Metal toxicity

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.^[1][2][3] Environmental pollution with heavy metals can result in contamination of drinking water, air, and waterways, accumulating in plants, crops, seafood, and meat.^[3] Such pollution may indirectly affect humans via the food chain and through occupational or domestic exposure by inhalation, ingestion, or contact with the skin.^[1][3]

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

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.^[2] Other heavy metals having no biological roles in animals, but with potential for toxicity include arsenic, cadmium, lead, mercury, and thallium.^[1][2][4]

Some metals are toxic when they form poisonous soluble compounds which interfere with enzyme systems, such as superoxide dismutase, catalase, or glutathione peroxidase.^[1] Only soluble metal-containing compounds are toxic by forming coordination complexes, which consist of a metal ion surrounded by ligands.^[1] 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.^[3]

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.^[1][5]

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.^[5] Commonly, there is no visible evidence of metals pollution in soil or water.^[5]

When metal toxicity in the environment is suspected, pathologies in fish, clams, and insects may serve as signals for contamination and toxicities.^[5] Physiological mechanisms of metal toxicity may have a spectrum of effects, ranging from changes in behavior to death of small animal species.^[5]

Major types of metal poisoning

Arsenic poisoning

Main article: 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.^[1][2]

Lead poisoning

Main article: Lead poisoning

Lead poisoning, in contrast to arsenic poisoning, is caused by industrial materials, such as leaded gasoline and lead leached from plumbing.^[1][2][3] Use of leaded gasoline has declined precipitously since the 1970s.^[6][7]

Toxicities from metals

Essential elements[8][9][10] 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 six basic organic elements   Quantity elements   Essential trace elements   Essentiality or function in mammals debated   No evidence for biological action in mammals, but essential or beneficial in some 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 chemical 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.[11]

Some metal elements are required for life, although they may be toxic in high exposure amounts.^[1][2][3] Included are cobalt, copper, iron, manganese,^[12] selenium,^[13] and zinc.^[14] 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.^[15]

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.^[16] Be has been classified by one agency as a carcinogen.^[17]
• 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.^[18] 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.^[19]
• Lithium toxicity arises from overdose of lithium-containing drugs.^[20]
• 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.^[21] 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.^[22]

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.^[23]

• Silver poisoning,^[24] like lithium poisoning, arises from misapplication of medications. A dramatic symptom of "argyria" is that the skin turns blue or bluish-grey.^[25]
• 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.^[26] 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.^[27]

Treatment for poisoning

Chelation therapy

Main article: Chelation

Further information: Heavy metal detoxification

Chelation therapy is a medical procedure that involves the administration of chelating agents to remove or deactivate heavy metals from the body.^[3] Chelating agents are molecules that form particularly stable coordination complexes with metal ions.^[3] Complexation prevents the metal ions from reacting with molecules in the body, and enable them to be dissolved in blood and eliminated in urine.^[3] It should only be used in people who have a diagnosis of metal intoxication.^[3] That diagnosis should be validated with tests done in appropriate biological samples.^{[3][28][29][30]}

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.^[1] Generally, increased exposure to heavy metals in the environment increases the risks for several diseases.^[1] 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.^[28]

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.^[31][32] 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.^[33][34] 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,^[35][36] and at least one child has died due to errors in administration of chelation therapy for this purpose.^[37][38][39]