EXS 100 Molecular, Clinical and Environmental Toxicology Volume 2: Clinical Toxicology Edited by Andreas Luch Birkhäuser Verlag Basel · Boston · Berlin Editor Andreas Luch Federal Institute for Risk Assessment Thielallee 88-92 14195 Berlin Germany Library of Congress Control Number: 2008938291 Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data is available in the Internet at http://dnb.ddb.de ISBN 978-3-7643-8337-4 Birkhäuser Verlag AG, Basel – Boston – Berlin This work is subject to copyright All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks For any kind of use, permission of the copyright owner must be obtained The publisher and editor can give no guarantee for the information on drug dosage and administration contained in this publication The respective user must check its accuracy by consulting other sources of reference in each individual case The use of registered names, trademarks etc in this publication, even if not identified as such, does not imply that they are exempt from the relevant protective laws and regulations or free for general use © 2010 Birkhäuser Verlag AG Basel – Boston – Berlin P.O Box 133, CH-4010 Basel, Switzerland Part of Springer Science+Business Media Printed on acid-free paper produced from chlorine-free pulp TCF ∞ Cover illustrations: by A Luch, J White, G.P Rossini and P Hess; with friendly permission Printed in Germany ISBN 978-3-7643-8337-4 987654321 e-ISBN 978-3-7643-8338-1 www birkhauser.ch V Contents List of contributors VII Preface XI James S Henkel, Michael R Baldwin and Joseph T Barbieri Toxins from bacteria Robert R M Paterson and Nelson Lima Toxicology of mycotoxins 31 Gian Paolo Rossini and Philipp Hess Phycotoxins: chemistry, mechanisms of action and shellfish poisoning 65 Robert H Poppenga Poisonous plants 123 Bryan A Hanson Toxic plants: a chemist’s perspective 177 Daniel Butzke and Andreas Luch High-molecular weight protein toxins of marine invertebrates and their elaborate modes of action 213 Julian White Venomous animals: clinical toxinology 233 Andreas Luch Mechanistic insights on spider neurotoxins 293 Hans H Maurer Analytical toxicology 317 Christine Rauber-Lüthy and Hugo Kupferschmidt Household chemicals: management of intoxication and antidotes 339 VI Contents Daniel E Rusyniak, Anna Arroyo, Jennifer Acciani, Blake Froberg, Louise Kao and Brent Furbee Heavy metal poisoning: management of intoxication and antidotes 365 Silas W Smith Drugs and pharmaceuticals: management of intoxication and antidotes 397 Amanda Hayes and Shahnaz Bakand Inhalation toxicology 461 David Vearrier, John A Curtis and Michael I Greenberg Biological testing for drugs of abuse 489 Ivan D Montoya and David J McCann Drugs of abuse: management of intoxication and antidotes 519 Kamil Kuˇca and Miroslav Pohanka Chemical warfare agents 543 Miroslav Pohanka and Kamil Kuˇca Biological warfare agents 559 Olaf H Drummer Forensic toxicology 579 Glossary 605 Index 611 VII List of contributors Jennifer Acciani, Department of Emergency Medicine, Division of Medical Toxicology, Indiana University School of Medicine, 1050 Wishard Boulevard, Room 2200, Indianapolis, IN 46202, USA; e-mail: jacciani@ iupui.edu Anna Arroyo, Department of Emergency Medicine, Division of Medical Toxicology, Indiana University School of Medicine, 1050 Wishard Boulevard, Room 2200, Indianapolis, IN 46202, USA; e-mail: aarroyo@iupui.edu Shahnaz Bakand, Department of Occupational Health, School of Public Health, Iran University of Medical Sciences, Tehran, Iran; Visiting Research Fellow, School of Risk and Safety Sciences, University of New South Wales, Sydney, NSW 2052, Australia; e-mail: s.bakand@unsw.edu.au Michael R Baldwin, Department of Molecular Microbiology and Immunology, University of Missouri, M616 Medical Sciences Building, Columbia, MO 65212, USA; e-mail: baldwinmr@health.missouri.edu Joseph T Barbieri, Medical College of Wisconsin, Department of Microbiology and Molecular Genetics, 8701 Watertown Plank Road, Milwaukee, WI 53151, USA; e-mail: jtb01@mcw.edu Daniel Butzke, Center for Alternatives to Animal Experiments (ZEBET), Federal Institute for Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany; e-mail: daniel.butzke@bfr.bund.de John A Curtis, Department of Emergency Medicine, Division of Medical Toxicology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; e-mail: jac129@gmail.com Olaf H Drummer, Victorian Institute of Forensic Medicine, Department of Forensic Medicine, Monash University, 57-83 Kavanagh St, Southbank 3006, Australia; e-mail: olaf@vifm.org Blake Froberg, Department of Pediatrics, Division of Medical Toxicology, Indiana University School of Medicine, 1050 Wishard Boulevard, Room 2200, Indianapolis, IN 46202, USA; e-mail: bfroberg@iupui.edu Brent Furbee, Department of Emergency Medicine, Division of Medical Toxicology, Indiana University School of Medicine, 1050 Wishard Boulevard, Room 2200, Indianapolis, IN 46202, USA; e-mail: bfurbee@clarian.org Michael I Greenberg, Department of Emergency Medicine, Division of Medical Toxicology, Drexel University College of Medicine, Philadelphia, PA 19102, USA, mgreenbe@drexelmed.edu Bryan A Hanson, Department of Chemistry and Biochemistry, Julian Science and Mathematics Center, 602 S College Ave., Room 363, DePauw University, Greencastle, IN 46135, USA; e-mail: hanson@depauw.edu VIII List of contributors Amanda Hayes, Chemical Safety and Applied Toxicology (CSAT) Laboratories, School of Risk and Safety Sciences, The University of New South Wales, Sydney, NSW 2052, Australia; e-mail: a.hayes@unsw.edu.au James S Henkel, Medical College of Wisconsin, Department of Microbiology and Molecular Genetics, 8701 Watertown Plank Road, Milwaukee, WI 53151, USA; e-mail: jhenkel@mcw.edu Philipp Hess, IFREMER, Department of Environment, Microbiology and Phycotoxins, 44311 Nantes Cedex 03, France; e-mail: philipp.hess@ ifremer.fr Louise Kao, Department of Emergency Medicine, Division of Medical Toxicology, Indiana University School of Medicine, 1050 Wishard Boulevard, Room 2200, Indianapolis, IN 46202, USA; e-mail: lkao@clarian.org Kamil Kuˇca, Center of Advanced Studies and Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 50001 Hradec Kralove, Czech Republic; e-mail: kucakam@pmfhk.cz Hugo Kupferschmidt, Swiss Toxicological Information Centre (STIC), Freiestrasse 16, 8032 Zürich, Switzerland; e-mail: hkupferschmidt@toxi ch, hugo.kupferschmidt@usz.ch Nelson Lima, Centre of Biological Engineering, IBB-Institute for Biotechnology and Bioengineering, Universidade Minho, 4710-057 Braga, Portugal; e-mail: micoteca@deb.uminho.pt Andreas Luch, Department of Product Safety, Center for Alternatives to Animal Experiments, Federal Institute for Risk Assessment, Thielallee 8892, 14195 Berlin, Germany; e-mail: andreas.luch@bfr.bund.de Hans H Maurer, Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University Hospital, Building 46, 66421 Homburg (Saar), Germany; e-mail: hans.maurer@uks.eu David J McCann, Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 6001 Executive Boulevard, Bethesda, MD 20892, USA; e-mail: dmccann@nida.nih.gov Ivan D Montoya, Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 6001 Executive Boulevard, Bethesda, MD 20892, USA; e-mail: imontoya@mail.nih.gov Robert R.M Paterson, Centre of Biological Engineering, IBB-Institute for Biotechnology and Bioengineering, Universidade Minho, 4710-057 Braga, Portugal; e-mail: russell.paterson@deb.uminho.pt Miroslav Pohanka, Center of Advanced Studies and Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 50001 Hradec Kralove, Czech Republic; e-mail: rau@ atlas.cz, pohanka@pmfhk.cz Robert H Poppenga, California Animal Health & Food Safety Laboratory System (CAHFS), School of Veterinary Medicine, University of California, List of contributors IX Davis, West Health Sciences Drive, Davis, CA 95616, USA, e-mail: rhpoppenga@ucdavis.edu Christine Rauber-Lüthy, Swiss Toxicological Information Centre (STIC), Freiestrasse 16, 8032 Zürich, Switzerland; e-mail: christine.rauber@usz.ch Gian Paolo Rossini, Università di Modena e Reggio Emilia, Dipartimento di Scienze Biomediche, Via Campi 287, 41100 Modena, Italy; e-mail: gianpaolo.rossini@unimo.it Daniel E Rusyniak, Department of Emergency Medicine, Division of Medical Toxicology, Indiana University School of Medicine, 1050 Wishard Boulevard, Room 2200, Indianapolis, IN 46202, USA; e-mail: drusynia@ iupui.edu Silas W Smith, New York City Poison Control Center, New York University School of Medicine, NYU Department of Emergency Medicine, Bellevue Hospital Center, 462 First Avenue, Room A-345A, New York, NY 10016, USA; e-mail: silas.smith@nyumc.org David Vearrier, Department of Emergency Medicine, Division of Medical Toxicology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; e-mail: david.vearrier@drexelmed.edu Julian White, Toxinology Department, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA 5006, Australia; e-mail: julian.white@adelaide.edu.au 605 Glossary AAPCC AC AChE ACTX ADH AFB1 ALI 6-AM APAP APCI ARDS ASP AST ATA AUC AZA BAL BIA BLL BoNT BTX BUN BWA CBC Cdt CE CFTR CIRL CK CNS COMT COPD CPK CPR CT CTX CWA DAD American Association of Poison Control Centers activated charcoal acetylcholinesterase atracotoxin alcohol dehydrogenase aflatoxin B1 acute lung injury 6-acetylmorphine (= 6-MAM) N-acetyl-p-aminophenol (acetaminophen, paracetamol) atmospheric pressure chemical ionization acute respiratory distress syndrome amnesic shellfish poisoning aspartate aminotransferase alimentary toxic aleukia area under the curve azaspiracid British anti-lewisite (2,3-dimercaptopropanol, dimercaprol) benzylisoquinoline alkaloid blood lead level botulinum neurotoxin PbTX, brevetoxin blood urea nitrogen biological warfare agents complete blood count cytolethal distending toxin capillary electrophoresis cystic fibrosis transmembrane conductance regulator calcium-independent receptor for latrotoxin creatine kinase central nervous system catechol O-methyltransferase chronic obstructive pulmonary disease creatinine phosphokinase cardio-pulmonary resuscitation computed tomography ciguatoxin chemical warfare agents diode-array detection 606 DIC DMSA DMSO DON DSP DTX ECG ED EDTA EEG EI ELISA EMIT EPA ERK ESI FDA FID FUM GABA Gb GC GCS GHB GI GOT GPCR GPT GSH HAB Hb HBV HCC Hck HCN HFV HIET HMWPT HPLC 5-HT3 i.c i.m i.p i.v IARC Glossary disseminated intravascular coagulation 2,3-dimercaptosuccinic acid dimethyl sulfoxide deoxynivalenol diarrheic shellfish poisoning dinophysistoxin electrocardiogram emergency department ethylenediamintetraacetic acid electroencephalogram electron ionization enzyme-linked immunosorbent assay enzyme multiplied immunoassay technique U.S Environmental Protection Agency extracellular signal-regulated kinase electrospray ionization U.S Food and Drug Administration flame ionization detector fumonisin γ-aminobutyric acid gambierol gas chromatography Glascow coma score γ-hydroxybutyrate gastrointestinal glutamic oxaloacetic transaminase G protein-coupled receptor glutamic pyruvic transaminase glutathione harmful algal bloom hemoglobin hepatitis B virus human hepatocellular carcinoma hematopoietic cell kinase hydrogen cyanide hemorrhagic fever virus high-dose insulin euglycemia therapy high-molecular weight protein toxins high-performance liquid chromatography 5-hydroxytryptamine (serotonin) intracutaneous intramuscular intraperitoneal intravenous International Agency for Research on Cancer Glossary IC50 IFN Ig IL INH IP3 IPCS IR JNK LAAO LC LD50 LDH LLE LOD LSD LTX mAb MAHA MALDI-TOF 6-MAM MAM MAPK MDAC MDMA MHC MRM MS MTX NAC NAPQI NICI NIDA NIV NMDA NMR NRU NSAID NSCC NSP OA OEL OTA OTC PA 607 inhibitory concentration 50% interferon immunoglobulin interleukin isoniazid inositol triphosphate International Programme on Chemical Safety infrared spectroscopy c-Jun N-terminal protein kinase L-amino acid oxidase liquid chromatography lethal dose 50% lactate dehydrogenase liquid-liquid extraction limit of detection D-lysergic acid diethylamide latrotoxin monoclonal antibody microangiopathic haemolytic anaemia matrix-assisted laser desorption/ionization time-of-flight 6-monoacetylmorphine (= 6-AM) methylazoxy-methanol mitogen-activated protein kinase multiple-dose AC 3,4-methylenedioxymethamphetamine major histocompatibility complex multiple-reaction monitoring mass spectrometry maitotoxin or methotrexate N-acetylcysteine N-acetyl-p-benzoquinone imine negative ion chemical ionization U.S National Institute of Drug Abuse nivalenol N-methyl-D-aspartate nuclear magnetic resonance neutral red uptake non-steroidal anti-inflammatory drug non-selective cation channels neurotoxic shellfish poisoning okadaic acid occupational exposure limits ochratoxin A ornithine transcarbamylase pyrrolizidine alkaloid 608 PBM PBTK PbTX PCP PDB PEEP PEG PEPCK PFT PKA PKC PKS PLA2 PLC PlTX PM PPase PSP PTX QSAR RBC REACH RIA ROS s.c SAg SAR SD SEB SIM SNARE SPE SPME STX SVDK TCA TCM TCR TDM TEM TeNT THC TLC TNF Glossary peripheral blood mononuclear (cells) physiologically based toxicokinetic (model) brevetoxin, BTX phencyclidine Protein Databank positive end-expiratory pressure polyethylene glycol phosphoenolpyruvate carboxy kinase pore-forming toxin protein kinase A protein kinase C polyketide synthases phospholipase A2 phospholipase C palytoxin particulate matter phosphoprotein phosphatase paralytic shellfish poisoning pectenotoxin quantitative structure-activity relationship red blood cell Registration, Evaluation, Authorization and Restriction of Chemicals radioimmunoassays reactive oxygen species subcutaneous superantigen structure activity relationship standard deviation staphylococcal enterotoxin B selected-ion monitoring soluble N-ethylmaleimide-sensitive factor attachment receptor solid-phase extraction solid-phase microextraction saxitoxin snake venom detection kit tricyclic antidepressant Traditional Chinese Medicine T cell receptor therapeutic drug monitoring transmission electron microscopy tetanus neurotoxin Δ9-tetrahydrocannabinol thin-layer chromatography tumor necrosis factor Glossary TSS TTX UDS UV VGNC VOC VPA WBCT WBI WHO YTX 609 toxic shock syndrome tetrodotoxin urine drug screening ultraviolet voltage-gated sodium channel volatile organic compound valproic acid whole blood clotting time whole bowel irrigation World Health Organization yessotoxin 611 Index abrin 553, 564 Abrus precatorius 553 absinthe 357 Acanthaster planci 226 acetaminophen (paracetamol) 405, 413, 598 acetylcholinesterase (AChE) 544 N-acetylcysteine (NAC) 52, 410, 413–415 N-acetyl-D,L-penicillamine 375 AChE reactivators (“oximes”) 545, 546 aconitine 304, 306, 580 Aconitum napellus 306 acrodynia 371, 374 actinoporin 220 activated charcoal (AC) 171, 405, 406 acute lung injury 343, 355 adamsite 552 adders 256, 266 aerosols 81, 83, 101, 102, 106, 462, 463 aflatoxicol 45 aflatoxicosis 32, 555 aflatoxins 32, 33, 36, 42, 46, 47, 554, 564 ω-agatoxins 302 Agelenopsis aperta 302 Agkistrodon 268 air freshener 357 airborne chemical exposure 463, 472 Akakabio-byo 32, 39 alcohol testing 580 Alexandrium 69 alfalfa 166 alimentary toxic aleukia (ATA) 32, 39 alkali disease 163 alkalinization, urinary 407, 408 aloe-emodin 200, 201 alopecia 385 alprazolame 599 amalgam 373 L-amino acid oxidase (LAAO) 214, 222–224 amnesic shellfish poisoning (ASP) 94, 103 AMPA receptor 92–94 amphetamine 322, 493, 502, 504, 505, 520, 524, 579, 582, 584, 587, 588, 593, 597 amygdalin 159 amyl nitrite 159, 550 anagyrine 156, 157 anaphylaxis 258, 275 anatoxin 556, 557 Androctonus australis 270, 303 angiotensin converting enzyme (ACE) inhibitor 430, 439 anhydroecgonine 493, 502, 509 anionic gap 348, 349, 353 anorexia 42, 53 Anthopleura xanthogrammica 303 anthopleurin-B 303 anthracyclines 426, 427 anthraquinones 36 anthrax 561, 564–566, 571 antiarrhythmics 322 anticholinergics 157, 545 anticonvulsants 322, 545 antidepressants 581, 584, 588, 593, 596, 597 antidiabetics 323 antifreeze agent 348, 353 antihistamines 322, 581 612 antipsychotic drugs 593, 597 antivenom 248, 251–253, 256, 258 anuric renal failure 168 Aplysia 214, 222 arachidonic acid 224 ARDS (acute respiratory distress syndrome) 346, 354 Aristolochia 124, 202 aristolochic acid 200, 202 arsenic 365–370, 580 arsine 369, 549, 550 Artemisia 193, 357 Aspergillus 32, 33, 554 asphyxia 354, 469 Astragalus 151 atracotoxins (ACTX) 293, 302–305, 307 Atrax 271, 294, 295, 301, 302 atraxin 301 atropine 157, 180, 181, 430, 545, 546, 580 Aum Shinrikyo 543, 561 autism 373, 377 avizafon 545, 546 Azadinium spinosum 74 azaspiracids (AZAs) 68, 70, 73–75, 85, 97–100, 106, 107 Bacillus anthracis 561, 564, 566 baicalein 199, 200 Balkan nephropathy 32 banana spiders 273, 294 barbiturates 322, 493, 502, 505, 506, 580, 582, 587, 588, 593, 597 batrachatoxin 277, 304, 306 beauvericin 36 benzalkonium chloride 341 benzodiazepine 322, 401, 412, 439, 440, 493, 502, 505, 506, 527, 529, 579–582, 584, 587, 588, 593, 595–597 benzoylecgonine 502, 510, 524, 491, 509, 588, 593 benzylisoquinoline alkaloids (BIAs) 182, 186, 194 Bitis 265, 266 Index black-spot disease (kokuten-byo) 39 blister – agents 545 – beetles 276 blood lead level (BLL) 378, 381, 382 blue ringed octopus (Hapalochlaena) 281 boomslang 261 Bordetella pertussis Bothrops 260, 267, 268 botulinum neurotoxin (BoNT) 13, 14, 16–18, 214, 553, 561, 564, 570 botulism 13, 564 box jellyfish 216–219, 278 bracken fern 162 breath analyzers 494, 503 brevenal 83, 85, 103, 105 brevetoxin (PbTX) 70, 79, 83, 85– 87, 89, 90, 102, 103, 303, 304, 306, 307 British anti-lewisite (BAL, dimercaprol) 369, 373, 374, 384, 547, 548 bromocriptine 412 brucellosis 564, 565, 567 bubonic plague 560, 569 bufadienolide 161 Bufo 277, 432 bufogenin 277 bufotoxins 277 Bungarus 262 buprenorphine 323, 432, 439, 494, 511, 520, 522, 593 Burkholderia 564 buthid scorpions 270 cadmium 359, 468, 470 calcium channel – antagonists (CCB) 323, 429– 431, 527 – voltage-gated (VGCC) 87–94, 98 camphor 180, 181, 357, 358 camptothecin 178, 179 Index cannabinoids 493, 506, 507, 508, 587 cannabis 130, 153, 579, 580–582, 585, 593 cantharadin 276 carbon – monoxide 344 – tetrachloride 354 cardenolides 125, 128, 133, 138, 141, 160 cardiac beriberi 32, 40 cardiotoxicity 160, 218, 221, 237, 267, 344, 354, 356, 526 Carukia barnesi (Irukandji jellyfish) 217, 259, 278, 280 Carybdea 218 castor bean plant 571 catecholamine storm 259, 270, 271, 280 Catharanthus roseus 195, 202 CDC agents 563, 564 Celery harvester’s disease 32 centipedes 241, 274 chelating therapy 360, 369, 373, 375, 383 Chironex fleckeri 216–219, 235, 241, 278 Chiropsalmus quadrigatus 218 chloracetophenone (CN) 551, 552 o-chlorobenzilidine malononitrile (CS) 551, 552 chloropicrin 551 chloroquine 440, 595, 597 cholera toxin 9, 564 Chondria armata 65, 73 chromated copper arsenate 370 chronic obstructive pulmonary disease (COPD) 469 cicutoxin 130, 152 ciguatoxin (CTX) 70, 79, 83–87, 89, 90, 104, 105, 304, 306 citreoviridin 40 citrinin 36, 46, 56, 57 Claviceps purpurea 32, 41 clonidine 400, 430, 439 613 Clostridium 14, 564, 570 coagulopathy 238, 247, 249, 265– 269, 271, 273, 276 cobras 236, 244, 259, 262, 264 cocaethylene 494, 509, 524 cocaine 180, 181, 493, 502, 508– 510, 520, 524, 579–582, 585, 587, 588, 593, 595–597 codeine 510, 511, 521, 588, 598 colchicine 180, 181, 192, 193 Colchicum autumnale 131, 181 colicins colubrid snakes 240, 261, 262 coma cocktail 398 cone snails 235, 241, 280, 302, 306, 308 coniine 131, 154, 180, 181, 580 Conium maculatum 151, 153, 181 conotoxins 236, 241, 280, 302, 304, 306, 308, 564 Conus 221, 236, 241, 280, 302, 306, 308 copperheads 236, 240, 268 Coxiella 11, 564 crack 509, 524 crotoxin 214 crown-of-thorns starfish 226 Cubozoa 216–219 cyanide 158, 159, 171, 550, 580, 595, 596 cyanoacrylate 358 cyanobacteria 65, 69, 556 cyanogens 549 cyclic imines 70, 82, 83, 86, 94, 107 cyclopamine 157 cyclophosphamide 426 cyclopia 157 cyclopiazonic acid 36, 42, 46, 55 cyclosarin 544 cytochalasins 36 cytolethal distending toxin (Cdt) 227 dantrolene 412 Datura 133, 151, 157, 580 614 deadly nightshade 128, 580 Dendroaspis 263 dendrodochiotoxicosis 32 Dengue 563, 564, 570 deoxynivalenol (DON) 33, 36, 555, 556 detergent – anionic 339, 340 – cationic 339, 341 – non-ionic 339, 340 diacetoxyscirpenol 44, 564 diarrheic shellfish poisoning (DSP) 74, 76, 77, 80, 103, 104, 106 diazepam 358, 401, 493, 499, 506, 527, 533, 545, 546 2,4-dichlorophenoxyacetic acid 407, 408 Digitalis purpurea 192 digitoxin 133, 192, 193, 432 digoxin 161, 431, 432, 593, 596, 597 digoxin-specific antibody 161, 171, 431, 432 dimercaprol (BAL, British antilewisite) 369, 373, 374, 384, 547, 548 2,3-dimercaptopropane sulfonate 375 dimethicon 340 4-dimethyl-aminophenol 171 dinoflagellate(s) 65, 69, 74–76, 80, 83, 84, 214, 303, 306 Dinophysis 75–77 dinophysistoxin (DTX) 75–77, 85 diosgenin 143, 200 diphtheria toxin 2, 4, 5, 297 disinfectants 341, 342, 352, 480 DMSA (meso-2, 3-dimercaptosuccinic acid) 369, 373–375, 383, 384 domoic acid 65, 68, 70, 72, 73, 86, 88, 92–94, 103 doping 317, 318, 321, 330, 581 drug testing 489, 500, 501, 509, 581, 584, 592 dry land drowning 547, 551 Index Ebola 561, 563, 564, 570 ecstasy (MDMA) 504, 593, 597 edetate calcium disodium (calcium EDTA) 383, 427 elapid snakes 236, 240, 262–265 ELISA (enzyme-linked immunosorbent assays) 491, 587 ephedrine 327, 524, 529 erethism 371–374 ergot alkaloids 33, 41, 43, 151 ergotism 32, 40 Erythroxylon/-um coca 508, 523 essential oils 142, 357 ETEC (enterotoxigenic E coli) ethanol 346, 494, 501–504, 580, 588, 593, 596 ethylene glycol 347–352 Fab antivenoms 251, 252 fatty acid ethyl esters (FAEEs) 494, 504 fire – ants 275 – coral 225, 226 flumazenil 398, 439, 440 fomepizole (4-methylpyrazole) 349, 350, 352, 410 food poisoning 5, 555 formaldehyde 342, 465, 466, 470, 477 Francisella tularensis 564, 567 freon (chlorofluorocarbons) 354, 355 fumonisins (FUMs) 33, 36, 40, 42, 43, 57 funnel-web spiders 271, 294, 301, 304 fusarenon X 50 fusarin C 39, 50 Fusarium 32, 33, 38–40, 42, 50, 555 GABA (γ-aminobutyric acid) 416, 424, 425, 439, 532 G-agents 544 galanthamine (galantamine) 131, 136, 141, 191, 192 Index Gambierdiscus 84, 85, 89, 90, 104, 214, 306 gambierol 70, 84, 86, 87, 89, 90, 91, 104, 105 genistein 151, 200, 201 GHB (γ-hydroxybutyrate) 580, 581, 593, 596 Glaucus atlanticus 221 gliotoxin 36, 41, 43, 55 glycosides – calcinogenic 151 – cardioactive 128, 142, 151, 160, 429, 430 – coumarin 151 – cyanogenic 151, 158 – goitrogenic 151 – triterpenoid 151 glycyrrhizin 136, 200 Gonyaulax 80, 306 gossypol 152 griseofulvin 36 gymnocin 83 gymnodimine 70, 82 Hadronyche 234, 271, 294, 301– 303 haemorrhagins 238, 240, 254 hair testing 506, 508, 510–512 Halichondria okadaji 65, 75 hallucinogens 322 harmful algal bloom (HAB) 66, 102, 105 hashish 506, 507, 530 Heloderma 244, 269 hemodialysis 347, 349, 352, 353, 409, 410 hemoglobinuria 167, 219, 369 hemolysin 8, 219 hemoperfusion 402, 409, 419 hemorrhagic fever viruses (HFVs) 564, 570 hepatocellular carcinoma (HCC) 32, 37 heroin 502, 510, 520, 521, 594, 595 homoanatoxin-a 556, 557 HT-2 toxin 564 615 hydrocarbons – aliphatic 354, 355 – aromatic 354 – halogenated 354 hydrocodone 520, 521 hydrofluoric acid 342, 344, 345 hydrogen – cyanide (HCN) 159, 468, 469, 549, 550 – peroxide (H2O2) 215, 222, 223, 342, 343 hymenopterans 275 hyoscyamine 128, 129, 133, 137, 157, 181, 430, 580 hypercalcemia 408, 431 hypericin 138, 152, 179 hyperthermia 140, 400, 410–412, 526–530 hypocalcemia 152, 164, 344, 384, 406, 417, 436 illicit drug 498, 500, 501, 519 incapacitating agents 543, 548, 549 indole alkaloids 37, 45, 138, 149, 151 indolizidine alkaloids 136, 151 indoor fungal exposure 56 ipecac 398, 403, 404, 531, 533 irritants 136, 147, 341, 343, 467, 469, 551 Irukandji syndrome 280 isocupressic acid 152, 166 isoflavones 151, 202 isoniazid (INH) 400, 410, 414, 423– 425, 440 isopropyl alcohol 352, 470, 494, 500, 503 jellyfish 215–219, 235, 278–280 jequirity pea 553 kainate receptor 93, 94 Kashin Beck disease 32 kraits 236, 244, 262 kwashiorkor 32, 35 lachrymatory gases 551 L-amino acid oxidase (LAAO) 214, 222–224 616 lamp oil 355, 356 Lassa fever 564, 570 latrodectin 298 latrodectism 272, 293, 296 Latrodectus 234, 272, 294, 295, 297, 309 latrophilin 295, 296, 299, 300 α-latrotoxin (α-LTX) 293, 295 lead 359, 378–384 lectin 125, 142, 145, 149, 163, 571 Legionnaire’s disease 11 Leiurus quinquestriatus 303 leucovorin 427–429 leukoencephalomalacia 42 lewisite 546, 547 lithium 359, 404, 406–409 lizards 269 Lonomia 240, 248, 276 Loxosceles 234, 241, 273, 294 loxoscelism 260, 273, 294 lung-damaging agents 543, 551 luteoskyrin 36, 46 D-lysergic acid diethylamide (LSD) 138, 548, 580, 588 magnoflorine 194 maitotoxin (MTX) 68, 70, 84, 86, 87, 89, 90, 104, 105, 214 6-MAM (6-monoacetylmorphine) 494, 502, 510, 511, 523, 588, 593, 597 mannitol 105, 106, 527 marijuana 130, 153, 196, 493, 496, 499, 506–509, 520, 530, 531 MDMA (3, 4-methylenedioxymethamphetamine) 493, 502, 504, 597 Mees’ lines 367, 368 meperidine 494, 511, 521, 522, 597 mercury 359, 370–377 methadone 400, 438, 494, 500, 511, 520, 522, 582, 588, 593, 596–598 methamphetamine 407, 493, 499, 502, 504, 505, 520, 524, 528– 530, 585, 597, 599 methanol 350–352, 409, 494, 503 methotrexate 408, 427–429 Index methoxime 545, 546 methylene – blue 168, 474 – chloride 342, 344, 354, 355, 467 methylmercury 374–377 microangiopathic haemolytic anaemia (MAHA) 241, 248, 269 microcystin 564 milleporin-1 225, 226 mimosine 152 Minamata disease 375 modeccin toxin 564 moniliformin 36 morphine 142, 180, 181, 183, 186, 195, 324, 494, 500, 502, 510, 520–523, 582, 588, 589, 593, 595, 597 multiple-dose activated charcoal (MDAC) 402, 404–406 muscle relaxants 510, 580, 593 mygalomorphs 271 myotoxicity 253, 263, 264 Myrmecia 275 N-acetylcysteine (NAC) 52, 410, 413–415 N-acetyl-D,L-penicillamine 375 naloxone 398, 438, 439, 521–523 necrotoxins 241, 254 nematocysts 216, 217, 221, 225, 279 nephrotoxin 44, 57, 240, 254 Nerium oleander 124, 141, 151, 161, 170, 432 nerve agents 544–546 neuroexcitatory envenoming 236, 246, 247, 259, 262, 270–272 neurotoxic shellfish poisoning (NSP) 83, 102, 103, 105 nickel 359, 468, 470 nicotine 130, 134, 141, 180, 181 nitrogen mustard 546, 547 nivalenol (NIV) 33, 50 Notechis 237, 249, 263 obidoxime 545, 546 Index ochratoxicosis 38, 41 ochratoxin A (OTA) 33, 36, 41–46, 49, 56, 57 octreotide 420–423 okadaic acid (OA) 65, 68, 70, 74– 77, 83, 85, 95–97, 103, 104 oleandrin 141, 161 opioids 322, 400, 401, 403, 415, 430, 438, 439, 494, 502, 510, 511, 520, 521, 524, 580, 584, 588, 593, 594, 596, 597 oral fluid testing 494, 498, 504, 508 organophosphates 544, 595 Orthopoxvirus variola 569 osmolar gap 347–349, 353 Ostreopsis 66, 67, 81, 105, 106 oxalates 125–129, 131–134, 141, 145, 147, 148, 150, 152, 164, 344 oxycodone 438, 494, 511, 520, 521, 588, 593, 598 paclitaxel 179, 193 Palythoa toxica 65, 70, 81 palytoxin (PlTX) 65, 68, 70, 81, 83, 86, 87, 91–93, 105, 106 Papaver somniferum 142, 181, 510 paralytic shellfish poisoning (PSP) 68, 102 patulin 33, 36, 43, 46, 50, 54, 57 pectenotoxin (PTX) 70, 77–79, 85, 99, 101 D-penicillamine 369, 373, 375, 384 penitrem A (tremortin) 45 phencyclidine (PCP) 322, 411, 494, 501, 511, 512, 520, 524, 532, 580, 588 phenobarbital 401, 405, 408, 410, 416, 527, 529 Phoneutria 234, 273, 294, 295, 304, 306 phosgene 466, 468, 551 phosphoprotein phosphatase (PPase) 77, 95, 96 photosensitization 44, 127, 133, 138, 147, 148, 156 Phyllobates 306 617 Physalia physalis (“bluebottle”, Portuguese Man-of-War) 216, 219, 221, 280 physalitoxin 219 Physostigma venenosum 181, 415 physostigmine 158, 180, 181, 189, 398, 415, 416, 548, 549 phytoestrogens 199, 200 pinnatoxin 82 piperidine alkaloids 151, 154, 156 plague 560, 566, 569 plancinin 226 plancitoxin I, II 226–228 pneumoconiosis 467–470, 480 pneumonic plague 569 pneumonitis, chemical 340, 354– 357 podophyllotoxin 138, 179, 181 Podophyllum peltatum 143, 181 poison hemlock 130, 131, 150–153, 580 polyethylene glycol (PEG) 384, 406, 407 pore forming toxins (PFTs) 3, 215, 219 pralidoxime 545, 546 prazosin 259, 270 procoagulant 238–240, 276 propoxyphene 400, 440, 494, 511, 521, 596, 597 n-propyl disulfide 126, 152, 167 prorocentrolide 70, 82 prunasin 144, 159 Prussian blue 387 Pseudechis 249, 250, 263 Pseudomonas aeruginosa 10 ptaquiloside 162 pteriatoxin 82 Pteridium aquilinum 152, 162 Pterois 277 Ptychodiscus brevis 83, 303, 306 puffer fish 71, 102, 306 pumiliotoxins 277 pyridostigmine 545 pyridoxine 126, 350, 401, 423–425 618 pyrogallol 144, 165 pyrrolizidine alkaloids (PAs) 187, 124, 154–156 QNB (3-quinuclidinyl benzilate) 548 quinine 180, 181, 188, 189, 400, 420, 422, 589, 593 quinolizidine alkaloids 130, 132, 139, 140, 151, 156, 184, 185 rattlesnakes 236, 240, 244, 267 recluse spiders 234, 241, 248, 273, 294 Reye’s syndrome 32, 35 rhodanese 159, 160 ricin 145, 163, 164, 553, 564, 571 ricinine 164 Ricinus communis 145, 152, 163, 564, 571 Rickettsia 564, 568 riot-control agents 543, 551, 552 robustoxin 302, 303 rubratoxin 44 sanitizers 341 sarafatoxins 264 sarin 544, 561 saxitoxin (STX) 65, 68, 69–73, 77, 80, 86–88, 102, 304, 306, 564 scopolamine 128, 129, 133, 137, 157, 200, 201, 327, 328, 523, 580 scorpion – α-toxin 303, 304, 307 – β-toxin 304, 307, 308 sea anemone toxins 303, 304, 307 selenosis 162, 163 senecionine 187 serotonin – reuptake inhibitors (SSRIs) 322, 597 – syndrome 411, 412 shellfish poisoning 68, 74, 76, 77, 80, 83, 94, 101–106 shiga toxin 57, 564 smallpox 560, 564, 569 snake venom detection kit (SVDK) 255 Index sodium thiosulfate 160, 171, 550 Solenopsis 275 soman 544 speedball 524 sphingofungin 36 sphingomyelinase D 241, 294 sporidesmin 36, 44 St Anthony’s fire 32 stachybotryotoxicosis 32, 40 staphylococcal enterotoxin B (SEB) 555, 564 sterigmatocystin 44–46, 49 strychnine 128, 180, 181, 398 sulfur mustard 545, 547 superantigen (SAg) 5, swainsonine 36 sweat testing 499, 500, 506, 510 syrup of ipecac 398, 403, 404, 531, 533 T-2 toxin 33, 37, 39, 43, 44, 52, 555, 556, 564 tabun 544 tacrine 548, 549 taipoxin 225 Taxus 124, 148, 193, 438 tear gases 551 tetanus neurotoxin (TeNT) 16, 17 tetrachloroethylene 354–356 Δ9-tetrahydrocannabinol (THC) 130, 196, 493, 494, 502, 507, 530– 532, 595, 596 tetrodotoxin (TTX) 72, 86, 88, 102, 214, 281, 303, 304, 306, 564 textilotoxin 214, 225 thallium 384–387, 580 THC (Δ9-tetrahydrocannabinol) 130, 196, 493, 494, 502, 507, 530– 532, 595, 596 therapeutic drug monitoring (TDM) 318, 327, 583, 592 Thevetia peruviana 148, 432 thiaminase 134, 152, 162 thimerosal 376 thujone 128, 148, 357 toxalbumin 125, 132, 137, 138, 142, Index 143, 145, 149, 163 toxic shock syndrome (TSS) tramadol 326, 521 tremorgens 37, 45, 55 trichloroethylene 354–356 trichothecene 33, 39, 42, 43, 45, 50–52, 555, 556 tricyclic antidepressant (TCA) 322, 324, 415, 436 trimedoxime 545, 546 tropane alkaloids 151, 157 tularemia 564, 565, 568 typhus – endemic 568 – epidemic 564, 568 urinary alkalinization 402, 407, 408, 427 urine drug screening (UDS) 401, 496 Urov disease 32 urushiol 148, 196 V-agents 544 valproic acid (VPA) 416–419 variola virus 563, 569 veratridine 304, 306, 307 Veratrum 149–151, 157, 306 verotoxin 564 versutoxin 302, 303 vesicants 545–548 Vibrio cholerae 9, 561, 564 vinblastine 149, 195 vincristine 149, 195 viperid snakes 236, 240, 264–266 viscumin 149, 564 volatile organic compounds (VOCs) 462, 479 volkensin 564 voltage-sensor trapping model 293, 307 vomiting agents 551, 552 vomitoxin 35 VX gas 544 Widmark’s equation 347 widow spiders 234, 272, 294, 295, 309 619 wortmannin 37, 56 Yersinia pestis 564, 569 yessotoxin (YTX) 70, 79, 80, 83, 85, 97–100 zearalenone 33, 37, 39, 43, 44, 46, 50, 54 zolpidem 593, 597 zopiclone 593, 597 [...]... the series focused on environmental toxicology to be published shortly Andreas Luch Berlin, October 2009 Molecular, Clinical and Environmental Toxicology Volume 2: Clinical Toxicology Edited by A Luch © 2010 Birkhäuser Verlag/Switzerland 1 Toxins from bacteria James S Henkel1, Michael R Baldwin2 and Joseph T Barbieri1 1 2 Medical College of Wisconsin, Department of Microbiology and Molecular Genetics,... to nicely and comprehensively cover a specific topic in the field of clinical toxicology (resp toxinology) The main goal of this volume was to outline and to communicate the diversity in this field and the great and exciting story of highly potent biogenic and synthetic toxins, as well as the routine and advanced means applied in the clinics to battle against Preface XIII accidental or intended intoxication... pleased to deliver the second volume of the series on Molecular, Clinical and Environmental Toxicology” to the public today All authors, the editorial office of Birkhäuser and I have been working very hard during the past months to get the promise made at the end of last year into reality After the first volume on molecular toxicology, this second part is dedicated to clinically relevant aspects of toxicology... toxicology, forensic toxicology, and – of course – the highly and publicly debated topics of chemical and biological warfare agents While analytical and forensic toxicology are key in detecting and elucidating compoundinduced tissue and organ damage or failure due to intoxication, poisoning and envenomation in living and dead patients alike, the chapter on inhalation toxicology is meant to put more emphasis... elongation factor-2 Diphtheria toxin is a 535-amino acid AB toxin; the N terminus encodes the ADP-ribosyltransferase activity and the C terminus comprises a translocation domain and a C-terminal receptor binding domain Diphtheria toxin binds to a growth factor receptor to traffic into early endosomes via receptor-mediated endocytosis where hydrophobic α-helixes of the translocation domain insert into the... Interestingly, among the “top 10” toxins, all of which are of biogenic origin, small molecules are scarce and actually only represented by two exceptionally sizeable compounds, i.e., maitotoxin (LD50 ~ 0.1 μg/kg) and palytoxin (LD50 ~ 0.15 μg/kg), and by batrachotoxin (LD50 ~ 2 μg/kg) By contrast, the remaining, usually well-known and more typical, small toxins (saxitoxin, tetrodotoxin, ciguatoxins, etc.) are... properties of protein toxins The determination that protein toxins were often organized into discrete domains, which comprise a catalytic, receptor binding, and translocation domain, allowed rapid development of vaccines to control disease The next chapter in the study of protein toxin action is to utilize our understanding of toxin structure function to develop toxins for immunological and therapeutic intervention... clathrin-mediated endocytosis [101] and ADP-ribosylation of ezrin/radixin/moesin caused cytoskeletal defects [102] ExoS binds a cellular cofactor to express ADP-ribosyltransferase activity The factor was termed ‘factor activating exoenzyme S’ (FAS) and later identified as a 14-3-3 protein [103] Activation of a cytotoxin upon binding to a host protein is becoming a common feature of toxin action Current... medicine and natural sciences, interested in gaining more insight into how potent toxins work in the body and into the issue of adequate counteractions and remedies to be applied in the clinics to help patients survive the imminent danger executed by potentially deadly chemicals, peptides or proteins intruding into their body Last but not least, I want to express my special gratitude to the editorial... protein subunits and has been implicated in the secretion process upon conformational changes [94] The needle tip proteins appear to be adaptors that link the translocator proteins within the host membrane to the needle body for efficient transfer of cytotoxins Translocator proteins form a host membrane-spanning pore for the TTSS effectors [95] The translocon protein complex prevents cytotoxin secretion