Arsenic - BIOL 415 Ecotoxicology Draft


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Arsenic - BIOL 415 Ecotoxicology Draft

  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. Mechanism (Continued) Hard to link the mechanism with specific symptoms but it is clear that As is toxic via many mechanisms Symptoms and health effects of As are most likely due to combination of the various mechanisms explained. There seems to be a gap in the literature between specific biochemistry studies and general health effects/epidemiological studies.
  20. 20. My sources
  21. 21. 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)
  22. 22. Health Effects and Symptoms Chronic arsenic poisoning  High oxidative stress  affect the structure of function of cardiovascular system  Vitamin A deficiency  Night blindness  Heart disease  Increases the risk of cancer  Skin color change  Eye inflammation  Hyperkeratosis and hyperpigmentation  Blushed complexion
  23. 23. 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
  24. 24. 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
  25. 25. Health Effects and Symptoms Japan (1995)  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
  26. 26. 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
  27. 27. 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.
  28. 28. Links for effectsADHD Arsenic Exposure and Body Size to Two Years of Age