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Insect Control: Biological and Synthetic Agents - Index of

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nAChR are comparable to the efficacy differences in<br />

adult bioassays (Rauch <strong>and</strong> Nauen, 2003).<br />

Daborn et al. (2001) described D. melanogaster<br />

mutants exhibiting an eight- <strong>and</strong> sevenfold resistance<br />

to imidacloprid <strong>and</strong> DDT, respectively,<br />

which showed an overexpression <strong>of</strong> the P-450 gene<br />

Cyp6g1. However, it was not tested whether recombinant<br />

Cyp6g1 itself can metabolize imidacloprid;<br />

potentially it could metabolize a trans-acting factor<br />

which then upregulates presently uncharacterized<br />

P-450 genes. However, it was demonstrated that<br />

the recombinant cytochrome P-450 isozyme<br />

CYP3A4 from human liver can selectively metabolize<br />

the imidazolidine moiety <strong>of</strong> imidacloprid,<br />

resulting in 5-hydroxy-imidacloprid as the major<br />

metabolite (Schulz-J<strong>and</strong>er <strong>and</strong> Casida, 2002). It<br />

would therefore be fruitful to investigate if homologs<br />

<strong>of</strong> Cyp6g1 <strong>and</strong> Cyp3a4, or similar genes, are<br />

present in the B. tabaci genome, <strong>and</strong> if overexpression<br />

<strong>of</strong> these genes is associated with neonicotinoid<br />

resistance.<br />

Although considerable resistance to neonicotinoid<br />

insecticides was also reported for populations<br />

<strong>of</strong> the Colorado potato beetle from Long Isl<strong>and</strong>,<br />

NY, the underlying mechanisms associated have<br />

not been very well studied. Pharmacokinetic investigations<br />

on susceptible <strong>and</strong> resistant strains did not<br />

reveal any differences in the uptake <strong>and</strong> excretion <strong>of</strong><br />

14 C-labeled imidacloprid, nor were there any differences<br />

in metabolic conversion found (Hollingworth<br />

et al., 2002). The authors suggested a modification<br />

<strong>of</strong> the target site to be responsible for the observed<br />

resistance. But, preliminary investigations revealed<br />

no differences between resistant <strong>and</strong> susceptible<br />

strains in receptor binding studies using [ 3 H]imidacloprid<br />

(Nauen <strong>and</strong> Hollingworth, unpublished<br />

data).<br />

Resistance development to imidacloprid would<br />

be disastrous in many regions, so there is a dem<strong>and</strong><br />

for an effective resistance management program,<br />

<strong>and</strong> interest in finding <strong>and</strong> developing new active<br />

ingredients for pest control.<br />

3.9.3. Resistance Management<br />

Monitoring <strong>and</strong> detection <strong>of</strong> insecticide resistance in<br />

order to recommend <strong>and</strong> implement effective resistance<br />

management strategies is currently one <strong>of</strong> the<br />

most important areas <strong>of</strong> applied entomology. This<br />

program is necessary to sustain the activity <strong>of</strong> as<br />

many active ingredients with different modes <strong>of</strong><br />

action as possible by using alternate spray regimes,<br />

rotation, <strong>and</strong> sophisticated application techniques<br />

(Denholm <strong>and</strong> Rowl<strong>and</strong>, 1992; McKenzie, 1996;<br />

Denholm et al., 1998, 1999; Horowitz <strong>and</strong><br />

Denholm, 2001). Historically, the problem <strong>of</strong><br />

insecticide resistance was tackled by continuously<br />

introducing new active ingredients for pest insect<br />

control. The number <strong>of</strong> insecticides available is<br />

high, but the biochemical mechanisms targeted by<br />

all these compounds is rather limited (Casida <strong>and</strong><br />

Quistad, 1998; Nauen <strong>and</strong> Bretschneider, 2002).<br />

A pronounced decline in the introduction <strong>of</strong> new<br />

insecticides since the late 1970s revealed the limitations<br />

<strong>of</strong> a strategy relying on the continuous<br />

introduction <strong>of</strong> new active compounds (Soderlund,<br />

1997).<br />

This problem has been recognized by the<br />

regulatory authorities; <strong>and</strong> the European Plant<br />

Protection Organization (EPPO) recently published<br />

guidelines outlining the background work on<br />

resistance required for registration <strong>of</strong> a new active<br />

ingredient (Heimbach et al., 2000). These requirements,<br />

which are provided by agrochemical companies<br />

as an essential part <strong>of</strong> the registration dossier,<br />

include<br />

. baseline susceptibility studies (testing several<br />

strains <strong>of</strong> a target species known to be prone to<br />

resistance development);<br />

. monitoring (continuous studies on the development<br />

<strong>of</strong> resistance <strong>of</strong> target species by simple bioassays<br />

after the launch <strong>of</strong> a new compound); <strong>and</strong><br />

. possible resistance management strategies (how<br />

the new compound should be combined with<br />

others in order to exp<strong>and</strong> its life time in the field).<br />

3.10. Applications in<br />

Nonagricultural Fields<br />

3: Neonicotinoid <strong>Insect</strong>icides 99<br />

Because <strong>of</strong> the high insecticidal efficacy together<br />

with its nonvolatility <strong>and</strong> stability under storage<br />

conditions, imidacloprid (Premise Õ ) has been successfully<br />

applied as a termiticide ( Jacobs et al.,<br />

1997a; Dryden et al., 1999), <strong>and</strong> has also been<br />

used for control <strong>of</strong> turf pests such as white grubs<br />

(Elbert et al., 1991). Furthermore, imidacloprid<br />

is the active ingredient <strong>of</strong> the insecticide Merit Õ ,<br />

<strong>and</strong> is commonly incorporated into fertilizers for<br />

early control <strong>of</strong> grubs in turf (Armbrust <strong>and</strong> Peeler,<br />

2002). In addition, imidacloprid was the first neonicotinoid<br />

to be used in a gel bait formulation<br />

for cockroach control. The imidacloprid gel showed<br />

outst<strong>and</strong>ing activity even after 27 months’ under<br />

various conditions (Pospischil et al., 1999). As an<br />

endoparasiticide imidacloprid exerted activity<br />

against the gastrointestinal nematode Haemonchus<br />

contortus in sheep only at higher concentrations<br />

(Mencke <strong>and</strong> Jeschke, 2002). Synergistic mixtures<br />

containing imidacloprid are patented <strong>and</strong> these<br />

are useful against textile-damaging insects, such as

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