Health Effects of Inorganic Arsenic in Drinking Water Laura Beane Freeman, Ph.D. Occupational and Environmental Epidemiology Branch November 9, 2011 - PowerPoint PPT Presentation

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Health Effects of Inorganic Arsenic in Drinking Water Laura Beane Freeman, Ph.D. Occupational and Environmental Epidemiology Branch November 9, 2011

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Title: Health Effects of Inorganic Arsenic in Drinking Water Laura Beane Freeman, Ph.D. Occupational and Environmental Epidemiology Branch November 9, 2011


1
Health Effects of Inorganic Arsenic in
Drinking Water Laura Beane Freeman,
Ph.D. Occupational and Environmental
Epidemiology Branch November 9, 2011
2
Outline
  • Background
  • Cancer
  • Cardiovascular
  • Pregnancy
  • Other Health Outcomes

3
Background
4
Arsenic in Drinking Water
  • Mostly naturally occurring
  • Some man-made sources
  • Some areas of world with very high levels
  • Historically, 400-600mg/L
  • Still many with gt50 mg/L
  • Previous US Standard was 50 mg/L
  • 2001
  • U.S. EPA issued new MCL of 10 mg/L

5
Arsenic concentrations found in at least 25 of
ground-water samples within a moving 50km radius
6
Cancer
7
Background
  • 1887
  • Skin tumors noticed in patients treated with
    arsenicals
  • 1920s
  • Villages in Taiwan switched to artesian wells
    with high arsenic concentration (400-600 mg/L)
  • Reports of skin lesions

8
Cancer
  • Sufficient evidence for inorganic arsenic as
    human carcinogen
  • Lung
  • Bladder
  • Non-melanoma skin
  • National Research Council (1999 and 2001)
  • International Agency for Research on Cancer
    (1980, 2004)

9
Types of studies contributing to knowledge of
drinking water arsenic
  • Ecologic Studies
  • Apply area level arsenic estimates to individuals
  • Compare with incidence (mortality) rates in
    general population
  • Reasonable when levels are very high and confined
    to defined areas
  • Limitations No individual estimates
  • Difficult for risk assessment, dose-response
    analyses

10
Bladder Cancer Ecologic Studies
Study Location Arsenic levels SMR
Tsai, 1999 SW Taiwan Arsenic endemic Female 14.1 (12.5-15.8) Male 8.9 (8.0-10.0)
Smith, 1998 Region II, Chile 420 mg/L Female 8.3 (6.3-10.5) Male 6.0 (4.8-7.4)
Hopenhayn-Rich, 1996, 1998 Argentina 178 mg/L Female 1.8 (1.2-2.6) Male 2.1 (1.8-2.5)
Chen 1990 Taiwan National Survey from regression 4.2 (0.5) 3.9 (0.5)
Wu 1989 Taiwan gt600 mg/L Rate Female 25.6 Male 22.6
Chen, 1985 Taiwan Blackfoot endemic region Female 20 (170-23.2) Male 11.0 (9.3-12.7)
11
Lung Cancer Ecologic Studies
Study Location Arsenic levels SMR
Tsai, 1999 SW Taiwan Arsenic endemic Female 4.1 (3.8-4.5) Male 3.1 (2.9-3.3)
Smith, 1998 Region II, Chile 420 mg/L Female 3.1 (2.7-3.7) Male 3.8 (3.5-4.1)
Hopenhayn-Rich, 1996, 1998 Argentina High Female 2.2 (1.8-2.5) Male 1.8 (1.6-1.9)
Wu 1989 Taiwan gt600 mg/L Female 122.2 Male 104.1
Chen, 1985 Blackfoot endemic region Female 4.1 Male 3.2
12
Types of studies contributing to knowledge of
drinking water arsenic
  • Cohort Studies
  • Compare disease rates in two populations, one
    exposed and one not exposed
  • Different than ecologic study because make
    exposure assignment at individual level
  • Case-control studies
  • Defined by identifying a case and control group
    and determining exposures at individual level

13
The New England Bladder Cancer Study
  • Persistent excess of bladder cancer in Maine, New
    Hampshire, Vermont
  • Arsenic is one hypothesis for excess
  • 1,193 cases 1,418 controls
  • Residential histories
  • Geocoded addresses
  • Measurements at current homes
  • Linked to public water supplies
  • Private well models

14
Exposure Assessment Issues
  • Chronic, low level exposures
  • Timing of exposure and relevant time period
  • Different for different diseases
  • Cancer vs. pregnancy

15
Arsenic exposure assessment in a population-based
bladder cancer study
Nuckols, Beane Freeman et al., Environ Hlth
Perspect 2011
16
Bladder Cancer Case-control Studies
Study Location Arsenic levels OR
Meliker 2010 Michigan gt10 mg/L 1.1 (0.7-1.9)
Bates 2004 Argentina gt10 mg/L 0.8 (0.4-1.7)
Steinmaus 2003 California/Nevada 80 mg/day 1.7 (0.7-4.0)
Kurttio, 1999 Finland Average gt0.5 mg/L 2.4 (1.1-5.4)
Bates 1995 Utah Cumulative 53 mg 1.4 (0.7-2.9)
17
Bladder Cancer Cohort Studies
Study Location Arsenic levels RR (SMR)
Chen 2010 Taiwan gt300 mg/L 7.8 (2.6-23.1)
Baastrup 2008 Denmark 0.7 mg/L 1.0 (0.9-1.1)
Chiou 2001 NE Taiwan gt100 mg/L 4.8
Lewis, 1999 Utah gt5,000 ppb-yr Female 1.1 Male 0.95
Chiou 1995 NE Taiwan Average gt0.71 mg/L Cumulative gt20 mg/L x yr 3.3 (1.0-11.1) 5.1 (1.5-17.3)
Tsuda 1995 Japan gt1.0 mg/L 31.2 (8.6-91.8)
Cuzick 1992 UK Total gt500 mg 5.0 (2.0-15)
18
Lung Cancer Case-control studies
Study Location Arsenic levels RR
Ferreccio 2000 Chile 200-400 mg/L (40 year avg) 8.9 (4.0-19.6)
Mostafa 1998 Bangladesh 101-400 mg/L 1.7 (1.7-2.2)
19
Lung Cancer Cohort Studies
Study Location Arsenic levels RR (SMR)
Chiou 1995 NE Taiwan Average gt0.71 mg/L Cumulative gt20 mg/L x yr 2.7 (0.7-10.2) 4.7 (1.2-18.9)
Tsuda 1995 Japan gt1.0 mg/L 15.7 (7.5-31.0)
Baastrup 2008 Denmark 0.7 mg/L 0.99 (0.9-1.1)
Chen 2004 Taiwan gt700 mg/L 3.3 (1.6-6.7)
Chen 2010 Taiwan gt300 mg/L 2.3 (1.4-3.6)
20
Estimates of lifetime cancer risks per 10,000
people in relation to arsenic concentration
Concentration Lung Lung Bladder Bladder
Females Males Females Males
3 µg/L 5 4 4 7
5 µg/L 9 7 6 11
10 µg/L 18 14 14 23
20 µg/L 36 27 24 45
21
Other considerations
22
Arsenic Metabolism
23
Other considerations?
  • Genetic Susceptibility
  • Co-exposures
  • Smoking

24
Other Cancer Sites with Some Evidence of
Association
  • Kidney
  • Cutaneous melanoma
  • Liver
  • Prostate

25
Cardiovascular Disease
26
Peripheral Vascular Disease
  • Blackfoot disease
  • Unique disease that ends with dry gangrene and
    spontaneous amputation
  • Prevalence rate in parts of Taiwan reported to be
    6.51 to 18.85/1000 residents
  • 1950s-60s was peak time

27
Cardiovascular Mortality
  • Increased risk of cardiovascular mortality
  • Several studies in Taiwan in endemic regions
  • Death Certificate Study (Engel 1994)
  • 30 counties in U.S.
  • SMR0.8
  • Cross-sectional survey in Wisconsin (Zierold
    2004)
  • Private well users
  • OR2.1 (1.1-4.3) for self-reported heart attack
    with gt10 ppb

28
Cardiovascular Disease
Study Location Arsenic levels Outcome
Wang 2002 Taiwan gt20 ppm yrs Carotid atherosclerosis
Wang 2003 Taiwan gt20 ppm yrs Increased QTc interval
Ahmad 2006 Bangladesh 500 mg/L ECG abnormalities
Wu 2006 Taiwan Up to 3590 mg/L Carotid atherosclerosis
Kwok 2007 China 100mg/L Hypertension
Yuan 2007 Chile Up to 860 mg/L Myocardial infarction
29
Pregnancy Outcomes
30
Pregnancy Outcomes
Study Location Arsenic levels Outcome
Borzsonyi 1992 Hungary 170-330 mg/L stillbirths and spontaneous abortion
Hopenhayn-Rich 2000 Chile 860 mg/L stillbirths and infant mortality
Ahmad 2001 Bangladesh 100mg/L spontaneous abortions, stillbirths, preterm births
Hopenhayn 2003 Chile Up to 50mg/L Reduced birth weight
Yang 2003 Taiwan Up to 3590 mg/L Reduced birth weight
Milton 2005 Bangladesh Average 279 mg/L spontaneous abortions and abortions
Kwok 2006 Bangladesh 300 mg/L No association stillbirth or low birth weight
Von Ehrenstein 2006 India 200 mg/L stillbirth, not spontaneous abortion
Huyck 2007 Bangladesh Up to 734 mg/L Reduced birth weight
Rahman 2007 Bangladesh 500mg/L Any pregnancy loss
31
Other Health Outcomes
32
Other Health Outcomes with at least Suggestive
Evidence
  • Diabetes
  • Neurological
  • Respiratory
  • Hepatotoxic
  • Hematological
  • Child cognitive function

33
National Research Council Recommendations
  • Epidemiologic evaluations needed for
    dose-response relationshipespecially at low
    doses
  • Critically important for validity of risk
    assessment
  • Cancer studies
  • Refine dose-response relationship between arsenic
    ingestion for cancer of the skin, bladder and
    lung and investigate cancer at other sites
  • Non-cancer effects
  • Emphasis on cutaneous effects, cardiovascular and
    cerebrovascular disease, diabetes mellitus and
    reproductive outcomes

34
Summary
  • Inorganic arsenic in drinking water linked to
    many diseases
  • Causal, at high levels
  • Lung, bladder and non-melanoma skin cancer
  • Lower levels?
  • Evidence of other health effects
  • Cardiovascular
  • Pregnancy

35
QA
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