldwide to detect the presence of dioxins. Dioxins have a unique mechanism of action.

6 What are the sources of Dioxins? Anthropogenic in origin "The only natural sources of dioxins are forest fires and volcano activities. Most are formed and released as by-products of human activities” (Marinkovic et al. 2010).

7 What are the sources of Dioxins? (Kulkarni et al. 2008) Dioxins are also found in herbicides and pesticides.

8 How are we exposed to dioxins? Industrial waste: (factories) ◦ improper disposal. Pesticides/herbicides: (Agent Orange) ◦ 11.4 million gallons dropped in Viet Nam between 1961 and 1970 at up to 55 times the suggested concentration. Exposed through: ◦ soil, sediments, food (dairy, meat, fish, shellfish), breast milk, and passage through the placental barrier. How can exposure be limited? ◦ Limit animal fat intake (especially pregnant women and nursing mothers)

9 Dioxin Poisoning How much is too much? Who is susceptible? What are the effects of dioxinexposure? Mechanism of action-AhR

10 How much is too much? At this time, the exact amount of unsafe exposure is unclear, but it is known that exposure to dioxins should be limited. Dioxin levels must not exceed 1,000 ppt (parts per trillion) toxic equivalent (TE) in soil and 100 ppt TE in sediments. Finding an acceptable safe dioxin level is complex.

11 How much is too much? Factors affecting complexity ◦ Exposure in the general population is usually to a mixture of dioxin-like compounds. ◦ Biomagnification: Even in areas where environmental levels are low, this can translate to high levels in certain organisms. ◦ “As they [dioxins] are not soluble in water, in aquatic environments most of them attach strongly to any material with high organic content, especially to microscopic plants and animals (plankton) which are eaten by larger animals” (Marinkovic et al. 2010).

12 How much is too much? How is toxicity measured? Dioxin toxic equivalency factor (TEF) is a number assigned based on potency compared to the most toxic dioxin, TCDD. TEF x Concentration = concentration equivalent to TCDD (toxic equivalent, TE) Sum TE of a mixture ◦ Add the partial equivalents of all compounds in the mixture. Important to note that these are based assumptions ◦ used “…as a proxy of the total toxic amount of dioxin like compounds” (Linden et al. 2010).

13 Dioxin poisoning-Who is susceptible? Fetus: the developing fetus is most susceptible. Exposure occurs through food and other materials that the mother ingests or that she is exposed to. Industrial workers: industrial workers are exposed to dioxins on a daily basis (i.e. hazardous material on the job, factory waste, etc.) Populations with high-fish/shellfish, high-animal fat diet: dioxins are dissolved in the fat of animals and marine animals in the environment. General population: through background exposure (Background exposure tends to be relatively low, except in Viet Nam, where environmental levels remain extremely high.)

14 What are the effects of Dioxin Exposure? Dioxin poisoning results in a spectrum of disorders Chloracne is the hallmark of dioxin exposure in humans ◦ Chlorance can persist for years, or even decades Example of TCDD-induced chloracne. The photograph shows the ear of a patient at approximately 1 year after TCDD intoxication. Courtesy of A. Geusau, Medical University of Vienna. (Bradshaw and Bell 2009)

15 What are the effects? Chloracne: the hallmark of dioxin exposure in humans Young woman with chloracne from dioxin exposure in Viet Nam. Courtesy of

16 What are the effects? Acute symptoms/short term ◦ skin lesions ◦ skin darkening ◦ liver dysfunction Chronic symptoms/long term ◦ diabetes ◦ cancer ◦ birth defects- physical deformities, mental disabilities, etc. ◦ infertility ◦ other disabilities Effects on babies and/or pregnant women ◦ impairs nervous system development ◦ impairs normal development ◦ dissolves in breast milk Effects on children/adolescents ◦ impaired immune function  cancer ◦ impaired endocrine function  diabetes, infertility ◦ impaired reproduction

17 Mechanism of Action Why are dioxins toxic? ◦ Interactions with the ligand-mediated transcription factor aryl hydrocarbon (AhR)  Dioxins are ligands of AhR

18 Mechanism of Action - AhR "The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that controls the expression of a diverse set of genes. The toxicity… is almost exclusively mediated through this receptor” (Beischlag et al. 2008). Figure courtesy of Chopra and Schrenk 2011

19 Mechanism of Action - AhR Roles of AhR in normal function ◦ Developmental roles ◦ Immune system function ◦ Targets genes involved in signaling pathways ◦ Cell cycle and apoptosis ◦ Targets genes involved in tumor initiation/promotion ◦ Tissue remodeling

20 Mechanism of Action - AhR Dioxins bind to AhR and cause changes in gene expression. “The inappropriate modulation of gene expression represents the initial steps in a series of bio-chemical, cellular and tissue changes that result in the toxicity observed” (Kulkarni et al. 2008).

21 Clean up How difficult are dioxins to clean up? Viet Nam – Agent Orange (AO) New technology: Biodegradation of dioxins

22 How difficult are dioxins to clean up? Half life of dioxins ◦ A) In the body: years ◦ B) On surfaces exposed to sun (plant leaves, etc.): 1-3 years  due to sun degradation ◦ C) Beneath soil/in sediments:100+ years At the industrial level, complete incineration is required to destroy dioxins. ◦ Temperatures for incineration must exceed degrees C.

23 Dioxins in Viet Nam-Agent Orange (AO) Who was affected? Viet Nam: researchers found dioxin levels of up to 365,000 ppt TE at Da Nang, 262,000 ppt TE on the Bien Hoa base and 236,000 ppt TE in former storage areas on the Phu Cat base. ◦ Note: These levels greatly exceed acceptable levels as described earlier-1,000 ppt TE in soil. Barrels of AO stored at the Da Nang Air Base. AO was named for the orange stripe painted on the storage barrels, like the ones pictured here. Da Nang, Viet Nam. Courtesy of

24 Viet Nam Who was affected? The Environment: AO was used to defoliate rainforests for airstrikes, to eliminate crops that were being grown for South Vietnamese troops, and to make it easier for troops to navigate on foot. In areas where it was sprayed, AO effectively killed all the foliage and crop plants. Planes during a low-altitude AO spraying mission to defoliate rainforests in Viet Nam. Photo courtesy of

25 Viet Nam Who was affected? The soldiers: Exposure to dioxins through handling, and from being in the regions where it was dumped. Civilians: Living in the areas where dioxin was dumped. Babies/pregnant women: Fetus most susceptible. Impaired normal development.

26 Viet Nam Who is still affected? The Environment: Dioxins penetrate deep into the soil and into sediments beneath water. “Hot spots” of AO contamination in Viet Nam remain to this day. a) Because of the long half life of the chemical, AO is still present in the environment in Viet Nam in high concentrations. b) The presence of AO in the soils has made the land unsuitable for crops and farming. c) AO exposure continues through food, (high fish/shellfish/pork consumption in Viet Nam), and exposure to AO in the environment.

27 Viet Nam Who is still affected? d) Defoliation with AO changed areas that were once rainforests into grasslands  AO killed all foliage, changed soil composition, etc.  Loss of trees led to erosion.  HUGE loss of biodiversity.  Most ecosystems have not recovered. Once dominated by rainforests, Viet Nam’s landscape is now largely made up of grasslands. Courtesy of

28 Photo showing the devastation of the rainforests in Viet Nam after AO was sprayed. Taken by a US soldier during the war. Courtesy of

29 Dioxins in Viet Nam-Agent Orange Who is still affected? Babies/pregnant women: a) AO persistence in the environment continues to cause debilitating birth defects, mental disabilities, etc. in children born and/or gestated in Viet Nam. b) Continued exposure after birth through breast milk and food. 20 year old Nguyen Thi Van Long suffers from one of the common birth defects believed to be caused by exposure to AO. Courtesy of

30 Dioxins in Viet Nam-Agent Orange Who is still affected? Vets: veterans of the Vietnamese-American War are developing cancer, diabetes, etc. This has been attributed to dioxin exposure. Civilians: continued exposure through food. AO still present at huge concentrations in soil.

31 Clean up in Viet Nam Estimated total of 234,780 cubic meters of soil and sediment needing clean up at Bien Hoa, Da Nang, and Phu Cat; the worst known sites of contamination in Viet Nam (does not include rest of country). In Viet Nam, 5 million acres of forest, 500,000 acres of crops, and villages were sprayed. AO seeped into soil and sediments. Expensive and labor intensive clean up ◦ To eradicate AO from top-soil, the soil must be dug up to a depth of 15 feet and cleaned. 1 square foot of dioxin- laden soil costs millions of dollars to clean up, while it cost just a few dollars to drop AO on that same square foot of soil.

32 New Technology: Biodegradation of Dioxins Research indicates that microorganisms may be used to break down dioxins. ◦ Some aerobic/anaerobic bacterial and fungal microorganisms are able to break down certain dioxins. Overall, there has been limited success, but hopes are that a microorganism will be engineered for this purpose.

33 Current and Future Challenges Although new technology and filter use has reduced industrial dioxin emissions, some researchers claim that overall emissions are increasing due to increasing sources of dioxin production. Challenge in pinpointing toxic effects of dioxin exposure: ◦ “…simultaneous exposure to other chemicals, often the main chemicals containing dioxins as minor impurities” (Linden et al. 2010). “Despite extensive and numerous studies over the last three decades, the ultimate reason for the extremely high acute toxicity of certain dioxins, foremost TCDD, has remained enigmatic” (Linden et al. 2010).

34 Conclusion On a daily basis, we are exposed to dioxins from many different sources. Dioxins are largely man-made. Dioxins cause a spectrum of debilitating diseases, including cancers. ◦ Most susceptible are infants, children, adolescents, and the elderly

35 Conclusion Unsafe levels are difficult to define, and even low levels are subject to biomagnification, so we must be be cautious to limit our exposure. Effects of AO in Viet Nam demonstrate the severity of dioxin contamination. Difficulties of dioxin removal, together with its long half life, highlight the need to create cleaner industrial and agricultural practices.

36 Conclusion “[Studies of dioxins]…have certainly helped us to understand the importance of proper hazardous substances management and the need to minimize their release in the environment at all times to protect human health” (Marinkovic et al. 2010).

37 Works cited Beischlag, T. V., J.L. Morales, B.D. Hollingshead, G.H. Perdew The aryl hydrocarbon receptor complex and the control of gene expression. Critical Reviews in Eukaryotic Gene Expression. 18(3): Bertazzi, P.A., I. Bernucci, G. Brambilla, D. Consonni, A.C. Pesatori The Seveso studies on early and long-term effects of dioxin exposure: A Review. Environmental Health Perspectives. 106(2): Bradshaw, T. D., D. R. Bell Relevance of the aryl hydrocarbon receptor (AhR) for clinical toxicology. Clinical Toxicology. 47: Chopra, M., D. Schrenk Dioxin toxicity, aryl hydrocarbon receptor signaling, and apoptosis-Persistant pollutants affect programmed cell death. Critical Reviews in Toxicology. 4(4): “Dioxins.” World Health Organization. Accessed Field, J. A., R. Sierra-Alvarez Microbial degradation of chlorinated dioxins. Chemosphere. 71: Furness S. G.B., F. Whelan The pleiotropy of dioxin toxicity-Xenobiotic misappropriation of the aryl hydrocarbon receptor's alternative physiological roles. Pharmacology & Therapeutics.124: Hatfield Consultants Summary of dioxin contamination at the Bien Hoa, Phu Cat and Da Nang Airbases, Viet Nam. Meeting of the US-Vietnam Dialogue Group On Agent Orange/Dioxin. Kulkarni, P. S, J. G. Crespo, C. A.M. Afonso Dioxins sources and current remediation technologies-A review." Environmental International. 34: Linden, J., S. Lensu, J. Tuomisto, R. Pohjanvirta Dioxins, the aryl hydrocarbon receptor and the central regulation of energy balance. Frontiers in Neuroendocrinology. 31: Marinkovic, N., D. Pasalic, G. Ferencak, B. Grskovic, A. Stavljenicrukavina Dioxins and Human Toxicity. Arh Hig Rada Toksikol. 6: Martin, M.F Vietnamese Victims of Agent Orange and U.S.-Vietnam Relations. Congressional Research Service Report for Congress. Schecter, A., L.C. Dai, L.T. Thuy, H.T. Quynh, D.Q. Minh, H.D. Cau, P.H. Phiet, N.T. Nguyen, J.D. Constable, R. Baughman Agent Orange and the Vietnamese: the persistence of elevated dioxin levels in human tissues. American Journal of Public Health. 85(4): Stellman, J.M., S.D. Stellman, R.Christian. T. Weber, C.Tomasallo The extent and patterns of usage of Agent Orange and other herbicides in Vietnam. Nature. 422: Schector, A., L. Birnbaum, J.J. Ryan, J.D. Constable Dioxins: An overview. Environmental Research. 101: Quy, Vo Statement of Vo Quy, Former Director, Centre for Natural Resources and Environmental Studies, Viet Nam National University, for United States House Committee hearing on Agent Orange. 26th International Symposium on Halogenated Persistent Organic Pollutants. Dwernychuk, L.W., T.M. Hung, T.G. Boivin, G.S. Bruce, P.T. Dung, L.K. Son, C.T. Hatfield, N.T. Dung, J.A. Allan, D.D. Nhu, P.V. Thuc, D.J. Moats, L.I. Borton The Agent Orange Dioxin Issue In Viet Nam: A Manageable Problem.


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