The fate of the rodenticide flocoumafen in the rat: Retention and elimination of a single oral dose

Huckle, Keith R.; Hutson, D. H.; Logan, C.; Morrison, Brian J.; Warburton, Paul A.

doi:10.1002/ps.2780250310

Cited by 19 publications

(9 citation statements)

References 4 publications

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“…After a single oral dose of flocoumafen of 0.14 mg ⁄ kg bw to rats, the absorption into blood was rapid, reaching maximum concentrations of 0.03 to 0.05 lg ⁄ mL in plasma within 4 h (Huckle et al, 1989a). Also, a high degree of body retention was found 7 days after repeated oral dosing, approximately half the dose was found in the liver of rats (Huckle et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

Vandenbroucke

Bousquet‐mélou

Backer

et al. 2008

Vet Pharm & Therapeutics

129

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The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one-half the lethal dose 50 (LD(50)), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC-ESI-MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half-lives in plasma for first-generation rodenticides were shorter than those for second-generation rodenticides. Coumatetralyl, a first-generation product, had a plasma elimination half-life of 0.52 days. Brodifacoum, a second-generation product, showed a plasma elimination half-life of 91.7 days. The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning.

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Section: Discussionmentioning

confidence: 99%

“…After a single oral dose of flocoumafen of 0.14 mg/kg bw to rats, the absorption into blood was rapid, reaching maximum concentrations of 0.03 to 0.05 μg/mL in plasma within 4 h (Huckle et al. , 1989a).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

Vandenbroucke

Bousquet‐mélou

Backer

et al. 2008

Vet Pharm & Therapeutics

129

View full text Add to dashboard Cite

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“…The compound is extremely slowly eliminated. For the closely related rodenticide, flocoumafen, the elimination half life for rat liver was 220 days (Huckle et al, 1989). Evidently, the main factor determining this persistence is the tight binding to the warfarin binding site.…”

Section: Discussionmentioning

confidence: 99%

The long‐term effects of the rodenticide, brodifacoum, on blood coagulation and vitamin K metabolism in rats

Mosterd

Thijssen

1991

British J Pharmacology

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The long‐term (30 days) effects of a single dose of brodifacoum (0.2 mg kg−1, orally) on blood clotting activity and on liver parameters of the vitamin K cycle were investigated in rats. Maximal effect on blood clotting activity was seen on day one. On day seven blood clotting activity had returned to normal. Liver microsomal vitamin KO reductase activity was maximally suppressed (10% of control activity) on day one, steadily recovered to about 40% on day 15 to remain at that level. The same time course was seen for the number of microsomal warfarin binding sites. The persistent inhibition of the vitamin K cycle was also verified in vivo; following vitamin K administration (10 mg kg−1, i.v.) on day 30, the brodifacoum‐treated rats accumulated vitamin KO in the liver. Although clotting factor synthesis was normal, brodifacoum‐treated rats were highly sensitive to warfarin. Brodifacoum rapidly accumulated in the liver until the saturation of the microsomal binding site. Brodifacoum binding to the target prevented its elimination from the liver; liver content on day 30 was not different from day 7. The results show (1) an over capacity for the hepatocellular vitamin K cycle, (2) a dissociation of the vitamin K epoxidation and the vitamin K‐dependent carboxylation, (3) the ‘superwarfarin’ rodenticides to be extremely persistent due to their binding to the target.

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“…The higher potency of second‐generation rodenticides is due to the greater affinity to binding sites in the liver, greater accumulation and persistence in the body (Huckle et al . ; Hadler and Buckle ; Watt et al . ).…”

Section: Introductionmentioning

confidence: 99%

Influence of brodifacoum and bromadiolone on growth of yoghurt cultures in milk

Hathurusinghe

Ibrahim

2015

Int J of Dairy Tech

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The influence of brodifacoum and bromadiolone on the growth of yoghurt culture in milk was determined. Milk samples inoculated with a commercial yoghurt culture and serially diluted rodenticides were incubated at 42°C for 6 h. The yoghurt cultures showed detectable sensitivity (significant change (P < 0.05) in pH in the medium) to brodifacoum at 0.12 mg/mL and to bromadiolone at 0.08 mg/mL. There were significant differences (P < 0.05) in the bacterial count and a-galactosidase and b-galactosidase activities in the presence of toxins in milk. The results indicate that brodifacoum and bromadiolone could inhibit the growth of yoghurt culture in milk.

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The fate of the rodenticide flocoumafen in the rat: Retention and elimination of a single oral dose

Cited by 19 publications

References 4 publications

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

The long‐term effects of the rodenticide, brodifacoum, on blood coagulation and vitamin K metabolism in rats

Influence of brodifacoum and bromadiolone on growth of yoghurt cultures in milk

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