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Toxicology Research Jun 2022Aldicarb, a carbamate pesticide banned in France since 2008, represents a persistent risk of human poisoning. There is no up-to-date picture of aldicarb intentional...
Aldicarb, a carbamate pesticide banned in France since 2008, represents a persistent risk of human poisoning. There is no up-to-date picture of aldicarb intentional poisonings associated to detailed diagnosis and clinical management of cases to evaluate the effect of its ban on intoxication risk reduction, including suicide. This retrospective epidemiological study describes cases of suicidal intoxication from the Hauts-de-France region between 2012 and 2021 and illustrates this situation through one analytically documented case. 60 cases were collected, mostly presenting a pathognomonic symptomatology. Thirty-five victims presented a muscarinic syndrome (58.3%), 14 a nicotinic syndrome (23.3%), and 37 a central nervous system impairment (61.7%). Hospitalization was necessary for 44 cases (73.3%), with 2 fatal evolutions. Diagnosis was based on the blood cholinesterase activities. Among the 25 cases with toxicology results, 45.8% presented a moderate decrease of acetylcholinesterase activity, whereas 87.5% presented a strong decrease of butyrylcholinesterase activity. Blood or urine detection of aldicarb and its metabolites may be considered in therapeutic management, although their quantification is unlikely to change the emergency medical care. Our study updates epidemiology of aldicarb poisoning at a regional level, highlighting a persisting health threatening situation with banned pesticides. More than 65% of national cases occurred in this agricultural area, aldicarb remaining available from storage of previously purchased products. Robust evidence is presented that acute poisoning is an ongoing major global public health challenge. There is a need for continued international efforts in risk reduction, knowledge, and information strategies.
PubMed: 35782643
DOI: 10.1093/toxres/tfac031 -
Ecotoxicology and Environmental Safety Aug 2021Studies investigating the association between pesticide exposure and colorectal cancer (CRC) risk have been inconclusive.
BACKGROUND
Studies investigating the association between pesticide exposure and colorectal cancer (CRC) risk have been inconclusive.
OBJECTIVES
Investigate the association between pesticide exposure and CRC risk through a systematic literature review.
METHODS
CRC has the fourth-highest rate of cancer-caused death in the US after lung cancer, breast cancer in women, and prostate cancer in men. Here we have conducted a systematic literature search on studies examining the association between any pesticide exposure and CRC risk using PubMed, MEDLINE via EBSCO host, and Embase according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.
RESULTS
Following the review, 139 articles were included for qualitative evaluation. Study participants were farmers, pesticide applicators, pesticide manufacturers, spouses of pesticide applicators, farm residents, Korean veterans of the Vietnam War, rural communities, and those who consumed food with pesticide residues. The studies' results were split between those with significant positive (39 significant results) and inverse (41 significant results) associations when comparing pesticide exposure and CRC risk.
DISCUSSION
From our literature review, we have identified a similar number of significant positive and inverse associations of pesticide exposure with CRC risk and therefore cannot conclude whether pesticide exposure has a positive or inverse association with CRC risk overall. However, certain pesticides such as terbufos, dicamba, trifluralin, S-ethyl dipropylthiocarbamate (EPTC), imazethapyr, chlorpyrifos, carbaryl, pendimethalin, and acetochlor are of great concern not only for their associated elevated risk of CRC, but also for the current legal usage in the United States (US). Aldicarb and dieldrin are of moderate concern for the positive associations with CRC risk, and also for the illegal usage or the detection on imported food products even though they have been banned in the US. Pesticides can linger in the soil, water, and air for weeks to years and, therefore, can lead to exposure to farmers, manufacturing workers, and those living in rural communities near these farms and factories. Approximately 60 million people in the US live in rural areas and all of the CRC mortality hotspots are within the rural communities. The CRC mortality rate is still increasing in the rural regions despite the overall decreasing of incidence and mortality of CRC elsewhere. Therefore, the results from this study on the relationship between pesticide exposure and CRC risk will help us to understand CRC health disparities.
Topics: Adult; Colorectal Neoplasms; Farmers; Female; Herbicides; Humans; Incidence; Male; Middle Aged; Occupational Exposure; Pesticide Residues; Pesticides
PubMed: 34029839
DOI: 10.1016/j.ecoenv.2021.112327 -
Genetics Aug 2021The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels....
The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole Caenorhabditis elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions. jph-1 null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 colocalizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68 RyR calcium channel, and is required for animal movement. In neurons, JPH-1 colocalizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) in the soma, and is present near presynaptic release sites. Interestingly, jph-1 and esyt-2 null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-2 have antagonistic roles in neuromuscular synaptic transmission. Additionally, we find an unexpected cell nonautonomous effect of jph-1 in axon regrowth after injury. Genetic double mutant analysis suggests that jph-1 functions in overlapping pathways with two PM-localized voltage-gated calcium channels, egl-19 and unc-2, and with unc-68 for animal health and development. Finally, we show that jph-1 regulates the colocalization of EGL-19 and UNC-68 and that unc-68 is required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channels in vivo.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Membrane Proteins; Neuromuscular Junction; Neuronal Outgrowth; Neurons; Protein Transport; Ryanodine Receptor Calcium Release Channel; Synaptic Transmission; Synaptotagmins
PubMed: 33871019
DOI: 10.1093/genetics/iyab063 -
Journal of Nematology 2020(peanut root-knot nematode (PRKN)) is a major pest of peanut. Nematicide application is an important tool for the management of PRKN. Nematicides with minimal effects...
(peanut root-knot nematode (PRKN)) is a major pest of peanut. Nematicide application is an important tool for the management of PRKN. Nematicides with minimal effects on free-living nematodes are desired. Fluopyram nematicide is recently introduced in peanut production and needs to be assessed. The objective of this research is to evaluate fluopyram and the established nematicides 1,3-Dichloropropene (1,3-D) and aldicarb for efficacy at managing PRKN and impacts on free-living nematodes. Nematicides were evaluated in field studies in 2017 and 2018 conducted in commercial peanut fields. All nematicides increased peanut yield in 2017 compared with untreated control, but did not affect soil PRKN abundances or root galling. In 2018, PRKN infestation was too low to accurately assess PRKN management by nematicides. Aldicarb and fluopyram did not affect any free-living nematode trophic group or individual genera. In contrast, 1,3-D decreased total fungivore and fungivore genera and soil abundances, but did not affect bacterivores, omnivore-predators, total herbivores, or any other nematode genera. In summary, 1,3-D, but not aldicarb or fluopyram, had non-target effects on free-living nematodes, particularly fungivores. (peanut root-knot nematode (PRKN)) is a major pest of peanut. Nematicide application is an important tool for the management of PRKN. Nematicides with minimal effects on free-living nematodes are desired. Fluopyram nematicide is recently introduced in peanut production and needs to be assessed. The objective of this research is to evaluate fluopyram and the established nematicides 1,3-Dichloropropene (1,3-D) and aldicarb for efficacy at managing PRKN and impacts on free-living nematodes. Nematicides were evaluated in field studies in 2017 and 2018 conducted in commercial peanut fields. All nematicides increased peanut yield in 2017 compared with untreated control, but did not affect soil PRKN abundances or root galling. In 2018, PRKN infestation was too low to accurately assess PRKN management by nematicides. Aldicarb and fluopyram did not affect any free-living nematode trophic group or individual genera. In contrast, 1,3-D decreased total fungivore and fungivore genera and soil abundances, but did not affect bacterivores, omnivore-predators, total herbivores, or any other nematode genera. In summary, 1,3-D, but not aldicarb or fluopyram, had non-target effects on free-living nematodes, particularly fungivores.
PubMed: 32298058
DOI: 10.21307/jofnem-2020-028 -
Annals of the New York Academy of... Nov 2020Aldicarb, a carbamate pesticide, is an acetylcholinesterase inhibitor, with oral median lethal dose (LD ) estimates in rats ranging from 0.46 to 0.93 mg/kg. A...
Aldicarb, a carbamate pesticide, is an acetylcholinesterase inhibitor, with oral median lethal dose (LD ) estimates in rats ranging from 0.46 to 0.93 mg/kg. A three-phase approach was used to comprehensively assess aldicarb as an oral-ingestion hazard. First, the solubility of aldicarb in popular consumer beverages (bottled water, apple juice, and 2% milk) was assessed. Lethality was then assessed by administering aldicarb in bottled water via gavage. A probit model was fit to 24-h survival data and predicted a median lethal dose of 0.83 mg/kg (95% CI: 0.54-1.45 mg/kg; slope: 4.50). Finally, organoleptic properties (e.g., taste, smell, and texture) were assessed by allowing rats to voluntarily consume 3.0 mL of the above beverages as well as liquid eggs adulterated with aldicarb at various concentrations. This organoleptic assessment determined that aldicarb was readily consumed at lethal and supralethal doses. Overt toxic signs presented within 5 min post-ingestion, and all rats died within 20 min after consuming the highest concentration (0.542 mg/mL), regardless of amount consumed. Because rats have more developed chemoreceptive capabilities than humans, these results suggest that aldicarb may be consumed in toxic or even lethal concentrations by humans in a variety of beverages or foods.
Topics: Aldicarb; Animals; Cholinesterase Inhibitors; Humans; Insecticides; Lethal Dose 50; Male; Models, Biological; Rats; Rats, Sprague-Dawley
PubMed: 32761625
DOI: 10.1111/nyas.14448 -
Ecotoxicology and Environmental Safety Apr 2024Mounting evidence has shown that the gut microbiota plays a key role in human health. The homeostasis of the gut microbiota could be affected by many factors, including...
Mounting evidence has shown that the gut microbiota plays a key role in human health. The homeostasis of the gut microbiota could be affected by many factors, including environmental chemicals. Aldicarb is a carbamate insecticide used to control a variety of insects and nematode pests in agriculture. Aldicarb is highly toxic and its wide existence has become a global public health concern. In our previous study, we have demonstrated that aldicarb disturbed the gut microbial community structure and composition. However, the impacts of aldicarb on gut microbiota-derived metabolites, bile acids, remain elusive. In present study, we performed targeted metabolomics analysis to explore the effects of aldicarb exposure on bile acids, as well as steroid hormones and oxylipins in the serum, feces and liver of C57BL/6 J mice. Our results showed that aldicarb exposure disturbed the level of various bile acids, steroid hormones and oxylipins in the serum and feces of C57BL/6 J mice. In the liver, the level of cortisol was decreased, meanwhile 15,16-dihydroxyoctadeca-9,12-dienoic acid was increased in aldicarb-treated mice. Metagenomic sequencing analysis showed that the relative abundance of a bile salt hydrolase, choloylglycine hydrolase (EC:3.5.1.24) and a sulfatase enzyme involved in steroid hormone metabolism, arylsulfatase, was significantly increased by aldicarb exposure. Furthermore, correlations were found between gut microbiota and various serum metabolites. The results from this study are helpful to improve the understanding of the impact of carbamate insecticides on host and microbial metabolism.
Topics: Humans; Mice; Animals; Aldicarb; Bile Acids and Salts; Oxylipins; Mice, Inbred C57BL; Insecticides; Hormones; Homeostasis
PubMed: 38564866
DOI: 10.1016/j.ecoenv.2024.116285 -
Frontiers in Nutrition 2022The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers...
The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106-1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all <1%. The limit of detection of the colloidal gold immunochromatographic strip was 30 μg/kg, and the average recoveries of aldicarb ranged from 80.4 to 110.5% in spiked samples. In the analysis of spiked samples, the test strip could accurately identify positive samples detected by the instrumental method in the GB 23200.112-2018 standard but produced some false positives for negative samples. This assay provides a rapid and accurate preliminary screening method for the determination of aldicarb in agricultural products and environments.
PubMed: 36082035
DOI: 10.3389/fnut.2022.976284 -
Annals of Neurosciences Jan 2021Alzheimer's disease (AD), a prevalent neurodegenerative disease with progressive dementia and neurotransmission (NT)-dysfunction-related complications in older adults,...
BACKGROUND
Alzheimer's disease (AD), a prevalent neurodegenerative disease with progressive dementia and neurotransmission (NT)-dysfunction-related complications in older adults, is known to be caused by abnormal Amyloid-β (Aβ) peptide and associated amyloid plaques in the brain. Drugs to cure AD are not in sight. Two major excitatory neurotransmitters, glutamate (Glu) and acetylcholine (ACh), and their signaling systems are implicated in AD.
OBJECTIVE
To determine the effect of various NT-altering compounds including fenobam, quisqualic acid, and dimethyl sulfoxide (DMSO) in the protection against Aβ toxicity. Further, to identify the potential mechanism through which the protection happens.
METHODS
The well-known AD model, CL4176, in which human Aβ expression is turned on upon a temperature shift to 25 °C that leads to paralysis, was screened for protection/delay in paralysis because of Αβ toxicity. While screening the compounds, dimethyl sulfoxide (DMSO), a universal solvent used to solubilize compounds, was identified to provide protection. Aldicarb and levamisole assays were performed to identify the contribution of ACh neurotransmission in Αβ toxicity protection by DMSO.
RESULTS
One percent and two percent DMSO delayed paralysis by 48% and 90%, respectively. DMSO was dominant over one of the Glu-NT pathway-related compounds, Fenobam-Group I mGluR antagonist. But DMSO provided only 30% to 50% protection against Quisqualic acid, the Glu-agonist. DMSO (2%) delayed ACh-NT, both presynaptic acetylcholine esterase inhibitor (AchEi)-aldicarb and postsynaptic-iAChR-agonst-levamisole induced paralysis, by ∼70% in CL4176. DMSO seems to be altering Ca ion permeability essential for NT as EthyleneDiamine Tetra-Acetic acid (EDTA) and DMSO provided similar aldicarb resistance either combined or alone in wildtype worms. But postsynaptic Ca depletion by EDTA could reverse DMSO-induced levamisole hypersensitivity. Surprisingly, the absence of FOrkhead boXO (FOXO) transcription factor homolog, (loss-of-function mutant), a critical transcription factor in the reduced IIS-mediated longevity in abolished DMSO-mediated Ald.
CONCLUSION
DMSO and Fenobam protect against Aβ toxicity through modulation of NT.
PubMed: 34733055
DOI: 10.1177/09727531211046369 -
Toxicological Sciences : An Official... Dec 2019Perfluorooctane sulfonate (PFOS) has been widely utilized in numerous industries. Due to long environmental and biological half-lives, PFOS is a major public health...
Perfluorooctane sulfonate (PFOS) has been widely utilized in numerous industries. Due to long environmental and biological half-lives, PFOS is a major public health concern. Although the literature suggests that PFOS may induce neurotoxicity, neurotoxic mechanisms, and neuropathology are poorly understood. Thus, the primary goal of this study was to determine if PFOS is selectively neurotoxic and potentially relevant to specific neurological diseases. Nematodes (Caenorhabditis elegans) were exposed to PFOS or related per- and polyfluoroalkyl substances (PFAS) for 72 h and tested for evidence of neuropathology through examination of cholinergic, dopaminergic, gamma-amino butyric acid (GABA)ergic, and serotoninergic neuronal morphologies. Dopaminergic and cholinergic functional analyses were assessed through 1-nonanol and Aldicarb assay. Mechanistic studies assessed total reactive oxygen species, superoxide ions, and mitochondrial content. Finally, therapeutic approaches were utilized to further examine pathogenic mechanisms. Dopaminergic neuropathology occurred at lower exposure levels (25 ppm, approximately 50 µM) than required to produce neuropathology in GABAergic, serotonergic, and cholinergic neurons (100 ppm, approximately 200 µM). Further, PFOS exposure led to dopamine-dependent functional deficits, without altering acetylcholine-dependent paralysis. Mitochondrial content was affected by PFOS at far lower exposure level than required to induce pathology (≥1 ppm, approximately 2 µM). Perfluorooctane sulfonate exposure also enhanced oxidative stress. Further, mutation in mitochondrial superoxide dismutase rendered animals more vulnerable. Neuroprotective approaches such as antioxidants, PFAS-protein dissociation, and targeted (mitochondrial) radical and electron scavenging were neuroprotective, suggesting specific mechanisms of action. In general, other tested PFAS were less neurotoxic. The primary impact is to prompt research into potential adverse outcomes related to PFAS-induced dopaminergic neurotoxicity in humans.
Topics: Alkanesulfonic Acids; Animals; Antioxidants; Caenorhabditis elegans; Cell Line; Dopamine; Environmental Pollutants; Fluorocarbons; Humans; Neurons; Neurotoxicity Syndromes; Oxidative Stress; Reactive Oxygen Species
PubMed: 31428778
DOI: 10.1093/toxsci/kfz191