This document provides an overview of arsenic, including its discovery, chemical properties, different forms (inorganic vs organic), sources (natural, anthropogenic), mechanisms of toxicity, health effects, and case studies. It discusses how arsenic interferes with cellular processes like glycolysis and the citric acid cycle through substituting for phosphate or binding to thiol groups. Both acute and chronic arsenic poisoning can cause nausea, vomiting, skin lesions, and increased cancer risk. Case studies highlight mass poisonings from contaminated food/water in Bangladesh, Japan and the UK.

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. 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. My sources
 http://www.sciencedirect.com/science/article/pii/S037842740200084X
 http://emedicine.medscape.com/article/812953-overview#a0104

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. 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 http://wewinwater.com/2011/09/03/addressing-arsenic-poisoning-in-bangladesh/
 Blushed complexion

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

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
http://www.beer100.com/beercalories.htm

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 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

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. 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. Links for effects
ADHD
http://www.sciencedirect.com/science/article/pii/S0013935111000739
Postnatal Arsenic Exposure and Body Size to Two Years of Age
http://www.ncbi.nlm.nih.gov/pubmed/22504586
Bangladesh
http://www.who.int/bulletin/archives/78(9)1093.pdf
Japan
http://www.ehjournal.net/content/5/1/31
UK
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1026413/pdf/westjmed0013