Carbamates and ICH M7 classification: Making use of expert knowledge.

PubMed

Hemingway, Rachel; Fowkes, Adrian; Williams, Richard V

2017-06-01

Carbamates are widely used in the chemical industry so understanding their toxicity is important to safety assessment. Carbamates have been associated with certain toxicities resulting in publication of structural alerts, including alerts for mutagenicity. Structural alerts for bacterial mutagenicity can be used in combination with statistical systems to enable ICH M7 classification, which allows assessment of the genotoxic risk posed by pharmaceutical impurities. This study tested a hypothetical bacterial mutagenicity alert for carbamates and examined the impact it would have on ICH M7 classifications using (Q)SAR predictions from the expert rule-based system Derek Nexus and the statistical-based system Sarah Nexus. Public datasets have a low prevalence of mutagenic carbamates, which highlighted that systems containing an alert for carbamates perform poorly for achieving correct ICH M7 classifications. Carbamates are commonly used as protecting groups and proprietary datasets containing such compounds were also found to have a low prevalence of mutagenic compounds. Expert review of the mutagenic compounds established that mutagenicity was often only observed under certain (non-standard) conditions and more generally that the Ames test may be a poor predictor for the risk of carcinogenicity posed by chemicals in this class. Overall a structural alert for the in vitro bacterial mutagenesis of carbamates does not benefit workflows for assigning ICH M7 classification to impurities. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.

EPA Science Inventory

The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans ra...

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

Code of Federal Regulations, 2010 CFR

2010-07-01

... derivative. 721.2025 Section 721.2025 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under this...

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

Code of Federal Regulations, 2011 CFR

2011-07-01

... derivative. 721.2025 Section 721.2025 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under this...

DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PESTICIDES

EPA Science Inventory

The US EPAs N-Methyl Carbamate Cumulative Risk Assessment (NMCRA) assesses the effect on acetylcholine esterase (AChE) activity of exposure to 10 N-methyl carbamate (NMC) pesticides through dietary, drinking water, and residential exposures.

Time-course, dose-response, and age comparative sensitivity of N-methyl carbamates in rats

EPA Science Inventory

N-Methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterease (ChE). Despite their widespread use, there are few studies of neurotoxicity in young animals. To study potential age-related differences, we evaluated seven carbamates (carba...

Discovery of Highly Selective and Nanomolar Carbamate-Based Butyrylcholinesterase Inhibitors by Rational Investigation into Their Inhibition Mode.

PubMed

Sawatzky, Edgar; Wehle, Sarah; Kling, Beata; Wendrich, Jan; Bringmann, Gerhard; Sotriffer, Christoph A; Heilmann, Jörg; Decker, Michael

2016-03-10

Butyrylcholinesterase (BChE) is a promising target for the treatment of later stage cognitive decline in Alzheimer's disease. A set of pseudo-irreversible BChE inhibitors with high selectivity over hAChE was synthesized based on carbamates attached to tetrahydroquinazoline scaffolds with the 2-thiophenyl compound 2p as the most potent inhibitor of eqBChE (KC = 14.3 nM) and also of hBChE (KC = 19.7 nM). The inhibitors transfer the carbamate moiety onto the active site under release of the phenolic tetrahydroquinazoline scaffolds that themselves act as neuroprotectants. By combination of kinetic data with molecular docking studies, a plausible binding model was probed describing how the tetrahydroquinazoline scaffold guides the carbamate into a close position to the active site. The model explains the influence of the carrier scaffold onto the affinity of an inhibitor just before carbamate transfer. This strategy can be used to utilize the binding mode of other carbamate-based inhibitors.

High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka - implications for global suicide prevention.

PubMed

Lamb, Thomas; Selvarajah, Liza R; Mohamed, Fahim; Jayamanne, Shaluka; Gawarammana, Indika; Mostafa, Ahmed; Buckley, Nicholas A; Roberts, Michael S; Eddleston, Michael

2016-09-01

Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452-1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.

A DOSE-RESPONSE STUDY OF THE TOXICITY OF A MIXTURE OF 7N-METHYL CARBAMATE PESTICIDES IN ADULT, MALE RATS.

EPA Science Inventory

There is scarce knowledge regarding the toxicity of pesticide mixtures, especially mixtures of the anticholinesterase N-methyl carbamates. A mixture study was conducted using 7 N-methyl carbamates (carbaryl, carbofuran, formetanate HCl, methiocarb, methomyl, oxamyl, and propoxur...

Low Catalyst Loadings in Olefin Metathesis: Synthesis of Nitrogen Heterocycles by Ring Closing Metathesis

PubMed Central

Kuhn, Kevin M.; Champagne, Timothy M.; Hong, Soon Hyeok; Wei, Wen-Hao; Nickel, Andrew; Lee, Choon Woo; Virgil, Scott C.; Grubbs, Robert H.; Pederson, Richard L.

2010-01-01

(eq 1) A series of ruthenium catalysts have been screened under ring closing metathesis (RCM) conditions to produce five-, six-, and seven-membered carbamate-protected cyclic amines. Many of these catalysts demonstrated excellent RCM activity and yields with as low as 500 ppm catalyst loadings. RCM of the five-membered carbamate-series could be run neat, the six-membered carbamate-series could be run at 1.0 M concentrations and the seven-membered carbamate-series worked best at 0.2 M to 0.05 M concentrations. PMID:20141172

Can Carbamates Undergo Radical Oxidation in the Soil Environment? A Case Study on Carbaryl and Carbofuran.

PubMed

Ćwieląg-Piasecka, Irmina; Witwicki, Maciej; Jerzykiewicz, Maria; Jezierska, Julia

2017-12-19

Radical oxidation of carbamate insecticides, namely carbaryl and carbofuran, was investigated with spectroscopic (electron paramagnetic resonance [EPR] and UV-vis) and theoretical (density functional theory [DFT] and ab initio orbital-optimized spin-component scaled MP2 [OO-SCS-MP2]) methods. The two carbamates were subjected to reaction with • OH, persistent DPPH • and galvinoxyl radical, as well as indigenous radicals of humic acids. The influence of fulvic acids on carbamate oxidation was also tested. The results obtained with EPR and UV-vis spectroscopy indicate that carbamates can undergo direct reactions with various radical species, oxidizing themselves into radicals in the process. Hence, they are prone to participate in the prolongation step of the radical chain reactions occurring in the soil environment. Theoretical calculations revealed that from the thermodynamic point of view hydrogen atom transfer is the preferred mechanism in the reactions of the two carbamates with the radicals. The activity of carbofuran was determined experimentally (using pseudo-first-order kinetics) and theoretically to be noticeably higher in comparison with carbaryl and comparable with gallic acid. The findings of this study suggest that the radicals present in soil can play an important role in natural remediation mechanisms of carbamates.

(BOSC) DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PRESTICIDES

EPA Science Inventory

THE US EPA'S N-METHYL CARBAMATE CUMULATIVE RISK ASSESSMENT (NMCRA) ASSESSES THE EFFECT ON ACETYLCHOLINE ESTERASE (AChE) ACTIVITY OF EXPOSURE TO 10 N-METHLY CARBAMATE (NMC)PESTICIDES THROUGH DIETARY, DRINKING WATER, AND RESIDENTIAL EXPOSURES. THESE DATA THUS INFORM, BUT DO NOT COM...

Benzimidazole Carbamate Residues in Milk: Detection by SPR Biosensor; using a Modified QuEChERS Method for Extraction

USDA-ARS?s Scientific Manuscript database

A surface plasmon resonance (SPR) biosensor screening assay was developed and validated to detect 11 benzimidazole carbamate (BZT) veterinary drug residues in milk. The polyclonal antibody used was raised in sheep against a methyl 5 (6)-[(carboxypentyl)-thio]-2-benzimidazole carbamate protein conjug...

Anticholinesterase activity of potential therapeutic 5-(1,3,3-trimethylindolinyl) carbamates. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lieske, C.N.; Gepp, R.T.; Clark, J.H.

1991-12-31

Six N-alkyl and N-aryl 5-(1,3,3-trimethylindolinyl) carbamates were synthesized and studied for their structure-activity relationships in inhibiting eel acetylcholinesterase (AChE). The carbamates were 5-(1,3,3,trimethylindolinyl) N,N-dimethylcarbamate (Cui Xing Ning) (I), 5-(1,3,3-trimethylindolinyl) N-methylcarbamate (II), 5-(1,3,3-trimethylindolinyl) N-ethylcarbamate (III), 5-(1,3,3-trimethylindolinyl) N,Ndiethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl) N-heptylcarbamate (V), and 5-(1,3,3-trimethylindolinyl) N-(3-cholorophenyl)carbamate (VI). The inhibition studies were carried out at 25.0 deg C at pH 7.60. The rank order of the ki values for eel AChE inhibition is 11 > V > I > Ill > Vi > IV. Compound 11 has a greater affinity for the enzyme than any irreversible inhibitor cited in the literature (Kd = 7.14more » x 10(-8)M). Our findings should aid in the application of these carbamates (1) for counteracting the cholinergic problems associated with various diseases,and (2) for developing potential pretreatment compounds for organophosphate poisoning. Acetylcholinesterase, carbamates, inhibition« less

O-Phenyl Carbamate and Phenyl Urea Thiiranes as Selective Matrix Metalloproteinase-2 Inhibitors that Cross the Blood-Brain Barrier

PubMed Central

Gooyit, Major; Song, Wei; Mahasenan, Kiran V.; Lichtenwalter, Katerina; Suckow, Mark A.; Schroeder, Valerie A.; Wolter, William R.; Mobashery, Shahriar; Chang, Mayland

2013-01-01

Brain metastasis occurs in 20% to 40% of cancer patients. Treatment is mostly palliative and the inability of most drugs to penetrate the brain presents one of the greatest challenges in the development of therapeutics for brain metastasis. Matrix metalloproteinase-2 (MMP-2) plays important roles in invasion and vascularization of the central nervous system and represents a potential target for treatment of brain metastasis. Carbonate, O-phenyl carbamate, urea, and N-phenyl carbamate derivatives of SB-3CT, a selective and potent gelatinase inhibitor were synthesized and evaluated. The O-phenyl carbamate and urea variants were selective and potent inhibitors of MMP-2. Carbamate 5b was metabolized to the potent gelatinase inhibitor 2, which was present at therapeutic concentrations in the brain. In contrast, phenyl urea 6b crossed the blood-brain barrier, however higher doses would result in therapeutic brain concentrations. Carbamate 5b and urea 6b show potential for intervention of MMP-2-dependent diseases, such as brain metastasis. PMID:24028490

New pyridine derivatives as inhibitors of acetylcholinesterase and amyloid aggregation.

PubMed

Pandolfi, Fabiana; De Vita, Daniela; Bortolami, Martina; Coluccia, Antonio; Di Santo, Roberto; Costi, Roberta; Andrisano, Vincenza; Alabiso, Francesco; Bergamini, Christian; Fato, Romana; Bartolini, Manuela; Scipione, Luigi

2017-12-01

A new series of pyridine derivatives with carbamic or amidic function has been designed and synthesized to act as cholinesterase inhibitors. The synthesized compounds were tested toward EeAChE and hAChE and toward eqBChE and hBChE. The carbamate 8 was the most potent hAChE inhibitor (IC 50  = 0.153 ± 0.016 μM) while the carbamate 11 was the most potent inhibitor of hBChE (IC 50  = 0.828 ± 0.067 μM). A molecular docking study indicated that the carbamate 8 was able to bind AChE by interacting with both CAS and PAS, in agreement with the mixed inhibition mechanism. Furthermore, the carbamates 8, 9 and 11 were able to inhibit Aβ 42 self-aggregation and possessed quite low toxicity against human astrocytoma T67 and HeLa cell lines, being the carbamate 8 the less toxic compound on both cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Copper(II) catalysis in cyanide conversion into ethyl carbamate in spirits and relevant reactions.

PubMed

Aresta, M; Boscolo, M; Franco, D W

2001-06-01

The role of copper(II) species in the oxidation of inorganic cyanide to cyanate and in the conversion of cyanate or urea into ethyl carbamate was investigated. The oxidation process has been shown to be independent from the dissolved oxygen. Elemental analysis and infrared spectroscopy have shown the formation of a mixed copper carbonate/hydroxide in the process of oxidation of cyanide to cyanate in water/ethanol. The complexation to Cu(II) of cyanate formed upon cyanide oxidation makes the former more susceptible to nucleophilic attack from ethanol, with conversion into ethyl carbamate. Comparatively, urea has a minor role with respect to cyanide in the formation of ethyl carbamate. Therefore, the urea present in some samples of Brazilian sugar cane spirit (cachaça) has been shown to have almost no influence on the ethyl carbamate content of cachaças, which comes essentially from cyanide. Fe(II,III) affords results similar to those found with Cu(II). Some suggestions are presented to avoid ethyl carbamate formation in spirits during distillation.

Quantitative estimation of cholinesterase-specific drug metabolism of carbamate inhibitors provided by the analysis of the area under the inhibition-time curve.

PubMed

Zhou, Huimin; Xiao, Qiaoling; Tan, Wen; Zhan, Yiyi; Pistolozzi, Marco

2017-09-10

Several molecules containing carbamate groups are metabolized by cholinesterases. This metabolism includes a time-dependent catalytic step which temporary inhibits the enzymes. In this paper we demonstrate that the analysis of the area under the inhibition versus time curve (AUIC) can be used to obtain a quantitative estimation of the amount of carbamate metabolized by the enzyme. (R)-bambuterol monocarbamate and plasma butyrylcholinesterase were used as model carbamate-cholinesterase system. The inhibition of different concentrations of the enzyme was monitored for 5h upon incubation with different concentrations of carbamate and the resulting AUICs were analyzed. The amount of carbamate metabolized could be estimated with <15% accuracy (RE%) and ≤23% precision (RSD%). Since the knowledge of the inhibition kinetics is not required for the analysis, this approach could be used to determine the amount of drug metabolized by cholinesterases in a selected compartment in which the cholinesterase is confined (e.g. in vitro solutions, tissues or body fluids), either in vitro or in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka – implications for global suicide prevention

PubMed Central

Lamb, Thomas; Selvarajah, Liza R.; Mohamed, Fahim; Jayamanne, Shaluka; Gawarammana, Indika; Mostafa, Ahmed; Buckley, Nicholas A.; Roberts, Michael S.; Eddleston, Michael

2016-01-01

Abstract Background: Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. Methods: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. Findings: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0–9.8); fenobucarb 6.3%, OR 3.0 (1.2–7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9–8.3); fenobucarb 18.9%, OR 3.6 (2.1–6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5–67.3), carbosulfan 21.3 h (11.5–71.3), and fenobucarb 25.3 h (17.3–72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5–118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. Conclusions: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452–1459; QJM 2006, 99:513–522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates. PMID:27252029

Chemistry and Chemical Equilibrium Dynamics of BMAA and Its Carbamate Adducts

PubMed Central

Diaz-parga, Pedro

2018-01-01

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. PMID:28921378

Chemistry and Chemical Equilibrium Dynamics of BMAA and Its Carbamate Adducts.

PubMed

Diaz-Parga, Pedro; Goto, Joy J; Krishnan, V V

2018-01-01

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.

A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs

NASA Astrophysics Data System (ADS)

Lee, Sehan; Barron, Mace G.

2016-04-01

Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π-π interaction with Trp86 is necessary for strong inhibition of AChE. Our combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency.

Distribution and function of carbamate hydrolase genes cehA and mcd in soils: the distinct role of soil pH.

PubMed

Rousidou, Constantina; Karaiskos, Dionysis; Myti, Despoina; Karanasios, Evangelos; Karas, Panagiotis A; Tourna, Maria; Tzortzakakis, Emmanuel A; Karpouzas, Dimitrios G

2017-01-01

Synthetic carbamates constitute a significant pesticide group with oxamyl being a leading compound in the nematicide market. Oxamyl degradation in soil is mainly microbially mediated. However, the distribution and function of carbamate hydrolase genes (cehA, mcd, cahA) associated with the soil biodegradation of carbamates is not yet clear. We studied oxamyl degradation in 16 soils from a potato monoculture area in Greece where oxamyl is regularly used. Oxamyl showed low persistence (DT50 2.4-26.7 days). q-PCR detected the cehA and mcd genes in 10 and three soils, respectively. The abundance of the cehA gene was positively correlated with pH, while both cehA abundance and pH were negatively correlated with oxamyl DT50. Amongst the carbamates used in the study region, oxamyl stimulated the abundance and expression only of the cehA gene, while carbofuran stimulated the abundance and expression of both genes. The cehA gene was also detected in pristine soils upon repeated treatments with oxamyl and carbofuran and only in soils with pH ≥7.2, where the most rapid degradation of oxamyl was observed. These results have major implications regarding the maintenance of carbamate hydrolase genes in soils, have practical implications regarding the agricultural use of carbamates, and provide insights into the evolution of cehA. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Development of Optimized Guidelines for Therapeutic Strategies for Organophosphate Poisoning

DTIC Science & Technology

2011-03-01

compounds (Cannard, 2006). Pyridostigmine bromide , a pretreatment for a potential soman exposure, is a member of the carbamate family (Cannard, 2006...others, 2005) and later expanded that model to incorporate the nerve agent pretreatment by carbamates such as pyridostigmine (Worek and others, 2007...model developed in 2005 to incorporate pretreatment by a carbamate such as pyridostigmine (Worek and others, 2007). Both sets of researchers show

40 CFR 180.254 - Carbofuran; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... than 5 ppm are carbamates) 25 12/31/09 Corn, sweet, kernel plus cob with husks removed (of which no... (of which no more than 1 ppm is carbamates) 2 12/31/09 Coffee, bean, green 0.1 12/31/09 Corn, field, forage (of which no more than 5 ppm are carbamates) 25 12/31/09 Corn, field, grain (of which no more than...

40 CFR 180.254 - Carbofuran; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... than 5 ppm are carbamates) 25 12/31/09 Corn, sweet, kernel plus cob with husks removed (of which no... (of which no more than 1 ppm is carbamates) 2 12/31/09 Coffee, bean, green 0.1 12/31/09 Corn, field, forage (of which no more than 5 ppm are carbamates) 25 12/31/09 Corn, field, grain (of which no more than...

40 CFR 180.254 - Carbofuran; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... than 5 ppm are carbamates) 25 12/31/09 Corn, sweet, kernel plus cob with husks removed (of which no... (of which no more than 1 ppm is carbamates) 2 12/31/09 Coffee, bean, green 0.1 12/31/09 Corn, field, forage (of which no more than 5 ppm are carbamates) 25 12/31/09 Corn, field, grain (of which no more than...

40 CFR 180.254 - Carbofuran; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... than 5 ppm are carbamates) 25 12/31/09 Corn, sweet, kernel plus cob with husks removed (of which no... (of which no more than 1 ppm is carbamates) 2 12/31/09 Coffee, bean, green 0.1 12/31/09 Corn, field, forage (of which no more than 5 ppm are carbamates) 25 12/31/09 Corn, field, grain (of which no more than...

Neuropsychological Functioning in Gulf War Veterans Exposed to Pesticides and Pyridostigmine Bromide

DTIC Science & Technology

2008-08-01

agents. Two subsets of these chemicals, organophosphates (OP) and carbamates , are known to produce chronic neurological symptoms with sufficient exposure ...e.g., organophosphates , carbamates ) on brain functioning and found different cognitive patterns with these exposures . For example, studies of...Krengel, Ph.D. & K. Sullivan, Ph.D. 52 more restricted organophosphate and carbamate pesticides products followed second in terms of increased exposures in

A Mechanism-based 3D-QSAR Approach for Classification ...

EPA Pesticide Factsheets

Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π–π interaction with Trp86

Design and Comparative Evaluation of the Anticonvulsant Profile, Carbonic-Anhydrate Inhibition and Teratogenicity of Novel Carbamate Derivatives of Branched Aliphatic Carboxylic Acids with 4-Aminobenzensulfonamide.

PubMed

Bibi, David; Mawasi, Hafiz; Nocentini, Alessio; Supuran, Claudiu T; Wlodarczyk, Bogdan; Finnell, Richard H; Bialer, Meir

2017-07-01

Epilepsy is one of the most common neurological diseases, with between 34 and 76 per 100,000 people developing epilepsy annually. Epilepsy therapy for the past 100 + years is based on the use of antiepileptic drugs (AEDs). Despite the availability of more than twenty old and new AEDs, approximately 30% of patients with epilepsy are not seizure-free with the existing medications. In addition, the clinical use of the existing AEDs is restricted by their side-effects, including the teratogenicity associated with valproic acid that restricts its use in women of child-bearing age. Thus, there is an unmet clinical need to develop new, effective AEDs. In the present study, a novel class of carbamates incorporating phenethyl or branched aliphatic chains with 6-9 carbons in their side-chain, and 4-benzenesulfonamide-carbamate moieties were synthesized and evaluated for their anticonvulsant activity, teratogenicity and carbonic anhydrase (CA) inhibition. Three of the ten newly synthesized carbamates showed anticonvulsant activity in the maximal-electroshock (MES) and 6 Hz tests in rodents. In mice, 3-methyl-2-propylpentyl(4-sulfamoylphenyl)carbamate(1), 3-methyl-pentan-2-yl-(4-sulfamoylphenyl)carbamate (9) and 3-methylpentyl, (4-sulfamoylphenyl)carbamate (10) had ED 50 values of 136, 31 and 14 mg/kg (MES) and 74, 53, and 80 mg/kg (6 Hz), respectively. Compound (10) had rat-MES-ED 50  = 13 mg/kg and ED 50 of 59 mg/kg at the mouse-corneal-kindling test. These potent carbamates (1,9,10) induced neural tube defects only at doses markedly exceeding their anticonvuslnat-ED 50 values. None of these compounds were potent inhibitors of CA IV, but inhibited CA isoforms I, II and VII. The anticonvulsant properties of these compounds and particularly compound 10 make them potential candidates for further evaluation and development as new AEDs.

Methyl N-phenyl carbamate synthesis from aniline and methyl formate: carbon recycling to chemical products.

PubMed

Yalfani, Mohammad S; Lolli, Giulio; Müller, Thomas E; Wolf, Aurel; Mleczko, Leslaw

2015-02-01

Methyl N-phenyl carbamate was synthesized from aniline by using methyl formate as a green and efficient carbonylating agent. High yields were obtained at milder reaction conditions compared to the conventional CO/CH3 OH route. Studies on the reaction sequence led to suggest an alternative and more efficient route to the carbamate via formanilide as intermediate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sunlight-Driven Forging of Amide/Ester Bonds from Three Independent Components: An Approach to Carbamates.

PubMed

Zhao, Yating; Huang, Binbin; Yang, Chao; Chen, Qingqing; Xia, Wujiong

2016-11-04

A photoredox catalytic route to carbamates enabled by visible irradiation (or simply sunlight) has been developed. This process leads to a novel approach to the construction of heterocyclic rings wherein the amide or ester motifs of carbamates were assembled from three isolated components. Large-scale experiments were realized by employing continuous flow techniques, and reuse of photocatalyst demonstrated the green and sustainable aspects of this method.

Synergism studies with binary mixtures of pyrethroid, carbamate and organophosphate insecticides on Frankliniella occidentalis (Pergande).

PubMed

Bielza, Pablo; Espinosa, Pedro J; Quinto, Vicente; Abellán, Jaime; Contreras, Josefina

2007-01-01

The major mechanism of resistance to most insecticides in Frankliniella occidentalis (Pergande) is metabolic, piperonyl butoxide (PBO) suppressible, mediated by cytochrome-P450 monooxygenases and conferring cross-resistance among insecticide classes. The efficacy of insecticide mixtures of acrinathrin, methiocarb, formetanate and chlorpyrifos was studied by topical exposure in strains of F. occidentalis selected for resistance to each insecticide. The method consisted in combining increasing concentrations of one insecticide with a constant low rate of the second one as synergist. Acrinathrin activity against F. occidentalis was enhanced by carbamate insecticides, methiocarb being a much better synergist than formetanate. Monooxygenase action on the carbamates would prevent degradation of the pyrethroid, hence providing a level of synergism by competitive substrate inhibition. However, the number of insecticides registered for control of F. occidentalis is very limited, and they are needed for antiresistance strategies such as mosaics and rotations. Therefore, a study was made of the synergist effect of other carbamates not used against thrips, such as carbofuran and carbosulfan, against a susceptible strain and a field strain. Neither carbamate showed synergism to acrinathrin in the susceptible strain, but both did in the field strain, carbosulfan being a better synergist than carbofuran. The data obtained indicate that low rates of carbamates could be used as synergists to restore some pyrethroid susceptibility in F. occidentalis. Copyright (c) 2006 Society of Chemical Industry.

A new method to characterize the kinetics of cholinesterases inhibited by carbamates.

PubMed

Xiao, Qiaoling; Zhou, Huimin; Wei, Hong; Du, Huaqiao; Tan, Wen; Zhan, Yiyi; Pistolozzi, Marco

2017-09-10

The inhibition of cholinesterases (ChEs) by carbamates includes a carbamylation (inhibition) step, in which the drug transfers its carbamate moiety to the active site of the enzyme and a decarbamylation (activity recovery) step, in which the carbamyl group is hydrolyzed from the enzyme. The carbamylation and decarbamylation kinetics decide the extent and the duration of the inhibition, thus the full characterization of candidate carbamate inhibitors requires the measurement of the kinetic constants describing both steps. Carbamylation and decarbamylation rate constants are traditionally measured by two separate set of experiments, thus making the full characterization of candidate inhibitors time-consuming. In this communication we show that by the analysis of the area under the inhibition-time curve of cholinesterases inhibited by carbamates it is possible to calculate the decarbamylation rate constant from the same data traditionally used to characterize only the carbamylation kinetics, therefore it is possible to obtain a full characterization of the inhibition with a single set of experiments. The characterization of the inhibition kinetics of human and dog plasma butyrylcholinesterase and of human acetylcholinesterase by bambuterol and bambuterol monocarbamate enantiomers was used to demonstrate the validity of the approach. The results showed that the proposed method provides reliable estimations of carbamylation and decarbamylation rate constants thus representing a simple and useful approach to reduce the time required for the characterization of carbamate inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis.

PubMed

Xie, Qiong; Zheng, Zhaoxi; Shao, Biyun; Fu, Wei; Xia, Zheng; Li, Wei; Sun, Jian; Zheng, Wei; Zhang, Weiwei; Sheng, Wei; Zhang, Qihong; Chen, Hongzhuan; Wang, Hao; Qiu, Zhuibai

2017-12-01

Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer's disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (-)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC 50 31.6 nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-β (Aβ) lowering effects (51.9% decrease of Aβ 42 ) superior to phenserine (31% decrease of total Aβ) in SH-SY5Y-APP 695 cells at 50 µM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents.

Suzuki–Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

PubMed Central

Quasdorf, Kyle W.; Antoft-Finch, Aurora; Liu, Peng; Silberstein, Amanda L.; Komaromi, Anna; Blackburn, Tom; Ramgren, Stephen D.; Houk, K. N.; Snieckus, Victor; Garg, Neil K.

2011-01-01

The first Suzuki–Miyaura cross-coupling reactions of the synthetically versatile O-aryl carbamate and O-sulfamate groups is described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups (EDGs, EWGs) are tolerated, in addition to those that possess ortho substitutents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative additions with carbamates and sulfamates occur via a five-centered transition state, resulting in the exclusive cleavage of the Ar–O bond. Water is found to stabilize the Ni–carbamate catalyst resting state, and thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest. PMID:21456551

Organophosphorus and carbamate pesticides

USGS Publications Warehouse

Glaser, L.C.

1999-01-01

The insecticidal properties of organophosphorus (OP) and carbamate compounds were first discovered in the 1930s, and the compounds were developed for pesticide use in the 1940s. They have been used increasingly since the 1970s when environmentally persistent organochlorine pesticides, such as DDT and dieldrin, were banned for use in the United States. Organophosphorus and carbamate pesticides are generally short-lived in the environment (usually lasting only days to months instead of years) and, generally, chemical breakdown is accelerated as temperatures or pH or both increase.

40 CFR 156.206 - General statements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (i.e., an organophosphorus ester that inhibits cholinesterase) or an N-methyl carbamate (i.e., an N-methyl carbamic acid ester that inhibits cholinesterase), the label shall so state. The statement shall...

40 CFR 156.206 - General statements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (i.e., an organophosphorus ester that inhibits cholinesterase) or an N-methyl carbamate (i.e., an N-methyl carbamic acid ester that inhibits cholinesterase), the label shall so state. The statement shall...

40 CFR 156.206 - General statements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (i.e., an organophosphorus ester that inhibits cholinesterase) or an N-methyl carbamate (i.e., an N-methyl carbamic acid ester that inhibits cholinesterase), the label shall so state. The statement shall...

40 CFR 156.206 - General statements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (i.e., an organophosphorus ester that inhibits cholinesterase) or an N-methyl carbamate (i.e., an N-methyl carbamic acid ester that inhibits cholinesterase), the label shall so state. The statement shall...

Ethyl carbamate levels in wine and spirits from markets in Hebei Province, China.

PubMed

Liu, Y P; Dong, B; Qin, Z S; Yang, N J; Lu, Y; Yang, L X; Chang, F Q; Wu, Y N

2011-01-01

Ethyl carbamate (EC) in wine, grain spirits and wine sauce (145 samples) was analysed using solid-phase extraction and stable isotope dilution GC/MS. Samples were obtained from markets in eight areas (Shijiazhuang, Baoding, Handan, Qinhuangdao, Langfang, Zhangjiakou, Xingtai and Cangzhou) of Hebei Province, China. The method had a limit of detection of 2 µg kg⁻¹, with recoveries varying from 95.7 to 102% and RSD ranging 2.3-5.6%. The average concentrations of ethyl carbamate in wines, grain spirits and wine sauce were 14.7 (<2.0-44.5) µg kg⁻¹, 33.8 (2.9-129) µg kg⁻¹ and 8.7 (<2.0-63.3) µg kg⁻¹, respectively. The results led to the development of limit standards that can be used to predict the concentration of ethyl carbamate in Chinese fermented wines.

Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates.

PubMed

Krátký, Martin; Štěpánková, Šárka; Vorčáková, Katarína; Švarcová, Markéta; Vinšová, Jarmila

2016-02-11

Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thio)carbamates were investigated using Ellman's method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 µM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thio)carbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)-phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenyl)carbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 µM), while 2-(phenylcarbamoyl)phenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 µM). Results from molecular docking studies suggest that carbamate compounds, especially N,N-diphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization.

[Direct determination of ethyl carbamate in Chinese rice wine and grape wine by ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry].

PubMed

Wang, Lijuan; Ke, Runhui; Wang, Bing; Yin, Jianjun; Song, Quanhou

2012-09-01

An ultra performance liquid chromatography-electrospray ionization tandem mass spectrometric (UPLC-ESI-MS/MS) method was established for the direct determination of ethyl carbamate in Chinese rice wine and grape wine. The Chinese rice wine and grape wine samples were diluted with distilled water, filtered through 0. 22 microm microporous membrane. The LC separation was performed on a Waters Acquity UPLC system with a BEH C18 column, acetonitrile and 0. 1% (v/v) acetic acid aqueous solution as the mobile phase. The ethyl carbamate was determined in the mode of electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM). The butyl carbamate (BC) was used as the internal standard for the quantitative determination. The calibration curve showed good linearity in the range of 2 - 500 microg/L with the correlation coefficient greater than 0.995. The limit of detection (LOD) was 1.7 microg/L and the limit of quantification (LOQ) was 5.0 microg/L. The recoveries of the ethyl carbamate in Chinese rice wine and grape wine was in the range of 90% - 102%. The relative standard deviations (RSDs) of intra-day and inter-day determinations were 0. 8% - 4.5% and 1.4% - 5.6% (n = 6). The results indicated that the proposed method is easy, fast, sensitive, and suitable for the determination of ethyl carbamate in Chinese rice wine and grape wine.

Protonation switching to the least-basic heteroatom of carbamate through cationic hydrogen bonding promotes the formation of isocyanate cations.

PubMed

Kurouchi, Hiroaki; Sumita, Akinari; Otani, Yuko; Ohwada, Tomohiko

2014-07-07

We found that phenethylcarbamates that bear ortho-salicylate as an ether group (carbamoyl salicylates) dramatically accelerate OC bond dissociation in strong acid to facilitate generation of isocyanate cation (N-protonated isocyanates), which undergo subsequent intramolecular aromatic electrophilic cyclization to give dihydroisoquinolones. To generate isocyanate cations from carbamates in acidic media as electrophiles for aromatic substitution, protonation at the ether oxygen, the least basic heteroatom, is essential to promote CO bond cleavage. However, the carbonyl oxygen of carbamates, the most basic site, is protonated exclusively in strong acids. We found that the protonation site can be shifted to an alternative basic atom by linking methyl salicylate to the ether oxygen of carbamate. The methyl ester oxygen ortho to the phenolic (ether) oxygen of salicylate is as basic as the carbamate carbonyl oxygen, and we found that monoprotonation at the methyl ester oxygen in strong acid resulted in the formation of an intramolecular cationic hydrogen bond (>CO(+) H⋅⋅⋅O<) with the phenolic ether oxygen. This facilitates OC bond dissociation of phenethylcarbamates, thereby promoting isocyanate cation formation. In contrast, superacid-mediated diprotonation at the methyl ester oxygen of the salicylate and the carbonyl oxygen of the carbamate afforded a rather stable dication, which did not readily undergo CO bond dissociation. This is an unprecedented and unknown case in which the monocation has greater reactivity than the dication. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of a Photoredox Catalyst that Enables the Direct Synthesis of Carbamate-Protected Primary Amines via Photoinduced, Copper-Catalyzed N-Alkylation Reactions of Unactivated Secondary Halides.

PubMed

Ahn, Jun Myun; Peters, Jonas C; Fu, Gregory C

2017-12-13

Despite the long history of S N 2 reactions between nitrogen nucleophiles and alkyl electrophiles, many such substitution reactions remain out of reach. In recent years, efforts to develop transition-metal catalysts to address this deficiency have begun to emerge. In this report, we address the challenge of coupling a carbamate nucleophile with an unactivated secondary alkyl electrophile to generate a substituted carbamate, a process that has not been achieved effectively in the absence of a catalyst; the product carbamates can serve as useful intermediates in organic synthesis as well as bioactive compounds in their own right. Through the design and synthesis of a new copper-based photoredox catalyst, bearing a tridentate carbazolide/bisphosphine ligand, that can be activated upon irradiation by blue-LED lamps, we can achieve the coupling of a range of primary carbamates with unactivated secondary alkyl bromides at room temperature. Our mechanistic observations are consistent with the new copper complex serving its intended role as a photoredox catalyst, working in conjunction with a second copper complex that mediates C-N bond formation in an out-of-cage process.

Tandem mass spectrometry measurement of the collision products of carbamate anions derived from CO2 capture sorbents: paving the way for accurate quantitation.

PubMed

Jackson, Phil; Fisher, Keith J; Attalla, Moetaz Ibrahim

2011-08-01

The reaction between CO(2) and aqueous amines to produce a charged carbamate product plays a crucial role in post-combustion capture chemistry when primary and secondary amines are used. In this paper, we report the low energy negative-ion CID results for several anionic carbamates derived from primary and secondary amines commonly used as post-combustion capture solvents. The study was performed using the modern equivalent of a triple quadrupole instrument equipped with a T-wave collision cell. Deuterium labeling of 2-aminoethanol (1,1,2,2,-d(4)-2-aminoethanol) and computations at the M06-2X/6-311++G(d,p) level were used to confirm the identity of the fragmentation products for 2-hydroxyethylcarbamate (derived from 2-aminoethanol), in particular the ions CN(-), NCO(-) and facile neutral losses of CO(2) and water; there is precedent for the latter in condensed phase isocyanate chemistry. The fragmentations of 2-hydroxyethylcarbamate were generalized for carbamate anions derived from other capture amines, including ethylenediamine, diethanolamine, and piperazine. We also report unequivocal evidence for the existence of carbamate anions derived from sterically hindered amines (Tris(2-hydroxymethyl)aminomethane and 2-methyl-2-aminopropanol). For the suite of carbamates investigated, diagnostic losses include the decarboxylation product (-CO(2), 44 mass units), loss of 46 mass units and the fragments NCO(-) (m/z 42) and CN(-) (m/z 26). We also report low energy CID results for the dicarbamate dianion ((-)O(2)CNHC(2)H(4)NHCO(2)(-)) commonly encountered in CO(2) capture solution utilizing ethylenediamine. Finally, we demonstrate a promising ion chromatography-MS based procedure for the separation and quantitation of aqueous anionic carbamates, which is based on the reported CID findings. The availability of accurate quantitation methods for ionic CO(2) capture products could lead to dynamic operational tuning of CO(2) capture-plants and, thus, cost-savings via real-time manipulation of solvent regeneration energies.

Organophosphorus and carbamate pesticides. Chapter 12 in Handbook of Ecotoxicology

USGS Publications Warehouse

Hill, Elwood F.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

1995-01-01

Organophosphorus and carbamate pesticides are used throughout the world to control a large variety of insects and other invertebrates, fungi, birds, mammals, and herbaceous plants. Over 100 different organophosphorus and carbamate chemicals are registered in the U.S. alone for use in thousands of products applied to widely diverse habitats including agricultural crops, forests, rangelands, wetlands, towns, and cities. These applications are estimated to be nearly 200 million acre-treatments (i.e., number of acres treated corrected for number of treatments) per year to control nuisance, depradating, and disease-bearing invertebrates and vertebrates, and to maintain landscape aesthetics. Except for mosquito control, most applications target terrestrial habitat. Due to drift or run-off, pesticide and degrades are inevitably detected in soils and water that are fundamental to the primary productivity of ecosystems. Thus, critical life-giving systems are frequently contaminated with organophosphorus and carbamate pesticides, however briefly, each year.

Ethyl carbamate

Integrated Risk Information System (IRIS)

Ethyl carbamate ; CASRN 51 - 79 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

METABOLISM OF CARBAMATE INSECTICIDES

EPA Science Inventory

The results of studies conducted to determine the metabolic fate of carbamate insecticides and its toxicological significance are presented. Methomyl metabolism in rats was investigated in detail as was Croneton in the rat, cow, pig and chicken. Carbaryl and carbofuran were admin...

40 CFR 180.254 - Carbofuran; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Parts per million (ppm) Expiration/Revocation date Alfalfa, forage (of which no more than 5 ppm are carbamates) 10 12/31/09 Alfalfa, hay (of which no more than 20 ppm are carbamates) 40 12/31/09 Banana 0.1 12...

pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.

PubMed

Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul

2018-05-04

The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.

Thermodynamic and mass transfer modeling of carbon dioxide absorption into aqueous 2-amino-2-methyl-1-propanol

DOE PAGES

Sherman, Brent J.; Rochelle, Gary T.

2016-12-16

Explanations for the mass transfer behavior of 2-amino-2-methyl-1-propanol (AMP) are conflicting, despite extensive study of the amine for CO 2 capture. At equilibrium, aqueous AMP reacts with CO 2 to give bicarbonate in a 1:1 ratio. While this is the same stoichiometry as a tertiary amine, the reaction rate of AMP is 100 times faster. This work aims to explain the mass transfer behavior of AMP, specifically the stoichiometry and kinetics. An eNRTL thermodynamic model was used to regress wetted-wall column mass transfer data with two activity-based reactions: formation of carbamate and formation of bicarbonate. Data spanned 40–100 C andmore » 0.15–0.60 mol CO 2/mol alk). The fitted carbamate rate constant is three orders of magnitude greater than the bicarbonate rate constant. Rapid carbamate formation explains the kinetics, while the stoichiometry is explained by the carbamate reverting in the bulk liquid to allow CO 2 to form bicarbonate. Understanding the role of carbamate formation and diffusion in hindered amines enables optimizing solvent amine concentration by balancing viscosity and free amine concentration. Furthermore, this improves absorber design for CO 2 capture.« less

CUMULATIVE EFFECTS OF ORGANOPHOSPHORUS OR CARBAMATE PESTICIDES.

EPA Science Inventory

This book chapter strives to summarize the body of literature exploring the toxic interaction of organophosphorus and carbamate pesticides in mixtures. This review represents one of the only reviews of the subject that has been published within the last 20 years. Specifically, th...

Benzoxazolinone detoxification by N-Glucosylation: The multi-compartment-network of Zea mays L.

PubMed Central

Schulz, Margot; Filary, Barbara; Kühn, Sabine; Colby, Thomas; Harzen, Anne; Schmidt, Jürgen; Sicker, Dieter; Hennig, Lothar; Hofmann, Diana; Disko, Ulrich; Anders, Nico

2016-01-01

ABSTRACT The major detoxification product in maize roots after 24 h benzoxazolin-2(3H)-one (BOA) exposure was identified as glucoside carbamate resulting from rearrangement of BOA-N-glucoside, but the pathway of N-glucosylation, enzymes involved and the site of synthesis were previously unknown. Assaying whole cell proteins revealed the necessity of H2O2 and Fe2+ ions for glucoside carbamate production. Peroxidase produced BOA radicals are apparently formed within the extraplastic space of the young maize root. Radicals seem to be the preferred substrate for N-glucosylation, either by direct reaction with glucose or, more likely, the N-glucoside is released by glucanase/glucosidase catalyzed hydrolysis from cell wall components harboring fixed BOA. The processes are accompanied by alterations of cell wall polymers. Glucoside carbamate accumulation could be suppressed by the oxireductase inhibitor 2-bromo-4´-nitroacetophenone and by peroxidase inhibitor 2,3-butanedione. Alternatively, activated BOA molecules with an open heterocycle may be produced by microorganisms (e.g., endophyte Fusarium verticillioides) and channeled for enzymatic N-glucosylation. Experiments with transgenic Arabidopsis lines indicate a role of maize glucosyltransferase BX9 in BOA-N-glycosylation. Western blots with BX9 antibody demonstrate the presence of BX9 in the extraplastic space. Proteomic analyses verified a high BOA responsiveness of multiple peroxidases in the apoplast/cell wall. BOA incubations led to shifting, altered abundances and identities of the apoplast and cell wall located peroxidases, glucanases, glucosidases and glutathione transferases (GSTs). GSTs could function as glucoside carbamate transporters. The highly complex, compartment spanning and redox-regulated glucoside carbamate pathway seems to be mainly realized in Poaceae. In maize, carbamate production is independent from benzoxazinone synthesis. PMID:26645909

Benzoxazolinone detoxification by N-Glucosylation: The multi-compartment-network of Zea mays L.

PubMed

Schulz, Margot; Filary, Barbara; Kühn, Sabine; Colby, Thomas; Harzen, Anne; Schmidt, Jürgen; Sicker, Dieter; Hennig, Lothar; Hofmann, Diana; Disko, Ulrich; Anders, Nico

2016-01-01

The major detoxification product in maize roots after 24 h benzoxazolin-2(3H)-one (BOA) exposure was identified as glucoside carbamate resulting from rearrangement of BOA-N-glucoside, but the pathway of N-glucosylation, enzymes involved and the site of synthesis were previously unknown. Assaying whole cell proteins revealed the necessity of H2O2 and Fe(2+) ions for glucoside carbamate production. Peroxidase produced BOA radicals are apparently formed within the extraplastic space of the young maize root. Radicals seem to be the preferred substrate for N-glucosylation, either by direct reaction with glucose or, more likely, the N-glucoside is released by glucanase/glucosidase catalyzed hydrolysis from cell wall components harboring fixed BOA. The processes are accompanied by alterations of cell wall polymers. Glucoside carbamate accumulation could be suppressed by the oxireductase inhibitor 2-bromo-4´-nitroacetophenone and by peroxidase inhibitor 2,3-butanedione. Alternatively, activated BOA molecules with an open heterocycle may be produced by microorganisms (e.g., endophyte Fusarium verticillioides) and channeled for enzymatic N-glucosylation. Experiments with transgenic Arabidopsis lines indicate a role of maize glucosyltransferase BX9 in BOA-N-glycosylation. Western blots with BX9 antibody demonstrate the presence of BX9 in the extraplastic space. Proteomic analyses verified a high BOA responsiveness of multiple peroxidases in the apoplast/cell wall. BOA incubations led to shifting, altered abundances and identities of the apoplast and cell wall located peroxidases, glucanases, glucosidases and glutathione transferases (GSTs). GSTs could function as glucoside carbamate transporters. The highly complex, compartment spanning and redox-regulated glucoside carbamate pathway seems to be mainly realized in Poaceae. In maize, carbamate production is independent from benzoxazinone synthesis.

Mechanism-Based Analysis of Acetylcholinesterase Inhibitory Potency of Organophosphates, Carbamates, and Their Analogs

EPA Science Inventory

Acetylcholinesterase (AChE) is a key enzyme in the nervous system of animals, terminating impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a s...

76 FR 34147 - Land Disposal Restrictions: Revision of the Treatment Standards for Carbamate Wastes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-13

... carbamate wastewaters to be treated using combustion, chemical oxidation, biodegradation or carbon..., biodegradation or carbon adsorption for wastewaters. The numeric treatment standard concentration limits were... in the table 40 CFR 268.42) for nonwastewaters; and, combustion, chemical oxidation, biodegradation...

DETERMINATION OF CARBAMATE, UREA, AND THIOUREA PESTICIDES AND HERBICIDES IN WATER

EPA Science Inventory

Microbe liquid chromatography and positive ion electrospray mass spectrometry are applied to the determination of 16 carbamate, urea, and thiourea pesticides and herbicides in water. The electrospray mass spectra of the analytes were measured and are discussed and mobile phase m...

Application of brain cholinesterase reactivation to differentiate between organophosphorus and carbamate pesticide exposure in wild birds

USGS Publications Warehouse

Smith, M.R.; Thomas, N.J.; Hulse, C.

1995-01-01

Brain cholinesterase activity was measured to evaluate pesticide exposure in wild birds. Thermal reactivation of brain cholinesterase was used to differentiate between carbamate and organophosphorus pesticide exposure. Brain cholinesterase activity was compared with gas chromatography and mass spectrometry of stomach contents. Pesticides were identified and confirmed in 86 of 102 incidents of mortality from 29 states within the USA from 1986 through 1991. Thermal reactivation of cholinesterase activity was used to correctly predict carbamates in 22 incidents and organophosphates in 59 incidents. Agreement (P < 0.001) between predictions based on cholinesterase activities and GC/MS results was significant.

Risk of Peripheral Nerve Disease in Military Working Dogs Deployed in Operations Desert Shield/Storm

DTIC Science & Technology

2003-01-01

Paramite (dip). Shampoos, dusts, and collars containing carbaryl or a carbamate generation ingredient were the carbamate formulations. Of all the...aerosol), and propoxur (14.7% liquid). The investigative health risk assessment on pesticide exposure concluded that the possibility exists that

TIME-COURSE OF ACUTE NEUROTOXICITY PRODUCED BY N-METHYL CARBAMATES IN PREWEANLING RATS.

EPA Science Inventory

N-methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterease (ChE). Despite their widespread and long-term use, we could find no studies of a systematic comparison of neurotoxicity in young animals across this group of chemicals. To ...

A Novel Approach for Evaluating Carbamate Mixtures for Dose Additivity

EPA Science Inventory

Two mathematical approaches were used to test the hypothesis ofdose-addition for a binary and a seven-chemical mixture ofN-methyl carbamates, toxicologically similar chemicals that inhibit cholinesterase (ChE). In the more novel approach, mixture data were not included in the ana...

Efficacy of insecticide mixtures against larvae of Culex quinquefasciatus (Say) (Diptera: Culicidae) resistant to pyrethroids and carbamates.

PubMed

Corbel, Vincent; Raymond, Michel; Chandre, Fabrice; Darriet, Frédéric; Hougard, Jean-Marc

2004-04-01

The efficacy of insecticide mixtures of permethrin (pyrethroid) and propoxur (carbamate) was tested by larval bioassays on two strains of Culex quinquefasciatus (Say), one resistant to pyrethroids and the other resistant to carbamates. The method consisted in combining one insecticide at the highest concentration causing no mortality (LC0) with increasing concentrations of the second one. The concentration-mortality regression lines were determined for permethrin and propoxur alone and in combination, and synergism ratios (SR) were calculated in order to determine the magnitude of an increase or decrease in efficacy with use of the mixtures. With the pyrethroid-resistant strain (BK-PER), the results showed that propoxur at LC0 significantly enhanced the insecticidal activity of permethrin (SR50 = 1.54), especially on the upper range of the concentration-mortality regression. Conversely, when permethrin at LC0 was tested with propoxur against the carbamate resistant strain (R-LAB), an antagonistic effect was observed (SR50 = 0.67). With the BK-PER strain, an increased oxidative detoxification (MFO) appeared to be the main mechanism responsible for the synergistic interaction. Nevertheless, antagonism in the R-LAB strain is probably due to a physiological perturbation implying different target sites for pyrethroid (ie sodium channel) and carbamate insecticides [ie acetylcholinesterase (EC 3.3.3.7) and choline acetyltransferase (EC 2.3.1.6)].

COMPARISON OF ACUTE NEUROBEHAVIORAL AND CHOLINESTERASE INHIBITORY EFFECTS OF N-METHYL CARBAMATES IN RAT

EPA Science Inventory

There are few studies evaluating direct functional and biochemical consequences of exposure. In the present study of the acute toxicity of seven N-methyl carbamate pesticides, we evaluated the dose-response profiles of cholinesterase (ChE) inhibition in brain and erythrocytes (R...

Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Rats

EPA Science Inventory

Environmental exposures generally involve multiple chemicals and pathways, and statistical methodologies now exist to evaluate interactions among any number of chemicals in defined mixtures. N-methyl carbamate pesticides are presumed to act through a common mode of action, that i...

Data-derived uncertainty factor approach in the revised N-methyl carbamate risk assessment.

EPA Science Inventory

EPA completed its Revised Cumulative Risk Assessment (CRA) of the N-methyl Carbamate (NMC) Pesticides in 2007. This assessment evaluated the joint risk to 10 pesticides from food, water, and residential exposure. NMCs share the ability to inhibit acetylcholinesterase (AChE) via c...

A SIMPLE HPLC METHOD FOR DETECTING CARBARYL AND 1-NAPHTHOL IN BIOLOGICAL TISSUES.

EPA Science Inventory

Carbamates are a class of pesticide used in both agricultural and residential applications. A simple HPLC method for detecting Carb and its metabolite 1-naphthol (Naph) in tissues was developed to try to correlate tissue levels of carbaryl (Carb) (a prototypical carbamate) with c...

Detection of benzimidazole carbamates and amino metabolites in liver by surface plasmon resonance-biosensor

USDA-ARS?s Scientific Manuscript database

Two surface plasmon resonance (SPR) biosensor screening assays were developed and validated to detect 11 benzimidazole carbamate (BZT) and four amino-benzimidazole veterinary drug residues in liver tissue. The assays used polyclonal antibodies, raised in sheep, to detect BZTs and amino-benzimidazole...

40 CFR 268.39 - Waste specific prohibitions-spent aluminum potliners; reactive; and carbamate wastes.

Code of Federal Regulations, 2013 CFR

2013-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Prohibitions on Land Disposal § 268.39 Waste specific prohibitions—spent aluminum potliners; reactive; and carbamate...-U411 are prohibited from land disposal. In addition, soil and debris contaminated with these wastes are...

40 CFR 268.39 - Waste specific prohibitions-spent aluminum potliners; reactive; and carbamate wastes.

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Prohibitions on Land Disposal § 268.39 Waste specific prohibitions—spent aluminum potliners; reactive; and carbamate...-U411 are prohibited from land disposal. In addition, soil and debris contaminated with these wastes are...

40 CFR 268.39 - Waste specific prohibitions-spent aluminum potliners; reactive; and carbamate wastes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Prohibitions on Land Disposal § 268.39 Waste specific prohibitions—spent aluminum potliners; reactive; and carbamate...-U411 are prohibited from land disposal. In addition, soil and debris contaminated with these wastes are...

40 CFR 268.39 - Waste specific prohibitions-spent aluminum potliners; reactive; and carbamate wastes.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Prohibitions on Land Disposal § 268.39 Waste specific prohibitions—spent aluminum potliners; reactive; and carbamate...-U411 are prohibited from land disposal. In addition, soil and debris contaminated with these wastes are...

40 CFR 268.39 - Waste specific prohibitions-spent aluminum potliners; reactive; and carbamate wastes.

Code of Federal Regulations, 2012 CFR

2012-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Prohibitions on Land Disposal § 268.39 Waste specific prohibitions—spent aluminum potliners; reactive; and carbamate...-U411 are prohibited from land disposal. In addition, soil and debris contaminated with these wastes are...

76 FR 34200 - Land Disposal Restrictions: Revision of the Treatment Standards for Carbamate Wastes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-13

... 2050-AG65 Land Disposal Restrictions: Revision of the Treatment Standards for Carbamate Wastes AGENCY... concentration limits before the wastes can be land disposed. The lack of readily available analytical standards.... List of Subjects 40 CFR Part 268 Environmental protection, Hazardous waste, Land disposal restrictions...

Effects of electronics, aromaticity, and solvent polarity on the rate of azaquinone-methide-mediated depolymerization of aromatic carbamate oligomers.

PubMed

Robbins, Jessica S; Schmid, Kyle M; Phillips, Scott T

2013-04-05

This paper uses physical-organic studies on well-defined oligomers to establish design principles for creating aromatic poly(carbamates) that depolymerize from head-to-tail in low dielectric constant environments when exposed to specific applied signals. We show that either increasing electron density or decreasing the aromaticity of aromatic repeating units in poly(carbamates) increase the overall depolymerization rate. For example, a methoxybenzene-based repeating unit provides depolymerization rates that are 143× faster than oligomers that contain a benzene-based repeating unit. Furthermore, the rate of depolymerization in the methoxybenzene-based system is tolerant to low dielectric environments, whereas the benzene-based oligomers are not.

Toxicity of carbamates for mammals

PubMed Central

Vandekar, M.; Pleština, R.; Wilhelm, K.

1971-01-01

Toxicity studies have been carried out with a number of monomethylcarbamates, most of which reached an advanced stage in the World Health Organization insecticide evaluation programme. Both quantitative and qualitative distinctions have been found between the carbamates studied, and certain common characteristics that distinguish them in several important aspects from organophosphorus insecticides have been demonstrated. PMID:4999482

USE OF EXPOSURE-RELATED DOSE ESTIMATING MODEL (ERDEM) FOR ASSESSMENT OF AGGREGATE EXPOSURE OF INFANT AND CHILDREN TO N-METHYL CARBAMATE INSECTICIDES

EPA Science Inventory

A physiologically based pharmacokinetic (PBPK) model was developed within the Exposure Related Dose Estimating Model (ERDEM) framework to investigate selected exposure inputs related to recognized exposure scenarios of infants and children to N-methyl carbamate pesticides as spec...

INTERLABORATORY STUDY OF A THERMOSPRAY-LIQUID CHROMATOGRAPHIC/MASS SPECTROMETRIC METHOD FOR SELECTED N-METHYL CARBAMATES, N-METHYL CARBAMOYLOXIMES, AND SUBSTITUTED UREA PESTICIDES

EPA Science Inventory

A thermospray-liquid chromatographic/mass spectrometric (TS-LC/MS) method was evaluated in an interlaboratory study for determining 3 N-methyl carbamates (bendiocarb, carbaryl, and carbofuran), 3-N-methyl carbamoyloximes (aldicarb, methomyl, and oxamyl), 2 substituted urea pestic...

Benchmark Dose Analysis from Multiple Datasets: The Cumulative Risk Assessment for the N-Methyl Carbamate Pesticides

EPA Science Inventory

The US EPA’s N-Methyl Carbamate (NMC) Cumulative Risk assessment was based on the effect on acetylcholine esterase (AChE) activity of exposure to 10 NMC pesticides through dietary, drinking water, and residential exposures, assuming the effects of joint exposure to NMCs is dose-...

RELATIONSHIPS BETWEEN TISSUE LEVELS OF CARBARYL, A PROTOTYPICAL CARBAMATE PESTICIDE, AND CHOLINESTERASE INHIBITION IN LONG EVANS RATS.

EPA Science Inventory

As part of an effort to link pharmacokinetics with biochemical and physiological endpoints, the relationships between cholinesterase (ChE) activity and tissue levels of a prototypical N-methyl carbamate pesticide were examined. In a dose-response study, carbaryl (0, 3, 7.5, 15, 3...

A Mechanism-based 3D-QSAR Approach for Classification and Prediction of Acetylcholinesterase Inhibitory Potency of Organophosphate and Carbamate Analogs

EPA Science Inventory

Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understandi...

Transition state-based ST6Gal I inhibitors: Mimicking the phosphodiester linkage with a triazole or carbamate through an enthalpy-entropy compensation.

PubMed

Montgomery, Andrew P; Skropeta, Danielle; Yu, Haibo

2017-10-31

Human β-galactoside α-2,6-sialyltransferase I (ST6Gal I) catalyses the synthesis of sialylated glycoconjugates. Overexpression of ST6Gal I is observed in many cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase inhibitors have been developed, with analogues structurally similar to the transition state exhibiting the highest inhibitory activity. To improve synthetic accessibility and pharmacokinetics of previously reported inhibitors, the replacement of the charged phosphodiester linker with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been investigated. Extensive molecular dynamics simulations have demonstrated that compounds with the alternate linkers could maintain key interactions with the human ST6Gal I active site, demonstrating the potential of a carbamate or a 1,2,3-triazole as a phosphodiester isostere. Free energy perturbation calculations provided energetic evidence suggesting that the carbamate and 1,2,3-triazole were slightly more favourable than the phosphodiester. Further exploration with free energy component, quasi-harmonic and cluster analysis suggested that there is an enthalpy-entropy compensation accounting for the replacement of the flexible charged phosphodiester with a neutral and rigid isostere. Overall, these simulations provide a strong rationale for the use of a carbamate or 1,2,3-triazole as a phosphodiester isostere in the development of novel inhibitors of human ST6Gal I.

Biodegradation of pyraclostrobin by two microbial communities from Hawaiian soils and metabolic mechanism.

PubMed

Chen, Xiaoxin; He, Sheng; Liang, Zhibin; Li, Qing X; Yan, Hai; Hu, Jiye; Liu, Xiaolu

2018-04-27

Pyraclostrobin has been widely and long-termly applicated to agricultural fields. The removal of pyraclostrobin from ecological environment has received wide attention. In this study, using sequential enrichments with pyraclostrobin as a sole carbon source, two microbial communities (HI2 and HI6) capable of catabolizing pyraclostrobin were obtained from Hawaiian soils. The microfloras analysis indicated that only Proteobacteria and Bacteroides could survive in HI2-soil after acclimatization, whereas the number of Proteobacteria in HI6-soil accounted for more than 99%. The percentages of Pseudomonas in the HI2 and HI6 microfloras were 69.3% and 59.3%, respectively. More than 99% of pyraclostrobin (C 0  = 100 mg L -1 ) was degraded by the HI2 and HI6 microorganisms within five days. A unique metabolite was identified by high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS/MS). A metabolic pathway involving carbamate hydrolysis was proposed. The tertiary amine group of pyraclostrobin was hydrolyzed to primary amine group with the decarboxylation, which facilitated pyraclostrobin detoxification because carboxylester was an important functional group. The metabolic mechanism suggested that Pseudomonas expressing carboxylesterase might be able to degrade carbamate chemicals. Therefore, Pseudomonas might be an ideal candidate for expression and cloning of carbamate-degrading gene in genomics studies. The current study would have important implications in detoxification and bioremediation of carbamates through the CN bond cleavage of methyl carbamate. Copyright © 2018 Elsevier B.V. All rights reserved.

The P450 CYP6Z1 confers carbamate/pyrethroid cross-resistance in a major African malaria vector beside a novel carbamate-insensitive N485I acetylcholinesterase-1 mutation.

PubMed

Ibrahim, Sulaiman S; Ndula, Miranda; Riveron, Jacob M; Irving, Helen; Wondji, Charles S

2016-07-01

Carbamates are increasingly used for vector control notably in areas with pyrethroid resistance. However, a cross-resistance between these insecticides in major malaria vectors such as Anopheles funestus could severely limit available resistance management options. Unfortunately, the molecular basis of such cross-resistance remains uncharacterized in An. funestus, preventing effective resistance management. Here, using a genomewide transcription profiling, we revealed that metabolic resistance through upregulation of cytochrome P450 genes is driving carbamate resistance. The P450s CYP6P9a, CYP6P9b and CYP6Z1 were the most upregulated detoxification genes in the multiple resistant mosquitoes. However, in silico docking simulations predicted CYP6Z1 to metabolize both pyrethroids and carbamates, whereas CYP6P9a and CYP6P9b were predicted to metabolize only the pyrethroids. Using recombinant enzyme metabolism and inhibition assays, we demonstrated that CYP6Z1 metabolizes bendiocarb and pyrethroids, whereas CYP6P9a and CYP6P9b metabolize only the pyrethroids. Other upregulated gene families in resistant mosquitoes included several cuticular protein genes suggesting a possible reduced penetration resistance mechanism. Investigation of the target-site resistance in acetylcholinesterase 1 (ace-1) gene detected and established the association between the new N485I mutation and bendiocarb resistance (odds ratio 7.3; P < 0.0001). The detection of multiple haplotypes in single mosquitoes after cloning suggested the duplication of ace-1. A TaqMan genotyping of the N485I in nine countries revealed that the mutation is located only in southern Africa with frequency of 10-15% suggesting its recent occurrence. These findings will help in monitoring the spread and evolution of carbamate resistance and improve the design of effective resistance management strategies to control this malaria vector. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

A PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC (PBPK/PD) MODEL FOR ESTIMATION OF CUMULATIVE RISK FROM EXPOSURE TO THREE N-METHYL CARBAMATES: CARBARYL, ALDICARB, AND CARBOFURAN

EPA Science Inventory

A physiologically-based pharmacokinetic (PBPK) model for a mixture of N-methyl carbamate pesticides was developed based on single chemical models. The model was used to compare urinary metabolite concentrations to levels from National Health and Nutrition Examination Survey (NHA...

Carbamate resistance in Anopheles albimanus

PubMed Central

Ariaratnam, Veluppillai; Georghiou, George P.

1974-01-01

Carbamate resistance induced in a field strain of A. albimanus from El Salvador by laboratory selection with propoxur remained fairly stable on relaxation of selection pressure for 12 generations. Studies on cross and multiple resistance showed that this strain was not resistant to the pyrethroids bioresmethrin, bioallethrin, and CRC 11451, although resistance to cismethrin was 2.3-fold. Resistance to 10 carbamates of various structural configurations covered a broad spectrum, being for example >100× to Bay 38799, Ciba 17474, and Ciba 18107, 74.8× to carbaryl, 20.57× to carbanolate, and 2.27× to Stauffer R 15396. The possible causes of the presence or absence of cross resistance and the implications of stability of resistance and cross resistance are discussed. PMID:4549614

Divergent effects of postmortem ambient temperature on organophosphorus- and carbamate-inhibited brain cholinesterase activity in birds

USGS Publications Warehouse

Hill, E.F.

1989-01-01

Time- and temperature-dependent postmortem changes in inhibited brain cholinesterase (ChE) activity may confound diagnosis of field poisoning of wildlife by anticholinesterase pesticide. Carbamate-inhibited ChE activity may return to normal within 1 to 2 days of exposure of intact carcass to moderate ambient temperature (18-32C). Organophosphorus-inhibited ChE activity becomes more depressed over the same time. Uninhibited ChE activity was resilient to above freezing temperature to 32C for 1 day and 25C for 3 days. Carbamate- and organophosphorus-inhibited ChE can be separated by incubation of homogenate for 1 hour at physiological temperatures; carbamylated ChE can be readily reactivated while phosphorylated ChE cannot.

O-(Triazolyl)methyl carbamates as a novel and potent class of FAAH inhibitors

PubMed Central

Colombano, Giampiero; Albani, Clara; Ottonello, Giuliana; Ribeiro, Alison; Scarpelli, Rita; Tarozzo, Glauco; Daglian, Jennifer; Jung, Kwang-Mook; Piomelli, Daniele; Bandiera, Tiziano

2015-01-01

Inhibition of fatty acid amide hydrolase (FAAH) activity is under investigation as a valuable strategy for the treatment of several disorders, including pain and drug addiction. A number of potent FAAH inhibitors belonging to different chemical classes have been disclosed. O-aryl carbamates are one of the most representative families. In the search for novel FAAH inhibitors, we synthesized a series of O-(1,2,3-triazol-4-yl)methyl carbamate derivatives exploiting the copper-catalyzed [3 + 2] cycloaddition reaction between azides and alkynes (click chemistry). We explored structure-activity relationships within this new class of compounds and identified potent inhibitors of both rat and human FAAH with IC50 values in the single-digit nanomolar range. PMID:25338703

Pressure injection of methyl 2-benzimidazole carbamate hydrochloride solution as a control for Dutch elm disease

Treesearch

Garold F. Gregory; Thomas W. Jones

1973-01-01

A preliminary evaluation of the effectiveness of injecting methyl 2-benzimidazole carbamate hydrochloride solution into elms for prevention or cure of Dutch elm disease is reported. Symptom development was diminished or prevented in elms injected with fungicide before inoculation. Symptom development was arrested in all crown-inoculated diseased trees injected with the...

A Pharmacokinetic Study of the Effects of Stress and Exercise on Chemical Exposure

DTIC Science & Technology

2001-03-20

Organophosphates such as diazinon and malathion are considered cholinesterase inhibitors, while carbamates such as physostigmine and pyridostigmine...bromide (PB) are considered reversible cholinesterase inhibitors. The possible Gulf War exposures to organophosphates such as diazinon and malathion...indicate that the physiological and protective effects of carbamates such as PB may depend on a narrow range of cholinesterase inhibition. Blood

Mechanism of inhibition of cyclo-oxygenase in human blood platelets by carbamate insecticides.

PubMed Central

Krug, H F; Hamm, U; Berndt, J

1988-01-01

Carbamates are a widely used class of insecticides and herbicides. They were tested for their ability to affect human blood platelet aggregation and arachidonic acid metabolism in platelets. (1) The herbicides of the carbamate type have no, or only little, influence up to a concentration of 100 microM; the carbamate insecticides, however, inhibit both aggregation and arachidonic acid metabolism in a dose- and time-dependent manner. (2) Carbaryl, the most effective compound, inhibits platelet aggregation and cyclo-oxygenase activity completely at 10 microM. The liberation of arachidonic acid from phospholipids and the lipoxygenase pathway are not affected, whereas the products of the cyclo-oxygenase pathway are drastically decreased. (3) By using [14C]carbaryl labelled in the carbamyl or in the ring moiety, it could be proved that the carbamyl residue binds covalently to platelet proteins. In contrast with acetylsalicylic acid, which acetylates only one protein, carbaryl carbamylates a multitude of platelet proteins. (4) One of the carbamylated proteins was found to be the platelet cyclo-oxygenase, indicating that carbaryl resembles in this respect acetylsalicylic acid, which is known to inhibit this enzyme specifically by acetylation. Images Fig. 4. PMID:3128272

Structure-activity relationships for amide-, carbamate-, and urea-linked analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).

PubMed

Blaser, Adrian; Palmer, Brian D; Sutherland, Hamish S; Kmentova, Iveta; Franzblau, Scott G; Wan, Baojie; Wang, Yuehong; Ma, Zhenkun; Thompson, Andrew M; Denny, William A

2012-01-12

Analogues of clinical tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824), in which the OCH(2) linkage was replaced with amide, carbamate, and urea functionality, were investigated as an alternative approach to address oxidative metabolism, reduce lipophilicity, and improve aqueous solubility. Several soluble monoaryl examples displayed moderately improved (∼2- to 4-fold) potencies against replicating Mycobacterium tuberculosis but were generally inferior inhibitors under anaerobic (nonreplicating) conditions. More lipophilic biaryl derivatives mostly displayed similar or reduced potencies to these in contrast to the parent biaryl series. The leading biaryl carbamate demonstrated exceptional metabolic stability and a 5-fold better efficacy than the parent drug in a mouse model of acute M. tuberculosis infection but was poorly soluble. Bioisosteric replacement of this biaryl moiety by arylpiperazine resulted in a soluble, orally bioavailable carbamate analogue providing identical activity in the acute model, comparable efficacy to OPC-67683 in a chronic infection model, favorable pharmacokinetic profiles across several species, and enhanced safety.

Anticholinesterase poisoning of birds: Field monitoring and diagnosis of acute poisoning

USGS Publications Warehouse

Hill, E.F.; Fleming, W.J.

1982-01-01

Organophosphorus and carbamate pesticides are cholinesterase (ChE) inhibiting chemicals that have been responsible for avian die-offs. Identification of chemicals implicated in these die-offs is difficult and sometimes conclusions are solely circumstantial. However, when marked depression (inhibition) of brain ChE activity accompanies organophosphorus or carbamate residues in body tissues or ingesta, cause-effect diagnosis is enhanced. To achieve this end, normal brain ChE activity is estimated for controls of the affected species and then die-off specimens are individually evaluated for evidence of ChE inhibition. This approach to evaluation of antiChE poisoning may also be used to monitor exposure of vertebrates to field application of organophosphorus or carbamate pesticides. Problems associated with this kind of evaluation, and the main topic of this report, include variability of brain ChE activity among species, postmortem influences of ambient conditions (storage or field) on ChE activity, and differential patterns of ChE activity when inhibited by organophosphorus or carbamate compounds. Other topics discussed are the ChE assay procedure, example case reports and interpretation, and research needed for improving the diagnostic utility of ChE activity in a field situation.

Ionic liquid polymer functionalized carbon nanotubes-doped poly(3,4-ethylenedioxythiophene) for highly-efficient solid-phase microextraction of carbamate pesticides.

PubMed

Wu, Mian; Wang, Liying; Zeng, Baizhao; Zhao, Faqiong

2016-04-29

A poly(3,4-ethylenedioxythiophene)-ionic liquid polymer functionalized multiwalled carbon nanotubes (PEDOT-PIL/MWCNTs) composite solid-phase microextraction (SPME) coating was fabricated by electrodeposition. After being dipped in Nafion solution, a Nafion-modified coating was obtained. The outer layer Nafion played a crucial role in enhancing the durability and stability of the coating, thus it was robust enough for replicated extraction for at least 150 times without decrease of extraction performance. The Nafion-modified coating exhibited much higher sensitivity than commercial coatings for the direct extraction of carbamate pesticides in aqueous solutions, due to its strong hydrophobic effect and π-π affinity based enrichment. When it was used for the determination of carbamate pesticides in combination with gas chromatography-flame ionization detection, good linearity (correlation coefficients higher than 0.9981), low limits of detection (15.2-27.2 ng/L) and satisfactory precision (relative standard deviation <8.2%, n=5) were achieved. The developed method was applied to the analysis of four carbamate pesticides in apple and lettuce samples, and acceptable recoveries (i.e. 87.5-106.5%) were obtained for the standard addition. Copyright © 2016 Elsevier B.V. All rights reserved.

Host-guest chemistry of cyclodextrin carbamates and cellulose derivatives in aqueous solution.

PubMed

Guo, Xin; Jia, Xiangxiang; Du, Jiaojiao; Xiao, Longqiang; Li, Feifei; Liao, Liqiong; Liu, Lijian

2013-10-15

Supramolecular polymer micelles were prepared on basis of the inclusion complexation between cyclodextrin carbamates and cellulose derivatives in aqueous media. Cyclodextrin carbamates were synthesized by microwave-assisted method from cyclodextrin and urea. The urea modified cyclodextrin shows the higher yield than the physical mixture of urea/cyclodextrin in the micellization with cellulose derivatives. The supramolecular structure of the core-shell micelles was demonstrated by (1)H NMR spectra, TEM images, and fluorescence spectra. The drug release behavior of the supramolecular polymer micelles was evaluated using prednisone acetate as a model drug. The drug loaded micelles showed steady and long time drug release behavior. With these properties, the supramolecular polymer micelles are attractive as drug carriers for pharmaceutical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evidence of carbamate resistance in urban populations of Anopheles gambiae s.s. mosquitoes resistant to DDT and deltamethrin insecticides in Lagos, South-Western Nigeria

PubMed Central

2012-01-01

Background Resistance monitoring is essential in ensuring the success of insecticide based vector control programmes. This study was carried out to assess the susceptibility status of urban populations of Anopheles gambiae to carbamate insecticide being considered for vector control in mosquito populations previously reported to be resistant to DDT and permethrin. Methods Two – three day old adult female Anopheles mosquitoes reared from larval collections in 11 study sites from Local Government Areas of Lagos were exposed to test papers impregnated with DDT 4%, deltamethrin 0.05% and propoxur 0.1% insecticides. Additional tests were carried out to determine the susceptibility status of the Anopheles gambiae population to bendiocarb insecticide. Members of the A. gambiae complex, the molecular forms, were identified by PCR assays. The involvement of metabolic enzymes in carbamate resistance was assessed using Piperonyl butoxide (PBO) synergist assays. The presence of kdr-w/e and ace-1R point mutations responsible for DDT-pyrethroid and carbamate resistance mechanisms was also investigated by PCR. Results Propoxur resistance was found in 10 out of the 11 study sites. Resistance to three classes of insecticides was observed in five urban localities. Mortality rates in mosquitoes exposed to deltamethrin and propoxur did not show any significant difference (P > 0.05) but was significantly higher (P < 0.05) in populations exposed to DDT. All mosquitoes tested were identified as A. gambiae s.s (M form). The kdr -w point mutation at allelic frequencies between 45%-77% was identified as one of the resistant mechanisms responsible for DDT and pyrethroid resistance. Ace-1R point mutation was absent in the carbamate resistant population. However, the possible involvement of metabolic resistance was confirmed by synergistic assays conducted. Conclusion Evidence of carbamate resistance in A. gambiae populations already harbouring resistance to DDT and permethrin is a clear indication that calls for the implementation of insecticide resistance management strategies to combat the multiple resistance identified. PMID:22686575

Identification and quantification of ethyl carbamate occurring in urea complexation processes commonly utilized for polyunsaturated fatty acid concentration.

PubMed

Vázquez, Luis; Prados, Isabel M; Reglero, Guillermo; Torres, Carlos F

2017-08-15

The concentration of polyunsaturated fatty acids by formation of urea adducts from three different sources was studied to elucidate the formation of ethyl carbamates in the course of these procedures. Two different methodologies were performed: with ethanol at high temperature and with hexane/ethanol mixtures at room temperature. It was proved that the amount of urethanes generated at high temperature was higher than at room temperature. Besides, subsequent washing steps of the PUFA fraction with water were efficient to remove the urethanes from the final products. The methodology at room temperature with 0.4mL ethanol and 3g urea provided good relationship between concentration and yield of the main bioactive PUFA, with the lowest formation of ethyl carbamates in the process. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Environmental Compliance Assessment and Management Program (ECAMP). Supplement for the Environmental Assessment and Management (TEAM) Guide. Revised September 1999

DTIC Science & Technology

1999-09-01

Verify that all personnel new to the career field receive a baseline physical exam prior to potential occupational exposure to pesticides and periodic...or using toilet facilities -persons working regularly with organophosphates and N-alkyl carbamate pesticides have periodic physical examinations...after fighting fires involving organophosphate or N-alkyl carbamate pesticides. 7-37 Pesticide 7-38 Pesticide COMPLIANCE CATEGORY

Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1.

PubMed

Tice, Colin M; Zhao, Wei; Krosky, Paula M; Kruk, Barbara A; Berbaum, Jennifer; Johnson, Judith A; Bukhtiyarov, Yuri; Panemangalore, Reshma; Scott, Boyd B; Zhao, Yi; Bruno, Joseph G; Howard, Lamont; Togias, Jennifer; Ye, Yuan-Jie; Singh, Suresh B; McKeever, Brian M; Lindblom, Peter R; Guo, Joan; Guo, Rong; Nar, Herbert; Schuler-Metz, Annette; Gregg, Richard E; Leftheris, Katerina; Harrison, Richard K; McGeehan, Gerard M; Zhuang, Linghang; Claremon, David A

2010-11-15

Synthesis of 2-adamantyl carbamate derivatives of piperidines and pyrrolidines led to the discovery of 9a with an IC(50) of 15.2 nM against human 11β-HSD1 in adipocytes. Optimization for increased adipocyte potency, metabolic stability and selectivity afforded 11k and 11l, both of which were >25% orally bioavailable in rat. Copyright © 2010 Elsevier Ltd. All rights reserved.

Phenyl thiazolyl urea and carbamate derivatives as new inhibitors of bacterial cell-wall biosynthesis.

PubMed

Francisco, Gerardo D; Li, Zhong; Albright, J Donald; Eudy, Nancy H; Katz, Alan H; Petersen, Peter J; Labthavikul, Pornpen; Singh, Guy; Yang, Youjun; Rasmussen, Beth A; Lin, Yang-I; Mansour, Tarek S

2004-01-05

Over 50 phenyl thiazolyl urea and carbamate derivatives were synthesized for evaluation as new inhibitors of bacterial cell-wall biosynthesis. Many of them demonstrated good activity against MurA and MurB and gram-positive bacteria including MRSA, VRE and PRSP. 3,4-Difluorophenyl 5-cyanothiazolylurea (3p) with clog P of 2.64 demonstrated antibacterial activity against both gram-positive and gram-negative bacteria.

Wild Raspberry Subjected to Simulated Gastrointestinal Digestion Improves the Protective Capacity against Ethyl Carbamate-Induced Oxidative Damage in Caco-2 Cells

PubMed Central

Chen, Wei; Xu, Yang; Zhang, Lingxia; Li, Ya; Zheng, Xiaodong

2016-01-01

Ethyl carbamate (EC), a probable human carcinogen, occurs widely in many fermented foods. Previous studies indicated that EC-induced cytotoxicity was associated with oxidative stress. Wild raspberries are rich in polyphenolic compounds, which possess potent antioxidant activity. This study was conducted to investigate the protective effect of wild raspberry extracts produced before (RE) and after in vitro simulated gastrointestinal digestion (RD) on EC-induced oxidative damage in Caco-2 cells. Our primary data showed that ethyl carbamate could result in cytotoxicity and genotoxicity in Caco-2 cells and raspberry extract after digestion (RD) may be more effective than that before digestion (RE) in attenuating toxicity caused by ethyl carbamate. Further investigation by fluorescence microscope revealed that RD may significantly ameliorate EC-induced oxidative damage by scavenging the overproduction of intracellular reactive oxygen species (ROS), maintaining mitochondrial function and preventing glutathione (GSH) depletion. In addition, HPLC-ESI-MS results showed that the contents of identified polyphenolic compounds (esculin, kaempferol O-hexoside, and pelargonidin O-hexoside) were remarkably increased after digestion, which might be related to the better protective effect of RD. Overall, our results demonstrated that raspberry extract undergoing simulated gastrointestinal digestion may improve the protective effect against EC-induced oxidative damage in Caco-2 cells. PMID:26788245

Estimation of hydrolysis rate constants for carbamates ...

EPA Pesticide Factsheets

Cheminformatics based tools, such as the Chemical Transformation Simulator under development in EPA’s Office of Research and Development, are being increasingly used to evaluate chemicals for their potential to degrade in the environment or be transformed through metabolism. Hydrolysis represents a major environmental degradation pathway; unfortunately, only a small fraction of hydrolysis rates for about 85,000 chemicals on the Toxic Substances Control Act (TSCA) inventory are in public domain, making it critical to develop in silico approaches to estimate hydrolysis rate constants. In this presentation, we compare three complementary approaches to estimate hydrolysis rates for carbamates, an important chemical class widely used in agriculture as pesticides, herbicides and fungicides. Fragment-based Quantitative Structure Activity Relationships (QSARs) using Hammett-Taft sigma constants are widely published and implemented for relatively simple functional groups such as carboxylic acid esters, phthalate esters, and organophosphate esters, and we extend these to carbamates. We also develop a pKa based model and a quantitative structure property relationship (QSPR) model, and evaluate them against measured rate constants using R square and root mean square (RMS) error. Our work shows that for our relatively small sample size of carbamates, a Hammett-Taft based fragment model performs best, followed by a pKa and a QSPR model. This presentation compares three comp

Toward rational design of amines for CO2 capture: Substituent effect on kinetic process for the reaction of monoethanolamine with CO2.

PubMed

Xie, Hongbin; Wang, Pan; He, Ning; Yang, Xianhai; Chen, Jingwen

2015-11-01

Amines have been considered as promising candidates for post-combustion CO2 capture. A mechanistic understanding for the chemical processes involved in the capture and release of CO2 is important for the rational design of amines. In this study, the structural effects of amines on the kinetic competition among three typical products (carbamates, carbamic acids and bicarbonate) from amines+CO2 were investigated, in contrast to previous thermodynamic studies to tune the reaction of amines with CO2 based on desirable reaction enthalpy and reaction stoichiometry. We used a quantum chemical method to calculate the activation energies (Ea) for the reactions of a range of substituted monoethanolamines with CO2 covering three pathways to the three products. The results indicate that the formation of carbamates is the most favorable, among the three considered products. In addition, we found that the Ea values for all pathways linearly correlate with pKa of amines, and more importantly, the kinetic competition between carbamate and bicarbonate absorption pathways varies with pKa of the amines, i.e. stronger basicity results in less difference in Ea. These results highlight the importance of the consideration of kinetic competition among different reaction pathways in amine design. Copyright © 2015. Published by Elsevier B.V.

Carbamate resistance in Anopheles albimanus

PubMed Central

Ariaratnam, Veluppillai; Georghiou, George P.

1975-01-01

The roles of increased metabolism and reduced penetration as possible mechanisms of resistance to carbaryl were investigated in a strain of A. albimanus from El Salvador in which carbamate and organophosphorus resistance had been induced by laboratory selection with propoxur. Carbaryl was metabolized to N-hydroxymethylcarbaryl, 5,6-dihydro-5,6-dihydroxycarbaryl and an unidentified metabolite A. The rate of metabolism by the resistant strain was only slightly higher than that by the parental strain. The rate of penetration of carbaryl in the parental strain was nearly twice that in the resistant strain during the first hour of exposure. However, this difference did not persist for as long as 90 min. Because of the low level of carbamate metabolism detected, it was concluded that the high resistance of the strain must be due to the action of some as yet unidentified mechanism, possibly enhanced by factors controlling the penetration and metabolism of the toxicant. PMID:813837

Enzyme-based electrochemical biosensors for determination of organophosphorus and carbamate pesticides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Everett, W.R.; Rechnitz, G.A.

1999-01-01

A mini review of enzyme-based electrochemical biosensors for inhibition analysis of organophosphorus and carbamate pesticides is presented. Discussion includes the most recent literature to present advances in detection limits, selectivity and real sample analysis. Recent reviews on the monitoring of pesticides and their residues suggest that the classical analytical techniques of gas and liquid chromatography are the most widely used methods of detection. These techniques, although very accurate in their determinations, can be quite time consuming and expensive and usually require extensive sample clean up and pro-concentration. For these and many other reasons, the classical techniques are very difficult tomore » adapt for field use. Numerous researchers, in the past decade, have developed and made improvements on biosensors for use in pesticide analysis. This mini review will focus on recent advances made in enzyme-based electrochemical biosensors for the determinations of organophosphorus and carbamate pesticides.« less

Highly conductive solid polymer electrolyte membranes based on polyethylene glycol-bis-carbamate dimethacrylate networks

NASA Astrophysics Data System (ADS)

Fu, Guopeng; Dempsey, Janel; Izaki, Kosuke; Adachi, Kaoru; Tsukahara, Yasuhisa; Kyu, Thein

2017-08-01

In an effort to fabricate highly conductive, stable solid-state polymer electrolyte membranes (PEM), polyethylene glycol bis-carbamate (PEGBC) was synthesized via condensation reaction between polyethylene glycol diamine and ethylene carbonate. Subsequently, dimethacrylate groups were chemically attached to both ends of PEGBC to afford polyethylene glycol-bis-carbamate dimethacrylate (PEGBCDMA) precursor having crosslinking capability. The melt-mixed ternary mixtures consisting of PEGBCDMA, succinonitrile plasticizer, and lithium trifluorosulphonyl imide salt were completely miscible in a wide compositional range. Upon photo-crosslinking, the neat PEGBCDMA network was completely amorphous exhibiting higher tensile strength, modulus, and extensibility relative to polyethylene glycol diacrylate (PEGDA) counterpart. Likewise, the succinonitrile-plasticized PEM network containing PEGBCDMA remained completely amorphous and transparent upon photo-crosslinking, showing superionic conductivity, improved thermal stability, and superior tensile properties with improved capacity retention during charge/discharge cycling as compared to the PEGDA-based PEM.

Structure-activity relationship of carbamate-linked cationic lipids bearing hydroxyethyl headgroup for gene delivery.

PubMed

Zhi, Defu; Zhang, Shubiao; Qureshi, Farooq; Zhao, Yinan; Cui, Shaohui; Wang, Bing; Chen, Huiying; Yang, Baoling; Zhao, Defeng

2013-12-01

A novel series of carbamate-linked cationic lipids containing hydroxyl headgroup were synthesized and included in formulations for transfection assays. The DNA-lipid complexes were characterized for their ability to bind DNA, their size, ζ-potential and cytotoxicity. Compared with our previously reported cationic transfection lipid DDCDMA lacking the hydroxyl group and the commercially available, these cationic liposomes exhibited relatively higher transfection efficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Workshop on Alternatives to Animals in Research Held in Suffield, Ralston, Alberta on 16-17 September 1987

DTIC Science & Technology

1989-10-01

UNCLASSIFIED UNCLASSIFIED 48 SUMMARY OF OP AND CARBAMATE INTERACTIONS IN THE ACUTE INHIBITION OF CHOLINESTERASE ACTIVITY IN RAT BRAIN NEURAL CELL AGGREGATE...for the past three years, we have been study- ing the toxicity of a number of organophosphates and carbamates on neural cell aggregate cultures. The...the temporary acute exposure to high concentrations of the chemical. In the occupational setting, accidental discharge may occur, resulting in acute

Di-tert-butyl-chlorido(N,N-dibenzyl-dithio-carbamato)tin(IV).

PubMed

Abdul Muthalib, Amirah Faizah; Baba, Ibrahim; Mohamed Tahir, Mohamed Ibrahim; Tiekink, Edward R T

2011-02-26

The Sn(IV) atom in the title diorganotin dithio-carbamate, [Sn(C(4)H(9))(2)(C(15)H(14)NS(2))Cl], is penta-coordinated by an asymmetrically coordinating dithio-carbamate ligand, a Cl atom and two C atoms of the Sn-bound tert-butyl groups. The resulting C(2)ClS(2) donor set defines a coordination geometry inter-mediate between square pyramidal and trigonal bipyramidal with a slight tendency towards the former.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels.

PubMed

Vyas, N B; Thiele, L A; Garland, S C

1998-07-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6-189.0 ppm) or carbofuran (31.7-253.6 ppm) via meatballs. Carbofuran-exposed owls ate either < or = 10% or > or = 80% of the meatball whereas all kestrels ate < or = 10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (< 10-100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P < 0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P = 0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels

USGS Publications Warehouse

Vyas, N.B.; Thiele, L.A.; Garland, S.C.

1998-01-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6–189.0 ppm) or carbofuran (31.7–253.6 ppm) via meatballs. Carbofuran-exposed owls ate either ≤10% or ≥80% of the meatball whereas all kestrels ate ≤10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (<10–100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P<0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P=0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Removal of carbamates and detoxification potential in a biomixture: Fungal bioaugmentation versus traditional use.

PubMed

Rodríguez-Rodríguez, Carlos E; Madrigal-León, Karina; Masís-Mora, Mario; Pérez-Villanueva, Marta; Chin-Pampillo, Juan Salvador

2017-01-01

The use of fungal bioaugmentation represents a promising way to improve the performance of biomixtures for the elimination of pesticides. The ligninolyitc fungus Trametes versicolor was employed for the removal of three carbamates (aldicarb, ALD; methomyl, MTM; and methiocarb, MTC) in defined liquid medium; in this matrix ALD and MTM showed similar half-lives (14d), nonetheless MTC exhibited a faster removal, with a half-life of 6.5d. Then the fungus was employed in the bioaugmentation of an optimized biomixture to remove the aforementioned carbamates plus carbofuran (CFN). Bioaugmented and non-bioaugmented systems removed over 99% ALD and MTM after 8d of treatment, nonetheless a slight initial delay in the removal was observed in the bioaugmented biomixtures (removal after 3d: ALD 87%/97%; MTM 86%/99%, in bioaugmented/non-bioaugmented systems). The elimination of the other carbamates was slower, but independent of the presence of the fungus: >98% for MTM after 35d and >99.5% for CFN after 22d. Though the bioaugmentation did not improve the removal capacity of the biomixture, it favored a lower production of transformation products at the first stages of the treatment, and in both cases, a marked decrease in the toxicity of the matrix was swiftly achieved along the process (from 435 to 448 TU to values <1TU in 16d). Copyright © 2016 Elsevier Inc. All rights reserved.

Optimization of microwave-assisted extraction and supercritical fluid extraction of carbamate pesticides in soil by experimental design methodology.

PubMed

Sun, Lei; Lee, Hian Kee

2003-10-03

Orthogonal array design (OAD) was applied for the first time to optimize microwave-assisted extraction (MAE) and supercritical fluid extraction (SFE) conditions for the analysis of four carbamates (propoxur, propham, methiocarb, chlorpropham) from soil. The theory and methodology of a new OA16 (4(4)) matrix derived from a OA16 (2(15)) matrix were developed during the MAE optimization. An analysis of variance technique was employed as the data analysis strategy in this study. Determinations of analytes were completed using high-performance liquid chromatography (HPLC) with UV detection. Four carbamates were successfully extracted from soil with recoveries ranging from 85 to 105% with good reproducibility (approximately 4.9% RSD) under the optimum MAE conditions: 30 ml methanol, 80 degrees C extraction temperature, and 6-min microwave heating. An OA8 (2(7)) matrix was employed for the SFE optimization. The average recoveries and RSD of the analytes from spiked soil by SFE were 92 and 5.5%, respectively except for propham (66.3+/-7.9%), under the following conditions: heating for 30 min at 60 degrees C under supercritical CO2 at 300 kg/cm2 modified with 10% (v/v) methanol. The composition of the supercritical fluid was demonstrated to be a crucial factor in the extraction. The addition of a small volume (10%) of methanol to CO2 greatly enhanced the recoveries of carbamates. A comparison of MAE with SFE was also conducted. The results indicated that >85% average recoveries were obtained by both optimized extraction techniques, and slightly higher recoveries of three carbamates (propoxur, propham and methiocarb) were achieved using MAE. SFE showed slightly higher recovery for chlorpropham (93 vs. 87% for MAE). The effects of time-aged soil on the extraction of analytes were examined and the results obtained by both methods were also compared.

Synthesis and Evaluation of Novel RSK Inhibitors in a Living Human Breast Model

DTIC Science & Technology

2015-09-01

the n- propyl carbamate analogue 9, and the sec-butyl carbamate analogue 10. The modified synthetic route could also be applied to the synthesis of...AWARD NUMBER: W81XWH-11-1-0068 TITLE: Synthesis and Evaluation of Novel RSK Inhibitors in a Living Human Breast Model PRINCIPAL INVESTIGATOR...DATES COVERED 01 Jul 2011 – 30 Jun 2015 4. TITLE AND SUBTITLE Synthesis and Evaluation of Novel RSK Inhibitors in a Living Human Breast Model 5a

Protecting Group and Solvent Control of Stereo- and Chemoselectivity in Glucal 3-Carbamate Amidoglycosylation

PubMed Central

Gupta, Ritu; Sogi, Kimberly M.; Bernard, Sarah E.; Decatur, John D.; Rojas, Christian M.

2009-01-01

In the Rh2(OAc)4-catalyzed amidoglycosylation of glucal 3-carbamates, anomeric stereoselectivity and the extent of competing C3–H oxidation depend on the 4O and 6O protecting groups. Acyclic protection permits high α-anomer selectivity with further improvement in less polar solvents, while electron-withdrawing protecting groups limit C3-oxidized byproducts. Stereocontrol and bifurcation between alkene insertion and C3–H oxidation reflect an interplay of conformational, stereoelectronic, and inductive factors. PMID:19254041

Di-tert-butyl­chlorido(N,N-dibenzyl­dithio­carbamato)tin(IV)

PubMed Central

Abdul Muthalib, Amirah Faizah; Baba, Ibrahim; Mohamed Tahir, Mohamed Ibrahim; Tiekink, Edward R. T.

2011-01-01

The SnIV atom in the title diorganotin dithio­carbamate, [Sn(C4H9)2(C15H14NS2)Cl], is penta­coordinated by an asymmetrically coordinating dithio­carbamate ligand, a Cl atom and two C atoms of the Sn-bound tert-butyl groups. The resulting C2ClS2 donor set defines a coordination geometry inter­mediate between square pyramidal and trigonal bipyramidal with a slight tendency towards the former. PMID:21522304

Heterologous expression of the methyl carbamate-degrading hydrolase MCD.

PubMed

Naqvi, Tatheer; Cheesman, Matthew J; Williams, Michelle R; Campbell, Peter M; Ahmed, Safia; Russell, Robyn J; Scott, Colin; Oakeshott, John G

2009-10-26

The methyl carbamate-degrading hydrolase (MCD) of Achromobacter WM111 has considerable potential as a pesticide bioremediation agent. However this potential has been unrealisable until now because of an inability to express MCD in heterologous hosts such as Escherichia coli. Herein, we describe the first successful attempt to express appreciable quantities of MCD in active form in E. coli, and the subsequent characterisation of the heterologously expressed material. We find that the properties of this material closely match the previously reported properties of MCD produced from Achromobacter WM111. This includes the presence of two distinct forms of the enzyme that we show are most likely due to the presence of two functional translational start sites. The purified enzyme catalyses the hydrolysis of a carbamate (carbaryl), a carboxyl ester (alpha-naphthyl acetate) and a phophotriester (dimethyl umbelliferyl phosphate) and it is relatively resistant to thermal and solvent-mediated denaturation. The robust nature and catalytic promiscuity of MCD suggest that it could be exploited for various biotechnological applications.

Blackberry subjected to in vitro gastrointestinal digestion affords protection against Ethyl Carbamate-induced cytotoxicity.

PubMed

Chen, Wei; Xu, Yang; Zhang, Lingxia; Su, Hongming; Zheng, Xiaodong

2016-12-01

Ethyl Carbamate (EC) was detected in many fermented foods. Previous studies indicated that frequent exposure to ethyl carbamate may increase the risk to suffer from cancers. Blackberry is rich in polyphenols and possesses potent antioxidant activity. This study aims to investigate the protective effect of blackberry homogenates produced before (BH) and after in vitro simulated gastrointestinal digestion (BD) on EC-induced toxicity in Caco-2 cells. Our results showed that blackberry homogenates after digestion (BD) was more effective than that before digestion (BH) in ameliorating EC-induced toxicity in Caco-2 cells. Further investigation revealed that BD remarkably attenuated EC-induced toxicity through restoring mitochondrial function, inhibiting glutathione depletion and decreasing overproduction of intracellular reactive oxygen species. Additionally, LC-MS result implied that the better protective capacity of BD may be related to the increased content of two anthocyanins (cyanidin-3-glucoside and cyanidin-3-dioxalyglucoside). Overall, the present study may give implication to prevent EC-induced health problem. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative Inhibition Study of Compounds Identified in the Methanolic Extract of Apamarga Kshara Against Trichomonas vaginalis Carbamate Kinase (TvCK): An Enzoinformatics Approach.

PubMed

Shaikh, Sibhghatulla; Aaqil, Hamida; Rizvi, Syed Mohd Danish; Shakil, Shazi; Abuzenadah, Adel M; Gupta, Pragya; Saxena, Soumya; Tiwari, Rohit Kr; Kumar, Ajai

2016-12-01

In the present study, we have identified ten compounds, namely dodecanol acid, myristic acid, neophytadiene, palmitic acid, heptadecanoic acid, linoleic acid, elaidic acid, 3-7-dimethyl acid, stearic acid and methyl eicos acid, of the methanolic extract of Apamarga Kshara by GC-MS analysis. Apamarga Kshara has been reported to be active against cervical erosion. Major causal organism for cervical erosion is Trichomonas vaginalis. However, there is a paucity of information about the mechanism of action and inhibitory effect of the biologically active natural compounds presented in A. Kshara against this organism (T. vaginalis). Therefore, present investigation was conducted to observe possible interactions of these compounds on T. vaginalis carbamate kinase using molecular docking software 'AutoDock 4.2.' Identification of the amino acid residues crucial for the interaction between T. vaginalis carbamate kinase and these natural compounds is of due scientific interest. The study will aid in efficacious and safe clinical use of the above-mentioned compounds.

Efficient hydrogenation of organic carbonates, carbamates and formates indicates alternative routes to methanol based on CO2 and CO

NASA Astrophysics Data System (ADS)

Balaraman, Ekambaram; Gunanathan, Chidambaram; Zhang, Jing; Shimon, Linda J. W.; Milstein, David

2011-08-01

Catalytic hydrogenation of organic carbonates, carbamates and formates is of significant interest both conceptually and practically, because these compounds can be produced from CO2 and CO, and their mild hydrogenation can provide alternative, mild approaches to the indirect hydrogenation of CO2 and CO to methanol, an important fuel and synthetic building block. Here, we report for the first time catalytic hydrogenation of organic carbonates to alcohols, and carbamates to alcohols and amines. Unprecedented homogeneously catalysed hydrogenation of organic formates to methanol has also been accomplished. The reactions are efficiently catalysed by dearomatized PNN Ru(II) pincer complexes derived from pyridine- and bipyridine-based tridentate ligands. These atom-economical reactions proceed under neutral, homogeneous conditions, at mild temperatures and under mild hydrogen pressures, and can operate in the absence of solvent with no generation of waste, representing the ultimate ‘green’ reactions. A possible mechanism involves metal-ligand cooperation by aromatization-dearomatization of the heteroaromatic pincer core.

Development of a simple and low-cost enzymatic methodology for quantitative analysis of carbamates in meat samples of forensic interest.

PubMed

Sabino, Bruno Duarte; Torraca, Tathiana Guilliod; Moura, Claudia Melo; Rozenbaum, Hannah Felicia; de Castro Faria, Mauro Velho

2010-05-01

Foods contaminated with a granulated material similar to Temik (a commercial pesticide formulation containing the carbamate insecticide aldicarb) are often involved in accidental ingestion, suicides, and homicides in Brazil. We developed a simple technique to detect aldicarb. This technique is based on the inhibition of a stable preparation of the enzyme acetylcholinesterase, and it is specially adapted for forensic purposes. It comprises an initial extraction step with the solvent methylene chloride followed by a colorimetric acetylcholinesterase assay. We propose that results of testing contaminated forensic samples be expressed in aldicarb equivalents because, even though all other carbamates are also potent enzyme inhibitors, aldicarb is the contaminant most frequently found in forensic samples. This method is rapid (several samples can be run in a period of 2 h) and low cost. This method also proved to be precise and accurate, detecting concentrations as low as 40 microg/kg of aldicarb in meat samples.

Efficient hydrogenation of organic carbonates, carbamates and formates indicates alternative routes to methanol based on CO2 and CO.

PubMed

Balaraman, Ekambaram; Gunanathan, Chidambaram; Zhang, Jing; Shimon, Linda J W; Milstein, David

2011-07-22

Catalytic hydrogenation of organic carbonates, carbamates and formates is of significant interest both conceptually and practically, because these compounds can be produced from CO2 and CO, and their mild hydrogenation can provide alternative, mild approaches to the indirect hydrogenation of CO2 and CO to methanol, an important fuel and synthetic building block. Here, we report for the first time catalytic hydrogenation of organic carbonates to alcohols, and carbamates to alcohols and amines. Unprecedented homogeneously catalysed hydrogenation of organic formates to methanol has also been accomplished. The reactions are efficiently catalysed by dearomatized PNN Ru(II) pincer complexes derived from pyridine- and bipyridine-based tridentate ligands. These atom-economical reactions proceed under neutral, homogeneous conditions, at mild temperatures and under mild hydrogen pressures, and can operate in the absence of solvent with no generation of waste, representing the ultimate 'green' reactions. A possible mechanism involves metal-ligand cooperation by aromatization-dearomatization of the heteroaromatic pincer core.

Multiresidue method for N-methyl carbamates and metabolite pesticide residues at the parts-per-billion level in selected representative commodities of fruit and vegetable crop groups.

PubMed

Podhorniak, Lynda V; Schenck, Frank J; Krynitsky, Alexander; Griffith, Francis

2004-01-01

A reversed-phase liquid chromatographic method with both fluorescence and mass spectrometric detection is presented for the determination of 13 parent N-methyl carbamate pesticides and their metabolites, as well as piperonyl butoxide, for a total of 24 compounds in selected fruits and vegetables. The commodities chosen were of special concern to the U.S. Environmental Protection Agency (EPA) because they had the least amount of monitoring data for dietary exposure estimates used in risk assessment. The method is based on a judicious selection of procedures from U.S. Food and Drug Administration sources such as the Pesticide Analytical Manual (Volume I), and Laboratory Information Bulletins, plus additional material from the chemical literature combined in a manner to recover the N-methyl carbamates and their metabolites at the 1 microg/kg or 1 part-per-billion level. The method uses an acetone extraction, followed by an aminopropyl solid-phase extraction cleanup. Determination of residues is by RP-LC, in which the liquid chromatograph is interfaced with either a fluorescence or a mass spectrometric detector. The method is designed so that a set of 6 samples can be prepared in 1 working day for overnight instrumental analysis. Recovery data are presented from analyses of selected commodities in some of EPA's fruit and vegetable crop groupings. A table listing relative retention times is presented for the N-methyl carbamates and their metabolites.

Sequential injection-bead injection-lab-on-valve coupled to high-performance liquid chromatography for online renewable micro-solid-phase extraction of carbamate residues in food and environmental samples.

PubMed

Vichapong, Jitlada; Burakham, Rodjana; Srijaranai, Supalax; Grudpan, Kate

2011-07-01

A sequential injection-bead injection-lab-on-valve system was hyphenated to HPLC for online renewable micro-solid-phase extraction of carbamate insecticides. The carbamates studied were isoprocarb, methomyl, carbaryl, carbofuran, methiocarb, promecarb, and propoxur. LiChroprep(®) RP-18 beads (25-40 μm) were employed as renewable sorbent packing in a microcolumn situated inside the LOV platform mounted above the multiposition valve of the sequential injection system. The analytes sorbed by the microcolumn were eluted using 80% acetonitrile in 0.1% acetic acid before online introduction to the HPLC system. Separation was performed on an Atlantis C-18 column (4.6 × 150 mm, 5 μm) utilizing gradient elution with a flow rate of 1.0 mL/min and a detection wavelength at 270 nm. The sequential injection system offers the means of performing automated handling of sample preconcentration and matrix removal. The enrichment factors ranged between 20 and 125, leading to limits of detection (LODs) in the range of 1-20 μg/L. Good reproducibility was obtained with relative standard deviations of <0.7 and 5.4% for retention time and peak area, respectively. The developed method has been successfully applied to the determination of carbamate residues in fruit, vegetable, and water samples. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relative bioavailability of generic and branded 250-mg and 500-mg oral chlorphenesin carbamate tablets in healthy Korean volunteers: a single-dose, randomized-sequence, open-label, two-period crossover trial.

PubMed

Yu, Ji-young; Song, Hyun Ho; Kim, Bo Gyeom; Park, Hyeon Ju; Choi, Kwang Sik; Kwon, Young Ee

2009-11-01

Chlorphenesin carbamate is a skeletal muscle relaxant approved in Korea for use in the treatment of pain and discomfort related to skeletal muscle trauma and inflammation. The aim of this study was to assess the bioequivalence of a generic formulation of chlorphenesin carbamate at doses of 250 and 500 mg and 2 branded formulations of the same doses in healthy Korean adults. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Korean male and female volunteers. Subjects were assigned to receive, in a randomized sequence, a single dose of the generic (test) and branded (reference) formulations of chlorphenesin carbamate at a dose of 250 or 500 mg. Blood samples were drawn at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, and 15 hours after administration. Pharmacokinetic properties (C(max), T(max), AUC(0-t) AUC(0-infinity), t(1/2), and ke) were determined using HPLC. The formulations were to be considered bioequivalent if the 90% CIs of the treatment ratios of the geometric means of C(max) and AUC(0-t) were within a predetermined range of log 0.80 to log 1.25 based on regulatory criteria. Tolerability was assessed by monitoring for adverse events (AEs) on physical examination and/or e-mail and personal interview at the beginning and end of each study period. Twenty-eight subjects (22 men, 6 women) received chlorphenesin carbamate at the 250-mg dose, and 24 male subjects received the 500-mg dose. The mean (SD) ages of the subjects were 24.0 (2.6) and 24.0 (1.9) years in the 250- and 500-mg groups, respectively. No significant differences were found between the test and reference formulations (90% CIs: C(max), 1.0048-1.1153 with the 250-mg dose and 0.9630-1.1189 with the 500-mg dose; AUC(0-t), 0.9882-1.0546 and 0.9842-1.0578, respectively). No clinically significant AEs (upper gastric pain, abdominal bloating, pyrexia, edema, nausea, heartburn, constipation, headache, dizziness, drowsiness, or fatigue) were reported throughout the study. In this single-dose study in these healthy Korean subjects, the generic and branded formulations of chlorphenesin carbamate 250 and 500 mg met the regulatory criteria for bioequivalence. All formulations were well tolerated. Copyright 2009 Excerpta Medica Inc. All rights reserved.

A four-component coupling reaction of carbon dioxide, amines, cyclic ethers and 3-triflyloxybenzynes for the synthesis of functionalized carbamates.

PubMed

Xiong, Wenfang; Qi, Chaorong; Cheng, Ruixiang; Zhang, Hao; Wang, Lu; Yan, Donghao; Jiang, Huanfeng

2018-04-27

A novel four-component coupling reaction of carbon dioxide, amines, cyclic ethers and 3-triflyloxybenzynes has been developed for the first time, providing an efficient method for the synthesis of a series of functionalized carbamate derivatives in moderate to high yields. The process proceeds under mild, transition metal-free and fluoride-free conditions, leading to the formation of two new C-O bonds, one new C-N bond and one C-H bond in a single step.

(N-Benzyl-N-ethyl-dithio-carbamato)di-tert-butyl-chloridotin(IV).

PubMed

Abdul Muthalib, Amirah Faizah; Baba, Ibrahim; Mohamed Tahir, Mohamed Ibrahim; Tiekink, Edward R T

2011-02-26

The Sn(IV) atom in the title diorganotin dithio-carbamate, [Sn(C(4)H(9))(2)Cl(C(10)H(12)NS(2))], is penta-coordinated by an asymmetrically coordinating dithio-carbamate ligand, a Cl and two C atoms of the Sn-bound tert-butyl groups. The resulting C(2)ClS(2) donor set defines a coordination geometry inter-mediate between square pyramidal and trigonal bipyramidal with a slight tendency towards the former. In the crystal structure, C-H⋯π contacts link centrosymmetrically related mol-ecules into dimeric aggregates.

CYP6 P450 enzymes and ACE-1 duplication produce extreme and multiple insecticide resistance in the malaria mosquito Anopheles gambiae.

PubMed

Edi, Constant V; Djogbénou, Luc; Jenkins, Adam M; Regna, Kimberly; Muskavitch, Marc A T; Poupardin, Rodolphe; Jones, Christopher M; Essandoh, John; Kétoh, Guillaume K; Paine, Mark J I; Koudou, Benjamin G; Donnelly, Martin J; Ranson, Hilary; Weetman, David

2014-03-01

Malaria control relies heavily on pyrethroid insecticides, to which susceptibility is declining in Anopheles mosquitoes. To combat pyrethroid resistance, application of alternative insecticides is advocated for indoor residual spraying (IRS), and carbamates are increasingly important. Emergence of a very strong carbamate resistance phenotype in Anopheles gambiae from Tiassalé, Côte d'Ivoire, West Africa, is therefore a potentially major operational challenge, particularly because these malaria vectors now exhibit resistance to multiple insecticide classes. We investigated the genetic basis of resistance to the most commonly-applied carbamate, bendiocarb, in An. gambiae from Tiassalé. Geographically-replicated whole genome microarray experiments identified elevated P450 enzyme expression as associated with bendiocarb resistance, most notably genes from the CYP6 subfamily. P450s were further implicated in resistance phenotypes by induction of significantly elevated mortality to bendiocarb by the synergist piperonyl butoxide (PBO), which also enhanced the action of pyrethroids and an organophosphate. CYP6P3 and especially CYP6M2 produced bendiocarb resistance via transgenic expression in Drosophila in addition to pyrethroid resistance for both genes, and DDT resistance for CYP6M2 expression. CYP6M2 can thus cause resistance to three distinct classes of insecticide although the biochemical mechanism for carbamates is unclear because, in contrast to CYP6P3, recombinant CYP6M2 did not metabolise bendiocarb in vitro. Strongly bendiocarb resistant mosquitoes also displayed elevated expression of the acetylcholinesterase ACE-1 gene, arising at least in part from gene duplication, which confers a survival advantage to carriers of additional copies of resistant ACE-1 G119S alleles. Our results are alarming for vector-based malaria control. Extreme carbamate resistance in Tiassalé An. gambiae results from coupling of over-expressed target site allelic variants with heightened CYP6 P450 expression, which also provides resistance across contrasting insecticides. Mosquito populations displaying such a diverse basis of extreme and cross-resistance are likely to be unresponsive to standard insecticide resistance management practices.

Is oxygen required before atropine administration in organophosphorus or carbamate pesticide poisoning? – A cohort study

PubMed Central

Konickx, L. A.; Bingham, K.

2014-01-01

Background Early and adequate atropine administration in organophosphorus (OP) or carbamate insecticide poisoning improves outcome. However, some authors advise that oxygen must be given before atropine due to the risk of inducing ventricular dysrhythmias in hypoxic patients. Because oxygen is frequently unavailable in district hospitals of rural Asia, where the majority of patients with insecticide poisoning present, this guidance has significant implications for patient care. The published evidence for this advice is weak. We therefore performed a patient cohort analysis to look for early cardiac deaths in patients poisoned by anticholinesterase pesticides. Methods We analysed a prospective Sri Lankan cohort of OP or carbamate-poisoned patients treated with early atropine without the benefit of oxygen for evidence of early deaths. The incidence of fatal primary cardiac arrests within 3 h of admission was used as a sensitive (but non-specific) marker of possible ventricular dysrhythmias. Results The cohort consisted of 1957 patients. The incidence of a primary cardiac death within 3 h of atropine administration was 4 (0.2%) of 1957 patients. The majority of deaths occurred at a later time point from respiratory complications of poisoning. Conclusion We found no evidence of a high number of early deaths in an observational study of 1957 patients routinely given atropine before oxygen that might support guidance that oxygen must be given before atropine. The published literature indicates that early and rapid administration of atropine during resuscitation is life-saving. Therefore, whether oxygen is available or not, early atropinisation of OP- and carbamate-poisoned patients should be performed. PMID:24810796

Exposure of nonbreeding migratory shorebirds to cholinesterase-inhibiting contaminants in the western hemisphere

USGS Publications Warehouse

Strum, K.M.; Hooper, M.J.; Johnson, K.A.; Lanctot, Richard B.; Zaccagnini, M.E.; Sandercock, B.K.

2010-01-01

Migratory shorebirds frequently forage and roost in agricultural habitats, where they may be exposed to cholinesterase-inhibiting pesticides. Exposure to organophosphorus and carbamate compounds, common anti-cholinesterases, can cause sublethal effects, even death. To evaluate exposure of migratory shorebirds to organophosphorus and carbamates, we sampled birds stopping over during migration in North America and wintering in South America. We compared plasma cholinesterase activities and body masses of individuals captured at sites with no known sources of organophosphorus or carbamates to those captured in agricultural areas where agrochemicals were recommended for control of crop pests. In South America, plasma acetylcholinesterase and butyrylcholinesterase activity in Buff-breasted Sandpipers was lower at agricultural sites than at reference sites, indicating exposure to organophosphorus and carbamates. Results of plasma cholinesterase reactivation assays and foot-wash analyses were inconclusive. A meta-analysis of six species revealed no widespread effect of agricultural chemicals on cholinesterase activity. however, four of six species were negative for acetylcholinesterase and one of six for butyrylcholinesterase, indicating negative effects of pesticides on cholinesterase activity in a subset of shorebirds. Exposure to cholinesterase inhibitors can decrease body mass, but comparisons between treatments and hemispheres suggest that agrochemicals did not affect migratory shorebirds' body mass. Our study, one of the first to estimate of shorebirds' exposure to cholinesterase-inhibiting pesticides, suggests that shorebirds are being exposed to cholinesterase- inhibiting pesticides at specific sites in the winter range but not at migratory stopover sites. future research should examine potential behavioral effects of exposure and identify other potential sitesand levels of exposure. ?? The Cooper Ornithological Society 2010.

Design and synthesis of biotin analogues reversibly binding with streptavidin.

PubMed

Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

2015-04-01

Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carbamate-linked cationic lipids with different hydrocarbon chains for gene delivery.

PubMed

Shi, Jia; Yu, Shijun; Zhu, Jie; Zhi, Defu; Zhao, Yinan; Cui, Shaohui; Zhang, Shubiao

2016-05-01

A series of carbamate-linked cationic lipids containing saturated or unsaturated hydrocarbon chains and quaternary ammonium head were designed and synthesized. After recrystallization, carbamate-linked cationic lipids with high purity (over 95%) were obtained. The structures of these lipids were proved by IR spectrum, HR-ESI-MS, HPLC, (1)H NMR and (13)C NMR. The liposomes were prepared by using these cationic lipids and neutral lipid DOPE. Particle size and zeta-potential were studied to show that they were suitable for gene transfection. The DNA-bonding ability of C12:0, C14:0 and C18:1 cationic liposomes was much better than others. The results of transfection showed that hydrophobic chains of these lipids have great effects on their transfection activity. The lipids bearing C12:0, C14:0 saturated chains or C18:1 unsaturated chain showed relatively higher transfection efficiency and lower cytotoxicity. So these cationic lipids could be used as non-viral gene carriers for further studies. Copyright © 2016 Elsevier B.V. All rights reserved.

A Novel Way To Radiolabel Human Butyrylcholinesterase for Positron Emission Tomography through Irreversible Transfer of the Radiolabeled Moiety.

PubMed

Sawatzky, Edgar; Al-Momani, Ehab; Kobayashi, Ryohei; Higuchi, Takahiro; Samnick, Samuel; Decker, Michael

2016-07-19

The enzyme butyrylcholinesterase (BChE) is known to be involved in the detoxification of xenobiotics in blood plasma and is associated with the progress of neurodegenerative disorders, diabetes type 2, obesity, and diseases of the cardiovascular system. In the present study, we developed carbamate-based inhibitors serving as positron emission tomography (PET) radiotracers with (18) F and (11) C as radioisotopes to visualize BChE distribution. These inhibitors are radiolabeled at the carbamate site and transfer this moiety onto BChE, which thus results in covalent and permanent radiolabeling of the enzyme. There are no comparable radiotracers for cholinesterases described to date. By ex vivo autoradiography experiments on mice brain slices and kinetic investigations, selective and covalent transfer of the radiolabeled carbamate moiety onto BChE was proven. These tracers might provide high resolution of BChE distribution in vivo to enable investigations into the pathophysiological mechanisms of diseases associated with alterations in BChE occurrence. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Co(II), Ni(II) and Cu(II) complexes of methyl-5-(Phenylthio) benzimidazole-2-carbamate: Molecular structures, spectral and DFT calculations

NASA Astrophysics Data System (ADS)

Mansour, Ahmed M.; El Bakry, Eslam M.; Abdel-Ghani, Nour T.

2016-05-01

[Co(FBZ)2(H2O)]·2NO3·0.5H2O (1), [Ni(FBZ)2X2]·zH2O (X = Cl​-, z = 0.5 (2) and X = CH3COO-, z = 1 (3)) and [Cu(FBZ)2(H2O) (NO3)]·NO3·1.5H2O (4) (FBZ = methyl-5-(Phenylthio) benzimidazole-2-carbamate; Fenbendazole) complexes were synthesized and characterized by elemental analysis, thermal, IR, EPR, UV-Vis, magnetic and conductance measurements. Geometry optimization, molecular electrostatic potential maps and natural bond orbital analysis were carried out at DFT/B3LYP/6-31G∗ level of theory. FBZ behaves as a neutral bidentate ligand via the pyridine-type nitrogen of the benzimidazole moiety and the carbamate group. Three-step ionization with pKa values of 3.38, 4.06 and 10.07 were reported for FBZ. The coordination of FBZ to the metal ions led to an increase in the antibacterial activity against the tested Staphylococcus aureus and Escherichia coli bacteria.

Equilibrium Dynamics of β-N-Methylamino-L-Alanine (BMAA) and Its Carbamate Adducts at Physiological Conditions

PubMed Central

Zimmerman, David; Goto, Joy J.; Krishnan, Viswanathan V

2016-01-01

Elevated incidences of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia complex (ALS/PDC) is associated with β-methylamino-L-alanine (BMAA), a non-protein amino acid. In particular, the native Chamorro people living in the island of Guam were exposed to BMAA by consuming a diet based on the cycad seeds. Carbamylated forms of BMAA are glutamate analogues. The mechanism of neurotoxicity of the BMAA is not completely understood, and BMAA acting as a glutamate receptor agonist may lead to excitotoxicity that interferes with glutamate transport systems. Though the interaction of BMAA with bicarbonate is known to produce carbamate adducts, here we demonstrate that BMAA and its primary and secondary adducts coexist in solution and undergoes a chemical exchange among them. Furthermore, we determined the rates of formation/cleavage of the carbamate adducts under equilibrium conditions using two-dimensional proton exchange NMR spectroscopy (EXSY). The coexistence of the multiple forms of BMAA at physiological conditions adds to the complexity of the mechanisms by which BMAA functions as a neurotoxin. PMID:27513925

Simple, specific analysis of organophosphorus and carbamate pesticides in sediments using column extraction and gas chromatography

USGS Publications Warehouse

Belisle, A.A.; Swineford, D.M.

1988-01-01

A simple, specific procedure was developed for the analysis of organophosphorus and carbamate pesticides in sediment. The wet soil was mixed with anhydrous sodium sulfate to bind water and the residues were column extracted in acetone:methylene chloride (1:l,v/v). Coextracted water was removed by additional sodium sulfate packed below the sample mixture. The eluate was concentrated and analyzed directly by capillary gas chromatography using phosphorus and nitrogen specific detectors. Recoveries averaged 93 % for sediments extracted shortly after spiking, but decreased significantly as the samples aged.

40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 3.95×10−3 1.27×10−3 Busan 40 [Potassium N-hydroxymethyl -N- methyldithiocarbamate] 5.74×10−3 1.87×10−3 Busan 85 [Potassium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Butachlor 5.19×10−3 1.54×10−3 Captafol 4.24×10−6 1.31×10−6 Carbam-S [Sodium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Carbaryl 1.6×10...

40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 3.95×10−3 1.27×10−3 Busan 40 [Potassium N-hydroxymethyl -N- methyldithiocarbamate] 5.74×10−3 1.87×10−3 Busan 85 [Potassium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Butachlor 5.19×10−3 1.54×10−3 Captafol 4.24×10−6 1.31×10−6 Carbam-S [Sodium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Carbaryl 1.6×10...

(N-Benzyl-N-ethyl­dithio­carbamato)di-tert-butyl­chloridotin(IV)

PubMed Central

Abdul Muthalib, Amirah Faizah; Baba, Ibrahim; Mohamed Tahir, Mohamed Ibrahim; Tiekink, Edward R. T.

2011-01-01

The SnIV atom in the title diorganotin dithio­carbamate, [Sn(C4H9)2Cl(C10H12NS2)], is penta­coordinated by an asymmetrically coordinating dithio­carbamate ligand, a Cl and two C atoms of the Sn-bound tert-butyl groups. The resulting C2ClS2 donor set defines a coordination geometry inter­mediate between square pyramidal and trigonal bipyramidal with a slight tendency towards the former. In the crystal structure, C—H⋯π contacts link centrosymmetrically related mol­ecules into dimeric aggregates. PMID:21522295

Indoline-3-propionate and 3-aminopropyl carbamates reduce lung injury and pro-inflammatory cytokines induced in mice by LPS.

PubMed

Finkin-Groner, E; Moradov, D; Shifrin, H; Bejar, C; Nudelman, A; Weinstock, M

2015-02-01

In the search for safer and effective anti-inflammatory agents, we investigated the effect of methyl indoline-3-propionate and indoline-3-(3-aminopropyl) carbamates on LPS-induced lung injury and pro-inflammatory cytokines in mice. Their mechanism of action was determined in murine peritoneal macrophages. Lung injury was induced by intratracheal infusion of LPS and assessed by the change in lung weight and structure by light microscopy after staining by haematoxylin and eosin. In LPS-activated macrophages, MAPK proteins and IκBα were measured by Western blotting and the transcription factors, AP-1 and NF-κB by electromobility shift assay. Cytokines in the plasma and spleen of mice injected with LPS were measured by elisa-based assay. AN917 and AN680 (1-10 pM) decreased TNF-α protein in macrophages by inhibiting phosphorylation of p38 MAPK, IκBα degradation and activation of AP-1 and NF-κB without affecting cell viability. In vivo, these compounds (10 μmol · kg(-1)) markedly decreased lung injury induced by LPS and the elevation of TNF-α and IL-6 in lung, plasma and spleen. Activation of α-7nACh receptors contributed to the reduction of TNF-α by AN917, which inhibited AChE in the spleen by 35%. Indoline carbamates are potent inhibitors of pro-inflammatory mediators in murine macrophages and in mice injected with LPS, acting via the p38 MAPK, AP-1 and NF-κB cascades. Indirect α-7nACh receptor activation by AN917, through inhibition of AChE, contributes to its anti-inflammatory effect. Indoline carbamates may have therapeutic potential for lung injury and other diseases associated with chronic inflammation without causing immunosuppression. © 2014 The British Pharmacological Society.

Efficacy of Recommended Pre-Hospital Human Equivalent Doses of Atropine and Pralidoxime against the Toxic Effects of Carbamate Poisoning in the Hartley Guinea Pig

PubMed Central

Brittain, Matthew K.; McGarry, Kevin G.; Moyer, Robert A.; Babin, Michael C.; Jett, David A.; Platoff, Gennady E.; Yeung, David T.

2016-01-01

Purpose Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning [muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride (2-PAM Cl),], could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates. Methods A protective ratio study was conducted in guinea pigs to evaluate the efficacy of atropine and 2-PAM Cl. ChE activity was determined in both the blood and cerebral cortex.. Results Co-administration of atropine free base (0.4 mg/kg) and 2-PAM Cl (25.7 mg/kg) demonstrated protective ratios of 2 and 3 against aldicarb and methomyl, respectively, relative to saline. The data reported here show that this protection was primarily mediated by the action of atropine. The reactivator 2-PAM Cl had neither positive nor negative effects on survival. Both blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were significantly reduced at 15 minutes post-challenge but gradually returned to normal within 24 h. Analysis of cerebral cortex showed that BChE, but not AChE, activity was reduced in animals that succumbed prior to 24 h after challenge. Conclusion The results suggest that co-administration of atropine and 2-PAM Cl at the currently recommended human equivalent doses for use in the pre-hospital setting to treat organophosphorus nerve agent and pesticide poisoning would likely also be effective against aldicarb or methomyl poisoning. PMID:27102179

Effect of carbamate pesticides on perforin, granzymes A-B-3/K, and granulysin in human natural killer cells.

PubMed

Li, Qing; Kobayashi, Maiko; Kawada, Tomoyuki

2015-09-01

We previously found that ziram, a carbamate pesticide, significantly reduced perforin, granzyme A (GrA), granzyme B (GrB), granzyme 3/K (Gr3/K), and granulysin (GRN) levels in NK-92MI cells, a human natural killer (NK) cell line. To investigate whether other carbamate pesticides also show similar toxicity on human NK cells, we conducted further experiments with NK-92CI cells, a human NK cell line, using a more sensitive assay. We previously confirmed that NK-92CI cells express CD56, perforin, GrA, GrB, Gr3/K, and GRN and are highly cytotoxic to K562 cells in a chromium release assay, which are more sensitive to organophosphorus pesticides and ziram than the NK-92MI cell line. NK-92CI cells were treated with ziram, thiram, maneb, or carbaryl at various concentrations for 4-24 h at 37°C in vitro. Thereafter, intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN were determined by flow cytometry. It was found that all carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells in a dose-dependent manner. However, the strength of the effect differed among the pesticides, and the order was thiram > ziram > maneb > carbaryl. In addition, it was also found that the degree of the reductions differed among the five proteins, with perforin more sensitive to pesticides than GRN, GrA, GrB, and Gr3/K, and the order was perforin > GRN > Gr3/K ≒ GrA ≒ GrB. © The Author(s) 2015.

Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory; determination of selected carbamate pesticides in water by high-performance liquid chromatography

USGS Publications Warehouse

Werner, S.L.; Johnson, S.M.

1994-01-01

As part of its primary responsibility concerning water as a national resource, the U.S. Geological Survey collects and analyzes samples of ground water and surface water to determine water quality. This report describes the method used since June 1987 to determine selected total-recoverable carbamate pesticides present in water samples. High- performance liquid chromatography is used to separate N-methyl carbamates, N-methyl carbamoyloximes, and an N-phenyl carbamate which have been extracted from water and concentrated in dichloromethane. Analytes, surrogate compounds, and reference compounds are eluted from the analytical column within 25 minutes. Two modes of analyte detection are used: (1) a photodiode-array detector measures and records ultraviolet-absorbance profiles, and (2) a fluorescence detector measures and records fluorescence from an analyte derivative produced when analyte hydrolysis is combined with chemical derivatization. Analytes are identified and confirmed in a three-stage process by use of chromatographic retention time, ultraviolet (UV) spectral comparison, and derivatization/fluorescence detection. Quantitative results are based on the integration of single-wavelength UV-absorbance chromatograms and on comparison with calibration curves derived from external analyte standards that are run with samples as part of an instrumental analytical sequence. Estimated method detection limits vary for each analyte, depending on the sample matrix conditions, and range from 0.5 microgram per liter to as low as 0.01 microgram per liter. Reporting levels for all analytes have been set at 0.5 microgram per liter for this method. Corrections on the basis of percentage recoveries of analytes spiked into distilled water are not applied to values calculated for analyte concentration in samples. These values for analyte concentrations instead indicate the quantities recovered by the method from a particular sample matrix.

Suspected foodborne carbamate pesticide intoxications associated with ingestion of hydroponic cucumbers.

PubMed

Goes, E A; Savage, E P; Gibbons, G; Aaronson, M; Ford, S A; Wheeler, H W

1980-02-01

In the period April 1--15, 1977, nine residents of one Nebraska town experienced violent illnesses with short duration following ingestion of locally grown hydroponic cucumbers. Despite a thorough investigation, the etiologic agent of illness was not determined. From July 16--25, 1978, a second similar outbreak occurred in an adjacent city. Five individuals experienced illness similar to that which occurred in 1977, also following ingestion of hydroponic cucumbers grown at the same greenhouse involved in the 1977 outbreak. The carbamate insecticide, aldicarb, was detected in some cucumbers grown at the hydroponic greenhouse. The source of this chemical in the greenhouse could not be determined.

Teaching Old Compounds New Tricks: DDQ-Photocatalyzed C-H Amination of Arenes with Carbamates, Urea, and N-Heterocycles.

PubMed

Das, Somnath; Natarajan, Palani; König, Burkhard

2017-12-22

The C-H amination of benzene derivatives was achieved using DDQ as photocatalyst and BocNH 2 as the amine source under aerobic conditions and visible light irradiation. Electron-deficient and electron-rich benzenes react as substrates with moderate to good product yields. The amine scope of the reaction comprises Boc-amine, carbamates, pyrazoles, sulfonimides and urea. Preliminary mechanistic investigations indicate arene oxidation by the triplet of DDQ to radical cations with different electrophilicity and a charge transfer complex between the amine and DDQ as intermediate of the reaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural characterization of two novel potential anticholinesterasic agents

NASA Astrophysics Data System (ADS)

Oliveira, Paulo R.; Wiectzycosky, Franciele; Basso, Ernani A.; Gonçalves, Regina A. C.; Pontes, Rodrigo M.

2003-09-01

Two novel compounds with possible anticholinesterase activity have been synthesized containing a carbamate and a dimethylamine group in 1,2-positions of a cyclohexane ring ( cis and trans isomers). Conformer populations were established by a combination of NMR 1H coupling constant analysis and DFT (B3LYP/6-311+G(d,p)) calculations. 13C chemical shifts were calculated in order to confirm signal attributions. The cis isomer adopts a conformation in which the carbamate group lies at the axial position (>99%), whereas the trans isomer adopts a diequatorial arrangement (98%). These preferences have been explained in terms of syn-1,3-diaxial interactions of the individual groups.

Vortex-Assisted Dispersive Micro-Solid Phase Extraction Using CTAB-Modified Zeolite NaY Sorbent Coupled with HPLC for the Determination of Carbamate Insecticides.

PubMed

Salisaeng, Pawina; Arnnok, Prapha; Patdhanagul, Nopbhasinthu; Burakham, Rodjana

2016-03-16

A vortex-assisted dispersive micro-solid phase extraction (VA-D-μ-SPE) based on cetyltrimethylammonium bromide (CTAB)-modified zeolite NaY was developed for preconcentration of carbamate pesticides in fruits, vegetables, and natural surface water prior to analysis by high performance liquid chromatography with photodiode array detection. The small amounts of solid sorbent were dispersed in a sample solution, and extraction occurred by adsorption in a short time, which was accelerated by vortex agitation. Finally, the sorbents were filtered from the solution, and the analytes were subsequently desorbed using an appropriate solvent. Parameters affecting the VA-D-μ-SPE performance including sorbent amount, sample volume, desorption solvent ,and vortex time were optimized. Under the optimum condition, linear dynamic ranges were achieved between 0.004-24.000 mg kg(-1) (R(2) > 0.9946). The limits of detection (LODs) ranged from 0.004-4.000 mg kg(-1). The applicability of the developed procedure was successfully evaluated by the determination of the carbamate residues in fruits (dragon fruit, rambutan, and watermelon), vegetables (cabbage, cauliflower, and cucumber), and natural surface water.

Improved sample preparation for GC-MS-SIM analysis of ethyl carbamate in wine.

PubMed

Nóbrega, Ian C C; Pereira, Giuliano E; Silva, Marileide; Pereira, Elainy V S; Medeiros, Marcelo M; Telles, Danuza L; Albuquerque, Eden C; Oliveira, Juliane B; Lachenmeier, Dirk W

2015-06-15

An improved sample preparation procedure for analysis of carcinogenic ethyl carbamate (EC) in wine by GC-MS-SIM is proposed. Differences over AOAC reference procedure were: (1) use of EC-d5 as internal standard instead of less similar propyl carbamate; (2) extraction by diethyl ether instead of more toxic dichloromethane, and (3) concentration by vacuum automated parallel evaporation instead of more time and work consuming rotary evaporation. Mean recovery was 104.4%, intraday precision was 6.7% (3.4 μg L(-)(1)) and 1.7% (88.5 μg L(-)(1)), regression coefficient was 0.999 in the linear working range of 3-89 μg L(-)(1), and limits of detection and quantification were 0.4 and 1.2 μg L(-)(1). Applicability was demonstrated by analysis (in triplicate) of 5 wine samples. EC concentration ranged from 5.2 ± 0.2 to 29.4 ± 1.5 μg L(-)(1). The analytical method is selective, accurate, repeatable, linear, and has similar method performance as the reference method along with the several mentioned advantages. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel codrugs with GABAergic activity for dopamine delivery in the brain.

PubMed

Denora, Nunzio; Cassano, Tommaso; Laquintana, Valentino; Lopalco, Antonio; Trapani, Adriana; Cimmino, Concetta Stefania; Laconca, Leonardo; Giuffrida, Andrea; Trapani, Giuseppe

2012-11-01

This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period. These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Carbamate derivatives of indolines as cholinesterase inhibitors and antioxidants for the treatment of Alzheimer's disease.

PubMed

Yanovsky, Inessa; Finkin-Groner, Efrat; Zaikin, Andrey; Lerman, Lena; Shalom, Hila; Zeeli, Shani; Weill, Tehilla; Ginsburg, Isaac; Nudelman, Abraham; Weinstock, Marta

2012-12-13

The cascade of events that occurs in Alzheimer's disease involving oxidative stress and the reduction in cholinergic transmission can be better addressed by multifunctional drugs than cholinesterase inhibitors alone. For this purpose, we prepared a large number of derivatives of indoline-3-propionic acids and esters. They showed scavenging activity against different radicals in solution and significant protection against cytotoxicity in cardiomyocytes and primary cultures of neuronal cells exposed to H2O2 species and serum deprivation at concentrations ranging from 1 nM to 10 μM depending on the compound. For most of the indoline-3-propionic acid derivatives, introduction of N-methyl-N-ethyl or N-methyl-N-(4-methoxyphenyl) carbamate moieties at positions 4, 6, or 7 conferred both acetyl (AChE) and butyryl (BuChE) cholinesterase inhibitory activities at similar concentrations to those that showed antioxidant activity. The most potent AChE inhibitors were 120 (3-(2-aminoethyl) indolin-4-yl ethyl(methyl)carbamate dihydrochloride) and 94 (3-(3-methoxy-3-oxopropyl)-4-(((4-methoxyphenyl)(methyl) carbamoyl)oxy)indolin-1-ium hydrochloride) with IC50s of 0.4 and 1.2 μM, respectively.

Quantitative structure-activity relationship (QSAR) for insecticides: development of predictive in vivo insecticide activity models.

PubMed

Naik, P K; Singh, T; Singh, H

2009-07-01

Quantitative structure-activity relationship (QSAR) analyses were performed independently on data sets belonging to two groups of insecticides, namely the organophosphates and carbamates. Several types of descriptors including topological, spatial, thermodynamic, information content, lead likeness and E-state indices were used to derive quantitative relationships between insecticide activities and structural properties of chemicals. A systematic search approach based on missing value, zero value, simple correlation and multi-collinearity tests as well as the use of a genetic algorithm allowed the optimal selection of the descriptors used to generate the models. The QSAR models developed for both organophosphate and carbamate groups revealed good predictability with r(2) values of 0.949 and 0.838 as well as [image omitted] values of 0.890 and 0.765, respectively. In addition, a linear correlation was observed between the predicted and experimental LD(50) values for the test set data with r(2) of 0.871 and 0.788 for both the organophosphate and carbamate groups, indicating that the prediction accuracy of the QSAR models was acceptable. The models were also tested successfully from external validation criteria. QSAR models developed in this study should help further design of novel potent insecticides.

Sources and Fates of Carbamyl Phosphate: A Labile Energy-Rich Molecule with Multiple Facets.

PubMed

Shi, Dashuang; Caldovic, Ljubica; Tuchman, Mendel

2018-06-12

Carbamyl phosphate (CP) is well-known as an essential intermediate of pyrimidine and arginine/urea biosynthesis. Chemically, CP can be easily synthesized from dihydrogen phosphate and cyanate. Enzymatically, CP can be synthesized using three different classes of enzymes: (1) ATP-grasp fold protein based carbamyl phosphate synthetase (CPS); (2) Amino-acid kinase fold carbamate kinase (CK)-like CPS (anabolic CK or aCK); and (3) Catabolic transcarbamylase. The first class of CPS can be further divided into three different types of CPS as CPS I, CPS II, and CPS III depending on the usage of ammonium or glutamine as its nitrogen source, and whether N -acetyl-glutamate is its essential co-factor. CP can donate its carbamyl group to the amino nitrogen of many important molecules including the most well-known ornithine and aspartate in the arginine/urea and pyrimidine biosynthetic pathways. CP can also donate its carbamyl group to the hydroxyl oxygen of a variety of molecules, particularly in many antibiotic biosynthetic pathways. Transfer of the carbamyl group to the nitrogen group is catalyzed by the anabolic transcarbamylase using a direct attack mechanism, while transfer of the carbamyl group to the oxygen group is catalyzed by a different class of enzymes, CmcH/NodU CTase, using a different mechanism involving a three-step reaction, decomposition of CP to carbamate and phosphate, transfer of the carbamyl group from carbamate to ATP to form carbamyladenylate and pyrophosphate, and transfer of the carbamyl group from carbamyladenylate to the oxygen group of the substrate. CP is also involved in transferring its phosphate group to ADP to generate ATP in the fermentation of many microorganisms. The reaction is catalyzed by carbamate kinase, which may be termed as catabolic CK (cCK) in order to distinguish it from CP generating CK. CP is a thermally labile molecule, easily decomposed into phosphate and cyanate, or phosphate and carbamate depending on the pH of the solution, or the presence of enzyme. Biological systems have developed several mechanisms including channeling between enzymes, increased affinity of CP to enzymes, and keeping CP in a specific conformation to protect CP from decomposition. CP is highly important for our health as both a lack of, or decreased, CP production and CP accumulation results in many disease conditions.

Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides.

PubMed

Gómez-Sanchez, Elena; Soriano, Elena; Marco-Contelles, José

2007-11-09

We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.

Combating highly resistant emerging pathogen Mycobacterium abscessus and Mycobacterium tuberculosis with novel salicylanilide esters and carbamates.

PubMed

Baranyai, Zsuzsa; Krátký, Martin; Vinšová, Jarmila; Szabó, Nóra; Senoner, Zsuzsanna; Horváti, Kata; Stolaříková, Jiřina; Dávid, Sándor; Bősze, Szilvia

2015-08-28

In the Mycobacterium genus over one hundred species are already described and new ones are periodically reported. Species that form colonies in a week are classified as rapid growers, those requiring longer periods (up to three months) are the mostly pathogenic slow growers. More recently, new emerging species have been identified to lengthen the list, all rapid growers. Of these, Mycobacterium abscessus is also an intracellular pathogen and it is the most chemotherapy-resistant rapid-growing mycobacterium. In addition, the cases of multidrug-resistant Mycobacterium tuberculosis infection are also increasing. Therefore there is an urgent need to find new active molecules against these threatening strains. Based on previous results, a series of salicylanilides, salicylanilide 5-chloropyrazinoates and carbamates was designed, synthesized and characterised. The compounds were evaluated for their in vitro activity on M. abscessus, susceptible M. tuberculosis H37Rv, multidrug-resistant (MDR) M. tuberculosis MDR A8, M. tuberculosis MDR 9449/2006 and on the extremely-resistant Praha 131 (XDR) strains. All derivatives exhibited a significant activity with minimum inhibitory concentrations (MICs) in the low micromolar range. Eight salicylanilide carbamates and two salicylanilide esters exhibited an excellent in vitro activity on M. abscessus with MICs from 0.2 to 2.1 μM, thus being more effective than ciprofloxacin and gentamicin. This finding is potentially promising, particularly, as M. abscessus is a threateningly chemotherapy-resistant species. M. tuberculosis H37Rv was inhibited with MICs from 0.2 μM, and eleven compounds have lower MICs than isoniazid. Salicylanilide esters and carbamates were found that they were effective also on MDR and XDR M. tuberculosis strains with MICs ≥1.0 μM. The in vitro cytotoxicity (IC50) was also determined on human MonoMac-6 cells, and selectivity index (SI) of the compounds was established. In general, salicylanilide derivatives substituted by halogens on both salicyl and aniline rings showed better activity, than 4-benzoylaniline derivatives. The ester or carbamate bond formation of parent salicylanilides mostly retained or improved antimycobacterial potency with moderate selectivity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Designed amyloid fibers as materials for selective carbon dioxide capture

PubMed Central

Li, Dan; Furukawa, Hiroyasu; Deng, Hexiang; Liu, Cong; Yaghi, Omar M.; Eisenberg, David S.

2014-01-01

New materials capable of binding carbon dioxide are essential for addressing climate change. Here, we demonstrate that amyloids, self-assembling protein fibers, are effective for selective carbon dioxide capture. Solid-state NMR proves that amyloid fibers containing alkylamine groups reversibly bind carbon dioxide via carbamate formation. Thermodynamic and kinetic capture-and-release tests show the carbamate formation rate is fast enough to capture carbon dioxide by dynamic separation, undiminished by the presence of water, in both a natural amyloid and designed amyloids having increased carbon dioxide capacity. Heating to 100 °C regenerates the material. These results demonstrate the potential of amyloid fibers for environmental carbon dioxide capture. PMID:24367077

A survey of levels of ethyl carbamate in alcoholic beverages in 2009-2012, Hebei Province, China.

PubMed

Liu, Yinping; Wang, Shuhui; Hu, Ping

2013-01-01

Results of a survey of levels of ethyl carbamate (EC) (urethane) in alcoholic beverages carried out in four successive years from 2009 to 2012 by gas chromatography-mass spectrometry (GC/MS) are presented. The beverages were purchased for sampling from Hebei Province of China, including eight main areas of production. The samples comprised wines (n = 212), grain spirits (n = 143) and wine sauces (n = 164). The data show that the average EC content in these kinds of alcoholic beverages remains nearly constant over the years. The results provide valuable data for food authorities to establish maximum limits for EC in China.

Ground-State Distortion in N-Acyl-tert-butyl-carbamates (Boc) and N-Acyl-tosylamides (Ts): Twisted Amides of Relevance to Amide N-C Cross-Coupling.

PubMed

Szostak, Roman; Shi, Shicheng; Meng, Guangrong; Lalancette, Roger; Szostak, Michal

2016-09-02

Amide N-C(O) bonds are generally unreactive in cross-coupling reactions employing low-valent transition metals due to nN → π*C═O resonance. Herein we demonstrate that N-acyl-tert-butyl-carbamates (Boc) and N-acyl-tosylamides (Ts), two classes of acyclic amides that have recently enabled the development of elusive amide bond N-C cross-coupling reactions with organometallic reagents, are intrinsically twisted around the N-C(O) axis. The data have important implications for the design of new amide cross-coupling reactions with the N-C(O) amide bond cleavage as a key step.

40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

Code of Federal Regulations, 2014 CFR

2014-07-01

...×10−3 1.87×10−3 Busan 85 [Potassium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Butachlor 5.19×10−3 1.54×10−3 Captafol 4.24×10−6 1.31×10−6 Carbam-S [Sodium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Carbaryl 1.6×10−3 7.3×10−4 Carbofuran 1.18×10−4 2.80×10−5 Chloroneb 8.16×10−2 3.31×10−2 Chlorothalonil 1.51...

40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

Code of Federal Regulations, 2012 CFR

2012-07-01

...×10−3 1.87×10−3 Busan 85 [Potassium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Butachlor 5.19×10−3 1.54×10−3 Captafol 4.24×10−6 1.31×10−6 Carbam-S [Sodium dimethyldithiocarbamate] 5.74×10−3 1.87×10−3 Carbaryl 1.6×10−3 7.3×10−4 Carbofuran 1.18×10−4 2.80×10−5 Chloroneb 8.16×10−2 3.31×10−2 Chlorothalonil 1.51...

SUSPECTED CARBARYL TOXICITY IN A CAPTIVE COLONY OF STRAW-COLORED FRUIT BATS ( EIDOLON HELVUM).

PubMed

Selig, Michael; Lewandowski, Albert

2017-12-01

Carbaryl was the first carbamate insecticide produced and remains the most widely used due to its perceived low level of toxicity in nontarget species. This report describes the management and evaluation of a group of straw-colored fruit bats, Eidolon helvum, that were exposed to carbaryl. Cholinesterase activity of blood, retina, and brain was evaluated to further investigate whether carbaryl was the causative agent. Decreased whole blood and retinal cholinesterase activity coupled with the response to atropine suggests that the cause of the clinical signs in this bat colony was due to carbaryl exposure. Whole blood and retinal tissue may be the best samples for confirming carbamate exposure in this species.

The kinetics of inhibition of erythrocyte cholinesterase by monomethylcarbamates

PubMed Central

Reiner, E.; Simeon-Rudolf, V.

1966-01-01

1. The kinetics of the interaction of erythrocyte cholinesterase with 1-naphthyl N-methylcarbamate, 2-isopropoxyphenyl N-methylcarbamate and phenyl N-methylcarbamate were studied. Rate constants for inhibition and rate constants for spontaneous reactivation were determined. The calculated rate constants for spontaneous reactivation agreed well with those obtained experimentally. 2. The degree of inhibition obtained after preincubation of enzyme and inhibitor was found to be independent of both the substrate concentration and the dilution of the inhibited enzyme. 3. The reaction between the enzyme and the inhibitor was consistent with carbamates being regarded as poor substrates of cholinesterases. There was no evidence for the formation of a reversible complex between the enzyme and the carbamate. PMID:5941343

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

PubMed Central

Čolović, Mirjana B; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

2013-01-01

Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases. PMID:24179466

The preparation, in vitro screening and molecular docking of symmetrical bisquaternary cholinesterase inhibitors containing a but-(2E)-en-1,4-diyl connecting linkage.

PubMed

Musilek, Kamil; Pavlikova, Ruzena; Marek, Jan; Komloova, Marketa; Holas, Ondrej; Hrabinova, Martina; Pohanka, Miroslav; Dohnal, Vlastimil; Dolezal, Martin; Gunn-Moore, Frank; Kuca, Kamil

2011-04-01

Carbamate inhibitors (e.g. pyridostigmine bromide) are used as a pre-treatment for the prevention of organophosphorus poisoning. They work by blocking the native function of acetylcholinesterases (AChE) and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, carbamate inhibitors are known for their many undesirable side effects related to the carbamylation of AChE. In this paper, we describe 17 novel bisquaternary compounds and have analysed their effect on AChE inhibition. The newly prepared compounds were evaluated in vitro using both human erythrocyte AChE and human plasmatic butyrylcholinesterase. Their inhibitory ability was expressed as the half maximal inhibitory concentration (IC₅₀) and then compared to the standard carbamate drugs and two AChE reactivators. One of these novel compounds showed promising AChE inhibition in vitro (nM range) and was better than the currently used standards. Additionally, a kinetic assay confirmed the non-competitive inhibition of hAChE by this novel compound. Consequently, the docking results confirmed the apparent π-π or π-cationic interactions with the key amino acid residues of hAChE and the binding of the chosen compound at the enzyme catalytic site.

Detection of Organophosphorus Pesticides with Colorimetry and Computer Image Analysis.

PubMed

Li, Yanjie; Hou, Changjun; Lei, Jincan; Deng, Bo; Huang, Jing; Yang, Mei

2016-01-01

Organophosphorus pesticides (OPs) represent a very important class of pesticides that are widely used in agriculture because of their relatively high-performance and moderate environmental persistence, hence the sensitive and specific detection of OPs is highly significant. Based on the inhibitory effect of acetylcholinesterase (AChE) induced by inhibitors, including OPs and carbamates, a colorimetric analysis was used for detection of OPs with computer image analysis of color density in CMYK (cyan, magenta, yellow and black) color space and non-linear modeling. The results showed that there was a gradually weakened trend of yellow intensity with the increase of the concentration of dichlorvos. The quantitative analysis of dichlorvos was achieved by Artificial Neural Network (ANN) modeling, and the results showed that the established model had a good predictive ability between training sets and predictive sets. Real cabbage samples containing dichlorvos were detected by colorimetry and gas chromatography (GC), respectively. The results showed that there was no significant difference between colorimetry and GC (P > 0.05). The experiments of accuracy, precision and repeatability revealed good performance for detection of OPs. AChE can also be inhibited by carbamates, and therefore this method has potential applications in real samples for OPs and carbamates because of high selectivity and sensitivity.

Pesticide residue determination in vegetables from western China applying gas chromatography with mass spectrometry.

PubMed

Qin, Guofu; Zou, Keting; Li, Yongbo; Chen, Yan; He, Fengrui; Ding, Guirong

2016-09-01

In this study,an effort has been made to evaluate the pesticide residues in vegetables from western China. Fifty-one pesticides, including organophosphorus, organochlorine, carbamate and pyrethroid, were detected in 369 commonly used vegetables by GC-MS. Concentrations of organophosphorus pesticides were detected ranging from 0.0008 to 18.8200 mg/kg, among which organophosphorus pesticide concentrations exceeded their maximum residue levels (MRLs) in five samples. Carbamate and organochlorine pesticides were determined to have concentrations in the range of 0.0012-0.7928 mg/kg. The residual concentrations of carbamate pesticides in six samples and organochlorine pesticides in four samples exceeded their MRLs. The residual concentrations of five pyrethroid pesticides were within the range of 0.0016-6.0827 mg/kg and the pyrethroid residues in two samples exceeded their MRLs. The results revealed that pesticide residues in 70.73% of the vegetables samples were not detected, while in the rest of vegetables there were one or more pesticide residues and some even exceeded their MRLs, which would threaten the health of consumers. Our work provides significant information for the food safety regulations to control the excessive use of some pesticides on those kinds of vegetables from western China. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

CAR1 deletion by CRISPR/Cas9 reduces formation of ethyl carbamate from ethanol fermentation by Saccharomyces cerevisiae.

PubMed

Chin, Young-Wook; Kang, Woo-Kyung; Jang, Hae Won; Turner, Timothy L; Kim, Hyo Jin

2016-11-01

Enormous advances in genome editing technology have been achieved in recent decades. Among newly born genome editing technologies, CRISPR/Cas9 is considered revolutionary because it is easy to use and highly precise for editing genes in target organisms. CRISPR/Cas9 technology has also been applied for removing unfavorable target genes. In this study, we used CRISPR/Cas9 technology to reduce ethyl carbamate (EC), a potential carcinogen, which was formed during the ethanol fermentation process by yeast. Because the yeast CAR1 gene encoding arginase is the key gene to form ethyl carbamate, we inactivated the yeast CAR1 gene by the complete deletion of the gene or the introduction of a nonsense mutation in the CAR1 locus using CRISPR/Cas9 technology. The engineered yeast strain showed a 98 % decrease in specific activity of arginase while displaying a comparable ethanol fermentation performance. In addition, the CAR1-inactivated mutants showed reduced formation of EC and urea, as compared to the parental yeast strain. Importantly, CRISPR/Cas9 technology enabled generation of a CAR1-inactivated yeast strains without leaving remnants of heterologous genes from a vector, suggesting that the engineered yeast by CRISPR/Cas9 technology might sidestep GMO regulation.

Assessing joint toxicity of four organophosphate and carbamate insecticides in common carp (Cyprinus carpio) using acetylcholinesterase activity as an endpoint.

PubMed

Wang, Yanhua; Chen, Chen; Zhao, Xueping; Wang, Qiang; Qian, Yongzhong

2015-07-01

Mixtures of organophosphate (OP) and carbamate (CB) pesticides are commonly detected in freshwater ecosystems. These pesticides inhibit the activity of acetylcholinesterase (AChE) and have potential to interfere with behaviors that may be essential for the survival of species. Although the effects of individual anticholinesterase insecticides on aquatic species have been studied for decades, the neurotoxicity of mixtures is still poorly understood. In the present study, brain AChE inhibition in carp (Cyprinus carpio) exposed to a series of concentrations of the organophosphates (malathion and triazophos) as well as the carbamates (fenobucarb and carbosulfan) was measured. In equitoxic mixtures, the observed AChE activity inhibition of the malathion plus triazophos, and triazophos plus carbosulfan mixtures, was synergism. In equivalent concentration mixtures, the combination of malathion plus fenobucarb mixture conformed to synergism, while the observed AChE activity inhibition of the remaining pairings was less than additive. Single pesticide risk assessments are likely to underestimate the impacts of these insecticides on carps in aquatic environment where mixtures occur. Moreover, mixtures of pesticides that have been commonly reported in aquatic ecosystems may pose a more important challenge than previously anticipated. Copyright © 2014 Elsevier Inc. All rights reserved.

Groups of Pesticides in Registration Review

EPA Pesticide Factsheets

Review cases are in groups of related pesticides: organophosphates, N-methyl carbamates, pyrethroids pyrethrins and synergists, sulfonylureas, neonicotinoids, fumigants, triazines, imidazolinones, isothiazolinones, and pyridines.

Diagnostic doses and times for Phlebotomus papatasi and Lutzomyia longipalpis sand flies (Diptera: Psychodidae: Phlebotominae) using the CDC bottle bioassay to assess insecticide resistance.

PubMed

Denlinger, David S; Creswell, Joseph A; Anderson, J Laine; Reese, Conor K; Bernhardt, Scott A

2016-04-15

Insecticide resistance to synthetic chemical insecticides is a worldwide concern in phlebotomine sand flies (Diptera: Psychodidae), the vectors of Leishmania spp. parasites. The CDC bottle bioassay assesses resistance by testing populations against verified diagnostic doses and diagnostic times for an insecticide, but the assay has been used limitedly with sand flies. The objective of this study was to determine diagnostic doses and diagnostic times for laboratory Lutzomyia longipalpis (Lutz & Nieva) and Phlebotomus papatasi (Scopoli) to ten insecticides, including pyrethroids, organophosphates, carbamates, and DDT, that are used worldwide to control vectors. Bioassays were conducted in 1,000-ml glass bottles each containing 10-25 sand flies from laboratory colonies of L. longipalpis or P. papatasi. Four pyrethroids, three organophosphates, two carbamates and one organochlorine, were evaluated. A series of concentrations were tested for each insecticide, and four replicates were conducted for each concentration. Diagnostic doses were determined only during the exposure bioassay for the organophosphates and carbamates. For the pyrethroids and DDT, diagnostic doses were determined for both the exposure bioassay and after a 24-hour recovery period. Both species are highly susceptible to the carbamates as their diagnostic doses are under 7.0 μg/ml. Both species are also highly susceptible to DDT during the exposure assay as their diagnostic doses are 7.5 μg/ml, yet their diagnostic doses for the 24-h recovery period are 650.0 μg/ml for Lu. longipalpis and 470.0 μg/ml for P. papatasi. Diagnostic doses and diagnostic times can now be incorporated into vector management programs that use the CDC bottle bioassay to assess insecticide resistance in field populations of Lu. longipalpis and P. papatasi. These findings provide initial starting points for determining diagnostic doses and diagnostic times for other sand fly vector species and wild populations using the CDC bottle bioassay.

Indoline-3-propionate and 3-aminopropyl carbamates reduce lung injury and pro-inflammatory cytokines induced in mice by LPS

PubMed Central

Finkin-Groner, E; Moradov, D; Shifrin, H; Bejar, C; Nudelman, A; Weinstock, M

2015-01-01

Background and Purpose In the search for safer and effective anti-inflammatory agents, we investigated the effect of methyl indoline-3-propionate and indoline-3-(3-aminopropyl) carbamates on LPS-induced lung injury and pro-inflammatory cytokines in mice. Their mechanism of action was determined in murine peritoneal macrophages. Experimental Approach Lung injury was induced by intratracheal infusion of LPS and assessed by the change in lung weight and structure by light microscopy after staining by haematoxylin and eosin. In LPS-activated macrophages, MAPK proteins and IκBα were measured by Western blotting and the transcription factors, AP-1 and NF-κB by electromobility shift assay. Cytokines in the plasma and spleen of mice injected with LPS were measured by elisa-based assay. Key Results AN917 and AN680 (1–10 pM) decreased TNF-α protein in macrophages by inhibiting phosphorylation of p38 MAPK, IκBα degradation and activation of AP-1 and NF-κB without affecting cell viability. In vivo, these compounds (10 μmol·kg−1) markedly decreased lung injury induced by LPS and the elevation of TNF-α and IL-6 in lung, plasma and spleen. Activation of α-7nACh receptors contributed to the reduction of TNF-α by AN917, which inhibited AChE in the spleen by 35%. Conclusion and Implications Indoline carbamates are potent inhibitors of pro-inflammatory mediators in murine macrophages and in mice injected with LPS, acting via the p38 MAPK, AP-1 and NF-κB cascades. Indirect α-7nACh receptor activation by AN917, through inhibition of AChE, contributes to its anti-inflammatory effect. Indoline carbamates may have therapeutic potential for lung injury and other diseases associated with chronic inflammation without causing immunosuppression. PMID:25322956

Survey of carbamate and organophosphorous pesticide export from a south Florida (U.S.A.) agricultural watershed: implications of sampling frequency on ecological risk estimation.

PubMed

Wilsont, P Chris; Foos, Jane Ferguson

2006-11-01

The objectives of the present study were to characterize the presence of selected carbamate and organophosphorous pesticides in Ten Mile Creek (Fort Pierce, FL, U.S.A.) and to evaluate the implications of sampling frequency on ecological risk estimates. Ten Mile Creek originates in a predominately agricultural watershed that is drained by an extensive network of cross-linked canals. Water samples were collected daily or every other day and were analyzed for azinphos-methyl, chlorpyrifos, diazinon, dimethoate, ethion, fenamiphos, malathion, methidathion, carbaryl, carbofuran, 3-hydroxycarbofuran, methiocarb, methomyl, oxamyl, and propoxur. A total of 457 samples were analyzed for the carbamate suite, and a total of 332 samples were analyzed for the organophosphorous suite. Carbaryl was detected in eight samples; half of these detections occurred on four consecutive days (October 26-29, 2001) at concentrations ranging from 0.33 to 0.95 microg/L. Methomyl was detected in samples collected on five consecutive days (March 30-April 3, 2002) at concentrations ranging from 1.0 to 2.2 microg/L. Oxamyl was detected in four samples, three of which occurred on three consecutive days (February 17-19, 2002) at concentrations ranging from 6.2 to 6.8 microg/L. The carbamates propoxur, 3-hydroxycarbofuran, carbofuran, and methiocarb were not detected. Diazinon and ethion were the only organophosphorous pesticides detected. Diazinon was detected at 0.9 and 0.7 microg/L on January 5, 2002, and on January 6, 2002, respectively. Ethion was detected in 18 consecutive samples (August 3-20, 2001). The mean, maximum, minimum, and median detected concentrations were 0.38, 0.61, 0.30, and 0.33 microg/L, respectively. Results indicate that frequent sampling is necessary to characterize the presence of these pesticides in this intensively drained watershed. This conclusion also may apply to similar canalized watersheds.

Chalcone-based carbamates for Alzheimer's disease treatment.

PubMed

Rampa, Angela; Montanari, Serena; Pruccoli, Letizia; Bartolini, Manuela; Falchi, Federico; Feoli, Alessandra; Cavalli, Andrea; Belluti, Federica; Gobbi, Silvia; Tarozzi, Andrea; Bisi, Alessandra

2017-05-01

Alzheimer's disease is a still untreatable multifaceted pathology, and drugs able to stop or reverse its progression are urgently needed. In this picture, the recent reformulation of the cholinergic hypothesis renewed the interest for acetylcholinesterase inhibitors. In this paper, a series of naturally inspired chalcone-based carbamates was designed to target cholinesterase enzymes and possibly generate fragments endowed with neuroprotective activity in situ. Results & methodology: All compounds presented in this study showed nanomolar potency for cholinesterase inhibition. Notably, fragment 11d also displayed an interesting neuroprotective profile. These new derivatives are able to simultaneously modulate different key targets involved in Alzheimer's disease, and could be regarded as promising starting points for the development of disease-modifying drug candidates. [Formula: see text].

Comparison of methods for extraction of ethyl carbamate from alcoholic beverages in gas chromatography/mass spectrometry analysis.

PubMed

Mirzoian, Armen; Mabud, Abdul

2006-01-01

A procedure to analyze ethyl carbamate (EC) by gas chromatography/mass spectrometry was optimized and validated. Deuterated EC (d5-EC) was added to the samples as an internal standard followed by extraction with polystyrene crosslinked polystyrene cartridges using minimal volumes of ethyl acetate. The EC response was measured in selective ion monitoring (SIM) mode and found to be linear in the range between the limit of quantitation (10 micro/L) and 1000 microg/L. EC recoveries varied from 92 to 112%, with the average value of 100 +/- 8%. The procedure compared well (r2 = 0.9970) with the existing AOAC Official Method with the added benefits of minimal solvent usage and reduced matrix interferences.

Lithium Diisopropylamide-Mediated Reactions of Imines, Unsaturated Esters, Epoxides, and Aryl Carbamates: Influence of Hexamethylphosphoramide and Ethereal Cosolvents on Reaction Mechanisms

PubMed Central

Ma, Yun

2010-01-01

Several reactions mediated by lithium diisopropylamide (LDA) with added hex-amethylphosphoramide (HMPA) are described. The N-isopropylimine of cyclohex-anone lithiates via an ensemble of monomer-based pathways. Conjugate addition of LDA/HMPA to an unsaturated ester proceeds via di- and tetra-HMPA-solvated dimers. Deprotonation of norbornene epoxide by LDA/HMPA proceeds via an intermediate metalated epoxide as a mixed dimer with LDA. Ortholithiation of an aryl carbamate proceeds via a mono-HMPA-solvated monomer-based pathway. Dependencies on THF and other ethereal cosolvents suggest that secondary-shell solvation effects are important in some instances. The origins of the inordinate mechanistic complexity are discussed. PMID:17985891

Comparison of methods for measuring cholinesterase inhibition by carbamates

PubMed Central

Wilhelm, K.; Vandekar, M.; Reiner, E.

1973-01-01

The Acholest and tintometric methods are used widely for measuring blood cholinesterase activity after exposure to organophosphorus compounds. However, if applied for measuring blood cholinesterase activity in persons exposed to carbamates, the accuracy of the methods requires verification since carbamylated cholinesterases are unstable. The spectrophotometric method was used as a reference method and the two field methods were employed under controlled conditions. Human blood cholinesterases were inhibited in vitro by four methylcarbamates that are used as insecticides. When plasma cholinesterase activity was measured by the Acholest and spectrophotometric methods, no difference was found. The enzyme activity in whole blood determined by the tintometric method was ≤ 11% higher than when the same sample was measured by the spectrophotometric method. PMID:4541147

(N-Benzyl-N-isopropyl-dithio-carbamato)chloridodiphenyl-tin(IV).

PubMed

Abdul Muthalib, Amirah Faizah; Baba, Ibrahim; Mohamed Tahir, Mohamed Ibrahim; Ng, Seik Weng; Tiekink, Edward R T

2010-08-11

The Sn(IV) atom in the title organotin dithio-carbamate, [Sn(C(6)H(5))(2)(C(11)H(14)NS(2))Cl], is penta-coordinated by an asymmetrically coordinating dithio-carbamate ligand, a Cl and two ispo-C atoms of the Sn-bound phenyl groups. The resulting C(2)ClS(2) donor set defines a coordination geometry inter-mediate between square-pyramidal and trigonal-bipyramidal with a slight tendency towards the latter. The formation of close intra-molecular C-H⋯Cl and C-H⋯S contacts precludes the Cl and S atoms from forming significant inter-molecular contacts. The presence of C-H⋯π contacts leads to the formation of supra-molecular arrays that stack along the b axis.

Chemically-related Groups of Active Ingredients

EPA Pesticide Factsheets

Many pesticide active ingredients affect pests in similar ways, and we re-evaluate them together as a group. Groups include carbamate insecticides, neonicotinoids, organochlorines, organophosphates, pyrethrins, and pyrethroids.

Development of an indirect ELISA for the determination of ethyl carbamate in Chinese rice wine.

PubMed

Luo, Lin; Lei, Hong-Tao; Yang, Jin-Yi; Liu, Gong-Liang; Sun, Yuan-Ming; Bai, Wei-Dong; Wang, Hong; Shen, Yu-Dong; Chen, Sui; Xu, Zhen-Lin

2017-01-15

The widespread occurrence of ethyl carbamate (EC, 89.09 Da), a group 2A carcinogen, in fermented foods and alcoholic beverages has raised worldwide public health concern. Immunoassay for EC is unavailable due to the simple and small structure of EC. In this work, an initial attempt to produce antibody specific for EC, by using 4-((ethoxycarbonyl)amino)butanoic acid as hapten, was made but failed. However, since EC can easily react with 9-xanthydrol to form xanthyl ethyl carbamate (XEC), two haptens based on XEC structure were designed and synthesized. Polyclonal antibody against XEC, instead of EC was obtained and then used to develop a competitive indirect ELISA for EC via a pre-analysis derivatization. After optimization, the ciELISA was applied in analyzing Chinese rice wine with detection limit of 166 μg/L, and negligible cross-reactivity with EC analogs. Recoveries of EC in fortified samples were from 84.4% to 100.9%, with coefficients of variation below 10%. Results for analysis of real samples by the ci-ELISA correlated well with that by reference method GC-MS, suggesting the good accuracy and reproducibility of the proposed method. This is the first report of an immunoassay capable of detecting EC, which is suitable for monitoring EC in a large amount of samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Cholinesterase depression and its association with pesticide exposure across the agricultural season among Latino farmworkers in North Carolina.

PubMed

Quandt, Sara A; Chen, Haiying; Grzywacz, Joseph G; Vallejos, Quirina M; Galvan, Leonardo; Arcury, Thomas A

2010-05-01

Farmworkers can be exposed to a wide variety of pesticides. Assessing cholinesterase activity over time can be used to monitor exposure to organophosphorus and carbamate pesticides. The goal of this study was to document patterns and variation in cholinesterase levels across the agricultural season (May-August) among field-workers, and to explore the association of cholinesterase depression with pesticide exposure across the agricultural season. Dried blood samples collected from 231 migrant farmworkers sampled from camps in eastern North Carolina up to four times across a summer agricultural season were analyzed for cholinesterase activity, and urine samples were analyzed for metabolites of organophosphorus and carbamate pesticides. Reductions of >or= 15% from an individual's highest value were identified and considered evidence of meaningful cholinesterase activity depression. The average cholinesterase activity levels were lowest in June, with significantly higher mean values in July and August. When adjusted for age, sex, minutes waited to shower, and days worked in the fields, the number of organophosphorus and carbamate pesticides detected in urine predicted reductions in cholinesterase activity. These data demonstrate that workers are experiencing pesticide exposure. Greater enforcement of existing safety regulations or strengthening of these regulations may be warranted. This study demonstrates that serial measurements of cholinesterase activity across an agricultural season can detect exposure to pesticides among field-workers.

Cholinesterase Depression and Its Association with Pesticide Exposure across the Agricultural Season among Latino Farmworkers in North Carolina

PubMed Central

Quandt, Sara A.; Chen, Haiying; Grzywacz, Joseph G.; Vallejos, Quirina M.; Galvan, Leonardo; Arcury, Thomas A.

2010-01-01

Background Farmworkers can be exposed to a wide variety of pesticides. Assessing cholinesterase activity over time can be used to monitor exposure to organophosphorus and carbamate pesticides. Objectives The goal of this study was to document patterns and variation in cholinesterase levels across the agricultural season (May–August) among field-workers, and to explore the association of cholinesterase depression with pesticide exposure across the agricultural season. Methods Dried blood samples collected from 231 migrant farmworkers sampled from camps in eastern North Carolina up to four times across a summer agricultural season were analyzed for cholinesterase activity, and urine samples were analyzed for metabolites of organophosphorus and carbamate pesticides. Reductions of ≥ 15% from an individual’s highest value were identified and considered evidence of meaningful cholinesterase activity depression. Results The average cholinesterase activity levels were lowest in June, with significantly higher mean values in July and August. When adjusted for age, sex, minutes waited to shower, and days worked in the fields, the number of organophosphorus and carbamate pesticides detected in urine predicted reductions in cholinesterase activity. Conclusions These data demonstrate that workers are experiencing pesticide exposure. Greater enforcement of existing safety regulations or strengthening of these regulations may be warranted. This study demonstrates that serial measurements of cholinesterase activity across an agricultural season can detect exposure to pesticides among field-workers. PMID:20085857

Consumption of fruits and vegetables and probabilistic assessment of the cumulative acute exposure to organophosphorus and carbamate pesticides of schoolchildren in Slovenia.

PubMed

Blaznik, Urška; Yngve, Agneta; Eržen, Ivan; Hlastan Ribič, Cirila

2016-02-01

Adequate consumption of fruits and vegetables is a part of recommendations for a healthy diet. The aim of the present study was to assess acute cumulative dietary exposure to organophosphorus and carbamate pesticides via fruit and vegetable consumption by the population of schoolchildren aged 11-12 years and the level of risk for their health. Cumulative probabilistic risk assessment methodology with the index compound approach was applied. Slovenia, primary schools. Schoolchildren (n 1145) from thirty-one primary schools in Slovenia. Children were part of the PRO GREENS study 2009/10 which assessed 11-year-olds' consumption of fruit and vegetables in ten European countries. The cumulative acute exposure amounted to 8.3 (95% CI 7.7, 10.6) % of the acute reference dose (ARfD) for acephate as index compound (100 µg/kg body weight per d) at the 99.9th percentile for daily intake and to 4.5 (95% CI 3.5, 4.7) % of the ARfD at the 99.9th percentile for intakes during school time and at lunch. Apples, bananas, oranges and lettuce contributed most to the total acute pesticides intake. The estimations showed that acute dietary exposure to organophosphorus and carbamate pesticides is not a health concern for schoolchildren with the assessed dietary patterns of fruit and vegetable consumption.

Pattern of acute food, drug, and chemical poisoning in Sari City, Northern Iran.

PubMed

Ahmadi, Amirhossein; Pakravan, Nasrin; Ghazizadeh, Zeynab

2010-09-01

This descriptive and retrospective study was conducted at the poisoning ward of Imam teaching hospital, Sari, Iran, with the aim of evaluating the pattern of poisoning. Hence, the medical profiles of 2057 patients, who were admitted, were carefully reviewed during the period from April 2006 to March 2008 for 2 years. During this period, 2057 cases, 53.9% female and 46.1% male, were admitted with the indication of acute poisoning. The greatest proportion of poisoning occurred between the ages of 18 and 29 years, with suicidal intentions. Most cases of poisoning were intentional (85%). The most common agents involved in acute poisoning were drugs (77.7%), especially sedatives/hypnotics such as benzodiazepines, followed by opioid analgesics. Organophosphate and carbamate insecticides were the third major agent that induced poisoning. Twenty-seven patients (1.3%) who were mostly females and young adults died. Death mostly occurred due to organophosphate and carbamate insecticides (19 cases) poisoning, followed by sedatives/hypnotics like benzodiazepines (3 cases). High prevalence of intentional overdose and mortality among young adults requires considerable attention and further studies to find out the underlying causes. In addition, strict rules must be followed regarding the sale of central nervous system drugs and pesticides, particularly organophosphate and carbamate insecticides. Establishing poison information centers in different parts of the country, preparing national treatment guidelines, training healthcare providers, and ensuring easy availability of the antidotes are also recommended.

Bioactive Paper Sensor Based on the Acetylcholinesterase for the Rapid Detection of Organophosphate and Carbamate Pesticides

PubMed Central

Badawy, Mohamed E. I.; El-Aswad, Ahmed F.

2014-01-01

In many countries, people are becoming more concerned about pesticide residues which are present in or on food and feed products. For this reason, several methods have been developed to monitor the pesticide residue levels in food samples. In this study, a bioactive paper-based sensor was developed for detection of acetylcholinesterase (AChE) inhibitors including organophosphate and carbamate pesticides. Based on the Ellman colorimetric assay, the assay strip is composed of a paper support (1 × 10 cm), onto which a biopolymer chitosan gel immobilized in crosslinking by glutaraldehyde with AChE and 5,5′-dithiobis(2-nitrobenzoic) acid (DTNB) and uses acetylthiocholine iodide (ATChI) as an outside reagent. The assay protocol involves introducing the sample to sensing zone via dipping of a pesticide-containing solution. Following an incubation period, the paper is placed into ATChI solution to initiate enzyme catalyzed hydrolysis of the substrate, causing a yellow color change. The absence or decrease of the yellow color indicates the levels of the AChE inhibitors. The biosensor is able to detect organophosphate and carbamate pesticides with good detection limits (methomyl = 6.16 × 10−4 mM and profenofos = 0.27 mM) and rapid response times (~5 min). The results show that the paper-based biosensor is rapid, sensitive, inexpensive, portable, disposable, and easy-to-use. PMID:25484901

Synthesis and fluorescence studies of multiple labeled oligonucleotides containing dansyl fluorophore covalently attached at 2'-terminus of cytidine via carbamate linkage.

PubMed

Misra, Arvind; Mishra, Satyendra; Misra, Krishna

2004-01-01

Synthesis of modified oligonucleotides in which the specific cytidine nucleoside analogues linked at 2'-OH position via a carbamate bond with an amino ethyl derivative of dansyl fluorophore is reported. For the multiple labeling of oligonucleotides, a strategy involving prelabeling at the monomeric level followed by solid phase assembly of oligonucleotides to obtain regiospecifically labeled probes has been described. The labeled monomer was phosphitylated using 2-cyanoethyl-N,N,N',N'-tetraisopropyl-phosphoramidite (Bis-reagent) and pyridiniumtrifluoro acetate (Py.TFA) as an activator. To ascertain the minimal number of labeled monomers required for a specific length of oligonucleotide for detection and also to assess the effect of carbamate linkage on hybridization, hexamer and 20-mer sequences were selected. Both were labeled with 1, 2, and 3 monomers at the 5'-end and hybridized with normal (unmodified) complementary sequences. As compared to midsequence or 3'-terminal labeling reported earlier, the 5'-terminal labeling has been found to have minimal contact-mediated quenching on duplex formation. This may be due to complementary deoxyguanosine (dG) rich oligonucleotide sequences or CG base pairs at a terminus that is known to yield stronger binding. This is one reason for selecting cytidine for labeling. The results may aid rational design of multiple fluorescent DNA probes for nonradioactive detection of nucleic acids.

Comparative toxicity of insecticides to Choristoneura species (Lepidoptera: Tortricidae)

Treesearch

Jacqueline L. Robertson; Nancy L. Gillette; Barbara A. Lucas; Robert M. Russell; N.E. Savin

1978-01-01

Selected carbamate, chlorinated hydrocarbon, organophosphorous, and pyrethroid insecticides were tested on six Choristoneura species: conflictana (Walker), fumiferana (Clemens), lambertiana ponderosana Obraztsov, occidentalis Freeman, pinus Freeman, and...

Occurrence of organophosphorus and carbamate pesticide residues in surface water samples from the Rangpur district of Bangladesh.

PubMed

Chowdhury, Alamgir Zaman; Jahan, Salina Akter; Islam, Mohammad Nazrul; Moniruzzaman, Mohammed; Alam, Mohammad Khorshed; Zaman, Mohammad A; Karim, Nurul; Gan, Siew Hua

2012-07-01

We report the presence of organophosphorus and carbamate residues in 24 surface water samples and five ground water samples from Pirgacha Thana, Rangpur district, Bangladesh using high-performance liquid chromatography. A number of samples of surface water from paddy fields were found to contain chlorpyriphos, carbofuran and carbaryl at concentrations ranging from 0-1.189, 0-3.395 and 0-0.163 μg/L, respectively. Surface water from the lakes had chlorpyriphos, carbofuran and carbaryl at concentrations ranging from 0.544-0.895, 0.949-1.671 and 0-0.195 μg/L, respectively. This result indicates that the general public living in the area of Rangpur is at high risk of pesticide exposure from contaminated waters in the environment.

Ethyl carbamate in alcoholic beverages from Mexico (tequila, mezcal, bacanora, sotol) and Guatemala (cuxa): market survey and risk assessment.

PubMed

Lachenmeier, Dirk W; Kanteres, Fotis; Kuballa, Thomas; López, Mercedes G; Rehm, Jürgen

2009-01-01

Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and of the sugarcane spirit cuxa (n=16) were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (<0.15 mg/L). Risk assessment found the Margin of Exposure (MOE) in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico.

Ethyl Carbamate in Alcoholic Beverages from Mexico (Tequila, Mezcal, Bacanora, Sotol) and Guatemala (Cuxa): Market Survey and Risk Assessment

PubMed Central

Lachenmeier, Dirk W.; Kanteres, Fotis; Kuballa, Thomas; López, Mercedes G.; Rehm, Jürgen

2009-01-01

Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and of the sugarcane spirit cuxa (n=16) were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (<0.15 mg/L). Risk assessment found the Margin of Exposure (MOE) in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico. PMID:19440288

(N-Benzyl-N-isopropyl­dithio­carbamato)chloridodiphenyl­tin(IV)

PubMed Central

Abdul Muthalib, Amirah Faizah; Baba, Ibrahim; Mohamed Tahir, Mohamed Ibrahim; Ng, Seik Weng; Tiekink, Edward R. T.

2010-01-01

The SnIV atom in the title organotin dithio­carbamate, [Sn(C6H5)2(C11H14NS2)Cl], is penta-coordinated by an asymmetrically coordinating dithio­carbamate ligand, a Cl and two ispo-C atoms of the Sn-bound phenyl groups. The resulting C2ClS2 donor set defines a coordination geometry inter­mediate between square-pyramidal and trigonal-bipyramidal with a slight tendency towards the latter. The formation of close intra­molecular C–H⋯Cl and C–H⋯S contacts precludes the Cl and S atoms from forming significant inter­molecular contacts. The presence of C–H⋯π contacts leads to the formation of supra­molecular arrays that stack along the b axis. PMID:21588504

21 CFR 520.434 - Chlorphenesin carbamate tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... sprains, traumatic injuries, stifle injuries—especially when administered before or after surgery—and...) Indications for use. For use as an adjunct to therapy of acute inflammatory and traumatic conditions of...

21 CFR 520.434 - Chlorphenesin carbamate tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... sprains, traumatic injuries, stifle injuries—especially when administered before or after surgery—and...) Indications for use. For use as an adjunct to therapy of acute inflammatory and traumatic conditions of...

21 CFR 520.434 - Chlorphenesin carbamate tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... sprains, traumatic injuries, stifle injuries—especially when administered before or after surgery—and...) Indications for use. For use as an adjunct to therapy of acute inflammatory and traumatic conditions of...

21 CFR 520.434 - Chlorphenesin carbamate tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... sprains, traumatic injuries, stifle injuries—especially when administered before or after surgery—and...) Indications for use. For use as an adjunct to therapy of acute inflammatory and traumatic conditions of...

21 CFR 520.434 - Chlorphenesin carbamate tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... sprains, traumatic injuries, stifle injuries—especially when administered before or after surgery—and...) Indications for use. For use as an adjunct to therapy of acute inflammatory and traumatic conditions of...

Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur

DOE Office of Scientific and Technical Information (OSTI.GOV)

Padilla, S.; Marshall, R.S.; Hunter, D.L.

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n = 4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 tomore » 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r {sup 2} = 0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r {sup 2} = 0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.« less

Association between quality of cheap and unrecorded alcohol products and public health consequences in Poland.

PubMed

Lachenmeier, Dirk W; Ganss, Sebastian; Rychlak, Bogumil; Rehm, Jürgen; Sulkowska, Urszula; Skiba, Michał; Zatonski, Witold

2009-10-01

The research aimed to study the quality of cheap alcohol products in Poland. These included unrecorded alcohols (i.e., home-produced or illegally imported), estimated to constitute more than 25% of total consumption and fruit wines. A sample of alcohol products (n = 52) was collected from local markets and chemical analyses were conducted. The parameters studied were alcoholic strength, volatiles (methanol, acetaldehyde, and higher alcohols), ethyl carbamate, inorganic elements, and food additives including preservatives, colors, and sweeteners. The compositions of the beverages were then toxicologically evaluated using international standards. With the exception of 1 fortified wine, the unrecorded alcohols were home-produced fruit-derived spirits (moonshine) and spirits imported from other countries. We did not detect any nonbeverage surrogate alcohol. The unrecorded spirits contained, on average, 45% vol of alcohol. However, some products with considerably higher alcoholic strengths were found (up to 85% vol) with no labeling of the content on the bottles. These products may cause more pronounced detrimental health effects (e.g., liver cirrhosis, injuries, some forms of malignant neoplasms, alcohol use disorders, and cardiovascular disease) than will commercial beverages, especially as the consumer may be unaware of the alcohol content consumed. Fruit wines containing between 9.5 and 12.2% vol alcohol showed problems in terms of their additive content and their labeling (e.g., sulfites, sorbic acid, saccharin, and artificial colors) and should be subjected to stricter control. Regarding the other components investigated, the suspected human carcinogens, acetaldehyde and ethyl carbamate, were found at levels relevant to public health concerns. While acetaldehyde is a typical constituent of fermented beverages, ethyl carbamate was found only in home-produced unrecorded alcohols derived from stone fruits with levels significantly above international guidelines. The contamination of unrecorded alcohols with ethyl carbamate should be analyzed in a larger sample that also should include legal alcoholic beverages. Furthermore, the impacts of unrecorded alcohol on the health of people with lower socioeconomic status should be studied in detail. Overall, given the extent of the alcohol-attributable disease burden in Poland, the highest priority should be given to the problem of ethanol and its very high content in unrecorded alcohol products.

A solid-phase microextraction-gas chromatographic approach combined with triple quadrupole mass spectrometry for the assay of carbamate pesticides in water samples.

PubMed

Cavaliere, Brunella; Monteleone, Marcello; Naccarato, Attilio; Sindona, Giovanni; Tagarelli, Antonio

2012-09-28

A simple and sensitive method was developed for the quantification of five carbamate pesticides in water samples using solid phase microextraction (SPME) combined with gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS). The performance of five SPME fibers was tested in univariate mode whereas the other variables affecting the efficiency of SPME analysis were optimized by the multivariate approach of design of experiment (DoE) and, in particular, a central composite design (CCD) was applied. The optimum working conditions in terms of response values were achieved by performing analysis with polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber in immersion mode for 45min at room temperature with addition of NaCl (10%). The multivariate chemometric approach was also used to explore the chromatographic behavior of the carbamates and to evaluate the importance of each variable investigated. An overall appraisement of results shows that the factor which gave a statistically significant effect on the response was only the injection temperature. Identification and quantification of carbamates was performed by using a gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS) system in multiple reaction monitoring (MRM) acquisition. Since the choice of internal standard represented a crucial step in the development of method to achieve good reproducibility and robustness for the entire analytical protocol, three compounds (2,3,5-trimethacarb, 4-bromo-3,5-dimethylphenyl-n-methylcarbamate (BDMC) and carbaryl-d7) were evaluated as internal standards. Both precision and accuracy of the proposed protocol tested at concentration of 0.08, 5 and 3 μg l⁻¹ offered values ranging from 70.8% and 115.7% (except for carbaryl at 3 μg l⁻¹) and from 1.0% and 9.0% for accuracy and precision, respectively. Moreover, LOD and LOQ values ranging from 0.04 to 1.7 ng l⁻¹ and from 0.64 to 2.9 ng l⁻¹, respectively, can be considered very satisfactory. Copyright © 2012 Elsevier B.V. All rights reserved.

Summary of Resource Conservation and Recovery Act State Authorization Rule Checklist 179

EPA Pesticide Factsheets

Land Disposal Restrictions -- Phase IV: Treatment Standards for Wood Preserving Wastes, Treatment Standards for Metal Wastes, Zinc Micronutrient Fertilizers, Carbamate Treatment Standards, and K088 Treatment Standards

Pesticides.

ERIC Educational Resources Information Center

Sherma, Joseph

1989-01-01

This review is devoted to methods for the determination of residues of pesticides and some related industrial chemicals. Topics include: residue methods, sampling, chromatography, organochlorine pesticides, organophosphorus pesticides, carbamate insecticides, herbicides, fungicides, pyrethrins, fumigants, and related chemicals. (MVL)

75 FR 60398 - California: Proposed Authorization of State Hazardous Waste Management Program Revision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

...) Hazardous Soils Treatment Standards and Exclusions; (8) Administrative Stay for Zinc Micronutrient... Hazardous Wastes from Carbamate Production; (10) Extension of Compliance Date for Characteristic Slags; (11...

Isolation and characterization of urethanase from Penicillium variabile and its application to reduce ethyl carbamate contamination in Chinese rice wine.

PubMed

Zhou, Nan-di; Gu, Xiao-lei; Tian, Ya-ping

2013-06-01

A strain with urethanase activity was isolated from mouse gastrointestine. By combination of morphological characterization of the colony, hyphae, and spore and the sequence analysis of its rDNA ITS, the strain was determined as Penicillium variabile and named as P. variabile JN-A525. The enzymatic properties of urethanase from P. variabile JN-A525 were further studied. The optimum temperature and pH value of urethanase are of 50 °C and 6.0, respectively. The enzyme maintains stability when the temperature is below 50 °C and the pH is in the range of 7.0-10.0. The enzyme also exhibits ethanol tolerance. It can remove ethyl carbamate from Chinese rice wine without the change of flavor substances in the wine.

Electro-Immobilization of Acetylcholinesterase Using Polydopamine for Carbaryl Microsensor

NASA Astrophysics Data System (ADS)

Ha, Trung B.; Le, Huyen T.; Cao, Ha H.; Binh, Nguyen Thanh; Nguyen, Huy L.; Dang, Le Hai; Do, Quan P.; Nguyen, Dzung T.; Lam, Tran Dai; Nguyen, Vân-Anh

2018-02-01

A simple and sensitive electrochemical acetylcholinesterase (AChE) biosensor for determination of carbaryl, one of the most commonly used carbamate pesticides, is described. The AChE enzyme was successfully entrapped by a polydopamine-graphene composite on polypyrrole nanowires that modified interdigitated planar platinum-film microelectrodes . The influence of different parameters on the operation of the biosensor was also studied. The selected parameters for the biosensor performance in detecting carbaryl were as follows: applied potential + 0.7 V, pH 7.4 at 25°C. The inhibition of carbaryl was proportional to its concentrations ranging from 0.05 to 1.5 μg/mL with the detection limit of 0.008 μg/mL using chronoamperometry. This study provides a promising approach in fabrication of sensitive biosensors for the analysis of carbamate pesticides as well as other hazardous compounds.

Carbamate and Pyrethroid Resistance in the Akron Strain of Anopheles gambiae

PubMed Central

Mutunga, James M.; Anderson, Troy D.; Craft, Derek T.; Gross, Aaron D.; Swale, Daniel R.; Tong, Fan; Wong, Dawn M.; Carlier, Paul R.; Bloomquist, Jeffrey R.

2015-01-01

Insecticide resistance in the malaria vector, Anopheles gambiae is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a “pseudo-pyrethroid.” There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety. PMID:26047119

NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta

2007-03-15

Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects ofmore » both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures.« less

Detection of methamphetamine in the presence of nicotine using in situ chemical derivatization and ion mobility spectrometry.

PubMed

Ochoa, Mariela L; Harrington, Peter B

2004-02-15

The detection of methamphetamine in the presence of nicotine has been successfully accomplished using in situ chemical derivatization with propyl chloroformate as the derivatization reagent and ion mobility spectrometry (IMS). The rapid detection of methamphetamine is important for forensic scientists in order to establish a chain of evidence and link criminals to the crime scene. Nicotine is pervasive in clandestine drug laboratories from cigarette smoke residue. It has been demonstrated that nicotine obscures the methamphetamine peaks in ion mobility spectrometers due to their similar charge affinities and ion mobilities, which makes their detection a challenging task. As a consequence, false positive or negative responses may arise. In situ chemical derivatization poses as a sensitive, accurate, and reproducible alternative to remove the nicotine background when detecting nanogram amounts of methamphetamine. The derivatization agent was coated onto the sample disk, and the derivatization product corresponding to propyl methamphetamine carbamate was detected. In the present study, in situ chemical derivatization was demonstrated to be a feasible method to detect methamphetamine hydrochloride as the carbamate derivative, which was baseline-resolved from the nicotine peak. Alternating least squares (ALS) was used to model the datasets. A mixture containing both compounds revealed reduced mobilities of 1.61 cm(2)/V.s and 1.54 cm(2)/V.s for methamphetamine and nicotine, respectively. The reduced mobility of propyl methamphetamine carbamate was found at 1.35 cm(2)/V.s.

Formation of Carbamate Anions by the Gas-phase Reaction of Anilide Ions with CO2

NASA Astrophysics Data System (ADS)

Liu, Chongming; Nishshanka, Upul; Attygalle, Athula B.

2016-05-01

The anilide anion ( m/z 92) generated directly from aniline, or indirectly as a fragmentation product of deprotonated acetanilide, captures CO2 readily to form the carbamate anion ( m/z 136) in the collision cell, when CO2 is used as the collision gas in a tandem-quadrupole mass spectrometer. The gas-phase affinity of the anilide ion to CO2 is significantly higher than that of the phenoxide anion ( m/z 93), which adds to CO2 only very sluggishly. Our results suggest that the efficacy of CO2 capture depends on the natural charge density on the nitrogen atom, and relative nucleophilicity of the anilide anion. Generally, conjugate bases generated from aniline derivatives with proton affinities (PA) less than 350 kcal/mol do not tend to add CO2 to form gaseous carbamate ions. For example, the anion generated from p-methoxyaniline (PA = 367 kcal/mol) reacts significantly faster than that obtained from p-nitroaniline (PA = 343 kcal/mol). Although deprotonated p-aminobenzoic acid adds very poorly because the negative charge is now located primarily on the carboxylate group, it reacts more efficiently with CO2 if the carboxyl group is esterified. Moreover, mixture of CO2 and He as the collision gas was found to afford more efficient adduct formation than CO2 alone, or as mixtures made with nitrogen or argon, because helium acts as an effective "cooling" gas and reduces the internal energy of reactant ions.

Organophosphate and carbamate insecticides in agricultural waters and cholinesterase (ChE) inhibition in common carp (Cyprinus carpio)

USGS Publications Warehouse

Gruber, S.J.; Munn, M.D.

1998-01-01

Cholinesterase (ChE) activity was used as a biomarker for assessing exposure of common carp (Cyprinus carpio) to organophosphate and carbamate insecticides from irrigated agricultural waters. Carp were collected from a lake (Royal Lake) that receives most of its water from irrigation return flows and from a reference lake (Billy Clapp Lake) outside of the irrigation system. Results indicated that the mean whole-brain ChE activity of carp from Royal Lake (3.47 μmol/min/g tissue) was 34.2% less than that of carp from Billy Clapp Lake (5.27 μmol/min/g tissue) (p = 0.003). The depressed ChE activity in brain tissue of Royal Lake carp was in response to ChE-inhibiting insecticides detected in water samples in the weeks prior to tissue sampling; the most frequently detected insecticides included chlorpyrifos, azinphos-methyl, carbaryl, and ethoprop. Neither sex nor size appears to be a covariable in the analysis; ChE activity was not correlated with fish length or weight in either lake and there was no significant difference in ChE activity between the two sexes within each lake. Although organophosphate and carbamate insecticides can break down rapidly in the environment, this study suggests that in agricultural regions where insecticides are applied for extended periods of the year, nontarget aquatic biota may be exposed to high levels of ChE-inhibiting insecticides for a period of several months.

MEASURING CHOLINESTERASE ACTIVITY IN HUMAN STUDIES.

EPA Science Inventory

Biomonitoring of organophosphorous and carbamate pesticides has focused primarily on the inhibition of blood cholinesterase. Blood biomonitoring, however, can be invasive, time-consuming, and costly, especially in young children and infants. Therefore, saliva biomonitoring ha...

Aldicarb

EPA Science Inventory

Aldicarb (CAS 116-06-3) is an N-methyl carbamate insecticide that rapidly and reversibly inhibits acetylcholinesterase. The nervous system is the most sensitive target, and there is little evidence of other forms of toxicity. Aldicarb is highly toxic to humans and wildlife. Gro...

40 CFR 180.581 - Iprovalicarb; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... iprovalicarb, [2-methyl-1[[[(1S)-(4-methylphenyl) ethyl] amino]carbonyl] propyl]carbamic acid methylethylester, in or on the following commodities. Commodity Parts per million Grape 1 2.0 Tomato 1 1.0 1There is no...

40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for cancer; 1.0 percent for other effects), (f), (g)(1)(ii), (g)(2)(ii), and (g)(5). In addition, the... substance may cause lung effects. (ii) Industrial, commercial, and consumer activities. Requirements as...

40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... for cancer; 1.0 percent for other effects), (f), (g)(1)(ii), (g)(2)(ii), and (g)(5). In addition, the... substance may cause lung effects. (ii) Industrial, commercial, and consumer activities. Requirements as...

40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... for cancer; 1.0 percent for other effects), (f), (g)(1)(ii), (g)(2)(ii), and (g)(5). In addition, the... substance may cause lung effects. (ii) Industrial, commercial, and consumer activities. Requirements as...

40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... for cancer; 1.0 percent for other effects), (f), (g)(1)(ii), (g)(2)(ii), and (g)(5). In addition, the... substance may cause lung effects. (ii) Industrial, commercial, and consumer activities. Requirements as...

40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for cancer; 1.0 percent for other effects), (f), (g)(1)(ii), (g)(2)(ii), and (g)(5). In addition, the... substance may cause lung effects. (ii) Industrial, commercial, and consumer activities. Requirements as...

Chemoproteomic Discovery of AADACL1 as a Novel Regulator of Human Platelet Activation

PubMed Central

Holly, Stephen P.; Chang, Jae Won; Li, Weiwei; Niessen, Sherry; Phillips, Ryan M.; Piatt, Raymond; Black, Justin L.; Smith, Matthew C.; Boulaftali, Yacine; Weyrich, Andrew S.; Bergmeier, Wolfgang; Cravatt, Benjamin F.; Parise, Leslie V.

2013-01-01

A comprehensive knowledge of the platelet proteome is necessary for understanding thrombosis and for conceiving novel antiplatelet therapies. To discover new biochemical pathways in human platelets, we screened platelets with a carbamate library designed to interrogate the serine hydrolase subproteome and used competitive activity-based protein profiling to map the targets of active carbamates. We identified an inhibitor that targets arylacetamide deacetylase-like 1 (AADACL1), a lipid deacetylase originally identified in invasive cancers. Using this compound, along with highly selective second-generation inhibitors of AADACL1, metabolomics and RNA interference, we show that AADACL1 regulates platelet aggregation, thrombus growth, RAP1 and PKC activation, lipid metabolism and fibrinogen binding to platelets and megakaryocytes. These data provide the first evidence that AADACL1 regulates platelet and megakaryocyte activation and highlight the value of this chemoproteomic strategy for target discovery in platelets. PMID:23993462

Synthesis of kenaf cellulose carbamate and its smart electric stimuli-response.

PubMed

Gan, Sinyee; Piao, Shang Hao; Choi, Hyoung Jin; Zakaria, Sarani; Chia, Chin Hua

2016-02-10

Cellulose carbamate (CC) was produced from kenaf core pulp (KCP) via a microwave reactor-assisted method. The formation of CC was confirmed by Fourier transform infrared spectroscopy and nitrogen content analysis. The degree of substitution, zeta potential and size distribution of CC were also determined. The CC was characterized with scanning electron microscopy, X-ray diffraction and thermogravimetry analysis. The CC particles were then dispersed in silicone oil to prepare CC-based anhydrous electric stimuli-responsive electrorheological (ER) fluids. Rhelogical measurement was carried out using rotational rheometer with a high voltage generator in both steady and oscillatory shear modes to examine the effect of electric field strength on the ER characteristics. The results showed that the increase in electric field strength has enhanced the ER properties of CC-based ER fluid due to the chain formation induced by electric polarization among the particles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unlocking the Potential of Phenacyl Protecting Groups: CO2-Based Formation and Photocatalytic Release of Caged Amines.

PubMed

Speckmeier, Elisabeth; Klimkait, Michael; Zeitler, Kirsten

2018-04-06

Orthogonal protection and deprotection of amines remain important tools in synthetic design as well as in chemical biology and material research applications. A robust, highly efficient, and sustainable method for the formation of phenacyl-based carbamate esters was developed using CO 2 for the in situ preparation of the intermediate carbamates. Our mild and broadly applicable protocol allows for the formation of phenacyl urethanes of anilines, primary amines, including amino acids, and secondary amines in high to excellent yields. Moreover, we demonstrate the utility by a mild and convenient photocatalytic deprotection protocol using visible light. A key feature of the [Ru(bpy) 3 ](PF 6 ) 2 -catalyzed method is the use of ascorbic acid as reductive quencher in a neutral, buffered, two-phase acetonitrile/water mixture, granting fast and highly selective deprotection for all presented examples.

Preparation, in vitro screening and molecular modelling of symmetrical 4-tert-butylpyridinium cholinesterase inhibitors--analogues of SAD-128.

PubMed

Musilek, Kamil; Roder, Jan; Komloova, Marketa; Holas, Ondrej; Hrabinova, Martina; Pohanka, Miroslav; Dohnal, Vlastimil; Opletalova, Veronika; Kuca, Kamil; Jung, Young-Sik

2011-01-01

Carbamate inhibitors (e.g., pyridostimine bromide) are used as a pre-exposure treatment for the prevention of organophosphorus poisoning. They work by blocking acetylcholinesterase's (AChE) native function and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, carbamate inhibitors are known for many undesirable side-effects related to the carbamylation of AChE. In this Letter, 19 analogues of SAD-128 were prepared and evaluated as cholinesterase inhibitors. The screening results showed promising inhibitory ability of four compounds better to used standards (pralidoxime, obidoxime, BW284c51, ethopropazine, SAD-128). Four most promising compounds were selected for further molecular docking studies. The SAR was stated from obtained data. The former receptor studies were reported and discussed. The further in vivo studies were recommended in the view of OP pre-exposure treatment. Copyright © 2010 Elsevier Ltd. All rights reserved.

Studies on synthesis and anticancer activity of selected N-(2-fluoroethyl)-N-nitrosoureas.

PubMed

Johnston, T P; Kussner, C L; Carter, R L; Frye, J L; Lomax, N R; Plowman, J; Narayanan, V L

1984-11-01

An activated carbamate, 2-nitrophenyl (2-fluoroethyl)nitrosocarbamate (3), was used to advantage in the synthesis of the water-soluble (2-fluoroethyl)nitrosoureas 6a--d from 2-aminoethanol, (1 alpha, 2 beta, 3 alpha)-2-amino-1,3-cyclohexanediol, cis-2-hydroxycyclohexanol, and 2-amino-2-deoxy-D-glucose. In a variation of this method, 2,4,5-trichlorophenyl (2-fluoroethyl)carbamate (4) was used to prepare the urea from which the essentially water-insoluble N-(2,6-dioxo-3-piperidinyl)-N-(2-fluoroethyl)-N-nitrosourea (6e) was derived. The anticancer activity of these nitrosoureas was determined against the murine tumors B16 melanoma and Lewis lung carcinoma and found to be significant and comparable to their chloroethyl counterparts. On the basis of results from both systems, the dihydroxycyclohexyl derivative 6b may be the most effective.

Genetic effects of methyl benzimidazole-2-yl-carbamate on Saccharomyces cerevisiae.

PubMed Central

Wood, J S

1982-01-01

The genetic effects of the mitotic inhibitor methyl benzimidazole-2-yl-carbamate (MBC) have been studied in Saccharomyces cerevisiae. MBC had little or no effect on the frequency of mutation. In some experiments MBC caused an increase in the frequency of mitotic recombination; however, this effect was small and not reproducible. The primary genetic effect of MBC was to induce mitotic chromosome loss at a high frequency. Chromosome loss occurred at equal frequencies for all chromosomes tested (13 of 16). Cells which had lost multiple chromosomes were found more frequently than predicted if individual chromosome loss events were independent. The probability of loss for a particular chromosome increased with length of time cells were incubated with MBC. MBC treatment also increased the frequency at which polyploid cells were found. These results suggested that MBC acted to disrupt the structure or function of the mitotic spindle and cause chromosome nondisjunction. PMID:6757720

A novel broad specificity fucosidase capable of core α1-6 fucose release from N-glycans labeled with urea-linked fluorescent dyes.

PubMed

Vainauskas, Saulius; Kirk, Charlotte H; Petralia, Laudine; Guthrie, Ellen P; McLeod, Elizabeth; Bielik, Alicia; Luebbers, Alex; Foster, Jeremy M; Hokke, Cornelis H; Rudd, Pauline M; Shi, Xiaofeng; Taron, Christopher H

2018-06-22

Exoglycosidases are often used for detailed characterization of glycan structures. Bovine kidney α-fucosidase is commonly used to determine the presence of core α1-6 fucose on N-glycans, an important modification of glycoproteins. Recently, several studies have reported that removal of core α1-6-linked fucose from N-glycans labeled with the reactive N-hydroxysuccinimide carbamate fluorescent labels 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (AQC) and RapiFluor-MS is severely impeded. We report here the cloning, expression and biochemical characterization of an α-fucosidase from Omnitrophica bacterium (termed fucosidase O). We show that fucosidase O can efficiently remove α1-6- and α1-3-linked core fucose from N-glycans. Additionally, we demonstrate that fucosidase O is able to efficiently hydrolyze core α1-6-linked fucose from N-glycans labeled with any of the existing NHS-carbamate activated fluorescent dyes.

A nucleotide substitution in one of the beta-tubulin genes of Trichoderma viride confers resistance to the antimitotic drug methyl benzimidazole-2-yl-carbamate.

PubMed

Goldman, G H; Temmerman, W; Jacobs, D; Contreras, R; Van Montagu, M; Herrera-Estrella, A

1993-07-01

We characterized a Trichoderma viride strain that is resistant to the antimitotic drug methyl benzimidazole-2-yl-carbamate (MBC). This species has two beta-tubulin genes (tub1 and tub2) and by reverse genetics we showed that a mutation in the tub2 gene confers MBC resistance in this strain. Comparison of the tub2 sequence of the mutant strain with that of the wild type revealed that a single amino acid substitution of tyrosine for histidine at a position 6 is responsible for the MBC tolerance. Furthermore, we showed that this gene can be used as a homologous dominant selectable marker in T. viride transformation. Both tubulin genes were completely sequenced. They differ by 48 residues and the degree of identity between their deduced amino acid sequences is 86.3%.

Effect of Microbial Interaction on Urea Metabolism in Chinese Liquor Fermentation.

PubMed

Wu, Qun; Lin, Jianchun; Cui, Kaixiang; Du, Rubin; Zhu, Yang; Xu, Yan

2017-12-20

Urea is the primary precursor of the carcinogen ethyl carbamate in fermented foods. Understanding urea metabolism is important for controlling ethyl carbamate production. Using Chinese liquor as a model system, we used metatranscriptome analysis to investigate urea metabolism in spontaneous food fermentation processes. Saccharomyces cerevisiae was dominant in gene transcription for urea biosynthesis and degradation. Lysinibacillus sphaericus was dominant for urea degradation. S. cerevisiae degraded 18% and L. sphaericus degraded 13% of urea in their corresponding single cultures, whereas they degraded 56% of urea in coculture after 12 h. Compared to single cultures, transcription of CAR1, DAL2, and argA, which are related to urea biosynthesis, decreased by 51, 36, and 69% in coculture, respectively. Transcription of DUR1 and ureA, which are related to urea degradation, increased by 227 and 70%, respectively. Thus, coexistence of the two strains promoted degradation of urea via transcriptional regulation of genes related to urea metabolism.

N,N'-disubstituted cinnamamide derivatives potentiate ciprofloxacin activity against overexpressing NorA efflux pump Staphylococcus aureus 1199B strains.

PubMed

Radix, Sylvie; Jordheim, Anne Doléans; Rocheblave, Luc; N'Digo, Serge; Prignon, Anne-Laure; Commun, Carine; Michalet, Serge; Dijoux-Franca, Marie-Geneviève; Mularoni, Angélique; Walchshofer, Nadia

2018-04-25

A multi-step procedure has been described which afforded satisfactory yields of N,N'-disubstituted cinnamamides derived from N-Boc-protected amino acids (Boc-Gly, Boc-Val, Boc-Phe). The key step of this synthesis was a regioselective RedAl reduction of an amide function in presence of a carbamate group. Next, these cinnamamides were evaluated in co-admnistration with ciprofloxacin as efflux pump inhibitors against two S. aureus strains, NorA overexpressing SA1199B and wild type SA1199. In parallel, their intrinsic toxicity was appreciated on human lung fibroblast MRC5 cells. Therefore, the cinnamamide combining both carbamate and indol-3-yl groups, was found to be the most active and one of the less toxic EPI and constituted a promising hit. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Studies on the physical dependence liability of chlorphenesin carbamate (author's transl)].

PubMed

Sasajima, M; Tarumoto, Y; Aihara, H; Tanaka, Y; Saito, S

1977-05-01

Physical dependence liability of chlorphenesin carbamate (CPC) was studied in parallel with phenobarbital-Na (PB). Beagle dogs were used and the overall duration of the experiment was 85 days, i.e. the first dosing period was 42 dyas (6 weeks) in which drugs were repeatedly administered orally once daily, followed by a withdrawal period (7 days), the second dosing period was continued from the 50th-78th day in which the form and schedule of drug administration was as in the first dosing period. The last 79th to 85th days were used for substitution experiments. In both dosing periods, PB but not CPC showed signs of tolerance formation. Severe withdrawal syndrome was observed in PB administered dogs whereas there were no changes of behavior observed in CPC-dogs by withdrawal and substitution procedures, respectively. CPC apparently does not have a physical dependence liability.

Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach.

PubMed

Lachenmeier, Dirk W; Przybylski, Maria C; Rehm, Jürgen

2012-09-15

Alcoholic beverages have been classified as carcinogenic to humans. As alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, a quantitative approach is necessary to compare the risks. Fifteen known and suspected human carcinogens (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, lead, 4-methylimidazole, N-nitrosodimethylamine, ochratoxin A and safrole) occurring in alcoholic beverages were identified based on monograph reviews by the International Agency for Research on Cancer. The margin of exposure (MOE) approach was used for comparative risk assessment. MOE compares a toxicological threshold with the exposure. MOEs above 10,000 are judged as low priority for risk management action. MOEs were calculated for different drinking scenarios (low risk and heavy drinking) and different levels of contamination for four beverage groups (beer, wine, spirits and unrecorded alcohol). The lowest MOEs were found for ethanol (3.1 for low risk and 0.8 for heavy drinking). Inorganic lead and arsenic have average MOEs between 10 and 300, followed by acetaldehyde, cadmium and ethyl carbamate between 1,000 and 10,000. All other compounds had average MOEs above 10,000 independent of beverage type. Ethanol was identified as the most important carcinogen in alcoholic beverages, with clear dose response. Some other compounds (lead, arsenic, ethyl carbamate, acetaldehyde) may pose risks below thresholds normally tolerated for food contaminants, but from a cost-effectiveness point of view, the focus should be on reducing alcohol consumption in general rather than on mitigative measures for some contaminants that contribute only to a limited extent (if at all) to the total health risk. Copyright © 2012 UICC.

Structural Basis for Inactivation of Giardia lamblia Carbamate Kinase by Disulfiram*

PubMed Central

Galkin, Andrey; Kulakova, Liudmila; Lim, Kap; Chen, Catherine Z.; Zheng, Wei; Turko, Illarion V.; Herzberg, Osnat

2014-01-01

Carbamate kinase from Giardia lamblia is an essential enzyme for the survival of the organism. The enzyme catalyzes the final step in the arginine dihydrolase pathway converting ADP and carbamoyl phosphate to ATP and carbamate. We previously reported that disulfiram, a drug used to treat chronic alcoholism, inhibits G. lamblia CK and kills G. lamblia trophozoites in vitro at submicromolar IC50 values. Here, we examine the structural basis for G. lamblia CK inhibition of disulfiram and its analog, thiram, their activities against both metronidazole-susceptible and metronidazole-resistant G. lamblia isolates, and their efficacy in a mouse model of giardiasis. The crystal structure of G. lamblia CK soaked with disulfiram revealed that the compound thiocarbamoylated Cys-242, a residue located at the edge of the active site. The modified Cys-242 prevents a conformational transition of a loop adjacent to the ADP/ATP binding site, which is required for the stacking of Tyr-245 side chain against the adenine moiety, an interaction seen in the structure of G. lamblia CK in complex with AMP-PNP. Mass spectrometry coupled with trypsin digestion confirmed the selective covalent thiocarbamoylation of Cys-242 in solution. The Giardia viability studies in the metronidazole-resistant strain and the G. lamblia CK irreversible inactivation mechanism show that the thiuram compounds can circumvent the resistance mechanism that renders metronidazole ineffectiveness in drug resistance cases of giardiasis. Together, the studies suggest that G. lamblia CK is an attractive drug target for development of novel antigiardial therapies and that disulfiram, an FDA-approved drug, is a promising candidate for drug repurposing. PMID:24558036

Kinetic characterization of arginine deiminase and carbamate kinase from Streptococcus pyogenes M49.

PubMed

Hering, Silvio; Sieg, Antje; Kreikemeyer, Bernd; Fiedler, Tomas

2013-09-01

Streptococcus pyogenes (group A Streptococcus, GAS) is an important human pathogen causing mild superficial infections of skin and mucous membranes, but also life-threatening systemic diseases. S. pyogenes and other prokaryotic organisms use the arginine deiminase system (ADS) for survival in acidic environments. In this study, the arginine deiminase (AD), and carbamate kinase (CK) from S. pyogenes M49 strain 591 were heterologously expressed in Escherichia coli DH5α, purified, and kinetically characterized. AD and CK from S. pyogenes M49 share high amino acid sequence similarity with the respective enzymes from Lactococcus lactis subsp. lactis IL1403 (45.6% and 53.5% identical amino acids) and Enterococcus faecalis V583 (66.8% and 66.8% identical amino acids). We found that the arginine deiminase of S. pyogenes is not allosterically regulated by the intermediates and products of the arginine degradation (e.g., ATP, citrulline, carbamoyl phosphate). The Km and Vmax values for arginine were 1.13±0.12mM (mean±SD) and 1.51±0.07μmol/min/mg protein. The carbamate kinase is inhibited by ATP but unaffected by arginine and citrulline. The Km and Vmax values for ADP were 0.72±0.08mM and 1.10±0.10μmol/min/mg protein and the Km for carbamoyl phosphate was 0.65±0.07mM. The optimum pH and temperature for both enzymes were 6.5 and 37°C, respectively. Copyright © 2013 Elsevier Inc. All rights reserved.

Organophosphorus and carbamate pesticide residues detected in water samples collected from paddy and vegetable fields of the Savar and Dhamrai Upazilas in Bangladesh.

PubMed

Chowdhury, Md Alamgir Zaman; Banik, Sanjoy; Uddin, Borhan; Moniruzzaman, Mohammed; Karim, Nurul; Gan, Siew Hua

2012-09-11

Several types of organophosphorous and carbamate pesticides have been used extensively by the farmers in Bangladesh during the last few decades. Twenty seven water samples collected from both paddy and vegetable fields in the Savar and Dhamrai Upazilas in Bangladesh were analyzed to determine the occurrence and distribution of organo-phosphorus (chlorpyrifos, malathion and diazinon) and carbamate (carbaryl and carbofuran) pesticide residues. A high performance liquid chromatograph instrument equipped with a photodiode array detector was used to determine the concentrations of these pesticide residues. Diazinon and carbofuran were detected in water samples collected from Savar Upazila at 0.9 μg/L and 198.7 μg/L, respectively. Malathion was also detected in a single water sample at 105.2 μg/L from Dhamrai Upazila. Carbaryl was the most common pesticide detected in Dhamrai Upazila at 14.1 and 18.1 μg/L, while another water sample from Dhamrai Upazila was contaminated with carbofuran at 105.2 μg/L. Chlorpyrifos was not detected in any sample. Overall, the pesticide residues detected were well above the maximum acceptable levels of total and individual pesticide contamination, at 0.5 and 0.1 μg/L, respectively, in water samples recommended by the European Economic Community (Directive 98/83/EC). The presence of these pesticide residues may be attributed by their intense use by the farmers living in these areas. Proper handling of these pesticides should be ensured to avoid direct or indirect exposure to these pesticides.

Ortho effects in quantitative structure-activity relationships for acetylcholinesterase inhibition by aryl carbamates.

PubMed

Lin, Gialih; Liu, Yu-Chen; Lin, Yan-Fu; Wu, Yon-Gi

2004-10-01

Ortho-substituted phenyl-N-butyl carbamates (1-9) are characterized as "pseudo-pseudo-substrate" inhibitors of acetylcholinesterase. Since the inhibitors protonate at pH 7.0 buffer solution, the virtual inhibition constants (K'is) of the protonated inhibitors are calculated from the equation, - logK'i = - logKi - logKb. The logarithms of the inhibition constant (Ki), the carbamylation constant (k(c)), and the bimolecular inhibition constant (k(i)) for the enzyme inhibitions by carbamates 1-9 are multiply linearly correlated with the Hammett para-substituent constant (sigma(p)), the Taft-Kutter-Hansch ortho steric constant (E(S)), and the Swan-Lupton ortho polar constant (F). Values of rho, delta, and f for the - logKi-, logk(c)-, and logk(i)-correlations are -0.6, -0.16, 0.7; 0.11, 0.03, -0.3; and - 0.5, - 0.12, 0.4, respectively. The Ki step further divides into two steps: 1) the pre-equilibrium protonation of the inhibitors, Kb step and 2) formation of a negatively charged enzyme-inhibitor Michaelis-Menten complex--virtual inhibition, K'i step. The Ki step has little ortho steric enhancement effect; moreover, the k(c)step is insensitive to the ortho steric effect. The f value of 0.7 for the Ki step indicates that ortho electron-withdrawing substituents of the inhibitors accelerate the inhibition reactions from the ortho polar effect; however, the f value of -0.3 for the k(c)step implies that ortho electron-withdrawing substituents of the inhibitors lessen the inhibition reactions from the ortho polar effect.

Cross-reactions between xanthates and rubber additives.

PubMed

Sasseville, Denis; Al-Sowaidi, Mowza; Moreau, Linda

2007-09-01

We previously described allergic contact dermatitis from xanthates used in the recovery of metals from mining ores. We observed cross-reactions with carbamates, believed to be due to the common "dithio" nucleus shared by both groups. The present study was undertaken to establish the rate of cross-reactions between xanthates and rubber additives. Between November 2002 and December 2005, 1,220 consecutive patients were patch-tested with sodium isopropyl xanthate 10% in petrolatum (pet) and with potassium amyl xanthate 10% pet and later 5% pet, in addition to the North American Contact Dermatitis Group standard series and other series as required by their conditions. Fifty-one patients reacted to xanthates, carbamates, or thiurams; 26 reacted to xanthates only, and these reactions were felt to be irritant. Twenty-five patients reacted to xanthates and/or to one or more of the rubber additives, 12 had positive reactions to xanthates and to either carba mix or thiuram mix, 10 reacted to xanthates and carba mix, 9 reacted to xanthates and thiuram mix, and 8 showed positive reactions to xanthates and both mixes. However, 13 patients had positive reactions to carba mix and thiuram mix but did not react to xanthates. Six patients reacted to other rubber additives such as mercaptobenzothiazole, black rubber mix, and mixed dialkyl thioureas. Five of these patients also reacted to xanthates, 4 reacted to xanthates and carba mix, and 3 reacted to xanthates, carba mix, and thiuram mix. Of patients sensitized to carbamates, thiurams, or mercaptobenzothiazole, 50% exhibit cross-reactions with xanthates. Xanthates are irritants, and their patch-test concentrations should be lowered to 5% or less.

Esterase metabolism of cholinesterase inhibitors using rat liver in vitro

EPA Science Inventory

A variety of chemicals, such as organophosphate (OP) and carbamate pesticides, nerve agents, and industrial chemicals, inhibit acetylcholinesterase (AChE) leading to overstimulation of the cholinergic nervous system. The resultant neurotoxicity is similar across mammalian species...

Estimation of hydrolysis rate constants for carbamates

EPA Science Inventory

Cheminformatics based tools, such as the Chemical Transformation Simulator under development in EPA’s Office of Research and Development, are being increasingly used to evaluate chemicals for their potential to degrade in the environment or be transformed through metabolism...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2011 CFR

2011-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

Are Pesticides Taking Away the Ability of Our Children to Learn?

ERIC Educational Resources Information Center

O'Brien, Mary

1991-01-01

The effects of neurotoxins on the development of the central and peripheral nervous systems are discussed. Organophosphates, carbamates, organic solvents, and dioxin are highlighted. The effects of long- and short-term exposure are described. (CW)

Acetylcholinesterases of Blood-feeding Flies and Ticks

USDA-ARS?s Scientific Manuscript database

Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer’s disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, ...

Diagnosis & Treatment of Poisoning by Pesticides.

ERIC Educational Resources Information Center

Environmental Protection Agency, Washington, DC. Office of Pesticide Programs.

This report succinctly discusses the steps necessary to diagnose and treat poisoning from pesticides, especially organophosphates, carbamates and chlorinated hydrocarbons. Immediate and continuing steps in the care of poisoning victims are outlined with supportive information on where to locate emergency assistance. (CS)

Evidence for non-acetylcholinesterase mechanisms in pesticide-induced developmental neurotoxicity#

EPA Science Inventory

Acetylcholinesterase inhibition is a well-established mode of action for adverse effects of organophosphorus and carbamate pesticides, and the use of this endpoint in regulatory considerations has been assumed to be protective of downstream cholinergic effects. It has been questi...

Evidence for non-acetylcholinesterase mechanisms in pesticide-induced developmental neurotoxicity

EPA Science Inventory

Acetyicholinesterase inhibition is a well-established mode of action for adverse effects of organophosphorus and carbamate pesticides, and the use of this endpoint in regulatory considerations has been assumed to be protective of downstream cholinergic effects. It has been questi...

DECREASED HEART RATE IS ASSOCIATED WITH CARBAMATE-INDUCED ACTIVATION OF PRO-INFLAMMATORY SERUM PROTEINS.

EPA Science Inventory

Previously we reported that chlorpyrifos (CHP), an irreversible cholinesterase (ChE) inhibitor, induces hypertension in rats. Concomitant with hypertension, we found an increase in C-reactive protein, macrophage inflammatory protein-2 , monocyte chemotactic protein-5 and interfer...

Age-related behavioral effects of methomyI in Brown Norway rats.

EPA Science Inventory

Methomyl is a cholinesterase-inhibiting carbamate pesticide that is used in the field on cotton and a variety of fruits and vegetables. Concerns have been raised generally about age-related differences in susceptibility to cholinesterase-inhibiting pesticides, especially for chil...

Behavioral changes in young and adult rats: Indications of cholinesterase inhibition

EPA Science Inventory

Inhibition of acetylcholinesterase (AChE) has long been accepted as the basis for neurotoxicity produced by organophosphorus (OP) and N-methyl carbamate chemicals. Functional or behavioral alterations result from acute exposure to these chemicals. We have conducted behavioral eva...

Behavioral changes in adult and young rats as indications of cholinesterase inhibition

EPA Science Inventory

Inhibition of acetylcholinesterase has long been accepted as the basis for neurotoxicity produced by organophosphorus (OP) and N-methyl carbamate chemicals. Functional or behavioral alterations result from acute exposure to these chemicals. We have evaluated behavioral changes an...

POTENT UREA AND CARBAMATE INHIBITORS OF SOLUBLE EPOXIDE HYDROLASES. (R825433)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

A Comparison of the Antimuscarinic Properties of Aprophen with Those of Some Other Anticholinergic Drugs,

DTIC Science & Technology

1980-09-01

DESCRIPTORS: 630 Cholinergic Blocking Agents 636 Aprophen 645 Acetylcholine Chloride Acetylcholinesterase Atropine Benactyzine Carbachol Carbamates...nervous systems by antagonism of carbachol -induced contractions of the guinea pig ileum, and antagonism of oxotremorine-induced tremors in mice

Effect of Cooking Process on the Residues of Three Carbamate Pesticides in Rice

PubMed Central

Shoeibi, Shahram; Amirahmadi, Maryam; Yazdanpanah, Hassan; Pirali-Hamedani, Morteza; Pakzad, Saied Reza; Kobarfard, Farzad

2011-01-01

A gas chromatography mass spectrometry with spike calibration curve method was used to quantify three carbamate pesticides residue in cooked white rice and to estimate the reduction percentage of the cooking process duration. The selected pesticides are three carbamate pesticides including carbaryl and pirimicarb that their MRL is issued by “The Institute of Standards of Iran” and propoxur which is used as a widely consumed pesticide in rice. The analytical method entailed the following steps: 1- Blending 15 g cooked sample with 120 mL acetonitrile for 1 min in solvent proof blender, 2- Adding 6 g NaCl and blending for 1 min, 3- Filtering upper layer through 25 g anhydrous Na2SO4, 4- Cleaning up with PSA and MgSO4, 5- Centrifuging for 7 min, 6- Evaporating about 0.3 mL and reconstituting in toluene till 1 mL, 7- Injecting 2 μL extract into GC/MS and analyzing by single quadruple selected ion monitoring GC/MS-SQ-SIM. The concentration of pesticides and the percentage of pesticides amounts after the cooking were determined by gas chromatography mass-spectrometry (GC/MS) using with interpolation of the relative peak areas for each pesticide to internal standard peak area in the sample on the spiked calibration curve. Calibration curve was linear over the range of 25 to 1000 ng/g, and LOQ was 25 ng/g for all three pesticides. The percent of loss for the three pesticides were 78%, 55% and 35% for carbaryl, propoxur and pirimicarb respectively. Different parameters such as vapor pressure, boiling point, and suspect ability of the compound to hydrolysis, could be responsible for the losing of pesticides during the cooking process. PMID:24363690

Kinetics of bulk photo-initiated copper(i)-catalyzed azide–alkyne cycloaddition (CuAAC) polymerizations†

PubMed Central

Song, Han Byul; Baranek, Austin; Bowman, Christopher N.

2016-01-01

Photoinitiation of polymerizations based on the copper(i)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction enables spatio-temporal control and the formation of mechanically robust, highly glassy photopolymers. Here, we investigated several critical factors influencing photo-CuAAC polymerization kinetics via systematic variation of reaction conditions such as the physicochemical nature of the monomers; the copper salt and photoinitiator types and concentrations; light intensity; exposure time and solvent content. Real time Fourier transform infrared spectroscopy (FTIR) was used to monitor the polymerization kinetics in situ. Six different di-functional azide monomers and four different tri-functional alkyne monomers containing either aliphatic, aromatic, ether and/or carbamate substituents were synthesized and polymerized. Replacing carbamate structures with ether moieties in the monomers enabled an increase in conversion from 65% to 90% under similar irradiation conditions. The carbamate results in stiffer monomers and higher viscosity mixtures indicating that chain mobility and diffusion are key factors that determine the CuAAC network formation kinetics. Photoinitiation rates were manipulated by altering various aspects of the photo-reduction step; ultimately, a loading above 3 mol% per functional group for both the copper catalyst and the photoinitiator showed little or no rate dependence on concentration while a loading below 3 mol% exhibited 1st order rate dependence. Furthermore, a photoinitiating system consisting of camphorquinone resulted in 60% conversion in the dark after only 1 minute of 75 mW cm−2 light exposure at 400–500 nm, highlighting a unique characteristic of the CuAAC photopolymerization enabled by the combination of the copper(i)’s catalytic lifetime and the nature of the step-growth polymerization. PMID:27429650

Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children

PubMed Central

Rowe, Christopher; Gunier, Robert; Bradman, Asa; Harley, Kim G.; Kogut, Katherine; Parra, Kimberly; Eskenazi, Brenda

2016-01-01

Background Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. Objectives To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. Methods We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. Results Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = −3.0; 95% Confidence Interval (CI) = (−5.6, −0.3)], Perceptual Reasoning [β = −4.0; (−7.6, −0.4)], and Working Memory [β = −2.8; (−5.6, −0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. Conclusions Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age. PMID:27281690

Proline-Based Carbamates as Cholinesterase Inhibitors.

PubMed

Pizova, Hana; Havelkova, Marketa; Stepankova, Sarka; Bak, Andrzej; Kauerova, Tereza; Kozik, Violetta; Oravec, Michal; Imramovsky, Ales; Kollar, Peter; Bobal, Pavel; Jampilek, Josef

2017-11-14

Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2 S )-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate (IC 50 = 46.35 μM) was the most potent agent. On the other hand, benzyl (2 S )-2-[(4-bromophenyl)-] and benzyl (2 S )-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC 50 = 28.21 and 27.38 μM, respectively) comparable with that of rivastigmine. The ortho -brominated compound as well as benzyl (2 S )-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure-inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA) and principal component analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3'-/4'-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE.

Low-density solvent based ultrasound-assisted emulsification microextraction and on-column derivatization combined with gas chromatography-mass spectrometry for the determination of carbamate pesticides in environmental water samples.

PubMed

Guo, Liang; Lee, Hian Kee

2012-04-27

A fast and efficient method for the determination of trace level of carbamate pesticides using a lower-density-than-water solvent for ultrasound-assisted emulsification microextraction coupled to on-column derivatization and analysis by GC-MS has been developed and studied. In this approach, a soft plastic Pasteur pipette was employed as a convenient extraction device. Fifty microliters of extraction solvent, of lower density than water, was injected into the sample solution held in the pipette. The latter was immediately immersed in an ultrasound water bath to form an emulsion. After 2 min extraction, the emulsion was fractionated into two layers by centrifugation. The upper layer (organic extract) could be collected conveniently by squeezing the bulb of the pipette, now held upside down, to move it into the narrow stem of the device, facilitating its retrieval for analysis. The extract was then combined with trimethylphenylammonium hydroxide and directly injected into a gas chromatography-mass spectrometry (GC-MS) system for on-column derivatization and analysis. The on-column derivatization provided an added convenience (since a separate step was not necessary). Parameters affecting the derivatization and extraction were investigated. Under the most favorable conditions, the method demonstrated high extraction efficiency with low limits of detection of between 0.01 and 0.1 μg/L, good linearity in the range of 0.05-50 μg/L, to 0.5-100 μg/L, and good repeatability (RSD below 9.2%, n=5). The proposed method was evaluated by determining carbamate pesticides in river water samples. Copyright © 2012 Elsevier B.V. All rights reserved.

Multi-enzyme inhibition assay for the detection of insecticidal organophosphates and carbamates by high-performance thin-layer chromatography applied to determine enzyme inhibition factors and residues in juice and water samples.

PubMed

Akkad, Rami; Schwack, Wolfgang

2010-05-15

Esterase inhibition assays provide an effect-directed tool of rapid screening for inhibitors in environmental and food samples. According to a multi-enzyme microtiter-plate assay, rabbit liver esterase (RLE), Bacillus subtilis esterase (BS2), and cutinase from Fusarium solani pisi (CUT) were used for the detection of 21 organophosphorus and carbamate pesticides by high-performance thin-layer chromatography-enzyme inhibition assays (HPTLC-EI). Staining was performed with Fast Blue Salt B coupling to alpha-naphthol enzymatically released from the respective acetate used as substrate. Quantitative analysis was achieved by densitometric evaluation at 533 nm. Enzyme inhibition factors derived from HPTLC-EI were calculated from the slopes of the linear calibration curves, which allowed comparisons to published inhibition constants and well correlated to sensitivity parameters. Limits of detection ranged from a few pg/zone for organophosphates as strongest inhibitors to a few ng/zone for most carbamates, when RLE and BS2 were used. Without oxidation, chlorpyrifos and parathion were directly detectable at approximately 60 and 14 ng/zone, respectively. As the enzyme of lowest sensitivity, CUT was able to detect insecticides of high and low inhibitory power from the ng to microg range per zone. Due to high selectivity of enzyme inhibition, oxon impurities of thionophosphate standards were strongly detected, although only present in low traces. The exemplary application of HPTLC-EI (RLE) to apple juice and drinking water samples spiked with paraoxon (0.001 mg/L), parathion (0.05 mg/L) and chlorpyrifos (0.5mg/L) resulted in mean recoveries between 71 and 112% with standard deviations of 2.0-18.3%. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Separation and aquatic toxicity of enantiomers of the pyrethroid insecticide lambda-cyhalothrin.

PubMed

Xu, Chao; Wang, Jiajia; Liu, Weiping; Daniel Sheng, G; Tu, Yunjie; Ma, Yun

2008-01-01

Chiral pollutants are receiving growing environmental concern due to differential biological activities of their enantiomers. In the present study, enantiomeric separation of the pyrethroid insecticide lambda-cyhalothrin (LCT) was investigated by high-performance liquid chromatography (HPLC) using the columns of Chiralpak AD (amylase tris[3,5-dimethyl-phenyl carbamate]), Chiralpak AS (amylase tris[(S)-1-phenyl carbamate]), Chiralcel OD (cellulose tris[3,5-dimethylphenyl carbamate]), and Chiralcel OJ (cellulose tris[4-methyl benzoate]) with different chiral stationary phases. The differential toxicities of the enantiomers in aquatic systems were evaluated using the acute zebrafish (Danio rerio) toxicity test and the zebrafish embryo test. The enantiomers of LCT were separated completely on all the columns tested and detected by circular dichroism at 236 nm. Better separations were achieved at lower temperatures (e.g., 20 degrees C) and lower levels of polar modifiers (162 times more toxic than its antipode to zebrafish in the acute test. The embryo test indicated that the exposure to LCT enantioselectively induced crooked body, yolk sac edema, and pericardial edema and that the (-)-enantiomer was 7.2 times stronger than the (+)-enantiomer in 96-h mortality. The malformations were induced by the racemate and its (-)-enantiomer at lower concentrations tested (e.g., 50 microg L(-1)), whereas the (+)-enantiomer induced malformations at relatively higher concentrations (>/=100 microg L(-1)). These results suggest that the toxicological effects of chiral pesticides must be evaluated using their individual enantiomers.

Structure of an Insecticide Sequestering Carboxylesterase from the Disease Vector Culex quinquefasciatus: What Makes an Enzyme a Good Insecticide Sponge?

PubMed

Hopkins, Davis H; Fraser, Nicholas J; Mabbitt, Peter D; Carr, Paul D; Oakeshott, John G; Jackson, Colin J

2017-10-17

Carboxylesterase (CBE)-mediated metabolic resistance to organophosphate and carbamate insecticides is a major problem for the control of insect disease vectors, such as the mosquito. The most common mechanism involves overexpression of CBEs that bind to the insecticide with high affinity, thereby sequestering them before they can interact with their target. However, the absence of any structure for an insecticide-sequestering CBE limits our understanding of the molecular basis for this process. We present the first structure of a CBE involved in sequestration, Cqestβ2 1 , from the mosquito disease vector Culex quinquefasciatus. Lysine methylation was used to obtain the crystal structure of Cqestβ2 1 , which adopts a canonical α/β-hydrolase fold that has high similarity to the target of organophosphate and carbamate insecticides, acetylcholinesterase. Sequence similarity networks of the insect carboxyl/cholinesterase family demonstrate that CBEs associated with metabolic insecticide resistance across many species share a level of similarity that distinguishes them from a variety of other classes. This is further emphasized by the structural similarities and differences in the binding pocket and active site residues of Cqestβ2 1 and other insect carboxyl/cholinesterases. Stopped-flow and steady-state inhibition studies support a major role for Cqestβ2 1 in organophosphate resistance and a minor role in carbamate resistance. Comparison with another isoform associated with insecticide resistance, Cqestβ1, showed both enzymes have similar affinity to insecticides, despite 16 amino acid differences between the two proteins. This provides a molecular understanding of pesticide sequestration by insect CBEs and could facilitate the design of CBE-specific inhibitors to circumvent this resistance mechanism in the future.

Impact of chemical proportions on the acute neurotoxicity of a mixture of seven carbamates in preweanling and adult rats.

PubMed

Moser, Virginia C; Padilla, Stephanie; Simmons, Jane Ellen; Haber, Lynne T; Hertzberg, Richard C

2012-09-01

Statistical design and environmental relevance are important aspects of studies of chemical mixtures, such as pesticides. We used a dose-additivity model to test experimentally the default assumptions of dose additivity for two mixtures of seven N-methylcarbamates (carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, and propoxur). The best-fitting models were selected for the single-chemical dose-response data and used to develop a combined prediction model, which was then compared with the experimental mixture data. We evaluated behavioral (motor activity) and cholinesterase (ChE)-inhibitory (brain, red blood cells) outcomes at the time of peak acute effects following oral gavage in adult and preweanling (17 days old) Long-Evans male rats. The mixtures varied only in their mixing ratios. In the relative potency mixture, proportions of each carbamate were set at equitoxic component doses. A California environmental mixture was based on the 2005 sales of each carbamate in California. In adult rats, the relative potency mixture showed dose additivity for red blood cell ChE and motor activity, and brain ChE inhibition showed a modest greater-than additive (synergistic) response, but only at a middle dose. In rat pups, the relative potency mixture was either dose-additive (brain ChE inhibition, motor activity) or slightly less-than additive (red blood cell ChE inhibition). On the other hand, at both ages, the environmental mixture showed greater-than additive responses on all three endpoints, with significant deviations from predicted at most to all doses tested. Thus, we observed different interactive properties for different mixing ratios of these chemicals. These approaches for studying pesticide mixtures can improve evaluations of potential toxicity under varying experimental conditions that may mimic human exposures.

Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children.

PubMed

Rowe, Christopher; Gunier, Robert; Bradman, Asa; Harley, Kim G; Kogut, Katherine; Parra, Kimberly; Eskenazi, Brenda

2016-10-01

Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age. Copyright © 2016 Elsevier Inc. All rights reserved.

Kinetics of bulk photo-initiated copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) polymerizations.

PubMed

Song, Han Byul; Baranek, Austin; Bowman, Christopher N

2016-01-21

Photoinitiation of polymerizations based on the copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction enables spatio-temporal control and the formation of mechanically robust, highly glassy photopolymers. Here, we investigated several critical factors influencing photo-CuAAC polymerization kinetics via systematic variation of reaction conditions such as the physicochemical nature of the monomers; the copper salt and photoinitiator types and concentrations; light intensity; exposure time and solvent content. Real time Fourier transform infrared spectroscopy (FTIR) was used to monitor the polymerization kinetics in situ . Six different di-functional azide monomers and four different tri-functional alkyne monomers containing either aliphatic, aromatic, ether and/or carbamate substituents were synthesized and polymerized. Replacing carbamate structures with ether moieties in the monomers enabled an increase in conversion from 65% to 90% under similar irradiation conditions. The carbamate results in stiffer monomers and higher viscosity mixtures indicating that chain mobility and diffusion are key factors that determine the CuAAC network formation kinetics. Photoinitiation rates were manipulated by altering various aspects of the photo-reduction step; ultimately, a loading above 3 mol% per functional group for both the copper catalyst and the photoinitiator showed little or no rate dependence on concentration while a loading below 3 mol% exhibited 1 st order rate dependence. Furthermore, a photoinitiating system consisting of camphorquinone resulted in 60% conversion in the dark after only 1 minute of 75 mW cm -2 light exposure at 400-500 nm, highlighting a unique characteristic of the CuAAC photopolymerization enabled by the combination of the copper(i)'s catalytic lifetime and the nature of the step-growth polymerization.

Strong cation exchange-type chiral stationary phase for enantioseparation of chiral amines in subcritical fluid chromatography.

PubMed

Wolrab, Denise; Kohout, Michal; Boras, Mario; Lindner, Wolfgang

2013-05-10

A new strong cation exchange type chiral stationary phase (SCX CSP) based on a syringic acid amide derivative of trans-(R, R)-2-aminocyclohexanesulfonic acid was applied to subcritical fluid chromatography (SFC) for separation of various chiral basic drugs and their analogues. Mobile phase systems consisting of aliphatic alcohols as polar modifiers and a broad range of amines with different substitution patterns and lipophilicity were employed to evaluate the impact on the SFC retention and selectivity characteristics. The observed results point to the existence of carbonic and carbamic acid salts formed as a consequence of reactions occurring between carbon dioxide, the alcoholic modifiers and the amine species present in the sub/supercritical fluid medium, respectively. Evidence is provided that these species are essential for affecting ion exchange between the strongly acidic chiral selector units and the basic analytes, following the well-established stoichiometric displacement mechanisms. Specific trends were observed when different types of amines were used as basic additives. While ammonia gave rise to the formation of the most strongly eluting carbonic and carbamic salt species, simple tertiary amines consistently provided superior levels of enantioselectivity. Furthermore, trends in the chiral SFC separation characteristics were investigated by the systematic variation of the modifier content and temperature. Different effects of additives are interpreted in terms of changes in the relative concentration of the transient ionic species contributing to analyte elution, with ammonia-derived carbamic salts being depleted at elevated temperatures by decomposition. Additionally, in an effort to optimize SFC enantiomer separation conditions for selected analytes, the impact of the type of the organic modifier, temperature, flow rate and active back pressure were also investigated. Copyright © 2013 Elsevier B.V. All rights reserved.

Recurrence of carbamoyl phosphate synthetase 1 (CPS1) deficiency in Turkish patients: characterization of a founder mutation by use of recombinant CPS1 from insect cells expression.

PubMed

Hu, Liyan; Diez-Fernandez, Carmen; Rüfenacht, Véronique; Hismi, Burcu Öztürk; Ünal, Özlem; Soyucen, Erdogan; Çoker, Mahmut; Bayraktar, Bilge Tanyeri; Gunduz, Mehmet; Kiykim, Ertugrul; Olgac, Asburce; Pérez-Tur, Jordi; Rubio, Vicente; Häberle, Johannes

2014-12-01

Carbamoyl phosphate synthetase 1 (CPS1) deficiency due to CPS1 mutations is a rare autosomal-recessive urea cycle disorder causing hyperammonemia that can lead to death or severe neurological impairment. CPS1 catalyzes carbamoyl phosphate formation from ammonia, bicarbonate and two molecules of ATP, and requires the allosteric activator N-acetyl-L-glutamate. Clinical mutations occur in the entire CPS1 coding region, but mainly in single families, with little recurrence. We characterized here the only currently known recurrent CPS1 mutation, p.Val1013del, found in eleven unrelated patients of Turkish descent using recombinant His-tagged wild type or mutant CPS1 expressed in baculovirus/insect cell system. The global CPS1 reaction and the ATPase and ATP synthesis partial reactions that reflect, respectively, the bicarbonate and the carbamate phosphorylation steps, were assayed. We found that CPS1 wild type and V1013del mutant showed comparable expression levels and purity but the mutant CPS1 exhibited no significant residual activities. In the CPS1 structural model, V1013 belongs to a highly hydrophobic β-strand at the middle of the central β-sheet of the A subdomain of the carbamate phosphorylation domain and is close to the predicted carbamate tunnel that links both phosphorylation sites. Haplotype studies suggested that p.Val1013del is a founder mutation. In conclusion, the mutation p.V1013del inactivates CPS1 but does not render the enzyme grossly unstable or insoluble. Recurrence of this particular mutation in Turkish patients is likely due to a founder effect, which is consistent with the frequent consanguinity observed in the affected population. Copyright © 2014 Elsevier Inc. All rights reserved.

[A pharmacological study of chlorphenesin carbamate. Tolerance to chlorphenesin carbamate (author's transl)].

PubMed

Sasajima, M; Aihara, H; Akiyama, F; Tsuchida, K; Otomo, S

1977-04-01

Tolerance to chlorphenesin carbamate (CPC) was investigated from the viewpoints of action of CPC, serum free CPC concentration, the activity of UDP-glucuronyltransferase and the content of cytochrome P-450. CPC was administered once daily for 7 or 14 days. In mice, the hypnotic action of hexobarbital injected 24 hours after the last administration of CPC and the motor incoordinating action of CPC significantly decreased on the 7th day, but slightly recovered on the 14th day. Serum free CPC concentration also decreased on the 7th day, but recovered on the 14th day. A significant relationship between the motor incoordinating action of CPC and serum free CPC concentration was observed. Therefore, the recovery of CPC effect on the 14th day was considered to be due to the recovery from the induction of drug-metabolizing enzymes. On the other hand, in rats, the weekly alteration of the motor incoordinating action of CPC was similar to that observed in mice. Serum free CPC concentration on the 7th and 14th days was lower than that on the 1st day, and enzyme induction was observed during CPC administration. Notwithstanding the low level of serum free CPC concentration, the recovery of CPC effect was observed on the 14th day and such was considered to be due to habituation to the rotarod. In mice and rats, it was demonstrated that the intensity of CPC effect was dependent on serum free CPC concentration to the extent that enzyme induction played an important role in the development of tolerance. From these results, the tolerance to CPC is attributed to induction of drug-metabolizing enzymes in liver microsomes.

Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

EPA Science Inventory

Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

JPRS Report, Science & Technology, Japan

DTIC Science & Technology

1987-06-29

analysis was con- ducted of the properties of adsorbents, operating conditions, and unit prices of materials. In the case of a four-layer structure with...organic adsorbents of the amidoxime system and dithio carbamate system, and new 29 adsorbents originating from biotic bodies such as tannin , are being

AN APPROACH FOR SCREENING CHOLINESTERASE INHIBITORS IN DRINKING WATER USING AN IMMOBILIZED ENZYME ASSAY

EPA Science Inventory

A simple, inexpensive and sensitive method for detecting organophosphate and carbamate insecticides is reported. Acetylcholinesterase was immobilized to PorexR Lateral-FloTM membrane material and remained active for several months at room temperature. The assay was sensitive ...

40 CFR 272.751 - Indiana state-administered program: Final authorization.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Hazardous Waste Management System; Testing and Monitoring Activities (Checklist 158) 62 FR 32452 June 13... Management System; Carbamate Production, Identification and Listing of Hazardous Waste; Land Disposal... Indiana Department of Environmental Management, signed by the Commissioner of the IDEM on February 14...

EFFECTS ON THE FETUS OF MATERNAL BENOMYL EXPOSURE IN THE PROTEIN-DEPRIVED RAT

EPA Science Inventory

The separate and combined effects of protein deprivation and benomyl ((methyl 1-butylcarbomoyl)2-benzimidazole carbamate) exposure were studied in the pregnant rat fed a diet containing 24% (control) or 8% (deficient) casein throughout gestation. Within each diet group, subgroups...

ORGANOPHOSPHATE PESTICIDE DEGRADATION IN THE PRESENCE OF NATURALLY OCCURRING AQUATIC CONSTITUENTS UNDER DRINKING WATER TREATMENT CONDITIONS

EPA Science Inventory

Little work to date has solely investigated the kinetics and pathways of pesticide transformations under drinking water treatment conditions. Free chlorine has been found to react with s-triazine, carbamate, and organophosphate pesticides. However, these experimental conditions...

76 FR 62303 - California: Final Authorization of State Hazardous Waste Management Program Revision

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

...) Land Disposal Restrictions Phase IV--Treatment Standards for Wood Preserving Wastes, Paperwork... the Carbamate Land Disposal Restrictions; (5) Clarification of Standards for Hazardous Waste LDR...) Emergency Revision of the Land Disposal Restrictions (LDR) Treatment Standards for Listed Hazardous Wastes...

Increased Risk of Dementia in Patients With Acute Organophosphate and Carbamate Poisoning

PubMed Central

Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Kao, Chia-Hung

2015-01-01

Abstract Organophosphate (OP) and carbamate (CM) are the most commonly used pesticides against insects. Little is known regarding the relationship between dementia and acute OP and CM poisoning. A nationwide population-based cohort study was conducted from the National Health Insurance Research Database in Taiwan. The incidence and relative risk of dementia were assessed in patients hospitalized for acute OP and CM poisoning from 2000 to 2011. The comparison cohort was matched with the poisoned cohort at a 4:1 ratio based on age, sex, and the year of hospitalization. During the follow-up period, the incidence of dementia was 29.4 per 10,000 person-years in the poisoned group, and represented a 1.98-fold increased risk of dementia compared with the control cohort (95% confidence interval, 1.59–2.47). This study provides evidence on the association between dementia and acute OP and CM poisoning. Regular follow-up of poisoned patients for dementia is suggested. PMID:26200627

Selected Schizosaccharomyces pombe Strains Have Characteristics That Are Beneficial for Winemaking

PubMed Central

Benito, Ángel; Jeffares, Daniel; Palomero, Felipe; Calderón, Fernando; Bai, Feng-Yan; Bähler, Jürg; Benito, Santiago

2016-01-01

At present, wine is generally produced using Saccharomyces yeast followed by Oenococus bacteria to complete malolactic fermentation. This method has some unsolved problems, such as the management of highly acidic musts and the production of potentially toxic products including biogenic amines and ethyl carbamate. Here we explore the potential of the fission yeast Schizosaccharomyces pombe to solve these problems. We characterise an extensive worldwide collection of S. pombe strains according to classic biochemical parameters of oenological interest. We identify three genetically different S. pombe strains that appear suitable for winemaking. These strains compare favourably to standard Saccharomyces cerevisiae winemaking strains, in that they perform effective malic acid deacidification and significantly reduce levels of biogenic amines and ethyl carbamate precursors without the need for any secondary bacterial malolactic fermentation. These findings indicate that the use of certain S. pombe strains could be advantageous for winemaking in regions where malic acid is problematic, and these strains also show superior performance with respect to food safety. PMID:27007548

Enhanced mechanical properties of hydrothermal carbamated cellulose nanocomposite film reinforced with graphene oxide.

PubMed

Gan, Sinyee; Zakaria, Sarani; Syed Jaafar, Sharifah Nabihah

2017-09-15

Cellulose carbamate (CC) was synthesized via hydrothermal process and mixed with graphene oxide (GO) to form a homogeneous cellulose matrix nanocomposite films. The properties of CC/GO nanocomposite films fabricated using simple solution-mixing method with different GO loadings were studied. Transmission electron microscope analysis showed the exfoliation of self-synthesized GO nanosheets within the CC matrix. X-ray diffraction results confirmed the crystalline structure of CC/GO films as the CC/GO mass ratio increased from 100/0 to 100/4. The mechanical properties of CC/GO film were significantly improved as compared to neat CC film. From thermogravimetric analysis result, the introduction of GO enhanced the thermal stability and carbon yields. The 3D homogeneous porous structures of the CC/GO films were observed under Field emission scanning electron microscope. These improvements in nanocomposite film properties could be confirmed by Fourier transform infrared spectroscopy due to the strong and good interactions between CC and GO. Copyright © 2017 Elsevier Ltd. All rights reserved.

Formation of ethyl carbamate and changes during fermentation and storage of yellow rice wine.

PubMed

Wu, Pinggu; Cai, Chenggang; Shen, Xianghong; Wang, Liyuan; Zhang, Jing; Tan, Ying; Jiang, Wei; Pan, Xiaodong

2014-01-01

Ethyl carbamate (EC) was analyzed during yellow rice wine production and storage. EC increased slowly during fermentation and rapidly after frying and sterilization. Less amount of EC was formed when cooled rapidly to 30 °C than when cooled naturally. High temperature and long storage time increased EC formation. After 400 days storage, EC increased from 74.0 to 84.2, 131.8 and 509.4 μg/kg at 4 °C, room temperature and 37 °C, respectively, and there was significantly difference between the fried wine and the wine on sale from 2011 (p<0.01). Urea increased during yellow rice wine fermentation and was above 20 mg/kg after the wine was fried; urea contributed to EC formation when the fried wine was cooled slowly. These results indicate that it is necessary for industry to optimize the wine frying conditions, such as temperature, time and cooling process in order to decrease EC formation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis of kenaf cellulose carbamate using microwave irradiation for preparation of cellulose membrane.

PubMed

Gan, Sinyee; Zakaria, Sarani; Chia, Chin Hua; Kaco, Hatika; Padzil, Farah Nadia Mohammad

2014-06-15

Cellulose carbamate (CCs) was produced from kenaf core pulp (KCP) using microwave reactor-assisted method. The effects of urea concentration and reaction time on the formation of nitrogen content in CCs were investigated. The CCs' solubility in LiOH/urea system was determined and its membranes were characterized. As the urea content and reaction time increased, the nitrogen content form in CCs increased which enhanced the CCs' solubility. The formation of CCs was confirmed by Fourier transform infrared spectroscopy (FT-IR) and nitrogen content analysis. The CCs' morphology was examined using Scanning electron microscopy (SEM). The cellulose II and crystallinity index of the membranes were confirmed by X-ray diffraction (XRD). The pore size of the membrane displayed upward trend with respect to the urea content observed under Field emission scanning electron microscope (FESEM). This investigation provides a simple and efficient procedure of CCs determination which is useful in producing environmental friendly regenerated CCs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Highly porous regenerated cellulose hydrogel and aerogel prepared from hydrothermal synthesized cellulose carbamate.

PubMed

Gan, Sinyee; Zakaria, Sarani; Chia, Chin Hua; Chen, Ruey Shan; Ellis, Amanda V; Kaco, Hatika

2017-01-01

Here, a stable derivative of cellulose, called cellulose carbamate (CC), was produced from Kenaf (Hibiscus cannabinus) core pulp (KCP) and urea with the aid of a hydrothermal method. Further investigation was carried out for the amount of nitrogen yielded in CC as different urea concentrations were applied to react with cellulose. The effect of nitrogen concentration of CC on its solubility in a urea-alkaline system was also studied. Regenerated cellulose products (hydrogels and aerogels) were fabricated through the rapid dissolution of CC in a urea-alkaline system. The morphology of the regenerated cellulose products was viewed under Field emission scanning electron microscope (FESEM). The transformation of allomorphs in regenerated cellulose products was examined by X-ray diffraction (XRD). The transparency of regenerated cellulose products was determined by Ultraviolet-visible (UV-Vis) spectrophotometer. The degree of swelling (DS) of regenerated cellulose products was also evaluated. This investigation provides a simple and efficient procedure of CC determination which is useful in producing regenerated CC products.

Coordination effect-regulated CO2 capture with an alkali metal onium salts/crown ether system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Zhen-Zhen; Jiang, Deen; Zhu, Xiang

2014-01-01

A coordination effect was employed to realize equimolar CO2 absorption, adopting easily synthesized amino group containing absorbents (alkali metal onium salts). The essence of our strategy was to increase the steric hindrance of cations so as to enhance a carbamic acid pathway for CO2 capture. Our easily synthesized alkali metal amino acid salts or phenolates were coordinated with crown ethers, in which highly sterically hindered cations were obtained through a strong coordination effect of crown ethers with alkali metal cations. For example, a CO2 capacity of 0.99 was attained by potassium prolinate/18-crown-6, being characterized by NMR, FT-IR, and quantum chemistrymore » calculations to go through a carbamic acid formation pathway. The captured CO2 can be stripped under very mild conditions (50 degrees C, N-2). Thus, this protocol offers an alternative for the development of technological innovation towards efficient and low energy processes for carbon capture and sequestration.« less

From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system.

PubMed

Dhouib, Ines; Jallouli, Manel; Annabi, Alya; Marzouki, Soumaya; Gharbi, Najoua; Elfazaa, Saloua; Lasram, Mohamed Montassar

2016-05-01

The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

Azole-Anion-Based Aprotic Ionic Liquids: Functional Solvents for Atmospheric CO2 Transformation into Various Heterocyclic Compounds.

PubMed

Zhao, Yanfei; Wu, Yunyan; Yuan, Guangfeng; Hao, Leiduan; Gao, Xiang; Yang, Zhenzhen; Yu, Bo; Zhang, Hongye; Liu, Zhimin

2016-10-06

The chemical transformation of atmospheric CO 2 is of great significance yet still poses a great challenge. Herein, azole-anion-based aprotic ionic liquids (ILs) were synthesized by the deprotonation of weak proton donors (e.g., 2-methylimidazole, 4-methylimidazole, and 2,4-dimethylimidazole) with tetrabutylphosphonium hydroxide, [Bu 4 P][OH]. We found that these ILs, such as [Bu 4 P][2-MIm], could activate atmospheric CO 2 through the formation of carbamates. The resultant carbamate intermediates could further react with various types of substrate, including propargylic alcohols, 2-aminobenzonitriles, ortho-phenylenediamines, and 2-aminothiophenol, thereby producing α-alkylidene cyclic carbonates, quinazoline-2,4(1 H,3 H)-diones, benzimidazolones, and benzothiazoline, respectively, in moderate-to-good yields. Thus, we have achieved the transformation of CO 2 at atmospheric pressure, and we expect this method to open up new routes for the synthesis of various oxygen-containing heterocyclic compounds under metal-free conditions. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molybdenum Carbamate Nanosheets as a New Class of Potential Phase Change Materials.

PubMed

Zhukovskyi, Maksym; Plashnitsa, Vladimir; Petchsang, Nattasamon; Ruth, Anthony; Bajpai, Anshumaan; Vietmeyer, Felix; Wang, Yuanxing; Brennan, Michael; Pang, Yunsong; Werellapatha, Kalpani; Bunker, Bruce; Chattopadhyay, Soma; Luo, Tengfei; Janko, Boldizsar; Fay, Patrick; Kuno, Masaru

2017-06-14

We report for the first time the synthesis of large, free-standing, Mo 2 O 2 (μ-S) 2 (Et 2 dtc) 2 (MoDTC) nanosheets (NSs), which exhibit an electron-beam induced crystalline-to-amorphous phase transition. Both electron beam ionization and femtosecond (fs) optical excitation induce the phase transition, which is size-, morphology-, and composition-preserving. Resulting NSs are the largest, free-standing regularly shaped two-dimensional amorphous nanostructures made to date. More importantly, amorphization is accompanied by dramatic changes to the NS electrical and optical response wherein resulting amorphous species exhibit room-temperature conductivities 5 orders of magnitude larger than those of their crystalline counterparts. This enhancement likely stems from the amorphization-induced formation of sulfur vacancy-related defects and is supported by temperature-dependent transport measurements, which reveal efficient variable range hopping. MoDTC NSs represent one instance of a broader class of transition metal carbamates likely having applications because of their intriguing electrical properties as well as demonstrated ability to toggle metal oxidation states.

β-d-Glucosidase as "key enzyme" for sorghum cyanogenic glucoside (dhurrin) removal and beer bioflavouring.

PubMed

Tokpohozin, Sedjro Emile; Fischer, Susann; Sacher, Bertram; Becker, Thomas

2016-11-01

Sorghum malt used during African beer processing contains a high level of cyanogenic glucoside (dhurrin), up to 1375 ppm. In traditional sorghum malting and mashing, dhurrin is not sufficiently hydrolyzed due to uncontrolled germination and a high gelatinization temperature. The cyanide content of traditional African beers (11 ppm) is higher than the minimum dose (1 ppm) required to form carcinogenic ethyl carbamate during alcoholic fermentation. In the detoxification process, aryl-β-d-glucosidase (dhurrinase) is the "key component". For significant dhurrin hydrolysis during mashing, optimizing dhurrinase synthesis during malting is a good solution to reduce dhurrin completely to below the harmful dose in the sorghum wort. Lactic acid bacteria which exhibit aryl-β-d-glucosidase prior to alcoholic fermentation may help to reduce ethyl carbamate content in alcoholic beverages. Moreover, some specific β-d-glucosidases have a dual property, being able to cleave and synthesize glucosides bonds and thereby generating good precursors for beer bioflavouring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis, biological evaluation, and 3D QSAR study of 2-methyl-4-oxo-3-oxetanylcarbamic acid esters as N-acylethanolamine acid amidase (NAAA) inhibitors.

PubMed

Ponzano, Stefano; Berteotti, Anna; Petracca, Rita; Vitale, Romina; Mengatto, Luisa; Bandiera, Tiziano; Cavalli, Andrea; Piomelli, Daniele; Bertozzi, Fabio; Bottegoni, Giovanni

2014-12-11

N-(2-Oxo-3-oxetanyl)carbamic acid esters have recently been reported to be noncompetitive inhibitors of the N-acylethanolamine acid amidase (NAAA) potentially useful for the treatment of pain and inflammation. In the present study, we further explored the structure-activity relationships of the carbamic acid ester side chain of 2-methyl-4-oxo-3-oxetanylcarbamic acid ester derivatives. Additional favorable features in the design of potent NAAA inhibitors have been found together with the identification of a single digit nanomolar inhibitor. In addition, we devised a 3D QSAR using the atomic property field method. The model turned out to be able to account for the structural variability and was prospectively validated by designing, synthesizing, and testing novel inhibitors. The fairly good agreement between predictions and experimental potency values points to this 3D QSAR model as the first example of quantitative structure-activity relationships in the field of NAAA inhibitors.

Biodegradation of carbamate pesticides by natural river biofilms in different seasons and their effects on biofilm community structure.

PubMed

Tien, Chien-Jung; Lin, Mon-Chu; Chiu, Wan-Hsin; Chen, Colin S

2013-08-01

This study investigated the ability of natural river biofilms from different seasons to degrade the carbamate pesticides methomyl, carbaryl and carbofuran in single and multiple pesticide systems, and the effects of these pesticides on algal and bacterial communities within biofilms. Spring biofilms had the lowest biomass of algae and bacteria but showed the highest methomyl degradation (>99%) and dissipation rates, suggesting that they might contain microorganisms with high methomyl degradation abilities. Degradation of carbofuran (54.1-59.5%) by biofilms in four seasons was similar, but low degradation of carbaryl (0-27.5%) was observed. The coexistence of other pesticides was found to cause certain effects on pesticide degradation and primarily resulted in lower diversity of diatoms and bacteria than when using a single pesticide. The tolerant diatoms and bacteria potentially having the ability to degrade test pesticides were identified. River biofilms could be suitable biomaterials or used to isolate degraders for bioremediating pesticide-contaminated water. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biodegradation of Ethyl Carbamate and Urea with Lysinibacillus sphaericus MT33 in Chinese Liquor Fermentation.

PubMed

Cui, Kaixiang; Wu, Qun; Xu, Yan

2018-02-14

It is important to reduce the concentration of ethyl carbamate (EC) in fermented foods. However, controlling the formation of EC and its precursor urea is difficult in spontaneous food fermentation because urea is a natural product of nitrogen metabolism. Biodegradation is a better solution to reduce the concentration of EC. This study aimed to reduce the concentration of EC in Chinese liquor via an indigenous strain Lysinibacillus sphaericus MT33. This strain produced urethanase (940 U/L) and urease (1580 U/L) and degraded 76.52% of EC and 56.48% of urea. After inoculation in liquor fermentation, the maximal relative abundance of Lysinibacillus increased from 0.02% to 8.46%, the final EC and urea contents decreased by 41.77% and 28.15%. Moreover, the concentration of EC decreased by 63.32% in liquor. The negative correlation between abundance of Lysinibacillus and contents of EC and urea indicated the effect of L. sphaericus on EC and urea degradation.

Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides.

PubMed

Miarinjara, Adélaïde; Boyer, Sébastien

2016-02-01

Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines). Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur). Only one insecticide (dieldrin) was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin) to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar.

Nitrosamine formation in amine scrubbing at desorber temperatures.

PubMed

Fine, Nathan A; Goldman, Mark J; Rochelle, Gary T

2014-01-01

Amine scrubbing is a thermodynamically efficient and industrially proven method for carbon capture, but amine solvents can nitrosate in the desorber, forming potentially carcinogenic nitrosamines. The kinetics of reactions involving nitrite and monoethanolamine (MEA), diethanolamine (DEA), methylethanolamine (MMEA), and methyldiethanolamine (MDEA) were determined under desorber conditions. The nitrosations of MEA, DEA, and MMEA are first order in nitrite, carbamate species, and hydronium ion. Nitrosation of MDEA, a tertiary amine, is not catalyzed by the addition of CO2 since it cannot form a stable carbamate. Concentrated and CO2 loaded MEA was blended with low concentrations of N-(2-hydroxyethyl) glycine (HeGly), hydroxyethyl-ethylenediamine (HEEDA), and DEA, secondary amines common in MEA degradation. Nitrosamine yield was proportional to the concentration of secondary amine and was a function of CO2 loading and temperature. Blends of tertiary amines with piperazine (PZ) showed n-nitrosopiperazine (MNPZ) yields close to unity, validating the slow nitrosation rates hypothesized for tertiary amines. These results provide a useful tool for estimating nitrosamine accumulation over a range of amine solvents.

Simultaneous analysis of D-alanine, D-aspartic acid, and D-serine using chiral high-performance liquid chromatography-tandem mass spectrometry and its application to the rat plasma and tissues.

PubMed

Karakawa, Sachise; Shimbo, Kazutaka; Yamada, Naoyuki; Mizukoshi, Toshimi; Miyano, Hiroshi; Mita, Masashi; Lindner, Wolfgang; Hamase, Kenji

2015-11-10

A highly sensitive and selective chiral LC-MS/MS method for D-alanine, D-aspartic acid and D-serine has been developed using the precolumn derivatization reagents, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQ-Tag) or p-N,N,N-trimethylammonioanilyl N'-hydroxysuccinimidyl carbamate iodide (TAHS). The thus N-tagged enantiomers of the derivatized amino acids were nicely separated within 20min using the cinchona alkaloid-based zwittterionic ion-exchange type enantioselective column, Chiralpak ZWIX(+). The selected reaction monitoring was applied for detecting the target d-amino acids in biological matrices. By using the present chiral LC-MS/MS method, the three d-amino acids and their l-forms could be simultaneously determined in the range of 0.1-500nmol/mL. Finally, the technique was successfully applied to rat plasma and tissue samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Highly porous regenerated cellulose hydrogel and aerogel prepared from hydrothermal synthesized cellulose carbamate

PubMed Central

Gan, Sinyee; Chia, Chin Hua; Chen, Ruey Shan; Ellis, Amanda V.; Kaco, Hatika

2017-01-01

Here, a stable derivative of cellulose, called cellulose carbamate (CC), was produced from Kenaf (Hibiscus cannabinus) core pulp (KCP) and urea with the aid of a hydrothermal method. Further investigation was carried out for the amount of nitrogen yielded in CC as different urea concentrations were applied to react with cellulose. The effect of nitrogen concentration of CC on its solubility in a urea-alkaline system was also studied. Regenerated cellulose products (hydrogels and aerogels) were fabricated through the rapid dissolution of CC in a urea-alkaline system. The morphology of the regenerated cellulose products was viewed under Field emission scanning electron microscope (FESEM). The transformation of allomorphs in regenerated cellulose products was examined by X-ray diffraction (XRD). The transparency of regenerated cellulose products was determined by Ultraviolet–visible (UV–Vis) spectrophotometer. The degree of swelling (DS) of regenerated cellulose products was also evaluated. This investigation provides a simple and efficient procedure of CC determination which is useful in producing regenerated CC products. PMID:28296977

[Degradation of urea and ethyl carbamate in Chinese Rice wine by recombinant acid urease].

PubMed

Zhou, Jianli; Kang, Zhen; Liu, Qingtao; Du, Guocheng; Chen, Jian

2016-01-01

Ethyl carbamate (EC) as a potential carcinogen commonly exists in traditional fermented foods. It is important eliminate urea that is the precursors of EC in many fermented foods, including Chinese Rice wine. On the basis of achieving high-level overexpression of food-grade ethanol-resistant acid urease, we studied the hydrolysis of urea and EC with the recombinant acid urease. Recombinant acid urease showed degraded urea in both the simulated system with ethanol and Chinese Rice wine (60 mg/L of urea was completely degraded within 25 h), indicating that the recombinant enzyme is suitable for the elimination of urea in Chinese Rice wine. Although recombinant acid urease also has degradation catalytic activity on EC, no obvious degradation of EC was observed. Further investigation results showed that the Km value for urea and EC of the recombinant acid urease was 0.7147 mmol/L and 41.32 mmol/L, respectively. The results provided theoretical foundation for realizing simultaneous degradation of urea and EC.

Whole Blood Cholinesterase Activity in 20 Species of Wild Birds.

PubMed

Horowitz, Igal H; Yanco, Esty G; Landau, Shmulik; Nadler-Valency, Rona; Anglister, Nili; Bueller-Rosenzweig, Ariela; Apelbom-Halbersberg, Tal; Cuneah, Olga; Hanji, Vera; Bellaiche, Michel

2016-06-01

Clinical signs of organophosphate and carbamate intoxication in wild birds can be mistaken for those of other diseases, thus potentially delaying diagnosis and implementation of life-saving treatment. The objective of this study was to determine the reference interval for blood cholinesterase activity in 20 different wild avian species from 7 different orders, thereby compiling a reference database for wildlife veterinarians. Blood was collected from birds not suspected of having organophosphate or carbamate toxicosis, and the modified Michel method, which determines the change in blood pH that directly correlates with cholinesterase activity, was used to measure blood cholinesterase levels. Results of change in blood pH values ranged from 0.11 for the white-tailed eagle ( Haliaeetus albicilla ) to 0.90 for the honey buzzard ( Pernis apivorus ). The results showed that even within the same family, interspecies differences in normal cholinesterase blood activity were not uncommon. The findings emphasized the importance of determining reference intervals for avian blood cholinesterase activity at the species level.

The arginine deiminase pathway of koji bacteria is involved in ethyl carbamate precursor production in soy sauce.

PubMed

Zhang, Jiran; Fang, Fang; Chen, Jian; Du, Guocheng

2014-09-01

Ethyl carbamate (EC) is a group 2A carcinogen generated from a few precursors in many fermented foods and alcoholic beverages. Citrulline, urea, carbamoyl phosphate, and ethanol are common precursors detected in fermented foods. In this study, citrulline was proved to be the main EC precursor in soy sauce, which was found to be accumulated in moromi mash period and correlated with the utilization of arginine by koji bacteria. Six koji isolates belonging to three genera were identified to be able to accumulate citrulline via the arginine deiminase (ADI) pathway. Among these strains, only Pediococcus acidilactici retained high activities in synthesis and accumulation of citrulline in the presence of high concentration of sodium chloride. These results suggested that P. acidilactici is responsible for the accumulation of citrulline, one of the EC precursors, in the process of soy sauce fermentation. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Detection of arc genes related with the ethyl carbamate precursors in wine lactic acid bacteria.

PubMed

Araque, Isabel; Gil, Joana; Carreté, Ramon; Bordons, Albert; Reguant, Cristina

2009-03-11

Trace amounts of the carcinogen ethyl carbamate can appear in wine by the reaction of ethanol with compounds such as citrulline and carbamyl phosphate, which are produced from arginine degradation by some wine lactic acid bacteria (LAB). In this work, the presence of arc genes for the arginine-deiminase pathway was studied in several strains of different species of LAB. Their ability to degrade arginine was also studied. To detect the presence of arc genes, degenerate primers were designed from the alignment of protein sequences in already sequenced LAB. The usefulness of these degenerate primers has been proven by sequencing some of the amplified PCR fragments and searching for homologies with published sequences of the same species and related ones. Correlation was found between the presence of genes and the ability to degrade arginine. Degrading strains included all heterofermentative lactobacilli, Oenococcus oeni , Pediococcus pentosaceus , and some strains of Leuconostoc mesenteroides and Lactobacillus plantarum .

Effect of gallic and protocatechuic acids on the metabolism of ethyl carbamate in Chinese yellow rice wine brewing.

PubMed

Zhou, Wanyi; Fang, Ruosi; Chen, Qihe

2017-10-15

It was studied that gallic and protocatechuic acids played important roles in ethyl carbamate (EC) forming. Gallic and protocatechuic acids can reduce the arginine consumption through inhibiting the arginine deiminase enzyme. Therefore, they are generally added to regulate EC catabolism in the course of yellow rice wine leavening at the third day. In this work, gallic and protocatechuic acids made little influence on the growth of Saccharomyces cerevisiae. Besides, the addition of 200mg/L gallic or protocatechuic acid could prevent the transformation from urea/citrulline to EC. Gallic acid showed better inhibiting effect that the content of EC could be reduced by 91.9% at most. Furthermore, the production of amino acids and volatile flavor compounds are not markedly affected by phenolic compounds. The discoveries reveal that EC can be reduced by supplying gallic acid or protocatechuic acid while yellow rice wine leavening. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ethyl Carbamate Formation Regulated by Lactic Acid Bacteria and Nonconventional Yeasts in Solid-State Fermentation of Chinese Moutai-Flavor Liquor.

PubMed

Du, Hai; Song, Zhewei; Xu, Yan

2018-01-10

This study aimed to identify specific microorganisms related to the formation of precursors of EC (ethyl carbamate) in the solid-state fermentation of Chinese Moutai-flavor liquor. The EC content was significantly correlated with the urea content during the fermentation process (R 2 = 0.772, P < 0.01). Differences in urea production and degradation were found at both species and functional gene levels by metatranscriptomic sequencing and culture-dependent analysis. Lactobacillus spp. could competitively degrade arginine through the arginine deiminase pathway with yeasts, and most Lactobacillus species were capable of degrading urea. Some dominant nonconventional yeasts, such as Pichia, Schizosaccharomyces, and Zygosaccharomyces species, were shown to produce low amounts of urea relative to Saccharomyces cerevisiae. Moreover, unusual urea degradation pathways (urea carboxylase, allophanate hydrolase, and ATP-independent urease) were identified. Our results indicate that EC precursor levels in the solid-state fermentation can be controlled using lactic acid bacteria and nonconventional yeasts.

Oxidative stress in the blood of farm workers following intensive pesticide exposure.

PubMed

Ogut, Serdal; Gultekin, Fatih; Kisioglu, A Nesimi; Kucukoner, Erdoğan

2011-10-01

The aim of this study was to evaluate oxidative stress in workers who formulate organophosphate, synthetic pyrethroid and carbamate pesticides. In this survey, blood erythrocytes from a group of 94 pesticide-formulating workers (at least 5-years experience in pest-control in apple and cherry production) and 45 control subjects were examined for oxidative stress parameters. The control group was composed of 45 healthy people living in the same region with no exposure to pesticides. Lipid peroxidation level, catalase, superoxide dismutase and glutathione peroxidase activities in erythrocytes were analysed as biomarkers of oxidative stress. In addition, the acetylcholinesterase activity was measured as a biomarker of toxicity. Results indicated that chronic exposure to organophosphate, synthetic pyrethroid and carbamate pesticides were associated with increased activities of catalase, SOD and lipid peroxidation in erythrocytes (p < 0.05). Acetylcholinesterase activity did not show any significant differences between the two groups (p > 0.05). It is concluded that human chronic exposure to pesticides may result in stimulated antioxidant enzymes.

Human Serum Butyrylcholinesterase: A Bioscavenger for the Protection of Humans from Organophosphorus Exposure

DTIC Science & Technology

2009-10-01

Current medical countermeasures against OP nerve agent poisoning include a combination of pretreatment with a carbamate, pyridostigmine bromide , to...The protection of primates against soman poisoning by pretreatment with pyridostigmine , J. Pharm. Pharmacol. 31 (1979) 295-299. [2] C.G. McLeod

CARBARYL EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF ADOLESCENT AND SENESCENT BROWN NORWAY RATS

EPA Science Inventory

Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is crucial in assessing the human health risks of chemicals. Growing evidence implicates as in carbamate toxicity in addition to cholinesterase-inhibit...

Assessment of Biochemical and Behavioral Effects of Carbaryl and Methomyl in Brown-Norway Rats from Preweaning to Sensecence

EPA Science Inventory

Factors impacting life stage-specific sensitivity to chemicals include toxicokinetic and toxicodynamic changes. To evaluate age-related differences in the biochemical and behavioral impacts of two typical N-methyl carbamate pesticides, we systematically compared their dose-respo...

Application of Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling in Cumulative Risk Assessment for N-Methyl Carbamate Insecticides

EPA Science Inventory

Human exposure to xenobiotics may occur through multiple pathways and routes of entry punctuated by exposure intervals throughout a work or leisure day. Exposure to a single environmental chemical along multiple pathways and routes (aggregate exposure) may have an influence on an...

Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Preweanling and Adult Rats

EPA Science Inventory

Statistical design and environmental relevance are important aspects of studies of chemical mixtures, such as pesticides. We used a dose-additivity model to test experimentally the default assumptions of dose-additivity for two mixtures of seven N-methylcarbamates (carbaryl, carb...

Age-related differences in acetylcholinesterase inhibition produced by organophosphorus and N-methyl carbamate pesticides

EPA Science Inventory

Introduction The concern that infants and children may be more susceptible to the toxic effects of chemicals, including pesticides, has received much attention in the scientific literature and the public media. Greater toxicity may be evident as long-term adverse outcomes, e.g.,...

AN ENVIRONMENTAL TECHNOLOGY VERIFICATION (ETV) TESTING OF ENZYMATIC TEST KITS FOR WARFARE AGENTS AND PESTICIDES IN DRINKING WATER

EPA Science Inventory

Enzymatic test kits, generally designed to be handheld and portable, detect the presence of chemical agents, carbamate pesticides, and/or organophosphate pesticides by relying on the reaction of the cholinesterase enzyme. Under normal conditions, the enzyme reacts as expected wi...

21 CFR 520.1380 - Methocarbamol tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet...

Chemical Control of Cottonwood Insects

Treesearch

F. L. Oliveria; L. P. Abrahamson

1976-01-01

Systemic insecticides provide the safest and most effective chemical control of defoliators, borers, and sapsucking insects of PopuLus sp. Carbamates and organo-phosphate sprays are good contact and stomach poisons for defoliators, adult borers, some miners, and immature borers. In many countries chlorinated hydrocarbons are still being used because they are economical...

METHOD FOR MEASURING BASE/NEUTRAL AND CARBAMATE PESTICIDES IN PERSONAL DIETARY SAMPLES

EPA Science Inventory

Dietary uptake may be a significant pathway of exposure to contaminants. As such,dietary exposure assessments should be considered an important part of the total exposure assessment process. The objective of this work was to develop reliable methods that are applicable to a wide ...

METHOD FOR MEASURING BASE/NEUTRAL AND CARBAMATE PESTICIDES IN PERSONAL DIETARY SAMPLES

EPA Science Inventory

Dietary uptake may be a significant pathway of exposure to contaminants. As such, dietary exposure assessments should be considered an important part of the total exposure assessment process. The objective of this work was to develop reliable methods that are applicable to a wide...

Bis(N-ethyl-N-methyl-dithio-carbamato-κS,S')diphenyl-tin(IV).

PubMed

Muthalib, Amirah Faizah; Baba, Ibrahim; Ng, Seik Weng

2010-03-03

The dithio-carbamate anions in the title compound, [Sn(C(6)H(5))(2)(C(4)H(8)NS(2))(2)], chelate to the Sn(IV) atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol-ecule lies across a twofold rotation axis.

Bis(N-isopropyl-N-methyl-dithio-carbamato-κS,S')diphenyl-tin(IV).

PubMed

Muthalib, Amirah Faizah; Baba, Ibrahim; Farina, Yang; Ng, Seik Weng

2010-03-03

The dithio-carbamate anions in the title compound, [Sn(C(6)H(5))(2)(C(5)H(10)NS(2))(2)], chelate to the Sn(IV) atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol-ecule lies across a twofold rotation axis.

CONSTRUCTION OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC (PBPK/PD) MODEL FOR CARBOFURAN USING THE EXPOSURE RELATED DOSE ESTIMATING MODEL (ERDEM)

EPA Science Inventory

Carbofuran, known as 2, 3-dihydro-2, 2-dimethyl-7-benzofuranyl-N-methylcarbamate, is a broad spectrum N-methyl carbamate pesticide. Carbofuran and its metabolite, 3-hydroxycarbofuran, exert their toxicity by reversibly inhibiting acetylcholinesterase (AChE). Carbofuran is widel...

A SURVEY OF EPA/OPP AND OPEN LITERATURE ON SELECTED PESTICIDE CHEMICALS III. MUTAGENICITY AND CARCINOGENICITY OF BENOMYL AND CARBENDAZIM

EPA Science Inventory

Abstract
The known aneuploidogens, benomyl and its metabolite, carbendazim (methyl 2- benzimidazole carbamate or MBC), were selected for the third in a series of ongoing projects with selected pesticides. Mutagenicity and carcinogenicity data submitted to the U.S. Environmen...

Control of live oak decline in Texas with Lignasan and Arbotech

Treesearch

R. Lewis

1978-01-01

Two systemic fungicides, Arbotect 20-S (2-(4-thiazolyl) benzimidazole) and Lignasan (methyl-2-benzimidazole carbamate phosphate), were tested as possible controls for live oak decline in Texas. Both fungicides killed Ceratocystis fagacearum in vitro at 1 μg/ml. Live oaks with incipient and advanced wilt were pressure injected with the...

76 FR 34978 - Petition Supplement Requesting Cancellation of Propoxur Pet Collar Uses; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... non-dietary oral exposure pathway presented in the Revised N-methyl Carbamate (NMC) Cumulative Risk... Cumulative Risk Assessment docket EPA-HQ- OPP-2007-0935; 2. A petition supplement, dated April 23, 2009... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2009-0207; FRL-8875-1] Petition Supplement Requesting...

THE EFFECTS OF AN ORGANOPHOSPHATE (OP)-CARBAMATE (CB) PESTICIDE MIXTURE ON CORE TEMPERATURE AND MOTOR ACTIVITY IN THE RAT.

EPA Science Inventory

Pesticide risk assessment has traditionally been based on the toxicological response to single agents. Dose-additivity has been the default in risk assessment evaluations of pesticides with a common mechanism of action, but there could be supra-additive or infra-additive inter...

40 CFR Table 10 to Part 455 - List of Appropriate Pollution Control Technologies

Code of Federal Regulations, 2014 CFR

2014-07-01

... Pollution Control Technologies 1 PAI name 2 PAI code 3 Shaughnessy code 4 Structural group 5 Treatment... 42002 EDB Activated Carbon. Vancide TH 004 82901 s-Triazine Activated Carbon. 1,3-Dichloropropene 005... Activated Carbon. Dichlorvos 012 84001 Phosphate Hydrolysis. Landrin-2 013 Carbamate Activated Carbon. 2,3,6...

40 CFR Table 10 to Part 455 - List of Appropriate Pollution Control Technologies

Code of Federal Regulations, 2013 CFR

2013-07-01

... Pollution Control Technologies 1 PAI name 2 PAI code 3 Shaughnessy code 4 Structural group 5 Treatment... 42002 EDB Activated Carbon. Vancide TH 004 82901 s-Triazine Activated Carbon. 1,3-Dichloropropene 005... Activated Carbon. Dichlorvos 012 84001 Phosphate Hydrolysis. Landrin-2 013 Carbamate Activated Carbon. 2,3,6...

40 CFR Table 10 to Part 455 - List of Appropriate Pollution Control Technologies

Code of Federal Regulations, 2012 CFR

2012-07-01

... Pollution Control Technologies 1 PAI name 2 PAI code 3 Shaughnessy code 4 Structural group 5 Treatment... 42002 EDB Activated Carbon. Vancide TH 004 82901 s-Triazine Activated Carbon. 1,3-Dichloropropene 005... Activated Carbon. Dichlorvos 012 84001 Phosphate Hydrolysis. Landrin-2 013 Carbamate Activated Carbon. 2,3,6...

Age-related behavorial changes in methomyl effects on the behavior of labroatory rats: Comparison of operant behavior nad motor activity

EPA Science Inventory

The rapid increase in older adults in the population highlights the importance of understanding the role of aging in susceptibility to environmental contaminants. Methomyl is a cholinesteraseinhibiting carbamate pesticide used on a variety of produce. Although the effects of pest...

Above ground performance of preservative-treated western wood species

Treesearch

Jeffrey J. Morrell; D.J. Miller; Stan T. Lebow

2000-01-01

Incised and non-incised Douglas-fir, western hemlock, and ponderosa pine L- joints were treated with ammoniacal-based pentachlorophenol, chromated zinc chloride, thiocyanomethylthiobenzothiazole (TCMBT) or TCMTB plus methylenebisthiocyanate or 3 iodo-2-propynyl carbamate with or without chlorpyrifos to retentions between 0.8 and 6.4 kg/m3 and exposed, uncoated, above...

Age-related differences in acquisiton, steady-state performance and carbaryl effects on the operant behavior of Brown Norway rats.

EPA Science Inventory

The rapid increase in older adults in the population highlights the importance of understanding the role of aging in susceptibility to environmental contaminants. As part of a larger program on life-stage susceptibility, this experiment determined the effect of the carbamate pest...

Cholinesterase-based biosensors.

PubMed

Štěpánková, Šárka; Vorčáková, Katarína

2016-01-01

Recently, cholinesterase-based biosensors are widely used for assaying anticholinergic compounds. Primarily biosensors based on enzyme inhibition are useful analytical tools for fast screening of inhibitors, such as organophosphates and carbamates. The present review is aimed at compilation of the most important facts about cholinesterase based biosensors, types of physico-chemical transduction, immobilization strategies and practical applications.

INHIBITION OF BRAIN CHOLINESTERASE AND THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS PRODUCED BY CARBARYL IN LONG EVANS RATS.

EPA Science Inventory

Carbaryl is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response often used to detect central nervous system (CNS) changes following expos...

BRAIN CHOLINESTERASE INHIBITION PRODUCED BY PROPOXUR AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS IN LONG EVANS RATS.

EPA Science Inventory

Propoxur is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response following stimulation of the visual system with flashes of light. They ar...

Density functional theory study on carbon dioxide absorption into aqueous solutions of 2-amino-2-methyl-1-propanol using a continuum solvation model.

PubMed

Yamada, Hidetaka; Matsuzaki, Yoichi; Higashii, Takayuki; Kazama, Shingo

2011-04-14

We used density functional theory (DFT) calculations with the latest continuum solvation model (SMD/IEF-PCM) to determine the mechanism of CO(2) absorption into aqueous solutions of 2-amino-2-methyl-1-propanol (AMP). Possible absorption process reactions were investigated by transition-state optimization and intrinsic reaction coordinate (IRC) calculations in the aqueous solution at the SMD/IEF-PCM/B3LYP/6-31G(d) and SMD/IEF-PCM/B3LYP/6-311++G(d,p) levels of theory to determine the absorption pathways. We show that the carbamate anion forms by a two-step reaction via a zwitterion intermediate, and this occurs faster than the formation of the bicarbonate anion. However, we also predict that the carbamate readily decomposes by a reverse reaction rather than by hydrolysis. As a result, the final product is dominated by the thermodynamically stable bicarbonate anion that forms from AMP, H(2)O, and CO(2) in a single-step termolecular reaction.

Effect of long-term exposure to pesticides on plasma esterases from plastic greenhouse workers.

PubMed

Hernández, Antonio; Gómez, M Amparo; Pena, Gloria; Gil, Fernando; Rodrigo, Lourdes; Villanueva, Enrique; Pla, Antonio

2004-07-23

Previous reports in animals considered beta-glucuronidase activity as a novel biomarker of anticholinesterase (organophosphates and carbamates) pesticides exposure. Acid phosphatase activity was also shown to increase after organophosphates exposure. In addition, there is evidence that the paraoxonase status influences sensitivity to specific pesticides. In this study, activities of beta-glucuronidase, acid phosphatase, cholinesterase, and paraoxonase were measured in plasma from plastic greenhouse workers exposed over the long term to different pesticides, including organophosphates and carbamates, in order to evaluate the potential chronic toxicity of pesticides at occupational level. Our results show that activities of paraoxonase and cholinesterase were decreased in applicators of pesticides compared to non-applicators. Likewise, it was found that activities of beta-glucuronidase and acid phosphatase were associated with pesticide exposure in humans, and that both biochemical parameters were related to each other. Interestingly, the paraoxonase B allele (phenotyped in plasma) was associated with a higher risk of inhibition of cholinesterase activity above a 25% level, which supports the hypothesis that paraoxonase phenotypes are associated with susceptibility of humans to anticholinesterase pesticides toxicity. Copyright Taylor and Francis Inc.

Trapping of muscle relaxant methocarbamol degradation product by complexation with copper(II) ion: Spectroscopic and quantum chemical studies

NASA Astrophysics Data System (ADS)

Mansour, Ahmed M.; Shehab, Ola R.

2014-07-01

Structural properties of methocarbamol (Mcm) were extensively studied both experimentally and theoretically using FT IR, 1H NMR, UV-Vis., geometry optimization, Mulliken charge, and molecular electrostatic potential. Stability arises from hyper-conjugative interactions, charge delocalization and H-bonding was analyzed using natural bond orbital (NBO) analysis. Mcm was decomposed in ethanol/water mixture at 80 °C to guaifenesin [(RS)-3-(2-methoxyphenoxy)propane-1,2-diol] and carbamate ion [NH2COO-], where the degradation mechanism was explained by trapping the carbamate ion via the complexation with copper(II) ion. The structure of the isolated complex ([Cu(NH2COO)2(H2O)]ṡ4H2O) was elucidated by spectral, thermal, and magnetic tools. Electronic spectra were discussed by TD-DFT and the descriptions of frontier molecular orbitals and the relocations of the electron density were determined. Calculated g-tensor values showed best agreement with experimental values from EPR when carried out using both the B3LYP and B3PW91 functional.

Determination of Ethyl Carbamate in Alcoholic Beverages and Fermented Foods Sold in Korea

PubMed Central

Ryu, Dayeon; Choi, Bogyoung; Kim, Eunjoo; Park, Seri; Paeng, Hwijin; Kim, Cho-il; Lee, Jee-yeon; Yoon, Hae Jung

2015-01-01

Ethyl carbamate (EC) classified as a probable human carcinogen (Group 2A) is naturally formed in alcoholic beverages and fermented foods during fermentation process and/or during storage. The objective of this study was to analyze EC in 34 food items including 14 alcoholic beverages and 20 fermented foods sold in Korea. Each food was collected from 18 supermarkets in 9 metropolitan cities in Korea, and then made into composite. According to food composition and alcohol content, samples were divided into four matrices such as apple juice, milk, Soju (liquor containing about 20% alcohol), and rice porridge. The maximum EC value of 151.06 µg/kg was found in Maesilju (liquor made from Maesil and Soju). Whisky and Bokbunjaju (Korean black raspberry wine) contained 9.90 µg/kg and 6.30 µg/kg, respectively. EC was not detected in other alcoholic beverages. Of 20 fermented foods, Japanese-style soy sauce had highest level of 15.59 µg/kg and traditional one contained 4.18 µg/kg. Soybean paste had 1.18 µg/kg, however, EC was not found in other fermented foods. PMID:26483888

Amino Acid Derivatives as Palmitoylethanolamide Prodrugs: Synthesis, In Vitro Metabolism and In Vivo Plasma Profile in Rats

PubMed Central

Vacondio, Federica; Bassi, Michele; Silva, Claudia; Castelli, Riccardo; Carmi, Caterina; Scalvini, Laura; Lodola, Alessio; Vivo, Valentina; Flammini, Lisa; Barocelli, Elisabetta; Mor, Marco; Rivara, Silvia

2015-01-01

Palmitoylethanolamide (PEA) has antinflammatory and antinociceptive properties widely exploited in veterinary and human medicine, despite its poor pharmacokinetics. Looking for prodrugs that could progressively release PEA to maintain effective plasma concentrations, we prepared carbonates, esters and carbamates at the hydroxyl group of PEA. Chemical stability (pH 7.4) and stability in rat plasma and liver homogenate were evaluated by in vitro assays. Carbonates and carbamates resulted too labile and too resistant in plasma, respectively. Ester derivatives, prepared by conjugating PEA with various amino acids, allowed to modulate the kinetics of PEA release in plasma and stability in liver homogenate. L-Val-PEA, with suitable PEA release in plasma, and D-Val-PEA, with high resistance to hepatic degradation, were orally administered to rats and plasma levels of prodrugs and PEA were measured at different time points. Both prodrugs showed significant release of PEA, but provided lower plasma concentrations than those obtained with equimolar doses of PEA. Amino-acid esters of PEA are a promising class to develop prodrugs, even if they need further chemical optimization. PMID:26053855

Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.

PubMed

Tsurkan, Lyudmila G; Hatfield, M Jason; Edwards, Carol C; Hyatt, Janice L; Potter, Philip M

2013-03-25

Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics. They tend to be expressed in tissues likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs. Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms. We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer's disease. For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used. Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy. Therefore drug:drug interactions should be carefully evaluated in individuals receiving ChE inhibitors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Microbial degradation of carbosulfan by carbosulfan--and carbofuran-retreated rice soil suspension.

PubMed

Sahoo, A; Sethunathan, N; Sahoo, P K

1998-07-01

The role of microorganisms in the degradation of carbosulfan (2,3-dihydro-2,2-dimethyl-7-benzofuranyl-(di-n-butyl)-aminosulfenyl++ + methyl carbamate), an analogue of carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl-N-methyl carbamate) was studied by selective enrichment of microorganisms degrading either or both insecticides by repeated application of the insecticides, individually or in combination to flooded soil. Soil suspension from the pots treated with carbosulfan and carbofuran, individually or in combination collected after two applications, effected distinctly more rapid hydrolysis of carbosulfan than did the suspension from untreated pots or the uninoculated medium. The rate of hydrolysis was further accelerated by soil suspensions collected after six applications of the insecticides in the order carbosulfan treated > carbofuran treated > carbosulfan + carbofuran treated. The ability of treated and untreated suspension to degrade carbofuran was also studied. The rate of degradation of carbofuran by the suspension was in the order carbofuran retreated > carbosulfan + carbofuran retreated > carbosulfan retreated soil. Further involvement of microorganism in the rapid degradation of carbosulfan was confirmed by testing the degradation in sterilized and nonsterilized enrichment culture.

Vibrational frequency analysis, FT-IR, DFT and M06-2X studies on tert-Butyl N-(thiophen-2yl)carbamate

NASA Astrophysics Data System (ADS)

Sert, Yusuf; Singer, L. M.; Findlater, M.; Doğan, Hatice; Çırak, Ç.

2014-07-01

In this study, the experimental and theoretical vibrational frequencies of a newly synthesized tert-Butyl N-(thiophen-2yl)carbamate have been investigated. The experimental FT-IR (4000-400 cm-1) spectrum of the molecule in the solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and DFT/M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with the 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The vibrational frequencies have been assigned using potential energy distribution (PED) analysis by using VEDA 4 software. The computational optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with related literature results. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and are depicted.

Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors

PubMed Central

Tsurkan, Lyudmila G.; Hatfield, M. Jason; Edwards, Carol C.; Hyatt, Janice L.; Potter, Philip M.

2012-01-01

Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics. They tend to be expressed in tissues likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs. Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms, We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer’s disease. For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used. Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy. Therefore drug:drug interactions should be carefully evaluated in individuals receiving ChE inhibitors. PMID:23123248

Determination of Ethyl Carbamate in Alcoholic Beverages and Fermented Foods Sold in Korea.

PubMed

Ryu, Dayeon; Choi, Bogyoung; Kim, Eunjoo; Park, Seri; Paeng, Hwijin; Kim, Cho-Il; Lee, Jee-Yeon; Yoon, Hae Jung; Koh, Eunmi

2015-09-01

Ethyl carbamate (EC) classified as a probable human carcinogen (Group 2A) is naturally formed in alcoholic beverages and fermented foods during fermentation process and/or during storage. The objective of this study was to analyze EC in 34 food items including 14 alcoholic beverages and 20 fermented foods sold in Korea. Each food was collected from 18 supermarkets in 9 metropolitan cities in Korea, and then made into composite. According to food composition and alcohol content, samples were divided into four matrices such as apple juice, milk, Soju (liquor containing about 20% alcohol), and rice porridge. The maximum EC value of 151.06 µg/kg was found in Maesilju (liquor made from Maesil and Soju). Whisky and Bokbunjaju (Korean black raspberry wine) contained 9.90 µg/kg and 6.30 µg/kg, respectively. EC was not detected in other alcoholic beverages. Of 20 fermented foods, Japanese-style soy sauce had highest level of 15.59 µg/kg and traditional one contained 4.18 µg/kg. Soybean paste had 1.18 µg/kg, however, EC was not found in other fermented foods.

Utilization of charge-transfer complexation for the detection of carcinogenic substances in foods: Spectroscopic characterization of ethyl carbamate with some traditional π-acceptors

NASA Astrophysics Data System (ADS)

Adam, Abdel Majid A.; Refat, Moamen S.; Saad, Hosam A.

2013-04-01

The study of toxic and carcinogenic substances in foods represents one of the most demanding areas in food safety, due to their repercussions for public health. One potentially toxic compound for humans is ethyl carbamate (EC). EC is a multi-site genotoxic carcinogen of widespread occurrence in fermented foods and alcoholic beverages. Structural and thermal stability of charge-transfer complexes formed between EC as a donor with quinol (QL), picric acid (PA), chloranilic acid (CLA), p-chloranil (p-CHL) and 1,3-dinitrobenzene (DNB) as acceptors were reported. Elemental analysis (CHN), electronic absorption spectra, photometric titration, IR, and 1H NMR spectra show that the interaction between EC and acceptors was stabilized by hydrogen bonding, via a 1:1 stoichiometry. Thermogravimetric (TG) analysis indicates that the formation of molecular CT complexes was stable, exothermic and spontaneous. Finally, the CT complexes were screened for their antibacterial and antifungal activities. The results indicated that the [(EC)(QL)] complex exhibited strong antimicrobial activities against various bacterial and fungal strains compared with standard drugs.

Immobilized Rhodotorula mucilaginosa: a novel urethanase-producing strain for degrading ethyl carbamate.

PubMed

Wu, Qun; Zhao, Yamin; Wang, Dong; Xu, Yan

2013-12-01

Rhodotorula mucilaginosa, producing the ethyl carbamate (EC)-degrading enzyme, urethanase, was newly isolated from the Chinese rice wine making process. It removed 80 % of EC when it was incubated with 5.0 g/L EC. It grew and stably produced urethanase, with pH ranging from 7.0 to 3.0. In addition, urethanase production by R. mucilaginosa was systematically optimized. Glucose, yeast extract, peptone, and inoculum size were selected with the Plackett-Burman design. They were further optimized via uniform design and determined to be 24.6 g/L, 2.5 g/L, 23.1 g/L, and 65.8 mL/500 mL, respectively. Urethanase activity reached 4,340.0 U/L in the optimal fermentation condition. Furthermore, cell immobilization of R. mucilaginosa in calcium alginate/chitosan was applied to improve cell resistance to environmental stresses. The immobilized cells removed 51.6 % of EC in commercial rice wine, which was 10 times more than that of the free cells. It indicated that the immobilized R. mucilaginosa was effective for degrading EC.

Suitability of cholinesterase of polychaete Diopatra neapolitana as biomarker of exposure to pesticides: In vitro characterization.

PubMed

Mennillo, Elvira; Casu, Valentina; Tardelli, Federica; De Marchi, Lucia; Freitas, Rosa; Pretti, Carlo

2017-01-01

Cholinesterases of Diopatra neapolitana were characterized for their activity in whole body and different body segments (apical, intermediate, posterior), substrate affinity (acetyl-, butyryl-, propionylthiocholine), kinetic parameters (K m and V max ) and in vitro response to model inhibitors (eserine hemisulfate, isoOMPA, BW284C51) and carbamates (carbofuran, methomyl, aldicarb and carbaryl). Results showed that the rate of hydrolysis for acetyl- and propionylthiocholine was higher in the posterior segment than the apical/intermediate segments and whole body. Cholinesterases of D. neapolitana showed a substrate preference for acetylthiocholine followed by propionylthiocholine; butyrylthioline was poorly hydrolyzed indicating, together with the absence of inhibition by the specific inhibitor and the absence of reactive bands in native electrophoresis, a lack of an active butyrylcholinesterase, differently than that observed in other Annelida species. The degree of inhibition by selected carbamates of cholinesterase activity with propionylthiocholine as substrate was higher than that observed with ATChI-ChE activity; aldicarb showed the highest inhibitory effect. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of the impact on food safety of a Lactobacillus coryniformis strain from pickled vegetables with degradation activity against nitrite and other undesirable compounds.

PubMed

Fang, Fang; Feng, Tingting; Du, Guocheng; Chen, Jian

2016-01-01

Four strains of lactic acid bacteria showing antimicrobial activity against some food-spoilage microorganisms or pathogens, including both Gram-negative and -positive strains, were isolated from naturally fermented pickled vegetables and a traditional cheese product. Among these isolates, Lactobacillus coryniformis strain BBE-H3, characterised previously to be a non-biogenic amine producer, showed a high level of activity in degrading sodium nitrite and exhibited the ability to eliminate ethyl carbamate and one of its precursors, urea. The antimicrobial substance produced by L. coryniformis BBE-H3 was found to be active at an acidic pH range of 4.0-4.5. The antimicrobial activity of this strain decreased differentially after treatment with proteolytic enzymes (pepsin, papain, trypsin and proteinase K), implying this growth inhibitory compound is either a protein or a polypeptide. The results of this study show the suitability of L. coryniformis BBE-H3 as a starter in food manufacturing processes, and demonstrate its potential role in eliminating food origin carcinogens such as sodium nitrite and ethyl carbamate.

Antinociceptive effect of chlorphenesin carbamate in adjuvant arthritic rats.

PubMed

Okuyama, S; Aihara, H

1987-02-01

The antinociceptive effect of chlorphenesin carbamate (CPC) and mephenesin were examined in adjuvant arthritic rats. In the behavioral study, CPC (100-400 mg/kg, p.o.) but not mephenesin (100-400 mg/kg, p.o.) had a dose-dependent antinociceptive effect, determined using the flexion test. In the electrophysiological study, CPC (25-50 mg/kg, i.v.) but not mephenesin (50 mg/kg, i.v.) depressed the evoked neuronal responses of nociceptive neurons in the ventrobasal thalamus (VB), while the evoked responses of non-nociceptive neurons were not depressed by either CPC (50 mg/kg, i.v.) or mephenesin (50 mg/kg, i.v.). The spontaneous firings of the VB nociceptive neurons were depressed by both CPC (50 mg/kg, i.v.) and mephenesin (50 mg/kg, i.v.). However, mephenesin (50 mg/kg, i.v.) but not CPC (50 mg/kg, i.v.) also depressed the spontaneous firings of the mesencephalic reticular formation (RF), in these adjuvant arthritic rats. These results indicate that CPC but not mephenesin, has an antinociceptive action in adjuvant arthritic rats.

An ATR-FTIR Study on the Effect of Molecular Structural Variations on the CO2 Absorption Characteristics of Heterocyclic Amines, Part II

PubMed Central

Robinson, Kelly; McCluskey, Adam; Attalla, Moetaz I

2012-01-01

This paper reports on an ATR-FTIR spectroscopic investigation of the CO2 absorption characteristics of a series of heterocyclic diamines: hexahydropyrimidine (HHPY), 2-methyl and 2,2-dimethylhexahydropyrimidine (MHHPY and DMHHPY), hexahydropyridazine (HHPZ), piperazine (PZ) and 2,5- and 2,6-dimethylpiperazine (2,6-DMPZ and 2,5-DMPZ). By using in situ ATR-FTIR the structure–activity relationship of the reaction between heterocyclic diamines and CO2 is probed. PZ forms a hydrolysis-resistant carbamate derivative, while HHPY forms a more labile carbamate species with increased susceptibility to hydrolysis, particularly at higher CO2 loadings (>0.5 mol CO2/mol amine). HHPY exhibits similar reactivity toward CO2 to PZ, but with improved aqueous solubility. The α-methyl-substituted MHHPY favours HCO3− formation, but MHHPY exhibits comparable CO2 absorption capacity to conventional amines MEA and DEA. MHHPY show improved reactivity compared to the conventional α-methyl- substituted primary amine 2-amino-2-methyl-1-propanol. DMHHPY is representative of blended amine systems, and its reactivity highlights the advantages of such systems. HHPZ is relatively unreactive towards CO2. The CO2 absorption capacity CA (mol CO2/mol amine) and initial rates of absorption RIA (mol CO2/mol amine min−1) for each reactive diamine are determined: PZ: CA=0.92, RIA=0.045; 2,6-DMPZ: CA=0.86, RIA=0.025; 2,5-DMPZ: CA=0.88, RIA=0.018; HHPY: CA=0.85, RIA=0.032; MHHPY: CA=0.86, RIA=0.018; DMHHPY: CA=1.1, RIA=0.032; and HHPZ: no reaction. Calculations at the B3LYP/6-31+G** and MP2/6-31+G** calculations show that the substitution patterns of the heterocyclic diamines affect carbamate stability, which influences hydrolysis rates. PMID:22517608

Resistance management strategies in malaria vector mosquito control. Baseline data for a large-scale field trial against Anopheles albimanus in Mexico.

PubMed

Penilla, R P; Rodríguez, A D; Hemingway, J; Torres, J L; Arredondo-Jiménez, J I; Rodríguez, M H

1998-07-01

A high level of DDT resistance and low levels of resistance to organophosphorus, carbamate and pyrethroid insecticides were detected by discriminating dose assays in field populations of Anopheles albimanus in Chiapas, southern Mexico, prior to a large-scale resistance management project described by Hemingway et al. (1997). Biochemical assays showed that the DDT resistance was caused by elevated levels of glutathione S-transferase (GST) activity leading to increased rates of metabolism of DDT to DDE. The numbers of individuals with elevated GST and DDT resistance were well correlated, suggesting that this is the only major DDT resistance mechanism in this population. The carbamate resistance in this population is conferred by an altered acetylcholinesterase (AChE)-based resistance mechanism. The level of resistance observed in the bioassays correlates with the frequency of individuals homozygous for the altered AChE allele. This suggests that the level of resistance conferred by this mechanism in its heterozygous state is below the level of detection by the WHO carbamate discriminating dosage bioassay. The low levels of organophosphate (OP) and pyrethroid resistance could be conferred by either the elevated esterase or monooxygenase enzymes. The esterases were elevated only with the substrate pNPA, and are unlikely to be causing broad spectrum OP resistance. The altered AChE mechanism may also be contributing to the OP but not the pyrethroid resistance. Significant differences in resistance gene frequencies were obtained from the F1 mosquitoes resulting from adults obtained by different collection methods. This may be caused by different insecticide selection pressures on the insects immediately prior to collection, or may be an indication that the indoor- and outdoor-resting A. albimanus collections are not from a randomly mating single population. The underlying genetic variability of the populations is currently being investigated by molecular methods.

Overcoming double-step CO2 adsorption and minimizing water co-adsorption in bulky diamine-appended variants of Mg2(dobpdc).

PubMed

Milner, Phillip J; Martell, Jeffrey D; Siegelman, Rebecca L; Gygi, David; Weston, Simon C; Long, Jeffrey R

2018-01-07

Alkyldiamine-functionalized variants of the metal-organic framework Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) are promising for CO 2 capture applications owing to their unique step-shaped CO 2 adsorption profiles resulting from the cooperative formation of ammonium carbamate chains. Primary , secondary (1°,2°) alkylethylenediamine-appended variants are of particular interest because of their low CO 2 step pressures (≤1 mbar at 40 °C), minimal adsorption/desorption hysteresis, and high thermal stability. Herein, we demonstrate that further increasing the size of the alkyl group on the secondary amine affords enhanced stability against diamine volatilization, but also leads to surprising two-step CO 2 adsorption/desorption profiles. This two-step behavior likely results from steric interactions between ammonium carbamate chains induced by the asymmetrical hexagonal pores of Mg 2 (dobpdc) and leads to decreased CO 2 working capacities and increased water co-adsorption under humid conditions. To minimize these unfavorable steric interactions, we targeted diamine-appended variants of the isoreticularly expanded framework Mg 2 (dotpdc) (dotpdc 4- = 4,4''-dioxido-[1,1':4',1''-terphenyl]-3,3''-dicarboxylate), reported here for the first time, and the previously reported isomeric framework Mg-IRMOF-74-II or Mg 2 (pc-dobpdc) (pc-dobpdc 4- = 3,3'-dioxidobiphenyl-4,4'-dicarboxylate, pc = para -carboxylate), which, in contrast to Mg 2 (dobpdc), possesses uniformally hexagonal pores. By minimizing the steric interactions between ammonium carbamate chains, these frameworks enable a single CO 2 adsorption/desorption step in all cases, as well as decreased water co-adsorption and increased stability to diamine loss. Functionalization of Mg 2 (pc-dobpdc) with large diamines such as N -( n -heptyl)ethylenediamine results in optimal adsorption behavior, highlighting the advantage of tuning both the pore shape and the diamine size for the development of new adsorbents for carbon capture applications.

Toxicological and biochemical characterizations of AChE in phosalone-susceptible and resistant populations of the common pistachio psyllid, Agonoscena pistaciae

PubMed Central

Alizadeh, Ali; Talebi-Jahromi, Khalil; Hosseininaveh, Vahid; Ghadamyari, Mohammad

2014-01-01

Abstract The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman Province, Iran. Nine A. pistaciae populations were collected from pistachio orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan, Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of Kerman province. The previous bioassay results showed these populations were susceptible or resistant to phosalone, and the Rafsanjan population was most resistant, with a resistance ratio of 11.3. The specific activity of AChE in the Rafsanjan population was significantly higher than in the susceptible population (Bam). The affinity ( KM ) and hydrolyzing efficiency ( Vmax ) of AChE on acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine odide as artificial substrates were clearly lower in the Bam population than that in the Rafsanjan population. These results indicated that the AChE of the Rafsanjan population had lower affinity to these substrates than that of the susceptible population. The higher Vmax value in the Rafsanjan population compared to the susceptible population suggests a possible over expression of AChE in the Rafsanjan population. The in vitro inhibitory effect of several organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was determined. Based on I50, the results showed that the ratios of AChE insensitivity of the resistant to susceptible populations were 23 and 21.7-fold to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran, respectively, suggesting negatively correlated sensitivity to organophosphate-insensitive AChE. Therefore, AChE from the Rafsanjan population showed negatively correlated sensitivity, being insensitive to phosphamidon and monocrotophos and sensitive to N -methyl carbamates. PMID:25373165

Sensitization to Rubber Accelerators in Northeastern Italy: The Triveneto Patch Test Database.

PubMed

Buttazzo, Silvia; Prodi, Andrea; Fortina, Anna Belloni; Corradin, Maria Teresa; Larese Filon, Francesca

2016-01-01

Natural and synthetic rubbers containing rubber accelerators are well-known causes of occupational skin disease. Allergic contact dermatitis caused by rubber gloves is frequent and has almost exclusively been attributed to contact sensitization to accelerators. This study aimed to evaluate the frequency of rubber accelerators sensitization in the population living in northeastern Italy, to find time trend and a correlation with occupations, and to investigate co-sensitization between rubber accelerators. A population of 23,774 subjects was patch tested in 6 cities in northeastern Italy in the years 1996 to 2012 using carba mix 3%, thiuram mix 1%, benzothiazole (MBT) mix 1%, and isopropyl phenyl paraphenylamine diamine (IPPD) mix 0.6%. The overall frequency of carbamates, MBT, thiurams, and IPPD mix sensitization was 3.4%, 0.65%, 1.75%, and 0.83%, respectively. On a logistic regression analysis (control group: white-collar workers), we found a statistically significant association to carbamates (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.03-1.7) and thiurams (OR, 1.6; 95% CI, 1.1-2.3) for health care workers. Thiuram sensitivity was also significantly associated with dermatitis in maids and restaurant workers (OR, 2.2; 95% CI, 1.4-3.6), hairdressers (OR, 3.6; 95% CI, 1.8-7.1), shop assistants (OR, 2.9; 95% CI, 1.2-6.8), construction workers (OR, 2.7; 95% CI, 1.7-4.1), mechanics (OR, 2.1; 95% CI, 1.3-3.4), and professional drivers (OR, 2.6; 95% CI, 1.2-5.9). In conclusion, our results demonstrated that rubber accelerators have an important role in allergic contact dermatitis in the northeast of Italy and their sensitization is associated significantly with occupations that wear gloves or use chemical substances. Between rubber accelerators tested, carbamates sensitization is prevalent and increasing during considered years.

Overcoming double-step CO 2 adsorption and minimizing water co-adsorption in bulky diamine-appended variants of Mg 2(dobpdc)

DOE PAGES

Milner, Phillip J.; Martell, Jeffrey D.; Siegelman, Rebecca L.; ...

2017-10-26

Alkyldiamine-functionalized variants of the metal–organic framework Mg 2(dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) are promising for CO 2 capture applications owing to their unique step-shaped CO 2 adsorption profiles resulting from the cooperative formation of ammonium carbamate chains. Primary,secondary (1°,2°) alkylethylenediamine-appended variants are of particular interest because of their low CO 2 step pressures (≤1 mbar at 40 °C), minimal adsorption/desorption hysteresis, and high thermal stability. Herein, we demonstrate that further increasing the size of the alkyl group on the secondary amine affords enhanced stability against diamine volatilization, but also leads to surprising two-step CO 2 adsorption/desorption profiles. This two-step behaviormore » likely results from steric interactions between ammonium carbamate chains induced by the asymmetrical hexagonal pores of Mg 2(dobpdc) and leads to decreased CO 2 working capacities and increased water co-adsorption under humid conditions. To minimize these unfavorable steric interactions, we targeted diamine-appended variants of the isoreticularly expanded framework Mg 2(dotpdc) (dotpdc 4- = 4,4''-dioxido-[1,1':4',1''-terphenyl]-3,3''-dicarboxylate), reported here for the first time, and the previously reported isomeric framework Mg-IRMOF-74-II or Mg 2(pc-dobpdc) (pc-dobpdc 4- = 3,3'-dioxidobiphenyl-4,4'-dicarboxylate, pc = para-carboxylate), which, in contrast to Mg 2(dobpdc), possesses uniformally hexagonal pores. By minimizing the steric interactions between ammonium carbamate chains, these frameworks enable a single CO 2 adsorption/desorption step in all cases, as well as decreased water co-adsorption and increased stability to diamine loss. Functionalization of Mg 2(pc-dobpdc) with large diamines such as N-(n-heptyl)ethylenediamine results in optimal adsorption behavior, highlighting the advantage of tuning both the pore shape and the diamine size for the development of new adsorbents for carbon capture applications.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milner, Phillip J.; Martell, Jeffrey D.; Siegelman, Rebecca L.

Alkyldiamine-functionalized variants of the metal–organic framework Mg 2(dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) are promising for CO 2 capture applications owing to their unique step-shaped CO 2 adsorption profiles resulting from the cooperative formation of ammonium carbamate chains. Primary,secondary (1°,2°) alkylethylenediamine-appended variants are of particular interest because of their low CO 2 step pressures (≤1 mbar at 40 °C), minimal adsorption/desorption hysteresis, and high thermal stability. Herein, we demonstrate that further increasing the size of the alkyl group on the secondary amine affords enhanced stability against diamine volatilization, but also leads to surprising two-step CO 2 adsorption/desorption profiles. This two-step behaviormore » likely results from steric interactions between ammonium carbamate chains induced by the asymmetrical hexagonal pores of Mg 2(dobpdc) and leads to decreased CO 2 working capacities and increased water co-adsorption under humid conditions. To minimize these unfavorable steric interactions, we targeted diamine-appended variants of the isoreticularly expanded framework Mg 2(dotpdc) (dotpdc 4- = 4,4''-dioxido-[1,1':4',1''-terphenyl]-3,3''-dicarboxylate), reported here for the first time, and the previously reported isomeric framework Mg-IRMOF-74-II or Mg 2(pc-dobpdc) (pc-dobpdc 4- = 3,3'-dioxidobiphenyl-4,4'-dicarboxylate, pc = para-carboxylate), which, in contrast to Mg 2(dobpdc), possesses uniformally hexagonal pores. By minimizing the steric interactions between ammonium carbamate chains, these frameworks enable a single CO 2 adsorption/desorption step in all cases, as well as decreased water co-adsorption and increased stability to diamine loss. Functionalization of Mg 2(pc-dobpdc) with large diamines such as N-(n-heptyl)ethylenediamine results in optimal adsorption behavior, highlighting the advantage of tuning both the pore shape and the diamine size for the development of new adsorbents for carbon capture applications.« less

A fluorescence-based method for cyanate analysis in ethanol/water media: correlation between cyanate presence and ethyl carbamate formation in sugar cane spirit.

PubMed

Ohe, Thiago Hideyuki Kobe; da Silva, Alexandre Ataide; Rocha, Thaís da Silva; de Godoy, Flávio Schutzer; Franco, Douglas Wagner

2014-10-01

Based on the fluorescence properties of 2,4-(1H,3H)-quinazolinedione, a product of the reaction between cyanate and 2-aminobenzoic acid, a simple, sensitive, selective, and reproducible method for the cyanate analysis in aqueous ethanolic media is proposed. In this method, λ(exc) and λ(em) are 310 and 410 nm, respectively, and the limits of detection and quantification are 2.2 × 10(-7) and 6.7 × 10(-7) mol/L, respectively. Under optimal conditions (pH = 4.5, 40% ethanol), a concentration of 5.0 × 10(-6) mol/L cyanate can be determined in a single measurement, at a 95% level of confidence, with an uncertainty of ± 0.13 × 10(-6) mol/L. Cyanide, thiocyanate, chloride, nitrate, and sulfate ions, as well as urea and urethane in concentrations 1 × 10(3) higher than that of cyanate do not interfere with the measurement. The methodology was applied to cyanate analyses in the different fractions of the sugarcane distillate and the data strongly suggest a correlation between the presence of urea in wine, and the cyanate and ethyl carbamate concentrations in the spirit. Based on the fluorescence properties of the reaction product between cyanate and 2-aminobenzoic acid, a method for assaying cyanate was devised. This procedure applied to the sugarcane distillate showed for the first time a correlation between cyanate presence and ethyl carbamate (EC) formation in the different fractions of the product. Therefore, the proposed methodology can be used to predict in freshly distillate sugar cane spirits the potential total concentration of EC to be formed. Therefore, these data could be used to advise about the necessity of implementing a procedure to reduce spirit EC concentration before the product reaches the market. © 2014 Institute of Food Technologists®

COMPARISON BETWEEN ELLMAN AND RADIOMETRIC METHODS FOR ASSESSING CHOLINESTERASE (CHE) INHIBITION IN RATS TREATED WITH N-METHYL CARBAMATE INSECTICIDES.

EPA Science Inventory

Carbamylated ChE is unstable and readily reactivates. This reactivation, promoted by increasing temperature and dilution, could have an impact on ex vivo ChE assays by decreasing apparent ChE inhibition. To assess the best method for measuring ChE inhibition in brain and RBCs f...

A Novel Carbamate Insecticide with Superior Selectivity for Cattle Tick (Boophilus microplus) and Sand Fly (Phlebotomus papatasi) Control

USDA-ARS?s Scientific Manuscript database

The cattle tick, Boophilus microplus, and the sand fly, Phlebotomus papatasi (Pp), are vectors of infectious agents affecting cattle and humans, respectively. The purpose of this study was to characterize the inhibitor profile of acetylcholinesterases from R. microplus(BmAChE1) and Pp (PpAchE) for c...

Malathion Administration: Effects on Physiological and Physical Performance in the Heat,

DTIC Science & Technology

1982-12-09

Physiol. 51:62-67, 1981. 12. Harris, L. W., D. L. Stitcher , and W. C. Heyl. The effects of pretreatments with carbamates, atropine and mecamylamine on...survival and on soman-induced alterations in rat and rabbit brain acetylcholine. Life Sci. 26:1885-1891, 1980. 13. Harris, L. W., D. L. Stitcher , W. C

Pyridostigmine-Induced Cholinesterase Inhibition: Effects on the Ability to Work in the Heat,

DTIC Science & Technology

1983-05-27

Physiol. Biochem. 5:370- 372, 1975. 11. Harris, L.W., D.L Stitcher , and W.C. Heyl. The effects of pretreatments with carbamates, atropine and mecamylamine...on survival and on soman-induced alterations in rat and rabbit brain acetylcholine. Life Sci. 26:1885-189 1, 1980. 12. Harris, L.W., D.L. Stitcher

Oxime-Induced Reactivation and Efficacy against Lethality in Phosphinate-Intoxicated Guinea Pigs.

DTIC Science & Technology

1988-03-01

poisoning by pretreatment with a carbamate. Toxicol. Appl. Pharmacol., 43, 207-216. 5. Heyl, W. C., Harris, L. W., and Stitcher , D. L. (1978). Effects of...Lieske, C. N. (1984). Unpublished results. 12. Harris, L. W., Stitcher , D. L., Heyl, W. C., Lieske, C. N., Lowe, J. R., Clark, J. H., and Broomfield, C

40 CFR Table 10 to Part 455 - List of Appropriate Pollution Control Technologies

Code of Federal Regulations, 2011 CFR

2011-07-01

... Technologies 1 PAI name 2 PAI code 3 Shaughnessy code 4 Structural group 5 Treatment technology Dicofol 001... Carbon. Vancide TH 004 82901 s-Triazine Activated Carbon. 1,3-Dichloropropene 005 29001 EDB Hydrolysis... 012 84001 Phosphate Hydrolysis. Landrin-2 013 Carbamate Activated Carbon. 2,3,6-T, S&E or Fenac 014...

A bill to extend the temporary suspension of duty on methyl-4-trifluoromethoxyphenyl-N-(chlorocarbonyl) carbamate.

THOMAS, 112th Congress

Sen. Coons, Christopher A. [D-DE

2012-05-07

Senate - 05/07/2012 Read twice and referred to the Committee on Finance. (All Actions) Notes: For further action, see H.R.366, which became Public Law 112-1 on 1/31/2011. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Knockdown and lethal effects of eight commercial nonconventional and two pyrethroid insecticides against moderately permethrin-resistant adult bed bugs, Cimex lectularius (L.) (Hemiptera: Cimicidae)

USDA-ARS?s Scientific Manuscript database

The common bed bug, Cimex lectularius (L.) (Hemiptera: Cimicidae) is undergoing a rapid resurgence in the United States during the last decade which has created a notable pest management challenge largely because the pest has developed resistance against DDT, organophosphates, carbamates, and pyreth...

COMPARISON OF EEG CHANGES PRODUCED BY CARBARYL (CARBAMATE), PERMETHRIN (TYPE I PYRETHROID), AND DELTAMETHRIN (TYPE II PYRETHROID)

EPA Science Inventory

We have reported that treatment with carbaryl may alter Theta activity in the EEG (Lyke et al., Toxicologist, 108(S-1):441, 2009). In this study, we examined the ability to detect changes in EEG activity produced by pesticides with different modes of action. Long Evans rats were ...

Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur

EPA Science Inventory

While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides. Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration o...

40 CFR Table 6 to Subpart Jj of... - VHAP of Potential Concern

Code of Federal Regulations, 2010 CFR

2010-07-01

... Formaldehyde 0.2 101144 4,4′-Methylene bis(2-chloroaniline) 0.02 107131 Acrylonitrile 0.03 106934 Ethylene... Chlorobenzilate 0.04 62737 Dichlorvos 0.02 75014 Vinyl chloride 0.02 75218 Ethylene oxide 0.09 96457 Ethylene... 51796 Ethyl carbamate (Urethane) 0.08 107062 Ethylene dichloride (1,2-Dichloroethane) 0.08 78875...

Bis(N-ethyl-N-methyl­dithio­carbamato-κ2 S,S′)diphenyl­tin(IV)

PubMed Central

Muthalib, Amirah Faizah; Baba, Ibrahim; Ng, Seik Weng

2010-01-01

The dithio­carbamate anions in the title compound, [Sn(C6H5)2(C4H8NS2)2], chelate to the SnIV atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol­ecule lies across a twofold rotation axis. PMID:21580470

Bis(N-isopropyl-N-methyl­dithio­carbamato-κ2 S,S′)diphenyl­tin(IV)

PubMed Central

Muthalib, Amirah Faizah; Baba, Ibrahim; Farina, Yang; Ng, Seik Weng

2010-01-01

The dithio­carbamate anions in the title compound, [Sn(C6H5)2(C5H10NS2)2], chelate to the SnIV atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol­ecule lies across a twofold rotation axis. PMID:21580469

Synthesis of Rhodamines from Fluoresceins Using Pd-Catalyzed C–N Cross-Coupling

PubMed Central

2011-01-01

A unified, convenient, and efficient strategy for the preparation of rhodamines and N,N′-diacylated rhodamines has been developed. Fluorescein ditriflates were found to undergo palladium-catalyzed C–N cross-coupling with amines, amides, carbamates, and other nitrogen nucleophiles to provide direct access to known and novel rhodamine derivatives, including fluorescent dyes, quenchers, and latent fluorophores. PMID:22091952

Oral Pyridostigmine Administration in Rats: Effects on Thermoregulation, Clinical Chemistry, and Performance in the Heat

DTIC Science & Technology

1984-01-01

216, 1978. 13. Harris, L.W., D.L. Stitcher , and W.C. Heyl, The effects of pretreatment with carbamates, atropine and nacamylamine an survival and on...scman-induced- alterations in rat and rabbit brain acetylcholine. Life Sci. 26:1885-1891, 1980. 14. Harris, L.W., D.L. Stitcher , W.C. Heyl, C.N. Lieske

Environmental Assessment: Bird Strike Risk Reduction at Laughlin Air Force Base, Texas

DTIC Science & Technology

2008-01-01

used carbamate general use insecticide with anticholinesterase activity . It however, has the important characteristic of rapid degradation and...Aircrew attention to these activities while at low altitudes often compromises their ability to successfully recover from unexpected wildlife...human activities and the dramatic increase in the population of some highly adaptable species compounds this problem. Experts within the FAA and

USE OF THE FUNGICIDE CARBENDAZIM AS A MODEL COMPOUND TO DETERMINE THE IMPACT OF ACUTE CHEMICAL EXPOSURE DURING OOCYTE MATURATION AND FERTILIZATION ON PREGNANCY OUTCOME IN THE HAMSTER

EPA Science Inventory

Here we use a hamster animal model to identify early pregnancy loss due to an acute chemical exposure to the female during the perifertilization interval. The fungicide carbendazim (methyl 1H-benzimidazole-2-carbamate), a microtubule poison with antimitotic activity, was selected...

Acetylcholinesterases of Rhipicephalus (Boophilus) microplus – Multiple gene expression presents an opportune model system for elucidation of multiple functions of AChEs.

USDA-ARS?s Scientific Manuscript database

Acetylcholinesterase (AChE) is a key neural enzyme of both vertebrates and invertebrates, and is the biochemical target of organophosphate and carbamate pesticides for invertebrates, as well as vertebrate nerve agents, e.g., soman, tabun, VX, and others. AChE inhibitors are also key drugs among thos...

TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

EPA Science Inventory

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...

Zectran fed orally to mice...cholinesterase levels in blood determined

Treesearch

Jean Marie Lang; Raymond R. Miskus

1967-01-01

Zectran, a carbamate insecticide, is being field-tested against the spruce budworm. Taken in sufficient quantity, it can induce cholinesterase (ChE) inhibition in mammals. In laboratory experiments, Zectran was fed orally to mice. Results indicated that maximum ChE inhibition occurred 15 to 30 minutes after ingestion of Zectran, and that a ChE test is unreliable in the...

DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS BY PHYSOSTIGMINE, CARBARYL AND PROPOXUR AND THE RELATIONSHIP TO INHIBITION OF BRAIN CHOLINESTERASE

EPA Science Inventory

The effects of N-methyl carbamate pesticides on the photic after discharge (PhAD) of flash evoked potentials (FEPs) and the relationship between inhibition of brain cholinesterase (ChE) activity and the PhAD were evaluated. FEPs were recorded in Long Evans rats treated with physo...

Evaluation of a new modified QuEChERS method for the monitoring of carbamate residues in high-fat cheeses by using UHPLC-MS/MS.

PubMed

Hamed, Ahmed M; Moreno-González, David; Gámiz-Gracia, Laura; García-Campaña, Ana M

2017-01-01

A simple and efficient method for the determination of 28 carbamates in high-fat cheeses is proposed. The methodology is based on a modified quick, easy, cheap, effective, rugged, and safe procedure as sample treatment using a new sorbent (Z-Sep + ) followed by ultra-high performance liquid chromatography with tandem mass spectrometry determination. The method has been validated in different kinds of cheese (Gorgonzola, Roquefort, and Camembert), achieving recoveries of 70-115%, relative standard deviations lower than 13% and limits of quantification lower than 5.4 μg/kg, below the maximum residue levels tolerated for these compounds by the European legislation. The matrix effect was lower than ±30% for all the studied pesticides. The combination of ultra-high performance liquid chromatography and tandem mass spectrometry with this modified quick, easy, cheap, effective, rugged, and safe procedure using Z-Sep + allowed a high sample throughput and an efficient cleaning of extracts for the control of these residues in cheeses with a high fat content. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of Ethyl Carbamate in Chinese Yellow Rice Wine by Diatomaceous Earth Extraction and GC/MS Method.

PubMed

Wu, Pinggu; Zhang, Liqun; Shen, Xianghong; Wang, Liyuan; Zou, Yan; Zhang, Jing; Tan, Ying; Tang, Jun; Ma, Bingjie; Pan, Xiaodong; Jiang, Wei

2015-01-01

A sensitive and rapid analytical method based on alkaline diatomaceous earth extraction followed by GC/MS was developed for the quantitative determination of the toxic contaminant ethyl carbamate (EC) in yellow rice wines. The optimal extraction conditions were investigated. With the application of diatomaceous earth extraction, the damage of organic acids to the capillary column was greatly reduced. By using d5-EC as an internal standard for quantitative analysis of EC, the linearity of the calibration curves was good between 10 and 1000 ng/mL. The LOD and LOQ were 1.7 and 5.0 μg/kg, respectively. The spiked level of EC was 5.0-300 μg/kg, and the average recovery of the spikes was between 78.4 and 98.2%, with an RSD between 4.3 and 8.3%. Upon validation by five laboratories when spiked with 50, 100, and 300 μg/kg, the average respective recoveries were 102.9, 102.2, and 98.7% with a RSD between 0.7 and 8.1%. The validation results demonstrated that the method is fast, simple, selective, and suitable for the determination of EC in yellow rice wines.

Biological and nonbiological modifications of carbamates

PubMed Central

Knaak, James B.

1971-01-01

Methylcarbamate insecticides undergo hydrolysis, oxidation, dealkylation, and conjugation in animals, plants, and insects to form similar or identical products. Carbaryl is hydroxylated in biological systems to form hydroxy, dihydro-dihydroxy, and N-hydroxymethyl carbaryl and is hydrolysed to form 1-naphthol. The products are conjugated, stored, or excreted. Carbofuran is hydroxylated at the 3 position and propoxur at the 5 position to form hydroxylated derivatives. N-hydroxymethyl derivatives of these two carbamates may also be formed. Hydrolysis appears to be the major metabolic pathway of carbofuran in the animal. Aldicarb is oxidized to its sulfoxide and then hydrolysed to the oxime sulfoxide in animals and plants. Plants hydrolyse the oxime sulfoxide to form the corresponding aldehyde, which is an intermediate in the formation of 2-methyl-2-(methyl-sulfinyl)propanol. Methomyl, which is structurally similar to aldicarb, is metabolized in plants to acetonitrile, carbon dioxide, and methylamine. Bux and Meobal undergo hydrolysis and hydroxylation to form N-hydroxy methylcarbamates, as well as hydroxybutylphenyl and hydroxymethylphenyl methylcarbamates. Zectran, which contains a dimethylamino group, is converted to the methylamino, amino, and methylformamido derivatives by insects and plants. In soil and water, methylcarbamate insecticides are hydrolysed to their respective phenols or oximes. PMID:4999481

Species-specific glucosylation of DIMBOA in larvae of the rice Armyworm.

PubMed

Sasai, Hiroaki; Ishida, Masahiro; Murakami, Kenjiro; Tadokoro, Naoko; Ishihara, Atsushi; Nishida, Ritsuo; Mori, Naoki

2009-06-01

DIMBOA [2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one] is a benzoxazinoid (Bx), part of the chemical defense system of graminaceous plants such as maize, wheat, and rye. When Bombyx mori larvae were fed artificial diets containing DIMBOA, they died in three days. In contrast, Mythimna separata larvae, a serious pest of rice, maize, sorghum, wheat etc., grew well on the same diets. Three kinds of glucosides [1-(2-hydroxy-4-methoxyphenylamino)-1-deoxy-beta-glucopyranoside-1,2-carbamate (methoxy glucoside carbamate), 2-O-beta-glucopyranosyl-4-hydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA-2-O-Glc), and 2-O-beta-glucopyranosyl-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (HMBOA-2-O-Glc)] were identified by LC-MS and NMR analyses from the frass of M. separata that had been fed on a DIMBOA-containing diet. Furthermore, the incubation of DIMBOA with a midgut tissue suspension of M. separata in the presence of UDP-D-glucose generated DIMBOA-2-O-Glc. These findings strongly suggest that glucosylation by UDP-glucosyltransferase(s) was important for detoxification to circumvent the defenses of host plants against M. separata larvae.

Alkyl amine and vegetable oil mixture-a viable candidate for CO2 capture and utilization.

PubMed

Uma Maheswari, A; Palanivelu, K

2017-02-01

In this present work, the absorption of CO 2 in alkyl amines and vegetable oil mixture has been evaluated. The results showed that the absorption is higher in alkyl amines and vegetable oil mixture compared with the aqueous alkyl amines. In addition to that, by employing the greener and non-toxic vegetable oil media, the CO 2 gas has been captured as well as converted into value-added products, such as carbamates of ethylenediamine, diethylenetriamine, and triethylenetetramine. The carbamates have been isolated and characterized by Fourier transform infrared and 1 H and 13 C nuclear magnetic resonance spectroscopic techniques. The formation of these products in precipitate form has not been observed in the case of aqueous medium. Among the various alkyl amine and vegetable oil combinations, triethylenetetramine in coconut oil medium showed the maximum CO 2 capture capacity of 72%. The coconut oil used for the process has been recovered, recycled, and reused for 3 cycles. Thus, this novel scheme seems to be a better alternative to conquer the drawback of aqueous amine-based CO 2 capture as well as for the capture and utilization of the CO 2 gas to gain the value-added products.

CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits

PubMed Central

Meigh, Louise; Greenhalgh, Sophie A; Rodgers, Thomas L; Cann, Martin J; Roper, David I; Dale, Nicholas

2013-01-01

Homeostatic regulation of the partial pressure of CO2 (PCO2) is vital for life. Sensing of pH has been proposed as a sufficient proxy for determination of PCO2 and direct CO2-sensing largely discounted. Here we show that connexin 26 (Cx26) hemichannels, causally linked to respiratory chemosensitivity, are directly modulated by CO2. A ‘carbamylation motif’, present in CO2-sensitive connexins (Cx26, Cx30, Cx32) but absent from a CO2-insensitive connexin (Cx31), comprises Lys125 and four further amino acids that orient Lys125 towards Arg104 of the adjacent subunit of the connexin hexamer. Introducing the carbamylation motif into Cx31 created a mutant hemichannel (mCx31) that was opened by increases in PCO2. Mutation of the carbamylation motif in Cx26 and mCx31 destroyed CO2 sensitivity. Course-grained computational modelling of Cx26 demonstrated that the proposed carbamate bridge between Lys125 and Arg104 biases the hemichannel to the open state. Carbamylation of Cx26 introduces a new transduction principle for physiological sensing of CO2. DOI: http://dx.doi.org/10.7554/eLife.01213.001 PMID:24220509

Acetylcholinesterase as a Biomarker in Environmental and Occupational Medicine: New Insights and Future Perspectives

PubMed Central

Caricato, Roberto; Calisi, Antonio; Giordano, Maria Elena; Schettino, Trifone

2013-01-01

Acetylcholinesterase (AChE) is a key enzyme in the nervous system. It terminates nerve impulses by catalysing the hydrolysis of neurotransmitter acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, acetylcholinesterase activity and its inhibition has been early recognized to be a human biological marker of pesticide poisoning. Measurement of AChE inhibition has been increasingly used in the last two decades as a biomarker of effect on nervous system following exposure to organophosphate and carbamate pesticides in occupational and environmental medicine. The success of this biomarker arises from the fact that it meets a number of characteristics necessary for the successful application of a biological response as biomarker in human biomonitoring: the response is easy to measure, it shows a dose-dependent behavior to pollutant exposure, it is sensitive, and it exhibits a link to health adverse effects. The aim of this work is to review and discuss the recent findings about acetylcholinesterase, including its sensitivity to other pollutants and the expression of different splice variants. These insights open new perspective for the future use of this biomarker in environmental and occupational human health monitoring. PMID:23936791

Mutant Potential Ubiquitination Sites in Dur3p Enhance the Urea and Ethyl Carbamate Reduction in a Model Rice Wine System.

PubMed

Zhang, Peng; Du, Guocheng; Zou, Huijun; Xie, Guangfa; Chen, Jian; Shi, Zhongping; Zhou, Jingwen

2017-03-01

Ubiquitination can significantly affect the endocytosis and degradation of plasma membrane proteins. Here, the ubiquitination of a Saccharomyces cerevisiae urea plasma membrane transporter (Dur3p) was altered. Two potential ubiquitination sites, lysine residues K556 and K571, of Dur3p were predicted and replaced by arginine, and the effects of these mutations on urea utilization and formation under different nitrogen conditions were investigated. Compared with Dur3p, the Dur3p K556R mutant showed a 20.1% decrease in ubiquitination level in yeast nitrogen base medium containing urea and glutamine. It also exhibited a >75.8% decrease in urea formation in yeast extract-peptone-dextrose medium and 41.3 and 55.4% decreases in urea and ethyl carbamate formation (a known carcinogen), respectively, in a model rice wine system. The results presented here show that the mutation of Dur3p ubiquitination sites could significantly affect urea utilization and formation. Modifying the ubiquitination of specific transporters might have promising applications in rationally engineering S. cerevisiae strains to efficiently use specific nitrogen sources.

Vibrational frequency analysis, FT-IR, DFT and M06-2X studies on tert-Butyl N-(thiophen-2yl)carbamate.

PubMed

Sert, Yusuf; Singer, L M; Findlater, M; Doğan, Hatice; Çırak, Ç

2014-07-15

In this study, the experimental and theoretical vibrational frequencies of a newly synthesized tert-Butyl N-(thiophen-2yl)carbamate have been investigated. The experimental FT-IR (4000-400 cm(-1)) spectrum of the molecule in the solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and DFT/M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with the 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The vibrational frequencies have been assigned using potential energy distribution (PED) analysis by using VEDA 4 software. The computational optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with related literature results. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and are depicted. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel mutations in β-tubulin gene in Trichoderma harzianum mutants resistant to methyl benzimidazol-2-yl carbamate.

PubMed

Li, M; Zhang, H Y; Liang, B

2013-01-01

Twelve-low resistant (LR) mutants of Trichoderma harzianum with the capability of grow fast at 0.8 μg/mL methyl benzimidazol-2-yl carbamate (MBC) were obtained using UV mutagenesis. MR and HR mutants which could grow fast at 10 and 100 μg/mL MBC, respectively, were isolated by step-up selection protocols in which UV-treated mutants were induced and mycelial sector screening was made in plates with growth medium. Subsequently, β-tubulin genes of 14 mutants were cloned to describe-the molecular lesion likely to be responsible-for MBC resistance. Comparison of the β-tubulin sequences of the mutant and sensitive strains of T. harzianum revealed 2 new MBC-binding sites differed from those in other plant pathogens. A single mutation at-amino acid 168, having Phe (TTC) instead of Ser (TCC)', was demonstrated for the HR mutant; a double mutation in amino acid 13 resulting in the substitution of Gly (GGC) by Val (GTG) was observed in β-tubulin gene of MR mutant. On the other hand, no substitutions were identified in the β-tubulin gene and its 5'-flanking regions in 12 LR mutants of T. harzianum.

Acute poisoning by pirimicarb: clinical and toxicological features.

PubMed

Hoffmann, Ulrich; Hecker, Ute; Abel, Peter

2008-08-01

Anticholinesterase compounds like organophosphorous and carbamates account for the majority of poisonings by the insecticides class agents. While the toxicokinetic depends on the extent of exposure and also on the chemical structure of the agent, the clinical symptoms range from the classic cholinergic syndrome to flaccid paralysis and intractable seizures. The carbamate ester pirimicarb (Pirimor), a toxic N-dimethylcarbamate pesticide, is used as insecticide. Our case presents the first poisoning associated with clinical and analytical findings. A 68-year-old male ingested an unknown amount of pirimicarb and developed cholinergic symptoms immediately, accompanied by seizures. He was admitted in the Intensive Care Unit (ICU) and received intensive care including intubation for hypoxemia following seizures and drug therapy of hypertensive dysregulation. No Atropine but benzodiazepines were administered. The patient recovered in the ICU after 3 days and was discharged after a week. Pirimicarb stomach, blood, and urine levels were determined on admission and during hospitalisation. Using an one-compartment model the pesticide elimination was estimated and its terminal half-life in plasma, t1/2, was found to be 3.8 hours. The butyryl cholinesterase (BChE) activity was at the lower level of detection on the admission and recovered during the following 24 hours.

Effect of carbaryl (carbamate insecticide) on acetylcholinesterase activity of two strains of Daphnia magna (Crustacea, Cladocera).

PubMed

Toumi, Hela; Bejaoui, Mustapha; Touaylia, Samir; Burga Perez, Karen F; Ferard, Jean François

2016-11-01

The present study was designed to investigate the effect of carbaryl (carbamate insecticide) on the acetylcholinesterase activity in two strains (same clone A) of the crustacean cladoceran Daphnia magna. Four carbaryl concentrations (0.4, 0.9, 1.8 and 3.7 µg L(-1)) were compared against control AChE activity. Our results showed that after 48 h of carbaryl exposure, all treatments induced a significant decrease of AChE activities whatever the two considered strains. However, different responses were registered in terms of lowest observed effect concentrations (LOEC: 0.4 µg L(-1) for strain 1 and 0.9 µg L(-1) for strains 2) revealing differences in sensitivity among the two tested strains of D. magna. These results suggest that after carbaryl exposure, the AChE activity responses can be also used as a biomarker of susceptibility. Moreover, our results show that strain1 is less sensitive than strain 2 in terms of IC50-48 h of AChE activity. Comparing the EC50-48 h of standard ecotoxicity test and IC50-48 h of AChE inhibition, there is the same order of sensitivity with both strains.

Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet.

PubMed

Corbel, Vincent; Stankiewicz, Maria; Pennetier, Cédric; Fournier, Didier; Stojan, Jure; Girard, Emmanuelle; Dimitrov, Mitko; Molgó, Jordi; Hougard, Jean-Marc; Lapied, Bruno

2009-08-05

N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system. By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase. These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.

Adsorption of 1-naphthyl methyl carbamate in water by utilizing a surface molecularly imprinted polymer

NASA Astrophysics Data System (ADS)

So, Juhyok; Pang, Cholho; Dong, Hongxing; Jang, Paeksan; U, Juhyok; Ri, Kumchol; Yun, Cholyong

2018-05-01

Surface molecularly imprinting polymer (SMIP) was utilized in the removal of a residual pesticide (carbaryl (CBL)) in water and simulated fruit juice. Being the crosslinking agent, ethylene glycol dimethacrylate (EGDMA) was copolymerized with the monomer, methacrylic acid (MAA) and CBL as the template molecules on the surface of the silica gel particles to produce the SMIP adsorbents. The SMIP adsorbents showed good selectivity and good adsorption capacity for CBL in the competitive adsorptions with two structurally related carbamate pesticides. The effect of the pretreatment solvents on the adsorption capacity of the SMIP adsorbent was investigated with the results of the numerical simulations. The adsorption isotherms and the adsorption kinetics were well described by the Freundlich equilibrium model and the pseudo-second-order kinetic model, respectively. Scatchard plot analysis revealed that there were two classes of binding sites populated in the SMIP adsorbents. In addition, the good selective adsorption of CBL by the SMIP adsorbent in a simulated fruit juice containing vitamin C and fructose indicated the great potential of the SMIP adsorbents to remove residual pesticide in food industry and processing industry for agricultural products.

The prognostic impact of psychotropic drugs in intentional drug overdose.

PubMed

Tournier, M; Grolleau, A; Cougnard, A; Verdoux, H; Molimard, M

2009-03-01

Psychotropic drugs belong to the drugs most frequently involved in intentional drug overdose (IDO). Few studies have explored their prognostic impact during hospitalisation for IDO. In order to assess which types of psychotropic drugs ingested during IDOs were associated with an increased morbidity, a cohort study included 1,974 patients consecutively hospitalised for IDO. IDOs were categorised as serious if associated with one of the following criteria: death, hospitalisation longer than 48 h, respiratory support, vasopressive drugs, cardiac massage or dialysis. Nearly all the patients ingested psychotropic medications during the IDO (88.4%), most often benzodiazepines (71.6%). Serious IDO was associated with tricyclics (OR 5.7; 95% CI 3.3-9.8), lithium (OR 4.3; 95% CI 1.6-11.6), carbamates (OR 2.7; 95% CI 1.8-4), anticonvulsants (OR 2.4: 95% CI 1.4-4.3), first-generation antipsychotics (OR 2.4; 95% CI 1.7-3.5) or selective serotonin reuptake inhibitors (SSRIs) (OR 1.6; 95% CI 1.1-2.3). Some drugs may be dangerous because of low toxic doses; hence, prescriptions of short duration may be recommended. Moreover, for safety reasons, prescribers may prefer SSRIs to tricyclics and benzodiazepines to carbamates or phenothiazines.

Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

PubMed Central

Corbel, Vincent; Stankiewicz, Maria; Pennetier, Cédric; Fournier, Didier; Stojan, Jure; Girard, Emmanuelle; Dimitrov, Mitko; Molgó, Jordi; Hougard, Jean-Marc; Lapied, Bruno

2009-01-01

Background N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system. Results By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase. Conclusion These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health. PMID:19656357

Determination of N-glycans by high performance liquid chromatography using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as the glycosylamine labeling reagent.

PubMed

Wu, Yike; Sha, Qiuyue; Du, Juan; Wang, Chang; Zhang, Liang; Liu, Bi-Feng; Lin, Yawei; Liu, Xin

2018-02-02

Robust, efficient identification and accurate quantification of N-glycans are of great significance in N-glycomics analysis. Here, a simple and rapid derivatization method, based on the combination of microwave-assisted deglycosylation and 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) labeling, was developed for the analysis of N-glycan by high performance liquid chromatography with fluorescence detection (HPLC-FLD). After optimizing various parameters affecting deglycosylation and derivatization by RNase B, the time for N-glycan labeling was shortened to 50 min with ∼10-fold enhancement in detection sensitivity comparing to conventional 2-aminobenzoic acid (2-AA) labeling method. Additionally, the method showed good linearity (correlation coefficients > 0.991) and reproducibility (RSD < 8.7%). These advantages of the proposed method were further validated by the analysis of complex samples, including fetuin and human serum. Investigation of serum N-glycome for preliminary diagnosis of human lung cancer was conducted, where significant changes of several N-glycans corresponding to core-fucosylated, mono- and disialylated glycans have been evidenced by a series of statistical analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of a muscle relaxant, chlorphenesin carbamate, on the spinal neurons of rats.

PubMed

Kurachi, M; Aihara, H

1984-09-01

The effects of chlorphenesin carbamate (CPC) and mephenesin on spinal neurons were investigated in spinal rats. CPC (50 mg/kg i.v.) inhibited the mono-(MSR) and poly-synaptic reflex (PSR), the latter being more susceptible than the former to CPC depression. Mephenesin also inhibited MSR and PSR, though the effects were short in duration. CPC had no effect on the dorsal root potential evoked by the stimulation of the dorsal root, while mephenesin reduced the dorsal root-dorsal root reflex. The excitability of motoneuron was reduced by the administration of CPC or mephenesin. The excitability of primary afferent terminal was unchanged by CPC, while it was inhibited by mephenesin. Neither CPC nor mephenesin influenced the field potential evoked by the dorsal root stimulation. Both CPC and mephenesin had no effect on the synaptic recovery. These results suggest that both CPC and mephenesin inhibit the firing of motoneurons by stabilizing the neuronal membrane, while mephenesin additionally suppresses the dorsal root reflex and the excitability of the primary afferent terminal. These inhibitory actions of CPC on spinal activities may contribute, at least partly, to its muscle relaxing action.

TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.

EPA Science Inventory

To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oi...

Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

DTIC Science & Technology

2014-10-01

between blood cholinesterase activity and neurobehavioral deficits (Rohlman et al., 2011). Finally, one additional argument against the premise that AChE...baseline scan (repeated exposure CPF group only). 2.4 Cholinesterase activity Cholinesterase activity was assessed in brain using the method of...Moser VC.2006. Behavioral toxicity of cholinesterase inhibitors. In: Gupta, RC., editor. Toxicology of Organophosphate and Carbamate Compounds

Chlordane Contamination of Government Quarters and Personal Property, Webb AFB, Texas

DTIC Science & Technology

1970-03-12

that chlorinated hydrocarbons do not inhibit cholinesterase as is the case with organophosphate and carbamate insecticides. Symptoms of acute poisoning...cardboard lined conduits within the concrete slab. Subsequent activation of the heating systems resulted in extensive human exposure and gross pesticide...they were considered ul.affected by their exposures to cholinesterase depressants. Such indexes of toxicity are now considered incomplete. 0. Table

USSR Report, Life Sciences, Biomedical and Behavioral Sciences

DTIC Science & Technology

1985-02-05

of the toxicity and anticholinesterase activity , of a number of organophosphorus compounds and carbamates, for females of the genus hybomitra and...house flies. Anticholinesterase activity and toxicity did not vary identically. 1842-6508] UDC: 619*616.981.42:612.017.1 ANTIGENTREACTIVE CELLS IN...Rukhlyada, M. Ye. Pillpenko; VETERINARIYA, No 8, Aug 84) 2 Toxicity and Anticholinesterase Action of Insecticides (Ye. K. Balashova, V. I

Behavioral Tolerance to Anticholinergic Agents

DTIC Science & Technology

1986-11-20

Medicine , 47, 137-141. 7. Kurtz, P.J. (1977) Behavioral and biochemical effects of the carbamate insecticide, mobam. Pharmacology Biochemistry & Behavior...tolerance to marihuana in rats. Pharmacology Biochemistry and Behavior, 1, 73-76. 43 40. Olson, J. and Carder, B. (1974) Behavioral tolerance to... marihuana as a function of amount of prior training. Pharmacology Biochemistry and Behavior, 2, 243-247. 41. Sidman, M. (1960) Tactics of Scientific

Susceptibility of Aedes aegypti, Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say to 19 Pesticides with Different Modes of Action

DTIC Science & Technology

2008-01-01

imidacloprid , spinosad, diazinon, and carbaryl showed slightly lower activity than permethrin (20-fold). However, bifenazate showed very low activity...acetylcholinesterase inhibitor representing organophosphates (LD50 6.7 10 4 g/mg) imidacloprid , a nicotinic acetylcholine re- ceptor...inhibitors (Carbamates) 1A Spinosad Nicotinic acetylcholine receptor agonists 5 Imidacloprid Nicotinic acetylcholine receptor agonist/antagonists 4

Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study

PubMed Central

Geraghty, Estella M.; Tancredi, Daniel J.; Delwiche, Lora D.; Schmidt, Rebecca J.; Ritz, Beate; Hansen, Robin L.; Hertz-Picciotto, Irva

2014-01-01

Background: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism. Objectives: We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Methods: The CHARGE study is a population-based case–control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997–2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316). Results: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified. Conclusions: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates. Citation: Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, Hansen RL, Hertz-Picciotto I. 2014. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect 122:1103–1109; http://dx.doi.org/10.1289/ehp.1307044 PMID:24954055

Effects of pesticides on Canada Geese

USGS Publications Warehouse

Blus, L.J.; Rusch, Donald H.; Samuel, Michael D.; Humburg, Dale D.; Sullivan, Brian D.

1998-01-01

This paper summarizes published and unpublished sources relating to exposure of Canada geese (Branta canadensis) to pesticides, emphasizing documented episodes of poisoning by organochlorine (OC), organophosphorus (OP), and carbamate compounds. Canada geese accumulate the lipid-soluble OC compounds, although they have a lower potential for biomagnification of these pesticides than animals at higher trophic levels in food webs. Low residues of p,p'-DDT and its metabolite p,p'-DDE were frequently found in tissues and eggs of Canada geese, but they had no apparent adverse effects on reproductive success or eggshell thickness. Likewise, in an orchard system in central Washington state, the OC rodenticide endrin accumulated in tissues and eggs of Canada geese without apparent adverse effect. In contrast, ingestion of seeds treated with the OC heptachlor caused mortality, lowered reproductive success, and caused a local population decline of geese in Oregon and Washington. In recent years, the most persistent OC's have been banned by law and replaced with less persistent carbamate and OP compounds that do not readily accumulate in animal tissues. However, many of these compounds are acutely toxic and have caused numerous die-offs of Canada geese. Among OP compounds, diazinon was responsible for most reported die-offs (41 incidents involving >535 geese), whereas parathion applied alone or jointly with methyl parathion accounted for most reported mortalities (8 incidents involving >3,000 geese). Three other OP's, a carbamate (carbofuran), zinc phosphide, and strychnine also caused goose die-offs. Mortality from anticholinesterase (antiChE) compounds occurs relatively soon after exposure and death can usually be diagnosed by evaluation of brain cholinesterase (thE) activity. Because geese are primarily grazers, the main route of exposure to antiChE's is apparently ingestion of contaminated grasses and forbs; dermal absorption and inhalation are other routes. Despite the widespread die-offs of Canada geese from antiChE insecticides, there is no evidence of adverse effects on population levels. It is not known how sublethal antiChE exposure relates to long-term survival and reproductive success of birds.

Spectroscopic study of carbaryl sorption on smectite from aqueous suspension.

PubMed

de Oliveira, Maurilio Fernandes; Johnston, Cliff T; Premachandra, G S; Teppen, Brian J; Li, Hui; Laird, David A; Zhu, Dongqiang; Boyd, Stephen A

2005-12-01

Sorption of carbaryl (1-naphthyl-N-methyl-carbamate) from aqueous suspension to smectite was studied using Fourier transform infrared (FTIR), high-performance liquid chromatography (HPLC) (for batch sorption), and quantum chemical methods. The amount of carbaryl sorbed was strongly dependent on the surface-charge density of the smectite with more sorption occurring on the two "low" surface-charge density smectites (SHCa-1 and SWy-2) compared to that of the high surface-charge SAz-1 smectite. In addition, the amount of carbaryl sorbed was strongly dependent on the nature of the exchangeable cation and followed the order of Ba approximately Cs approximately Ca > Mg approximately K > Na approximately Li for SWy-2. A similartrend was found for hectorite (SHCa-1) of Cs > Ba > Ca > K approximately Mg > Na approximately Li. Using the shift of the carbonyl stretching band as an indicator of the strength of interaction between carbaryl and the exchangeable cation, the observed order was Mg > Ca > Ba approximately K > Na > Cs. The position of the carbonyl stretching band shifted to lower wavenumbers with increasing ionic potential of the exchangeable cation. Density functional theory predicted a cation-induced lengthening of the C=O bond, resulting from the carbonyl group interacting directly with the exchangeable cation in support of the spectroscopic observations. Further evidence was provided by a concomitant shift in the opposite direction by several vibrational bands in the 1355-1375 cm(-1) region assigned to stretching bands of the carbamate N-Ccarbonyl and Oether-Ccarbonyl bonds. These data indicate that carbaryl sorption is due, in part, to site-specific interactions between the carbamate functional group and exchangeable cations, as evidenced by the FTIR data. However, these data suggest that hydrophobic interactions also contribute to the overall amount of carbaryl sorbed. For example, the FTIR data indicated thatthe weakest interaction occurred when Cs+ was the exchangeable cation. In contrast, the highest amount of carbaryl sorption was observed on Cs-exchanged smectite. Of all the cations studied, Cs has the lowest enthalpy of hydration. It is suggested that this low hydration energy provides the carbaryl with greater access to the hydrophobic regions of the siloxane surface.

Synergistic Actions of Pyridostigmine Bromide and Insecticides on Muscle and Vascular Nociceptors

DTIC Science & Technology

2014-01-01

2000. Flannigan, S. A., S. B. Tucker, et al. (1985). "Primary irritant contact dermatitis from synthetic pyrethroid insecticide exposure." Arch...between synthetic pyrethroid insecticides. Contact Dermatitis . 1985;13:140-7. Ginsburg K, Narahashi T. Time course and temperature dependence of...and other carbamates or organophosphates with which they had voluntary and/or involuntary contact (Fricker et al., 2000; Haley et al., 2012; see

An Integrated Chemical Reactor-Heat Exchanger Based on Ammonium Carbamate (POSTPRINT)

DTIC Science & Technology

2012-10-01

With the scrubber and exhaust operating, the test cell ammonia concentration remains below 5 ppm. To further reduce NH3 release into the test cell...material has a high decomposition enthalpy and exhibits decomposition over a wide range of temperatures. AC decomposition produces ammonia and carbon...installation due to toxic gas ( ammonia ) generation during operation. Therefore, the experiment is intended to be remotely operated. A secondary control

Circadian Rhythms of Heart Rate and Locomotion After Treatment With Low-Dose Acetylcholinesterase Inhibitors

DTIC Science & Technology

2006-01-01

with pyridostigmine bromide (PB), a carbamate AChE by air conditioned vans and air-freight to the Laboratory inhibitor that does not cross the blood ...15. SUBJECT TERMS Nerve agents, sarin, pyridostigmine bromide, cerebral glucose utilization, cerebrovascular circulation, low dose cholinesterase ...March 2006" Accepted 12 May 2006 ABSTRACT: This study tested the hypothesis that repeated exposure to low levels of sarin, pyridostigmine bromide (PB

Microglia as Primary Mediators of Nerve Agent Neuropathy

DTIC Science & Technology

2010-01-01

16. Thomas DM, Francescutti-Verbeem DM and Kuhn DM. Methamphetamine -induced neurotoxicity and microglial activation are not mediated by fractalkine...1-24. Berry WK and Davies DR. The use of carbamates and atropine in the protection of animals against poisoning by 1,2,2-trimethylpropyl...633-8. Dirnhuber P, French MC, Green DM, Leadbeater L and Stratton JA. The protection of primates against soman poisoning by pretreatment with

Bioavailability of Oral Pyridostigmine and Inhibition of Red Blood Cell Acetylcholinesterase by Oral and Intravenous Pyridostigmine

DTIC Science & Technology

1989-03-22

Case Report Forms 134 1. INTRODUCTION Studies in animals have indicated that carbamate acetyl- cholinesterase inhibitors have protective effects...effect compartment with a rate constant KE0. Furthermore, it was assumed that pyridostigmine behaves as a standard competitive inhibitor of the...really reversible, at least in the classical sense of almost instantaneous association and dissociation of eruzyme with inhibitor . After carbamylation

Pesticides Curbing Soil Fertility: Effect of Complexation of Free Metal Ions.

PubMed

Kaur, Sukhmanpreet; Kumar, Vijay; Chawla, Mohit; Cavallo, Luigi; Poater, Albert; Upadhyay, Niraj

2017-01-01

Researchers have suggested that the reason behind infertility is pernicious effect of broad spectrum pesticides on non target, beneficial microorganism of soil. Here, studying the chelating effect of selective organophosphate and carbamate pesticides with essential metal ions, at all possible combinations of three different pH (4 ± 0.05, 7 ± 0.05 and 9 ± 0.05) and three different temperatures (15 ± 0.5°C, 30 ± 0.5°C and 45 ± 0.5°C), shows very fast rate of reaction which further increases with increase of pH and temperature. Carbonyl oxygen of carbamate and phosphate oxygen of organophosphate were found to be common ligating sites among all the complexes. Formed metal complexes were found to be highly stable and water insoluble on interaction with essential metal ions in solvent medium as well as over silica. Density functional theory (DFT) calculations not only reinforced the experimental observations, but, after a wide computational conformational analysis, unraveled the nature of the high stable undesired species that consist of pesticides complexed by metal ions from the soil. All in all, apart from the direct toxicity of pesticides, the indirect effect by means of complexation of free metal ions impoverishes the soil.

Simultaneous determination of ethyl carbamate and 4-(5-)methylimidazole in yellow rice wine and soy sauce by gas chromatography with mass spectrometry.

PubMed

Wu, Pinggu; Zhang, Liqun; Wang, Liyuan; Zhang, Jing; Tan, Ying; Tang, Jun; Ma, Bingjie; Pan, Xiaodong; Jiang, Wei

2014-08-01

We developed a new method, based on alkaline diatomite solid-phase extraction followed by gas chromatography with mass spectrometry, for the simultaneous determination of the toxic contaminants ethyl carbamate (EC) and 4-(5-)methylimidazole (4-MEI) in yellow rice wine and soy sauce. The optimal extraction conditions were defined. With the application of alkaline diatomite solid-phase extraction, damage to the capillary column by organic acids was greatly reduced. With deuterated EC used as the internal standard, the linearity of the calibration curves for EC and 4-MEI was good with correlation coefficient above 0.99. In a spiked experiment with EC and 4-MEI in yellow rice wine and soy sauce, recovery of the added EC was 80.5-102.5% and that of 4-MEI was 78.3-92.8%. The limit of quantification and limit of detection for EC were 6.0 and 2.0 μg/kg, respectively, and for 4-MEI were 15.0 and 5.0 μg/kg, respectively. The validation results demonstrate that the method is fast, simple, and selective, and therefore is suitable for simultaneously determining the presence of EC and 4-MEI in fermented food. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reduced production of ethyl carbamate for wine fermentation by deleting CAR1 in Saccharomyces cerevisiae.

PubMed

Guo, Xue-Wu; Li, Yuan-Zi; Guo, Jian; Wang, Qing; Huang, Shi-Yong; Chen, Ye-Fu; Du, Li-Ping; Xiao, Dong-Guang

2016-05-01

Ethyl carbamate (EC), a pluripotent carcinogen, is mainly formed by a spontaneous chemical reaction of ethanol with urea in wine. The arginine, one of the major amino acids in grape musts, is metabolized by arginase (encoded by CAR1) to ornithine and urea. To reduce the production of urea and EC, an arginase-deficient recombinant strain YZ22 (Δcarl/Δcarl) was constructed from a diploid wine yeast, WY1, by successive deletion of two CAR1 alleles to block the pathway of urea production. The RT-qPCR results indicated that the YZ22 almost did not express CAR1 gene and the specific arginase activity of strain YZ22 was 12.64 times lower than that of parent strain WY1. The fermentation results showed that the content of urea and EC in wine decreased by 77.89 and 73.78 %, respectively. Furthermore, EC was forming in a much lower speed with the lower urea during wine storage. Moreover, the two CAR1 allele deletion strain YZ22 was substantially equivalent to parental strain in terms of growth and fermentation characteristics. Our research also suggested that EC in wine originates mainly from urea that is produced by the arginine.

Dissecting the mechanisms responsible for the multiple insecticide resistance phenotype in Anopheles gambiae s.s., M form, from Vallée du Kou, Burkina Faso

PubMed Central

Kwiatkowska, Rachel M.; Platt, Naomi; Poupardin, Rodolphe; Irving, Helen; Dabire, Roch K.; Mitchell, Sara; Jones, Christopher M.; Diabaté, Abdoulaye; Ranson, Hilary; Wondji, Charles S.

2013-01-01

With the exception of target site mutations, insecticide resistance mechanisms in the principle malaria vector Anopheles gambiae, remains largely uncharacterized in Burkina Faso. Here we detected high prevalence of resistance in Vallée du Kou (VK) to pyrethroids, DDT and dieldrin, moderate level for carbamates and full susceptibility to organophosphates. High frequencies of L1014F kdr (75%) and Rdl (87%) mutations were observed showing strong correlation with pyrethroids/DDT and dieldrin resistance. The frequency of ace1R mutation was low even in carbamate resistant mosquitoes. Microarray analysis identified genes significantly over-transcribed in VK. These include the cytochrome P450 genes, CYP6P3 and CYP6Z2, previously associated with pyrethroid resistance. Gene Ontology (GO) enrichment analysis suggested that elevated neurotransmitter activity is associated with resistance, with the over-transcription of target site resistance genes such as acetylcholinesterase and the GABA receptor. A rhodopsin receptor gene previously associated with pyrethroid resistance in Culex pipiens pallens was also over-transcribed in VK. This study highlights the complex network of mechanisms conferring multiple resistance in malaria vectors and such information should be taken into account when designing and implementing resistance control strategies. PMID:23380570

Susceptibility of Australian Myzus persicae (Hemiptera: Aphididae) to Three Recently Registered Insecticides: Spirotetramat, Cyantraniliprole, and Sulfoxaflor.

PubMed

de Little, Siobhan C; Umina, Paul A

2017-08-01

The green peach aphid, Myzus persicae (Sulzer), is a significant agricultural pest that has developed resistance to a large number of insecticides globally. Within Australia, resistance has previously been confirmed for multiple chemical groups, including pyrethroids, carbamates, organophosphates, and neonicotinoids. In this study, we use leaf-dip and topical bioassays to investigate susceptibility and potential cross-resistance of 12 field-collected populations of Australian M. persicae to three recently registered insecticides: sulfoxaflor, spirotetramat, and cyantraniliprole. Despite all 12 populations carrying known resistance mechanisms to carbamates, organophosphates, and pyrethroids, and two populations also exhibiting low-level metabolic resistance to neonicotinoids, we found little evidence of variation in susceptibility to sulfoxafor, spirotetramat, or cyantraniliprole. This provides further evidence that cross-resistance to spirotetramat, cyantraniliprole, and sulfoxaflor in M. persicae is not conferred by the commonly occurring resistance mechanisms MACE, super-kdr, amplification of the E4 esterase gene, or enhanced expression and copy number of the P450 gene, CYP6CY3. Importantly, this study also established toxicity baseline data that will be important for future monitoring of insecticide responses of M. persicae from both broadacre and horticultural crops. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pesticides Curbing Soil Fertility: Effect of Complexation of Free Metal Ions

NASA Astrophysics Data System (ADS)

Kaur, Sukhmanpreet; Kumar, Vijay; Chawla, Mohit; Cavallo, Luigi; Poater, Albert; Upadhyay, Niraj

2017-07-01

Researchers have suggested that the reason behind infertility is pernicious effect of broad spectrum pesticides on non target, beneficial microorganism of soil. Here, studying the chelating effect of selective organophosphate and carbamate pesticides with essential metal ions, at all possible combinations of three different pH (4±0.05, 7±0.05 and 9±0.05) and three different temperatures (15±0.5°C, 30±0.5°C and 45±0.5°C), shows very fast rate of reaction which further increases with increase of pH and temperature. Carbonyl oxygen of carbamate and phosphate oxygen of organophosphate were found to be common ligating sites among all the complexes. Formed metal complexes were found to be highly stable and water insoluble on interaction with essential metal ions in solvent medium as well as over silica. Density functional theory (DFT) calculations not only reinforced the experimental observations, but, after a wide computational conformational analysis, unraveled the nature of the high stable undesired species that consist of pesticides complexed by metal ions from the soil. All in all, apart from the direct toxicity of pesticides, the indirect effect by means of complexation of free metal ions impoverishes the soil.

Ethyl carbamate induces cell death through its effects on multiple metabolic pathways.

PubMed

Liu, Huichang; Cui, Bo; Xu, Yi; Hu, Chaoyang; Liu, Ying; Qu, Guorun; Li, Dawei; Wu, Yongning; Zhang, Dabing; Quan, Sheng; Shi, Jianxin

2017-11-01

Ethyl carbamate (EC), a multisite carcinogenic chemical causing tumors in various animal species, is probably carcinogenic to humans. However, information about the possible carcinogenic and toxicological effects of EC in humans is quite limited. Because EC is found in many dietary foods (such as fermented foods) and tobacco and its products, and exposure of humans to EC often occurs inevitably, its toxicological effects in humans need to be studied. This study was conducted to understand the metabolomic and transcriptomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 100 mM EC for short term (4 h) and long term (12 h) period, respectively. The results revealed multiple influences of EC on the metabolome and transcriptome of HepG2 cells, which was exposure time-dependent and well correlated with the kinetic changes of cell viability and mortality. EC treatment affected multiple metabolic pathways, inducing oxidative stress, reducing detoxification capacity, depleting energy, decreasing reducing power, disrupting membrane integrity, and damaging DNA and protein. These metabolomic and transcriptomic biomarkers of EC on human cell metabolism identified in this study would facilitate further studies on the risk assessment and the mitigation of dietary EC. Copyright © 2017 Elsevier B.V. All rights reserved.

Diffusion coefficients significant in modeling the absorption rate of carbon dioxide into aqueous blends of N-methyldiethanolamine and diethanolamine and of hydrogen sulfide into aqueous N-methyldiethanolamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, M.E.; Marshall, T.L.; Rowley, R.L.

1998-07-01

Absorption rates of gaseous CO{sub 2} into aqueous blends of N-methyldiethanolamine (MDEA) and diethanolamine (DEA) and of gaseous H{sub 2}S into aqueous MDEA were measured in a quiescent, inverted-tube diffusiometer by monitoring the rate of pressure drop. A numerical model for absorption, diffusion, and reaction of CO{sub 2} and H{sub 2}S in blends of MDEA, DEA, and water was developed. The model was used to regress diffusion coefficients of bicarbonate, carbamate, and MDEAH{sub 2}CO{sub 3} for the case of CO{sub 2} absorption and of bisulfide ion for the case of H{sub 2}S absorption from measured absorption rates. CO{sub 2} absorptionmore » rates and diffusion coefficients of bicarbonate, carbamate, and MDEAH{sub 2}CO{sub 3} were obtained at 298.2 K and 318.2 K in aqueous solutions containing 50 mass % total amine at DEA:MDEA mole ratios of 1:20, 1:4, 1L3, and 2:3. H{sub 2}S absorption rates and diffusion coefficients of bisulfide ion were obtained at 298.2 K and 318.2 K in aqueous solutions containing 20, 35, and 50 mass % MDEA.« less

Optical monitoring of gases with cholesteric liquid crystals.

PubMed

Han, Yang; Pacheco, Katherine; Bastiaansen, Cees W M; Broer, Dirk J; Sijbesma, Rint P

2010-03-10

A new approach to optical monitors for gases is introduced using cholesteric liquid crystals doped with reactive chiral compounds. The approach is based on cholesteric pitch length changes caused by a change in helical twisting power (HTP) of the chiral dopants upon reaction with the analyte. The concept is demonstrated for monitoring carbon dioxide via reversible carbamate formation and for oxygen using the irreversible oxidation of a chiral dithiol to a disulfide. Monitoring of CO(2) was achieved by doping a commercial cholesteric liquid crystalline mixture (E7) with 1.6% mol of the 1:1 complex of an optically pure diamine with a TADDOL derivative. Upon exposure to carbon dioxide, the reflection band of a thin film of the mixture shifted from 637 to 495 nm as a consequence of dissociation of the complex after carbamate formation of the diamine. An O(2) monitor was obtained by doping E7 with a chiral binaphthyl dithiol derivative and a nonresponsive codopant. The reflection band of the oxygen monitor film changed from 542 to 600 nm, due to the conformational change accompanying oxidation of the dithiol to disulfide. These monitoring mechanisms hold promise for application in smart packaging, where carbon dioxide and oxygen are of special interest because of their roles in food preservation.

Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

PubMed Central

Romero Durán, Francisco J.; Alonso, Nerea; Caamaño, Olga; García-Mera, Xerardo; Yañez, Matilde; Prado-Prado, Francisco J.; González-Díaz, Humberto

2014-01-01

In a multi-target complex network, the links (Lij) represent the interactions between the drug (di) and the target (tj), characterized by different experimental measures (Ki, Km, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (cj). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%–90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally. PMID:25255029

Binding of Rasagiline-related Inhibitors to Human Monoamine Oxidases

PubMed Central

Binda, Claudia; Hubálek, Frantisek; Li, Min; Herzig, Yaacov; Sterling, Jeffrey; Edmondson, Dale E.; Mattevi, Andrea

2008-01-01

Monoamine oxidases A and B (MAO A and B) catalyze neurotransmitters degradation and represent drug targets for the treatment of neurodegenerative disorders. Rasagiline is an irreversible, MAO B-selective inhibitor that has been approved as a novel anti-Parkinson’s drug. In this study we investigate the inhibition of recombinant human MAO A and MAO B by several rasagiline analogues. Different substituents added onto the rasagiline scaffold alter the binding affinity depending on the position on the aminoindan ring and on the size of the substituent. Compounds with a hydroxyl group on either the C4 or the C6 atom inhibit both isozymes, whereas a bulkier substituent such as a carbamate is tolerated only at the C4 position. The 1.7 Å crystal structure of MAO B in complex with 4-(N-methyl-N-ethyl-carbamoyloxy)-N-methyl-N-propargyl-1(R)-aminoindan shows that the binding mode is similar to that of rasagiline with the carbamate moiety occupying the entrance cavity space. 1(R)-aminoindan, the major metabolic product of rasagiline, and its analogues reversibly inhibit both MAO A and MAO B. The crystal structure of N-methyl-1(R)-aminoindan bound to MAO B shows that its aminoindan ring adopts a different orientation compared to that of rasagiline. PMID:16366596

Decreased ethyl carbamate generation during Chinese rice wine fermentation by disruption of CAR1 in an industrial yeast strain.

PubMed

Wu, Dianhui; Li, Xiaomin; Shen, Chao; Lu, Jian; Chen, Jian; Xie, Guangfa

2014-06-16

Saccharomyces cerevisiae metabolizes arginine to ornithine and urea during wine fermentations. In the fermentation of Chinese rice wine, yeast strains of S. cerevisiae do not fully metabolize urea, which will be secreted into the spirits and spontaneously reacts with ethanol to form ethyl carbamate, a potential carcinogenic agent for humans. To block the pathway of urea production, we genetically engineered two haploid strains to reduce the arginase (encoded by CAR1) activity, which were isolated from a diploid industrial Chinese rice wine strain. Finally the engineered haploids with opposite mating type were mated back to diploid strains, obtaining a heterozygous deletion strain (CAR1/car1) and a homozygous defect strain (car1/car1). These strains were compared to the parental industrial yeast strain in Chinese rice wine fermentations and spirit production. The strain with the homozygous CAR1 deletion showed significant reductions of urea and EC in the final spirits in comparison to the parental strain, with the concentration reductions by 86.9% and 50.5% respectively. In addition, EC accumulation was in a much lower tempo during rice wine storage. Moreover, the growth behavior and fermentation characteristics of the engineered diploid strain were similar to the parental strain. Copyright © 2014 Elsevier B.V. All rights reserved.

Constitutive expression of the DUR1,2 gene in an industrial yeast strain to minimize ethyl carbamate production during Chinese rice wine fermentation.

PubMed

Wu, Dianhui; Li, Xiaomin; Lu, Jian; Chen, Jian; Zhang, Liang; Xie, Guangfa

2016-01-01

Urea and ethanol are the main precursors of ethyl carbamate (EC) in Chinese rice wine. During fermentation, urea is generated from arginine by arginase in Saccharomyces cerevisiae, and subsequently cleaved by urea amidolyase or directly transported out of the cell into the fermentation liquor, where it reacts with ethanol to form EC. To reduce the amount of EC in Chinese rice wine, we metabolically engineered two yeast strains, N85(DUR1,2) and N85(DUR1,2)-c, from the wild-type Chinese rice wine yeast strain N85. Both new strains were capable of constitutively expressing DUR1,2 (encodes urea amidolyase) and thus enhancing urea degradation. The use of N85(DUR1,2) and N85(DUR1,2)-c reduced the concentration of EC in Chinese rice wine fermented on a small-scale by 49.1% and 55.3%, respectively, relative to fermentation with the parental strain. All of the engineered strains showed good genetic stability and minimized the production of urea during fermentation, with no exogenous genes introduced during genetic manipulation, and were therefore suitable for commercialization to increase the safety of Chinese rice wine. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mulberry Fruit Extract Affords Protection against Ethyl Carbamate-Induced Cytotoxicity and Oxidative Stress.

PubMed

Chen, Wei; Li, Yuting; Bao, Tao; Gowd, Vemana

2017-01-01

Ethyl carbamate (EC) is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE) on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502.43 ± 5.10 and 219.12 ± 4.45 mg QE/100 g FW. Cyanidin -3-O- glucoside and cyanidin -3-O- rutinoside were the major anthocyanins in MFE. In vitro antioxidant studies (DPPH, ABTS, and FRAP assays) jointly exhibited the potent antioxidant capacity of MFE. Further study indicated that MFE protected human liver HepG2 cells from EC-induced cytotoxicity by scavenging overproduced cellular ROS. EC treatment promoted intracellular glutathione (GSH) depletion and caused mitochondrial membrane potential (MMP) collapse, as well as mitochondrial membrane lipid peroxidation, whereas MFE pretreatment significantly inhibited GSH depletion and restored the mitochondrial membrane function. Overall, our study suggested that polyphenolic-rich MFE could afford a potent protection against EC-induced cytotoxicity and oxidative stress.

Mulberry Fruit Extract Affords Protection against Ethyl Carbamate-Induced Cytotoxicity and Oxidative Stress

PubMed Central

Li, Yuting; Bao, Tao; Gowd, Vemana

2017-01-01

Ethyl carbamate (EC) is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE) on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502.43 ± 5.10 and 219.12 ± 4.45 mg QE/100 g FW. Cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside were the major anthocyanins in MFE. In vitro antioxidant studies (DPPH, ABTS, and FRAP assays) jointly exhibited the potent antioxidant capacity of MFE. Further study indicated that MFE protected human liver HepG2 cells from EC-induced cytotoxicity by scavenging overproduced cellular ROS. EC treatment promoted intracellular glutathione (GSH) depletion and caused mitochondrial membrane potential (MMP) collapse, as well as mitochondrial membrane lipid peroxidation, whereas MFE pretreatment significantly inhibited GSH depletion and restored the mitochondrial membrane function. Overall, our study suggested that polyphenolic-rich MFE could afford a potent protection against EC-induced cytotoxicity and oxidative stress. PMID:28819542

Physical, chemical, and biological data for detailed study of irrigation drainage in the Klamath Basin, California and Oregon, 1990-92

USGS Publications Warehouse

MacCoy, D.E.

1994-01-01

Physical, chemical, and biological data were collected between 1990 and 1992 as part of a detailed study by the U.S. Department of Interior of the effects of irrigation drainage on aquatic resources in the Klamath Basin of California and Oregon. Most of the sites for data collection were in and around the upper and lower sump of Tule Lake, in the Tule Lake National Wildlife Refuge, and along major drains in Lower Klamath National Wildlife Refuge. The physical and chemical data consist of particle-size determinations and concentrations of carbon, mercury, arsenic, chlorophenoxy acid, and organochlorine, organophosphate, and carbamate pesticides in bottom sediment; and concentrations of organophosphate, carbamate, and pyrethroid pesticides, major and trace inorganic constituents, nitrogen, phosphorus, and organic carbon in water. Continuous dissolved oxygen, pH, specific conduc- tance, and temperature data from selected sites in 1991 and 1992 are presented in graphical form to summarize the diel water-quality conditions. The biological data consists of concentrations of inorganic constituents and organochlorine pesticides in tissue, invertebrate and fish population surveys, fish health surveys, frog call surveys, egg shell thickness of avian eggs, and in situ and static toxicity bioassay data collected in 1991 and 1992 using aquatic bacteria, plants, invertebrates, fish, and bird species as test organisms.

Magnetically Alignable Bicelles with Unprecedented Stability Using Tunable Surfactants Derived from Cholic Acid.

PubMed

Matsui, Ryoichi; Uchida, Noriyuki; Ohtani, Masataka; Yamada, Kuniyo; Shigeta, Arisu; Kawamura, Izuru; Aida, Takuzo; Ishida, Yasuhiro

2016-12-05

Five novel surfactants were prepared by modifying the three hydroxy groups of sodium cholate with triethylene glycol chains endcapped with an amide (SC-C 1 , SC- n C 4 , and SC- n C 5 ) or a carbamoyl group (SC-O n C 4 and SC-O t C 4 ). The phase behavior of aqueous mixtures of these surfactants with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) was systematically studied by 31 P NMR spectroscopy. The surfactants endcapped with carbamate groups (SC-O n C 4 and SC-O t C 4 ) formed magnetically alignable bicelles over unprecedentedly wide ranges of conditions, in terms of temperature (from 21-23 to >90 °C), lipid/surfactant ratio (from 5 to 8), total lipid content (5-20 wt %), and lipid type [DMPC, 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine (DLPC), or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC)]. In conjunction with appropriate phospholipids, the carbamate-endcapped surfactants afforded unique bicelles, characterized by exceptional thermal stabilities (from 0 to >90 °C), biomimetic lipid compositions (DMPC/POPC=25:75 to 50:50), and extremely large 2 H quadrupole splittings (up to 71 Hz). © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The action of chlorphenesin carbamate on the frog spinal cord.

PubMed

Aihara, H; Kurachi, M; Nakane, S; Sasajima, M; Ohzeki, M

1980-02-01

Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

Current Pyridostigmine Bromide and Huperzine A Studies and Future Cholinesterase Screening Using the WRAIR Whole Blood Cholinesterase Assay

DTIC Science & Technology

2004-11-15

1 CURRENT PYRIDOSTIGMINE BROMIDE AND HUPERZINE A STUDIES AND FUTURE CHOLINESTERASE SCREENING USING THE WRAIR WHOLE BLOOD...selective (e.g. Huperzine A ) and non-selective (carbamate) inhibitors (e.g. pyridostigmine bromide, PB). We found that volunteers given pyridostigmine...profile of healthy elderly volunteers receiving Huperzine A . 52.7 ± 1.5% inhibition was observed at the end of an increasing dose regimen (final dose

Molecular Targets for Organophosphates in the Central Nervous System

DTIC Science & Technology

2006-04-01

above and cholinesterase activity was measured in the supernatants after 0, 15, 30 and 60 min= exposure to PB (100 nM). Drugs and biological...a quaternary carbamate that does not cross the blood brain barrier (BBB) appreciably and inhibits reversibly AChE and BuChE with similar potencies... activity could be maintained by ACh released from cholinergic neurons in our culture. In the continuous presence of atropine, exposure of the neurons to

Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

DTIC Science & Technology

2010-09-01

or VX. Guinea pigs chronically instrumented for concurrent recordings of EEG, cardiorespiratory activities , diaphragm and skeletal muscle EMG were... activities , or any debilitating effects. The animals were asymptomatic within 30 min following therapy and survived the agent challenge 24 hr later. In...For a thorough efficacy evaluation, the animals were chronically instrumented to permit concurrent recordings of central nervous system activity

Buprofezin inhibits acetylcholinesterase activity in B-biotype Bemisia tabaci.

PubMed

Cottage, Emma L A; Gunning, Robin V

2006-01-01

B-biotype Bemisia tabaci is a severe insect pest worldwide in many ornamental, agricultural, and horticultural industries. Control of this insect is hampered by resistance to many acetylcholinesterase (AChE)-inhibiting insecticides, such as organophosphates and carbamates. Consequently, insect growth regulators such as buprofezin, which act by inhibiting chitin synthesis, are being investigated for use against B-biotype B. tabaci in Australia. This study discusses the effects of buprofezin on B. tabaciAChE.

A Thermal Management System Using Ammonium Carbamate as an Endothermic Heat Sink (POSTPRINT)

DTIC Science & Technology

2017-04-01

Niedbalski and Soumya S. Patnaik Mechanical and Thermal Systems Branch Power and Control Division Douglas J. Johnson and Jamie S. Ervin University...failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE...and Control Division Air Force Research Laboratory, Aerospace Systems Directorate Wright-Patterson Air Force Base, OH 45433-7542 Air Force Materiel

BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR.

EPA Science Inventory

Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indic...

Lipophilic nalmefene prodrugs to achieve a one-month sustained release.

PubMed

Gaekens, Tim; Guillaume, Michel; Borghys, Herman; De Zwart, Loeckie L; de Vries, Ronald; Embrechts, Roger C A; Vermeulen, An; Megens, Anton A H P; Leysen, Josée E; Herdewijn, Piet; Annaert, Pieter P; Atack, John R

2016-06-28

Nalmefene is an opioid antagonist which as a once-a-day tablet formulation has recently been approved for reducing ethanol intake in alcoholic subjects. In order to address the compliance issue in this patient population, a number of potential nalmefene prodrugs were synthesized with the aim of providing a formulation that could provide plasma drug concentrations in the region of 0.5-1.0ng/mL for a one-month period when dosed intramuscular to dogs or minipigs. In an initial series of studies, three different lipophilic nalmefene derivatives were evaluated: the palmitate (C16), the octadecyl glutarate diester (C18-C5) and the decyl carbamate (CB10). They were administered intramuscularly to dogs in a sesame oil solution at a dose of 1mg-eq. nalmefene/kg. The decyl carbamate was released relatively quickly from the oil depot and its carbamate bond was too stable to be used as a prodrug. The other two derivatives delivered a fairly constant level of 0.2-0.3ng nalmefene/mL plasma for one month and since there was no significant difference between these two, the less complex palmitate monoester was chosen to demonstrate that dog plasma nalmefene concentrations were dose-dependent at 1, 5 and 20mg-eq. nalmefene/kg. In a second set of experiments, the effect of the chain length of the fatty acid monoester promoieties was examined. The increasingly lipophilic octanoate (C8), decanoate (C10) and dodecanoate (C12) derivatives were evaluated in dogs and in minipigs, at a dose of 5mg-eq. nalmefene/kg and plasma nalmefene concentrations were measured over a four-week period. The pharmacokinetic profiles were very similar in both species with Cmax decreasing and Tmax increasing with increasing fatty acid chain length and the target plasma concentrations (0.5-1.0ng/mL over a month-long period) were achieved with the dodecanoate (C12) prodrug. These data therefore demonstrate that sustained plasma nalmefene concentrations can be achieved in both dog and minipig using nalmefene prodrugs and that the pharmacokinetic profile of nalmefene can be tuned by varying the length of the alkyl group. Copyright © 2016 Elsevier B.V. All rights reserved.

Overcoming double-step CO2 adsorption and minimizing water co-adsorption in bulky diamine-appended variants of Mg2(dobpdc)† †Electronic supplementary information (ESI) available: Additional experimental details, and full characterization (powder X-ray diffraction, infrared spectra, diamine loadings, dry N2 decomposition profiles, and CO2 adsorption data) for all new adsorbents. CCDC 1577354. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04266c

PubMed Central

Milner, Phillip J.; Martell, Jeffrey D.; Siegelman, Rebecca L.; Gygi, David; Weston, Simon C.

2017-01-01

Alkyldiamine-functionalized variants of the metal–organic framework Mg2(dobpdc) (dobpdc4– = 4,4′-dioxidobiphenyl-3,3′-dicarboxylate) are promising for CO2 capture applications owing to their unique step-shaped CO2 adsorption profiles resulting from the cooperative formation of ammonium carbamate chains. Primary,secondary (1°,2°) alkylethylenediamine-appended variants are of particular interest because of their low CO2 step pressures (≤1 mbar at 40 °C), minimal adsorption/desorption hysteresis, and high thermal stability. Herein, we demonstrate that further increasing the size of the alkyl group on the secondary amine affords enhanced stability against diamine volatilization, but also leads to surprising two-step CO2 adsorption/desorption profiles. This two-step behavior likely results from steric interactions between ammonium carbamate chains induced by the asymmetrical hexagonal pores of Mg2(dobpdc) and leads to decreased CO2 working capacities and increased water co-adsorption under humid conditions. To minimize these unfavorable steric interactions, we targeted diamine-appended variants of the isoreticularly expanded framework Mg2(dotpdc) (dotpdc4– = 4,4′′-dioxido-[1,1′:4′,1′′-terphenyl]-3,3′′-dicarboxylate), reported here for the first time, and the previously reported isomeric framework Mg-IRMOF-74-II or Mg2(pc-dobpdc) (pc-dobpdc4– = 3,3′-dioxidobiphenyl-4,4′-dicarboxylate, pc = para-carboxylate), which, in contrast to Mg2(dobpdc), possesses uniformally hexagonal pores. By minimizing the steric interactions between ammonium carbamate chains, these frameworks enable a single CO2 adsorption/desorption step in all cases, as well as decreased water co-adsorption and increased stability to diamine loss. Functionalization of Mg2(pc-dobpdc) with large diamines such as N-(n-heptyl)ethylenediamine results in optimal adsorption behavior, highlighting the advantage of tuning both the pore shape and the diamine size for the development of new adsorbents for carbon capture applications. PMID:29629084

Facile N-Arylation of Amines and Sulfonamides and O-Arylation of Phenols and Arenecarboxylic Acids

PubMed Central

Liu, Zhijian; Larock, Richard C.

2008-01-01

An efficient, transition-metal free procedure for the N-arylation of amines, sulfonamides and carbamates and O-arylation of phenols and carboxylic acids has been achieved by allowing these substrates to react with a variety of o-silylaryl triflates in the presence of CsF. Good to excellent yields of arylated products are obtained under very mild reaction conditions. This chemistry readily tolerates a variety of functional groups. PMID:16599619

Effects of permethrin treated wood on the subterranean termite Reticulitermes flavipes (Kollar) and comparison of solvent extraction for HPLC analysis of permethrin in wood

Treesearch

Mark Mankowski; Blossie Boyd; Geoffrey Webb

2016-01-01

Permethrin is a common insecticide used in wood preservation. It is an effective synthetic pyrethroid that is considered to be less toxic to higher organisms than organochlorine insecticides. In wood preservation, it can be used in combination with fungicides such as 3-iodo-2-propynyl butyl carbamate (IPBC). Permethrin has a dual mode of action as it is a repellent and...

Dihydropyranone Formation by Ipso C–H Activation in a Glucal 3-Carbamate-Derived Rhodium Acyl Nitrenoid

PubMed Central

Hurlocker, Brisa; Abascal, Nadia C.; Repka, Lindsay M.; Santizo-Deleon, Elsy; Smenton, Abigail L.; Baranov, Victoria; Gupta, Ritu; Bernard, Sarah E.; Chowdhury, Shenjuti; Rojas, Christian M.

2011-01-01

By using (N-tosyloxy)-3-O-carbamoyl-D-glucal 10, which removes the need for a hypervalent iodine(III) oxidant, we provide evidence for rhodium nitrenoid-mediated ipso C–H activation as the origin of a C3-oxidized dihydropyranone product 3. This system may be especially susceptible to such a pathway due to the ease of forming a cation upon hydride transfer to the rhodium-complexed acyl nitrene. PMID:21381715

Di-tert-butyl-bis(N-isopropyl-N-methyl-dithio-carbamato-κS,S')tin(IV).

PubMed

Muthalib, Amirah Faizah; Baba, Ibrahim; Samsudin, Mohd Wahid; Ng, Seik Weng

2010-03-03

The dithio-carbamate anions in the title compound, [Sn(C(4)H(9))(2)(C(5)H(10)NS(2))(2)], chelate to the Sn(IV) atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol-ecule lies across a twofold rotation axis. The crystal studied was a non-merohedral twin, the ratio of the twin components being 0.82 (1):0.18 (1).

Improving the developability profile of pyrrolidine progesterone receptor partial agonists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.

2010-09-17

The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

Poisoning severity score, APACHE II and GCS: effective clinical indices for estimating severity and predicting outcome of acute organophosphorus and carbamate poisoning.

PubMed

Sam, Kishore Gnana; Kondabolu, Krishnakanth; Pati, Dipanwita; Kamath, Asha; Pradeep Kumar, G; Rao, Padma G M

2009-07-01

Self-poisoning with organophosphorus (OP) compounds is a major cause of morbidity and mortality across South Asian countries. To develop uniform and effective management guidelines, the severity of acute OP poisoning should be assessed through scientific methods and a clinical database should be maintained. A prospective descriptive survey was carried out to assess the utility of severity scales in predicting the outcome of 71 organophosphate (OP) and carbamate poisoning patients admitted during a one year period at the Kasturba Hospital, Manipal, India. The Glasgow coma scale (GCS) scores, acute physiology and chronic health evaluation II (APACHE II) scores, predicted mortality rate (PMR) and Poisoning severity score (PSS) were estimated within 24h of admission. Significant correlation (P<0.05) between PSS and GCS and APACHE II and PMR scores were observed with the PSS scores predicting mortality significantly (P< or =0.001). A total of 84.5% patients improved after treatment while 8.5% of the patients were discharged with severe morbidity. The mortality rate was 7.0%. Suicidal poisoning was observed to be the major cause (80.2%), while other reasons attributed were occupational (9.1%), accidental (6.6%), homicidal (1.6%) and unknown (2.5%) reasons. This study highlights the application of clinical indices like GCS, APACHE, PMR and severity scores in predicting mortality and may be considered for planning standard treatment guidelines.

Vibrational spectra and normal coordinate analysis of 2-hydroxy-3-(2-methoxyphenoxy) propyl carbamate

NASA Astrophysics Data System (ADS)

Muthu, S.; Renuga, S.

2014-11-01

In this work, the vibrational spectral analysis was carried out by using FT-Raman and FTIR spectroscopy in the range 50-4000 cm-1 and 450-4000 cm-1 respectively, for 2-hydroxy-3-(2-methoxyphenoxy) propyl carbamate (2H3MPPLC) molecule. The molecular structure, fundamental vibrational frequencies and intensities of the vibrational bands were interpreted with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) and ab initio HF methods with 6-31G(d,p) basis set. The complete vibrational assignments of wave numbers were made on the basis of potential energy distribution (PED). The results of the calculations were applied to simulated spectra of the title compound, which show excellent agreement with observed spectra. The scaled B3LYP/6-31G(d,p) results show the best agreement with the experimental values over the other method. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The results confirm the occurrence of intramolecular charge-transfer (ICT) within the molecule. The dipole moment (μ), polarizability (α) and hyperpolarizability (β) of the investigated molecule has been computed using B3LYP/6-31G(d,p) method. Mulliken population analysis on atomic charges was also calculated. Besides, frontier molecular orbitals, molecular electrostatic potential (MEP) and thermodynamic properties were performed.

[Perspectives in the treatments of poisonings by organophosphorus insecticides and warfare nerve agents].

PubMed

Sogorb-Sánchez, M A; Vilanova-Gisbert, E; Carrera-González, V

Organophosphorus compounds are worldwide employed as insecticides and are yearly responsible of several millions of poisonings. The chemical structure of most of the warfare nerve agents also corresponds with an organophosphorus compound. Organophosphorus insecticides and warfare nerve agents exert their main toxicological effects through inhibition of acetylcholinesterase. Current treatments of patients poisoned with organophosphorus compounds include atropine (in order to protect muscarinic receptors), oximes (in order to accelerate the reactivation of the inhibited acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). The administration of phosphotriesterases (enzymes involved in the detoxication of organophosphorus compounds through hydrolysis) is a very effective treatment against poisonings by organophosphorus insecticides and warfare nerve agents. There are experimental preventive treatments based on the simultaneous administration of carbamates and certain antimuscarinic drugs, different from atropine, which notably improve the efficacy of the classical treatments applied after poisonings by warfare nerve agents. The treatments based in the administration of phosphotriesterases might be the response to the call of the World Health Organization for searching new treatments with capability to reduce the high mortality recorded in the cases of poisonings by organophosphorus compounds. These treatments can be applied in a preventive way without the intrinsic neurotoxicity associated to the preventive treatments based on carbamates and antimuscarinic drugs. Therefore, these treatments are specially interesting for people susceptible to suffer severe exposures, i.e. sprayers in the farms.

Electrochemical latent redox ratiometric probes for real-time tracking and quantification of endogenous hydrogen sulfide production in living cells.

PubMed

Manibalan, Kesavan; Mani, Veerappan; Chang, Pu-Chieh; Huang, Chih-Hung; Huang, Sheng-Tung; Marchlewicz, Kasper; Neethirajan, Suresh

2017-10-15

Hydrogen sulfide (H 2 S) was discovered as a third gasotransmitter in biological systems and recent years have seen a growing interest to understand its physiological and pathological functions. However, one major limiting factor is the lack of robust sensors to quantitatively track its production in real-time. We described a facile electrochemical assay based on latent redox probe approach for highly specific and sensitive quantification in living cells. Two chemical probes, Azido Benzyl ferrocene carbamate (ABFC) and N-alkyl Azido Benzyl ferrocene carbamate (NABFC) composed of azide trigger group were designed. H 2 S molecules specifically triggered the release of reporters from probes and the current response was monitored using graphene oxide film modified electrode as transducer. The detection limits are 0.32µM (ABFC) and 0.076µM (NABFC) which are comparable to those of current sensitive methods. The probes are successful in the determination of H 2 S spiked in whole human blood, fetal bovine serum, and E. coli. The continuous monitoring and quantification of endogenous H 2 S production in E. coli were successfully accomplished. This work lays first step stone towards real-time electrochemical quantification of endogenous H 2 S in living cells, thus hold great promise in the analytical aspects of H 2 S. Copyright © 2017 Elsevier B.V. All rights reserved.

Observations on the influence of water and soil pH on the persistence of insecticides.

PubMed

Chapman, R A; Cole, C M

1982-01-01

The pH-disappearance rate profiles were determined at ca. 25 degrees C for 24 insecticides at 4 or 5 pH values over the range 4.5 to 8.0 in sterile phosphate buffers prepared in water-ethanol (99:1 v/v). Half-lives measured at pH 8 were generally smaller than at lower pH values. Changes in half lives between pH 8.0 and 4.5 were largest (greater than 1000x) for the aryl carbamates, carbofuran and carbaryl, the oxime carbamate, oxamyl, and the organophosphorus insecticide, trichlorfon. In contrast, half lives of phorate, terbufos, heptachlor, fensulfothion and aldicarb were affected only slightly by pH changes. Under the experimental conditions described half lives at pH8 varied from 1-2 days for trichlorfon and oxamyl to greater than 1 year for fensulfothion and cypermethrin. Insecticide persistence on alumina (acid, neutral and basic), mineral soils amended with aluminum sulfate or calcium hydroxide to different pH values and four natural soils of different pH was examined. No correlation was observed between the measured pH of these solids and the rate of disappearance of selected insecticides applied to them. These observations demonstrate the difficulty of extrapolating the pH dependent disappearance behaviour observed in homogeneous solution to partially solid heterogeneous systems such as soil.

[Susceptibility of natural populations of dengue vector to insecticides in Colombia].

PubMed

Santacoloma, Liliana; Chaves, Bernardo; Brochero, Helena Luisa

2012-09-01

Physiological resistance of natural population of Aedes aegypti to insecticides contribute to the decreased efficacy of chemical control as a main control strategy during dengue outbreaks. The susceptibility status of Ae. aegypti was assessed for the carbamate propoxur, the adulticide malathion and the larvicide temephos on 13 natural populations of Ae. aegypti immature forms were taken from 8 Colombian localities. These included the following: Bucaramanga (1), Sabana de Torres (2), Girardot (2), La Mesa (2), Villavicencio (2), Puerto López (2), San José del Guaviare (1) and Florencia (1). Susceptibility tests mainly consisted of the standardized bioassay outlined by WHO (1981) and CDC bottles (1998). Colorimetric tests were undertaken to determine enzyme levels possibly responsible for the reduction of susceptibility to organophosphate and carbamate insecticides. All specimens demonstrated susceptibility to malathion and propoxur insecticides. Four of the 13 populations revealed susceptibility to the temephos larvicide. Seven of 11 populations showed a limited increase in values for nonspecific esterase enzymes. The Bucaramanga population was the only one which showed an increase in the cytochrome P450 monooxygenases enzymes. Neither population was found with modified acetilcolinesterase. The widespread susceptibility to organophosphates used as adulticides indicated that malathion, the most used insecticide in Colombia, remains effective in interrupting the transmission of dengue. Physiological resistance to insecticides occurring in communities of a single township proved to be a localized phenomenon.

[Reactivity of several classes of pesticides with UV, ozone and permanganate].

PubMed

Liu, Chao; Qiang, Zhi-min; Tian, Fang; Zhang, Tao

2009-01-01

The reactivity of eight classes of 26 extensively used pesticides, namely, organochlorines, thiadiazole, dinitroanaline, acetamides, triazines, uracil and carbamates, with three common disinfectants or oxidants including UV254 (average intensity of 10.8 mW x cm(-2)), ozone (dosage of 4.1 - 6.2 mg x L(-1)) and permanganate (dosage of 15.8 mg x L(-1)) was investigated. The reactions were allowed to proceed for 30 min at pH 7.0 and ambient temperature (25 degrees C +/- 3 degrees C). Results indicate that under the applied experimental conditions, more than 95% of chlorobenzilate, etridiazole, alachlor, butachlor, metolachlor, propachlor, atrazine, simazine, aldicarb, oxamyl and methiocarb could be effectively removed by UV254; and the removal efficiencies of other pesticides were in a range of 12.9%-77.7%. Ozone could completely degrade chloroneb, dichlorvos, bromacil, aldicarb, carbaryl, carbofuran, oxamyl and methiocarb; prometon and aldicarb sulfone were resistant to ozonation; and the removal efficiencies of other pesticides varied from 19.0% to 93.1%. Permanganate could fully degrade dichlorvos, aldicarb and methiocarb; organochlorines, dinitroanaline, thiadiazole, acetamides and other carbamates were resistant to permanganate oxidation; and the removal efficiencies of other pesticides ranged from 16.0% to 88.2%. If the practical dosage applied in drinking water treatment is considered, it is expected that most of the pesticides will be completely degraded by ozone, a few by permanganate, but probably none by UV254 .

Prediction of multi-target networks of neuroprotective compounds with entropy indices and synthesis, assay, and theoretical study of new asymmetric 1,2-rasagiline carbamates.

PubMed

Romero Durán, Francisco J; Alonso, Nerea; Caamaño, Olga; García-Mera, Xerardo; Yañez, Matilde; Prado-Prado, Francisco J; González-Díaz, Humberto

2014-09-24

In a multi-target complex network, the links (L(ij)) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K(i), K(m), IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

Simultaneous determination of ethyl carbamate and urea in Korean rice wine by ultra-performance liquid chromatography coupled with mass spectrometric detection.

PubMed

Lee, Gyeong-Hweon; Bang, Dae-Young; Lim, Jung-Hoon; Yoon, Seok-Min; Yea, Myeong-Jai; Chi, Young-Min

2017-10-15

In this study, a rapid method for simultaneous detection of ethyl carbamate (EC) and urea in Korean rice wine was developed. To achieve quantitative analysis of EC and urea, the conditions for Ultra-performance liquid chromatography (UPLC) separation and atmospheric-pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) detection were first optimized. Under the established conditions, the detection limit, relative standard deviation and linear range were 2.83μg/L, 3.75-5.96%, and 0.01-10.0mg/L, respectively, for urea; the corresponding values were 0.17μg/L, 1.06-4.01%, and 1.0-50.0μg/L, respectively, for EC. The correlation between the contents of EC and its precursor urea was determined under specific pH (3.5 and 4.5) and temperature (4, 25, and 50°C) conditions using the developed method. As a result, EC content was increased with greater temperature and lower pH. In Korean rice wine, urea was detected 0.19-1.37mg/L and EC was detected 2.0-7.7μg/L. The method developed in this study, which has the advantages of simplified sample preparation, low detection limits, and good selectivity, was successfully applied for the rapid analysis of EC and urea. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel gemini cationic lipids with carbamate groups for gene delivery

PubMed Central

Zhao, Yi-Nan; Qureshi, Farooq; Zhang, Shu-Biao; Cui, Shao-Hui; Wang, Bing; Chen, Hui-Ying; Lv, Hong-Tao; Zhang, Shu-Fen; Huang, Leaf

2014-01-01

To obtain efficient non-viral vectors, a series of Gemini cationic lipids with carbamate linkers between headgroups and hydrophobic tails were synthesized. They have the hydrocarbon chains of 12, 14, 16 and 18 carbon atoms as tails, designated as G12, G14, G16 and G18, respectively. These Gemini cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. The DNA-bonding ability of these Gemini cationic liposomes was much better than their mono-head counterparts (designated as M12, M14, M16 and M18, respectively). In the same series of liposomes, bonding ability declined with an increase in tail length. They were tested for their gene-transferring capabilities in Hep-2 and A549 cells. They showed higher transfection efficiency than their mono-head counterparts and were comparable or superior in transfection efficiency and cytotoxicity to the commercial liposomes, DOTAP and Lipofectamine 2000. Our results convincingly demonstrate that the gene-transferring capabilities of these cationic lipids depended on hydrocarbon chain length. Gene transfection efficiency was maximal at a chain length of 14, as G14 can silence about 80 % of luciferase in A549 cells. Cell uptake results indicate that Gemini lipid delivery systems could be internalised by cells very efficiently. Thus, the Gemini cationic lipids could be used as synthetic non-viral gene delivery carriers for further study. PMID:25045521

Carcinogenic compounds in alcoholic beverages: an update.

PubMed

Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

2016-10-01

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

Enhancement of the efficacy of a carbamate nematicide against the potato cyst nematode, Globodera pallida, through mycorrhization in commercial potato fields.

PubMed

Deliopoulos, T; Minnis, S T; Jones, P W; Haydock, P P J

2010-03-01

Two experiments were conducted over 2 years in commercial potato fields in Shropshire, UK, to evaluate the compatibility of the nematicide aldicarb with commercial inocula of arbuscular mycorrhizal fungi (AMF) in the control of the potato cyst nematode Globodera pallida. The AMF used were Vaminoc (mixed-AMF inoculum), Glomus intraradices (BioRize BB-E) and G. mosseae (isolate BEG 12). In the absence of AMF, the in-soil hatch of G. pallida increased 30% (P < 0.01) from wk-2 to wk-4 after planting. Inoculation of physiologically-aged potato (cv. Golden Wonder) tubers with AMF eliminated this delay in G. pallida hatch by stimulating a mean increase of 32% (P < 0.01) in hatch within 2 wk after planting. In the aldicarb-treated plots in Experiment 1, G. pallida multiplication rate was 38% lower (P < 0.05) in roots of AMF-inoculated than noninoculated plants, but in Experiment 2, this effect was slightly lower (P = 0.07). In these plots, the single AMF inocula showed also a weak trend (P = 0.10) towards greater tuber yields relative to their noninoculated counterparts. Mycorrhization therefore appears to enhance the efficacy of carbamate nematicides against G. pallida and consequently more research is proposed to validate these findings and fully explore the potential of this model.

Graduate Education and Simulation Training for CBRNE Disasters Using a Multimodal Approach to Learning. Part 2: Education and Training from the Perspectives of Educators and Students

DTIC Science & Technology

2013-08-01

anesthetized NHPs exposed to the carbamate nerve-agent simulant physostigmine, which is FDA-approved for the diagnosis and treatment of myasthenia ... gravis . Physostigmine is a short-acting drug that reliably induces the cholinergic signs of increased secretions (lacrimation, hypersalivation...the experience. One insightful comment is provided below. “As an MD, I have treated myasthenia crisis and delirium tremens. I can say definitely

tert-Butyl N-hydr­oxy-N-[(1S*,2R*)-2-(1-naphth­yl)cyclo­pent-3-en-1-yl]carbamate

PubMed Central

Lough, Alan J.; Machin, Ben P.; Tam, William

2009-01-01

The relative stereochemistry of the title compound, C20H23NO3, was established by X-ray analysis. The asymmetric unit contains two independent mol­ecules. In the crystal structure, each type of mol­ecule forms a centrosymmetric dimer via pairs of inter­molecular O—H⋯O hydrogen bonds, resulting in an R 2 2(10) loop in each case. PMID:21582783

Whole Blood Robotic Cholinesterase Assay for Organophosphate Exposure - Testing Soldiers, First Responders, and Civilians in the Field and Laboratory

DTIC Science & Technology

2004-12-01

inhibited by selective (e.g. huperzine A ) and non-selective (carbamate) inhibitors (e.g. pyridostigmine bromide, PB). Both studies supported Federal...week). Huperzine A was well tolerated by these patients and warrants study as a future prophylaxis for OP poisoning. Due to the documented use...reversal of ChE inhibition by PB). 3.4 Measurement of huperzine A induced ChE inhibi- tion (RBC-AChE): Aliquots of whole blood from twelve healthy

The anthelmintic efficacy of fenbendazole in the control of Moniezia expansa and Trichuris ovis in sheep.

PubMed

Townsend, R B; Kelly, J D; James, R; Weston, I

1977-11-01

The anthelmintic efficacy of fenbendazole (methyl 5-(phenyl-thio)-2-benzimidazole-carbamate) against Moniezia expansa and Trichuris ovis was tested. At dose rates of 5 mg per kg and above, efficacies were found to be greater than 91 percent against M expansa and greater than 92 per cent against T ovis. At these dose rates efficacy on egg suppression was 100 per cent for Moniezia and greater than 97 per cent for Trichuris.

Update on capecitabine alone and in combination regimens in colorectal cancer patients.

PubMed

Silvestris, N; Maiello, E; De Vita, F; Cinieri, S; Santini, D; Russo, A; Tommasi, S; Azzariti, A; Numico, G; Pisconti, S; Petriella, D; Lorusso, V; Millaku, A; Colucci, G

2010-11-01

Capecitabine is an orally administered fluoropyrimidine carbamate which has been developed as a prodrug of 5-FU with the goal to improve its tolerability and intratumoral drug concentration. The review aims to provide an evidence-based update of clinical trials investigating the clinical efficacy, adverse-event profile, dosage and administration of this drug, alone or in combination with conventional chemotherapeutics and/or new target-oriented drugs, in the management of colorectal cancer patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Prophylactic and Treatment Drugs for Organophosphorus Poisoning

DTIC Science & Technology

1990-08-01

Synthesis of e-Mercapto-a- aminocaproic Acid and Its S- Alkyl and N-Sulfanilyl Derivatives." Yuan C.E.; Shchukina, M.N. Zhur. Obshchei Khim, 1957, 27... acids , carbamates, 07 0 1,AT( Isynthes is. 19. BSTACT(Continue on rveberl of newcesary and odentify by block number) The program is directed at the...cis-4-chlorobuten-l-ol and 4-chlorobutanol, one alicylaryl disulfide, two chlo’oalky(aryl) carboxylic acids , i,3.5-tris-2’-chloroethylbernzene I and d

Green-Light-Sensitive BODIPY Photoprotecting Groups for Amines

PubMed Central

2018-01-01

We describe a series of easily accessible, visible-light-sensitive (λ > 500 nm) BODIPY (boron-dipyrromethene)-based photoprotecting groups (PPGs) for primary and secondary amines, based on a carbamate linker. The caged compounds are stable under aqueous conditions for 24 h and can be efficiently uncaged in vitro with visible light (λ = 530 nm). These properties allow efficient photodeprotection of amines, rendering these novel PPGs potentially suitable for various applications, including the delivery of caged drugs and their remote activation. PMID:29369628

Di-tert-butyl­bis(N-isopropyl-N-methyl­dithio­carbamato-κ2 S,S′)tin(IV)

PubMed Central

Muthalib, Amirah Faizah; Baba, Ibrahim; Samsudin, Mohd Wahid; Ng, Seik Weng

2010-01-01

The dithio­carbamate anions in the title compound, [Sn(C4H9)2(C5H10NS2)2], chelate to the SnIV atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol­ecule lies across a twofold rotation axis. The crystal studied was a non-merohedral twin, the ratio of the twin components being 0.82 (1):0.18 (1). PMID:21580471

Molecular Targets and Synaptic Effects of Carbamates, Organophosphates, Oximes, and Pyridiniums: Implications for Prophylaxis and Therapy of Organophosphate Toxicity

DTIC Science & Technology

1994-03-16

excitability in the latter studies , it does seem that block of gK by PC, is an important factor in the pathopharmacological eltfect- of PC? in causing...muscle following acute and subacute exposure to pyridostigmine. Studies on muscle contractility and cellular mechanisms. Proc. Fourth Annual Chemical...receptor-ionic chauinel complex II. Patch dlamp studies . Mol. Pharmacol. 0 25:102-112, 1984. 7. Albuquerque, E.X., Aguayo, L., Swanson, K.L., Idriss, M

[Detection of methyl carbamate and ethyl carbamate in yellow rice wine by gas chromatography-mass spectrometry].

PubMed

Wu, Ping-gu; Ma, Bing-jie; Wang, Li-yuan; Shen, Xiang-hong; Zhang, Jing; Tan, Ying; Jiang, Wei

2013-11-01

To establish the method of simultaneous determination of methylcarbamate (MC) and ethylcarbamate (EC) in yellow rice wine by gas chromatography-mass spectrometry (GC/MS). MC and EC in yellow rice wine were derived by 9-xanthydrol, and then the derivants were detected by GC/MS; and quantitatively analyzed by D5-EC isotope internal standard method. The linearity of MC and EC ranged from 2.0 µg/L to 400.0 µg/L, with correlation coefficients at 0.998 and 0.999, respectively. The limits of quantitation (LOQ) and detection (LOD) were 0.67 and 2.0 µg/kg. When MC and EC were added in yellow rice wine at the range of 2.0-300.0 µg/kg, the intraday average recovery rate was 78.8%-102.3%, relative standard deviation was 3.2%-11.6%; interday average recovery rate was 75.4%-101.3%, relative standard deviation was 3.8%-13.4%. 20 samples of yellow rice wine from supermarket were detected using this method, the contents of MC were in the range of ND (no detected) to 1.2 µg/kg, the detection rate was 6% (3/20), the contents of EC in the range of 18.6 µg/kg to 432.3 µg/kg, with the average level at 135.2 µg/kg. The method is simple, rapid and useful for simultaneous determination of MC and EC in yellow rice wine.

Metabolic Engineering of the Regulators in Nitrogen Catabolite Repression To Reduce the Production of Ethyl Carbamate in a Model Rice Wine System

PubMed Central

Zhao, Xinrui; Zou, Huijun; Fu, Jianwei; Chen, Jian

2014-01-01

Rice wine has been one of the most popular traditional alcoholic drinks in China. However, the presence of potentially carcinogenic ethyl carbamate (EC) in rice wine has raised a series of food safety issues. During rice wine production, the key reason for EC formation is urea accumulation, which occurs because of nitrogen catabolite repression (NCR) in Saccharomyces cerevisiae. NCR represses urea utilization by retaining Gln3p in the cytoplasm when preferred nitrogen sources are present. In order to increase the nuclear localization of Gln3p, some possible phosphorylation sites on the nuclear localization signal were mutated and the nuclear localization regulation signal was truncated, and the disruption of URE2 provided an additional method of reducing urea accumulation. By combining these strategies, the genes involved in urea utilization (DUR1,2 and DUR3) could be significantly activated in the presence of glutamine. During shake flask fermentations of the genetically modified strains, very little urea accumulated in the medium. Furthermore, the concentrations of urea and EC were reduced by 63% and 72%, respectively, in a model rice wine system. Examination of the normal nutrients in rice wine indicated that there were few differences in fermentation characteristics between the wild-type strain and the genetically modified strain. These results show that metabolic engineering of the NCR regulators has great potential as a method for eliminating EC during rice wine production. PMID:24185848

Underpinning Sustainable Vector Control through Informed Insecticide Resistance Management

PubMed Central

Hemmings, Kay; Hughes, Angela J.; Chanda, Emmanuel; Musapa, Mulenga; Kamuliwo, Mulakwa; Phiri, Faustina N.; Muzia, Lucy; Chanda, Javan; Kandyata, Alister; Chirwa, Brian; Poer, Kathleen; Hemingway, Janet; Wondji, Charles S.; Ranson, Hilary; Coleman, Michael

2014-01-01

Background There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. Methodology/Principal Findings A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. Conclusions/Significance Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan. PMID:24932861

Differential toxic effects of Carbofuran and Diazinon on time of flight in pigeons (Columba livia): Potential for pesticide effects on migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brasel, Jeffrey M.; Environmental Sciences and Health Graduate Program, University of Nevada, Reno, NV 89557; Collier, Abby C.

Cholinesterase inhibiting compounds such as carbamates and organophosphate insecticides have been widely used in agriculture since the ban on organochlorines in the 1970s. Carbofuran, a carbamate, and diazinon, an organophosphate, are among the most commonly implicated cholinesterase inhibitors in episodes of accidental avian toxicity and mortality. Despite the apparent effects of these compounds, little work has been done to study effects of low-level, environmentally relevant doses at the population level in migratory bird species. In this study, homing pigeons were used as surrogate species to assess the differences in the effect of incrementally low doses (0.0, 0.25, 0.5, and 1.0more » mg/kg) of carbofuran and diazinon on time of flight and determine whether there was a threshold dose of either or both xenobiotics when orally administered at these levels. The results indicate that there is a significant dose-dependent increase in flight time in pigeons dosed with carbofuran while diazinon exposed pigeons showed little effect. More profound effects were noted with carbofuran with pigeons falling off the pace of the flock and a dose for highly significant increase in flight time elucidated between 0.5 and 1.0 mg/kg. The results of the studies validate the homing pigeon as a good subject for comparative studies of cholinesterase inhibitors in birds and the need for further research on repeated low-level exposures on populations of avian species.« less

A meta-analysis synthesizing the effects of pesticides on swim speed and activity of aquatic vertebrates.

PubMed

Shuman-Goodier, Molly E; Propper, Catherine R

2016-09-15

Pesticide contaminants are ubiquitous in aquatic environments and pose a threat to biodiversity. Pesticides also have diverse mechanisms of action that make it difficult to identify impacts on exposed wildlife. Behavioral measures represent an important link between physiological and ecological processes, and are often used to generalize sub-lethal effects of pesticide exposure. In order to bridge the toxicological and behavioral literature, and identify chemical classes that denote the largest threat, we conducted a meta-analysis summarizing the effects of pesticides on swim speed and activity of aquatic vertebrates. We found that exposure to environmentally relevant concentrations of pesticides reduced the swim speed of exposed amphibians and fish by 35%, and reduced overall activity by 72%. There were also differences in the magnitude of this effect across chemical classes, which likely reflect underlying physiological processes. Pyrethroids, carbamates, and organophosphates all produced a large decrease in swim speed, where as phosphonoglycines and triazines showed no overall effect. Pyrethroids, carbamates, organophosphates, organochlorines, and organotins also produced a large decrease in activity, while phosphonoglycines had no overall effect, and triazines had the opposite effect of increasing activity. Our results indicate that even sub-lethal concentrations of pesticides have a strong effect on critical behaviors of aquatic vertebrates, which can affect fitness and alter species interactions. We expect our synthesis can be used to identify chemical classes producing the largest sub-lethal effects for further research and management. Copyright © 2016 Elsevier B.V. All rights reserved.

Physical Properties and CO2 Reaction Pathway of 1-Ethyl-3-Methylimidazolium Ionic Liquids with Aprotic Heterocyclic Anions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, S; DeSilva, MA; Brennecke, JF

2014-12-25

Ionic liquids (ILs) with aprotic heterocyclic anions (AHA) are attractive candidates for CO2 capture technologies. In this study, a series of AHA ILs with 1-ethyl-3-methylimidazolium ([emim](+)) cations were synthesized, and their physical properties (density, viscosity, and ionic conductivity) were measured. In addition, CO2 solubility in each IL was determined at room temperature using a volumetric method at pressures between 0 and 1 bar. The AHAs are basic anions that are capable of reacting stoichiometrically with CO2 to form carbamate species. An interesting CO2 uptake isotherm behavior was observed, and this may be attributed to a parallel, equilibrium proton exchange processmore » between the imidazolium cation and the basic AHA in the presence of CO2, followed by the formation of "transient" carbene species that react rapidly with CO2. The presence of the imidazolium-carboxylate species and carbamate anion species was verified using H-1 and C-13 NMR spectroscopy. While the reaction between CO2 and the proposed transient carbene resulted in cation-CO2 binding that is stronger than the anion-CO2 reaction, the reactions of the imidazolium AHA ILs were fully reversible upon regeneration at 80 degrees C with nitrogen purging. The presence of water decreased the CO2 uptake due to the inhibiting effect of the neutral species (protonated form of AHA) that is formed.« less

The influence of organophosphate and carbamate on sperm chromatin and reproductive hormones among pesticide sprayers.

PubMed

Jamal, Farrukh; Haque, Quazi S; Singh, Sangram; Rastogi, S K

2016-08-01

This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes. © The Author(s) 2015.

Occupational pesticide use and Parkinson's disease in the Parkinson Environment Gene (PEG) study.

PubMed

Narayan, Shilpa; Liew, Zeyan; Bronstein, Jeff M; Ritz, Beate

2017-10-01

To study the influence of occupational pesticide use on Parkinson's disease (PD) in a population with information on various occupational, residential, and household sources of pesticide exposure. In a population-based case control study in Central California, we used structured interviews to collect occupational history details including pesticide use in jobs, duration of use, product names, and personal protective equipment use from 360 PD cases and 827 controls. We linked reported products to California's pesticide product label database and identified pesticide active ingredients and occupational use by chemical class including fungicides, insecticides, and herbicides. Employing unconditional logistic regression, we estimated odds ratios and 95% confidence intervals for PD and occupational pesticide use. Ever occupational use of carbamates increased risk of PD by 455%, while organophosphorus (OP) and organochlorine (OC) pesticide use doubled risk. PD risk increased 110-211% with ever occupational use of fungicides, herbicides, and insecticides. Using any pesticide occupationally for >10years doubled the risk of PD compared with no occupational pesticide use. Surprisingly, we estimated higher risks among those reporting use of personal protective equipment (PPE). Our findings provide additional evidence that occupational pesticide exposures increase PD risk. This was the case even after controlling for other sources of pesticide exposure. Specifically, risk increased with occupational use of carbamates, OPs, and OCs, as well as of fungicides, herbicides, or insecticides. Interestingly, some types of PPE use may not provide adequate protection during pesticide applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

INHIBITION OF HUMAN ACETYL- AND BUTYRYLCHOLINESTERASE BY NOVEL CARBAMATES OF (−)- AND (+)-TETRAHYDROFUROBENZOFURAN AND METHANOBENZODIOXEPINE

PubMed Central

Luo, Weiming; Yu, Qian-sheng; Kulkarni, Santosh S.; Parrish, Damon A.; Holloway, Harold W.; Tweedie, David; Shafferman, Avigdor; Lahiri, Debomoy K.; Brossi, Arnold; Greig, Nigel H.

2008-01-01

A new enantiomeric synthesis utilizing classical resolution provided two novel series of optically active inhibitors of cholinesterase: (−)- and (+)- O-carbamoyl phenols of tetrahydrofurobenzofuran and methanobenzodioxepine. An additional two series of (−)- and (+)-O-carbamoyl phenols of pyrroloindole and furoindole were obtained by known procedures, and their anticholinesterase actions were similarly quantified against freshly prepared human acetyl- (AChE) and butyrylcholinesterase (BChE). Both enantiomeric forms of each series demonstrated potent cholinesterase inhibitory activity (with IC50 values as low as 10 nM for AChE and 3 nM for BChE), with the exception of the (+)-O-carbamoyl phenols of pyrroloindole that lacked activity (IC50 values > 1 µM). Based on the biological data of these four series, a SAR analysis was provided by molecular volume calculations. In addition, a probable transition state model was established according to the known X-ray structure of a transition state complex of Torpedo californica AChE-m-(N,N,N,trimethylammonio)-2,2,2-trifluoroacetophenone (TcAChE-TMTFA). This model proved valuable in explaining the enantio-selectivity and enzyme subtype selectivity of each series. These carbamates are more or similarly potent to anticholinesterases in current clinical use; providing not only inhibitors of potential clinical relevance but also pharmacological tools to define drug-enzyme binding interactions within an enzyme crucial in the maintenance of cognition and numerous systemic physiological functions in health, aging and disease. PMID:16570913

Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review.

PubMed

Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

2011-09-01

Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.

Nano carbon black-based screen printed sensor for carbofuran, isoprocarb, carbaryl and fenobucarb detection: application to grain samples.

PubMed

Della Pelle, Flavio; Angelini, Claudia; Sergi, Manuel; Del Carlo, Michele; Pepe, Alessia; Compagnone, Dario

2018-08-15

An electrochemical screening assay for the detection of phenyl carbamates (i.e. carbaryl, carbofuran, isoprocarb and fenobucarb) was developed and applied to grains samples (i.e. durum wheat, soft wheat and maize). Nano carbon black (CB) was strategically employed to realize an effective, reproducible, fouling resistant, low cost, delocalisable screen printed sensor (CB-SPE). CB-SPEs morphology (SEM and FEM) and electrochemical property (CV and EIS) were studied. The final pesticides analysis protocol consist of: (i) extraction of the analyte (just by mixing), (ii) alkaline hydrolysis (10 min R.T.), (iii) DPV detection directly of 100 µL of extract on the CB-SPE surface. Linear range between 1.0 × 10 -7 and 1.0 × 10 -4 mol L -1 , good determination coefficients (R 2 ≥ 0.9971) and satisfactory sensitivity (≥ 3.90 × 10 -1 A M -1 cm -2 ) and LODs (≤ 8.0 × 10 -8 mol L -1 ) were obtained for all the analytes. Excellent recoveries (78-102%) and accuracy (relative error vs. HPLC-MS/MS between 9.0% and -7.8%) resulted from the analysis of grains samples. The proposed CB-SPE based approach has demonstrated to be able to detect carbaryl at Maximum residue limits levels (MRLs), allowing class selective detection of commonly employed phenyl carbamates in food samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa Is Driven by Metabolic Resistance Mechanisms

PubMed Central

Mulamba, Charles; Riveron, Jacob M.; Ibrahim, Sulaiman S.; Irving, Helen; Barnes, Kayla G.; Mukwaya, Louis G.; Birungi, Josephine; Wondji, Charles S.

2014-01-01

Background Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms. Methodology/Principal Findings Female An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance. Conclusion The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management. PMID:25333491

Metabolic engineering of the regulators in nitrogen catabolite repression to reduce the production of ethyl carbamate in a model rice wine system.

PubMed

Zhao, Xinrui; Zou, Huijun; Fu, Jianwei; Zhou, Jingwen; Du, Guocheng; Chen, Jian

2014-01-01

Rice wine has been one of the most popular traditional alcoholic drinks in China. However, the presence of potentially carcinogenic ethyl carbamate (EC) in rice wine has raised a series of food safety issues. During rice wine production, the key reason for EC formation is urea accumulation, which occurs because of nitrogen catabolite repression (NCR) in Saccharomyces cerevisiae. NCR represses urea utilization by retaining Gln3p in the cytoplasm when preferred nitrogen sources are present. In order to increase the nuclear localization of Gln3p, some possible phosphorylation sites on the nuclear localization signal were mutated and the nuclear localization regulation signal was truncated, and the disruption of URE2 provided an additional method of reducing urea accumulation. By combining these strategies, the genes involved in urea utilization (DUR1,2 and DUR3) could be significantly activated in the presence of glutamine. During shake flask fermentations of the genetically modified strains, very little urea accumulated in the medium. Furthermore, the concentrations of urea and EC were reduced by 63% and 72%, respectively, in a model rice wine system. Examination of the normal nutrients in rice wine indicated that there were few differences in fermentation characteristics between the wild-type strain and the genetically modified strain. These results show that metabolic engineering of the NCR regulators has great potential as a method for eliminating EC during rice wine production.

RP-HPLC method using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate incorporated with normalization technique in principal component analysis to differentiate the bovine, porcine and fish gelatins.

PubMed

Azilawati, M I; Hashim, D M; Jamilah, B; Amin, I

2015-04-01

The amino acid compositions of bovine, porcine and fish gelatin were determined by amino acid analysis using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as derivatization reagent. Sixteen amino acids were identified with similar spectral chromatograms. Data pre-treatment via centering and transformation of data by normalization were performed to provide data that are more suitable for analysis and easier to be interpreted. Principal component analysis (PCA) transformed the original data matrix into a number of principal components (PCs). Three principal components (PCs) described 96.5% of the total variance, and 2 PCs (91%) explained the highest variances. The PCA model demonstrated the relationships among amino acids in the correlation loadings plot to the group of gelatins in the scores plot. Fish gelatin was correlated to threonine, serine and methionine on the positive side of PC1; bovine gelatin was correlated to the non-polar side chains amino acids that were proline, hydroxyproline, leucine, isoleucine and valine on the negative side of PC1 and porcine gelatin was correlated to the polar side chains amino acids that were aspartate, glutamic acid, lysine and tyrosine on the negative side of PC2. Verification on the database using 12 samples from commercial products gelatin-based had confirmed the grouping patterns and the variables correlations. Therefore, this quantitative method is very useful as a screening method to determine gelatin from various sources. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antagonism at combined effects of chemical fertilizers and carbamate insecticides on the rice-field N2-fixing cyanobacterium Cylindrospermum sp. in vitro

PubMed Central

Nayak, Nabakishore; Rath, Shakti

2014-01-01

Effects of chemical fertilizers (urea, super phosphate and potash) on toxicities of two carbamate insecticides, carbaryl and carbofuran, individually to the N2-fixing cyanobacterium, Cylindrospermum sp. were studied in vitro at partially lethal levels (below highest permissive concentrations) of each insecticide. The average number of vegetative cells between two polar heterocysts was 16.3 in control cultures, while the mean value of filament length increased in the presence of chemical fertilizers, individually. Urea at the 10 ppm level was growth stimulatory and at the 50 ppm level it was growth inhibitory in control cultures, while at 100 ppm it was antagonistic, i.e. toxicity-enhancing along with carbaryl, individually to the cyanobacterium, antagonism was recorded. Urea at 50 ppm had toxicity reducing effect with carbaryl or carbofuran. At 100 and 250 ppm carbofuran levels, 50 ppm urea only had a progressive growth enhancing effect, which was marked well at 250 ppm carbofuran level, a situation of synergism. Super phosphate at the 10 ppm level only was growth promoting in control cultures, but it was antagonistic at its higher levels (50 and 100 ppm) along with both insecticides, individually. Potash (100, 200, 300 and 400 ppm) reduced toxicity due to carbaryl 20 and carbofuran 250 ppm levels, but potash was antagonistic at the other insecticide levels. The data clearly showed that the chemical fertilizers used were antagonistic with both the insecticides during toxicity to Cylindrospermum sp. PMID:26038669

Crystal structures and Hirshfeld surface analyses of bis-[N,N-bis-(2-meth-oxy-eth-yl)di-thio-carbamato-κ2S,S']di-n-butyl-tin(IV) and [N-(2-meth-oxy-eth-yl)-N-methyl-dithio-carbamato-κ2S,S']tri-phenyl-tin(IV).

PubMed

Mohamad, Rapidah; Awang, Normah; Kamaludin, Nurul Farahana; Jotani, Mukesh M; Tiekink, Edward R T

2018-03-01

The crystal and mol-ecular structures of the two title organotin di-thio-carbamate compounds, [Sn(C 4 H 9 ) 2 (C 7 H 14 NO 2 S 2 ) 2 ], (I), and [Sn(C 6 H 5 ) 3 (C 5 H 10 NOS 2 )], (II), are described. Both structures feature asymmetrically bound di-thio-carbamate ligands leading to a skew-trapezoidal bipyramidal geometry for the metal atom in (I) and a distorted tetra-hedral geometry in (II). The complete mol-ecule of (I) is generated by a crystallographic twofold axis (Sn site symmetry 2). In the crystal of (I), mol-ecules self-assemble into a supra-molecular array parallel to (10-1) via methyl-ene-C-H⋯O(meth-oxy) inter-actions. In the crystal of (II), supra-molecular dimers are formed via pairs of weak phenyl-C-H⋯π(phen-yl) contacts. In each of (I) and (II), the specified assemblies connect into a three-dimensional architecture without directional inter-actions between them. Hirshfeld surface analyses confirm the importance of H⋯H contacts in the mol-ecular packing of each of (I) and (II), and in the case of (I), highlight the importance of short meth-oxy-H⋯H(but-yl) contacts between layers.

The current insecticide resistance status of Anopheles gambiae (s.l.) (Culicidae) in rural and urban areas of Bouaké, Côte d'Ivoire.

PubMed

Zoh, Dounin Danielle; Ahoua Alou, Ludovic Phamien; Toure, Mahama; Pennetier, Cédric; Camara, Soromane; Traore, Dipomin François; Koffi, Alphonsine Amanan; Adja, Akré Maurice; Yapi, Ahoua; Chandre, Fabrice

2018-03-02

Several studies were carried out in experimental hut station in areas surrounding the city of Bouaké, after the crisis in Côte d'Ivoire. They reported increasing resistance levels to insecticide for malaria transmiting mosquitoes. The present work aims to evaluate the current resistance level of An. gambiae (s.l.) in rural and urban areas in the city of Bouaké. Larvae of Anopheles gambiae (s.l.) were collected from five different study sites and reared to adult stages. The resistance status was assessed using the WHO bioassay test kits for adult mosquitoes, with eight insecticides belonging to pyrethroids, organochlorines, carbamates and organophosphates classes. Molecular assays were performed to identify the molecular forms of An. gambiae (s.l.), the L1014F kdr and the ace-1R alleles in individual mosquitoes. The synergist PBO was used to investigate the role of enzymes in resistance. Biochemical assays were performed to detect potential increased activities in mixed function oxidase (MFO) levels, non-specific esterases (NSE) and glutathione S-transferases (GST). High resistance levels to pyrethroids, organochlorines, and carbamates were observed in Anopheles gambiae (s.l.) from Bouaké. Mortalities ranged between 0 and 73% for the eight tested insecticides. The pre-exposure to PBO restored full or partial susceptibility to pyrethroids in the different sites. The same trend was observed with the carbamates in five sites, but to a lesser extent. With DDT, pre-exposure to PBO did not increase the mortality rate of An. gambiae (s.l.) from the same sites. Tolerance to organophosphates was observed. An increased activity of NSE and higher level of MFO were found compared to the Kisumu susceptible reference strain. Two molecular forms, S form [(An. gambiae (s.s)] and M form (An. coluzzi) were identified. The kdr allele frequencies vary from 85.9 to 99.8% for An. gambiae (s.s.) and from 81.7 to 99.6% for An. coluzzii. The ace-1R frequencies vary between 25.6 and 38.8% for An. gambiae (s.s.) and from 28.6 to 36.7% for An. coluzzii. Resistance to insecticides is widespread within both An. gambiae (s.s.) and An. coluzzii. Two mechanisms of resistance, i.e. metabolic and target-site mutation seemed to largely explain the high resistance level of mosquitoes in Bouaké. Pyrethroid resistance was found exclusively due to the metabolic mechanism.

Phase Separation During the Curing of a Cyanate Ester Oligomer

NASA Astrophysics Data System (ADS)

Gurov, D. A.; Novikov, G. F.

2018-07-01

It is found during the curing of a cyanate ester oligomer that there are such features as a step and a maximum in the frequency dependences (in a range of 10-2-105 Hz) of the real parts of the complex electric conductivity and loss tangent, respectively. In the frequency range where these features are observed, the diagrams of complex electric modulus are semicircles with centers near the abscissas. Subsequent analysis shows these features are due to the formation of the microphase of the intermediate product, carbamate.

Gelation of Oil Slicks by Amine Carbamates as an Adjunct to U.S. Navy Oil Spill Recovery Operations

DTIC Science & Technology

1977-01-14

plan for a field test in Boston Harbor was to be developed and submitted to the EPA, Coast Guard, state and municipal water control authorities. Di ...Residual Special Fuel Oil #6, and similar oils) was found to be a mixture of 40 g. dodecylamine, 25 R. tetradecylamine, and 4.5 g. hexadecylamine In...solution with 100 g. methyl alcohol. By far the best system, however, was a mixture of 70% dehydroabletylamine ("Amine D", as manufactured by Hercules Corp

Ab initio study of the alkaline hydrolysis of a thio-β-lactam structure

NASA Astrophysics Data System (ADS)

Coll, Miguel; Frau, Juan; Vilanova, Bartolomé; Donoso, Josefa; Muñoz, Francisco

2000-08-01

The alkaline hydrolysis of a thio-β-lactam in the gas phase was examined in the light of RHF and DFT ab initio calculations. The solvent effect was considered via IPCM computations. The tetrahedral intermediate for the thio-β-lactam studied is unstable, so the compound evolves directly to the corresponding thio-azethidin-2-one open ring with cleavage of the C-S bond. The end-products obtained bear a carbamate group, which suggests that the thio-β-lactam might be an effective inhibitor for β-lactamases.

Metal vinylidenes and allenylidenes in catalysis: applications in anti-Markovnikov additions to terminal alkynes and alkene metathesis.

PubMed

Bruneau, Christian; Dixneuf, Pierre H

2006-03-27

The involvement of a catalytic metal vinylidene species was proposed for the first time in 1986 to explain the regioselective formation of vinyl carbamates directly from terminal alkynes, carbon dioxide, and amines. Since this initial report, various metal vinylidenes and allenylidenes, which are key activation intermediates, have proved extremely useful for many alkyne transformations. They have contributed to the rational design of new catalytic reactions. This 20th anniversary is a suitable occasion to present the advancement of organometallic vinylidenes and allenylidenes in catalysis.

Is contaminated unrecorded alcohol a health problem in the European Union? A review of existing and methodological outline for future studies.

PubMed

Lachenmeier, Dirk W; Schoeberl, Kerstin; Kanteres, Fotis; Kuballa, Thomas; Sohnius, Eva-Maria; Rehm, Jürgen

2011-03-01

Some European countries with high levels of unrecorded alcohol consumption have anomalously high rates of death attributable to liver cirrhosis. Hepatotoxic compounds in illegally produced spirits may be partly responsible. Based on a review of the evidence on the chemical composition and potential harm from unrecorded alcohol, the Alcohol Measures for Public Health Research Alliance (AMPHORA) project's methodology for identifying, analysing and toxicologically evaluating such alcohols is provided. A computer-assisted literature review concentrated on unrecorded alcohol. Additionally, we refer to our work in the capacity of governmental alcohol control authority and a number of pilot studies. The risk-oriented identification of substances resulted in the following compounds probably posing a public health risk in unrecorded alcohol: ethanol, methanol, acetaldehyde, higher alcohols, heavy metals, ethyl carbamate, biologically active flavourings (e.g. coumarin) and diethyl phthalate. Suggestions on a sampling strategy for identifying unrecorded alcohol that may be most prone to contamination include using probable distribution points such as local farmers and flea markets for selling surrogate alcohol (including denatured alcohol) to focusing on lower socio-economic status or alcohol-dependent individuals, and selecting home-produced fruit spirits prone to ethyl carbamate contamination. Standardized guidelines for the chemical and toxicological evaluation of unrecorded alcohol that will be used in a European-wide sampling and are applicable globally are provided. These toxicological guidelines may also be used by alcohol control laboratories for recorded alcohol products, and form a scientific foundation for establishing legislative limits. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug.

PubMed

de Graaf, M; Boven, E; Oosterhoff, D; van der Meulen-Muileman, I H; Huls, G A; Gerritsen, W R; Haisma, H J; Pinedo, H M

2002-03-04

Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme beta-glucuronidase. The sequences encoding C28 and human enzyme beta-glucuronidase were joined by a sequence encoding a flexible linker, and were preceded by the IgGkappa signal sequence for secretion of the fusion protein. A CHO cell line was engineered to secrete C28-beta-glucuronidase fusion protein. Antibody specificity and enzyme activity were retained in the secreted fusion protein that had an apparent molecular mass of 100 kDa under denaturing conditions. The fusion protein was able to convert a non-toxic prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-beta-glucuronyl carbamate to doxorubicin, resulting in cytotoxicity. A bystander effect was demonstrated, as doxorubicin was detected in all cells after N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-beta-glucuronyl carbamate administration when only 10% of the cells expressed the fusion protein. This is the first fully human and functional fusion protein consisting of an scFv against epithelial cell adhesion molecule and human enzyme beta-glucuronidase for future use in tumour-specific activation of a non-toxic glucuronide prodrug. Copyright 2002 Cancer Research UK

Optimizing high-performance liquid chromatography method for quantification of glucosamine using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate derivatization in rat plasma: application to a pharmacokinetic study.

PubMed

Wang, Xianhuo; Chen, Xiang; Chen, Lijuan; Wang, Biqin; Peng, Cheng; He, Chunmei; Tang, Minghai; Zhang, Fan; Hu, Jia; Li, Rui; Zhao, Xia; Wei, Yuquan

2008-11-01

A sensitive and reliable HPLC method with fluorescence detection based on the precolumn derivatization of glucosamine with 6-aminoquinolyl-N-hydroxylsuccinimidyl carbamate (AQC) was established for the quantitative determination of glucosamine in rat plasma. The plasma protein was precipitated by acetonitrile, followed by vortex mixing and centrifugation. The supernatant was divided into the organic layer and aqueous layer by adding sodium chloride, and then the aqueous layer was derivatized with AQC in 0.2 M borate buffer of pH 8.8 before the HPLC analysis. An amino acid analysis column (3.9 x 150 mm, 4 microm) was applied, with 140 mM sodium acetate buffer (pH = 5.25) and acetonitrile as mobile phase at a flow rate of 1 mL/min. A linear correlation coefficient of 0.9987 was calculated within the range of 0.1-30 microg/mL of the standard curve for glucosamine. The limit of detection was 30 ng/mL. The intra- and inter-day precisions (as RSD) were less than 7.38 and 12.72%, respectively. The intra- and inter-day accuracy ranged from 91.8 to 110.0%. Extraction recoveries of glucosamine in plasma were more than 90%. The validated method was successfully applied for the quantitative determination of glucosamine in rat plasma and evaluation for pharmacokinetic study of glucosamine. It was also possible to be applied for the quantitative determination of other compounds containing amino group in biological samples.

Impact of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the costs of mitigation

PubMed Central

Kafy, Hmooda Toto; Ismail, Bashir Adam; Mnzava, Abraham Peter; Lines, Jonathan; Abdin, Mogahid Shiekh Eldin; Eltaher, Jihad Sulieman; Banaga, Anuar Osman; West, Philippa; Bradley, John; Cook, Jackie; Thomas, Brent; Subramaniam, Krishanthi; Hemingway, Janet; Knox, Tessa Bellamy; Malik, Elfatih M.; Yukich, Joshua O.; Donnelly, Martin James; Kleinschmidt, Immo

2017-01-01

Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36–3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40–0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions. PMID:29229808

Insecticide resistance in bedbugs in Thailand and laboratory evaluation of insecticides for the control of Cimex hemipterus and Cimex lectularius (Hemiptera: Cimicidae).

PubMed

Tawatsin, Apiwat; Thavara, Usavadee; Chompoosri, Jakkrawarn; Phusup, Yutthana; Jonjang, Nisarat; Khumsawads, Chayada; Bhakdeenuan, Payu; Sawanpanyalert, Pathom; Asavadachanukorn, Preecha; Mulla, Mir S; Siriyasatien, Padet; Debboun, Mustapha

2011-09-01

Bedbugs are found in many countries around the world, and in some regions they are resistant to numerous insecticides. This study surveyed bedbugs in Thailand and determined their resistance to insecticides. The surveys were carried out in six provinces that attract large numbers of foreign tourists: Bangkok, Chonburi, Chiang Mai, Ubon Ratchathani, Phuket, and Krabi. Bedbugs were collected from hotels and colonized in the laboratory to evaluate their resistance to insecticides. Cimex hemipterus (F.) was found in some hotels in Bangkok, Chonburi, Phuket, and Krabi, whereas Cimex lectularius L. was found only in hotels in Chiang Mai. No bedbugs were found in Ubon Ratchathani. The colonized bedbugs showed resistance to groups of insecticides, including organochlorines (dichlorodiphenyl trichloroethane, dieldrin), carbamates (bendiocarb, propoxur), organophosphates (malathion, fenitrothion), and pyrethroids (cyfluthrin, deltamethrin, permethrin, lambda-cyhalothrin, etofenprox) in tests using World Health Organization insecticide-impregnated papers. The new insecticides imidacloprid (neonicotinoid group), chlorfenapyr (pyrrole group), and fipronil (phenylpyrazole group) were effective against the bedbugs; however, organophosphate (diazinon), carbamates (fenobucarb, propoxur), and pyrethroids (bifenthrin, cypermethrin, esfenvalerate, etofenprox) were ineffective. Aerosols containing various pyrethroid insecticides with two to four different active ingredients were effective against the bedbugs. The results obtained from this study suggested that both species of bedbugs in Thailand have developed marked resistance to various groups of insecticides, especially those in the pyrethroid group, which are the most common insecticides used for pest control. Therefore, an integrated pest management should be implemented for managing bedbugs in Thailand.

Secondary Amine Functional Disiloxanes as CO2 Sorbents

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Brien, MJ; Farnum, RL; Perry, RJ

2014-05-01

A series of two different types of secondary amine functional disiloxanes were prepared and screened as CO2 capture solvents. The first group of materials contained RNHCH2CH2CH2 side chains where the R groups were C1-6 alkyls. When R was a primary alkyl group, these materials exhibited CO2 uptake values slightly in excess of theoretical. As the alkyl groups were changed to more sterically hindered secondary or tertiary alkyls, the uptake was less efficient. Heats of absorption values for these materials were generally in the range 2000-2200 kJ/kg of CO2, values significantly lower than those obtained for primary amine functional disiloxanes (2500-2700more » kJ/kg of CO2). Also explored were a series of secondary amine functional disiloxanes with X-CH2CH2NH-CH2CH2CH2 - substituents. When X was an electron-donating group (RO-, R2N-, RO-CH2-) the CO2 uptake was also in excess of theoretical. Interestingly, these compounds were generally found to produce carbamate salts that were flowable, low-viscosity oils. Furthermore, the heat of absorption values determined for these materials were even lower. Most compounds gave values below 2000 kJ/kg of CO2. Overall the most promising results were obtained with a methoxyethylaminopropyl derivative, an ethoxyethylaminopropyl-containing material, and a dimethylaminoethylaminopropyl-based compound. These materials showed excellent CO2 uptake, had low heats of absorption, and produced carbamate salts that were flowable liquids even at room temperature.« less

Small Quaternary Inhibitors K298 and K524: Cholinesterases Inhibition, Absorption, Brain Distribution, and Toxicity.

PubMed

Karasova, Jana Zdarova; Hroch, Milos; Musilek, Kamil; Kuca, Kamil

2016-02-01

Inhibitors of acetylcholinesterase (AChE) may be used in the treatment of various cholinergic deficits, among them being myasthenia gravis (MG). This paper describes the first in vivo data for promising small quaternary inhibitors (K298 and K524): acute toxicity study, cholinesterase inhibition, absorption, and blood-brain barrier penetration. The newly prepared AChE inhibitors (bis-quinolinium and quinolinium compounds) possess a positive charge in the molecule which ensures that anti-AChE action is restricted to peripheral effect. HPLC-MS was used for determination of real plasma and brain concentration in the pharmacokinetic part of the study, and standard non-compartmental analysis was performed. The maximum plasma concentrations were attained at 30 min (K298; 928.76 ± 115.20 ng/ml) and 39 min (K524; 812.40 ± 54.96 ng/ml) after i.m. Both compounds are in fact able to target the central nervous system. It seems that the difference in the CNS distribution profile depends on an active efflux system. The K524 brain concentration was actively decreased to below an effective level; in contrast, K298 progressively accumulated in brain tissue. Peripheral AChE inhibitors are still first-line treatment in the mild forms of MG. Commonly prescribed carbamates have many severe side effects related to AChE carbamylation. The search for new treatment strategies is still important. Unlike carbamates, these new compounds target AChE via apparent π-π or π-cationic interaction aside at the AChE catalytic site.