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PRINCIPLES OF TOXICOLOGY ...a discussion of the fundamental means by which toxicological properties are determined. DEFINITIONS Toxicology Science that studies the harmful or toxic properties of substances TOXICITY vs HAZARD [an important distinction] Toxicity The ability of a substance to have an adverse effect on the health or well-being of a human – The toxicity of a chemical depends on the degree of exposure and absorption Hazard The probability that the concentration will occur at that site in the body Toxicity vs. Hazard Two chemicals can possess the same degree of toxicity, but present different degrees of hazard. Ex. Odorless and non-irritating vs. pungent odor The chemical with warning properties may present a lesser degree of hazard. TOXICOLOGY Early interest was in “how to poison” In 1800’s, tests to identify poisons were developed (i.e., forensic medicine) Only in 20th century has toxicology been applied to defining safe work conditions TOXICOLOGY IS MULTIDISCIPLINARY CHEMISTRY BIOCHEMISTRY PHYSIOLOGY PATHOLOGY IMMUNOLOGY PHYSICS ENGINEERING STATISTICS ROUTES OF EXPOSURE Inhalation Ingestion Skin contact Injection EFFECTS OF EXPOSURE ACUTE - a “one-time” event rapid absorption of material exposure sudden & severe critical period for death/survival CHRONIC - small doses over long time rate of intake > rate of elimination material remains in tissue; injures Comparison of Chemical Exposures [Industrial vs Non-Industrial] Route of Exposure inhalation ingestion skin absorption Type of Contact acute chronic Number of Agents Other Aspects TYPES OF TOXIC EFFECT mortality pathological change growth rate change physiological injury biochemical change behavioral effects reproductive system damage mutagenic, etc. Toxic Effect by Target Organ irritant asphyxiant anesthetic hepatotoxic nephrotoxic neurotoxic pulmonary Factors Influencing Intensity of Toxic Action route of entry rate of exposure age of host prior exposure environment host factors gender, genetics other factors Dose-Response Relationship Correlation between the amount of exposure and the resulting effect Lethal Dose/Lethal Concentration LD50 - Dose required to kill 50% of population LC50 – Concentration required to kill 50% of population How is toxicological data obtained? animal toxicological studies accidental human overexposures controlled exposures of human volunteers epidemiological studies descriptive retrospective (conventional) prospective (cutting edge) Sources of Toxicological Information Material Safety Data Sheet Identity Hazardous Ingredients/Identify Information Physical/Chemical Characteristics Fire and Explosion Hazard Data Reactivity Data Health Hazard Data Precautions for Safe Handling and Use Control Measures Information Resources http://msds.ehs.cornell.edu/msdssrch.asp http://hazard.com/msds/index.php