Editing Arsenic poisoning (section)

===Kinetics===
The two forms of inorganic arsenic, reduced (trivalent As(III)) and oxidized (pentavalent As(V)), can be absorbed, and accumulated in tissues and body fluids.<ref name="Ueki">{{cite journal|vauthors=Ueki K, Kondo T, Tseng YH, Kahn CR |title=Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse |journal=[[Proceedings of the National Academy of Sciences of the United States of America]] |volume=101 |issue=28 |pages=10422–7 |date=July 2004 |pmid=15240880 |pmc=478587 |doi=10.1073/pnas.0402511101|bibcode = 2004PNAS..10110422U |doi-access=free }}</ref> In the liver, the metabolism of arsenic involves enzymatic and non-enzymatic methylation; the most frequently excreted metabolite (≥ 90%) in the urine of mammals is [[dimethylarsinic acid]] or cacodylic acid, DMA(V).<ref name="Vigo"/> Dimethylarsenic acid is also known as [[Agent Blue]] and was used as herbicide in the American war in [[Vietnam]].

In humans inorganic arsenic is reduced nonenzymatically from pentoxide to trioxide, using glutathione or it is mediated by enzymes. Reduction of arsenic pentoxide to arsenic trioxide increases its toxicity and bio availability, Methylation occurs through methyltransferase enzymes. S-adenosylmethionine (SAM) may serve as methyl donor. Various pathways are used, the principal route being dependent on the current environment of the cell.<ref name="thom">{{cite journal|author=Thompson DJ |title=A chemical hypothesis for arsenic methylation in mammals |journal=[[Chemico-Biological Interactions]] |volume=88 |issue=2–3 |pages=89–114 |date=September 1993 |pmid=8403081 |doi=10.1016/0009-2797(93)90086-E|bibcode=1993CBI....88...89T }}</ref> Resulting metabolites are monomethylarsonous acid, MMA(III), and dimethylarsinous acid, DMA(III).

Methylation had been regarded as a detoxification process, {{by whom|date=December 2013}} but reduction from +5 As to +3 As may be considered as a bioactivation {{clarify|date=December 2013}} instead.<ref name="vaht">{{cite journal|vauthors=Vahter M, Concha G |title=Role of metabolism in arsenic toxicity |journal=[[Pharmacology & Toxicology]] |volume=89 |issue=1 |pages=1–5 |date=July 2001 |pmid=11484904 |doi=10.1034/j.1600-0773.2001.d01-128.x|doi-broken-date=21 December 2024 }}</ref> Another suggestion is that methylation might be a detoxification if "As[III] intermediates are not permitted to accumulate" because the pentavalent organoarsenics have a lower affinity to [[thiol group]]s than inorganic pentavalent arsenics.<ref name="thom"/> Gebel (2002) stated that methylation is a detoxification through accelerated excretion.<ref name=Gebel2002>{{cite journal|author=Gebel TW |title=Arsenic methylation is a process of detoxification through accelerated excretion |journal=International Journal of Hygiene and Environmental Health |volume=205 |issue=6 |pages=505–8 |date=October 2002 |pmid=12455273 |doi=10.1078/1438-4639-00177|bibcode=2002IJHEH.205..505G }}</ref> With regard to carcinogenicity it has been suggested that methylation should be regarded as a toxification.<ref name=Kitchin2001>{{cite journal|author=Kitchin KT |title=Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites |journal=[[Toxicology and Applied Pharmacology]] |volume=172 |issue=3 |pages=249–61 |date=May 2001 |pmid=11312654 |doi=10.1006/taap.2001.9157|bibcode=2001ToxAP.172..249K |url=https://zenodo.org/record/1229982 }}</ref><ref name=Kenyon2001>{{cite journal|vauthors=Kenyon EM, Fea M, Styblo M, Evans MV |title=Application of modelling techniques to the planning of in vitro arsenic kinetic studies |journal=Alternatives to Laboratory Animals |volume=29 |issue=1 |pages=15–33 |year=2001 |pmid=11178572|doi=10.1177/026119290102900109 |s2cid=594362 |doi-access=free }}</ref><ref name=Styblo2002>{{cite journal|vauthors=Styblo M, Thomas DJ |title=Selenium modifies the metabolism and toxicity of arsenic in primary rat hepatocytes |journal=Toxicology and Applied Pharmacology |volume=172 |issue=1 |pages=52–61 |date=April 2001 |pmid=11264023 |doi=10.1006/taap.2001.9134|bibcode=2001ToxAP.172...52S }}</ref>

Arsenic, especially +3 As, binds to single, but with higher affinity to [[vicinal (chemistry)|vicinal]] [[sulfhydryl group]]s, thus reacts with a variety of [[protein]]s and inhibits their activity. It was also proposed that binding of arsenite at nonessential sites might contribute to detoxification.<ref name=Aposhian1989>{{cite journal|doi=10.1038/clpt.1989.67 |vauthors=Aposhian HV, Maiorino RM, Dart RC, Perry DF |title=Urinary excretion of meso-2,3-dimercaptosuccinic acid in human subjects |journal=Clinical Pharmacology and Therapeutics |volume=45 |issue=5 |pages=520–6 |date=May 1989 |pmid=2541962|s2cid=25174222 }}</ref> Arsenite inhibits members of the disulfide oxidoreductase family like glutathione reductase<ref name=Rodriguez2005>{{cite journal|vauthors=Rodríguez VM, Del Razo LM, Limón-Pacheco JH |title=Glutathione reductase inhibition and methylated arsenic distribution in Cd1 mice brain and liver |journal=[[Toxicological Sciences]] |volume=84 |issue=1 |pages=157–66 |date=March 2005 |pmid=15601678 |doi=10.1093/toxsci/kfi057|display-authors=etal|doi-access=free }}</ref> and thioredoxin reductase.<ref name="willi">{{cite book |first1=William N. |last1=Rom |first2=Steven B. |last2=Markowitz |title=Environmental and Occupational Medicine |publisher=Lippincott Williams & Wilkins |year=2007 |pages=1014–5 |url=https://books.google.com/books?id=H4Sv9XY296oC&pg=RA2-PA1014 |isbn=978-0-7817-6299-1 |url-status=live |archive-url=https://web.archive.org/web/20170910145312/https://books.google.com/books?id=H4Sv9XY296oC&pg=RA2-PA1014&lpg=RA2-PA1014#PRA2-PA1014,M1 |archive-date=2017-09-10 }}</ref>

The remaining unbound arsenic (≤ 10%) accumulates in cells, which over time may lead to skin, bladder, kidney, liver, lung, and prostate cancers.<ref name="Vigo">{{cite journal|author1=Vigo, J. B. |author2=J. T. Ellzey  | title = Effects of Arsenic Toxicity at the Cellular Level: A Review | journal = Texas Journal of Microscopy | volume = 37 | issue = 2 | year = 2006 | pages = 45–49}}</ref> Other forms of arsenic toxicity in humans have been observed in blood, bone marrow, cardiac, central nervous system, gastrointestinal, gonadal, kidney, liver, pancreatic, and skin tissues.<ref name="Vigo"/>

The acute minimal lethal dose of arsenic in adults is estimated to be 70 to 200&nbsp;mg or 1&nbsp;mg/kg/day.<ref name="dart">{{cite Q|Q126687121|pp=1393–1401}}</ref>