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Arsenic in drinking water threatening the health of millions?

Arsenic in drinking water threatening the health of millions?. Marie Vahter Institute of Environmental Medicine Karolinska Institutet Stockholm. Arsenic – occurrence. Ubiquitous in soil and bedrock Drinking water (ground water) Seafood, mainly organic As Arsenic containing minerals :.

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Arsenic in drinking water threatening the health of millions?

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  1. Arsenic in drinking water threatening the health of millions? Marie Vahter Institute of Environmental Medicine Karolinska Institutet Stockholm Utrecht Vahter 2006

  2. Arsenic – occurrence • Ubiquitous in soil and bedrock • Drinking water (ground water) • Seafood, mainly organic As Arsenic containing minerals: Arsenopyrite (FeAsS) Realgar (As4S4) Orpiment (As2S3) Utrecht Vahter 2006

  3. Decreasing use in most products • Wood preservatives • Insecticides (ants) • Herbicides (weed killers and defoliants) • Fungicides • Cotton desiccants • Cattle and sheep dips • Paints and pigments • Antifouling paints • Medicine(acute promyelocytic leukemia, antiparacitic drugs, kelp-containing health foods) Utrecht Vahter 2006

  4. Industrial processes with arsenic • Non-ferrous smeltering • Purification industrial gases (removal of sulfur) • Burning fossil fuels (brown coal) • Electronics(microwave devices, lasers, light-emitting diodes, photoelectric cells, semiconductors) • Hardening metal alloys • Preservation animals, hides • Bronze plating • Clarifying glass Utrecht Vahter 2006

  5. Arsenic in drinking waterGlobal public health problem: • Elevated concentrations in ground water – up to several thousand µg/L; WHO guideline 10 µg/L • Surface water < 1 µg/l • Ambient air < 50 ng/m3:< 1 µg As/day • Organic As in seafood, arsenobetaine, arsenocholine, arsenosugars, arsenolipids. Less toxic, but must be considered when U-As is used as exposure biomarker. . Vahter 2001 Utrecht Vahter 2006

  6. As Algea and bivalwes Arsenosugar Food and water Inorg. AsIII, AsV Fish, seafood Arsenobetaine Metabolism Arseno- betaine Inorg.As MMA DMA DMA - 1,000 µg/l 1-10 µg/l in urine 5-100µg/L Utrecht Vahter 2006

  7. Common arsenosugars in biological samples Adenosin Schmeisser et al, 2004 Utrecht Vahter 2006

  8. Fred Pearce, 2003, New Scientist Elevated concentrations in ground water Up to several thousand µg/L; WHO standard 10 µg/L Utrecht Vahter 2006

  9. Elevated As in tube-wells in Bangladesh • ~50% of the 10-11 million tube-wells in Bangladesh have > 10 µg/L ( WHO guideline) • > 50 million people affected • Difficult mitigation • Tube-well water used for irrigation => contamination soil, rice and vegetables. BGS, 2002 Utrecht Vahter 2006

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  12. Acute arsenic toxicity • Gastrointestinal form: Nausea, intense GI pain, vomiting, diarrhea, loss of water, anuria, drop in blood pressure, heart disturbances, failure of brain function, circulatory collaps • Paralytic form: Severe shock - paralysis of the capillaries, acute excitability of the brain, general paralysis • Lethal dose: from a few mg/Kg b.wt. Considered in evaluation of contaminated soil Utrecht Vahter 2006

  13. Arsenic – Acute and subacute effects 1900 in Manchester, UK: Several thousands intoxicated, beer with 1.5-3 mg As/l 1950s in Japan: • 12000 infants, dry milk powder 15-24 mg As/kg; => 1.3-3.6 mg As/day for some weeks; 130 fatalities • 400 poisoned by soy sause, 100 ml As/l, 3 mg As/day for 2-3 weeks => poisoning symptoms WHO, 1981; Dakeishi et al, 2006 Utrecht Vahter 2006

  14. Chronic effects of As Targets ubiquitous enzyme reactions => nearly all organs systems affected: • Cancer: skin, lung, bladder, kidney (IARC, 2004) • Skin: melanosis and hyperkeratosis • Chronic cough • Diabetes • Cardio-vascular • Polyneuritis • Liver, Kidney • Reproduction? • Child development? Utrecht Vahter 2006

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  16. As classified as carcinogen • Group 1 carcinogen (IARC, 2004) • Sufficient evidence in humans that arsenic in drinking-water causes cancers of the: Urinary bladder Lung Skin • Some indications for cancers in: • Kidney • Liver • Prostate Utrecht Vahter 2006

  17. Skin cancer prevalence in Taiwan Water As µg/l Prevalence per 1000 exposed Age group, y Tseng et al, 1968 Utrecht Vahter 2006

  18. Age-adjusted mortality in internalcancers in Taiwan Males Females As in water, µg/l Deaths per 100,000 exposed Wu et al, 1989 Utrecht Vahter 2006

  19. Cancer risks in northern Chile (W-As 200 => 800 µg As/L, 1950-74) SMR Smith et al, 1998 Utrecht Vahter 2006

  20. Health Risk Assessments • WHO/IPCS EHC 18, 1981 • NAS/NRC Arsenic in drinking water 1999 • NAS/NRC Arsenic in drinking water: 2001 update • WHO/IPCS EHC 224, 2001 • IARC Some drinking water disinfectants and contaminants, including arsenic, 2004 Utrecht Vahter 2006

  21. Extrapolation from 1% excess risk of bladder and lung cancer (NRC, 2001) Utrecht Vahter 2006

  22. Mechanisms of As toxicityMainly AsIII, MMAIII • Enzyme inhibition • DNA repair inhibition • Hormone interaction GR, ER • Chromosomal damage, micro nuclei, SCE? • DNA hypo/hyper methylation • Uncoupling cell respiration (AsV, AsIII) • Oxidative stress (lipids, DNA, proteins?) • Cell proliferation, apoptosis, necrosis Utrecht Vahter 2006

  23. Cancer risks in Region II Chile Gender differences in susceptibility SMR Smith et al, 1998 Utrecht Vahter 2006

  24. Men more affected by As-related skin effects Hyperkeratosis Pigmentation changes Skin cancer ♂more affected than♀ Social implications: ♀ more affected than♂ Tseng 1977; Chen et al 1992; Guha Mazumder et al 1998; Smith et al 2000; Watanabe et al 2001; Kadono et al 2002; Chen et al 2003 Rahman et al 2005 Hassan et al 2005 Vahter 2005 Utrecht Vahter 2006

  25. Skin effects of arsenic Utrecht Vahter 2006

  26. Cancer risks in Region II Chile Gender differences in susceptibility? SMR Smith et al, 1998 Utrecht Vahter 2006

  27. Gender differences internal cancers Wu et al, 1989; Smith et al, 1998, Tsai et al, 1999; Steinmaus et al, 2000; Waalkes et al, 2003 Chiu et al, 2004 • Bladder cancer • Lung cancer • Chronic Cough ♀>> ♂?? More studies needed! Vahter 2005 Utrecht Vahter 2006

  28. Transplacental carcinogenicityof As in female mice In female mice also ovarian tumors: 2, 6, 9 mice with tumors, mainly carcinoma, in control, 42 and 85 ppm group, respectively (p= 0.015) Waalkes et al, 2003 Utrecht Vahter 2006

  29. Transplacental carcinogenicity of As in male mice In male mice also adrenal tumors: 0.71, 1.1 and 1.6 tumors/mouse in control, 42 and 85 ppm group, respectively Waalkes et al, 2003 Utrecht Vahter 2006

  30. Arsenic passes to the fetus A few studies indicate increased fetal and infant mortality, low birth weight, impaired child development. But, no conclusions. Need for further studies! Utrecht Vahter 2006

  31. Neonatal mortality rate, Antofagasta High water-As 1958-70 Years Asµg/l 50-57 90 58-70 860 71-79 110 80-87 70 88-96 40 RR 1.53; CI 1.40-1.66 Hopenhayn-Rich et al, 2000 Utrecht Vahter 2006

  32. Dhonagoda River Matlab Study Area BANGLADESH Legend Govt. Service Area Embankment ■ ICDDR,B Hospital ● ICDDR,B Subcenter Rajshahi Sylhet ● Main river Dhaka Block - C @ ● Block - D Matlab Khulna Chittagong Barisal Govt. Service Area Bay of Bengal ● Block - B ■ Main rivers Dhonagoda River Divisional boundaries ● Meghna River Block - A GIS unit, ICDDR,B KM 0 1 2 3 4 N  Matlab study area Water As: <0.5 – 3,600 g/L Utrecht Vahter 2006

  33. Infant survival in relation to maternal exposure to water-As in a cohort of pregnancies 1991-2000 in Matlab, Bangladesh (Rahman A., Am J Epidemiol, accepted) Utrecht Vahter 2006

  34. Test of child development ‘The deliberate execution of a sequence of steps to achieve a goal’ Support Test Search Test 1. Pull the cloth 1. Reveal the toy 2. Fixation of eye 2. Fixation of eye 3. Grasp the toy 3. Grasp the toy Utrecht Vahter 2006

  35. Metabolites of inorganic As in humans New! Most toxic (trivalent)! Raml et al, 2006 Utrecht Vahter 2006

  36. HPLC-HG-ICPMS Agilent 7500 csHighPerformance Liquid Chromatography-Hydride Generation- Inductively Coupled Plasma Mass Spectrometry Utrecht Vahter 2006

  37. DMA, 1.0 µg/L DMA AsIII, 0.2 µg/L MMA, 0.2 µg/L AsV, 0.2 µg/L Utrecht Vahter 2006

  38. Inter-individual variation in As methylation Factors: exposure level, nutrition, age, genetics… Utrecht Vahter 2006

  39. Population variation in As methylation Hopenhayn-Rich et al 1993 ; Vahter et al, 1995; Chiou et al, 1997; Vahter et al, 2006 Utrecht Vahter 2006

  40. Species differences in As metabolism Rat Marmo- Human Chim- Rabbit Hamster Dog Mouse set panzee Vahter et al, 1999 Utrecht Vahter 2006

  41. Arsenic Management inCopper Smelters • As a consequence of environmental regulations there is a significant increase in the amount of arsenic residues, which will have to be managed in a safe way, whether for its recovery or disposal. (A Valenzuela, K. Fytas, M. Sánchez,Environmental Business Network for the Americas, 05  February  2001) Utrecht Vahter 2006

  42. Karolinska Institutet Campus Solna Thank you for your attention! Utrecht Vahter 2006

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