# Insecticide Mode of Action — Quick Reference Compendium
## Extracted from Dr. Michael Scharf's GTBOP Presentation (October 18, 2017)

**Prepared by:** Rich Braman, UGA Cooperative Extension / Center for Urban Agriculture
**For:** Dr. Dan Suiter & Dr. Michael Scharf — Bulletin revision reference
**Source:** GTBOP_ProseTranscript_2017-10-18_InsecticideMOA.md

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## Purpose

This document consolidates every insecticide class, target site, product name, and relationship mentioned in Dr. Scharf's presentation into reference tables. These can serve as:

- Quick-check references during the writing process
- Source material for bulletin tables and figures
- Verification that all content is accounted for in the revised bulletin

All content below is derived exclusively from the presentation transcript. Items marked with ⚠️ may benefit from updating with current information.

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## TABLE 1: Master Classification — All Nine Insecticide Classes

### Neurotoxic Insecticides (5 classes)

| # | Class | Target Site | Location on Neuron | Mode of Action | Effect on Insect | Representative Products |
|---|-------|-------------|-------------------|----------------|-----------------|------------------------|
| 1 | Pyrethroids / Pyrethrins / DDT | Sodium channels | Axon | Stimulation (modulation) | Excitation → knockdown, incoordination | Pyrethroids (various), pyrethrins |
| 2a | Oxadiazines | Sodium channels | Axon | Blockage | Inhibition → paralysis ("on switch stuck off") | Indoxacarb |
| 2b | Semicarbazones | Sodium channels | Axon | Blockage | Inhibition → paralysis | Metaflumizone |
| 3a | Phenylpyrazoles | Chloride channels (GABA receptor) | Post-synaptic | Blockage | Excitation (blocks mellowing effect) | Fipronil |
| 3b | Isoxazolines | Chloride channels | Post-synaptic | Blockage | Excitation | Fluralaner, sarolaner |
| 3c | Avermectins | Chloride channels (glutamate receptor) | Post-synaptic | Stimulation | Inhibition → paralysis (opposite of fipronil) | Abamectin |
| 4a | Neonicotinoids / Nicotinoids | Acetylcholine receptor | Post-synaptic (synapse) | Stimulation | Excitation | Imidacloprid (nicotinoid), clothianidin (neonicotinoid) |
| 4b | Sulfoximines | Acetylcholine receptor | Post-synaptic (synapse) | Stimulation | Excitation | Sulfoxaflor |
| 4c | Spinosyns | Acetylcholine receptor | Post-synaptic (synapse) | Stimulation | Excitation | Spinosad |
| 5 | Organophosphates / Carbamates | Acetylcholinesterase enzyme | Synapse | Inhibition | Excitation (ACh accumulates) | Various ⚠️ |

### Non-Neurotoxic Insecticides (4 classes)

| # | Class | Target Site | Mode of Action | Effect on Insect | Representative Products |
|---|-------|-------------|----------------|-----------------|------------------------|
| 6 | Diamides | Neuromuscular calcium channels | Stimulation | Contraction → energy depletion → paralysis → death | Chlorantraniliprole, cyantraniliprole |
| 7a | Juvenile hormone analogs (IGR) | Hormonal regulation of molting | Mimicry | Cuticle deformation, extra juvenile stages, population crash | Pyriproxyfen |
| 7b | Chitin synthesis inhibitors (IGR) | Chitin synthesis enzyme | Inhibition | Death during molting; "jackknife effect" in termites | Various ⚠️ |
| 8 | Mitochondrial respiration inhibitors | Mitochondria (respiratory chain) | Inhibition | Energy production failure → death | Hydramethylnon, chlorfenapyr, sulfuryl fluoride, methyl bromide ⚠️, DSOBTH, boric acid |
| 9 | Cuticle dehydrating dusts | Epicuticular wax layer | Physical abrasion | Water loss → dehydration → death | Silica gel, diatomaceous earth |

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## TABLE 2: Four Basic Modes of Action

| Mode of Action | What It Does | Example Target | Example Insecticide Class |
|----------------|-------------|----------------|--------------------------|
| **Stimulation** | Causes target to become more active | Sodium channels → fire more | Pyrethroids |
| **Blockage** | Shuts target off | Sodium channels → can't fire | Indoxacarb |
| **Modulation** | Subtly changes target shape/function | Sodium channel conformation | Pyrethroids (also modulators) |
| **Inhibition** | Prevents an enzyme from functioning | Acetylcholinesterase → can't degrade ACh | Organophosphates, carbamates |

*Note: Scharf emphasized that ALL insecticide effects can be categorized into just these four types.*

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## TABLE 3: Target Sites on the Neuron — Spatial Relationships

| Location | Structure | Natural Function | Insecticides Targeting It |
|----------|-----------|-----------------|--------------------------|
| **Axon** (long body of nerve) | Sodium channels | "On switch" — opening initiates nerve impulse | Pyrethroids, pyrethrins, DDT (stimulate); Indoxacarb, metaflumizone (block) |
| **Post-synaptic membrane** | GABA-gated chloride channels | "Mellowing" — negative chloride dampens activity | Fipronil, isoxazolines (block → excitation) |
| **Post-synaptic membrane** | Glutamate-gated chloride channels | "Mellowing" — inhibitory | Avermectins/abamectin (stimulate → paralysis) |
| **Post-synaptic membrane** | Acetylcholine receptors (nAChR) | Carry signal across synapse (sodium channel) | Neonicotinoids, sulfoximines, spinosyns (stimulate) |
| **Synapse** | Acetylcholinesterase enzyme | Breaks down ACh after signal transmission | Organophosphates, carbamates (inhibit) |
| **Neuromuscular junction** | Calcium channels | Trigger muscle contraction | Diamides (stimulate → sustained contraction) |

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## TABLE 4: Products and Active Ingredients Mentioned

| Active Ingredient / Product | Chemical Class | Target Site | Primary Use Mentioned | Notes |
|----------------------------|---------------|-------------|----------------------|-------|
| Pyrethrins | Natural pyrethroid | Sodium channels | General knockdown | Rapid knockdown; repellent |
| Pyrethroids (various) | Synthetic pyrethroids | Sodium channels | General pest control | "Like pepper spray" — highly repellent; widespread bedbug resistance |
| DDT | Organochlorine | Sodium channels | Historical reference | Same target site as pyrethroids |
| Indoxacarb | Oxadiazine | Sodium channels (blocker) | Urban pest control | "Really big urban insecticide" |
| Metaflumizone | Semicarbazone | Sodium channels (blocker) | Ectoparasites; possible urban | Newer product at time of presentation |
| Fipronil | Phenylpyrazole | Chloride channels (blocker) | Urban pest control | Off-patent; consumer products available; "one of our biggest" |
| Fluralaner | Isoxazoline | Chloride channels | Veterinary/pet (fleas) | Cross-resistance potential with fipronil |
| Sarolaner | Isoxazoline | Chloride channels | Veterinary/pet (fleas) | Cross-resistance potential with fipronil |
| Abamectin | Avermectin | Chloride channels (stimulator) | Gel baits | Opposite effect from fipronil despite similar target |
| Imidacloprid | Nicotinoid | Acetylcholine receptor | Various | Example of "nicotinoid" (looks more like nicotine) |
| Clothianidin | Neonicotinoid | Acetylcholine receptor | Various | Example of "neonicotinoid" (structurally evolved from nicotine) |
| Sulfoxaflor | Sulfoximine | Acetylcholine receptor | Newer product | New class at same target site as neonics |
| Spinosad | Spinosyn | Acetylcholine receptor | Landscape market | Same target site as neonics |
| Nicotine | Natural alkaloid | Acetylcholine receptor | Historical (tobacco) | The original — toxic to insects and mammals |
| Organophosphates (various) | Organophosphate | Acetylcholinesterase | Declining urban use | Not insect-specific; heavy restrictions |
| Carbamates (various) | Carbamate | Acetylcholinesterase | Declining urban use | Not insect-specific; heavy restrictions |
| Chlorantraniliprole | Diamide | Calcium channels (muscle) | Various | No signal word required by EPA; manufacturers added "Caution" |
| Cyantraniliprole | Diamide | Calcium channels (muscle) | Various | Newer diamide |
| Pyriproxyfen | Juvenile hormone analog | Hormonal (IGR) | Cockroach control | Wing twist indicator in cockroaches |
| Hydramethylnon | Amidinohydrazone | Mitochondria | Cockroach bait | Energy production inhibitor |
| Chlorfenapyr | Pyrrole | Mitochondria | Various (has food label) | Relatively safe; resistance potential noted |
| Sulfuryl fluoride | Inorganic fluoride | Mitochondria | Fumigation | |
| Methyl bromide | Halogenated hydrocarbon | Mitochondria | Fumigation | ⚠️ Largely phased out |
| DSOBTH | Borate | Mitochondria/respiration | Wood treatment | Disodium octaborate tetrahydrate |
| Boric acid | Borate | Mitochondria + gut lining | Various | Dual mode: chemical (respiration) + physical (abrasive/desiccant) |
| Silica gel | Inorganic dust | Epicuticular wax | Dust application | Physical mode — abrades waxy layer |
| Diatomaceous earth | Inorganic dust (biogenic) | Epicuticular wax | Dust application | Silicon from ground diatom exoskeletons |

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## TABLE 5: Combination Products

| Component 1 | Component 2 | Mechanism | Notes |
|------------|------------|-----------|-------|
| Neonicotinoid (acetylcholine receptor) | Pyrethroid (sodium channels) | Potentiation — two target sites simultaneously; "1+1=3" synergy | "All start with tea"; dual resistance observed in roach populations; still require rotation |

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## TABLE 6: Insect-Specificity Spectrum

| Insecticide Class | Mammalian Safety | Notes |
|-------------------|-----------------|-------|
| **Diamides** | Extremely high | No signal word required by EPA; 10,000+ x selectivity |
| **Avermectins** | High | Insect-specific target |
| **Isoxazolines** | High | Primarily vet/pet products |
| **IGRs (JH analogs, CSIs)** | High | Target insect-specific developmental processes |
| **Neonicotinoids** | Moderate-High | Insect-specific receptor but systemic/pollinator concerns |
| **Fipronil** | Moderate-High | GABA receptor differences provide selectivity |
| **Pyrethroids** | Moderate | Generally safe for mammals but repellent to insects |
| **Organophosphates / Carbamates** | **Low** | **Not insect-specific; work against mammals equally** |

*Spectrum based on Scharf's characterizations in the presentation. Not a quantitative ranking.*

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## TABLE 7: Practical Field Indicators Mentioned

| What You See | What It Means | Relevant Product/Class |
|-------------|--------------|----------------------|
| Immediate knockdown/incoordination | Sodium channel excitation | Pyrethroids, pyrethrins |
| Paralysis (insect immobile but alive) | Sodium channel blockage OR chloride stimulation | Indoxacarb, abamectin |
| Wing twist in cockroach nymphs/adults | Juvenile hormone disruption | Pyriproxyfen (JH analog IGR) |
| "Jackknife" body curl in termites | Malformed cuticle from chitin synthesis disruption | Chitin synthesis inhibitors |
| Lethargy and desiccation | Epicuticular wax loss | Silica gel, diatomaceous earth |
| Sustained muscle contraction → stillness | Calcium channel stimulation → energy depletion | Diamides (chlorantraniliprole, cyantraniliprole) |

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## TABLE 8: Key Physiological Barriers to Insecticide Penetration

| Barrier | Location | Challenge for Insecticide | Relevant Formulation Strategy |
|---------|----------|--------------------------|------------------------------|
| Cuticle | External body surface | Multi-layered; waterproof; waxy epicuticle | Contact formulations must penetrate all layers |
| Gut lining | Digestive tract interior | The "tube" inside is technically external to the body | Baits must cross gut wall to reach internal targets |
| Tracheal system | Throughout body | Physical tubes, not blood-carried oxygen | Fumigants exploit this unique insect anatomy |

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## TABLE 9: Key Terminology and Definitions from Presentation

| Term | Definition (as explained by Scharf) |
|------|--------------------------------------|
| **LD50** | Lethal dose that kills 50% of test population; inverse relationship with toxicity (lower LD50 = more toxic) |
| **Mode of action** | The action of an insecticide at its target site (stimulation, blockage, modulation, or inhibition) |
| **Target site** | The specific protein or physiological location within the insect where an insecticide acts |
| **Signal word** | EPA-required label indicator of acute toxicity (Danger, Warning, Caution); diamides so safe none was required |
| **Potentiation** | Synergistic effect from hitting two target sites simultaneously; "one plus one equals three" |
| **Trophallaxis** | Food sharing among social insects (from mouth and anus); insecticide transfer mechanism |
| **Allogrooming** | Mutual grooming among social insects; insecticide transfer mechanism |
| **Secondary kill** | Death of an individual from consuming insecticide-contaminated feces or carcass of a treated individual |
| **Tertiary kill** | Death of a third individual from insecticide passed through two prior digestive tracts |
| **IRAC** | Insecticide Resistance Action Committee; industry body that classifies MOAs and publishes rotation guidance |
| **Wing twist** | Visible cuticle deformation in cockroaches exposed to juvenile hormone analog IGRs; field diagnostic indicator |
| **Jackknife effect** | Body curling in termites with malformed cuticle from chitin synthesis inhibitor exposure |
| **Epicuticle** | Outermost waxy/oily layer of insect cuticle; target of dehydrating dusts |
| **Synapse** | Gap between neurons where electrical signals convert to chemical (neurotransmitter) signals |
| **Acetylcholine** | Primary neurotransmitter that crosses synapses in the insect nervous system |
| **GABA receptor** | Chloride channel type at post-synaptic membrane; target of fipronil |
| **Glutamate receptor** | Chloride channel type; target of avermectins |

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## Cross-Reference: Same Target Site, Different Effects

One of the presentation's key teaching points was that different insecticide classes can target the same site but have opposite effects:

| Target Site | Insecticide A | Effect A | Insecticide B | Effect B |
|------------|--------------|---------|--------------|---------|
| Sodium channels | Pyrethroids | Stimulation → excitation | Indoxacarb | Blockage → paralysis |
| Chloride channels | Fipronil | Blockage → excitation | Abamectin | Stimulation → paralysis |

*This contrast is valuable for teaching and for resistance management — switching between classes at the same site may still provide different selection pressures.*

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*All data extracted exclusively from the October 18, 2017 GTBOP presentation by Dr. Michael Scharf as transcribed and corrected through the GTBOP archive pipeline. Items marked ⚠️ may have changed since the presentation date.*