Acute poisoning of Red Kites (Milvus milvus) in France: data from the Sagir network

Red Kites (Milvus milvus) are avian scavengers limited to Europe, and they currently are listed as an endangered species worldwide. Accidental poisoning is often listed as one of the threats to Red Kites throughout their range of distribution. The purpose of this article is to investigate the suspected poisoning cases reported to the French Wildlife Disease Surveillance System. Dead animals are submitted to a local veterinary laboratory for necropsy and when poisoning is suspected, samples are submitted to the Toxicology Laboratory of the College of Veterinary Medicine, Lyon, France. Over the period 1992-2002, 62 Red Kites suspected of poisoning were submitted, and poisoning was the confirmed cause of death for greater than 80% of these cases. The major toxicants found were cholinesterase inhibitors (carbamates and organophosphate insecticides) and anticoagulant compounds. The circumstances of exposure include secondary poisoning after the use of anticoagulants over vast areas to control water vole (Arvicola terrestric) populations, but they also include malicious poisoning with carbamates (aldicarb and cabofuran) in meat baits. Cases of poisoning vary throughout France, with observed mortality rates ranging between 0.1/100 hundred breeding pairs/10 yr and four cases/100 hundred breeding pairs/10 yr. Additional cases of poisoning likely go undetected, and our results suggest that acute poisoning is not uncommon in Red Kites and that it should be considered in the current restoration plans.     

Chloride channels as tools for developing selective insecticides

Ligand-gated chloride channels underlie inhibition in excitable membranes and are proven target sites for insecticides. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for a number of currently used insecticides, such as lindane, endosulfan, and fipronil. These compounds act as antagonists by stabilizing nonconducting conformations of the chloride channel. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system, convulsions, and death. We recently investigated the mode of action of the silphinenes, plant-derived natural compounds that structurally resemble picrotoxinin. These materials antagonize the action of GABA on insect neurons and block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner. In mammals, avermectins have a blocking action on the GABA-gated chloride channel consistent with a coarse tremor, whereas at longer times and higher concentrations, activation of the channel suppresses neuronal activity. Invertebrates display ataxia, paralysis, and death as the predominant signs of poisoning, with a glutamate-gated chloride channel playing a major role. Additional target sites for the avermectins or other chloride channel-directed compounds might include receptors gated by histamine, serotonin, or acetylcholine.The voltage-sensitive chloride channels form another large gene family of chloride channels. Voltage-dependent chloride channels are involved in a number of physiological processes including: maintenance of electrical excitability, chloride ion secretion and resorption, intravesicular acidification, and cell volume regulation. A subset of these channels is affected by convulsants and insecticides in mammals, although the role they play in acute lethality in insects is unclear. Given the wide range of functions that they mediate, these channels are also potential targets for insecticide development.     

Effects of succinylcholine in an organotypic spinal cord-skeletal muscle coculture of embryonic mice

Intoxication with organophosphorus compounds is an important clinical problem worldwide. Although the core treatments – atropine, oximes and diazepam – are defined, high case fatalities were reported for intoxication with organophosphorus insecticides. In particular the role of oximes is not completely understood since they might benefit only patients poisoned by specific pesticides or patients with moderate poisoning and few randomised trials of such poisoning have been performed. This justifies the need for new in vitro test-systems like cocultures of spinal cord and muscle tissue, which have been recently introduced. However this test-system is not yet fully characterized. In order to estimate the applicability of cocultures of spinal cord and muscle tissue their sensitivity to succinylcholine (di-acetylcholine), a depolarizing muscle relaxant in clinical use, was tested.     

Simultaneous quantification of carbamate insecticides in human plasma by liquid chromatography/tandem mass spectrometry

Carbofuran (CFN), carbosulfan (CSN) and fenobucarb (FBC) are carbamate pesticides that are widely used in gardening and agriculture for the control of insects. Human poisoning due to occupational or self-poisoning exposures is also reported, so assays are required to quantify the plasma concentration of these insecticides. An LC-MS/MS method was developed and validated for the simultaneous quantification of these three carbamate insecticides in the plasma of patients with acute intentional self-poisoning. Plasma samples were pretreated by acetonitrile for protein precipitation. Chromatography was carried out on a Luna C18(2) analytical column with gradient elution using a mobile phase containing acetonitrile and water with 10mM ammonium acetate. Mass spectrometric analysis was performed by an Applied Biosystems MDS Sciex API 2000 triple quadrupole mass spectrometer coupled with electrospray ionization (ESI) source in the positive ion mode. The total run time was 7 min. The assay was validated over a concentration range from 10 to 1000 ng/ml for CSN and FBC and 20-2000 ng/ml for CFN. The precision and accuracy for both intra- and inter-day determination of all analytes were acceptable (<15%). No significant matrix effect was observed. Stability of compounds was established for short term bench and autosampler storage as well as freeze/thaw cycles. The method was effectively applied to 270 clinical samples from patients with a history of acute intentional carbamate self-poisoning.     

Something old, something transgenic, or something fungal for mosquito control?

In spite of the current research emphasis on the use of transgenic mosquitoes, insecticides are still the main method for controlling malarial mosquitoes. Although pyrethroids are the compounds of choice, insecticide resistance is now threatening the effective life of these invaluable compounds. Two recent studies have re-focused interest on entomopathogenic fungi as useful alternatives to conventional insecticides, suggesting that these fungi could be used as alternative control methods, which would thus also prolong the effective lifetime of pyrethroids.     

The effects of chemical and physical stress on the concentrations of amino compounds in the haemolymph and nervous system of locusts and cockroaches

Locusts and cockroaches were subjected to stress by poisoning with various insecticides, and by enforced walking. Chromatographic analysis of the dansyl derivatives of the amino compounds in the haemolymph and nervous tissue revealed that taurine more than doubled in concentration. Other amino acids showed changes in concentration, generally of a lower statistical significance. Electrophysiological tests on isolated nerve cords showed that taurine had an inhibitory effect on the spontaneous activity. This effect was found with concentrations occurring in vivo, and was proportional to concentration.     

Hematological Disorders Following Exposure to Insecticides

The medical literature dealing with hematological disorders following exposure to insecticides (chiefly chlorinated hydrocarbons and organic phosphorus compounds) is briefly reviewed. The development of blood dyscrasias as a consequence of exposure to insecticides is considered unlikely. Reported cases are few in number and often involve persons with little contact with these materials. It is often impossible to prove (or to disprove) a cause-and-effect relation in the individual case. Pointers which may be of assistance in evaluating this relationship are described. Purpura as a result of allergic vascular changes after exposure to insecticides is also discussed.     

Misuse,perceived risk,and safety issues of household insecticides: Qualitative findings from focus groups in Arequipa,Peru

BackgroundThe current body of research on insecticide use in Peru deals primarily with application of insecticides offered through Ministry of Health-led campaigns against vector-borne disease. However, there is a gap in the literature regarding the individual use, choice and perceptions of insecticides which may influence uptake of public health-based vector control initiatives and contribute to the thousands of deaths annually from acute pesticide poisoning in Peru.MethodsResidents (n = 49) of the Alto Selva Alegre and CC districts of peri-urban Arequipa participated in seven focus group discussions (FGD). Using a FGD guide, two facilitators led the discussion and conducted a role-playing activity. this activity, participants insecticides (represented by printed photos of insecticides available locally) and pretended to “sell” the insecticides to other participants, including describing their qualities as though they were advertising the insecticide. The exercise was designed to elicit perceptions of currently available insecticides. The focus groups also included questions about participants’ preferences, use and experiences related to insecticides outside the context of this activity. Focus group content was transcribed, and qualitative data were analyzed with Atlas.ti and coded using an inductive process to generate major themes related to use and choice of insecticides, and perceived risks associated with insecticide use.ResultsThe perceived risks associated with insecticides included both short- and long-term health impacts, and safety for children emerged as a priority. However, in some cases insecticides were reportedly applied in high-risk ways including application of insecticides directly to children and bedding. Some participants attempted to reduce the risk of insecticide use with informal, potentially ineffective personal protective equipment and by timing application when household members were away. Valued insecticide characteristics, such as strength and effectiveness, were often associated with negative characteristics such as odor and health impacts. “Agropecuarios” (agricultural supply stores) were considered a trusted source of information about insecticides and their health risks.ConclusionsIt is crucial to characterize misuse and perceptions of health impacts and risks of insecticides at the local level, as well as to find common themes and patterns across populations to inform national and regional programs to prevent acute insecticide poisoning and increase community participation in insecticide-based vector control campaigns. We detected risky practices and beliefs about personal protective equipment, risk indicators, and safety levels that could inform such preventive campaigns, as well as trusted information sources such as agricultural stores for partnerships in disseminating information.     

Nicotinic acetylcholine receptors: targets for commercially important insecticides

Nicotinic acetylcholine receptors (nAChRs) are major excitatory neurotransmitter receptors in both vertebrates and invertebrates. In insects, nAChRs are the target site for several naturally occurring and synthetic compounds that exhibit potent insecticidal activity. Several compounds isolated from plants are potent agonists or antagonists of nAChRs, suggesting that these may have evolved as a defence mechanism against insects and other herbivores. Nicotine, isolated from the tobacco plant, has insecticidal activity and has been used extensively as a commercial insecticide. Spinosad, a naturally occurring mixture of two macrocyclic lactones isolated from the microorganism Saccharopolyspora spinosa, acts upon nAChRs and has been developed as a commercial insecticide. Since the early 1990s, one of the most widely used and rapidly growing classes of insecticides has been the neonicotinoids. Neonicotinoid insecticides are potent selective agonists of insect nAChRs and are used extensively in both crop protection and animal health applications. As with other classes of insecticides, there is growing evidence for the evolution of resistance to insecticides that act on nAChRs.     

Chondromatous hamartoma treated by transpleural bronchotomy; report of a case with review of the literature

Since parathion and other cholinesterase insecticides are being used extensively, safety precautions are important, and the need for prompt and adequate therapy if poisoning does occur must be emphasized. This paper stresses the acute nature of the poisoning and attempts to outline the basic principles of therapy so that practicing physicians may handle cases with more confidence, which should help prevent prolonged periods of functional disturbances due to anxiety following poisoning.     

Pyrethroid-Acarophenax lacunatus interaction in suppressing the beetle Rhyzopertha dominica on stored wheat

Any biocontrol agent used against stored grain insects will have to interact with insecticides used as grain protectants due to their heavy use especially in tropical areas. Therefore, the interaction between the pyrethroid insecticides bifenthrin and deltamethrin and Acarophenax lacunatus (Cross & Krantz) (Prostigmata: Acarophenacidae), an egg parasite of the stored cereal pest Rhyzopertha dominica(F.) (Coleoptera: Bostrichidae), was assessed in a range of mite densities and insecticide doses for each compound. Despite the mite species presence on all insecticide doses, the lowest instantaneous rate of increase of A.lacunatus was recorded with the highest doses of insecticides. The presence of the biological control agent at all doses of both insecticides suggests its tolerance to these compounds. A. lacunatusshowed higher parasitism rate with bifenthrin than with deltamethrin indicating a higher selectivity of the first compound to the biocontrol agent. This revised version was published online in August 2006 with corrections to the Cover Date.     

Pesticides for locust control.

The factors influencing the choice of insecticides for locust control are effectiveness, safety in use, relative cost, and the formulations available. The relative importance of these factors varies with the scale of control. In small scale control by farmers safety and simplicity are paramount and a BHC dust is commonly used, but in large scale control operations by specialized organizations more toxic formulations ultra-low-volume (u.l.v.) concentrates and methods of application requiring considerable skills can be used. The remarkable effectiveness of dieldrin as a stomach poison appears to be due to its conversion to photodieldrin after application. Cases of poisoning following large scale control operations are rare, and fatalities in man unknown. Alternatives to organochlorine insecticides include fenitrothion, already recommended and used on a large scale against adults. Against nymphs the correct dosage of fenitrothion would cost nearly 11 times as much as that of dieldren. Recent experimental work with new insecticides has included safety tests with domestic animals and measurements of persistence. 1 microgram deposits of cyanofenphos, decamethrin and mecarphon, as well as of dieldrin and photodieldrin, on wheat seedlings left in the open under tropical conditions for two days, killed 80% or more first instar nymphs of the Desert Locust which fed on them.     

Bispyridinium Compounds Inhibit Both Muscle and Neuronal Nicotinic Acetylcholine Receptors in Human Cell Lines

Standard treatment of poisoning by organophosphorus anticholinesterases uses atropine to reduce the muscarinic effects of acetylcholine accumulation and oximes to reactivate acetylcholinesterase (the effectiveness of which depends on the specific anticholinesterase), but does not directly address the nicotinic effects of poisoning. Bispyridinium molecules which act as noncompetitive antagonists at nicotinic acetylcholine receptors have been identified as promising compounds and one has been shown to improve survival following organophosphorus poisoning in guinea-pigs. Here, we have investigated the structural requirements for antagonism and compared inhibitory potency of these compounds at muscle and neuronal nicotinic receptors and acetylcholinesterase. A series of compounds was synthesised, in which the length of the polymethylene linker between the two pyridinium moieties was increased sequentially from one to ten carbon atoms. Their effects on nicotinic receptor-mediated calcium responses were tested in muscle-derived (CN21) and neuronal (SH-SY5Y) cells. Their ability to inhibit acetylcholinesterase activity was tested using human erythrocyte ghosts. In both cell lines, the nicotinic response was inhibited in a dose-dependent manner and the inhibitory potency of the compounds increased with greater linker length between the two pyridinium moieties, as did their inhibitory potency for human acetylcholinesterase activity in vitro. These results demonstrate that bispyridinium compounds inhibit both neuronal and muscle nicotinic receptors and that their potency depends on the length of the hydrocarbon chain linking the two pyridinium moieties. Knowledge of structure-activity relationships will aid the optimisation of molecular structures for therapeutic use against the nicotinic effects of organophosphorus poisoning.     

Topoisomerase II poisoning by indazole and imidazole complexes of ruthenium

Trans-imidazolium (bis imidazole) tetrachloro ruthenate (RuIm) and trans-indazolium (bis indazole) tetrachloro ruthenate (RuInd) are ruthenium coordination complexes, which were first synthesized and exploited for their anticancer activity. These molecules constitute two of the few most effective anticancer ruthenium compounds. The clinical use of these compounds however was hindered due to toxic side effects on the human body. Our present study on topoisomerase II poisoning by these compounds shows that they effectively poison the activity of topoisomerase II by forming a ternary cleavage complex of DNA, drug and topoisomerase II. The thymidine incorporation assays show that the inhibition of cancer cell proliferation correlates with topoisomerase II poisoning. The present study on topoisomerase II poisoning by these two compounds opens a new avenue for renewing further research on these compounds. This is because they could be effective lead candidates for the development of more potent and less toxic ruthenium containing topoisomerase II poisons. Specificity of action on this molecular target may reduce the toxic effects of these ruthenium-containing molecules and thus improve their therapeutic index.     

A review of chemical control options for invasive social insects in island ecosystems

Social insects present unique challenges to chemically based management strategies, especially because fast‐acting compounds commonly applied for many pest insects may not be the most effective for colony elimination. The reproductive caste of a colony is the most protected from direct damage by insecticides, and compounds that cause rapid mortality among foragers frequently do not impact the reproductive members or even markedly reduce overall colony size. With recent bans on persistent insecticides that previously have been used to control social insects, especially termites, new compounds must be used. Island and coastal ecosystems are particularly sensitive to the effects of widespread pesticide use and concerns about unintentional water pollution and runoff are common, and international attention is being paid to developing sustainable pesticide options for agricultural and urban pest insects in particularly sensitive environments. Given the precarious status of many native insects and arthropods care must be taken to minimize exposure to potentially harmful insecticides and the non‐target impacts of these chemicals. However, recent developments in the synthesis and discovery of highly selective insecticides with low mammalian and non‐target toxicity provide viable alternatives to the broad‐spectrum persistent organochlorine insecticides that have been largely deregistered. Novel technologies, particularly synthetic analogues of biologically active compounds, yield new chemical control options and management strategies for island and other sensitive ecosystems; case studies from Australia, the Galapagos Islands and New Zealand highlight current challenges and successes.     

Changes in membrane fluidity evoked by organophosphorus insecticide bromfenvinfos and its methylated analogue

The interaction of organophosphorus insecticides bromfenvinfos and methyl bromfenvinfos with model and native membranes was investigated by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH), a probe located in the hydrophobic core of the bilayer and 1,3-bis-(1-pyrene)propane, a probe distributed in the outer region of the bilayer. DPH reported a broadening of the transition profile and solidifying effects in the fluid phase of liposomes formed from dimyristoyl (DMPC), dipalmitoyl (DPPC), and distearoyl (DSPC) phosphatidylcholine in the presence of the insecticides. A shift of the transition temperature towards a lower temperature was observed in DPPC- and DSPC-bromfenvinfos-treated vesicles. Py(3)Py detected an ordering effect of the insecticides in the fluid state of the lipids and abolished pre-transition in DPPC and DSPC vesicles. These results suggest that the insecticides localize in the co-operative region of the bilayer. Cholesterol added to DMPC decreased the influence of the insecticides as reported by both DPH and Py(3)Py. The effect of the insecticides on the fluidity of some native membranes, namely erythrocytes, lymphocytes, brain microsomes, and sarcoplasmic reticulum, depended on the cholesterol content in these membranes, the higher the cholesterol content, the smaller the solidifying effect. The physical mechanism of action of the insecticides on membrane lipids can be similar to that of cholesterol. All observed effects were more pronounced for bromfenvinfos than for its methylated analogue which correlates with the toxicity of these compounds for mammals.     

Studies on the Organophosphorus Insecticides

During the course of investigation on organophosphorus insecticides, many organophosphorus compounds having methyl-, methyl-chloro-, methyl-nitro-, methyl-cyano-, methyl-thiocyano-, methoxy-nitro-, acyloxy-nitro-, and chloro-cyano-phenyl groups were prepared and their biological activities tested. As the results of these studies, two compounds were found as new low toxic organophosphorus insecticides, namely, O,O-dimethyl-O- (3-methyl-4-nitro-phenyl) and O,O-dimethyl-O- (4-cyanophenyl) phosphorothioates.     

Amitriptyline and Imipramine Poisoning in Children

The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.     

Tandem use of selective insecticides and natural enemies for effective,reduced-risk pest management

Selective chemical insecticides have become the dominant approach for management of recalcitrant and resistant insect pests, and the prospects for use of these chemicals in combination with biocontrol agents are on the rise. These chemical compounds, when used in combination with an effective natural enemy, may provide more comprehensive prophylactic and remedial treatments in the context of an integrated pest management program (IPM) than either approach alone. Many of these compounds have promise for a diversity of applications, including sustainable agriculture, control of urban pests, and invasive species eradication. Unfortunately, there are only a limited number of studies in which the effect of these insecticides on natural enemies has been examined. In this article, we examine the risk of several classes of insecticidal compounds to non-target animals, particularly natural enemies and pollinators, and review the most promising compounds for combined deployment with biological agents.     

Susceptibility of Alphitobius diaperinus (Coleoptera: Tenebrionidae) from broiler facilities in Texas to four insecticides

Lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), adults were collected from six eastern Texas broiler facilities and examined for susceptibility to four formulated insecticides. Data indicate that A. diaperinus adults exposed to filter papers treated with the label rates of the insecticides exhibit some level of recovery. Approximately 20% or less A. diaperinus adults treated with Tempo SC Ultra (8 ml/92.9 m2, 11.8% beta-cyfluthrin) or Talstar WP Insecticide/Miticide (23.3 ml/92.9 m2, 10% bifenthrin) and recorded as moribund at the 4-h observation period recovered by the 24-h observation period. A. diaperinus adults treated with Tempo SC Ultra and Talstar WP also had the greatest percentage of mortality for both observation periods. A. diaperinus adults treated with Dragnet SFR (49.7 ml/92.9 m2, 36.8% permethrin) had the greatest level of recovery at approximately 50-60% overall, which was similar to that recorded for the water-only control. Additionally, five of the six A. diaperinus populations treated with Dragnet SFR resulted in < 10% mortality for both observation periods. Unlike the other insecticides examined, Talstar Professional Insecticide (10 ml/92.9 m2, "Talstar Pro," 7.9% bifenthrin) resulted in approximately 50% more A. diaperinus mortality at the 24-h than the 4-h observation period due primarily to increased mortality recorded for Farm F. A. diaperinus adults from farm D had > or = 87% knockdown 4 h after treatment to all compounds examined, indicating a high degree of sensitivity to these compounds. However, approximately 90% of the A. diaperinus adults from this population treated with Dragnet SFR and recorded as moribund recovered by the 24-h observation. A. diaperinus adults from this population treated with the other insecticides exhibited limited recovery. Susceptible adult A. diaperinus populations are still present in Texas, based on the populations examined. But, identifying these populations is difficult and time-consuming. Consequently, screening populations before treatment might not be feasible. However, newer generation pyrethroids examined in this study seem to be suitable for suppressing A. diaperinus populations in broiler facilities.