1) Synthetic pyrethroids are derived from natural pyrethrins produced by chrysanthemum flowers and were developed in the 1970s-80s to be more toxic to insects and less degradable. 2) Pyrethroids are metabolized through ester hydrolysis and oxidation reactions catalyzed by cytochrome P450 enzymes. Metabolism typically proceeds through phase I oxidation and phase II conjugation and excretion. 3) Major metabolites include various acids, alcohols, and carbon dioxide produced through ester cleavage and oxidation of different parts of the pyrethroid structure. Metabolism pathways can differ between species and individual pyrethroid compounds.

1. METABOLISM OF SYNTHETIC
PYRETHROIDS
Kishor Pujar
First Ph.D.
PALB 9014
Agricultural Entomology
University of Agricultural Sciences Bangalore

2. Introduction
Many developed in 1970’s and 80’s by Bayer AG Co.
 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 lipophilic, low water solubility
Structure of compound (I or II) has different effects and associated poisoning symptoms
Isomerism around the cyclopropane ring greatly influences toxicity

6. Half life
Half life for pyrethroids in aquatic medium has been reported between 19 hours
(permethrin in pond water, Rawn et al., 1982) to 13.5 weeks (Fenpropathrin in distilled
water, Takahashi et al., 1985)
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

7. Mode of Entry into Organisms
Since pyrethroids are highly lipophilic, will readily be absorbed through the gills of aquatic
animals
In mammals, toxicity occurs when ingested, not readily absorbed through skin
Mode of Action
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

8. Metabolism
Steps
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)
1- Ester cleavage
2- Oxidation
3- Oxidation

9. Metabolism is typically a two stage process
Phase I – Primary
Phase II – Secondary Xenobiotics
Oxidation, Hydrolysis,Reduction Primary
Primary Products
Secondary Products
Secondary
Conjugation with sugars, amino
acids, Glutathione, phosphate,
sulphate etc.
Excretion
Accumulated as
residues
Toxicity causes
death
SP *
SP *

11. Cytochrome P450 (CYPs)
Co- factor component in Electron transport chain
Can metabolize a large number of substrates
Exist in numerous different isoforms
They have several functional roles, in the metabolism of xenobiotics.

12. Dehydrogenase enzymes
Alcohol & Aldehyde dehydrogenases
Generally used for the oxidation of aldehyde & alcohol
ALCOHOL
ALDEHYDE
CARBOXYLIC ACID

13. Metabolism of Pyrethrin
 For many years, it is said that the detoxification is by hydrolyzing the ester linkage and
splitting the molecule into acids and alcohols.
 Methylene - di - oxyphenyl type synergist – inhibit oxidative metabolism.
 The major metabolic pathway – oxidation of MFO’s system of trans- methyl isobutenyl
group to the hydroxymethyl metabolite.
The initial oxidation step is sensitive to inhibition by synergists. Then it is conjugated and
excreted and further oxidized to aldehyde  acid form.
(Yamamoto and Cassida 1966)

14. In Mammals and Birds
Pyrethroids show lower toxicity when compared to other pesticides.
More than 90% of pyrethroids being excreted as metabolites in urine within 24
hours after exposure.
Rapid metabolism in the blood and liver.
Although extensively used, there are relatively few reports of human &
domestic animal

15. In Insects
Metabolic pathway include oxidation at one or more sites in the
molecule along with ester hydrolysis followed by secondary oxidation,
to yield a large number of polar and non polar metabolites
In soil
Pyrethroids strongly bind to soil and are rapidly degraded to CO2 in
moist soil types under both aerobic and anaerobic conditions

16. In Plants
In field – rapid degradation,
Green house- half-life 1-6 weeks.
Ester cleavage - Photo induced reactions.
Metabolites + sugars or amino acids.
Pyrethroids are not translocated inside the plant system.
Aerobic condition , the metabolite converts into
 CO2 - rapid degradation takes place

17. Allethrin
 Allethrin metabolized in housefly Mixed Function Oxidase system by attack at the trans
(major site) and cis trans (minor site) methyl groups of the iso butenyl side chain in the
acid forming in succession, the corresponding hydroxymethyl, aldehyde, and acid
compounds.
 No hydrolysis or attack on the alcoholic part of the ester is detected, but there are trace
amount of unidentified metabolites.
Piperonyl butoxide inhibits hydroxylation of the methyl groups by the MFO system.
Living house fly conjugate and excrete the hydroxy methyl compounds, probably a
glucosides .
Pyrethrin I ,phthalthrin and dimethrin are similarly metabolized in vitro and in vivo by
oxidation of trans methyl group.

18. Cyclo –propanoid pyrethroids
Permethrin, cypermethrin, decamethrin
Permethrin
 Ester cleavage gives cis and trans isomers of Dichloro
vinylchrysanthemic(DV) acid and m-phenoxybenzyl alchohol.
 cis permethrin is an active isomer first changes to trans permethrin and
finally gives the cleavage products as cis trans mixtures DV acids.

19. Cypermethrin and Decamethrin
 Same as permethrin, however the 3-phenoxybenzyl group in these
compounds acts as UV filter and imparts additional degree of
stability to them.
 Instead of dimeric products it will give methyl-m-phenoxy
benzoate and dibromochrysanthemic acid.

20. Step 3: Oxidation
Step 2: Oxidation
Step 4: Excretion
Step1: Ester cleavage
Metabolism of Permethrin

21. In rats, trans- isomer(susceptible to esterase attack) is metabolized and
eliminated faster than cis- isomer.
Major route – Ester cleavage, and oxidase attack as well as hydroxylation of
terminal aromatic ring
In Mammals (Metabolism of permethrin)

22. Step1: Ester cleavage
Hydrolytic oxidation at
aromatic ring
Step2: Oxidation
Step3: Oxidation

23. Deltamethrin:
When photolyzed (>290 nm) in
various solvents ,
cis-trans isomerization and ester
cleavage reactions.
The cis-trans isomerization is the
major reaction on glass or silica gel.
Pyrethroids undergo complex
reaction mechanisms and products.
Photoreaction
Photodegradation of deltamethrin

25. Chemical compound Major metabolite Short form
1 Most of pyrethroids 3-phenoxybenzoic acid 3PBA
2 Fluorine-substituted
pyrethroid insecticides
4fluoro-3-
phenoxybenzoic acid
4F3PBA
3 Cypermethrin and
cyfluthrin
cis- and trans-(2,2-
dichlorovinyl)-3,3
dimethylcyclopropane-
l-carboxylic acid
Cis- and trans-DCCA
4 Deltamethrin Cis(2,2-dibromovinyl)-
3,3-
dimethylcyclopropane-
l-carboxylic acid)
DBCA

26. Chemical Half –life period Metabolite change
to
Permethrin 5-55 days Carbon – di - oxide
Cypermethrin 1- 10 weeks Carbon – di –
oxide
Fenvalerate 2 – 14 weeks Carbon – di - oxide
Immobile in soils( due to lipophilic in nature)
Will not translocate to any other part of the plant

27. Decarboxylation Dechlorinization- Dimerization
Fenvalerate

30. Fluvalinate Flucythrinate

31. ⅄- cyhalothrin

33. References
 N.K.Roy (2002).Chemistry of pesticides. CBS publishers: New Delhi.
 Junshi Miyamoto (1976). Degradation, Metabolism and Toxicity of Synthetic
Pyrethroids. Environmental Health Perspectives Vol. 14, pp. 15-28.
 Pornpimol Rongnoparut, Sirikun Pethuan, Songklod Sarapusit and Panida
Lertkiatmongkol . Metabolism of Pyrethroids by Mosquito Cytochrome P450
Enzymes: Impact on Vector Control .

34. Thank you