ROTENONE Rotenone is an odourless, colourless , crystalline 

ketonic chemical compound used as a broad-

spectrum insecticide, piscicide, and pesticide. It occurs

naturally in the seeds and stems of several plants, such as

the jicama vine plant; and the roots of several members

of Fabaceae.

hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4-b]furo(2,3-h)chromen-6-one

Molecular formula C23H22O6

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.

• The active chemical component was first isolated by a

French botanist Emmanuel Geoffroy in 1895 and called

it nicouline, from a specimen of Robinia nicou, now

called Lonchocarpus nicou, while traveling in French

GuianaIn 1902, a Japanese chemist, Nagai isolated a pure

crystalline compound from Derris elliptica which he called

rotenone, after the Japanese name of the plant roten. By

1930, nicouline and rotenone were established to be

chemically the same.[

Mechanism 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). Cellular oxygen is reduced to the

radical, creating a Reactive Oxygen Species, which

can damage DNA and other components of the

mitochondria

Uses• Rotenone is used as a pesticide, insecticide, and as a

nonselective piscicide• It is commercialized as cubé, tuba, or derris, in single

preparation or in synergistic combination with other insecticides.

• Rotenone has historically been used by indigenous peoples to catch fish. Typically, rotenone-containing plants in the Fabaceaefamily of legumes are crushed and introduced into a body of water, and as rotenone interferes with cellular respiration, the affected fish rise to the surface in an attempt to gulp air, where they are more easily caught.

• Rotenone is also used in powdered form to

treat scabies and head lice on humans,

and parasitic mites on chickens, livestock, and pet animals.

• Rotenone has been used as an organic pesticide dust for

gardens

• It kills potato beetles, cucumber beetles, flea beetles, cabbage

worms, raspberry beetles, and asparagus beetles, as well as

most other arthropods. It rapidly biodegrades under warm

conditions, so harmful residues are minimal. A light dusting on

the leaves of plants will control insects for several days.

Toxicity• 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 because

the lipophilic rotenone is easily taken up through

the gills or trachea, but not as easily through the skin or

thegastrointestinal tract. Rotenone is toxic to erythrocytes in

vitro. 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 decomposes when exposed to

sunlight and usually has an activity of six days in

the environment.It oxidises to rotenolone, which is

less toxic than rotenone. In water, the rate of

decomposition depends upon several factors,

including temperature, pH, water hardness and

sunlight. The half-life in natural waters ranges

from half a day at 24°C to 3.5 days at 0°C.

Pyrethroids

+

=Piperonyl butoxide

Pyrethroids• Derived from pyrethrins;

natural compounds produced by chrysanthemum flowers (C. cinerariaefolium and C. cineum

• Pyrethrins will paralyze insect; animal will recover (enzyme detoxification)

• Pyrethroids are synthetic esters derived from pyrethrins; engineered for insect death, “knockdown” effect

• Synthetic modifications (addition of synergists) make these compounds more toxic to organisms, less degradable in environment

Pyrethroid Structures

• Pyrethrins are esters of chrysanthemic (I) or pyrethric (II) acid; have been synthetically modified into complex mixture of isomers

• Type 1 and 2 pyrethroids• Very lipophillic, low

water solubility• Structure of compound (I

or II) has different effects and associated poisoning symptoms

• Isomerism around the cyclopropane ring greatly influences toxicity

All pyrethroids have an acid moiety, acentral ester bond, and an alcohol moiety

Permethrin

• Pyrethroids are synthetic analogs of pyrethrins, made to last longer and be more toxic to insects.• Type I – shorter duration of effects• Type II – longer acting, enhanced by

addition of cyano group

• Type I - pesticides

Pyrethrins,bioallethrin,cismethrin

Type I - poisonings

•Severe fine tremor

• Marked reflex hyperexcitability

• Sympathetic activation

• Paresthesia (dermal exposure)

• Type II (cyano) - pesticides• fenvalerate• cyhalothrin• deltamethrin• cypermethrinType II - poisonings

• Profuse watery salivation

• Coarse tremor

• Sympathetic activation

• Choreoathetosis

• Seizures (dermal exposure)

Uses of pyrethroid• Domestic – e.g. bug bombs, mosquito nets, insect sprays• Medical - e.g. treatment of scabies and lice• Commercial – e.g. insecticide for agriculture• Veterinary – e.g. pet shampoos, fleas

Mode of entry into aquatic environment

• Spray drift; pyrethroids often applied aerially and can contaminate nearby waters

• Runoff from fields, wastewater from manufacturing facilities

Mode of Entry into Organisms

• Rapidly absorbed to particulate matter in water due to high lipophillicity/low solubility

• Half life for pyrethroids in aquatic medium has been reported between 19 hours

• Most pyrethroid half lives in water range from 1-2 days

• Its speciation varies greatly with compound’s structure, exposure to sunlight, and pH, temperature, and salinity of water medium

• Since pyrethroids are highly lipophillic, will readily be absorbed through the gills of aquatic animals

• In mammals, toxicity occurs when ingested, not readily absorbed through skin

• Absorption:• GI: moderate• Respiratory Tract: moderate• Dermal: poor

• Usually metabolized quickly by the liver • Excreted primarily in urine, less in feces• Half life – usually 5-20 hours, can be days• Often combined with synergist (e.g. piperonyl) to

enhance killing power & slow degradation• Lipophilic, may concentrate in fat tissues

Mechanism of Action

Acts primarily on voltage dependent sodium channels leading to hyperexcitable state, also affects chloride channels to increase excitability

• Increases adrenal activation – increasing adrenaline

• Duration of effect is determined by the structure of the offending pyrethroid

Mode of Toxic Interaction: Neurotoxicity

• Acute neurotoxicity is caused by binding to sodium channels--> slows down its activation and inactivation properties which leads to a hyperexcitable state

• A normal action potential is converted into double or continuous discharges in nerve and muscle

• Current duration dependant on pyrethroid structure; action stereospecific

• Insect sodium channels 100x more susceptible than mammals

Other Toxic Interactions

• Most pyrethroids stimulate protein kinase C-dependant protein phosphorylation (channel activity modulated by phosphorylation state)

• Antagonism of GABA-mediated inhibition (seizures)• Enhancement of noradrenalin release• Direct actions on calcium or chloride ion channels

(type II only)• Type II pyrethroids produce a more complex

poisoning syndrome and act on wider range of tissues

Metabolism and Breakdown

• Biological activity destroyed by ester hydrolysis, major route, creates oxidative metabolites

• Oxidative reactions catalyzed by cytochrome P450 (CYP) enzymes in all animals (CYP6 family important for insects). Is thought that insecticidal properties of pyrethroids terminated by oxidative metabolism . Resistance to pyrethroids due to detoxification by CYP monooxygenases

• Resistance associated with elevated CYP activity.