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Bromadiolone

Development and use

Bromadiolone is a second-generation anticoagulant rodenticide (SGAR) that was developed in France in the 1960s and introduced in 1978 (Grand, 1976). While being chemically similar to first-generation anticoagulants like warfarin and coumatetralyl (all are hydroxycoumarins), bromadiolone is classified as an SGAR because it is more potent (i.e. a smaller amount of bait is needed for a kill) and effective against rodents that are resistant to earlier compounds (Hadler and Buckle, 1991). Bromadiolone is registered in all Australian states and territories for controlling introduced rat and mice species.

Mode of action

Bromadiolone 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 bromadiolone develop progressively and include haemorrhage, shock, loss of consciousness and eventual death (Petterino and Paolo, 2001).

Bromadiolone 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 poisons). Despite this, bromadiolone is not recommended as a single-application rodenticide. Baits should be re-applied weekly for several weeks to allow rodents to feed sufficiently to acquire a lethal dose (Hadler and Buckle, 1991). Bromadiolone undergoes minimal metabolism and is mainly excreted in the faeces of rodents. In both rats and mice, an initial phase of rapid excretion occurs for the first 4–8 days after exposure before slowing down to a rate comparative to other second-generation rodenticides (Poché, 1988). The half-life of bromadiolone is 170 days in rat liver and 28 days in mice liver (Kamil, 1987; 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 (Meehan, 1978; Redfern and Gill, 1980)
  • Mice: 3–19 days (Meehan, 1978; Redfern and Gill, 1980; Rowe et al., 1981)

Evidence of resistance

There is some evidence of cross-resistance with warfarin (Rowe et al., 1981) and difenacoum (MacNicoll et al., 1996), although not widespread (Endepols et al., 2007). Evidence exists of reduced efficacy in Norway rat species carrying specific resistance mutations in The Netherlands (Meerberg et al., 2014). To date, no resistance studies have been conducted in Australian pest rodent species.

APVMA-registered products containing bromadiolone

Alley Cat, Bromakil, Bromakil Rat Drink (0.5g/L), Contrac, Generation Green, Maki, MouseOff, Muskil (dual blend bromadiolone 0.025g/kg and difenacoum 0.025g/kg), Ratsak (dual blend bromadiolone 0.025g/kg and difenacoum 0.025g/kg), Rat Stop, Rentokil Bromard, Rodemise, Surefire Broma, TomCat

NB: All products listed above have a bromadiolone concentration of 0.05g/kg unless otherwise stated.

Available formulations

  • Grain bait
  • Liquid concentrate
  • Pelleted bait
  • Paste bait
  • Soft bait
  • Sachet bait
  • Wax block
  • Extruded block

Acute toxicity

SpeciesLD50Average bodyweightAmount of bait consumed for a LD50Reference (for LD50)
Mouse0.86–1.75mg/kg20g0.4–0.8g*Meehan, 1978
Norway rat0.57–0.75mg/kg320g3.6–4.8g*Meehan, 1978
*Calculated using a bait concentration of 0.05g/kg

The table above shows the oral median lethal dose (LD50) values of bromadiolone 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). Bromadiolone rodenticides have a standard active concentration of 0.005% (0.05g/kg). Therefore, 3.6–4.8 grams of bait would be considered a lethal dose for rats and 0.4–0.8 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

Bromadiolone is a Schedule 6 poison with a moderate potential for causing harm. Products containing bromadiolone 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 bromadiolone.

Handling, storage and user safety

Wear gloves, safety glasses and appropriate clothing to avoid skin and eye contact. Do not inhale dust. Do not touch the bait; use the scoop or measure. If on skin and after each baiting, wash thoroughly with soap and water.

Containers that have been used to house bait should not be used for any other purpose. Store in tightly sealed original containers in a dry secure place away from fertilisers, seed, feed and food. Store out of direct sunlight. Keep out of reach of children, unauthorised persons and animals.

Read the label before use. For detailed instructions on handling and user safety, please refer to the relevant Safety Data Sheet.

References

Grand, M. (1976). Experimental data on a new anticoagulant raticide: Bromadiolone. Phytiatrie, Phytopharmacie 25:69-88.

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.

Kamil, N. (1987). Kinetics of bromadiolone, anticoagulant rodenticide, in the Norway rat (Rattus norvegicus). Pharmacological research communications, 19(11), 767-775.

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.

Meehan, A. P. (1978). Rodenticidal activity of Bromadiolone—a new anticoagulant. In Proceedings of the Eighth Vertebrate Pest Conference. 31. 122-126.

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.

Petterino, C. and Paolo, B. (2001). Toxicology of various anticoagulant rodenticides in animals. Veterinary and Human Toxicology, 43:353-360.

Poché, R. M. (1988). Rodent tissue residue and secondary hazard studies with bromadiolone. EPPO Bulletin, 18(2), 323-330.

Redfern, R. and Gill, J. E. (1980). Laboratory evaluation of bromadiolone as a rodenticide for use against warfarin-resistant and non-resistant rats and mice. Journal of Hygiene, 84:263-268.

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.

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