Register      Login
Wildlife Research Wildlife Research Society
Ecology, management and conservation in natural and modified habitats
RESEARCH ARTICLE (Open Access)

Apparent resistance to brodifacoum in Rattus rattus in a New Zealand site with no history of anticoagulant-based rodent control

Suman P. K. Sran https://orcid.org/0000-0002-9657-9138 A * , Brett G. Gartrell https://orcid.org/0000-0002-8062-9313 B , Penny Fisher C and Doug P. Armstrong A
+ Author Affiliations
- Author Affiliations

A Wildlife Ecology Group, School of Agriculture and Environment, Massey University, PB 11222, Palmerston North, New Zealand.

B School of Veterinary Science, Massey University, PB 11222, Palmerston North, New Zealand.

C Research Associate, Landcare Research, Lincoln 7608, New Zealand.

* Correspondence to: S.sran@massey.ac.nz

Handling Editor: Steven Belmain

Wildlife Research 50(1) 28-38 https://doi.org/10.1071/WR21064
Submitted: 7 July 2020  Accepted: 16 April 2022   Published: 7 July 2022

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

Context: Anticoagulants have been used in New Zealand for decades, but few data are available on the sustainability of these toxins for rodent control. It is important to regularly monitor for resistance in long-term brodifacoum-use areas and establish a database for future references.

Aims: This study aimed to estimate the effective dose (ED50) of brodifacoum for ship rats from an area of New Zealand with no history of brodifacoum use, in order to establish a blood-clotting response test for assessing resistance in rodent populations from other areas.

Methods: A ranging study was conducted whereby successive groups of ship rats were administered brodifacoum doses that were increased or decreased progressively, until an International Normalised Ratio (INR) of 3.6 was reached. Linear regression was used to model the relationship between dose and INR, and ED50 dose was estimated using the resulting model.

Results: None of the rats appeared susceptible to brodifacoum at previously reported LD50 exposures for this species. The ED50 of brodifacoum was estimated to be 2.88 mg/kg for males and 3.81 mg/kg for females. These values are 6–8 times greater than the previously published lethal dose values for ship rats in New Zealand.

Conclusions: Blood-clotting inhibition was detected in the rats only following high doses of brodifacoum, which may indicate resistance within the sampled population.

Implications: Relatively low susceptibility, or resistance, to brodifacoum in New Zealand ship rats may be mediated by spatial connections between areas with different histories and patterns of anticoagulant rodenticide use.

Keywords: anticoagulants, blood clotting response test, brodifacoum, effective dose, pest management, Rattus rattus, resistance, rodent control.


References

Akçay, A (2013). The calculation of LD50 using probit analysis. The FASEB Journal 27, 1217.28.
The calculation of LD50 using probit analysis.Crossref | GoogleScholarGoogle Scholar |

Andru, J, Cosson, JF, Caliman, JP, and Benoit, E (2013). Coumatetralyl resistance of Rattus tanezumi infesting oil palm plantations in Indonesia. Ecotoxicology 22, 377–386.
Coumatetralyl resistance of Rattus tanezumi infesting oil palm plantations in Indonesia.Crossref | GoogleScholarGoogle Scholar | 23264020PubMed |

Barron M, Griffiths J, Thomson C, Perry M, Clarke D, Sweetapple P (2014) How rapidly do rat populations recover after control with 1080? Kararehe Kino Issue 23. Manaaki Whenua, New Zealand.

Beausoleil, NJ, Fisher, P, Littin, KE, Warburton, B, Mellor, DJ, Dalefield, RR, and Cowan, P (2016). A systematic approach to evaluating and ranking the relative animal welfare impacts of wildlife control methods: poisons used for lethal control of brushtail possums (Trichosurus vulpecula) in New Zealand. Wildlife Research 43, 553–565.
A systematic approach to evaluating and ranking the relative animal welfare impacts of wildlife control methods: poisons used for lethal control of brushtail possums (Trichosurus vulpecula) in New Zealand.Crossref | GoogleScholarGoogle Scholar |

Bentley, EW (1968). The warfarin resistance problem in England and Wales. Schriftenreihe des Vereins fur Wasser-, Boden- und Lufthygiene 32, 19–25.

Bentley, EW, and Taylor, EJ (1965). Growth of laboratory-reared ship rats (Rattus rattus L.). Annals of Applied Biology 55, 193–205.
Growth of laboratory-reared ship rats (Rattus rattus L.).Crossref | GoogleScholarGoogle Scholar |

Berny P, Esther A, Jacob J, Prescott C (2018) Development of resistance to anticoagulant rodenticides in rodents in anticoagulant rodenticides and wildlife. In ‘Emerging Topics in Ecotoxicology’. (Eds NW Van den Brick, JE Elliot, RF Shore, BA Rattner) pp. 259–286. (Springer International Publishing AG)

Boyle, CM (1960). Case of apparent resistance of Rattus norvegicus Berkenhout to anticoagulant poisons. Nature 188, 517.
Case of apparent resistance of Rattus norvegicus Berkenhout to anticoagulant poisons.Crossref | GoogleScholarGoogle Scholar |

Bruce, RD (1985). An up-and-down procedure for acute toxicity testing. Fundamental Applied Toxicology 5, 151–157.
An up-and-down procedure for acute toxicity testing.Crossref | GoogleScholarGoogle Scholar | 3987991PubMed |

Buckle, A, Endepols, S, Klemann, N, and Jacob, J (2013). Resistance testing and the effectiveness of difenacoum against Norway rats (Rattus norvegicus) in a tyrosine139cysteine focus of anticoagulant resistance, Westphalia, Germany. Pest Management Science 69, 233–239.
Resistance testing and the effectiveness of difenacoum against Norway rats (Rattus norvegicus) in a tyrosine139cysteine focus of anticoagulant resistance, Westphalia, Germany.Crossref | GoogleScholarGoogle Scholar | 23208747PubMed |

Carpenter JR, Kenward MG (2013) ‘Multiple Imputation and its Application.’ (John Wiley & Sons Ltd: Chichester, UK)

Cowan, PE, Gleeson, DM, Howitt, RLJ, Ramón-Laca, A, Estherd, A, and Pelz, H-J (2017). Vkorc1 sequencing suggests anticoagulant resistance in rats in New Zealand. Pest Management Science 73, 262–266.
Vkorc1 sequencing suggests anticoagulant resistance in rats in New Zealand.Crossref | GoogleScholarGoogle Scholar | 27117082PubMed |

Cunningham DM, Moors PJ (1996) ‘Guide to the Identification and Collection of New Zealand Rodents.’ (Department of Conservation: Wellington, New Zealand)

Desidiri, D, Aldighieri, R, Le Louet, M, and Tardieu, A (1978). Supplementary report on the study of resistance to coumafene in Rattus rattus observed at Marseilles. Bulletin de la Société de Pathologie Exotique 71, 301–303.

Dowding, JE, and Murphy, EC (1994). Ecology of ship rats (Rattus rattus) in a kauri (Agathis australis) forest in Northland, New Zealand. New Zealand Journal of Ecology 18, 19–27.

Dubock AC, Kaukeinen DE (1978) Brodifacoum (Talon rodenticide), a novel concept. In ‘Proceedings of the 8th Vertebrate Pest Conference’, 7–9 March 1978, Sacramento, CA, USA. (Ed. AWE Howard) pp. 127–137. (University of California: Davis, CA, USA)

Eason, CT, Murphy, EC, Wright, GRG, and Spurr, EB (2002). Assessment of risks of brodifacoum to non-target birds and mammals in New Zealand. Ecotoxicology 11, 35–48.
Assessment of risks of brodifacoum to non-target birds and mammals in New Zealand.Crossref | GoogleScholarGoogle Scholar | 11898799PubMed |

Erica Gill, J, Kerins, GM, Langton, SD, and MacNicoll, AD (1993). The development of a blood clotting response test for discriminating between difenacoum resistant and susceptible Norway rats (Rattus norvegicus Berk.). Comparative Biochemistry and Physiology Part C: Comparative Pharmacology 104, 29–36.
The development of a blood clotting response test for discriminating between difenacoum resistant and susceptible Norway rats (Rattus norvegicus Berk.).Crossref | GoogleScholarGoogle Scholar |

Fisher P (2005) Review of house mouse (Mus musculus) susceptibility to anticoagulant poisons. Department of Conservation Science Internal Series 198. (Department of Conservation: Wellington, New Zealand)

Foster, S, King, C, Patty, B, and Miller, S (2011). Tree-climbing capabilities of Norway and ship rats. New Zealand Journal of Zoology 38, 285–296.
Tree-climbing capabilities of Norway and ship rats.Crossref | GoogleScholarGoogle Scholar |

Fu, X, Booth, SL, and Smith, DE (2007). Vitamin K contents of rodent diets: a review. Journal of the American Association for Laboratory Animal Science 46, 8–12.
| 17877321PubMed |

Garg, N, and Singla, N (2015). Blood clotting response test for detecting resistance to second generation anticoagulant bromadialone in house rat (Rattus rattus). Indian Journal of Animal Research 49, 607–611.

Garg, N, Singla, N, Jindal, V, and Babbar, BK (2017). Studies on bromadiolone resistance in Rattus rattus populations from Punjab, India. Pesticide Biochemistry and Physiology 139, 24–31.
Studies on bromadiolone resistance in Rattus rattus populations from Punjab, India.Crossref | GoogleScholarGoogle Scholar | 28595918PubMed |

Goulois, J, Chapeuzet, A, Lambert, V, Chatron, N, Tchartanov, L, Legros, L, Benoît, E, and Lattard, V (2016). Evidence of a target resistance to antivitamin K rodenticides in the roof rat Rattus rattus: identification and characterisation of a novel Y25F mutation in the Vkorc1 gene. Pest Management Science 72, 544–550.
Evidence of a target resistance to antivitamin K rodenticides in the roof rat Rattus rattus: identification and characterisation of a novel Y25F mutation in the Vkorc1 gene.Crossref | GoogleScholarGoogle Scholar | 25847836PubMed |

Greaves JH, Cullen-Ayers PB (1988) Genetics of difenacoum resistance in the rat. In ‘Current advances in Vitamin K Research’. (Ed. JW Suttie) pp. 389–397. (Elsevier: New York, NY, USA)

Greaves, JH, and Rennison, BD (1973). Population aspects of warfarin resistance in the brown rat, Rattus norvegicus. Mammal Review 3, 27–29.
Population aspects of warfarin resistance in the brown rat, Rattus norvegicus.Crossref | GoogleScholarGoogle Scholar |

Hadler, MR, and Shadbolt, RS (1975). Novel 4-hydroxycoumarin anticoagulants active against resistant rats. Nature 253, 275–277.
Novel 4-hydroxycoumarin anticoagulants active against resistant rats.Crossref | GoogleScholarGoogle Scholar | 1113846PubMed |

Hadler, MR, Redfern, R, and Rowe, FP (1975). Laboratory evaluation of difenacoum as a rodenticide. Journal of Hygiene 74, 441–448.
Laboratory evaluation of difenacoum as a rodenticide.Crossref | GoogleScholarGoogle Scholar | 1056964PubMed |

Harper, GA, and Rutherford, M (2016). Home range and population density of black rats (Rattus rattus) on a seabird island: a case for a marine subsidised effect? New Zealand Journal of Ecology 40, 219–228.
Home range and population density of black rats (Rattus rattus) on a seabird island: a case for a marine subsidised effect?Crossref | GoogleScholarGoogle Scholar |

Innes JG, Williams D (1991) The impact of aerial 1080 poisoning on ship rat populations at Mapara and Kaharoa. Forest Research institute Contract Report FWE 91/30. (Forest Research Institute: Rotorua)

Innes, J, Warburton, B, Williams, D, Speed, H, and Bradfield, P (1995). Large-scale poisoning of ship rats (Rattus rattus) in Indigenous Forests of the North-Island, New Zealand. New Zealand Journal of Ecology 19, 5–17.

Ishizuka, M, Okajima, F, Tanikawa, T, Min, H, Tanaka, KD, Sakamoto, KQ, and Fujita, S (2007). Elevated warfarin metabolism in warfarin-resistant roof rats (Rattus rattus) in Tokyo. Drug Metabolism and Disposition 35, 62–66.
Elevated warfarin metabolism in warfarin-resistant roof rats (Rattus rattus) in Tokyo.Crossref | GoogleScholarGoogle Scholar | 17012541PubMed |

Jackson WB, Ashton AD (1979) Present distribution of anticoagulant resistance in the United States. In ‘Vitamin K Metabolism and Vitamin K-dependent Protiens’. (Ed. JW Suttie) pp. 392–397. (University Park Press: Baltimore, MD, USA)

Kaukeinen D, Rampaud MA (1986) A review of brodifacoum efficacy in the U.S. and worldwide. In ‘Proceedings of the 12th Vertebrate Pest Conference, 4–6 March 1986, San Diego, CA, USA’. (Ed. TP Salmon) pp. 9–85. (University of California: Davis, CA, USA)

Lefebvre, S, Rannou, B, Besse, S, Benoit, E, and Lattard, V (2016). Origin of the gender differences of the natural resistance to antivitamin K anticoagulants in rats. Toxicology 344, 34–41.
Origin of the gender differences of the natural resistance to antivitamin K anticoagulants in rats.Crossref | GoogleScholarGoogle Scholar | 26860702PubMed |

Li, T, Chang, CY, Jin, DY, Lin, PJ, Khvorova, A, and Stafford, DW (2004). Identification of the gene for vitamin K epoxide reductase. Nature 427, 541–544.
Identification of the gene for vitamin K epoxide reductase.Crossref | GoogleScholarGoogle Scholar | 14765195PubMed |

Liang, L (2005). The resistance of Rattus flavipectus and R. norvegicus to Anticoagulant Rodenticide in Zhanjiang proper. Chinese Journal of Vector Biology and Control 16, 21–22.

Lund, M (1969). Resistance to anticoagulants in Denmark. Schriftenreihe des Vereins für Wasser-, Boden- und Lufthygiene 32, 27–38.
| 5293929PubMed |

Lund M (1984) Resistance to the second generation anticoagulant rodenticides. In ‘Proceedings of the 11th Vertebrate Pest Conference, 6–8 March 1984, Sacramento, CA, USA’. (Ed. DO Clark) (University of California: David, CA, USA)

Markussen, M, Heiberg, A, Fredholm, M, and Kristensen, M (2008). Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats: a possible role for pharmacokinetics in bromadiolone resistance. Pest Management Science 64, 239–248.
Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats: a possible role for pharmacokinetics in bromadiolone resistance.Crossref | GoogleScholarGoogle Scholar | 18080289PubMed |

Marsh, RE (1977)). Bromadiolone, a new anticoagulant rodenticide. EPPO Bulletin 7, 495–502.

Mathur, RP, and Prakash, I (1981). Evaluation of brodifacoum against T. indica, M. hurrianae and R. rattus. Journal of Hygiene 87, 179–184.
Evaluation of brodifacoum against T. indica, M. hurrianae and R. rattus.Crossref | GoogleScholarGoogle Scholar | 7288172PubMed |

Moussa BR (2005) Biological and toxicology studies on some rodents. Masters thesis, Zagazig University, Zagazig, Egypt. Available at https://bu.edu.eg/portal/uploads/discussed_thesis/finalabsrtract/10812645.pdf

Myllymäki, A (1995). Anticoagulant resistance in Europe: appraisal of the data from the 1992 EPPO Questionnaire. Pesticide Science 43, 69–72.
Anticoagulant resistance in Europe: appraisal of the data from the 1992 EPPO Questionnaire.Crossref | GoogleScholarGoogle Scholar |

O’Connor CE, Booth LH (2001) Palatability of rodent baits to wild house mice. In ‘Science for Conservation, Vol. 184’, p. 11. (Department of Conservation: Wellington, New Zealand)

Pelz HJ, Prescott C (2015) Resistance to anticoagulant rodenticides. In ‘Rodent Pests and their Control’. (Ed. AP Buckle, RH Smith) pp. 195–201. (CAB International: Wallingford, Oxfordshire, UK)

Pelz, H-J, Rost, S, Hünerberg, M, Fregin, A, Heiberg, A-C, Baert, K, Macnicoll, AD, Prescott, CV, Walker, A-S, Oldenburg, J, and Müller, CR (2005). The genetic basis of resistance to anticoagulants in rodents. Genetics 170, 1839–1847.
The genetic basis of resistance to anticoagulants in rodents.Crossref | GoogleScholarGoogle Scholar | 15879509PubMed |

Prescott, CV, and Buckle, AP (2000). Blood-clotting response tests for resistance to diphacinone and chlorophacinone in the Norway rat (Rattus Norvegicus Berk.). Crop Protection 19, 291–296.
Blood-clotting response tests for resistance to diphacinone and chlorophacinone in the Norway rat (Rattus Norvegicus Berk.).Crossref | GoogleScholarGoogle Scholar |

Prescott, CV, Buckle, AP, Hussain, I, and Endepols, S (2007). A standardised BCR resistance test for all anticoagulant rodenticides. International Journal of Pest Management 53, 265–272.
A standardised BCR resistance test for all anticoagulant rodenticides.Crossref | GoogleScholarGoogle Scholar |

Pryde, M, Dilks, P, and Fraser, I (2005). The home range of ship rats (Rattus rattus) in beech forest in the Eglinton Valley, Fiordland, New Zealand: a pilot study. New Zealand Journal of Zoology 32, 139–142.
The home range of ship rats (Rattus rattus) in beech forest in the Eglinton Valley, Fiordland, New Zealand: a pilot study.Crossref | GoogleScholarGoogle Scholar |

Quy, RJ, Cowan, DP, Prescott, CV, Gill, JE, Kerins, GM, Dunsford, G, Jones, A, and Macnicoll, AD (1995). Control of a population of Norway rats resistant to anticoagulant rodenticides. Pesticide Science 45, 247–256.
Control of a population of Norway rats resistant to anticoagulant rodenticides.Crossref | GoogleScholarGoogle Scholar |

Redfern, R, and Gill, JE (1978). The development and use of a test to identify resistance to the anticoagulant difenacoum in the Norway rat (Rattus norvegicus). Journal of Hygiene 81, 427–431.
The development and use of a test to identify resistance to the anticoagulant difenacoum in the Norway rat (Rattus norvegicus).Crossref | GoogleScholarGoogle Scholar | 731023PubMed |

Redfern, R, Gill, JE,, and Hadler, MR (1976). Laboratory evaluation of WBA 8119 as a rodenticide for use against warfarin-resistant and non-resistant rats and mice. Journal of Hygiene 77, 419–426.
| 1069820PubMed |

Rost, S, Fregin, A, Ivaskevicius, V, Conzelmann, E, Hortnagel, K, and Pelz, HJ (2004). Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427, 537–541.
Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2.Crossref | GoogleScholarGoogle Scholar | 14765194PubMed |

Rost, S, Pelz, H-J, Menzel, S, MacNicoll, VL, León, V, Song, K-J, Jäkel, T, Oldenburg, J, and Müller, C (2009). Novel mutations in the VKORC1 gene of wild rats and mice – a response to 50 years of selection pressure buy warfarin. BMC Genetics 10, 4.
Novel mutations in the VKORC1 gene of wild rats and mice – a response to 50 years of selection pressure buy warfarin.Crossref | GoogleScholarGoogle Scholar | 19200363PubMed |

Rymer DJ (2017) Anticoagulant resistance in Norway rats conferred by VKORC1 mutations in South-East England. PhD Thesis, University of Reading, UK.

Spiegelhalter D, Thomas A, Best N, Lunn D (2014) ‘OpenBUGS User Manual, Version 3.2.3.’ (MRC Biostatistics Unit: Cambridge, UK)

Wheeler, R, Priddel, D, O’Dwyer, T, Carlile, N, Portelli, D, and Wilkinson, I (2019). Evaluating the susceptibility of invasive black rats (Rattus rattus) and house mice (Mus musculus) to brodifacoum as a prelude to rodent eradication on Lord Howe Island. Biological Invasions 21, 833–845.
Evaluating the susceptibility of invasive black rats (Rattus rattus) and house mice (Mus musculus) to brodifacoum as a prelude to rodent eradication on Lord Howe Island.Crossref | GoogleScholarGoogle Scholar |

Wodzicki KA (1978). Review of existing control methods. In ‘The Ecology and Control of Rodents in New Zealand Nature Reserves’. (Eds PR Dingwall, IAE Atkinson, C Hay) pp. 195–205. (Department of Lands and Survey: Wellington, New Zealand)