Qualitative identification of imidacloprid in postmortem animal tissue by gas chromatography-tandem mass spectrometry.

During an avian mass mortality event investigation at the National Fish and Wildlife Forensic Laboratory in Ashland, OR, imidacloprid became an insecticide of concern. A qualitative analytical toxicology screen of seeds, plucks (tongue, esophagus, and trachea), and ventricular contents was requested. A method for the extraction and qualitative analysis of the insecticide in animal tissues was therefore developed. The procedure relies on a combined Food Emergency Response Network (FERN) and QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) approach to sample extraction followed by qualitative analysis by gas chromatography-tandem mass spectrometry. Since imidacloprid is not amenable to the conditions of gas chromatography, a trimethylsilyl derivative was created and characterized. Proposed mechanisms for the creation of this derivative and its mass spectrum are described. The imidacloprid-trimethylsilyl (TMS) derivative was detected in all samples submitted.

[Determination of 3-nitropropionic acid in poisoning samples by ultra-performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: An ultra-performance liquid chromatography-tandem mass spectrometric method was established for determination of 3-nitropropionic acid of sugarcane, sugarcane bagasse, vomit, serum and urine. METHODS: The 3-nitropropionic acid in poisoning samples was extracted by acetonitrile in super-sonic instrument. The supernatant was cleaned up with PSA column and eluted with 10% ammonia water-methanol (10: 90, V/V), then the purified solution was concentrated by nitrogen, dissolved with water (containing 0.4% formic acid) and cleaned by 0.22 µm millipore filter. The filtrate was detected by ultra-performance liquid chromatography-tandem mass spectrometry, identified by electrospray ionization (ESI) in negative mode using multiple reaction monitoring, and quantified with external standards of sample matrix matching. The sample extract was separated on an acquity BEH C18 column (2.1 mm x 150 mm x 1.7 µm) by gradient elution in 10 minutes with acetronitrile-water as mobile phase. RESULTS: The calibration curves of 3-nitropropionic acid residues showed good linearity in the range of 1.0 - 50 µg/kg with correlation coefficient of 0.9993 or 0.9998. The detection limits of the method were from 0.06 µg/kg to 0.30 µg/kg, and limits of quantitation ranged from 0.20 µg/kg to 1.0 µg/kg. The recoveries of three spiking levels (1.0, 10.0 and 100.0 µg/kg) ranged from 86.9% to 102.0%, and the relative standard deviations of 1.80%- 4.19% were obtained. CONCLUSION: The method for determination of 3-nitropropionic acid in poisoning samples by UPLC-MS/MS is of operation convenience, less interference from impurities and good accuracy, which could provide evidence and treatment for mouldy sugarcane poisoning.

[Analysis of the literature on acute aromatic amino or nitro-compounds poisoning].

OBJECTIVE: To review the clinical features of acute toxicity of aromatic amino and nitro compounds. METHODS: A total of 110 papers reporting 1240 cases of acute toxicity induced by aromatic amino and nitro compounds from 1979 to 2013 were collected from CNKI, VIP, and Wanfang database, and were analyzed in this study. RESULTS: Of all included cases, 939 were caused by occupational exposure, and 301 were caused by exposure in daily life. A total of 1044 cases were male, and 196 were female. Age ranged from 9 days to 75 years. There were 13 cases of contact reaction. The numbers of mild, moderate, and severe toxicities were 358, 348, and 139, respectively, and the other 382 cases were not graded for severity. The average incubation period was 4.50±5.71 h (M = 3 h). The average incubation period of aniline toxicity was significantly shorter than that of nitrobenzene toxicity. Methemoglobinemia was found in 1146 cases, while cases of poisonings with 5-nitro-o-toluidine, 2-methyl-4-nitroaniline, and 3-chloro-2-methyl aniline were not found to have methemoglobinemia. The detection rates of MHb and HzB were 83.73% (674/805) and 40.19% (129/321), respectively. Sixty-two (19.31%) out of 321 cases were complicated by intravascular hemolysis, 270 (30.93%) out of 873 cases suffered hepatic impairment, 50 (12.25%) out of 408 cases were accompanied by renal damage. Consciousness disorders were found in 66 cases, and chemical cystitis was found in 36 cases. Oral poisoning could immediately induce severe symptoms including cyanosis, unconsciousness, and hemolysis. In prognosis analysis, it was found that the cure rate was 98.71% (1224/1240), and 14 cases of death were caused by multiple organ dysfunction syndrome, renal failure, uncontrolled hemorrhagic shock, myocardial infarction, and sudden death. Two cases were left with neurological sequelae. CONCLUSION: The clinical manifestations of poisoning with aromatic amino and nitro compounds are methemoglobinemia, intravascular hemolysis, liver damage, and renal damage. Treatment with specific medicine methylene blue can produce ideal clinical prognosis, but severe poisoning may cause death from multiple organ failure.

N-Acetylcysteine reverses mitochondrial dysfunctions and behavioral abnormalities in 3-nitropropionic acid-induced Huntington's disease.

Mitochondrial dysfunction is a major event involved in the pathogenesis of Huntington's disease (HD). The present study evaluates the role of N-acetyl-L-cysteine (NAC) in preventing mitochondrial dysfunctions in a 3-nitropropionic acid (3-NP)-induced model of HD. Administration of 3-NP to rats (Wistar strain) resulted in significant inhibition of mitochondrial complexes II, IV and V in the striatum. However, no significant effect on complex I was observed. Increased generation of reactive oxygen species and lipid peroxidation was observed in mitochondria of 3-NP-treated animals. Endogenous antioxidants (thiols and manganese-superoxide dismutase) were lowered in mitochondria of 3-NP-treated animals. 3-NP-treated animals showed increased cytosolic cytochrome c levels and mitochondrial swelling. Increased expressions of caspase-3 and p53 were also observed in 3-NP-treated animals. Histopathological examination of the striata of 3-NP-treated animals revealed increased neural space, neurodegeneration and gliosis. This was accompanied by cognitive and motor deficits. NAC treatment, on the other hand, was found to be effective in reversing 3-NP-induced mitochondrial dysfunctions and neurobehavioral deficits. Our findings suggest a beneficial effect of NAC in HD.

The clinical toxicity of imidacloprid self-poisoning following the introduction of newer formulations.

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.

Acute multiple organ failure with imidacloprid and alcohol ingestion.

Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals due to nicotinic receptor resistance. Human poisoning is usually mild, and reports are quite limited. Here, we report a case of ingestion of alcohol with an insecticide containing imidacloprid. Clinical manifestation included mild disorientation, followed by bradycardia, ventricular arrhythmia, and cardiopulmonary arrest. Acute multiple organ failure, including oliguric kidney injury, acute lung injury, hypotension, and metabolic acidosis developed within hours of ingestion. Renal replacement therapy, including intermittent hemodialysis and continuous venovenous hemodialysis, quickly corrected the metabolic acidosis with better blood pressure. Despite original belief that imidacloprid has low mammalian toxicity, there is increasing evidence that imidacloprid may cause heart, kidney, and other organ damages and even death besides gastrointestinal irritation and neurological symptoms. The role of aldehyde oxidase, imidacloprid metabolites, and ethanol alcohol consumption in the pathogenesis of imidacloprid toxicity needs further study.

[Acute inhalation imidacloprid poisoning--a case report]. / Ostre wziewne zatrucie imidachloprydem--opis przypadku.

According to the best of my knowledge this is the first report of acute intoxication with imidacloprid in Poland. The 48-years old women was admitted to the hospital because of the symptoms of gastroenteritis, which occurred after inhaled exposure to imidacloprid. Mild increase in leukocyte count was found in laboratory examination. The symptoms disappeared after 2 days of the treatment. For imidacloprid, regarded as safe for humans being, toxicity can occur through inhalation exposure.

Imidacloprid poisoning case series: potential for liver injury.

Introduction: Imidacloprid is a commonly used neonicotinoid insecticide in Thailand. Limited reports suggest it may be associated with liver injury.Case series: A retrospective poison center case series identified 128 cases of imidacloprid ingestion from 2010-2016, of which four developed liver injury.Results: Three patients ingested soluble liquid concentrates and one ingested water-dispersible granules of imidacloprid. The estimated doses of ingestion ranged from 2-35 g. One patient developed cholestatic liver injury, two developed hepatocellular liver injury, and the remaining patient, who ingested the highest dose, developed a mixed pattern of liver injury. Median onset of liver injury was 5.5 days.Discussion: In prior case reports and animal studies, these cases suggest imidacloprid toxicity is associated with liver injury that may be delayed. This is consistent with our finding. The cases also demonstrated a possible dose-response relationship of imidacloprid ingestion with severity and type of liver injury. All findings suggested that imidacloprid might contribute to liver injury.Conclusion: We report four cases of liver injury, which are possibly related to ingestion of imidacloprid. In management, consideration should be given to repeating liver tests as an outpatient if initial tests are normal, with counseling on the possibility of delayed liver injury.

Imidacloprid poisoning: a case report.

Imidacloprid is a systemic, chloronicotinyl insecticide. It is generally considered nontoxic to humans based on available literature. Its effects are mediated through acetylcholine receptor blockade. We report a patient with such poisoning who had respiratory arrest, for which he had to be mechanically ventilated, and who subsequently recovered. This is only the second such case report.

Severe central nervous system depression in a patient with acute imidacloprid poisoning.

Imidacloprid belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. We report a case of acute ingestion of an insecticide formulation containing imidacloprid. Clinical manifestations included respiratory failure and coma. A previously healthy 67-year-old male patient ingested an unknown quantity of imidacloprid for suicidal purpose. Disorientation, drowsiness, and increased salivation had developed by the time of arrival to a local hospital. On admission, his mental status was decreased (Glasgow Coma Scale score, 3/15). He was intubated and mechanically ventilated. Symptomatic and supportive treatments were given. At the fourth day, the patient was discharged from the hospital. None of the symptoms can be considered characteristic and specific for imidacloprid poisoning as a neonicotinoid compound. Although the symptoms can be resolved with supportive measures, none of them can be considered characteristic and specific for imidacloprid poisoning as a neonicotinoid compound.

Imidacloprid Poisoning of Songbirds Following a Drench Application of Trees in a Residential Neighborhood in California, USA.

In March 2017, 26 American goldfinches (Spinus tristis) were found dead following a drench application of imidacloprid in California (USA). Identical seed fragments were present in the digestive tracts. Imidacloprid was detected in 4 separate pooled samples from 18 birds, in crop/gizzard contents (4.8 ± 1.3 ppm; range 2.2-8.5 ppm) and liver tissues (3.9 ± 0.6 ppm; range 2.1-4.8 ppm). We suspect that fallen elm (Ulmus sp.) seeds were contaminated with imidacloprid during the drench application and subsequently ingested, resulting in acute toxicity and death. Environ Toxicol Chem 2019;38:1724-1727. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Fatal intoxication with imidacloprid insecticide.

Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, CAS 138261-41-3] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals. Despite wide usage in some countries, the understanding of human poisoning is quite limited. Here we report a fatal case of rapid ingestion of an insecticide formulation containing imidacloprid. Clinical manifestation included severe vomiting, hypertension, tachycardia, mydriasis with sluggish reaction to light, and loss of consciousness. In the course of toxicity, the patient manifested bradycardia, bradypnea, and cardiopulmonary arrest and death. Because moderate- to high-dose imidacloprid in animals causes central nervous system activation similar to nicotine, including tremors, impaired papillary function, and hypothermia, it is more likely that the formulation ingredients caused most of the clinical symptoms including central nervous system depression and gastrointestinal irritation.

Analytical confirmation of imidacloprid poisoning in granivorous Cape spurfowl (Pternistis capensis).

Reports were received that Cape spurfowl (Pternistis capensis) fell during flight and scrambled uncoordinatedly for cover and some died. Three carcases were submitted for necropsy examination, which revealed mainly congestion of the carcases and haemorrhages. Common causes of acute mortalities in birds were first excluded, but there was a history of possible exposure to imidacloprid-treated barley seeds. Imidacloprid, a neonicotinoid insecticide, is used to protect various crops against invertebrate pests. The combined crop contents and pooled liver samples collected from the Cape spurfowl during necropsy were submitted for liquid chromatography-high-resolution mass spectrometry (LC-HRMS) for imidacloprid analysis. Imidacloprid and several of its metabolites were detected in the samples. Farmers should cover sown seeds with a layer of soil and remove any spilled seeds, as granivorous birds are susceptible to imidacloprid intoxication. Regulatory authorities should re-evaluate the risk posed by imidacloprid-treated seeds for pollinators and granivorous birds.

Toxicology of the newer neonicotinoid insecticides: imidacloprid poisoning in a human.

Imidacloprid, a potent neonicotinoid insecticide, is currently one of the best selling insecticides. We report a patient with clinical toxicity due to the ingestion of imidacloprid in a deliberate suicide attempt. The structure and mode of action of imidacloprid are discussed.

Field evidence of bird poisonings by imidacloprid-treated seeds: a review of incidents reported by the French SAGIR network from 1995 to 2014.

The large-scale use of neonicotinoid insecticides has raised growing concerns about their potential adverse effects on farmland birds, and more generally on biodiversity. Imidacloprid, the first neonicotinoid commercialized, has been identified as posing a risk for seed-eating birds when it is used as seed treatment of some crops since the consumption of a few dressed seeds could cause mortality. But evidence of direct effects in the field is lacking. Here, we reviewed the 103 wildlife mortality incidents reported by the French SAGIR Network from 1995 to 2014, for which toxicological analyses detected imidacloprid residues. One hundred and one incidents totalling at least 734 dead animals were consistent with an agricultural use as seed treatment. Grey partridges (Perdix perdix) and "pigeons" (Columba palumbus, Columba livia and Columba oenas) were the main species found. More than 70% of incidents occurred during autumn cereal sowings. Furthermore, since there is no biomarker for diagnosing neonicotinoid poisonings, we developed a diagnostic approach to estimate the degree of certainty that these mortalities were due to imidacloprid poisoning. By this way, the probability that mortality was due to poisoning by imidacloprid-treated seeds was ranked as at least "likely" in 70% of incidents. As a result, this work provides clear evidence to risk managers that lethal effects due to the consumption by birds of imidacloprid-treated seeds regularly occur in the field. This in turn raises the question of the effectiveness of the two main factors (seed burying and imidacloprid-treated seeds avoidance) that are supposed to make the risk to birds negligible. Risk factors and the relevance of mitigation measures are discussed.

[The research of the pathogen responsible for Pleurocybella porrigens related encephalopathy: investigation of 3-nitropropionic acid hypothesis].

Pleurocybella porrigens related encephalopathy exhibits consciousness disturbance and convulsion in the patients after taking and patients show bilateral basal ganglia lesion resulted in high mortality rate. This encephalopathy is a very similar to the moldy sugarcane encephalopathy epidemic in China in the past. We investigated the relationship between Pleurocybella porrigens related encephalopathy and 3-nitropropionic acid which had caused the moldy sugarcane encephalopathy. We have tried to detect 3-NPA in the various specimens from patients and Pleurocybella porrigens, but failed. Further examinations for elucidating the causation of Pleurocybella porrigens related encephalopathy are needed.