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PubMed1982

Field trials of second-generation anticoagulants against difenacoum-resistant Norway rat populations.

Trials of rodenticidal baits containing 50 p.p.m. difenacoum, 50 p.p.m. bromadiolone or 20 p.p.m. brodifacoum were carried out on farmsteads against populations of Rattus norvegicus containing difenacoum-resistant individuals. Six difenacoum treatments failed in 14--42 days of baiting. Two treatments with bromadiolone succeeded in 23 and 33 days, but four further treatments lasting 35--56 days failed to eradicate the populations. Brodifacoum gave virtually complete control of six populations in 21--73 days and of the ten residual populations left behind by the other two compounds, after baiting for a further 11--85 days. The performance of both bromadiolone and brodifacoum was well below that reported by previous investigators, indicating the possibility of low-grade resistance to these compounds in the difenacoum-resistant strain.

4-Hydroxycoumarins↗
PubMed2005

Construction and evaluation of a humic acid column: implication for pesticide risk assessment.

In this paper, humic acid (HA), known to play a large role in the binding and transport of pesticides in soil, was immobilized on a chromatographic support. Then, the association of some herbicides and rodenticides with the main soil component HA was examined using this novel chromatographic column. It appeared that HA has a lower affinity for neutral than for charged pesticides. Moreover, the influence of various parameters was investigated on the pesticide retention in order to providevaluable information about both the binding mechanism and the utilization conditions of the HA column. For all the pesticides studied, a change was clearly vizualized in the HA-pesticide association mechanism at a critical value of the Na+ concentration in the bulk solvent, x(c), equal to 0.6 M. Around this value, the HA structure balanced between a flexible linear conformation for x < x(c) and a random coil form for x > x(c). This work confirmed the conformation change on HA immobilized on silica. As well, only for the charged pesticides, it was clearly pointed out that below a Na+ concentration equal to 0.3 M, the pesticide binding to HA decreased when the salt concentration was enhanced due to an ion pair formation and a competition effect between the sodium cation and pesticide to bind to the HA molecule. Furthermore, it was established that the HA column was stable during an extended period of time, indicating that the HA column could soon become very attractive to determine the risk assessment of pesticides.

Herbicides↗
PubMed1999

Cyclodextrin-based optosensor for the determination of warfarin in waters.

A flow-through optosensor for warfarin is described. The sensor is developed in conjunction with flow analysis systems and uses a commercial bound beta-cyclodextrin material as the sensing phase. A strong fluorescence signal was observed as a result of the formation of an inclusion complex between warfarin and beta-cyclodextrin. The analytical performance characteristics of the proposed sensor for analysis of low levels of warfarin were as follows: the detection limits for continuous and flow injection analysis systems were 2 and 19 ppb, respectively; the observed relative standard deviations at 0. 5 ppm warfarin level were less than 2.3%. A study of the interference of other naphthalenic toxic substances was carried out. The continuous flow method was satisfactorily applied to the determination of the rodenticide in natural waters.

Agriculture↗
PubMed2002

Assessment of risks of brodifacoum to non-target birds and mammals in New Zealand.

The risks to non-target birds and other wildlife from the use of vertebrate pesticides, including anticoagulant rodenticides, are determined to a significant extent by species' intrinsic susceptibility, and the toxicokinetics of the compounds used. Brodifacoum is highly toxic to birds and mammals. The acute toxicity of brodifacoum to birds in New Zealand varies from <1 mg/kg in pukeko (Porphyrio p. melanotus), the native swamp hen, to >20 mg/kg in the paradise shelduck (Tadorna variegata). Like other second-generation anticoagulants brodifacoum is strongly bound to vitamin K epoxide reductase and will persist, apparently for at least 6 months, in organs and tissue containing this enzyme, e.g., liver, kidney, and pancreas. The unique toxicokinetics of this class of compound exacerbates the risk of primary and secondary poisoning of non-target species. Vertebrate pest control programmes in New Zealand using bait containing brodifacoum have resulted in the primary and secondary poisoning and sub-lethal contamination of non-target species. These include native raptors, such as the Australasian harrier (Circus approximans) and morepork (Ninox novaeseelandiae), other native birds such as the pukeko, weka (Gallirallus australis), southern black-backed gull (Larus dominicanus), and kiwi (Apteryx spp.), and introduced mammals, including game animals. There are increasing numbers of reports worldwide of wildlife contamination and toxicosis after the use of second-generation anticoagulants. All pest control activities require careful risk-benefit assessment in view of their potential to cause adverse environmental impact. Monitoring of wildlife for pesticide residues will provide data that can be used to reduce the risk of anticoagulant bioaccumulation and mortality in non-target species.

4-Hydroxycoumarins↗
PubMed2002

A prospective study of acute, unintentional, pediatric superwarfarin ingestions managed without decontamination.

STUDY OBJECTIVE: We determine the incidence of clinically important bleeding in children with superwarfarin rodenticide ingestions not treated with gastrointestinal decontamination or prophylactic vitamin K. METHODS: We prospectively studied patients younger than 6 years of age who reported to our poison center with acute unintentional superwarfarin ingestions. Patients who received gastrointestinal decontamination or prophylactic vitamin K were excluded. Forty-eight- to 96-hour prothrombin time or international normalized ratio (INR) blood tests were recommended, and telephone contact was attempted at least 3 days after ingestion. RESULTS: A total of 595 consecutive patients were enrolled during the 16-month study period. Fifty patients were excluded: 8 who were known to have ingested 1 pellet or less; 25 who received activated charcoal; 15 who were treated with induced emesis; and 2 who received prophylactic vitamin K. The resulting study group contained 545 patients. Eighty-two patients were lost to follow-up. Follow-up was obtained for 463 patients, including 222 by telephone contact alone, 62 by 48- to 96-hour INR, and 179 by both methods. None of the patients had clinically important coagulopathy. Two patients had an INR of 1.5 or greater (1.5 and 1.8) without symptoms. Single nosebleeds were reported in another 2 patients with normal 48-hour INRs. Another child had a small amount of blood crusted in the nose with no other symptoms and no laboratory work available. One child with a normal 48-hour INR had blood-streaked stools that were thought to be caused by an anal fissure. CONCLUSION: Children with acute unintentional superwarfarin ingestions of less than 1 box may be managed without gastric decontamination or prophylactic vitamin K. Laboratory testing for coagulopathy should be reserved for cases involving clinically evident bleeding abnormalities.

4-Hydroxycoumarins↗
PubMed2001

Environmental factors associated with rodent infestations in Argentine poultry farms.

1. Seasonal variations in rodent infestations were studied at poultry farms in central Argentina as well as the environmental factors associated with rodent infestations at poultry farms. 2. During the summer and winter of 1998 rodent infestation was monitored at 10 poultry farms by means of tracking stations, and 21 environmental variables were selected that a priori could be related with the extent of rodent infestation. 3. There was a higher rodent infestation in winter than in summer. 4. Species detected by rodent sightings at the poultry farms included Akodon azarae, Calomys spp. (C. laucha and possibly C. musculinus) and Mus musculus. 5. In summer, rodent infestation was positively associated with the perimeter of the farm, whereas there was an inverse relationship with the maintenance conditions of the sheds. In winter, rodent infestation was positively associated with the percentage of the borders of the farm covered with vegetation, and with the amount of plant cover, especially the amount of plant cover which was above 20 cm in height. 6. There was no significant relationship between rodent infestation and the time lag since the last application of rodenticide (first-generation anticoagulant) at the farms. 7. These results suggest that strategies for controlling rodents based solely on chemical methods may not be good enough for efficient rodent control. Farms which are properly managed, with a better control of vegetation growth at both the perimeter and within the internal area, in addition to a higher maintenance of sheds have appreciably lower rodent infestations.

Animal Husbandry↗
PubMed2001

Suppression of CYP3A2 mRNA expression in the warfarin-resistant roof rat, Rattus rattus: possible involvement of cytochrome P450 in the warfarin resistance mechanism.

1. The continual use of warfarin as a rodenticide has caused the development of populations of warfarin-resistant roof rat. To study the biochemical mechanism of warfarin resistance, the mRNA expression levels of the major P450 forms in the warfarin-resistant and -susceptible roof rat liver following exposure to warfarin were quantified by competitive RT-PCR. 2. The constitutive levels of CYP2C11 and CYP3A2 mRNAs in the warfarin-resistant and -susceptible roof rat were extremely low compared with those in the STD rat. In response to warfarin administration, the CYP3A2 mRNA level in the warfarin-susceptible rat increased to about 3-fold of that before the treatment, whereas in the warfarin-resistant roof rat, CYP3A2 mRNA remained at a low level. 3. The present results suggest the possibility that reduced synthesis of CYP3A2 mRNA is involved in the warfarin-resistant mechanism in the roof rat.

Animals↗
PubMed1992

The development of cleanup criteria for an acutely toxic pesticide at a contaminated industrial facility.

Sodium fluoroacetate, a restricted-use rodenticide, was improperly applied to kill rats in a South American steel mill. As a result of this application, several workers were seriously injured. During plant decontamination, cleanup levels were developed to ensure that any residual material remaining at the plant did not pose a health risk. Cleanup levels were developed to prevent significant exposure of workers, who could inhale contaminated dust, contact dust, or soil dust in outdoor areas or on plant floors and who could contact contaminated surfaces. On the basis of a health risk analysis, the following cleanup levels for sodium fluoroacetate were developed--air cleanup levels, 0.05 mg/m3; soil/dust cleanup levels, 100 mg/kg; and wipe sample cleanup levels, 0.2 mg/100 cm2. These risk-based cleanup levels were ultimately used to assist the regulatory agencies in reaching a decision to reopen the plant.

Air Pollutants, Occupational↗
PubMed2005

Epidemiology of hydrogen phosphide exposures in humans reported to the poison center in Mainz, Germany, 1983-2003.

BACKGROUND: Poisonings with rodenticides containing hydrogen phosphide-releasing compounds may lead to deleterious organ dysfunction and death. Since data of hydrogen phosphide poisonings is limited to case reports/series, this study was intended to elucidate hydrogen phosphide poisonings based on a 20-year data collection. METHODS: Explorative data analysis of the Poison Center Mainz database looking for route of exposure, symptoms, and severity using the Poisoning Severity Score. RESULTS: From 1983-2003, 188 hydrogen phosphide poisonings were reported. Sixty-five percent of these were unintentional residential, 28% attempts to commit suicide (intentional), 5% occupational, and 2% undetermined. In the majority of intentional poisonings the poison was ingested, whereas in unintentional poisoning of adults inhalation exposure dominated, caused by inappropriate self-protection from the released hydrogen phosphide gas during usage. Frequently observed symptoms in unintentional poisonings were nausea, vomiting, pain, coughing, and dizziness with no further worsening of symptoms. In intentional poisonings frequent symptoms were vomiting, somnolence, seizures, coma, and shock with two initially fatal poisonings. Follow-up on these cases showed a significant worsening of symptoms and a two-fold increase in fatal poisonings. CONCLUSION: Route of exposure, severity of symptoms, and the necessary treatment differs substantially between unintentional and intentional poisonings. In this study, two initially symptomatic intentional poisonings were later reported fatal. Careful monitoring is recommended in symptomatic intentional poisonings.

Adolescent↗
PubMed2003

1H NMR spectroscopy and GC-MS analysis of alpha-chloralose. Application to two poisoning cases.

Alpha-chloralose, a compound widely used as a rodenticide and in the control of bird pests, is readily available. Two cases of intentional poisoning are reported. Both patients became comatose and presented hypersialorrhea and myoclonal crises in the legs. They were discharged from hospital after several days. As clinical signs of alpha-chloralose poisoning lack specificity, anamnesis might be difficult, particularly in the case of delayed diagnosis. Toxicological analysis is therefore critical, and this article reports the investigation of serum and urine samples by gas chromatography-mass spectrometry (GC-MS) in the electron-impact mode, and by 1H nuclear magnetic resonance (1H NMR) spectroscopy. Non-hydrolyzed urinary samples and those hydrolyzed by beta-glucuronidase were taken into consideration. After acetylation, GC-MS analysis was based on characteristic mass-to-charge ratio values of 272 for alpha-chloralose and 206 for beta-hydroxyethyltheophylline, which was used as internal standard. Characterization of alpha-chloralose species by 1H NMR spectroscopy was performed taking two parameters into account: chemical shift and coupling-constant values. Without any pretreatment, 1H NMR spectroscopy revealed the presence of free (5.50 and 6.15 ppm) and conjugated forms of alpha-chloralose by characteristic resonances of H1 and chloral-type protons, respectively. Quantitative analysis was performed by relative integration of peak areas. Serum alpha-chloralose showed concentrations below the quantitation limit of both methods. In urine samples, the free chemical species rapidly decreased. GC-MS analysis revealed the predominence of conjugation after a beta-glucuronidase hydrolysis step. 1H NMR analysis directly showed that on admission of the first patient, average urinary concentrations were 1.73 mmol/L (535 mg/L) for the free form and 13.72 and 6.25 mmol/L for the two conjugated forms. A later enzymatic treatment confirmed the total concentration of alpha-chloralose chemical species. Analysis of alpha-chloralose in urine by either GC-MS or 1H NMR spectroscopy methods proved to be comparable.

Adult↗
PubMed2004

Strychnine overdose following ingestion of gopher bait.

A 52-year-old male was discovered supine on his bed in a state of early decomposition. Commercial strychnine-treated gopher pellets were found in the home, and suicide notes were present at the scene. Biological fluids and tissues were tested for basic, acidic, and neutral drugs using gas chromatography-mass spectrometry. Concentrations of strychnine in heart and femoral blood were 0.96 and 0.31 mg/L, respectively. Vitreous fluid, bile, urine, liver, and brain specimens contained 0.36 mg/L, 1.17 mg/L, 2.92 mg/L, 4.59 mg/kg, and 0.86 mg/kg strychnine, respectively. No other drugs were detected in any of the samples. The cause of death was attributed to rodenticide poisoning, and the manner of death was suicide.

Animals↗
PubMed2006

Acute bromadiolone intoxication.

A 55-year-old man came to the hospital with a bleeding wound on his tongue. The coating of his tongue was green, and his sputum was red. Because an increased international normalized ratio-value was measured, a blood sample was sent to our laboratory with the suspicion of coumarin intoxication. Liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis confirmed the poisoning was by bromadiolone, with its maximum serum concentration at 440 microg/L. The analysis of further samples resulted in a calculated elimination half-life of 140 h. The analytical method described was developed for the determination and quantitation of bromadialone using LC-MS. This method is suitable for the simultaneous identification and quantitation of 10 indirect anticoagulants in human serum, which include five superwarfarins (brodifacoum, bromadiolone, difenacoum, difethialone, and flocoumafen) as rodenticides licenced in Germany and five other vitamin K antagonists (acenocoumarol, coumatetralyl, coumachlor, phenprocoumon, and warfarin). The method is based on an acidic (pH 4.2) liquid-liquid extraction followed by LC-ESI-MS analysis. Analytical separation was carried out using an Atlantis C18 column (2.1 x 20 mm, 3 microm). The mobile phase consisted of methanol/0.1% formic acid; the flow rate was 0.6 mL/min, and the time needed for analysis was 5 min. The lower limit of quantitation was 5 microg/L (signal-to-noise > 10).

4-Hydroxycoumarins↗
PubMed1987

Common household poisonings.

Readily available household products represent a source of potential toxicity when ingested accidentally by children. Despite the large number of patients seen by physicians and a familiarity with many of these substances, patient management often remains a difficult problem. The current literature is reviewed with respect to appropriate management of ingestions of household cleaners, caustics, hydrocarbons, insecticides, rodenticides, plants, and other products often taken by children.

Child↗
PubMed2002

Acute, unintentional pediatric brodifacoum ingestions.

BACKGROUND: Brodifacoum is the major rodenticide used in the United States today. It is similar to warfarin but has more potent and prolonged effects. Large overdoses and chronic intoxication have been associated with significant coagulopathies and death. Currently, the management of acute unintentional ingestions by young children is controversial. METHODS: American Association of Poison Control Centers (AAPCC) data from 1993 to 1996 were retrospectively searched for acute, unintentional brodifacoum exposures without coingestions followed-up to a known outcome in children aged 6 years and younger. The cases were analyzed by management site, symptoms, therapy, and outcome. Cases coded as having clinical or laboratory evidence of coagulopathy were further evaluated for severity. RESULTS: Our study reviewed 10,762 cases that involved single, acute, unintentional ingestions of brodifacoum. All of the patients were followed-up to a known outcome as defined by AAPCC data collection standards. In this cohort, there were no deaths or major effects reported. Although 67 patients reported evidence of coagulopathy, no major effects or deaths were reported. Minor and moderate effects were reported in 38 and 54 children, respectively. Management occurred outside of a healthcare facility in 5404 (50.2 %) cases. Approximately half of all the children received some form of gastrointestinal decontamination. Decontamination had no effect on the distribution of outcomes. Adverse effects from decontamination therapy were reported in 42 patients. CONCLUSION: Acute pediatric ingestions of brodifacoum rarely caused clinical effects and were not associated with life-threatening symptoms or death in young children. It seems reasonable that acute unintentional ingestions of small quantities of brodifacoum by young children can be adequately managed with home observation and parent education.

4-Hydroxycoumarins↗
PubMed1977

Pediatric pesticide poisonings in North Carolina: epidemiologic observations.

In four years, 218 pesticide exposures were reported among North Carolina children. Epidemiologic follow-up revealed 50 symptomatic cases with nine fatalities. Mean age of exposed children was 27 months; boys were involved twice as frequently as girls. Agents most often implicated were anticoagulant rodenticides (17%) and organophosphate insecticides (16%). Sixty-eight percent of exposures were to products intended for household use. Special characteristics of pesticides that contribute to morbidity include exceptional toxicity, dermal penetration, and frequent application as food baits. Exposure histories indicate that high petroleum distillate content often adds to product toxicity.

Child↗
PubMedDate not supplied

Coagulopathic effects and therapy of brodifacoum toxicosis in dogs.

The clinical signs and laboratory changes of brodifacoum (BDF) intoxicated dogs and their response to vitamin K1 treatment were examined. Brodifacoum, a second-generation anticoagulant rodenticide, was fed to four dogs for 3 consecutive days producing a cumulative dose of 1.1 mg BDF/kg body weight. Clinical observations of the animals were made daily throughout the study. Monitored laboratory parameters included: one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), activated coagulation time (ACT), complete blood counts, thrombocyte counts, and serum chemistry values. Response to vitamin K1 therapy was evaluated clinically and by laboratory tests. Serum BDF concentrations were monitored. Inappetence and hemorrhagic tendencies were exhibited by day 5 postrodenticide exposure. One-stage prothrombin time, APTT, and ACT were 25% greater than time zero values at 24, 24, and 72 hours postdosing, respectively. All laboratory parameters returned to normal within 48 hours of initiating vitamin K1 therapy (0.83 mg/kg orally, TID for 5 days). Serum brodifacoum concentrations were highest (1065-1215 ng/mL) during the 3 days after BDF dosing and were detectable (3.0-7.5 ng/mL) until day 24 postexposure. A mean BDF elimination half-life of 6 +/- 4 days was observed.

4-Hydroxycoumarins↗
PubMed2006

Elevated warfarin metabolism in warfarin-resistant roof rats (Rattus rattus) in Tokyo.

Wild roof rats (Rattus rattus) live in proximity to human habitats, and they may carry numerous pathogens of infectious diseases. Pest control is important for public health, and warfarin is a commonly used rodenticide worldwide. However, continual use of warfarin may cause drug resistance in rodents and lead to failure of their control, especially in urbanized areas. In warfarin-resistant rats, the warfarin level in plasma was significantly lower after oral administration than that in the control warfarin-sensitive rats. Warfarin is metabolized by cytochrome P450 (P450), and hydroxylation of warfarin by P450 isoforms was significantly higher in warfarin-resistant rats (2-fold). Western blot analysis indicated that the level of CYP3A2 expression in warfarin-resistant rats was significantly larger than in warfarin-sensitive rats. The NADPH-P450 reductase activities in resistant rats were 8-fold higher than those in sensitive rats. In vivo, the administration of the P450 potent inhibitor proadifen (SKF-525A) increased the mortality of warfarin in the warfarin-resistant roof rats. We concluded that the mechanism of warfarin resistance in Tokyo roof rats is caused by increased clearance of warfarin.

Animals↗
PubMed1973

Anticoagulant-resistant rats: possible control by the use of the chloro analog of vitamin K 1 .

Strains of wild rats that are resistant to the anticoagulant action of coumarins and derivatives of indandione have been discovered in a number of geographic areas. These rats have now been shown to be more susceptible than normal rats are to the anticoagulant action of the vitamin K antagonist, 2-chloro-3-phytyl-1,4-naphthoquinone. This compound, either alone or in combination with warfarin, would appear to be an effective rodenticide in areas where resistance to the indirect anticoagulants is a problem.

Animals↗