FSHN 480

Basic Toxicology

FSHN 480, ENVS 480, CB 449, CS433

Fall 2015

Course Syllabus

The course emphasizes basic toxicology principles and the pharmacokinetics, absorption, distribution, metabolism and excretion of drugs, non-nutrient dietary supplements and other compounds foreign to the body. Toxic effects on major target organ systems are discussed, including an introduction to how foreign compounds can initiate, enhance or prevent the carcinogenic process. Briefly surveys diverse areas of toxicology such as eco-, forensic , and reproductive toxicology and reviews the regulatory aspects and studies involved in product safety assessment and consumer protection.

Meeting Time and Location

Monday, Wednesday and Friday from 1:00-1:50pm in 242 Bevier Hall

Course Coordinators

(office hours by appointment)

Michael Biehl (Primary Course Coordinator). Dr. Biehl will have office hours by appointment.

3422 Vet Med Basic Sciences Bldg (VMBSB)

244-4649

biehlml@illinois.edu

Zeynep Madak-Erdogan (Co-Course Coordinator)

294 Burrill Hal

333-7838

zmadake2@illinois.edu

 Course Sections

Introduction

History of Toxicology; definitions of toxicology; fields of toxicology; toxic substances; toxicology endpoints; the basic paradigm (Chapter 1, Timbrell).

Principles of Toxic Action

Quantitation of toxicological effects; building a toxicology glossary; dose-response and frequency plots; LD5, ED5 andTD50; cumulative response; efficacy and potency; receptors (agonists and antagonists); mechanisms of toxicity (Chapters 1 and 2, Timbrell).

Exposure, Absorption, Distribution, and Excretion.

The ADE of ADME, routes of exposure; membranes; the Henderson-Hasselback Equation; compartments (plasma, extracellular, intracellular); distribution of toxic substances to compartments and organs; plasma-protein drug binding; storage of toxic substances in bone and fat; kidney function; the filtration, re-adsorption, and secretion of xenobiotics; measurement of excretion, competition for excretion, inhibition of excretion; disposition and excretion of metals; species differences in ADME (Chapter 3, Timbrell).

Metabolism (Biotransformation)

Phase I/Phase II metabolic processes; P450 mechanism, P450 genes (CYP) and variations; glucuronidation, sulfation, glutathinone (GSH) conjugation; bioactivation and detoxification; benzopyrene, bromobenzene, acetyl aminofluorene and acetaminophen metabolism; metabolic induction and inhibition (Chapters 4 & 5, Timbrell).

Pharmacokinetics and Toxicokinetics

The quantitative description of the absorption, distribution, metabolism and excretion from the body of foreign compounds (drugs, toxic substances, or even non-nutritive food components) and their metabolites.

Clinical Toxicology

Principles of the clinical management of the poisoned patient; the toxicity of common poisons in humans; the use of animal models in toxicology.

Genetic and Molecular Toxicology; Carcinogenesis

Overview of genetic and molecular toxicology and carcinogenesis; DNA damage and repair; mutagenesis and carcinogenesis (Chapter 6.7-6.8, and 7.1Timbrell).

Additional Topics

Hepatic, Renal, Pulmonary, Reproductive and Neuro- toxicology, Toxigenomics, Regulatory Toxicology, Safety Assessment, Food Safety, Ecotoxiology, Forensic Toxicology and Nanotoxicology.

Learning Objectives

  • Learn the vocabulary of toxicology and build a Glossary of key terms
  • To understand and be able to apply basic toxicology concepts to effectively assess the hazard of animal exposures to potentially toxic agents.
  • Understand how chemicals are absorbed into the body and what happens to them after that occurs, both qualitatively and quantitatively.
  • Develop an understanding of how toxic substances interact with organ and cellular systems at the clinical, physiological, biochemical and molecular level.
  • Learn to perform and interpret simple quantitative analysis of toxicological data
  • Become familiar with the various professional fields and applications of toxicology and the methods used in animal research.
  • Explore the application of toxicology and safety assessment within regulatory agencies, the setting of public policy, forensics, and rationale for environmental protection policies.

Textbook. Principles of Biochemical Toxicology (Timbrell), Fourth Edition. The textbook is listed as required. This is our way of strongly recommending that you purchase the text. It is ultimately the student’s choice. This is a team taught course. All instructors will try to insure that all questions on the exams will be based on theory and concepts covered in class lectures and discussions. All Powerpoint lectures will be posted on Illinois Compass 2g as pdf files prior to class.

Examinations (3) and Quizzes (3). There will be 3 non-cumulative exams valued at 100 pts each and 3 quizzes valued at 10 points each. The 3rd exam will be taken during the time allocated by the university to the Final exam period for this class. The 3rd exam will not be provided prior to this date. Exam/Quizz questions may be multiple-choice, True/False, matching, short answer, calculations and/or thought problems. Each exam will be divided between instructors based on their proportion of the lectures since the last exam.

Exam I:               Friday, Sept 25 (100 pts; First 13 lectures through Reproductive Toxicology)

Exam II:              Friday Oct 30 (100 pts; next 13 lectures through Molecular Toxicology)

Exam III:            TBD (100 pts; last 13 lectures through Nanotoxicology)

Quizzes (3):     Sept 9, Oct 12 and Nov 13 (10 points each; material covered since last exam)

Term Paper

70 pts –  The term paper will be due at midnight, Sunday, November 30 or before. This paper should have a minimum of 8 pages written text (not counting space allowed for a cover page, figures, tables, references etc.), double-spaced, size 11 font (all papers will be converted to this font size if not already and # pages evaluated from that). The paper will provide an assessment and student insights regarding a scientific publication that will be provided in class. Your paper should discuss how various principles and concepts of toxicology discussed in class apply to the topic of the publication provided. More detail will be provided in class.

Class participation and attendance. There is no credit earned or lost for not attending and/or participating. The instructors strongly urge you to do both. Not only does attendance and participation enhance your educational experience, but your questions and comments contribute to the value of the class to other students. Exam questions will be drawn from material presented in lectures. The only persons who ever received poor grades (e.g. D or E) in the class were those who did not attend class and whose exam performance was reflective of that behavior.

Missed examinations and rescheduling an exam. There will be no make-up examinations permitted. If you cannot be present at an exam due to an unavoidable, academic (e.g. non-personal) activity, you may take the exam by prior arrangement (except for the 3rd exam) at an earlier date (not to exceed 2 days) from the scheduled exam date. If necessary, contact Professor Biehl (biehlml@illinois.edu) at least one full week prior to the desired exam date to make arrangements. In cases of true, documented medical or family emergency, the instructor will consider a make-up exam. Realize, however, that no two tests can ever be equally difficult so it is inherently unfair to the exam taker or to the other students to allow someone to take an alternate exam.

Grading. Grading will be on a point basis and will be somewhat based on a curve; however, raw scores above 90 will always be an “A,” 80 = “B,” 70 = “C.”. There are 400 total points possible for the semester. In the past there has been little difference in the scores of graduate and undergraduate students. This is a graduate/advanced undergraduate course. Students can normally be expected to earn A or B grades if they put forth the effort, perform well on the exams/quizzes and satisfactorily complete the other course requirements.

Systems Biology of Nuclear Receptors in Metabolic Disease and Cancer