Toxicity of arsenic

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 As 2 lll O 3 Arsenic pentoxide As 2 V O 5 Sodium arsenite NaAs III O 2 Sodium arsenate Na 2 HAs V O 4 As III (OH) 3 As V O(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 (MMA III ) Dimethyl arsenous acid (DMA III ) 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 (As 2 O 3 - Arsenite) with charcoal As 2 O 3 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.

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

13. 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

14. 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

15. 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)

16. 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 As 3+ to furnish a new fluorescent species (termed a chemodosimeter).

17. 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 As 3+ 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 As 3+ revealed that the C 6 derivatives are the ultimate end-products of this chemistry with the formation of C6 being the principle photoproduct responsible for the As 3+ specific turn-ON

18. Structures of The As 3+ Sensors (AF1 and AF2) And The Reaction Product

19. The Fluorescence Profiles Of The AFs and Their Potential As 3+ Reaction Product

20. References http://www.sciencedirect.com/science/article/pii/S037842740200084X Michael.F.Hughes,Toxicology letters,Science direct,Volume-133. Inorg. Chem. 2013, 52, 2323−2334,Acs.Org .