Download Toxicologic Course - Health - Lecture Slides and more Slides Public Health in PDF only on Docsity! Epidemiologic Side of Toxicology (6th of 10 Lectures on Toxicologic Epidemiology) Taken in the early ’90s, when desktop computers were still a luxury. Three Case Studies for the Epidemiologic Side of Toxicology: 1. Jamaica Ginger Epidemic 2. London Smog of 1952 3. Multistage Model of Carcinogenesis Ginger Paralysis: Syndrome & Cause • Characterized by ataxia, muscular weakness, unsteady gait, flaccid paralysis of the legs. • Also known as jake leg, wrist drop, and foot drop. • Caused by exposure to TOCP, with delayed onset of 1 to 3 weeks. Ginger Paralysis: History and Toxicity • The syndrome known for a century; and later, as ginger paralysis due to its first major episode in the USA. • TOCP is the most toxic isomer of TCP; both, like some other OP, can induce delayed neurotoxicity. • The initial effects likely involve the inhibition of neurotoxic esterase. Ginger Paralysis: The Lesson (and Speculation) •Despite the Jamaica ginger episode, there were still numerous outbreaks involving cooking oil contaminated with TOCP. •Delayed neurotoxicity is extremely specific to chemical structure. •It was epidemiologic evidence that advanced the toxicology of TOCP. London Smog: History & the Epidemic • 4,000 premature deaths, with most being elderly or having preexisting diseases, from breathing heavily polluted air in London in 1952. • Smog is a mixture of smoke and fog, now also involving the equally irritating photochemical air pollution. • Air pollution is predictable, and was recognized back in the Roman period. London Smog: Toxicity of the Air Pollutants • Sulfur dioxide is an upper airway irritant. • Carbon dioxide is a potent asphyxiant. • Nitrogen dioxide causes severe irritation of the innermost parts of the lungs. • Ozone is a reactive and toxic form of elemental oxygen. London Smog: The Lesson • The older winter smog problem in London and worldwide is now being replaced with summer smogs from photochemical formation. • The adverse health effects of the winter or summer air pollutants cannot be investigated using classic toxicology studies alone. Multistage Model: The Course of Carcinogenesis • Carcinogenesis is the biochemical process characterizing the progression of normal cells to neoplastic and later into tumor cells. • Multistage model is a quantitative as well as a mechanistic theory used to characterize this biochemical process. • Two of the stages basic to the model are presumably initiation and promotion. Multistage Model: The Underlying Theories • In addition to being an initiator or a promoter, an agent initially can be a precarcinogen and later be transformed into a harmful ultimate carcinogen. • Initiation is usually irreversible, of short duration, and invisible, whereas promotion has the opposite effects. • As an outgrowth of the challenge to the single stage and the multicell theories. Multistage Model: The Lesson & Its Utilities • Leading to the use of more proper mitigation measures; and to the adoption by regulatory agencies for cancer risk assessment. • Toxicologists using animal studies, without this epidemiology-based theory, would likely fail to elucidate or make fuller use of the mechanistic process of carcinogenesis. Overview of Next Lectures Human Exposure Assessment I & II • Human exposure assessment is one of the key components in the health risk assessment. • Lecture 7 (Assessment I) will cover the direct measurement methods. • Lecture 8 (Assessment II) will focus on the indirect measurement methods.
