Page 537 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

504 SECTION | VI Insecticides

VetBooks.ir TOXICITY twitching of muscles, tremors, followed by convulsions and
seizures. This condition may lead to paralysis. The central
Most animal poisoning cases in the field are acute in
effects include apprehension and stimulation, followed by
nature. Onset of clinical signs usually occurs within
depression. The affected animals may also show restless-
15 min to 1 h, followed by signs of maximal severity.
ness, ataxia, stiffness of the neck, and coma. Death occurs
However, timings of maximal severity signs tend to vary
due to respiratory failure and cardiac arrest. It is important
depending upon the OP/CM compound and its dose, and
to mention that not all poisoned animals show all the clinical
species. For example, onset of clinical signs is delayed
signs (as described above) with every OP or CM compound.
with chlorpyrifos (Dursban) and dimethoate (Rogor).
Furthermore, at nonlethal doses, the signs of toxicity caused
Clinical signs observed in poisoned animals can be
by each OP or CM can vary widely. This can be due to the
divided into local and systemic effects. The local effects
fact that each OP or CM reacts not only with AChE but also
involve the eyes and the lungs, owing to their exposure to
with other targets, such as butyrylcholinesterase, carboxy-
vapors or droplets of the insecticides. These effects, how-
lesterases, neuropathy target esterase (NTE), acylpeptide
ever, are of significance in the case of animals only when
hydrolase, arylformamidase, proteases, trypsin, chymotryp-
exposure is via spraying. The systemic effects are primar-
sin, cannabinoid CB1 receptor, albumin, and many other
ily on the brain, skeletal muscles, lungs, heart and other
enzymes, receptors, and proteins (Gupta, 2004; Lockridge
organs.
and Schopfer, 2006; Gupta and Milatovic, 2012; Mangas
The clinical signs can also be classified as muscarinic,
et al., 2017). While surviving animals usually recover within
nicotinic and central. Fig. 37.7 describes the sequence of
3 6 h with CMs and within 24 h with OPs; animals
events involved in OP/CM toxicity. Muscarinic ACh recep-
exposed to OP nerve agents may show signs of toxicity for
tor (mAChR)-associated effects are manifested by vomiting,
several days.
abdominal pain, salivation, lacrimation, urination, diarrhea
Poisoning cases of OP or CM are usually diagnosed
(SLUD), miosis (pinpoint pupils), tracheobronchial secre-
based on clinical signs and quantified levels of AChE
tion, lung edema, and cyanosis. The nicotinic ACh receptor
inhibition in blood from a live animal and brain from a
(nAChR)-associated effects are produced on autonomic gan-
dead animal. Inhibition of AChE activity .70% is con-
glia and skeletal muscles, and the affected animals show
sidered a positive case of poisoning. It should be noted
that great species variability exists in normal values of
AChE activity (Table 37.4). In addition, there is more
than a sixfold variability in AChE activity in different
brain areas with preference given to the cortex and not
Organophosphates
and carbamates the striatum for AChE analysis (Gupta, 2004). Therefore,
interpretation should be made with great caution. Residue
analysis of an insecticide and/or its metabolite(s), and by
confirmation with GC/MS or LC/MS, seems an ideal
Inhibition of AChE
(phosphorylation approach for diagnosis.
by OPs and
carbamylation by
CMs)
Accumulation of ACH
TABLE 37.4 Normal Acetylcholinesterase (AChE)
Activity in Brain Cortex of Different Species
Species AChE (μmol/g/h)
Stimulation Stimulation
of muscarinic of nicotinic Cattle 160
receptors receptors Swine 163
Sheep 170
Salivation Horse 124
Muscle
lacrimation fasciculations Chicken 1098
urination
defecation convulsions Dog 200
Rat 255
FIGURE 37.7 Important steps involved in mechanism of toxicity of
OPs and CMs.