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Clinical Toxicology: Principles and Mechanisms

Chapter · January 2010

DOI: 10.3109/9781420092264

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Clinical Toxicology: Principles and Mechanisms
Barile, Frank A.
ISBN-13: 9781420092257

Table of Contents
Introduction to Basic Toxicological Principles. Introduction. Basic Definitions. Toxicology. Clinical Toxicology. Types of
Toxicology. General Toxicology. Mechanistic Toxicology. Regulatory Toxicology. Descriptive Toxicology. Types Of
Toxicologists. Forensic Toxicologist. Clinical Toxicologist. Research Toxicologist. Regulatory Toxicologist. Academic
Toxicologist. Consultant Toxicologist. References. Suggested readings. Review Articles. Risk Assessment and Regulatory
Toxicology. Risk Assessment. Hazard Identification. Dose-Response Evaluation. Exposure assessment. Risk
Characterization. Regulatory Toxicology. Nuclear Regulatory Commission. Environmental Protection Agency. Food and Drug
Administration. Drug Enforcement Administration. Consumer Products Safety Commission. Occupational Safety and Health
Administration. References. Suggested readings. Review Articles. Therapeutic Monitoring of Adverse Drug Reactions.
Adverse Drug Reactions in Clinical Practice. Factors That Contribute to ADRs. Monitoring. Adherence. Over Prescribing and
Drug Interactions. Allergic Reactions. Medication warnings. Treatment of ADRs and Poisoning In Patients. History. Poison
Control Center (PCC). Clinical Management of Toxicologic Emergencies. References. Suggested readings. Review Articles.
Classification. Introduction. Target Organ Classification. Agents Affecting the Hematopoietic System. Immunotoxic Agents.
Hepatotoxic Agents. Nephrotoxic Agents. Pulmonary Toxic Agents. Agents Affecting the Nervous System. Agents Affecting the
Cardiovascular System. Dermatotoxic Agents. Agents Affecting the Reproductive System. Agents Affecting the Endocrine
System. Classification According to Use in the Public Domain. Insecticides, Herbicides, Rodenticides. Food and Color
Additives. Therapeutic Drugs. By-products of Chemical Combustion. Classification According to Source. Botanical.
Environmental Classification According to Effects. Pathologic. Mutagenic. Carcinogenic. Classification According to Physical
State. Solid. Liquid. Gas. Classification According to Biochemical Properties. Chemical Structure. Mechanism of Toxicity.
Target Organ Toxicity. References. Suggested readings. Review Articles. Exposure. Introduction. Route of exposure. Oral.
Intranasal. Inhalation. Parenteral. Duration and Frequency. Acute Exposure. Chronic Exposure. Single-dose exposure.
Repeated-dose exposure. Accumulation. According to Physiologic Compartment. According to Chemical Structure. According
to Duration and Frequency. References. Suggested readings. Review Articles. Effects. General Classification. Chemical
allergies. Idiosyncratic Reactions. Immediate vs. Delayed Hypersensitivity Reactions. Reversible vs. Irreversible Reactions.
Local vs. Systemic Effects. Target Therapeutic Effects. Chemical Interactions. Potentiation. Additive. Synergistic. Antagonistic.
References. Suggested readings. Review Articles. Dose-Response. General Assumptions. Types of Dose-Response
Relationships. Concentration-Effect and Presence at the Receptor Site. Criteria for Measurement. LD50 (Lethal Dose 50%).
Definition. Experimental Protocol. Factors Which Influence the LD50. ED50 (Effective Dose 50%), TD50 (Toxic Dose 50%) and
TI (Therapeutic Index). Relationship to LD50. Assumptions Using TI. IC50 (Inhibitory Concentration 50%). Definition.
Experimental Determination. In In Vitro Systems. References. Suggested readings. Review Articles. Descriptive Animal
Toxicity Tests. Correlation with Human Exposure. Human Risk Assessment. Predictive Toxicology and Extrapolation to Human
Toxicity. Species Differentiation. Selection of Suitable Animal Species. Cost-Effectiveness. Institutional Animal Care and Use
Committee (IACUC). Descriptive Tests. Required LD50 and Two Routes. Chronic and Subchronic Exposure. Types of Tests.
References. Suggested readings. Review Articles. In Vitro Alternatives to Animal Toxicity. In Vitro Methods. Cell Culture
Methods. Organ System Cytotoxicity. Applications to Clinical Toxicology. Relationship to Animal Experiments. Correlation with
Human Exposure. Risk Assessment. Extrapolation to Human Toxicity. Predictive Toxicology. References. Suggested
readings. Review Articles. Toxicokinetics. Toxicokinetics. Relationship to Pharmacokinetics. Zero-Order Kinetics. First-Order
Kinetics. Second-Order Kinetics. Application to Clinical Toxicology. Absorption. Ionic and Non-ionic Principles. Henderson-
Hasselbach Equation. Route of administration. Drug solubility. Membrane barriers & permeation. Drug trapping - degree of
ionization. Absorption in Nasal and Respiratory Mucosa. Transport of Molecules. Distribution. Fluid Compartments. Ionic and
Nonionic Principles. Factors Affecting Distribution. Plasma Protein Binding. Lipids. Liver and Kidney. Blood-Brain Barrier.
Placenta. Metabolism. Principles of Detoxification. Phase I Reactions. Phase II Reactions. Organ Systems. Biochemical
Pathways. Excretion. Urinary. First-Order elimination. Zero-Order elimination. Fecal. Pulmonary. Mammary Glands.
Secretions. References. Suggested readings. Review Articles. Chemical- and Drug-Receptor Interactions. Chemistry of
Chemical & Drug Receptors. Types of Chemical and Drug Receptors. Ion Channels. G-Protein-Coupled receptors. Kinases
and Enzyme coupled Receptors. Intracellular Receptors. Signal Transduction. References. Suggested readings. Review
Articles. Toxic Exposure and Surveillance in the U.S. Survey of Human and Animal Exposure. Sunstance
Information/Identification. Causes of Toxic Exposures. Distribution of Exposures. Age. Gender. Route. Demographic. Clinical
Effects. Therapeutic Interventions. Medical Outcomes. References. Suggested readings. Review Articles. Toxicogenomics.
Introduction. Human Genomic Variation. Genomic Variation in Target Molecules. Genomic Variation in Drug metabolism.
Gene Structure and Function. Epigenetic Toxicology. DNA Alterations and Genotoxic Effects. DNA Repair Mechanisms.
Experimental Monitoring for Epigenetic Toxicity. Clinical Monitoring for Epigenetic Toxicity. Toxicity of Therapeutic Agents.
Sedative/Hypnotics. Barbiturates. History and Classification. Medicinal Chemistry. Pharmacology and Clinical Use.
Toxicokinetics and Metabolism. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical Management of Acute
Overdose. Tolerance and Withdrawal. Methods of Detection. Benzodiazepines. Incidence. Medicinal Chemistry.
Pharmacology and Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Clinical Management of
Acute Overdose. Tolerance and Withdrawal. Methods of Detection. Miscellaneous Sedative/Hypnotics. Chloral Hydrate.
Meprobamate (Miltown®, Equanil®). Zolpidem tartrate (Ambien®). Buspirone (Buspar®). Flunitrazepam (Rohypnol®).
GHB (Gamma hydroxybutyrate). Methods of Detection. References. Suggested Readings. Review Articles. Opioids and
Derivatives. Opioids. History and Classification. Classification. Medicinal Chemistry. Opioid Receptors. Pharmacology.
Mechanism of Toxicity. Signs and Symptoms of Clinical Toxicity. Clinical Management of Acute Overdose. Tolerance and
Withdrawal. Clinical Management of Addiction. Specific Opioid Derivatives. Codeine. Diphenoxylate. Fentanyl. Meperidine.
Pentazocine. Propoxyphene. Oxycodone / Hydrocodone. Clonidine. Methods of Detection. References. Suggested readings.
Review Articles. Sympathomimetics. Amphetamines and Related Sympathomimetic Agents. Incidence and Classification.
Medicinal Chemistry. Pharmacology and Clinical Use. Toxicokinetics. Effects and Mechanism of Toxicity. Tolerance and
Withdrawal. Methods of Detection. Cocaine. Incidence and Occurrence. Medicinal Chemistry. Pharmacology and Clinical Use.
Toxicokinetics. Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Overdose. Tolerance and Withdrawal.
Methods of Detection. Xanthine Derivatives. Source and Medicinal Chemistry. Occurrence. Pharmacology and Clinical Use.
Toxicokinetics. Signs and Symptoms and Clinical Management of Caffeine Toxicity. Signs and Symptoms and Clinical
Management of Theophylline. Toxicity. Tolerance and Withdrawal. Methods of Detection. Other Sympathomimetic Agents.
Strychnine. Nicotine. Ephedrine. Phenylpropranolamine (PPA). References. Suggested Readings. Review Articles.
Hallucinogenic Agents. History and Description. Ergot Alkaloids. Incidence and Occurrence. Medicinal Chemistry.
Pharmacology and Clinical Use. Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Overdose. Methods of
Detection. Lysergic Acid. Diethylamide (LSD). Incidence and Occurrence. Mechanism of Toxicity. Hallucinogenic Effects.
Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Overdose. Tolerance and Withdrawal. Methods of
Detection. Tryptamine Derivatives. Incidence and Occurrence. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity.
Clinical Management of Acute Overdose. Tolerance and Withdrawal. Methods of Detection. Phenethylamine Derivatives.
Incidence and Occurrence. Medicinal Chemistry. Mescaline. DOM (2, 5-dimethoxy-4-methylamphetamine, STP). MDMA (3, 4-
methylenedioxy-methamphetamine, XTC). Methods of Detection. Phencyclidine. Incidence and Occurrence. Toxicokinetics.
Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Overdose. Tolerance and Withdrawal. Methods of
Detection. Marijuana. Incidence and Occurrence. Medicinal Chemistry. Clinical Uses and Effects. Toxicokinetics. Acute
Toxicity and Clinical Management. Tolerance, Withdrawal, and Chronic Effects. Methods of Detection. Miscellaneous Agents
Ketamine (Special K). Gamma-hydroxybutyrate (GHB). References. Suggested Readings. Review Articles. Anticholinergic
and Neuroleptic Drugs. Introduction to Drugs Possessing Anticholinergic Effects. Antihistamines, Gastrointestinal and
Antiparkinson Drugs. Incidence. Medicinal Chemistry, Pharmacology and Clinical Use. Signs and Symptoms of Acute Toxicity.
Clinical Management of Acute Overdose. Methods of Detection. Tricyclic Antidepressants. Incidence. Medicinal Chemistry.
Pharmacology and Clinical Use. Toxicokinetics. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical
Management of Acute Overdose. Tolerance and Withdrawal. Methods of Detection. Phenothiazine, Phenylbutylpiperidine and
Thioxanthine Antipsychotics. Classification and Indications. Pharmacology and Clinical Use. Toxicokinetics. Mechanism and
Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Overdose. Tolerance and Withdrawal. Methods of
Detection. Selective Serotonin Reuptake Inhibitors (SSRIs). Classification and Indications. Pharmacology and Clinical Use.
Toxicokinetics. Mechanism and Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Overdose. Tolerance
and Withdrawal. Methods of Detection. References. Suggested Readings. Review Articles. Acetaminophen, Salicylates, Non-
steroidal Anti-inflammatory Drugs (NSAIDs). History and Description. Acetaminophen. Incidence. Medicinal Chemistry and
Pharmacology. Clinical Use. Metabolism and Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical
Management of Acute Overdose. Salicylates. Incidence and Clinical Use. Toxicokinetics. Mechanism of Toxicity. Signs and
Symptoms of Acute Toxicity. Clinical Management of Toxicity. Methods of Detection. Non-Steroidal Anti-Inflammatory Drugs
(NSAIDs). History and Description. Classification, Pharmacology and Clinical Use. Signs and Symptoms of Acute Toxicity.
Clinical Management of Acute Overdose. Methods of Detection. References. Suggested readings. Review Articles. Steroids.
The Endocrine System. Neuroendocrine Physiology. Description. Steroids and Public Health. Anabolic-Androgenic Steroids.
Definitions and Incidence. Pharmacology and Clinical Use. Adverse Reactions. Addiction and Withdrawal Syndrome.
Treatment of the Consequences of Chronic Steroid Use. Methods of Detection. Estrogens and Progestins. Physiology.
Pharmacology and Clinical Use. Clinical Toxicity of Prolonged Estrogen and/or Progestin. Administration. Methods of
Detection. References. Suggested readings. Review Articles. Cardiovascular drugs. History and Description. Review of
Cardiovascular Physiology. Digitalis Glycosides. Incidence. Medicinal Chemistry. Pharmacology and Clinical Use.
Toxicokinetics. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Overdose.
Withdrawal. Methods of Detection. Beta-Adrenergic Receptor Antagonists. Other Cardiovascular Drugs. Organic Nitrates.
Calcium Channel Blockers. ACE Inhibitors. Vasodilators. Anti-arrhythmic Drugs. Antineoplastic Agents. Description. Review of
the Cell Cycle. Antimetabolites. Pharmacology and Clinical Use. Acute Toxicity. Clinical Management of Acute. Overdose.
Methods of Detection. Alkylating Agents. Pharmacology and Clinical Use. Acute Toxicity. Clinical Management of ADRs.
Methods of Detection. Miscellaneous Chemotherapeutic Drugs. Natural Products. Hormones and Antagonists. Platinum
Coordination Complexes. Substituted Urea. References. Suggested Readings. Review Articles. Vitamins. Introduction. Fat-
Soluble Vitamins. Vitamin A and Retinoic Acid Derivatives. Vitamin D. Vitamin E. Vitamin K. Water-Soluble Vitamins.
Thiamin. Riboflavin. Niacin. Folic Acid. Cyanocobalamin. Ascorbic Acid. Pyridoxine. Pantothenic Acid. References.
Suggested Readings. Review Articles. Herbal Remedies. Introduction. Nomenclature and Classification. Nomenclature.
Therapeutic Categories. Indications. Other Therapeutic and Toxicologic Information of Herbal Products. References.
Suggested readings. Review Articles. Toxicity of Non-Therapeutic Agents. Alcohols and Aldehydes. Ethanol. Chemical
Characteristics. Mechanism of Toxicity. Toxicokinetics. Calculation of Blood Alcohol Concentrations. Signs and Symptoms of
Acute Toxicity. Signs and Symptoms of Chronic Toxicity. Alcoholic Hepatotoxicity. Alcoholic Coma. Treatment of Acute
Intoxication and Coma. Tolerance and Withdrawal. Fetal Alcohol Syndrome. Methods of Detection. Methanol. Description.
Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Treatment of Acute Intoxication and Coma.
Isopropanol. Description. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Treatment of Acute
Intoxication and Coma. Formaldehyde. Description. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute
Toxicity. Treatment of Acute Intoxication. References. Suggested Readings. Review Articles. Gases. Introduction. Pulmonary
Irritants. Simple Asphyxiants. Introduction. Gaseous Agents. Toxic Products of Combustion (TCP). Introduction. Clinical
Toxicity. Lacrimating Agents. Introduction. Chemical Agents. Chemical Asphyxiants. Carbon Monoxide. Incidence. Chemical
Characteristics and Sources of Exposure. Toxicokinetics. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity.
Treatment of Acute Poisoning. Methods of Detection. Cyanide. Chemical Characteristics, Occurrence and Uses. Mechanism
of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Treatment of Acute Poisoning. Methods of Detection.
References. Suggested readings. Review Articles. Metals. Introduction. Exposure. Industrial Applications. Physiological Role
of Metals. Chelation Therapy. Description. Dimercaprol. Calcium Disodium EDTA. Penicillamine. Deferoxamine. Succimer.
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Antimony. Chemical Characteristics. Occurrence and Uses. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of
Acute Toxicity. Treatment of Acute Poisoning. Application to Forensic Toxicology. Methods of Detection. Arsenic. Chemical
Characteristics. Occurrence and Uses. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Signs
and Symptoms of Chronic Toxicity. Treatment of Acute Poisoning. Application to Forensic Toxicology. Methods of Detection.
Asbestos. Chemical Characteristics. Occurrence and Industrial Uses. Mechanism of Toxicity. Toxicokinetics. Signs and
Symptoms of Acute Toxicity. Signs and Symptoms of Chronic Toxicity. Treatment of Poisoning. Application to Forensic
Toxicology. Methods of Detection. Cadmium. Chemical Characteristics. Occurrence and Uses. Mechanism of Toxicity.
Toxicokinetics. Signs and Symptoms of Acute Toxicity. Treatment of Acute Poisoning. Application to Forensic Toxicology.
Methods of Detection. Copper. Chemical Characteristics. Occurrence and Uses. Physiological Role. Mechanism of Toxicity.
Toxicokinetics. Signs and Symptoms of Acute Toxicity. Signs and Symptoms of Chronic Toxicity. Treatment of Acute
Poisoning. Application to Forensic Toxicology. Methods of Detection. Iron. Chemical Characteristics. Occurrence and Uses.
Physiological Role. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Signs and Symptoms of
Chronic Toxicity. Treatment of Acute Poisoning. Clinical Monitoring of Iron Toxicity. Methods of Detection. Lead. Chemical
Characteristics. Occurrence and Uses. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Signs
and Symptoms of Chronic Toxicity. Treatment of Acute Poisoning. Clinical Monitoring of Lead Toxicity. Methods of Detection.
Mercury. Chemical Characteristics. Occurrence and Uses. Occupational and Non-occupational Exposure. Mechanism of
Toxicity. Toxicokinetics Signs and Symptoms of Acute Toxicity by Inhalation. Signs and Symptoms of Acute Toxicity by
Ingestion. Subacute or Chronic Inorganic Poisoning. Acrodynia. Methyl Mercury Intoxication. Clinical Management of Mercury
Poisoning. Application to Forensic Toxicology. Methods of Detection. Selenium. Chemical Characteristics. Occurrence and
Uses. Physiological Role. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity. Signs and
Symptoms of Chronic Toxicity. Clinical Management of Poisoning. Methods of Detection. Zinc. Chemical Characteristics.
Occurrence and Uses. Physiological Role. Mechanism of Toxicity. Toxicokinetics. Signs and Symptoms of Acute Toxicity.
Signs and Symptoms of Chronic Toxicity. Clinical Management of Poisoning. Methods of Detection. References. Suggested
Readings. Review Articles. Aliphatic & Aromatic Hydrocarbons. Introduction. Aliphatic and Alicyclic Hydrocarbons (HCs).
Aromatic HCs. Signs and Symptoms of Acute Toxicity. Methods of Detection. Petroleum Distillates. Occurrence and Uses.
Mechanism of Toxicity. Aromatic Hydrocarbons. Occurrence and Uses. Mechanism of Toxicity. Halogenated Hydrocarbons.
Occurrence and Uses. Mechanism of Toxicity. Miscellaneous Hydrocarbons. Glycol Ethers. References. Suggested readings.
Review Articles. Insecticides. Introduction. Organophosphorus Compounds. Chemical Characteristics. Occurrence and Uses.
Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical Management of Acute Poisoning. Methods of
Detection. Carbamates. Chemical Characteristics. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical
Management of Acute Poisoning. Methods of Detection. Organochlorine (OC) Insecticides. Chemical Characteristics.
Occurrence and Uses. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical Management of Acute
Poisoning. Methods of Detection. Miscellaneous Insecticides. Pyrethroid Esters. Nicotine. Boric Acid. Rotenone.
Diethyltoluamide (DEET). References. Suggested readings. Review Articles. Herbicides. Introduction. Chlorphenoxy
Compounds. Chemical Characteristics. Occurrence and Uses. Signs and Symptoms of Acute Toxicity and Mechanism of
Toxicity. Clinical Management of Acute Poisoning. Methods of Detection. Bipyridyl Herbicides. Chemical Characteristics,
Occurrence and Uses. Toxicokinetics. Mechanism of Toxicity. Signs and Symptoms of Acute Toxicity. Clinical Management of
Acute Poisoning. Methods of Detection. References. Suggested readings. Review Articles. Rodenticides. Introduction.
Anticoagulants. Chemical Characteristics. Commercial and Clinical Use. Toxicokinetics. Mechanism of Toxicity. Signs and
Symptoms of Acute Toxicity. Clinical Management of Acute Poisoning. Methods of Detection. Phosphorus. Chemical
Characteristics. Toxicokinetics. Mechanism and Signs and Symptoms of Acute Toxicity. Clinical Management of Acute
Poisoning. Methods of Detection. Red Squill. Chemical Characteristics. Mechanism and Signs and Symptoms of Acute
Toxicity. Clinical Management of Acute Poisoning. Methods of Detection. Metals: Thallium, Barium. Thallium. Barium.
References. Suggested readings. Review Articles. Chemical Carcinogenesis and Mutagenesis. Introduction. History and
Development. Mechanisms of Chemical Carcinogenesis. Metabolism. Chemistry. Free Radicals. Pathophysiology of
Carcinogenic Induction. DNA Repair. Pathogenesis. Stages of Carcinogenesis. Carcinogenic Agents. Classification.
Identification and Occurrence. Carcinogenic Potential. Regulation. Carcinogenicity and Mutagenicity Testing. Tobacco Smoke
as a Source of Chemical Carcinogens. Epidemiology. Identification of Components of Tobacco Smoke. Carcinogenic
Potential. Mechanism of Toxicity. Clinical Toxicology and Pathophysiology. Clinical Management. References. Suggested
Readings. Review Articles. Reproductive and Developmental Toxicity. Introduction. History and Development. Maternal-Fetal
Physiology. Development. First Trimester. Second and Third Trimesters. Mechanisms of Developmental Toxicity.
Susceptibility. Dose-Response and Threshold. Drugs Affecting Embryonic and Fetal Development. Classification. Drug
Classes. Methods of Detection. References. Suggested readings. Review Articles. Radiation Toxicity. Principles of
Radioactivity. Ionizing Radiation. Biological Effects of Ionizing Radiation. Sources. Clinical Manifestations. Nuclear Terrorism
and Health Effects. Ultraviolet Radiation (UV). Biological Effects of Ultraviolet Radiation. Sources. Clinical Manifestations.
Nonionizing Radiation. Sources. Biological Effects and Clinical Manifestations of Nonionizing. Radiation. References.
Suggested readings. Review Articles. Chemical and Biological Threats to Public Safety (expanded). Introduction. Biological
Pathogenic Toxins as Threats to Public Safety. Anthrax (Bacillus anthracis). Plague (Yersinia pestis). Brucellosis (Brucella
suis). Salmonellosis. (Salmonella species). Typhoid fever. Shigellosis (Shigella species). Escherichia coli O157:H7. Cholera
(Vibrio cholera). Smallpox. Tularemia (Francisella tularensis), Q Fever (Coxiella burnetti), Viral Hemorrhagic Fevers (VHF).
Chemical Agents as Threats to Public Safety. Nerve Gases. Vesicants, Chemical Asphyxiants, and Pulmonary Irritants. Ricin
(Ricinus communis). References. Suggested readings. Review Articles.