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Lecture Materials

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Module 1: General Principles

> Lecture 1: Absorption, Distribution, and Excretion (Trush)

  • Describe the characteristics of the various types of cellular transport
  • Identify the major routes of exposure and excretion of xenobiotics
  • State factors which affect the distribution and excretion of xenobiotics
  • Illustrate how consideration of PBPK modeling to estimate the level of exposure to a reactive metabolite can be used to improve the risk assessment process

> Lecture 2: Xenobiotic Biotransformation (Trush)

  • Distinguish the differences between Phase I and Phase II reactions
  • Recognize the enzymes involved in this process and identify factors that affect this process
  • Recognize that one of the possible consequences of biotransformation is the conversion of xenobiotics to reactive intermediates, and that depending upon their chemical nature, these intermediates can modify molecular targets through different mechanisms

> Lecture 3: Environmental Carcinogenesis (Yager)

  • Describe the role of the environment in carcinogenesis
  • Discuss the multistage nature of the carcinogenic process
  • Relate experimental findings to humans
  • Apply knowledge to prevention strategies

> Lecture 4: Cancer Biomarkers and Susceptibility Factors (Kensler)

  • Relate the selection of biomarkers to the toxicological paradigm
  • Discuss analytical approaches used for measuring biomarkers of exposure to environmental carcinogens
  • Describe the criteria for selecting useful biomarkers for human studies
  • Assess the contributions of inter-individual variability in biotransformation and DNA repair to risk of cancer
  • Summarize the uses of biomarkers in public health research

> Lecture 5: Elements of Risk Assessment (Yager)

  • Describe the main components of the risk assessment process
  • Identify the fundamental differences in determining risk for exposure to non-carcinogens and to carcinogens

Module 2: Case Studies

> Lecture 6: Hepato and Renal Toxicology (Yager)

  • Describe the cellular composition and basic structure of the hepatic acinus and kidney nephron.
  • Describe the main functions of the liver and kidney.
  • Describe the mechanisms of hepatic toxicity caused by ethanol and carbon tetrachloride.
  • Describe the mechanisms responsible for xenobiotic-xenobiotic interactions and give specific examples.
  • Describe the process of lipid peroxidation.
  • Describe the mechanisms of hepatic and renal toxicity caused by chloroform.
  • Discuss the animal hepatic and renal carcinogenicity data for chloroform and describe its use for determination of very safe doses in the risk assessment for human exposure.
  • Discuss the importance of considering the route of exposure and predictions derived from PBPK modeling in determinations of the very safe dose level for human exposure.

> Lecture 7: Reproductive and Developmental Toxicology (Yager)

  • Describe the basic structures and cellular composition of the testis and ovary.
  • Describe the concept of "windows of susceptibility" or "toxic windows" for developmental toxicity.
  • Discuss the reproductive and developmental toxicity in humans of 3 chemicals, 1,2-dibromo-3-chloropropane, diethylstilbestrol and thalidomide.
  • Discuss the mechanisms of these toxicities and factors that my influence the extent of toxicity that can occur upon exposure.
  • Evaluate reproductive toxicity data in light of the possible mechanisms causing the adverse effects.
  • Better interpret the potential significance of the findings to possible adverse health effects to exposed humans.

> Lecture 8: Persistent Organic Pollutants (POPs) and Dioxins (Trush)

  • Recognize and differentiate between the various types of compounds classified as POPs
  • Identify sources of dioxins
  • Diagram routes of dioxin exposure to humans
  • Describe toxicological manifestations of dioxins
  • Explain why the Ah receptor (AhR) is a critical target in the mechanism of dioxin toxicity
  • Describe mechanisms by which dioxin could disrupt the endocrine system

> Lecture 9: Neurotoxicology (Guilarte)

  • Describe features of the nervous system that influence its vulnerability to neurotoxicants.
  • Identify structural and molecular targets of neurotoxicants.
  • Understand the rationale for the increased vulnerability of the developing central nervous system to neurotoxic insult.
  • Describe mechanisms of action for specific neurotoxicants discussed in the lecture.

> Lecture 10: Immunotoxicology (Trush)

  • Describe various ways chemicals affect the immune system.
  • Explain the organs, cells, and cytokines involved in the immune system.
  • Describe how cells of the immune system respond to antigen.
  • Describe how activation of the immune system can result in pathology.
  • Explain through case study examples how chemical exposures result in hypersensitivity in people.

> Lecture 11: Air Toxicants (Trush)

  • Identify sources of exposure and describe components related to the toxicokinetics and toxicodynamics of these two agents
  • Recognize the human effects related to exposure to ozone or benzene
  • Identify sources of benzene exposure and describe components related to the toxicokinetics and toxicodynamics of benzene
  • Recognize the human health effects related to exposure to benzene
  • Be able to identify differences between different bone marrow pathologies

> Lecture 12: Food-Borne Toxicants and Prevention in Toxicology (Kensler)

  • Define mycotoxin and summarize sources of exposure
  • Evaluate the role of mycotoxins as environmental toxins impacting human health
  • Describe the role of metabolism in the toxicity of the mycotoxin aflatoxin
  • Propose means to prevent aflatoxin-induced liver cancer in high-risk populations and apply knowledge to other environmental carcinogens

> Lecture 13: Metal Toxicology (Culotta)

  • Discuss a broad overview of metals in the environment and heavy metal toxicity
  • Describe some of the ways in which we can protect ourselves from metal poisoning, both through man-made agents and natural chelators of heavy metals
  • Gain a detailed understanding of two heavy metals that have an important impact on human health: mercury and cadmium