Introduction ealth is fundamental to the study rN if statistics and public h hn te a xicology for nel tele Jie COU ee chemical on a cell, ti Tee | Introduction eficial effects of icals that may be Antiquity Ebers Papyrus (circa 1500 B.C.) Contains information pertaining to many recognize poisonsAntiquity Hippocrates (circa 400 B.C.) Number of poisons and clinical toxicology principles pertaining to bioavailability in therapy and overdosage classifying poisonous plants, animals, and minerals in his book De Material Medica Antiquity Maimonides (Moses ben Maimon; A.D. 1135-1204) Treatise on Poisons and Their Antidotes, 1198 Describe the subjects of bioavailability noting that milk, butter and cream could delay intestinal absorption.Antiquity Catherine de Medec! Tested toxic concoctions, carefully noting the rapidity of the toxic response, the effectiveness of the compound, the degree of response of the parts of the body, the complaints of the victim Philippus Aureolus Theophrastus Bombastus von Hohenheim- Paracelsus (1493-1541) Formulated many revolutionary views that remain integral to the structure of toxicology and pharmacology and therapeutics today “te. only digurag _bedwern PosM™ is vA dow" Renaissance Philippus Aureolus Theophrastus Bombastus von Hohenheim- Paracelsus (1493-1541) Experimentation is essential in the examination of responses to chemicals One should make a distinction between the therapeutic properties of Chemicals These properties are sometimes but not always indistinguishable except by dose One can ascertain a degree of specificity of chemicals and their therapeutic or toxic effects. holnva onda =aRenaissance Ellenbog (circa 1480) Warned on the toxicity of mercury from goldsmithing and Agricola published short treatise on mining disease In 1556, Renaissance Bernardino Ramazzini 4700 his discourse on published in of the Workers: the Disease Renaissance percival Potts (1775) Recognition on the role of soot In scrotal cancer among chimney sweeps was the first report of polyaromatic hydrocarbon carcinogenicity.Age of enlightenment Orla (sed autopsy material and chemical analysis gystematically as legal proof of porsoning Age of Enlightenment Magendie Studied the mechanism of action of emetine and strychnineAge of Enlightenment Oswald Schmiedeberg (1838- 1921), Louis Lewin (1850-1929) Schmeideberg trained approximately 120 students who later populated the most important laboratories of pharmacology and toxicology throughout the world Lewin published much of the early work on the toxicity of narcotics, methanol, glycerol, acrolein, and chloroform. . Definition of Terms Toc Risk f recbityota Telenor 1 a ( chemical agent to ‘Injury wiloccuriNd cable aft ring couse injury given situation oF from exposure oa setting. chemical or physical agent. HozardHazard azard, one needs to have knowledge about poth the e (qualitative aspect) and the Toassess h liable to be exposed inherent toxicity of the substanc amount to which individuals are (quantitative aspect) | F ‘ Definition of Terms Symptom Poison mentand Any evidence of Any substance applied The manage! care of a patient or disease or of a patient’s condition a Treatment to the body, ingested, inhaled or developed the overcoming or within the body which combating of a change in a patient’s ne ia damage or — disorder. condition indicative of ince of some bodily or mental state functionDefinition of Terms Average Dose Maximum Dose Minimum Dose thesmallest amount the dose which may the largest amount produced be expected ordinarily which can be safely Ms rapeutic effects or to produce the used in ordinary case - neficial action upon therapeutic effects for le sick which the preparations is employed, o Oe Definition of Terms Toxic Dose Lethal Dose p50 ne amount (d0se) The dose that Is The dose which kilsor 7 hamfultoboththe the dose which Is wich kills 50% ofa just suficient 0 couse group of test animals (usually 10 or more) oF healthy and the sick, but is not fatal. death tested on 50 animalsDefinition of Terms 1p 100 argin of atey MLD spe mount se rhe magnitude ofthe a smallest sé ils 10080 ronge of 4056S experiment foun roup of test animals involved 0 to kill any ane anima (usualy 10 01 more) oF progressing from of atest group. tested on 100 animals non-effective dose t0 alethal dose| ochure 2The identification of the cause of toxicity of a chemical at the cellular or tissue level. In any of these events, the classification of toxicity of a chemical, therefore, may be expressed in terms of its mechanis: of toxicity. : Seeks to answer the biochemical, physiological, or organic.basis ofa chemical's effect on eukaryotic systems. ative codes associated with the availability of 's encountered in society: systematic approach that defines, directs, and dictates the rate at which an individual may encounter 2 synthetic or naturally occurring toxin Based on the scientific basis of evaluation of the toxic characteristics of a chemical, government administrative agencies establish guidelines for the chemical, drug, or molecule and regulate its maintenance in the environment or within the therapeutic market. Administ potential toxin: Genetic toxicology — incorporates molecular biology principles in applications of forensic sciences, such as DNA testing, as legal evidence in court proceeding Occupation toxicology — examines hazards associated with toxic exposure in the workplace In vitro toxicology - refers to the development of cell culture techniques as alternatives to animal toxicity testingEnvironmental Toxicology cee Toxicology Economic Tey diaellel°) + Limitations have been placed on the amount that may be used and on the time when such additives must be withdrawn if the animals are to be used for human food. The use of pesticides and insecticides in agriculture has enabled the farmer to produce more and better products, but is the Beet, of residues of ese chemicals bein: food is consumed. ee erg - Such pollution of the air and water is not only aesthetically undesirable, but exposes large populations to an unlimited variety if potentially harmful chemicals, which are capable of producing known acute harmful effects and possible chronic debilitating illness in humans. « Abranch of toxicology which deals with the harmful effects of chemicals that are intentionally administered to biologic tissue for the purpose of achieving a specific effect.micals (drugs) may be selective in that they exert their effect on specific tissues Or functions of tissues within an organism and thus are used to modify only a single function erolalelaaiio of the organism. +a, Selectivity in regard to site of action Toxicology - 2. Reversibility of action + 3. Its ability to produce some useful effect which is generally defined as a therapeutic effect * Specific che peers “A branch of toxicology which deals with phasirabie te the medical and legal aspects of the cd harmful effects of chemicals on humans. - Involves both the intentional and accidental conditions of exposure to Forensic Toxicology chemicals.«Concerned with disease caused by or Clinical uniquely associated with toxic substances Toxicology - The study of adverse effects on the developing Developmental organism that may result from exposure to Peer ten] chemical or physical agents be at conception (either parent), during prenatal development, or postnatally until the time of puberty. * Study of the occurrence of adverse effects on the male or female reproductive system that may result from exposure to chemical or physical agents. Reproductive Toxicologyai 7th Poisoning Nol Poisoning Pee Cael oltre tES] « Acute Pois: + Accidental- those + Suicidal- those in which the poison + Homicidal- those in - Undetermined- those + Circumfer - symptomatic evidenc - Chemical evidence- - Experimental evi ‘oning- produced by taking an excessive single dose of a poison, or several small doses with such frequency as to result in prompt and marked disturbance of function or death within a definite period. « Chronic Poisoning- produced by taking or absorbing for a protracted period small doses of a poison. inwhich the poison was taken without intention to cause death. was taken by the ly for the purpose of taking his own life. which the poison w tent to cause death in which the history is hazy as to tained and why it was victim voluntaril as given willfully and with in tothe victim. how the poison was 0 administered. ential evidence the attributed by the ‘or deduced from various circumstance J for poisoning, possession OF purcl facts, motives poison. toms. e- contributed by the symp’ ed by means of osed to have ited or of the evidence obtain: chemical analysis of the substance SUPP Cgused the poisoning, or what has been vom material found in the secretion. dence- obtained by administering the suspected substance to some living animal and observing the effects.- Adecision must be made about whether the poisoning is sufficiently serious to require further treatment. + Exposure to a known poisol VEN Eyed} . Exposure to an unknown su! poison + Disease of undetermined cause in which poisoning must be considered as part of the differential diagnosis n bstance that may bea Diagnosis and up of a patient who may be ing consists © :The diagnostic workt ized poison! a victim of unrecogn + Acomplete history + Complete physical e « Appropriate laboratory tests iene amination DiagnosisLachine 5According to origin Plant — morphine, atropine, aconitine, nicotine Animal — snake venom, epinephrine, insulin s Minerals — calcium, potassium, magnesium Metals — arsenic, mercury, antimony, gold, iron —— Synthetic — barbiturates, antihistamines and tranquilizers According to characteristic effect or properties or lungs * Corrosive poisons —in the alkalies. «system polson ~ act on the nervous system of SFL the heart, liver, kidneys, with having any special corrosive oF irritant effect ‘such as strychnine, brucine, cyanides ym the ingestion of food contaminated ‘cludes such substances as the mineral acids, glacial acetic acid and and aconitine. «Biological poisons - poisoning that may result fro! with dangerous pathogenic bacteria. ical properties According to chem | + Organic + Inorganic = Volatile non-metallic poisons + Volatile organic poisons + Alkaloids * Metallic poisons + Animal poison + Mineral acids + Bacterial food poisoning = Mineral alkalies + Organic acids * GlucosidesAccording to Physio logical effects + Corrosiveness — highly irritant poisons which cause local destructi jon of tissues and characterized by nausea, vomiting, great local distress a + Irritants - one which produces irritation or Inflamm lation of the mucous membranes and characterized by pain in the abdomen, vomiting and purging + Asphyxiants exerts their effects by interfering with the oxidation of the tissues «simple — inert gases that act principally by dilutior = Chemical — through chemical action either preven! n of the atmospheric oxygen tthe blood from transporting oxyBen crea jungs or prevent normal oxygenation of the tissues = Narcotics— those agents which produce stupor co! anesthethics ~is one which acts chi « Tetanics —are agents which act directly UPON the spi and continuous contraction of the muscles asa resul parts to which they are attached. which act upon the bral + Neurotic poison «+ Deliriants—are those agents and produce confusion of will power oF delirium lefly in the diluted state UP nal cord, producing such spasmodic Tt of stiffness or immobility of the mplete or incomplete insensibility or yon the nervous system- nasto disorder the mental facultiesI | are agents which produce f vital or muscular power | | + Asthenics or Exhaustives — exhaustion and cause marked loss o} According to Site of action * Local effect + Corrosion or chemical destruction —is illustrated by the effects of the strong mineral acids and alkalies « Initation or Inflammation — which ranges from simple redness in its Irrldest form to ulceration or gangrene in its more severe form « Specific effect — is shown by the effect on the extremities of the nerves ite of action According to S ‘ose influencing organs at some distance from the part to which the poison has been applied Combined effects the effect of the poison is not only localized at the site but also affects remote organs Remote effects — are thethods of isolation According to m * Volatile poisons are those isolated by distillation with or without current jon with organic of steam * Non-volatile poisons — those that are isolated by extracti solvents. + Metallic poisons + Substances for which special methods of isolation are required Kinds of Poisons eye @ Sopha oo ee eee tS eae + Corrosive poison ~ is one which by contact chemically causes local destruction of tissue. When swallowed it usually produces nausea, vomiting and great local distress. —is still poisonous no matter how highly diluted is one which increases suddenly in its intensity of * True poison + Cumulative poison — action after slow addition of it. Poisons with both local and remote effects mote effect is upon the brain remote effect is the kidney | + Arsenic— local effect is upon the stomach, rei « Cantharidines — local effect produces blisters; and the urinary bladder. intestinal tract; remote effect is + Phenol - local corrosion of gastroil convulsive action on the spinal cord.Organ affecting poisons + Opium, barbiturates, alcohol ~ affect Cantharides — urinary organs aout Ergot — uterus | strychnine —spinal cord + Curare - motor system of nerves Chlorine (gas) lungs Carbon monoxide — blood Digitalis, oxalic acid — heart + Antimony, arsenic ~ stomach Conditions Influencing the Rapidity of absorption oe ot be «The solubility ofthe poison ~ some poisons are insoluble and therefore it can absorbed «The character of the surface to which the poison is applied - if the skin is removed the absorption Is more rapid els if the vessels contains little blood the poison Is + The quantity of blood in the blood vest more rapidly absorbed. effects of poisons Factors modifying the a ae eal + pete by neal + hee + Mabe + se + Ghaston + Wonyecrny era rpc tate of the ind + Heath condition of ue stomach + Seen 1) Gharecter and aunt ofthe stomach content Ceens Factors modifying the effects of Poiso . Those attributed to the poison | + Physical state or form the polson | + Mode of administration | + Size of the dose «Association with other polsons (chemical, mechanical) | * Dilution Administration of Poison » Mouth + Nose (lungs) + Skin + Rectum and vagina + Eye and ear + Hypodermically and intravenously | Elimination of Poison * Saliva * Pancreatic juices «Tears + Feces * Sweat + Emesis * Bile * Respiration * Urine | | |ts of Chemicals n of Harmful Effec + prugs represent special types of Classificatio Sas bielogreally reactive chemicals which are + chemical group peartionally administered, usually in «+ Type of toxic responses Specffc doses and usually to humans or at east animals, for the purpose of «+ Direct and indirect effects of chemicals crn some desired effect. Drug Induced Toxicity + Functional toxicities — are due to the pharmacologic effects that are not necessary for the achievement ‘of the desired action of the drugs. + Biochemical toxicity — refers to the changes that do not produce gross ‘evidence of organ pathology but can be detected with suitable chemical methods. al change of the organ, tissue, or cell * Structural toxicity — involves actu group which, of course, also involves biochemical and function al components. Rigor Mortis + The stiffening of the muscles of, the body throughout its entire extent and probably due to the coagulation of the myosin in the musclesModes of Death « Death beginning at the brain * Death beginning at the heart + Death beginning at the lungs EE Causes of Death + Death from asphyxiation of oxygen Due to inhibition of the respiratory m‘ blocking agent + Circulatory failure Agent Ethyl alcohol Sodium chioride Ferrous sulfate Morphine sulfate Phenobarbital sodium Picrotoxin Due to interference with the carriage jovernents by neuromuscularnae