Development and use
Difethialone is a second-generation rodenticide from the hydroxyl-4-benzothiopyranone chemical family that was developed in France and first used in 1986 (Lechevin, 1986). It is classified as an SGAR because it is more potent (i.e. a smaller amount of bait is required for a kill) and effective against rodents resistant to earlier compounds (Hadler and Buckle, 1991). Compared to other SGARs, difethialone is more toxic to birds and fish, and tolerated better by dogs and pigs (Lechevin and Poché, 1988). It is also incorporated into commercial baits at a lower active concentration (0.025mg/kg instead of 0.05mg/kg) to reduce the risk to non-target species. Difethialone is registered in all Australian states and territories for controlling introduced rat and mice species.
Mode of action
Despite being from a different chemical family to other commercially available second-generation rodenticides, difethialone exhibits the same anticoagulant mode of action (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 eventually, when the existing supply of clotting factors are 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 difethialone develop progressively and include haemorrhage, shock, loss of consciousness and eventual death (Petterino and Paolo, 2001).
Difethialone is highly potent. It is possible for rodents to consume a lethal dose in a single feed as a fraction of daily food requirement (see Acute toxicity). However, users are advised to re-apply bait weekly for several weeks to allow rodents to feed sufficiently to acquire a lethal dose (Hadler and Buckle, 1991). Difethialone is not metabolised well by rodents and is mainly excreted through faeces (McLeod and Saunders, 2013). Difethialone persists in rodent liver tissue with a half-life of 108 days for rats and 29 days for mice (Lechevin and Poché, 1988; Vandenbroucke et al., 2008). Therefore, rodent carcases should be removed from production areas as soon as possible to reduce secondary poisoning risk.
Time to death
- Rats: 2–16 days (Lechevin and Poché, 1988; Nahas et al., 1989; Saxena et al., 1992)
- Mice: 2–20 days (Lechevin and Poché, 1988; Nahas et al., 1989; Saxena et al., 1992)
Evidence of resistance
There is no evidence of resistance to difethialone. To date, no resistance studies have been conducted on Australian pest rodent species.
APVMA-registered products containing difethialone
Generation Blue (0.025g/kg), Rodilon Pro (0.025g/kg)
Available formulation
- Extruded bait
- Grain bait
- Wax blocks
Acute toxicity
| Species | LD50 | Average bodyweight | Amount of bait consumed for a LD50 | Reference (for LD50) |
|---|---|---|---|---|
| Mouse | 0.47–1.29mg/kg | 20g | 0.38–1.03g* | Vandenbroucke et al., 2008 |
| Norway rat | 0.29–0.51mg/kg | 320g | 3.7–6.5g* | Lorgue et al., unpublished (Lechevin, 1988) |
| *Calculated using a bait concentration of 0.025g/kg | ||||
The table above shows the oral median lethal dose (LD50) values of difethialone 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). Difethialone rodenticides have a standard active concentration of 0.0025% (0.025g/kg). Therefore, 3.7–6.5 grams of bait would be considered a lethal dose for rats and 0.38–1.03 grams of bait is lethal for mice. Because these volumes are within the daily food requirement of target species, it is possible for a lethal dose to be consumed in a single feed.
Poison schedule and regulatory requirements
Difethialone is a Schedule 6 poison with a moderate potential for causing harm. Products containing difethialone 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 difethialone.
Handling, storage and user safety
Avoid contact with skin, eyes and clothing. Wash hands immediately after handling.
Store in original container. Keep containers tightly closed in a dry, cool and well-ventilated place that is accessible by authorised persons only. Keep away from direct sunlight. Keep away from food, drink and animal feedstuffs.
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
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.
Lechevin, J. C. (1986). Preliminary experimental results obtained with a new anticoagulant rodenticide LM-2219. Parsitis. Geneva, Switzerland (In French).
Lechevin, J. C., and Poché, R. M. (1988). Activity of LM 2219 (difethialone), a new anticoagulant rodenticide, in commensal rodents. In Proceedings of the Thirteenth Vertebrate Pest Conference.
Lorgue, G. (1984, 1986, 1987). Studies with LM-2219. Eco-toxicology Laboratory (INRA-ENVL). National Veterinarian School. Lyon, France. Unpublished reports. (In French).
McLeod, L., & Saunders, G. (2013). Pesticides used in the management of vertebrate pests in Australia: A review. NSW Department of Primary industries.
Nahas, K., Lorgue, G. and M. Mazallon, M. (1989). Difethialone (LM-2219) – a new anticoagulant rodenticide for use against warfarin-resistant and warfarin-susceptible strains of Rattus norvegicus and Mus musculus. Annales De Recherches Veterinaires, 20:159-164.
Petterino, C. and Paolo, B. (2001). Toxicology of various anticoagulant rodenticides in animals. Veterinary and Human Toxicology, 43:353-360.
Saxena, Y., Kumar, D., Bhandari, T., & Bhasin, H. (1992). Laboratory and field evaluation of difethialone, a new anticoagulant rodenticide. In Proceedings of the Fifteenth Vertebrate Pest Conference, 15.
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.
