Science behind of arsenic toxicity

1. TOXICITY OF ARSENIC
Submitted by: Anuradha Dixit
2015IMSCH002

2. General Information Of Arsenic
 Chemical Formula = As
 Atomic Number =33
 Color =Lead gray, White
 Nonmagnetic
 Metalloid
 Poor Conductor Of Heat & Electricity

3. Inorganic Vs. Organic Arsenic
Inorganic Arsenic
Occurs only in soil and many
minerals
Can not be used in agricultural
Used to pressure treated wood
Arsenate(V) is found in water
• Arsenic trioxide
As2
lllO3
• Arsenic pentoxide
As2
VO5
• Sodium arsenite
NaAsIIIO2
• Sodium arsenate
Na2HAsVO4
• AsIII(OH)3
• AsVO(OH)3
Inorganic form

4. Organic arsenic
 Mainly found in marine organisms.
 Can still be used on agriculture.
 Improve properties when added to an alloy or
metal.
 Greatest use in lead acid batteries.
 Arsenite (lll) is found in water.
• Mono methyl
arsenous acid
(MMAIII)
• Dimethyl arsenous
acid (DMAIII)
Organic form

5. Environmental Sources Of Arsenic
 Marine animals
 In drinking water
 ~200 mineral species
 Most common is arsenopyrite
 Emitted from volcanoes

6. Anthropogenic Sources Of Arsenic
 Reduction of Arsenic Trioxide (As2O3 - Arsenite) with
charcoal
As2O3 is created during the metal smelting process.
 Industrial uses
Ammunition production, pigments, insecticides, rat
poison, wood preservative, semiconductors, & others

7. Routes Of Exposure To Arsenic
of the dust particles settle onto the lining of the lungs.
Majority of arsenic enters the body in the trivalent inorganic
form As(III) via a simple diffusion mechanism.
 Small amount of pentavalent inorganic arsenic can cross cell
membranes via an energy‐dependent transport system, after
which it is immediately reduced to trivalent arsenic.
When air containing arsenic dusts is breathed in, the majority

8. Mechanism Of Arsenic
 Inorganic arsenic includes arsenite [As(III)] and arsenate [As(V)]
 Arsenite – exists in +3 oxidation state
 Arsenate – exists in +5 oxidation state

9. Metabolism of inorganic arsenic involves a two‐electron reduction of
pentavalent arsenic to trivalent arsenic, mediated by glutathione, followed
by oxidative methylation to form pentavalent organic arsenic.

10. What happens to Arsenic absorbed
by body ?
 Absorption of arsenic in inhaled airborne particles is highly dependent on the solubility and
the size of particles.
 Both pentavalent and trivalent soluble arsenic compounds are rapidly and
extensively absorbed from the gastrointestinal tract.
 In many species arsenic metabolism is characterized by two main types of reactions:
(1) reduction reactions of pentavalent to trivalent arsenic, and
(2) oxidative methylation reactions in which trivalent forms of arsenic are sequentially
methylated to form mono-, di- and trimethylated products using S-adenosyl methionine (SAM)
as the methyl donor and glutathione (GSH) as an essential co-factor.
 Methylation of inorganic arsenic facilitates the excretion of inorganic arsenic from the
body, as the end-products MMA and DMA are readily excreted in urine.

11. Toxicity Of Trivalent As
Inhibits pyruvate dehydrogenase by binding to the sulfhydryl groups of dihydrolipoamide,
 resulting in a reduced conversion of Pyruvate to acetyl coenzyme A (CoA).
Citric acid cycle activity and production of cellular ATP are decreased.
Inhibits numerous other cellular enzymes through sulfhydryl group binding.
Inhibits the uptake of glucose into cells, gluconeogenesis, fatty acid oxidation and further
production of acetyl CoA.
Inhibits the production of glutathione, which protects cells against oxidative damage.

13. Toxicity Of Pentavalent As
 Pentavalent toxicity
 Very similar to phosphate
 Can substitute for inorganic phosphate in glycolytic and
cellular respiration pathways

14. Toxicity Of Pentavalent As
 Toxicity of pentavalent inorganic As is due to it’s conversion to trivalent As.
 Emulates inorganic phosphate and replaces phosphate in glycolytic and
cellular respiration pathways.
 Uncoupling of oxidative phosphorylation occurs because the normal
high‐energy phosphate bonds are not formed.
 In the presence of pentavalent arsenic, adenosine diphosphate (ADP) forms
ADP‐arsenate instead of ATP with the absence of the high‐energy ATP
phosphate bonds

15. Health Effects And Symptoms
 Acute As poisoning
 Nausea
 Vomiting
 Blood in the urine
 Cramping muscle
 Hair loss
 Stomach pain
 Organ failure
 Comma to death
 Night blindness
 Skin color change

16. Health Effects And Symptoms
77 million people (1/2 population of crowded Bangladesh) may have been
exposed to toxic levels of arsenic
Groundwater is contaminated with As.
Combustion of fossil fuels also pollutes the environment with arsenic
through atmospheric deposition when water from rains brings the arsenic to the
ground.
Recommended level of arsenic in water are less than 10-50 ug/L (10-50 parts
per billion)

17. Arsenic(III)-Reactive Coumarin
- Appended Benzothiazolines
A New Approach for Inorganic Arsenic detection.
The EPA has established a maximum contaminant level (MCL) of 10 ppb
for arsenic (As) in drinking water requiring sensitive and selective detection
methodologies.
 In this challenge scientist have been active in constructing small
molecules that react specifically with As3+ to furnish a new
fluorescent species (termed a chemodosimeter).

18.  Report in this contribution, the synthesis and spectroscopy of two small-
molecule fluorescent probes that we term ArsenoFluors (or AFs) as As-specific
chemodosimeters.
 The AFs (AF1 and AF2) incorporate a coumarin fluorescent reporter coupled
with an As-reactive benzothiazoline functional group.
 AFs react with As3+ to yield the highly fluorescent coumarin-6 dye (C6)
resulting in a 20−25 fold fluorescence enhancement at λ ∼ 500 nm with
detection limits of 0.14−0.23 ppb in tetrahydrofuran (THF) at 298 K.
 Reaction of AFs with As3+ revealed that the C6 derivatives are the ultimate end-
products of this chemistry with the formation of C6 being the principle
photoproduct responsible for the As3+ specific turn-ON

19. Structures of The As3+ Sensors (AF1 and AF2)
And The Reaction Product

20. The Fluorescence Profiles Of The AFs and
Their Potential As3+ Reaction Product

21. References
http://www.sciencedirect.com/science/article/pii/S037842740200084
X Michael.F.Hughes,Toxicology letters,Science direct,Volume-133.
 Inorg. Chem. 2013, 52, 2323−2334,Acs.Org.