生物钟基因研究进展

world.
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History of Toxicology
• Morden toxicology: 1900-
– Development of early advances in analytic methods: heavy metals
– Early mechanistic studies: drugs, plants
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Toxicology Branch
• According to field of study:
– Environmental Toxicology
– Food Toxicology
– Occupational Toxicology
– Clinical Toxicology
gathering phase, whereas the art of
toxicology consists of the utilization of the
data to predict outcomes of exposure in
human and animal population.
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– Neurotoxicology
– Immunotoxicology
– Productive Toxicology
– Hemotoxicolgy
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Toxicology Branch
• According to mechanism of study: – Cellular Toxicology – Molecular Toxicology – Membrane Toxicology – Biochemical Toxicology – Genetic Toxicology
• 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.
– Forensic Toxicology
– Analytic Toxicology
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Toxicology Branch
• According to target organ of study:
– Liver Toxicology
– Kidney Toxicology
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ห้องสมุดไป่ตู้
Three eras of development of experimental toxicology
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Toxicology Branch
• According to object of study: – Animal Toxicology – Human Toxicology – Plant Toxicology – Insect Toxicology – Livestock 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.
– 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.
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History of Toxicology
• The Silent Spring (Rachel Carson, 1962)
“The earth’s 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.”
– Introduction of new toxicants and antidotes: nitrite and thiosulfate for cyanide; DDT (1944); organophophorus compounds(1952)
– Development of new branches
• 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.”
– The incidence of allergic asthma has increased substantially in recent years.
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Spectrum of Undesired Effects (2)
• Idiosyncratic reactions
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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.
Chapter 1
Introduction to Toxicology
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Toxicology
The study of the adverse effects of chemicals on living
organisms and the underlying mechanisms
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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.
Oswald Schmiedeberg (1838-1921) – the first
toxicologist to train 120 students who later
populated the most important laboratories of
pharmacology and toxicology throughout the
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Main Areas of Toxicology Study
• Regulatory Toxicology :
– To perform the risk assessment of a potential hazard to the human health and the ecosystem.
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Toxicology Branch
• According to area of study: – Descriptive Toxicology – Mechanistic Toxicology – Regulatory Toxicology
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Main Areas of Toxicology Study
• Descriptive Toxicology :
– To test toxicity in experimental animals to provide important clues to a chemical’s mechanism of action.
– To yield information that can be used to evaluate risks posed to humans and the environment.
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Main Areas of Toxicology Study
• Mechanistic Toxicology :
– To establish standards for the amount of chemicals permitted in ambient air, industrial atmosphere, and drinking water.
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Spectrum of Toxic Dose
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Toxicology
Like medicine, toxicology is both a science
and an art. The science of toxicology is
defined as the observational and data-
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Spectrum of Undesired Effects (3)
• Immediate versus delayed toxicity
– Most chemicals produce immediate toxic effects but not delayed effects.
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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