Metal toxicity explained

Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, or are toxic when in a certain form.^[1] In the case of lead, any measurable amount may have negative health effects.^[2] There is a popular misconception that only heavy metals can be toxic, but lighter metals such as beryllium and lithium can be toxic too.^[3] Not all heavy metals are particularly toxic, and some are essential, such as iron. The definition may also include trace elements when abnormally high doses may be toxic. An option for treatment of metal poisoning may be chelation therapy, a technique involving the administration of chelation agents to remove metals from the body.

Toxic metals sometimes imitate the action of an essential element, interfering with the metabolic processes resulting in illness. Many metals, particularly heavy metals are toxic, but some are essential, and some, such as bismuth, have a low toxicity. Metals in an oxidation state abnormal to the body may also become toxic: chromium(III) is an essential trace element, but chromium(VI) is a carcinogen.

Only soluble metal-containing compounds are toxic. Soluble metals are called coordination complexes, which consist of a metal ion surrounded by ligands. Ligands can range from water in metal aquo complexes to methyl groups as in tetraethyl lead. Usually metal complexes consist of a mixture of ligands.

Toxic metal complexes can be detoxified by conversion to insoluble derivatives or (ii) by encasing in rigid molecular environments using chelating agents. Alternatively, when very dilute, metal complexes are often innocuous.^[4] This method uses plants to extract and lower the concentration of toxic heavy metals in the soil. An aspirational method of decontamination of heavy metals is phytoremediation or bioremediation, but these approaches have solved few real world problems.

Toxic metals can bioaccumulate in the body and in the food chain.^[5] Therefore, a common characteristic of toxic metals is the chronic nature of their toxicity. This is particularly notable with radioactive heavy metals such as radium, which imitates calcium to the point of being incorporated into human bone, although similar health implications are found in lead or mercury poisoning.

Major types of metal poisoning

Arsenic poisoning

See main article: Arsenic poisoning. A dominant kind of metal toxicity is arsenic poisoning. This problem mainly arises from ground water that naturally contains high concentrations of arsenic. A 2007 study found that over 137 million people indicates that more than 70 countries may be affected by arsenic poisoning from drinking water.^[6]

Lead poisoning

Lead poisoning, in contrast to arsenic poisoning, is inflicted by industry. Most lead on the planet is immobilized as minerals, which are relatively harmless. Two major sources of lead poisoning are leaded gasoline and lead leached from plumbing (from Latin, plumbus for lead). Use of leaded gasoline has declined precipitously since the 1970s.^{[7] [8]} One lead-containing pigments is lead chromate (the yellow-orange of U.S. school buses), but this material is so stable and so insoluble that little evidence exists for its toxicity.

Toxicities from essential metals

Many metal ions are required for life. Even in these cases, a large excess of these ions can prove toxic.

• Cobalt poisoning
• Copper poisoning
• Iron poisoning
• Manganese poisoning was first identified in 1837 by James Couper.^[9]
• Selenium poisoning has been observed even though Se is an essential trace element. The Tolerable Upper Intake Level is 400 micrograms per day. Additional Se intake can lead to selenosis.^[10] Signs and symptoms of selenosis include a garlic odor on the breath, gastrointestinal disorders, hair loss, sloughing of nails, fatigue, irritability, and neurological damage.
• Zinc toxicity has been seen to occur at ingestion of greater than 225 mg of zinc.^[11] Excessive absorption of zinc can suppress copper and iron absorption. The free zinc ion in solution is highly toxic to bacteria, plants, invertebrates, and even vertebrate fish.^{[12] [13] [14]}

Toxicities from nonessential metals

No global mechanism exists for the toxicities of these metal ions. Excessive exposure, when it occurs, typically is associated with industrial activities.

• Beryllium poisoning is attributed to the ability of Be²⁺ to replace Mg²⁺ in some enzymes. Be has been classified by one agency as a carcinogen.^[15]
• Cadmium poisoning came into focus with the discovery of the Itai-itai disease due to cadmium contaminated waters resulting from mining in the Toyama Prefecture starting around 1912.^[16] The term refers to the severe pains (Japanese: 痛い itai) people with the condition felt in the spine and joints. Cd2+ is thought to accumulate in the kidneys, where it tightly binds to the sulfur in cysteine-containing proteins.
• Lithium toxicity arises from overdose of lithium-containing drugs.^[17]
• Mercury poisoning came into sharp focus with the discovery of Minamata disease, named for the Japanese city of Minamata. In 1956, a factory in that city released of methylmercury in the industrial wastewater resulting in thousands of deaths and many other health problems.^[18] This incident alerted the world to the phenomenon of bioaccumulation. While all mercury compounds are toxic, organomercury compounds are especially dangerous because they are more mobile. Methyl mercury and related compounds are thought to bind to the sulfur of cysteinyl residues in proteins.

• Silver poisoning,^[19] like lithium poisoning, arises from misapplication of medications. A dramatic symptom of "argyria" is that the skin turns blue or bluish-grey.^[20]
• Thallium poisoning has been observed on several occasions, and it is well known that thallium compounds are highly toxic. Nonetheless, incidents of thallium poisoning are few.^[21] Tl is located on the periodic table near two other highly toxic metals, mercury and lead.
• Tin poisoning from tin metal, its oxides, and its salts are "almost unknown"; on the other hand certain organotin compounds are almost as toxic as cyanide. Such organotin compounds were once widely used as anti-fouling agents.^[22]

Treatment for poisoning

Chelation therapy

See main article: Chelation. Chelation therapy is a medical procedure that involves the administration of chelating agents to remove or deactivate heavy metals from the body. Chelating agents are molecules that form particularly stable coordination complexes with metal ions. Complexation prevents the metal ions from reacting with molecules in the body, and enable them to be dissolved in blood and eliminated in urine. It should only be used in people who have a diagnosis of metal intoxication.^[23] That diagnosis should be validated with tests done in appropriate biological samples.^[24]

Other conditions

It is difficult to differentiate the effects of low level metal poisoning from the environment with other kinds of environmental harms, including nonmetal pollution.^[25] Generally, increased exposure to heavy metals in the environment increases risk of developing cancer.^[26]

Without a diagnosis of metal toxicity and outside of evidence-based medicine, but perhaps because of worry about metal toxicity, some people seek chelation therapy to treat autism, cardiovascular disease, Alzheimer's disease, or any sort of neurodegeneration.^{[24] [24]}

External links

• Dartmouth Toxic Metals Superfund Research Program
• Toxic Metals (OSHA)

Notes and References

1. Web site: A Metals Primer . 2012-05-30 . . 2013-12-29 . live . https://web.archive.org/web/20131230235623/http://www.dartmouth.edu/~toxmetal/toxic-metals/metals-primer.html . 2013-12-30.
2. Web site: Announcement: Response to the Advisory Committee on Childhood Lead Poisoning Prevention Report, Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention . 2012-05-25 . . live . https://web.archive.org/web/20170430094541/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6120a6.htm . 2017-04-30.
3. 2024 . Metal Toxicity . Dictionary of Toxicology . Springer . 10.1007/978-981-99-9283-6_1678.
4. Ali . Hazrat . Khan . Ezzat . Sajad . Muhammad Anwar . 2013-05-01 . Phytoremediation of heavy metals—Concepts and applications . Chemosphere . en . 91 . 7 . 869–881 . 10.1016/j.chemosphere.2013.01.075 . 23466085 . 2013Chmsp..91..869A . 0045-6535.
5. Okereafor . Uchenna . Makhatha . Mamookho . Mekuto . Lukhanyo . Uche-Okereafor . Nkemdinma . Sebola . Tendani . Mavumengwana . Vuyo . January 2020 . Toxic Metal Implications on Agricultural Soils, Plants, Animals, Aquatic life and Human Health . International Journal of Environmental Research and Public Health . en . 17 . 7 . 2204 . 10.3390/ijerph17072204 . 1660-4601 . 7178168 . 32218329. free .
6. See:
   • "Arsenic in drinking water seen as threat," USAToday.com, August 30, 2007.
   • See page 6 of: Peter Ravenscroft, "Predicting the global distribution of arsenic pollution in groundwater." Paper presented at: "Arsenic -- The Geography of a Global Problem," Royal Geographic Society Arsenic Conference held at: Royal Geographic Society, London, England, August 29, 2007. This conference is part of The Cambridge Arsenic Project .
7. Book: 10.1002/14356007.a15_249 . Lead Compounds . Ullmann's Encyclopedia of Industrial Chemistry . 2000 . Carr . Dodd S. . 978-3-527-30385-4 .
8. Web site: O'Malley . R. . O'Malley . G. . February 2018 . Lead Poisoning (Plumbism) . Merck Manual.
9. Couper . J. . Sur les effets du peroxide de manganèse . Journal de chimie médicale, de pharmacie et de toxicologie . 1837 . 3 . 223–225 . live . https://web.archive.org/web/20140722061529/http://books.google.com/books?id=WpQ3AAAAMAAJ&pg=PA233 . 2014-07-22 .
10. Web site: Dietary Supplement Fact Sheet: Selenium . National Institutes of Health; Office of Dietary Supplements . 2009-01-05.
11. Fosmire . Gary J . Zinc toxicity . The American Journal of Clinical Nutrition . 51 . 2 . 225–7 . 1990 . 2407097 . 10.1093/ajcn/51.2.225.
12. Book: Rout . Gyana Ranjan . Das . Premananda . Effect of Metal Toxicity on Plant Growth and Metabolism: I. Zinc . 873–84 . 10.1007/978-90-481-2666-8_53 . . Eric . Lichtfouse . Mireille . Navarrete . Philippe . Debaeke . Souchere . Véronique . Caroline . Alberola . 2009 . Sustainable Agriculture . limited . 978-90-481-2666-8. 84595949 .
13. Smith . SE . Larson . EJ . Zinc toxicity in rats; antagonistic effects of copper and liver . The Journal of Biological Chemistry . 163 . 29–38 . 1946 . 10.1016/S0021-9258(17)41344-5 . 21023625 . free .
14. Muyssen . Brita T.A. . De Schamphelaere . Karel A.C. . Janssen . Colin R. . Mechanisms of chronic waterborne Zn toxicity in Daphnia magna . Aquatic Toxicology . 77 . 4 . 393–401 . 2006 . 16472524 . 10.1016/j.aquatox.2006.01.006 . 2006AqTox..77..393M .
15. Web site: IARC Monograph, Volume 58. International Agency for Research on Cancer. 1993. 2008-09-18. live. https://web.archive.org/web/20120803081509/http://www.inchem.org/documents/iarc/vol58/mono58-1.html. 2012-08-03.
16. ICETT Itai-itai disease (1998) Web site: 1998 . Preventative Measures Against Water Pollution . dead . https://web.archive.org/web/20080415154342/http://www.icett.or.jp/lpca_jp.nsf/a21a0d8b94740fbd492567ca000d5879/b30e2e489f4b4ff1492567ca0011ff90?OpenDocument . 2008-04-15 . 2008-05-01 . International Center for Environmental Technology Transfer.
17. Book: Hedya . Shireen A. . Avula . Akshay . Swoboda . Henry D. . StatPearls . 2019 . StatPearls Publishing . https://www.ncbi.nlm.nih.gov/books/NBK499992/ . 22 December 2019 . Lithium Toxicity. 29763168 .
18. Official government figure as of March 2001. See "Minamata Disease: The History and Measures, ch2"
19. Book: William D. . James . Timothy G. . Berger . Dirk M. . Elston . Richard B. . Odom . Andrews' diseases of the skin: clinical dermatology . limited . Saunders Elsevier . 2006 . 858 . 0-7216-2921-0 . 62736861.
20. Verena Isak . Tobias Beerli . Antonio Cozzio . Lukas Flatz . January–April 2019 . A Rare Case of Localized Argyria on the Face . Case Reports in Dermatology . 11 . 1 . 23–27 . 10.1159/000494610 . free. 31043936 . 6477469 .
21. Book: 10.1002/14356007.a26_607 . Thallium and Thallium Compounds . Ullmann's Encyclopedia of Industrial Chemistry . 2000 . Micke . Heinrich . Wolf . Hans Uwe . 3-527-30673-0 .
22. Book: Graf . Günter G. . Tin, Tin Alloys, and Tin Compounds . 2000 . Ullmann's Encyclopedia of Industrial Chemistry . Wiley . 10.1002/14356007.a27_049 . 978-3-527-30673-2 .
23. Xiao, Zhiguang; Wedd, Anthony G.; "Coping with Toxic Metals", pp 271-298 in "Metals, Microbes and Minerals: The Biogeochemical Side of Life" (2021) pp xiv + 341. Walter de Gruyter, Berlin. "Metals, Microbes and Minerals: . Walter de Gruyter, Berlin. Editors Kroneck, Peter M.H. and Sosa Torres, Martha. Gruyter.com/document/doi/10.1515/9783110589771-009 DOI 10.1515/9783110589771-009
24. , which cites
    • Medical Letter consultants. Nonstandard uses of chelation therapy. The Medical Letter on Drugs and Therapeutics. September 20, 2010. 1347. 75–6. 20847718. 52. live. https://web.archive.org/web/20140714190248/http://secure.medicalletter.org/w1347c. July 14, 2014.
    • Kosnett. M J. Chelation for Heavy Metals (Arsenic, Lead, and Mercury): Protective or Perilous?. Clinical Pharmacology & Therapeutics. 88. 3. 2010. 412–415. 0009-9236. 10.1038/clpt.2010.132. 20664538. 28321495.
25. Liu. J. Lewis. G. Environmental toxicity and poor cognitive outcomes in children and adults.. Journal of Environmental Health. Jan–Feb 2014. 76. 6. 130–8. 24645424. 4247328.
26. Tabrez. Shams. Priyadarshini. Medha. Priyamvada. Shubha. Khan. Mohd Shahnawaz. NA. Arivarasu. Zaidi. Syed Kashif. Gene–environment interactions in heavy metal and pesticide carcinogenesis. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 760. 1–9. 10.1016/j.mrgentox.2013.11.002. 2014. 24309507. 2014MRGTE.760....1T .