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Evaluation of a novel rodenticide: acute sub-lethal effects of a methaemoglobin-inducing agent

Published online by Cambridge University Press:  01 January 2023

RJ Quy
Affiliation:
Animal and Plant Health Agency, York, UK
TJ Gibson*
Affiliation:
Department of Production and Population Health, Royal Veterinary College, University of London, UK
MS Lambert
Affiliation:
Animal and Plant Health Agency, York, UK
CT Eason
Affiliation:
Lincoln University and Connovation Research Ltd, Auckland, New Zealand
NG Gregory
Affiliation:
Department of Production and Population Health, Royal Veterinary College, University of London, UK
*
* Contact for correspondence and requests for reprints: [email protected]

Abstract

In a series of experiments the welfare of para-aminovalerophenone (PAVP) sub-lethally poisoned rats (Rattus norvegicus) was assessed. The experiments: (i) examined the acute methaemoglobin (MetHb) profile over time; (ii) refined the LD50 estimate for PAVP in adult female rats; (iii) developed and validated three neurological tests; and (iv) assessed rats for neurological deficit following prolonged methaemoglobinaemia. The results from the first three experiments were used to refine the sub-lethal study. In the sub-lethal experiment 20 rats were gavaged with a single dose of 40 mg kg−1 PAVP (based on an LD50 estimate of 43.3 mg kg−1). Control rats (n = 10) were treated with the carrier only. Eleven (surviving) PAVP-treated rats and controls were assessed over a two-week period. Rats were tested for forelimb grip strength, stability on an inclined plane and the ability to remove tape wrapped around a forepaw in order to determine deficits in motor functions and sensorimotor integration. Signs of recovery began 3-6 h post-dosing, with all animals showing no outward signs of poisoning within 48 h, and over the 14-day post-treatment monitoring period they gained weight and increased their food consumption. There was no significant overall difference in performance between PAVP-treated and control rats in any of the three neurological tests. In the inclined plane test, performance of sub-lethally PAVP-poisoned rats appeared to be temporarily impaired with treated animals slipping at a lower angle than controls on day two. During the tape removal test, four PAVP-treated rats failed to remove the tape within the 3-min time limit on one occasion each (4/77 occasions) up to seven days post-dosing. The severity and duration of signs following acute sub-lethal PAVP poisoning appeared to be lower than those reported for existing rodenticides. It is likely that the results presented in this study extend to other MetHb-inducers.

Type
Research Article
Copyright
© 2015 Universities Federation for Animal Welfare

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References

Albertsmeier, M, Teschendorf, P, Popp, E, Galmbacher, R, Vogel, P and Böttiger, BW 2007 Evaluation of a tape removal test to assess neurological deficit after cardiac arrest in rats. Resuscitation 74: 552558. http://dx.doi.org/10.1016/j.resuscitation.2007.01.040CrossRefGoogle ScholarPubMed
Aronowski, J, Samways, E, Strong, R, Rhoades, HM and Grotta, JC 1996 An alternative method for the quantitation of neuronal damage after experimental middle cerebral artery occlusion in rats: analysis of behavioral deficit. Journal of Cerebral Blood Flow and Metabolism 16: 705713. http://dx.doi.org/10.1097/00004647-199607000-00022CrossRefGoogle ScholarPubMed
Baskin, SI and Fricke, RF 1992 The pharmacology of p-aminopropio-phenone in the detoxification of cyanide. Cardiovascular Drug Reviews 10:358375. http://dx.doi.org/10.1111/j.1527-3466.1992.tb00256.xCrossRefGoogle Scholar
Bentley, EW 1958 Biological methods for the evaluation of rodenticides. Technical Bulletin No 8. HMSO: London, UKGoogle Scholar
Bright, JE, Woodman, AC, Marrs, TC and Wood, SG 1987 Sex differences in the production of methaemoglobinaemia by 4-aminopropiophenone. Xenobiotica 17: 7983. http://dx.doi.org/10.3109/00498258709047177CrossRefGoogle ScholarPubMed
CRD 2012 Humaneness for vertebrate control agents. Chapter 9, Data Requirements Handbook v 2.2. Chemicals Regulation Directorate, Health & Safety Executive: York, UKGoogle Scholar
Dieke, SH and Richter, CP 1946 Comparative assays of roden-ticides on wild Norway rats I. Toxicity. Public Health Reports 61:672679. http://dx.doi.org/10.2307/4585662CrossRefGoogle Scholar
Durie, RH and Doull, J 1968 Factors influencing the toxicity of para-aminopropiophenone in rats. Pharmacologist 10: 172Google Scholar
Eason, C, Ogilvie, S, Miller, A, Henderson, R, Shapiro, L, Hix, S, MacMorran, D and Murphy, E 2008 Smarter pest control tools with low-residue and humane toxins. In: Proceedings of the Vertebrate Pest Conference 23: 148153. 17-20 March 2008, University of California, Davis, USACrossRefGoogle Scholar
Eason, C, Ross, J, Blackie, H and Fairweather, A 2013 Toxicology and ecotoxicology of zinc phosphide as used for pest control in New Zealand. New Zealand Journal of Ecology 37: 111Google Scholar
EPPO 1982 Guidelines for the biological evaluation of rodenticides: No.1 - Laboratory tests for evaluation of the toxicity and acceptability of rodenticides and rodenticide preparations. European and Mediterranean Plant Protection Organization: Paris, FranceGoogle Scholar
Fisher, P, Beaulsoeil, NJ, Warburton, B and Mellor, DJ 2010 How humane are our pest control tools? MAF Biosecurity New Zealand Technical Paper No: 2011/01. Ministry of Agriculture and Forestry: Wellington, New ZealandGoogle Scholar
Fisher, P and O’Connor, C 2007 Oral toxicity of p-aminopro-piophenone to ferrets. Wildlife Research 34: 1924. http://dx.doi.org/10.1071/WR06125CrossRefGoogle Scholar
Fisher, P, O’Connor, CE and Morriss, G 2008 Oral toxicity of p-aminopropiophenone to brushtail possums (Trichosurus vulpecu-la), dama wallabies (Macropus eugenii), and mallards (Anas platyrhynchos). Journal of Wildlife Diseases 44: 655663. http://dx.doi.org/10.7589/0090-3558-44.3.655Google ScholarPubMed
Fisher, PM, O’Connor, CE and Murphy, EC 2005 Acute toxi-city of p-aminopropiophenone to stoats (Mustela erminea). New Zealand Journal of Zoology 32: 163169. http://dx.doi.org/10.1080/03014223.2005.9518409Google Scholar
Gibson, TJ, Quy, RJ, Eason, CT and Gregory, NG 2015 Evaluation of a novel rodenticide: welfare assessment of fatal methaemoglobinaemia in adult rats (Rattus norvegicus). Animal Welfare 24: 417425. http://dx.doi.org/10.7120/09627286.24.4.417CrossRefGoogle Scholar
Greaves, JH, Redfern, R and Tinworth, H 1974 Laboratory tests of 5-p-chlorophenyl silatrane as a rodenticide. Journal of Hygiene 73: 3943. http://dx.doi.org/10.1017/S0022172400023810CrossRefGoogle ScholarPubMed
Gunja, N, Coggins, A and Bidny, S 2011 Management of intentional superwarfarin poisoning with long-term vitamin K and brodifacoum levels. Clinical Toxicology 49: 385390. http://dx.doi.org/10.3109/15563650.2011.587126Google ScholarPubMed
Hall, AH, Kulig, KW and Rumack, BH 1986 Drug- and chem-ical-induced methaemoglobinaemia clinical features and manage-ment. Medical Toxicology 1: 253260CrossRefGoogle Scholar
Hood, GA 1972 Zinc phosphide – a new look at an old rodenti-cide for field rodents. Proceedings of the Vertebrate Pest Conference 5: 85-92. 7-9 March 1972, University of California, Davis, USAGoogle Scholar
Huckle, KR, Hutson, DH, Logan, CJ, Morrison, BJ and Warburton, PA 1989 The fate of the rodenticide flocoumafen in the rat: retention and elimination of a single oral dose. Pesticide Science 25: 297312. http://dx.doi.org/10.1002/ps.2780250310CrossRefGoogle Scholar
Hui, C, Lie, A, Lam, C and Bourke, C 1996 ‘Superwarfarin’ poi-soning leading to prolonged coagulopathy. Forensic Science International 78: 1318. http://dx.doi.org/10.1016/0379-0738(95)01835-2CrossRefGoogle Scholar
Laakso, S, Suomalainen, K and Koivisto, S 2010 Literature review on residues of anticoagulant rodenticides in non-target animals. Nordic Council of Ministers: Copenhagen, DenmarkGoogle Scholar
Littin, KE, O’Connor, CE, Gregory, NG, Mellor, DJ and Eason, CT 2002 Behaviour, coagulopathy and pathology of brush-tail possums (Trichosurus vulpecula) poisoned with brodifacoum. Wildlife Research 29: 259267. http://dx.doi.org/10.1071/WR01068CrossRefGoogle Scholar
Lubics, A, Reglödi, D, Tamás, A, Kiss, P, Szalai, M, Szalontay, L and Lengvári, I 2005 Neurological reflexes and early motor behaviour in rats subjected to neonatal hypoxic-ischemic injury. Behavioural Brain Research 157: 157165. http://dx.doi.org/10.1016/j.bbr.2004.06.019CrossRefGoogle ScholarPubMed
Marks, CA, Gigliotti, F, Busana, F, Johnston, M and Lindeman, M 2004 Fox control using a para-aminopropiophenone formulation with the M-44 ejector. Animal Welfare 13: 401407Google Scholar
Mason, G and Littin, KE 2003 The humaneness of rodent pest control. Animal Welfare 12: 137Google Scholar
McGraw, KO and Wong, SP 1996 Forming inferences about some intraclass correlation coefficients. Psychological Methods 1:3046. http://dx.doi.org/10.1037/1082-989X.1.1.30CrossRefGoogle Scholar
Meyer, OA, Tilson, HA, Byrd, WC and Riley, MT 1979 A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehavioral Toxicology 1: 233236Google ScholarPubMed
Morgan, DR and Milne, L 2002 Cholecalciferol-induced bait shy-ness in possums (Trichosurus vulpecula). International Journal of Pest Management 48: 113119. http://dx.doi.org/10.1080/09670870110096592CrossRefGoogle Scholar
Murphy, EC, Shapiro, L, Hix, S, MacMorran, D and Eason, CT 2011 Control and eradication of feral cats: field trials of a new toxin. Island Invasives: Eradication and Management pp 213216. IUCN: Gland, SwitzerlandGoogle Scholar
Pan, HP, Savarie, PJ, Elias, DJ and Felton, RR 1983 Alkyl chain length and acute oral toxicity of p-aminophenones. General Pharmacology 14: 465467. http://dx.doi.org/10.1016/0306-3623(83)90032-0CrossRefGoogle ScholarPubMed
Prescott, CV, El-Amin, M and Smith, RH 1992 Calciferols and bait shyness in the laboratory rat. Proceedings of the Vertebrate Pest Conference 15: 218223. 3-5 March 1992, University of California, Davis, USAGoogle Scholar
PSD (Pesticide Safety Directorate) 1997 Assessment of Humaneness of Vertebrate Control Agents: Evaluation of Fully Approved or Provisionally Approved Products, No 171 (December 1997). Pesticides Safety Directorate: York, UKGoogle Scholar
Quy, RJ, Cowan, DP, Haynes, P, Inglis, IR and Swinney, T 1992 The influence of stored food on the effectiveness of farm rat con-trol. In: Proceedings of the Brighton Crop Protection Conference – Pests and Diseases pp 291300. 23-26 November 1992, Brighton, UKGoogle Scholar
Quy, RJ, Cowan, DP, Haynes, P, Inglis, IR and Swinney, T 1994 Predicting the outcome of rodenticide trials against Norway rats living on farms. Proceedings of the Vertebrate Pest Conference 16: 133137. 1-3 March 1994, University of California, Davis, USAGoogle Scholar
Quy, RJ, Cowan, DP and Lambert, MS 2003 Adapting baiting tactics to match the foraging behaviour of Norway rats: a balance between efficacy and safety. In: Singleton, GR, Hinds, LA, Krebs, CJ and Spratt, D (eds) Rats, Mice and People: Rodent Biology and Management pp 451456. Australian Centre for International Agricultural Research Monograph: Canberra, ACT, AustraliaGoogle Scholar
Reglödi, D, Tarnás, A and Lengvári, I 2003 Examination of sen-sorimotor performance following middle cerebral artery occlusion in rats. Brain Research Bulletin 59: 459466. http://dx.doi.org/10.1016/S0361-9230(02)00962-0CrossRefGoogle Scholar
Rennison, D, Conole, D, Tingle, MD, Yang, J, Eason, CT and Brimble, MA 2013 Synthesis and methemoglobinemia-inducing properties of analogues of para-aminopropiophenone designed as humane rodenticides. Bioorganic & Medicinal Chemistry Letters 23:66296635. http://dx.doi.org/10.1016/j.bmcl.2013.10.046CrossRefGoogle ScholarPubMed
Rivlin, AS and Tator, CH 1977 Objective clinical assessment of motor function after experimental spinal cord injury in the rat. Journal of Neurosurgery 47: 577581. http://dx.doi.org/10.3171/jns.1977.47.4.0577CrossRefGoogle ScholarPubMed
Ross, JG and Henderson, RJ 2006 Micro-encapsulated zinc phosphide for the control of the brushtail possum (Trichosurus vulpecula) in New Zealand: An old poison finding new favour. Advances in Vertebrate Pest Management 4: 211224Google Scholar
Saverie, PJ, Pan, HP, Hayes, DJ, Roberts, JD, Dasch, GJ, Felton, R and Schafer, EW Jr 1983 Comparative acute toxicity of para-aminopropiophenone (PAPP) in mammals and birds. Bulletin of Environmental Contamination and Toxicology 30: 122126. http://dx.doi.org/10.1007/BF01610109CrossRefGoogle Scholar
Scawin, JW, Swanston, DW and Marrs, TC 1984 The acute oral and intravenous toxicity of p-aminopropiophenone (PAPP) to laboratory rodents. Toxicology Letters 23: 359365. http://dx.doi.org/10.1016/0378-4274(84)90034-1CrossRefGoogle ScholarPubMed
Schallert, T and Whishaw, IQ 1984 Bilateral cutaneous stimu-lation of the somatosensory system in hemidecorticate rats. Behavioral Neuroscience 98: 518540. http://dx.doi.org/10.1037/0735-7044.98.3.518CrossRefGoogle Scholar
Sharp, T and Saunders, G 2011 A model for assessing the relative humaness of pest animal control methods, Second Edition. Australian Government Department of Agriculture, Fisheries and Forestry: Canberra, ACT, AustraliaGoogle Scholar
Shrout, PE and Fleiss, JL 1979 Intraclass correlations: uses in assessing rater reliability. Psychological Bulletin 86: 420428. http://dx.doi.org/10.1037/0033-2909.86.2.420CrossRefGoogle ScholarPubMed
Vandenbelt, JM, Pfeiffer, C, Kaiser, M and Sibert, M 1944 Methemoglobinemia after administration of p-aminoacetophe-none and p-aminopropiophenone. Journal of Pharmacology and Experimental Therapeutics 80: 3138Google Scholar
Witmer, G, Eisemann, JD and Howald, G 2007 The use of rodenticides for conservation efforts. In: Proceedings of the Wildlife Damage Management Conference 12: 160167. 9-12 April 2007, University of Nebraska, Lincoln, USAGoogle Scholar
Yonemori, F, Yamaguchi, T, Yamada, H and Tamura, A 1998 Evaluation of a motor deficit after chronic focal cerebral ischemia in rats. Journal of Cerebral Blood Flow and Metabolism 18: 10991106. http://dx.doi.org/10.1097/00004647-199810000-00006CrossRefGoogle ScholarPubMed