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Arsenic
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                                 www.en.wikipedia.com



       German chemist
       First to isolate in 1250 AD
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   http://periodictable.com/Elements/033/index.html
Inorganic vs. Organic
                                    Arsenic
Inorganic                                                                               Organic
Occurs  naturally in soil and many minerals
and 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

                            http://www.finegardening.com/design/articles/pressure-treated-wood-in-beds.aspx
Uses of Arsenic
   ‘Poison of Kings’
       Marsh and Reinsch Tests

   Bronze alloy
   Lead alloy
   Medicinal uses
       Syphili, yaws, psoriasis, and other viruses

   Industrial uses
                                                              http://biologyze.com/tag/arsenic-and-bacteria/

       Ammunition production, pigments, insecticides, rat
        poison, wood preservative, semiconductors, & others
Environmental Sources of
                        Arsenic
   Marine animals
   In drinking water
   ~200 mineral species                                                                      http://deepbluehome.blogspot.com/2010/10/deep-blue-home-
                                                                                                               snapshot-2000-2010.html
       Most common is arsenopyrite

   Emitted from volcanoes



                                      http://ebt2010.blogspot.com/2010/07/understand-whats-
                                                       arsenic-and-how-it.html




                                                                                                http://www.ecowaternorthwest.com/arsenic.php
Anthropogenic Sources of
                        Arsenic
   Reduction of Arsenic Trioxide
    (As2O3 - Arsenite) with charcoal
       As2O3 is created during the metal
        smelting process

   Industrial uses                                                                   http://www.ehow.com/how_6160537_preserve-pressure-treated-wood.html



       Ammunition production,
        pigments, insecticides, rat    http://www.indiamart.com/alchemylaboratories
                                                  /analytical-reagents.html


        poison, wood preservative,
        semiconductors, & others



                                                                                          http://serc.carleton.edu/woburn/issues/pesticides.html
Mechanism
   Inorganic
         Arsenate – exists in +5 oxidation state




         Arsenite – exists in +3 oxidation state
Mechanism (Continued)
   Organic As – methylated (both in +3 oxidation state)


       Monomethylarsonous acid (MMAIII)

       Dimethylarsinous acid (DMAIII)
Mechanism (Continued)
+ 5 oxidation state (pentavalent)   + 3 oxidation state (trivalent)


  Arsenate                          Monomethylarsonous acid (MMAIII)

                                    Dimethylarsinous acid (DMAIII)

                                    Arsenite
Mechanism (Continued)
   In general, As terrorizes the metabolic processes of
    the mitochondria




          http://www.phschool.com/science/biology_place/biocoach/cellresp/overview.html
Mechanism (Continued)
   Pentavalent toxicity


       Very similar to phosphate




       Can substitute for inorganic phosphate in glycolytic and
        cellular respiration pathways
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
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
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


                                                    http://upload.wikimedia.org/wikipedia/commons/0/0b/Citric_acid_cycle_with_aconitate_2.svg
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
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
Mechanism (Continued)
   Carcinogenicity

         ROS accumulation

         DNA Excision Repair and DNA Ligase inhibited by
          Arsenic
               Co-mutagenic effect with ROS, UV radiation,   http://www.biol.unt.edu/~jajohnson/DNA_sequencing_process


                X-Rays, and other chemicals

         DNA methylation alterations

         Also noted as a tumor promoter in mouse ovarian
          cancers
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)
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         http://wewinwater.com/2011/09/03/addressing-arsenic-poisoning-in-bangladesh/




           Blushed complexion
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




                   http://www.who.int/topics/arsenic/en/
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




                                                              http://www.beer100.com/beercalories.htm
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                                                  http://romanianrecipes.wikia.com/wiki/Milk


           blurred vision, hard of hearing, low score in school
            record, abnormal brainwave, epilepsy, headache,
            dizziness, cold hands and feet
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
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.
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
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
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
References
http://www.sciencedirect.com/science/article/pii/S037842740200084X


http://emedicine.medscape.com/article/812953-overview#a0104


http://www.sciencedirect.com/science/article/pii/S0013935111000739


http://www.ncbi.nlm.nih.gov/pubmed/22504586


http://www.who.int/bulletin/archives/78(9)1093.pdf


http://www.ehjournal.net/content/5/1/31

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Arsenic Almost Final Slides

  • 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 www.en.wikipedia.com  German chemist  First to isolate in 1250 AD
  • 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 http://periodictable.com/Elements/033/index.html
  • 4. Inorganic vs. Organic Arsenic Inorganic Organic Occurs naturally in soil and many minerals and 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 http://www.finegardening.com/design/articles/pressure-treated-wood-in-beds.aspx
  • 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 http://biologyze.com/tag/arsenic-and-bacteria/  Ammunition production, pigments, insecticides, rat poison, wood preservative, semiconductors, & others
  • 6. Environmental Sources of Arsenic  Marine animals  In drinking water  ~200 mineral species http://deepbluehome.blogspot.com/2010/10/deep-blue-home- snapshot-2000-2010.html  Most common is arsenopyrite  Emitted from volcanoes http://ebt2010.blogspot.com/2010/07/understand-whats- arsenic-and-how-it.html http://www.ecowaternorthwest.com/arsenic.php
  • 7. Anthropogenic Sources of Arsenic  Reduction of Arsenic Trioxide (As2O3 - Arsenite) with charcoal  As2O3 is created during the metal smelting process  Industrial uses http://www.ehow.com/how_6160537_preserve-pressure-treated-wood.html  Ammunition production, pigments, insecticides, rat http://www.indiamart.com/alchemylaboratories /analytical-reagents.html poison, wood preservative, semiconductors, & others http://serc.carleton.edu/woburn/issues/pesticides.html
  • 8. Mechanism  Inorganic  Arsenate – exists in +5 oxidation state  Arsenite – exists in +3 oxidation state
  • 9. Mechanism (Continued)  Organic As – methylated (both in +3 oxidation state)  Monomethylarsonous acid (MMAIII)  Dimethylarsinous acid (DMAIII)
  • 10. Mechanism (Continued) + 5 oxidation state (pentavalent) + 3 oxidation state (trivalent) Arsenate Monomethylarsonous acid (MMAIII) Dimethylarsinous acid (DMAIII) Arsenite
  • 11. Mechanism (Continued)  In general, As terrorizes the metabolic processes of the mitochondria http://www.phschool.com/science/biology_place/biocoach/cellresp/overview.html
  • 12. Mechanism (Continued)  Pentavalent toxicity  Very similar to phosphate  Can substitute for inorganic phosphate in glycolytic and cellular respiration pathways
  • 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. 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. 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 http://upload.wikimedia.org/wikipedia/commons/0/0b/Citric_acid_cycle_with_aconitate_2.svg
  • 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. 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. Mechanism (Continued)  Carcinogenicity  ROS accumulation  DNA Excision Repair and DNA Ligase inhibited by Arsenic  Co-mutagenic effect with ROS, UV radiation, http://www.biol.unt.edu/~jajohnson/DNA_sequencing_process X-Rays, and other chemicals  DNA methylation alterations  Also noted as a tumor promoter in mouse ovarian cancers
  • 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. 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 http://wewinwater.com/2011/09/03/addressing-arsenic-poisoning-in-bangladesh/  Blushed complexion
  • 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 http://www.who.int/topics/arsenic/en/
  • 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 http://www.beer100.com/beercalories.htm
  • 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 http://romanianrecipes.wikia.com/wiki/Milk  blurred vision, hard of hearing, low score in school record, abnormal brainwave, epilepsy, headache, dizziness, cold hands and feet
  • 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. 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. 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. 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. 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