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Rodenticides in bubonic-plague control.

The relatively recent development of more-effective pulicides has been paralleled by the discovery of more-efficient rodenticides. Eight of the latter-namely, warfarin, pival, red squill, alpha-naphthylthiourea (ANTU), zinc phosphide, arsenic trioxide, thallium sulfate, and sodium fluoroacetate (1080)-are discussed with particular reference to the criteria of effectiveness against rodents and relative safety to humans and pets. Although the perfect rodenticide has not yet been found, the authors consider that, at present, warfarin appears the most successful in domestic-rat control campaigns. However, the true value of warfarin has still to be determined, and in the meantime it is necessary to select the rodenticide and bait which appear to be most appropriate in each case. In addition, the authors point out that, if the initial poisoning has been ineffective, follow-up with a second rodenticide and bait can produce good results.

Fluoroacetates↗

[Ingestion of a rodenticide with subsequent prolonged coagulopathy].

BACKGROUND: Free-selling rodenticides contain highly potent and long-acting coumarins that may cause severe and prolonged coagulopathies. CASE REPORT: A 46-year-old male was admitted after accidental ingestion of a rodenticide with spontaneous hematomas and a nonmeasurable prothrombin time (International Normalized Ratio [INR]). He had a prolonged coagulopathy and required high doses of vitamin K(1) to normalize the prothrombin time. A dose reduction of vitamin K(1) was followed by a new rise in the INR. CONCLUSION: In cases of coagulopathy and suspicion of an intoxication with anticoagulants, an ingestion of rodenticides containing highly potent coumarins should be taken into account. Intoxications with these "superwarfarins" require high doses of vitamin K(1) given for several weeks.

Coumarins↗

Laboratory tests of 5-p-chlorophenyl silatrane as a rodenticide.

The properties of 5-p-chlorophenyl silatrane as a rodenticide against Rattus norvegicus and Mus musculus were investigated in the laboratory. The high oral toxicity of the compound was confirmed. When the compound was given to laboratory rats and mice by stomach tube at lethal dosages, signs of poisoning were observed within a minute. When caged wild rats and mice were given a choice between plain and poisoned baits the optimum rodenticidal concentration in the bait was about 0.5% for both species, producing 50% mortality in wild rats and 95% mortality in wild mice. The results are discussed in relation to safety in use and the probable effectiveness of the compound as a rodenticide in field conditions.

Administration, Oral↗

Simultaneous determination of eight anticoagulant rodenticides in blood serum and liver.

A liquid chromatographic method was developed for the analysis of indandione and 4-hydroxycoumarin anticoagulant rodenticides in blood serum and liver. The method enabled the measurement of serum and liver concentrations of eight anticoagulant rodenticides: brodifacoum, bromadiolone, chlorophacinone, coumafuryl, coumatetralyl, diphacinone, difenacoum, and warfarin. Anticoagulants were extracted from serum and liver with acetonitrile. Extracts were applied to solid-phase extraction columns, which contained mixed packings. Column eluates were evaporated to dryness, reconstituted, and subjected to reversed-phase liquid chromatography. Hydroxycoumarins were detected by fluorescence at an excitation wavelength of 318 nm and an emission wavelength of 390 nm. Indandiones were detected by UV absorption at 285 nm. Extraction efficiencies of greater than 75% for serum and greater than 69% for liver were obtained. The within-run precision (CV) ranged from 2.4 to 8.6% for serum and 2.6 to 8.7% for liver. The between-run precision (CV) ranged from 1.5 to 12.2% for serum and from 2.1 to 11.8% for liver. Hydroxycoumarin rodenticides were detected at 1 ng/mL of serum and 1 ng/g of liver. Indandiones were detected at 10 ng/mL of serum and 10 ng/g of liver.

4-Hydroxycoumarins↗

Reversed-phase HPLC determination of eight anticoagulant rodenticides in animal liver.

A reversed-phase high-performance liquid chromatographic method was developed for the analysis of eight anticoagulant rodenticides in animal liver. Coumarinic anticoagulant rodenticides (brodifacoum, bromadiolone, coumachlor, coumatetralyl, difenacoum, and warfarin) were detected by using a gradient elution and a fluorimetric detection. Indanedione anticoagulant rodenticides (chlorophacinone and diphacinone) were detected by using an isocratic elution and an UV detection. Anticoagulants were extracted from liver with mixtures of acetone/diethylether and acetone/chloroform. Extracts were applied to solid-phase extraction cartridges. Linearity was checked over the concentration range 0.1-0.6 microgram/g. Relative standard deviations of within-run and between-run variability were all between 5.7 and 10.3%. Recoveries from spiked liver samples were between 51.7 (difenacoum) and 78.2% (warfarin). Limits of detection were between 0.01 (difenacoum and warfarin) and 0.11 microgram/g (chlorophacinone).

Animals↗

Shortfalls using second-generation anticoagulant rodenticides.

Second-generation anticoagulant rodenticides can give rise to unexpected casualties in nontarget species in zoos. The first two offspring of a pair of turkey vultures (Cathartes aura) died of brodifacoum toxicosis. The adult birds fed rodenticide-killed mice to their offspring. There are previous case reports of small carnivorous birds (Dacelo novae-guinae and Tockus deckeni) killed eating poisoned (difenacoum and brodifacoum) mice. Even a granivorous species (Rollulus roulroul) died, probably by contamination of its food by cockroaches that transported the rodenticide.

4-Hydroxycoumarins↗

Salmonella-based rodenticides and public health.

Several countries still permit strains of Salmonella enterica serotype Enteritidis, a leading cause of gastrointestinal illness in humans, to be used in rat baits. To assess the human health risk associated with such rat bait, we first reviewed historic data on health hazards associated with Ratin, a rodenticide that was used in Europe until the early 1960s. Ratin caused outbreaks of human illness, including several deaths. We then compared S. Enteritidis isolated from a current commercial product, Biorat, with S. Enteritidis from Ratin and found that the strains were both phage type 6a. Based on the similarity of the strains, currently available Salmonella-based rodenticides likely are as great a threat to public health as past strains were. Health officials should be aware that the continued use of Salmonella-based rodenticides is a risk to public health and should take appropriate measures to prevent use in their jurisdictions.

Animals↗

Hematometra secondary to anticoagulant rodenticide toxicity.

An adult, intact female Australian shepherd presented for frank vaginal bleeding of unknown duration. The only coagulation profile abnormality upon presentation was mild prolongation of the partial thromboplastin time (PTT). The uterus was removed at surgery and contained a large amount of coagulated blood. Clotting profiles were markedly abnormal 48 hours postoperatively. Serum analysis was positive for brodifacoum, an anticoagulant rodenticide. Preoperative coagulation was most likely normalized by vitamin K1 therapy administered prior to presentation. The only manifestation of anticoagulant rodenticide was hematometra. Rodenticide intoxication should be considered in the differential diagnosis list of hematometra or metrorrhagia.

4-Hydroxycoumarins↗

Toxicology and histopathology of some rodenticides and palatable food items combinations on the common mice Mus musculus var. albus in Egypt.

In this study the palatability tests of certain food items as attractants in the poisoned-baits for the albino mouse Mus musculus var. albus showed that the food items of treacle, maize oil, dry or wet sugar and milk powder act as more attractive pleasant materials that encourage the mice to consume more of those baits containing such items. The most palatable combination of tested food items to the mouse Mus musculus was that consisting of crushed maize + treacle + maize oil + milk powder. The least amount of food consumed by the mice was that of rice and or rice + treacle + oil + milk powder. The use of wheat grain alone was much better than crushed maize alone or and combined with wet or dry sugar. The tested anticoagulant rodenticides were greatly effective against the albino mouse Mus musculus var. albus, since they could cause a final mortality of hundred percent in a mean time ranging merely between 7 & 9 days. Chlorophacinone was more potent and effective than coumachlor; at its lowered concentrations of 25 and 44.5 ppm was more acceptable than coumachlor. The consumed amounts of zinc phosphide baits were comparatively utmost lower than those of anticoagulants poisoned baits. Feeding the pregnant females on prepared baits consisting of crushed maize, treacle, milk powder, maize oil and lower concentration of each of coumachlor, chlorophacinone and zink phosphide, to a more or less extent, reduced females weight according to the tested lower concentration, versus the weight of pregnant females in control treatment which was increased by 14.4%. In comparison to both the tested anticoagulant rodenticides, the measured reduction of females weight caused by zinc phosphide (6 ppm) was, to a more extent, higher as the mean weight gradually decreased from 27.4 up to 16.3 g. Chlorophacinone at its minimized concentrations was least effective in reducing the number and mean weight of developing fetuses. However, coumachlor at its tested concentration of 2 ppm caused abortion after the first and the second weeks of pregnancy reached to 100%. Zinc phosphide at both tested concentrations of 0.6 and 6 ppm was ineffective on the abortion and resorption of fetuses; the fed females on baits containing 0.6 and/or 6.0 ppm zinc phosphide ate their youngsters at the 2nd and 4th day after birth, respectively. The histopathological changes of liver, kidney, lung and intestine due to feeding of the Mouse Mus musculus var. albus on the poisoned baits of tested different rodenticides were recorded and photographed.

Abortion, Induced↗

Difethialone (LM-2219): a new anticoagulant rodenticide for use against warfarin-resistant and -susceptible strains of Rattus norvegicus and Mus musculus.

Data on the efficacy of difethialone, a new anticoagulant rodenticide derived from 4-hydroxybenzothiopyranone against rats and mice, are reported. After one day of feeding with 25 mg/kg of bait, 100 and 85%, respectively, male and female warfarin-susceptible Rattus norvegicus were killed. With the resistant strain, mortality was 90 and 94% for males and females, respectively. 100 and 96% of warfarin-sensitive males and females, respectively, were killed after 3 days of feeding with the same bait. Those of the resistant strain were respectively, 100 and 93%. In Mus musculus, after one day of feeding, mortality was 97, 94, 95 and 93% for males and females of susceptible and resistant strains, respectively, and 100, 97, 100 and 91% after 3 days of feeding. No significant difference in bait intake was observed between 25 mg/kg difethialone bait and a control bait. Compared to other anticoagulant rodenticides, these results show that difethialone is a promising rodenticide.

4-Hydroxycoumarins↗

Toxicity of a vitamin D3 rodenticide to dogs.

As a follow-up to an investigation of 2 dogs that died as a result of apparent toxicosis attributable to a cholecalciferol-containing rodenticide, we tested the toxicity of this product in dogs. Two groups of 2 dogs each were fed amounts of rodenticide that provided 20 and 10 mg of cholecalciferol/kg of body weight (approx one fourth and one eighth of the published LD50, respectively). All dogs developed hypercalcemia and hyperphosphatemia and then died. Major lesions were gastrointestinal hemorrhage, myocardial necrosis, and mineralization of vascular walls. Our data indicate that cholecalciferol-containing rodenticides pose a much greater hazard to dogs than was previously believed.

Animals↗

A comparative assessment of efficacy of three anticoagulant rodenticides.

Results are presented of feeding tests carried out with three common anticoagulant rodenticides viz., coumatetralyl, fumarin and warfarin on three common species of commensal rodents i.e., Rattus rattus, Rattus norvegicus and Bandicota bengalensis. All three species of rodents were susceptible to anticoagulant rodenticides. However, the action of these compounds in B. bengalensis was comparatively slow. Coumatetralyl was found to be the most effective rodenticide followed by fumarin and warfarin. Liquid baits of these compounds are more effective in comparison to food baits.

4-Hydroxycoumarins↗

Rodenticides in British barn owls.

Out of 145 Barn Owls found dead through accidents (66%), starvation (32%), shooting (2%) and poisoning (<1%), 10% contained residues of rodenticides, difenacoum or brodifacoum, in their livers. Difenacoum was in the range 0.005-0.106 microg g(-1) fresh weight, and brodifacoum was in the range 0.019-0.515 microg g(-1). Minimum levels of detection were about 0.005 microg g(-1) for both chemicals. Mice fed for 1 day on food containing difenacoum and brodifacoum died after 2-11 days. Within these mice residues were present at greater concentration in the liver than in the rest of the carcass. The mean mass of residue in a whole 35g mouse was estimated at 10.17 microg (range 4.73-20.65 microg) for difenacoum and 15.36 microg (range 8.07-26.55) for brodifacoum. Such poisoned mice were fed to Barn Owls for successive periods of 1, 3 and 6 days. All six owls fed on difenacoum-dosed mice survived all three treatments, in which up to an estimated 101.7 microg of difenacoum was consumed, and the coagulation times of their blood returned to near normal in less than 5-23 days. Four of the six owls fed on brodifacoum-dosed mice died 6-17 days after the 1-day treatment, but the survivors also survived the 3-day and 6-day treatments. Those that died had each eaten 3 mice, with a combined weight of about 105g and a total brodifacoum content of about 46.07 microg, which was equivalent to a dose of 0.150-0.182 mg kg(-1) of owl body weight. After death these owls had 0.63-1.25 micro g(-1) of brodifacoum in their livers. Blood from the survivors would not coagulate at 9 days post-treatment, but did so at 16 days in one bird and between 38 and 78 days in the other. It is concluded that: (1) Barn Owls in Britain are now widely exposed to second-generation rodenticides; (2) not all owls exposed to these chemicals are likely to receive a lethal dose; (3) brodifacoum is more toxic to owls than difenacoum; and (4) while there is yet no evidence that rodenticides have had any appreciable effect on Barn Owl populations in Britain, further monitoring of residue levels and population trends in desirable.

Journal Article↗

Rodenticide grain bait ingredient acceptance by Norway rats (Rattus norvegicus), California ground squirrels (Spermophilus beecheyi) and pocket gophers (Thomomys bottae).

Vertebrate pest control in California is often accomplished through the use of rodenticide grain baits. These grain baits are composed of steam-rolled oats (SRO), a toxicant, an indicator dye and an oil combination. A series of tests were performed to determine the effects of various dye and oil formulations on acceptance of grain bait by Norway rats [Rattus norvegicus (Berk)], California ground squirrels [Spermophilus beecheyi (Richardson)] and pocket gophers (Thomomys bottae Eyd & Gerv). Seven different dyes, four oil formulations and clean (untreated) oats were tested for acceptance. The addition of the selected oils and dyes to grain resulted in no significant differences in consumption. This indicates that there is a wide variety of dyes that could be used in the formulation of rodenticides. These alternatives could aid in proper pesticide use, the deterrence of bait consumption by birds and possibly in ingredient adhesion to the finished bait.

Animals↗

Bleeding problems associated with occupational exposure to anticoagulant rodenticides.

OBJECTIVE: Sporadic reports have occurred on adverse health effects due to occupational exposure to anticoagulant rodenticides. We report a case of coagulation derangement in a pest-control officer and present the results of a survey of his colleagues. METHODS AND RESULTS: A 48-year-old man worked as a part-time pest-control officer applying rodenticides 3 h a week using gloves, but no mask, and without washing his hands between applications. He developed a symptomatic coagulation disturbance, probably caused by absorption of the poisons during work. No signs of coagulopathy were found in the patient's colleagues ( n=16), although basic hygiene measures were not always taken. CONCLUSION: Occupational exposure to anticoagulants should be considered in cases of unexplained bleeding. We recommend that measures be taken to minimize the risk of occupational intoxication.

Anticoagulants↗

Determination of five 4-hydroxycoumarin rodenticides in animal liver tissues by ion chromatography with fluorescence detection.

A novel analytical method is proposed for rapid simultaneous determination of five 4-hydroxycoumarin rodenticides in animal liver tissues by eluent generator reagent free ion chromatography (RFIC) with fluorescence detection. Rodenticides were initially extracted from homogenized animal liver tissues with ethyl acetate and the extracts subjected to a solid-phase extraction process using Oasis HLB cartridges. The IC separation was carried out on an IonPac AS11 analytical column (250 mm x 4.0 mm) using gradient KOH containing 10% acetonitrile as organic modifier at a constant flow rate of 1.0 mL/min. The analytes were detected by fluorescence at an excitation wavelength of 270 nm and an emission wavelength of 380 nm. The average recoveries of the objective compounds spiked in animal liver tissues were between 81% and 98%. The limits of quantification (LOQs) were 0.004-0.010 mg/kg for them. Within-day and day-to-day relative standard deviations (RSD) were less than 8.5% and 9.7%, respectively. It was confirmed that this method could be used in a toxicological analysis.

4-Hydroxycoumarins↗

Determination of coumarin anticoagulant rodenticide residues in animal tissue by high-performance liquid chromatography. I. Fluorescence detection using post-column techniques.

A multi-residue method was developed for the determination of the rodenticides warfarin, coumatetralyl, bromadiolone, difenacoum and brodifacoum in animal tissues by high-performance liquid chromatography with fluorescence detection. Extracts were cleaned-up by gel permeation chromatography on Bio-Beads SX-3 and residues determined by normal and reversed-phase high-performance liquid chromatography using post-column pH-switching, with chloroform -sec.-butylamine and borate buffer (pH 10.4) respectively, to maximise the native fluorimetric responses. Confirmation of identification was possible by re-chromatographing extracts in the absence of the post-column reagent. Chloroform-acetone (1:1) was significantly better than chloroform for the extraction of residues of these rodenticides from liver tissues. Recoveries from spiked liver tissue were generally greater than 90% at levels of 0.05-1 mg kg-1. Detection limits in animal tissues of 0.002 mg kg-1 for coumatetratyl, difenacoum and brodifacoum, 0.01 mg kg-1 for bromadiolone and 0.02 mg kg-1 for warfarin and could be routinely achieved.

Animals↗

Haemorrhage in seven cats with suspected anticoagulant rodenticide intoxication.

Clinical features were evaluated in seven adult cats (six males, one female) with haemorrhage and presumptive anticoagulant rodenticide intoxication. Haemorrhage appeared as thoracic haemorrhage, otic bleeding, haematoma, melena, haematochezia, and petechiation. The most common other presenting signs were lethargy, anorexia, and tachypnoea or dyspnoea. Six cats were anaemic, four cats were mildly thrombocytopenic (58000-161000/ microL), and three had slightly decreased plasma protein or albumin values. The prothrombin time (30.3->100 s, reference range: 16.5-27.5 s) and activated partial thromboplastin time values (32.6->100 s; reference range: 14-25 s) were markedly prolonged in all cats. All cats received vitamin K(1)subcutaneously or orally (3.7-5 mg/kg body weight initially) and depending on severity of signs five cats were transfused with fresh whole blood. Plasma coagulation times improved in all cats and returned to normal in 1-5 days. Rodenticide poisons represent an important but relatively rare cause of haemorrhage in cats and can be effectively treated.

Administration, Oral↗