Pyrethroids are synthetic pesticides derived from natural pyrethrins produced by chrysanthemum flowers. They are designed to be more toxic to insects and less degradable than pyrethrins. Pyrethroids come in Type I and Type II variants, with Type II having enhanced toxicity due to cyano groups. They are absorbed through ingestion, inhalation, and dermal contact. Pyrethroids act by altering sodium and chloride channel function in nerves, causing hyperexcitability. They are metabolized in the liver but their lipophilicity allows accumulation in fat tissues. Their mechanism of toxicity involves prolonged nerve and muscle stimulation.

1. Pyrethroids
+
=
Piperonyl butoxide

2. Pyrethroids
• Derived from pyrethrins; natural
compounds produced by
chrysanthemum flowers (C.
cinerariaefolium and C. cineum
• Pyrethrins will paralyze insect;
animal will recover (enzyme
detoxification)
• Pyrethroids are synthetic esters
derived from pyrethrins;
engineered for insect death,
“knockdown” effect
• Synthetic modifications (addition
of synergists) make these
compounds more toxic to
organisms, less degradable in
environment

3. Pyrethroid
Structures
• Pyrethrins are esters of
chrysanthemic (I) or
pyrethric (II) acid; have
been synthetically modified
into complex mixture of
isomers
• Type 1 and 2 pyrethroids
• Very lipophillic, low water
solubility
• Structure of compound (I
or II) has different effects
and associated poisoning
symptoms
• Isomerism around the
cyclopropane ring greatly
influences toxicity
All pyrethroids have an acid moiety, a
central ester bond, and an alcohol moiety
Permethrin

4. • Pyrethroids are synthetic
analogs of pyrethrins, made to
last longer and be more toxic
to insects.
– Type I – shorter duration of
effects
– Type II – longer acting,
enhanced by addition of
cyano group
• Type I - pesticides
Pyrethrins,bioallethrin,cismethrin
Type I -
poisonings
•Severe fine tremor
• Marked reflex
hyperexcitability
• Sympathetic
activation
• Paresthesia
(dermal exposure)

5. • Type II (cyano) - pesticides
• fenvalerate
• cyhalothrin
• deltamethrin
• cypermethrin
Type II - poisonings
• Profuse watery salivation
• Coarse tremor
• Sympathetic activation
• Choreoathetosis
• Seizures (dermal exposure)

6. Uses of pyrethroid
• Domestic – e.g. bug bombs, mosquito nets,
insect sprays
• Medical - e.g. treatment of scabies and lice
• Commercial – e.g. insecticide for agriculture
• Veterinary – e.g. pet shampoos, fleas

8. Mode of entry into
aquatic
environment
• Spray drift; pyrethroids often applied
aerially and can contaminate nearby
waters
• Runoff from fields, wastewater from
manufacturing facilities

9. Mode of Entry into Organisms
• Rapidly absorbed to particulate matter in water due to
high lipophillicity/low solubility
• Half life for pyrethroids in aquatic medium has been
reported between 19 hours
• Most pyrethroid half lives in water range from 1-2 days
• Its speciation varies greatly with compound’s
structure, exposure to sunlight, and pH, temperature,
and salinity of water medium
• Since pyrethroids are highly lipophillic, will readily be
absorbed through the gills of aquatic animals
• In mammals, toxicity occurs when ingested, not readily
absorbed through skin

10. • Absorption:
– GI: moderate
– Respiratory Tract: moderate
– Dermal: poor
• Usually metabolized quickly by the liver
• Excreted primarily in urine, less in feces
• Half life – usually 5-20 hours, can be days
• Often combined with synergist (e.g. piperonyl) to
enhance killing power & slow degradation
• Lipophilic, may concentrate in fat tissues

11. Mechanism of Action
Acts primarily on voltage dependent sodium channels
leading to hyperexcitable state, also affects chloride
channels to increase excitability
• Increases adrenal activation – increasing adrenaline
• Duration of effect is determined by the structure of the
offending pyrethroid

12. Mode of Toxic Interaction:
Neurotoxicity
• Acute neurotoxicity is caused by binding to sodium
channels--> slows down its activation and
inactivation properties which leads to a
hyperexcitable state
• A normal action potential is converted into double or
continuous discharges in nerve and muscle
• Current duration dependant on pyrethroid structure;
action stereospecific
• Insect sodium channels 100x more susceptible than
mammals

13. Other Toxic Interactions
• Most pyrethroids stimulate protein kinase C-
dependant protein phosphorylation (channel activity
modulated by phosphorylation state)
• Antagonism of GABA-mediated inhibition (seizures)
• Enhancement of noradrenalin release
• Direct actions on calcium or chloride ion channels
(type II only)
• Type II pyrethroids produce a more complex poisoning
syndrome and act on wider range of tissues

14. Metabolism and Breakdown
• Biological activity destroyed by ester hydrolysis,
major route, creates oxidative metabolites
• Oxidative reactions catalyzed by cytochrome P450
(CYP) enzymes in all animals (CYP6 family important
for insects). Is thought that insecticidal properties of
pyrethroids terminated by oxidative metabolism .
Resistance to pyrethroids due to detoxification by CYP
monooxygenases
• Resistance associated with elevated CYP activity.