Insect Control: Biological and Synthetic Agents - Index of

observed that both indoxacarb and its activated
metabolite were similarly potent in intoxicating
Lepidoptera (Wing et al., 1998; Tsurubuchi et al.,
2001). This again argues for efficient bioactivation
in this order of insects.
Indoxacarb bioactivation was also studied in
the hemipteran cotton pest, the tarnished plantbug
(Lygus lineolaris), compared to its hemipteran predator,
big-eyed bug (Geochoris punctipes) (Tillman
et al., 2001). These studies again demonstrate that
the onset of neurotoxic symptoms in both bugs was
well correlated with the appearance of the activated
metabolite DCMP (albeit at slower rates than observed
in Lepidoptera). The importance of oral uptake
as a major route of bioactivation/intoxication,
compared to tarsal absorption of residues or
through dermal uptake, was clearly evident. Interestingly,
laboratory studies showed both pest and
predator to be similarly sensitive to indoxacarb,
although Geochoris could tolerate higher levels of
indoxacarb before showing signs of intoxication.
However, in treated cotton fields, Lygus has been
found to be more sensitive to indoxacarb treatment
while Geochoris has been relatively refractory; further
studies showed that this was largely due to
infield behavior and the preference of Geochoris
to feed on pest insects and their eggs as opposed to
foliage, which significantly slowed oral indoxacarb
uptake (Tillman et al., 2001).
In addition, all current evidence points to a SCBI
structural requirement for an underivatized urea linkage
to be present to exert strong, quasi-irreversible
insect Na þ channel blocking effects, as opposed to
derivatized ureas.
2.3.2. Catabolism of Indoxacarb and
Other Na + Channel Blocker Insecticides
Relatively little is known about the metabolic breakdown
of indoxacarb or other SCBIs in insects. On
balance, it is clear that bioactivation is occurring
much more rapidly than degradation after field
application, when satisfactory insect control is
observed. However, like any other novel insecticide,
resistance management will be a key to maintaining
the agricultural utility of this insecticide class.
Indeed, several field populations of North American
oblique-banded leafroller (Choristoneura rosaceana)
have shown a degree of insensitivity to indoxacarb,
which is unique for Lepidoptera (Ahmad et al., 2002).
Though this insect has never been exposed to indoxacarb
for commercial control in the field, it has been
treated with several other insecticide classes, including
a number of organophosphates. Current studies
indicate that resistant strains of this leafroller
maybeabletocatabolizeindoxacarbmorerapidly
2: Indoxacarb and the Sodium Channel Blocker Insecticides 39
than susceptible strains; the specific mechanisms
and metabolites are currently being characterized
(Hollingworth et al., unpublished data).
Interestingly, indoxacarb is apparently degraded
primarily by higher animals via routes including
cytochrome p450 mediated attack of the indanone
and oxadiazine rings, while N-decarbomethoxylation
is a relatively minor pathway (EPA, 2000; Scott,
2000). The rapid metabolic degradation is a critical
factor responsible for the high nontarget animal safety
of indoxacarb.
2.4. Physiology and Biochemistry of
the Na + Channel Blockers
2.4.1. Symptoms of SCBI Poisoning
in Insects: Pseudoparalysis
Pyrazolines and indoxacarb produce identical acute
neurotoxic symptoms in the American cockroach
Periplaneta americana, progressing through initial
incoordination (5–20 min after 1–10 mg injection),
then tremors and prostration, and finally a distinctive
pseudoparalysis, so named because the apparently
paralyzed insects produce violent convulsions
when disturbed. This pseudoparalysis was maintained
for 3–4 days, after which the ability to
move when disturbed waned. By 4–6 days, the
insects could be considered dead. Lower doses
caused a similar progression of symptoms, but the
time before appearance of symptoms was delayed.
This unusual pseudoparalysis was key to unraveling
the complex mode of action of this family in insects.
Irreversible pseudoparalysis was also observed in
lepidopterous larvae, with disturbance during the
pseudoparalyzed state leading to squirming, and
tremors of legs and mandibles evident upon microscopic
examination. Higher doses of pyrazolines,
especially in lepidopterous larvae, led within a few
hours to flaccid paralysis (Salgado, 1990). Injection
of 10 mgg 1 indoxacarb into fifth instar Manduca
sexta larvae produced excitatory neurotoxic symptoms
leading to convulsions and then relatively
rapidly to flaccid paralysis (Wing et al., 1998). As
discussed above, indoxacarb itself is converted
in vivo to DCMP by esterase-like enzymes. The pseudoparalytic
symptoms caused by indoxacarb have
also been clearly observed in Spodoptera frugiperda
larvae treated by injection of 20 mgg 1 indoxacarb or
DCJW, and also in male P. americana injected with 1,
3, or 10 mg g 1 DCJW (Salgado, unpublished data).
Under field conditions, after ingesting or being
directly sprayed with indoxacarb, insects will
irreversibly stop feeding within a few minutes to 4 h;
higher doses cause more rapid onset of symptoms.