Definition of a Definition of a Pesticide Pesticide Any substance intended for preventing, destroying, repelling, or Any substance intended for preventing, destroying, repelling, or mitigating any pest mitigating any pest Insecticides Insecticides Herbicides Herbicides Fungicides Fungicides
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Definition of a Pesticide Any substance intended for preventing, destroying, repelling, or mitigating any pest Any substance intended for preventing, destroying,
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Definition of a PesticideDefinition of a Pesticide
Any substance intended for preventing, destroying, repelling, or mitigating Any substance intended for preventing, destroying, repelling, or mitigating any pestany pest
There is No Such Thing as a There is No Such Thing as a Completely SAFE PesticideCompletely SAFE Pesticide
• But Pesticides can be USED safely.But Pesticides can be USED safely.• All Pesticides have some type of All Pesticides have some type of
biological activitybiological activity• The trick is to balance efficacy and The trick is to balance efficacy and
safety. safety.
Pesticide RegulationsPesticide Regulations
Wiley or Sherman Act (1906)Wiley or Sherman Act (1906) Federal Food, Drug, and Cosmetic Act (1938)Federal Food, Drug, and Cosmetic Act (1938)
• Pesticide tolerances set in 1954 and 1958Pesticide tolerances set in 1954 and 1958• 1958: Delaney Act1958: Delaney Act
No additive is deemed safe if found to cause cancerNo additive is deemed safe if found to cause cancer• Pesticides were one type of additivePesticides were one type of additive
Federal Insecticide, Fungicide, and Rodenticide ActFederal Insecticide, Fungicide, and Rodenticide Act• 1947 (initially administered by USDA)1947 (initially administered by USDA)• 1972 (switch to EPA)1972 (switch to EPA)
Defines registration and labeling requirementsDefines registration and labeling requirements Can cancel registrationCan cancel registration Set tolerancesSet tolerances
~25 in use~25 in use Originally developed as fungicides (1930s)Originally developed as fungicides (1930s)
• CarbarylCarbaryl Physostigmine (alkaloid from Calabar Physostigmine (alkaloid from Calabar
bean)bean)
Interference With Neurotransmitter Interference With Neurotransmitter
(Acetylcholine) Function(Acetylcholine) Function
AcetylcholineAcetylcholine• Synthesized in neuron cell bodySynthesized in neuron cell body• Release triggered by an action potentialRelease triggered by an action potential
Sudden influx CaSudden influx Ca2+2+ ---> ACh release ---> ACh release
• Broken down by acetylcholinesteraseBroken down by acetylcholinesterase• Primary neurotransmitter in PNSPrimary neurotransmitter in PNS
Smooth and skeletal muscleSmooth and skeletal muscle
• CNS (distributed throughout)CNS (distributed throughout)• In the developing brain, every neuron In the developing brain, every neuron
expresses cholinesterase activity even if it expresses cholinesterase activity even if it isn’t cholinergic in adulthood. isn’t cholinergic in adulthood.
Leptophos, mipafox, chlorpyrifos, DFPLeptophos, mipafox, chlorpyrifos, DFP All organophosphates are required to be All organophosphates are required to be
tested for their ability to produce OPIDN tested for their ability to produce OPIDN before they are marketed (Hen test)before they are marketed (Hen test)
include pyrethrin I, include pyrethrin I, pyrethrin II, jasmolin pyrethrin II, jasmolin I, jasmolin II, cinerin I I, jasmolin II, cinerin I and cinerin II.3 and cinerin II.3
PyrethroidsPyrethroids• Synthetic insecticidesSynthetic insecticides• Slightly more Slightly more
PyrethroidsPyrethroids Natural pyrethrins are light sensitive and undergo rapid Natural pyrethrins are light sensitive and undergo rapid
photodegradation photodegradation Pyrethroids that contain a cyano substituent at the Pyrethroids that contain a cyano substituent at the
alpha-carbon of the phenoxy-benzyl moiety have been alpha-carbon of the phenoxy-benzyl moiety have been classified as type II; pyrethroids which lack this alpha classified as type II; pyrethroids which lack this alpha cyano moiety as type Icyano moiety as type I• Type I (T syndrome): Type I (T syndrome): TremorsTremors, tachypnea, "running fits," , tachypnea, "running fits,"
hyperthermia, and salivation within 1-2 hours of injectionhyperthermia, and salivation within 1-2 hours of injection AllethrinAllethrin Pyrethrin IPyrethrin I ResmethrinResmethrin TetramethrinTetramethrin
• Type II (CS syndrome): Whole body tremors, Type II (CS syndrome): Whole body tremors, hypersensitivity, occasional running fits, hypersensitivity, occasional running fits, choreoathetosischoreoathetosis (sinuous writhing), hypothermia, and generalized (sinuous writhing), hypothermia, and generalized seizuresseizures
Mode of Action Mode of Action (Overstimulation of the Nervous System)(Overstimulation of the Nervous System)
Interference with voltage gated Interference with voltage gated sodium channels.sodium channels.• Type I keep channels open for Type I keep channels open for
shorter period vs. Type IIshorter period vs. Type II• Enhanced sodium ion conductanceEnhanced sodium ion conductance
““Mectins” (Nicotinic receptor agonists, Mectins” (Nicotinic receptor agonists, specific for non-mammalian receptors)specific for non-mammalian receptors)• AvermectinAvermectin• IvermectinIvermectin
Anthelmentic, insecticideAnthelmentic, insecticide Management of river blindness (Onchocerca)Management of river blindness (Onchocerca) Low dermal absorptionLow dermal absorption Minimal biotransformationMinimal biotransformation
Final ThoughtsFinal Thoughts
Most of what has been presented Most of what has been presented relates to acute toxicology.relates to acute toxicology.
What about long term effects of low What about long term effects of low level exposure to pesticides?level exposure to pesticides?
What about effects on the developing What about effects on the developing nervous system?nervous system?