Synthetic Pyrethroids are mostly used in agricultural ecosystem, knowing their mode of action, structure is main vision of this presentation

1. STRUCTURE &MODE OF ACTION OF PYRETHROIDS
ENT 506 TOXICOLOGY OF INSECTICIDE
TERMPAPER PRESENTATION
Submitted to
Dr. S. Upendhar
Associate Professor
Dept. of Entomology
Submitted by
Kishore S.M
RAM/2021-59
MSc (Ag) 1st year
Dept. of Entomology

2. INTRODUCTION
 Pyrethroids is an organic compound similar to the natural pyrethrins.
 Obtained from dried and powdered flowers, daisy-like plant Chrysanthemum
cinerariaefolium.
 Name given to the active insecticidal component of dried flower “Pyrethrins”.
 Combination of two carboxylic acid and three keto alcohols.
 Grown in Kenya, Tanzania, Ecuador, Japan, Uganda, Rwanda and other
countries.
 Recently Australia has become the world’s second largest producer after Kenya.

3. Natural Pyrethrins
Pyrethrins I or Chrysanthemates Pyrethrins II or Pyrethrates
Pyrethrin I 35% Pyrethrin II 32%
Cinerin I 10% Cinerin II 14%
Jasmolin I 5% Jasmolin II 4%
Total 50% Total 50%
 Highly effective botanical insecticide used for centuries against all manner of insect pests.
 Occur in the daisy-like plant Chrysanthemum cinerariaefolium.
 Found in tiny oil containing glands on the surface of seed case in tightly packed flower head.
 Insecticidal activity was discovered in Iran around 1800.
 Made up of six complex organic esters formed by combination of carboxylic acid and keto alcohols.

4. Synthetic Pyrethroids
 Pyrethroids are synthetic, or man-made, versions of Pyrethrins.
These are grouped into two classes
 Type I pyrethroids are derivatives of pyrethrin. Include non-α-
cyano-pyrethroids. Eg: Allethrin, Bifenthrin, Permethrin,
Phenothrin, Resmethrin, Tefluthrin, Tetramethrin
 Type II pyrethroids are α-cyano-pyrethroids having a cyano-
group. Eg: Cyfluthrin, Cyhalothrin, Cypermethrin, Deltamethrin,
Fenvalerate, Fenpropathrin, Flucythrinate, Flumethrin,
Fluvalinate Chemical structure of pyrethroids :
Pyrethroid I (R = CH3), Pyrethroid II
(R = CO2CH3 )

5. Response/action Type I Type II
Poisoning symptoms
• Rapid onset of symptoms even at
sublethal levels
• Slow onset of symptoms
• Hyperactivity often leading to
knockdown
• Convulsion followed by paralysis
• Low kill with high recovery • High kill with low recovery
• Inversely related to changes in
temperature
• Little effect of temperature change
Electrophysiological response in
nerve tissue
• Repetitive discharges in axons • Blockage of conduction at synapses
Action on sodium-channel
function
• Monophasic and rapid decay of tail
currents
• Biphasic and very slow decay of tail
currents
• Bind preferentially to closed channels • Bind preferentially to open channels
Level of resistance due to
resistant houseflies with super-
kdr mechanism
• Below 100-fold • Over 200-fold

6. PYRETHRINS v/s PYRETHROIDS
Pyrethrins Pyrethroids
 Pyrethrins are the active chemicals in pyrethrum, and are 100%
natural
 Pyrethroids are synthetic, or man-made, versions of Pyrethrins
 Pyrethrum is composed of 6 esters (collectively called the
Pyrethrins), all of which have insecticidal properties. This
means that the pyrethrum is attacking the insect on 6 different
fronts, using 6 different insecticides.
 Pyrethroids, which are synthetic, are composed of only one
chemically active compound.
 Pyrethrins are naturally broken down by UV rays and PH
variances and therefore have shorter environmental persistence.
 synthetic Pyrethroids are manufactured to overcome that
problem.
 Pyrethrins have a unique ability to induce excitation behaviour
in insects, characterized by erratic and increased movement by
insects. This has the benefit of 'flushing' the insects out of
hiding places, resulting in increased exposure to the Pyrethrins
 Synthetic Pyrethroids do not have this flushing effect

7. Properties of Pyrethroids
 Rapid action: Contact insecticide that attack on nervous system of insects almost immediately.
 Broad spectrum of insecticides: because it consists of group of complex compounds.
 Lack of persistence: Degraded by sunlight and air, so they have less environmental hazards.
 Repellency: Powerful insect repellent and have Knockdown effect.
 Low mammalian toxicity: One of least toxic domestic insecticide

8. Sources of different species:
1. Chrysanthemum cinerariefolium
2. C . coccineum
3. C.roseum
4. C.marshalli
5. C.tamrutene
Chrysanthemum coccineum

9. Chrysanthemum marshalli
Chrysanthemum roseum
Chrysanthemum cinerariefolium

10. Mode of Entry into Organisms
 Pyrethroids exposure in insects is predominantly through the insect cuticle. Rapid absorption,
particularly with the halogen-containing pyrethroids, causes disruption of insect
neurotransmission. In contrast to insects, human dermal absorption of pyrethroids is low relative
to absorption via lung or gut. Humans absorb approximately 1% of pyrethroid exposure through
skin but upto 36% through ingestion.
 Several other modes of entry have also been reported like through mouthparts and spiracles.
 After absorption, pyrethroids are distributed throughout the body and can cross blood-brain
barrier to access the nervous system.
 Gastro-intestinal : moderate
 Respiratory Tract : moderate
 Dermal : poor

11. MODE OF ACTION

12. STIMULI
1.Resting state
2.Depolarization
3.Repolarization

14. COMPOUNDS OF SYNTHETIC PYRETHROIDS
1.ALLETHRIN
2.CYPERMETHRIN
3.CYFLUTHRIN
4.LAMBDA CYHALOTHRIN
5.CYPERMETHRIN
6.DELATMETHRIN
7.IMIPROTHRIIN
8.BIFENTHRIN
9.CYPHENOTHRIN

15. 10.FENPROTHRIN
11.FENVELARATE
12.PERMETHRIN
13.PRALLETHRIN
14.TRANSFLUTHGRIN
15.ETOFENPROX

16. Type I Pyrethroids
• Type I pyrethroids prolong the sodium current during
excitation, causing depolarizing after-potential.
• When the after-potential exceeds the membrane threshold
repetitive action potentials are generated, leading to
hyperexcitation.
• High concentrations reduce the amplitude of the action
potential due to suppression of the sodium currents.
• These changes in sodium channel and sodium current are
responsible for the symptoms of poisoning leading to
paralysis and death.
• Type I, among other physiological responses, have a
negative temperature coefficient, resembling that of DDT.

17. Type II Pyrethroids
• Type II pyrethroids also act on the sodium channel, prolong sodium current and depolarize
the nerve membrane more strongly than type II pyrethroids.
• However, the pattern of changes in excitability is different from that caused by type I
pyrethroids.
• Because of membrane depolarization, nerve fibers do not initiate repetitive discharges, but
sensory neurons discharges bursts of impulses and synaptic transmission is disturbed.
• The cockroach strain with a kdr type of resistance shows cross resistance to pyrethrins and
other type I pyrethroids, but not to type II like cypermethrin and deltamethrin.
• Type II have a positive temperature coefficient, showing increased kill with increase in
ambient temperature. Pyrethroids affect both the peripheral and central nervous system of
the insect. The stimulating effect of pyrethroids is much more pronounced than that of DDT.

18. Symptoms of Toxicity
Type I Pyrethroids
 Hyperexcitability and convulsions in insects and a wholebody tremour in mammals.
 Core temperature is markedly increased, probably due to excessive muscular activity associated with tremours.
Occasionally a state of rigour preceded death.
 In insects, the effects of Type I pyrethroids can develop very rapidly after treatment and can result in knockdown,
characterized by incoordination, and hyperactivity, followed by prostration and paralysis, similar to those produced
by DDT.
Type II Pyrethroids
 In insects cause predominantly ataxia and incoordination.
 In mammals, it cause increased startle response, abnormal locomotion involving the hind limbs and in the final
stages of intoxication cause choreoathemosis (sinous writhing convulsions) and profuse salivation .
 The response to painful mechanical and thermal stimuli was delayed and the rectal temperatures steadily decline.
Death is sometimes preceded by clonic seizures.

19. 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

20. 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.

21. Merits of Pyrethroids
 Extremely high insecticidal activity at extremely low doses
 Biodegradable in nature
 Effective against lepidopterous pests and beetles, leaf miners and bugs.
 Effective against eggs, larval and adult stages of insects
 Powerful antifeedant and repellent properties
 Not readily washed off from the plant by rain
 Movement from site of application is limited in air due to low volatility

22. Demerits of Pyrethroids
 Not systemic and do not have translaminar action
 Constant use of synthetic pyrethroids increase resistance in insects pest
 Harmful for beneficial organisms (honey bees, beetles, spiders, centipedes and
predatory mites)
 Highly toxic to fish
 On prolonged storage, pyrethrum looses its insecticidal action. Hence; antioxidants like
hydroquinolene are added.

23. EVALUATION OF PIPERONYL BUTOXIDE IN ENHANCING THE EFFICACY OF
PYRETHROID INSECTICIDESAGAINST RESISTANT Anopheles gambiae s.l. IN GHANA
Samuel K. Dadzie, JosephChabi,AndyAsafu-Adjaye,Otubea Owusu-Akrofi,AbaBaffoe-Wilmot, Keziah Malm, ConstanceBart-Plange, SylvesterColeman, MaxwellA.Appawuand
DanielA. Boakye
 Background: Malaria vector control methods involving the use of pyrethroids including the use of long-lasting
insecticidal nets and indoor residual spraying remain the strategies being used against malaria vectors in Ghana.
However, there was evidence that pyrethroid resistance is widespread in many areas. Hence this study investigated
the effect of piperonyl butoxide (PBO) on the susceptibility status of An. gambiae s.l. across some sentinel sites in
Ghana.
 Methods: Three to five day old An. gambiae s.l. reared from larvae were used in WHO susceptibility tube assays.
Batches of 20–25 female adult An. gambiae s.l. were exposed simultaneously to the insecticide alone and to the
PBO + insecticide. The knock down rate after 60 min and mortality at 24 h were recorded.
 Results: Deltamethrin and permethrin resistance of An. gambiae s.l. was observed in all the sites in 2015 and
2016. The mortality after 24 h post exposure for deltamethrin ranged from 16.3% in Weija to 82.3% in Kade,
whereas that for permethrin ranged from 3.8% in Gomoa Obuasi to 91.3% in Prestea. A significant increase in
susceptibility to deltamethrin and permethrin was observed during both 2015 and 2016 years in most of the sites
when An. gambiae s.l. mosquitoes were pre-exposed to PBO.
CASE STUDY

24. Trends and prediction of the percentage increment in susceptibility of Anopheles gambiae s,l. against PBO + deltamethrin/permethrin in relation to
deltamethrin/permethrin alone.Significant increment in susceptibility was observed with the addition of PBO
 Conclusion: Findings from this study showed that the use of PBO significantly enhanced the susceptibility of A.
gambiae s.l. mosquitoes in most of the sentinel sites. It is recommended that vector control strategies incorporating
PBO as a synergist can be effective in killing mosquitoes in the presence of deltamethrin and permethrin resistance.

25. CONCLUSION
 Pyrethroids are classified in the category of sodium channel modulators according to IRAC
classification based on mode of action.
 It causes hyperexcitation and convulsions and disrupts the transmission of impulses. The sequence of
poisoning symptoms are excitation, convulsions, paralysis and death.
 These are effective neurotoxins against insect pests. Still there are a lot of concerns such as
development of resistance in insect pests, harmful for beneficial organisms, toxicity towards fish, etc.

26. Toxicology and Mode of Action
of Pyrethroid Insecticides
DAVID M. SODERLUND
CORNELL UNIVERSITY, GENEVA, NEW YORK

27. Pyrethroids are a class of synthetic insecticides that have been designed and optimized
based on the structures of the pyrethrins ,the six insecticidal constituents of the natural
insecticide pyrethrum (Elliott, 1995). Pyrethrum is arguably the most effective natural
insecticide, but its use is limited by its instability in light and air, which limits its
effectiveness in crop protection and other insect control contexts in which residual
activity is essential. The development of pyrethroids involved an iterative process of
structural modification and biological evaluation in an effort to identify compounds with
increased photostability that retained the potent and rapid insecticidal activity and
relatively low acute mammalian toxicity of pyrethrum.
Introduction

28. The registration in the late 1970s of the first pyrethroids with sufficient
environmental stability for agricultural applications led to the rapid expansion of the
use of these compounds as replacements for older organochlorine and
organophosphorus insecticides. Although originally developed and registered for
agricultural markets, pyrethroids are also used to control vectors of human disease
and arethe most common class of insecticides in household insecticide products
available to the general public. In 2002, pyrethroid use represented approximately
18% of the U.S. dollar value of the world insecticide market, ranking second only to
organophosphorus compounds among insecticide classes

29. REFERENCE
 Gour, T. B. and Sridevi D. 2012. Chemistry, toxicology and mode of action of insecticides. Kalyani
Publishers. New Delhi-316.
 Henk P. M. Vijverberg and Joep van den Bercken. 1990. Neurotoxicological effects and mode of action of
pyrethroid insecticides. Critical reviews in toxicology. 21 (2). p.105-126.
 https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/pyrethroid
 Samuel K. Dadzie, Joseph Chabi, Andy Asafu-Adjaye, Otubea Owusu-Akrofi, Aba Baffoe-Wilmot, Keziah
Malm, Constance Bart-Plange, Sylvester Coleman, Maxwell A. Appawu and Daniel A. Boakye. 2017.
Evaluation of piperonyl butoxide in enhancing the efficacy of pyrethroid insecticides against resistant
Anopheles gambiae s.l. in Ghana. Malaria Jounal. 16:342.

30. THANK YOU…