Editing Arsenic (section)

== Toxicity and precautions ==
{{Main|Arsenic poisoning}}
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| NFPA_ref =<ref>{{cite web |url=https://www.osha.gov/chemicaldata/528 |title=Arsenic, inorganic compounds (as As) |access-date=April 1, 2025 |website=Occupational Safety and Health Administration |date=April 3, 2024 }}</ref>}}
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Arsenic and many of its compounds are especially potent poisons (e.g. [[arsine]]). Small amount of arsenic can be detected by pharmacopoial methods which includes reduction of arsenic to arsenious with help of zinc and can be confirmed with mercuric chloride paper.<ref>{{Cite web |title=GENERAL TESTS, PROCESSES AND APPARATUS |url=https://www.pmda.go.jp/files/000217651.pdf|access-date=11 October 2022 |website=pmda.go.jp}}</ref>

=== Classification ===

Elemental arsenic and arsenic sulfate and trioxide compounds are classified as "[[toxicity|toxic]]" and "dangerous for the environment" in the European Union under [[directive 67/548/EEC]].
<!-- INDEX 033-001-00-X (arsenic) R23/25-50/53; S1/2-20/21-28-45-60-61 -->
<!-- INDEX 033-002-00-5 (other compounds) pareil -->The [[International Agency for Research on Cancer]] (IARC) recognizes arsenic and inorganic arsenic compounds as [[List of IARC Group 1 carcinogens|group 1 carcinogens]], and the EU lists arsenic trioxide, [[arsenic pentoxide]], and [[arsenate]] salts as category 1 [[carcinogen]]s.

Arsenic is known to cause [[Arsenic poisoning|arsenicosis]] when present in drinking water, "the most common species being arsenate [{{chem2|HAsO4(2-)}}; As(V)] and arsenite [{{chem2|H3AsO3}}; As(III)]".

=== Legal limits, food, and drink ===

In the United States since 2006, the maximum concentration in drinking water allowed by the [[Environmental Protection Agency]] (EPA) is 10&nbsp;ppb<ref>[http://water.epa.gov/lawsregs/rulesregs/sdwa/arsenic/regulations.cfm Arsenic Rule]. U.S. [[Environmental Protection Agency]]. Adopted 22 January 2001; effective 23 January 2006.</ref> and the FDA set the same standard in 2005 for bottled water.<ref name="fda_metals">{{cite web|url=https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ChemicalContaminantsMetalsNaturalToxinsPesticides/ucm360023.htm |title=Supporting Document for Action Level for Arsenic in Apple Juice |publisher=Fda.gov |access-date=2013-08-21 }}</ref> The Department of Environmental Protection for New Jersey set a drinking water limit of 5&nbsp;ppb in 2006.<ref>{{cite web|url=http://www.state.nj.us/dep/dsr/arsenic/guide.htm |title=A Homeowner's Guide to Arsenic in Drinking Water |publisher=New Jersey Department of Environmental Protection |access-date=2013-08-21 }}</ref> The [[IDLH]] (immediately dangerous to life and health) value for arsenic metal and inorganic arsenic compounds is 5&nbsp;mg/m<sup>3</sup> (5&nbsp;ppb). The [[Occupational Safety and Health Administration]] has set the [[permissible exposure limit]] (PEL) to a time-weighted average (TWA) of 0.01&nbsp;mg/m<sup>3</sup> (0.01&nbsp;ppb), and the [[National Institute for Occupational Safety and Health]] (NIOSH) has set the [[recommended exposure limit]] (REL) to a 15-minute constant exposure of 0.002&nbsp;mg/m<sup>3</sup> (0.002&nbsp;ppb).<ref name="PGCH">{{PGCH|0038}}</ref> The PEL for organic arsenic compounds is a TWA of 0.5&nbsp;mg/m<sup>3</sup>.<ref>{{PGCH|0039}}</ref> (0.5&nbsp;ppb).

In 2008, based on its ongoing testing of a wide variety of American foods for toxic chemicals,<ref>[https://www.fda.gov/Food/FoodScienceResearch/TotalDietStudy/default.htm Total Diet Study] and [https://www.fda.gov/Food/FoodborneIllnessContaminants/ChemicalContaminants/ucm2006907.htm Toxic Elements Program]</ref> the U.S. [[Food and Drug Administration]] set the "level of concern" for inorganic arsenic in apple and pear juices at 23&nbsp;ppb, based on non-carcinogenic effects, and began blocking importation of products in excess of this level; it also required recalls for non-conforming domestic products.<ref name="fda_metals" /> In 2011, the national ''[[The Dr. Oz Show|Dr. Oz]]'' television show broadcast a program highlighting tests performed by an independent lab hired by the producers. Though the methodology was disputed (it did not distinguish between organic and inorganic arsenic) the tests showed levels of arsenic up to 36&nbsp;ppb.<ref>{{cite news|author=Kotz, Deborah |url=http://www.boston.com/community/moms/articles/2011/09/14/does_apple_juice_have_unsafe_levels_of_arsenic/ |title=Does apple juice have unsafe levels of arsenic? – The Boston Globe |newspaper=Boston.com |date=14 September 2011 |access-date=2013-08-21 }}</ref> In response, the FDA tested the worst brand from the ''Dr.'' ''Oz'' show and found much lower levels. Ongoing testing found 95% of the apple juice samples were below the level of concern. Later testing by [[Consumer Reports]] showed inorganic arsenic at levels slightly above 10&nbsp;ppb, and the organization urged parents to reduce consumption.<ref>{{cite web|url=http://consumerist.com/2011/11/30/consumer-reports-study-finds-high-levels-of-arsenic-lead-in-apple-juice/|title=Consumer Reports Study Finds High Levels of Arsenic & Lead in Some Fruit Juice|author=Morran, Chris |work=Consumerist |date=30 November 2011|publisher=consumerist.com }}</ref> In July 2013, on consideration of consumption by children, chronic exposure, and carcinogenic effect, the FDA established an "action level" of 10&nbsp;ppb for apple juice, the same as the drinking water standard.<ref name="fda_metals" />

Concern about arsenic in rice in Bangladesh was raised in 2002, but at the time only Australia had a legal limit for food (one milligram per kilogram, or 1000 ppb).<ref>{{cite journal|url=http://www.nature.com/news/2002/021122/full/news021118-11.html |title= Arsenic contamination of Bangladeshi paddy field soils: Implications for rice contribution to arsenic consumption|journal=Nature |date=22 November 2002 |doi=10.1038/news021118-11 |access-date=2013-08-21 }}</ref><ref>{{cite magazine|url=https://www.newscientist.com/article/dn3141-tainted-wells-pour-arsenic-onto-food-crops.html#.UhPasx-37Vs |title=Tainted wells pour arsenic onto food crops |magazine=New Scientist |date=6 December 2002 |access-date=2013-08-21 }}</ref> Concern was raised about people who were eating U.S. rice exceeding WHO standards for personal arsenic intake in 2005.<ref>{{cite journal|author=Peplow, Mark |doi=10.1038/news050801-5 |title=US rice may carry an arsenic burden |journal= Nature News|date=2 August 2005 }}</ref> In 2011, the People's Republic of China set a food standard of 150&nbsp;ppb for arsenic.<ref>{{cite web |url = http://medicalxpress.com/news/2011-12-rice-source-arsenic-exposure.html |title = Rice as a source of arsenic exposure}}</ref>

In the United States in 2012, testing by separate groups of researchers at the Children's Environmental Health and Disease Prevention Research Center at [[Dartmouth College]] (early in the year, focusing on urinary levels in children)<ref>{{Cite journal|doi=10.1289/ehp.1205014|title=Rice Consumption and Urinary Arsenic Concentrations in U.S. Children|year=2012|last1=Davis|first1=Matthew A.|last2=MacKenzie|first2=Todd A.|last3=Cottingham|first3=Kathryn L.|last4=Gilbert-Diamond|first4=Diane|last5=Punshon|first5=Tracy|last6=Karagas|first6=Margaret R.|journal=Environmental Health Perspectives|volume=120|issue=10|pages=1418–1424|pmid=23008276|pmc=3491944|bibcode=2012EnvHP.120.1418D }}</ref> and [[Consumer Reports]] (in November)<ref>{{cite web|url=https://www.npr.org/2012/03/02/147781035/high-levels-of-arsenic-found-in-rice |title=High Levels of Arsenic Found in Rice |website=NPR.org |date=2 March 2012 |access-date=2013-08-21 }}</ref><ref name="cr_rice">{{cite web|url=http://www.consumerreports.org/cro/magazine/2012/11/arsenic-in-your-food/index.htm |title=Arsenic in Your Food {{pipe}} Consumer Reports Investigation |work=Consumer Reports |date=1 November 2012 |access-date=2013-08-21 }}</ref> found levels of arsenic in rice that resulted in calls for the FDA to set limits.<ref name="foodsafetynews">[http://www.foodsafetynews.com/2012/02/lawmakers-urge-fda-to-act-on-arsenic-standards/ Lawmakers Urge FDA to Act on Arsenic Standards]. Foodsafetynews.com (24 February 2012). Retrieved 2012-05-23.</ref> The FDA released some testing results in September 2012,<ref>{{cite web|url=https://www.fda.gov/forconsumers/consumerupdates/ucm319827.htm |title=FDA Looks for Answers on Arsenic in Rice |publisher=Fda.gov |date=19 September 2012 |access-date=2013-08-21 }}</ref><ref>{{cite web|url=https://www.fda.gov/Food/FoodborneIllnessContaminants/Metals/ucm319870.htm |title=Arsenic in Rice |publisher=Fda.gov |access-date=2013-08-21 }}</ref> and as of July 2013, is still collecting data in support of a new potential regulation. It has not recommended any changes in consumer behavior.<ref>{{cite web|url=https://www.fda.gov/Food/FoodborneIllnessContaminants/Metals/ucm319948.htm |title=Questions & Answers: FDA's Analysis of Arsenic in Rice and Rice Products |publisher=Fda.gov |date=21 March 2013 |access-date=2013-08-21 }}</ref>

Consumer Reports recommended:
# That the EPA and FDA eliminate arsenic-containing fertilizer, drugs, and pesticides in food production;
# That the FDA establish a legal limit for food;
# That industry change production practices to lower arsenic levels, especially in food for children; and
# That consumers test home water supplies, eat a varied diet, and cook rice with excess water, then draining it off (reducing inorganic arsenic by about one third along with a slight reduction in vitamin content).<ref name="cr_rice" />
# Evidence-based public health advocates also recommend that, given the lack of regulation or labeling for arsenic in the U.S., children should eat no more than 1.5 servings per week of rice and should not drink rice milk as part of their daily diet before age 5.<ref name="berkeleywellness">{{cite web|title=Arsenic in Rice: What You Need to Know|url=http://www.berkeleywellness.com/healthy-eating/food-safety/article/arsenic-rice-should-you-worry|website=UC Berkeley Wellness|access-date=3 September 2014}}</ref> They also offer recommendations for adults and infants on how to limit arsenic exposure from rice, drinking water, and fruit juice.<ref name="berkeleywellness" />
A 2014 [[World Health Organization]] advisory conference was scheduled to consider limits of 200–300&nbsp;ppb for rice.<ref name="cr_rice" />

====Reducing arsenic content in rice====
[[File:Improved rice cooking approach to maximise arsenic removal while preserving nutrient elements.jpg|thumb|300px|An improved rice cooking approach to maximise arsenic removal while preserving nutrient elements<ref name="cookingmethod" />]]
In 2020, scientists assessed multiple preparation procedures of rice for their capacity to reduce arsenic content and preserve nutrients, recommending a procedure involving [[Parboiling#Parboiled rice|parboiling]] and water-absorption.<ref>{{cite news |title=New way of cooking rice removes arsenic and retains mineral nutrients, study shows |url=https://phys.org/news/2020-11-cooking-rice-arsenic-retains-mineral.html |access-date=10 November 2020 |work=phys.org |language=en}}</ref><ref name="cookingmethod">{{cite journal |title=Improved rice cooking approach to maximise arsenic removal while preserving nutrient elements |journal=Science of the Total Environment |date=29 October 2020 |pages=143341 |doi=10.1016/j.scitotenv.2020.143341 |last1=Menon |first1=Manoj |last2=Dong |first2=Wanrong |last3=Chen |first3=Xumin |last4=Hufton |first4=Joseph |last5=Rhodes |first5=Edward J. |volume=755 |issue=Pt 2 |pmid=33153748 |doi-access=free }}</ref><ref>{{cite news |title=How much arsenic is in your rice? Consumer Reports' new data and guidelines are important for everyone but especially for gluten avoiders |url=https://www.consumerreports.org/cro/magazine/2015/01/how-much-arsenic-is-in-your-rice/index.htm |access-date=15 February 2022 |work=consumerreports.org}}</ref>

=== Occupational exposure limits ===

{| class="wikitable"
!Country
!Limit<ref>{{Cite web|url = https://www.cdc.gov/niosh-rtecs/CG802C8.html|title = Arsenic|website = RTECS|date = 28 March 2018|publisher = National Institute for Occupational Safety and Health (NIOSH)}}</ref>
|-
|[[Argentina]]
|Confirmed human carcinogen
|-
|Australia
|TWA 0.05&nbsp;mg/m<sup>3</sup> – Carcinogen
|-
|[[Belgium]]
|TWA 0.1&nbsp;mg/m<sup>3</sup> – Carcinogen
|-
|[[Bulgaria]]
|Confirmed human carcinogen
|-
|Canada
|TWA 0.01&nbsp;mg/m<sup>3</sup>
|-
|[[Colombia]]
|Confirmed human carcinogen
|-
|[[Denmark]]
|TWA 0.01&nbsp;mg/m<sup>3</sup>
|-
|[[Finland]]
|Carcinogen
|-
|[[Egypt]]
|TWA 0.2&nbsp;mg/m<sup>3</sup>
|-
|[[Hungary]]
|Ceiling concentration 0.01&nbsp;mg/m<sup>3</sup> – Skin, carcinogen
|-
|India
|TWA 0.2&nbsp;mg/m<sup>3</sup>
|-
|Japan
|Group 1 carcinogen
|-
|[[Jordan]]
|Confirmed human carcinogen
|-
|Mexico
|TWA 0.2&nbsp;mg/m<sup>3</sup>
|-
|New Zealand
|TWA 0.05&nbsp;mg/m<sup>3</sup> – Carcinogen
|-
|[[Norway]]
|TWA 0.02&nbsp;mg/m<sup>3</sup>
|-
|[[Philippines]]
|TWA 0.5&nbsp;mg/m<sup>3</sup>
|-
|[[Poland]]
|TWA 0.01&nbsp;mg/m<sup>3</sup>
|-
|Singapore
|Confirmed human carcinogen
|-
|[[South Korea]]
|TWA 0.01&nbsp;mg/m<sup>3</sup><ref>[http://www.kosha.or.kr/content/safetyinfo/안전보건기술지침_제정현황1.xls Korea Occupational Safety & Health Agency] {{Webarchive|url=https://web.archive.org/web/20170123114742/http://www.kosha.or.kr/content/safetyinfo/%EC%95%88%EC%A0%84%EB%B3%B4%EA%B1%B4%EA%B8%B0%EC%88%A0%EC%A7%80%EC%B9%A8_%EC%A0%9C%EC%A0%95%ED%98%84%ED%99%A91.xls |date=23 January 2017 }}. kosha.or.kr</ref>
|-
|Sweden
|TWA 0.01&nbsp;mg/m<sup>3</sup>
|-
|[[Thailand]]
|TWA 0.5&nbsp;mg/m<sup>3</sup>
|-
|[[Turkey]]
|TWA 0.5&nbsp;mg/m<sup>3</sup>
|-
|United Kingdom
|TWA 0.1&nbsp;mg/m<sup>3</sup>
|-
|United States
|TWA 0.01&nbsp;mg/m<sup>3</sup>
|-
|[[Vietnam]]
|Confirmed human carcinogen
|}

=== Ecotoxicity ===

Arsenic is [[bioaccumulation|bioaccumulative]] in many organisms, marine species in particular, but it does not appear to biomagnify significantly in food webs.<ref>{{cite journal |last1=Gaion |first1=Andrea |last2=Sartori |first2=Davide |last3=Scuderi |first3=Alice |last4=Fattorini |first4=Daniele |title=Bioaccumulation and biotransformation of arsenic compounds in Hediste diversicolor (Muller 1776) after exposure to spiked sediments |journal=Environmental Science and Pollution Research |date=May 2014 |volume=21 |issue=9 |pages=5952–5959 |doi=10.1007/s11356-014-2538-z |pmid=24458939 |bibcode=2014ESPR...21.5952G |s2cid=12568097 }}</ref> In polluted areas, plant growth may be affected by root uptake of arsenate, which is a phosphate analog and therefore readily transported in plant tissues and cells. In polluted areas, uptake of the more toxic arsenite ion (found more particularly in reducing conditions) is likely in poorly-drained soils.

=== Toxicity in animals ===
{| class="wikitable"
!Compound
!Animal
!LD<sub>50</sub>
!Route
|-
|Arsenic
|Rat
|763&nbsp;mg/kg
|oral
|-
|Arsenic
|Mouse
|145&nbsp;mg/kg
|oral
|-
|[[Calcium arsenate]]
|Rat
|20&nbsp;mg/kg
|oral
|-
|Calcium arsenate
|Mouse
|794&nbsp;mg/kg
|oral
|-
|Calcium arsenate
|Rabbit
|50&nbsp;mg/kg
|oral
|-
|Calcium arsenate
|Dog
|38&nbsp;mg/kg
|oral
|-
|[[Lead arsenate]]
|Rabbit
|75&nbsp;mg/kg
|oral
|}

{| class="wikitable"
!Compound
!Animal
!LD<sub>50</sub><ref name="Hughes" />
!Route
|-
|Arsenic trioxide (As(III))
|Mouse
|26&nbsp;mg/kg
|oral
|-
|Arsenite (As(III))
|Mouse
|8&nbsp;mg/kg
|im
|-
|Arsenate (As(V))
|Mouse
|21&nbsp;mg/kg
|im
|-
|MMA (As(III))
|Hamster
|2&nbsp;mg/kg
|ip
|-
|MMA (As(V))
|Mouse
|916&nbsp;mg/kg
|oral
|-
|DMA (As(V))
|Mouse
|648&nbsp;mg/kg
|oral
|-
| colspan="4" |im = injected intramuscularly
ip = administered intraperitoneally
|}

=== Biological mechanism ===

Arsenic's toxicity comes from the affinity of arsenic(III) oxides for [[thiol]]s. Thiols, in the form of [[cysteine]] residues and [[Cofactor (biochemistry)|cofactors]] such as [[lipoic acid]] and [[coenzyme A]], are situated at the active sites of many important [[enzyme]]s.<ref name="Ullmann" />

Arsenic disrupts [[Adenosine triphosphate|ATP]] production through several mechanisms. At the level of the [[citric acid cycle]], arsenic inhibits [[lipoic acid]], which is a cofactor for [[pyruvate dehydrogenase]]. By competing with phosphate, arsenate uncouples [[oxidative phosphorylation]], thus inhibiting energy-linked reduction of [[Nicotinamide adenine dinucleotide|NAD+]], mitochondrial respiration and ATP synthesis. Hydrogen peroxide production is also increased, which, it is speculated, has potential to form reactive oxygen species and oxidative stress. These metabolic interferences lead to death from multi-system [[organ failure]]. The organ failure is presumed to be from [[necrotic]] cell death, not [[apoptosis]], since energy reserves have been too depleted for apoptosis to occur.<ref name="Hughes">{{cite journal |doi = 10.1016/S0378-4274(02)00084-X |title = Arsenic toxicity and potential mechanisms of action |date = 2002 |last1 = Hughes |first1 = Michael F. |journal = Toxicology Letters |volume = 133 |pages = 1–16 |pmid = 12076506 |issue = 1| url = https://zenodo.org/record/1260065 }}</ref>
<!--A [[post mortem]] in an arsenic poisoning death reveals brick-red-colored [[mucosa]], owing to severe [[hemorrhage]]. copyright violation from http://rfppl.com/subscription/upload_pdf/Art%204_415.pdf if we need it there is another ref 10.1080/10643389991259227 -->

=== Exposure risks and remediation ===

Occupational exposure and [[arsenic poisoning]] may occur in people working in industries involving the use of inorganic arsenic and its compounds, such as wood preservation, glass production, nonferrous metal alloys, and electronic semiconductor manufacturing. Inorganic arsenic is also found in coke oven emissions associated with the smelter industry.<ref>{{cite web
|url= https://www.osha.gov/SLTC/arsenic/index.html
|title=OSHA Arsenic
|access-date=2007-10-08
|publisher=United States Occupational Safety and Health Administration
| archive-url= https://web.archive.org/web/20071012033424/https://www.osha.gov/SLTC/arsenic/index.html| archive-date= 12 October 2007|url-status = live}}</ref>

The conversion between As(III) and As(V) is a large factor in arsenic environmental contamination. According to Croal, Gralnick, Malasarn and Newman, "[the] understanding [of] what stimulates As(III) oxidation and/or limits As(V) reduction is relevant for [[bioremediation]] of contaminated sites (Croal). The study of chemolithoautotrophic As(III) oxidizers and the heterotrophic As(V) reducers can help the understanding of the oxidation and/or reduction of arsenic.<ref>{{cite journal |title=The Genetics of Geochemisty |journal=Annual Review of Genetics |volume=38 |date=2004 |pages=175–206 |pmid=15568975 |doi=10.1146/annurev.genet.38.072902.091138 |last1=Croal |first1=Laura R. |last2=Gralnick |first2=Jeffrey A. |last3=Malasarn |first3=Davin |last4=Newman |first4=Dianne K. |url=http://authors.library.caltech.edu/286/ |access-date=30 August 2017 |archive-date=18 September 2021 |archive-url=https://web.archive.org/web/20210918094902/http://authors.library.caltech.edu/286/ |url-status=dead }}</ref>

=== Treatment ===

Treatment of chronic arsenic poisoning is possible. British anti-lewisite ([[dimercaprol]]) is prescribed in doses of 5&nbsp;mg/kg up to 300&nbsp;mg every 4&nbsp;hours for the first day, then every 6&nbsp;hours for the second day, and finally every 8&nbsp;hours for 8 additional days.<ref>{{cite book|author1=Giannini, A. James |author2=Black, Henry Richard |author3=Goettsche, Roger L. |title=The Psychiatric, Psychogenic and Somatopsychic Disorders Handbook|isbn=978-0-87488-596-5 |location=New Hyde Park, NY|publisher=Medical Examination Publishing Co |date=1978 |pages=81–82}}</ref> However the USA's [[Agency for Toxic Substances and Disease Registry]] (ATSDR) states that the long-term effects of arsenic exposure cannot be predicted.<ref name="atsdr.cdc.gov" /> Blood, urine, hair, and nails may be tested for arsenic; however, these tests cannot foresee possible health outcomes from the exposure.<ref name="atsdr.cdc.gov" /> Long-term exposure and consequent excretion through urine has been linked to [[Bladder cancer|bladder]] and [[kidney cancer]] in addition to cancer of the liver, prostate, skin, lungs, and [[nasal cavity]].<ref>{{cite web |url=http://www.atsdr.cdc.gov/toxguides/toxguide-2.pdf?id=21&tid=3 |title=The tox-guide for arsenic |year=2007 |series=The US [[Agency for Toxic Substances and Disease Registry]] |publisher=U.S. [[Center for Disease Control]] |via=atsdr.cdc.gov }}</ref>