Laboratory Examination in Nerve Agent Intoxication
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Routine Multipesticide Analysis Orbitrap
Routine Multi-Pesticide Residue Analysis by Orbitrap MS Technology Osama Abu-Nimreh CMD Sales Support Specialist MECEC , Dubai The world leader in serving science Challenges of Pesticide-Residues Analysis • Sample variability (matrix) • Different compound characteristics • Large number of samples • Hundreds of analytes monitored • Low levels controlled • Baby food (MRL for all pesticides = 0.01 mg/kg) • Fast response required 2 Former Pesticide Multi-Residue Method Setup . Extraction Acetonitrile, Ethyl Mostly replaced acetate, Methanol... by QuEChERS today . Clean-up GPC, SPE, LLE, LC . Determination GC, LC, GC-MS, LC-MS, Thermo Scientific™ QuEChERS™ GC-MS/MS, LC-MS/MS... method 3 Simplified Extraction Procedure Applied 10 g of sample is weighed into Quechers extraction tube + 20 mL of water + 10 mL of ACN shaking 10 min Centrifugation 5 min @ 5000 rpm Injection to LC-HRAM 4 Consumables Used Consumables/Chemicals Part Number Acetonitrile A/0638/17 QuEChERS extraction tube, 50 mL, 250 pack 60105-216 QuEChERS pouches, 50 pack 60105-344 Apparatus/Columns Part Number Horizontal shaker 1069-3391 Horizontal shaker plate 1053-0102 Thermo Scientific™ Barnstead™ EASYpure™II water 3125753 Thermo Scientific™ Heraeus™ Fresco™ 17 micro centrifuge 3208590 Thermo Scientific™ Accucore™ aQ column 100x2.1, 2.6 µm 17326-102130 5 Improving QuEChERS Extraction Tips & Tricks: • Dry food (cereals/dried food, < 25 % water content): • Addition of water to enable adequate partitioning and reducing interaction of pesticides with matrix • Food containing fat/wax (avocado/oil): • After extraction step add a freezing out step and transfer supernatant to clean-up tube • More clean-up might be needed of raw extract (PSA+C18) • Food containing complex matrix (tea/spices) • Additional clean-up with GCB might be necessary (potential loss of planar structure pesticides like thiabendazole) • Acidic food (citrus): • Adjust pH (5-5.5) to increase recovery (e.g. -
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Review of the Mammalian Toxicology
REVIEW OF THE MAMMALIAN TOXICOLOGY AND METABOLISM/TOXICOKINETICS OF FENTHION The APVMA Review of Fenthion © Australian Pesticides and Veterinary Medicines Authority 2012 ISBN 978-0-9873591-5-5 (electronic) This document was originally published in 2005 as part of the preliminary review findings report for Part 1 of the fenthion review. It was subsequently updated in 2007, and revised in 2008. Ownership of intellectual property rights in this publication Unless otherwise noted, copyright (and any other intellectual property rights, if any) in this publication is owned by the Australian Pesticides and Veterinary Medicines Authority (APVMA). Creative Commons licence With the exception of the Coat of Arms, this publication is licensed under a Creative Commons Attribution 3.0 Australia Licence. This is a standard form agreement that allows you to copy, distribute, transmit and adapt this publication provided that you attribute the work. A summary of the licence terms is available from www.creativecommons.org/licenses/by/3.0/au/deed.en. The full licence terms are available from www.creativecommons.org/licenses/by/3.0/au/legalcode. The APVMA’s preference is that you attribute this publication (and any approved material sourced from it) using the following wording: Source: Licensed from the Australian Pesticides and Veterinary Medicines Authority (APVMA) under a Creative Commons Attribution 3.0 Australia Licence. This report was prepared for the APVMA by the Department of Health and Aging Office of Chemical Safety. In referencing this document the Department of Health and Aging Office of Chemical Safety should be cited as the author and the Australian Pesticides and Veterinary Medicines Authority as the publisher and copyright owner. -
Neuroactive Insecticides: Targets, Selectivity, Resistance, and Secondary Effects
EN58CH06-Casida ARI 5 December 2012 8:11 Neuroactive Insecticides: Targets, Selectivity, Resistance, and Secondary Effects John E. Casida1,∗ and Kathleen A. Durkin2 1Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy, and Management, 2Molecular Graphics and Computational Facility, College of Chemistry, University of California, Berkeley, California 94720; email: [email protected], [email protected] Annu. Rev. Entomol. 2013. 58:99–117 Keywords The Annual Review of Entomology is online at acetylcholinesterase, calcium channels, GABAA receptor, nicotinic ento.annualreviews.org receptor, secondary targets, sodium channel This article’s doi: 10.1146/annurev-ento-120811-153645 Abstract Copyright c 2013 by Annual Reviews. Neuroactive insecticides are the principal means of protecting crops, people, All rights reserved livestock, and pets from pest insect attack and disease transmission. Cur- ∗ Corresponding author rently, the four major nerve targets are acetylcholinesterase for organophos- phates and methylcarbamates, the nicotinic acetylcholine receptor for neonicotinoids, the γ-aminobutyric acid receptor/chloride channel for by Public Health Information Access Project on 04/29/14. For personal use only. Annu. Rev. Entomol. 2013.58:99-117. Downloaded from www.annualreviews.org polychlorocyclohexanes and fiproles, and the voltage-gated sodium channel for pyrethroids and dichlorodiphenyltrichloroethane. Species selectivity and acquired resistance are attributable in part to structural differences in binding subsites, receptor subunit interfaces, or transmembrane regions. Additional targets are sites in the sodium channel (indoxacarb and metaflumizone), the glutamate-gated chloride channel (avermectins), the octopamine receptor (amitraz metabolite), and the calcium-activated calcium channel (diamides). Secondary toxic effects in mammals from off-target serine hydrolase inhibi- tion include organophosphate-induced delayed neuropathy and disruption of the cannabinoid system. -
Appendix H EPA Hazardous Waste Law
Appendix H EPA Hazardous Waste Law This Appendix is intended to give you background information on hazardous waste laws and how they apply to you. For most U.S. Environmental Protection Agency (EPA) requirements that apply to the University, the Safety Department maintains compliance through internal inspections, record keeping and proper disposal. In Wisconsin, the Department of Natural Resources (DNR) has adopted the EPA regulations, consequently EPA and DNR regulations are nearly identical. EPA defines This Appendix only deals with "hazardous waste" as defined by the EPA. hazardous waste as Legally, EPA defines hazardous waste as certain hazardous chemical waste. This hazardous chemical Appendix does not address other types of regulated laboratory wastes, such as waste; radioactive, infectious, biological, radioactive or sharps. Chapter 8 descibes disposal procedures infectious and biohazardous waste for animals. Chapter 9 describes disposal procedures for sharps and other waste that are regulated by can puncture tissue. Chapter 11 discusses Radiation and the Radiation Safety for other agencies. Radiation Workers provides guidelines for the disposal of radioactive waste. Procedures for medical waste are written by the UW Hospital Safety Officer. The Office of Biological Safety can provide guidance for the disposal of infectious and biological waste. EPA regulations focus on industrial waste streams. As a result, many laboratory chemical wastes are not regulated by EPA as hazardous chemical waste. However, many unregulated chemical wastes do merit special handling and disposal If a waste can be procedures. Thus, Chapter 7 and Appendix A of this Guide recommend disposal defined as: procedures for many unregulated wastes as if they were EPA hazardous waste. -
Nerve Agent - Lntellipedia Page 1 Of9 Doc ID : 6637155 (U) Nerve Agent
This document is made available through the declassification efforts and research of John Greenewald, Jr., creator of: The Black Vault The Black Vault is the largest online Freedom of Information Act (FOIA) document clearinghouse in the world. The research efforts here are responsible for the declassification of MILLIONS of pages released by the U.S. Government & Military. Discover the Truth at: http://www.theblackvault.com Nerve Agent - lntellipedia Page 1 of9 Doc ID : 6637155 (U) Nerve Agent UNCLASSIFIED From lntellipedia Nerve Agents (also known as nerve gases, though these chemicals are liquid at room temperature) are a class of phosphorus-containing organic chemicals (organophosphates) that disrupt the mechanism by which nerves transfer messages to organs. The disruption is caused by blocking acetylcholinesterase, an enzyme that normally relaxes the activity of acetylcholine, a neurotransmitter. ...--------- --- -·---- - --- -·-- --- --- Contents • 1 Overview • 2 Biological Effects • 2.1 Mechanism of Action • 2.2 Antidotes • 3 Classes • 3.1 G-Series • 3.2 V-Series • 3.3 Novichok Agents • 3.4 Insecticides • 4 History • 4.1 The Discovery ofNerve Agents • 4.2 The Nazi Mass Production ofTabun • 4.3 Nerve Agents in Nazi Germany • 4.4 The Secret Gets Out • 4.5 Since World War II • 4.6 Ocean Disposal of Chemical Weapons • 5 Popular Culture • 6 References and External Links --------------- ----·-- - Overview As chemical weapons, they are classified as weapons of mass destruction by the United Nations according to UN Resolution 687, and their production and stockpiling was outlawed by the Chemical Weapons Convention of 1993; the Chemical Weapons Convention officially took effect on April 291997. Poisoning by a nerve agent leads to contraction of pupils, profuse salivation, convulsions, involuntary urination and defecation, and eventual death by asphyxiation as control is lost over respiratory muscles. -
Warning: the Following Lecture Contains Graphic Images
What the новичок (Novichok)? Why Chemical Warfare Agents Are More Relevant Than Ever Matt Sztajnkrycer, MD PHD Professor of Emergency Medicine, Mayo Clinic Medical Toxicologist, Minnesota Poison Control System Medical Director, RFD Chemical Assessment Team @NoobieMatt #ITLS2018 Disclosures In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards, the American Nurses Credentialing Center’s Commission (ANCC) and the Commission on Accreditation for Pre-Hospital Continuing Education (CAPCE), states presenters must disclose the existence of significant financial interests in or relationships with manufacturers or commercial products that may have a direct interest in the subject matter of the presentation, and relationships with the commercial supporter of this CME activity. The presenter does not consider that it will influence their presentation. Dr. Sztajnkrycer does not have a significant financial relationship to report. Dr. Sztajnkrycer is on the Editorial Board of International Trauma Life Support. Specific CW Agents Classes of Chemical Agents: The Big 5 The “A” List Pulmonary Agents Phosgene Oxime, Chlorine Vesicants Mustard, Phosgene Blood Agents CN Nerve Agents G, V, Novel, T Incapacitating Agents Thinking Outside the Box - An Abbreviated List Ammonia Fluorine Chlorine Acrylonitrile Hydrogen Sulfide Phosphine Methyl Isocyanate Dibotane Hydrogen Selenide Allyl Alcohol Sulfur Dioxide TDI Acrolein Nitric Acid Arsine Hydrazine Compound 1080/1081 Nitrogen Dioxide Tetramine (TETS) Ethylene Oxide Chlorine Leaks Phosphine Chlorine Common Toxic Industrial Chemical (“TIC”). Why use it in war/terror? Chlorine Density of 3.21 g/L. Heavier than air (1.28 g/L) sinks. Concentrates in low-lying areas. Like basements and underground bunkers. Reacts with water: Hypochlorous acid (HClO) Hydrochloric acid (HCl). -
A Screening Tool for Acetylcholinesterase Inhibitors
RESEARCH ARTICLE Comparative biophysical characterization: A screening tool for acetylcholinesterase inhibitors 1 1 2 1 Devashree N. Patil , Sushama A. Patil , Srinivas SistlaID , Jyoti P. JadhavID * 1 Department of Biotechnology, Shivaji University, Kolhapur, MS, India, 2 Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia, United States * [email protected] a1111111111 a1111111111 a1111111111 a1111111111 Abstract a1111111111 Among neurodegenerative diseases, Alzheimer's disease (AD) is one of the most grievous disease. The oldest cholinergic hypothesis is used to elevate the level of cognitive impairment and acetylcholinesterase (AChE) comprises the major targeted enzyme in AD. Thus, acetylcholinesterase inhibitors (AChEI) constitutes the essential remedy for the treat- OPEN ACCESS ment of AD. The study aims to evaluate the interactions between natural molecules and Citation: Patil DN, Patil SA, Sistla S, Jadhav JP AChE by Surface Plasmon Resonance (SPR). The molecules like alkaloids, polyphenols (2019) Comparative biophysical characterization: A screening tool for acetylcholinesterase inhibitors. and substrates of AChE have been considered for the study with a major emphasis on affin- PLoS ONE 14(5): e0215291. https://doi.org/ ity and kinetics. To better understand the activity of small molecules, the investigation is sup- 10.1371/journal.pone.0215291 ported by both experimental and theoretical approach such as fluorescence, Circular Editor: David A. Lightfoot, College of Agricultural Dichroism (CD) and molecular docking studies. Amongst the screened ones tannic acid Sciences, UNITED STATES showed promising results compared with others. The methodology followed here have Received: September 26, 2018 highlighted many molecules with a higher affinity towards AChE and these findings may Accepted: March 30, 2019 take lead molecules generated in preclinical studies to treat neurodegenerative diseases. -
12.2% 116000 125M Top 1% 154 4200
We are IntechOpen, the world’s leading publisher of Open Access books Built by scientists, for scientists 4,200 116,000 125M Open access books available International authors and editors Downloads Our authors are among the 154 TOP 1% 12.2% Countries delivered to most cited scientists Contributors from top 500 universities Selection of our books indexed in the Book Citation Index in Web of Science™ Core Collection (BKCI) Interested in publishing with us? Contact [email protected] Numbers displayed above are based on latest data collected. For more information visit www.intechopen.com Chapter 14 Evolution and Expectations of Enzymatic Biosensors for Pesticides Rafael Vargas-Bernal, Esmeralda Rodríguez-Miranda and Gabriel Herrera-Pérez Additional information is available at the end of the chapter http://dx.doi.org/10.5772/46227 1. Introduction The successful use of pesticides around the world has been due to their excellent control of pests such as insects, algaes, bacterias, viruses, rodents, or nematodes in agriculture, medicine, household, and industry. Since 9 of the 12 most dangerous and persistent organic pollutants are pesticides, therefore their qualitative and/or quantitative detection continue being one of the most strategic technological areas, given that these can be found in substances in contact with humans and other animals. The effects associated with their consumption and control, are related to human health and environmental toxicity. One of the most important contributions of the environmental chemistry is the control of pesticide residues and metabolites in food, water and soil; where plants, animal and human contacts are possible. Several methods to detect pesticides have been developed, chromatographic methods such as gas chromatography (GC) and high performance liquid chromatography (HPLC), which are coupled with mass spectrometry (MS). -
Acetylcholinesterase — New Roles for Gate a Relatively Long Distance to Reach the Active Site, Ache Is One of the Fastest an Old Actor Enzymes14
PERSPECTIVES be answered regarding AChE catalysis; for OPINION example, the mechanism behind the extremely fast turnover rate of the enzyme. Despite the fact that the substrate has to navi- Acetylcholinesterase — new roles for gate a relatively long distance to reach the active site, AChE is one of the fastest an old actor enzymes14. One theory to explain this phe- nomenon has to do with the unusually strong electric field of AChE. It has been argued that Hermona Soreq and Shlomo Seidman this field assists catalysis by attracting the cationic substrate and expelling the anionic The discovery of the first neurotransmitter — understanding of AChE functions beyond the acetate product15. Site-directed mutagenesis, acetylcholine — was soon followed by the classical view and suggest the molecular basis however, has indicated that reducing the elec- discovery of its hydrolysing enzyme, for its functional heterogeneity. tric field has no effect on catalysis16.However, acetylcholinesterase. The role of the same approach has indicated an effect on acetylcholinesterase in terminating From early to recent discoveries the rate of association of fasciculin, a peptide acetylcholine-mediated neurotransmission The unique biochemical properties and phys- that can inhibit AChE17. made it the focus of intense research for iological significance of AChE make it an much of the past century. But the complexity interesting target for detailed structure–func- of acetylcholinesterase gene regulation and tion analysis. AChE-coding sequences have recent evidence for some of the long- been cloned so far from a range of evolution- a Peripheral Choline binding site suspected ‘non-classical’ actions of this arily diverse vertebrate and invertebrate binding enzyme have more recently driven a species that include insects, nematodes, fish, site profound revolution in acetylcholinesterase reptiles, birds and several mammals, among Active site research. -
Medical Aspects of Chemical Warfare
Medical Diagnostics Chapter 22 MEDICAL DIAGNOSTICS † ‡ § BENEDICT R. CAPACIO, PHD*; J. RICHARD SMITH ; RICHARD K. GORDON, PHD ; JULIAN R. HAIGH, PHD ; JOHN ¥ ¶ R. BARR, PHD ; AND GENNADY E. PLATOFF JR, PHD INTRODUCTION NERVE AGENTS SULFUR MUSTARD LEWISITE CYANIDE PHOSGENE 3-QUINUCLIDINYL BENZILATE SAMPLE CONSIDERATIONS Summary * Chief, Medical Diagnostic and Chemical Branch, Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, 3100 Rickets Point Road, Aberdeen Proving Ground, Maryland 21010-5400 † Chemist, Medical Diagnostic and Chemical Branch, Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, 3100 Rickets Point Road, Aberdeen Proving Ground, Maryland 21010-5400 ‡ Chief, Department of Biochemical Pharmacology, Biochemistry Division, Walter Reed Army Institute of Research, 503 Robert Grant Road, Silver Spring, Maryland 20910-7500 § Research Scientist, Department of Biochemical Pharmacology, Biochemistry Division, Walter Reed Army Institute of Research, 503 Robert Grant Road, Silver Spring, Maryland 20910-7500 ¥ Lead Research Chemist, Centers for Disease Control and Prevention, 4770 Buford Highway, Mailstop F47, Atlanta, Georgia 30341 ¶ Colonel, US Army (Retired); Scientific Advisor, Office of Biodefense Research, National Institute of Allergies and Infectious Disease, National Institutes of Health, 6610 Rockledge Drive, Room 4069, Bethesda, Maryland 20892-6612 691 Medical Aspects of Chemical Warfare INTRODUCTION In the past, issues associated with chemical war- an -
744 Hydrolysis of Chiral Organophosphorus Compounds By
[Frontiers in Bioscience, Landmark, 26, 744-770, Jan 1, 2021] Hydrolysis of chiral organophosphorus compounds by phosphotriesterases and mammalian paraoxonase-1 Antonio Monroy-Noyola1, Damianys Almenares-Lopez2, Eugenio Vilanova Gisbert3 1Laboratorio de Neuroproteccion, Facultad de Farmacia, Universidad Autonoma del Estado de Morelos, Morelos, Mexico, 2Division de Ciencias Basicas e Ingenierias, Universidad Popular de la Chontalpa, H. Cardenas, Tabasco, Mexico, 3Instituto de Bioingenieria, Universidad Miguel Hernandez, Elche, Alicante, Spain TABLE OF CONTENTS 1. Abstract 2. Introduction 2.1. Organophosphorus compounds (OPs) and their toxicity 2.2. Metabolism and treatment of OP intoxication 2.3. Chiral OPs 3. Stereoselective hydrolysis 3.1. Stereoselective hydrolysis determines the toxicity of chiral compounds 3.2. Hydrolysis of nerve agents by PTEs 3.2.1. Hydrolysis of V-type agents 3.3. PON1, a protein restricted in its ability to hydrolyze chiral OPs 3.4. Toxicity and stereoselective hydrolysis of OPs in animal tissues 3.4.1. The calcium-dependent stereoselective activity of OPs associated with PON1 3.4.2. Stereoselective hydrolysis commercial OPs pesticides by alloforms of PON1 Q192R 3.4.3. PON1, an enzyme that stereoselectively hydrolyzes OP nerve agents 3.4.4. PON1 recombinants and stereoselective hydrolysis of OP nerve agents 3.5. The activity of PTEs in birds 4. Conclusions 5. Acknowledgments 6. References 1. ABSTRACT Some organophosphorus compounds interaction of the racemic OPs with these B- (OPs), which are used in the manufacturing of esterases (AChE and NTE) and such interactions insecticides and nerve agents, are racemic mixtures have been studied in vivo, ex vivo and in vitro, using with at least one chiral center with a phosphorus stereoselective hydrolysis by A-esterases or atom.