E3260 Applied toxicology and pharmacology

Faculty of Science
Autumn 2024

The course is not taught in Autumn 2024

Extent and Intensity
2/1/0. 3 credit(s) (fasci plus compl plus > 4). Type of Completion: zk (examination).
In-person direct teaching
Teacher(s)
doc. RNDr. Pavel Babica, Ph.D. (lecturer)
prof. RNDr. Luděk Bláha, Ph.D. (lecturer)
doc. Mgr. Klára Hilscherová, Ph.D. (lecturer)
RNDr. Iva Sovadinová, Ph.D. (lecturer)
Guaranteed by
doc. RNDr. Pavel Babica, Ph.D.
RECETOX – Faculty of Science
Contact Person: doc. RNDr. Pavel Babica, Ph.D.
Supplier department: RECETOX – Faculty of Science
Prerequisites
The course does not have any specific pre-requisites. Basic knowledge in (molecular and cell) biology and (bio) chemistry is advantagoues.
Course Enrolment Limitations
The course is also offered to the students of the fields other than those the course is directly associated with.
fields of study / plans the course is directly associated with
Course objectives
The aim of the course is to introduce the basic principles and methods used in toxicology and pharmacology, with an emphasis on contemporary approaches that leverage mechanistic knowledge to understand therapeutic effects or adverse health outcomes at both individual and population levels. Students will learn fundamental concepts in the assessment of toxicokinetics and pharmacokinetics for various chemicals, including environmental and food toxicants and drug candidates. The course will address toxicodynamics and pharmacodynamics by covering the key mechanisms underlying toxicological and pharmacological activities and the methods for their evaluation using various computational and experimental models and assays. Additionally, it will explore how mechanistic knowledge can be interpreted and extrapolated to higher levels of biological organization or translated from in vitro to in vivo settings. The applications of these tools and approaches in preclinical research, hazard identification or chemical risk assessment will be presented. Students will also gain an understanding of the current legislative framework for the use of advanced, animal-free assays in toxicity testing, as well as the emerging trends and concepts in predictive toxicology and preclinical research.
Learning outcomes
A student who successfully completes the course will be able to:
- Describe the fundamental mechanisms of toxicity and pharmacological activity at different levels of biological organization (molecular, cellular, tissue, organ, organism), including their connections to therapeutic effects and adverse health outcomes at both the individual and population levels.
- Explain major computational and experimental methods, models and approaches used to assess pharmacological activity or to evaluate perturbations in key toxicity mechanisms leading to therapeutic or harmful effects.
- Understand the principles, applications, and current validation status of in vitro assays used to assess specific adverse outcomes and therapeutic effects, and how these assays can be extrapolated from in vitro to in vivo contexts.
- Recognize the regulations and guidelines for chemical assessment related to evaluating chemical effects, including the application of advanced, animal-free assays in toxicological and pharmacological testing.
- Understand the applicability and domains of use for alternative (in vitro) vs. standard (in vivo) methods for toxicity and pharmacology testing, including their strengths, limitations, and potential for routine use.
- Navigate contemporary concepts and approaches in toxicology and pharmacology that enhance the reliability and predictivity of chemical testing and assessment.
Syllabus
  • Mechanisms of Toxicity Across Biological Organization Levels:
  • Introduction to mechanisms of toxicity at molecular, cellular, tissue, organ, and systemic levels.
  • Overview of Adverse Outcome Pathways (AOPs).
  • Basic concepts and terminology: hazard, risk, points of departure, safety, efficacy, POM, POC.
  • Toxicokinetics and Pharmacokinetics:
  • Concepts of Toxicokinetics/Pharmacokinetics (ADME): Assessment of Absorption, Distribution, Metabolism, and Excretion.
  • Methods for studying ADME: Approaches to study ADME in vitro and in vivo, including experimental techniques and model systems.
  • Physiologically Based Pharmacokinetic (PBPK) and Toxicokinetic (PBTK) Modeling.
  • Toxicodynamics and Basic Mechanisms of Toxicity:
  • Interactions with biomacromolecules: Mechanisms of chemical interactions with nucleic acids, proteins, and (phospho)lipids.
  • Cellular level: Cytotoxicity, cell injury and death, oxidative stress, and dysregulation of the cell cycle.
  • Tissue level: Disruption of intercellular communication, tissue homeostasis, and inflammation.
  • Organ level: Specific target organ toxicities including neurotoxicity, hepatotoxicity, and endocrine disruption.
  • Organism level: Topical and systemic toxicity.
  • In Vitro Models for Cellular, Tissue, and Organ Toxicity:
  • Overview of various in vitro models used in toxicology and preclinical drug research, including primary cells, cell lines, organotypic cultures, 3D cell cultures, organoids, and organ-on-a-chip systems.
  • Application and limitations of these models in evaluating toxicity and therapeutic effects.
  • New Approach Methodologies (NAMs) and In Vitro-In Vivo Extrapolation:
  • Introduction to New Approach Methodologies (NAMs) for toxicity testing and risk assessment.
  • Techniques for extrapolating in vitro data to in vivo contexts, including quantitative in vitro-to-in vivo extrapolation (QIVIVE).
  • Advances in next-generation risk assessment approaches.
  • Pre-validation and validation of testing methods.
  • Chemical Safety and Pharmaceutical Assessment:
  • Overview of the regulatory landscape for chemical safety and pharmaceutical evaluation.
  • Integration of alternative testing methods within regulatory frameworks.
Literature
  • Translational medicine : molecular pharmacology and drug discovery. Edited by Robert A. Meyers. Weinheim: Wiley-VCH, 2018, 1064 stran. ISBN 9783527336593. info
  • KUBINCOVÁ, Petra, Jiří NOVÁK and Iva SOVADINOVÁ. Acute Systemic Toxicity: Alternative in Vivo and in Vitro Methods. CHEMICKÉ LISTY. Praha: Česká společnost chemická, 2016, vol. 110, No 2, p. 118-125. ISSN 0009-2770. info
  • FOWLER, Bruce A. Molecular biological markers for toxicology and risk assessment. Amsterdam: Elsevier, 2016, ix, 153. ISBN 9780128095898. info
  • Predictive toxicology : from vision to reality. Edited by Friedlieb Pfannkuch - Laura Suter-Dick. Weinheim: Wiley-VCH, 2015, xxv, 404. ISBN 9783527336081. info
Teaching methods
The course combines (i) lectures, i.e. presentations and face-to-face interactions (12 x 2 hours per week, attendance non obligatory), (ii) homework - a written report and evaluation of a written report form colleague (4 h), preparation for interactive seminar (6 h), (iii) 2 x interactive 2 h seminars, with each student presenting on a topic selected in the start of the course.
Assessment methods
The final assessment is based on the fulfillment of the following obligations:
1) Preparation of a research/report on a selected chemical substance according to the given template (submission in the middle of the term).
2) Assessment and feedback on the research prepared by another student (in the middle of the term).
3) Preparation a presentation (approximately 15 minutes) on current approaches to evaluating the selected type of toxicity/adverse outcome (end of the semester - 13th/14th week of the term).
4) Final written test with the possibility of a follow-up oral examination (during the examination period). The test consists of 24 closed-ended questions and 2 open questions, min. score 60% is required to pass the exam, evaluated as A-F. After the test, there is an option for an oral examination.
Without completing assignments 1-3 during the term (evaluated as completed/incompleted), it is not possible to pass the exam. The final grade is determined by the final exam (item 4).
Náhradní absolvování
For the theoretical parts, students can be provided with study materials (slides, texts, videorecordings of the lectures). Practical / seminar case studies can be agreed on individual basis.
Language of instruction
Czech
Further Comments
The course is taught annually.
The course is taught every week.
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