S2 L3 Insecticides - synthetic

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S2 L3 Insecticides - synthetic

• Anna Drew
• with slide contribution from Martin Wilks,
  Syngenta
• Diane Alston Joel Coats

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World Insecticide Market
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Old classes (nerve poisons)

• ORGANOCHLORINES
• Most famous DDT
• (Dichloro-Diphenyl-Trichloroethane)
• 4,4'-(2,2,2-trichloroethane -1,1-diyl)
  bis(chlorobenzene)
• 1874 synthesized
• 1939 insecticidal properties discovered
• 1942 first introduced for malaria control in India

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• Although useful
• tends to accumulate in body fat
• not really excreted
• tended to build up in food chains
• eg birds -gt thin egg shells endangering species
• resistance developed
• Banned in the US, UK etc
• Use extensive use in developing countries
• mosquito, tsetsi fly control malaria, typhus
• Action
• delays closing sodium channels
• inhibition of axonal Na-, K- and Mg2-ATPase
• interaction with GABAA receptor chloride
  ionophores

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Lindane

• gamma hexa chloro benzene
• benzene hexachloride
• still used in Sri Lanka
• similar to DDT
• more rapidly metabolised
• less stable
• Other cycloalkanes
• dieldrin
• aldrin
• Methoxychlor

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• ORGANOPHOSPHATES
• Esters of phosphoric acid - examples

eg dichlorvos (orthophosphate)
eg diazinon (orthothionphosphate)
eg parathion
eg chlorpyrifos
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• Selection
• solubility
• volatility
• relative toxicity (insects v mammals)
• stability
• Action
• mimic acetylcholine by binding with
  acetylcholinesterase
• prevents ACh breakdown
• duration of toxicity depends on how quickly
  enzyme is rehydrolysed
• generally more toxic to vertebrates
• persist less in environment
• Uses before contact, now systemic
• aphids, spiders
• Problems
• Handling absorbed through skin

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Mortality rates of poison admissions at
Anuradhapura General Hospital, Sri Lanka (2.4.02
13.1.03)
  Admissions Deaths Mortality Rates ()
Oleander 350 25 7.1
Organophosphate 277 39 14.1
Other Pesticides 141 6 4.3
Medicines 101 1 1.0
Carbamates 57 4 7.0
Hydrocarbons 44 0 0
Paraquat 45 21 46.7
Unknown 56 3 5.4
Unknown Pesticides 93 9 9.7
Organochlorines 5 3 60.0
Acid 3 0 0
Alkali 4 0 0
TOTAL 1176 111 9.4
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Target site
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• CARBAMATES
• Derivatives of carbamic acid examples
• Action
• also inhibits AChE resulting in accumulation of
  ACh at neuromuscular junctions or synapses
• causes rapid twitching of voluntary muscles and
  finally paralysis
• Use some contact, some systemic

eg propoxur
eg aldicarb
eg methomyl
eg carbaryl
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• SUBSTITUTED PHENOLS
• Good on woody plants and outdoors
• 1950 fungicide as a winterwash
• then acaricide (mites, ticks)
• then foliage control of mildew on fruits mites
  on apple trees
• Very toxic, protection for handling
• Highly toxic to birds, slightly toxic to fish

Dinitroorthocresol
Dinocap
CH3CHC6H13
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Why preferentially toxic to insects?

• Ease of access to site of action differs
• eg pyrethroids
• easily absorbed through insect exoskeleton but
  not skin
• Action at site differs
• insect sodium channels 100x more sensitive than
  mammalian channels
• the proportion of sodium channels affected and
  hence the degree of hyperexcitability is
  dose-dependent
• the duration of the hyperexcitable state and
  hence the nature of the effect is structure
  dependent
• Variability of metabolism
• eg OPs
• insects convert S -gt O forming much more active
  compounds
• mammals esterase cleaves off ester group and
  compound is much easier to excrete

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• INSECT GROWTH REGULATORS
• Class benzoylureas
• diflubenzuron, lufenuron, novaluron
• Cyromazine (triazine)
• Use leafminers in vegetable crops ornamentals
• Action interfere with chitin synthesis
• act at the larval stage
• greatest value for control of caterpillars,
  beetle larvae
• cause ruptured cuticle or death by starvation
• taken up more by ingestion than contact

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• PYRAZOLES
• Fipronil
• Use
• systemic material with contact and stomach
  activity
• control of soil and foliar insects eg rice water
  weevil
• baits for cockroaches, ants, termites
• effective against insects resistant or tolerant
  to pyrethroid, OP and carbamates
• Action
• inhibitor at the gamma-aminobutyric acid (GABA)
  receptor
• non-competitive blockers at the GABA-gated
  chloride channels in neurons

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• OTHERS
• Since 1995 29 new compounds, 57 brands - Utah
• Chlorfenapyr
• broad-spectrum insecticide
• ? interferes with oxidative phosphorylation
• Sulfluramid
• Buprofezin
• inhibits chitin synthesis
• similar to benzoyl phenylureas
• Diafenthiuron (thiourea)
• inhibits ATPase in mitochondria

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• Indoxacarb (oxadiazine)
• blocks sodium channel in nerve axon
• inhibits propagation of nerve potential
• Metaflumizone
• blocks sodium channel in nerves
• Pymetrozine (pyridine azomethine)
• inhibits feeding of sucking insects aphids
• neuromuscular effects, prevents insertion of
  insect stylets
• Flonicamid (nicotine-derived)
• antifeedant mode of action undetermined
• Clofentezine, Hexythiazox, Etoxazole
• mite growth inhibitor ovicide (kills eggs)
  apply early

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• Pyridazinones
• inhibits mitochondrial electron transport
• affects respiration
• like rotenone
• Acequinocyl
• inhibits mitochondrial electron transport
• affects respiration
• different site of action to other METI compounds
• Bifenazate (carbazate)
• related to carbamates
• neurotoxic but mechanism unknown