Toxicology

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The Toxicology Learning Framework was created by the Society of Toxicology's Learning Objectives Work Group, a group appointed by the Education Committee with the charge of creating a guide to facilitate the creation or modification of undergraduate courses in toxicology. The group included Joshua Gray (chair), Chris Curran, Vanessa Fitsanakis, Sid Ray, and Karen Stine with significant contributions from Betty Eidemiller. For more background see “Society of Toxicology Develops Learning Framework for Undergraduate Toxicology Courses Following the Vision and Change Core Concepts Model,” Toxicological Sciences, Volume 170, Issue 1, July 2019, Pages 20–24, https://doi.org/10.1093/toxsci/kfz090.

The objectives were modeled after the Core Concepts of the Vision and Change report and are aligned with similar Core Concepts which have been developed for other life science courses by their professional scientific societies and which are published at CourseSource. The Learning Framework was developed following an analysis of undergraduate toxicology syllabi submitted to the SOT’s teaching resource collection as well as an analysis of undergraduate toxicology texts of all genres. We endorse the Vision and Change Core Competencies and Disciplinary Practices as analytical, experimental, and technical skills are desired course outcomes.

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Toxicology Learning Framework

Society Learning Goals	Articles	Sample Learning Objectives

Evolution
How is the use of model organisms fundamental to toxicology?	Contribute an article in this area.	show Describe features of ideal model systems. Describe common model systems, including Drosophila, C. elegans, mouse, rat, and non-human primate. Describe how evolution is fundamental to the use of model systems in toxicology. Describe ethical reasons for using model organisms
How have toxins evolved?	Contribute an article in this area.	show Contrast toxins and toxicants. Explain the role of toxins in organismal defense. Explain mechanisms of avoidance of poisoning by toxins. Explain the importance of secondary metabolites. Discuss how important toxins have been helpful in characterizing basic biological properties.
How have xenobiotic defense mechanism evolved?	Contribute an article in this area.	show Discuss the role of xenobiotic defense mechanisms in protection of organisms from toxicants and toxins. Explain how evolution informs the development of the cytochrome P450 superfamily of genes. Explain how evolution drives resistance to toxicants, toxins, metals, and radiation. Describe how knowledge of genetic information can predict function of similar genes within the same organism or in other organisms.
How do toxicants exert selection pressures?	Contribute an article in this area.	show Describe, using examples, the role that toxicants can play in exerting selection pressures on populations.

Biological information
How does carcinogenesis occur in response to genotoxic and nongenotoxic carcinogens?	Contribute an article in this area.	show Describe the general characteristics of cells that have undergone neoplastic conversion. Describe the mutational theory of carcinogenesis and explain the evidence that supports it. Explain the roles that protooncogenes can play in normal cell function; then relate these, using specific examples, to the role of proto-oncogenes in carcinogenesis. Describe the role of tumor suppressor genes; using specific examples, explain how they can play a role in preventing and/ or genetically predisposing to cancer. Compare and contrast the effects of point and frameshift mutations on a gene. Identify the parts of the DNA molecule which are most vulnerable to damage by physical and chemical agents and describe the mechanisms through which the damage occurs. Explain the differences between pro-carcinogens and carcinogens and name examples of each. Explain the concept of promotion and discuss the various mechanisms through which toxicants can act as promoters. Describe the excision repair and mismatch repair systems for repairing DNA damage. Compare and contrast the threshold versus the non-threshold models for risk following exposure to carcinogens and be able to discuss the public policy implications of both. Explain the concepts behind in vitro tests for mutagenic potential of toxicants and compare and contrast the strengths and weaknesses of these test versus animal bioassay studies.
What effects can the environment have on gene expression?	Contribute an article in this area.	show Discuss the role that nutrition plays in regulating transcription factors. List the changes that toxicants may induce in the protein structure, nucleic acid sequence, and/or fatty acid metabolites. Describe mechanisms of epigenetic transfer of information. Describe how toxicants can induce changes in epigenetic information that can be transferred to subsequent generations. Describe how gene/ environment/time interactions affect developmental disorders and disorders of aging. Describe features of model systems used to examine gene/ environment interactions. Describe toxicant/toxin effects on gene expression. Describe genetic polymorphisms that affect toxicokinetics and risk.
How do biomarkers indicate exposure to toxicants?	Contribute an article in this area.	show Describe how biomarkers can be used to indicate exposure to a toxicant. List the types of biomarkers that are currently used. Describe the role of validation in evaluating biomarkers of epigenetic changes.
What differences occur in how individuals or populations are affected by exposure to different doses of a toxicant?	Contribute an article in this area.	show Explain how differences in individuals result in differences in susceptibility of a population to toxicants. Explain why inbred animals are used in many toxicological tests. Contrast idiosyncratic reactions with other kinds of variation in a population’s response to a toxicant. Contrast Margin of Safety with Therapeutic Index with regards to prediction of drug safety in a population. Explain the concept of dose spacing in terms of toxicity. Describe the concept of hormesis as it applies to toxicology.
How do predisposing factors such as variations in health, gender, and age affect the response of a population to a toxicant?	Contribute an article in this area.	show Describe how endocrine disruptors affect the development and function of the reproductive system. Describe how partial agonists such as tamoxifen function to block hormone signaling pathways. Describe the effects of sex hormones on adolescents and adults. Relate the sequence of human development to time periods in which teratogen exposure results in developmental toxicity. Explain why children may be more susceptible to toxicants than adults. Describe the effect of pregnancy on susceptibility of females to toxicants. Explain how epigenetic mechanisms can play a role in DNA gene expression and carcinogenesis.

Risk assessment and risk management
What is the connection between toxicology and epidemiology?	Contribute an article in this area.	show Compare the strengths and weaknesses of different epidemiological study designs. Differentiate correlation and causation and incidence versus prevalence. Interpret relative risk and odd ratios. Differentiate statistical significance and biological significance. Compare and contrast the various forms of bias and how to control for them.
Why are certain populations at greater risk from exposure to toxicants?	Contribute an article in this area.	show Describe causes for the major at-risk populations: infants and young children, pregnant omen, older adults, people with weakened immune systems, people with inflammatory conditions, and elderly.
How are organisms living in the natural environment affected by natural and anthropogenic toxicants?	Contribute an article in this area.	show Describe the effects of exposure to gaseous environmental pollutants to organisms and to the environment. Explain the environmental consequences of incomplete combustion of organic material such as hydrocarbon fuels. Discuss the findings linking exposure to particulate matter to adverse effects on human health. Compare and contrast point and nonpoint source water pollution in terms of sources, typical content, and options for control. Describe the environmental impacts of oil spills and the remediation processes used to combat them. Explain the mechanisms behind the process of eutrophication, as well as the consequences for aquatic life. Compare and contrast the major categories of pesticides in terms of their mechanisms of action, persistence in the environment, and risks to human health and the ecosystem. Describe some of the sources of metal pollution in water and give examples of effects of environmental exposure to metals on human health and/or ecological function. Describe the hazards associated with the presence of plastics in the environment. Compare and contrast the options of incineration, detoxication, biodegradation, and burial of hazardous waste in terms of the risks and benefits of each. Discuss the natural radioactive sources that contribute to toxicology and current issues involving safe long-term disposal of radioactive wastes.
How is the science of toxicology applied to government regulations to ensure the protection of individuals and the environment?	Contribute an article in this area.	show Describe the controversy of threshold versus non-threshold assumptions with regard to regulatory policy regarding toxicants. Describe the major environmental laws of the United States (and/or other nations). Discuss the importance of regulatory harmonization across various markets. Describe how toxicology testing is used to inform regulatory policy. Describe efforts to reduce the use of animals in research. Contrast risk assessment and risk management.
How does poison management protect human health through a knowledge of poisons and their antidotes?	Contribute an article in this area.	show List various ways that poisons enter the body. List signs and symptoms associated with poisoning. Describe the general treatment of drug overdose. Discuss the emergency medical care for the patient with possible overdose and/or suspected poisoning. Describe the importance of poisoning andoverdose,their manifestations,and prevention strategies utilized in the management of a few prototype toxins. Explain the role and function of Poison Control Centers and TESS (Toxic Exposure Surveillance System).
How have historical incidents impacted the development of the regulatory laws concerning toxicology?	Contribute an article in this area.	show Describe the impact of historical events in workplace toxicology on the development of regulatory law. Describe the history of key events in toxicology, including the mechanism of toxicity of the toxicant behind the event and the related public policy. Describe what brownfields are.

Systems toxicology
How do cells respond to exposure to toxicants?	Contribute an article in this area.	show Describe the types of chemical bonds that can characterize the interaction of toxicants with the major classes of cellular macromolecules. Explain the interaction of toxicants with enzymes in terms of sites of action and enzyme kinetics, including the differences between competitive and noncompetitive inhibition. Describe the major categories of receptors found in cells and differentiate between toxicants classified as agonists, antagonists, and partial agonists in terms of their interactions with those receptors. Explain the potential impact of toxicants on ion channels in terms of membrane potentials. Describe the sources and characteristics of free radicals and explain the mechanisms behind the process of lipid peroxidation. Explain what alkylating agents are and discuss how they interact with DNA. Explain the circumstances under which cells produce stress proteins and describe examples of some of their protective mechanisms and effects (including the role of several stress proteins as chaperones). Compare and contrast the mechanisms behind cell death, including apoptosis, necrosis, and autophagy.
How are organs affected by exposure to toxicants?	Contribute an article in this area.	show Identify and describe organ toxicity emanating from therapeutic and nontherapeutic (intentional and unintentional) drug/chemical exposures. Recognize system-specific and organ-specific toxic effects on humans and other experimental models. Predict/explain possible toxicological consequences after exposure to one or more drugs/chemicals within safe limits. Describe the importance of the bioactivation process for prodrugs. Decipher the mechanisms for drug and chemical-induced toxicity in in vivo and in vitro models and appropriately design and interpret drug screenings. Discuss the important role the liver plays in xenobiotic metabolism. List the characteristics that enable the kidney to efficiently excrete xenobiotics. Recognize system-specific and organ-specific toxic effects on humans and other experimental models. Describe the characteristics of the nervous system that make it vulnerable to many toxicants.
How are body systems affected by exposure to toxicants?	Contribute an article in this area.	show Discuss the role that the circulatory system plays in exacerbating or limiting toxicity. Explain adverse reactions originating from toxic exposures in any setting and medication errors in a healthcare setting. Predict/explain possible toxicological consequences after exposure to drugs/chemicals below and above safe limits. Evaluate and interpret relevant information from the toxicology literature, explain toxicological interactions, and identify preventable causes. Describe various analytical, molecular, and computational tools used to interpret information from toxicology studies to understand toxicological interactions and to describe preventable causes. Describe various analytical, molecular, and computational tools used to interpret information from toxicology studies to understand toxicological interactions and to describe preventable causes.
How do toxicants affect an organism’s development and reproduction?	Contribute an article in this area.	show Contrast the four reproductive endpoints: fertility, menstrual cycle, sperm count and viability, and sexual behavior. Contrast the primary developmental toxicological endpoints. Discuss the downstream effects that occur from exposure to an endocrine disrupting compound. Contrast the effects of environmental toxicants on R strategists versus K strategists. Describe, using examples, the role that toxicants can play in exerting selection pressures on populations. Describe, using examples, the role that toxicants can play in exerting selection pressures on populations. Discuss how toxicants can alter ecosystem structure in terms of effects on energy flow and the trophic pyramid. Explain the concept of residence times for toxicants in the environment and compare and contrast the ways in which toxicants move through soil, atmosphere, and water. Explain the concepts of bioavailability and bioconcentration. Discuss examples of typical species used in ecotoxicological single-species testing. Compare and contrast the strengths and limitations of the most common methods of ecotoxicological testing including microcosms, mesocosms, field studies, and mathematical modeling. Identify important concepts in ecotoxicological risk assessment.
How do toxicants move through the environment to affect ecosystems?	Contribute an article in this area.	show Contrast the effects of environmental toxicants on r strategists versus K strategists. Describe, using examples, the role that toxicants can play in exerting selection pressures on populations. Contrast the effects of toxicants on predator populations, prey populations, and the interactions between them. Discuss how toxicants can alter ecosystem structure in terms of effects on energy flow and the trophic pyramid. Explain the concept of residence times for toxicants in the environment and compare and contrast the ways in which toxicants move through soil, atmosphere, and water. Explain the concepts of bioavailability and bioconcentration. Discuss examples of typical species used in ecotoxicological single-species testing. Compare and contrast the strengths and limitations of the most common methods of ecotoxicological testing including microcosms, mesocosms, field studies, and mathematical modeling. Identify important concepts in ecotoxicological risk assessment

Pathways and transformations of energy and matter
How do toxicants affect homeostasis for exposed organisms?	Contribute an article in this area.	show Describe how toxicants disrupt homeostasis. Describe the role of xenobiotic defense mechanisms in maintaining homeostasis. Contrast a physiological versus a pathological adaptation to a stimulus. Contrast physiological and pathological cellular adaptations.
How does the concept of dose-response relate to toxicology?	Contribute an article in this area.	show Describe the different protocols for dosing: exposure time, administration, absorbance, internal, and delivered. Describe a dose-response curve, labeling the axes and identifying important regions of the plot. Describe the features of a dose- response curve. Explain differences in dose- responses in a population of individuals. Describe why individuals who have idiosyncratic responses (either hypersensitivity or hyperresistance to toxicants) are outliers and propose mechanisms for their differences. Describe how alterations in homeostasis can affect an individual’s dose-response.
How do concepts of administration, distribution, metabolism, and elimination(ADME) help characterize the mechanism of action of toxicants?	Contribute an article in this area.	show Describe the fundamental basis of xenobiotic defense through ADME. Explain why LD50is commonly used as a measure of toxicity of a compound. Describe the concept of ADME as it relates to toxicant exposure. Contrast the major sites of entry for toxicants and how site of entry affects dose and risk. Describe features of chemicals and barriers that affect absorption of compounds. Contrast the mechanisms of elimination, including excretion, storage, and biotransformation.
How can ADME be quantified using toxicodynamics and toxicokinetics (TDTK)?	Contribute an article in this area.	show Define toxicokinetics, pharmacokinetics, toxicodynamics, and pharmacodynamics. Explain how toxicokinetic studies are used to determine changes in concentration of a chemical and its metabolites over time in blood and other tissues. Explain several methods of toxicokinetic analysis. Describe how one-, two-, or multi-compartment models are used to approximate toxicokinetics. Describe how saturation affects the elimination of a compound. Contrast zero-order versus first- order kinetics of elimination. Describe how barriers (e.g., blood-brain barrier or placenta) alter toxicokinetics. Apply mathematical and computation methods to toxicokinetics.
What is the relationship between toxicology and pharmacology?	Contribute an article in this area.	show Contrast measurements of drug safety. Explain the concept of dose spacing. Describe the role of toxicology in the drug development process, including preclinical studies and clinical trials.
How does oxidative stress contribute to toxicology?	Contribute an article in this area.	show Describe free radical forms of oxygen and nitrogen. Describe the mechanism of lipid peroxidation. Describe the defenses organisms have against free radicals. Describe the nrf2 pathway and how it signals defense against oxidative stress.
What effects can toxicants have on energy metabolism?	Contribute an article in this area.	show Discuss the role that glycolysis plays in energy production. Describe the importance of ATP in cellular homeostasis. List the implications of a high- fat/high-energy diet. Describe the central role of oxidative phosphorylation in energy generation.

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Society of Toxicology

Founded in 1961, the Society of Toxicology (SOT) is a professional and scholarly organization of scientists from academic institutions, government, and industry representing the great variety of scientists who practice toxicology in the US and abroad. The Society’s mission is to create a safer and healthier world by advancing the science and increasing the impact of toxicology.

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