DOCSLIB.ORG

Principles of Toxicology: the Study of Poisons

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Principles of Toxicology: the Study of Poisons Principles of Toxicology: The Study of Poisons Arizona Water Issues The University of Arizona – HWR 203 1 Adopted from: Casarez/ Donnelly The study of the adverse effects of a toxicant on living organisms • Adverse effects – any change from an organism’s normal state – dependent upon the concentration of active compound at the target site for a sufficient time. • Toxicant (Poison) – any agent capable of producing a deleterious response in a biological system Arizona Water Issues The University of Arizona – HWR 203 2 Adopted from: Casarez/ Donnelly Axioms of Toxicology • There is a dosage or exposure level that has no observable effect on the health of animals – as measured by methods which have a finite sensitivity to measure dysfunction or injury. (NOAEL) Does this mean it is safe? • Any substance can provoke a dysfunction or injury at some degree of exposure – the dose makes the poison. Attenuation of injury can often be achieved by dilution. Complications can occur when there is exposure to more than one agent – even at “non-toxic” doses. In general, laboratory studies do not look at these complicated cases. What does this say about the state of our knowledge? Arizona Water Issues The University of Arizona – HWR 203 3 Adopted from: Casarez/ Donnelly Axioms of Toxicology • There is essential uniformity in the biochemistry in similar species – among biological mechanisms in mammals. This means animal data is extrapolated for predictions in humans. What are advantages/disadvantages of animal testing? • Toxicological data from animal experiments can be used to assess the degree of exposure or dosage that will NOT adversely affect human health. However, potential or real differences between animals and humans require that judgmental factors be applied when extrapolating animal threshold doses in order to insure an adequate margin of safety for humans. Animal testing must be extrapolated carefully We should error on the side of caution Arizona Water Issues The University of Arizona – HWR 203 4 Adopted from: Casarez/ Donnelly Dose Dose: The amount of chemical entering the body This is usually given as mg of chemical/kg of body weight = mg/kg The dose is dependent upon: * The environmental concentration * The properties of the toxicant *The frequency of exposure *The length of exposure * The exposure pathway (route) Arizona Water Issues The University of Arizona – HWR 203 5 Adopted from: Casarez/ Donnelly What is a Response? The degree and spectra of responses depend upon the dose and the organism • Change from normal state – could be on the molecular, cellular, organ, or organism level--the symptoms • Local vs. Systemic • Reversible vs. Irreversible • Immediate vs. Delayed • Graded or Quantal – continually varying vs. all-or-none Arizona Water Issues The University of Arizona – HWR 203 6 Adopted from: Casarez/ Donnelly Dose-Response Relationship: As the dose of a toxicant increases, so does the response 4 Limitations • Often derived from acute exposure data. • Species variation 3 RESPONSE Ranges: 4 Maximum Response 2 2-3 Linear Range 0-1 NOAEL 0 1 DOSE Dose determines the biological response Arizona Water Issues The University of Arizona – HWR 203 7 Adopted from: Casarez/ Donnelly LD50 • If Mortality is the 100% response, the dose that is lethal to 50% of the population LD50 can be generated from this 50% curve Not everybody reacts in the same way to a toxic exposure LD (or ED) 50 Dose 10-30 fold variation w/in a population! Arizona Water Issues The University of Arizona – HWR 203 8 Adopted from: Casarez/ Donnelly LD50 Comparison Chemical LD50 (mg/kg) Ethyl Alcohol 10,000 Sodium Chloride 4,000 Ferrous Sulfate 1,500 Morphine Sulfate 900 Strychnine Sulfate 150 Nicotine 1 (1 mg) Black Widow 0.55 Curare 0.50 Rattle Snake 0.24 Dioxin (TCDD) 0.001 Botulinum toxin 0.0001 Different toxicants can be compared--lowest dose is most potent Arizona Water Issues The University of Arizona – HWR 203 9 Adopted from: Casarez/ Donnelly Sources of Caffeine Source Amount Dose if 150lbs mg / 12 oz ie. 68 kg Coffee - brew 137-260 250/16oz or 3.6 mg/kg Coffee - decaf 5 Iced tea 70 Nestea 25 Coke 34 102/36oz or 1.5 mg/kg Mt. Dew 55 Monster, RedBull 80-160 240/24oz or 3.5 mg/kg Source: www.energyfiend.com/the-caffeine-database Arizona Water Issues The University of Arizona – HWR 203 10 Adopted from: Casarez/ Donnelly Read Carefully! “The actual caffeine content for many energy drinks is not easily identified on product packaging or via the Internet. The total amount of caffeine contained in some cans or bottles of energy drinks can exceed 500 mg (equivalent to 14 cans of common caffeinated soft drinks) and is clearly high enough to result in caffeine toxicity.23 A lethal dose of caffeine is considered to be 200 to 400 mg/kg.24” Clinical Report–Sports Drinks and Energy Drinks for Children and Adolescents: Are They Appropriate? Guidance for the Clinician in Rendering Pediatric Care: www.pediatrics.org/cgi/doi/10.1542/peds.2011-0965 WARNING: distinguish amount from dose Arizona Water Issues The University of Arizona – HWR 203 11 Adopted from: Casarez/ Donnelly Toxicity vs. Health Impacts “MY COUSIN IS 16 YEARS OLD AND HE WOULD DRINK UP TO FIVE MONSTERS A DAY. FOR THE PAST MONTH HES BEEN ACTING REALLY WEIRD. HE TALKS TO HIMSELF, HES REALLY SHAKY, HE CANT SIT NOT EVEN FOR A MINUTE. HE HAS TO BE MOVING AND HE SLEEPS ALOT THE FAMILY IS SO WORRIED. ITS SCARY TO SEE WHAT A ENERGY DRINK IS DOING TO MY TEENAGE COUSIN.” Anonymous www.aboutlawsuits.com/energy-drink-health-risk-warnings-1161/ Arizona Water Issues The University of Arizona – HWR 203 12 Adopted from: Casarez/ Donnelly Exposure Routes & Doses Chemical Animal Route LD50 Dose Caffeine Mouse Oral 620 mg/kg Rat Oral 192 mg/kg Rat IV 105 mg/kg Mouse IV 68 mg/kg Amt: 200 g rat 38 mg; 70 kg person 13,440 mg = 54 cups HgCl (II) Rat Oral 37 mg/kg Mouse Oral 10 mg/kg Dimethylarsenic Rat Oral 700 mg/kg (cotton defoilant) Arizona Water Issues The University of Arizona – HWR 203 13 Adopted from: Casarez/ Donnelly Factors Influencing Toxicity • Related to the: – chemical –person – exposure – environment Arizona Water Issues The University of Arizona – HWR 203 14 Adopted from: Casarez/ Donnelly The Human Factors • Gender •Age • Duration • Route of exposure • Genetics • Species variation Arizona Water Issues The University of Arizona – HWR 203 15 Adopted from: Casarez/ Donnelly Individual Susceptibility There can be 10-30 fold difference in response to a toxicant in a population • Genetics-species, strain variation, interindividual variations (yet still can extrapolate between mammals--similar biological mechanisms) • Gender (gasoline nephrotox in male mice only) • Age--young (old too) – underdeveloped excretory mechanisms – underdeveloped biotransformation enzymes – underdeveloped blood-brain barrier Arizona Water Issues The University of Arizona – HWR 203 16 Adopted from: Casarez/ Donnelly Individual Susceptibility • Age--old – changes in excretion and metabolism rates, body fat • Nutritional status • Health conditions • Previous or Concurrent Exposures – additive --antagonistic – Synergistic The disadvantaged are often more susceptible Arizona Water Issues The University of Arizona – HWR 203 17 Adopted from: Casarez/ Donnelly Exposure: Duration Acute < 24hr usually 1 exposure Subacute 1 month repeated doses Subchronic 1-3mo repeated doses Chronic > 3mo repeated doses Over time, the amount of chemical in the body can build up, it can redistribute, or it can overwhelm repair and removal mechanisms Arizona Water Issues The University of Arizona – HWR 203 18 Adopted from: Casarez/ Donnelly Exposure: Pathways • Routes and Sites of Exposure – Injection • intravenous – Inhalation (Lungs) – Injection • Intraperitoneal, intramuscular – Ingestion (Gastrointestinal Tract) – Dermal/Topical (Skin) • Typical Effectiveness of Route of Exposure iv > inhale > ip > im > ingest > topical Arizona Water Issues The University of Arizona – HWR 203 19 Adopted from: Casarez/ Donnelly Response to Toxic Substances • Skin/eyes • Central Nervous system • Respiratory tract • Circulation system • Liver / Kidneys • Digestive system • Reproductive system • Bones and joints • Cancer and others Arizona Water Issues The University of Arizona – HWR 203 20 Adopted from: Casarez/ Donnelly Target Organs: adverse effect is dependent upon the concentration of active compound at the target site for enough time • Not all organs are affected equally – greater susceptibility of the target organ – higher concentration of active compound • Liver--high blood flow, oxidative reactions • Kidney--high blood flow, concentrates chemicals • Lung--high blood flow, site of exposure • Neurons--oxygen dependent, irreversible damage • Myocardium--oxygen dependent • Bone marrow, intestinal mucosa--rapid divide Arizona Water Issues The University of Arizona – HWR 203 21 Adopted from: Casarez/ Donnelly ADME: Absorption, Distribution, Metabolism, and Excretion • Once a living organism has been exposed to a toxicant, the compound must get into the body and to its target site in an active form in order to cause an adverse effect. • The body has defenses: – Membrane barriers • passive and facilitated diffusion, active transport – Biotransformation enzymes, antioxidants – Elimination mechanisms Arizona Water Issues The University of Arizona – HWR 203 22 Adopted from: Casarez/ Donnelly Absorption: ability of a chemical to enter the blood • Inhalation--readily absorb gases into the blood stream via the alveoli. (Large alveolar surface, high blood flow, and proximity of
Load more

Recommended publications
  • Ethylene Glycol
    NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Ethylene Glycol January 2004 NIH Publication No. 04-4481 Table of Contents Preface .............................................................................................................................................v Introduction .................................................................................................................................... vi NTP Brief on Ethylene Glycol .........................................................................................................1 References ........................................................................................................................................4 Appendix I. NTP-CERHR Ethylene Glycol / Propylene Glycol Expert Panel Preface ..............................................................................................................................I-1 Expert Panel ......................................................................................................................I-2 Appendix II. Expert Panel Report on Ethylene Glycol ............................................................... II-i Table of Contents ........................................................................................................... II-iii Abbreviations ...................................................................................................................II-v List of Tables ...............................................................................................................
    [Show full text]
  • TOXICOLOGY and EXPOSURE GUIDELINES ______(For Assistance, Please Contact EHS at (402) 472-4925, Or Visit Our Web Site At
    (Revised 1/03) TOXICOLOGY AND EXPOSURE GUIDELINES ______________________________________________________________________ (For assistance, please contact EHS at (402) 472-4925, or visit our web site at http://ehs.unl.edu/) "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy." This early observation concerning the toxicity of chemicals was made by Paracelsus (1493- 1541). The classic connotation of toxicology was "the science of poisons." Since that time, the science has expanded to encompass several disciplines. Toxicology is the study of the interaction between chemical agents and biological systems. While the subject of toxicology is quite complex, it is necessary to understand the basic concepts in order to make logical decisions concerning the protection of personnel from toxic injuries. Toxicity can be defined as the relative ability of a substance to cause adverse effects in living organisms. This "relative ability is dependent upon several conditions. As Paracelsus suggests, the quantity or the dose of the substance determines whether the effects of the chemical are toxic, nontoxic or beneficial. In addition to dose, other factors may also influence the toxicity of the compound such as the route of entry, duration and frequency of exposure, variations between different species (interspecies) and variations among members of the same species (intraspecies). To apply these principles to hazardous materials response, the routes by which chemicals enter the human body will be considered first. Knowledge of these routes will support the selection of personal protective equipment and the development of safety plans. The second section deals with dose-response relationships.
    [Show full text]
  • Lead Poisoning
    3 Dec 2003 21:51 AR AR206-ME55-13.tex AR206-ME55-13.sgm LaTeX2e(2002/01/18) P1: GBC 10.1146/annurev.med.55.091902.103653 Annu. Rev. Med. 2004. 55:209–22 doi: 10.1146/annurev.med.55.091902.103653 Copyright c 2004 by Annual Reviews. All rights reserved First published online as a Review in Advance on Aug. 18, 2003 LEAD POISONING Herbert Needleman Professor of Psychiatry and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; email: [email protected] ■ Abstract Understanding of lead toxicity has advanced substantially over the past three decades, and focus has shifted from high-dose effects in clinically symptomatic individuals to the consequences of exposure at lower doses that cause no symptoms, particularly in children and fetuses. The availability of more sensitive analytic methods has made it possible to measure lead at much lower concentrations. This advance, along with more refined epidemiological techniques and better outcome measures, has lowered the least observable effect level until it approaches zero. As a consequence, the segment of the population who are diagnosed with exposure to toxic levels has expanded. At the same time, environmental efforts, most importantly the removal of lead from gasoline, have dramatically reduced the amount of lead in the biosphere. The remaining major source of lead is older housing stock. Although the cost of lead paint abatement is measured in billions of dollars, the monetized benefits of such a Herculean task have been shown to far outweigh the costs. INTRODUCTION In recent years, the focus in lead poisoning has shifted away from adults exposed to high doses in industrial settings to the larger population of asymptomatic chil- dren with lesser exposures.
    [Show full text]
  • Mercury Study Report to Congress
    United States EPA-452/R-97-007 Environmental Protection December 1997 Agency Air Mercury Study Report to Congress Volume V: Health Effects of Mercury and Mercury Compounds Office of Air Quality Planning & Standards and Office of Research and Development c7o032-1-1 MERCURY STUDY REPORT TO CONGRESS VOLUME V: HEALTH EFFECTS OF MERCURY AND MERCURY COMPOUNDS December 1997 Office of Air Quality Planning and Standards and Office of Research and Development U.S. Environmental Protection Agency TABLE OF CONTENTS Page U.S. EPA AUTHORS ............................................................... iv SCIENTIFIC PEER REVIEWERS ...................................................... v WORK GROUP AND U.S. EPA/ORD REVIEWERS ......................................viii LIST OF TABLES...................................................................ix LIST OF FIGURES ................................................................. xii LIST OF SYMBOLS, UNITS AND ACRONYMS ........................................xiii EXECUTIVE SUMMARY ......................................................... ES-1 1. INTRODUCTION ...........................................................1-1 2. TOXICOKINETICS ..........................................................2-1 2.1 Absorption ...........................................................2-1 2.1.1 Elemental Mercury ..............................................2-1 2.1.2 Inorganic Mercury ..............................................2-2 2.1.3 Methylmercury .................................................2-3 2.2 Distribution
    [Show full text]
  • From Murder to Mechanisms 7000 Years of Toxicology's Evolution
    From Murder to Mechanisms 7000 Years of Toxicology’s Evolution 7000 Years of Toxicology’s Evolution Michael A. Gallo, PhD, DABT (ret), Emeritus Fellow ATS Professor Emeritus Environmental and Occupational Health Sciences Institute Rutgers-Robert Wood Johnson Medical School Piscataway, New Jersey Toxicants: Friends or Foes? “The dose makes the poison” Paracelsus 1493-1541 Objectives This presentation provides a history of toxicology with a few classic examples. The Family of Toxicology Poisons Signs, Symptoms, Adverse Reactions & Antidotes Drugs Patent Medicines and Chemotherapeutics Food Natural toxicants Industrial Chemicals Occupational and Environmental Toxicity Safety Evaluation Hazard Identification Tools to Elucidate Biology Toxicology the Borrowing Science • Pharmacology • Pathology • Physiology • Biochemistry • Synthetic Chemistry • Analytical Chemistry • Molecular and Cellular Biology • High Resolution Imaging Earliest Humans* • Use of natural toxins • Oral history evolved • Animal venoms • Toxic metals • Plant extracts – Hunting* – Warfare – Assassination * still used by indigenous people in S. America, Borneo, Pacific Islanders Ebers Papyrus ~1500 BCE • Hemlock • Aconite (buttercup family) • Opium • Lead • Copper • Antimony • Venoms Hippocrates and Friends • Defined effective dosages of toxin • Described bioavailability • Theophastus (370-286 BCE) – De Historia Plantanum • Socrates- Hemlock • Dioscorides (Nero)poison classes through 19th • Discovery of BellaDonna (scopolamine) • Discovery of Digitalis (foxglove)Dioscorides
    [Show full text]
  • Early Changes in Striatal Neuron Morphology and Dopamine Metabolism
    Disease-Toxicant Interactions in Manganese Exposed Huntington Disease Mice: Early Changes in Striatal Neuron Morphology and Dopamine Metabolism Jennifer L. Madison1,2, Michal Wegrzynowicz2, Michael Aschner1,3,4,5,6, Aaron B. Bowman2,3,4,5,6* 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 2 Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 3 Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 4 Vanderbilt University Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 5 Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 6 Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America Abstract YAC128 Huntington’s disease (HD) transgenic mice accumulate less manganese (Mn) in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl2-4H2O (50 mg/kg) on days 0, 3 and 6. Striatal medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13 weeks (7 days from initial exposure) and 16 weeks (28 days from initial exposure). No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age- dependent increase in dendritic length and branching complexity.
    [Show full text]
  • Taking an Exposure History
    Case Studies in Environmental Medicine Course: SS3046 Revision Date: June 2000 Original Date: October 1992 Expiration Date: June 30, 2006 TAKING AN EXPOSURE HISTORY Environmental Alert Because many environmental diseases either manifest as common medical problems or have nonspecific symptoms, an exposure history is vital for correct diagnosis. By taking a thorough exposure history, the primary care clinician can play an important role in detecting, treating, and preventing disease due to toxic exposure. This monograph is one in a series of self-instructional publications designed to increase the primary care provider’s knowledge of hazardous substances in the environment and to aid in the evaluation of potentially exposed patients. This course is also available on the ATSDR Web site, www.atsdr.cdc. gov/HEC/CSEM/. See page 3 for more information about continuing medical education credits, continuing nursing education units, and continuing education units. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency for Toxic Substances and Disease Registry Division of Toxicology and Environmental Medicine Taking an Exposure History Table of Contents ATSDR/DHEP Revision Authors: William Carter, MD; Deanna K. Case Study ............................................................................................. 5 Harkins, MD, MPH; Ralph O’Connor Jr, PhD; Darlene Johnson, RN, BSN, MA; Pamela Tucker, MD Introduction ............................................................................................ 5 ATSDR/DHEP Revision Planners: Diane Dennis-Flagler,
    [Show full text]
  • Toxidrome-Based Approach to Common Poisonings
    ASIA PACIFIC JOURNAL of MEDICAL TOXICOLOGY APJMT 3;1 http://apjmt.mums.ac.ir March 2014 REVIEW ARTICLE Toxidrome-based Approach to Common Poisonings BRUNO MÉGARBANE* Reanimation and Medical Toxicology Department, University Paris-Diderot, Paris, France Abstract Poisoning remains a major cause of hospital admission into the emergency department and intensive care unit. Proper diagnosis is the cornerstone for optimal management of poisoned patients. Since the definitive analytical confirmation of the nature of the toxicant involved in the poisoning cannot be rapidly obtained in the majority of healthcare facilities, diagnosis relies on the medical history and the rigorous clinical examination of the patients well as results of the routine biological tests and the electrocardiogram. Identification of the toxidromes addresses not only the correct diagnosis but also rules out other differential diagnoses. Despite no definitive predictive value, this clinical approach facilitates making decision on empirical treatments and emergent antidotes. Pharmacodynamic tests using specific antidotes including naloxone for opioids and flumazenil for benzodiazepines and its analogues are also helpful to assess the final diagnosis in comatose patients. The objective of this article is to review the toxidrome- based approach to common poisonings before toxicological analysis enables the confirmation of the initially suspected toxic etiology. Keywords: Anticholinergic Syndrome; Poisoning; Serotonin Syndrome; Substance Withdrawal Syndrome; Toxidrome How to cite this article: Mégarbane B. Toxidrome-based Approach to Common Poisonings. Asia Pac J Med Toxicol 2014;3:2-12. be individualized for each patient (4): INTRODUCTION 1) The patient has been exposed intentionally or Drug poisoning, either accidental or intentional, accounts accidentally to a toxic agent, but his/her clinical for one of the most common causes of admission to the examinations are normal.
    [Show full text]
  • Toxicity Identification Evaluation: Characterization of Chronically Toxic Effluents, Phase I
    United States Office of Research and EPA/600/6-91/005F Environmental Protection Development May 1992 Agency Washington, DC 20460 EPA Toxicity Identification Evaluation: Characterization of Chronically Toxic Effluents, Phase I EPA/600/6-91/005F May, 1992 Toxicity Identification Evaluation: Characterization of Chronically Toxic Effluents, Phase I T.J. Norberg-King Environmental Research Laboratory Duluth, MN 55804 D.I. Mount, J.R. Amato, D.A. Jensen, and J.A. Thompson AScl Corporation Duluth, MN 55804 National Effluent Toxicity Assessment Center Technical Report 02-92 Environmental Research Laboratory Office of Research and Development U.S. Environmental Protection Agency Duluth, MN 55804 Printed on Recycled Paper Disclaimer This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. ii Foreword This guidance document has been prepared to assist dischargers and/or their consultant laboratories in conducting chronic aquatic toxicity identification evaluations (TIES). TIES may be required by the state or federal agencies as a result of enforcement actions or as a condition of the discharger’s National Pollutant Discharge Elimination System (NPDES) permit or may be conducted voluntarily by permittees. This document will assist the state and federal agencies and permittees in overseeing and determining the adequacy of the TIE in toxicity reduction evaluations (TREs). This document
    [Show full text]
  • Introduction to Toxicology
    Toxicology TRAINING FOR THE HEALTH SECTOR Introduction to Toxicology Children's Health and the Environment CHEST Training Package for the Health Sector <<NOTE TO USER: Please add details of the date, time, place and sponsorship of the meeting for which you are using this presentation.>> 1 Toxicology Definition Toxicology Definition of toxicology is "the study of the adverse effects of chemicals or physical agents on living organisms The traditional definition of toxicology is "the science of poisons." As our understanding of how various agents can cause harm to humans and other organisms, a more descriptive definition of toxicology is "the study of the adverse effects of chemicals or physical agents on living organisms". Adverse effects may occur in many forms, ranging from immediate death to subtle changes not realized until months or years later. They may occur at various levels within the body, such as an organ, a type of cell, or a specific biochemical. Knowledge of how toxic agents damage the body has progressed along with medical knowledge. It is now known that various observable changes in anatomy or body functions actually result from previously unrecognized changes in specific biochemicals in the body. The textbooks listed below are quite comprehensive and widely used in basic toxicology training courses. Casarett and Doull's Toxicology (C. Klaassen, M. Amdur, and J. Doull, eds.) Principles and Methods of Toxicology (A. W. Hayes, ed.) Basic Environmental Toxicology (L. Cockerham and B. Shane, eds.) 2 Toxicology Philippus Theophrastus Aureolus Bombastus von Hohenheim PARACELSUS (Einsiedeln, Zürich, 1493 - Salzburg, 1541) All substances are poisons; it is the dose that makes the poison The historical development of toxicology began with early cave dwellers who recognized poisonous plants and animals and used their extracts for hunting or in warfare.
    [Show full text]
  • Forensic Toxicity Testing
    CHAPTER 14 Forensic Toxicity Testing I. Forensic toxicity testing A. Analytic chemistry melded with organ damage consistent with the compound and concentration found (consonance of data) 1. Most intentional poisoning deaths ϭ suicide; most unintentional poisoning deaths from overdose of opioids and cocaine; toxicity from ethanol, drugs of abuse, overuse of medications lead car crash causes; unintentional nonfatal poisonings causes by opioids Ͼ benzodiazepines 2. Most exposures were oral 3. Sampling of tissues a. Living being is preferred as death results in tissue destruction, possible loss of toxicant, and redistribution of toxicant (from organ to plasma resulting in false poisoning indication if plasma is the key item utilized) For humans: take 15 mL of blood for ethanol/toxicants Take 30 mL urine for metabolites Hair samples (pulled not cut) for drugs of abuse (e.g., methamphetamine in child’s hair from house manufacturing this drug) → extraction with HCl → enzymatic treatment ␤ → → (Pronase or -glucuronidase) hot CH3OH extraction hot NaOH disintegration and extraction Metals → urine, blood, and hair samples ϩ possibly fingernails (As especially) Teeth for chronic exposure to Pb in children (1) Therapeutic drug monitoring (a) Required for highly lipophilic medications or pharmacokinetics, vary widely by patient (b) Also may be a function of a larger loading dose, long half-life, and narrow therapeutic range for action vs. toxicity (digitalis as loading dose needed to establish 0.5–1.5 or 2.0 ng/mL therapeutic range, 2 ng/mL toxicity,
    [Show full text]
  • Ontogeny of Venom Use and Venom Composition in the Western Widow Spider Latrodectus Hesperus David Roger Nelsen
    Loma Linda University TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works Loma Linda University Electronic Theses, Dissertations & Projects 6-2013 Ontogeny of Venom Use and Venom Composition in the Western Widow Spider Latrodectus Hesperus David Roger Nelsen Follow this and additional works at: http://scholarsrepository.llu.edu/etd Part of the Behavior and Ethology Commons, Biology Commons, Developmental Biology Commons, Public Health Commons, and the Social and Behavioral Sciences Commons Recommended Citation Nelsen, David Roger, "Ontogeny of Venom Use and Venom Composition in the Western Widow Spider Latrodectus Hesperus" (2013). Loma Linda University Electronic Theses, Dissertations & Projects. 292. http://scholarsrepository.llu.edu/etd/292 This Dissertation is brought to you for free and open access by TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. It has been accepted for inclusion in Loma Linda University Electronic Theses, Dissertations & Projects by an authorized administrator of TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. For more information, please contact [email protected]. LOMA LINDA UNIVERSITY School of Public Health in conjunction with the Faculty of Graduate Studies ____________________ Ontogeny of Venom Use and Venom Composition in the Western Widow Spider Latrodectus hesperus By David Roger Nelsen ____________________ A Dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Biology ____________________ June 2013 UMI Number: 3566117 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted.
    [Show full text]