1,Introduction to Toxicology,Chapter 1,2,The study of the adverse effects of chemicals on living organisms and the underlying mechanisms,Toxicology,3,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,4,History of Toxicology,Antiquity: Ebers papyrus (1500 B.C.), Ben Chao Gong Mu (Ming dynasty) Middle ages: Renaissance - Poisons and Their Antidotes (1198), arsenic-containing products Age 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.”,5,History of Toxicology,Age 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.,6,History of Toxicology,Morden toxicology: 1900- Development of early advances in analytic methods: heavy metals Early mechanistic studies: drugs, plants Introduction of new toxicants and antidotes: nitrite and thiosulfate for cyanide; DDT (1944); organophophorus compounds(1952) Development of new branches,7,8,History of Toxicology,The 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.”,9,Three eras of development of experimental toxicology,10,Toxicology Branch,According to object of study: Animal Toxicology Human Toxicology Plant Toxicology Insect Toxicology Livestock Toxicology,11,Toxicology Branch,According to field of study: Environmental Toxicology Food Toxicology Occupational Toxicology Clinical Toxicology Forensic Toxicology Analytic Toxicology,12,Toxicology Branch,According to target organ of study: Liver Toxicology Kidney Toxicology Neurotoxicology Immunotoxicology Productive Toxicology Hemotoxicolgy,13,Toxicology Branch,According to mechanism of study: Cellular Toxicology Molecular Toxicology Membrane Toxicology Biochemical Toxicology Genetic Toxicology,14,Toxicology Branch,According to area of study: Descriptive Toxicology Mechanistic Toxicology Regulatory Toxicology,16,Main Areas of Toxicology Study,Descriptive 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.,17,Main Areas of Toxicology Study,Mechanistic 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.,18,Main Areas of Toxicology Study,Regulatory 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.,19,Spectrum of Toxic Dose,Among 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.,20,21,Spectrum of Undesired Effects (1),Allergic reactions Chemical 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.,22,Spectrum of Undesired Effects (2),Idiosyncratic reactions Referring 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.,23,Spectrum of Undesired Effects (3),Immediate versus delayed toxicity Most 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).,24,Spectrum of Undesired Effects (4),Reversible versus irreversible toxic effects The ability of exposed tissue to regenerate largely determines where the effects is reversible or irreversible. Carcinogenic and teratogenic effects are usually considered irre