1. Arsenic

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

29. 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