MAMMALIAN TOXICOLOGY

(Biology 666, 3 credit, Spring 2003, 2005, 2007...)

Campbell website:

http://kcampbell.bio.umb.edu

SCHEDULE FOR MAMMALIAN TOXICOLOGY
Biology 666, Spring 2005, Weekly Sessions
# Topic; Text Readings (Casarette and Doull = C)

1. Organization, e-mail addresses, student/instructor introductions, overview of course, projects. Definition and derivation of toxicology and sister sciences endocrinology and pharmacology; definition of toxins and toxicants; Key features of toxicology and study of toxicants; Modes of exposure, elimination, bioavailability, partition; C 1-3, 5, 7
2. Toxicant targets; Physiologic dose-response; C 2, 21; The role of intercellular chemical communication: hormone, receptor, transducer, effector; agonist, antagonist; Interconnections of transduction mechanisms; C 3; End of Add/Drop (January 31)
3. Organismal regulation, feedback circuits; C 20, 21; Cell cycle controls: current models; C 3
4. Project Discussion
5. Cell death: necrosis, apoptosis; C 3,10,18,20; Neural and immune function overview; C 3,12,16,19
6. Finalization of Project Choices
7. Biochemistry of toxicant metabolism, enterohepatic circulation; Toxicodynamics and toxicokinetics C 5,6,7,13
8. Spring Break
9. Project Drafts Due. Gamete production in mammals; Gestation in mammals; C 9,10,20
10. Mammalian toxicity testing: in vivo, in vitro, multigeneration; C 2, 8, 9, 10, 20; Molecular methods, high throughput testing; C 9,31 (Dr. Campbell is traveling, reschedule?)
11. Stress and dose interactions; Diet as modulator or mode of exposure; Developmental status/age and toxicity; C 10,29
12. Predispositions to toxic risk; Moderators of toxic risk; C 4, 9; Carcinogenesis : Are the toxicity models correct?; C 8,9,25
13. Discussion of Draft Projects
14. Adequacy of models for developmental toxicity; C 10, 29; Steroid disruptors: estrogen, androgen, progestin, corticoid; C 20, 21, 29; Thyroid, retinoid and other disruptors; C 10,20,21
15. Final Projects Due. Summary Discussion. (Dr. Campbell is traveling, reschedule?)
16. Final Exam Period/ Final Exam
    
<><><>

<>Prerequisites:

General and Organic Chemistry plus General Biology and at least one advanced course in Cell Biology, Biochemistry, or Physiology; or Permission of the Instructor.

Mammalian Toxicology (Biology 666) is a 3 credit graduate course offered to students with appropriate prerequisites in chemistry and biology.

This course provides a background in principles of toxicology as they are applied to mammalian systems. Coverage will include: basic concepts in evaluation of poisons and their commonalities with evaluations of drugs and hormones; toxicant exposure routes, uptake, sites and mechanisms of action, storage, metabolism, activation, and clearance; toxicant roles in carcinogenesis, development, endocrine, and reproductive functions; exploration of the role of diet, lifestyle, and concurrent exposures; methods of toxicant evaluation with emphasis on multigeneration and high throughput testing; and environmental and medical implications of toxicant or toxin exposures on individual and ecological health.

The course will cover basic tenets of toxicology but will also underline the similarities and commonalities of this science with those of endocrinology and pharmacology. It will emphasize the integrative nature of these disciplines and will feature the applied nature of toxicology as an investigative and regulatory science.

Course resources will include a major text but will also draw heavily on Internet resources and original papers. Case studies may be used to cover parts of the material and active discussion will be encouraged through the use of a threaded discussion and one or more writing assignments. Development of Web-based resources will be an aim in projects associated with this class.

Specific Objectives:

1. Learn the basic framework of testing and evaluation that forms the foundation of toxicology.

2. Explore the commonalities and links between toxicology, endocrinology, and pharmacology.

3. Demonstrate how toxicology integrates and synthesizes the knowledge gleaned from a spectrum of other disciplines and applies it to investigating the nature of and risks associated with exposure to toxicants and toxins.

4. Investigate the problems of health and the environment encountered in mammalian systems as a result of exposure to xenobiotics.

5. Apply the knowledge base to help uncover the existing gaps in knowledge of mammalian toxicology.

Students will be graded on one in-class, closed book exam given as a final (25%). Participation in class, discussion, and peer critiquing of student projects will constitute 35% of the grade. A writing project involving exploration of a topic jointly chosen with the instructor will constitute 40% of the grade. The project will be submitted as an .HTML compatible document that explores a gap or questionable aspect of current toxicological practice or a topic that will not be covered fully within the context of the course, e.g., appropriateness for classifying toxicants as initiators, promotors, or progressors of carcinogenesis; current knowledge of the impact of phytoestrogens on apoptosis within the rat endometrium; or the molecular relatedness of P450 enzymes involved in Type I metabolism across multiple species as ascertained using online molecular databases. This document can use figures, models, and tables as well as a narrative argument to make or illustrate points. It should incorporate standard references for all texts and journal articles cited as well as complete URLs for Internet or Web resources. No materials should be copied or reproduced without alteration in production of this document. The penultimate version of the project should be submitted electronically one month prior to the end of the term. This will be critiqued by the instructor and at least two student peers. The final version of the project will be due at the time of the final and must be submitted electronically. The documents may be added to the course Website at the end of the term including appropriate information on their authorship. Communications with the instructor may occur in person, via e-mail, or via links within the course web pages.

Students are expected to take in-class exam on the date scheduled. Should there be an unavoidable problem, the Instructor may, at his discretion provide a makeup exam or a second project. For the Online course, an expectation is that a total of at least 3 hours per week will be spent interacting with material posted on the Website. Prior reading of assigned materials and familiarity with linked Internet sites is expected prior to any scheduled meeting times.

Readings:

Chapters in assigned texts will be indicated within the syllabus. These provide some background for the lectures or weekly meetings. These will be supplemented by readings in other texts, journal articles, or Web documents. Whenever possible, these will be drawn from sources that are accessible through the Internet or in every science library. In other instances, I will have a copy in my office or available in the Biology Offices.

Required Text:

Casarett & Doull's Toxicology: The Basic Science of Poisons, 6th Ed. C.D. Klaassen. McGraw-Hill:New York, NY. 2001. 1236 pp. ISBN 0-07-134721-6.

Supplemental Texts:

(Readings may be drawn from these. However, they are listed here as a source for more extended reading, not necessarily for acquisition in association with this course.)

Silent Spring. R. Carson. Fawcett Crest: New York, NY. 1970. [Many other editions are available.]

Our Stolen Future. T. Colburn, D. Dumanoski, J.P. Myers. Penguin Books: New York, NY. 1997.

Hormonally Active Agents in the Environment. Committee on Hormonally Active Agents in the Environment, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. National Academy Press: Washington, D.C. 1999.

Endocrine and Hormonal Toxicology. P.W. Harvey, K.C. Rush, A. Cockburn. John Wiley & Sons Ltd.: Chichester, UK. 1999.

Casarett & Doull's Toxicology: The Basic Science of Poisons, 5th Ed: Companion Handbook. C.D. Klaassen, J.B. Watkins III. McGraw-Hill: New York, NY. 1999.

Generations at Risk: Reproductive Health and the Environment. T. Schettler, G. Solomon, M. Valenti, A. Huddle. The MIT Press: Cambridge, MA. 1999.

Toxicology for the Next Millennium. R.J. Isfort, J. Lederberg. Annals of the New York Academy of Sciences, Volume 919. New York Academy of Sciences: New York, NY. 2000.

Hormonal Chaos: The Scientific and Social Origins of the Environmental Endocrine Hypothesis. S. Krimsky. Johns Hopkins University Press: Baltimore, MD. 2000.

Pills, Potions, Poisons: How Drugs Work. T. Stone, G. Darlington. Oxford University Press: Oxford, UK. 2000.

Introduction to Biochemical Toxicology, 3rd Ed., E. Hodgson, R.C. Smart. John Wiley & Sons, Inc.: New York, NY. 2001.

Toxicology Secrets: Questions You Will Be Asked ... on Rounds, in the Ed, on Bedside Oral Exams.
L.J. Ling, R.F. Clark, T.B. Erickson, J.H. Trestrail III. Hanley and Belfus, Inc.: Philadelphia, PA. 2001.

Gilman, A.G., T.W. Rall, A.S. Nies, P. Taylor (eds) Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th Ed., Pergamon Press, Inc.: Elmsford, NY, 1990.