S2 L3 Insecticides - synthetic
Anna Drew
with slide contribution from Martin Wilks, Syngenta
Diane Alston & Joel Coats
World Insecticide Market
“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
• Although useful
– tends to accumulate in body fat
– not really excreted
– tended to build up in food chains
» eg birds -> 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
Lindane
• gamma hexa chloro
benzene
• benzene hexachloride
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still used in Sri Lanka
similar to DDT
more rapidly metabolised
less stable
• Other cycloalkanes:
• dieldrin
• aldrin
• [Methoxychlor]
• ORGANOPHOSPHATES
• Esters of phosphoric acid - examples:
eg diazinon
(orthothionphosphate)
eg chlorpyrifos
eg dichlorvos
(orthophosphate)
eg parathion
• Selection:
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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
– Self-poisoning – major public health problem
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
1176
111
9.4
TOTAL
Target site
• CARBAMATES
• Derivatives of carbamic acid – examples:
eg methomyl
eg aldicarb
eg carbaryl
eg propoxur
• 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
• SUBSTITUTED PHENOLS
Dinitroorthocresol
Dinocap
CH3CHC6H13
• 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
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 -> O forming much more active compounds
– mammals: esterase cleaves off ester group and compound is
much easier to excrete
• INSECT GROWTH REGULATORS
• Class: benzoylureas
» diflubenzuron, lufenuron, novaluron
» Cyromazine (triazine)
» Use: leafminers in vegetable crops & ornamentals
• Action: interfere with chitin synthesis
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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
• 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
• 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
• 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
• 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