Development and use
Diphacinone is a first-generation indandione rodenticide developed as a more effective alternative to warfarin that had no patent restrictions (Correll et al., 1952). The emergence of rat and mouse strains in the UK, Europe and the USA with cross-resistance to all first-generation rodenticides caused a decline in diphacinone use, and stimulated the development of more potent second-generation anticoagulant rodenticides (Greaves and Ayres, 1969). Despite this, diphacinone is still registered in all Australian states and territories to control introduced rats and mice although only one product, Ramik®, is commercially available.
Mode of action
Diphacinone has the same anticoagulant mode of action shared by 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 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. Effects develop progressively and include haemorrhage, shock, loss of consciousness, and eventual death (Petterino and Paolo, 2001).
Diphacinone belongs to the indandione group of anticoagulants observed to have other effects, including muscle twitching and spasms before death, when large quantities are consumed (Cahill and Crowder, 1979). The compound accumulates in the liver of rodents but is metabolised quicker than other anticoagulants. It has a half-life of 3 days in rat liver (Fisher et al., 2003); in mice, 75% of the active compound is eliminated in 2–4 days (Cahill and Crowder 1979). This short metabolic half-life means that for effective control using diphacinone, repeated feeding is required (Hadler and Buckle, 1992). Therefore, users 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: 3–14 days (Bentley and Larthe, 1959)
- Mice: 3–21 days (Bentley and Larthe, 1959)
Evidence of resistance
Evidence of the existence of cross-resistance to all first-generation anticoagulants has 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.
APVMA-registered products containing diphacinone
Ramik (0.05g/kg)
Available formulation
Bait concentrate and ready-to-use nugget bait
Acute toxicity
| Species | LD50 | Average bodyweight | Amount of bait consumed for a LD50 | Reference (for LD50) |
|---|---|---|---|---|
| Mouse | 141–340mg/kg | 20g | 56.4–136g* | Correll et al., 1952; Humphreys, 1988 |
| Norway rat | 0.3–3mg/kg | 320g | 1.92–19.2g* | Correll et al., 1952; Krieger, 2001 |
| *Calculated using a bait concentration of 0.05g/kg | ||||
The table above shows the oral median lethal dose (LD50) values of diphacinone 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). Diphacinone rodenticides have a standard active concentration of 0.005% (0.05g/kg). Therefore, 1.92–19.2 grams of bait would be considered a lethal dose for rats and 56.4–136 grams of bait is lethal for mice. For both species, this is greater than the daily feed requirement, therefore repeated feeding of bait is needed.
Poison schedule and regulatory requirements
Diphacinone is a Schedule 6 poison with a moderate potential for causing harm. Products containing diphacinone 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 diphacinone.
Handling, storage and user safety
Recommended for controlling mice in and around industrial, commercial, agricultural and domestic buildings. Do not apply bait directly to ground surface or in grass or other ground cover.
Store the material in a well-ventilated, secure area out of reach of children and domestic animals. Do not store food, beverages or tobacco products in the storage area. Prevent eating, drinking, tobacco use, and cosmetic application in areas where there is a potential for exposure to the material. Wash thoroughly with soap and water after handling.
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.
Cahill, W. P. and Crowder, L.A. (1979). Tissue distribution and excretion of diphacinone in the mouse. Pesticide Biochemistry and Physiology, 10:259-267.
Correll, J. T., Coleman, L. L., Long, S. and Willy, R. F. (1952). Diphenylacetyl-1,3-indandione as a potent hypoprothrombinemic agent. In Proceedings of the Society for Experimental Biology and Medicine 80:139-143.
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.
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.
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.
