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[Effort to eradicate a focus of tularemia and leptospirosis].

An endemic area of tularemia and field fever was submitted to a complex surveillance over a period of more than 10 years. In 1977 an epizootic outbreak of tularemia appeared in all four localities studied. The infection rate in small mammals exceeded 10%. F. tularensis was isolated also from different species of ectoparasites. During 1978 the epizootic stopped in 3 foci, but continued to spread in one. Rodenticides (zinc phosphide) were therefore applied in this focus twice annually for 2 1/2 years. Since 1978, tularemia infections disappeared in small mammals as well as in man. The application of rodenticides did not influence the circulation of Leptospira grippotyphosa in small mammals. Their infection rate ranged between 3 and 6%. The reason for this striking difference is seen in the different pathogenesis and transmission of both infections.

Animals↗

The use of biomarkers to measure the interactive effects of chemicals.

Biomarker assays that provide measures of the toxic effects of chemicals on key organisms are of particular interest in ecotoxicology and environmental risk assessment. Typically, such assays provide measures of the molecular mechanisms that underlie toxicity (e.g., inhibition of brain acetylcholinesterase activity by organophosphorus insecticides and retardation of the vitamin K cycle by anticoagulant rodenticides). They are particularly valuable for detecting and quantifying toxicity where organisms are exposed to mixtures of compounds and for identifying cases of potentiation. In birds, inhibition of brain acetylcholinesterase activity can provide an index of potentiation of organophosphorus and carbamate insecticides by other pesticides. Inhibition of serum butyrylcholinesterase also is very useful as a nondestructive assay but is not simply related to inhibition of brain acetylcholinesterase. Assays for DNA damage can indicate where there is an increase in the rate of activation of carcinogens and mutagens due to induction of the cytochrome P450 system. Assays for blood levels of retinol (vitamin A) and thyroxine can establish thyroxine antagonism by metabolites of 3,3,4,4-tetrachlorobiphenyl. Assays for changes in levels of clotting protein in serum can give an indication of the effect of mixtures of anticoagulant rodenticides on the vitamin K cycle. The interactive effects of mixtures of pesticides in the field are starting to be investigated by this approach (e.g., a recent study of the combined action of malathion and prochloraz in the red-legged partridge).

Animals↗

Pesticide poisoning in domestic animals and livestock in Austria: a 6 years retrospective study.

A 6 years retrospective study of pesticide poisonings in domestic animals and livestock from 1999 to 2004 submitted to the Institute for Medical Chemistry, University of Veterinary Medicine, Vienna in Austria was compiled and analysed. Totally 380 pesticide analysis requests were referred by veterinary practitioners, from the Institute for Pathology of the above university, by regional and central governments as well as local police departments and district administrations, animal protectionist groups, public health authorities and private clients. Among the total number of suspected samples for pesticides, 175 (46.1%) cases were found positive to contain pesticides of various kinds. Among the pesticides found, carbamate insecticides were most prominent, representing 50.3% of the total positive cases. These compounds were followed by rodenticides-anticoagulants with 18.9% of the positive results, by organophosphate insecticides 5.1%, and by the rodenticides-nonanticoagulant 3.4%, the other 22.3% included molluscicides, herbicides, etc. In totally 225 animals, 123 animals were found positive for pesticide intoxication, among them 47.2% were dogs, 34.1% were cats 9.8% of other species and 8.9% of unspecified animal samples. The pesticides were characterized by HPLC-techniques using commercially available standards. The aim of this Austrian survey was to determine the incidence and frequency of confirmed pesticide intoxications in animals in Austria and to emphasize its relevance in veterinary practice for livestock and domestic animals.

Animals↗

Cereal aversion in behaviourally resistant house mice in Birmingham, UK.

In 1986, house mice in a small defined area of inner Birmingham were reported as not taking a variety of rodenticides from bait containers, a phenomenon labelled 'behavioural resistance'. This study investigated behavioural resistance by comparing the food preferences of West Midlands behaviourally resistant (WMBR) mice with those of normal (BC) mice. Nine bait boxes each containing one of nine different foods (cheese, chicken, tuna fish, peanut butter, canary seed, Cat stars, wheat, PCD (MOD) pellets and Non-tox) were introduced to 12 WMBR and seven BC sites (Experiment 1). The experiment was repeated in the laboratory with six pens of WMBR and six of BC mice (Experiment 2), and to investigate whether the preferences had a genetic basis the offspring were similarly assayed (Experiment 3). In each experiment the consumption of each food was measured over 7 days and the droppings around the bait boxes were counted to assess mouse activity. Food neophobia was noted in some populations of BC mice. Tested in the wild and in the laboratory WMBR mice showed an aversion to foods containing cereals, as did their offspring. These results, with other lines of evidence, strongly suggest that cereal aversion in WMBR mice has a physiological/genetic basis. Since cereal aversion allows WMBR mice to survive cereal-based rodenticidal baits, we conclude that WMBR mice have genetically based behaviours that allow them to survive poisoning regimes that kill other strains.

Journal Article↗

Teratogenic effects of 6-aminonicotinamide in mice.

6-Aminonicotinamide (6-AN), a potential broad-spectrum rodenticide, was examined for embryotoxic and teratogenic potential. Mice of the BALB/c strain were given a single oral dose of 1, 17, 34, 51 or 136 mg/kg on one of days 8 to 13 of gestation. Fetuses were either examined on day 18 post coitum (prenatal study), or allowed to go to term and examined 2 days after birth. Dam weights were significantly reduced (p less than 0.01) at dose levels of 17 mg/kg and greater. These same dose levels caused a significant decrease (p less than 0.01) in litter size and in mean fetal weight. They also caused an increase in the number of resorptions. Hydrocephalus and cleft palate were the most frequent visceral anomalies and were dose-dependent. Skeletal anomalies were also dose-dependent, and the fetus was most susceptible on days 8 to 10 post coitum. A significant (p less than 0.05) increase in the ratio of female to male fetuses was observed at dose levels of 34 mg/kg and greater. Surviving 2-day-old pups had few visceral anomalies but skeletal anomalies were more frequent. Because of its teratogenic properties, it would be difficult to register 6-AN for use against commensal rodents or as a broad-spectrum rodenticide for use in agricultural crops.

6-Aminonicotinamide↗

Aluminum phosphide fatalities, new local experience.

Aluminum phosphide (AlP) pesticide is a highly toxic, low cost, and easily accessible rodenticidal agent. Its toxicity results from the liberation of phosphine gas upon exposure to moisture, which leads to multisystem involvement, resulting in serious consequences. The highly toxic parathion insecticide was a common cause of mortality in pesticide fatalities, prior to its banning. Its toxicity was familiar to the public as well as to physicians. Recently, ten fatalities due to AlP were encountered within a three-month period during spring, when it was used as a rodenticide in the vicinity of grain stores. The victims' ages ranged from 1-34 years. The circumstances of death were accidental in six cases, suicidal in two and possibly homicidal in two cases. Retrospectively, the clinical manifestations, scene investigation, autopsy, histological and toxicological findings supported the diagnosis of AlP intoxication. Immediate recognition was difficult due to unfamiliarity of the agent to the physicians. The occurrence of these fatalities might suggest changes of pattern in pesticide poisoning. This should raise the attention of the physician to the problem of AlP poisoning and also necessitates the awareness of the public to the hazards of this poison. Education, proper handling, strict observation and abiding by the regulations controlling this material are good protective measures against AlP poisoning.

Adolescent↗

Aspects of anticoagulant action: a review of the pharmacology, metabolism and toxicology of warfarin and congeners.

Warfarin is the most widely used anticoagulant in the treatment of thromboembolism in man. It has also been used extensively as a rodenticidal agent. Insofar as its clinical use is concerned, it is now clear that many of the drug interactions observed in patients are mediated via metabolic or pharmacokinetic factors. An understanding of the disposition of warfarin is therefore essential if one is to predict the likely response in patients undergoing anticoagulant therapy with this compound. Warfarin-resistance has been reported in both man and rodents. Understanding resistance in both man and rodents is important for effective anticoagulant therapy, and in control of resistant strains of rodents. Warfarin resistance in rat strains does not appear to have a metabolic or pharmacokinetic basis; in this species, resistance is thought to be due to differences in permeability to, or affinity for a receptor. Apart from its clinical and rodenticidal uses, warfarin is an excellent substrate for probing the heterogeneity of cytochrome P.450, since its metabolic oxidation is mediated by this mixed function oxidase. This review draws together much of the current published literature on the pharmacology, metabolism and toxicology of warfarin and related congeners.

Animals↗

Acute pesticide poisoning in England and Wales.

Between 1979 and 1983 less than 1% of admissions from acute poisoning in the UK were due to pesticides and fewer than 4% of admissions in those under 5 years were from this cause. Organochlorine, organophosphorus and carbamate insecticides account for only 10% of the total in both children and adults. Suspected pesticide poisoning was the cause of fewer than 0.3% of home accidents in those under 10 years of age and less than 4% of suspected poisonings documented by the Home Accident Surveillance System. Rodenticides were thought to be involved in 62% of these cases. Of children who presented to hospital 42% were admitted and 93% of these were discharged home within 2 days. In the UK, the morbidity from acute pesticide poisoning in children is low and the mortality is nil and there is therefore no evidence to support the view that paediatric pesticide intoxication is a significant clinical problem. Though no fatalities were recorded in children, pesticides were responsible for 1.3% of all deaths due to poisoning in the UK between 1979 and 1983. In adults admitted to hospital, the mortality from pesticide poisoning is approximately 12% and three quarters of these deaths are due to the deliberate ingestion of paraquat. The general term pesticide refers to a group of products that are used as insecticides, acaricides, fungicides, herbicides, rodenticides, and plant growth agents. Chemically, the group includes bipyridilium compounds, carbamates, chloralose, chlorates, coumarins, dinitro compounds, dithiocarbamates, fluoroacetates, organochlorine organophosphorus and organotin compounds, pentachlorophenol, phenoxyacetates, phosphine (as magnesium and aluminium phosphides), pyrethrins, pyrethroids and triazines.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Animal poisonings: the 10-year experience of a veterinary analytical toxicology laboratory.

Data on 10-y of chemical toxicological analyses carried out in a veterinary laboratory in Barcelona, Spain for suspected wild and domestic animal poisonings are summarized. The 218 cases involved more than 1 million animals, some 7,500 of which died. Pesticides, especially insecticides (46.6%) and rodenticides (37.9%), were frequently involved. Strychnine (n = 11) and aldicarb (n = 10) were the most usual toxic agents in baits prepared for intentional poisonings; other cases involved pentachlorophenol, hexachlorocyclohexane or anticoagulant rodenticides. Service to veterinarians and others could be improved if a coordinated network of national and regional Animal Poison Centers were created.

Animal Diseases↗

Common causes of poisoning in dogs and cats in a Brazilian veterinary teaching hospital from 1998 to 2000.

A retrospective study at the University Veterinary Teaching Hospital of São Paulo city, Brazil, describes the pattern of poisoning that occurred from 1998 to 2000. During this period 5,136 animals were sent to the emergency sector, and 250 of these cases were reported as poisonings: 203 dogs (81.2%) and 47 cats (18.8%). The common causes of poisoning in dogs were 28.9% therapeutic products (86.4% non-steroidal anti-inflammatory drugs, 6.8% other drugs, 3.4% antibiotics, 3.4% tranquilizing agents), 15.8% rodenticides, 13.9% pesticides for farm use (39.3% organophosphorous and 35.7% carbamate insecticides, 25.0% amitraz), 11.8% unknown agents, 8.4% plants, 6.8% industrial products, and 5.0% pesticides for domestic use. The common causes of poisoning in cats were 29.9% therapeutic products (50.0% non-steroidal anti-inflammatory drugs, 42.8% others, 7.2% antibiotics), 27.6% pesticides for farm use (46.1% carbamate insecticides, 38.5% organophosphorous insecticides, 15.4% others), 14.9% pesticides for domestic use, 12.8% unknown agents, 10.6% rodenticides, and 4.2% industrial products. These data show it is essential to create an awareness of the toxicity of these agents to reduce poisoning incidence.

Accidents↗

[Experience of the Toxicology Information Center in Prague with pesticides].

The Toxicological Information Centre replied in 1988 and 1989 some 5500 inquiries. This number comprised 5-7% concerning treatment of acute intoxications with pesticides. More than half of them concerned children who ingested pesticides. In adults in half of inquiries possible intoxication after ingestion was involved, in half intoxication was a result of inhalation or percutaneous intoxication. 10.5% and 12.5% of the inquiries concerning pesticide intoxications in adults were attempted suicide. The number of inquiries regarding occupational diseases during spraying was small (some 5 and 3 cases). The inquiries were divided by groups of pesticides into herbicides, insecticides, rodenticides, fungicides and others. From the analysis ensued that children were intoxicated most frequently by preparations against harmful animals (rodenticides, insecticides), in particular rodents and ants. In adults the stratification of intoxications into groups was less marked.

Adult↗

Incidence of ethylene glycol intoxication in dogs and cats seen at Colorado State University Veterinary Teaching Hospital.

The number of cases of ethylene glycol intoxication in dogs and cats seen at the Colorado State University Veterinary Teaching Hospital between 1979 and 1986 was compared with the number of cases of rodenticide, insecticide, herbicide, simple organic compound and food poisonings for the same time period. Of 104 intoxications, ethylene glycol (30/104), rodenticide (53/104), and food poisonings (6/104), were major contributors. Case-fatality rates were 43.3%, 11.3% and 16.7% respectively. Data available from records of ethylene glycol intoxication in dogs and cats occurring between 1968 and 1986 facilitated description of cases by sex, age and season. Of the 60 cases, dogs (35/60) and cats (25/60) yielded uneven or skewed distributions when considering sex, age and/or season of intoxication.

Animals↗

The baseline susceptibility levels of Chunya Praomys natalensis, the commonest plague reservoir and crop pest in Tanzania, to warfarin.

P. natalensis were live-trapped at Kibwawa (Chunya district) in November 1977 and November 1979. An F3 generation was raised from animals which tolerated 0.025% a.i. warfarin. All three populations were tested using the WHO standard method (WHO/VBC/75.595), with 0.025% warfarin. The populations tested were fully susceptible to the rodenticide, and the latter was well acceptable to the rodents. In this area, warfarin can be successfully used for controlling P. natalensis. Failure to obtain 100% mortality with the 1977-caught wild population was probably due to vigour tolerance. Regular seminars are recommended to train staff in the rodenticide application.

Animals↗

Pesticide registration in the United States: overview and new directions.

This paper provides an overview of EPA's pesticide registration program and a discussion of recent activities. The registration of pesticides is the responsibility of the Office of Pesticide Programs, an office of the U.S. Environmental Protection Agency (EPA). EPA's pesticide regulatory authority derives from the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) and the Federal Food, Drug and Cosmetic Act (FFDCA). FIFRA governs the registration or licensing of pesticide products including insecticides, herbicides, fungicides, rodenticides, disinfectants, plant growth regulators, and biological agents. FFDCA governs pesticide residue levels in food and feed crops. FIFRA gives EPA authority for registering pesticides to ensure that when used according to label directions, they will not pose unreasonable adverse effects to the environment. FIFRA requires EPA to balance the risks and benefits of a pesticide in deciding whether or not to grant a pesticide registration. In a typical year EPA reviews over 5000 registration submissions that vary from routine label amendments to the review of a new active ingredient. About 20 applications for registration of a new active ingredient are received each year. Registration for a new active ingredient requires a significant investment in time and money by the registrant. Data development for a major agricultural chemical can cost 10 million dollars or more and take several years to complete. EPA is embarking on a number of new initiatives in the registration program designed to reduce the use of chemical pesticides, limit the regulatory burden on lower risk and reduced risk products, and streamline the review process generally.

Agriculture↗

Superwarfarin ingestion and detection.

Because of the emergence of warfarin resistance, new potent long-acting anticoagulants are now readily available in several over-the-counter rodenticide products. The availability of these "superwarfarin" compounds has led to accidental and purposeful human ingestions, one of which has resulted in a death. We summarize the prior case reports and report a second death. In addition, we report the availability of an assay to detect the presence of brodifacoum (a superwarfarin compound) in human plasma and tissues.

4-Hydroxycoumarins↗

Reproductive success of bromadiolone-resistant rats in absence of anticoagulant pressure.

Resistance to anticoagulant rodenticides in brown rats (Rattus norvegicus Berk.) is associated with pleiotropic effects, notably with an increased dietary vitamin K requirement. Owing to this disadvantage, resistance is believed to be selected against if anticoagulant selection is absent. In small experimental populations of wild brown rats, an investigation was carried out to establish whether tolerance to anticoagulant exposure changed over a period of 2 years. In the same populations, DNA microsatellite markers were used to infer parentage, and this made it possible to estimate reproductive success of sensitive and resistant rats and estimate effective population size, Ne. Even though there was evidence for a selection against resistant rats with high vitamin K requirement, anticoagulant tolerance was not seen to be significantly influenced in the absence of bromadiolone selection. As the population size under investigation was small, random genetic drift may have played a role in this. In the presence of bromadiolone selection, however, the tolerance was significantly increased, suggesting that continuous selection will increase the proportion of highly resistant rats in the population. It was found that, for both males and females, surprisingly few individuals contributed to the next generation with numerous offspring, and most breeders contributed with none or a single offspring. The expected higher reproductive success and consequent increase in proportional numbers of sensitive rats in the absence of anticoagulant selection could not be observed. Among the resistant rats, moderately resistant females were found to be better breeders than highly resistant breeders, but for resistant males the reverse was true. This could be explained by the fact that the increased vitamin K requirement results in sex differential selection; in highly resistant males the selection presumably takes place at the immature stage, whereas in females the vitamin K requirement becomes crucial at the reproductive stage, as vitamin K is not only essential for the blood clotting process but also for bone formation.

4-Hydroxycoumarins↗

Regressors of whole-carcass zinc phosphide/phosphine residues in voles: indirect evidence of low hazards to predators/scavengers.

Whole-carcass residues of the rodenticide zinc phosphide (Zn3P2) and hydrolyzed phosphine (PH3) were determined for voles (Microtus spp.) that died following ingestion of a 2% Zn3P2 steam rolled oat (SRO) groats bait. Procedures involved: a three-day acceptance test to assess vole consumption (n = 27) of control SRO groats and several one-day Zn3P2- (n = 13) or control-bait (n = 4) tests to characterize onset of pharmacotoxic signs and to obtain fatally-dosed carcasses for residue analyses. Carcasses were stored in liquid nitrogen (LN2) to maximize retention of Zn3P2/PH3 residues prior to chemical determinations. Linear regressions were computed between pairs of consumption and residue variables. Main results were the following: (1) mean (+/- SD) consumption of control bait was 2.5 (+/- 0.9), 3.0 (+/- 0.9), and 2.8 (+/- 0.8) g on days 1, 2, and 3, respectively (> or = 10.6 +/- 4.6% of body weight); (2) all test-bait voles (n = 13) died approximately 4-12 h after bait presentation, with lethargy and respiratory distress key signs of toxicosis; (3) whole-carcass Zn3P2 residues averaged 1.73 mg (min-max: 0.31-4.95), and PH3 residues averaged 10.6 micrograms (min-max: 0.5-21.0); and (4) significant linear regressions were found between bait consumption/Zn3P2 intake and body weight (r2 = 0.64, p < or = 0.001), carcass Zn3P2 and bait consumption/Zn3P2 intake (r2 = 0.32, p < or = 0.043), and carcass Zn3P2 and body weight (r2 = 0.60, p < or = 0.002). Certain analytical and hazards issues are discussed.

Animals↗

Vacor inhibits insulin release from islets in vitro.

It has been reported that Vacor, a rodenticide containing N-3-pyridylmethyl-N'-p-nitrophenyl urea, causes insulin-dependent diabetes mellitus. The pathomechanism of Vacor-induced diabetes mellitus has not been clarified yet. The effect of Vacor, therefore, was studied in terms of insulin release from isolated rat pancreatic islets. Vacor suppressed glucose-stimulated insulin release, but did not affect the insulin release induced by theophylline or 12-o-tetra-decanoylphorbol 13-acetate. It is suspected that the suppression of insulin release from pancreatic islets by Vacor may contribute to the pathogenesis of Vacor-induced diabetes mellitus and that this suppression might not be related to cAMP and C-kinase.

Animals↗