Arsenic is a metalloid occurring in several minerals. It can be found in both organic and inorganic forms, as well as in combination with sulfur and metals. Arsenic is also the topic of this blog post for metal toxicity.
My name is Stacey Dillion, and I chose this metal for – even I will admit – a slightly bizarre reason; I love the musical “Chicago”. When selecting metals for this post, I read the list and a got a very clear mental image of a specific scene after seeing “arsenic” as an option. For that reason, I elected to dive into further research. Please be advised; the media in the content below are derived from both multimedia and published literature. Figures with numeric representation are those found in the corresponding literature, those with alphabetic representation are derived from multimedia.
(there is a link here for the scene itself, but given the…nature…of the content, I’ll leave it at that ) .
So, without further ado, I present to you an overview of arsenic!
(a)
- Source (1, 7)
- Inorganic arsenic compounds are found in soil, sediments, and ground water
- Occur naturally as a result of mining, ore smelting, and industrial use of arsenic
- Ground water is the leading source of arsenic exposure
- Organic arsenic compounds are found mainly in fish and shellfish
- Organic arsenic compounds are typically considered less toxic than inorganic compounds
- Inorganic arsenic compounds are found in soil, sediments, and ground water
- Biotransformation (2)
- Methylation occurs in the body by alternating reduction of pentavalent arsenic to trivalent with the addition of a methyl group from S-adenosylmethionine.
- Glutathione may also serve as a reducing agent
- The liver is the most important site of arsenic methylation
- The end metabolites are methylarsonic acid (MMA) and dimethylarsinic acid (DMA)
- MMA and DMA are less reactive and excreted in the urine
- Intermediate reduced forms of MMA and DMA can be formed
- MMA(III) and DMA(III) are methylated metabolites that are highly toxic and detectible in urine
- Reactive intermediates may be formed, such as absorbed arsenate (As(V))
- (As(V)) reduces rapidly in the blood to As(III) and is highly toxic
- Methylation occurs in the body by alternating reduction of pentavalent arsenic to trivalent with the addition of a methyl group from S-adenosylmethionine.
- Toxicokinetics (3)
- Absorbed through the GI tract
- Distributes to all tissues
- Metabolized in the liver
- Eliminated through bile and kidneys, primarily excreted through urine
- Elimination can be direct through feces without absorption, or through feces and urine following plasma or tissue absorption
(3)
- Carcinogenicity (4)
- Chronic exposure to arsenic through drinking water has been linked to an increased risk of bladder cancer and skin cancer
- Medical exposure to arsenic has been linked to skin cancer
- Cancers of the lung, digestive tract, liver, kidney, lymphatic, and hematopoietic systems have also been linked to arsenic
- Mechanism of action (6, 7)
- The exact mechanism of action is unknown
- Several theories exist
- Inorganic arsenic in a pentavalent state may replace phosphate in several reactions
- Inorganic and organic (methylated) arsenic in the trivalent state may react with critical thiols in proteins and inhibit their activity
- Potential mechanisms of carcinogenicity include genotoxicity, altered DNA methylation, oxidative stress, altered cell proliferation, co-carcinogenesis, and tumor promotion
- Arsenic may inactivate up to 200 enzymes, particularly those associated with cellular energy pathways and DNA synthesis and repair
- Target organs (8)
(c)
- Kidney and liver
- Highest concentrations are typically found in the liver (as demonstrated in figure (c) ). Concentrations above 0.01 parts per million (ppm) are considered toxic.
- Kidney and liver
- Signs and Symptoms of Toxicity (1,5,7,9)
- Acute
- Nausea, vomiting, diarrhea, abdominal pain, dehydration, shock
- Extreme cases can include numbness and tingling in the extremities, muscle cramping, and death
- Treatment for acute poisoning includes:
-
- IV fluids and gastric lavage
- Administration of activated charcoal with a cathartic such as sorbitol is frequently recommended
- The efficacy of activated charcoal is still under consideration
- If diarrhea is severe, cathartics should not be administered
- Hemodialysis may be beneficial if the patient presents with concomitant renal failure
- Dimercaperol (BAL), DMPS, and DMSA are the most common chelating agents recommended for acute arsenic poisoning
- These should be used with caution due to their known adverse side effects
-
- Chronic
- Skin disorders, increased risk of diabetes, high blood pressure, several types of cancer
- Skin disorders can include changes in pigmentation, lesions, and hard patches (hyperkeratosis) of the palms and soles of feet
- These occur after at least 5 years of chronic exposure and may be a precursor to skin cancer
- Skin disorders can include changes in pigmentation, lesions, and hard patches (hyperkeratosis) of the palms and soles of feet
- Treatment for chronic exposure includes the removal of high-level drinking water
-
- Substitution of high-arsenic sources with low-arsenic sources such as rain water treated with surface water
- Identifying handpumps of high-arsenic sources with a different color paint than the handpumps attached to low-arsenic sources, or “do not drink” labels (as shown in figure (d) )
- Blend high and low sources to achieve a lower concentration
- Installation of arsenic removal systems
- Technologies for this technique include oxidation, coagulation-precipitation, absorption, ion exchange, and membrane techniques.
- There are no evidence-based treatments for chronic arsenic poisoning
- Antioxidants have been proposed, but their benefit is not proven
-
- Skin disorders, increased risk of diabetes, high blood pressure, several types of cancer
- Acute
(d)
- Genetic Susceptibility or Heritable Traits (5, 8, 10)
- In utero and early childhood exposure has been linked to cognitive development deficit and deaths in young adults
- Arsenic exposure has been associated with elevated Reactive Oxygen Species (ROS) and disruption of neuro-skeletal integrity
- Increased ROS can lead to oxidative stress, DNA damage, dopaminergic neuron degeneration, decreased antioxidant enzymes, and increased lipid peroxidation
- Associated conditions include impaired learning and memory and Parkinson’s Disease
- Disruption of neuro-skeletal integrity can reduce nerve conduction velocity leading to peripheral neuropathy and neuropathic pain
- A visual representation of this is shown in figure 8
- Increased ROS can lead to oxidative stress, DNA damage, dopaminergic neuron degeneration, decreased antioxidant enzymes, and increased lipid peroxidation
- Data collected from 2011-2012 nutrition examination surveys indicate Asian Americans tend to have significantly higher levels of arsenic detected in their urine as compared to several other races
- This is thought to be due to dietary patterns
- A graph representing this data is shown in figure 10
(8) 
(10)
- Historical or Unique Exposures (1, 5)
- People are most likely exposed to arsenic through drinking water
- Exposure can also be due to foods such as rice or seafood
- WHO recognizes at least 140 million people in 50 countries consuming drinking water containing arsenic above the provisional guideline of 10ug/L. A visual representation of countries at risk, as well as those without data, is shown in figure (b).
- Arsenic recognition and contamination prevention gathered significant attention in 1990s when Bangladesh was identified to have highly toxic levels found in well-water. Since then, the number of people exposed has dropped by roughly 40%, however in 2012 it was estimated roughly 21% of all deaths in the country were arsenic related.
- Arsenic poisoning has also been a theme in both fiction and non-fiction. Please see the video at the bottom this post!
(b)
- Monitoring (10, 11)
- Biomonitoring is used for acute exposure risks rather than chronic
- X-ray fluorescence is a promising technology used for detecting and measuring inorganic arsenic in soil without requiring aqueous soil extractions
- Testing (12)
- Acute exposures can be tested through urine
- Environmental testing can be completed through chromatography, optical methods, and mass spectrometry
- Biomarkers (10, 13)
- Acute exposure can be determined by detection of arsenic in the hair, nails, blood, or urine
- Presence of arsenic in these samples can indicate systemic absorption, but can also be complicated by potential external sources
- I.E.; arsenic found in samples of nails can be due to systemic absorption or because the patient touched something contaminated with arsenic but never ingested it.
- Evidence of arsenic in finger nails can be seen with Mees’ Lines, as show in figure (f)
(f)
- Presence of arsenic in these samples can indicate systemic absorption, but can also be complicated by potential external sources
- Acute exposure can be determined by detection of arsenic in the hair, nails, blood, or urine
- Essentiality (14, 15)
- Trace levels of arsenic are thought to be essential to grow and maintain a healthy nervous system
- Levels above 0.00001% are considered greater-than-trace
- Several animal studies have demonstrated that trace levels of arsenic are essential when methionine metabolism is stressed (pregnancy, lactation), however these results have not been translated to human nutritional guidelines
- Recommendations based on this article are 12µg/day for humans, however these recommendations have not been substantiated in the 30 years since publication
- Trace levels of arsenic are thought to be essential to grow and maintain a healthy nervous system
- Deficiency
- I have not been able to find a single source with substantial evidence of concerns related to arsenic deficiency
- Notes of Special Interest
- Arsenic poisoning is a common theme in both fiction and history – I refer back to my original inspiration for choosing this metal, briefly mentioned in “Chicago”
- This short video (complete with more rubber ducks than I’ve ever known a single person to own…) gives a brief summary of a few historical and fictional recounts of arsenic poisoning, antiquated methods of arsenic detection, and finishes with a minor rant about the salt content of soy sauce (not related, but the rest of the video is interesting, enjoy!)
(e)
Links to all sources can be found below in Content References:
1) Arsenic Factsheet | National Biomonitoring Program | CDC. www.cdc.gov. Published May 24, 2019. https://www.cdc.gov/biomonitoring/Arsenic_FactSheet.html#:~:text=Inorganic%20arsenic%20compounds%20are%20in. Accessed June 4, 2022
2) Vahter M. Mechanisms of arsenic biotransformation. Toxicology. 2002;181-182:211-217. doi:10.1016/s0300-483x(02)00285-8
To read more, please follow this link: https://pubmed.ncbi.nlm.nih.gov/12505313/
3) Chakraborti, Dipankar & Rahman, Mohammad Mahmudur & Das, B. & Nayak, Bishwajit & Pal, Arup & Sengupta, Mrinal & Hossain, Md & Ahamed, Sad & Sahu, Manabendranath & Saha, Kshitish & Mukherjee, Subhash & Pati, Shyamapada & Dutta, Rathindra & Quamruzzaman, Quazi. (2013). Groundwater arsenic contamination in Ganga–Meghna–Brahmaputra plain, its health effects and an approach for mitigation. Environmental Earth Sciences. 70. 10.1007/s12665-013-2699-y.
To read more, please follow this link: https://www.researchgate.net/figure/Illustration-of-the-absorption-distribution-metabolism-and-elimination-ADME-of_fig1_258168267
4) Arsenic – Cancer-Causing Substances. National Cancer Institute. Published December 31, 2018. https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/arsenic#:~:text=Which%20cancers%20are%20associated%20with
To read more, please follow this link: https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/arsenic#:~:text=Which%20cancers%20are%20associated%20with,skin%20cancer%20in%20epidemiological%20studies.
5) WHO. Arsenic. Who.int. Published February 15, 2018. https://www.who.int/news-room/fact-sheets/detail/arsenic. Accessed June 4, 2022
To read more, please follow this link: https://www.who.int/news-room/fact-sheets/detail/arsenic
6) Hughes MF. Arsenic toxicity and potential mechanisms of action. Toxicol Lett. 2002;133(1):1-16. doi:10.1016/s0378-4274(02)00084-x
To read more, please follow this link: https://pubmed.ncbi.nlm.nih.gov/12076506/
7) Ratnaike RN. Acute and chronic arsenic toxicity. Postgraduate Medical Journal. 2003;79(933):391-396. doi:10.1136/pmj.79.933.391
To read more, please follow this link: https://pmj.bmj.com/content/79/933/391
8) Kaur T, Singh A, Goel R. Mechanisms pertaining to arsenic toxicity. Toxicology International. 2011;18(2):87. doi:10.4103/0971-6580.84258
To read more, please follow this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183630/#:~:text=%5B62%2C63%5D%20The%20kidney,both%20hepatic%20and%20renal%20tissue
9) Arsenic Toxicity: How Should Patients Overexposed to Arsenic Be Treated and Managed? | Environmental Medicine | ATSDR. www.atsdr.cdc.gov. Published February 9, 2021. https://www.atsdr.cdc.gov/csem/arsenic/patient_exposed.html
To read more, please follow this link: https://www.atsdr.cdc.gov/csem/arsenic/patient_exposed.html
10) Biomonitoring Arsenic: Facts and Figures – MN Data. State.mn.us. Published 2009. https://data.web.health.state.mn.us/biomonitoring_arsenic
To read more, please follow this link: https://data.web.health.state.mn.us/biomonitoring_arsenic
11) Monitoring Arsenic in the Environment: A Review of Science and Technologies for Field Measurements and Sensors. Accessed June 4, 2022. https://clu-in.org/download/char/arsenic_paper.pdf
To read more, please follow this link: https://clu-in.org/download/char/arsenic_paper.pdf
12) Rajakovic L, Rajakovic-Ognjanovic V. Arsenic in Water: Determination and Removal. IntechOpen; 2018. https://www.intechopen.com/chapters/61143
To read more, please follow this link: https://www.intechopen.com/chapters/61143
13) Hughes MF. Biomarkers of exposure: a case study with inorganic arsenic. Environ Health Perspect. 2006;114(11):1790-1796. doi:10.1289/ehp.9058
To read more, please follow this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665401/#:~:text=Arsenic%20biomarkers%20of%20exposure%20include,can%20complicate%20the%20exposure%20analysis.
14) Pedersen T. Facts About Arsenic. Live Science. Published July 28, 2016. https://www.livescience.com/29522-arsenic.html
To read more, please follow this link: https://www.livescience.com/29522-arsenic.html
15) Uthus EO. Evidence for arsenic essentiality. Environ Geochem Health. 1992;14(2):55-58. doi:10.1007/BF01783629
To read more, please follow this link: https://pubmed.ncbi.nlm.nih.gov/24197927/
Multimedia References:
a) Team HJ. Arsenic sources, arsenic in food and water. Arsenic poisoning symptoms. Health Jade. Published October 21, 2018. https://healthjade.net/arsenic/. Accessed June 4, 2022
b) map_showing_estimated_risk.png. serc.carleton.edu. Accessed June 4, 2022. https://serc.carleton.edu/details/images/150833.html
c) New drug targets for a rare kidney and liver disease. Drug Target Review. Published 2017. https://www.drugtargetreview.com/news/25147/new-drug-targets-kidney-liver-disease/
d) Bangladesh failing to spare millions from arsenic poisoning. Tampa Bay Times. https://www.tampabay.com/news/world/bangladesh-failing-to-spare-millions-from-arsenic-poisoning/2272251/
e) Dr. Joe Schwarcz: All about arsenic. www.youtube.com. Accessed November 13, 2021. https://www.youtube.com/watch?v=7hUw6_t_Y4o
f) Team HJ. Mees lines fingernails causes, symptoms & treatment. Health Jade. Published March 25, 2020. https://healthjade.net/mees-lines/