Rotenone

Rotenone
IUPAC name (2R,6aS,12aS)-1,2,6,6a,12,12a- hexahydro-2-isopropenyl-8,9- dimethoxychromeno[3,4-b] furo(2,3-h)chromen-6-one
Other names Tubatoxin, Paraderil
Identifiers
CAS number	83-79-4 Y
PubChem	6758
UNII	03L9OT429T Y
KEGG	C07593 Y
MeSH	Rotenone
ChEMBL	CHEMBL429023 N
Jmol-3D images	Image 1
SMILES CC(=C)[C@H]1CC2=C(O1)C=CC3=C2O[C@@H]4COC5=CC(=C(C=C5[C@@H]4C3=O)OC)OC
InChI InChI=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
Properties
Molecular formula	C23H22O6
Molar mass	394.41
Exact mass	394.14164
Appearance	Colorless to red
Density	1.27 g/cm3 @ 20°C
Melting point	165-166°C
Boiling point	210-220°C at 0.5 mmHg
Solubility	Soluble in ether and acetone, slightly soluble in ethanol
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Rotenone is an odorless chemical that is used as a broad-spectrum insecticide, piscicide, and pesticide. It occurs naturally in the roots and stems of several plants such as the jicama vine plant. In mammals, including humans, it is linked to the development of Parkinson's disease.^[1]

History

Emmanuel Geoffroy first isolated rotenone from a specimen of Robinia nicou, now called Lonchocarpus nicou, while traveling in French Guiana.^[2] He wrote about this research in his thesis, published posthumously in 1895 after his death from a parasitic disease.^[3] Researchers later determined that the substance that Geoffroy termed nicouline was identically rotenone.

Uses

Rotenone is used in solution as a pesticide and insecticide, or in emulsified liquid form as a piscicide.^[4]

In the United States and in Canada, all uses of rotenone except as a piscicide (fish killer) are being phased out.^[5][6]

People catch fish by extracting rotenone from plants and releasing it into water. Poisoned fish come to the surface and are easily caught. This method was first practiced by various indigenous tribes^[7] who smashed the roots. Fish caught this way can be eaten because rotenone is very poorly absorbed by the gastrointestinal tract of humans, whereas it is lethal to fish because it readily enters the blood stream of the fish through the gills.^{[citation needed]}

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. Rotenone is the most effective tool available because only small quantities are necessary. It has only minor and transient environmental side-effects.^[8]

Rotenone is also used in powdered form to reduce parasitic mites on chickens and other fowl.

Rotenone is sold as an organic pesticide dust for the garden. Unselective in action, it kills potato beetles, cucumber beetles, flea beetles, cabbage worms, raspberry bugs, and asparagus bugs, as well as most other arthropods. Rotenone rapidly bio-degrades under warm conditions so there is minimal harmful residue. A light dusting on the leaves of plants will control insects for several days.

Use of Rotenone is controversial as it is not a selective piscicide (kills all species of fish), and in general is not able to kill 100% of the fish from a body of water, thus resulting in eventual return of the species targeted for killing.

Method of action

Rotenone works by interfering with the electron transport chain in mitochondria. To be specific, it inhibits the transfer of electrons from iron-sulfur centers in complex I to ubiquinone. This interferes with NADH during the creation of usable cellular energy (ATP). This is much like the action of amytal.

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 genus Lonchocarpus or 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^[9]
  • The root extract is referred to as Cubé resin
• Barbasco (Lonchocarpus urucu) – South America^[9]
  • The root extract is referred to as Cubé resin
• Tuba Plant (Derris elliptica) – southeast Asia & southwest Pacific islands
  • The root extract is referred to as Derris or Derris root
• Jewel Vine (Derris involuta) – southeast Asia & southwest Pacific islands
• Among the Mizo tribes of India (Derris walchii/D. thyrsiflora) the tender root is eaten as vegetable^{[citation needed]}
  • The root extract is referred to as Derris or Derris root
• Duboisia – This shrub grows in Australia and bears white clusters of flowers and berry like fruit. The crushed plants were used by the Aboriginals for poisoning fish for food.^{[citation needed]}
• Verbascum thapsus^{[citation needed]}
• Cork-Bush (Mundulea sericea) – southern Africa^[10]
• Florida fishpoison tree (Piscidia piscipula) – southern Florida, Caribbean^[11]

Toxicity

Rotenone is classified by the World Health Organization as moderately hazardous.^[12] It is mildly toxic to humans and other mammals, but extremely toxic to insects and aquatic life including fish. This higher toxicity in fish and insects is due to the fact that the lipophilic rotenone is easily taken up through the gills or trachea, but not as easily through the skin or through the gastrointestinal tract.

The lowest lethal dose for a child is 143 mg/kg. Human deaths from rotenone poisoning are rare because its irritating action causes vomiting.^[13] Deliberate ingestion of rotenone can be fatal.^[14]

The compound breaks down when exposed to sunlight and usually has a lifetime of six days in the environment.^[15] In water rotenone may last six months.^{[citation needed]}

Rotenone is classified by the USDA National Organic Program as a nonsynthetic and was allowed to be used to grow organic produce until 2005, when it was added to the list of prohibited substances due to concerns about its safety. However, it has since been re-approved.^[16]

Parkinson's disease

In 2000, it was reported that injecting rotenone into rats causes the development of symptoms similar to those of Parkinson's disease (PD). Rotenone was continuously applied over a period of five weeks, mixed with DMSO and PEG to enhance tissue penetration, and injected into the jugular vein.^[17] The study does not directly suggest that 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.^[18]

In addition, studies with primary cultures of rat neurons and microglia have shown that low doses of rotenone (below 10 nM) induce oxidative damage and death of dopaminergic neurons^[19] 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.^[20] This toxicity was exacerbated by an additional cell stressor - elevated intracellular calcium concentration - adding support to the 'multiple hit hypothesis' of dopaminergic neuron death.

It had been known earlier that the neurotoxin MPTP causes 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. However, further studies involving MPTP have failed to show development of Lewy bodies, a key component to PD pathology. Therefore, the mechanism behind MPTP as it relates to Parkinson's Disease is not fully understood.^[21] 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.^[22]

In 2011, a US National Institutes of Health study showed a link between rotenone use and Parkinson's disease in farm workers.^[1]

See also

• NADH dehydrogenase

References

1. ^ ^{a b} Tanner, Caroline M.; Freya Kamel, G. Webster Ross, Jane A. Hoppin, Samuel M. Goldman, Monica Korell, Connie Marras, Grace S. Bhudhikanok, Meike Kasten, Anabel R. Chade, Kathleen Comyns, Marie Barber Richards, Cheryl Meng, Benjamin Priestley, Hubert H. Fernandez, Franca Cambi, David M. Umbach, Aaron Blair, Dale P. Sandler, J. William Langston (2011). "Rotenone, Paraquat and Parkinson’s Disease". Environmental Health Perspectives. doi:10.1289/ehp.1002839. ISSN 0091-6765. PMID 21269927. http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1289%2Fehp.1002839. Retrieved 2011-02-14. 
2. ^ Ambrose, Anthony M.; Harvey B. Haag (1936). "Toxicological study of Derris". Industrial & Engineering Chemistry 28 (7): 815–821. doi:10.1021/ie50319a017. 
3. ^ "Useful tropical plants". ASNOM. 2008-01-02. http://www.asnom.org/en/730_plantes_tropicales_utiles.html. Retrieved 2008-03-16. 
4. ^ Peter Fimrite (2007-10-02). "Lake poisoning seems to have worked to kill invasive pike". San Francisco Chronicle. http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2007/10/02/BAOHSI41V.DTL. 
5. ^ Reregistration Eligibility Decision for Rotenone, EPA 738-R-07-005, March 2007, United States Environmental Protection Agency
6. ^ Re-evaluation Note: Rotenone (REV2008-01, 29 January 2008), Consumer Product Safety, Health Canada
7. ^ National Toxicology Program - Rotenone at ntp.niehs.nih.gov
8. ^ Robertson, D. Ross; Smith-Vaniz, William F. (2008). "Rotenone: An Essential but Demonized Tool for Assessing Marine Fish Diversity". BioScience 58 (2): 165. doi:10.1641/B580211. 
9. ^ ^{a b} Fang N, Casida J (1999). "Cubé resin insecticide: identification and biological activity of 29 rotenoid constituents". J Agric Food Chem 47 (5): 2130–6. doi:10.1021/jf981188x. PMID 10552508. 
10. ^ Coates Palgrave, Keith (2002). Trees of Southern Africa. Struik. ISBN 0869770810. 
11. ^ Nellis, David N. (1994). Seashore plants of South Florida and the Caribbean. Pineapple Press. 160 p.
12. ^ IPCS, International Programme on Chemical Safety; United Nations Environment Programme; International Labour Organization; World Health Organization. (2007). The WHO Recommended Classification of Pesticides by Hazard. World Health Organization. ISBN 92-4-154663-8. http://www.who.int/ipcs/publications/pesticides_hazard/en/. Retrieved 2007-12-02. 
13. ^ "Rotenone". Pesticides News 54: 20–21. 2001. http://www.pan-uk.org/pestnews/Actives/rotenone.htm. 
14. ^ Wood DM, Alsahaf H, Streete P, Dargan PI, Jones AL (June 2005). "Fatality after deliberate ingestion of the pesticide rotenone: a case report". Critical Care 9 (3): R280–4. doi:10.1186/cc3528. PMC 1175899. PMID 15987402. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1175899. 
15. ^ Vitax Safety Data Sheet for Derris dust, revised October 1998
16. ^ NOP Approved Substances. List of substances approved by the National Organic Program (from the Electronic Code of Federal Regulations).
17. ^ Caboni P, Sherer T, Zhang N, Taylor G, Na H, Greenamyre J, Casida J (2004). "Rotenone, deguelin, their metabolites, and the rat model of Parkinson's disease". Chem Res Toxicol 17 (11): 1540–8. doi:10.1021/tx049867r. PMID 15540952. 
18. ^ Summary of the article by Dr. Greenamyre on pesticides and Parkinson's Disease at ninds.nih.gov
19. ^ Gao HM, Liu B, Hong JS (July 2003). "Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons". The Journal of Neuroscience 23 (15): 6181–7. PMID 12867501. http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=12867501. 
20. ^ Freestone PS, Chung KK, Guatteo E, Mercuri NB, Nicholson LF, Lipski J (November 2009). "Acute action of rotenone on nigral dopaminergic neurons--involvement of reactive oxygen species and disruption of Ca2+ homeostasis". The European Journal of Neuroscience 30 (10): 1849–59. doi:10.1111/j.1460-9568.2009.06990.x. PMID 19912331. 
21. ^ Neurotransmitters and Disorders of the Basal Ganglia -- Basic Neurochemistry -- NCBI Bookshelf, American Society for Neurochemistry
22. ^ Pan-Montojo, Francisco; Anichtchik, Oleg; Dening, Yanina; Knels, Lilla; Pursche, Stefan; Jung, Roland; Jackson, Sandra; Gille, Gabriele et al. (2010). Kleinschnitz, Christoph. ed. "Progression of Parkinson's Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice". PLoS ONE 5 (1): e8762. doi:10.1371/journal.pone.0008762. PMC 2808242. PMID 20098733. http://precedings.nature.com/documents/3352/version/3. 

External links

• Rotenone, Molecule of the Month at chm.bris.ac.uk
• Compendium of Pesticide Common Names at alanwood.net
• Cornell University. Rotenone. Resource Guide for Organic and Disease Management.
• Rotenone. ARS Pesticide Properties Database
• Rotenone use in research on the biodiversity of marine fishes, English language paper in Bioscience, with Spanish, Portuguese and French translations