Health Effects Of Arsenic: An Old Problem And Emerging New Concerns
Health Effects of Arsenic: an old problem and emerging new concerns Joshua W. Hamilton Ph.D. Senior Scientist, Bay Paul Center, Marine Biological Laboratory (MBL), Woods Hole MA Professor, Pathology & Laboratory Medicine, Brown University, Providence RI Project Leader, Dartmouth’s Superfund Research Program on Toxic Metals, Hanover NH JWH 8/23/2012
Arsenic and Old Concerns “It is an uncanny thought that this lurking poison (arsenic) is everywhere around us, ready to gain unsuspected entrance to our bodies in the food we eat, the water we drink and the air we breathe.” Karl Vogel, 1928 JWH 8/23/2012
METALS: Toxic Metals, Heavy Metals, Essential Metals three-fourths of all elements are metals or metalloids a “heavy metal” refers to its atomic weight, not its toxicity many metals are essential or play a normal role in biology many toxic metals that are not essential can mimic essential metals like all chemicals, all metals are toxic at high enough doses like all chemicals, all metals are non-toxic at very low doses JWH 8/23/2012
Toxic metals in the environment Toxic metals are a major concern at both Superfund / toxic waste sites and in the environment in general Eight of the top fifty substances on the CDC’s ATSDR priority list are metals, including the top three chemicals of concern in the environment: arsenic, lead and mercury Eight of the twenty-two substances on the EPA’s OSWER list of chemicals of highest concern at Superfund sites are metals: arsenic, lead, mercury, cadmium, chromium, nickel, zinc and copper JWH 8/23/2012
Arsenic: “poison of kings and king of poisons” Ancient Rome - Women’s club used arsenic to poison husbands Renaissance - The Borgias used arsenic to poison rivals and increase their wealth Were Napolean and Mozart poisoned by arsenic? Cesare Borgia “The death of Napolean” a lock of Napolean’s hair JWH 8/23/2012
Arsenic as an environmental contaminant Previous US and WHO drinking water standard (Maximum Contaminant Level, MCL) for arsenic was 50 parts per billion (ppb) from 1950’s through 2001 US recently lowered MCL to 10 ppb (Jan. 2006), but 7-14 year implementation current WHO and EU arsenic standard is 10 ppb WHO program of digging tube wells in India, Bangledesh to alleviate cholera problem led to massive population exposure to excess arsenic in drinking water highly contaminated areas (India, South America) can contain as much as 1800 ppb (180 times the WHO standard) Estimated 250 million to 1 billion people affected worldwide by excess arsenic JWH 8/23/2012
Arsenic as a causative agent in human disease Chronic human exposure to inorganic arsenic at sub-acute doses has been linked to increased risk of: Cancers- esp. lung, skin and bladder but also liver, kidney, and other malignancies Diabetes (type 2, non-insulin-dependent, “adult-onset”) Vascular and cardiovascular disease Reproductive and developmental problems Neurological problems U.S. & South America - range is typically 1-100 ppb Asia - range is typically 10-1000 ppb JWH 8/23/2012
Arsenic as an environmental contaminant in New England In New Hampshire, 40% of the population gets its drinking water from private, unregulated wells Of these wells, greater than one in five has excess arsenic, representing about 10% of the state’s population ( 120,000 people) Similar ratios are found in Maine ( 150,000 people) In the U.S. as a whole, as many as 25 million people may be drinking excess arsenic in their drinking water NH and ME also have elevated levels of arsenic in soil both naturally and from lead arsenate pesticide use (avg. 20 ppm vs. 1-5 ppm in most of U.S.) JWH 8/23/2012
Dartmouth Center for Environmental Health Sciences at Dartmouth Project 7 - Carol Folt & Celia Chen ecotoxicology of metals Project 4 - Margaret Karagas epidemiology of arsenic Project 9 – Tracy Punshon & MaryLou Guerinot uptake of arsenic by rice Project 2 - Joshua Hamilton molecular toxicology of arsenic Project 8 - Bruce Stanton molecular toxicology of arsenic TOXIC METALS Research Program “Toxic Metals in the Northeast” NIH-NIEHS Sponsored Dartmouth Superfund Basic Research Program Project on Toxic Metals An interdisciplinary research program on toxic metals in the environment and their impact on ecosystems and human health JWH 8/23/2012
Arsenic as an endocrine disruptor What is an endocrine disruptor? “Collectively, chemicals with the potential to interfere with the function of endocrine systems are called endocrine disrupting chemicals (EDCs). EDCs have been defined as exogenous agents that interfere with the production, release, transport, metabolism, binding, action, or elimination of the natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes.” Strategic Research Plan for Endocrine Disruptors, 1998 Office of Research and Development U.S. EPA JWH 8/23/2012
Hormone receptor biology and endocrine disruption organic Endocrine Disrupting Chemicals - EDCs (pesticides, etc.) competitive agonists mimic hormone, bind to receptor, activate receptor competitive antagonists mimic hormone, bind to receptor, block normal hormone binding and activation JWH 8/23/2012
Arsenic has opposite effects on steroid receptor function at lower (0.01-1.0 µM) and higher (2-3 µM) doses 2-2.5 fold enhancement 0.01-1 µM, 0.7-70 ppb No Observed Effect Level (NOEL) No Observed Effect Level (NOEL) 50-90% suppression 2-3 µM, 140-210 ppb JE Bodwell et al. Chem Res Toxicol 17:1064-1076, 2004 JWH 8/23/2012
Thyroid hormone mediated metamorphosis - Xenopus Plasma TH Human Age (month) -6 -4 -2 0 2 4 6 8 10 12 14 Human 100 Xenopus 75 50 TR active 25 Xenopus Stage 35/36 45 51 55 58 61 63 66 As Prometamorphosis Premetamorphosis Metamorphic Climax YB Shi. et al.(2002) Pharmacol Ther 94:235-251 JWH 8/23/2012
Effects of arsenic on thyroid hormone-mediated ex vivo tail shrinkage in Xenopus JC Davey et al. Environ Hlth Perspect 116:165-172, 2008 JWH 8/23/2012
Summary of arsenic as an endocrine disruptor Arsenic affects all five steroid hormone receptors: Estrogen Receptor Progesterone Receptor Androgen (Testosterone) Receptor Glucocorticoid (Cortisol) Receptor Mineralocorticoid (Aldosterone) Receptor Arsenic affects other nuclear hormone receptors: Retinoic Acid Receptor Thyroid Hormone Receptor PPAR Receptors Arsenic enhances hormone signaling at very low doses Arsenic suppresses hormone signaling at higher doses JWH 8/23/2012
Arsenic and lung disease Arsenic exposure is associated with increased risk of: Lung Cancer Bronchiectasis COPD Emphysema Chronic Lung Infections Arsenic is unique in increasing lung disease risk via ingestion rather than (or in addition to) inhalation Arsenic synergistically increases risk of lung disease from other lung toxicants including tobacco smoke, environmental air contaminants, bacterial and viral infections JWH 8/23/2012
Arsenic and long-term risk of bronchiectasis in Region II of Chile Marshall, J Natl Canc Inst 2000 -- Ferreccio, Epidemiology 2000 -- Smith, Environ Hlth Perspect 2006 JWH 8/23/2012
Arsenic in drinking water (100 ppb) increases H1N1 flu-induced morbidity in mice CD Kozul et al., Environ Hlth Perspect 117: 1441-1447, 2009 JWH 8/23/2012
Arsenic and metabolic diseases Arsenic exposure has been associated with: Changes in serum cholesterol and triglycerides Development of type 2 diabetes and other metabolic disorders Lower than normal birth weights Decreases in body weight and growth during early childhood Vascular and cardiovascular disease JWH 8/23/2012
Effects of arsenic on mouse fetal and maternal health CD Kozul Horvath et al., PLoS One 2012 JWH 8/23/2012
Arsenic at 10 ppb in drinking water affects mouse fetal growth and development Pregnant C57BL/6J mice were given 10 ppb arsenic in drinking water during the in utero only, post-natal weaning only, or in utero and post-natal periods CD Kozul Horvath et al., PLoS One 2012 JWH 8/23/2012
Arsenic at 10 ppb in drinking water affects mouse maternal breast milk nutrients Pregnant C57BL/6J mice were given 10 ppb arsenic in drinking water during the in utero only, post-natal weaning only, or in utero and post-natal periods CD Kozul Horvath et al., PLoS One 2012 JWH 8/23/2012
Arsenic at 10 ppb in drinking water causes fatty liver in pregnant mice Pregnant C57BL/6J mice were given 10 ppb arsenic in drinking water during the in utero only, post-natal weaning only, or in utero and post-natal periods CD Kozul Horvath et al., PLoS One 2012 JWH 8/23/2012
Acknowledgements Hamilton lab (past & present): Ron Kaltreider Mike Ihnat Jennifer Davey Tom Hampton Athena Nomikos Julie Gosse Courtney Kozul-Horvath FJ Zandbergen Vansa Chatikavanij Maggie Vantangoli Adeola Adebayo Collaborators: Dean Wilcox (Dartmouth) Jack Bodwell (Dartmouth) Lynn Sheldon (Dartmouth) Bruce Stanton (Dartmouth) Mike Ihnat (Oklahoma) Richard Enelow (Dartmouth) Monique Depaepe (Brown) JWH 8/23/2012
excess arsenic, representing about 10% of the state's population ( 120,000 people) Similar ratios are found in Maine ( 150,000 people) In the U.S. as a whole, as many as 25 million people may be drinking excess arsenic in their drinking water NH and ME also have elevated levels of arsenic in soil both naturally and from lead arsenate
arsenic legally allowed in tap water, for example. Arsenic also contaminates many of your favorite foods, including fish, rice and chicken. Some food contamination stems from intentional uses of arsenic. In this report we clearly connect arsenic residues in chicken meat to the decades-old practice of intentionally putting arsenic into chicken .
carbon and hydrogen, creating organic arsenic. Most forms of arsenic are either white or colorless powders that do not evaporate. They also have no notable smell or taste; therefore, one cannot tell if arsenic is present in food, water, or air. Inorganic arsenic is the form of arsenic that poses the greater risk to human health (ATSDR 2000).
Chapter 4 Geothermal Arsenic The source, transport and fate of arsenic in geothermal systems Jenny G. ebster' and D. Kirk ordstrom ' University qfAuckland, Auckland, New Zealand 2 Geological Survey, Boulder, CO, USA The release of arsenic from geothermal system
0.1. Separate solutions containing arsenic in the form of arsenite (using arsenic trioxide, Anachemia Chemicals) and arsenate (using sodium arsenate, Anachemia Chemicals) were used to test the effect of arsenic speciation on the process. SMW also contained calcium (210 12 mg/L), magnesium (63 4
spectrometric area that . organic arsenic compounds other than simple methylated arsenic acids in algae was made chiefly by lH NMR spectrometry after isolation of the compounds. The major forms of water-soluble arsenic in marine algae were shown to be 5-dimethylarsinoyl . appropriate for the identification of compounds of previously unknown .
COLORIMETRIC DETERMINATION OF ARSENIC IN FERROUS AND NONFERROUS ALLOYS 1 By Clement J. Rodden ABSTRACT A method is described for the determination of arsenic and has been applied successfully to iron, steel, copper-base alloys, tin-and lead-base bearing metals, and pig lead. The arsenic is first separated from the other constituents of the
Arsenic and old lace script pdf. Arsenic and old lace script free. ARSENIC AND OLD LACE Written by Julius J. & Philip G. Epstein Adapted from the play by Joseph Kesselring CREDITS Credits roll, in white letters, on several funny cartoons, all of them about witches and witchcraft (a caldron over a fire, with two witches on either side of it - A .
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