Small Animal Toxicology Essentials (Poppenga/Small Animal Toxicology Essentials) || Other Pesticides

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<ul><li><p>137</p><p> 19 Other Pesticides INTRODUCTION A pesticide is defi ned as any substance or mixture of sub-stances intended for preventing, destroying, repelling, or mitigating any pest. A pesticide may be a chemical sub-stance, a biological agent (such as a virus or bacterium), an antimicrobial, a disinfectant, or a device used against any pest. Pests include insects, plant pathogens, weeds, molluscs, birds, mammals, fi sh, parasites, and microbes that destroy property, spread disease, or are a vector for disease or cause a nuisance. Pesticides can be categorized based upon the type of pest they are intended to control (i.e., insecticides, rodenticides, herbicides, fungicides, avi-cides, etc.). There are literally hundreds of different chemi-cals used as pesticides with diverse chemical structures, formulations, and toxicities. Although there are obvious benefi ts to the use of pesticides, there are also potential risks such as potential toxicity to humans and other animals. </p><p> Insecticides and rodenticides are commonly involved in animal intoxications and are discussed in separate chap-ters. This chapter is intended to discuss several other diverse pesticides that have been associated with pet intox-ication; it is not intended to be comprehensive in its scope. Interested readers are referred to an excellent website under the auspices of the National Pesticide Information Center (NPIC) that has a wealth of information on various pesticides: This website has numerous pesticide fact sheets and toxicity informa-tion and a section specifi cally addressing pesticide use on or around animals. The USEPA - sponsored publication entitled Recognition and Management of Pesticide Poi-</p><p>sonings , 5th edition, is a valuable source of information regarding the toxicology and general treatment approaches for a large number of pesticides typically not discussed in veterinary textbooks (Riegart and Roberts 1999 ). The entire manual is available from rmpp.htm. It is important to keep in mind that there is limited species - specifi c toxicity data for many pesticides and that for the majority of pesticides discussed below, treatment of poisoned animals involves appropriate and timely decontamination along with symptomatic and supportive care; specifi c antidotes are typically not available. </p><p> MISCELLANEOUS INSECTICIDES AND REPELLANTS </p><p> Boric Acid and Borates Sources and Formulations Boric acid is formulated as tablets and powders to kill insect larvae in livestock confi nement areas and cock-roaches, ants, and other insects in residences. Powders and tablets scattered on fl oors present a hazard for pets; cats can be exposed by grooming paws after contact with powders spread on fl oors. </p><p> Kinetics and Toxicity Absorption of boric acid from the GI tract is rapid (Welch 2004 ). Following absorption it is found at highest concen-trations in the brain, liver, and kidneys. It is eliminated unchanged by the kidneys with a half - life of 5 to 21 hours. The acute oral LD 50 reported for rats range from 2 to approximately 5 g/kg. Thus, it is considered slightly toxic. </p><p>Small Animal Toxicology Essentials, First Edition. Edited by Robert H. Poppenga, Sharon Gwaltney-Brant. 2011 John Wiley and Sons, Inc. Published 2011 by John Wiley and Sons, Inc.</p><p> Robert H. Poppenga </p></li><li><p>138 Section 3 / Specifi c Toxicants</p><p> Prognosis Most exposures result in rather mild GI signs; in such cases the prognosis is good. With large acute ingestions or chronic exposures, the prognosis is more guarded. </p><p> Diethyltoluamide ( DEET ) Sources and Formulations DEET is a widely used liquid insect repellant suitable for application to skin or fabrics. Products contain a range of concentrations from 5% to 100%. </p><p> Kinetics and Toxicity DEET is well absorbed following dermal or oral exposures (Dorman 2004 ). The amount absorbed increases with increasing concentrations, and the solvents used in many products enhance absorption as well (Riegart and Roberts 1999 ). The clearance of absorbed DEET is rapid with a half - life measured in hours. It is primarily eliminated via the urine. The toxicity of DEET is low with rat oral LD 50 ranging from 1.8 to 2.7 g/kg body weight. Dermal toxicity is also low based on studies in rabbits where single appli-cations of 2 to 4 g/kg did not cause any clinical signs. </p><p> Mechanism of Action The mechanism of toxic action of DEET is unknown. </p><p> Signs Repeated topical exposures can cause dermal and ocular irritation. Clinical signs observed in dogs and cats with suspected acute DEET intoxication include vomiting, tremors, excitation, ataxia, and seizures (Dorman 1990 ). There are no characteristic laboratory fi ndings associated with DEET intoxication. </p><p> Diagnostics Antemortem An antemortem diagnosis relies on a history of exposure (perhaps noticing a residue on skin or hair). Testing for DEET is not widely available, although contacting a vet-erinary diagnostic laboratory might be helpful; detection of residues on hair or in biological specimens only con-fi rms exposure and not necessarily intoxication. </p><p> Postmortem There are no characteristic postmortem fi ndings. </p><p> Management of Exposures Treatment involves standard dermal, ocular, and GI decon-tamination procedures including induction of emesis if early after an oral ingestion, washing skin and hair with </p><p>However, chronic exposure to lower doses is a potential problem. </p><p> Mechanism of Action The mechanism of action of boric acid is unknown, but it is considered to be cytotoxic. </p><p> Clinical Effects The GI tract, vascular system, brain, and kidneys are primary target organs. In acute, single - dose, oral expo-sures, signs include hypersalivation, vomiting, depression, anorexia, diarrhea, and abdominal pain. Depending on the dose ingested, weakness, ataxia, tremors, focal or general-ized seizures, oliguria or anuria, renal tubular nephrosis, and liver damage may occur, although the latter is uncom-mon (Welch 2004 ). Seizures can be followed by metabolic acidosis, depression, coma, and death. Chronic, toxic exposures cause anorexia, weight loss, vomiting, loose stools, rashes, alopecia, anemia, and death. </p><p> Diagnostics Antemortem A history of exposure, occurrence of compatible clinical signs, and possibly the detection of elevated levels of boron in blood, plasma, or urine support a diagnosis. </p><p> Postmortem Signifi cant lesions can be found in target organs such as the GI tract, kidneys, brain, liver, and skin. No lesions are unique to boric acid, but a constellation of lesions might support a diagnosis. Measurement of boron in kidneys and liver might also be helpful to confi rm exposure. </p><p> Management of Exposures Standard decontamination procedures should be followed with suspected exposures. Exposed hair and skin should be washed with mild soap or shampoo and water followed by thorough rinsing. Emetics or cathartics might not be indicated if an animal has already vomited or exhibited diarrhea. Activated charcoal is generally not administered due to poor adsorption of boric acid. Symptomatic and supportive care is often needed. Intravenous balanced electrolyte solutions and glucose are administered as needed. GI protectants and antiemetics might be indicated. Maintaining urine fl ow is important to prevent or correct kidney damage. Although dialysis (hemo - or peritoneal dialysis) might be indicated if renal failure occurs, it does not appear to increase borate clearance. Benzodiazepines can be given to control seizures. </p></li><li><p> Chapter 19 / Other Pesticides 139</p><p>A genetic polymorphism in some breeds of dogs causes a defect in the P - glycoprotein of a multidrug resistant pump (coded for by the MDR1, or ABCB1, gene) in the blood - brain barrier. As a consequence of this defect, the blood - brain barriers of affected dogs do not exclude certain xenobiotics (including the macrolides) from the brain. Additionally, the same P - glycoprotein acts within the intestine to limit absorption of macrolides, so dogs with the MDR1 defect may absorb more drug after ingestion and attain higher blood concentrations of macrolides (Lanusse et al. 2009 ). Higher blood and CNS concentra-tions of macrolide put MDR - 1 defective dogs at risk for toxicosis at dosages of macrolides that are well tolerated by dogs without this genetic polymorphism. However, the doses of macrolides commonly used for heartworm pre-ventative are well below the levels expected to cause clini-cal signs in MDR - 1 defective dogs, and no problems are expected with the monthly heartworm treatments even in affected dogs. Table 19.1 lists the dog breeds that to date have had the MDR1 defect confi rmed through genetic testing. Because this defect is an autosomal recessive trait, only a fraction of dogs within these breeds would be expected to be affected. </p><p> The minimum toxic dose of ivermectin in MDR1 - defective dogs is 100 mcg/kg, which is approximately 16 times higher than the monthly heartworm preventive dose; moxidectin toxicosis has been reported in a collie at 90 mcg/kg (30 times the monthly heartworm preventive dose); milbemycin toxicosis has been reported in MDR1 - defective collies at 5 mg/kg (10 times the monthly heart-worm preventive dose); and selamectin caused ataxia when administered orally to MDR1 - defective collies at 2.5 times the therapeutic dose. In contrast, dogs without the MDR1 defect can generally tolerate ivermectin dosages up to 600 mcg/kg and milbemycin dosages up to 1.6 mg/kg for treatment of ectoparasites (Mealey 2006 ). Based on results in laboratory dogs, the minimum toxic dosage of ivermectin had been reported to be 2.5 mg/kg. A recent review of ivermectin toxicosis in dogs revealed that some </p><p>mild soap and water followed by a thorough rinse, and fl ushing eyes following an ocular exposure. Initially, sei-zures should be treated with a benzodiazepine such as diazepam. Other symptomatic and supportive care is pro-vided as needed. </p><p> Prognosis Most animals with mild DEET intoxication recover uneventfully in several days. </p><p> Macrocyclic Lactone Parasiticides Sources and Formulations Macrocyclic lactone parasiticides (also known as macro-lides ) are compounds used to treat or prevent a variety of parasitic diseases in domestic animals and humans. These products are derived from fermentation products of Strep-tomyces avermitilis and S. cyaneogriseus. They are often referred to as endectocides due to their ability to kill both internal ( endo ) and external ( ecto ) parasites (Lanusse et al. 2009 ). Macrolides include ivermectin, abamectin, dora-mectin, eprinomectin, milbemycin oxime, moxidectin, and selamectin. These products are used for prevention of heartworms in dogs and cats, treatment of feline ear mites, prevention of internal nematode infestation, and manage-ment of a variety of other parasitic diseases such as scabies and infestations of lice (Mealey 2006 ). Several macrolides are used in food animals and horses for the prevention and treatment of internal and external parasites. Abamectin b 1 is a macrocyclic lactone that is present in some household insecticides, in ant and roach bait stations, and in agricul-tural insecticides. Products containing macrolides include tablets, chewable tablets, spot - on products, gels, pour - on liquids, injectable solutions, otic solutions, premixes, and granules. </p><p> Kinetics and Toxicity In general, macrolides are well absorbed orally and some (e.g., selamectin) are also well absorbed dermally (Mealey 2006 ). Many of these compounds are lipophilic, with mox-idectin being the most lipophilic of the group (Lanusse et al. 2009 ). The macrolides have relatively long half - lives due to their wide tissue distribution, lipophilicity (fat storage), extensive biliary, and intestinal secretion and enterohepatic recycling (Lanusse et al. 2009 ). </p><p> The macrolides have a wide margin of safety in mammals due to the fact that they do not cross the blood - brain barrier under normal circumstances (Lanusse et al. 2009 ). Animals with blood - brain barrier defects are at increased risk for toxicosis from doses of macrolides that would not affect animals with intact blood - brain barriers. </p><p> Table 19.1. Breeds known to carry the MDR 1 P - glycoprotein genetic polymorphism </p><p> Collie W ller Longhaired whippet White Swiss shepherd Shetland sheepdog Old English sheepdog Miniature Australian shepherd Border collie Australian shepherd German shepherd dog </p></li><li><p>140 Section 3 / Specifi c Toxicants</p><p>helpful in identifying dogs that are at increased risk for macrolide toxicosis. </p><p> Management of Exposures The goals of managing exposures to macrolides are patient stabilization, decontamination, and supportive care for recumbent animals. In recent ingestions with no serious clinical signs, induction of emesis should be considered. Because of the rapid absorption of macrolides from liquids and gels, if more than 30 to 60 minutes have elapsed from ingestion, it may be more benefi cial to administer acti-vated charcoal. Repeated doses of activated charcoal should be administered to all animals showing more than mild signs in order to try to reduce the half - lives of the macrolides. Animals that become comatose will need intensive nursing care to prevent hypothermia, decubital ulcers, and aspiration. Recently, intravenous lipid solution infusions (ILS) have been used to successfully manage severe macrolide toxicosis (Crandell 2009 ), although anecdotally not all animals appear to respond to this treat-ment modality. </p><p> Prognosis The prognosis depends on the dosage ingested, the MDR1 status of a dog, and the availability of good nursing care to manage comatose animals. Comatose animals surviving more than 24 hours have a reasonable chance of recovery if adequate nursing care is provided. </p><p> FUNGICIDES Fungicides constitute a chemically diverse group of pesti-cides. The risk of intoxication from fungicides is low given use restrictions, available formulations, and low bioavail-ability of these compounds (Osweiler, 1996 ; Riegart and Roberts 1999 ). Many fungicides are formulated as suspen-sions of wettable powders or granules, which prevent rapid and effi cient absorption from sites of exposure. Most pets are likely to be exposed to fungicides as a result of their application to lawns. The reader is referred to several sources for additional information (Gerken 1995 ; Osweiler 1996 ; Riegart and Roberts 1999 ; and Yeary 2000 ; the NPIC website). </p><p> Toxicity Fungicides vary in terms of their acute toxicity. Many are almost nontoxic with rodent LD 50 greater than 0.5 g/kg body weight (Osweiler 1996 ). However, some have relatively low rodent oral LD 50 (e.g., cyclohexamide with a rat LD 50 of 2 mg/kg). The four fungicides listed by Yeary (2000) for lawn use fl utolonil, iprodione, propi-</p><p>individuals are...</p></li></ul>


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