Metal toxicity

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] It is often thought that only heavy metals can be toxic, but lighter metals such as beryllium and lithium may also be in certain circumstances. 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.

Structure of a metal aquo complex, a typical soluble form for many metal ions in water.

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.^[3] This method uses plants to extract and lower the concentration of toxic heavy metals in the soil.^[3] 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.^[4] 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

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.^[5]

Lead poisoning

Main article: 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.^[6][7] 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

Essential elements^[8]^[9]^[10]^[11]^[12] v t e
H																		He
Li	Be												B	C	N	O	F	Ne
Na	Mg												Al	Si	P	S	Cl	Ar
K	Ca		Sc	Ti	V	Cr	Mn	Fe	Co	Ni	Cu	Zn	Ga	Ge	As	Se	Br	Kr
Rb	Sr		Y	Zr	Nb	Mo	Tc	Ru	Rh	Pd	Ag	Cd	In	Sn	Sb	Te	I	Xe
Cs	Ba	*	Lu	Hf	Ta	W	Re	Os	Ir	Pt	Au	Hg	Tl	Pb	Bi	Po	At	Rn
Fr	Ra	**	Lr	Rf	Db	Sg	Bh	Hs	Mt	Ds	Rg	Cn	Nh	Fl	Mc	Lv	Ts	Og
		*	La	Ce	Pr	Nd	Pm	Sm	Eu	Gd	Tb	Dy	Ho	Er	Tm	Yb
		**	Ac	Th	Pa	U	Np	Pu	Am	Cm	Bk	Cf	Es	Fm	Md	No

Legend:   The four basic organic elements   Quantity elements   Essential trace elements   Essentiality or function in mammals debated   No evidence for biological action in mammals, but essential in some lower organisms. (In the case of the lanthanides, the definition of an essential nutrient as being indispensable and irreplaceable is not completely applicable due to their extreme similarity. The stable early lanthanides La–Nd are known to stimulate the growth of various lanthanide-using organisms, and Sm–Gd show lesser effects for some such organisms. The later elements in the lanthanide series do not appear to have such effects.)^[13]

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.^[14]
• 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.^[15] 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.^[16] 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.^[17][18][19]

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.^[20] Be has been classified by one agency as a carcinogen.^[21]
• 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.^[22] 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.^[23]
• Lithium toxicity arises from overdose of lithium-containing drugs.^[24]
• 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.^[25] 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.^[26]

 

A 92-year-old Caucasian man (right) with pigmentary changes had used nose drops containing silver for many years. His skin biopsy showed silver deposits in the dermis, confirming the diagnosis of generalized argyria.^[27]

• Silver poisoning,^[28] like lithium poisoning, arises from misapplication of medications. A dramatic symptom of "argyria" is that the skin turns blue or bluish-grey.^[29]
• 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.^[30] 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.^[31]

Society and culture

It is difficult to differentiate the effects of low level metal poisoning from the environment with other kinds of environmental harms, including nonmetal pollution.^[32] Generally, increased exposure to heavy metals in the environment increases risk of developing cancer.^[33]

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.^[34] Chelation therapy does not improve outcomes for those diseases.^[34]

Treatment for poisoning

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.^[35] That diagnosis should be validated with tests done in appropriate biological samples.^[34]

References

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2. "Announcement: Response to the Advisory Committee on Childhood Lead Poisoning Prevention Report, Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention". Centers for Disease Control and Prevention. 2012-05-25. from the original on 2017-04-30.
3. Ali, Hazrat; Khan, Ezzat; Sajad, Muhammad Anwar (2013-05-01). "Phytoremediation of heavy metals—Concepts and applications". Chemosphere. 91 (7): 869–881. Bibcode:2013Chmsp..91..869A. doi:10.1016/j.chemosphere.2013.01.075. ISSN 0045-6535. PMID 23466085.
4. 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. 17 (7): 2204. doi:10.3390/ijerph17072204. ISSN 1660-4601. PMC 7178168. PMID 32218329.
5. 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." 2013-07-01 at the Wayback Machine Paper presented at: "Arsenic -- The Geography of a Global Problem," 2013-07-01 at the Wayback Machine Royal Geographic Society Arsenic Conference held at: Royal Geographic Society, London, England, August 29, 2007. This conference is part of The Cambridge Arsenic Project 2012-11-17 at the Wayback Machine.
6. . doi:10.1002/14356007.a15_249. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
7. O'Malley, R.; O'Malley, G. (February 2018). "Lead Poisoning (Plumbism)". Merck Manual.
8. Ultratrace minerals. Authors: Nielsen, Forrest H. USDA, ARS Source: Modern nutrition in health and disease / editors, Maurice E. Shils ... et al. Baltimore: Williams & Wilkins, c1999., p. 283-303. Issue Date: 1999 URI: [1]
9. Szklarska D, Rzymski P (May 2019). "Is Lithium a Micronutrient? From Biological Activity and Epidemiological Observation to Food Fortification". Biol Trace Elem Res. 189 (1): 18–27. doi:10.1007/s12011-018-1455-2. PMC 6443601. PMID 30066063.
10. Enderle J, Klink U, di Giuseppe R, Koch M, Seidel U, Weber K, Birringer M, Ratjen I, Rimbach G, Lieb W (August 2020). "Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates". Nutrients. 12 (8): 2489. doi:10.3390/nu12082489. PMC 7468710. PMID 32824874.
11. McCall AS, Cummings CF, Bhave G, Vanacore R, Page-McCaw A, Hudson BG (June 2014). "Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture". Cell. 157 (6): 1380–92. doi:10.1016/j.cell.2014.05.009. PMC 4144415. PMID 24906154.
12. Zoroddu, Maria Antonietta; Aaseth, Jan; Crisponi, Guido; Medici, Serenella; Peana, Massimiliano; Nurchi, Valeria Marina (2019). "The essential metals for humans: a brief overview". Journal of Inorganic Biochemistry. 195: 120–129. doi:10.1016/j.jinorgbio.2019.03.013.
13. Daumann, Lena J. (25 April 2019). "Essential and Ubiquitous: The Emergence of Lanthanide Metallobiochemistry". Angewandte Chemie International Edition. doi:10.1002/anie.201904090. Retrieved 15 June 2019.
14. Couper, J. (1837). "Sur les effets du peroxide de manganèse". Journal de chimie médicale, de pharmacie et de toxicologie. 3: 223–225. from the original on 2014-07-22.
15. "Dietary Supplement Fact Sheet: Selenium". National Institutes of Health; Office of Dietary Supplements. Retrieved 2009-01-05.
16. Fosmire, Gary J (1990). "Zinc toxicity". The American Journal of Clinical Nutrition. 51 (2): 225–7. doi:10.1093/ajcn/51.2.225. PMID 2407097.
17. Rout, Gyana Ranjan; Das, Premananda (2009). "Effect of Metal Toxicity on Plant Growth and Metabolism: I. Zinc". In Lichtfouse, Eric; Navarrete, Mireille; Debaeke, Philippe; Véronique, Souchere; Alberola, Caroline (eds.). Sustainable Agriculture. pp. 873–84. doi:10.1007/978-90-481-2666-8_53. ISBN 978-90-481-2666-8. S2CID 84595949. INIST 14709198.
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19. Muyssen, Brita T.A.; De Schamphelaere, Karel A.C.; Janssen, Colin R. (2006). "Mechanisms of chronic waterborne Zn toxicity in Daphnia magna". Aquatic Toxicology. 77 (4): 393–401. doi:10.1016/j.aquatox.2006.01.006. PMID 16472524.
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21. "IARC Monograph, Volume 58". International Agency for Research on Cancer. 1993. from the original on 2012-08-03. Retrieved 2008-09-18.
22. ICETT Itai-itai disease (1998) . International Center for Environmental Technology Transfer. 1998. Archived from the original on 2008-04-15. Retrieved 2008-05-01.
23. Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. p. 1225. ISBN 978-0-08-037941-8.
24. Hedya, Shireen A.; Avula, Akshay; Swoboda, Henry D. (2019). "Lithium Toxicity". StatPearls. StatPearls Publishing. PMID 29763168. Retrieved 22 December 2019.
25. Official government figure as of March 2001. See "Minamata Disease: The History and Measures, ch2"
26. Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. p. 1226. ISBN 978-0-08-037941-8.
27. Fred, Herbert (2008). Images of Memorable Cases: 50 Years at the Bedside. Long Tail Press/Rice University Press. ISBN 978-0-89263-000-4.
28. James, William D.; Berger, Timothy G.; Elston, Dirk M.; Odom, Richard B. (2006). Andrews' diseases of the skin: clinical dermatology. Saunders Elsevier. p. 858. ISBN 0-7216-2921-0. OCLC 62736861.
29. 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. doi:10.1159/000494610. PMC 6477469.
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31. Graf, Günter G. (2000). "Tin, Tin Alloys, and Tin Compounds". Ullmann's Encyclopedia of Industrial Chemistry. Wiley. doi:10.1002/14356007.a27_049. ISBN 978-3-527-30673-2.
32. Liu, J; Lewis, G (Jan–Feb 2014). "Environmental toxicity and poor cognitive outcomes in children and adults". Journal of Environmental Health. 76 (6): 130–8. PMC 4247328. PMID 24645424.
33. Tabrez, Shams; Priyadarshini, Medha; Priyamvada, Shubha; Khan, Mohd Shahnawaz; NA, Arivarasu; Zaidi, Syed Kashif (2014). "Gene–environment interactions in heavy metal and pesticide carcinogenesis". Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 760: 1–9. doi:10.1016/j.mrgentox.2013.11.002. PMID 24309507.
34. American College of Medical Toxicology; American Academy of Clinical Toxicology (February 2013), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, American College of Medical Toxicology and American Academy of Clinical Toxicology, from the original on 4 December 2013, retrieved 5 December 2013, which cites
    • Medical Letter consultants (September 20, 2010). "Nonstandard uses of chelation therapy". The Medical Letter on Drugs and Therapeutics. 52 (1347): 75–6. PMID 20847718. from the original on July 14, 2014.
    • Kosnett, M J (2010). "Chelation for Heavy Metals (Arsenic, Lead, and Mercury): Protective or Perilous?". Clinical Pharmacology & Therapeutics. 88 (3): 412–415. doi:10.1038/clpt.2010.132. ISSN 0009-9236. PMID 20664538. S2CID 28321495.
35. Zhiguang, Xiao; 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

External links

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