DOCSLIB.ORG

Cholinesterase Inhibitors: Including Pesticides and Chemical Warfare Nerve Agents

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cholinesterase Inhibitors: Including Pesticides and Chemical Warfare Nerve Agents Agency for Toxic Substances and Disease Registry Case Studies in Environmental Medicine Cholinesterase Inhibitors: Including Pesticides and Chemical Warfare Nerve Agents Course: WB1102 CE Original Date: October 17, 2007 CE Expiration Date: October 17, 2010 Table of Contents Table of Contents..................................................................................................... 1 Table of Figures ....................................................................................................... 2 Table of Figures ....................................................................................................... 2 How to Use This Course ............................................................................................ 5 Learning Objectives.................................................................................................. 6 Initial Check.......................................................................................................... 10 Part 1: Community Preparedness for Mass Casualty Events Involving Cholinesterase Inhibitors.............................................................................................................. 14 Part 2: What are cholinesterase inhibitors? ................................................................ 18 Part 3: What types of pathology do cholinesterase inhibitors cause?.............................. 23 Part 4: The Cholinergic Toxidrome............................................................................ 25 Section 1: What is the Cholinergic Toxidrome?........................................................ 25 Section 2: Nicotinic Acetylcholine Receptors ........................................................... 28 Section 3: Muscarinic Acetylcholine Receptors......................................................... 32 Section 4: Clinical Findings in Cholinesterase Inhibitor Toxicity Are Due to a Mixture of Nicotinic and Muscarinic Effects ............................................................................ 37 Section 5: Signs and Symptoms by Route of Exposure and Chemical Structure of the Involved Cholinesterase Inhibitor (Optional Reading) ............................................... 43 Section 6: Effects on Routine Laboratory Tests........................................................ 46 Section 7: Differential Diagnosis of the Cholinergic Toxidrome................................... 48 Section 8: Signs and Symptoms: Differences in Pediatric Cases................................. 52 Section 9: Importance of the Exposure History ....................................................... 54 Section 10: Laboratory Assessment of the Cholinergic Toxidrome .............................. 58 Red Blood Cell (RBC) and Serum Cholinesterase Levels......................................... 58 Direct Measurement of Cholinesterase Inhibitors and Their Metabolic Byproducts...... 62 Section 11: Management of the Cholinergic Toxidrome ............................................ 64 Management Strategy 1: Prevention of Secondary Exposure ..................................... 65 Management Strategy 2: Supportive Care .............................................................. 69 Management Strategy 3: Medications .................................................................... 70 Medications: Atropine ...................................................................................... 71 Medications: 2-PAM (2-Pyridine Aldoxime Methylchloride) (Pralidoxime) .................. 83 Medications: Diazepam .................................................................................... 95 Antidote Stocking (Optional Reading) ................................................................. 97 Section 12: Public Health and Medico-Legal Issues .................................................102 Part 5: The Intermediate Syndrome.........................................................................104 Part 6: Organophosphate-Induced Delayed Neuropathy (OPIDN) .................................108 Part 7: Organophosphorus Ester-Induced Chronic Neurotoxicity (OPICN) ......................111 Part 8: Other Issues Related to Cholinesterase Inhibitor Exposure................................113 Posttest Instructions..............................................................................................116 References...........................................................................................................129 Answers to Progress Check Questions ......................................................................140 Agency for Toxic Substances and Disease Registry Case Studies in Environmental Medicine Cholinesterase Inhibitors: Including Pesticides & Chemical Warfare Nerve Agents Table of Figures Figure 1. Breakdown of acetylcholine. ....................................................................... 18 Figure 2. Partially electropositive phosphorus is attracted to partially electronegative serine. ........................................................................................................................... 19 Figure 3. Transition state showing which bonds break and which ones form.................... 19 Figure 4. Cholinesterase inhibitor attached to acetylcholinesterase preventing the attachment of acetylcholine..................................................................................... 19 Figure 5. Summary diagram showing where nicotinic and muscarinic receptors are found. Refer back to this when reading the following sections. ............................................... 26 Figure 6. The nicotinic receptor. Figure modified with permission from: Guyton AC, Hall JE: Textbook of Medical Physiology (2006) Elsevier Saunders, Philadelphia. P.87. Used with permission. ........................................................................................................... 29 Figure 7. The muscarinic (G-protein) receptor. Modified with permission from: Guyton AC, Hall JE: Textbook of Medical Physiology (2006) Elsevier Saunders, Philadelphia. p. 561. Used with permission. ............................................................................................ 33 Figure 8. Frequency of Signs and Symptoms in Cholinesterase Inhibitor Toxicity. ............ 40 Figure 9. Pediatric signs and symptoms. Data from: Sofer S, Tal A, Shahak E. Carbamate and organophosphate poisoning in early childhood. Pediatric Emergency Care. 1989; 5:222- 225...................................................................................................................... 52 Figure 10. Military MARK I Kit containing atropine and 2-PAM autoinjectors. Source: U.S. Army Soldier and Biological Chemical Command (SBCCOM). ........................................ 74 Figure 11. X-ray showing autoinjector effectiveness. The rapid absorption of antidote following automatic injection is enhanced by the degree of tissue dispersion achieved by the autoinjector. The X-ray shows autoinjector doses (on left) compared to standard syringe IM doses (on right). The autoinjector medication is obviously more efficiently diffused into surrounding muscle due to the force with which it is expelled from the injector (as seen in inset photo.) Source: U.S. Army, SBCCOM. (Note: the correct way to view an X-ray is as if the patient was facing you. Thus, the patient’s left side is shown on the right.)............... 75 Figure 13. How the positively charged nitrogen in the acetylcholine molecule is attracted to the ionic site on acetylcholinesterase, and hydrolysis is catalyzed at the esteric site to form choline and acetic acid............................................................................................ 84 Figure 14. Partially electropositive phosphorus is attracted to partially electronegative serine................................................................................................................... 85 Figure 15. Transition state showing which bonds break and which ones form. ................. 85 Figure 16. Cholinesterase inhibitor attached to acetylcholinesterase preventing the attachment of acetylcholine..................................................................................... 85 Figure 17. Cholinesterase is blocked, but it can: ......................................................... 86 Figure 18. The “aged” bond ..................................................................................... 86 Figure 19. How 2-PAM works. .................................................................................. 87 Figure 20. Partially electropositive nitrogen on 2-PAM is attracted to electronegative anionic site on cholinesterase. ............................................................................................ 87 Figure 21. Regenerated cholinesterase. ..................................................................... 87 Page 2 of 153 Agency for Toxic Substances and Disease Registry Case Studies in Environmental Medicine Cholinesterase Inhibitors: Including Pesticides & Chemical Warfare Nerve Agents Key Concepts • Cholinesterase inhibitors are a class of compounds that includes chemical warfare nerve agents and certain insecticides. • Fatalities occur mainly due to effects on respiration due depression of respiratory drive, paralysis of muscles of respiration, bronchoconstriction, and airway obstruction from profuse respiratory tract secretions. • Treatment includes the use of atropine, 2-PAM, diazepam, and aggressive supportive care. About This and This educational case
Load more

Recommended publications
  • Severe Organophosphate Poisoning with Delayed Cholinergic Crisis, Intermediate Syndrome and Organophosphate Induced Delayed Polyneuropathy on Succession
    Organophosphate Poisoning… Aklilu A 203 CASE REPORT SEVERE ORGANOPHOSPHATE POISONING WITH DELAYED CHOLINERGIC CRISIS, INTERMEDIATE SYNDROME AND ORGANOPHOSPHATE INDUCED DELAYED POLYNEUROPATHY ON SUCCESSION Aklilu Azazh ABSTRACT Organophosphate compounds are the organic derivatives of Phosphorous containing acids and their effect on neuromuscular junction and Autonomic Synapses is clinically important. After exposure these agents cause acute and sub acute manifestations depending on the type and severity of the agents like Acute Cholinergic Manifestations, Intermediate Syndrome with Nicotinic features and Delayed Central Nervous System Complications. The patient reported here had severe Organophosphate Poisoning with various rare complications on a succession. This is the first report of Organophosphates Poisoning complicated by Intermediate Syndrome and Organophosphate Induced Delayed Polyneuropathy in Ethiopia and it is reported to increase awareness of health care workers on these rare complications of a common problem. INTRODUCTION phosphorylated by the Phosphate end of Organophosphates; then the net result is Organophosphate compounds are the organic accumulation of excessive Acetyl Chlorine with derivatives of Phosphorous containing acids and resultant effect on Muscarinic, Nicotinic and their effect on Neuromuscular Junction and central nervous system (Figure 2). Autonomic synapses is clinically important. In the Neuromuscular Junction Acetylcholine is released Following classical OP poisoning, three well when a nerve impulse reaches
    [Show full text]
  • 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.
    [Show full text]
  • Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Frontiers - Publisher Connector REVIEW published: 18 January 2017 doi: 10.3389/fnins.2016.00590 Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds Jaymie R. Voorhees 1, 2*, Diane S. Rohlman 2, 3, Pamela J. Lein 4 and Andrew A. Pieper 1, 2, 5, 6, 7, 8, 9* 1 Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA, 2 Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of Medicine, Iowa City, IA, USA, 3 Department of Occupational and Environmental Health, University of Iowa College of Public Health, Iowa City, IA, USA, 4 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA, 5 Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA, 6 Department of Free Radical and Radiation Biology Program, University of Iowa Carver College of Medicine, Iowa City, IA, USA, 7 Department of Radiation Oncology Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA, 8 Department of Veteran Affairs, University of Iowa Carver College of Medicine, Iowa City, IA, USA, 9 Weill Cornell Autism Research Program, Weill Cornell Medical College, New York, NY, USA Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high Edited by: OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests Stefano L.
    [Show full text]
  • Neurology of Acute Organophosphate Poisoning
    Indian Perspective Neurology of acute organophosphate poisoning Gagandeep Singh, Dheeraj Khurana1 Departments of Neurology, Dayanand Medical College, Ludhiana, and 1Postgraduate Institute of Medical Education and Research, Chandigarh, India Abstract Acute organophosphate (OP) poisoning is one of the most common poisonings in emergency medicine and toxicological practice in some of the less-developed nations in South Asia. Traditionally, OP poisoning comes under the domain of emergency physicians, internists, intensivists, and toxicologists. However, some of the complications following OP poisoning are neurological and involve neurologists. The pathophysiological basis for the clinical manifestations of OP poisoning is inactivation of the enzyme, acetylcholinesterase at the peripheral nicotinic and muscarinic and central nervous system (CNS) nerve terminals and junctions. Nicotinic manifestations occur in severe cases and late in the course; these comprise of fasciculations and neuromuscular paralysis. There is a good correlation between the electrophysiological abnormalities and the severity of the clinical manifestations. Neurophysiological abnormalities characteristic of nicotinic junctions (mainly neuromuscular junction) dysfunction include: (1) single, supramaximal electrical-stimulus-induced repetitive response/s, (2) decrement–increment response to high frequency (30 Hz) repetitive nerve stimulation (RNS), and (3) decremental response to high frequency (30 Hz) RNS. Atropine ameliorates muscarinic manifestations. Therapeutic Address for correspondence: Dr. Gagandeep Singh, agents that can ameliorate nicotinic manifestations, mainly neuromuscular, are oximes. Department of Neurology, However, the evidence for this effect is inconclusive. This may be due to the fact that Dayanand Medical College, there are several factors that determine the therapeutic effect of oximes. These factors Ludhiana - 141 001, include: The OP compound responsible for poisoning, duration of poisoning, severity of Punjab, India.
    [Show full text]
  • The Role of Serotonin in Memory: Interactions with Neurotransmitters and Downstream Signaling
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Bushehr University of Medical Sciences Repository Exp Brain Res (2014) 232:723–738 DOI 10.1007/s00221-013-3818-4 REVIEW The role of serotonin in memory: interactions with neurotransmitters and downstream signaling Mohammad Seyedabadi · Gohar Fakhfouri · Vahid Ramezani · Shahram Ejtemaei Mehr · Reza Rahimian Received: 28 April 2013 / Accepted: 20 December 2013 / Published online: 16 January 2014 © Springer-Verlag Berlin Heidelberg 2014 Abstract Serotonin, or 5-hydroxytryptamine (5-HT), is there has been an alteration in the density of serotonergic found to be involved in many physiological or pathophysi- receptors in aging and Alzheimer’s disease, and serotonin ological processes including cognitive function. Seven dis- modulators are found to alter the process of amyloidogen- tinct receptors (5-HT1–7), each with several subpopulations, esis and exert cognitive-enhancing properties. Here, we dis- have been identified for serotonin, which are different in cuss the serotonin-induced modulation of various systems terms of localization and downstream signaling. Because involved in mnesic function including cholinergic, dopa- of the development of selective agonists and antagonists minergic, GABAergic, glutamatergic transmissions as well for these receptors as well as transgenic animal models as amyloidogenesis and intracellular pathways. of cognitive disorders, our understanding of the role of serotonergic transmission in learning and memory has Keywords Serotonin · Memory · Signaling pathways improved in recent years. A large body of evidence indi- cates the interplay between serotonergic transmission and Abbreviations other neurotransmitters including acetylcholine, dopamine, 2PSDT Two-platform spatial discrimination task γ-aminobutyric acid (GABA) and glutamate, in the neu- 3xTg-AD Triple-transgenic mouse model of Alzheimer’s robiological control of learning and memory.
    [Show full text]
  • 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.
    [Show full text]
  • Malathion Human Health and Ecological Risk Assessment Final Report
    SERA TR-052-02-02c Malathion Human Health and Ecological Risk Assessment Final Report Submitted to: Paul Mistretta, COR USDA/Forest Service, Southern Region 1720 Peachtree RD, NW Atlanta, Georgia 30309 USDA Forest Service Contract: AG-3187-C-06-0010 USDA Forest Order Number: AG-43ZP-D-06-0012 SERA Internal Task No. 52-02 Submitted by: Patrick R. Durkin Syracuse Environmental Research Associates, Inc. 5100 Highbridge St., 42C Fayetteville, New York 13066-0950 Fax: (315) 637-0445 E-Mail: [email protected] Home Page: www.sera-inc.com May 12, 2008 Table of Contents Table of Contents............................................................................................................................ ii List of Figures................................................................................................................................. v List of Tables ................................................................................................................................. vi List of Appendices ......................................................................................................................... vi List of Attachments........................................................................................................................ vi ACRONYMS, ABBREVIATIONS, AND SYMBOLS ............................................................... vii COMMON UNIT CONVERSIONS AND ABBREVIATIONS.................................................... x CONVERSION OF SCIENTIFIC NOTATION ..........................................................................
    [Show full text]
  • Beyond the Cholinergic Crisis Galle Medical Association Oration 2015
    Reviews Beyond the cholinergic crisis Galle Medical Association Oration 2015 Jayasinghe S S Department of Pharmacology, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka. South Asian Clinical Toxicology Research Collaboration, Department of Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka. Correspondence: Dr. Sudheera S Jayasinghe e-mail: [email protected] ABSTRACT Introduction: Organophosphates (OP) are the most frequently involved pesticides in acute poisoning. In Sri Lanka it has been ranked as the sixth or seventh leading cause of hospital deaths for many years. Neurotoxic effects of acute OP have been hitherto under-explored. The aims of the studies were to assess the effects of acute OP poisoning on somatic, autonomic nerves, neuro- muscular junction (NMJ), brain stem and cognitive function. Methods: Patients following self-ingestion of OP were recruited to cohort studies to evaluated the function of somatic, autonomic nerves, NMJ, brain stem and cognition. Motor and sensory nerve function was tested with nerve conduction studies. Cardiovascular reflexes based autonomic function tests and sympathetic skin response (SSR) was used to evaluate autonomic function. NMJ function was assessed with slow repetitive supramaximal stimulation of the median nerve of the dominant upper limb. Brain stem function and cognitive function were assessed with Brain Stem Evoked Response Audiometry (BERA) and Mini Mental State Examination (MMSE) respectively. The data of the patients were compared with age, gender and occupation matched controls. Results: There were 60-70 patients and equal number of controls in each study. Motor nerve conduction velocity, amplitude and area of compound muscle action potential on distal stimulation, sensory nerve conduction velocity and F-wave occurrence were significantly reduced.
    [Show full text]
  • Failed Reversal of Neuromuscular Blockade Despite Sugammadex: a Case of Undiagnosed Pseudocholinesterase Deficiency
    CASE REPORT Failed reversal of neuromuscular blockade despite sugammadex: A case of undiagnosed pseudocholinesterase deficiency Gozde Inan, MD*, Elif Yayla, MD** and Berrin Gunaydin, MD*** *Consultant; **Resident; ***Professor Department of Anesthesiology and Reanimation, Gazi University, School of Medicine, Besevler, Ankara (Turkey) Correspondence: Gozde Inan, MD, Gazi University School of Medicine, Department of Anaesthesiology and Reanimation, Besevler, Ankara (Turkey); Tel: +90 312 202 4166; Fax: +90 312 202 4166; E-mail address: [email protected] ABSTRACT The management of an undetected pseudocholinesterase deficiency in a parturient who underwent urgent cesarean section has been presented. After rapid sequence induction with succinylcholine, rocuronium was used for maintenance of neuromuscular block. At the end of the operation neostigmine was given to antagonize the residual block. Upon persistent prolonged neuromuscular blockade sugammadex was administered. Probable reasons, drug interactions, the importance of suspecting pseudocholinesterase deficiency and the need of neuromuscular monitoring have been argued in this case report. Key words: Pseudocholinesterase deficiency; Cesarean section; Sugammadex Citation: Inan G, Yayla E, Gunaydin B. Failed reversal of neuromuscular blockade despite sugammadex: A case of undiagnosed pseudocholinesterase deficiency. Anaesth Pain & Intensive Care 2015;19(2):184- 186 INTRODUCTION induction of neuromuscular block was provided by succinylcholine and maintained with rocuronium, Prolonged neuromuscular blockade is a common neostigmine and sugammadex were administered complication that every anesthesiologist has to antagonize the blockade. We aimed to discuss the experienced sometime in his clinical practice. management of prolonged neuromuscular block Pseudocholinesterase (PChE) deficiency should probably due to an undetected PChE deficiency in be suspected in case of prolonged neuromuscular a parturient who underwent emergency cesarean blockade.1 PChE is an enzyme synthesized in the liver, section (C/S).
    [Show full text]
  • Cholinesterase Activity As Biomarker of Neurotoxicity: Utility in The
    Revista da Gestão Costeira Integrada 13(4):525-537 (2013) Journal of Integrated Coastal Zone Management 13(4):525-537 (2013) http://www.aprh.pt/rgci/pdf/rgci-430_Jebali.pdf | DOI:10.5894/rgci430 Cholinesterase activity as biomarker of neurotoxicity: utility in the assessment of aquatic environment contamination * Actividade da colinesterase como biomarcador de neurotoxicidade: avaliação da contaminação em ambientes aquáticos ** Jamel Jebali @, 1, Sana Ben Khedher 1, Marwa Sabbagh 1, Naouel Kamel 1, Mohamed Banni 1, Hamadi Boussetta 1 ABSTRACT Cholinesterase can take place in aquatic organisms under a series of environmental adverse conditions. The study of cholinesterases in these organisms can give important information about their physiological status and about environmental health. However, it is very important to know how the environmental factors such as fluctuation of physicochemical parameters associated to the presence of pollutants might affect these cholinesterase activities. We studied the response of cholinesterase activity in the caged cockleCerastoderma glaucum. In addition, we evaluated the potential uses of cholinesterase activity in the common sole, which inhabit the Tunisian coast, subjected to different stress conditions, such as the exposure to different contaminants. This review summarizes the data obtained in some studies carried out in organisms from the Tunisian aquatic environment. Keywords: Cholinesterases, Environmental stress, Biomonitoring, Aquatic Environments. RESUMO A colinesterase está presente nos organismos aquáticos em condições de stress ambiental. O estudo da colinesterase fornece informações acerca da condição fisiológica e saúde ambiental. Contudo é importante averiguar de que modo os factores ambientais, tais como a flutuação dos parâmetros físico-químicos, associados à presença de poluentes afectam a actividade das colinesterases.
    [Show full text]
  • Probabilistic Assessment of the Cumulative Acute Exposure to Organophosphorus and Carbamate Insecticides in the Brazilian Diet E.D
    Toxicology 222 (2006) 132–142 Probabilistic assessment of the cumulative acute exposure to organophosphorus and carbamate insecticides in the Brazilian diet E.D. Caldas a,∗, P.E. Boon b, J. Tressou c a Department of Pharmaceutical Sciences, College of Health Sciences, University of Bras´ılia, 70919-970 Bras´ılia, DF, Brazil b RIKILT, Institute of Food Safety, Wageningen University and Research Centre, 6708 PD Wageningen, The Netherlands c INRA, Unit´eM´et@risk, Methodologies d’analyse de risque alimentaire INA-PG, 75231 Paris, France Received 10 October 2005; received in revised form 1 February 2006; accepted 13 February 2006 Available online 6 March 2006 Abstract In the present study, the cumulative exposure of 25 acetylcholinesterase (AChE) inhibiting pesticides through the consumption of nine fruits and vegetables by the Brazilian population was assessed. Food consumption data were obtained from a household budget survey conducted in all Brazilian states from July 2002 to June 2003. Residue data from 4001 samples were obtained from the Brazilian national monitoring program on pesticide residues. Relative potency factors (RPF) were calculated with methamidophos or acephate as index compounds (IC), using BMD10 or NOAEL for AChE inhibition, mostly in rat brain, obtained from national and international pesticide evaluations. Monocrotophos and triazophos, in addition to aldicarb, had the highest calculated RPF in any scenario. The exposure to AChE inhibiting pesticides for the general population at P99.9, represented 33.6% of the ARfD as methamidophos and 70.2% ARfD as acephate. The exposure calculated as acephate could exceed the ARfD at the upper bound of the 95% confidence interval for this percentile.
    [Show full text]
  • Neuronal Nicotinic Receptors
    NEURONAL NICOTINIC RECEPTORS Dr Christopher G V Sharples and preparations lend themselves to physiological and pharmacological investigations, and there followed a Professor Susan Wonnacott period of intense study of the properties of nAChR- mediating transmission at these sites. nAChRs at the Department of Biology and Biochemistry, muscle endplate and in sympathetic ganglia could be University of Bath, Bath BA2 7AY, UK distinguished by their respective preferences for C10 and C6 polymethylene bistrimethylammonium Susan Wonnacott is Professor of compounds, notably decamethonium and Neuroscience and Christopher Sharples is a hexamethonium,5 providing the first hint of diversity post-doctoral research officer within the among nAChRs. Department of Biology and Biochemistry at Biochemical approaches to elucidate the structure the University of Bath. Their research and function of the nAChR protein in the 1970’s were focuses on understanding the molecular and facilitated by the abundance of nicotinic synapses cellular events underlying the effects of akin to the muscle endplate, in electric organs of the acute and chronic nicotinic receptor electric ray,Torpedo , and eel, Electrophorus . High stimulation. This is with the goal of affinity snakea -toxins, principallyaa -bungarotoxin ( - Bgt), enabled the nAChR protein to be purified, and elucidating the structure, function and subsequently resolved into 4 different subunits regulation of neuronal nicotinic receptors. designateda ,bg , and d .6 An additional subunit, e , was subsequently identified in adult muscle. In the early 1980’s, these subunits were cloned and sequenced, The nicotinic acetylcholine receptor (nAChR) arguably and the era of the molecular analysis of the nAChR has the longest history of experimental study of any commenced.
    [Show full text]