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{{Infobox disease
{{Infobox medical condition (new)
| Name = Chromium toxicity
| name = Chromium toxicity
| Image = Cr-TableImage.png
| synonyms =
| Caption = [[Chromium]]
| image = Cr-TableImage.svg
| DiseasesDB =
| caption = [[Chromium]]
| ICD10 = {{ICD10|T|56|2|t|51}}
| pronounce =
| ICD9 = {{ICD9|985.6}}
| field = [[Toxicology]]
| ICDO =
| symptoms =
| OMIM =
| complications =
| MedlinePlus =
| onset =
| eMedicineSubj =
| duration =
| eMedicineTopic =
| types =
| MeshID =
| causes =
| risks =
| diagnosis =
| differential =
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
| deaths =
}}
}}


'''Chromium toxicity''' refers to any poisonous toxic
'''Chromium toxicity''' refers to any poisonous effect in an [[organism]] or [[Cell (biology)|cell]] that results from exposure to specific forms of [[chromium]]—especially [[hexavalent chromium]]. Hexavalent chromium and its compounds are toxic when inhaled or ingested. [[Trivalent chromium]] is a [[trace mineral]] that is essential to human nutrition. There is a hypothetical risk of [[genotoxicity]] in humans if large amounts of trivalent chromium were somehow able to enter living cells, but normal metabolism and cell function prevents this.
effect in an [[organism]] or [[Cell (biology)|cell]] that results from exposure to specific forms of [[chromium]]—especially [[hexavalent chromium]].<ref>{{Cite web |date=2021-02-09 |title=Chromium (Cr) Toxicity: What Are the Physiologic Effects of Chromium Exposure? {{!}} Environmental Medicine {{!}} ATSDR |url=https://www.atsdr.cdc.gov/csem/chromium/physiologic_effects_of_chromium_exposure.html |access-date=2022-06-05 |website=www.atsdr.cdc.gov |language=en-us}}</ref> Hexavalent chromium and its compounds are toxic when inhaled or ingested. [[Trivalent chromium]] is a [[trace mineral]] that is essential to human nutrition. There is a hypothetical risk of [[genotoxicity]] in humans if large amounts of trivalent chromium were somehow able to enter living cells, but normal metabolism and cell function prevent this.<ref>{{cite journal | vauthors = Hartwig A, Arand M, Epe B, Guth S, Jahnke G, Lampen A, Martus HJ, Monien B, Rietjens IM, Schmitz-Spanke S, Schriever-Schwemmer G, Steinberg P, Eisenbrand G | display-authors = 6 | title = Mode of action-based risk assessment of genotoxic carcinogens | journal = Archives of Toxicology | volume = 94 | issue = 6 | pages = 1787–1877 | date = June 2020 | pmid = 32542409 | pmc = 7303094 | doi = 10.1007/s00204-020-02733-2 }}</ref>


==Forms of chromium==
==Forms of chromium==
[[Hexavalent chromium]] and [[trivalent chromium]] are chromium [[ion]]s—they have different numbers of [[electron]]s and, therefore, different properties. Trivalent chromium, or chromium(III), is the form of chromium that is essential to human health. Hexavalent chromium, or chromium(VI) is an unequivocally toxic form.
[[Hexavalent chromium]] and [[trivalent chromium]] are chromium [[ion]]s—they have different numbers of [[electron]]s and, therefore, different properties. Trivalent chromium, or chromium(III), is the form of chromium that is essential to human health.<ref name="Bogden">{{cite book |title=Clinical Nutrition of the Essential Trace Elements and Minerals: The Guide for Health Professionals | veditors = Bogden JD, Klevay LM |chapter=Trace Elements and Minerals in the Elderly § Chromium |page=[https://archive.org/details/clinicalnutritio0000unse_l0q5/page/189 189] |chapter-url=https://books.google.com/books?id=UHUoBgAAQBAJ&pg=PA189 |publisher=Springer Science+Business Media |year=2000 |isbn=978-1-61737-090-8 |via=Google Books |url=https://archive.org/details/clinicalnutritio0000unse_l0q5/page/189 }}</ref> Hexavalent chromium, or chromium(VI), is an unequivocally toxic form.


===Hexavalent chromium===
===Hexavalent chromium===
{{Main|Hexavalent chromium#Toxicity}}
{{Main|Hexavalent chromium#Toxicity}}


[[Hexavalent chromium]], also called chromium(VI), is [[hemotoxic]], [[genotoxic]], and [[carcinogenic]].<ref name="Barceloux">{{cite journal | vauthors = Barceloux DG | title = Chromium | journal = Journal of Toxicology. Clinical Toxicology | volume = 37 | issue = 2 | pages = 173–194 | year = 1999 | pmid = 10382554 | doi = 10.1081/CLT-100102418 }}</ref> When hexavalent chromium enters the bloodstream, it damages [[blood cell]]s by causing [[oxidation]] reactions. This [[oxidative damage]] can lead to [[hemolysis]] and, ultimately, [[Renal|kidney]] and [[liver]] failure. Patients might be treated with [[Kidney dialysis|dialysis]].<ref name="Dayan">{{cite journal | vauthors = Dayan AD, Paine AJ | title = Mechanisms of chromium toxicity, carcinogenicity and allergenicity: review of the literature from 1985 to 2000 | journal = Human & Experimental Toxicology | volume = 20 | issue = 9 | pages = 439–451 | date = September 2001 | pmid = 11776406 | doi = 10.1191/096032701682693062 | s2cid = 31351037 | doi-access = free }}</ref>
[[Hexavalent chromium]], also called chromium(VI), is [[hemotoxic]], [[genotoxic]], and [[carcinogenic]].<ref name="Barceloux">{{cite journal
|title = Chromium
|first = Donald G.
|last = Barceloux
|journal = Clinical Toxicology
|volume = 37
|issue = 2
|pages = 173–194
|year = 1999
|url =
|doi = 10.1081/CLT-100102418
|pmid = 10382554
|last2 = Barceloux
|first2 = Donald }}</ref> When hexavelent chromium enters the bloodstream, it damages [[blood cell]]s by causing [[oxidation]] reactions. This [[oxidative damage]] can lead to [[hemolysis]] and, ultimately, [[Renal|kidney]] and [[liver]] failure. Patients might be treated with [[dialysis]].<ref name="Dayan">{{cite journal
|title = Mechanisms of chromium toxicity, carcinogenicity and allergenicity: Review of the literature from 1985 to 2000
|first = A. D.
|last = Dayan
|journal = Human & Experimental Toxicology
|volume = 20
|issue = 9
|pages = 439–451
|year = 2001
|url =
|doi = 10.1191/096032701682693062
|pmid = 11776406
|last2 = Paine
|first2 = AJ }}</ref>


The [[median lethal dose]] of hexavalent chromium is 50–150&nbsp;mg/kg.<ref name="Katz"/> The [[World Health Organization]] recommends a [[maximum allowable concentration]] of 0.05 [[milligram]]s per [[litre]] of chromium(VI) in [[drinking water]].<ref name="WHOCr">{{cite web | title = WHO Guidelines on Drinking-Water Quality | url =https://www.who.int/water_sanitation_health/dwq/chemicals/chromiumsum.pdf |at=Section 12.30: Chromium |website=WHO.int |publisher=World Health Organization}}</ref> In Europe, the use of hexavalent chromium is regulated by the [[Restriction of Hazardous Substances Directive]].
In the second half of the 20th century, this form of chromium caused widespread illness among the people of [[Hinkley, California]] when the [[Pacific Gas and Electric Company]] [[Hinkley groundwater contamination|contaminated groundwater]] in the area.


Hexavalent chromium can be found in some [[dye]]s and [[paint]]s, as well as in some [[Tanning (leather)|leather tanning]] products. [[Primer (paint)|Primer paint]] containing hexavalent chromium is widely used in [[aerospace]] and [[automobile]] refinishing applications. Metal workers (such as welders)—as well as people with a [[surgical implant]] made from cobalt-chromium [[alloy]]—may also be exposed to hexavalent chromium.<ref>{{cite journal | vauthors = Merritt K, Brown SA | title = Release of hexavalent chromium from corrosion of stainless steel and cobalt-chromium alloys | journal = Journal of Biomedical Materials Research | volume = 29 | issue = 5 | pages = 627–633 | date = May 1995 | pmid = 7622548 | doi = 10.1002/jbm.820290510 }}</ref> Chromium concentrations in whole blood, plasma, serum, or urine may be measured to monitor for safety in exposed workers, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation in a case of fatal overdosage.<ref>{{cite book | vauthors = Baselt R |title=Disposition of Toxic Drugs and Chemicals in Man |edition=8th |publisher=Biomedical Publications |location=Foster City |year=2008 |pages=305–7 |isbn=978-0962652370}}</ref>
The [[median lethal dose]] of hexavalent chromium is 50–150&nbsp;mg/kg.<ref name="Katz"/> The [[World Health Organization]] recommends a [[maximum allowable concentration]] of 0.05 [[milligram]]s per [[litre]] of chromium(VI) in [[drinking water]].<ref name="WHOCr">{{cite web | title = WHO Guidelines on Drinking-Water Quality -- Chromium | url = https://www.who.int/water_sanitation_health/dwq/chemicals/chromiumsum.pdf}}</ref>


In the [[U.S. state]] of [[California]], an epidemic of hexavalent chromium exposure led to a class-action lawsuit in 1993: ''Anderson,'' et al. ''v. Pacific Gas and Electric''. The [[Pacific Gas and Electric Company]] had dumped more than 1.4 billion litres (370 million gallons) of wastewater tainted with hexavalent chromium into the [[Mojave Desert]]. This [[Hinkley groundwater contamination|contaminated the groundwater]], and caused widespread illness among the people of [[Hinkley, California]], a small community nearby. As of May 2017, the mandated [[environmental remediation]] measures are ongoing.<ref>{{cite journal |journal=Open-file Report |issn=2331-1258 |title=Natural and Man-Made Hexavalent Chromium, Cr(VI), in Groundwater near a Mapped Plume, Hinkley, California—Study Progress as of May 2017, and a Summative-Scale Approach to Estimate Background Cr(VI) Concentrations | vauthors = Izbicki JA, Groover K |publisher=United States Geological Survey |url=https://www.waterboards.ca.gov/rwqcb6/water_issues/projects/pge/docs/midtermreport_032018.pdf |access-date=2018-05-15}}</ref>
Hexavalent chromium can be found in some [[dye]]s and [[paint]]s, as well as in some [[Tanning (leather)|leather tanning]] products. [[Primer (paint)|Primer paint]] containing hexavalent chromium is widely used in [[aerospace]] and [[automobile]] refinishing applications. In Europe, the use of hexavalent chromium is limited by the [[Restriction of Hazardous Substances Directive]]. When hexavalent chromium leeches into soil and [[groundwater]], [[environmental cleanup]] and [[Environmental remediation|remediation]] are required.


====Chromate====
====Chromate====
{{See also|Chromate and dichromate#Toxicity}}
[[Chromate]]s (chromium salts) formed from hexavalent chromium are used to manufacture leather products, paints, cement, mortar, anti-corrosives, and other things. They are carcinogenic and allergenic. The [[carcinogenity]] of chromate dust has been documented since the late 19th century. Workers in a chromate dye company were found.<ref>{{cite journal
|title = A case of adeno-carcinoma of the left inferior turbinated body, and perforation of the nasal septum, in the person of a worker in chrome pigments
|first = D.
|last = Newman
|journal = Glasgow Med J
|volume = 33
|issue =
|pages = 469–470
|year = 1890
|url =
|doi = }}</ref><ref name="Langard">{{cite journal
|title = One Hundred Years of Chromium and Cancer: A Review of Epidemiological Evidence and Selected Case Reports
|first = Sverre
|last = Langard
|journal = American Journal of Industrial Medicine
|volume = 17
|issue = 2
|pages = 189–215
|year = 1990
|url =
|doi = 10.1002/ajim.4700170205
|pmid = 2405656}}</ref> Chromate enters cells by means of the same transport mechanism that carries [[sulfate]] and [[phosphate]] ions into cells.


[[Chromates]] (chromium salts) formed from hexavalent chromium are used to manufacture leather products, paints, cement, mortar, anti-corrosives, and other things.<ref>{{Cite journal | vauthors = Hedberg Y, Lidén C, Wallinder IO |date= March 2015 |title=Corrigendum to "Correlation between bulk- and surface chemistry of Cr-tanned leather and the release of Cr(III) and Cr(VI)" [J. Hazard. Mater. 280 (2014) 654–661] |url=http://dx.doi.org/10.1016/j.jhazmat.2014.12.062 |journal=Journal of Hazardous Materials |volume=285 |pages=542 |doi=10.1016/j.jhazmat.2014.12.062 |issn=0304-3894|doi-access=free }}</ref> They are carcinogenic and allergenic. The [[carcinogenity]] of chromate dust has been documented since the late 19th century, when workers in a chromate dye company were found to exhibit high incidence of cancer.<ref>{{cite journal |title = A case of adeno-carcinoma of the left inferior turbinated body, and perforation of the nasal septum, in the person of a worker in chrome pigments | vauthors = Newman D |journal = [[Glasgow Medical Journal]] |volume = 33 |pages = 469–470 |year = 1890}}</ref><ref name="Langard">{{cite journal | vauthors = Langård S | title = One hundred years of chromium and cancer: a review of epidemiological evidence and selected case reports | journal = American Journal of Industrial Medicine | volume = 17 | issue = 2 | pages = 189–215 | year = 1990 | pmid = 2405656 | doi = 10.1002/ajim.4700170205 }}</ref> Chromate enters cells by means of the same transport mechanism that carries [[sulfate]] and [[phosphate]] ions into cells.
Contact with products containing chromates can lead to allergic [[contact dermatitis]] and irritant dermatitis, resulting in ulceration of the skin—a condition sometimes called ''chrome ulcers''. Workers that have been exposed to strong chromate solutions in electroplating, tanning, and chrome-producing manufacturers may also develop chrome ulcers.<ref>{{cite web|publisher = DermNet NZ|title = Chrome Contact Allergy|url = http://dermnetnz.org/dermatitis/chrome-allergy.html}}</ref><ref name="BasketterHorev2001">{{cite journal

|title = Investigation of the threshold for allergic reactivity to chromium
Contact with products containing chromates can lead to allergic [[contact dermatitis]] and irritant dermatitis, resulting in ulceration of the skin—a condition sometimes called ''chrome ulcers''. Workers that have been exposed to strong chromate solutions in electroplating, tanning, and chrome-producing manufacturers may also develop chrome ulcers.<ref>{{cite web|publisher = DermNet NZ|title = Chrome Contact Allergy|url = http://dermnetnz.org/dermatitis/chrome-allergy.html}}</ref><ref name="BasketterHorev2001">{{cite journal | vauthors = Basketter D, Horev L, Slodovnik D, Merimes S, Trattner A, Ingber A | title = Investigation of the threshold for allergic reactivity to chromium | journal = Contact Dermatitis | volume = 44 | issue = 2 | pages = 70–74 | date = February 2001 | pmid = 11205406 | doi = 10.1034/j.1600-0536.2001.440202.x | s2cid = 45426346 }}</ref><ref name="BasketterBriatico-Vangosa1993">{{cite journal | vauthors = Basketter DA, Briatico-Vangosa G, Kaestner W, Lally C, Bontinck WJ | title = Nickel, cobalt and chromium in consumer products: a role in allergic contact dermatitis? | journal = Contact Dermatitis | volume = 28 | issue = 1 | pages = 15–25 | date = January 1993 | pmid = 8428439 | doi = 10.1111/j.1600-0536.1993.tb03318.x | s2cid = 35966310 }}</ref>
|first = David
|last = Basketter
|journal = Contact Dermatitis
|volume = 44
|issue = 2
|pages = 70–74
|year = 2000
|url =
|doi = 10.1034/j.1600-0536.2001.440202.x
|pmid = 11205406
|last2 = Horev
|first2 = L
|last3 = Slodovnik
|first3 = D
|last4 = Merimes
|first4 = S
|last5 = Trattner
|first5 = A
|last6 = Ingber
|first6 = A }}</ref><ref name="BasketterBriatico-Vangosa1993">{{cite journal
|title = Nickel, cobalt and chromium in consumer products: a role in allergic contact dermatitis?
|first = D. A.
|last = Basketter
|journal = Contact Dermatitis
|volume = 28
|issue = 1
|pages = 15–25
|year = 1992
|url =
|doi = 10.1111/j.1600-0536.1993.tb03318.x
|pmid = 8428439
|last2 = Briatico-Vangosa
|first2 = G
|last3 = Kaestner
|first3 = W
|last4 = Lally
|first4 = C
|last5 = Bontinck
|first5 = WJ }}</ref>


====Genotoxicity====
====Genotoxicity====
Hexavalent chromium is [[genotoxic]]: it damages genetic information in living cells, which results in DNA [[mutation]]s, and possibly the formation of cancerous [[tumor]]s. As of 2021, the mechanism of the [[genotoxic]] action of chromium(VI) is understood to involve the formation of [[reactive oxygen species]] as it is reduced to Cr(III), as well as interactions between [[DNA]] and Cr(V)/(IV) intermediates in the [[metabolism]] of Cr(VI).<ref name="aaem2021">{{cite journal |last1=Sawicka |first1=E |last2=Jurkowska |first2=K |last3=Piwowar |first3=A |doi=10.26444/aaem/118228 |pmid=33775062| title=Chromium (III) and chromium (VI) as important players in the induction of genotoxicity - current view |journal=Annals of Agricultural and Environmental Research |date=18 March 2021 |volume=28 |issue=1 |pages=1-10|doi-access=free }}</ref> However, the carcinogenic potential of Cr intermediates and the mechanisms of Cr-induced carcinogenicity remain to be further defined.
Three mechanisms have been proposed to describe the [[genotoxicity]] of chromium(VI).{{citation needed|date=April 2018}} The first mechanism includes highly reactive [[hydroxyl radical]]s and other reactive radicals which are byproducts of the reduction of chromium(VI) to chromium(III). The second process includes the direct binding of [[chromium(V)]], produced by reduction in the cell, and [[chromium(IV)]] compounds, to the [[DNA]]. The last mechanism attributes the genotoxicity to the binding to the DNA of the end product of the chromium(III) reduction.<ref name="Cohen">{{cite journal

|title = Mechanisms of chromium carcinogenicity and toxicity
The potential [[genotoxicity]] of chromium(III) has been explored in recent literature, and it has been observed ''[[in vitro]]'' generating [[hydroxyl radicals]] and binding to [[DNA]]; however, ''[[in vivo]]'' genotoxicity of Cr(III) is not well-established and the toxicity of Cr(III) compounds is generally considered to be at least 100 times lower than that of [[Chromium (VI)|Cr(VI)]] compounds.<ref name="aaem2021"/> This is in part due to the fact that Cr(III) is not an [[anion]] and therefore, unlike [[Chromium (VI)|Cr(VI)]] anions like [[Chromate and dichromate|chromate]], cannot be transported across [[cell membranes]] by [[ion channel|anion channels]].
|first = Cohen
|last = M. D.
|journal = Critical Reviews in Toxicology
|volume = 23
|issue = 3
|pages = 255–81
|year = 1993
|url =
|doi = 10.3109/10408449309105012
|pmid = 8260068
|last2 = Kargacin
|first2 = B
|last3 = Klein
|first3 = CB
|last4 = Costa
|first4 = M }}</ref>


===Trivalent chromium===
===Trivalent chromium===
{{See also|Chromium deficiency}}
{{See also|Chromium deficiency}}


[[Trivalent chromium]], or chromium(III), is an essential [[trace mineral]] in the human diet. In some [[nutritional supplement]]s, chromium(III) occurs as [[chromium(III) picolinate]]—in which chromium is bound to [[picolinic acid]]—or [[chromium(III) nicotinate]]—in which chromium is bound to [[nicotinic acid]] (the [[B vitamin]] [[niacin]]).
[[Trivalent chromium]], or chromium(III), is an essential [[trace mineral]] in the human diet.<ref name="Bogden"/> In some [[nutritional supplement]]s, chromium(III) occurs as [[chromium(III) picolinate]] (in which chromium is bound to [[picolinic acid]]) or [[chromium(III) nicotinate]] (in which chromium is bound to [[nicotinic acid]]). Nicotinic acid is also known as the [[B vitamin]] [[Niacin (substance)|niacin]].


Chromium(III) is poorly absorbed in humans; most dietary chromium is excreted in the urine.<ref>{{cite web |url=http://lpi.oregonstate.edu/mic/minerals/chromium#toxicity |title=Chromium § Toxicity |website=Micronutrient Information Center |publisher=[[Oregon State University]] |access-date=2018-04-15}}</ref> The threshold for [[Acute toxicity|acute]] oral toxicity is 1900–3300&nbsp;µg/kg.<ref name="Katz">{{cite journal |title = The toxicology of chromium with respect to its chemical speciation: A review |first = Sidney A.|last = Katz|journal = Journal of Applied Toxicology |volume = 13 |issue = 3|pages = 217–224 |year = 1992 |url = |doi = 10.1002/jat.2550130314 |pmid = 8326093 |last2 = Salem |first2 = H }}</ref> In rats, [[nonsteroidal anti-inflammatory drug]]s such as [[aspirin]] and [[indometacin]] can increase chromium absorption.<ref>{{cite web |url=http://lpi.oregonstate.edu/mic/minerals/chromium#drug-interactions |title=Chromium § Drug interactions
Chromium(III) is poorly absorbed in humans; most dietary chromium is excreted in the urine.<ref>{{cite web |url=http://lpi.oregonstate.edu/mic/minerals/chromium#toxicity |title=Chromium § Toxicity |website=Micronutrient Information Center |date=22 April 2014 |publisher=[[Oregon State University]] |access-date=2018-04-15}}</ref> The threshold for [[Acute toxicity|acute]] oral toxicity is 1900–3300&nbsp;mg/kg.<ref name="Katz">{{cite journal | vauthors = Katz SA, Salem H | title = The toxicology of chromium with respect to its chemical speciation: a review | journal = Journal of Applied Toxicology | volume = 13 | issue = 3 | pages = 217–224 | year = 1992 | pmid = 8326093 | doi = 10.1002/jat.2550130314 | s2cid = 31117557 }}</ref> In rats, [[nonsteroidal anti-inflammatory drug]]s such as [[aspirin]] and [[indometacin]] can increase chromium absorption.<ref>{{cite web |url=http://lpi.oregonstate.edu/mic/minerals/chromium#drug-interactions |title=Chromium § Drug interactions |website=Micronutrient Information Center |date=22 April 2014 |publisher=[[Oregon State University]] |access-date=2018-04-15}}</ref>
|website=Micronutrient Information Center |publisher=[[Oregon State University]] |access-date=2018-04-15}}</ref>


Ordinarily, cellular transport mechanisms in humans and some other animals limit the amount of chromium(III) that enters a cell. Hypothetically, if an excessive amount was able to enter a cell, [[free radical damage to DNA]] might result.<ref name="Eastmond">{{cite journal |last = Eastmond |first = David A. |year = 2008 |title = Trivalent Chromium: Assessing the Genotoxic Risk of an Essential Trace Element and Widely Used Human and Animal Nutritional Supplement |journal = Critical Reviews in Toxicology |volume = 38 |issue = 3 |pages = 173–190 |doi = 10.1080/10408440701845401 |pmid = 18324515 |last2 = MacGregor |first2 = JT |last3 = Slesinski |first3 = RS}}</ref>
Ordinarily, cellular transport mechanisms in humans and some other animals limit the amount of chromium(III) that enters a cell. Hypothetically, if an excessive amount was able to enter a cell, [[free radical damage to DNA]] might result.<ref name="Eastmond">{{cite journal | vauthors = Eastmond DA, Macgregor JT, Slesinski RS | title = Trivalent chromium: assessing the genotoxic risk of an essential trace element and widely used human and animal nutritional supplement | journal = Critical Reviews in Toxicology | volume = 38 | issue = 3 | pages = 173–190 | year = 2008 | pmid = 18324515 | doi = 10.1080/10408440701845401 | s2cid = 21033504 }}</ref>

==Measuring exposure in humans==
Overexposure to chromium{{which|date=April 2018}} can occur in welders and other metal workers, patients who have received metallic surgical implants, and individuals who ingest industrial chromate. Chromium concentrations in whole blood, plasma, serum, or urine may be measured to monitor for safety in exposed workers, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation in a case of fatal overdosage.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 305-307.</ref>

==References==
{{reflist|30em}}


== References ==
{{Reflist}}


== External links ==
{{Medical resources
| DiseasesDB =
| ICD10 = {{ICD10|T|56|2|t|51}}
| ICD9 = {{ICD9|985.6}}
| ICDO =
| OMIM =
| MedlinePlus =
| eMedicineSubj =
| eMedicineTopic =
| MeshID =
}}
{{Poisoning and toxicity}}
{{Poisoning and toxicity}}
{{Elements in biology}}


[[Category:Toxic effects of metals]]
[[Category:Toxic effects of metals]]

Latest revision as of 11:16, 28 January 2024

Chromium toxicity
Chromium
SpecialtyToxicology

Chromium toxicity refers to any poisonous toxic effect in an organism or cell that results from exposure to specific forms of chromium—especially hexavalent chromium.[1] Hexavalent chromium and its compounds are toxic when inhaled or ingested. Trivalent chromium is a trace mineral that is essential to human nutrition. There is a hypothetical risk of genotoxicity in humans if large amounts of trivalent chromium were somehow able to enter living cells, but normal metabolism and cell function prevent this.[2]

Forms of chromium

[edit]

Hexavalent chromium and trivalent chromium are chromium ions—they have different numbers of electrons and, therefore, different properties. Trivalent chromium, or chromium(III), is the form of chromium that is essential to human health.[3] Hexavalent chromium, or chromium(VI), is an unequivocally toxic form.

Hexavalent chromium

[edit]
Main article: Hexavalent chromium § Toxicity

Hexavalent chromium, also called chromium(VI), is hemotoxic, genotoxic, and carcinogenic.[4] When hexavalent chromium enters the bloodstream, it damages blood cells by causing oxidation reactions. This oxidative damage can lead to hemolysis and, ultimately, kidney and liver failure. Patients might be treated with dialysis.[5]

The median lethal dose of hexavalent chromium is 50–150 mg/kg.[6] The World Health Organization recommends a maximum allowable concentration of 0.05 milligrams per litre of chromium(VI) in drinking water.[7] In Europe, the use of hexavalent chromium is regulated by the Restriction of Hazardous Substances Directive.

Hexavalent chromium can be found in some dyes and paints, as well as in some leather tanning products. Primer paint containing hexavalent chromium is widely used in aerospace and automobile refinishing applications. Metal workers (such as welders)—as well as people with a surgical implant made from cobalt-chromium alloy—may also be exposed to hexavalent chromium.[8] Chromium concentrations in whole blood, plasma, serum, or urine may be measured to monitor for safety in exposed workers, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation in a case of fatal overdosage.[9]

In the U.S. state of California, an epidemic of hexavalent chromium exposure led to a class-action lawsuit in 1993: Anderson, et al. v. Pacific Gas and Electric. The Pacific Gas and Electric Company had dumped more than 1.4 billion litres (370 million gallons) of wastewater tainted with hexavalent chromium into the Mojave Desert. This contaminated the groundwater, and caused widespread illness among the people of Hinkley, California, a small community nearby. As of May 2017, the mandated environmental remediation measures are ongoing.[10]

Chromate

[edit]
See also: Chromate and dichromate § Toxicity

Chromates (chromium salts) formed from hexavalent chromium are used to manufacture leather products, paints, cement, mortar, anti-corrosives, and other things.[11] They are carcinogenic and allergenic. The carcinogenity of chromate dust has been documented since the late 19th century, when workers in a chromate dye company were found to exhibit high incidence of cancer.[12][13] Chromate enters cells by means of the same transport mechanism that carries sulfate and phosphate ions into cells.

Contact with products containing chromates can lead to allergic contact dermatitis and irritant dermatitis, resulting in ulceration of the skin—a condition sometimes called chrome ulcers. Workers that have been exposed to strong chromate solutions in electroplating, tanning, and chrome-producing manufacturers may also develop chrome ulcers.[14][15][16]

Genotoxicity

[edit]

Hexavalent chromium is genotoxic: it damages genetic information in living cells, which results in DNA mutations, and possibly the formation of cancerous tumors. As of 2021, the mechanism of the genotoxic action of chromium(VI) is understood to involve the formation of reactive oxygen species as it is reduced to Cr(III), as well as interactions between DNA and Cr(V)/(IV) intermediates in the metabolism of Cr(VI).[17] However, the carcinogenic potential of Cr intermediates and the mechanisms of Cr-induced carcinogenicity remain to be further defined.

The potential genotoxicity of chromium(III) has been explored in recent literature, and it has been observed in vitro generating hydroxyl radicals and binding to DNA; however, in vivo genotoxicity of Cr(III) is not well-established and the toxicity of Cr(III) compounds is generally considered to be at least 100 times lower than that of Cr(VI) compounds.[17] This is in part due to the fact that Cr(III) is not an anion and therefore, unlike Cr(VI) anions like chromate, cannot be transported across cell membranes by anion channels.

Trivalent chromium

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See also: Chromium deficiency

Trivalent chromium, or chromium(III), is an essential trace mineral in the human diet.[3] In some nutritional supplements, chromium(III) occurs as chromium(III) picolinate (in which chromium is bound to picolinic acid) or chromium(III) nicotinate (in which chromium is bound to nicotinic acid). Nicotinic acid is also known as the B vitamin niacin.

Chromium(III) is poorly absorbed in humans; most dietary chromium is excreted in the urine.[18] The threshold for acute oral toxicity is 1900–3300 mg/kg.[6] In rats, nonsteroidal anti-inflammatory drugs such as aspirin and indometacin can increase chromium absorption.[19]

Ordinarily, cellular transport mechanisms in humans and some other animals limit the amount of chromium(III) that enters a cell. Hypothetically, if an excessive amount was able to enter a cell, free radical damage to DNA might result.[20]

References

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  1. ^ "Chromium (Cr) Toxicity: What Are the Physiologic Effects of Chromium Exposure? | Environmental Medicine | ATSDR". www.atsdr.cdc.gov. 2021-02-09. Retrieved 2022-06-05.
  2. ^ Hartwig A, Arand M, Epe B, Guth S, Jahnke G, Lampen A, et al. (June 2020). "Mode of action-based risk assessment of genotoxic carcinogens". Archives of Toxicology. 94 (6): 1787–1877. doi:10.1007/s00204-020-02733-2. PMC 7303094. PMID 32542409.
  3. ^ a b Bogden JD, Klevay LM, eds. (2000). "Trace Elements and Minerals in the Elderly § Chromium". Clinical Nutrition of the Essential Trace Elements and Minerals: The Guide for Health Professionals. Springer Science+Business Media. p. 189. ISBN 978-1-61737-090-8 – via Google Books.
  4. ^ Barceloux DG (1999). "Chromium". Journal of Toxicology. Clinical Toxicology. 37 (2): 173–194. doi:10.1081/CLT-100102418. PMID 10382554.
  5. ^ Dayan AD, Paine AJ (September 2001). "Mechanisms of chromium toxicity, carcinogenicity and allergenicity: review of the literature from 1985 to 2000". Human & Experimental Toxicology. 20 (9): 439–451. doi:10.1191/096032701682693062. PMID 11776406. S2CID 31351037.
  6. ^ a b Katz SA, Salem H (1992). "The toxicology of chromium with respect to its chemical speciation: a review". Journal of Applied Toxicology. 13 (3): 217–224. doi:10.1002/jat.2550130314. PMID 8326093. S2CID 31117557.
  7. ^ "WHO Guidelines on Drinking-Water Quality" (PDF). WHO.int. World Health Organization. Section 12.30: Chromium.
  8. ^ Merritt K, Brown SA (May 1995). "Release of hexavalent chromium from corrosion of stainless steel and cobalt-chromium alloys". Journal of Biomedical Materials Research. 29 (5): 627–633. doi:10.1002/jbm.820290510. PMID 7622548.
  9. ^ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City: Biomedical Publications. pp. 305–7. ISBN 978-0962652370.
  10. ^ Izbicki JA, Groover K. "Natural and Man-Made Hexavalent Chromium, Cr(VI), in Groundwater near a Mapped Plume, Hinkley, California—Study Progress as of May 2017, and a Summative-Scale Approach to Estimate Background Cr(VI) Concentrations" (PDF). Open-file Report. United States Geological Survey. ISSN 2331-1258. Retrieved 2018-05-15.
  11. ^ Hedberg Y, Lidén C, Wallinder IO (March 2015). "Corrigendum to "Correlation between bulk- and surface chemistry of Cr-tanned leather and the release of Cr(III) and Cr(VI)" [J. Hazard. Mater. 280 (2014) 654–661]". Journal of Hazardous Materials. 285: 542. doi:10.1016/j.jhazmat.2014.12.062. ISSN 0304-3894.
  12. ^ Newman D (1890). "A case of adeno-carcinoma of the left inferior turbinated body, and perforation of the nasal septum, in the person of a worker in chrome pigments". Glasgow Medical Journal. 33: 469–470.
  13. ^ Langård S (1990). "One hundred years of chromium and cancer: a review of epidemiological evidence and selected case reports". American Journal of Industrial Medicine. 17 (2): 189–215. doi:10.1002/ajim.4700170205. PMID 2405656.
  14. ^ "Chrome Contact Allergy". DermNet NZ.
  15. ^ Basketter D, Horev L, Slodovnik D, Merimes S, Trattner A, Ingber A (February 2001). "Investigation of the threshold for allergic reactivity to chromium". Contact Dermatitis. 44 (2): 70–74. doi:10.1034/j.1600-0536.2001.440202.x. PMID 11205406. S2CID 45426346.
  16. ^ Basketter DA, Briatico-Vangosa G, Kaestner W, Lally C, Bontinck WJ (January 1993). "Nickel, cobalt and chromium in consumer products: a role in allergic contact dermatitis?". Contact Dermatitis. 28 (1): 15–25. doi:10.1111/j.1600-0536.1993.tb03318.x. PMID 8428439. S2CID 35966310.
  17. ^ a b Sawicka, E; Jurkowska, K; Piwowar, A (18 March 2021). "Chromium (III) and chromium (VI) as important players in the induction of genotoxicity - current view". Annals of Agricultural and Environmental Research. 28 (1): 1–10. doi:10.26444/aaem/118228. PMID 33775062.
  18. ^ "Chromium § Toxicity". Micronutrient Information Center. Oregon State University. 22 April 2014. Retrieved 2018-04-15.
  19. ^ "Chromium § Drug interactions". Micronutrient Information Center. Oregon State University. 22 April 2014. Retrieved 2018-04-15.
  20. ^ Eastmond DA, Macgregor JT, Slesinski RS (2008). "Trivalent chromium: assessing the genotoxic risk of an essential trace element and widely used human and animal nutritional supplement". Critical Reviews in Toxicology. 38 (3): 173–190. doi:10.1080/10408440701845401. PMID 18324515. S2CID 21033504.
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