Development and use
First registered in the UK in 1975, difenacoum was one of the earliest commercially available second-generation rodenticides (SGAR). While being chemically similar to first-generation anticoagulants (i.e. warfarin and coumatetralyl), SGARs like difenacoum are so called because they are effective against rodents that are resistant to earlier compounds, and are much more potent (i.e. smaller amounts of bait are required to be consumed for a kill). Difenacoum is registered in all Australian states and territories for controlling introduced rat and mice species.
Mode of action
Difenacoum 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, and 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 the onset of symptoms. The effects of difenacoum develop progressively, and include haemorrhage, shock, loss of consciousness and eventual death (Petterino and Paolo, 2001).
Difenacoum is more potent than first-generation rodenticides (i.e. coumatetralyl, diphacinone and warfarin) but is the least potent second-generation compound. It is possible for mice, but unlikely that rats will consume a lethal dose in a single feed (see Acute poisons). Therefore, difenacoum baits should be applied for several weeks to allow rodents to feed sufficiently to acquire a lethal dose (Hadler and Buckle, 1991). Difenacoum is excreted mainly through the faeces, but also through the urine of rodents. The half-life of difenacoum is 120 days in rat liver and 62 days in mice liver (Parmar et al., 1987; Vandenbroucke et al., 2008; Anon, 2009). Therefore, rodent carcases should be removed from production areas as soon as possible to reduce secondary poisoning risk.
Time to death
- Rats: 4–13 days (Rowe and Bradfield, 1976; Rowe, 1981)
- Mice: 4–22 days (Hadler et al., 1975; Lund, 1981)
Evidence of resistance
Resistance was discovered in Norway rats specifically in Europe within a few years of commercial use (Redfern and Gill, 1978). More recently, cross-resistance has been observed with warfarin and bromadiolone (Greaves et al., 1982; Cowan et al., 1995; MacNicoll et al., 1996; Meerberg et al., 2014). There are no reports of resistance in house mice or black rats. To date, no resistance studies have been conducted in Australian pest rodent species.
APVMA-registered products containing difenacoum
Atlas, Cougar, Effect, Muskil (dual blend bromadiolone 0.025g/kg and difenacoum 0.025g/kg), Patrol, PCT Pro Formula, Ratsak (dual blend bromadiolone 0.025g/kg and difenacoum 0.025g/kg), Ratshot, Ratshot-G, Roban, Rodemise Difenacoum, Sorexa Pro, Surefire Difenate, The Big Cheese, Time’s Up, Victor
NB: The products listed above have an active difenacoum concentration of 0.05g/kg unless otherwise specified.
Available formulation
- Extruded bait
- Grain bait
- Liquid concentrate
- Pelleted bait
- Paste bait
- Wax block
Acute toxicity
| Species | LD50 | Average bodyweight | Amount of bait consumed for a LD50 | Reference (for LD50) |
|---|---|---|---|---|
| Mouse | 0.8mg/kg | 20g | 0.32g* | Bull, 1976 |
| Norway rat | 1.8–2.5mg/kg | 320g | 11.6–16g* | Bull, 1976 |
| *Calculated using a bait concentration of 0.05g/kg | ||||
The table above shows the oral median lethal dose (LD50) values of difenacoum 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). Difenacoum rodenticides have a standard active concentration of 0.005% (0.05g/kg). Therefore, 11.6–16 grams of bait would be considered a lethal dose for rats and 0.32 grams of bait is lethal for mice. For mice, this is a fraction of daily food requirement, so it is possible for a lethal dose to be consumed in a single feed. For rats, because it is unlikely for a lethal dose to be consumed in a single feed, repeated feeding is required for effective control.
Poison schedule and regulatory requirements
Difenacoum is a Schedule 6 poison with a moderate potential for causing harm. Products containing difenacoum are required to have distinctive packaging with strong warnings and safety directions on the label. There are no special regulations restricting the availability, possession, storage or use of products containing difenacoum.
Handling, storage and user safety
Avoid contact with eyes and skin. Do not smoke, eat or drink while handling. Wash hands and face after handling.
Store in a cool, dry, well-ventilated area. Keep away from food and animal feedstuffs. Keep away from oxidising agents.
Read the label before use. For detailed instructions on handling and user safety, please refer to the relevant Safety Data Sheet for the product.
References
Anon. (2009). Assessment report – Difenacoum, product-type 14 (Rodenticides). Directive 98/8/EC concerning the placing of biocidal products on the market. Finland.
Bull, J. O. (1976). Laboratory and field investigations with Difenacoum, a promising new rodenticide. In Proceedings Seventh Vertebrate Pest Conference, 5, 72-84.
Cowan, D., Dunsford, G., Gill, E., Jones, A., Kerins, G., Macnicoll, A., and Quy, R. (1995). The impact of resistance on the use of second‐generation anticoagulants against rats on farms in Southern England. Pesticide Science, 43(1), 83-93.
Greaves, J. H., Shepherd, D. S. and Gill, J. E. (1982). An investigation of difenacoum resistance in Norway rat populations in Hampshire. Annals of Applied Biology, 100:581-587.
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., Redfern, R., & Rowe, F. P. (1975). Laboratory evaluation of difenacoum as a rodenticide. Epidemiology & Infection, 74(3), 441-448.
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.
MacNicoll, A. D., Kerbms, G. M., Dennis, N. J., & Gill, J. E. (1996). The distribution and significance of anticoagulant-resistant Norway rats (Rattus norvegicus) in England and Wales, 1988-95. In Proceedings of the Seventeenth Vertebrate Pest Conference, 34. 179-185.
Meerburg, B. G., Van Gent‐Pelzer, M. P., Schoelitsz, B., and Van Der Lee, T. A. (2014). Distribution of anticoagulant rodenticide resistance in Rattus norvegicus in the Netherlands according to Vkorc1 mutations. Pest management science, 70(11), 1761-1766.
Parmar, G., Bratt, H., Moore, R., & Batten, P. L. (1987). Evidence for common binding site in vivo for the retention of anticoagulants in rat liver. Human Toxicology, 6:431-432.
Petterino, C. and Paolo, B. (2001). Toxicology of various anticoagulant rodenticides in animals. Veterinary and Human Toxicology, 43:353-360.
Redfern, R. and Gill, J. E. (1978). The development and use of a test to identify resistance to the anticoagulant difenacoum in the Norway rat (Rattus norvegicus). The Journal of Hygiene, 81:427-431.
Rowe, F. P. and Bradfield, A. (1976). Trials of the anticoagulant rodenticide WBA 8119 against confined colonies of warfarin-resistant house mice (Mus musculus L.). Epidemiology & Infection, 77(3), 427-431.
Rowe, F. P., Plant, C. J., & Bradfield, A. (1981). Trials of the anticoagulant rodenticides bromadiolone and difenacoum against the house mouse (Mus musculus L.). Epidemiology & Infection, 87(2), 171-177.
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.
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.
