1. Arthropod Environmental Management 2
Topics for Session 2
Botanical Insecticides
Sabadilla, Nicotine, Ryanodine, Quassia, Rotenone, Pyrethrum, Neem Extracts, Essential Oils
Synthetic Insecticides
Organochlorides, Pyrethroids, Organophosphates, Carbamates, Neonicotinoids
Growth Regulators
Moulting hormone mimics, Juvenile hormone mimics, Chitin Synthesis Inhibitors

2. Arthropod Environmental Management 2
Botanical Insecticides
Phytochemicals (plant chemicals)
Often Secondary Plant Substances (in contrast to primary substances)
Examples include alkaloids (eg nicotine), phenolic compounds, and terpenoids
Use dates back ca years (continues in native cultures)
Western use since 16th C explorations

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Botanical Insecticides – Current Interest
Cost of developing new insecticides
Small proportion of plants evaluated
Previous success with carbamates and pyrethroids
Newer successes with neonicotinoids and with neem extracts
Still used in native cultures

4. Arthropod Environmental Management 2
(some) Plants Still Used in Native Cultures for Pest Control
Custard Apple, Sweet Flag, Chrysanthemum, Spearmint, Derris, Garlic, Sabadilla, Neem, Quassia, Chilli, Turmeric
Some authors suggest that ca. 2,400 species are used at the local level

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Botanical Insecticides – Issues with Commercial Development
Farmers regard botanicals as old-fashioned
Not on official lists
Often do not get dramatic kills of pests
Light and Air may inactivate
May be seasonal availability
Costs may be high
May be of variable toxicity

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Botanical Insecticides - Examples
Sabadilla
Nicotine
Ryanodine
Quassia
Rotenone
Pyrethrum
Neem Extracts
Essential Oils

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Sabadilla
Powdered seeds used by S. American Indians to protect crops from insect attack (from Sabadilla officinarum – a plant in the Lily family)
Discovered by European explorers
Exported to Europe from 16th C to WWII (over 120,000 tonnes to USA in 1940s, use declined because of advent of DDT)
Actives are alkaloids, rapidly inactivated by exposure to sunlight and air (as are many botanicals)

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Sabadilla
Contact and Stomach poison that is neurotoxic (sodium channels). This is similar to DDT and the pyrethroids
Good for pre-harvest treatments (because it is rapidly inactivated)
Use has largely been phased out because of cheaper alternatives, cannot be synthesised, must be extracted – still used in native cultures

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Nicotine
Alkaloid nicotine from tobacco plants
Discovered by European explorers, in use by American Indians
By 17th/18th Century widely used in Europe
AI was named nicotine in 1828, in 1904 it was chemically synthesised

10. Arthropod Environmental Management 2
Nicotine
Contact insecticide that works as an agonist for acetylcholine receptors on post-synaptic membranes
Not very selective (high mammalian toxicity in contrast to sabadilla), rapidly inactivated (48 hrs)
Still available for use in Europe in professional situations
More costly than modern synthetics so use largely phased out (originally made from low grade tobacco)
Like sabadilla is still used in native cultures

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Quassia
From Central American tree Quassia amara
Exported from 18th C to WWII to Europe (from commercial plantations in Venezuela)
Contact and stomach poison from bark and branches. Active ingredient is called quassin. Has not yet been synthesised

12. Arthropod Environmental Management 2
Quassia
May have some systemic activity (nicotine and sabadilla do not, they are contact and stomach poisons)
Has not been synthesized and exact mode-of-action not clear
Like most botanicals it is too costly in comparison to modern chemicals
Still used in native cultures and there is a revival of interest in quassia in the West.

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Ryanodine
First botanical to be discovered as a result of an official screening programme (in 1940s in USA)
Active is an alkaloid from a South American shrub in the genus Ryania
It is a contact/stomach poison and is much more stable than other botanicals (up to a week)

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Ryanodine
Mode-of-action is to bind to calcium channels. Cells then are flooded with calcium molecules and poisoned species die
It has a moderate mammalian toxicity (750mg/kg in contrast to more than 4,000 for sabadilla and to 50 for nicotine)
It cannot be synthesised and so costs associated with its commercial production are prohibitive. Still used in native cultures.

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Rotenone
Extracts from plants of American & Asian origin (unlike other botanicals)
Used in native cultures as fish poison
Used in Western countries from 1840s but has now declined because of cheaper alternatives

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Rotenone
Chemical structure was determined in 1930s. At least 10 related chemicals called rotenoids have now been described from over 70 different plant species. Cannot be synthesised.
AIs disrupt mitochondria reducing oxygen uptake so poisoned species suffocate. Is of moderate mammalian toxicity
Rapidly inactivated by exposure to light and air
In 2000 could still buy amateur and professional formulations in the UK. Still used in native cultures

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Pyrethrum
Best known botanical. From Chryanthemum. Extracts from flower heads
Use since start of 19th C to present. Still used today. Kenya and Tanzania grow most of the plants that are used commercially
Very unstable, good pre-harvest and safe to use in domestic situations

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Pyrethrum
Natural pyrethrins are a mixture of AIs. All are contact insecticides that act on sodium channels. Mammalian toxicity is 1,600 mg/kg.
Synthetic versions of natural pyrethrins have now been produced (first in 1949/1950 was an AI called Allethrin)

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Neem Extracts
Extracts from Asian neem tree. Main active is thought to be azadirachtin
These trees are now grown throughout the world including the USA (plantations in California and in Florida)
Best extracts from seed but all plant parts have been used
Azadirachtin cannot be synthesised. Full chemical structure published in 1985

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Neem Extracts
Main AI is azadirachtin but further AIs are continually being discovered, e.g. nimbin and sallanin. Crude extracts always more potent than azadirachtin.
Since 1990s has been increasing interest in these extracts and a number of formulations now exist
Works by disrupting development of larvae (hormonal interference) and as an antifeedant (has systemic activity). Very high mammalian toxicity (> 5,000 mg/kg)
Inactivated by sunlight. Interest in neem formulations continues to grow

21. Arthropod Environmental Management 2
Essential Oils
Many are recorded as having insecticidal activity, primarily as repellents rather than as toxicants
Most well known are eucalyptus, peppermint and citronella
Most are highly volatile and are extracted in such small amounts that they are uneconomic to develop on a large scale
Still used in native cultures

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Botanicals - Summary
Most success with Pyrethrum, neem is of current interest
All contact/stomach poisons except neem and quassia extracts (systemic)
Most act of nervous system, some on respiration (rotenone), some on development (neem)
Most are unstable (except ryanodine) and difficult to synthesise (except pyrethroids and nicotine)

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Botanicals – Questions?

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Chemical Insecticides
Organochlorides
Pyrethroids
Organophosphates
Carbamates
Neonicotinoids
Growth Regulators

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Organochloride Insecticides
First extensively used group of insecticides
Comprised of three groups: DDT group, HCH group, and cyclodienes

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Organochloride Insecticides - DDT
DDT (DichloroDiphenylTrichloroethane)
First prepared in 1874, insecticidal properties discovered in 1939
Used during war to control vectors of malaria and typhus (mosquitoes and fleas)
1948 – Paul Muller was awarded Nobel prize for medicine for his discovery of DDT
Cheap and stable molecule
Now banned throughout Europe and other Western countries

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Organochloride Insecticides - DDT
Fat soluble (lipophilic) so biomagnifies or bioconcentrates
Species Group DDT Concentration Concentration Factor
Water ppm not applicable
Zooplankton 0.04 ppm ca. 13,000
Small Fish 0.5 ppm ca. 17,000
Large Fish 2 ppm ca. 700,000
Fish-Eating Birds 25 ppm ca. 8 million

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Organochloride Insecticides - DDT
Toxicity of DDT
DDT appears to disrupt calcium metabolism in birds leading to egg-shell thinning
This caused particular problem for predatory birds (e.g. eagles)
Main mode-of-action is as neurotoxin
Interferes with sodium channels on nerve axons
Is a contact/feeding poison with no systemic activity
Still used in Africa and Asia for mosquito control

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Organochloride Insecticides - Summary
Extremely stable group, half lives measured in years
Chemically composed of C, H, and CL groups
10 – 20 actives developed are marketed
No longer used in Western countries, most used in developing countries
They are cheap, stable and effective, especially for control of vectors of disease

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Pyrethroid Insecticides
Synthetic pyrethroids
First was marketed in 1950 (allethrin), since then ca. 30 AIs have been produced. Examples include permethrin, deltamethrin, cypermethrin
Synthetic development has focussed on stabilising the natural version (pyrethrum) of the active molecule

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Pyrethroid Insecticides
Comparisons between pyrethum and synthetic versions

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Pyrethroid Insecticides
Comparisons between pyrethum and synthetic versions

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Pyrethroid Insecticides
Comparisons between pyrethum and synthetic versions
Much more photostable, sites of auto-oxidative attack removed. Natural pyrethrum open to hydrolytic, esteratic and oxidative attack
Synthetic chemicals are cheaper to produce
Much more toxic than natural pyrethrum, can be applied at far lower application rates

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Pyrethroid Insecticides – Mode of Action
Contact & stomach poisons, no systemic activity
Interfere with sodium channels on nerve axons (like DDT)
Have a rapid knock-down effect suggesting that the peripheral nervous system is affected immediately

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Organophosphate Insecticides
Developed from wartime research on potential nerve agents (sarin and tabun)
First insecticide was schradan (now replaced), 80 – 100 AIs developed
All tri-esters of phosphoric acid

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Organophosphate Insecticides
Break down in days – weeks
Some are systemic
Examples of OPs include malathion, parathion, chlorpyrifos
Very widely used group of insecticides worldwide

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Organophosphate Insecticides
Mode of Action
Neurotoxins – interfere with synaptic transmission of nerve impulses
Block the enzyme that breaks down acetylcholine
Acetylcholinesterase binds OPs and the neurotransmitter builds up in synapses
In human poisoning the acetylcholine inhibitor atropine is administered

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Carbamate Insecticides
First (carbaryl) marketed in 1956
Developed from knowledge that a natural carbamate (physostigmine) had anti-cholinesterase activity
Ca. 30 AIs developed, all with an N-methyl carbamate group

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Carbamate Insecticides
Physostigmine is very hydrophilic, synthetic carbamates are much more lipophilic
Examples include pirimicarb and aldicarb, the most toxic insecticide marketed to date
Overall, their use is declining but they are still widely available.

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Carbamate Insecticides – Mode of Action
Like OPs they block the enzyme acetylcholinesterase
The process is called carbamylation (rather than phosphorylation)
Like OPs atropine is used in cases of poisoning

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Carbamate Insecticides – Bhopal
1984 – factory in India producing carbaryl released a cloud of Methyl Isocyanate
Of the 800,000 people living in Bhopal, 2,000 died immediately, at least 10,000 have died subsequently and at least 300,000 people were affected
This remains the world’s worst industrial accident where human lives are concerned
In 1989 a final settlement was supposed to have been reached ($470 million)
Many people think that more still needs to be done – Bhopal is still contaminated

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Neonicotinoids
Newest group of synthetic insecticides
Imidacloprid was marketed in 1991, now 4 others available
All have contact and systemic activity
Based on the alkaloid nicotine

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Neonicotinoids
Like nicotine they work as agonists to acetylcholine
This leads to a build up of acetylcholine which causes death
Now one of the most extensively used group of insecticides worldwide

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Synthetic Insecticides - Summary
Environmental Exposure Number
Stability and Toxicity of A.I.’s
Organochlorides Months to Contact & ca
Years Feeding Poisons.
Organophosphates Weeks Contact, Feeding ca
& Systemic
Poisons
Pyrethroids Weeks Contact & ca
Feeding Poisons
Carbamates Weeks Contact, Feeding ca
Neonicontinoids Weeks Contact, Feeding ca. 5-7

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Insect Growth Regulators
Chemicals that affect growth and development
Usually applied through conventional application equipment
Mostly effective against juvenile stages (timing important)
Three groups: juvenile hormones, moulting hormones, chitin synthesis inhibitors

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Insect Growth & Development
All arthropods have exoskeletons (support, movement & prevent dehydration)
These must be shed to grow, a process controlled by hormones
Moulting hormone: determines whether a moult occurs
Juvenile hormone: determines type of moult
Studies on hormones for back 40 years (not new)

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Juvenile Hormone (JH) Mimics
Studies on plant extracts (firs & ferns) indicated compounds with JH activity
Led to production of farnesol (first synthetic hormone)
Keeps insects in juvenile stage (limited use), does not penetrate cuticles well
Some commercial successes: kinoprene, methoprene

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Juvenile Hormone (JH) Mimics
Most uses against pests of public and animal health (i.e. fleas)
Break down fairly rapidly on exposure to light and air
Compounds with Anti-JH activity have been developed but none sufficiently active

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Moulting Hormone (MH) Mimics
MH causes a moult to occur
Can be used against juvenile stages
Examples include: tebufenozide, halofenozide
They cause a precocious moult to occur in treated pest species
Used against a range of pest species

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Chitin Synthesis Inhibitors
Most successfully developed group of IGRs
> 10 formulations marketed
All cause a reduction in chitin synthesis (structural polysaccharide)
Disrupt the enzyme chitin synthetase
Insects die from dehydration, predation, etc.
Very successfully used in locust control operations in Africa

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Insect Growth Regulators – Summary
Most success with CSIs (only effective against juveniles, adults do not moult!)
Some other successes with MH and JH mimics, particularly for control of public health pests
All highly specific with zero impact on vertebrates
Overall, still a relatively small section of pest control market