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Fatal brodifacoum rodenticide poisoning: autopsy and toxicologic findings.

This report details the pathologic and toxicologic findings in the case of a 15-year-old girl who deliberately and fatally ingested brodifacoum, a commonly used rodenticide. The mechanism of death, massive pulmonary hemorrhage, has not been previously reported. Brodifacoum was quantitated in liver, spleen, lung, brain, bile, vitreous humor, heart blood, and femoral blood using HPLC with fluorescence detection. The highest brodifacoum concentrations were detected in bile (4276 ng/mL) and femoral blood (3919 ng/mL). No brodifacoum was detected in brain or vitreous humor. A brodifacoum concentration of 50 ng/g was observed in frozen liver while formalin fixed liver exhibited a concentration of 820 ng/g. A very high blood:liver brodifacoum concentration ratio suggested acute poisoning but the historical and pathologic findings suggested a longer period of anticoagulation. Though most cases of brodifacoum poisoning in humans are non-fatal, this compound can be deadly because of its very long half-life. Forensic pathologists and toxicologists should suspect superwarfarin rodenticides when confronted with cases of unexplained bleeding. Anticoagulant poisoning can mimic fatal leukemia or infectious diseases such as bacterial sepsis, rickettsioses, plague, and leptospirosis. A thorough death scene investigation may provide clues that a person has ingested these substances.

4-Hydroxycoumarins↗

Trials of the anticoagulant rodenticide WBA 8119 against confined colonies of warfarin-resistant house mice (Mus musculus L.).

The efficacy of the newly developed anticoagulant rodenticide WBA 8119 was evaluated against the house mouse (Mus musculus L.) using individual and family groups of warfarin-resistant animals. WBA 8119 at 0-002%, 0-005% and 0-01% in pinhead oatmeal bait gave complete kills of mice in 'no-choice' feeding tests carried out in cages and small pens. In replicated 21-day treatments on families of mice confined in larger pens conditioned to feeding on plain foods, the overall mortalities obtained using the three formulated poison baits were 71/72, 62/63 and 57/57 respectively. The results of the WBA 8119 toxicity tests are considered in relation to previous findings on other anticoagulant rodenticides, particularly difenacoum. In equivalents tests, WBA 8119 performed better than difenacoum. The data thus suport the laboratory findings that WBA 8119 is the most active anticoagulant so far tested for the control of warfarin-resistant house mice.

4-Hydroxycoumarins↗

Trials of the anticoagulants rodenticide WBA 8119 against confined colonies of warfarin-resistant house mice (Mus musculus L.).

The efficacy of the newly developed anticoagulant rodenticide WBA 8119 was evaluated against the house mouse (Mus musculus L.) using individual and family groups of warfarin-resistant animals. WBA 8119 at 0-002%, 0-005% and 0-01% in pinhead oatmeal bait gave complete kills of mice in 'no-choice' feeding tests carried out in cages and small pens. In replicated 21-day treatments on families of mice confined in larger pens and conditioned to feeding on plain foods, the overall mortalities obtained using the three formulated poison baits were 71/72, 62/63 and 57/57 respectively. The results of the WBA 8119 toxicity tests are considered in relation to previous findings on other anticoagulant rodenticides, particularly difenacoum. In equivalent tests, WBA 8119 performed better than difenacoum. The data thus support the laboratory findings that WBA 8119 is the most active anticoagulant so far tested for the control of warfarin-resistant house mice.

4-Hydroxycoumarins↗

Acquired coagulopathy due to anticoagulant rodenticide poisoning.

A 35-year-old woman was admitted to hospital because of epistaxis, hematomas, and metrorrhagia. Laboratory data indicated severe coagulopathy with prolonged prothrombin time and decreased serum concentrations of vitamin K-dependent clotting factors II, VII, IX, and X. The patient denied taking any oral anticoagulants. She was given transfusions of red blood cells, fresh frozen plasma (1,180 mL) and phytomenadione daily for 6 weeks (total dose 550 mg), which normalized the coagulation factors concentration. After all other possible causes of acquired coagulopathy had been excluded, rodenticide poisoning was suspected on the basis of her epidemiologic history. The patient was a war refugee from Bosnia and Herzegovina. During her absence, the troops of United Nations Protection Force performed rodent extermination in and around her house. History data and therapeutic effects suggested that the coagulopathy had been caused by prolonged exposure to long-acting anticoagulant rodenticide. This could also explain the need for protracted phytomenadione therapy.

4-Hydroxycoumarins↗

Rodenticidal activity of two natural coumarines from ether extract of Citrus bergamia.

The rodenticidal activity, expressed by LD50 values of ether and petroleum ether extracts of Citrus bergamina pulp against two rat species, Rattus norvegicus (Norway rat) and Rattus rattus (roof rat) was evaluated. Based on LD50 values, ether extract was nearly 1.6 and 1.3 times more toxic to Norway rat and roof rat than ethanol respectively, while pet. ether extract was non toxic to the two rat species. From ether extract, two natural coumarines, Bergapten and Coumurrayin were isolated and tried against the two rat species as anticoagulant rodenticides. Norway rats were more susceptible to both compounds than the roof ones. A direct parallel relationship was found between the toxicity and changes in the blood picture.

5-Methoxypsoralen↗

Rodenticide-induced hepatotoxicity.

Hepatotoxicity following acute poisoning with rodenticides has been infrequently reported in literature. To emphasize the fact that this form of clinical presentation is not unusual we are reporting two cases of rodenticide poisoning masquerading as severe hepatic dysfunction.

Adult↗

Clinical and pathological features of anticoagulant rodenticide intoxications in dogs.

Ten dogs underwent clinical monitoring and laboratory investigations following accidental poisoning with anticoabulant rodenticide products. Hematobiochemical parameters, coagulation profiles and toxicologic analyses of plasma and/or tissues were monitored. In 2 cases necropsy examinations were done. The clinical-pathological aspects of anticoagulant rodenticide poisonings of dogs are then discussed.

Animals↗

Field evaluation of difethialone, a new second generation anticoagulant rodenticide in the rice fields.

A new second generation anticoagulant rodenticide, difethialone (0.0025%), was evaluated in the rice fields at three different cropping stages, viz. Milky, Panicle formation and Panicle maturation, during Kuruvai and Thaladi seasons. The difethailone (0.0025%) yielded satisfactory control success suggesting a great potential as a rodenticide especially in the early stages of rice.

4-Hydroxycoumarins↗

Evaluation of secondary poisoning of difethialone, a new second-generation anticoagulant rodenticide to barn owl, Tyto alba Hartert under captivity.

Secondary toxcity of difethialone to Barn owl (Tyto alba) has been investigated. Difethialone was fed to owls for successive periods of 1 (phase 1), 3 (phase 2) and 6 (phase 3) days via-rodenticide dosed rats. The owls survived after the treament of rodenticide on phase 1 and phase 2 experiments but they died during phase 3 experiment. The results suggest that the difethialone could cause more secondary toxicity to owls.

4-Hydroxycoumarins↗

A case of tetramine poisoning: a lethal rodenticide.

We report a fatal case of suicide presenting with convulsions and subsequently multi-organ failure. Rodenticide poisoning was not suspected until the next day when tetramine was detected in the patient's blood, urine, and food residues. Tetramine is a potent rodenticide with a rapid action and high mortality. The poison has been banned worldwide but is still readily available in Mainland China. Outbreaks of poisoning are reported frequently and doctors should be alert for this lethal toxin.

Bridged-Ring Compounds↗

Hypercalcemia secondary to cholecalciferol rodenticide toxicosis in two dogs.

Hypercalcemia secondary to cholecalciferol rodenticide toxicosis was identified in two dogs. The first dog died shortly after admission. The second dog responded to treatment with sodium chloride solution, prednisolone, furosemide, and calcitonin. Treatment was needed for a longer period than anticipated and the serum calcium concentration did not stabilize for approximately one month. Although not conclusively demonstrated, calcitonin was considered the cause of severe anorexia. This new class of rodenticides has great toxic potential for dogs, and it is recommended that serum calcium concentration be carefully monitored as treatment for hypercalcemia is gradually withdrawn.

Animals↗

[Toxicity to rodenticides and its treatment].

A case is presented of exposure to a rodenticide which caused a severe disorder of hemostasis, including macroscopic hematuria, several months after the patient was exposed to it. Response to treatment with vitamin K and barbiturates came only after 70 days. The cause-and-effect relationship between exposure to the rodenticide and the disorder in hemostasis is based on the clinical course and on the late response to treatment.

Adult↗

Hypercalcemia associated with rodenticide poisoning in three cats.

Hypercalcemia (12.0 to 18.3 mg/dl) was detected in 3 cats that had eaten a rodenticide that contained cholecalciferol. Clinical signs included lethargy, anorexia, vomiting, and polydipsia. Treatment with furosemide and fluids administered IV resulted in normalization of the serum calcium concentration and in remission of the clinical signs in 2 cats. One cat with a serum calcium concentration of 18.3 mg/dl did not have clinical signs, was not treated, and was reportedly normal 9 months after initial examination. We attributed the uniformly favorable outcome of exposure to the rodenticide in these cats to the small quantity of the toxin ingested.

Animals↗

Rodent resistance to the anticoagulant rodenticides, with particular reference to Denmark.

Inherited resistance to anticoagulant rodenticides was discovered in populations of Rattus norvegicus about 14 years ago. Similar resistance has now been reported from several countries in north-western Europe and from the USA. In order to detect resistance and to control it effectively, basic data on the susceptibility of rat populations are required for each country, and trapping surveys should be made in any area where resistance is suspected. Acute poisons are needed to control resistant rats although the shift from anticoagulants to acute poisons is a retrograde step as far as efficiency is concerned, and increases the hazard of control operations to man and other animals. Resistance to anticoagulants in Mus musculus has been reported from England, and resistant mice are probably to be found in other countries also in view of the great individual variation in susceptibility of this species to these rodenticides.

Animals↗

A critical review of currently used single-dose rodenticides.

The introduction of the anticoagulants in the early 1950s, with their much greater safety to nontarget animals, resulted in a general decline in the use of single-dose rodenticides. However, the appearance of rodent resistance to the anticoagulants, first in the United Kingdom, later elsewhere in Europe, and still more recently in the USA, has revived interest in the use of single-dose rodenticides. Unfortunately, owing to their danger to nontarget mammals, the use of several of these compounds must be restricted; others, despite their long use, are now recognized to be unsatisfactory because of their poor acceptance or reacceptance by rats and mice. Thus, only very few compounds of this type are available for unrestricted use and there is an urgent need for the development of effective alternatives.

Amides↗

Rodenticide-induced coagulopathy in a young child. A case of Munchausen syndrome by proxy.

PURPOSE: To present the diagnosis and management of superwarfarin ingestion, a cause of serious and prolonged coagulopathy. METHODS: Specific identification of the anticoagulant was made by high-pressure liquid chromatography. RESULTS: A 24 month-old child developed bruises and a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) after receiving multiple doses of brodifacoum, a superwarfarin rodenticide. The coagulopathy was treated successfully with large doses of parenteral and oral vitamin K1; fresh frozen plasma was administered as a precautionary measure on two occasions. After the first 10 days of the child's hospitalization, the mother was identified as the source of brodifacoum, exemplifying the behavior described as Munchausen syndrome by proxy. Oral vitamin K1 was initiated and continued in an outpatient setting with tapering doses over nine months, using the PT as a guide for therapy. CONCLUSIONS: This report emphasizes the necessity of recognizing rodenticide poisoning and investigating its source. Frequent monitoring of the PT is essential to prevent hemorrhagic complications due to repeat exposure, inadequate vitamin K1 therapy, or noncompliance.

4-Hydroxycoumarins↗

Detection of anticoagulant rodenticides (4-hydroxycoumarins) by thin-layer chromatography and reversed-phase high-performance liquid chromatography with fluorescence detection.

The detection of 4-hydroxycoumarin rodenticides in poisoned domestic animals requires a highly sensitive method as tissue and serum levels of anticoagulants may be very low owing to rapid elimination, metabolism or post-mortem degradation. Thin-layer chromatography (TLC) and reversed-phase high-performance liquid chromatography (RP-HPLC) with fluorescence detection were used to identify the anticoagulants in spiked tissues and in suspicious samples. The analysis of ten suspicious samples highlighted the limitations of both methods. Only the three samples of baits were found positive by TLC whereas one of the five anticoagulants was detected in eight samples by RP-HPLC with fluorescence detection. Therefore, RP-HPLC with fluorescence detection proved to be the more sensitive method for detecting low levels of 4-hydroxycoumarins in blood serum, liver and ingesta, whereas TLC is usually sufficient for analysing baits.

4-Hydroxycoumarins↗

Separation of estrogens and rodenticides using capillary electrophoresis with aqueous-methanolic buffers.

Capillary electrophoresis (CE) has proven to be an efficient method for the separation of various charged and neutral analytes. For analytes having limited solubility in water, the CE mode of separation has been micellar electrokinetic capillary chromatography (MECC). However, another approach is the direct addition of an organic solvent to a non-MECC CE separation system. Walbroehl and Jorgenson and also Balchunas and Sepaniak have reported on the use of organics in CE but the focus of their work was using MECC to separate small organic compounds. This work examines the use of aqueous-methanolic buffers in non-MECC CE separations of estrogens and rodenticides.

Buffers↗