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Molecules (Basel, Switzerland) Jan 2022Pesticides are synthetic compounds that may become environmental contaminants through their use and application. The high productivity achieved in the agricultural... (Review)
Review
Pesticides are synthetic compounds that may become environmental contaminants through their use and application. The high productivity achieved in the agricultural industry can be credited to the use and application of pesticides by way of pest and insect control. As much as pesticides have a positive impact on the agricultural industry, some disadvantages come with their application in the environment because they are intentionally toxic, and this is more towards non-target organisms. They are grouped into chlorophenols, organochlorines, synthetic pyrethroid, carbamates, and organophosphorus based on their structure. The symptoms of exposure to carbamate (CM) and organophosphates (OP) are similar, although poisoning from CM is of a shorter duration. The analytical evaluation of carbamate and organophosphate pesticides in human and environmental matrices are reviewed using suitable extraction and analytical methods.
Topics: Carbamates; Environmental Exposure; Environmental Monitoring; Humans; Organophosphorus Compounds; Pesticides
PubMed: 35163876
DOI: 10.3390/molecules27030618 -
Chemico-biological Interactions Mar 2013The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants... (Review)
Review
The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades. About 90 of these compounds are still in use - the largest number for any insecticide chemotype or mode of action. In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death. The cholinergic system of insects is located centrally (where it is protected from ionized OPs and MCs) but not at the neuromuscular junction. Structural differences between insect and mammalian AChE are also evident in their genomics, amino acid sequences and active site conformations. Species selectivity is determined in part by inhibitor and target site specificity. Pest population selection with OPs and MCs has resulted in a multitude of modified AChEs of altered inhibitor specificity some conferring insecticide resistance and others enhancing sensitivity. Much of the success of antiChE insecticides results from a suitable balance of bioactivation and detoxification by families of CYP450 oxidases, hydrolases, glutathione S-transferases and others. Known inhibitors for these enzymes block detoxification and enhance potency which is particularly important in resistant strains. The current market for OPs and MCs of 19% of worldwide insecticide sales is only half of that of 10 years ago for several reasons: there have been no major new compounds for 30 years; resistance has eroded their effectiveness; human toxicity problems are still encountered; the patents have expired reducing the incentive to update registration packages; alternative chemotypes or control methods have been developed. Despite this decline, they still play a major role in pest control and the increasing knowledge on their target sites and metabolism may make it possible to redesign the inhibitors for insensitive AChEs and to target new sites in the cholinergic system. The OPs and MCs are down but not out.
Topics: Acetylcholinesterase; Animals; Carbamates; Catalytic Domain; Cholinesterase Inhibitors; Drug Resistance; History, 20th Century; History, 21st Century; Humans; Insecta; Insecticides; Models, Molecular; Organophosphorus Compounds; Phylogeny
PubMed: 22926007
DOI: 10.1016/j.cbi.2012.08.002 -
Neurotoxicity Research Jan 2018Beta-N-methylamino-L-alanine (BMAA) has been demonstrated to contribute to the onset of the ALS/Parkinsonism-dementia complex (ALS/PDC) and is implicated in the...
Beta-N-methylamino-L-alanine (BMAA) has been demonstrated to contribute to the onset of the ALS/Parkinsonism-dementia complex (ALS/PDC) and is implicated in the progression of other neurodegenerative diseases. While the role of BMAA in these diseases is still debated, one of the suggested mechanisms involves the activation of excitatory glutamate receptors. In particular, the excitatory effects of BMAA are shown to be dependent on the presence of bicarbonate ions, which in turn forms carbamate adducts in physiological conditions. The formation of carbamate adducts from BMAA and bicarbonate is similar to the formation of carbamate adducts from non-proteinogenic amino acids. Structural, chemical, and biological information related to non-proteinogenic amino acids provide insight into the formation of and possible neurological action of BMAA. This article reviews the carbamate formation of BMAA in the presence of bicarbonate ions, with a particular focus on how the chemical equilibrium of BMAA carbamate adducts may affect the molecular mechanism of its function. Highlights of nuclear magnetic resonance (NMR)-based studies on the equilibrium process between free BMAA and its adducts are presented. The role of divalent metals on the equilibrium process is also explored. The formation and the equilibrium process of carbamate adducts of BMAA may answer questions on their neuroactive potency and provide strong motivation for further investigations into other toxic mechanisms.
Topics: Amino Acids, Diamino; Animals; Biological Transport; Carbamates; Cations, Divalent; Cyanobacteria Toxins; Kinetics; Nuclear Magnetic Resonance, Biomolecular
PubMed: 28921378
DOI: 10.1007/s12640-017-9801-2 -
Environment International Dec 2020Early-life carbamate exposure during developmental period has been linked with adverse health effects and attracted attention.
BACKGROUND
Early-life carbamate exposure during developmental period has been linked with adverse health effects and attracted attention.
METHODS
Three hundred and three children at age of seven were included in the current study. Urinary carbofuranphenol concentrations were measured using gas chromatography-tandem mass spectrometry. Verbal, performance and full-scale intelligence quotients (IQ, IQ, and IQ) were assessed using Wechsler Intelligence Scale for Children-Chinese Revised. Generalized linear models were used to explore the associations between carbofuranphenol levels and IQs. Generalized estimating equations were used to explore long-term health effect and sensitive time window.
RESULTS
Carbofuranphenol was detected in 96.6% of the seven-year-old urinary samples, the geometric mean, median, and inter quartile range of the carbofuranphenol concentrations were 0.67 μg/L, 0.30 μg/L, and 0.09-3.72 μg/L, respectively, which were similar with the level of three-year-old children from the SMBCS cohort. Seven-year-old carbofuranphenol level was negatively associated with IQ [β = -0.044; 95% confidence interval (CI): -0.087, -0.001; p = 0.045]. Three-year-old carbofuranphenol level was negatively associated with IQ (β = -0.100; 95% CI: -0.186, -0.014; p = 0.022) and IQ (β = -0.087; 95% CI: -0.173, -0.001; p = 0.047). Carbamate exposure of maternal and children at both three and seven years old had negative associations with IQ (β = -0.089; 95% CI: -0.171, -0.007; p = 0.034), and IQ (β = -0.064; 95% CI: -0.127, -0.000; p = 0.049) of children at age of seven.
CONCLUSION
Results of the present study verify that children in an agricultural region of China were widely exposed to carbamate pesticides. Carbamate exposure in utero and at three and seven years may adversely impact children's neurodevelopment.
Topics: Carbamates; Child; Child, Preschool; China; Female; Gas Chromatography-Mass Spectrometry; Humans; Intelligence; Intelligence Tests; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 32919260
DOI: 10.1016/j.envint.2020.106105 -
Environmental Health Perspectives Nov 2023Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic are rare.
OBJECTIVES
This investigation assessed the qualitative and quantitative strength of epidemiological evidence regarding adult exposure to two classes of contemporary use insecticides-organophosphates (OPs) and -methyl carbamates (NMCs)-and sperm concentration using robust and reproducible systematic review and meta-analysis methods.
METHODS
Three scientific databases (PubMed, Scopus, and Web of Science), two U.S. government databases (NIOSHTIC-2 and Science.gov), and five nongovernmental organization websites were searched for relevant primary epidemiological studies published in any language through 11 August 2022. Risk of bias and strength of evidence were evaluated according to Navigation Guide systematic review methodology. Bias-adjusted standardized mean difference effect sizes were calculated and pooled using a three-level, multivariate random-effect meta-analysis model with cluster-robust variance estimation.
RESULTS
Across 20 studies, 21 study populations, 42 effect sizes, and 1,774 adult men, the pooled bias-adjusted standardized mean difference in sperm concentration between adult men more- and less-exposed to OP and NMC insecticides was (95% CI: , ; ). Sensitivity and subgroup analyses explored statistical heterogeneity and validated the model robustness. Although the pooled effect estimate was modified by risk of bias, insecticide class, exposure setting, and recruitment setting, it remained negative in direction across all meta-analyses. The body of evidence was rated to be of moderate quality, with sufficient evidence of an association between higher adult OP and NMC insecticide exposure and lower sperm concentration.
DISCUSSION
This comprehensive investigation found sufficient evidence of an association between higher OP and NMC insecticide exposure and lower sperm concentration in adults. Although additional cohort studies can be beneficial to fill data gaps, the strength of evidence warrants reducing exposure to OP and NMC insecticides now to prevent continued male reproductive harm. https://doi.org/10.1289/EHP12678.
Topics: Humans; Male; Adult; Insecticides; Organophosphates; Semen; Carbamates; Spermatozoa
PubMed: 37966213
DOI: 10.1289/EHP12678 -
Molecules (Basel, Switzerland) Mar 2024Benzimidazole fungicides are a class of highly effective, low-toxicity, systemic broad-spectrum fungicides developed in the 1960s and 1970s, based on the fungicidal... (Review)
Review
Benzimidazole fungicides are a class of highly effective, low-toxicity, systemic broad-spectrum fungicides developed in the 1960s and 1970s, based on the fungicidal activity of the benzimidazole ring structure. They exhibit biological activities including anticancer, antibacterial, and antiparasitic effects. Due to their particularly outstanding antibacterial properties, they are widely used in agriculture to prevent and control various plant diseases caused by fungi. The main products of benzimidazole fungicides include benomyl, carbendazim, thiabendazole, albendazole, thiophanate, thiophanate-methyl, fuberidazole, methyl (1-{[(5-cyanopentyl)amino]carbonyl}-1-benzimidazol-2-yl) carbamate, and carbendazim salicylate. This article mainly reviews the physicochemical properties, toxicological properties, disease control efficacy, and pesticide residue and detection technologies of the aforementioned nine benzimidazole fungicides and their main metabolite (2-aminobenzimidazole). On this basis, a brief outlook on the future research directions of benzimidazole fungicides is presented.
Topics: Fungicides, Industrial; Benzimidazoles; Carbamates; Thiophanate; Anti-Bacterial Agents
PubMed: 38542855
DOI: 10.3390/molecules29061218 -
Epilepsia Mar 2021Since 1955, several alkyl-carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine,... (Comparative Study)
Comparative Study Review
Since 1955, several alkyl-carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine, carisbamate, and cenobamate. They have each enjoyed varying levels of success as antiseizure drugs; however, they have all been plagued by the emergence of serious and sometimes life-threatening adverse events. In this review, we compare and contrast their predominant molecular mechanisms of action, their antiseizure profile, and where possible, their clinical efficacy. The preclinical, clinical, and mechanistic profile of the prototypical γ-aminobutyric acidergic (GABAergic) modulator phenobarbital is included for comparison. Like phenobarbital, all of the clinically approved alkyl-carbamates share an ability to enhance inhibitory neurotransmission through modulation of the GABA receptor, although the specific mechanism of interaction differs among the different drugs discussed. In addition, several alkyl-carbamates have been shown to interact with voltage-gated ion channels. Flupirtine and retigabine share an ability to activate K currents mediated by KCNQ (Kv7) K channels, and felbamate, carisbamate, and cenobamate have been shown to block Na channels. In contrast to other alkyl-carbamates, cenobamate seems to be unique in its ability to preferentially attenuate the persistent rather than transient Na current. Results from recent randomized controlled clinical trials with cenobamate suggest that this newest antiseizure alkyl-carbamate possesses a degree of efficacy not witnessed since felbamate was approved in 1993. Given that ceno-bamate's mechanistic profile is unique among the alkyl-carbamates, it is not clear whether this impressive efficacy reflects an as yet undescribed mechanism of action or whether it possesses a unique synergy between its actions at the GABA receptor and on persistent Na currents. The high efficacy of cenobamate is, however, tempered by the risk of serious rash and low tolerability at higher doses, meaning that further safety studies and clinical experience are needed to determine the true clinical value of cenobamate.
Topics: Anticonvulsants; Carbamates; Chlorophenols; Epilepsy; Humans; Tetrazoles; Treatment Outcome
PubMed: 33580520
DOI: 10.1111/epi.16832 -
Journal of Environmental and Public... 2022Intentional ingestion of organophosphate (OP) and carbamate is a significant health issue worldwide. It causes adverse health effects on the liver. This study aimed to...
BACKGROUND
Intentional ingestion of organophosphate (OP) and carbamate is a significant health issue worldwide. It causes adverse health effects on the liver. This study aimed to determine liver transaminases (AST and ALT) and bilirubin levels to assess the severity of poisoning in patients with acute OP and carbamate poisoning.
METHODS
A descriptive cross-sectional study was conducted on patients admitted to a selected hospital in Sri Lanka with acute OP and carbamate poisoning. The severity of poisoning was measured by RBC cholinesterase and Peradeniya Organophosphorus Poisoning scale (POP), where six clinical features were assessed based on a 3-point scale. A score of 0-3 was considered mild, 4-7 to be moderate, and 8-11 to be severe poisoning. Liver parameters such as AST, ALT, and total and direct bilirubin were measured.
RESULTS
Among the 188 screened patients, 166 were recruited. Majority were males (112, 67.5%). Kruskal-Wallis test showed significant differences in AST and ALT on admission and AST on discharge, across POP groups (( (2, = 166) = 26.48, ≤ 0.001), ( (2, = 166) = 14.31, =0.001), and ( (2, = 157) = 11.34, =0.003), respectively)). Mann-Whitney test showed significantly higher AST and ALT in the moderate POP group compared to the mild POP group (AST: = 1709, = -4.50, ≤ 0.001, = 0.36; ALT: = 2114, = -3.04, =0.002, = 0.26) on admission. In addition, the treatment outcomes (duration of hospital stay and duration of ventilator assistance) were significantly correlated ( ≤ 0.001) with the severity of poisoning and serum AST and ALT at the time of admission.
CONCLUSION
AST and ALT levels on admission and AST level at discharge showed significant correlations with the severity of poisoning. Treatment outcomes significantly correlated with the severity of poisoning and serum AST and ALT levels.
Topics: Bilirubin; Carbamates; Cross-Sectional Studies; Female; Humans; Liver; Male; Organophosphates; Prospective Studies
PubMed: 35755887
DOI: 10.1155/2022/7826396 -
Medicina (Kaunas, Lithuania) Jul 2023Cenobamate (CNB), ([(R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl], is a novel tetrazole alkyl carbamate derivative. In November 2019, the Food and Drug... (Review)
Review
Cenobamate (CNB), ([(R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl], is a novel tetrazole alkyl carbamate derivative. In November 2019, the Food and Drug Administration approved Xcopri, marketed by SK Life Science Inc., (Paramus, NJ, USA) for adult focal seizures. The European Medicines Agency approved Ontozry by Arvelle Therapeutics Netherlands B.V.(Amsterdam, The Neatherlands) in March 2021. Cenobamate is a medication that could potentially change the perspectives regarding the management and prognosis of refractory epilepsy. In this way, this study aims to review the literature on CNB's pharmacological properties, pharmacokinetics, efficacy, and safety. CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure freedom. This finding is remarkable in the antiseizure medication literature. The mechanism of action of CNB is still poorly understood, but it is associated with transient and persistent sodium currents and GABAergic neurotransmission. In animal studies, CNB showed sustained efficacy and potency in the 6 Hz test regardless of the stimulus intensity. CNB was revealed to be the most cost-effective drug among different third-generation antiseizure medications. Also, CNB could have neuroprotective effects. However, there are still concerns regarding its potential for abuse and suicidality risk, which future studies should clearly assess, after which protocols should be changed. The major drawback of CNB therapy is the slow and complex titration and maintenance phases preventing the wide use of this new agent in clinical practice.
Topics: United States; Animals; Drug Resistant Epilepsy; Carbamates; Chlorophenols; Tetrazoles; Seizures
PubMed: 37629678
DOI: 10.3390/medicina59081389 -
The Israel Medical Association Journal... Nov 2008Organophosphate and carbamate are mainly used to kill insects, thereby protecting livestock, crops, homes and communities. Yet, these compounds also convey great danger.... (Review)
Review
Organophosphate and carbamate are mainly used to kill insects, thereby protecting livestock, crops, homes and communities. Yet, these compounds also convey great danger. OP and CRB poisoning is an important clinical problem, often life-threatening, especially in the pediatric population in rural areas where reaching a physician or hospital on time is difficult. We present a summary of accumulated toxicological knowledge as well as clinical and laboratory experience from a medical center serving a relatively vast rural area and pediatric population. We stress the importance of knowing how to recognize the classic signs of OP and CRB poisoning and when it is appropriate to investigate for such poisoning even in the absence of those signs. Like any medical emergency, OP and CRB poisoning requires prompt resuscitation and use of antidotes. Atropine, oxygen and fluids are the mainstay of therapy. Oximes, which were found useful in some cases of OP poisoning and useless in some cases of CRB poisoning, are absolutely safe as empiric treatment, which is often needed since the major differential diagnosis of OP poisoning is CRB poisoning, which is clinically indistinguishable. We hope that continuing research will offer further insights into the management of such events, and we are confident that improved medical management of OP and CRB poisoning will result in a reduction of morbidity and other complications associated with intensive care procedures and hospitalization.
Topics: Atropine; Carbamates; Humans; Israel; Muscarinic Antagonists; Organophosphate Poisoning; Poisoning; Treatment Outcome
PubMed: 19070283
DOI: No ID Found