PRINCIPLES OF TOXICOLOGY
Instructor: Professor. R. A. Coulombe, Jr.
Office Hours: by appointment, or just drop by my office at Animal Science 213
Meeting time and location: T, Th, 7:30-8:50 Animal Science 315
The aim of this course is to provide an in-depth knowledge of the mechanisms of interactions between foreign compounds and biological systems.� Toxins of agricultural and environmental significance are emphasized.� Students enrolled in this course must have a working knowledge of biochemistry, pharmacology and physiology. Prerequisites for this course are Environmental Toxicology (ADVS 5400/6400), General Pharmacology (ADVS 6350) and the Biochemistry series (Chem 5700, 5710).� If you have not had one or more of these classes, see me.
Grading will be based on two mid-term examinations (20% each), a comprehensive final examination (40%), and a grant proposal (20%). The final examination is scheduled for Tuesday, December 11, 7:00-8:50 am.� Examinations, which consist mainly of short answer/essay questions, are intended to evaluate your ability to synthesize answers from knowledge gained from lectures, handouts and reading material.�
Toxicology on the Web. Course materials, such as this syllabus, old examinations, announcements, homework assignments, and course tutorials, are available at http://toxicology.usu.edu/660/6600.htm. The USU Toxicology Graduate Program website is at http://toxicology.usu.edu/.
Review on the Web:� Background materials that were previously presented during lecture (History of Toxicology, Basic Principles of Toxicology, Toxicity Testing, Disposition of Drugs and Chemicals, Basic Metabolism, Genetic Toxicology) are now available on the web at http://advs.usu.edu/rogerc/index.htm.� Students are responsible to review this material.�
Required textbook:� Casarett and Doull's Toxicology, The Basic Science of Poisons. C.D. Klassen, editor. 6th edition. McGraw Hill, New York. A course reader (Principles of Toxicology: Lecture Notes and Study Guide) is available from the USU Bookstore at a nominal fee.�
Goodman and Gillman's The Pharmacological Basis of Therapeutics. 9th Edition. Editors: A.G. Gilman, L.S. Goodman, A. Gilman. Macmillan Publishing, New York, 1996.
Textbook of Medical Physiology A. C. Guyton and J.E. Hall.� 9th edition. W.B. Saunders and Co., 1996, Philadelphia.
Special needs. Any student with a disability who requires accommodation must contact the instructor. The disability must be documented with the Disability Resource Center. Course material may be requested in alternative formats.
APPROXIMATE LECTURE OUTLINE
Metabolism and biotransformation. Role of cytochrome P-450 (CYP), arachidonic acid-dependent and FMO-mediated metabolism. Factors influencing biotransformation. CYP induction and inhibition. Glutathione S-transferase (Chapters 3 and 6)
Chemical carcinogenesis: Definitions. Historical aspects.� Types and classes of carcinogens. Mutational mechanisms. Tissue susceptibility. Carcinogen metabolism. Cancer epidemiology. Factors influencing cancer incidence.� Oncogenes and tumor suppressor genes. In vitro and in vivo predictive assays for carcinogens. (Chapters 8, 9)
Central Nervous System Toxicology: Blood-brain barrier. ��� Classes of anoxia. Specific agents. Cholinesterase inhibitors. Organophosphates. DDT, CNS stimulants and depressants. Drugs of abuse. Hallucinogens. (Chapters 16, 31)
Toxicity to Blood and Blood-Forming Organs: Review of blood cell histology. Effects of benzene, radiation, lead, arsenic. Mechanisms of compound-induced anemia (Chapter 11).
Hepatic Toxicology: Review of hepatic anatomy and physiology. Markers of hepatic damage.� Specific hepatotoxicants (Chapter 13)
Renal Toxicology: Review of renal physiology and structure. Indices of renal damage. Specific renal toxicants. (Chapter 14)
Pulmonary Toxicology: Pulmonary anatomy, histology and function. Gases, vapors, particles. Oxidants and lung damage. Paraquat.� Free radical mechanisms (Chapters 15,28)
Biomarkers in toxicology: Characteristics of biomarkers. Predictive toxicology using biomarkers. (Chapter 29)
Natural Toxins: Introduction. Mycotoxins, algal toxins, animal and plant toxins. Induced toxicants. Nitrosamines. Food additives and contaminants. Anti-carcinogens and anti-toxicants. (Chapters 26-27, 30)