Arsenic Almost Final Slides


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Arsenic Almost Final Slides

  1. 1. Arsenic
  2. 2. Brief History of Arsenic Discovery History is convoluted  Not sure who first discovered Greeks and Romans had slaves mine for arsenic Used in Alchemy Albertus Magnus  German chemist  First to isolate in 1250 AD
  3. 3. General Information of Arsenic Chemical Formula = As Atomic Number = 33 Molecular Weight = 74.92 grams Color = lead gray, gray, white Hardness of 3.5  Similar to calcite or flourite  Talc is 1 and diamond is 10 Nonmagnetic Metallic Poor conductor of heat & electricity
  4. 4. Inorganic vs. Organic ArsenicInorganic OrganicOccurs naturally in soil and many mineralsand ores that contain copper and lead Mainly found in marine organisms  When heated, arsenic rises up smokestack as a fine dust Can still be used on agricultureCannot be used in agriculture  Primarily cottonUsed to pressure treat wood Improve properties when added toArsenate V is found in water an allow or metal Greatest use in lead acid batteries Semiconductors and LED’s Arsenate III found in water
  5. 5. Uses of Arsenic ‘Poison of Kings’  Marsh and Reinsch Tests Bronze alloy Lead alloy Medicinal uses  Syphili, yaws, psoriasis, and other viruses Industrial uses  Ammunition production, pigments, insecticides, rat poison, wood preservative, semiconductors, & others
  6. 6. Environmental Sources of Arsenic Marine animals In drinking water ~200 mineral species snapshot-2000-2010.html  Most common is arsenopyrite Emitted from volcanoes arsenic-and-how-it.html
  7. 7. Anthropogenic Sources of Arsenic Reduction of Arsenic Trioxide (As2O3 - Arsenite) with charcoal  As2O3 is created during the metal smelting process Industrial uses  Ammunition production, pigments, insecticides, rat /analytical-reagents.html poison, wood preservative, semiconductors, & others
  8. 8. Mechanism Inorganic  Arsenate – exists in +5 oxidation state  Arsenite – exists in +3 oxidation state
  9. 9. Mechanism (Continued) Organic As – methylated (both in +3 oxidation state)  Monomethylarsonous acid (MMAIII)  Dimethylarsinous acid (DMAIII)
  10. 10. Mechanism (Continued)+ 5 oxidation state (pentavalent) + 3 oxidation state (trivalent) Arsenate Monomethylarsonous acid (MMAIII) Dimethylarsinous acid (DMAIII) Arsenite
  11. 11. Mechanism (Continued) In general, As terrorizes the metabolic processes of the mitochondria
  12. 12. Mechanism (Continued) Pentavalent toxicity  Very similar to phosphate  Can substitute for inorganic phosphate in glycolytic and cellular respiration pathways
  13. 13. Mechanism (Continued) Pentavalent toxicity  ADP-phosphate = ATP  ADP-arsenate = biologically useless  High energy phosphate bonds are lost  Stopping the production of ATP will stop all processes that require ATP
  14. 14. Mechanism (Continued) Trivalent toxicity  Reacts readily with thiol-containing molecules (-SH functional group)  Amino acid cysteine contains thiol group  Cysteine rich proteins are vulnerable to As binding but if binding does not have detrimental effects on the protein, this may serve as a detoxification mechanism
  15. 15. Mechanism (Continued) Trivalent toxicity  Pyruvate Dehydrogenase (PDH) requires lipoic acid cofactor – a dithiol  As inhibits this enzyme by binding to the cofactor  The citric acid cycle cannot proceed because the pathway is terminated
  16. 16. Mechanism (Continued) Oxidative Stress  Reductase enzymes are present in the cell to reduce reactive oxygen species (ROS)  As binds and inhibits some of these reductases, resulting in the accumulation of ROS  ROS can bind/damage DNA and other cellular components  Part of As carcinogenicity
  17. 17. Mechanism (Continued) Carcinogenicity  Researchers have yet to fully elucidate carcinogenic mechanisms of As  It is widely accepted that As is a carcinogen and several mechanisms have been proposed
  18. 18. Mechanism (Continued) Carcinogenicity  ROS accumulation  DNA Excision Repair and DNA Ligase inhibited by Arsenic  Co-mutagenic effect with ROS, UV radiation, X-Rays, and other chemicals  DNA methylation alterations  Also noted as a tumor promoter in mouse ovarian cancers
  19. 19. Health Effects and Symptoms Acute As poisoning  Nausea  Vomiting  Blood in the urine  Cramping muscle  Hair loss  Stomach pain  Convulsions  Organ failure  Comma to death (interferes with glycolysis)
  20. 20. Health Effects and Symptoms Chronic arsenic poisoning  High oxidative stress  affect the structure of function of cardiovascular system  Increases the risk of cancer  Vitamin A deficiency  Night blindness  Heart disease  Skin color change  Eye inflammation  Hyperkeratosis and hyperpigmentation  Blushed complexion
  21. 21. Health Effects and Symptoms Bangladesh  77 million people (1/2 population of crowded Bangladesh) may have been exposed to toxic levels of arsenic.  More than 20% of deaths are caused by arsenic.  Groundwater is contaminated with As
  22. 22. Health Effects and Symptoms United Kingdom (1990 and 1991)  In UK, 6000 people had the arsenic poisoning and 70 of them died.  The beer contained 15ppm of arsenic  Glucose (ingredient of beer) is contaminated to arsenic  Contaminated during the refining process
  23. 23. Health Effects and Symptoms Japan (1955)  In Japan, 12,130 children suffered from the arsenic poisoning and 130 of them died.  Milk from Tokushima factory was contaminated to arsenic  Symptoms  loss of appetite, vomiting, diarrhea, boil, skin color changed to black, anemia, hypertrophy of the liver  Aftereffect  blurred vision, hard of hearing, low score in school record, abnormal brainwave, epilepsy, headache, dizziness, cold hands and feet
  24. 24. Health Effects and Symptoms Arsenic and ADHD study (Roy et al 2010)  526 6-7 years old children in Torreon Mexico  Urinary arsenic levels were measured  No significant relationship found between any measure of urinary arsenic and parents ratings of behavior  However, higher urinary arsenic was associated with high scores on Cognitive Problem exams
  25. 25. Health Effects and Symptoms Pre- and Postnatal Arsenic Exposure and Body Size – a cohort study (Saha et al 2012)  Purpose - to assess potential effects of early life As exposure on weight and length of children from birth to 2 years of age  2372 children born in Bangladesh.  Measured arsenic concentrations in urine (U-As) with child body weight and length  Compared to girls in the first quintile of U-As (<16 µg/L), those in the fourth quintile (26-46 µg/L) were almost 300 g lighter and 0.7 cm shorter.  Postnatal arsenic exposure was associated with lower body weight and length among girls, but not boys.
  26. 26. Arsenic Regulation & Legislation EPA  Proposed a maximum contaminant level (MCL) of 5mcg/L in 2000 and established at 10mcg/L on Jan 22, 2001  This rule became enforceable on Jan 23, 2006  This standard protects public health based on the best available science and ensures that the cost of the standard is achievable
  27. 27. Arsenic Regulation & Legislation FDA  Currently only has a standard for maximum levels of As in bottled water  No inorganic As regulations in Europe and U.S. in relation to food  Only China has a regulatory limit (150 ppb)  Today, FDA is testing apple juice and trying to determine an appropriate level  Apple juice containing >23 ppb of organic arsenic represent a potential health risk
  28. 28. Arsenic Regulation & Legislation Organic Food  Organic food is not exempt from being contaminated by toxic chemicals  Organic standard do not prohibit the presence of As  Two brands of organic infant formula – 20 times more As than other regular brands  Institute for Agriculture and Trade Policy (IATP) and FDA move toward regulating As contaminant levels in the food supply
  29. 29. References