Arsenic
The Poison of
Kings
Claire M. Waggoner
Aquatic Toxicology
Structures, Physical and Chemical Properties
Symbol As
Atomic Number 33
Atomic Mass 74.9216
Electron Configuration [Ar] 3d104s24p3
Density @ 293 K 5.72 g/cm3
Melting Point 1090 K
Boiling Point 886 K (sublimes)
•Metalloid
•Yellow, white, red, gray or metallic solid
•garlic odor
•similar to phosphorous
Anthropogenic Production History
• Emerald Green paint
• Wallpaper (2.5kg/100m)
• Quack medicines
-treat syphilis pre penicillin
-Mixed w/ vinegar and chalk, eaten to whiten skin,
prevent wrinkles, and improve complexion by Victorian women
• Favorite murder weapon of the Middle Ages & Renaissance
(cholera symptoms)
• Industrial, Mining and byproducts
• Chromated copper arsenate
• Arsenopesticides: Weed killer, Rat poison, orchard/crop pesticide
• Storage batteries, Light-emitting diodes (LEDs) , solar cells, bullets
52,380 tons of As2O3 used globally in 1989
28,530 tons imported by the United States
80% used for Pesticides and wood preservatives
Chemical reactivity with water, chemical speciation, physical half-life etc
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Does not react with water in the absence of air
As pH decreases, solubility increases, becomes more mobile
Arsenic is NOT Biodegradable
Arsenic: As (metal)
Arsenic acid, sodium salt: AsH3O4.xNa
*** Arsenic trioxide (white): As2O3
Arsenic trioxide: As4O6
Arsine: AsH3
Arsenic sulphide (red): AsS, As2S2
Arsenic trisulphide (yellow): As2S3
Chromated copper arsenate (CCA)
***Inorganic arsenite: AsIII
***Inorganic arsenate: AsV
Monomethylarsonous acid (MMA)
Dimethylarsinous acid (DMA)
Organic Arsenic:
Arsenobetaine -most seafood, crustaceans
Arsenosugars –seaweed & bivalves
“Natural” As Abundance:
• 20th most abundant element in Earth’s crust
Abundance of Arsenic:
Earth's Crust: 3.4 ppm
Seawater:
•Pacific Surface: 1.45 µg/L
•Pacific Deep: 1.75 µg/L
•Colorado Lagoon: 4.9-11.3 µg/L
Sediment:
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Natural: 1-40mg/kg Ave:5mg/kg
Colorado Lagoon: 4.7-9.2 µg/dry kg
Atmosphere:
•Remote:1-3ng/m3
•Urban: 20-100 ng/m3
“Natural” As Abundance (cont):
Freshwater: 1-5000μg/L
**World Health Organization recommends 10µg/L
• Average person drinks 2L of water per day
=2-10,000μg
Levels In Humans:
•Daily Dietary Intake: 40-140 μg
•We need ~5-50 μg As a day
Total Daily intake = 42-10,140μg
.
Mode of Entry in Aquatic Environment
• Aerial deposition, rock weathering & volcanoes
• Coal & wood combustion, waste incineration
• CCA treated wood
• Seepage, leeching
• Stormwater run-off
(As-pesticides, mines, Industrial waste)
• Marsh plants can make
metals bioavailable
Mode of entry into organisms
Terrestrial:
• Inhalation
• Ingestion
• Skin and/or eye contact
Aquatic:
• Gills
• Membranes
• Ingestion
• Mantle
Toxic effects noted in Humans
Target Organs: Skin, respiratory system, kidneys, central nervous system, liver,
gastrointestinal tract, reproductive system
Direct contact with the skin: redness & swelling.
Acute:
• nausea, vomiting, and diarrhea
• abnormal heartbeat, circulatory collapse
• Respiratory failure
• Gastrointestinal, kidney & liver damage
Chronic:
• build up in skin & hair
• small corns or warts on hands & feet
• reproductive complications
• Skin, prostate, lymph, bladder, kidneys, liver, and lung cancer
• CNS damage
LD50 pure arsenic:
• 763 mg/kg (by ingestion)
• 13 mg/kg (by intraperitoneal injection)
• For a 70 kg (~155 lb) human, about 53 grams
Toxicity to aquatic life
Copepod 96-h LC50 : 27.5 μg/L for arsenic
FW Clam 96-h LC50: 20.74 mg/L (20,740 μg/L)
• As(III) bioaccumulate 300-1,000 μg/L
• As(III) regulated below 100 μg/L
Juvenile milkfish 96-h LC50: 7.29 mg/L (7,290 μg/L)
Toxic effects
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Premature Anaphase
Alteration of Chromosome Number,
Doubling of chromosome number (left)
Endoreduplication (right)
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multi-system organ failure
teratogenesis
cancer
death
Molecular mode of toxic interaction of As(III) and As(V)
Disrupts ATP Production @ Citric Acid Cycle
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Inhibits pyruvate and alpha-ketoglutarate dehydrogenase
Competes with phosphate-> uncouples oxidative phosphorylation
Toxic effects:
• Prevents reduction of NAD+
• reduces mitochondrial respiration
• Inhibits ATP synthesis
• ↑ H2O2 production
• ↑ oxidative stress
• ↑ Substrates before dehydrogenase steps (pyruvate and lactate)
Molecular mode of toxic interaction of As(III)
Binds thiol containing amino acids, peptides and proteins
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Binds to key sulfhydryl groups, inhibiting enzyme action
Glutathione(GSH) is key xenobiotic detoxifying thiol enzyme
Low protein diet  low GSH  higher arsenite induced cellular toxicity
Binds to glucocorticoid receptor
• Glucose metabolism
• Growth
• Reporoduction
• Immune function
• Anti-inflammatory response
• Fetal development
Clam up or swim away
Active transport
Sequestering via metallothionene
*Proper Diet is necessary
Blocks receptor from
activating genes
Biochemical metabolism and breakdown via METHYLATION
As(III) or As(V)
Arsenobetaine
Arsenosugars
Methyltransferase
CH3
S-adenosylmethionine
Monomethylarsonous acid (MMA)
Dimethylarsinous acid (DMA)
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Plankton and aquatic organisms have similar mechanism
Excreted in
Urine
The problem with Arsenic and METHYLATION
•DNA is also typically methylated in order to regulate the expression
genes, including oncogenes
•DNA methylation requires same methyl donor that is consumed in arsenic
methylation
•DNA is undermethylated, or hypomethylated, unable to properly regulate
gene expression
Defense strategies for detoxification by humans
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Bioassesment assays (ex. using a LacZ reporter gene to produce a pH
response to the input of arsenate/arsenite molecules)
Dried roots from water hyacinth plant can rapidly remove arsenic from water
(93-95% removal)
Specific Anion Nanoengineered Sorbents (SANS)
Bibliography
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assessment". Int J Environ Res Public Health 3 (4): 316–22. PMID 17159272
Chung-Min Liao, Sheng-Feng Jau, Wei-Yu Chen, Chieh-Ming Lin, Li-John Jou, Chen-Wuing Liu, Vivian Hsiu-Chuan Liao, Fi-John
Chang. 2008. Acute toxicity and bioaccumulation of arsenic in freshwater clam Corbicula fluminea. Environmental Toxicology.
PMID: 18344212
Elder, J.F. 1988. Metal Biogeochemistry in Surface-Water Systems - A Review of Principles and Concepts. U.S. Geological Survey
Circular 1013.
Fisher B. Testing their metal. Environ Health Perspect. 1999 May;107(5):A244-5
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Malathion, Ecotoxicology and Environmental SafetyVolume 40, Issue 3, , July 1998, Pages 239-244.
(http://www.sciencedirect.com/science/article/B6WDM-45JB84T-2T/1/8de1563c332d793057b8a0f8fef511e1) Keywords:
copepods; metals; pesticides; 96-h LC50 Knobeloch LM, Zierold KM, Anderson HA (2006). "Association of arsenic-contaminated
drinking-water with prevalence of skin cancer in Wisconsin's Fox River Valley". J Health Popul Nutr 24 (2): 206–13. PMID
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Thompson, DS. 1993. A chemical hypothesis for arsenic methylation in mammals. Chem Biol Interact. 88:89-114
Weis, J.S. and Weis, P. 2002. Contamination of saltmarsh sediments and biota by CCA treated wood walkways. Marine Pollution
Bulletin 44, 504-510
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Websites
www.usm.maine.edu/toxicology/research/arsenic.phpchromosome pictures
http://www.bnl.gov/csc/projects/Adv_Sci_Computing/Vis_Coll
aboratory/default.asp EM gill
http://www.newsobserver.com/content/news/health_science/w
ater/story_graphics/20060326_water1ArsenicEffects.jpg
***www.environmentalchemistry.comGeneral Info
****http://books.google.com/books?id=KAu4rP
foplcC&pg=PA203&lpg=PA203&dq=arsenic+mi
cronutrient&source=web&ots=Kq0245lV_Y&si
g=8knIdycB1xkNQ6BZ0NAA7H2Dywo&hl=en#
PPA211,M1 –Overview and Mechanisms
Questions. . .