Metal toxicity#Toxic metals

Image:M(H2O)6 cation.png, a typical soluble form for many metal ions in water]]

Metal toxicity or metal poisoning is the toxic effect of certain metals that accumulate in the environment and damage ecosystems, plants and animals, including human health.{{cite journal |vauthors=Jomova K, Alomar SY, Nepovimova E, Kuca K, Valko M |title=Heavy metals: toxicity and human health effects |journal=Archives of Toxicology |volume=99 |issue=1 |pages=153–209 |date=January 2025 |pmid=39567405 |pmc=11742009 |doi=10.1007/s00204-024-03903-2}}{{cite web |vauthors=Fisher RM, Gupta V |title=Heavy metals |url=https://www.ncbi.nlm.nih.gov/books/NBK557806/ |publisher=StatPearls, US National Library of Medicine |access-date=17 April 2025 |date=27 February 2024}}{{cite web |vauthors=Rajkumar V, Lee VR, Gupta V |title=Heavy metal toxicity |url=https://www.ncbi.nlm.nih.gov/books/NBK560920/ |publisher=StatPearls, US National Library of Medicine |access-date=17 April 2025 |date=23 March 2023}} Environmental pollution with heavy metals can result in contamination of drinking water, air, and waterways, accumulating in plants, crops, seafood, and meat. Such pollution may indirectly affect humans via the food chain and through occupational or domestic exposure by inhalation, ingestion, or contact with the skin.

At low concentrations, heavy metals such as copper, iron, manganese, and zinc are essential nutrients obtained through the diet supporting health, but have toxicity at high exposure concentrations. Other heavy metals having no biological roles in animals, but with potential for toxicity include arsenic, cadmium, lead, mercury, and thallium.{{cite dictionary |year=2024 |entry=Metal Toxicity |title=Dictionary of Toxicology |publisher=Springer |doi=10.1007/978-981-99-9283-6}}

Some metals are toxic when they form poisonous soluble compounds which interfere with enzyme systems, such as superoxide dismutase, catalase, or glutathione peroxidase. Only soluble metal-containing compounds are toxic by forming 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.

Toxic metal complexes can be detoxified by conversion to insoluble derivatives or by binding them in rigid molecular environments using chelating agents. An option for treatment of metal poisoning may be chelation therapy, which involves the administration of chelation agents to remove metals from the body.

Sources and site evidence

Heavy metals are found throughout natural ecosystems, including rocks, soils, and water, and originate from diverse sources, such as natural weathering, erosion, mining, industrial and urban runoff, sewage, pesticides on crops, metal pipes carrying potable water, traffic pollution, coal-burning emissions, and various other industrial and urban outputs.{{cite web |title=Metals |url=https://www.epa.gov/caddis/metals |publisher=Causal Analysis and Diagnosis Decision Information System (CADDIS), US Environmental Protection Agency |access-date=17 April 2025 |date=10 March 2025}}

Toxic metal particles in ecosystems may remain for hundreds or even thousands of years, with potentially millions of people exposed to high concentrations at some point in their lives. Commonly, there is no visible evidence of metals pollution in soil or water.

When metal toxicity in the environment is suspected, pathologies in fish, clams, and insects may serve as signals for contamination and toxicities. Physiological mechanisms of metal toxicity may have a spectrum of effects, ranging from changes in behavior to death of small animal species.

Major types of metal poisoning

=Arsenic poisoning=

A dominant kind of metal toxicity is arsenic poisoning, which mainly arises from ground water naturally containing high concentrations of arsenic in the supply of drinking water.

=Lead poisoning=

Lead poisoning, in contrast to arsenic poisoning, is caused by industrial materials, such as leaded gasoline and lead leached from plumbing. Use of leaded gasoline has declined precipitously since the 1970s.{{cite book |doi=10.1002/14356007.a15_249 |chapter=Lead Compounds |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2000 |last1=Carr |first1=Dodd S. |isbn=978-3-527-30385-4 }}{{cite web |last1=O'Malley |first1=R. |last2=O'Malley |first2=G. |date=February 2018 |title=Lead Poisoning (Plumbism) |url=https://www.merckmanuals.com/professional/injuries-poisoning/poisoning/lead-poisoning#v1119464 |website=Merck Manual}}

Toxicities from metals

Some metal elements are required for life, although they may be toxic in high exposure amounts. Included are cobalt, copper, iron, manganese,{{cite journal | last = Couper | first = J. | title = Sur les effets du peroxide de manganèse | journal = Journal de chimie médicale, de pharmacie et de toxicologie | year = 1837 | volume = 3 | pages = 223–225 | url = https://books.google.com/books?id=WpQ3AAAAMAAJ&pg=PA233 | url-status = live | archive-url = https://web.archive.org/web/20140722061529/http://books.google.com/books?id=WpQ3AAAAMAAJ&pg=PA233 | archive-date = 2014-07-22 }} selenium,{{cite web |url=https://ods.od.nih.gov/factsheets/selenium-HealthProfessional/|title= Dietary Supplement Fact Sheet: Selenium |publisher=Office of Dietary Supplements, US National Institutes of Health |access-date=April 17, 2025|date=April 15, 2024}} and zinc.{{cite journal |last1=Fosmire |first1=Gary J |title=Zinc toxicity |journal=The American Journal of Clinical Nutrition |volume=51 |issue=2 |pages=225–7 |year=1990 |pmid=2407097 |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=2407097 |doi=10.1093/ajcn/51.2.225}} Excessive absorption of zinc can suppress copper and iron absorption. The free zinc ion in solution is highly toxic to bacteria, plants, invertebrates, and fish.{{cite book |last1=Rout |first1=Gyana Ranjan |last2=Das |first2=Premananda |chapter=Effect of Metal Toxicity on Plant Growth and Metabolism: I. Zinc |pages=[https://archive.org/details/sustainableagric00lich/page/n843 873]–84 |doi=10.1007/978-90-481-2666-8_53 |id={{INIST|14709198}} |editor1-first=Eric |editor1-last=Lichtfouse |editor2-first=Mireille |editor2-last=Navarrete |editor3-first=Philippe |editor3-last=Debaeke |editor4-first=Souchere |editor4-last=Véronique |editor5-first=Caroline |editor5-last=Alberola |year=2009 |title=Sustainable Agriculture |url=https://archive.org/details/sustainableagric00lich |url-access=limited |isbn=978-90-481-2666-8|s2cid=84595949 }}

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.{{Greenwood&Earnshaw2nd|page=107}} Be has been classified by one agency as a carcinogen.{{Cite web|url = http://www.inchem.org/documents/iarc/vol58/mono58-1.html|publisher = International Agency for Research on Cancer|title = IARC Monograph, Volume 58|year = 1993|access-date = 2008-09-18|url-status = live|archive-url = https://web.archive.org/web/20120803081509/http://www.inchem.org/documents/iarc/vol58/mono58-1.html|archive-date = 2012-08-03}}
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.ICETT Itai-itai disease (1998) {{Cite web |date=1998 |title=Preventative Measures Against Water Pollution |url=http://www.icett.or.jp/lpca_jp.nsf/a21a0d8b94740fbd492567ca000d5879/b30e2e489f4b4ff1492567ca0011ff90?OpenDocument |url-status=dead |archive-url=https://web.archive.org/web/20080415154342/http://www.icett.or.jp/lpca_jp.nsf/a21a0d8b94740fbd492567ca000d5879/b30e2e489f4b4ff1492567ca0011ff90?OpenDocument |archive-date=2008-04-15 |access-date=2008-05-01 |website=International Center for Environmental Technology Transfer}} 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.{{Greenwood&Earnshaw2nd|page=1225}}
Lithium toxicity arises from overdose of lithium-containing drugs.{{cite book |last1=Hedya |first1=Shireen A. |last2=Avula |first2=Akshay |last3=Swoboda |first3=Henry D. |title=StatPearls |date=2019 |publisher=StatPearls Publishing |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK499992/ |access-date=22 December 2019 |chapter=Lithium Toxicity|pmid=29763168 }}
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.Official government figure as of March 2001. See [http://www.env.go.jp/en/chemi/hs/minamata2002/ch2.html "Minamata Disease: The History and Measures, ch2"] 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.{{Greenwood&Earnshaw2nd|page=1226}}

File:Argyria_2a.jpg

Silver poisoning,{{cite book |first1=William D. |last1=James |first2=Timothy G. |last2=Berger |first3=Dirk M. |last3=Elston |first4=Richard B. |last4=Odom |title=Andrews' diseases of the skin: clinical dermatology |url=https://archive.org/details/andrewsdiseasess00mdwi_659 |url-access=limited |publisher=Saunders Elsevier |year=2006 |page=[https://archive.org/details/andrewsdiseasess00mdwi_659/page/n868 858] |isbn=0-7216-2921-0 |oclc=62736861}} like lithium poisoning, arises from misapplication of medications. A dramatic symptom of "argyria" is that the skin turns blue or bluish-grey.{{cite journal |author=Verena Isak |author2=Tobias Beerli |author3=Antonio Cozzio |author4=Lukas Flatz |date=January–April 2019 |title=A Rare Case of Localized Argyria on the Face |journal=Case Reports in Dermatology |volume=11 |issue=1 |pages=23–27 |doi=10.1159/000494610 |doi-access=free|pmid=31043936 |pmc=6477469 }}
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.{{cite book |doi=10.1002/14356007.a26_607 |chapter=Thallium and Thallium Compounds |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2000 |last1=Micke |first1=Heinrich |last2=Wolf |first2=Hans Uwe |isbn=3-527-30673-0 }} 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.{{cite book |last1=Graf |first1=Günter G. |chapter=Tin, Tin Alloys, and Tin Compounds |year=2000 |title=Ullmann's Encyclopedia of Industrial Chemistry |publisher=Wiley |doi=10.1002/14356007.a27_049 |isbn=978-3-527-30673-2 }}

Treatment for poisoning

=Chelation therapy=

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. That diagnosis should be validated with tests done in appropriate biological samples.{{Citation |author1 = American College of Medical Toxicology |author1-link = American College of Medical Toxicology |author2 = American Academy of Clinical Toxicology |author2-link = American Academy of Clinical Toxicology |date = February 2013 |title = Five Things Physicians and Patients Should Question |publisher = American College of Medical Toxicology and American Academy of Clinical Toxicology |work = Choosing Wisely: an initiative of the ABIM Foundation |url = http://www.choosingwisely.org/doctor-patient-lists/american-college-of-medical-toxicology-and-the-american-academy-of-clinical-toxicology/ |access-date = 5 December 2013 |url-status = live |archive-url = https://web.archive.org/web/20131204163006/http://www.choosingwisely.org/doctor-patient-lists/american-college-of-medical-toxicology-and-the-american-academy-of-clinical-toxicology/ |archive-date = 4 December 2013 }}{{cite journal|author1=Medical Letter consultants|title=Nonstandard uses of chelation therapy|journal=The Medical Letter on Drugs and Therapeutics|date=September 20, 2010|issue=1347|pages=75–6|pmid=20847718|url=http://secure.medicalletter.org/w1347c|volume=52|url-status=live|archive-url=https://web.archive.org/web/20140714190248/http://secure.medicalletter.org/w1347c|archive-date=July 14, 2014}}{{cite journal|last1=Kosnett|first1=M J|title=Chelation for Heavy Metals (Arsenic, Lead, and Mercury): Protective or Perilous?|journal=Clinical Pharmacology & Therapeutics|volume=88|issue=3|year=2010|pages=412–415|issn=0009-9236|doi=10.1038/clpt.2010.132|pmid=20664538|s2cid=28321495}}

=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. Generally, increased exposure to heavy metals in the environment increases the risks for several diseases. Despite a lack of evidence to support its use, some people seek chelation therapy to treat a wide variety of conditions such as autism, cardiovascular disease, Alzheimer's disease, or any sort of neurodegeneration.

Treatment of autism by chelation therapy has been promoted by alternative medicine practitioners based on an unsupported hypothesis that autism is a result of heavy metal poisoning. This hypothesis likely emerged from the more specific claim that autism was caused by the preservative thiomersal, which in the past has been used in multi-dose vials of vaccines. Despite extensive study, no connection has been found between vaccines and autism diagnosis rates.{{Cite journal |last=Price |first=Cristofer S. |last2=Thompson |first2=William W. |last3=Goodson |first3=Barbara |last4=Weintraub |first4=Eric S. |last5=Croen |first5=Lisa A. |last6=Hinrichsen |first6=Virginia L. |last7=Marcy |first7=Michael |last8=Robertson |first8=Anne |last9=Eriksen |first9=Eileen |last10=Lewis |first10=Edwin |last11=Bernal |first11=Pilar |last12=Shay |first12=David |last13=Davis |first13=Robert L. |last14=DeStefano |first14=Frank |date=2010-10-01 |title=Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism |url=https://publications.aap.org/pediatrics/article/126/4/656/65633/Prenatal-and-Infant-Exposure-to-Thimerosal-From |journal=Pediatrics |language=en |volume=126 |issue=4 |pages=656–664 |doi=10.1542/peds.2010-0309 |issn=0031-4005}}{{Cite journal |last=Madsen |first=Kreesten M. |last2=Lauritsen |first2=Marlene B. |last3=Pedersen |first3=Carsten B. |last4=Thorsen |first4=Poul |last5=Plesner |first5=Anne-Marie |last6=Andersen |first6=Peter H. |last7=Mortensen |first7=Preben B. |date=2003-09-01 |title=Thimerosal and the Occurrence of Autism: Negative Ecological Evidence From Danish Population-Based Data |url=https://publications.aap.org/pediatrics/article/112/3/604/28678/Thimerosal-and-the-Occurrence-of-Autism-Negative |journal=Pediatrics |language=en |volume=112 |issue=3 |pages=604–606 |doi=10.1542/peds.112.3.604 |issn=0031-4005}} Despite this lack of evidence, thimerosal was removed from vaccines out of an abundance of caution by 2001; autism diagnosis rates did not decrease in response to the exclusion of thimerosal, disproving the association.{{Cite journal |last=Schechter |first=Robert |last2=Grether |first2=Judith K. |date=2008-01-01 |title=Continuing Increases in Autism Reported to California's Developmental Services System: Mercury in Retrograde |url=http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archgenpsychiatry.2007.1 |journal=Archives of General Psychiatry |language=en |volume=65 |issue=1 |pages=19 |doi=10.1001/archgenpsychiatry.2007.1 |issn=0003-990X}}{{Cite journal |last=Fombonne |first=Eric |date=2008-01-01 |title=Thimerosal Disappears but Autism Remains |url=http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archgenpsychiatry.2007.2 |journal=Archives of General Psychiatry |language=en |volume=65 |issue=1 |pages=15 |doi=10.1001/archgenpsychiatry.2007.2 |issn=0003-990X}} Regardless of the removal of thimerosal and the evidence that it never influenced autism in the first place, the idea of heavy metal exposure causing autism has persisted, and thus has the use of chelation therapy as treatment. Systematic reviews of available evidence do not support the use of chelation therapy for autism,{{Cite journal |last=Sinha |first=Yashwant |last2=Silove |first2=Natalie |last3=Williams |first3=Katrina |date=2006-10-07 |title=Chelation therapy and autism |url=https://www.bmj.com/lookup/doi/10.1136/bmj.333.7571.756 |journal=BMJ |language=en |volume=333 |issue=7571 |pages=756.1 |doi=10.1136/bmj.333.7571.756 |issn=0959-8138 |pmc=1592402 |pmid=17023484}}{{Cite journal |last=Brent |first=Jeffrey |date=2013-12-01 |title=Commentary on the Abuse of Metal Chelation Therapy in Patients with Autism Spectrum Disorders |url=https://link.springer.com/article/10.1007/s13181-013-0345-4 |journal=Journal of Medical Toxicology |language=en |volume=9 |issue=4 |pages=370–372 |doi=10.1007/s13181-013-0345-4 |issn=1937-6995 |pmc=3846967 |pmid=24113859}} and at least one child has died due to errors in administration of chelation therapy for this purpose.{{Cite web |date=2005-08-25 |title=Boy with autism dies after chelation therapy |url=https://www.nbcnews.com/id/wbna9074208 |access-date=2025-04-16 |website=NBC News |language=en}}{{Cite journal |last=Baxter |first=Arla J. |last2=Krenzelok |first2=Edward P. |date=January 2008 |title=Pediatric fatality secondary to EDTA chelation |url=http://www.tandfonline.com/doi/full/10.1080/15563650701261488 |journal=Clinical Toxicology |language=en |volume=46 |issue=10 |pages=1083–1084 |doi=10.1080/15563650701261488 |issn=1556-3650}}{{Cite web |last=Philadelphia |first=The Children's Hospital of |title=Death of an Autistic Child From Chelation Therapy - Op-ed {{!}} Children's Hospital of Philadelphia |url=https://www.chop.edu/news/death-autistic-child-chelation-therapy-oped |access-date=2025-04-16 |website=www.chop.edu |language=en}}

References

External links

[http://www.dartmouth.edu/~toxmetal/ Dartmouth Toxic Metals Superfund Research Program]
[https://www.osha.gov/SLTC/metalsheavy/index.html Toxic Metals] (OSHA)

Category:Metals

Category:Element toxicology