DOCSLIB.ORG

Applications of Computational Chemistry Towards Combatting Challenges in Chemical Warfare and Renewable Energy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Applications of Computational Chemistry Towards Combatting Challenges in Chemical Warfare and Renewable Energy Applications of Computational Chemistry towards Combatting Challenges in Chemical Warfare and Renewable Energy DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Ryan J. Yoder Graduate Program in Chemistry The Ohio State University 2013 Dissertation Committee: Professor Christopher M. Hadad, Advisor Professor Jonathan R. Parquette Professor James P. Stambuli Copyright by Ryan J. Yoder 2013 Abstract Across the globe, chemists are constantly seeking to provide answers to the challenges threatening our society. Both long-term obstacles and short-term hazards are being confronted with the commitment of time, money, and intellectual acumen. The challenges faced in this thesis span both the imminent threat of the deployment of chemical warfare agents, and the long-term challenge of renewable energy. One strategy towards combatting the toxic effects of these chemical warfare agents will focus on reversing the result of exposure to organophosphorus (OP) compounds. The other strategy will examine the use of synthetic molecular baskets as a macromolecule designed to entrap OP compounds before victims can feel their adverse effects. Also in this thesis, our contribution towards the pursuit of sources for renewable energy, namely the synthesis of important small molecules from chemical feedstocks, will be presented. OP compounds are a grave threat to military and civilian populations, especially in the context of increasing acts of terror around the globe. These nerve agents are toxic due to their inhibition of the acetylcholinesterase (AChE) active site. Although some methods of enzyme recovery are known to exist, they succumb to the need to be presented to affected victims in an extremely short amount of time. Currently, there are no known therapeutics to recover aged AChE, a permanently dead form of the enzyme upon prolonged inhibition as a result of OP binding to the enzyme. Part of this thesis will ii present efforts towards the development of a small molecule therapeutic designed as an alkylating agent to reverse the aging process and ultimately recover the active enzyme. Our efforts have focused on the synthesis of a library of quinone methide precursors (QMPs) that have been shown to alkylate a model phosphonate, making them promising candidates for further study with the native enzyme. An alternate strategy to the reversal of the inhibition of the enzyme by OP compounds would be to sequester the nerve agent before it binds with AChE. In collaboration with the Badjic research group at The Ohio State University, molecular baskets have been synthesized to accomplish this goal. A rigorous computational protocol was established to examine the conformational flexibility of the molecular baskets, and further modeling studies were performed to determine the recognition of various OP compounds by molecular baskets. An imidazole-capped basket, mimicking a decarboxylated histidine residue, has been shown to bind the small OP compound, dimethoxy methylphosphonate (DMMP). Finally, this thesis will present efforts in collaboration with the Stambuli research group at The Ohio State University towards the development of a metal catalyst to transform a saturated fatty acid into an unsaturated fatty acid. This novel chemistry would allow access to value-added chemicals as identified by the Department of Energy. Our molecular modeling studies provided important insight to experimental results. These insights included the inability to dehydrogenate a pendant fatty acid and reasoning for the selective dehydrogenation of an acyl phosphine ligand. iii Acknowledgments The work presented in this thesis could not be possible without the contributions of several important people towards my growth as an educator, scientist, and person. First, I must thank my advisor, Dr. Christopher Hadad, for your valuable mentorship and support over the past five years. Your continuing guidance was instrumental in helping me to realize my scientific, academic, and personal goals, and I hope our relationship will only grow in future years. I would also like to thank collaborators at The Ohio State University who played pivotal roles in my maturation as a research scientist, namely Dr. James Stambuli and Dr. Jovica Badjic. To my fellow members of the Hadad Research Group, thank you for your unconditional assistance in allowing me to become a successful researcher. Each of you, whether past or present, remains a part of creating the unique atmosphere that allows our group to function so well. Special thanks go to Dr. Jeremy Beck, Dr. Shubham Vyas, Dr. Daniel Turner, and Dr. Hashem Taha for your patience and mentorship as you passed on the wealth of knowledge you possess. Thank you also to Jason Brown for your friendship and collaboration within the Hadad Group on our nerve agent work. I would also like to thank all of the experimental researchers who assisted in advancing this work through their collaborative efforts. iv Specifically, I would like to thank Katelyn Cody, an undergraduate researcher in Dr. Christopher Callam’s research group at The Ohio State University who I have taken an active role in mentoring the past year. Thank you for your tireless efforts towards completing and presenting our research to many different audiences. Hopefully, I have been a positive influence in your development towards reaching your personal and professional goals. I am thankful to the funding agencies that made this research possible. These agencies include the Defense Threat Reduction Agency (DTRA) and the Ohio Supercomputer Center (OSC). As much as I’ve grown as a scientist during my graduate career, I feel I’ve matured just as much as a teacher. Through the generosity and guidance of several influential mentors, I’ve been able to realize my true calling in life as an educator. Certainly, I must thank Dr. Hadad for allowing me to pursue several opportunities to teach while completing my graduate research. Also, I have to thank Dr. Christopher Callam and Dr. Noel Paul for their mentorship while serving as their Teaching Assistant at The Ohio State University. Although both of you have your own unique style and personality, you each taught me invaluable lessons in and out of the classroom. I hold the utmost respect for both of you and look forward to our friendship continuing for years to come. Thanks also to those at Capital University and Ohio Wesleyan University for allowing me the opportunity to be an adjunct instructor during my graduate career. Thank you especially to my undergraduate advisor, Dr. Katie Hervert, for your continued friendship and support in nurturing my chosen career path. v Finally, thank you to my friends and family for your unconditional love and support over the last five years. To my wife and best friend Stefanie, thank you for helping me through every step of this experience. I know we have had significant challenges to overcome in the last five years, but through our growing love and faith, we have reached a new stage in our life’s journey together. You have undoubtedly been the best thing that has ever happened to me and I promise to continue my career knowing it is in loving devotion to you and our family. Although you may never read or understand the contents of this dissertation, it would not have been possible without the love and support from you, Boo, and Beaker. To my mother and father, thank you for your unending love and support in cultivating my potential to allow me to reach this point in my life. Hopefully I have made you proud by following in your footsteps with a career in academia. Every day of my life I have sought to live by the principles and values you have taught me. I will continue to do so to the best of my abilities as I begin my career and family. Surely, I would not be where I am today without the sacrifices you have made. And lastly, thank you to my twin brother Matt. I would be nowhere without your love, support, and companionship for the last twenty-seven years. My sincere hope is that our relationship will continue to stay strong as we both encounter the exciting changes and challenges ahead in each of our lives, wherever that may lead us. Onward and upward. vi Vita 2004 ............................................................... Urbana High School 2008 ............................................................... B.A. Chemistry, Ohio Wesleyan University 2008 to present ............................................. Graduate Research Associate, Department of Chemistry, The Ohio State University Publications 1) Whittemore, S. M.; Yoder, R. J.; Stambuli, J. P. “Site-Selective Alkyl Dehydrogenation of a Coordinated Acylphosphine Ligand” Organometallics, 2012, 31 (17), 6124. 2) Hermann, K.; Sardini, S.; Ruan, Y.; Yoder, R. J.; Chakraborty, M.; Vyas, S.; Hadad, C. M.; Badjic, J. D. “Method for the Preparation of Derivatives of Heptiptycene: Toward Dual–Cavity Baskets” J. Org. Chem. 2013, 78 (7), 2984. 3) Ruan, Y.; Taha, H. A.; Yoder, R. J.; Maslak, V.; Hadad, C. M.; Badjic, J. D. “The Prospect of Selective Recognition of Nerve Agents with Modular Basket-like Hosts. A Structure–Activity Study of the Entrapment of a Series of Organophosphonates in Aqueous Media” J. Phys. Chem. B. 2013, 117 (11), 3240. vii Fields of Study Major Field: Chemistry viii Table of Contents Abstract ............................................................................................................................... ii Acknowledgments
Load more

Recommended publications
  • Organic & Biomolecular Chemistry
    Organic & Biomolecular Chemistry Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/obc Page 1 of 7 Organic & Biomolecular Chemistry Journal Name RSCPublishing ARTICLE Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) Cite this: DOI: 10.1039/x0xx00000x with a unique probe based on a boron dipyrromethene (BODIPY) dye Manuscript Received 00th January 2012, Accepted 00th January 2012 Andrea Barba-Bon,a,b Ana M. Costero,a,b* Salvador Gil,a,b Ramón Martínez- a,c,d a,c,d DOI: 10.1039/x0xx00000x Máñez, * and Félix Sancenón www.rsc.org/ A novel colorimetric probe (P4) for the selective differential detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) was prepared.
    [Show full text]
  • Environmental Assessment Proposed Changes to the Sanitary Biosolids Land Application Program on the Oak Ridge Reservation, Oak Ridge, Tennessee
    DOE/EA-1779 Environmental Assessment Proposed Changes to the Sanitary Biosolids Land Application Program on the Oak Ridge Reservation, Oak Ridge, Tennessee June 2011 U.S. Department of Energy Oak Ridge Office This page intentionally left blank. DOE/EA-1779 Environmental Assessment Proposed Changes to the Sanitary Biosolids Land Application Program on the Oak Ridge Reservation, Oak Ridge, Tennessee Date Issued—June 2011 Bechtel Jacobs Company, LLC and CDM Federal Services Inc. contributed to the preparation of this document and may not be considered for review of the document U.S. Department of Energy Office of Environmental Management This page intentionally left blank. CONTENTS FIGURES...................................................................................................................................................... v TABLES ....................................................................................................................................................... v ACRONYMS..............................................................................................................................................vii EXECUTIVE SUMMARY ......................................................................................................................... ix 1. INTRODUCTION.................................................................................................................................. 1 1.1 PURPOSE AND NEED FOR AGENCY ACTION.....................................................................
    [Show full text]
  • Universidade Federal Do Espírito Santo Centro De Ciências Da Saúde
    UNIVERSIDADE FEDERAL DO ESPÍRITO SANTO CENTRO DE CIÊNCIAS DA SAÚDE PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS FARMACÊUTICAS IGOR SIMÕES ASSUNÇÃO FELIPPE Avaliação in vitro e in vivo dos efeitos da intoxicação aguda com o inseticida organofosforado, clorpirifós, e da eficácia do tratamento farmacológico empregado na intoxicação sobre a modulação cardiorrespiratória tônica e reflexa. VITÓRIA 2017 IGOR SIMÕES ASSUNÇÃO FELIPPE Avaliação in vitro e in vivo dos efeitos da intoxicação aguda com o inseticida organofosforado, clorpirifós, e da eficácia do tratamento farmacológico empregado na intoxicação sobre a modulação cardiorrespiratória tônica e reflexa Dissertação apresentada ao Programa de Pós- Graduação em Ciências Farmacêuticas da Universidade Federal do Espírito Santo como requisito para obtenção do título de mestre em ciências farmacêuticas. Orientadora: Profa. Dra. Karla Nívea Sampaio. Co-Orientadora: Profa. Dra. Vanessa Beijamini Harres VITÓRIA 2017 Dados Internacionais de Catalogação-na-publicação (CIP) (Biblioteca Setorial do Centro de Ciências da Saúde da Universidade Federal do Espírito Santo, ES, Brasil) Felippe, Igor Simões Assunção, 1990 - F315a Avaliação in vitro e in vivo dos efeitos da intoxicação aguda com o inseticida organofosforado, clorpirifós, e da eficácia do tratamento farmacológico empregado na intoxicação sobre a modulação cardiorrespiratória tônica e reflexa / Igor Simões Assunção Felippe – 2017. 158 f. : il. Orientador: Karla Nívea Sampaio. Coorientador: Vanessa Beijamini Harres. Dissertação (Mestrado em Ciências
    [Show full text]
  • Differentiating Nerve Agent Poisoning from Opioid Poisoning – Clinical Signs, Detection and Diagnostics
    SANITÄTSDIENST DIFFERENTIATING NERVE AGENT POISONING FROM OPIOID POISONING – CLINICAL SIGNS, DETECTION AND DIAGNOSTICS PD Dr. Timo Wille LtCol (MC) German Armed Forces Bundeswehr Institute of Pharmacology and Toxicology Disclosures Presenter’s has no relevant financial or non-financial interests to disclose. Disclosure will be made when a product is discussed for an unapproved use. This continuing education activity is managed and accredited by AffinityCE in collaboration with AMSUS. AffinityCE and AMSUS staff as well as Planners and Reviewers, have no relevant financial or non-financial interests to disclose. Commercial Support was not received for this activity Objectives • List clinical signs of nerve agent and opioid poisoning • Know that highly potent opioids might be misused as chemical weapon • Know on-site devices for diagnosis of opioid and nerve agent poisoning NERVE AGENTS – RELEVANCE Tabun (GA) Sarin (GB) Soman (GD) Cyclosarin (GF) Salisbury / Amesbury 2018: one death, min. four injured Kuala Lumpur 2017: one death Syria 2013-2017: thousands dead and injured Halabja 1988: 5.000 deaths, 10.000 injured VX Novichok? 5 S a n i t ä t s d i e n s MECHANt ISM OF NERVE AGENT POISONING – INHIBITION OF ACETYLCHOLINESTERASE Physiology: Pathophysiology: Acetylcholinesterase (AChE) cleaves Binding of OP to AChE, renders the enzyme inactive acetylcholine in acetate and choline and ACh overflow at muscarinic and nicotinic synapses terminates its action as a neurotransmitter muscarinic nicotinic cns diarrhea muscle fasciculations seizures
    [Show full text]
  • Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial
    cells Review Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial Diego Caicedo 1,* , Pablo Devesa 2, Clara V. Alvarez 3 and Jesús Devesa 4,* 1 Department of Angiology and Vascular Surgery, Complejo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain 2 Research and Development, The Medical Center Foltra, 15886 Teo, Spain; [email protected] 3 . Neoplasia and Endocrine Differentiation Research Group. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela, 15782. Santiago de Compostela, Spain; [email protected] 4 Scientific Direction, The Medical Center Foltra, 15886 Teo, Spain * Correspondence: [email protected] (D.C.); [email protected] (J.D.); Tel.: +34-981-800-000 (D.C.); +34-981-802-928 (J.D.) Received: 29 November 2019; Accepted: 25 March 2020; Published: 27 March 2020 Abstract: Despite the important role that the growth hormone (GH)/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium is considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effects, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy is described. All the elements that trigger the local and systemic production of GH/IGF-I, as well as their possible roles both in physiological and pathological conditions are analyzed.
    [Show full text]
  • Central Intelligence Agency (CIA) Document: the Biological and Chemical Warfare Threat, January 1997
    Description of document: Central Intelligence Agency (CIA) document: The Biological and Chemical Warfare Threat, January 1997 Requested date: 01-July-2015 Released date: 02-December-2015 Posted date: 04-January-2016 Source of document: Freedom of Information Act Request Information and Privacy Coordinator Central Intelligence Agency Washington, D.C. 20505 Fax: 703-613-3007 Filing a FOIA Records Request Online The governmentattic.org web site (“the site”) is noncommercial and free to the public. The site and materials made available on the site, such as this file, are for reference only. The governmentattic.org web site and its principals have made every effort to make this information as complete and as accurate as possible, however, there may be mistakes and omissions, both typographical and in content. The governmentattic.org web site and its principals shall have neither liability nor responsibility to any person or entity with respect to any loss or damage caused, or alleged to have been caused, directly or indirectly, by the information provided on the governmentattic.org web site or in this file. The public records published on the site were obtained from government agencies using proper legal channels. Each document is identified as to the source. Any concerns about the contents of the site should be directed to the agency originating the document in question. GovernmentAttic.org is not responsible for the contents of documents published on the website. Central Intelligence Agency Washington,• D.C. 20505 2 December 2015 Reference: F-2015-02095 This is a final response to your 1July2015 Freedom of Information Act (FOIA) request for "a copy of the following six CIA documents: 1.
    [Show full text]
  • Universidade Federal De Santa Catarina Centro De Ciências
    Universidade Federal de Santa Catarina Centro de Ciências Físicas e Matemáticas Departamento de Química Curso de Pós-Graduação em Química ÁCIDO POLI(ACRÍLICO) FUNCIONALIZADO COMO NANOREATOR NA DEGRADAÇÃO DE ÉSTERES Doutorando: Luciano Albino Giusti Orientador: Prof. Faruk J. Nome Aguilera Coorientadora: Prof.ª Haidi D. Fiedler Nome Florianópolis, março de 2014. UNIVERSIDADE FEDERAL DE SANTA CATARINA PROGRAMA DE PÓS-GRADUAÇÃO EM QUÍMICA Luciano Albino Giusti ÁCIDO POLI(ACRÍLICO) FUNCIONALIZADO COMO NANOREATOR NA DEGRADAÇÃO DE ÉSTERES Tese submetida ao Programa de Pós-Graduação em Química da Universidade Federal de Santa Catarina para a obtenção do grau de Doutor em Química. Orientado: Prof. Faruk J. Nome Aguilera Coorientadora: Prof.ª Haidi D. Fiedler Nome Florianópolis 2014 Catalogação na fonte pela Biblioteca Universitária da Universidade Federal de Santa Catarina Luciano Albino Giusti ÁCIDO POLI(ACRÍLICO) FUNCIONALIZADO COMO NANOREATOR NA DEGRADAÇÃO DE ÉSTERES Esta tese foi julgada adequada para obtenção do Título de “Doutorado em Química” e aprovada em sua forma final pelo Programa de Pós- Graduação em Química da Universidade Federal de Santa Catarina. Florianópolis, 21 de março de 2014. _________________________ Prof. Hugo Alejandro Gallardo Olmedo, Dr. Coordenador do programa Banca Examinadora: ___________________________ ___________________________ Prof. Faruk José Nome Aguilera, Prof.ª Haidi D. Fiedler Nome, Dr. Orientador UFSC Dra. Coorientadora UFSC ___________________________ ___________________________ Prof.ª Elisane Longhinotti, Dra. Prof.ª Elisa Souza Orth, Dra. Relatora UFC UFPR ___________________________ ___________________________ Prof.ª Vera Lúcia Azzolin Prof. Gustavo Amadeu Micke, Dr. Frescura Bascuñan, Dra. UFSC UFSC ___________________________ Prof. Antonio Luiz Braga, Dr. UFSC Aos meus pais, à minha noiva e a Deus. AGRADECIMENTOS Agradeço a minha noiva pelo apoio e paciência.
    [Show full text]
  • Nerve Agent Tables
    Report any release of WMD to the National Response Center 1-800-424-8802 NRT Quick Reference Guide: For References, Please See: Key References Cited/Used* in National Response Team Soman (GD) (NRT) Quick Reference Guides (QRGs) for Chemical Warfare Agents. Agent Classification: Chemical Warfare Nerve Agent CAS: 96-64-0 Description: Colorless liquid; generally odorless, possibly fruity. GD was manufactured as a warfare agent and is a lethal cholinesterase inhibitor. It has the same mechanism of toxicity as organophosphate insecticides but is much more potent. GD is considered to have low persistence; though it is less volatile than sarin (GB), it is much more vola- tile than persistent agents VX or sulfur mustard (HD). While considered relatively non-persistent, liquid GD could be present for hours to days if in large amounts, or in cold or enclosed environments. Breakdown/hydrolysis in water (especially treated water) is expected. Environmental breakdown products of GD are relatively nontoxic. Signs/symp- toms of exposure to GD will occur within minutes or hours, depending on the dose. Even relatively low dose exposure to GD can be fatal; administration of antidotes within 2 minutes of exposure may be effective. (See First Aid/Decon below) Persistence: vapor: minutes-hours; liquid: hours to days depending on amount, temperature, rain or other weather conditions, and type of surface. Molecular Weight: 182.18 g/mol Vapor Density: 6.33 (air = 1) Aqueous Solubility: 21 g/L 68°F Volatility: 3900 mg/m3 77°F Boiling Point: 388°F Soluble: organic solvents Agent Characteristics Freezing point: -44°F Flashpoint: 250°F Specific Gravity: 1.02 g/ml 68°F Vapor Pressure: 0.4 mm Hg @ 77°F Conversion Factors: 1ppm= 7.5 mg/m3; °C = 0.56 × (°F – 32) Air Release: Because it is somewhat volatile, GD is not generally considered a “persistent” agent.
    [Show full text]
  • Catalytic Efficiencies of Directly Evolved Phosphotriesterase Variants with Structurally Different Organophosphorus Compounds in Vitro
    Arch Toxicol DOI 10.1007/s00204-015-1626-2 MOLECULAR TOXICOLOGY Catalytic efficiencies of directly evolved phosphotriesterase variants with structurally different organophosphorus compounds in vitro Moshe Goldsmith2 · Simone Eckstein1 · Yacov Ashani2 · Per Greisen Jr.3 · Haim Leader4 · Joel L. Sussman5 · Nidhi Aggarwal5 · Sergey Ovchinnikov3 · Dan S. Tawfik2 · David Baker3 · Horst Thiermann1 · Franz Worek1 Received: 27 July 2015 / Accepted: 22 October 2015 © Springer-Verlag Berlin Heidelberg 2015 Abstract The nearly 200,000 fatalities following expo- catalytic efficiencies of V-agent hydrolysis by two newly sure to organophosphorus (OP) pesticides each year and selected PTE variants were determined. Moreover, in order the omnipresent danger of a terroristic attack with OP to establish trends in sequence–activity relationships along nerve agents emphasize the demand for the development of the pathway of PTE’s laboratory evolution, we examined effective OP antidotes. Standard treatments for intoxicated kcat/KM values of several variants with a number of V-type patients with a combination of atropine and an oxime are and G-type nerve agents as well as with different OP pes- limited in their efficacy. Thus, research focuses on develop- ticides. Although none of the new PTE variants exhibited 7 1 1 ing catalytic bioscavengers as an alternative approach using kcat/KM values >10 M− min− with V-type nerve agents, OP-hydrolyzing enzymes such as Brevundimonas diminuta which is required for effective prophylaxis, they were phosphotriesterase (PTE). Recently, a PTE mutant dubbed improved with VR relative to previously evolved variants. C23 was engineered, exhibiting reversed stereoselectivity The new variants detoxify a broad spectrum of OPs and and high catalytic efficiency (kcat/KM) for the hydrolysis of provide insight into OP hydrolysis and sequence–activity the toxic enantiomers of VX, CVX, and VR.
    [Show full text]
  • Current Awareness in Clinical Toxicology Editors: Damian Ballam Msc and Allister Vale MD
    Current Awareness in Clinical Toxicology Editors: Damian Ballam MSc and Allister Vale MD August 2015 CONTENTS General Toxicology 6 Metals 34 Management 17 Pesticides 35 Drugs 19 Chemical Warfare 38 Chemical Incidents & 28 Plants 39 Pollution Chemicals 29 Animals 39 CURRENT AWARENESS PAPERS OF THE MONTH Child poisonings with methadone in France: a 6-year prospective national survey since the availability of capsules in 2008 Torrents R, Picot C, Glaizal M, Courne M-A, Schmitt C, Richard N, Simon N, Cardona F, de Haro L. Clin Toxicol 2015; 53: 819-22. Background Methadone for opiate substitution was available only in syrup formulation prior to 2008. In 2007, the French Health Authorities made solid forms available. A national survey was performed in order to evaluate the modification of child poisonings induced by such a new pharmaceutical formulation. Methods A prospective study was set up (April 15, 2008 to April 15, 2014) with the analysis of cases of unintentional ingestion of methadone by patients under 18 years old and managed by the 10 French poison control centers at the national level. As soon as a new pediatric exposure was recorded in the informatics data bank of the Poison Centers, a telephone survey was performed by the Marseilles' Poison Center to obtain the evolution and all the necessary details. Current Awareness in Clinical Toxicology is produced monthly for the American Academy of Clinical Toxicology by the Birmingham Unit of the UK National Poisons Information Service, with contributions from the Cardiff, Edinburgh, and Newcastle Units. The NPIS is commissioned by Public Health England 2 Results 87 cases of child poisonings with the 2 forms were reviewed (syrup, 56 patients; capsules, 31 patients).
    [Show full text]
  • Thermal Desorption Accessories & Consumables
    Thermal Desorption Accessories & Consumables 2013/2014 World-leading products for thermal desorption 1 Contents Section Page Ordering information 2 Sorbent tubes 3 Tube accessories 17 Sorbents 23 Pumped sampling 31 Diffusive (passive) sampling 35 Contents Canister sampling 39 Calibration and standards 43 Sampling accessories 49 Starter kits 63 Instrument spares 67 Laboratory accessories 81 GC/MS software 85 Applications Guides 91 Application Notes 92 Index 93 List of part numbers 96 T: +44 (0)1443 230935 T: 886-483-5684 (USA toll-free) 2 Ordering information Ordering from Markes couldn’t be simpler, either by phone, fax, email or online. Payment is accepted by credit card (Mastercard or Visa) on account. If you need help with your order, simply contact one of our highly experienced chemists or customer service agents at either of Markes’ main sales locations: • Markes International Ltd Gwaun Elai Medi Science Campus Llantrisant RCT CF72 8XL United Kingdom Quality-assured accessories and Tel: +44 (0)1443 230935 consumables from the TD experts Fax: +44 (0)1443 231531 Web: http://shop.markes.com/ When it comes to accessories and consumables for thermal Email:[email protected] desorption, we offer our customers nothing but the best: • Markes International, Inc. • Application expertise that is second-to-none 11126 Kenwood Road • Fast delivery and excellent customer service How How to order Cincinnati OH 45242 • Innovative technologies and product enhancements USA • World-leading, patented technologies for thermal desorption • Stringent quality control of our manufacturing procedures Tel: +1 866 483 5684 (toll-free) Fax: +1 513 745 0741 • ISO 9001 accreditation Web: http://shop.markesus.com/ • Worldwide distributor and user base Email:[email protected] • Online shop for simple and rapid ordering Orders may also be placed with any of our global distributors: • Custom service – if you want something special, we can do it www.markes.com/Global-Distributors.aspx And most importantly..
    [Show full text]
  • Environmental Assessment Proposed Changes to the Sanitary Biosolids Land Application Program on the Oak Ridge Reservation Oak Ridge, Tennessee
    DOE/EA-1356 Environmental Assessment Proposed Changes to the Sanitary Biosolids Land Application Program on the Oak Ridge Reservation Oak Ridge, Tennessee February 2003 U.S. Department of Energy Oak Ridge Operations ACRONYMS AND ABBREVIATIONS ac acres ALARA as low as reasonably achievable AMSA American Metropolitan Sewer Association CEQ Council on Environmental Quality CSF cancer slope factor DOE U.S. Department of Energy EA environmental assessment EFPC East Fork Poplar Creek EPA U.S. Environmental Protection Agency EPS Effluent Polishing System (West End Treatment Facility) FONSI Finding of No Significant Impact ggram ha hectares HEAST Health Effects Assessment Summary Tables HI hazard index HQ hazard quotient IDP Industrial Discharge Permit IRIS Integrated Risk Information System kg kilogram l liter LET linear energy transfer LOAEL Lowest Observed Adverse Effect Level mg milligram mrem/yr millirem per year MSL mean sea level NEPA National Environmental Policy Act NOAEL No Observed Adverse Effect Level NPDES National Pollutant Discharge Elimination System NRC Nuclear Regulatory Commission ORNL Oak Ridge National Laboratory ORR Oak Ridge Reservation i PCB polychlorinated biphenyl POTW Publicly Owned Treatment Works PPE Personnel Protective Equipment RCRA Resource Conservation and Recovery Act RESRAD Residual Radioactivity computer model RfC reference concentration RfD reference dose ROI Region of Influence SHPO State Historic Preservation Office TDEC Tennessee Department of Environment and Conservation TWRA Tennessee Wildlife Resources Agency USFWS U.S. Fish and Wildlife Service WETF West End Treatment Facility WSMS Westinghouse Safety Management Systems ii EXECUTIVE SUMMARY The U.S. Department of Energy (DOE) proposes to raise the biosolids land application radionuclide loading limits from the current, self-imposed 4 mrem/yr lifetime loading to the Tennessee Department of Environment and Conservation (TDEC)-approved level of 10 mrem/yr.
    [Show full text]