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The Ve t e ri na ri a n s Gui de t o a c c i d e n t a l r o d e n t i c i d e i n g e s t i o n b y d o g s & c a t s Liphatech, Inc W. Elm Street Milwaukee, WI
The Ve t e ri na ri a n s Gui de t o a c c i d e n t a l r o d e n t i c i d e i n g e s t i o n b y d o g s & c a t s Liphatech, Inc W. Elm Street Milwaukee, WI Common examples of trade names are mentioned in this publication. This does not imply endorsement of these products by either the authors or their respective affiliations. BootHill, FastDraw, FirstStrike, Generation, Maki, Resolv and Rozol are registered trademarks of Liphatech, Inc. (Milwaukee, WI). BlueMax, Borderline, Hombre and Revolver are trademarks of Liphatech, Inc. (Milwaukee, WI). Contrac, Ditrac, Final, Hawk, Jaguar and TomCat are registered trademarks of Bell Laboratories/Motomco (Madison, WI). A-C Formula 90 is a trademark of JT Eaton & Co. Inc. (Twinsburg, OH). Just One Bite is a registered trademark of Farnham Companies, Inc. (Phoenix, AZ). Di-Kill and Ramik are registered trademarks of Neogen Corporation (Lansing, MI). Rodex is a trademark of Neogen Corporation (Lansing, MI). Ratoxin is a registered trademark of Agrium Advanced Technologies RP, Inc. (Brantford, ON). d-con is a registered trademark of Reckitt Benckiser (Parsippany, NJ). Kaput Doom, Kaput and Kaput -D are registered trademarks of Scimetrics LTD. Corporation (Fort Collins, CO). Havoc, Talon -G, Ratak and WeatherBlok XT are registered trademarks of the Syngenta Group Company (Greensboro, NC). Sorexa is a trademark of BASF Corporation (Florham Park, NJ). Multi-Kill is a registered trademark of Woodstream Corporation (Lititz, PA). Brigand is a trademark of AB Bait Company (Bethlehem, PA). Ratimor is a registered trademark of Unichen d.o.o. (Slovenia). Bitrex is a registered trademark of McFarlan Smith (Scotland). NOTE: The information in this brochure does not represent labeling and does not replace information on rodenticide labels relating to exposure of non-target species to anticoagulants. Please read and follow all label directions on all rodenticide products. A complete version of this guide is available online at Liphatech, Inc W. Elm Street Milwaukee, WI Revised: April, 2013 Preface This brochure addresses the problem of accidental rodenticide ingestion by dogs and cats. It is intended to be of help to veterinarians faced with treating rodenticide-poisoned animals and is based on the research and experience of leading experts in the fields of rodent control and veterinary science. This revision of the guide includes new brands in the marketplace and additional toxicity information. Despite efforts by all parties concerned to reduce the risk of accidental poisonings by improving product labels, packaging and use patterns, such incidents continue to occur. The US Environmental Protection Agency now requires rodenticides marketed to consumers to be pre-packaged with tamper-resistant bait stations [32], which is expected to significantly reduce the potential for exposure to both children and pets. The new EPA rules also limit the types of rodenticide that may be sold to consumers, which is intended to further reduce the risks to children and pets, and also the potential risk to non-target wildlife from primary exposure (direct eating of bait) or secondary exposure (feeding on poisoned or dead rodents). Even with these precautions, veterinarians will continue to play a vital role in case diagnosis and saving animals exposed to rodenticides. Recent work indicates that multiple exposures to anticoagulant rodenticides, over the course of multiple days, result in greater toxicity than is reflected by the standard single-dose acute oral toxicity LD 50 test [33]. Veterinarians should consider this factor, especially for secondary exposure to dogs, cats and wildlife. Even though the amount of rodenticide contained in a poisoned rodent is small, repeated consumption over a prolonged period may result in toxicity to the predator or scavenger. This brochure is intended to help veterinarians understand the differences in toxic action between the various active ingredients. Tables 1 and 2 (pages 2 & 3) compare the acute toxicities of first- and second-generation anticoagulant rodenticides for dogs and cats. A table is also included outlining recommendations for treatment of rodenticide poisoning. This edition includes updated active ingredient trade names in the tables and corresponding footnotes to better reflect brands now found in the marketplace. Preparation of the first edition of the Vet Guide would not have been possible without special input from W. Jean Dodds, D.V.M. and Stephen C. Frantz, Ph.D. who served as Chief of Laboratory of Hematology and Rodent & Bat Specialist, Wadsworth Center for Laboratories and Research, New York State Department of Health (NYSDH) respectively at the time of these studies. Dr. Dodds received many awards for excellence in the field of veterinary medicine and has published more than 150 papers in the field of blood disorders. Dr. Frantz conducted research and taught rodent behavioral ecology and integrated pest management in the United States and abroad. He was technical consultant for Center for Disease Control s (CDC) Federal Rat Evaluation Laboratory. Drs. Dodds and Frantz have also conducted research on poisoning of animals by anticoagulant rodenticides; the clinical data and recommendations reported here are drawn largely from their work. We also wish to express our appreciation to those people who have reviewed this brochure and for their valuable comments, including R. O. Baker, R.A. Green, P.L. Hegdal, W.W. Jacobs, R.E. Marsh, M.E. Mount and V. Perman. Special credit is due Keith Story for his overall guidance and editorial input. We d also like to acknowledge Dr. Cheryl Roge for her expertise and assistance with the most recent updates to this guide. Liphatech, Inc. has sponsored the production of this brochure as a service to veterinarians. As a leading developer and marketer of first- and second-generation anticoagulant rodenticides, as well as other rodent control products, we are committed to helping achieve effective and safe rodent control worldwide. By providing this information to veterinarians, we hope it will help maintain the good safety record, not only for our innovative rodenticides, but for all anticoagulants. While veterinary skills, if applied in time, can prevent most animal deaths, we recognize our responsibility to continue product improvements and user education aimed at minimizing exposure incidents. We thank everyone who, through their guidance and research efforts, made this brochure possible. 1 Table 1 Acute Oral Toxicities (LD 50 ) of Anticoagulant Rodenticides to Dogs Generic Name LD 50 of Usual % Quantity of Bait Source of Data (Active Trade Name a ) Active Ingredient Active Ingredient to Give LD 50 in for LD 50 Info (mg/kg) b in Bait 10 kg (22 lb) Dog (see Endnotes) brodifacoum (d-con, Final, Havoc, Jaguar, Ratak, Talon -G, Weatherblok XT) bromadiolone (BootHill, Brigand TM, Contrac, Hawk, Just One Bite, Kaput Doom, Maki, Ratimor, Ratoxin, Resolv, Revolver TM ) g (1.8 oz) 4, 5, c to g (25.4 oz) d ,200 g (77.6 oz) 2, to ,000 g (141.1 oz) 30 chlorophacinone ,000 g (352.7 oz) 29 (A-C Formula 90 TM, to 22 Borderline, Rozol ) ,000 g (705.5 oz) 29 difenacoum ,000 g (352.7 oz) 19 (Di-Kill, Multi-Kill, Sorexa ) difethialone 1,600 g (56.4 oz) (BlueMax, d-con, to 17 FastDraw, FirstStrike, ,720 g (166.5 oz) 31 Generation, Hombre ) diphacinone g (6.2 oz) 21 (Ditrac, Kaput -D, to 18, 27, 29 Ramik, TomCat ) ,000 g (105.8 oz) 6, 9, 23 warfarin 800 g (28.2 oz) 7, 8, 20, 28 (Kaput, Rodex ) e to 2,000 g (70.5 oz) Table 1 Footnotes a. See the inside of the front cover for additional information regarding trademark ownership and affiliation. b. Underscored LD 50 range used in calculating Quantity of Bait to Give LD 50 in 10 kg Dog. c. This active ingredient is also available in.0025 (100 g to 1,440 g to reach LD 50 in 10 kg dog.) d. This is derived from a study which was not designed to obtain an LD 50. e. This LD 50 range was originally established by the U.S. Fish and Wildlife Service, Table 2 Acute Oral Toxicities (LD 50 ) of Anticoagulant Rodenticides to Cats Generic Name LD 50 of Usual % Quantity of Bait Source of Data (Active Trade Name a ) Active Ingredient Active Ingredient to Give LD 50 in for LD 50 Info (mg/kg) b in Bait 2 kg (4.4 lb) Cat (see Endnotes) brodifacoum (d-con, Final, Havoc, Jaguar, Ratak, Talon -G, Weatherblok XT) bromadiolone (BootHill, Brigand TM, Contrac, Hawk, Just One Bite, Kaput Doom, Maki, Ratimor, Ratoxin, Resolv, Revolver TM ) c 1,000 g (35.3 oz) 3, 5, d ,000 g (35.3 oz) 1 chlorophacinone (A-C Formula 90 TM, unknown Borderline TM, Rozol ) difenacoum (Di-Kill, Multi-Kill, Sorexa ) ,000 g (141.0 oz) 19 difethialone (BlueMax, d-con, ,280 g (45.2 oz) 25 FastDraw, FirstStrike, Generation, Hombre ) diphacinone g (7.1 oz) 6, 9, 23 (Ditrac, Kaput -D, to 3 Ramik, TomCat ) 600 g (21.2 oz) warfarin 5-50 e 20 g (0.71 oz) 7, 10 (Kaput, Rodex ) to ,400 g (84.7 oz) Table 2 Footnotes a. See the inside of the front cover for additional information regarding trademark ownership and affiliation. b. Underscored LD 50 range used in calculating Quantity of Bait to Give LD 50 in 2 kg Cat. c. This active ingredient is also available in.0025 (2,000 g to reach LD 50 in 2 kg cat.) d. This figure is actually the maximum tolerated oral dosage (MTD). e. Cats are generally regarded as being as susceptible as dogs to warfarin. The range of LD 50 may be partly explained by increased susceptibility to poisoning during estrus (Spencer, 1950). 3 Recommendations for Treatment The principles of treatment and management of anticoagulant rodenticide poisoning are summarized in the table below. Basically, once blood samples have been collected for the requisite diagnostic tests, the affected animal should receive a parenteral injection of vitamin K 1. This form of the vitamin is preferred because vitamin K 3 has little or no effect for the acute stages of poisoning [26]. Also, vitamin K 1 should not be given intravenously, as the manufacturer's insert clearly recognizes the hazard of anaphylaxis from intravenous use of this product. On numerous occasions, the authors have been informed of situations where anaphylaxis was associated with intravenous vitamin K 1. Treatment with vitamin K 1 should continue for up to 4-6 weeks unless laboratory monitoring of coagulation shows that values have returned to normal limits sooner. In cases where the toxicant is known to be warfarin rather than generically referred to as such, vitamin K 1 supplementation is usually needed for up to 5-7 days. However, when identity of the toxicant is unknown, it is prudent to assume that one of the more toxic, longer-lasting products is involved. The dosage of vitamin K 1 given should generally not exceed 1 mg/lb/day, or at least should be given cautiously if higher doses are deemed necessary [11]. Doses exceeding 2 mg/lb/day may be dangerous and have been shown recently to induce Heinz body hemolytic anemia [12]. In our extensive experience with the monitoring and treatment of rodenticide poisoning cases, we have not had to exceed 1 mg/lb/day of vitamin K 1 for successful control of bleeding [11]. This regimen is about half the dosage recommended by Mount and Feldman [26, 27]. Regardless of the anticoagulant involved, it is important to initiate therapy promptly. When the product has not been identified, as frequently occurs, it is necessary to follow the regimen of prolonged treatment outlined in the table below to avoid relapse and to reduce the overall cost to the client. For severely poisoned cases, bleeding may have caused serious anemia and therefore also necessitates one or more transfusions with fresh compatible whole blood. In addition to transfusions, where animals have bled in the pulmonary, pleural or pericardial cavities, surgical intervention may be necessary to remove blood to give space for lung or cardiac function. Once the poisoned animals are under treatment and are recovering, it is important to keep them quiet, confined and on a softened diet, for another 2-7 days (depending on the toxicant involved) to minimize hemorrhage in locations such as the central nervous system. As vitamin K 1 replenishes circulating clotting factors in a time course consonant with their respective synthetic halflives, it takes several days for severely depleted animals to resynthesize these factors and no longer be at risk for bleeding complications. Treatment of Rodenticide Poisoning Therapy Dosage Comments Vitamin K 1 Parenteral initial dose*, not to exceed 1 mg/lb/day, and followed by the same parenteral or oral dosage for another six days. Reduce to ½ mg/lb/day for the second week and then reduce by ½ for another two weeks. After 1 month of treatment dosage is continued 2-3 times a week for another 2 weeks. Six weeks of therapy needed to correct longterm effects of the more potent products. If less toxic anticoagulants are known to be involved or monitoring of coagulation tests shows return to normal values sooner, the length of treatment can be reduced accordingly. Whole blood transfusions Compatible fresh blood given at 5-7 cc/lb body weight, if needed in severe cases. The blood should be fresh to ensure the activity of clotting factors, which are labile on storage. * Given subcutaneously and not intravenously (see above). 4 Endnotes 1. ANONYMOUS. (Undated). Maki bromadiolone. Rodenticide technical bulletin. Chempar Chemical Co. Inc., New York, NY. 9pp. 2. ANONYMOUS. (Undated). Rozol and Maki, Chempar Rodent Control Products. Chempar Chemical Co. Inc., New York, NY. 11pp. 3. ANONYMOUS. (Undated). Klerat, ICI Public Health Products. ICI Surrey, England. 39pp. 4. ANONYMOUS. (Undated). Talon technical information: for experimental use only. ICI Americas Inc., Goldsboro, NC. 4pp. 5. ANONYMOUS Talon rodenticide technical information: for experimental use only. ICI Americas Inc., Wilmington, DE. 4pp. 6. ANONYMOUS Rodent eradication and poisoning programs. U.S. Dept. H.E.W., P.H.S., CDC, Atlanta, GA. 83pp. 7. ANONYMOUS U.S.D.I. Fish and Wildlife Service, Denver, CO. Special report, BENTLEY, E.W. and Y. LARTHE The comparative rodenticidal efficiency of five anticoagulants. Journal of Hygiene, 57(2): BROOKS, J.E Properties, uses and hazards of common rodenticides. NYS Dept. Health, Albany, NY, 10pp. 10. BUCK, W.B., G. D. OSWEILER and G.A. VAN GELDER Clinical and diagnostic veterinary toxicology, 2nd Edition. Kendall/Hunt Publishing Co., Dubuque, IA. pp DODDS, W.J. and S.C. FRANTZ Dog and cat poisonings. Pest Control Technology, 12(3): FERNANDEZ, F.R., A.P. DAVIES, D.J. TEACHOUT, A. KRAKE, M.M. CHRISTOPHER and V. PERMAN Vitamin K-induced Heinz body formation in dogs. Journal of American Animal Hospital Association, 20: GODFREY, M.E.R., T.C. REID and H.J.F. McALLUM The oral toxicity of brodifacoum to rabbits. N.Z. Journal of Experimental Agriculture, 9: GRAND, M Experimental data on a new anticoagulant raticide: bromadiolone. Phytiatrie-Phytopharmacie, 25: HADLER, M.R Brodifacoum a potent new rodenticide. Proceedings Fifth British Pest Control Conference, Stratford-upon-Avon, England. September 26-29, pp HAGAN, E.C. and J.L. RADOMSKI The toxicity of 3- (acetonylbenzyl)-4-hydroxycoumarin (warfarin) to laboratory animals. Journal of American Pharmaceutical Association. 52(6): HARLING, R., P. BUFORD, and S. FREYER LM2219 (difethialone) oral toxicity study in beagle dogs (13 weeks). Huntindon Research Center, UK. Unpublished study. 18. HAZELTON LABORATORIES Inc Report on diphacinone (2- diphenylacetyl-1,3-indandione). Hazelton Laboratories Inc., Falls Church, VA, April 19, I.N.D.I.A. Industrie Chimiche Technical Data Sheet for NOCURAT WAX BLOCKS undated. 20. KAUKEINEN, D.E Experimental rodenticide (Talon) passes lab tests; moving to field trials in pest control industry. Pest Control 46(1): KOSMIN, M. and J.N. BARLOW Rodent control using a novel formulation of diphacinone, Ramik. Proceedings First Afro-Asian Vertebrate Pest Congress. Nov. 8-11, Cairo, Egypt. 7pp. 22. LABE, J. and G. LORGUE Intoxication des carnivores domestiques par les raticides anticoagulants. pp Notes de Toxicologie Veterinaire, No. 3. Centre d'informations Toxicologiques Veterinaire, Ecole Nationale Veterinaire, Marcy L'Etoile, France. 23. LISELLA, F.S., K.R. LONG and H.G. SCOTT Toxicology of rodenticides and their relationship to human health. Part II, Journal of Environmental Health, 33(4): LORGUE, G Bromadiolone toxicity in the dog: an antidotal therapy in the intoxicated dog. Laboratory of Toxicology, Ecole National Veterinaire de Lyon and Lyonnaise Industrielle Pharmaceutique, Lyon, France. 25. LORGUE, G Acute oral toxicity study of LM2219 (difethialone) in cats. Ectoxicology Laboratory (INRA-ENVL), National Veterinary School, Lyon, France. Unpublished study. 26. MOUNT, M.E. and B.F. FELDMAN Vitamin K and its therapeutic importance. Journal of American Veterinary Medical Association, 180: MOUNT, M.E. and B.F. FELDMAN Mechanism of diphacinone rodenticide toxicosis in the dog and its therapeutic implications. American Journal of Veterinary Research, 44: PAPWORTH, D.S A review of the dangers of warfarin poisoning to animals other than rodents. Royal Society of Health Journal, 78: RAMPAUD, M Toxicologie des raticides. Conference Prononcee en Novembre 1981 au Collogue de Moulins (Allier) POCHE, R.M Rodent tissue residue and secondary hazard studies with bromadiolone. Bull. OEPP/EPPO Bull. 18: U.S. ENVIRONMENTAL PROTECTION AGENCY Potential Risks of Nine Rodenticides to Birds and Nontarget Mammals: a Comparative Approach. 23pp. 32. U.S. ENVIRONMENTAL PROTECTION AGENCY Risk Mitigation Decision for Ten Rodenticides. Dated May 28, pp. 33. VYAS, N.B., AND RATTNER, B.A Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides. Human and Ecological Risk Assessment 18: Additional Sources ANONYMOUS. (Undated). Technical report on chlorophacinone (approved name). Lipha Laboratories, Lyon, France. 72pp. DODDS, W.J Von Willebrand's disease in dogs. Modern Veterinary Practice, 95: EBELING, W Urban entomology. University of California Press, Berkeley. 695pp. HOUPT, K., J.C. ZGODA and C.C. STAHLBAUM Use of taste repellents and emetics to prevent accidental poisoning of dogs. American Journal of Veterinary Research, 45: KECK, P Diagnostic analytique et traitement des intoxications des carnivores. Department of Pharmacology and Toxicology, National Veterinary School, Lyon, France. 19(2): PLESTINA, R Prevention, diagnosis and treatment of insecticide poisoning. WHO/VBC/ SPENCER, H. J U.S.D.I. Report of Activities, Wildlife Research Laboratory, Denver, CO. 1st Quarter, 12. 5 Liphatech Professional Rodent Control Products FirstStrike A revolutionary concept in rodenticides providing outstanding palatability. Excellent for high infestation areas, or whenever you need your bait to work. Available in a soft bait formulation. Contains difethialone (25 ppm), a single-feed, second-generation anticoagulant. High rodent acceptance, even when competing food is available. Contains no wax, enhancing its palatability to rats and mice. Resolv The everyday baiting solution. A soft bait formulation that provides superior palatability and a low cost per placement when compared to traditional blocks. Contains bromadiolone, a single-feed, second-generation anticoagulant. Contains no wax, enhancing palatability to rats and mice. Doesn t melt in hot temperatures. Generation Specially formulated to be highly palatable to rats and mice. Generation is offered in mini blocks, bulk pellets, and pellet place pack formulations. Contains difethialone (25 ppm), a single-feed, second-generation anticoagulant. Best block for palatability; active ingredient is almost non-detectable by rodents. Whole grains combined with less wax and dye contribute to bait attractiveness. BlueMax TM A low crumb/low scatter bait with mold protection perfect for the stringent requirements of food processing and com
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