Rotenone
Encyclopedia
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
.
first isolated rotenone from a specimen of Robinia nicou, now called Lonchocarpus nicou, while traveling in French Guiana
. He wrote about this research in his thesis, published posthumously in 1895 after his death from a parasitic disease
. Researchers later determined that the substance that Geoffroy termed nicouline was identically rotenone.
In the United States and in Canada, all uses of rotenone except as a piscicide (fish killer) are being phased out.
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 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.
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.
Rotenone is also used in powdered form to reduce parasitic mite
s 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.
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.
or Derris
.
Some of the plants containing rotenone:
as moderately hazardous. 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 due to the fact that the lipophilic
rotenone is easily taken up through the gill
s 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. Deliberate ingestion of rotenone can be fatal.
The compound breaks down
when exposed to sunlight and usually has a lifetime of six days in the environment. In water rotenone may last six months.
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.
(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
. 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.
In addition, studies with primary cultures of rat neuron
s and microglia
have shown that low doses of rotenone (below 10 nM) induce oxidative damage and death of dopaminergic
neurons 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. 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. 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.
In 2011, a US National Institutes of Health study showed a link between rotenone use and Parkinson's disease in farm workers.
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
, piscicide
Piscicide
A piscicide is a chemical substance which is poisonous to fish. The primary use for piscicides is to eliminate a dominant species of fish in a body of water, as the first step in attempting to populate the body of water with a different fish...
, and pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...
. It occurs naturally in the roots and stems of several plants such as the jicama
Jícama
Pachyrhizus erosus, commonly known as Jícama , Yam, and Mexican Turnip, is the name of a native Mexican vine, although the name most commonly refers to the plant's edible tuberous root. Jícama is one species in the genus Pachyrhizus. Plants in this genus are commonly referred to as yam bean,...
vine plant. In mammals, including humans, it is linked to the development of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
.
History
Emmanuel GeoffroyEmmanuel Geoffroy
Emmanuel Geoffroy was a French botanist and explorer.Geoffroy traveled to Martinique and French Guiana in search of latex-yielding trees, but also studied the region's native plants in the genus Robinia after learning that forest Indians of French Guiana used Robinia as fish poisons...
first isolated rotenone from a specimen of Robinia nicou, now called Lonchocarpus nicou, while traveling in French Guiana
French Guiana
French Guiana is an overseas region of France, consisting of a single overseas department located on the northern Atlantic coast of South America. It has borders with two nations, Brazil to the east and south, and Suriname to the west...
. He wrote about this research in his thesis, published posthumously in 1895 after his death from a parasitic disease
Parasitic disease
A parasitic disease is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases. Parasitic diseases can affect practically all living organisms, including plants and mammals...
. 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.In the United States and in Canada, all uses of rotenone except as a piscicide (fish killer) are being phased out.
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 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.
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.
Rotenone is also used in powdered form to reduce parasitic mite
Mite
Mites, along with ticks, are small arthropods belonging to the subclass Acari and the class Arachnida. The scientific discipline devoted to the study of ticks and mites is called acarology.-Diversity and systematics:...
s on chickens and other fowl
Fowl
Fowl is a word for birds in general but usually refers to birds belonging to one of two biological orders, namely the gamefowl or landfowl and the waterfowl...
.
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 chainElectron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...
in mitochondria. To be specific, it inhibits the transfer of electrons from iron-sulfur centers in complex I to ubiquinone. This interferes with NADH
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
during the creation of usable cellular energy (ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
).
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 LonchocarpusLonchocarpus
Lonchocarpus is a plant genus in the legume family . The species are called lancepods due to their fruit resembling an ornate lance tip or a few beads on a string....
or Derris
Derris
Derris is a climbing leguminous plant of Southeast Asia and the southwest Pacific islands, including New Guinea. Its roots contain rotenone, a strong insecticide and fish poison....
.
Some of the plants containing rotenone:
- Hoary Pea or Goat’s Rue (Tephrosia virginianaTephrosia virginianaTephrosia virginiana, also known as Goat's Rue, is a perennial dicot in Fabaceae. This subshrub has alternate compound leaves. All parts of the plant are pubescent giving it a silvery, hoary appearance. The terminal, compact racemes of cream and deep pink flowers bloom May to August. This plant...
) – North America - Jícama (Pachyrhizus erosus) – North America
- Cubé Plant or Lancepod (Lonchocarpus utilisLonchocarpus utilisLonchocarpus utilis is part of the Fabaceae family. It is native to the tropical forests of Peru, as well as of Brazil and Guyana, growing from 100–1,800 meters above sea level....
) – South America- The root extract is referred to as Cubé resin
- Barbasco (Lonchocarpus urucuLonchocarpus urucuLonchocarpus urucu is part of the Fabaceae family. It is native to the tropical forests of Peru, as well as of Brazil and Guyana, growing from 100 to 1,800 meters above sea level....
) – South America- 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
- The root extract is referred to as Derris or Derris root
- DuboisiaDuboisiaDuboisia is a genus of small perennial shrubs to trees about 14 m tall, with extremely light wood and a thick corky bark. There are four species; all occur in Australia, and one also occurs in New Caledonia....
– 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. - Verbascum thapsus
- Cork-Bush (Mundulea sericea) – southern Africa
- Florida fishpoison tree (Piscidia piscipulaPiscidia piscipulaPiscidia piscipula, commonly named Florida fishpoison tree, Jamaican dogwood or Fishfuddle, is a medium-sized, deciduous, tropical tree endemic to southern Florida, the Florida Keys, Texas, Caribbean, and Latin America. Native Americans of the West Indies discovered extracts from the tree could...
) – southern Florida, Caribbean
Toxicity
Rotenone is classified by the World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
as moderately hazardous. It is mildly toxic to human
Human
Humans are the only living species in the Homo genus...
s and other mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s, 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
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
rotenone is easily taken up through the gill
Gill
A gill is a respiratory organ found in many aquatic organisms that extracts dissolved oxygen from water, afterward excreting carbon dioxide. The gills of some species such as hermit crabs have adapted to allow respiration on land provided they are kept moist...
s or trachea
Invertebrate trachea
The invertebrate trachea refers to the open respiratory system composed of spiracles, tracheae, and tracheoles that terrestrial arthropods have to transport metabolic gases to and from tissues....
, but not as easily through the skin or through the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
.
The lowest lethal dose for a child is 143 mg/kg. Human deaths from rotenone poisoning are rare because its irritating action causes vomiting. Deliberate ingestion of rotenone can be fatal.
The compound breaks down
Chemical decomposition
Chemical decomposition, analysis or breakdown is the separation of a chemical compound into elements or simpler compounds. It is sometimes defined as the exact opposite of a chemical synthesis. Chemical decomposition is often an undesired chemical reaction...
when exposed to sunlight and usually has a lifetime of six days in the environment. In water rotenone may last six months.
Rotenone is classified by the USDA National Organic Program
National Organic Program
In the United States, the National Organic Program is the federal regulatory framework governing organic food. It is also the name of the organization in the Department of Agriculture responsible for administering and enforcing the regulatory framework. The Organic Food Production Act of 1990 In...
as a nonsynthetic and was allowed to be used to grow organic
Organic farming
Organic farming is the form of agriculture that relies on techniques such as crop rotation, green manure, compost and biological pest control to maintain soil productivity and control pests on a farm...
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.
Parkinson's disease
In 2000, it was reported that injecting rotenone into rats causes the development of symptoms similar to those of Parkinson's diseaseParkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
(PD). Rotenone was continuously applied over a period of five weeks, mixed with DMSO
Dimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
and PEG
Polyethylene glycol
Polyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
to enhance tissue penetration, and injected into the jugular vein
Jugular vein
The jugular veins are veins that bring deoxygenated blood from the head back to the heart via the superior vena cava.-Internal and external:There are two sets of jugular veins: external and internal....
. 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.
In addition, studies with primary cultures of rat neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s and microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
have shown that low doses of rotenone (below 10 nM) induce oxidative damage and death of dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neurons and it is these neurons in the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
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. 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
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
MPTP
MPTP
MPTP is a neurotoxin precursor to MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain...
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. Because of these developments, rotenone was investigated as a possible Parkinson-causing agent. Both MPTP and rotenone are lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
and can cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
.
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.
In 2011, a US National Institutes of Health study showed a link between rotenone use and Parkinson's disease in farm workers.
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