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  1. Welcome to the CLU-IN Internet Seminar Arsenic - Health and Remediation Applications, Session 2 - Emerging Issues in Arsenic Exposure and DiseaseSponsored by: NIEHS Superfund Research ProgramDelivered: November 2, 2012, 2:00 PM - 4:00 PM, EDT (19:00-21:00 GMT) Instructors:Allan H. Smith, M.D., Ph.D., University of California, Berkeley, School of Public Health (ahsmith@berkeley.edu) Joshua W. Hamilton, Ph.D., Dartmouth College SRP Center (jhamilton@mbl.edu) Moderator: 1 Visit the Clean Up Information Network online atwww.cluin.org

  2. Housekeeping Please mute your phone lines, Do NOT put this call on hold Q&A Turn off any pop-up blockers Move through slides using # links on left or buttons This event is being recorded Archives accessed for free http://cluin.org/live/archive/ Download slides as PPT or PDF Go to slide 1 Submit comment or question Report technical problems Move back 1 slide Go to seminar homepage Go to last slide Move forward 1 slide 2

  3. The Astonishing Long-Term Effects of In Utero & Early Childhood Exposure to Arsenic Allan H. Smith MD, PhD Professor of Epidemiology University of California, Berkeley Recent findings from the Arsenic Health Effects Research Program With support from NIH including the NIEHS Superfund Program

  4. The Berkeley Arsenic Health Effects Research Group (ASRG) Arsenic Research Group Not Allan Smith’s Research Group Associate Director: Craig Steinmaus

  5. When I first started research on arsenic in water over 20 years ago, we only knew it caused skin lesions and skin cancer.

  6. Lung cancer and arsenic in Taiwanadapted from CJ Chen et al 1988 • Comparison population, all of Taiwan • vertical axis: age adjusted rate ratios (relative risk)

  7. It is surprising that arsenic in drinking water would have major effects in the lungs

  8. smoking passive smoking asbestos radon silica chromium diesel exhaust coke oven PAHs bischlormethyl ether nickel arsenic Known causes of lung cancer involve inhalation

  9. Cancer risks from arsenic in drinking water At the current standard of 50 ug/L, the lifetime risk of dying from cancer from drinking 1 L/day of water could be as high as 13 per 1000 persons Environmental Health Perspectives 97:259-267, 1992 Martyn Smith

  10. The lost and forgottenarsenic-exposed population “the number of people consuming water from private wells with arsenic concentrations above 10 µg/L could be over 2 million people” Where is this population? Right here in the USA Steinmaus et al. In Press.

  11. There are high concentrations of arsenic in private wells in the U.S. too Steinmaus CM, George CM, Kalman DA, Smith AH. Environ Sci Technology, 40:3362-3366, 2006

  12. People with private wells are on their own Gearoge CM …… Steinmaus C. Arch Environ Occup Health 61:171-175, 2006.

  13. CHILE Region II Region V

  14. Lung Cancer Mortality Region II Chile, 1989-1993 Mario Goycolea Smith et al. American Journal of Epidemiology, 1998. Smith AH et al. American Journal of Epidemiology, 1998.

  15. Increased lung cancer risks are similar whether arsenic is ingested or inhaled. Smith AH, Ercumen A, Yuan Y, Steinmaus CM.. J Exposure Science and Environmental Epidemiology 19:343-8, 2009

  16. The estimated cancer risk at the drinking water standard of 50 µg/L for arsenic is more than 100 times greater than that for any other drinking water contaminant Smith AH, Lopipero PA, Bates MN, Steinmaus CM. Arsenic epidemiology and drinking water standards. Science 296: 2145-6, 2002

  17. Cancer risk from contaminants in drinking water other than arsenic Per 100,000 Top of the list: Ethylene dibromide

  18. Cancer risk from contaminants in drinking water including arsenic Per 100,000 Cancer risks from arsenic at the old drinking water standard were >100 times higher than the next highest risk contaminant

  19. Cancer risks from arsenic in drinking water Lung cancer and smoking married to a smoker active smoker • 10 ug/L 1 in 500 die • 50 ug/L 1 in 100 die • 500 ug/L 1 in 10 die • 5000 ug/L all die And arsenic in water looks good, does not smell and has no taste. So the risks are unbelievable

  20. Marshall G, Ferreccio C, et al.Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water.J Natl Cancer Inst 99:920-928, 2007 Mortality data were already available computerized for 1971-2000. For the years 1950-1971, 200,000 death certificates were digitally photographed and coded for this study.

  21. Peak exposure started stopped Mortality from lung cancer among men, Region II Chile Marshall et al, J. Natl Cancer Inst, 2007

  22. Respiratory Cancers of the lung and larynx, reduced lung function, bronchiectasis, chronic cough and shortness of breath. Tuberculosis mortality increased? Renal tract Bladder and kidney cancer, chronic renal failure Cardiovascular Myocardial infarction, cerebrovascular effects, hypertension. Neurological Peripheral neuropathy, reduced cognitive function in children Other Skin pigmentation changes, skin cancer, liver cancer, diabetes So what do we now think arsenic in drinking water causes?

  23. Effect of early life exposure In utero and in the first few years of childhood

  24. Source: Project Well, West Bengal, India, 2003

  25. Arsenic concentrations in drinking water in the city of Antofagasta (popn 200,000) in Chile

  26. Liaw J, et al Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile. Cancer Epidemiol Biomarkers Prev. 2008. p=0.01

  27. Lung cancer mortality in men accordingto exposure in childhood | born | | 1989 1998 peak arsenic | | | | | | 1950 1960 1970 1980 1990 2000

  28. Lung cancer mortality in older men (SMR = standardized mortality ratio = observed/expected deaths) Age at death 60 – 69 SMR | born 1920-38 | | 1989 1998 peak arsenic | | | | | | 1950 1960 1970 1980 1990 2000 p < 0.001

  29. Lung cancer mortality in men accordingto exposure in childhood(SMR = standardized mortality ratio = observed/expected deaths) Age at death 35 – 39 SMR | born 1953-57 | | 1989 1998 peak arsenic | | | | | | 1950 1960 1970 1980 1990 2000 p < 0.001

  30. Lung cancer mortality in men accordingto exposure in childhood(SMR = standardized mortality ratio = observed/expected deaths) Age at death 30 – 34 SMR | born after 1957 | | 1989 1998 peak arsenic | | | | | | 1950 1960 1970 1980 1990 2000 p < 0.001

  31. Childhood exposures and young adult lung cancer relative risks • Atomic bomb survivors Hiroshima and Nagasaki aged 10-20 in 1945. No cases in those exposed in utero or under age 10. • A study giving lung cancer relative risks in the age range 30-39 following many hours of daily passive smoking as children (only four cases). • Lung cancer relative risks in age range 30-39 in Region II of Chile following early life exposure to arsenic in water. There were 32 lung cancer deaths with 3.8 expected (RR=8.4, p<0.001). Smith AH et al. Environmental Health Perspectives 2006

  32. End Stage Lung Disease Obstruction, Infection, Hemoptysis, Bronchiectasis

  33. High resolution computed tomography (HRCT) with readings in India and the United States without knowing who had arsenic skin lesions. Dr. D. N. Guha Mazumder Craig Steinmaus

  34. Study design, x-ray (HRCT) study in West Bengal, India Assessed in this study Referred for HRCT 10-fold increased prevalence of bronchiectasis OR=10.1, p<0.01 Epidemiology 2005

  35. Lung function findings of reduced FEV1 adjusted for age and height • For all men combined P=0.007 • Among men in this population, arsenic- caused skin lesions were associated with a greater FEV1 reduction (-256ml) than from smoking (-156ml) Von Ehrenstein OS et al. Am J Epidemiol 162: 533-41, 2005

  36. Mortality (SMRs) from Chronic Obstructive Pulmonary Disease, age 30-49, for those born in the very high exposure period (in utero exposure) or just before (child) p<0.001 except other COPD p=0.004

  37. A dugwell with modified design to reducebacterial contamination

  38. Intervention program in West BengalDirector: Meera HiraSmith • Modern design dugwell program to provide arsenic free water in West Bengal • Funded by private donors • for more information http://www.projectwellusa.org

  39. Distribution of Children’s Arsenic Exposure (ug/L) In Utero

  40. Excess deaths among men in Region II of Chile from acute MI, lung cancer and bladder cancer.Yuan Y et al. Am J Epidemiol 166:1381-1391, 2007 At the peak more than 1 in 10 of all deaths were due to arsenic

  41. Early life exposure and myocardial infarction mortality in young adults The highest rate ratios were for young adult men aged 30–49 years who were born during the high-exposure period with probable exposure in utero and in early childhood (rate ratio = 3.23, 95% CI: 2.79, 3.75; p < 0.001) Yuan Y et al. Am J Epidemiol 2007