ABSTRACT
Among several factors that impact the bean culture productivity there are pest insects, which affect the plant since seeding until postharvest, causing loss in the culture yield. The fall armyworm (Spodoptera frugiperda) stands out among the main pests of common bean (Phaseolus vulgaris). The aim of this work was to evaluate the effectiveness of insecticides of the neonicotinoid group in the control of the fall armyworm in the bean crop, comparing dinotefuran, acetamiprid, thiamethoxam and imidacloprid performance. Experimental design was composed of blocks entirely randomized, with 9 treatments and 10 replicates. Three caterpillars, at the stage of second instar, were used in each experiment, focusing on the ingestion of leaves containing the treatments. Evaluations were realized in the intervals of 1, 3, 6 and 8 days after every application, counting the number of caterpillars alive in the Petri's dish, attributing visual notes on bean leaves, according to the foliar area affected (consumed). The dinotefuran treatment with the highest dose presented superior efficiency at 80% in the first evaluation. The thiamethoxam treatment with the lowest dose, in the latest analyses, showed efficient superior at 90%. The major doses of all treatments presented efficiency higher than 80% in the last evaluations, being efficient in the S. frugiperda control.
Subject(s)
Pest Control/methods , Spodoptera , Phaseolus/parasitology , Neonicotinoids/administration & dosage , Neonicotinoids/analysisABSTRACT
Endocrine-disrupting compounds as pesticides affect the hormonal balance, and this can result in several diseases. Therefore, the analysis of representative hormones with acetamiprid (AC) and azoxystrobin (AZ) was a good strategy for the investigation of the endocrine-disrupting activity of pesticides. Hence, a sensitive and rapid analytical method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The method was validated for the analysis of AC, AZ, estriol, estrone, progesterone, and testosterone in the serum, testis, and liver of rats. The correlation between the residues of pesticides and the disturbance of the endocrine system was evaluated. The different mass parameters, mobile phase types, analytical columns, injection volumes, and extraction solvents were compared to get the lowest limit of detection of the studied compounds. The detection limits of AC, AZ, estriol, estrone, progesterone, and testosterone were 0.05, 0.05, 1.0, 10, and 1.0 ng/ml, respectively. The method developed was applied to evaluate the changes in these hormones induced by the duration of exposure to AC and AZ in rat testis and serum. The hormones level in rat serum and testis had a significant decrease as they were oral gavage treated with different high concentrations of studied pesticides. Both pesticides were distributed in the body of rats by the multi-compartment model (liver, testis, and serum).
Subject(s)
Endocrine Disruptors/toxicity , Gonadal Steroid Hormones/analysis , Neonicotinoids/toxicity , Pyrimidines/toxicity , Strobilurins/toxicity , Animals , Calibration , Chromatography, Liquid/methods , Endocrine Disruptors/administration & dosage , Endocrine Disruptors/analysis , Endocrine Disruptors/pharmacokinetics , Estriol/analysis , Estrone/analysis , Limit of Detection , Male , Neonicotinoids/administration & dosage , Neonicotinoids/analysis , Neonicotinoids/pharmacokinetics , Pesticides/toxicity , Pyrimidines/administration & dosage , Pyrimidines/analysis , Pyrimidines/pharmacokinetics , Rats, Wistar , Reproducibility of Results , Strobilurins/administration & dosage , Strobilurins/analysis , Strobilurins/pharmacokinetics , Tandem Mass Spectrometry/methods , Testosterone/analysis , Tissue DistributionABSTRACT
Imidacloprid is an insecticide belonging to neonicotinoids, a class of agonists of the nicotinic acetylcholine receptors that shows higher affinities in insects compared to mammals. However, recent evidence show that neonicotinoids can bind to the mammalian receptors, leading to detrimental responses in cultured neurons. We developed an analytical strategy which uses mass spectrometry with multiple reaction monitoring (targeted approach) and high-resolution acquisitions (untargeted approach), which were applied to quantify imidacloprid and to identify its metabolites in biological tissues after oral treatments of mice. Mouse dams were treated with doses from 0.118 mg/kg bw day up to 41 mg/kg day between gestational days 6-9. Results showed quantifiable levels of imidacloprid in plasma (from 30.48 to 5705 ng/mL) and brain (from 20.48 to 5852 ng/g) of treated mice, proving the passage through the mammalian blood-brain barrier with a high correspondence between doses and measured concentrations. Untargeted analyses allowed the identification of eight metabolites including imidacloprid-olefin, hydroxy-imidacloprid dihydroxy-imidacloprid, imidacloprid-nitrosimine, desnitro-imidacloprid, 6-chloronicotinic acid, 5-(methylsulfanyl)pyridine-2-carboxylic acid and N-imidazolidin-2-ylidenenitramide in plasma and brain. Moreover, analysis of embryonic tissues after oral treatment of mouse dams showed detectable levels of imidacloprid (816.6 ng/g after a dose of 4.1 mg/Kg bw day and 5646 ng/g after a dose of 41 mg/Kg bw day) and its metabolites, proving the permeability of the placenta barrier. Although many studies have been reported on the neurotoxicity of neonicotinoids, our study paves the way for a risk assessment in neurodevelopmental toxicity, demostrating the capability of imidacloprid and its metabolites to pass the biological barriers.
Subject(s)
Insecticides/pharmacokinetics , Mass Spectrometry/methods , Neonicotinoids/pharmacokinetics , Nitro Compounds/pharmacokinetics , Administration, Oral , Animals , Blood-Brain Barrier/metabolism , Brain/metabolism , Dose-Response Relationship, Drug , Female , Fetus/metabolism , Insecticides/analysis , Male , Mice , Neonicotinoids/administration & dosage , Neonicotinoids/analysis , Nitro Compounds/administration & dosage , Nitro Compounds/analysis , Placenta/metabolism , Pregnancy , Tissue DistributionABSTRACT
Indoor residual spraying (IRS) is one of the main malaria vector control strategies in Mozambique alongside the distribution of insecticide treated nets. As part of the national insecticide resistance management strategy, Mozambique introduced SumiShield™ 50WG, a third generation IRS product, in 2018. Its residual efficacy was assessed in southern Mozambique during the 2018-2019 malaria season. Using a susceptible Anopheles arabiensis strain, residual efficacy was assessed on two different wall surfaces, cement and mud-plastered walls, using standard WHO (World Health Organization) cone bioassay tests at three different heights. Female mosquitoes of two age groups (2-5 and 13-26 day old) were exposed for 30 minutes, after which mortality was observed 24h, 48h, 72h, and 96h and 120h post-exposure to assess (delayed) mortality. Lethal times (LT) 90, LT50 and LT10 were estimated using Bayesian models. Mortality 24h post exposure was consistently below 80%, the current WHO threshold value for effective IRS, in both young and old mosquitoes, regardless of wall surface type. Considering delayed mortality, residual efficacies (mosquito mortality equal or greater than 80%) ranged from 1.5 to ≥12.5 months, with the duration depending on mortality time post exposure, wall type and mosquito age. Looking at mortality 72h after exposure, residual efficacy was between 6.5 and 9.5 months, depending on wall type and mosquito age. The LT50 and LT10 (i.e. 90% of the mosquitoes survive exposure to the insecticides) values were consistently higher for older mosquitoes (except for LT10 values for 48h and 72h post-exposure mortality) and ranged from 0.9 to 5.8 months and 0.2 to 7.8 months for LT50 and LT10, respectively. The present study highlights the need for assessing mosquito mortality beyond the currently recommended 24h post exposure. Failure to do so may lead to underestimation of the residual efficacy of IRS products, as delayed mortality will lead to a further reduction in mosquito vector populations and potentially negatively impact disease transmission. Monitoring residual efficacy on relevant wall surfaces, including old mosquitoes that are ultimately responsible for malaria transmission, and assessing delayed mortalities are critical to provide accurate and actionable data to guide vector control programmes.
Subject(s)
Anopheles , Guanidines/administration & dosage , Insecticides/administration & dosage , Mosquito Control/methods , Neonicotinoids/administration & dosage , Thiazoles/administration & dosage , Aerosols , Age Factors , Animals , Female , Housing , MozambiqueABSTRACT
BACKGROUND: We evaluated the efficiency of an ex vivo feeding technique using a silicone membrane-based feeding chamber to (i) assess the anti-feeding and acaricidal efficacy of a spot-on combination of dinotefuran, pyriproxyfen and permethrin (DPP, Vectra® 3D) against adult Ixodes scapularis and Ixodes ricinus ticks, and to (ii) explore its effect on blocking the acquisition of Borrelia burgdorferi sensu stricto. METHODS: Eight purpose-bred dogs were randomly allocated to two equal-size groups based on body weight assessed on day 2. DPP was administered topically, as spot-on, to four dogs on day 0. Hair from the eight dogs was collected individually by brushing the whole body on days 2, 7, 14, 21, 28 and 35. On each day of hair collection, 0.05 g of sampled hair was applied on the membrane corresponding to each feeding unit (FU). Seventy-two FU were each seeded with 30 adults of I. scapularis (n = 24 FU) or I. ricinus ticks (n = 48 FU). Bovine blood spiked with B. burgdorferi sensu stricto (strain B31) was added into each unit and changed every 12 h for 4 days. Tick mortality was assessed 1 h after seeding. One additional hour of incubation was added for live/moribund specimens and reassessed for viability. All remaining live/moribund ticks were left in the feeders and tick engorgement status was recorded at 96 h after seeding, and the uptake of B. burgdorferi s.s. was examined in the collected ticks by applying quantitative real-time PCR. RESULTS: Exposure to DPP-treated hair was 100% effective in blocking B. burgdorferi s.s. acquisition. The anti-feeding efficacy remained stable (100%) against both Ixodes species throughout the study. The acaricidal efficacy of DPP evaluated at 1 and 2 h after exposure was 100% throughout the study for I. ricinus, except the 1-h assessment on day 28 (95.9%) and day 35 (95.3%). The 1-h assessment of acaricidal efficacy was 100% at all time points for I. scapularis. CONCLUSIONS: The ex vivo feeding system developed here demonstrated a protective effect of DPP against the acquisition of B. burgdorferi without exposing the animals to the vectors or to the pathogen.
Subject(s)
Dog Diseases/prevention & control , Guanidines/administration & dosage , Insecticides/administration & dosage , Ixodes/drug effects , Lyme Disease/prevention & control , Neonicotinoids/administration & dosage , Nitro Compounds/administration & dosage , Permethrin/administration & dosage , Pyridines/administration & dosage , Administration, Topical , Animals , Borrelia burgdorferi/physiology , Dog Diseases/microbiology , Dogs , Drug Combinations , Feeding Behavior , Female , Ixodes/classification , Ixodes/microbiology , Lyme Disease/transmission , MaleABSTRACT
This study aimed to (i) develop a sensitive method for simultaneous detection and quantification of imidacloprid (IMI) and seven of its metabolites in tissue specimens, and to (ii) determine the biodistribution of the IMI compounds in tissues of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of no observable adverse effect level of IMI) through a powdered diet for 24 weeks. We successfully developed a method which was accurate (recoveries were ≥ 70% for most compounds), sensitive (LODs ≤ 0.47 ng/mL and LOQs ≤ 1.43 ng/mL were recorded for all detected compounds, R2 ≥ 0.99) and precise (RSDs ≤ 20%) for routine analysis of IMI and seven of its metabolites in blood and various tissue matrices. After bio-distributional analysis, IMI and five of its metabolites were detected in mice. Brain, testis, lung, kidney, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, blood and mesenteric white adipose tissue mainly accumulated IMI-olefin; liver mainly accumulated desnitro-IMI; pancreas predominately accumulated 4-hydroxy-IMI. The desnitro-dehydro-IMI and the desnitro-IMI metabolites recorded tissue-blood concentration ratios ≥ 1.0 for testis, brain, lung and kidney. The cumulative levels of the six detected IMI compounds (Σ6 IMI compounds) were found in the decreasing order: blood > testis > brain > kidney > lung > iWAT > gWAT > mWAT > liver > pancreas. Altogether, this study provided essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species.
Subject(s)
Chromatography, Liquid , Insecticides/pharmacokinetics , Neonicotinoids/pharmacokinetics , Nitro Compounds/pharmacokinetics , Tandem Mass Spectrometry , Adipose Tissue, White/metabolism , Animals , Brain/metabolism , Insecticides/administration & dosage , Insecticides/analysis , Insecticides/blood , Kidney/metabolism , Liver/metabolism , Male , Mice, Inbred C57BL , Neonicotinoids/administration & dosage , Neonicotinoids/analysis , Neonicotinoids/blood , Nitro Compounds/administration & dosage , Nitro Compounds/analysis , Nitro Compounds/blood , Testis/metabolism , Tissue DistributionABSTRACT
Indoor residual spraying (IRS) is one of the main malaria vector control strategies in Mozambique alongside the distribution of insecticide treated nets. As part of the national insecticide resistance management strategy, Mozambique introduced SumiShield™ 50WG, a third generation IRS product, in 2018. Its residual efficacy was assessed in southern Mozambique during the 20182019 malaria season. Using a susceptible Anopheles arabiensis strain, residual efficacy was assessed on two different wall surfaces, cement and mud-plastered walls, using standard WHO (World Health Organization) cone bioassay tests at three different heights. Female mosquitoes of two age groups (25 and 1326 day old) were exposed for 30 minutes, after which mortality was observed 24h, 48h, 72h, and 96h and 120h post-exposure to assess (delayed) mortality. Lethal times (LT) 90, LT50 and LT10 were estimated using Bayesian models. Mortality 24h post exposure was consistently below 80%, the current WHO threshold value for effective IRS, in both young and old mosquitoes, regardless of wall surface type. Considering delayed mortality, residual efficacies (mosquito mortality equal or greater than 80%) ranged from 1.5 to ≥12.5 months, with the duration depending on mortality time post exposure, wall type and mosquito age. Looking at mortality 72h after exposure, residual efficacy was between 6.5 and 9.5 months, depending on wall type and mosquito age. The LT50 and LT10 (i.e. 90% of the mosquitoes survive exposure to the insecticides) values were consistently higher for older mosquitoes (except for LT10 values for 48h and 72h post-exposure mortality) and ranged from 0.9 to 5.8 months and 0.2 to 7.8 months for LT50 and LT10, respectively. The present study highlights the need for assessing mosquito mortality beyond the currently recommended 24h post exposure. Failure to do so may lead to underestimation of the residual efficacy of IRS products, as delayed mortality will lead to a further reduction in mosquito vector populations and potentially negatively impact disease transmission. Monitoring residual efficacy on relevant wall surfaces, including old mosquitoes that are ultimately responsible for malaria transmission, and assessing delayed mortalities are critical to provide accurate and actionable data to guide vector control programmes.
Subject(s)
Guinea Pigs , Mosquito Control/methods , Insecticides/administration & dosage , Thiazoles/administration & dosage , Mortality , Aerosols/isolation & purification , Neonicotinoids/administration & dosage , Guanidines/administration & dosage , Anopheles , MozambiqueABSTRACT
Microplastics (MPs) and pesticides are two kinds of ubiquitous pollutants that can pose a health risk to aquatic organisms. However, researches about the combined effects of MPs and pesticides are very limited. A simple combined exposure model was established in this study, adult zebrafish were exposed to 100 µg/L imidacloprid (IMI), 20 µg/L polystyrene microplastics (PS), and a combination of PS and IMI (PS + IMI) for 21 days. The results demonstrated that exposure to PS and IMI inhibited the growth of zebrafish and altered the levels of glycolipid metabolism and oxidative stress-related biochemical parameters. While gene expression analysis revealed that, compared with PS or IMI treatment group, combined exposure caused a greater change in gene expression levels involving the process of glycolipid metabolism (Gk, Hk1, Aco, PPar-α, Cpt1, Acc, Fas, PPar-γ, Apo) and inflammatory response (IL-1ß, IL-6, IL-8, TNF-α, IL-10). The results demonstrated that even combined exposure of low concentrations of PS and IMI could cause more severe hepatotoxicity in zebrafish, especially in terms of gene transcription. And more combined toxicity studies are essential for MPs and pesticides risk assessment.
Subject(s)
Chemical and Drug Induced Liver Injury/pathology , Gene Expression Regulation/drug effects , Insecticides/toxicity , Microplastics/toxicity , Neonicotinoids/toxicity , Nitro Compounds/toxicity , Water Pollutants, Chemical/toxicity , Animals , Drug Therapy, Combination , Insecticides/administration & dosage , Liver/drug effects , Liver/pathology , Neonicotinoids/administration & dosage , Nitro Compounds/administration & dosage , RNA, Messenger/genetics , RNA, Messenger/metabolism , ZebrafishABSTRACT
Neonicotinoid pesticides, originally developed to target the insect nervous system, have been reported to interact with human receptors and to activate rodent neurons. Therefore, we evaluated in how far these compounds may trigger signaling in human neurons, and thus, affect the human adult or developing nervous system. We used SH-SY5Y neuroblastoma cells as established model of nicotinic acetylcholine receptor (nAChR) signaling. In parallel, we profiled dopaminergic neurons, generated from LUHMES neuronal precursor cells, as novel system to study nAChR activation in human post-mitotic neurons. Changes of the free intracellular Ca2+ concentration ([Ca2+]i) were used as readout, and key findings were confirmed by patch clamp recordings. Nicotine triggered typical neuronal signaling responses that were blocked by antagonists, such as tubocurarine and mecamylamine. Pharmacological approaches suggested a functional expression of α7 and non-α7 nAChRs on LUHMES cells. In this novel test system, the neonicotinoids acetamiprid, imidacloprid, clothianidin and thiacloprid, but not thiamethoxam and dinotefuran, triggered [Ca2+]i signaling at 10-100 µM. Strong synergy of the active neonicotinoids (at low micromolar concentrations) with the α7 nAChR-positive allosteric modulator PNU-120596 was observed in LUHMES and SH-SY5Y cells, and specific antagonists fully inhibited such signaling. To provide a third line of evidence for neonicotinoid signaling via nAChR, we studied cross-desensitization: pretreatment of LUHMES and SH-SY5Y cells with active neonicotinoids (at 1-10 µM) blunted the signaling response of nicotine. The pesticides (at 3-30 µM) also blunted the response to the non-α7 agonist ABT 594 in LUHMES cells. These data show that human neuronal cells are functionally affected by low micromolar concentrations of several neonicotinoids. An effect of such signals on nervous system development is a toxicological concern.
Subject(s)
Dopaminergic Neurons/drug effects , Neonicotinoids/toxicity , Pesticides/toxicity , Receptors, Nicotinic/drug effects , Calcium/metabolism , Cell Line , Cell Line, Tumor , Dopaminergic Neurons/pathology , Dose-Response Relationship, Drug , Humans , Neonicotinoids/administration & dosage , Neuroblastoma/metabolism , Patch-Clamp Techniques , Receptors, Nicotinic/metabolism , Signal Transduction/drug effectsABSTRACT
Neonicotinoids, which act as agonists of the nicotinic acetylcholine receptors of insects, are widely used pesticides worldwide. Although epidemiological studies revealed that the detection amounts of neonicotinoids in urine are higher in the elderly population than other age-groups, there is no available information regarding the risks of neonicotinoids to older mammals. This study was aimed to investigate aging-related differences in the behavioral effects of the neonicotinoid pesticide clothianidin (CLO). We acutely administered a sub-NOAEL level (5 mg/kg) of CLO to adult (12-week-old) and aging (90-week-old) mice and conducted four behavioral tests focusing on the emotional behavior. In addition, we measured the concentrations of CLO and its metabolites in blood, brain and urine. There were age-related changes in most parameters in all behavioral tests, and CLO significantly decreased the locomotor activity in the open field test and elevated plus-maze test in the aging group, but not in the adult group. The concentrations of most CLO and its metabolites were significantly higher in the blood and brain and were slightly lower in the urine in the aging group compared to the adult group. These findings should contribute to our understanding of age-related differences in the adverse effects of neonicotinoids in mammals.
Subject(s)
Behavior, Animal/drug effects , Guanidines/toxicity , Insecticides/toxicity , Neonicotinoids/toxicity , Thiazoles/toxicity , Aging , Animals , Dose-Response Relationship, Drug , Guanidines/administration & dosage , Insecticides/administration & dosage , Male , Mice , Mice, Inbred C57BL , Neonicotinoids/administration & dosage , Thiazoles/administration & dosageABSTRACT
Co-occurrence of pesticide residues in food commodities raises a potential safety issue as their mixture effects on human health are largely unknown. In a previous study, we reported the toxicological effects (pathology and histopathology) of imazalil (IMZ), thiacloprid (THI), and clothianidin (CTD) alone and in binary mixtures in a 28-day oral gavage study in female Wistar rats. Five dose levels (up to 350 mg/kg body weight/day) ranging from a typical toxicological reference value to a clear effect dose were applied. In the present study, we undertook a transcriptomics analysis of rat livers by means of total RNA sequencing (RNA-Seq). Bioinformatic data analysis involving Ingenuity Pathway Analysis (IPA) was used to gain mechanistic information on hepatotoxicity-related pathways affected after treatment with the pesticides, alone and in mixtures. Our data show that 2986 genes were differentially regulated by CTD while IMZ and THI had effects on 194 and 225 genes, respectively. All three individual compounds shared a common subset of genes whose network is associated with xenobiotic metabolism and nuclear receptor activation. Similar networks were retrieved for the mixtures. Alterations in the expression of individual genes were in line with the assumption of dose addition. Our results bring new insight into the hepatotoxicity mechanisms of IMZ, THI, and CTD and their mixtures.
Subject(s)
Chemical and Drug Induced Liver Injury/etiology , Guanidines/toxicity , Imidazoles/toxicity , Neonicotinoids/toxicity , Thiazines/toxicity , Thiazoles/toxicity , Animals , Chemical and Drug Induced Liver Injury/genetics , Dose-Response Relationship, Drug , Female , Gene Expression Profiling , Guanidines/administration & dosage , Imidazoles/administration & dosage , Neonicotinoids/administration & dosage , Pesticides/toxicity , Rats , Rats, Wistar , Sequence Analysis, RNA , Thiazines/administration & dosage , Thiazoles/administration & dosageABSTRACT
Imidacloprid is a neonicotinoid insecticide that acts selectively as an agonist on insect nicotinic acetylcholine receptors. It is used for crop protection worldwide, as well as for non-agricultural uses. Imidacloprid systemic accumulation in food is an important source of imidacloprid exposure. Due to the undisputable need for investigations of imidacloprid toxicity in non-target species, we evaluated the effects of a 28-day oral exposure to low doses of imidacloprid (0.06â¯mg/kg b. w./day, 0.8â¯mg/kg b. w./day and 2.25â¯mg/kg b. w./day) on cholinesterase activity, oxidative stress responses and primary DNA damage in the blood and brain tissue of male Wistar rats. Exposure to imidacloprid did not cause significant changes in total cholinesterase, acetylcholinesterase and butyrylcholinesterase activities in plasma and brain tissue. Reactive oxygen species levels and lipid peroxidation increased significantly in the plasma of rats treated with the lowest dose of imidacloprid. Activities of glutathione-peroxidase in plasma and brain and superoxide dismutase in erythrocytes increased significantly at the highest applied dose. High performance liquid chromatography with UV diode array detector revealed the presence of imidacloprid in the plasma of all the treated animals and in the brain of the animals treated with the two higher doses. The alkaline comet assay results showed significant peripheral blood leukocyte damage at the lowest dose of imidacloprid and dose-dependent brain cell DNA damage. Oral 28-day exposure to low doses of imidacloprid in rats resulted in detectable levels of imidacloprid in plasma and brain tissue that directly induced DNA damage, particularly in brain tissue, with slight changes in plasma oxidative stress parameters.
Subject(s)
Acetylcholinesterase/blood , Brain/enzymology , Brain/pathology , Butyrylcholinesterase/blood , DNA Damage , Neonicotinoids/administration & dosage , Nitro Compounds/administration & dosage , Oxidative Stress , Acetylcholinesterase/metabolism , Administration, Oral , Animals , Biomarkers/metabolism , Body Weight/drug effects , Brain/drug effects , Butyrylcholinesterase/metabolism , Catalase/metabolism , Comet Assay , Glutathione/metabolism , Lipid Peroxidation/drug effects , Male , Organ Size/drug effects , Oxidative Stress/drug effects , Rats, Wistar , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: Self-poisoning with imidacloprid has been previously shown to have low toxicity in humans. Since 2007 newer formulations of Imidacloprid with unknown solvents have been introduced and the potential clinical consequences of these products have not been described. METHODS: Clinical and demographic data were prospectively collected from admissions following oral ingestion of imidacloprid from seven hospitals in Sri Lanka. Data was collected from 2002 to 2007 in an already published study. We compared this data on poisonings collected from 2010 to 2016 following the introduction of new formulations of imidacloprid. RESULTS: From 2002-2007, there were 56 patients with ingestion to imidacloprid compared to 67 patients post 2010 The median time to presentation prior to 2007 was 4 h (IQR 2.3-6.0 hrs) and post 2010 was only 2.0 hr (IQR 1.5 to 3.1 hrs). The median amount ingested was 15 ml (IQR 10.0-50.0mls) prior to 2007 and 27.5mls (IQR 5.0-71.8mls) post 2010. In both studies most patients developed non-specific symptoms including nausea, vomiting, epigastric pain and headache. However, prior to 2007 only 1.9% of the cohort required mechanical ventilation due to respiratory failure and there were no reported deaths. In contrast, post 2010; deaths occurred in 3.0% of the cohort and 6.0% required mechanical ventilation for respiratory failure. The cause of mortality was due to one case of cardiorespiratory failure and the other due to a prolonged admission complicated with lobar pneumonia leading to decompensated liver failure on the background of undiagnosed liver cirrhosis. CONCLUSION: Although acute exposure to imidacloprid is usually associated with mild non-specific symptoms, since the introduction of new formulations of imidacloprid, the toxic profile has changed with reported cases of death as well as an increase in cases requiring mechanical ventilation. The change in toxicity could be due to the solvents used in the newer formulations but also due to higher dose of imidacloprid described in our latter cohort. Further research into these solvents needs to be done and continued toxicovigilance is required.
Subject(s)
Insecticides/poisoning , Neonicotinoids/poisoning , Nitro Compounds/poisoning , Administration, Oral , Humans , Insecticides/administration & dosage , Insecticides/toxicity , Male , Middle Aged , Neonicotinoids/administration & dosage , Neonicotinoids/toxicity , Nitro Compounds/administration & dosage , Nitro Compounds/toxicity , Prospective Studies , Respiration, Artificial , Respiratory Insufficiency/chemically induced , Respiratory Insufficiency/therapy , Sri LankaABSTRACT
Canine heartworm disease (CHD) results from infection with Dirofilaria immitis and while it is of global concern, it is most prevalent in tropical climates where conditions support the parasite and vector life cycles. Melarsomine dihydrochloride is the sole treatment for CHD recommended by the American Heartworm Society. However, in cases where cost or access to melarsomine precludes treatment of an infected dog, therapeutic alternatives are warranted. This randomized, controlled field study evaluated the adulticidal efficacy of a combination therapeutic protocol using 10 % imidacloprid + 2.5 % moxidectin spot-on and a single 28-day course of doxycycline and compared with that of a 2-dose melarsomine dihydrochloride protocol. Of 37 naturally-infected domestic dogs with class 1, 2 or early class 3 CHD enrolled in the study, 30 were evaluated for a minimum of 12 months. Seven dogs were withdrawn due to canine ehrlichiosis, non-compliance, or wrongful inclusion. Dogs were randomly assigned to a control (CP, nâ¯=â¯15) or investigational (IVP, nâ¯=â¯15) treatment group. CP dogs received two injections of melarsomine dihydrochloride (2.5â¯mg/kg) 24â¯-hs apart and maintained on monthly ivermectin/pyrantel. IVP dogs were treated with oral doxycycline (10â¯mg/kg twice daily for 28 days) and topical 10 % imidacloprid + 2.5 % moxidectin once monthly for 9 months. Dogs were evaluated up to 18 months - monthly for the first 9 months, then every 3 months. Parasiticidal efficacy was based on antigen status using the IDEXX PetChek® 34 Heartworm-PF Antigen test. By month 18, antigen was not detected in any study dog except one from the IVP group. One other IVP dog was persistently antigenemic and treated with melarsomine at month 12 according to the initial study protocol. Mean antigen concentration (based on optical density) decreased more rapidly in the CP group and by month 15 was 0.11 for the IVP and 0.07 for CP groups, with equivalent median concentrations (0.04) in both groups. Conversion following heat-treatment of antigen-negative samples occurred frequently and at similar rates in both treatment groups. Based on the bias of diagnostic tests towards detection of female worms, we conclude that monthly application of 10 % imidacloprid + 2.5 % moxidectin for 9 months combined with a course of doxycycline twice daily for 28 days resulted in effective therapy against female adults in CHD. This therapeutic option may be particularly useful in cases where financial constraint or access to melarsomine precludes treatment of an infected individual. This study was supported by Bayer Animal Health.
Subject(s)
Dirofilariasis/drug therapy , Dirofilariasis/prevention & control , Dog Diseases/drug therapy , Dog Diseases/prevention & control , Drug Therapy, Combination/veterinary , Filaricides/therapeutic use , Animals , Dirofilaria immitis , Dogs , Doxycycline/administration & dosage , Female , Grenada , Macrolides/administration & dosage , Neonicotinoids/administration & dosage , Nitro Compounds/administration & dosageSubject(s)
Cat Diseases/parasitology , Dermatitis/veterinary , Dirofilaria/classification , Dirofilariasis/pathology , Skin Diseases, Parasitic/veterinary , Animals , Anorexia/chemically induced , Anorexia/veterinary , Antidepressive Agents/therapeutic use , Cat Diseases/pathology , Cats , Dermatitis/parasitology , Dermatitis/pathology , Dirofilaria/genetics , Dirofilariasis/parasitology , Doxycycline/adverse effects , Doxycycline/therapeutic use , Florida , Insecticides/administration & dosage , Insecticides/therapeutic use , Macrolides/administration & dosage , Macrolides/therapeutic use , Male , Mirtazapine/therapeutic use , Neonicotinoids/administration & dosage , Neonicotinoids/therapeutic use , Nitro Compounds/administration & dosage , Nitro Compounds/therapeutic use , Phylogeny , Skin Diseases, Parasitic/drug therapy , Skin Diseases, Parasitic/parasitology , Skin Diseases, Parasitic/pathologyABSTRACT
The widespread prophylactic usage of neonicotinoid insecticides has a clear impact on non-target organisms. However, the possible effects of long-term exposure on soil-dwelling organisms are still poorly understood especially for social insects with long-living queens. Here, we show that effects of chronic exposure to the neonicotinoid thiamethoxam on black garden ant colonies, Lasius niger, become visible before the second overwintering. Queens and workers differed in the residue-ratio of thiamethoxam to its metabolite clothianidin, suggesting that queens may have a superior detoxification system. Even though thiamethoxam did not affect queen mortality, neonicotinoid-exposed colonies showed a reduced number of workers and larvae indicating a trade-off between detoxification and fertility. Since colony size is a key for fitness, our data suggest long-term impacts of neonicotinoids on these organisms. This should be accounted for in future environmental and ecological risk assessments of neonicotinoid applications to prevent irreparable damages to ecosystems.
Subject(s)
Ants/drug effects , Insecticides/pharmacology , Neonicotinoids/pharmacology , Animals , Environmental Exposure/adverse effects , Guanidines/adverse effects , Insecticides/administration & dosage , Larva/drug effects , Neonicotinoids/administration & dosage , Neonicotinoids/adverse effects , Ovum/drug effects , Pesticide Residues/adverse effects , Population Dynamics , Pupa/drug effects , Thiamethoxam/adverse effects , Thiazoles/adverse effectsABSTRACT
Acetamiprid, a selective agonist of nicotinic acetylcholine recetors, is one of the most widely used neonicotinoids. There is limited data about toxicity of acetamiprid on male reproductive system. Therefore, the study aimed to investigate the reproductive toxic potential of acetamiprid in male rats orally treated with acetamiprid with low (12.5 mg/kg) medium (25 mg/kg) or high dose (35 mg/kg) for 90 days. According to our results, sperm concentration and plasma testosterone levels decreased in dose dependent manner. Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormeone (FSH), luteinizing hormone (LH) levels increased at low and medium dose groups and acetamiprid caused lipid peroxidation and glutathione (GSH) depletion in the testes. Histologic examinations revealed that acetamiprid induced apoptosis in medium and high dose groups and proliferation index dramatically decreased in high dose group. In conclusion, acetamiprid caused toxicity on male reproductive system in the high dose. The mechanism of the toxic effect may be associated with oxidative stress, hormonal disruptions and apoptosis.
Subject(s)
Genitalia, Male/drug effects , Genitalia, Male/metabolism , Insecticides/toxicity , Neonicotinoids/toxicity , Sperm Count , Administration, Oral , Animals , Dose-Response Relationship, Drug , Glutathione/metabolism , Gonadotropin-Releasing Hormone/blood , Lipid Peroxidation , Luteinizing Hormone/blood , Male , Neonicotinoids/administration & dosage , Rats, Sprague-Dawley , Testis/metabolism , Testosterone/bloodABSTRACT
Recent studies have reported interspecific differences in how bee species respond to various stressors. Evaluating the exposure and responses of different bee species to plant protection products is considered an essential part of their risk assessment. This study was conducted to assess the impacts of thiacloprid-prochloraz mixture on buff-tailed bumblebees (Bombus terrestris) and red mason bees (Osmia bicornis) in a worst-case scenario under semi-field conditions. Bumblebee colonies or solitary bee trap nests were confined in tunnels with flowering oilseed rape. The recommended maximum application rates of 72 g thiacloprid/ha and 675 g prochloraz/ha were applied as a tank mixture during bee flight in full flowering oilseed rape. Several parameters such as flight and foraging activity, population parameters, and exposure level were investigated. Our results show adverse effects of the combination of thiacloprid and prochloraz on the reproductive performance of red mason bees. The number of cocoons produced by O. bicornis was significantly reduced in the treatment compared to the control group. Regarding bumblebees, we found no effects of the thiacloprid-prochloraz mixture on any observed parameters of colony development. The maximum detected concentrations of both active substances three days after application were higher in O. bicornis pollen mass compared to B. terrestris stored pollen. We conclude that this worst-case scenario of thiacloprid-prochloraz exposure poses a high risk to solitary bees and thus the use of such mixture should be restricted.
Subject(s)
Bees/drug effects , Flight, Animal/drug effects , Imidazoles/administration & dosage , Insecticides/administration & dosage , Neonicotinoids/administration & dosage , Thiazines/administration & dosage , Animals , Feeding Behavior/drug effects , Germany , Population Dynamics , ReproductionABSTRACT
We previously demonstrated that the cockroach α-bungarotoxin-sensitive nicotinic acetylcholine receptors, nAChR1 and nAChR2 subtypes, are differently sensitive to intracellular calcium pathways. Here, using whole cell patch-clamp recordings, we studied the effects of the diacylglycerol (DAG) analogue 1,2-dioctanoyl-sn-glycerol (DiC8) on nicotine- and clothianidin-evoked currents under an α-bungarotoxin treatment. Our results demonstrated that DiC8 reduced nicotine and clothianidin evoked currents. 10⯵M DiC8 suppressed the increase in nicotine-induced currents which was brought about by application of 5â¯mM caffeine or 9â¯mM Ca2+, whereas DiC8 did not affect the decrease in nicotine-induced currents induced by BAPTA. Similarly, bath application of caffeine or 9â¯mM Ca2+ did not change the clothianidin effects, and the amplitude of clothianidin-induced currents was not affected. However, co-application of both 10⯵M DiC8 with 9â¯mM Ca2+, caffeine or BAPTA reduced clothianidin current amplitudes. We conclude that nicotine and clothianidin differently modulate nAChR1 and nAChR2 subtypes under DiC8 treatment, and that nicotine activates nAChR1, whereas clothianidin activates both nAChR1 and nAChR2 subtypes.
Subject(s)
Bungarotoxins/administration & dosage , Diglycerides/administration & dosage , Guanidines/administration & dosage , Membrane Potentials/drug effects , Neonicotinoids/administration & dosage , Neurons/drug effects , Nicotine/administration & dosage , Receptors, Nicotinic/administration & dosage , Receptors, Nicotinic/physiology , Thiazoles/administration & dosage , Animals , Calcium Signaling/drug effects , Cockroaches , Male , Neurons/physiology , Nicotinic Agonists/administration & dosageABSTRACT
BACKGROUND: In three randomized, controlled laboratory efficacy studies, the efficacy in the prevention of patent infections of a topical combination of imidacloprid 10%/moxidectin 1% (Advocate® spot-on formulation for cats, Bayer Animal Health GmbH) against larval stages and immature adults of Aelurostrongylus abstrusus, as well as the treatment efficacy of a single or three monthly treatments against adult A. abstrusus, were evaluated. METHODS: Cats were experimentally inoculated with 300-800 third-stage larvae (L3). Each group comprised 8 animals and the treatment dose was 10 mg/kg bodyweight (bw) imidacloprid and 1 mg/kg bw moxidectin in each study. Prevention of the establishment of patent infections was evaluated by two treatments at a monthly interval at three different time points before and after challenge infection. Curative efficacy was tested by one or three treatments after the onset of patency. Worm counts at necropsy were used for efficacy calculations. RESULTS: In Study 1, the control group had a geometric mean (GM) of 28.8 adult nematodes and the single treatment group had a GM of 3.4 (efficacy 88.3%). In Study 2, the control group had a GM of 14.3, the prevention group had a GM of 0 (efficacy 100%), while the treatment group had a GM of 0.1 (efficacy 99.4%). In Study 3, the GM worm burden in the control group was 32.6 compared to 0 in all three prevention groups (efficacy 100% for all of those groups). CONCLUSIONS: The monthly administration of Advocate® reliably eliminated early larval stages and thereby prevented lung damage from and patent infections with A. abstrusus in cats. Regarding treatment, a single application of Advocate® reduced the worm burden, but it did not sufficiently clear the infection. In contrast, three monthly treatments were safe and highly efficacious against A. abstrusus.