Development and use
Warfarin, originally developed as a therapeutic treatment for thrombosis, was identified as a potential rodenticide after exposed laboratory rodents died of haemorrhage (Mills, 1955). The first controlled trials were carried out in London in 1946-47. Due to its anticoagulant mode of action and delayed onset of symptoms, warfarin performed more favourably than traditional fast-acting single-dose poisons. Warfarin was the dominant rodenticide used worldwide from 1950 to 1965 (Hadler and Buckle, 1992). The emergence of resistant rat and mouse strains in the UK, Europe and the USA caused a decline in warfarin use and stimulated the development of more potent second-generation anticoagulant rodenticides (Greaves and Ayres, 1969). Although unlikely to control resistant strains, warfarin is registered in all Australian states and territories for controlling introduced rats and mice.
Mode of action
Warfarin exhibits the same mode of action as all anticoagulant rodenticides (Silverman, 1980). When a rodent eats the bait, the active anticoagulant blocks the epoxide reductase enzyme and stops the recycling of activated vitamin K. This severely reduces the production of blood-clotting factors. When the existing supply of clotting factors are eventually degraded, the clotting mechanism fails and haemorrhaging begins. As with all anticoagulants, there is a considerable delay between consumption of a lethal dose and onset of symptoms. The effects of warfarin develop progressively; they include haemorrhage, shock, loss of consciousness and eventual death (Petterino and Paolo, 2001).
Warfarin accumulates in plasma and liver tissue, and is metabolised comparatively quickly compared to other anticoagulant rodenticides. A total of 90% of the compound is excreted in the urine and faeces within 14 days, while the half-life in liver tissue is 10–26 days for rats and 67 days for mice (Link et al., 1965; Barker et al., 1970; Coon and Willis, 1972; Thijssen, 1995; Fisher et al., 2003; Vandenbroucke et al., 2008). Due to this short metabolic half-life, warfarin (along with all first-generation anticoagulant rodenticides) is more effective if administered in small daily doses rather than a large single dose (Hadler and Buckle, 1992). Therefore, for effective rodent control, users of warfarin need to ensure that fresh bait is continually available. Dead or dying rodents should also be cleared from production areas as soon as possible to reduce secondary poisoning risk.
Time to death
- Rats: 3–17 days
- Mice: 6–8 days
This is dependent on dose rate and frequency of feeding (Hagan and Radomski, 1953; Bentley and Larthe, 1959; Lund, 1981; Hadler and Buckle, 1992).
Evidence of resistance
Warfarin resistance has been observed in all three common pest rodent species (Norway rats, black rats and house mice) in the UK, the USA, throughout Europe and in Asia (Boyle, 1960; Rowe and Redfern, 1965; Greaves et al., 1976). Cross-resistance to all first-generation anticoagulants has also been observed in Europe (Rowe and Redfern, 1965; Greaves and Ayres, 1969; Hadler and Shadbolt, 1975). To date, no resistance studies have been conducted in Australian pest rodent species, but the emergence of resistant strains worldwide means it is likely to exist within Australian rodent populations.
APVMA-registered products containing warfarin
Double Strength Ratsak (0.5g/kg), Ratblitz (0.25g/kg), Rat Kill (0.25g/kg), Rat ’N’ Mouse Killer (0.25g/kg)
Available formulation
- Paste bait
- Tracking powder
- Wax block
Acute toxicity
| Species | LD50 | Average bodyweight | Amount of bait consumed for a LD50 | Reference (for LD50) |
|---|---|---|---|---|
| Mouse | 374mg/kg | 20g | 15–29.9g* | Dubock, 1978 |
| Norway rat | 58mg/kg | 320g | 37–74g* | Thomson, 1991 |
| *Calculated using a bait concentration range of 0.25–0.5g/kg | ||||
The table above shows the oral median lethal dose (LD50) values of warfarin for the house mouse and Norway rat, the typical bodyweight for an adult animal from each species, and the total amount of commercial bait needed to be eaten to cause death. An adult rat (bodyweight 320 grams) will eat about 20–30 grams of food daily and an adult mouse (bodyweight 20 grams) will eat 2–5 grams of food daily (Hadler and Buckle, 1991). Warfarin rodenticides have an active concentration of 0.25 to 0.5g/kg. Therefore, 37–74 grams of bait would be considered a lethal dose for rats and 15–29.9 grams of bait is lethal for mice. For both pest rodent species, this is greater than their daily food requirement. Therefore, repeated feeding of bait is needed for effective control.
Poison schedule and regulatory requirements
Warfarin is a Schedule 5 poison with a low potential for causing harm. Products containing warfarin are required to have appropriate packaging with simple warnings and safety directions on the label. There are no special regulations restricting the availability, possession, storage or use of products containing warfarin.
Handling, storage and user safety
Avoid skin and eye contact and inhaling dust when handling baits.
Store bait in a cool, dry, well-ventilated place, out of direct sunlight and away from foodstuffs. Containers housing bait should be closed when not in use and checked regularly for spills.
Read the label before use. For detailed instructions on handling and user safety, please refer to the relevant Safety Data Sheet.
References
Bentley, E. W. and Larthe Y. (1959). The comparative rodenticidal efficiency of five anti-coagulants. Journal of Hygiene, 57:135-149.
Boyle, C. M. (1960). Case of apparent resistance of Rattus norvegicus Berkenhout to anticoagulant poisons. Nature, 188:517.
Coon, W. W. and Willis, P. W. (1972). Some aspects of the pharmacology of oral anticoagulants. Clinical Pharmacology and Therapeutics 11:312-336.Dubock, A. C., & Kaukeinen, D. E. (1978). Brodifacoum (TalonTM rodenticide), a novel concept. Proceedings of the Eighth Vertebrate Pest Conference (1978). 16.
Fisher, P., O’Connor, C., Wright, G., & Eason, C. T. (2003). Persistence of four anticoagulant rodenticides in the livers of laboratory rats. DOC Science Internal Series, 139, 1-19.
Greaves, J. H. and Ayres, P. (1969). Some rodenticidal properties of coumatetralyl. Journal of Hygiene, 67:311-315.
Greaves, J. H., Rennison, B. D., & Redfern, R. (1976). Resistance of the ship rat, Rattus rattus L. to warfarin. Journal of Stored Products Research, 12(2), 65-70.
Hadler, M. R., & Buckle, A. P. (1992). Forty-five years of anticoagulant rodenticides – past, present and future trends. In Proceedings of the Fifteenth Vertebrate Pest Conference, 15.
Hadler, M. R., & Shadbolt, R.S. (1975). Novel 4-hydroxycoumarin anticoagulants active against resistant rats. Nature, 253:275-277.
Hagan, E. C. and Radomski, J. L. (1953). The toxicity of 3-(acetonylbenzyl)-4-hydroxycoumarin (warfarin) to laboratory animals. Journal of the American Pharmaceutical Association, 42:379-382.
Link, K. P., Berg, D. and Barker, W. M. (1965). Partial fate of warfarin in the rat. In Science (Vol. 150, No. 3694, p. 378).
Lund, M. (1981). Comparative effect of the three rodenticides warfarin, difenacoum and brodifacoum on eight rodent species in short feeding periods. Epidemiology & Infection, 87(1), 101-107.
Mills, E. M. (1955). How anticoagulant rodenticides were developed. Pest Control, 23(9), 14-16.
Petterino, C. and Paolo, B. (2001). Toxicology of various anticoagulant rodenticides in animals. Veterinary and Human Toxicology, 43:353-360.
Rowe, F. P. and Redfern, R. (1965). Toxicity tests on suspected warfarin resistant house mice (Mus musculus L.). Epidemiology & Infection, 63(3), 417-425.
Silverman, R.B. (1980). A model for the molecular mechanism of anticoagulant activity of 3-substituted 4-hydroxycoumarins. Journal of the American Chemical Society, 102(16), 5421-5423.
Thijssen, H. H. W. (1995). Warfarin-based rodenticides – mode of action and mechanism of resistance. Pesticide Science, 43:73-78.
Thomson, W. T. (1991). Agricultural Chemicals Book III – Miscellaneous agricultural chemicals: fumigants, growth regulators, seed safeners, repellents, fish toxicants, bird toxicants, pheromones, rodenticides and others. Thomson publications.
Vandenbroucke, V., Bousquet-Melou, A., De Backer, P., & Croubels, S. (2008). Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration. Journal of veterinary pharmacology and therapeutics, 31(5), 437-445.
