1-st-Introduction to Toxicology.ppt

Introduction to Toxicology

Toxicology - Chaper 1

The study of the adverse effects of chemicals on living organisms and the underlying mechanismsToxicology


Like medicine, toxicology is both a science and an art. The science of toxicology is defined as the observational and data-gathering phase, whereas the art of toxicology consists of the utilization of the data to predict outcomes of exposure in human and animal population.Toxicology


History of ToxicologyAntiquity: Ebers papyrus (1500 B.C.), Ben Chao Gong Mu (Ming dynasty)Middle ages: Renaissance - Poisons and Their Antidotes (1198), arsenic-containing productsAge of enlightenment: Parcelsus (1493-1548) All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.


History of ToxicologyAge of enlightenment: Orfila (1787-1853) the first toxicologist to use autopsy material and chemical analysis systematically as legal proof of poisoning. Oswald Schmiedeberg (1838-1921) the first toxicologist to train 120 students who later populated the most important laboratories of pharmacology and toxicology throughout the world.


History of ToxicologyMorden toxicology: 1900-Development of early advances in analytic methods: heavy metalsEarly mechanistic studies: drugs, plantsIntroduction of new toxicants and antidotes: nitrite and thiosulfate for cyanide; DDT (1944); organophophorus compounds(1952)Development of new branches


History of ToxicologyThe Silent Spring (Rachel Carson, 1962)The earths vegetation is a part of a web of life in which there are intimate and essential relations between plants and the earth, between plants and other plants, between plants and animals. Sometimes we have no other choice but to disturb these relationships, but we should do so thoughtfully, with full awareness that what we do may have consequences remote in time and place.


Three eras of development of experimental toxicology


Toxicology BranchAccording to object of study:Animal ToxicologyHuman Toxicology Plant ToxicologyInsect ToxicologyLivestock Toxicology


Toxicology BranchAccording to field of study:Environmental ToxicologyFood Toxicology Occupational ToxicologyClinical ToxicologyForensic ToxicologyAnalytic Toxicology


Toxicology BranchAccording to target organ of study:Liver ToxicologyKidney Toxicology NeurotoxicologyImmunotoxicologyProductive ToxicologyHemotoxicolgy


Toxicology BranchAccording to mechanism of study:Cellular ToxicologyMolecular Toxicology Membrane ToxicologyBiochemical ToxicologyGenetic Toxicology


Toxicology BranchAccording to area of study:Descriptive ToxicologyMechanistic ToxicologyRegulatory Toxicology


Main Areas of Toxicology StudyDescriptive Toxicology :To test toxicity in experimental animals to provide important clues to a chemicals mechanism of action. To yield information that can be used to evaluate risks posed to humans and the environment.


Main Areas of Toxicology StudyMechanistic Toxicology :To identify and understand the cellular, biochemical and molecular mechanisms by which chemicals exert toxic effects on living organisms. To design and produce safer alternative chemicals for therapy of poisoning and treatment of diseases.


Main Areas of Toxicology StudyRegulatory Toxicology :To perform the risk assessment of a potential hazard to the human health and the ecosystem.To establish standards for the amount of chemicals permitted in ambient air, industrial atmosphere, and drinking water.


Spectrum of Toxic DoseAmong chemicals there is a wide spectrum of doses needed to produce deleterious effects, serious injury, or death.However, the measures of acute lethality such as LD50 may not accurately reflect the full spectrum of toxicity associated with exposure, e.g., carcinogenic or teratogenic effects.


Spectrum of Undesired Effects (1)Allergic reactionsChemical allergy is an immunologically mediated adverse reaction to a chemical and is dose-related for a given individual.The incidence of allergic asthma has increased substantially in recent years.


Spectrum of Undesired Effects (2)Idiosyncratic reactionsReferring to a genetically determined abnormal reactivity to a chemical, i.g., extreme sensitive to low doses or extreme insensitive to high doses. Examples of chemical idiosyncrasy include exposures to succinylcholine and methemoglobin-inducing chemicals.


Spectrum of Undesired Effects (3)Immediate versus delayed toxicityMost chemicals produce immediate toxic effects but not delayed effects.Delayed toxicity can be seen in carcinogenic chemicals (years) and organophosphorus pesticides (weeks) such as TOCP to inhibit the neuropathy target esterase (NTE).


Spectrum of Undesired Effects (4)Reversible versus irreversible toxic effectsThe ability of exposed tissue to regenerate largely determines where the effects is reversible or irreversible.Carcinogenic and teratogenic effects are usually considered irreversible toxic effects once they occur.


Spectrum of Undesired Effects (5)Local versus systemic toxicityLocal effects occur at the site of first contact of chemicals, e.g., ingestion of caustic substances or inhalation of irritant materials.Systemic effects require absorption and distribution of a toxicant from its entry point to a distant site to produce damages, some of the affected organs are referred to as the target organs of a particular chemical.


Overview of Toxicology StudyXenobioticTarget OrganismCommunity/PopulationEcosystemAbsorptionTarget TissueTarget CellExposureDistributionMetabolismClassicalToxicologyXenobioticMembrane TransportOrganismToxicityTissueToxicityRegulatoryToxicologyExcretionEpidemiology/Environmental ToxicologyTargetMoleculeCellular andMolecular EventsCellularToxicityMolecularand CellularToxicologyGenetic SusceptibilityBiomarkersRisk assessmentMechanisms and treatment of toxicityRisk characterizationBiologyResponseMetabolism


Information Resource ofToxicology, Hazardous Chemicals, and the Environment

Chemical Information Identify chemical, its synonyms, and CAS number

www.chemfinder.com find chemical structure, chemical surrogate based on structure similarity. Can be searched by using a chemical name, CAS Number, molecular formula, or molecular weight toxnet.nlm.nih.gov/ (ChemID) find which National Library of Medicine (NLM) databases contain information on the chemical.


2. Toxicology Information

http://toxnet.nlm.nih.gov/ Summarize toxicological study results, etc. http://toxnet.nlm.nih.gov/ search for original studies. http://ntp-server.niehs.nih.gov/ National Toxicology Program http://ehis.niehs.nih.gov/Environmental Health Information Service www.epa.gov Environmental Protection Agencywww.fda.gov Food and Drug Administrationwww.osha.gov Occupational Safety and Health Administrationwww.atsdr.cdc.gov Agency for Toxic Substances and Disease Registrywww.acgih.org American Conference of Governmental industrial Hygienist www.iarc.fr The International Agency for Research on Cancerwww.fao.org Food and Agriculture Organization of the United Nationshttp://www.toxicology.org/Information/siteofinterest/sites.html#Government


Toxicology is a science for the wellbeing of mankind


Documents

1-st-Introduction to Toxicology.ppt