Dioxins and Related Persistent Organic Pollutants (POPs)

Arnold Schecter, MD, MPH

Professor, Division of Environmental and Occupational Health Sciences, University of Texas School of Public Health, Dallas, TX, USA

Vietnam July 26-30,2010

Email: arnold.schecter@utsouthwestern.edu

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Dibenzo-p-dioxins

2,3,7,8-tetrachlorodibenzo-p-dioxin

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Introduction• Dioxins are in all humans.• Elevated dioxins can persist in people 35+ years.• Patterns of dioxins varies by source:

– Paper and pulp bleaching: TCDF and TCDD.– Agent Orange: 2,3,7,8-TCDD.– Pentachlorophenol: 5-8 Cl PCDD/PCDF.– Incineration: All congeners, especially OCDD.– PCB transformer fires: PCDFs predominate.

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Introduction (cont.)• Toxicity of dioxins understood by:

– Toxicology – in vivo animal studies. – Toxicology – in vitro mechanistic studies.– Human epidemiology

• “Safe” exposure level:– US EPA: 0.01 pg TEQ/kg BW per day x 70 yrs.– World Health Organization: 1 - 4 pg/kg BW per day

x 70 yrs.

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Major incidents 1. Agent Orange in Vietnam: TCDD, 1962 - 19712. Times Beach, USA: TCDD, 1970-19723. Binghamton, USA: Transformer fire. PCB, PCDF/D 19814. Seveso, Italy, TCDD: 19765. Yusho rice oil poisoning, Japan: PCB, PCDF, 1968 6. Yucheng rice oil poisoning, Taiwan: PCB, PCDF, 1976.7. Belgium “dioxin” food poisoning: PCB/PCDF. 1990s.

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Diagnosis

• Potential Environmental Exposure

• Certain signs and symptoms (e.g., skin rash)

• Blood Dioxin Measurements(By gas chromatography-mass spectroscopy)

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Known Dioxin Sources

• Incineration(e.g., Household Garbage; Toxic Waste; Hospitals)

• Herbicides(e.g., Phenoxyherbicides)

• Pesticides(e.g., Chlorinated Phenols)

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Known Dioxin Sources (cont.)

• Smelters(e.g., Aluminum and Copper)

• Paper and Pulp Bleaching with Chlorine

• Reservoir Sources (e.g., Sediment; Soil)

• Cement kilns

• Other

Agent Orange

• Agent Orange: Sprayed in Vietnam 1962-1971

– Spraying stopped due to science but mostly public outcry

• Agent Orange was half 2,4-D and half 2,4,5-T

• 2,4,5-T phenoxyherbicide contaminated with 2,3,7,8-TCDD (the most toxic dioxin)

• Spraying was in parts of southern Vietnam only

Ranch Hand Herbicide Spraying MissionsRed Area Indicates Sprayed Areas

Barrels of Agent Orange

History of Dioxin Exposure Determination

• The Beginning: Harvard University• Research in the 1970’s:

– Baughman, Meselson, Constable– Most toxic dioxin found in very high levels in:– Vietnamese nursing mothers’ milk (1345, now 1.0

parts per trillion, lipid)– Vietnamese fish from sprayed area – Not detected in US nursing mothers’ milk – US fish were not studied

Vietnam/US Agent Orange History

• 1983-92: Agent Orange Conferences (Vietnam)

• 1984-2010: J. Constable & A. Schecter with the 10-80 Committee, Vietnam Red Cross and Committee 33

Worldwide Research

• Dioxin can cause:

– Cancer

– Immune deficiency

– Nervous system problems

– Reproductive problems

– Developmental problems

Worldwide Research (Continued)

– Endocrine system damage

– Skin pathology (including chloracne)

– Liver damage

– Elevated blood lipids

– Heart attacks

– Others

Vietnam and U.S. Human Milk Dioxin (TCDD) Levels- 1970-80’s

Location n Year Level

(ppt, lipid)

Dong Nai River Village1 1 1970’s 1,832

Dong Nai River Village1 1 1970’s 1,465

Can Gio Village1 1 1970’s 732

Sai Gon River Village1 1 1970’s 257

Boston, MA, USA1 1 1970’s ND (LD = 29)

Binghamton, NY, and Los Angeles, CA, USA2 42 (mean) 1980's 3.3

Hanoi2 28 (mean) 1980's 2.2

Ho Chi Minh City2 38 (mean) 1980's 7.1

Northern Vietnam3 36 (mean) 1980’s-90’s 1.9

Southern Vietnam3 90 (mean) 1980’s-90’s 7.5

1Baughman RW. Tetracholodibenzo-p-dioxins in the environment: high resolution mass spectrometry at the pictogram level. Cambridge, MA: Harvard University; 1974. PhD thesis.2Olie K, Schecter A, Constable JD, Kooke RMM, Serné P, Slot PC, deVries P. Chemosphere. 1989; 19(1-6): 493-496.3 Schecter A, Dai LC, Thuy LTB, Quynh HT, Minh DQ, Cau HD, Phiet PH, Phuong NTN, Constable JD, Baughman R, Päpke O, Ryan JJ, Fürst P, Räisänen S. American Journal of Public Health. 1995;85(4):516-522.

2,3,7,8 TCDD levels in Vietnamese fish, crustaceans, and U.S. imported

Vietnamese food

Food Year

Collected Location Collected

TCDD Level, ppt total wet body weight

Prawn1 1970 Can Gio Village

(seacoast) 14

Catfish1 1970 Dong Nai River

(interior) 1020

Supermarket Samples2

1990's Dallas, TX <0.1

Supermarket Samples2

1990's California <0.1

1Baughman RW, Meselson M. Environ Health Perspect. 1973;5:27-35.2Schecter A, Pavuk M, Malisch R, Ryan JJ. Journal of Toxicology and Env. Health. 2003;66(15), 1391-404

2,3,7,8 TCDD and Dioxin Toxic Equivalents (TEQ) (lipid, ppt) in Vietnamese Pooled Blood

Collected 1991-92

Region n Range of TCDD Range of TEQ

Northern Vietnam 168 1 - 3 12 - 18

Central Vietnam 490 3 - 19 23 - 118

Southern Vietnam 2062 1 - 33 9 - 105

Schecter A, Dai LC, Thuy LTB, Quynh HT, Minh DQ, Cau HD, Phiet PH, Phuong NTN, Constable JD,Baughman R, Päpke O, Ryan JJ, Fürst P, Räisänen S. American Journal of Public Health. 1995;85(4):516-522.

TCDD and TEQ in Food From Bien Hoa, 2003 ( ppt ww )

Samples TCDD Total TEQTCDD % of

TEQ

Fish* 65 66 99%

Duck 331 343 97%

Pork 0.025 0.6 4.2%

Chicken 0.031 0.83 3.7%

*Channa Striatta (snakehead)

Schecter AJ et al. J Occup Environ Med. 2003; 45:781-788

Recent TCDD TEQ from Bien Hoa City and Aluoi Valley ‘hot spots’ (ppt)

1. Dwernychuk L, et al. Chemosphere 2002. 47:117-137.2 Schecter A et al. J Occup Environ Med. 2003; 45:781-788.

*EU Maximum Level 4 ppt (lipid) ** EU Max Level 8 ppt (ww) *** EU Max Level 1.5 ppt (lipid)

Aluoi Valley1 Samples Based on Bien Hoa2

85 Duck Lipid 550*

50 Lipid 15,349

N/A Wet Weight 66**

5 Pork Lipid 2.1***

46 Human blood Lipid 413

901 Soil Dry wt. 1,100,000

Fish

Recent Dioxin concentrations (>90% TEQ 2,3,7,8-TCDD) in soil and lake sediment at

three airport “dioxin hotspots”

Location n Range (I-TEQ,pg/g dry wt.)

Estimation for dioxin-cleanup area

Da Nang 63 4.3 - 200,338 ~104,000m2 Bien Hoa 54 nd - 409,818 ~30,000m2 Phu Cat 12 0.1-49,462 >2,000m2

1. Son LK, Sau TK, Lanh DN, Net NX, Truong NX, Minh NV, Tam TN. Organohalogen Compounds. 2007; 69:881-883.2. Hoai, DX, Tam, TN 2009 Organohalogen Compounds 71, 85-87

Da Nang Airbase1 (2009)• High TCDD levels in localized areas:

– Soil up to 365,000 ppt TEQ– Sediment up to 6,270 ppt TEQ– Fish up to 3,000– Vegetables up to 2,174

• However, newest data is not public.

1. Le Thi Haoi 2009 Organohalogen Compounds. Dioxin 2009

Remediation Da Nang Airbase (2008)

• $ Ford Foundation + USEPA + US Congress• Progress:

– Construction of integrated facilities:• Preventing infiltration and land erosion• Monitoring• Special filtration systems• New reservoir and overflow dam• Warnings and bans in contaminated areas

Canh, P.N. Organohalogen Compounds, Volume 70, 2008, 547-549.

Bien Hoa City Residents (2008)

• Knowledge of dioxins is limited• Unaware of routes of exposure• Little concern for health impacts of dioxins• Few are taking preventive measures• 65.5 % of people surveyed did not care or did

not know the sources of foods that they consumed daily.

Le Vu Anh et al. Organohalogen Compounds Volume 70, 2008, 535-538.

Pesticides, PCDFs, and PCBs in Vietnam: Milk and Food (ppt ww)

• α-HCH (α-hexachlorocyclohexane)• β-HCH (β-hexachlorocyclohexane)• γ-HCH (γ-hexachlorocyclohexane or lindane)• Hexachlorobenzene • DDT• DDT metabolites• PCBs• DibenzofuransSchecter AJ et al. J Occup Environ Med. 2003; 45:781-788.

Shelepchikov, AA et al. Organohalogen Compounds 2009; 71, 538-543

Long Term Remediation Technologies for Dioxin Contamination

Technology Status

Offsite Thermal Proven Effective, Very Expensive

Onsite Thermal Effective, Less Expensive

Solidification/Stabilization Proven, Less expensive

Physical/Chemical Piloted with some success

Bioremediation Unproven with pilots underway

Move to Toxic Waste Site Effective, Inexpensive

Containment Effective, Least expensive

After Fong VS, Coakley W, Farland W, Tien NQ, Ha DTC, L PH, Minh DV, Portier C, Brown D, Ball G, Killeen D, Sweeney MH, Son LK, Duong NN. Organohalogen Compounds. 2007; 69:898-901.

Seveso TCDD Site at Present

http://www.legambienteseveso.org/html/circolo/Foto/sito.jpg

Current Vietnam/US Collaboration – Da Nang

• Vietnam Ministry of National Defense, and Office of National Steering Committee 33, Hatfield Group, Ford Foundation

• Assess environmental contamination and effectiveness of current mitigation efforts

• Measure bio-accumulation of dioxin in the food chain and in people

• Enhance awareness, government management, scientific exchange

University of Texas Agent Orange and TCDD Research

• US Vietnam Veterans, Agent Orange Sprayer Ranch Hands– TCDD alters human thyroid axis1

– TCDD associated with prostate and skin cancers2

– TCDD associated with lower incidence rates of benign prostate hyperplasia (BPH)

– TCDD found in semen could suggest a possible mechanism for male-mediated adverse reproductive3

1 Pavuk M, Schecter AJ, Akhtar FZ, Michalek JE. Ann Epidemiol. 2003 May;13(5):335-43; 2Pavuk M, Michalek JE, Schecter A, Ketchum NS, Akhtar FZ, Fox KA. J Occup Environ Med. 2005 Apr;47(4):335-42; 3Schecter A, McCee H, Stanley J, Boggess K, Brandt-Rauf P. AJIM. 1996 (30):647-654.

Other US TCDD Research Findings

• WHO IARC: TCDD is a human carcinogen1

• WHO IARC: TCDD associated with multiple human pathologies1

• National Toxicology Program: TCDD is a human carcinogen2

• US EPA: Dioxin is a human carcinogen3

• US EPA: Dioxin causes multiple human effects3

1WHO IARC Monograph 69, PCDD/F, 1997 ; 2NTP. 9th Report of Carcinogens. 2000, Rev. 2001; 3US EPA Draft Dioxin Reassessment. http://www.epa.gov/ncea/pdfs/dioxin/nas-review/

Sufficient Evidence of Association

A. Soft-tissue sarcoma (including heart)

B. Non-Hodgkin’s lymphoma

C. Chronic lymphocytic Leukemia (CLL) (including B cell leukemias, such as hairy cell leukemia)

D. Hodgkin’s Disease

E. Chloracne

(US) “Veterans and Agent Orange, Update 2009”

Institute of Medicine (IOM) US National Academy of Sciences (NAS)

Veterans and Agent Orange Update 2009, IOM/NAS (Continued)

Limited Evidence of Association

A. Laryngeal cancerB. Cancer of the lung, bronchus or tracheaC. Prostate cancerD. Multiple myelomaE. Light Chain (AL) amyloidosisF. Early-onset transient peripheral neuropathy

Veterans and Agent Orange Update 2009, IOM/NAS (Continued)

Limited Evidence of Association

G. Parkinson’s disease H. Porphyria cutanea tardaI. HypertensionJ. Ischemic heart diseaseK. Type 2 diabetes (mellitus)L. Spina bifida in offpsring of exposed people

Current Vietnam Activities (?)• Remediation- planning and implementation• Assistance to “Agent Orange Victims”• Education of the public, exposed and others• Agent Orange health research• Agent Orange remediation research• Agent Orange environmental research• Scientific publications and presentations• Government to Government cooperation