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Lecturer(s)
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Opršal Jakub, Ing.
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Pouzar Miloslav, prof. Ing. Ph.D.
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Course content
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1) Introduction to Toxicokinetics - Absorption, distribution, metabolism, and excretion (ADME) of toxic substances; key parameters influencing chemical disposition in the human body; application of QSAR tools to predict critical toxicokinetic parameters. 2) Mechanisms of Toxic Action I - Induction of apoptosis and necrosis, oxidative stress, disruption of cellular metabolism; in vitro viability assays and the use of QSAR models to predict assay outcomes. 3) Mechanisms of Toxic Action II - Neurotoxic substances and their modes of action. 4) Mechanisms of Toxic Action III - Testing of acute and chronic toxicity; dose-response relationships and identification of key points on the dose-response curve. 5) Mechanisms of Toxic Action IV - Interaction of chemicals with DNA; genotoxic and carcinogenic substances; in vitro and in vivo genotoxicity and carcinogenicity assays; use of QSAR tools for result prediction. 6) Mechanisms of Toxic Action V - Reproductive and developmental toxicity, teratogenic effects of substances; testing approaches and suitable QSAR tools for predicting reproductive and developmental toxicity. 7) Mechanisms of Toxic Action VI - Corrosive, irritant, and sensitizing agents; inhalation toxicity; prediction of these properties based on physicochemical characteristics and through in vitro, ex vivo, and alternative in vivo assays; relevant QSAR tools. 8) Fundamentals of Epidemiological Research in Toxicology - Relative risk and odds ratio; interpretation using 2x2 contingency tables. 9) Introduction to Hazard Assessment and Risk Analysis - Core concepts including toxicity and exposure assessment, their interrelationship, critical threshold values for risk characterization, and illustrative examples. 10) Key Exposure Limits for Chemicals in Occupational and Environmental Settings - Definitions and calculation methods for OEL, ADI, TDI, PDE, etc.; Occupational Exposure Bands (OEB) - classification principles, practical examples, relevant information sources, and software tools. 11) Exposure Assessment in Chemical Risk Analysis - Measurement and modeling approaches for exposure evaluation; case study analysis using open-source tools such as ECETOC TRA and RiskOfDERM. 12) Modeling the Impact of Hazardous Chemical Releases in Environmental and Occupational Contexts - Utilization of open-source platforms and artificial intelligence methods. 13) Early Warning Systems for Hazardous Products and Foodstuffs - RAPEX and RASFF as practical examples of risk management implementation.
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Learning activities and teaching methods
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unspecified, Methods of individual activities, Řízená praxe
- Preparation for a final test
- 38 hours per semester
- Term paper
- 60 hours per semester
- Contact teaching
- 52 hours per semester
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Learning outcomes
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The objective of the course is to familiarize students with the fundamental mechanisms by which toxic substances affect the human body, as well as the core principles for evaluating these effects. This evaluation will draw on data from in vitro and in vivo toxicity testing, epidemiological studies, and in silico approaches, including the application of (Q)SAR models and artificial intelligence tools. Furthermore, the course aims to introduce students to the concepts of chemical hazard and health risk assessment. These concepts will be applied in practical case studies addressing real-world scenarios such as the selection of appropriate personal protective equipment for specific chemical-handling tasks, the development of response strategies for incidents involving hazardous substance releases, and the establishment of occupational exposure limits.
A graduate of the course Fundamentals of Risk Analysis will first acquire a basic understanding of the individual phases of toxicant interaction with the human body, including absorption, distribution, metabolism, and excretion (ADME), and will develop skills to estimate key toxicokinetic parameters using QSAR tools. The student will also gain knowledge of fundamental biochemical mechanisms of toxic action, including oxidative stress, apoptosis, neurotoxicity, genotoxicity, and reproductive and developmental toxicity, and will be able to interpret the outcomes of relevant in vitro and in vivo toxicity assays. They will be capable of assessing both acute and chronic toxicity and of applying the dose-response concept in risk characterization. The graduate will be able to identify risks associated with exposure to irritant, corrosive, sensitizing, and inhalation-toxic substances, and utilize physicochemical properties of chemicals to estimate their hazardous characteristics. The course also introduces the basics of epidemiological evaluation and key principles of risk analysis, including the relationship between toxicity and exposure. Students will understand the significance of exposure limits (e.g., OEL, ADI, TDI, OEB) and learn to apply tools for their estimation and for the categorization of occupational activities according to these limits. Graduates will be able to apply both measurement-based and modeling approaches for exposure assessment (e.g., ECETOC TRA, RiskOfDERM), including the use of open-source tools and AI-based methods for modeling the impact of chemical incidents. They will also gain an overview of early warning systems (e.g., RAPEX, RASFF) and acquire essential communication skills to effectively convey risk-related findings to both professional and lay audiences.
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Prerequisites
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Basic knowledge of probability theory and statistics will be an advantage, but not a prerequisite for completing the course.
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Assessment methods and criteria
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Didactic test, Self project defence
Test on basic risk analysis concepts - 70%, Case study analysis for a selected substance - 30%
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Recommended literature
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Linhart, Igor. Toxikologie . Praha: Vysoká škola chemicko-technologická v Praze, 2022. ISBN 978-80-7592-103-1.
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Miloslav Pouzar. ppt prezentace předmětu Základy analýzy rizik. .
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Paustenbach, Dennis J. Human and Ecological Risk Assessment: Theory and Practice. 2015.
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van Leeuwen, C.J.; Vermeire T.G. Risk Assessment of Chemicals: An Introduction 2nd ed. 2007 Edition. .
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