Page 267 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

234 SECTION | II Organ Toxicity

VetBooks.ir hyperammonemia, metabolic acidosis that expressed itself pigs, and 800 mg/kg b.w. in sheep. Similarly, among car-
bamates, methomyl has an LD 50 of 17 mg/kg b.w. for
on the cardiac system as ventricular tachycardia translat-
dogs and 17 24 mg/kg b.w. for rats.
ing into ventricular fibrillation and death, though on post
mortem no alterations were noted in the histopathological Animals are exposed to OPs in a large number of
examination of the heart. There is no specific antidote for ways. For control of cattle grubs (Hypoderma lineatum),
fertilizer poisoning. the cattle are sprayed with OPs and poisoning may occur
(Khan et al., 1961; Khan, 2001). Feedstock treated with
terbufos has also led to poisoning with cardiac signs in
HERBICIDES
cattle. Animals that are kept indoors, e.g., marmosets, are
There are a large number of herbicides (Gupta, 2012), also liable for poisoning (Brack and Rothe, 1982).
characterized by differing chemical constituents, causing Classic signs of OP poisoning include prolonged QT
various effects on the heart. The ingestion of plants trea- interval (Abraham et al., 2001), ST T changes, sinus
ted with herbicide can induce electrolyte abnormalities tachycardia or bradycardia, and hypertension or hypoten-
and lower blood pressure. sion (Saadeh et al., 1997; Karki et al., 2004).
Paraquat is a widely used herbicide meant for killing Antidotes for OP poisoning are anticholinergics that
green plants on contact although its use is restricted in the are antagonistic to anticholinesterase activity at musca-
United States. Paraquat accumulates in the lungs and gen- rinic receptors. Atropine, which is widely used as a mus-
erates ROS (Ge et al., 2010). In rats, e.g., paraquat causes carinic antagonist, does not bind to nicotinic receptors.
severe heart damage as seen on an ECG (Noguchi et al., Also, oximes are available to counter inhibition of AChE
1990) including hemorrhage in the myocardium. Paraquat (Boelsterli, 2007; Kose et al., 2009).
also elicits sinus tachycardia but no arrhythmia.
The oral LD 50 in monkeys is 50 mg/kg b.w., and 48 mg/ Amitraz
kg b.w. in cats. Dermal LD 50 is 236 325 mg/kg b.w. in
rabbits. An effective antidote is not available but activated Amitraz is a triazapentadiene compound used in flea col-
charcoal, for oral ingestion, has been used. lars of dogs, and is a member of the amidine chemical
family. As an insecticide and acaricide, it exerts toxicity
by inhibiting the activity of the enzyme monoamine oxi-
INSECTICIDES AND OTHER PESTICIDES dase and works as an alpha2-adrenergic receptor agonist.
The cardiac effects of alpha2-adrenergic agonists include
Organophosphates and Carbamates
bradycardia, first- and second-degree AV blockage, and
While insecticides are specifically formulated against diminished cardiac output (Malmasi and Ghaffari, 2010).
insects, pesticides in addition work on plants, weeds and ECGs performed on an English bulldog poisoned with
fungi. Animals by contact or ingestion may develop dan- amitraz showed QT elongation, a precursor to ventricular
gerous cardiac symptoms. arrhythmia. Amitraz apparently lengthened the QT inter-
Pesticides used in agriculture and around the house val by reduction of the heart rate. Thermogenesis was
contain organophosphates (OP) or carbamates. OP and car- also affected. Hypothermia decreased the depolarization
bamates differ, though their effects are similar. Their mode of the pacemaker cells, so that bradycardia ensued (Aslan
of action is similar, as they bind to an active site serine of et al., 2007). The EPA classifies it as Class III, which is
AChE and inhibit its functionality, thus reducing the slightly toxic. The oral LD 50 of amitraz in rats is
availability of AChE so that overstimulation of cholinergic 523 800 mg/kg b.w., .1600 mg/kg for mice, and
system occurs. The inhibitory effect of carbamates on 788 mg/kg b.w., for bobwhite quail.
AChE is shorter than that of OPs. The function of AChE is
to hydrolyze acetylcholine (ACh) to choline and acetic Metaldehyde
acid. Inhibition of AChE results in excessive ACh accumu-
lation in synapses and at neuromuscular junctions, leading The molluscicide metaldehyde, used to kill slugs and snails
to muscarinic and nicotinic ACh receptor associated hyper and for the protection of crops, comes in the form of sprays
cholinergic signs. Carbamates do not age AChE, and pellets. It is toxic when inhaled or ingested. Upon
while some OPs do. Aging refers to the fact that OPs irre- ingestion, mataldehyde is partially hydrolyzed by the acids
versibly inactivate AChE, thereby preventing its normal in the stomach to acetaldehyde, which decreases serotonin
physiological function. in the brain, noradrenaline, and γ-aminobutyric acid (inhib-
OPs are extremely toxic and cause severe electrophys- itory neurotransmitter of the CNS). Severe muscle tremors
iological abnormalities. Acute toxicity of OPs widely ensue. The LD 50 in rats is 227 690 mg/kg b.w., in rabbits
vary in different species, e.g., chlorpyrifos has an LD 50 of 290 1250 mg/kg, and in cats 100 300 mg/kg. Cardiac
32 mg/kg b.w. in chickens, 500 mg/kg b.w. in guinea symptoms (Longstreth and Pierson, 1982) include