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Botulinum toxin
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==Society and culture== ===Economics=== {{Update|date=October 2017}} {{As of|2018}}, botulinum toxin injections are the most common cosmetic operation, with 7.4 million procedures in the United States, according to the [[American Society of Plastic Surgeons]].<ref>{{cite web |url=https://www.plasticsurgery.org/news/press-releases/new-plastic-surgery-statistics-reveal-trends-toward-body-enhancement |title=New plastic surgery statistics reveal trends toward body enhancement |date=11 March 2019 |website=Plastic Surgery |archive-url=https://web.archive.org/web/20190312062815/https://www.plasticsurgery.org/news/press-releases/new-plastic-surgery-statistics-reveal-trends-toward-body-enhancement |archive-date=12 March 2019}}</ref> The global market for botulinum toxin products, driven by their cosmetic applications, was forecast to reach $2.9 billion by 2018. The facial aesthetics market, of which they are a component, was forecast to reach $4.7 billion ($2 billion in the US) in the same timeframe.<ref>{{cite web |url=http://www.companiesandmarkets.com/News/Healthcare-and-Medical/The-global-botox-market-forecast-to-reach-2-9-billion-by-2018/NI2991 |title=The global botox market forecast to reach $2.9 billion by 2018 |date=10 May 2012 |access-date=5 October 2012 |vauthors=Chapman L |archive-url=https://web.archive.org/web/20120806230249/http://www.companiesandmarkets.com/News/Healthcare-and-Medical/The-global-botox-market-forecast-to-reach-2-9-billion-by-2018/NI2991 |archive-date=6 August 2012 |url-status=dead}}</ref> ====US market==== In 2020, 4,401,536 botulinum toxin Type A procedures were administered.<ref>{{cite web |title=2020 National Plastic Surgery Statistics: Cosmetic Surgical Procedures |url=https://www.plasticsurgery.org/documents/News/Statistics/2020/plastic-surgery-statistics-report-2020.pdf |publisher=American Society of Plastic Surgeons |access-date=22 May 2021 |archive-date=23 June 2021 |archive-url=https://web.archive.org/web/20210623232536/https://www.plasticsurgery.org/documents/News/Statistics/2020/plastic-surgery-statistics-report-2020.pdf |url-status=live }}</ref> In 2019 the botulinum toxin market made US$3.19 billion.<ref name="FBI">{{cite web |title=Botulinum Toxin Market |url=https://www.fortunebusinessinsights.com/industry-reports/botulinum-toxin-market-100996 |work=Fortune Business Insights |access-date=22 May 2021 |archive-date=27 June 2021 |archive-url=https://web.archive.org/web/20210627192718/https://www.fortunebusinessinsights.com/industry-reports/botulinum-toxin-market-100996 |url-status=live }}</ref> ====Botox cost==== Botox cost is generally determined by the number of units administered (avg. $10β30 per unit) or by the area ($200β1000) and depends on the physician's expertise, clinic location, number of units, and treatment complexity.<ref>{{Cite web |title=How Much Does Botox Cost |url=https://www.cosmeticassociation.org/cosmetic-procedures/botox/how-much-does-botox-cost/ |access-date=13 March 2013 |website=American Cosmetic Association |archive-date=13 March 2023 |archive-url=https://web.archive.org/web/20230313122938/https://www.cosmeticassociation.org/cosmetic-procedures/botox/how-much-does-botox-cost/ |url-status=live }}</ref> ====Insurance==== In the US, Botox for medical purposes is usually covered by insurance if deemed medically necessary by a doctor and covers a plethora of medical problems including overactive bladder (OAB), urinary incontinence due to neurologic conditions, headaches and migraines, TMJ, spasticity in adults, cervical dystonia in adults, severe axillary hyperhidrosis (or other areas of the body), blepharospasm, upper or lower limb spasticity.<ref>{{cite web |title=Medicare Guidelines for Botox Treatments |url=https://www.medicarefaq.com/faqs/medicare-coverage-for-botox-treatments |work=MedicareFAQ.com |date=27 September 2021 |access-date=22 May 2021 |archive-date=23 May 2021 |archive-url=https://web.archive.org/web/20210523024145/https://www.medicarefaq.com/faqs/medicare-coverage-for-botox-treatments/ |url-status=live }}</ref><ref>{{cite web |title=BOTOX (onabotulinumtoxinA) for injection, for intramuscular, intradetrusor, or intradermal use |work=Highlights of Prescribing Information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103000s5302lbl.pdf |publisher=U.S. [[Food and Drug Administration]] (FDA) |access-date=22 May 2021 |archive-date=28 March 2021 |archive-url=https://web.archive.org/web/20210328131433/https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103000s5302lbl.pdf |url-status=live }}</ref> ====Cosmetic==== Botox's potential to reduce facial wrinkles was discovered in the 1990s, leading to its FDA approval for cosmetic use in 2002. Standard areas for aesthetics Botox injections include areas on the face or neck that can form fine lines and wrinkles due to every day muscle contractions and/or facial expressions such as smiling, frowning, squinting, and raising eyebrows. These areas include the glabellar region between the eyebrows, horizontal lines on the forehead, crow's feet around the eyes, and even circular bands that form around the neck secondary to platysmal hyperactivity.<ref>{{cite web | vauthors = Cosentino S |title=What Is Botox |website=Empire Medical Training |date=2021-02-13 |url=https://www.empiremedicaltraining.com/blog/what-is-botox/ |access-date=2025-05-01}}</ref> ====Hyperhidrosis==== Botox for excessive sweating is FDA approved.<ref name="pmid20418969">{{cite journal |vauthors = Nigam PK, Nigam A |title = Botulinum toxin |journal = Indian Journal of Dermatology |volume = 55 |issue = 1 |pages = 8β14 |date = 2010 |pmid = 20418969 |pmc = 2856357 |doi = 10.4103/0019-5154.60343 |doi-access = free }}</ref> ===Bioterrorism=== Botulinum toxin has been recognized as a potential agent for use in [[bioterrorism]].<ref>{{cite web |vauthors=Koirala J, Basnet S |date=14 July 2004 |title=Botulism, Botulinum Toxin, and Bioterrorism: Review and Update |work=[[Medscape]] |publisher=Cliggott Publishing |url=http://www.medscape.com/viewarticle/482812 |access-date=14 July 2010 |url-status=dead |archive-url=https://web.archive.org/web/20110601225033/http://www.medscape.com/viewarticle/482812 |archive-date=1 June 2011}}</ref> It can be absorbed through the eyes, mucous membranes, respiratory tract, and non-intact skin.<ref>{{cite web |url=https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/clostridium-botulinum.html |title=Pathogen Safety Data Sheets: Infectious Substances β ''Clostridium botulinum'' |author=Public Health Agency of Canada |date=19 April 2011 |access-date=24 January 2022 |archive-date=24 January 2022 |archive-url=https://web.archive.org/web/20220124011913/https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/clostridium-botulinum.html |url-status=live }}</ref> The effects of botulinum toxin are different from those of nerve agents involved insofar in that botulism symptoms develop relatively slowly (over several days), while nerve agent effects are generally much more rapid. Evidence suggests that nerve exposure (simulated by injection of [[atropine]] and [[pralidoxime]]) will increase mortality by enhancing botulinum toxin's mechanism of toxicity.<ref>{{cite book |vauthors=Fleisher LA, Roizen MF, Roizen J |url=https://books.google.com/books?id=RSQmDwAAQBAJ&q=nerve+exposure++will+increase+mortality+by+enhancing+botulinum+toxin's&pg=PA56 |title=Essence of Anesthesia Practice E-Book |date=31 May 2017 |publisher=Elsevier Health Sciences |isbn=978-0-323-39541-0 |access-date=10 June 2022 |archive-date=11 November 2021 |archive-url=https://web.archive.org/web/20211111023438/https://books.google.com/books?id=RSQmDwAAQBAJ&q=nerve+exposure++will+increase+mortality+by+enhancing+botulinum+toxin%27s&pg=PA56 |url-status=live }}</ref> With regard to detection, protocols using [[NBC (weapon)|NBC]] detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when samples containing botulinum toxin are tested.<ref>{{cite web |url=https://www.wmddetectorselector.army.mil/PDFs/328.pdf |title=M8 Paper |author=<!--Not stated--> |date=<!--Not stated--> |publisher=U.S. Army |access-date=16 September 2020 |quote="M8 paper is a chemically-treated, dye-impregnated paper used to detect liquid substances for the presence of V- and G-type nerve agents and H- and L-type blister agents." |archive-date=23 October 2020 |archive-url=https://web.archive.org/web/20201023152924/https://www.wmddetectorselector.army.mil/PDFs/328.pdf |url-status=dead }}</ref> To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in death investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12β24 mouse LD<sub>50</sub> units per milliliter have been detected in poisoned people.<ref>{{cite book |author=Baselt RC |title=Disposition of toxic drugs and chemicals in man |year=2014 |publisher=Biomedical Publications |location=Seal Beach, Ca. |isbn=978-0-9626523-9-4 |pages=260β61}}</ref> During the early 1980s, German and French newspapers reported that the police had raided a [[Baader-Meinhof]] gang safe house in Paris and had found a makeshift laboratory that contained flasks full of ''[[Clostridium botulinum]]'', which makes botulinum toxin. Their reports were later found to be incorrect; no such lab was ever found.<ref>{{cite book |vauthors=McAdams D, Kornblet S |veditors=Pilch RF, Zilinskas RA |title=Encyclopedia of Bioterrorism Defense |year=2011 |publisher=Wiley-Liss |isbn=978-0-471-68678-1 |chapter=Baader-Meinhof Group (OR Baader-Meinhof Gang |pages=1β2 |doi=10.1002/0471686786.ebd0012.pub2}}</ref> ===Brand names=== {{Globalize|article|USA|2name=the United States|date=April 2017}} Commercial forms are marketed under the brand names Botox (onabotulinumtoxinA),<ref name="Botox FDA label" /><ref name="FDA Botulinum">{{cite web |title=OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc) Information |publisher=U.S. [[Food and Drug Administration]] (FDA) |date=3 November 2018 |url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/onabotulinumtoxina-marketed-botoxbotox-cosmetic-abobotulinumtoxina-marketed-dysport-and |access-date=18 December 2022 |archive-date=18 December 2022 |archive-url=https://web.archive.org/web/20221218020508/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/onabotulinumtoxina-marketed-botoxbotox-cosmetic-abobotulinumtoxina-marketed-dysport-and |url-status=dead }}</ref><ref>{{cite web |title=Botulinum Toxin Type A Product Approval Information - Licensing Action 4/12/02 |publisher=U.S. [[Food and Drug Administration]] (FDA) |date=9 February 2009 |url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080509.htm |archive-url=https://web.archive.org/web/20170113111252/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080509.htm |archive-date=13 January 2017 |url-status=dead |access-date=18 December 2022}}</ref> Dysport/Azzalure (abobotulinumtoxinA),<ref name="FDA Botulinum" /><ref>{{cite web |title=Drug Approval Package: Dysport (abobotulinumtoxin) NDA #125274s000 |publisher=U.S. [[Food and Drug Administration]] (FDA) |date=17 August 2011 |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/125274s000_dysport_toc.cfm |access-date=23 November 2019 |archive-date=24 November 2019 |archive-url=https://web.archive.org/web/20191124011534/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/125274s000_dysport_toc.cfm |url-status=dead }}</ref> Letybo (letibotulinumtoxinA),<ref name="Letybo FDA label" /><ref name="Letybo APMDS">{{Cite web |url=https://www.tga.gov.au/resources/auspmd/letybo |title=Letybo | Therapeutic Goods Administration (TGA) |access-date=18 December 2022 |archive-date=18 December 2022 |archive-url=https://web.archive.org/web/20221218020505/https://www.tga.gov.au/resources/auspmd/letybo |url-status=live }}</ref><ref>{{cite press release |title=Hugel's 'Letybo' First in Korea to Obtain Marketing Approval from Australia |website=Hugel |via=PR Newswire |date=24 November 2022 |url=https://www.prnewswire.com/news-releases/hugels-letybo-first-in-korea-to-obtain-marketing-approval-from-australia-301686683.html |access-date=18 December 2022 |archive-date=18 December 2022 |archive-url=https://web.archive.org/web/20221218020505/https://www.prnewswire.com/news-releases/hugels-letybo-first-in-korea-to-obtain-marketing-approval-from-australia-301686683.html |url-status=live }}</ref> Myobloc (rimabotulinumtoxinB),<ref name="Myobloc FDA label" /><ref name="FDA Botulinum" /> Xeomin/Bocouture (incobotulinumtoxinA),<ref>{{cite web |title=Drug Approval Package: Xeomin (incobotulinumtoxinA) Injection NDA #125360 |publisher=U.S. [[Food and Drug Administration]] (FDA) |date=24 December 1999 |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125360s0000TOC.cfm |access-date=23 November 2019 |archive-date=27 July 2020 |archive-url=https://web.archive.org/web/20200727030043/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125360s0000TOC.cfm |url-status=dead }}</ref> and Jeuveau (prabotulinumtoxinA).<ref>{{cite web |title=Drug Approval Package: Jeuveau |publisher=U.S. [[Food and Drug Administration]] (FDA) |date=5 March 2019 |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761085Orig1s000TOC.cfm |access-date=22 November 2019 |url-status=dead |archive-url=https://web.archive.org/web/20191123073132/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761085Orig1s000TOC.cfm |archive-date=23 November 2019}} {{PD-notice}}</ref><ref name="Krause_2019">{{cite web |url=https://www.refinery29.com/en-us/jeuveau-newtox-injections-for-wrinkles |title=Jeuveau, The Most Affordable Wrinkle Injectable |vauthors=Krause R |date=10 June 2019 |website=refinery29.com |access-date=9 July 2019 |archive-date=18 March 2021 |archive-url=https://web.archive.org/web/20210318023749/https://www.refinery29.com/en-us/jeuveau-newtox-injections-for-wrinkles |url-status=live }}</ref> Botulinum toxin A is sold under the brand names Jeuveau, Botox, and Xeomin. Botulinum toxin B is sold under the brand name Myobloc.<ref name="Myobloc FDA label" /> In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A US supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 [[indication (medicine)|indications]] approved by Government agencies around the world" with less than one gram of raw botulinum toxin.<ref>{{cite web |url=http://www.allergan.com/assets/pdf/2011AnnualReport.pdf |title=2011 Allergan Annual Report |publisher=[[Allergan]] |access-date=3 May 2012 |archive-date=15 November 2012 |archive-url=https://web.archive.org/web/20121115061406/http://www.allergan.com/assets/pdf/2011AnnualReport.pdf |url-status=live }} See PDF p. 7.</ref> Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured by [[Galderma]] in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the US and other countries.<ref name=FDA09hc>{{cite web |title=Information for Healthcare Professionals: OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc) |publisher=U.S. [[Food and Drug Administration]] (FDA) |date=13 September 2015 |url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174949.htm |archive-url=https://web.archive.org/web/20150913185039/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174949.htm |archive-date=13 September 2015 |url-status=dead |access-date=1 September 2015}} {{PD-notice}}</ref> LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024.<ref name="Letybo FDA label" /> Besides the three primary US manufacturers, numerous other botulinum toxin producers are known. Xeomin, manufactured in Germany by [[Merz Pharma|Merz]], is also available for both therapeutic and cosmetic use in the US.<ref name="Available Neurotoxins">{{cite journal |vauthors = Walker TJ, Dayan SH |title = Comparison and overview of currently available neurotoxins |journal = The Journal of Clinical and Aesthetic Dermatology |volume = 7 |issue = 2 |pages = 31β39 |date = February 2014 |pmid = 24587850 |pmc = 3935649 }}</ref> Lanzhou Institute of Biological Products in China manufactures a botulinum toxin type-A product; as of 2014, it was the only botulinum toxin type-A approved in China.<ref name="Available Neurotoxins" /> Botulinum toxin type-A is also sold as Lantox and Prosigne on the global market.<ref>{{cite web |title=Botulinum Toxin Type A |publisher=Hugh Source (International) Limited |url=http://www.btxa.com/ |access-date=14 July 2010 |archive-date=24 July 2008 |archive-url=https://web.archive.org/web/20080724102749/http://www.btxa.com/ |url-status=live }}</ref> Neuronox, a botulinum toxin type-A product, was introduced by Medy-Tox of South Korea in 2009.<ref>{{cite news |vauthors=Petrou I |date=Spring 2009 |title=Medy-Tox Introduces Neuronox to the Botulinum Toxin Arena |newspaper=The European Aesthetic Guide |url=http://www.miinews.com/pdf/MedyTox_Ed_EAGsp09v2_022809.pdf |access-date=9 December 2009 |archive-url=https://web.archive.org/web/20130320010107/http://www.miinews.com/pdf/MedyTox_Ed_EAGsp09v2_022809.pdf |archive-date=20 March 2013 |url-status=dead}}</ref> ===Toxin production=== Botulism toxins are produced by bacteria of the genus ''Clostridium,'' namely ''C. botulinum'', ''[[Clostridium butyricum|C. butyricum]]'', ''[[Clostridium baratii|C. baratii]]'' and ''[[Clostridium argentinense|C. argentinense]],''<ref>{{cite journal |vauthors = Schantz EJ, Johnson EA |title = Properties and use of botulinum toxin and other microbial neurotoxins in medicine |journal = Microbiological Reviews |volume = 56 |issue = 1 |pages = 80β99 |date = March 1992 |pmid = 1579114 |pmc = 372855 |doi = 10.1128/MMBR.56.1.80-99.1992 }}</ref> which are widely distributed, including in soil and dust. Also, the bacteria can be found inside homes on floors, carpet, and countertops even after cleaning.<ref name=CDC2018Gen>{{cite web|title=About Botulism |url=https://www.cdc.gov/botulism/general.html|date=9 October 2018|website=U.S. [[Centers for Disease Control and Prevention]] (CDC) |access-date=13 May 2020|archive-date=27 April 2020|archive-url=https://web.archive.org/web/20200427164333/https://www.cdc.gov/botulism/general.html|url-status=live}}</ref> Complicating the problem is that the taxonomy for ''C. botulinum'' remains chaotic. The toxin has likely been [[horizontal gene transfer|horizontally transferred]] across lineages, contributing to the multi-species pattern seen today.<ref>{{cite journal |vauthors = Poulain B, Popoff MR |title = Why Are Botulinum Neurotoxin-Producing Bacteria So Diverse and Botulinum Neurotoxins So Toxic? |journal = Toxins |volume = 11 |issue = 1 |pages = 34 |date = January 2019 |pmid = 30641949 |pmc = 6357194 |doi = 10.3390/toxins11010034| doi-access = free }}</ref><ref>{{cite journal |vauthors = Hill KK, Xie G, Foley BT, Smith TJ, Munk AC, Bruce D, Smith LA, Brettin TS, Detter JC |title = Recombination and insertion events involving the botulinum neurotoxin complex genes in Clostridium botulinum types A, B, E and F and Clostridium butyricum type E strains |journal = BMC Biology |volume = 7 |issue = 1 |pages = 66 |date = October 2009 |pmid = 19804621 |pmc = 2764570 |doi = 10.1186/1741-7007-7-66 |doi-access = free }}</ref> Food-borne botulism results, indirectly, from ingestion of food contaminated with ''Clostridium'' spores, where exposure to an [[hypoxia (environmental)|anaerobic environment]] allows the spores to germinate, after which the bacteria can multiply and produce toxin.<ref name=CDC2018Gen/> Critically, ingestion of toxin rather than spores or vegetative bacteria causes [[botulism]].<ref name=CDC2018Gen/> Botulism is nevertheless known to be transmitted through canned foods not cooked correctly before canning or after can opening, so is preventable.<ref name=CDC2018Gen/> Infant botulism arising from consumption of honey or any other food that can carry these spores can be prevented by eliminating these foods from diets of children less than 12 months old.<ref>{{cite web |title=Botulism |website=U.S. [[Centers for Disease Control and Prevention]] (CDC) |date=19 August 2019 |url=https://www.cdc.gov/botulism/ |access-date=28 August 2019 |archive-date=3 August 2016 |archive-url=https://web.archive.org/web/20160803091921/http://www.cdc.gov/botulism/ |url-status=live }}</ref> ===Organism and toxin susceptibilities=== {{Expand section|1=modern content and referencing on antibiotic susceptibilities |small=no|date=February 2015}} Proper refrigeration at temperatures below {{convert|4.4|C|F}} slows the growth of ''C. botulinum''.<ref>{{Cite web |date=29 March 2011 |title=Clostridium botulinum Toxin Formation |url=https://www.fda.gov/files/food/published/Fish-and-Fishery-Products-Hazards-and-Controls-Guidance-Chapter-13-Download.pdf |access-date=12 March 2023 |website=U.S. [[Food and Drug Administration]] (FDA) |page=246 |archive-date=8 February 2021 |archive-url=https://web.archive.org/web/20210208183813/https://www.fda.gov/files/food/published/Fish-and-Fishery-Products-Hazards-and-Controls-Guidance-Chapter-13-Download.pdf |url-status=live }}</ref> The organism is also susceptible to high salt, high oxygen, and low pH levels.<ref name="WHO2018" />{{failed verification|date=December 2022}} The toxin itself is rapidly destroyed by heat, such as in thorough cooking.<ref>{{cite journal |vauthors = Licciardello JJ, Nickerson JT, Ribich CA, Goldblith SA |title = Thermal inactivation of type E botulinum toxin |journal = Applied Microbiology |volume = 15 |issue = 2 |pages = 249β256 |date = March 1967 |pmid = 5339838 |pmc = 546888 |doi = 10.1128/AEM.15.2.249-256.1967 }}</ref> The spores that produce the toxin are heat-tolerant and will survive boiling water for an extended period of time.<ref>{{cite journal |vauthors = Setlow P |title = I will survive: DNA protection in bacterial spores |journal = Trends in Microbiology |volume = 15 |issue = 4 |pages = 172β180 |date = April 2007 |pmid = 17336071 |doi = 10.1016/j.tim.2007.02.004 }}</ref> The botulinum toxin is [[denaturation (biochemistry)|denatured]] and thus deactivated at temperatures greater than {{convert|85|C|F}} for five minutes.<ref name="WHO2018">{{cite web |title=Fact sheets - Botulism |url=https://www.who.int/news-room/fact-sheets/detail/botulism |work=World Health Organization |access-date=23 March 2019 |date=10 January 2018 |archive-date=23 March 2019 |archive-url=https://web.archive.org/web/20190323162924/https://www.who.int/news-room/fact-sheets/detail/botulism |url-status=live }}</ref> As a zinc [[metalloprotease]] (see below), the toxin's activity is also susceptible, post-exposure, to [[enzyme inhibition|inhibition]] by [[protease inhibitor (pharmacology)|protease inhibitors]], e.g., zinc-coordinating [[hydroxamate]]s.<ref name=Bowlin11>{{cite journal |vauthors = Li B, Peet NP, Butler MM, Burnett JC, Moir DT, Bowlin TL |title = Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication |journal = Molecules |volume = 16 |issue = 1 |pages = 202β220 |date = December 2010 |pmid = 21193845 |pmc = 6259422 |doi = 10.3390/molecules16010202 |doi-access = free |title-link = doi }}</ref><ref name=Janda0911>{{cite journal |vauthors = CapkovΓ‘ K, Salzameda NT, Janda KD |title = Investigations into small molecule non-peptidic inhibitors of the botulinum neurotoxins |journal = Toxicon |volume = 54 |issue = 5 |pages = 575β582 |date = October 2009 |pmid = 19327377 |pmc = 2730986 |doi = 10.1016/j.toxicon.2009.03.016 |bibcode = 2009Txcn...54..575C }}</ref>
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