Dioxin in Viet Nam 40 Years after the American War€¦ · Dioxin analysis Congener pattern is characteristic of source.(Agent Orange has mostly TCDD.) Method must be extremely sensitive;

Dioxin in Viet Nam 40 Years

after the American War

Daniel Robie, Department of Chemistry, York College, CUNY

Jean Grassman, Health & Nutrition Sciences/CUNY School of Public Health

April 10, 2014

Dioxin

What is dioxin?

Why should we care about it?

◦ From exposure to health effects

Seeking chemical justice for Vietnam

Dioxins are a class of compounds

with two aromatic rings.

Properties of TCDD

Molar mass 322 g/mol

Melting point 305C

Boiling point Decomposes

Saturated vapor pressure ~1 ntorr

Water solubility 20 ng/L

Octanol-water partition ratio 107

2 + 2HCl

How TCDD is made

Pentachlorophenol is a fungicide for wood. Since 1872 it has been known that it dimerizes with loss of HCl to OCDD.

2,4,5-trichlorophenol dimerizes with loss of HCl to TCDD, as shown in 1957.

2,4,5-trichlorophenol 2,3,7,8-tetrachlorodibenzo-p-dioxin

(TCDD)

How TCDD is made

• Minor product in manufacture of

2,4,5-trichlorophenoxyacetic acid (2,4,5-T).

• Originally 60 ppm, then reduced to .005 ppm

through temperature control.

2,4,5-trichlorophenoxyacetic acid

(2,4,5-T)

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

(TCDD)

Small amounts of dibenzodioxins and

dibenzofurans are generated in nearly

all low-temperature combustion

systems that have C, H, O, and Cl. (E.g.,

polyvinyl chloride combustion.) It’s

ubiquitous.

In the dark, it’s not very reactive. • At water surface, 1/2 = 21 hr in summer

• Underground, 1/2 = 12 yr

• No bacterial degradation.

Dioxin analysis

Congener pattern is characteristic of source. (Agent Orange has mostly TCDD.)

Method must be extremely sensitive; therefore easy to overwhelm; limit of detection must be ~1 fg/g (.001 parts per trillion). Maximum contaminant level in dirt from EPA is .03 ppt. Human blood TCDD is usually <10 ppt.

Depends on matrix: blood, tissue, water, soil, dust, herbicide

GC separation followed by isotope dilution MS with 13C12

Mass spectrum of TCDD from Agilent 6890/5973

50 pg/g = 50 ppt

Famous cases

Agent Orange in Vietnam, 1961-71

Seveso, Italy in 1976: explosion in ICMESA

plant

Vienna, Austria poisonings in 1997

Yushchenko poisoning in Ukraine, 2004

Dioxin

What is it?

Why should we care about dioxin? ◦ Environmental contamination: US/Vietnam

◦ Exposure

◦ Health effects

Seeking chemical justice in Vietnam

municipal solid waste incineration

backyard barrel burning

medical waste incineration

secondary copper smelting

Dioxin releases have declined

USA: Sources of dioxins

Vietnam-Volume of herbicide used

(1961-1971)

Units are liter/grid (~1.2 km2)

Agent Orange Agent White Agent Blue

Stellman et al., 2003

~~77 million liters (20 million gallons) of herbicides, including 49.3 million

liters (13 million gallons) of Agent Orange

http://ehp.niehs.nih.gov/docs/1998/106-2/focus.html

Global circulation of POPs

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DDT_chain.gif

Biomagnification

Dioxin exposure pathway for humans: Most exposure comes from dietary animal fats

jan.ucc.nau.edu/

Global distribution Formation/release Biomagnification Consumption

The good news/bad news about dioxin metabolism in humans

The bad news is humans have limited capacity for

metabolism: TCDD ½=7-10 years

The good news is because of the long half life, it is

possible to detect long term accumulation of dose:

Measure TCDD/dioxins in blood lipids.

Patterson et al., 2005

USA: Dioxin body burdens as Total TEQ:

Age specific 90th percentiles

Age range (years) Dioxin TEQ (ppt)

15-29 14

30-44 21

45-59 30

>60 73

TCDD ppt Lipid adjusted

Bien Hoa

n=43

North

n=5

<10 7 (16%) 5 (100%)

10 to <50 10 (23%)

50 to <100 11 (26%)

100 to <200 10 (23%)

>200 to 413 5 (12%)

Vietnam: Serum TCDD levels in adults as

measured in 1999-2001

Schecter et al., 2002 JOEM 44: 218-220

Compare with age specific 90th percentile of 70 ppt

amongst US residents > 60 years old

Dioxin Reassessment USEPA http://cfpub.epa.gov/ncea/CFM/nceaQFind.cfm?keyword=Dioxin

Adults

1-3 pg/kg-day

Breast-fed infants

~70 pg/kg-day

USA: Estimated intake of TCDD

EPA TCDD Reference Dose

0.7 pg/kg-day!

0.7 pg/kg-day!

Adults

1-3 pg/kg-day

Breast-fed infants

~70 pg/kg-day

EPA TCDD Reference Dose

Schecter et al., Dioxin 2008 An update on Agent Orange: Vietnamese and US Collaboration

TCDD in breast milk

1970 location n TCDD ppt

Dong Nai Village 1 1,832

Dong Nai Village 1 1,465

Can Gio Village 1 732

Sai Gon Village 1 257

Boston, MA, USA 1 BDL (29 ppt)

1980s

USA NY & LA 42 x = 3.3

Hanoi 28 x = 2.2

Ho Chi Minh City 38 x = 7.1

• Developed countries: 10-35 pg/g milk fat

• Developing countries: <10 pg/g milk fat

TCDD

adapted from http://dir.niehs.nih.gov/dirlcbra/mechanism.gif

TCDD alters transcription

Epidemiology provides evidence that TCDD

is a carcinogen

Ranch Hand update by Michalek and Pavuk (2008)

• Diabetes and cancer: Based on stratification by years of spraying and time spent in Southeast Asia

New Zealand Vietnam vets cohort follow-up 1988-2008 by McBride, et al. (2013)

• Significantly increased incidence of chronic lymphocytic leukemia

• Non-significantly increased incidence of all cancer, prostate cancer, lung cancer, multiple myeloma, Hodgkin Disease, etc.

Boehringer-Ingelheim cohort follow-up through 2007 by Manuwald, et al. (2012) • 1,589 workers, with TCDD measurements

• Increased all-cause and all-cancer (SMR=1.37; 95% CI 1.21-1.56) mortality

• Increased respiratory, esophageal and other cancer deaths in males

• Increased breast cancer (SMR=1.86; 95% CI 1.12-2.91) in female workers

• Significant trend with increasing TCDD levels

Adapted from Richard Clapp, 2013

Seveso twenty-year cancer incidence update by Pesatori, et al.

(2009)

• Excess lymphatic and hematopoietic cancer in Zones A and B

• Excess breast cancer in Zone A (RR=1.43; 95% CI 0.71-2.87)

Seveso Women’s Health Study second follow-up by Warner, et al.

(2011)

• All cancer HR was 1.80 (95% CI 1.29-2.52) for each 10-fold increase in

serum TCDD

• Breast cancer HR was 1.44 (95% CI 0.89-2.33)


Epidemiology provides evidence that TCDD

is a carcinogen

What is known about the

developmental effects with--- 1) Maternal exposure in animal models--

• Biochemical, immunological, and endocrine abnormalities

2) Prenatal and/or breast milk exposure due to maternal environmental

exposure

• alterations in play behavior in Japan (Nakajima et al., 2006)

• delayed breast development in Belgium (Leijs et al., 2008)

• significant decline in growth measures over 3 years with increasing TEQ

in Chapaevsk, Russia boys (Burns, et al. 2009, 2011)

3) Maternal exposure to an accidental release in Seveso, Italy

• persistent alteration in thyroid function (Baccarelli et al., 2008)

4) Exposure during adolescence in Seveso, Italy

• Alterations in sperm count and motility upon maturation (Mocarelli et al., 2008)

5) Vietnam-Perinatal/paternal/maternal exposure after exposure to Agent Orange

• congenital abnormalities (during the war) (Phuong et al., 1989)

• altered growth and neurodevelopment with contemporary exposure

(Nishijo et al., 2012)

Evidence of developmental effects

6) Transgenerational impact of dioxins (Manikkam et al., 2012)

• changes to germ line inherited in absence of direct exposure

• Differential epimutations in 50 promoter regions

Evidence of developmental effects 5) Transgenerational impact of dioxins (Manikkam et al., 2012)

• changes to germ line inherited in absence of direct exposure

• differential epimutations in 50 promoter regions

Dioxin

What is it?

Why should we care about it?

◦ Health effects

◦ Widespread environmental contaminant

◦ Intentional use in Vietnam

◦ Exposure

Seeking chemical justice in Vietnam

Public Health/Science Committee

Vietnam Agent Orange Relief & Responsibility Campaign

Dr. Michael McGarvey

Ms. Marie Elivert

Dr. Franklin Mirer

Dr. Carole Baraldi

Ms. Susan Schnall

Dr. Daniel Robie

Dr. Jean Grassman

With Dr. Tran Ngoc Tam

Thai Binh

Hue A Luoi Danang

Ho Chi Minh City

Hanoi

Exposure scenarios that may result

in health effects from Agent Orange

1) Exposure during the conflict due to aerial spraying

2) Contemporary exposures from residual and ongoing contamination

3) Contemporary manifestation of exposure sustained during the war due

to transgenerational effects of dioxins

Questions that emerged:

1) Contemporary exposure: Is the populace exposed to dioxins

due to sites that remain contaminated?

2) Health impact of past exposure: Has the health of the populace

been affected by the historical spraying of Agent Orange?




Observation of contaminated sites



Danang

Reference

A Luoi–site of former airbase

A Luoi today






Investigated evidence of chronic illness & developmental effects

Visits to the homes of affected veterans….

And affected children….

Peace Village in

Ho Chi Minh City

Children’s home in Danang

Friendship Village in Danang

Discussions with medical and public

health practitioners

Dr. Phuong

Remediation of contaminated sites

$77 million appropriated for remediation and health care up to 2012, mostly since 2007.

U.S. agreement with Viet Nam 12/30/09 for remediation at Da Nang

Vietnamese target of 150 ppt, between the USEPA’s preliminary remediation goals of 50 ppt for residential areas and 664 ppt for industrial areas

Dioxin mass to be removed between 150 and 0.1 kg.

In Pile Thermal Desorption

(IPTD®) 77000 m3 of dirt moved, heated under

vacuum; will remove between 0.1 and 150 kg dioxins

Must remove water to get to 335C

Capture of vapor on activated carbon and porous polymer. Effluent into the air.

We saw some evidence of preliminary work in June 2012.

Construction and dirt accumulation completed. Heating begins April 2014.

Project to complete by December 2016.

H.R. 2519

Victims of Agent Orange Relief Act of 2013

Introduced to the U.S. House of Representatives on June 26, 2013 by Congresswoman Barbara Lee for herself and 7 others.

This act will:

◦ Provide medical assistance and disability benefits to affected children of American Vietnam veterans

◦ Provide health care and social services for affected Vietnamese

◦ Provide health care for affected Vietnamese Americans and their offspring, and

◦ Clean up the lands and restore the ecosystems contaminated by dioxins in Vietnam

Veterans and Agent Orange:

Update 2010

Limited or Suggestive Evidence of an Association

Laryngeal cancer

Cancer of the lung, bronchus, or trachea

Prostate cancer

Multiple myeloma

AL amyloidosis

Early-onset peripheral neuropathy

Parkinson disease

Porphyria cutanea tarda

Hypertension

Ischemic heart disease

Type 2 diabetes (mellitus)

Spina bifida in offspring of exposed people

Veterans and Agent Orange:

Update 2010 Eighth biennial review since 1994, published by National

Academies Press (2011)

Confirmed “Sufficient Evidence of an Association” for soft tissue sarcoma, non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma and chloracne

Confirmed “Limited or Suggestive Evidence of an Association” for several other cancers, early-onset peripheral neuropathy, Parkinson disease, diabetes, spina bifida in offspring, and other diseases (see www.books.nap.edu)


Conclusions • The health impact of dioxins is well-documented; possibility of

transgenerational effects.

• Everyone is exposed, but some are exposed more than others.

• Long half life enables assessment for years after the release of dioxins.

• Some areas of Vietnam are still contaminated with dioxins. • Desirable contaminated sites (Danang airbase, Bien Hoa) will be remediated while other

sites (A Luoi) have received relatively little attention

• We observed children with severe congenital anomalies.

• Variety of anomalies; cannot comment on causation

• Hazard exists and the population merits further support and monitoring

for the impact of Agent Orange/dioxin. • Little is known about paternal exposure and possible transgenerational effects.

References

Collins, et al. AJE, 2009

Baccarelli, et al., PLOS, 2008

Burns, et al., EHP, 2009 and 2011

Pesatori, et al., Env Health, 2009

McBride, et al., OEM, 2013

Michalek and Pavuk, JOEM, 2008

Warner, et al., EHP, 2011

Manuwald, et al., OEM, 2012

Mocarelli, et al., EHP, 2008

National Academies Press, 2011


References Baccarelli A, Giacomini SM, Corbetta C, Landi MT, Bonzini M, Consonni D, Grillo P, Patterson DG, Pesatori AC,

Bertazzi PA (2008) Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin. PLoS Med 5(7):

e161

Hatfield Consultants and Office of the National Steering Committee 33 (2009), Comprehensive Assessment of Dioxin

Contamination in Da Nang Airport, Viet Nam,

Leijs MM, Koppe JG, Olie K, van Aalderen WM, Voogt Pd, Vulsma T, Westra M, Tusscher GW (2008) Delayed initiation

of breast development in girls with higher prenatal dioxin exposure; a longitudinal cohort study. Chemosphere

73(6):999-1004.

Nakajima S, Saijo Y, Kato S, Sasaki S, Uno A, Kanagami N, Hirakawa H, Hori T, Tobiishi K, Todaka T, Nakamura Y,

Yanagiya S, Sengoku Y, Lida T, Sata F, Kishi R (2006) Effects of prenatal exposure to polychlorinated biphenyls and

dioxins on mental and motor development in Japanese children at 6 months of age. Environ Health Persp 114: 773-

778. Doi 10.1289/ehp8614

Nishijo M, Tai PT, Nakagawa H, Maruzeni S, Anh NT, Luong HV, Anh TH, Honda R, Morikawa Y, Kido T, Nishijo H

(2012) Impact of perinatal dioxin exposure on infant growth: a cross-sectional and

longitudinal studies in dioxin-contaminated areas in Vietnam. PLoS One 7(7):e40273.

Phuong NTG, Thuy TT, Phuong PK (1989) An estimate of reproductive abnormalities in women inhabiting herbicide

sprayed and non-herbicide sprayed areas in the south of Vietnam, 1952-1982. Chemosphere 18 (1-6) 843-846

Stellman JM, Stellman SD, Christian R, Weber T, Tomasallo C (2003) The extent and patterns of usage of Agent

Orange and other herbicides in Vietnam. Nature 422: 681-687

.

Documents

Dioxin in Viet Nam 40 Years after the American War€¦ · Dioxin analysis Congener pattern is characteristic of source.(Agent Orange has mostly TCDD.) Method must be extremely sensitive;