Page 561 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

528 SECTION | VI Insecticides

VetBooks.ir nausea, vomiting, hypersalivation, ataxia, lethargy, seda- liver are more significant and no kidney lesions appear in
mice poisoned by technical amitraz, but that degeneration
tion, CNS and respiratory depression, bradycardia, mydri-
and necrosis develop in the tubular epithelial cells in the
asis, hypotension, and hypothermia are the most common
signs of acute poisoning. It has been reported that geriat- kidneys of the mice poisoned by amitraz-containing
ric animals and those younger than 3 months are more xylene indicates that xylene increases the toxicity of
susceptible. Besides this, it is not recommended to apply amitraz (Filazi et al., 2004).
amitraz to toy breeds such as Chihuahua and Pomeranian, In horses, it was reported that a 3-year-old mare was
and to horses and cats because of species specific suscep- brought to the clinic 2 days after the topical administra-
tibility (Andrade et al., 2006; Bonsall and Turnbull, 1983; tion of a nondiluted veterinary preparation that contains
Cullen and Reynoldson, 1990; Grossman, 1993). 12.5% of amitraz with the complaints of anorexia,
In biochemical analyses, hyperglycemia and increased anxiety, perspiration, nondefecation and anuria, the clini-
liver enzyme (transaminase) activity were detected. cal examination performed revealed depression, pawing,
Amitraz was found to cause damage in the liver by oxida- chewing, ataxia, and moderate abdominal distension
tive stress due to cellular membrane damage (Filazi et al., (Phetudomsinsuk et al., 2014).
1998b). Amitraz and its BTS-27271 were found to inhibit In cattle, it was reported that anorexia, depression,
the secretion of insulin from beta cells of the pancreas scleral congestion, abdominal distension and the loss of
and increase the secretion of glucagon from the alpha pupillary reflexes developed right after the accidental
cells in the Langerhans islets (Abu-Basha et al., 1999) intramuscular administration of a 12.5% amitraz formula-
in vitro. Therefore, clinical signs may worsen in diabetic tion to a 7-year-old cow and a 1-year-old heifer (19 and
animals. It has been reported that amitraz delivered once 10 mL, respectively) (Kizil et al., 2008).
orally to mice leads to a dose-related decrease in hemato- Animals that are not treated may enter a coma or die
crit and hemoglobin values and leukocyte count, a due to respiratory failure. Animals that survive recover
decrease of erythrocyte numbers, and an increase in neu- from nearly all symptoms within 7 10 days even if
trophil and basophil ratios (Filazi et al., 2003). they are exposed to high doses (Bonsall and Turnbull,
Different clinical and necropsy signs are observed by 1983).
amitraz poisoning in dogs. QT interval on the electrocar-
diographic examination of English Bulldogs were found
Chronic Toxicity
to be prolonged in amitraz poisoning (Malmasi and
Ghaffari, 2010). Cortical necrosis and hemorrhages were Amitraz was found to have endocrine disrupting effects
observed in the kidney of a Scottish Terrier breed dog and that cause reproductive and developmental toxicity.
that died from acute kidney failure after drinking a bath- As a α 2 -adrenergic agonist, amitraz attaches to presyn-
ing liquid that contained amitraz (Oglesby et al., 2006). aptic α 2 -adrenergic receptors in the hypothalamus and
In an experimental poisoning induced by intravascular adversely impacts the reproductive system of mammals
administration of 1 mg/kg of amitraz in cats, showed that and inhibits the secretion of noradrenaline and reduces
the blood profile, urea, creatinine, alanine aminotransfer- the secretion of gonadotropin releasing hormone
ase, and aspartate aminotransferase were unaffected, (Altobelli et al., 2001). Some in vivo and in vitro stud-
but sedation, loss of reflexes, hypothermia, bradycardia, ies have confirmed that amitraz is a fertility poison
bradyarrhythmia, hypotension, bradypnea, mydriasis, (Young et al., 2005).
hyperglycemia, hypoinsulinemia, and reduced cortisol According to the studies in mice (Al-Thani et al.,
levels occurred (Andrade et al., 2007). In an experimental 2003) and rats (Omoja et al., 2016), mice were more sus-
study, cats poisoned by external administration of a bath- ceptible to the reproductive toxicity of amitraz than rats.
ing solution containing 0.4% amitraz caused reduced Whereas, in general rats are more sensitive to amitraz tox-
heart and respiratory rates. Although the signs of poison- icity according to the LD 50 values (Table 41.1). Since the
ing in cats started 30 min after the administration of the LD 50 of BTS-27271 is lower in mice than it is in rats, it is
bathing solution that contains amitraz, it was reported predicted that BTS-27271 is more involved in the repro-
that the most critical signs developed within approxi- ductive toxicity of amitraz that amitraz itself.
mately 2 4 h and that it could become difficult to treat European Medicines Agency (EMEA) defined
cats not intervened within this period (Marafon et al., NOAEL dose for developmental toxicity of amitraz as
2010). 1.5 mg/kg/day in general (EMEA, 2004). It has also been
Clinical signs such as depression, ataxia, stupor, and shown that amitraz and its metabolite 2,4-dimethylaniline
coma that occur in amitraz formulations are mainly are teratogenic for frog embryos (Xenopus laevis)(Osano
related to its xylene or propylene oxide content (Jones, et al., 2002). Since the developmental toxicity studies of
1990). Hydropic degeneration and fatty changes in the amitraz have many deficiencies according to the Federal