bromadiolone and chlorophacinone

To assess the rate and extent of ruminal degradation of warfarin, chlorophacinone, and bromadiolone in vitro and determine the oral availability and clinical and hemostatic effects of each anticoagulant rodenticide in adult sheep.. 3 Texel sheep.. Samples of ruminal fluid were incubated with each of the anticoagulants to assess the kinetics of ruminal degradation over 24 hours. To determine the plasma kinetics of the anticoagulants, each sheep received each of the anticoagulants IV or via a rumenimplanted cannula at 2-month intervals (3 rodenticide exposures/sheep). At intervals during a 240- to 360- hour period after treatment, prothrombin time (PT) was measured, plasma anticoagulant concentration was assessed, and clinical signs of rodenticide poisoning were monitored. In plasma and rumen extracts, anticoagulant concentrations were determined via high-performance liquid chromatography.. In the rumen extracts, anticoagulants were slightly degraded (< 15%) over 24 hours. In vivo, oral availability of warfarin, chlorophacinone, and bromadiolone was estimated at 79%, 92%, and 88%, respectively. Although maximum PT was 80 seconds after chlorophacinone and bromadiolone treatments, no clinical signs of toxicosis were detected; PT returned to baseline values within 2 weeks.. In sheep, warfarin, chlorophacinone, and bromadiolone were not degraded in the rumen but their bioavailabilities were high after oral administration; the kinetics of these compounds in sheep and other mammals are quite similar. These data suggest that the lack of susceptibility of ruminants to these anticoagulant rodenticides cannot be explained by either ruminal degradation or the specific toxicokinetics of these anticoagulants.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Biological Availability; Indans; Male; Rodenticides; Rumen; Sheep; Sheep Diseases; Warfarin

Cyclic water vole population explosions can be controlled in some European countries with anticoagulant rodenticides leading sometimes to wildlife poisonings due to the toxin's tissue persistence. Here, we analyzed the pharmacokinetics of rodenticide residues in voles and we explored potential ways of improving the mass application of these agents based on the concept of stereoisomers. We demonstrated the dramatic persistence of bromadiolone in vole tissues with a hepatic half-life of about 10-30 days, while the tissue persistence of chlorophacinone is rather short with a hepatic half-life of about one day. The dramatic persistence of bromadiolone is due to the trans-isomer group (the major compound in bromadiolone), while the cis-isomer group has a short half-life. Because of resistance to chlorophacinone, the cis-bromadiolone isomers may constitute an excellent compromise between efficacy and ecotoxicological risk to control voles. A mathematical model is proposed to favor the development of baits mixed with cis-isomer groups.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Arvicolinae; Female; Indans; Liver; Male; Models, Biological; Rodent Control; Rodenticides; Stereoisomerism

Anticoagulant rodenticides (ARs) are used worldwide to control populations of agricultural and urban rodents, but these pesticides may be accumulated in and poisoned non-target species of wildlife. Slugs may feed on rodenticide bait following field applications. Thus, it can be assumed that their predators are exposed to rodenticides through food chain transfer. However, AR exposure in the slugs has not been systematically studied. We investigated the accumulation of three ARs (chlorophacinone, bromadiolone or brodifacoum) in the slug Deroceras reticulatum exposed for a period of 5days followed by depuration time of 4days in the laboratory. Moreover, we studied the exposure of slugs to brodifacoum in the field. In the laboratory exposure, the slugs consumed rodenticide baits, but no mortality was observed. After 1day, their concentrations were stable over the time and no differences were detected between the concentrations of the three ARs. After 5days of exposure, mean concentrations in slugs were 1.71, 1.91 and 0.44mg/kg wet weight for chlorophacinone, bromadiolone and brodifacoum respectively. A significant decrease of bromadiolone and brodifacoum in slugs was observed in the post exposure period. In the field study, brodifacoum was detected in >90% of analyzed slugs after application of brodifacoum baits. Then, based on a toxicity-exposure ratio approach, we found that slug consumption may represent a risk of secondary poisoning for three of their predators under acute, repeated or subchronic exposure scenarios. These results suggest that the slugs are not only the potential subject to primary exposure, but also the source of secondary exposure for their predators following application of rodenticide baits.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Food Chain; Gastropoda; Indans; Rodenticides

An analytical method based on ultra-high performance liquid chromatography (UHPLC) coupled to Orbitrap high resolution mass spectrometry was developed for the determination of rodenticides (bromadiolone, brodifacoum, difenacoum, chlorophacinone, diphacinone, coumachlor and warfarin) in liver matrix. Different extraction conditions were tested, obtaining the best results when the "dilute and shoot" method (acidified acetonitrile as extraction solvent) and a clean-up step with primary secondary amine (PSA) were used. The optimized method was validated, obtaining recoveries ranging from 60 to 120%. Repeatability and reproducibility were evaluated obtaining values lower than 20%, except for brodifacoum at 10μg/kg. Limits of quantification (LOQs) ranged from 0.1 to 0.5μg/kg, except for brodifacoum, which was 100μg/kg. Six liver samples were analyzed and diphacinone and chlorophacinone were detected in three samples at concentrations ranging from 4μg/kg to 13μg/kg. Moreover a retrospective screening of rodenticide metabolites in those samples and in animal forensic samples was developed based on Orbitrap capabilities. Brodifacoum was detected in three samples, and warfarin alcohol, which is a metabolite of warfarin, was also detected in one sample.

Topics: 4-Hydroxycoumarins; Acetonitriles; Animals; Chromatography, Liquid; Coumarins; Indans; Liver; Mass Spectrometry; Phenindione; Rabbits; Reproducibility of Results; Retrospective Studies; Rodenticides; Warfarin

From 1971 through 1997, we documented 51 cases (55 individual animals) of poisoning of non-target wildlife in New York (plus two cases in adjoining states) (USA) with anticoagulant rodenticides--all but two of these cases occurred in the last 8 yrs. Brodifacoum was implicated in 80% of the incidents. Diphacinone was identified in four cases, bromadiolone in three cases (once in combination with brodifacoum), and chlorophacinone and coumatetralyl were detected once each in the company of brodifacoum. Warfarin accounted for the three cases documented prior to 1989, and one case involving a bald eagle (Haliaeetus leucocephalus) in 1995. Secondary intoxication of raptors, principally great horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis), comprised one-half of the cases. Gray squirrels (Sciurus carolinensis), raccoons (Procyon lotor) and white-tailed deer (Odocoileus virginianus) were the most frequently poisoned mammals. All of the deer originated from a rather unique situation on a barrier island off southern Long Island (New York). Restrictions on the use of brodifacoum appear warranted.

Topics: 4-Hydroxycoumarins; Animals; Animals, Wild; Anticoagulants; Bird Diseases; Deer; Hemorrhage; Indans; New York; Phenindione; Poisoning; Raccoons; Raptors; Rodenticides; Sciuridae; Warfarin

This paper presents the result of a 4 year survey in France (1991-1994) based on the activity of a wildlife disease surveillance network (SAGIR). The purpose of this study was to evaluate the detrimental effects of anticoagulant (Ac) rodenticides in non-target wild animals. Ac poisoning accounted for a very limited number of the identified causes of death (1-3%) in most species. Predators (mainly foxes and buzzards) were potentially exposed to anticoagulant compounds (especially bromadiolone) via contaminated prey in some instances. The liver concentrations of bromadiolone residues were elevated and species-specific diagnostic values were determined. These values were quite similar to those reported in the literature when secondary anticoagulant poisoning was experimentally assessed.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Birds; Environmental Monitoring; Foxes; France; Indans; Liver; Rodenticides; Seasons; Species Specificity

Voluntary ingestion of concentrated anticoagulant rodenticides leads to prolonged hypocoagulability sometimes accompanied by haemorrhage. The authors report 11 cases referred to the Paris Anti-Poisons Centre. The products implicated were chlorophacinone, bromadiolone, and warfarin. The time interval before medical intervention ranged from 90 minutes to 3 weeks. The absence of early clinical signs probably explains the number of late admissions. Haemorrhage of variable severity was observed in 8 cases. The prothrombin time varied with the administered dose of Vitamin K and/or coagulation factors. Three patients were lost to follow-up at days 9, 24 and 68. The other patients were treated for several weeks (27 to 82 days). Massive overdose with these rodenticides justifies stomach washout when the patients are seen early, daily check-ups of coagulability and treatment with Vitamin K at a dosage adapted to the biochemical abnormalities. Severe haemorrhage requires transfusion and the administration of factors of coagulation. The duration of the abnormalities is unpredictable; the prothrombin time should therefore be checked 48 hours after stopping Vitamin K therapy to detect any recurrence.

Topics: 4-Hydroxycoumarins; Adolescent; Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Humans; Indans; Male; Middle Aged; Rodenticides; Suicide, Attempted; Warfarin