Editing Gadolinium (section)

==Safety==
{{Main|MRI contrast agent|Nephrogenic systemic fibrosis}}

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As a free ion, gadolinium is reported often to be highly toxic, but MRI contrast agents are [[chelation|chelated]] compounds and are considered safe enough to be used in most persons. The toxicity of free gadolinium ions in animals is due to interference with a number of calcium-ion channel dependent processes. The [[LD50|50% lethal dose]] is about 0.34&nbsp;mmol/kg (IV, mouse)<ref>Bousquet et coll., 1988</ref> or 100–200&nbsp;mg/kg. Toxicity studies in rodents show that chelation of gadolinium (which also improves its solubility) decreases its toxicity with regard to the free ion by a factor of 31 (i.e., the lethal dose for the Gd-chelate increases by 31 times).<ref>{{Cite web|url=https://www.acadpharm.org/dos_public/Academie_de_pharmacie_2014_JM_Idee_V2.pdf|title=Profil toxicologique des chélates de gadolinium pour l'IRM : où en est-on ?}}</ref><ref>{{Cite journal|last1=Ersoy|first1=Hale|last2=Rybicki|first2=Frank J.|date=November 2007|title=Biochemical Safety Profiles of Gadolinium-Based Extracellular Contrast Agents and Nephrogenic Systemic Fibrosis|journal=Journal of Magnetic Resonance Imaging |volume=26|issue=5|pages=1190–1197|doi=10.1002/jmri.21135|issn=1053-1807|pmc=2709982|pmid=17969161}}</ref><ref>{{cite journal |vauthors= Penfield JG, Reilly RF |title= What nephrologists need to know about gadolinium |journal= Nature Clinical Practice. Nephrology |volume= 3 |issue= 12 |pages= 654–68 |date= December 2007 |pmid= 18033225 |doi= 10.1038/ncpneph0660 |s2cid= 22435496 }}</ref> It is believed therefore that clinical toxicity of gadolinium-based contrast agents (GBCAs<ref name="GDD">{{cite web|url=https://gadoliniumtoxicity.com/tag/gadolinium-deposition-disease/|title=Gadolinium Deposition Disease (GDD) in Patients with Normal Renal Function|date=1 November 2015|website=Gadolinium Toxicity|access-date=3 February 2016}}</ref>) in humans will depend on the strength of the chelating agent; however this research is still not complete.{{When|date=August 2016}} About a dozen different Gd-chelated agents have been approved as MRI contrast agents around the world.<ref>{{cite web |url= http://www.ismrm.org/special/EMEA2.pdf |archive-url=https://web.archive.org/web/20071129121817/http://www.ismrm.org/special/EMEA2.pdf |archive-date=2007-11-29 |url-status=live|title= Questions and Answers on Magnetic resonance imaging |access-date= 6 June 2009|work=International Society for Magnetic Resonance in Medicine}}</ref><ref>{{cite web|title=Information on Gadolinium-Containing Contrast Agents |url=https://www.fda.gov/Cder/Drug/infopage/gcca/default.htm |work=US Food and Drug Administration |url-status=dead |archive-url=https://web.archive.org/web/20080906211904/https://www.fda.gov/Cder/Drug/infopage/gcca/default.htm |archive-date=6 September 2008}}</ref><ref name="Gray">Gray, Theodore (2009). ''The Elements'', Black Dog & Leventhal Publishers, {{ISBN|1-57912-814-9}}.</ref>

Use of gadolinium-based contrast agents results in deposition of gadolinium in tissues of the brain, bone, skin, and other tissues in amounts that depend on [[Ultrafiltration (kidney)|kidney function]], structure of the chelates (linear or macrocyclic) and the dose administered.<ref name="Tweedle 2021">{{cite journal | last=Tweedle | first=Michael F. | title=Gadolinium Retention in Human Brain, Bone, and Skin | journal=Radiology | volume=300 | issue=3 | date=2021 | issn=0033-8419 | doi=10.1148/radiol.2021210957 | pages=570–571| pmid=34128728 }}</ref> In patients with kidney failure, there is a risk of a rare but serious illness called [[nephrogenic systemic fibrosis]] (NSF)<ref>{{cite journal |vauthors= Thomsen HS, Morcos SK, Dawson P |title= Is there a causal relation between the administration of gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF)? |journal= Clinical Radiology |volume= 61 |issue= 11 |pages= 905–06 |date= November 2006 |pmid= 17018301 |doi= 10.1016/j.crad.2006.09.003 }}</ref> that is caused by the use of gadolinium-based contrast agents. The disease resembles [[scleromyxedema]] and to some extent [[scleroderma]]. It may occur months after a contrast agent has been injected. Its association with gadolinium and not the carrier molecule is confirmed by its occurrence with various contrast materials in which gadolinium is carried by very different carrier molecules. Because of the risk of NSF, use of these agents is not recommended for any individual with end-stage kidney failure as they may require emergent dialysis.

Included in the current guidelines from the Canadian Association of Radiologists<ref name="CARguidelines">{{cite journal |vauthors= Schieda N, Blaichman JI, Costa AF, Glikstein R, Hurrell C, James M, Jabehdar Maralani P, Shabana W, Tang A, Tsampalieros A, van der Pol CB, Hiremath S |title= Gadolinium-Based Contrast Agents in Kidney Disease: A Comprehensive Review and Clinical Practice Guideline Issued by the Canadian Association of Radiologists |journal= Canadian Journal of Kidney Health and Disease |volume= 5 |pages= 2054358118778573 |date= 2018 |pmid= 29977584 |pmc= 6024496 |doi= 10.1177/2054358118778573}}</ref> are that dialysis patients should receive gadolinium agents only where essential and that they should receive dialysis after the exam. If a contrast-enhanced MRI must be performed on a dialysis patient, it is recommended that certain high-risk contrast agents be avoided but not that a lower dose be considered.<ref name="CARguidelines" /> The American College of Radiology recommends that contrast-enhanced MRI examinations be performed as closely before dialysis as possible as a precautionary measure, although this has not been proven to reduce the likelihood of developing NSF.<ref>{{cite book |author1=ACR Committee on Drugs |author2=Contrast Media |title= ACR Manual on Contrast Media Version 7 |date= 2010 |publisher=American College of Radiology |isbn= 978-1-55903-050-2}}</ref> The FDA recommends that potential for gadolinium retention be considered when choosing the type of GBCA used in patients requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions.<ref>{{cite web|url=https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm|publisher=Drug Safety and Availability – FDA Drug Safety Communication |title=FDA warns that gadolinium-based contrast agents (GBCAs) are retained in the body; requires new class warnings|author=Center for Drug Evaluation and Research|website=www.fda.gov|language=en|access-date=20 September 2018}}</ref>

[[Anaphylactoid reaction]]s are rare, occurring in approximately 0.03–0.1%.<ref>{{cite journal|vauthors=Murphy KJ, Brunberg JA, Cohan RH|date=October 1996|title=Adverse reactions to gadolinium contrast media: a review of 36 cases|journal=AJR. American Journal of Roentgenology|volume=167|issue=4|pages=847–49|doi=10.2214/ajr.167.4.8819369|pmid=8819369|doi-access=free}}</ref>

Long-term environmental impacts of gadolinium contamination due to human usage are a topic of ongoing research.<ref>{{cite journal|last1=Gwenzi|first1=Willis|last2=Mangori|first2=Lynda|last3=Danha|first3=Concilia|last4=Chaukura|first4=Nhamo|last5=Dunjana|first5=Nothando|last6=Sanganyado|first6=Edmond|date=15 September 2018|title=Sources, behaviour, and environmental and human health risks of high-technology rare-earth elements as emerging contaminants|journal=The Science of the Total Environment|volume=636|pages=299–313|doi=10.1016/j.scitotenv.2018.04.235|issn=1879-1026|pmid=29709849|bibcode=2018ScTEn.636..299G|s2cid=19076605}}</ref><ref>{{cite journal |vauthors= Rogowska J, Olkowska E, Ratajczyk W, Wolska L |title= Gadolinium as a new emerging contaminant of aquatic environments |journal= Environmental Toxicology and Chemistry |volume= 37 |issue= 6 |pages= 1523–34 |date= June 2018 |pmid= 29473658 |doi= 10.1002/etc.4116|doi-access= free |bibcode= 2018EnvTC..37.1523R }}</ref>