Editing Botulinum toxin (section)

===Cosmetic===<!-- Much of this is already covered under history – should be merged/removed -->

The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, a plastic surgeon from [[Sacramento, California]]. In 1987 Clark was challenged with eliminating the disfigurement caused by only the right side of the forehead muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped and she emoted with deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Clark was aware that botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report on the cosmetic use of botulinum toxin to treat a cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal ''Plastic and Reconstructive Surgery'' in 1989.<ref name="Clark_1989">{{cite journal |vauthors = Clark RP, Berris CE |title = Botulinum toxin: a treatment for facial asymmetry caused by facial nerve paralysis |journal = Plastic and Reconstructive Surgery |volume = 84 |issue = 2 |pages = 353–355 |date = August 1989 |pmid = 2748749 |doi = 10.1097/01.prs.0000205566.47797.8d }}</ref> Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."<ref name="Rohrich_2003" />

J. D. and J. A. Carruthers also studied and reported in 1992 the use of botulinum toxin type-A as a cosmetic treatment.[78] They conducted a study of participants whose only concern was their glabellar forehead wrinkle or furrow. Study participants were otherwise normal. Sixteen of seventeen participants available for follow-up demonstrated a cosmetic improvement. This study was reported at a meeting in 1991. The study for the treatment of [[glabella]]r frown lines was published in 1992.<ref name="Carruthers JD 19922" /> This result was subsequently confirmed by other groups (Brin, and the Columbia University group under Monte Keen<ref name="Keen_1994">{{cite journal |vauthors = Keen M, Kopelman JE, Aviv JE, Binder W, Brin M, Blitzer A |title = Botulinum toxin A: a novel method to remove periorbital wrinkles |journal = Facial Plastic Surgery |volume = 10 |issue = 2 |pages = 141–146 |date = April 1994 |pmid = 7995530 |doi = 10.1055/s-2008-1064563 |s2cid = 29006338 }}</ref>). The FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials.<ref>{{cite web |date=29 October 2009 |title=Botulinum Toxin Type A Product Approval Information – Licensing Action 4/12/02 |publisher=U.S. [[Food and Drug Administration]] (FDA) |url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080509.htm |access-date=26 July 2010 |archive-url=https://web.archive.org/web/20100308063343/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080509.htm |archive-date=8 March 2010 |url-status=dead}} {{PD-notice}}</ref> Well before this, the cosmetic use of botulinum toxin type A became widespread.<ref>{{cite journal |doi=10.1509/jm.10.0406 |title=How Doppelgänger Brand Images Influence the Market Creation Process: Longitudinal Insights from the Rise of Botox Cosmetic |year=2012 |vauthors=Giesler M |journal=Journal of Marketing |volume=76 |issue=6 |pages=55–68 |s2cid=167319134}}</ref> The results of Botox Cosmetic can last up to four months and may vary with each patient.<ref>{{cite web |date=22 January 2014 |title=Botox Cosmetic (onabotulinumtoxinA) Product Information |publisher=[[Allergan]] |url=http://www.botox.com/ |access-date=1 March 2018 |archive-date=21 July 2021 |archive-url=https://web.archive.org/web/20210721001858/https://www.botox.com/ |url-status=live }}</ref> The US [[Food and Drug Administration]] (FDA) approved an alternative product-safety testing method in response to increasing public concern that [[LD50]] testing was required for each batch sold in the market.<ref name="Allergan_2011">{{cite web |date=24 June 2011 |title=Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for Botox and Botox Cosmetic (onabotulinumtoxinA) |publisher=Allergan |url=http://agn.client.shareholder.com/releasedetail.cfm?ReleaseID=587234 |access-date=26 June 2011 |url-status=dead |archive-url=https://web.archive.org/web/20110626185759/http://agn.client.shareholder.com/releasedetail.cfm?ReleaseID=587234 |archive-date=26 June 2011}}</ref><ref name="The Washington Post_2008">{{cite news |date=12 April 2008 |title=In U.S., Few Alternatives To Testing On Animals |newspaper=[[The Washington Post]] |url=https://www.washingtonpost.com/wp-dyn/content/article/2008/04/11/AR2008041103733.html |access-date=26 June 2011 |archive-date=12 November 2012 |archive-url=https://web.archive.org/web/20121112163835/http://www.washingtonpost.com/wp-dyn/content/article/2008/04/11/AR2008041103733.html |url-status=live }}</ref>

Botulinum toxin type-A has also been used in the treatment of [[gums|gummy]] smiles;<ref name="pmid25654058">{{cite journal |vauthors = Nayyar P, Kumar P, Nayyar PV, Singh A |title = BOTOX: Broadening the Horizon of Dentistry |journal = Journal of Clinical and Diagnostic Research |volume = 8 |issue = 12 |pages = ZE25–ZE29 |date = December 2014 |pmid = 25654058 |pmc = 4316364 |doi = 10.7860/JCDR/2014/11624.5341 }}</ref> the material is injected into the hyperactive muscles of upper lip, which causes a reduction in the upward movement of lip thus resulting in a smile with a less exposure of [[gums|gingiva]].<ref name="pmid19123705">{{cite journal |vauthors = Hwang WS, Hur MS, Hu KS, Song WC, Koh KS, Baik HS, Kim ST, Kim HJ, Lee KJ |title = Surface anatomy of the lip elevator muscles for the treatment of gummy smile using botulinum toxin |journal = The Angle Orthodontist |volume = 79 |issue = 1 |pages = 70–77 |date = January 2009 |pmid = 19123705 |doi = 10.2319/091407-437.1 |doi-access = free |title-link = doi }}</ref> Botox is usually injected in the three lip elevator muscles that converge on the lateral side of the ala of the nose; the [[levator labii superioris]] (LLS), the [[levator labii superioris alaeque nasi muscle]] (LLSAN), and the [[Zygomaticus minor muscle|zygomaticus minor]] (ZMi).<ref name="pmid20529632">{{cite journal |vauthors = Gracco A, Tracey S |title = Botox and the gummy smile |journal = Progress in Orthodontics |volume = 11 |issue = 1 |pages = 76–82 |date = May 2010 |pmid = 20529632 |doi = 10.1016/j.pio.2010.04.004 }}</ref><ref name="pmid21093661">{{cite journal |vauthors = Mazzuco R, Hexsel D |title = Gummy smile and botulinum toxin: a new approach based on the gingival exposure area |journal = Journal of the American Academy of Dermatology |volume = 63 |issue = 6 |pages = 1042–1051 |date = December 2010 |pmid = 21093661 |doi = 10.1016/j.jaad.2010.02.053 }}</ref>