Pesticides: Types and Modes of Action ENY 3225 or ENY 5226

Learning Objectives Learn and internalize definitions Be able to list the steps for each mode of action for the pesticide groups presented Familiarize yourself with the various products and which class of insecticide they belong to

Insecticide Any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating insects. Often associated with skin irritation

Vocabulary Acetylcholine (ACh). An acetic acid ester of choline-a substance that functions as a neurotransmitter. Acetylcholinesterase. An enzyme in the membrane of postsynaptic cells that catalyzes the conversion of ACh into choline and acetic acid. This enzymatic reaction inactivates the neurotransmitter. Cholinergic. Denoting nerve endings that liberate acetylcholine as a neurotransmitter, such as those of the parasympathetic system. http://www.mhhe.com/biosci/abio/glossary.mhtml

Vocabulary GABA Gamma-aminobutyric acid; believed to function as an inhibitory neurotransmitter in the central nervous system. GABA agonist. Chemical that binds to and activates GABA receptors GABAergic. GABA Antagonists: chemicals that bind to but do not activate GAMMA-AMINOBUTYRIC ACID receptors, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID or GAMMA-AMINOBUTYRIC ACID agonists. Suffix “-ergic” is used to describe the type of neurotransmitter a neuron releases

Vocabulary Enzyme. A protein catalyst that increases the rate of specific chemical reactions.

Types of Pesticides Insecticide -- kills insects Herbicide -- kills weeds Fungicide -- kills fungi Nematicide -- kills nematodes Rodenticide -- kills rodents Pisicide -- kills fish

Other pesticide terms Ovicide -- kills eggs Larvicide -- kills larvae Adulticide -- kill adults Insect growth regulator -- disrupts normal growth and development of insects Dessicants -- cause insect death by dehydration Repellents -- repel insects and other arthropods Attractants -- attract insects and vertebrates Synergists -- chemicals used to enhance the insecticidal activity of other chemicals piperonyl butoxide MGK 264

Pesticide terms for route of entry Stomach poison -- enter orally usually in a food material Insect baits -- composed of attractive food and a toxicant Dusts -- applied to surfaces pests contact, pest crawls through residue, grooming results in ingestion Liquid baits -- boric acid and some rodenticides are water soluble and can be put in water sources of pests

Pesticide terms for route of entry Contact poisons -- enter through cuticle of insects most pesticides are contact poisons most are lipophilic and enter the insect through the cuticular waxes and oils Fumigants -- vapors enter the insect through the spiracles during respiration are true gases at room temperature methyl bromide, sulfuryl fluoride, paradichlorobenzene, napthalene are true fumigants

Insecticides in UPM Inorganics Botanicals Synthetic Organics “Natural” Ex. Bora-Care, Disodium Octaborate Tetrahydrate Botanicals Ex. Pyrethrum Synthetic Organics Ex. Pyrethroids “Natural” Ex. Avermectins

Modes of Action of Insecticides Nervous System Water Balance Energy Production Cuticle Production Endocrine System

Nervous System Lethal spasms and seizures Insects flip on back Legs wiggle uncontrollably

Insecticides that Affect the Nervous System Sodium Channel DDT Pyrethroids permethrin deltamethrin

Pyrethrins and Pyrethroids Pyrethrum -- dust derived from ground chrysanthemum flowers Pyrethrins -- chemicals within pyrethrum that have insecticidal properties

Pyrethrins and Pyrethroids Pyrethroids -- synthetically produced chemicals with similar chemistry and mode of action as pyrethrins, axonic poisons Type I Short residual, Fast flushing, and Quick knockdown, Negative temperature correlation: more effective at low temps Ex.: Allethrin, d-phenothrin, resemethrin Type II Long residual, Slower flushing, and Slower knockdown, Better killing power than type 1 Positive temperature correlation Ex.: Permethrin, cypermethrin, cyfluthrin, lambdacyhalothrin Synergists -- used to deactivate mixed function oxidases (MFOs) within insects

Pyrethroids Permethrin Deltamethrin Bifenthrin

Talstar PL Granular: bifenthrin Unique sand core granular Provides a 2 to 4 month residual, supplying effective, long-term protection. Penetrates mulch and grass, with no watering needed. No odor Low application rates

Pyrethroids Effects Action on Human System - Irritant Systemic Effects - Minimal Irritation Effects - Stinging, burning, itching, tingling, numbness of skin.

MOA: Pyrethroids Axonic poisons Bind to a protein called the voltage-gated sodium channel Normally, the sodium channel opens, causing stimulation of the nerve and closes to end the nerve signal Pyrethroids find to the socium channel and prevent it from closing normally Result: continuous nerve stimulation Symptoms: Tremors, uncoordinated movement From Valles and Koehler. 1998. Insecticides Used in the Urban Environment: Mode of Action. ENY-282

Nerves and Pyrethroids Repeated nerve firing Sodium Channels Direction of Nerve Impulse

Nervous System Why does this happen? Let’s look at a “normal” nerve impulse.

“Diagram of a neuron illustrating the subcellular locations of voltage-gated sodium channels.” #5. Presynaptic #7. Postsynaptic #6. Apical dendrites #4. Myelinated U of Colorado Health Science #3. Unmyelinated

Axon Membrane at Rest “Leaky membrane” K+: many leaky channels Na-: few leaky channels Outside: >Na- Inside: > K+ Rensselar Polytechnic Institute

Axon Membrane An action potential is initiated whenever there is a stimulus. A stimulus is an event that causes depolarization or decrease in the membrane potential Rensselar Polytechnic Institute

Axon Membrane Opening of external Na gates Results in influx of Na

Axon Membrane Eventually reach Na equilibrium

Axon Membrane As a result of the depolarization, the internal Na+ gates shut and remain closed for about ½ millisecond. The rapid decrease causes the membrane potential to return to the K equilibrium potential.

Pyrethroid Kill Fast action -- 30 minutes to kill Excessive nerve firing --spasms

Pyrethrins and Pyrethroid Labels Demon WP Demand CS Talstar G Dragnet Deltadust

Insecticides that Affect the Nervous System Acetyl- cholinesterase Sodium Channel Carbamates Phosphates DDT Pyrethroids permethrin deltamethrin chlorpyrifos malathion diazinon propoxur carbaryl

MOA: Carbamates and OPs Synaptic poisons Carbamates and organophosphorus insecticides bind to an enzyme called acetylcholinesterase (AChE) AChE is found at the nerve synapse AChE is designed to stop a nerve impulse after it has crossed the synapse From Valles and Koehler. 1998. Insecticides Used in the Urban Environment: Mode of Action. ENY-282

MOA: Carbamates and OPs OPs and carbamates bind to AChE This prevents AChE from working (i.e., breaking down Ach) Therefore, nerve impulses continue to fire across the synapse Symptoms similar to pyrethroid poisoning—tremors and uncontrolled movement From Valles and Koehler. 1998. Insecticides Used in the Urban Environment: Mode of Action. ENY-282

Cholinesterase Inhibitors Organophosphates Carbamates Causes repeated nerve firing

Organophosphate Effects Action on Human System - Inhibits acetylcholinesterase enzyme in tissues. Systemic Effects - Headache, dizziness, weakness, shaking, nausea, stomach cramps, diarrhea, sweating. Irritation Effects - Minimal rashes, but readily absorbed through the skin. Delayed/Allergic Effects - Loss of appetite, weakness, weight loss, and general feeling of sickness. Occasionally permanent harm to brain and nervous system. Irreversible inhibition of AChE

N-Methyl Carbamates Effects Action on Human System - Reversible changes in acetylcholinesterase enzyme in tissues. Systemic Effects - Headache, dizziness, weakness, shaking, nausea, stomach cramps, diarrhea, sweating. Irritation Effects - Minimal rashes, but readily absorbed through the skin. Delayed/Allergic Effects - Loss of appetite, weakness, weight loss, and general feeling of sickness. Reversible inhibition of AChE

Organophosphates and Carbamates Chlorpyrifos* Diazinon* Trichlorfon* Parathion* Carbamates Carbaryl (Sevin) Propoxur (Baygon)* Chemicals which are derived from phosphoric and carbamic acid and bond with cholinesterase Acute toxicity Not persistent Hyper-excitation Insect flips on back with legs twitching Sulfur in formulation often causes strong odor *EPA hit list or not common in UPM

Organophosphates O -- H H -- O -- P Phosphoric Acid O O -- R’ R -- O -- P O O -- R’ S -- R” Phosphorothioate H -- O -- P O -- H Phosphoric Acid Chlorpyrifos ((Dursban)

Carbamates O CH3 -- N -- C O -- H Carbamic Acid O -- R Carbaryl (Sevin)

Dursban Kill Vomit and excretion in 8 hours Death in 9 hours

Dursban: Chlorpyrifos Proven Residual Control Effective control makes it the perfect product for maintenance accounts. Ability to provide control for several weeks, keeps customers protected between treatments. Broad Label for Varied Applications Broad labeling allows use for almost any application indoors or out. Designed to be used in homes and apartments, hospitals, stores, manufacturing plants and warehouses.

Organophosphate and Carbamate Labels Dursban Pro Dursban TC Diazinon G

Insecticides that Affect the Nervous System Sodium Channel Acetyl-cholinesterase Acetylcholine receptor Carbamates Phosphates DDT Pyrethroids Neonicotinoids permethrin deltamethrin Spinosyns chlorpyrifos malathion diazinon imidacloprid thiamethoxam propoxur carbaryl

Acetylcholine Receptor Mimics acetylcholine on the receptor Nicotinic receptor is a type of ACh receptor that is sensitive to nicotine Cannot be broken down by AChE Imidacloprid turns nerve impulse on but AChE does not degrade it Similar overstimulation as seen with OPs and Carbs

Neonicotinoids Imidacloprid (subgroup: pyridylmethylamine) Advantage – pet treatment Merit -- turf ornamentals Water soluble Systemic in plants Premise – termites Affects insects first by paralyzing mouthparts Bayer Advantage OTC Thiamethoxam (subgroup: nitroguanidine) Used in crops Working on urban and landscape/turf/ornamentals label (Subgroup: nitromethylene)

Premise: Imidacloprid No odor Not repellent to termites Low risk to your family, your pets, your home Premise causes a range of effects: Pests stop feeding Premise Plus Nature™. This phenomenon makes termites susceptible to infection by naturally occurring organisms. Lateral Soil Movement causes spread to ensure thorough soil coverage

Neonictinoid Labels Premise Advantage Bayer Advantage

Spinosyns Saccharopolyspora spinosa fermetation product Soil dwelling Success*, Naturalyte*, Tracer* (Dow AgroSciences) Testing for UPM

Insecticides that Affect the Nervous System Sodium Channel GABA Receptor Cholinesterase Acetylcholine receptor Carbamates Phosphates DDT Pyrethroids Cyclodienes Phenyl pyrazoles Neonicotinoids permethrin deltamethrin Spinosyns chlorpyrifos malathion diazinon chlordane heptachlor imidacloprid thiamethoxam fipronil propoxur carbaryl

MOA: GABA Antagonist Phenylpyrazole (fipronil), cyclodienes Antagonists of GABA activated chloride channels GABA Antagonists: chemicals that bind to but do not activate GAMMA-AMINOBUTYRIC ACID receptors, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID or GAMMA-AMINOBUTYRIC ACID agonists. GABA can’t bind to receptor Doesn’t activate channel (doesn’t open) Interferes with (prevents) the passage of chlorine ions through the channel. Concerns with cross resistance with other GABAergic insecticides

GABA Receptor in Central Nervous System Phenylpyrazoles or Fiproles GABA GABA receptor Chloride ions Fipronil GABA GABA-receptors

Phenyl pyrazoles Most lipophilic insecticide ever discovered Fipronil Chipco Choice -- mole crickets & grubs Firestar, Ouver-N-Out, (Ceasefire)--fireants Termidor -- termites Regent -- corn Frontline -- flea & tick MaxForce FC -- cockroaches and ants Most lipophilic insecticide ever discovered Persistent in soil Spread among social insects on bodies 4 months of residual on dogs (binds to oils in sebaceous glands)

MaxForce FC kill Loss of muscle control at 17 hours Death at about 20 hours

MaxForce FC: Fipronil Unique mode of action: long-term control faster results than other ant and cockroach bait products Fipronil is a highly active, broad-spectrum insecticide from the phenyl pyrazole family discovered in 1987 low doses highly effective against a broad range of insect pests, including ants and roaches

Phenyl Pyrazole Labels MaxForce FC Bait Stations Termidor

Insecticides that Affect the Nervous System Sodium Channel GABA Receptor Cholinesterase Carbamates Phosphates Avermectins DDT Pyrethroids Cyclodienes permethrin deltamethrin abamectin Phenylpyrazoles chlorpyrifos malathion diazinon chlordane heptachlor fipronil propoxur carbaryl

MOA: GABA Agonist Avermectins Bind to GABA (Gamma-Amino-Butyric Acid gated chloride channel Opens channel Chloride influx Cannot reach threshold for action potential Causes membrane to hyperpolarize, making it less excitatory, decreasing nerve transmission Result: flaccid paralysis and death

Avermectins Abamectin Avert -- cockroaches Advance -- ants Produced from soil microbials. Stomach poison for ants and cockroaches slow acting low toxicity to mammals

Avert Kill 22 hours to nerve effects 40 hours to kill

Avert and Advance Attractive, long-lasting bait formulations Highly effective active ingredient

Abamectin Labels Avert Advance Raid cockroach bait (class)

Chlordane kill 15 hours to loss of muscle control 33 hours to kill

Modes of Action of Insecticides Nervous System Water Balance Energy Production Cuticle Production Endocrine System