Insecticides

definitions of pest and pesticide 

What is a pesticide?

• Any drug or mixture of substance which is intended for preventing, destroying, repelling or mitigating any pest

• Pesticides include nematicides, rodenticides, insecticides, herbicides and fungicides

• Not always very selective

What is a pest?

• Any species which has a harmful effect to humans: food, living conditions etc

• Destructive effects on food, crops, livestock

• Often species which evade natural enemies

• Often worse when non endemic

why do we need insecticides

• Population growth – more people to feed, clothe and house when we lose 1/5 of the worlds crops to pests

• Crop yield needs to increase, more natural fibres needed to be produced

• Most pesticides are not selectively toxic to invertebrates

Why do we need to understand the mode of action of these drugs?

• Protecting pollinators

• Use them safely

• Insects have good resistant mechanisms – genetics and fast reproduction time allow them to adapt many niches

• Pest management needs to be specific – applied at a specific time, specific compounds

characteristics of pests 

Characteristsic of pest species

• R selecting species

  • High growth rate

  • Parents can produce many offspring

  • Usually pests

• K selecting species

  • Low growth rate

  • Few offspring

  • Usually not pests

what is an outbreak 

• large sporadic populations of insect pests usually cause outbreaks

• an outbreak is when population level rises above equilibrium level

• E.g: armyworm on maize

causes of pest outbreaks

• monocultures – when one crop is grown over a large area of land which attracts pests

• highly nutritious crops

• also removes natural enemies when growing crops

• food is grown all year round

• were now reliant on these chemicals which leads to resistance

5 common scenarios which lead to these outbreaks

1. moved into a new environment —> for example due to climate change animals migrate to different environments

2. introduction from abroad

3. destruction of natural enemies —> insecticides take out their predators

4. development of resistance

5. higher quality standards —> we demand perfect fruits and vegetables which puts pressures on farmers

economic consequence of pests: injury vs damage 

Injury vs Damage

• injury is defined as the physical harm caused to a plant or destruction of a valued commodity caused by the presence or activity of a pest (E.g: feeding on leaves, feeding on blood etc)

• damage is the monetary value lost to the commodity as a result of injury by the pest (E.g: spoilage, reduction in yield, loss of quality etc)

• any level of pest infestation causes injury, but not all levels of injury cause damage à important to know when to intervene

economic injury

Economic injury level

• trying to control a population not eradicate it

• economic injury level is the pest density at which there is a greatest difference between the cost and the benefit of pest control

• ideally you want a large distance between these two curves

• EIL is the economic injury level

• Something becomes a pest when the equilibrium abundance is above the economic injury

  

• Something is not a pest is the equilibrium abundance is below the economic injury

 

why do we still use pesticides

Stakeholders in pest management

• Governments and funding agencies

• Research scientists

• Farmers and growers

• Commercial companies

Dependence on pesticides varies by crop and pest

• Some crops are entirely reliat on insecticide use

• Some crops produce similar yield but the quality fs lower

• Some have very marginal benefits

types of insecticides

• Varies between dusts, aerosols, bait, granules etc

• We can be more selective through the way that we apply these —> method of application can aid selective toxicity

• Often not pure, mixed with inert materials which change the physical and chemical properties of the compounds

• Need to protect the crop at all different levels, when its harvested, when its packaged etc

Insecticide uptake

• 3 main routes of entering the organism:

  • Permeating though the cuticle

  • Gas exchange

  • Direct ingestion of insecticides

Permeating the cuticle

• Insects have cuticle to waterproof —> keeps moisture in the body

• Epicuticle, exocuticle, endocuticle then epidermis

  • Epicuticle is external membrane

  • Exocuticle is lipophilic

  • Endocuticle is hydrophilic

• Carbaryl (topical insecticide) penetrates through insect cuticle of insect species at dif rates

• Some insects such as boll weevil and rice weevil have thick exocuticles

times to target the insect cuticle

• Hemimetabolous insects – likely that any drug will have the same level of permeability at all stages of its life cycle

• Holometabolous insects have different life stages where the degree of cuticle permeability varies

• Hemimetabolous insects go through nymphal stages where they grow and then form etc, but from hatching the cuticle is fully formed —> unlikely we can be time specific in developmental stages

• From an egg they go through larval stage, prepupateon stage and then pupateon stage, adulthood

• Insects have different structures, in larval stages have very thick endocuticle (water soluble) and thin exocuticle, in adulthood this switches —> can target different life stages.

Insecticide uptake

• 3 main routes of entering the organism:

  • Permeating though the cuticle

  • Gas exchange

  • Direct ingestion of insecticides

Gas exchange

• Trachea through abdomen and thorax which undergoes gas exchange

Direct ingestion

• Systemic ingestion

• Usually applied to the seeds and dispersed through the plant

• Can also be applied to the surface of the plant – sometimes can be washed off though

• Insects then consume the plant

insect diversity

• 29 insect orders

  • Coleoptera (beetles), diptera (flies), Hymenoptera (bees and wasps) and lepidoptera (moths)

grouping insecticides

Grouping insecticides

• Often grouped by chemical class, target site or mode of action

• Generally 4 ways in which insecticides act

  •  Modulate target site

  • Cause excitation

  • Blockage of membrane proteins

  • Inhibition

target the nervous system

• Toxicity is measured using LD50 à low LD50 is a very toxic drug

• Not all insect nervous systems are the same, both fly and cockroach have a brain structure, suboesophageal ganglion, The main difference is whether they have compound ganglion or thoracic ganglia and abdominal ganglia

• Insects with ganglia throughout have a greater surface area of nervous tissue to attack

• Mainly works by interrupting the electrical or chemical communication

Organochlorines - DDT

• DDT one of the first insecticides, now banned

• Targets voltage gated sodium channels in axons of neurons

• Modulates the sodium channels —> keeps the channel open so sodium fluxes in

• Highly hydrophobic —> penetrates through waxy cuticle as contact poison

• Little interaction with water, not hydrolysed, bioaccumulates in lipid tissues of high order animals

• Very stable

• LD50 is 250mg/kg for a rat

• Binds within the lipid membrane

• By sodium fluxing into the cell results in a slow long after potential, causes repeated action potentials —> leads to cell exhaustion

  

• We dot have a lipophilic membrane, so was deemed safe for humans, does cause issues when penetrated into the lipid membranes of tissues

• Mosquitos developed resistance

pyrethroids

• Similar in target site and mode of action, also keep sodium pores open

• LD50 is 1500mg/kg in rats, much less toxic drug for mammals

• 2 types of pyrethroids

  • Type 1: repetitive discharge (multiple spikes), slow after potentials (also found with DDT)

  • Type 2: no repetitive discharge, very slow after potential

• Pyrethroids have ester bonds which can be cleaved by hydrolysis, microorganisms can metabolise the products

• Main drugs used today

• Synthetic but based off pyrethrum produced by chrysanthemum flowers

phenylpyrazoles

• Small group of insecticides

• Target is GABA and glutamate-gated chloride channels, block GABA and glutamate binding

• Usually chloride influxes as negative ion, important for post-synaptic control, bringing cells back to resting potential

• When chloride can't move into the cell, sustained potential

• Selectively toxic as we only find glutamate gated chloride channels in invertebrates

• Figure shows the difference between a normal situation on the left with GABA returning to memb potentials, and then on the right when fipronil (phenylpyrazole) is added

neonicatnoids

• Nicotine is an alkaloid produced naturally by plants to deter herbivory

• Agonists of ach, bind to ach receptors

• More chemical than electrical intervention

• Causes sustained excitation of neurons and is not hydrolysed by acetylcholinesterase

organophosphates

• Dominant group in terms of number of compounds

• Derivatives of phosphoric acid, oxygen can be replaced by S, C and N to yield different derivatives

• Extremely toxic

• Targets acetylcholinesterase, inhibits action by phosphorylation

• Can be dephosphorylated by hydrolysis but can take days and weeks, so is classed as irreversible

non neurotoxic insecticides

• insect growth regulators 

• cuticle dehydrators 

Insect growth regulators

• Juvenoids are one type which mimic juvenile hormones

• Methoprene a type of juvenoid and is a mimic of juvenile hormone

• Can pause malting, cause early or late malting (E represents a malting stage on the figure)

• If timed properly, the insect will develop into an adult but will not be able to reproduce

• If we intervene with these malting stages the insect doesn’t develop properly __. Fly reproduce etc

• Slower approach than neurotoxins

non neurotoxic insecticides

• insect growth regulators 

• cuticle dehydrators 

Cuticle dehydrators

• Disrupts the lipid membrane of the insect, water passively leaves the body, insect dehydrates and dies

• E.g: diatomaceous earth, fossilised diatoms

• Safest for humans

combinations

Combinations

• When applying insecticides we aim to only expose insects to one at a time but in reality insects in their natural environments are exposed to a whole cocktail of naturally produced insecticides

insecticides in food chains

• Assumed safe for mammals as we don’t have a waxy cuticle

• Actually enters food chains – first noticed when there was a decrease in bird population

• Highly lipophilic, doesn’t biodegrade – half-life in soil between 3 and 10 years

• DDT applied to treat the insects which cause Dutch Elms disease

• Worms in soil passively accumulating in worms and in robins brain —> the concentration of DDT in the tissues of birds was higher than the concentration used to treat the insects

• 7000 fold increase in the bioaccumulation between mud sample (bottom of the food chain) and herring guls (top of the food chain)

• Even found in breast milk

• Modern drugs much more likely to be biodegraded by UV light

impact on birds

• However bird population is still declining

  • Even though a low concentration, these birds still exposed to modern drugs

  • The insects which the birds feed on are being killed —> no food source

• Turns out that egg shells were thinning – just a mother sitting on the egg could break the egg

• Turns out that DDT was causing egg shell thinning as it interfered with calcium transport in shell gland

• The amount of pigmentation in sparrowhawk eggs is also an indicator if insecticide contamination

• When concentrations of imidacloprid is high, we lose biodeiversity

modern insecticides

affect on bees

• 70% of crops depend on pollination

• Very reliant on crops to feed the increasing population

• Bees are very dependent on a range of plants to thrive

• Often bees are transported to monoculture fields to pollinate them but this places them under a lot of environmental stress (not diverse food source, placed in trucks and carted to different area, exposed to insecticides etc)

• Leads to a 30% decline in bee colonies

• Other effects of neonictanoids on bees:

neonictanoids

• Systemic drug – applied to the seeds but as the plant develiops is transported to al the tissues via the xyxlem

• End up in nectar and pollen

• Exposure level very low (1-5ppb)

•   Is water soluble

• As its present in root tissue makes its way into the environment

classical conditioning of bees

• Complex set of visual and olfactory cues produced by flowers that pollinators use to identify and discriminate flowers

• Can classically condition bees to remember certain odours and incentivise them to seek out these odours

  •  Conditioned stimulus: odour (what we want the bee to remember)

  • Unconditioned stimulus: reward

• Bees taste with their antenna and mouth parts which projects to the suboesophageal ganglion

• If the stimulus is sufficient it triggers a reflex called the proboscis extension reflex causing the bee to seek out this odour

• In the lab we touch the antenna with a sucrose solution whilst blowing the odour over the bee we can incentivise it to seek out this odour

• We can follow this up to a reward (sucrose) to classically condition the bee so that if they smell the odour they will taste the compound without the stimulus touch of the sucrose on the antenna

• However, neonicotinoids inhibit honeybees' ability to recall a learned association between nectar reward and floral scent.

where do neonictanoids target the bee brain

• Mushroom bodies house Kenyon cells which receive sensory information and converting it into learned memory (red parts are mushroom bodies)

• These cells are important for converting electrical signals into learned memories

• Cells are receptive to these insecticides (clothianodin) – if you expose them to insecticides, you increase the Kenyon cell membrane excitability

• Graph on the left shows that the cells respond to clothianodin (common insecticide in the US but sustained exposure prevents action potentials from occurring (shown on the right)

• Coumpahos (an organophosphate that inhibits AchE) shows a similar response but causes slower depolarisation initially. The action potentials then cease due to voltage gated Ca2+ and calcium activate dpotassium current in kenyon cells

• Suggest theres mechanisms in place to prevent cell death

• However, both of these drugs also have effects of redicung the cells responsiveness to their natural agonists

impact in immune function

• Clothianodin weakens honeybees' immune functions

• The innate immune system tries to encapsulate a foreign body so can illicit immune response by inserting a nylon rod into the insect body and measuring the effect in response to drugs

• Clothianodin decreases the insect's immune response (dose dependent effect)

• Deformed wing virus (caused by parasites) is more prevalent in insects exposed to clothianodin

• Bees actually prefer diets containing neonictanoid insecticides

response to food sources

• Honeybees gilius (taste structures) sensilla respond strongly to sucrose and to nicotine. Don’t respond more strongly when sucrose and nicotine present

• Suggests that they cant taste the drugs

• What is it that gives them this preference for this?

• Likely that theres pharmacological action on nicotinic ACh receptors in the brain

• Caffeine does however have a bitter taste and can be tasted by bees and is produced naturally by some plants as a deterrent

• as we increase caffeine concentration we increase the bees memory and ability to learn

• Caffeine increases Kenyon cell responsiveness to Ach

• This is because adenosine receptors are much more responsive to Ach when caffeine is also present —> more active cells allows them to form this association

• Could be that the insecticides are drugging the bees to come back to them