Literature Review

t the beginning of World War II, the insecticide selection was limited to several
arsenicals, petroleum oils, nicotine, pyrethrum, rotenone, sulfur, hydrogen
cyanide gas, and cryolite. After World War II, there have been major increases
in agricultural productivity accompanied by an increase in efficiency, with
fewer farmers on fewer farms producing more food for more people (Rasmussen
et al. 1!". #he focus was shifted towards development of more effective and
biodegradable pesticides. As a result $synthetic pyrethroids% came into
e&istence. 'ver the past two decades many synthetic pyrethrin(li)e materials
have become available. #hey were originally referred to as synthetic
pyrethroids. *urrently, the better nomenclature for all such synthetic products
is simply pyrethroids.
A
+ynthetic pyrethroids are synthesi,ed derivatives of naturally occurring
pyrethrins, which are ta)en from pyrethrum, the oleoresin e&tract of dried
chrysanthemum flowers (Chrysanthemum cinariaefolium". -atural pyrethrins were
widely used in .urope during the 1th century, when few effective insecticides were
available (.lliott et al. 1/!". #he insecticidal properties of pyrethrins are derived from
)etoalcoholic esters of chrysanthemic and pyrethroic acids. #hese acids are strongly
lipophilic and rapidly penetrate many insects and paraly,e their nervous system.
0owever, they are e&pensive to produce and have low photostability and high
biodegradability (0aya 1!1 Williamson et al. 1!". 2odern synthetic pyrethroids
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2.2 Synthetic pyrethroids-A general
overview
Literature Review
have been designed to provide enhanced residual activity through greater photostability
and greater resistance to chemical and biological degradation, greater insecticidal
activity, diminished mammalian to&icity and greater cost effectiveness (+mith and
+tratton 1!41 *oats et al. 1!1 0aya 1!1 5ijverberg and 6erc)en 17".
2.2.1. Chemistry and evolution
All pyrethroids can e&ist in at least four stereoisomers, each with different
biological activities. #hey are mar)eted as racemic mi&tures or as single isomers. 2ost
commercial formulations have a fi&ed isomeric ratio. 8ormulations made of a single
isomer (deltamethrin, for e&ample" are li)ely to be much more to&ic than those with four
to eight isomers (6radbury and *oats 1!b". In commercial formulations, the activity
of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl
buto&ide, which inhibits metabolic degradation of the active ingredient (6radberry et al.
977:".
#he physical and chemical properties of a chemical can be used to determine its
behavior and potential fate in the a;uatic environment. <yrethroids generally have low
vapor pressures and 0enry=s >aw constants which suggest that they are not easily
volatili,ed into the atmosphere. #hey have high octanol?water partition coefficients
(@ow" so they tend to partition into lipids. #hey also have very high water?organic
carbon (@oc" partition coefficients, which suggests that the greatest ris) to a;uatic
organisms would be through e&posure to pyrethroid contaminated sediments.
6ased on demands the pyrethroid generations have gone through an interesting
evolution, which is conveniently divided into four generations (#able 9.1". #he present
wor) dealt with one fourth and one third generation pyrethroid, deltamethrin and
fenvalerate. A detailed review on the two pyrethroids has been documented later in this
chapter.
1:
Literature Review
Table 2.1: Table showing evolution of different generation of pyrethroid. Year of
introduction is given in parentheses (URL 4)
First generation Second generation Third generation Fourth generation
o Allethrin (13"
o #etramethrin
(14:"
o Resmethrin
(14/"
o 6ioresmethrin
(14/"
o 6ioallethrin(r"
(14"
o <honothrin
(1/A"

o 8envalerate and
permethrin
(1/9(/A"
(8irst agricultural
pyrethroids"
o 6ifenthrin
o >lambda(
cyhalothrin
o *ypermethrin
o Beltamethrin
o .sfenvalerate
o 8enpropathrin
o 8lucythrinate
o 8luvalinate
o <rallethrin
o #efluthrin
o #ralomethrin
o Ceta(
cypermethrin
2.2.2. Uses
6oth pyrethrins and synthetic pyrethroids are sold as commercial pesticides
used to control pest insects in agriculture, homes, communities, restaurants, hospitals,
schools, and to treat topical head lice and scabies (6radberry et al. 977:". <yrethroids are
applied in urban areas primarily for structural pest control, in agricultural areas on row
crops and orchards, and for various household and veterinary purposes (+mith and
+traton 1!41 Wardhough 977:". In a;uaculture, pyrethroids are used to control some
parasitic diseases caused by proto,oa e.g. Lepeophtheirus salmonis in +almon farming
(#oovey and >yndon 9777".
2.2.3. Accumulation and Toxicity
#he route of accumulation of pyrethroid is very important for its relative to&icity.
8or e&ample in birds and mammals they are generally accumulated through oral route. In
fish the pyrethroids gain access directly into the blood stream through gills (+mith and
+tratton 1!4" because of their lipophilicity. 6ecause of this the to&icity of pyrethroids
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Literature Review
to birds and mammals is relatively low as compared to fish. >imited absorption of some
pyrethroids, and rapid biodegradation by mammalian liver en,ymes (ester hydrolysis and
o&idation" also ma)e these pyrethroids less to&ic to mammals. Insects, without this liver
function, e&hibit greater susceptibility to the chemicals.
While the development of the synthetic pyrethroids was heralded with claims of
selective to&icity to insects, both pyrethroids and pyrethrins have been found e&tremely
to&ic to non target a;uatic organisms particularly fish (D+.<A 97791 'udou 9773".
>obster, shrimp, mayfly nymphs and ,ooplan)ton are the most susceptible non(target
a;uatic organisms (2ueller(6eilschmidt 17". +maller and?or younger organisms and
life(stages are more sensitive than larger?adult organisms. *urrently, .<A
(.nvironmental <rotection Agency" is assessing ris)s to non(target organisms for
different synthetic pyrethroids. #o&ic effects of pyrethroids on non target organisms have
been reviewed and reported to be in the parts per billion values of to&icity (+mith and
+tratton 1!4". <yrethroids are more to&ic to fish at lower temperatures and appear to be
more to&ic to smaller fish than larger fish (0ill 1!:".
<yrethroid to&icity is highly dependent on stereochemistry, the three dimensional
configuration of the molecule (6radbury and *oats 1!b". As indicated above these
occur as mi&tures of stereoisomeric forms, and the to&icity of individual isomers can
vary (>iu et al. 977:".
2.2.4. Mode o action
All synthetic pyrethroids are potent neuroto&icants that interfere with nerve cell
function by interacting with voltage(dependent sodium channels as well as other ion
channels, resulting in repetitive firing of neurons and eventually causing paralysis (*lar)
and 2astsumura 1!91 6radbury and *oats 1!a1 5ijverberg

and 6erc)en 171
1/
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#atebayashi and -arahashi 131 +hafer and 2eyer 9773". Bepending upon the mode of
to&icity the synthetic pyrethroids are classified into two typesE #ype I and II (#able 9.9".
Table 2.2: Table showing the types of pyrethroids according to mechanism of toxicity
(Ray and orshaw 2!!!" #radberry et al. 2!!$" %R& '(
Type I
Type II
Without an alfa(cyano group
(e.g. permethrin"
*ause a moderate prolongation of
the transient increase in sodium
permeability of the nerve
membrane during e&citation
resulting in relatively short trains
of repetitive nerve impulses in
sense organs, sensory (afferent"
nerve fibres and nerve terminals
0ave a negative temperature
coefficient, resembling that of
BB#.
With alfa(cyano group
(e.g. cypermethrin, deltamethrin,
fenvalerate"
*ause a long(lasting prolongation
of the transient increase in sodium
permeability of the nerve
membrane during e&citation
resulting in long(lasting trains of
repetitive impulses in sense organs
and a fre;uency(dependent
depression of the nerve impulse in
nerve fibers.
0ave a positive temperature
coefficient, showing increased )ill
with increase in ambient
temperature.
Both type I and II pyrethroid insecticides affect the sodium channels in the nerve
membranes, causing repetitive neuronal discharge, with effects being quite similar to
those produced by DDT. Type II syndrome involves primarily an action in the central
nervous system, whereas with the type I syndrome, peripheral nerves are also involved.
Type II pyrethroids prolongs the sodium channel open-time much more drastically than
type I pyrethroids. Therefore they are considered more potent neurotoxicants (Narahashi
1992; .isler 19). There appears to be a prolongation of sodium influx with a delay in
the closing of the sodium activation gate, resulting in an increased and prolonged sodium
tail current (Narahashi 1992; Bradbury and Coats 1989a; Bradberry et al 2005).
1!
Literature Review
Advanced electrophysiological e&periments using voltage clamp and patch clamp,
together with ligand(binding and ionic flu& e&periments, have unveiled uni;ue actions of
pyrethroids of )eeping the -a
F
channel in the open state for an e&tremely long period,
sometimes as long as several seconds.
#his modification of -a
F
channel properties leads to hyperactivity of the nervous
system (-arahashi 19). In addition, #ype II pyrethroids can also affect chloride and
calcium channels (6urr and Ray 9773". <yrethroids also inhibit acetycholinesterase
activity (2ushigeri and Bavid 977:".
+econdarily, pyrethroids have been shown to inhibit A#<ases associated with
active transport (2ichelangeli et al. 17, Reddy et al. 11a" and therefore may affect
ion movement and osmoregulation. +ince freshwater a;uatic organisms live in an
e&tremely dilute environment, the processes involved in maintaining ionic balance and
osmoregulation are critical to the maintenance of homeostasis (@nut +chmidt ( -ielson
1/". .&posure to pyrethroid insecticides under a;uatic condition may therefore affect
the fish=s ability to maintain ion balance, resulting in increased susceptibility. +imilar
effects have been reported in fish in which e&posure to pyrethroids disrupts respiratory
surfaces and ion regulation (6radbury and *oats 1!a, Reddy and <hillip 19"
Some other sites of action have also been noted for the pyrethroid insecticides.
Some of them inhibit Ca
2+
Mg
2+
ATPase, thereby interfering with calcium removal from
the nerve endings, resulting in increased neurotransmitter release in the postsynaptic gap
(@adous et al. 13". In addition, the protein calmodulin, responsible for the intracellular
binding of calcium ions to reduce spontaneous neurotransmitter release, can be inhibited.
Type II pyrethroids have also been shown to bind to the GABA-receptor chloride
channel complex, blocking chloride ion transport into the nerve cell (6radberry et al.
977:". It happens probably as a conse;uence of binding of a *- group, present in a
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Literature Review
pyrethroid to nicotine(acetylcholine receptor of GA6A receptor. #his in turn ma)es
impossible the transfer of the functional potentials in the synapses (+algado 1!". #hey
can also inhibit receptors for acetylcholine

(Abbassy et al. 1!A", serotonin

('ortgiesen
et al. 1!" and ben,odia,epine (Bevaud and 2urray

1!!".
To summarize, there are many similarities between the mechanism of action of
pyrethriod insecticides and organochlorines. Consequently there is a risk for additive or
even synergistic effects. <yrethroids are also found to affect '
9
consumption which leads
to a decrease

in the activity of mitochondrial en,ymes (Reddy and <hilip 19".
2.2.!. Acute and su" lethal eects
#he primary site of action by the pyrethroids is the central nervous system
symptomised by hyperactivity, lac) of coordination, tremors and convulsions followed
by paralysis and eventual death (Roy 9779". 0owever, they are )nown to affect both the
peripheral and central nervous system of the insect (+oderland and 6loom;uist 1!".
Bue to the lipophilic nature of pyrethroids, biological membranes and tissues readily
ta)e up pyrethroids. .&posed organisms may e&hibit symptoms of hypere&citation,
tremors, convulsions, followed by lethargy and paralysis. In the first phase the
into&ication symptoms are clonic reactions resulting from overstimulation, while in the
ne&t muscle paralysis results.
In fishes sublethal concentration of pyrethroids cause changes, which become
visible after certain time(periods (9(3 wee)s". Among the changes areE osmoregulation
disorders, increase of en,ymatic activity in the )idney and liver (@o,u(be) et al. 191
+a)r and Hamal al lail 977:", changes in hematological parameters of the erythrocyte
system (@umar et al.11 +eth and +a&ena 977A1 <impao et al. 977/", decrease in total,
structural and soluble proteins (Reddy et al. 11b1 +a)r and Hamal al lail 977:", change
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Literature Review
in plasma calcium and phosphate level (+rivastav et al. 1/", delayed spawning (#anner
and @nuth 14", reduced fertili,ation success (2oore and Waring 9771", decreased
fecundity (Werner et al. 9779", and histopathologic changes of internal organs (+a)r and
Hamal al lail 977:1 *engi, and Dnlu 9774". +ublethal levels of some pyrethroids li)e
fenvalerate also affect the immune system of fishes as evidenced by reduced disease
resistance (Celi)off 1!1 *lifford et al. 977:". Increased e&pression of cellular stress
proteins was detected in juvenile *hinoo) salmon when e&posed to .sfenvalerate which
indicates significant protein damage in cells and tissues (.der et al. 97731 #eh et al.
977:).

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