Editing Rotenone

{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 456665070
| ImageFile1 = Rotenone Structural Formula V.1.svg
| ImageSize1 = 200
| ImageAlt1 = Skeletal formula of rotenone
| ImageFile2 = rotenone-3D-spacefill.png
| ImageSize2 = 200
| ImageAlt2 = Space-filling model of the rotenone molecule
| IUPACName = (5′′''R'')-4′,5′-Dimethoxy-5′′-(prop-1-en-2-yl)-4′′,5′′-dihydrofuro[2′′,3′′:7,8]rotenan-4-one
| SystematicName = (2''R'',6a''S'',12a''S'')-8,9-Dimethoxy-2-(prop-1-en-2-yl)-1,2,12,12a-tetrahydro[1]benzopyrano[3,4-''b'']furo[2,3-''h''][1]benzopyran-6(6a''H'')-one
| OtherNames = Tubatoxin, Paraderil, nicouline 
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 83-79-4
| PubChem = 6758
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 28201
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 429023
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 6500
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C07593
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 03L9OT429T
| SMILES = CC(=C)[C@H]1Cc2c(O1)ccc3c2O[C@@H]4COc5cc(OC)c(OC)cc5[C@@H]4C3=O
| InChI = 1/C23H22O6/c1-11(2)16-8-14-15(28-16)6-5-12-22(24)21-13-7-18(25-3)19(26-4)9-17(13)27-10-20(21)29-23(12)14/h5-7,9,16,20-21H,1,8,10H2,2-4H3/t16-,20-,21+/m1/s1
| MeSHName = Rotenone
 }}
|Section2={{Chembox Properties
| C=23
| H=22
| O=6
| Appearance = Colorless to red crystalline solid<ref name=PGCH />
| Odor = odorless<ref name=PGCH />
| Density = 1.27 g/cm<sup>3</sup> @ 20&nbsp;°C
| MeltingPtC = 165 to 166
| BoilingPtC = 210 to 220
| BoilingPt_notes = at 0.5 mmHg
| SolubleOther = Soluble in [[diethyl ether|ether]] and [[acetone]], slightly soluble in [[ethanol]]
| VaporPressure = <0.00004 mmHg (20°C)<ref name=PGCH />
 }}
|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
| IDLH = 2500 mg/m<sup>3</sup><ref name=PGCH>{{PGCH|0548}}</ref>
| REL = TWA 5 mg/m<sup>3</sup><ref name=PGCH />
| PEL = TWA 5 mg/m<sup>3</sup><ref name=PGCH />
| LD50 = 60 mg/kg (oral, rat)<br />132 mg/kg (oral, rat)<br />25 mg/kg (oral, rat)<br />2.8 mg/kg (oral, mouse)<ref>{{IDLH|83794|Rotenone}}</ref>
 }}
}}

'''Rotenone''' is an odorless, colorless, [[crystalline]] [[isoflavone]]. It occurs naturally in the seeds and stems of several plants, such as the [[Pachyrhizus erosus|jicama]] vine, and in the roots of several other members of the [[Fabaceae]]. It was the first-described member of the family of chemical compounds known as [[rotenoid]]s. Rotenone is approved for use as a piscicide to remove [[Introduced species|alien fish species]],<ref name=":12">{{Cite journal |vauthors=Rytwinski T, Taylor JJ, Donaldson LA, Britton JR, Browne DR, Gresswell RE, Lintermans M, Prior KA, Pellatt MG, Vis C, Cooke SJ |year=2018 |title=The effectiveness of non-native fish removal techniques in freshwater ecosystems: A systematic review |url=http://eprints.bournemouth.ac.uk/31355/1/Rytwinski%20et%20al_Fish%20removal%20SR_FINAL.pdf |journal=Environmental Reviews |language=English |volume=27 |issue=1 |pages=71–94 |doi=10.1139/er-2018-0049 |s2cid=92554010 |postscript=, summary in French}}</ref> see ''Uses.'' It has also been used as a broad-spectrum [[insecticide]], but its use as an insecticide has been banned in many countries.

== Discovery ==

The earliest written record of the now-known rotenone-containing plants used for killing leaf-eating [[caterpillars]] was in 1848; for centuries, these same plants had been used to [[piscicide|poison fish]].<ref name="Metcalf">{{cite book |title=The Mode of Action of Organic Insecticides |publisher=National Research Council, Washington DC |year=1948 |url=https://books.google.com/books?id=PmcrAAAAYAAJ&q=rotenone+isolated&pg=PA29 |author=Metcalf, R. L.}}</ref> The active chemical component was first isolated in 1895 by a French botanist, [[Emmanuel Geoffroy]], who called it ''nicouline'', from a specimen of ''[[Robinia]] nicou'', now called ''[[Deguelia utilis]]'', while traveling in [[French Guiana]].<ref>{{cite journal| last1=Ambrose | first1=Anthony M. |author2=Harvey B. Haag | year=1936 | title=Toxicological study of ''Derris'' | journal=Industrial & Engineering Chemistry | volume=28 | issue=7 | pages=815–821 | doi=10.1021/ie50319a017}}</ref> He wrote about this research in his thesis, published in 1895 after his death from a [[parasitic disease]].<ref>{{cite web| title=Useful tropical plants | publisher=ASNOM | url=http://www.asnom.org/en/730_plantes_tropicales_utiles.html | date=2008-01-02 | access-date=2008-03-16}}</ref> In 1902 [[Kazuo Nagai]], Japanese [[chemical engineer]] of the [[Government-General of Taiwan]], isolated a pure crystalline compound from ''[[Derris elliptica]]'' which he called rotenone, after the Taiwanese name of the plant 蘆藤 ({{Langx|nan|lôo-tîn}}) translated into Japanese {{Nihongo|2=ローテン|3=rōten}}.<ref name="Nagai1902">{{cite journal
 | author = Nagai, Kazuo
 | title = 魚籘有毒成分の研究 第一報 [First report of research on toxic ingredients in fish rattan]
 | journal = 東京化學會誌 [Tokyo Kagaku Kaishi = Tokyo Chemical Society Journal]
 | volume = 23
 | number = 7
 | pages = 744–777
 | doi = 10.1246/nikkashi1880.23.744
 | doi-access = free
 | year = 1902
 | language = ja
}}</ref> By 1930, nicouline and rotenone were established to be chemically the same.<ref>{{cite journal |year=1933 |title=The Determination of the structure of rotenone |journal=Chemical Reviews |volume=18 |issue=2 |pages=181–213 |doi=10.1021/cr60042a001| vauthors=La Forge FB, Haller HL, Smith LE}}</ref>

== Uses ==

=== Use as piscicide in fisheries management ===
When absorbed through the gills, rotenone disrupts cellular respiration in fish, and may lead to their death, depending on the concentration used. Due to this, it has become a key tool in managing ecosystems affected by invasive or unwanted fish species, and as of 2024 there are no viable options that can replace its versatile value in fish removal actions.

Its value in ecosystem restoration is appreciated due to its rapid degradation, when exposed to light and warm temperatures, making it a temporary measure with minimal long-term environmental effects, see ''Rotenone and Ecosystem Impact''.

Rotenone is used as a nonselective piscicide (fish killer).<ref>{{cite news
 |url=http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2007/10/02/BAOHSI41V.DTL
 |title=Lake poisoning seems to have worked to kill invasive pike
 |author=Peter Fimrite
 |newspaper=[[San Francisco Chronicle]]
 |date=2007-10-02
}}</ref> Rotenone has historically been used by [[indigenous peoples]] to catch fish. Typically, rotenone-containing plants in the [[legume]] family, [[Fabaceae]], are crushed and introduced into a body of water, and as rotenone interferes with [[cellular respiration]], the affected fish rise to the surface, where they are more easily caught.

In modern times it is frequently used as a tool to remove [[Introduced species|alien fish species]],<ref name=":1">{{Cite journal |vauthors=Rytwinski T, Taylor JJ, Donaldson LA, Britton JR, Browne DR, Gresswell RE, Lintermans M, Prior KA, Pellatt MG, Vis C, Cooke SJ |title=The effectiveness of non-native fish removal techniques in freshwater ecosystems: A systematic review |journal=Environmental Reviews |year=2018 |volume=27 |pages=71–94 |language=English |postscript=, summary in French |doi=10.1139/er-2018-0049 |issue=1|s2cid=92554010 |url=http://eprints.bournemouth.ac.uk/31355/1/Rytwinski%20et%20al_Fish%20removal%20SR_FINAL.pdf }}</ref> as it has a relatively short [[half-life]] (days) and is gone from rivers in the course of days and from lakes within a few months, depending on (seasonal) stirring, [[Organic matter|organic]] content, availability of sunlight and temperature.<ref name=":0">{{Cite book |title=Planning and Standard Operating Procedures for the Use of Rotenone in Fish Management – Rotenone SOP Manual |vauthors=Finlayson B, Schnick R, Skaar D, Anderson J, Demong L, Duffield D, Horton W, Steinkjer J |publisher=American Fisheries Society |year=2018 |isbn=978-1-934874-49-3 |edition=2nd |location=Bethesda, Maryland |publication-date=May 2018 |pages= |language=English}}</ref> Rotenone has been used by government agencies to kill fish in rivers and lakes in the United States since 1952,<ref>{{cite journal |last=Schmidt |first=Peter |date=28 February 2010 |title=One Strange Fish Tale |journal=The Chronicle of Higher Education |url=http://chronicle.com/article/One-Strange-Fish-Tale/64348/ |access-date=24 September 2015}}</ref> and in Canada<ref>{{Cite web |title=Invasive Goldfish management |date=10 January 2023 |url=https://www.rmwb.ca/en/parks-and-recreation/invasive-goldfish-management.aspx#Why-are-we-using-Rotenone}}</ref> and Norway<ref>{{Cite book |last1=Mo |first1=TO |title=Har myndighetene lyktes i kampen mot Gyrodactylus salaris? |last2=Holthe |first2=E |last3=Andersen |first3=O |publisher=Norsk institutt for naturforskning, NINA rapport |year=2022 |isbn=978-82-426-4950-8 |issue=2157 |pages=1–62 |language=Norwegian |postscript=, summary in English |type=Report}}</ref> since the 1980s. It is less frequently used in EU countries, due to strict regulations, but has seen some use in selected countries such as the UK ([[Stone moroko|Topmouth gudgeon]]), Sweden ([[Northern pike|pike]] and [[pumpkinseed]]), Spain ([[Stone moroko|Topmouth gudgeon]], [[Gambusia]]) and Hungary ([[Prussian carp]]).

Rotenone has also seen some use in other field studies in the marine environment needing only small quantities. Small-scale sampling with rotenone is used by fish researchers studying the biodiversity of marine fishes to collect cryptic, or hidden, fishes, which represent an important component of shoreline fish communities, since it has only minor, local and transient environmental side effects.<ref>{{cite journal |last1=Robertson |first1=D. Ross |last2=Smith-Vaniz |first2=William F. |year=2008 |title=Rotenone: An Essential but Demonized Tool for Assessing Marine Fish Diversity |journal=BioScience |volume=58 |issue=2 |pages=165 |doi=10.1641/B580211 |doi-access=free}}</ref>

==== Rotenone degradation and ecosystem impact ====
Rotenone primarily affects gilled organisms such as fish and aquatic invertebrates. Terrestrial animals such as birds, mammals, and amphibians (except tadpoles/larvae) are much less affected by rotenone.<ref>{{cite web |last1=Skaar |first1=Donald R. |display-authors=etal |title=Effects of Rotenone on Amphibians and Macroinvertebrates in Yellowstone |url=https://www.nps.gov/articles/effects-of-rotenone-on-amphibians-and-macroinvertebrates-in-yellowstone.htm |publisher=U.S. National Park Service |access-date=29 September 2024 |language=en}}</ref> When applied in freshwater systems, the treatment dose kills the target fish and usually other gilled species like tadpoles and zooplankton are affected, depending on dosage. However, timing treatments in the fall or winter, when many species are less active, can reduce these impacts. Some taxa may also recover through natural life cycles, such as resting eggs. Its use is more benign for the environment (as compared to drying ponds, or using other piscicides), and studies show that most ecosystems naturally recover within one or two years after rotenone application- with aquatic invertebrates repopulating affected areas,<ref>{{Cite book |last=Kjærstad |first=Gaute |title=The eradication of invasive species using rotenone and its impact on freshwater macroinvertebrates |publisher=Doctoral theses at NTNU |year=2022 |isbn=978-82-326-6270-8 |location=Trondheim |pages=1–100 |language=English}}</ref><ref>{{Cite journal |last=Fjellheim |first=A. |year=2004 |title=Virkning av rotenonbehandling på bunndyrsamfunnene I et område ved Stigstu, Hardangervidda |url=http://hdl.handle.net/11250/2630458 |journal=Lfi-122 |language=Norwegian |publisher=LFI, University of Bergen |pages=1–60 |issn=0801-9576 |hdl=11250/2630458}}</ref><ref>{{Cite journal |last1=Vinson |first1=V |last2=Dinger |first2=EC |last3=Vinson |first3=DK |year=2010 |title=Piscicides and invertebrates: after 70 years, does anyone really know? |journal=Fisheries |volume=35 |issue=2 |pages=61–71 |bibcode=2010Fish...35...61V |doi=10.1577/1548-8446-35.2.61}}</ref> thus restoring initial local biodiversity to its status prior to the introduction of the invasive species.

Rotenone decays through [[metabolite]]s and its final product is reduced to [[water]] and [[carbon dioxide]].<ref name=":0" />  It oxidizes to rotenolone, which is about an order of magnitude less toxic than rotenone. In water, the rate of decomposition depends upon several factors, including temperature, pH, water hardness and sunlight. The half-life of rotenone in a pond of 1.1 mean depth ranged from half a day at 24&nbsp;°C to 3.5 days at 0&nbsp;°C,<ref>{{cite web |author=Kevin C. Ott |title=Rotenone. A Brief Review of its Chemistry, Environmental Fate, and the Toxicity of Rotenone Formulations |url=http://www.newmexicotu.org/Rotenone%20summary.pdf |url-status=dead |archive-url=https://web.archive.org/web/20120904171741/http://www.newmexicotu.org/Rotenone%20summary.pdf |archive-date=2012-09-04}}</ref> but in deeper oligotrophic systems (thus less degradation due to sunlight and organic content) the half-life may be considerably longer.

==== Notable administrations as piscicide ====
Norwegian authorities have been using rotenone since the mid-1980s to eradicate the salmon fluke [[Gyrodactylus salaris]],<ref>{{Cite journal |last=Adolfsen |first=Pål |last2=Bardal |first2=Helge |last3=Aune |first3=Svein |date=2021 |title=Fighting an invasive fish parasite in subarctic Norwegian rivers –  The end of a long story? |url=http://dx.doi.org/10.3391/mbi.2021.12.3 |journal=Management of Biological Invasions |volume=12 |issue=1 |pages=49–65 |doi=10.3391/mbi.2021.12.3 |issn=1989-8649|doi-access=free }}</ref> and as of 2024 48 out of 54 affected river catchments have been treated. Additionally, many lakes and ponds have been rotenone treated in an effort to remove national or regional invasive species, such as [[Northern pike]], [[Common roach|roach]], [[minnow]], [[crucian carp]], [[Tench]] and [[European perch|perch]].<ref>Bardal, H. 2019. Small- and large-scale eradication of invasive fish and fish parasites in freshwater systems in Norway. In: C.R. Veitch, M.N. Clout, A.R. Martin, J.C. Russell, and C.J. West (eds.). Island invasives: scaling up to meet the challenge, pp. 457-451. Occasional paper SSC no. 62. Gland, Switzerland: IUCN.</ref>

In 1992, [[Florida Fish and Wildlife Conservation Commission]] (FWC) officials used rotenone to eradicate an established population of invasive [[Parachromis managuensis|jaguar cichlids]] from a small pond in [[Miami-Dade County, Florida|Miami-Dade County]]. Officials were successful in killing every jaguar cichlid (along with every other fish) in the pond, but unsuccessful in eradicating them from [[Florida]]; the cichlids had already spread throughout the [[Miami Canal]] and its connected [[waterway]]s, and by 1994, jaguar cichlids had successfully established themselves throughout [[Southern Florida|Southern]] and [[Central Florida]].<ref name="Shaffland1996">{{cite journal |last=Shafland |first=Paul L. |date=23 December 2008 |orig-date=1996 |title=Exotic fishes of Florida — 1994 |url=https://files.catbox.moe/7mtmdp.pdf |url-status=live |journal=Reviews in Fisheries Science & Aquaculture |publisher=Taylor & Francis |volume=4 |issue=2 |pages=101–122 |doi=10.1080/10641269609388581 |archive-url=https://web.archive.org/web/20240424220601/https://files.catbox.moe/7mtmdp.pdf |archive-date=24 April 2024 |access-date=24 April 2024}}</ref>

In September 2010, [[Oregon Department of Fish and Wildlife]] officials used rotenone to kill an established population of [[invasive species|invasive]] [[goldfish]] present in eastern Oregon's [[Mann Lake]], with the intention of not disrupting the lake's native [[Lahontan cutthroat trout]] population. Rotenone successfully achieved these aims, killing between 179,000–197,000 goldfish and [[fathead minnow]]s, and only three trout.<ref>{{cite news |last=Monroe |first=Bill |date=December 3, 2010 |title=Mann Lake Gets a Second Round of Rotenone for Cutthroat Restoration |url=http://www.oregonlive.com/sports/oregonian/bill_monroe/index.ssf/2010/12/mann_lake_gets_a_second_round.html |url-status=live |archive-url=https://web.archive.org/web/20110424075200/http://www.oregonlive.com/sports/oregonian/bill_monroe/index.ssf/2010/12/mann_lake_gets_a_second_round.html |archive-date=April 24, 2011 |access-date=2012-12-20 |work=The Oregonian |publisher=Oregon Live LLC}}</ref>

Beginning May 1, 2006, [[Panguitch Lake]], a reservoir in the southeastern portion of the U.S. state of Utah, was treated with rotenone, to potentially eradicate and control the invasive population of [[Utah chub]], which were probably introduced accidentally by [[Fisherman|anglers]] who used them as [[bait (luring substance)|live bait]]. The lake was restocked with 20,000 [[rainbow trout]] in 2006; as of 2016, the lake's fish population has recovered.

In 2012, rotenone was used to kill all remaining fish in [[Stormy Lake (Alaska)]] due to invasive pike destroying native species, which were reintroduced once the treatment was concluded.<ref>Earl, Elizabeth, [http://peninsulaclarion.com/news/2015-10-07/fish-population-booms-in-stormy-lake Fish population booms in Stormy Lake] [[Peninsula Clarion]], 10/7/2015</ref>
 
In 2014, rotenone was used to kill all remaining fish in San Francisco's Mountain Lake, which is located in [[Mountain Lake Park]], in order to rid it of invasive species introduced since the migration of European settlers to the region.<ref>{{cite web |last=Fimrite |first=Peter |date=12 November 2014 |title=Alien fish poisoned by the thousands to save S.F.'s Mountain Lake |url=http://www.sfgate.com/bayarea/article/Workers-pour-poison-into-Mountain-Lake-begin-5888355.php |access-date=24 September 2015 |publisher=SFGate / Hearst}}</ref>

==== Deactivation ====
Rotenone can be deactivated in water with the use of [[potassium permanganate]] to lower toxicity to acceptable levels.<ref>{{citation |author=Donald L Archer |title=Rotenone Neutralization Methods |date=2001 |url=http://www.fisheriessociety.org/rotenone/rewards/01archer.pdf |archive-url=https://web.archive.org/web/20171107024940/http://www.fisheriessociety.org/rotenone/rewards/01archer.pdf |archive-date=2017-11-07 |url-status=dead |publisher=American Fisheries Society}}</ref>

=== Use as insecticide ===
Rotenone was commercialized as ''[[Lonchocarpus utilis|cubé]]'', [[Derris elliptica|''tuba'', or ''derris'']], in single preparation or in [[synergy|synergistic]] combination with other insecticides.<ref name="Hayes">{{cite book |author=Hayes W. J. |url=https://books.google.com/books?id=sUrLT9z9i3IC&q=rotenone+millettia&pg=PA135 |title=Handbook on Pesticides |publisher=[[Academic Press]] |year=1991 |isbn=978-0-12-334161-7 |volume=1}}</ref> It has high acute toxicity to mammals,<ref>{{Cite web |date=March 2007 |title=Reregistration Eligibility Decision for Rotenone |url=https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/red_PC-071003_31-Mar-07.pdf |access-date=22 October 2024 |website=United States Environmental Protection Agency}}</ref> and all insecticidal uses were banned in the United States and Canada,<ref>[https://web.archive.org/web/20110607121038/http://www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rev2008-01/index-eng.php Re-evaluation Note: Rotenone (REV2008-01, 29 January 2008)],{{dead link|date=January 2020}} Consumer Product Safety, Health Canada</ref><ref>{{cite journal |last= |first= |date= |title=7 CFR § 205.602 - Nonsynthetic substances prohibited for use in organic crop production |url=https://www.law.cornell.edu/cfr/text/7/205.602 |journal=Cornell Law School Legal Information Institute |access-date=20 May 2021}}</ref> in the EU,<ref name=":3" /> in the UK,<ref>{{cite web |date=2 October 2008 |title=RHS advice for the garden - Rotenone withdrawal |url=https://www.telegraph.co.uk/gardening/gardeningadvice/3350291/RHS-advice-for-the-garden.html |access-date=20 October 2019 |website=Telegraph Gardening}}</ref> and in Switzerland.<ref name=":3">{{Cite web |last=Dowle |first=Joanna |date=2 August 2024 |title=How safe are natural insecticides? |url=https://www.epa.govt.nz/community-involvement/science-at-work/how-safe-is-natural-taking-a-look-at-four-plant-based-pesticides-from-natures-arsenal/ |access-date=4 August 2024 |website=Environmental Protection Agency of New Zealand}}</ref> It remains legal as a pesticide in a number of other countries, including Australia<ref>{{cite web |url=https://www.apvma.gov.au/chemicals-and-products/active-constituents/exempt |title=Active constituents exempt from the requirements of APVMA approval for use in agricultural or veterinary chemical products |access-date=2 December 2024 |website=Australian Pesticides and Veterinary Medicines Authority}}</ref> and New Zealand;<ref>{{cite web |url=https://www.epa.govt.nz/assets/RecordsAPI/Rotenone_HSR003076.pdf |title=Approval for Rotenone (HSR003076) |website=Environmental Protection Agency of New Zealand |date=30 April 2021 |access-date=2 December 2024}}</ref> the status and effective date of ban in select countries is provided in the table below.

{| class="wikitable"
|+ Legal status of rotenone as a pesticide, by country
|-
! Country !! Status !! Ban effective
|-
| Australia || legal || -
|-
| Canada || banned || 31 December 2012
|-
| EU || banned || 10 October 2008
|-
| New Zealand || legal || -
|-
| Switzerland || banned || 1 January 2014
|-
| United Kingdom || banned || 10 October 2008
|-
| United States || banned || 23 March 2011 (EPA); 28 January 2019 (USDA)
|}

Rotenone was used in powdered form to treat [[scabies]] and [[head lice]] on humans, and [[parasitic]] [[mite]]s on [[chickens]], [[livestock]], and [[pet]] animals.

In agriculture it was unselective in action and killed [[potato beetle]]s, [[cucumber beetle]]s, [[flea beetle]]s, [[cabbage worm]]s, [[raspberry beetle]]s, and [[asparagus beetle]]s, as well as most other arthropods. It biodegrades rapidly in soil, with 90% degraded after 1–3 months at {{convert|20|C|F}} and three times faster at {{convert|30|C|F}}.<ref>{{Cite journal |last1=Cavoski |first1=Ivana |last2=Caboni |first2=Pierluigi |last3=Sarais |first3=Giorgia |last4=Miano |first4=Teodoro |date=2008-08-06 |title=Degradation and Persistence of Rotenone in Soils and Influence of Temperature Variations |journal=Journal of Agricultural and Food Chemistry |language=EN |volume=56 |issue=17 |pages=8066–8073 |doi=10.1021/jf801461h |pmid=18681442}}</ref> The compound [[Chemical decomposition|decomposes]] when exposed to sunlight and usually has an activity of six days in the environment.<ref name=":2">Vitax Safety Data Sheet for Derris dust, revised October 1998</ref>

== Mechanism of action ==
Rotenone works by interfering with the [[electron transport chain]] within [[Respiratory complex I|complex I]] in [[mitochondria]], which places it in [[Insecticide Resistance Action Committee|IRAC]] [[mechanism of action|MoA]] class 21 (by itself in 21B).<ref name="IRAC-MoAs">{{cite web|url=http://irac-online.org/documents/moa-classification/|date=March 2020|publisher=[[Insecticide Resistance Action Committee]]|title=IRAC Mode of Action Classification Scheme Version 9.4|author=IRAC International MoA Working Group}}</ref> It inhibits the transfer of electrons from iron-sulfur centers in [[complex I]] to [[ubiquinone]]. This interferes with [[Nicotinamide adenine dinucleotide|NADH]] during the creation of usable cellular energy ([[Adenosine triphosphate|ATP]]).<ref name="Hayes" />  Complex I is unable to pass off its electron to [[CoQ]], creating a back-up of electrons within the mitochondrial matrix.  Cellular oxygen is reduced to the radical, creating [[reactive oxygen species]], which can damage [[DNA]] and other components of the mitochondria.<ref name=Nature>{{cite journal |last=Mehta |first=Suresh |title=Neuroprotective role of mitochondrial uncoupling protein 2 in cerebral stroke |journal=Journal of Cerebral Blood Flow and Metabolism |pmid=19240738 |volume=29 |doi=10.1038/jcbfm.2009.4 |year=2009 |issue=6 |pages=1069–78 |doi-access=free}}</ref>

Rotenone is used in biomedical research to study the oxygen consumption rate of cells, usually in combination with [[antimycin A]] (an [[electron transport chain Complex III]] inhibitor), [[oligomycin]] (an ATP synthase inhibitor) and [[Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone|FCCP]] (a mitochondrial [[uncoupler]]).<ref>{{cite journal |vauthors=Divakaruni AS, Rogers GW, Murphy AN |year=2014 |title=Measuring Mitochondrial Function in Permeabilized Cells Using the Seahorse XF Analyzer or a Clark-Type Oxygen Electrode |journal=Curr Protoc Toxicol |volume=60 |pages=25.2.1–16 |doi=10.1002/0471140856.tx2502s60 |pmid=24865646 |s2cid=21195854}}</ref>

Rotenone also inhibits [[microtubule]] assembly.<ref>{{cite journal| vauthors=Heinz S, Freyberger A, Lawrenz B, Schladt L, Schmuck G, Ellinger-Ziegelbauer H| title=Mechanistic Investigations of the Mitochondrial Complex I Inhibitor Rotenone in the Context of Pharmacological and Safety Evaluation| journal=Scientific Reports| volume=7| pages=45465| doi=10.1038/srep45465| pmid=28374803| pmc=5379642| year=2017| bibcode=2017NatSR...745465H}}</ref>

== Presence in plants ==
Rotenone is produced by extraction from the roots and stems of several tropical and subtropical plant species, especially those belonging to the genera ''[[Lonchocarpus]]'' and ''[[Derris]]''.

Some of the plants containing rotenone:
* Hoary pea or goat's rue (''[[Tephrosia virginiana]]'') – North America
* Jícama (''[[Pachyrhizus erosus]]'') – North America
* Cubé plant or lancepod  (''[[Lonchocarpus utilis]]'') – South America<ref name="Fang">{{cite journal |vauthors=Fang N, Casida J |title=Cubé resin insecticide: identification and biological activity of 29 rotenoid constituents |journal=J Agric Food Chem |volume=47 |issue=5 |pages=2130–6 |year=1999 |pmid=10552508 |doi=10.1021/jf981188x}}</ref>
** The root extract is referred to as cubé resin
* Barbasco (''[[Lonchocarpus urucu]]'') – South America<ref name="Fang" />
** The root extract is referred to as cubé resin
* Tuba plant (''[[Derris elliptica]]'') – southeast Asia and southwest Pacific islands
** The root extract is referred to as derris or derris root
* Jewel vine (''[[Derris involuta]]'') – southeast Asia and southwest Pacific islands
** The root extract is referred to as derris or derris root
* Common Mullein (''[[Verbascum thapsus]] L.)''<ref>{{cite book |title= Peterson Field Guides to Medicinal Plants and Herbs of Eastern and Central North America |edition= 2nd |pages= 130–131 }}</ref>
* Cork-bush (''[[Mundulea sericea]]'') – southern Africa<ref name="Palgrave">{{cite book |last=Coates Palgrave |first=Keith |title=Trees of Southern Africa |publisher=[[Struik]] |year=2002 |isbn=978-0-86977-081-8}}</ref>
* Florida fishpoison tree (''[[Piscidia piscipula]]'') – southern Florida, Caribbean<ref name=Nellis>Nellis, David N. (1994). Seashore plants of South Florida and the Caribbean. Pineapple Press. 160 p.</ref>
* Several species of ''[[Millettia]]'' and ''[[Tephrosia]]'' in [[Southeast asia|South-east Asian regions]]<ref name="Barton">{{cite book |title=Comprehensive Natural Products Chemistry |publisher=[[Pergamon]] |isbn=978-0-08-091283-7 |year=1999 |url=https://books.google.com/books?id=AqdTiNIaA74C&q=rotenone+millettia&pg=PT10698 |vauthors=Barton D, Meth-Cohn O}}</ref>

== Mammalian toxicity ==
Rotenone is classified by the [[World Health Organization]] as moderately hazardous.<ref name="who">{{cite book |author1=International Programme on Chemical Safety |author2=[[United Nations Environment Programme]] (UNEP)|author3=International Labour Organization |author4=World Health Organization |title=The WHO Recommended Classification of Pesticides by Hazard |publisher=[[World Health Organization]] |isbn=978-92-4-154663-8 |year=2007 |url=https://www.who.int/ipcs/publications/pesticides_hazard/en/ |archive-url= https://web.archive.org/web/20040708001948/http://www.who.int/ipcs/publications/pesticides_hazard/en/ |url-status=dead |archive-date=July 8, 2004 |access-date=2007-12-02}}</ref> It is mildly toxic to [[human]]s and other [[mammal]]s, but extremely toxic to insects and aquatic life, including fish. This higher toxicity in fish and insects is because the [[lipophilic]] rotenone is easily taken up through the [[gill]]s or [[Invertebrate trachea|trachea]], but not as easily through the skin or the [[gastrointestinal tract]]. Rotenone is toxic to [[erythrocytes]] ''[[in vitro]]''.<ref>{{cite journal |pmid=22727881 |doi=10.1016/j.tox.2012.06.007 |volume=300 |issue=3 |title=Induction of apoptotic erythrocyte death by rotenone |date=October 2012 |pages=132–7 |last1=Lupescu |first1=Adrian |last2=Jilani |first2=Kashif |last3=Zbidah |first3=Mohanad |last4=Lang |first4=Florian |journal=Toxicology|bibcode=2012Toxgy.300..132L }}</ref>

The lowest lethal dose for a child is not known, but death occurred in a 3.5-year-old child who had ingested 40&nbsp;mg/kg rotenone solution.<ref name="wood" /> Human deaths from rotenone poisoning are rare because its irritating action causes vomiting.<ref>{{cite journal|journal=Pesticides News |volume=54 |year=2001 |pages=20–21 |title=Rotenone |url=http://www.pan-uk.org/pestnews/Actives/rotenone.htm}}</ref> Deliberate ingestion of rotenone can be fatal.<ref name="wood">{{cite journal |vauthors=Wood DM, Alsahaf H, Streete P, Dargan PI, Jones AL |title=Fatality after deliberate ingestion of the pesticide rotenone: a case report |journal=Critical Care |volume=9 |issue=3 |pages=R280–4 |date=June 2005 |pmid=15987402 |pmc=1175899 |doi=10.1186/cc3528 |doi-access=free }}</ref>

A 2018 study, which examined the effects of rotenone administration on cell cultures that mimicked properties of developing brains, found that rotenone may be a developmental [[neurotoxicant]]; that is, that rotenone exposure in the developing fetus may impede proper human brain development, with potentially profound consequences later in life. The study found that rotenone was particularly damaging to [[dopaminergic neurons]], consistent with prior findings.<ref>{{Cite journal |last1=Pamies |first1=David |last2=Block |first2=Katharina |last3=Lau |first3=Pierre |last4=Gribaldo |first4=Laura |last5=Pardo |first5=Carlos A. |last6=Barreras |first6=Paula |last7=Smirnova |first7=Lena |last8=Wiersma |first8=Daphne |last9=Zhao |first9=Liang |last10=Harris |first10=Georgina |last11=Hartung |first11=Thomas |last12=Hogberg |first12=Helena T. |date=2018-09-01 |title=Rotenone exerts developmental neurotoxicity in a human brain spheroid model |journal=Toxicology and Applied Pharmacology |series=Alternative Approaches to Developmental Neurotoxicity Evaluation |language=en |volume=354 |pages=101–114 |doi=10.1016/j.taap.2018.02.003 |issn=0041-008X |pmc=6082736 |pmid=29428530|bibcode=2018ToxAP.354..101P }}</ref>

=== Parkinson's disease ===
In 2000, injecting rotenone into rats was reported to cause the development of symptoms similar to those of [[Parkinson's disease]] (PD). Rotenone was continuously applied over a period of five weeks, mixed with [[Dimethyl sulfoxide|DMSO]] and [[Polyethylene glycol|PEG]] to enhance tissue penetration, and injected into the [[jugular vein]].<ref>{{cite journal |vauthors=Caboni P, Sherer T, Zhang N, Taylor G, Na H, Greenamyre J, Casida J |title=Rotenone, deguelin, their metabolites, and the rat model of Parkinson's disease |journal=Chem Res Toxicol |volume=17 |issue=11 |pages=1540–8 |year=2004 |pmid=15540952 |doi= 10.1021/tx049867r }}</ref>  The study does not directly suggest rotenone exposure is responsible for PD in humans, but is consistent with the belief that [[chronic exposure]] to [[environmental toxins]] increases the likelihood of the disease.<ref>[http://www.ninds.nih.gov/parkinsonsweb/greenamyre_summary.htm Summary of the article by Dr. Greenamyre on pesticides and Parkinson's Disease at ninds.nih.gov]</ref> In 2011, a US [[National Institutes of Health]] study showed a link between rotenone use and Parkinson's disease in farm workers, suggesting a link between neural damage and pulmonary uptake by not using [[protective gear]].<ref name="Tanner 2011">{{cite journal |vauthors=Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW |year=2011 |title=Rotenone, Paraquat and Parkinson's Disease |journal=Environmental Health Perspectives |volume=119 |issue=6 |pages=866–72 |doi=10.1289/ehp.1002839 |issn=0091-6765 |pmc=3114824 |pmid=21269927}}</ref> Exposure to the chemical in the field can be avoided by wearing a gas mask with filter, which is standard [[Health, Safety and Environment|HSE]] procedure in modern application of the chemical.

Studies with primary cultures of rat [[neuron]]s and [[microglia]] have shown low doses of rotenone (below 10 nM) induce oxidative damage and death of [[dopaminergic]] [[neurons]],<ref>{{cite journal |vauthors=Gao HM, Liu B, Hong JS |title=Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons |journal=The Journal of Neuroscience |volume=23 |issue=15 |pages=6181–7 |date=July 2003 |pmid=12867501 |pmc=6740554 |doi=10.1523/JNEUROSCI.23-15-06181.2003 }}</ref> and it is these neurons in the [[substantia nigra]] that die in Parkinson's disease. Another study has also described toxic action of rotenone at low concentrations (5 nM) in dopaminergic neurons from acute rat brain slices.<ref>{{cite journal |vauthors=Freestone PS, Chung KK, Guatteo E, Mercuri NB, Nicholson LF, Lipski J |title=Acute action of rotenone on nigral dopaminergic neurons--involvement of reactive oxygen species and disruption of Ca2+ homeostasis |journal=The European Journal of Neuroscience |volume=30 |issue=10 |pages=1849–59 |date=November 2009 |pmid=19912331 |doi=10.1111/j.1460-9568.2009.06990.x |s2cid=205515222}}</ref> This toxicity was exacerbated by an additional cell stressor – elevated intracellular calcium concentration – adding support to the 'multiple hit hypothesis' of dopaminergic neuron death.

The [[neurotoxin]] [[MPTP]] had been known earlier to cause PD-like symptoms (in humans and other primates, though not in rats) by interfering with complex I in the electron transport chain and killing dopaminergic neurons in the [[substantia nigra]]. Further studies involving MPTP have failed to show development of [[Lewy bodies]], a key component to PD pathology. However at least one study recently has found evidence of [[protein aggregation]] of the same chemical makeup as that which makes up Lewy bodies with similar pathology to Parkinson's disease in aged [[rhesus monkey]]s from MPTP.<ref>{{Cite journal |vauthors=Huang B, Wu S, Wang Z, Ge L, Rizak JD, Wu J, Li J, Xu L, Lv L, Yin Y, Hu X |date=2018-05-21 |title=Phosphorylated α-Synuclein Accumulations and Lewy Body-like Pathology Distributed in Parkinson's Disease-Related Brain Areas of Aged Rhesus Monkeys Treated with MPTP |journal=Neuroscience |language=en |volume=379 |pages=302–315 |doi=10.1016/j.neuroscience.2018.03.026 |pmid=29592843 |s2cid=4969894 |issn=0306-4522}}</ref> Therefore, the mechanism behind MPTP as it relates to Parkinson's disease is not fully understood.<ref>[https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.3223 Neurotransmitters and Disorders of the Basal Ganglia] -- Basic Neurochemistry -- NCBI Bookshelf, American Society for Neurochemistry</ref> Because of these developments, rotenone was investigated as a possible Parkinson-causing agent. Both MPTP and rotenone are [[lipophilic]] and can cross the [[blood–brain barrier]].

In 2010, a study was published detailing the progression of Parkinson's-like symptoms in mice following chronic intragastric ingestion of low doses of rotenone. The concentrations in the central nervous system were below detectable limits, yet still induced PD pathology.<ref>{{cite journal |vauthors=Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S, Gille G, Spillantini MG |date=2010 |title=Progression of Parkinson's Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice |journal=PLOS ONE |volume=5 |issue=1 |pages=e8762 |editor1-last=Kleinschnitz |editor1-first=Christoph |doi=10.1371/journal.pone.0008762 |pmc=2808242 |pmid=20098733 |bibcode=2010PLoSO...5.8762P |doi-access=free }}</ref>

== See also ==
* [[Fenpropathrin]]
* [[NADH dehydrogenase]]

== References ==
{{reflist}}

== External links ==
* [http://www.chm.bris.ac.uk/motm/rotenone/startpageh.htm Rotenone], [http://www.chm.bris.ac.uk/motm/motm.htm Molecule of the Month at chm.bris.ac.uk]
* [http://www.nysaes.cornell.edu/pp/resourceguide/mfs/11rotenone.php Cornell University.  Rotenone.  Resource Guide for Organic and Disease Management.] {{Webarchive|url=https://web.archive.org/web/20070609164832/http://www.nysaes.cornell.edu/pp/resourceguide/mfs/11rotenone.php |date=2007-06-09 }}
* [http://www.ars.usda.gov/SP2UserFiles/ad_hoc/12755100DatabaseFiles/PesticidePropertiesDatabase/IndividualPesticideFiles/ROTENONE.TXT Rotenone. ARS Pesticide Properties Database]
* [http://striweb.si.edu/rotenone_and_marine_research Rotenone use in research on the biodiversity of marine fishes]
* [http://www.pan-uk.org/pestnews/Actives/rotenone.htm Rotenone Factsheet]
* [http://www.epa.gov/oppsrrd1/reregistration/rotenone/ Rotenone registration at US Environmental Protection Agency]
* [https://www.cdc.gov/niosh/npg/npgd0548.html CDC – NIOSH Pocket Guide to Chemical Hazards]
* [http://www.bioblast.at/index.php/Rotenone Rotenone at Bioblast]
* [http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28201 Chemical Description]

{{Monoamine neurotoxins}}
{{Androgen receptor modulators}}
{{Estrogen receptor modulators}}
{{Rotenoid}}

[[Category:Aldehyde dehydrogenase inhibitors]]
[[Category:Aromatase inhibitors]]
[[Category:Rotenoids]]
[[Category:Hydroxyquinol ethers]]
[[Category:Isoflavones]]
[[Category:NADH dehydrogenase inhibitors]]
[[Category:Mitochondrial toxins]]
[[Category:Plant toxin insecticides]]
[[Category:Respiratory toxins]]
[[Category:Microtubule inhibitors]]
[[Category:Monoaminergic neurotoxins]]
[[Category:Isopropenyl compounds]]
[[Category:Parkinson's disease]]