1. Columbia University Superfund Research Program
9/15/2018
Emerging Issues:
Arsenic Exposure
Joseph H. Graziano, Ph.D.
Program Director
Columbia University Superfund Research Program 1

2. Arsenic Presents a Major Public Health Problem
Known carcinogen
Lung, liver, skin, bladder, kidney, and more
Early life exposure → increased risk as adults
Multiple potential health effects on essentially every bodily system
Skin
Respiratory system
Cardiovascular system
Endocrine system (e.g., diabetes)
Immune system
Nervous system
And more…
Arsenic rated #1 on the ATSDR 2011 Substance Priority List as the top chemical of concern as a public health hazard 2

3. History of SRP Arsenic Research
SRP has been committed to arsenic research since the inception of SRP in 1987
SRP takes a “soup-to-nuts” approach to arsenic research and development
Detection systems
Remediation
Identifying and reducing exposures
Health effects
Training and education of scientists and community partners
Community and government engagement
Transdisciplinary partnerships to solve problems in communities 3

4. History of SRP Arsenic Research
9/15/2018
History of SRP Arsenic Research
Started funding arsenic research from SRP’s inception in 1987
Currently funding numerous arsenic-related projects at 19 university SRP research centers
SRP researchers have published over 150 arsenic- related scientific papers since 2006 4

5. SRP Activities to Address Arsenic Challenges
9/15/2018
SRP Activities to Address Arsenic Challenges
Identifying sources of contamination
Characterizing toxic arsenic species and biomarkers of exposure in humans
Identifying arsenic-related health effects and mechanisms of toxicity
Exploring ways to mitigate health effects
Engaging communities, government, and stakeholders as partners in solving real-life problems related to arsenic
Training scientists in arsenic research 5

6. Variable Toxicity of Arsenic Metabolites LD50 (Toxicity)
9/15/2018
Variable Toxicity of Arsenic Metabolites LD (Toxicity)
Inorganic Arsenic
As+3 Arsenite mg/kg
As+5 Arsenate mg/kg
Mammalian Metabolites
MMA+3 Monomethylarsonous Acid 2 mg/kg
MMA+5 Monomethylarsonic Acid mg/kg
DMA+5 Dimethylarsinic Acid mg/kg
Fish Metabolites
AsB Arsenobetaine ~10,000 mg/kg
AsC Arsenocholine
LD50 (Toxicity) 6

7. What We Have Learned: Arsenic Exposure
Naturally occurring element in Earth’s crust
Industrial sources (e.g., former smelters)
Some types of chemically treated wood
Some homeopathic remedies
Drinking water
Diet (e.g., rice)
Soil and dust 7

8. Arsenic in Groundwater: An International Problem
Taiwan
China
Chile
Argentina
Mexico
United States
India
Bangladesh
Nepal
Vietnam
Cambodia
Mongolia
U.S. EPA Maximum Contaminant Level for arsenic: 10 µg/L.
Concentrations reported in some regions of many of these countries reached over 3,000 µg/L. 8

9. Arsenic in Groundwater in the U.S.9

10. Global and U.S. Activities Funded by NIEHS SRP
9/15/2018
Global and U.S. Activities Funded by NIEHS SRP
Large cohort studies
Bangladesh
Chile
Global/U.S. studies of exposures and health effects
Identify and reduce exposures
Identify health effects
Identify mechanisms of toxicity
Explore approaches to mitigating toxicity
Taking action at the local level
Outreach to encourage private well testing
Helping provide safe water sources 10

11. SRP-funded Cohort Studies
Health Effects and Longitudinal Study (HEALS) in Bangladesh
• Population exposed via tube wells
• Revealing information about exposure, health effects, susceptibilities, and nutritional factors
Chilean Cohort
• Population exposed for a defined period of time
• Population followed for >50 years
• Revealing information about health effects and latency 11

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13. HEALS Cohort Recruitment and Follow-up
Baseline
HEALS Cohort Recruitment and Follow-up
Follow-up 1
7/2000-5/2002
Follow-up 3
HEALS Original Cohort
~12,000 adults
Follow-up 2
HEALS Expanded Cohort
~8,000 adults
~20,000 adults:
HEALS original and
Expanded cohort
113 deaths
120 deaths
174 deaths
A validated verbal autopsy was used to classify deaths using WHO’s ICD-10
9/ /2004
12/ /2006
6/2007-1/2009
4/2010-
6/2006-8/2008
11/ /2009 13

14. All-cause and Chronic Disease Mortality
Table 2. Hazard ratio for mortality of HEALS participants in relation to baseline arsenic exposure, Bangladesh
 Arsenic exposure
No. of deaths
All-cause
mortality*
Chronic disease mortality* HR
95% CI
Well water arsenic (μg/L)
0.1–10 74
1.00
Referent 58
10.1–50 90
1.34
0.99, 1.82 69
1.33
0.94, 1.87
50.1–150 98
1.09
0.81, 1.47 83
1.22
0.87, 1.70
150.1–854
131
1.68
1.26, 2.23
101
1.21, 2.33
P for trend
0.003
0.005
Daily arsenic dose (μg/day)
0.041–35.0 87 66
35.1–163.0 97
1.10
0.83, 1.47 80
1.21
0.88, 1.67
163.1–401.0 91
0.81, 1.46 76
0.88, 1.71
401.1–4898.0
118
1.54
1.17, 2.04 89
1.58
1.15, 2.18
0.004
0.007
Urinary total arsenic (μg/g Cr)
7.0–105.0 64
105.1–199.0 96
1.07
0.80, 1.43
1.17
0.84, 1.62
199.1–352.0
100
0.91, 1.63
1.37
0.98, 1.90
352.1–5000.0
105
1.45
1.09, 1.94 77
1.47
1.05, 2.06
0.008
0.01
HR=hazard ratio; CI=confidence interval; Cr=creatinine.
* Multivariate estimates adjusted for age, sex, body mass index, systolic blood pressure, education, and smoking status.
All-cause and Chronic Disease Mortality
Argos et al Lancet 376: 252 14

15. Early Life Exposure Can Have Effects into Adulthood
Increased infant mortality
Reduced birthweight
Increased infections during infancy and childhood
Neurological and motor impairments in children
Increased cancer risks as children (liver cancer)
Increased cancer risks as adults (lung, bladder, and kidney cancer)
Vahter 2008.
Basic Clin Pharmacol Toxicol 102(2):204. 15

16. Early Life Exposure Can Have Life-long Effects
Environ Health Perspect 114:1293–1296 (2006). doi: /ehp.8832 available via ttp://dx.doi.org/ 16

17. SRP: Making a Difference in the Community
Columbia University SRP in Bangladesh
Installation of >150 deep community wells that provide low-arsenic water to thousands of residents
Providing primary medical care to the >20,000 HEALS participants 17

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20. Inter-School Art Contest School-Based Educational Intervention in Araihazar, Bangladesh20

21. SRP: Making a Difference in the Community
Columbia University SRP in Maine
Established a Community Engagement Core
Disseminating knowledge about the hazards of local well water arsenic contamination
Disseminating technologies to filter arsenic 21

22. Community Engagement in Maine
Arsenic concentrations in 1,428 domestic wells from 17 towns central Maine
31% of the wells contain >10 ug/L arsenic (source: Yang 2010).
Columbia Community Engagement Core aims to double the testing and treatment rate for arsenic in these towns. A survey is underway to determine the current rates. 22

23. Assessment of Exposures to High Concentrations of Arsenic in Well Water in Maine
[As] >10 ug/L in Maine Total Exposed = 12, yr olds = (2000 Census) 23

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25. 9/15/2018
Bill Suk, NIEHS 25