ArsenicArsenic

Claire M. WaggonerAquatic Toxicology

The Poison The Poison of Kingsof Kings

Structures, Physical and Chemical PropertiesStructures, 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 HistoryAnthropogenic 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 198928,530 tons imported by the United States

80% used for Pesticides and wood preservatives

Chemical reactivity with water, chemical speciation, physical half-life etcChemical reactivity with water, chemical speciation, physical half-life etc

• Does not react with water in the absence of air• As pH decreases, solubility increases, becomes more mobile• Arsenic is NOT BiodegradableArsenic 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, crustaceansArsenosugars –seaweed & bivalves

““Natural” As AbundanceNatural” 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/LColorado Lagoon: 4.9-11.3 µg/L

Sediment:•Natural: 1-40mg/kg Ave:5mg/kg•Colorado Lagoon: 4.7-9.2 µg/dry kgColorado Lagoon: 4.7-9.2 µg/dry kg

Atmosphere: •Remote:1-3ng/m3 •Urban: 20-100 ng/m3

““Natural” As Abundance (cont)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 EnvironmentMode of Entry in Aquatic Environment

• Aerial deposition, rock weathering & volcanoesAerial deposition, rock weathering & volcanoes

• Coal & wood combustion, waste incinerationCoal & wood combustion, waste incineration

• CCA treated woodCCA treated wood

• Seepage, leechingSeepage, leeching

• Stormwater run-off Stormwater run-off (As-pesticides, mines, Industrial waste)(As-pesticides, mines, Industrial waste)

• Marsh plants can make Marsh plants can make metals bioavailablemetals bioavailable

Mode of entry into organismsMode of entry into organisms

Terrestrial: Terrestrial: • InhalationInhalation• IngestionIngestion• Skin and/or eye contactSkin and/or eye contact

Aquatic: Aquatic: • GillsGills• MembranesMembranes• IngestionIngestion• MantleMantle

Toxic effects noted in HumansToxic 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 lifeToxicity 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 effectsToxic effects

• Premature Anaphase• Alteration of Chromosome Number,• Doubling of chromosome number (left)• Endoreduplication (right)

• multi-system organ failure• teratogenesis• cancer• death

Molecular mode of toxic interaction of As(III) and As(V)Molecular mode of toxic interaction of As(III) and As(V)

Disrupts ATP Production @ Citric Acid Cycle

• 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)Molecular mode of toxic interaction of As(III)

Binds thiol containing amino acids, peptides and proteins

• 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 awayActive transportSequestering via metallothionene

*Proper Diet is necessary

Blocks receptor from activating genes

Biochemical metabolism and breakdown via METHYLATIONBiochemical metabolism and breakdown via METHYLATION

As(III) or As(V)

Methyltransferase

S-adenosylmethionine

CH3

Monomethylarsonous acid (MMA) Dimethylarsinous acid (DMA)

Excreted in Urine

Arsenobetaine

Arsenosugars

• Plankton and aquatic organisms have similar mechanismPlankton and aquatic organisms have similar mechanism

The problem with Arsenic and METHYLATIONThe 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 humansDefense strategies for detoxification by humans

• 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)

BibliographyBibliography

Chu HA, Crawford-Brown DJ (2006). "Inorganic arsenic in drinking water and bladder cancer: a meta-analysis for dose-response 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):A244-5J. Forget, J. F. Pavillon, M. R. Menasria, G. Bocquene, Mortality and LC50Values for Several Stages of the Marine

CopepodTigriopus brevicornis(Muller) Exposed to the Metals Arsenic and Cadmium and the Pesticides Atrazine, Carbofuran, Dichlorvos, and 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 17195561

Johnson, B.L. and DeRosa, C.T. (1997) The toxicological hazard of superfund hazardous waste sites. Rev. Environ. Health.,12(4): 235-251

Kohnhorst,A., L. Allan, and P. Pokethitiyoke. Groundwater arsenic in central Thailand . SUSTAINABLE ENVIRONMENTAL SANITATION AND WATER SERVICES. 28th WEDC Conference. Kolkata (Calcutta), India, 2002. http://wedc.lboro.ac.uk/conferences/pdfs/28/Kohnhorst.pdf

Meinrut 0. Andreae. Arsenic speciation in seawater and interstitial waters: The influence of biological-chemical interactions on the chemistry of a trace element’ . Limnol. Oceanogr., 24(3), 1979,440-452 .

Shaban W. Al Rmalli, Chris F. Harrington, Mohammed Ayub and Parvez I. Haris. A biomaterial based approach for arsenic removal from water. J. Environ. Monit., 2005, 7, 279 - 282, DOI: 10.1039/b500932d

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Santos, H M; Diniz, M S; Costa, P M; Peres, I; Costa, M H; Alves, S; Capelo, J L. Environmental Toxicology [Environ. Toxicol.]. Vol. 22, no. 5, pp. 502-509. Oct 2007. MT induction

Thompson, DS. 1993. A chemical hypothesis for arsenic methylation in mammals. Chem Biol Interact. 88:89-114Weis, J.S. and Weis, P. 2002. Contamination of saltmarsh sediments and biota by CCA treated wood walkways. Marine

Pollution Bulletin 44, 504-510.  

Websiteswww.usm.maine.edu/toxicology/research/arsenic.php-chromosome pictureshttp://www.bnl.gov/csc/projects/Adv_Sci_Computing/Vis_Collaboratory/default.asp EM gillhttp://www.newsobserver.com/content/news/health_science/water/story_graphics/20060326_water1ArsenicEffects.jpg

***www.environmentalchemistry.com- General Info

****http://books.google.com/books?id=KAu4rPfoplcC&pg=PA203&lpg=PA203&dq=arsenic+micronutrient&source=web&ots=Kq0245lV_Y&sig=8knIdycB1xkNQ6BZ0NAA7H2Dywo&hl=en#PPA211,M1 –Overview and Mechanisms

Questions. . .