Module One Introduction to Toxicology
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Understanding Lead Uptake and Effects Across Species Lines: a Conservation Medicine Based Approach
UNDERSTANDING LEAD UPTAKE AND EFFECTS ACROSS SPECIES LINES: A CONSERVATION MEDICINE BASED APPROACH MARK A. POKRAS AND MICHELLE R. KNEELAND Center for Conservation Medicine, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Rd., North Grafton, MA 01536, USA. E-mail: [email protected] ABSTRACT.—Conservation medicine examines the linkages among the health of people, animals and the environment. Few issues illustrate this approach better than an examination of lead (Pb) toxicity. We briefly review the current state of knowledge on the toxicity of lead and its effects on wildlife, humans, and domestic animals. Lead is cheap and there is a long tradition of its use. But the toxic effects of Pb have also been recognized for centuries. As a result, western societies have greatly reduced many traditional uses of Pb, including many paints, gasoline and solders because of threats to the health of humans and the environment. Legisla- tion in several countries has eliminated the use of lead shot for hunting waterfowl. Despite these advances, a great many Pb products continue to be readily available. Conservationists recognize that hunting, angling and shooting sports deposit thousands of tons of Pb into the environment each year. Because of our concerns for human health and over 100 years of focused research, we know the most about lead poisoning in people. Even today, our knowledge of the long-term sublethal effects of Pb on human health continues to grow dramatically. Our knowledge about lead poisoning in domestic animals is signifi- cantly less. For wild animals, our understanding of lead poisoning is roughly where our knowledge about humans was in the mid-1800s when Tanquerel Des Planches made his famous medical observations (Tan- querel Des Planches 1850). -
HISTORY of LEAD POISONING in the WORLD Dr. Herbert L. Needleman Introduction the Center for Disease Control Classified the Cause
HISTORY OF LEAD POISONING IN THE WORLD Dr. Herbert L. Needleman Introduction The Center for Disease Control classified the causes of disease and death as follows: 50 % due to unhealthy life styles 25 % due to environment 25% due to innate biology and 25% due to inadequate health care. Lead poisoning is an environmental disease, but it is also a disease of life style. Lead is one of the best-studied toxic substances, and as a result we know more about the adverse health effects of lead than virtually any other chemical. The health problems caused by lead have been well documented over a wide range of exposures on every continent. The advancements in technology have made it possible to research lead exposure down to very low levels approaching the limits of detection. We clearly know how it gets into the body and the harm it causes once it is ingested, and most importantly, how to prevent it! Using advanced technology, we can trace the evolution of lead into our environment and discover the health damage resulting from its exposure. Early History Lead is a normal constituent of the earth’s crust, with trace amounts found naturally in soil, plants, and water. If left undisturbed, lead is practically immobile. However, once mined and transformed into man-made products, which are dispersed throughout the environment, lead becomes highly toxic. Solely as a result of man’s actions, lead has become the most widely scattered toxic metal in the world. Unfortunately for people, lead has a long environmental persistence and never looses its toxic potential, if ingested. -
Acute Poisoning: Understanding 90% of Cases in a Nutshell S L Greene, P I Dargan, a L Jones
204 REVIEW Postgrad Med J: first published as 10.1136/pgmj.2004.027813 on 5 April 2005. Downloaded from Acute poisoning: understanding 90% of cases in a nutshell S L Greene, P I Dargan, A L Jones ............................................................................................................................... Postgrad Med J 2005;81:204–216. doi: 10.1136/pgmj.2004.024794 The acutely poisoned patient remains a common problem Paracetamol remains the most common drug taken in overdose in the UK (50% of intentional facing doctors working in acute medicine in the United self poisoning presentations).19 Non-steroidal Kingdom and worldwide. This review examines the initial anti-inflammatory drugs (NSAIDs), benzodiaze- management of the acutely poisoned patient. Aspects of pines/zopiclone, aspirin, compound analgesics, drugs of misuse including opioids, tricyclic general management are reviewed including immediate antidepressants (TCAs), and selective serotonin interventions, investigations, gastrointestinal reuptake inhibitors (SSRIs) comprise most of the decontamination techniques, use of antidotes, methods to remaining 50% (box 1). Reductions in the price of drugs of misuse have led to increased cocaine, increase poison elimination, and psychological MDMA (ecstasy), and c-hydroxybutyrate (GHB) assessment. More common and serious poisonings caused toxicity related ED attendances.10 Clinicians by paracetamol, salicylates, opioids, tricyclic should also be aware that severe toxicity can result from exposure to non-licensed pharmaco- -
Toxicity Forecaster (Toxcasttm)
science in ACTION www.epa.gov/research INNOVATIVE RESEARCH FOR A SUSTAINABLE FUTURE Toxicity Forecaster (ToxCastTM) ADVANCING THE NEXT GENERATION OF CHEMICAL SAFETY EVALUATION Tens of thousands of chemicals are currently in commerce, and hundreds more are introduced every year. Because current chemical testing is expensive and time consuming, only a small fraction of chemicals have been fully evaluated for potential human health effects. Through its computational toxicology research (CompTox), the U.S. Environmental Protection Agency (EPA) is working to figure out how to change the current approach used to evaluate the safety of chemicals. CompTox research integrates advances in biology, biotechnology, chemistry, and computer science to identify important biological processes that may be disrupted by the chemicals and tracing those biological the potential to limit the number of of sources; including industrial and disruptions to a related dose and required laboratory animal-based consumer products, food additives, human exposure. The combined toxicity tests while quickly and and potentially “green” chemicals information helps prioritize efficiently screening large numbers that could be safer alternatives to chemicals based on potential human of chemicals. existing chemicals. These 2,000 health risks. Using CompTox, chemicals were evaluated in over thousands of chemicals can be The first phase of ToxCast, 700 high-throughput assays that evaluated for potential risk at a small appropriately called “Proof of cover a range of high-level cell cost in a very short amount of time. Concept”, was completed in responses and approximately 2009 and it evaluated over 300 300 signaling pathways. ToxCast A major part of EPA’s CompTox well studied chemicals (primarily research is the Toxicity Forecaster research is ongoing to determine pesticides) in over 500 high- which assays under what conditions (ToxCast™). -
Environmental Risk Assessment of Chemicals
Society of Environmental Toxicology and Chemistry Technical Issue Paper Environmental Risk Assessment of Chemicals Environmental Risk exposure to a chemical for organisms, such as animals, plants, or microbes, in the environment, which could be Assessment of Chemicals water, soil, or air. Effects can be assessed at different levels of biological organization, which is to say in Environmental risk assessment determines the single cells, individuals, populations, ecosystems, or nature and likelihood of harmful effects occurring landscapes. to organisms such as humans, animals, plants, or microbes, due to their exposure to stressors. A stressor can be a chemical (such as road salt runoff to a lake), Applications of Environmental exotic species (such as a foreign plant), or a change Risk Assessment of Chemicals in physical conditions (such as dredging a channel). Here, we focus on risk assessment of chemicals. The Environmental risk assessments of chemicals can be chemicals can be something that is found in nature, used at many scales. They can take place at the small- such as copper, or something created by humans, such scale site level (such as a release at a manufacturing as pharmaceuticals. Depending on whether humans plant), at the field-scale level (for example, spraying or other organisms or ecosystems are exposed, a plant protection products or pesticides on crops), risk assessment is called either a “human health” or at a regional level (such as a river catchment or an “ecological” risk assessment. Here, the term or bay). Policy makers, including government “environmental risk assessment” is used to include both. agencies, and industries use risk assessments to support environmental management decisions. -
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. -
A Toxicology Curriculum for Communities
A Toxicology Curriculum For Communities 43 Module One Introduction to Toxicology 44 Objectives Upon completion of this module, the learner will be able to: Define toxicology and commonly associated terms Differentiate the sub-disciplines of toxicology Describe the classifications of toxic agents Describe the field of toxicology Understand the roles of various agencies Identify potential sources for additional information 45 What is Toxicology? 46 Toxicology Involves all aspects of the adverse effects of chemicals on living systems. 47 General Toxicology Questions 48 What are Harmful or Adverse Effects? Those effects which are damaging to either the survival or normal function of the individual 49 What is Toxicity? The term “toxicity”is used to describe the nature of adverse effects produced and the conditions necessary for their production. Before toxicity can develop, a substance must come into contact with a body surface such as skin, eye or mucosa of the alimentary or respiratory tract. 50 What is Toxic? This term relates to poisonous or deadly effects on the body 51 What is a Toxicant? The term “toxicant” refers to toxic substances that are produced by or are a by- product of human-made activities. 52 What is a Toxin? The term “toxin” refers to toxic substances that are produced naturally. 53 What is a Toxic Symptom? What is a Toxic Effect ? A toxic symptom is any feeling or sign indicating the presence of a poison in the system. Toxic effects refers to the health effects that occur due to exposure to a toxic substance. 54 What is Selective Toxicity? This means that a chemical will produce injury to one kind of living matter without harming another form of life, even though the two may exist close together. -
Ethylene Glycol Ingestion Reviewer: Adam Pomerlau, MD Authors: Jeff Holmes, MD / Tammi Schaeffer, DO
Pediatric Ethylene Glycol Ingestion Reviewer: Adam Pomerlau, MD Authors: Jeff Holmes, MD / Tammi Schaeffer, DO Target Audience: Emergency Medicine Residents, Medical Students Primary Learning Objectives: 1. Recognize signs and symptoms of ethylene glycol toxicity 2. Order appropriate laboratory and radiology studies in ethylene glycol toxicity 3. Recognize and interpret blood gas, anion gap, and osmolal gap in setting of TA ingestion 4. Differentiate the symptoms and signs of ethylene glycol toxicity from those associated with other toxic alcohols e.g. ethanol, methanol, and isopropyl alcohol Secondary Learning Objectives: detailed technical/behavioral goals, didactic points 1. Perform a mental status evaluation of the altered patient 2. Formulate independent differential diagnosis in setting of leading information from RN 3. Describe the role of bicarbonate for severe acidosis Critical actions checklist: 1. Obtain appropriate diagnostics 2. Protect the patient’s airway 3. Start intravenous fluid resuscitation 4. Initiate serum alkalinization 5. Initiate alcohol dehydrogenase blockade 6. Consult Poison Center/Toxicology 7. Get Nephrology Consultation for hemodialysis Environment: 1. Room Set Up – ED acute care area a. Manikin Set Up – Mid or high fidelity simulator, simulated sweat if available b. Airway equipment, Sodium Bicarbonate, Nasogastric tube, Activated charcoal, IV fluid, norepinephrine, Simulated naloxone, Simulate RSI medications (etomidate, succinylcholine) 2. Distractors – ED noise For Examiner Only CASE SUMMARY SYNOPSIS OF HISTORY/ Scenario Background The setting is an urban emergency department. This is the case of a 2.5-year-old male toddler who presents to the ED with an accidental ingestion of ethylene glycol. The child was home as the father was watching him. The father was changing the oil on his car. -
Introduction to Environmental Toxicology
Introduction to Toxicology WATER BIOLOGY PHC 6937; Section 4858 Andrew S. Kane, Ph.D. Department of Environmental & Global Health College of Public Health & Health Professions [email protected] ? “The problem with toxicology is not the practicing toxicologists, but chemists who can detect, precisely, toxicologically insignificant amounts of chemicals” Rene Truhaut, University of Paris (1909-1994) Toxicology………… • Is the study of the harmful effects of chemicals and physical agents on living organisms • Examines adverse effects ranging from acute to long-term chronic • Is used to assess the probability of hazards caused by adverse effects • Is used to predict effects on individuals, populations and ecosystems 1 An interdisciplinary field… Clinical Toxicology: Diagnosis and treatment of poisoning; evaluation of methods of detection and intoxication, mechanism of action in humans (human tox, pharmaceutical tox) and animals (veterinary tox). Integrates toxicology, clinical medicine, clinical biochemistry/pharmacology. Environmental Toxicology: Integrates toxicology with sub- disciplines such as ecology, wildlife and aquatic biology, environmental chemistry. Occupational Toxicology: Combines occupational medicine and occupational hygiene. An interdisciplinary field… Descriptive Toxicology: The science of toxicity testing to provide information for safety evaluation and regulatory requirements. Mechanistic Toxicology: Identification and understanding cellular, biochemical & molecular basis by which chemicals exert toxic effects. Regulatory Toxicology: -
Small Dose... Big Poison
Traps for the unwary George Braitberg Ed Oakley Small dose... Big poison All substances are poisons; Background There is none which is not a poison. It is not possible to identify all toxic substances in a single The right dose differentiates a poison from a remedy. journal article. However, there are some exposures that in Paracelsus (1493–1541)1 small doses are potentially fatal. Many of these exposures are particularly toxic to children. Using data from poison control centres, it is possible to recognise this group of Poisoning is a frequent occurrence with a low fatality rate. exposures. In 2008, almost 2.5 million human exposures were reported to the National Poison Data System (NPDS) in the United Objective States, of which only 1315 were thought to contribute This article provides information to assist the general to fatality.2 The most common poisons associated with practitioner to identify potential toxic substance exposures in children. fatalities are shown in Figure 1. Polypharmacy (the ingestion of more than one drug) is far more common. Discussion In this article the authors report the signs and symptoms Substances most frequently involved in human exposure are shown of toxic exposures and identify the time of onset. Where in Figure 2. In paediatric exposures there is an over-representation clear recommendations on the period of observation and of personal care products, cleaning solutions and other household known fatal dose are available, these are provided. We do not discuss management or disposition, and advise readers products, with ingestions peaking in the toddler age group. This to contact the Poison Information Service or a toxicologist reflects the acquisition of developmental milestones and subsequent for this advice. -
Effects of Temperature and Storage Conditions on the Electrophoretic, Toxic and Enzymatic Stability of Venom Components Sean M
Comp. Biochem. Physiol. Vol. 119B, No. 1, pp. 119±127, 1998 ISSN 0305-0491/98/$19.00 Copyright 1998 Elsevier Science Inc. All rights reserved. PII S0305-0491(97)00294-0 Effects of Temperature and Storage Conditions on the Electrophoretic, Toxic and Enzymatic Stability of Venom Components Sean M. Munekiyo and Stephen P. Mackessy Department of Biological Sciences, 501 20th St., University of Northern Colorado, Greeley, CO 80639, U.S.A. ABSTRACT. Rattlesnake venoms are complex biological products containing potentially autolytic compo- nents, and they provide a useful tool for the study of long-term maintenance of enzymes in a competent state, both in vivo and in vitro. To evaluate the stability of venom components, 15 aliquots of freshly extracted venom (from Crotalus molossus molossus) were subjected to 15 different temperature and storage conditions for 1 week and then lyophilized; conditions varied from storage at 280°C (optimal preservation of activities) to dilution (1:24) and storage at 37°C (maximal degradation potential). Effects of different storage conditions were evalu- ated using SDS-PAGE, metalloprotease zymogram gels, a cricket LD50 assay and enzyme assays (metalloprotease, serine proteases, phosphodiesterase, l-amino acid oxidase and phospholipase A2). Venom samples were remark- ably refractive to widely varying conditions; enzyme activities of some samples were variable, particularly l- amino acid oxidase, and one sample treatment showed higher toxicity, but electrophoretic results indicated very little effect on venom proteins. This study suggests that most venom activities should remain stable even if stored or collected under potentially adverse conditions, and freezing samples is not necessarily advantageous. -
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