94275 - TOXICOLOGICAL PERSPECTIVE

Anno Accademico 2021/2022

Conoscenze e abilità da conseguire

At the end of the course the student will acquire knowledge of the basis of human and environmental toxicology. The student will know the most appropriate analytical techniques for assessing human and environmental toxicity of chemicals. The student is expected to be able to: 1. assess a chemical substance from a toxicologial point of view; 2. apply the most appropriate technique for the toxicological evaluation of chemical substances.

Contenuti

TOXICOLOGICAL ASSESSMENT

The course includes the modules :Principles of Toxicological Assessment - Genotoxicity Assessment - Biosafety

In vitro and in vivo models of toxicity. Cell culture models and specialized techniques, such as light and florescence microscopy, flow cytometry, colorimetric and fluorescent bioassays, electrophoresis, use of specific inhibitors of intracellular transduction pathways. The issue of in vitro-in vivo correlations.

Mutagenesis and carcinogenesis. Mechanisms of carcinogenesis. Three-stage model of carcinogenesis. Evaluating genotoxicity in prokaryotes and in vertebrates. Bacterial mutation assays. Mammalian cell mutation assays. In vitro chromosome abnormalities assays. In vivo cytogenetics. In vivo carcinogenicity assays.

Types of organisms and biological agents. Organisms genetically modified. Others (plasmids, prions, biological fluids...). List of the different categories of biological agents. Biosafety in different types of work place (Industry, laboratories, Animal Experimentation Centres, Hospitals). Special working permission (biological agents group 3 and 4, GMOs). Preventive measures. Possible infection pathways. Vaccination. Biological safety practices and risk assessment.

TOXICOLOGICAL PERSPECTIVE

The course includes the modules : Toxicology - Principles of Toxicological Assessment – Metals in Toxicology and Health

General concepts in toxicology. ADME – Absorption, distribution, metabolism and excretion of xenobiotics. Toxicokinetics and toxicodynamics. Species and organ-specific toxicity and pathophysiology. Cellular and molecular mechanisms of xenobiotic toxicity. Hazard and risk assessment. Basic concepts of toxicokinetics, such as dose-response, route of exposure, Toxicity parameters (eg. toxic dose, lethal dose, NOEL/LOEL) clearance, half-life, bioavailability, one and two compartment models. Biotransformation, sites of action, elimination. Application to specific cases of directed toxicity (eg. hepatic, cardiovascular, neurological). Analysis of specific toxicants, such as hydrocarbons, metals, air pollutants, nanomaterials, endocrine disruptors, therapeutic drugs.

In vitro and in vivo models of toxicity. Cell culture models and specialized techniques, such as light and florescence microscopy, flow cytometry, colorimetric and fluorescent bioassays, electrophoresis, use of specific inhibitors of intracellular transduction pathways. The issue of in vitro-in vivo correlations.

Evaluating toxicity in vertebrates. Relevance of organism, developmental age and gender.

Systemic and tissue-specific toxicity. Protocols of risk assessment. Inter-species differences in toxicity. The issue of extrapolating results to humans. The 3 Rs. Regulatory issues (OECD, EU, EPA).

HUMAN TOXICOLOGY

The course includes the modules: Toxicology - Genotoxicity Assessment - Toxicokinetics and toxicogenetics

Introduction to human toxicology. ADME – Absorption, distribution, metabolism and excretion of xenobiotics. Toxicokinetics and toxicodynamics. Species and organ-specific toxicity and pathophysiology. Cellular and molecular mechanisms of xenobiotic toxicity. Toxicogenomics. Hazard and risk assessment.

Basic concepts of toxicokinetics, such as dose-response, routes of exposures, clearance, half-life, bioavailability, one and two compartment models.

Biotransformation, sites of action, elimination.

Testi/Bibliografia

Lecture notes and selected papers will be available for students

- Nielsen, E, Ostergaard,G, Larsen, JC: Toxicological Risk Assessment of Chemicals: A Practical Guide. Informa Healthcare, 2008. ISBN-10: 0849372658

- Xu, Jinghai; Urban Laszlo. Predictive Toxicology in Drug Safety. Cambridge University Press. 2011.

- Barile, F.A. Clinical Toxicology- Principles and Mechanisms. 2004. CRC Press.

- Barile, F.A. Principles of Toxicology Testing. 2008. Informa Health Care.

- Boelsterli UA. (2007) Mechanistic toxicology: the molecular basis of how chemicals disrupt biological targets. Boca Raton: CRC Press

- Casarett, Louis J.; Doull, John; Klaassen, Curtis D. Casarett and Doull's toxicology: the basic science of poisons, 7th ed. : New York : McGraw-Hill, cop. 2008 - xv, 1310 s. ISBN:978-0-07-147051-3.

- Lodola and Stadler. Pharmaceutical Toxicology in Practice- A Guide to Non-Clinical Development. Wiley and Sons. 2011.

- Nielsen, E, Ostergaard, G, Larsen, JC: Toxicological Risk Assessment of Chemicals: A Practical Guide. Informa Healthcare, 2008. ISBN-10: 0849372658

- Plant,N, Molecular Toxicology, Taylor & Francis, 2003, ISBN-10: 1859963455

- Timbrell, J. (2008) Principles of Biochemical toxicology 4th ed. Informa Healthcare

-Xu, Jinghai; Urban Laszlo. Predictive Toxicology in Drug Safety. Cambridge University Press. 2011.

Metodi didattici

Expository classes to present the basic concepts and the state of the art in the area of toxicology and biosafety, including discussion of published articles and specific examples of real-life situations.

Modalità di verifica e valutazione dell'apprendimento

The evaluation will consist of written tests, short works of analysis of the literature, or exercises to solve specific cases. The Curricular Unit grade will be the arithmetic mean of grades from the three modules.

Orario di ricevimento

Consulta il sito web di Vera Linda Ribeiro Marques

Consulta il sito web di Maria Teresa Henriques De Faria Fernandes

Consulta il sito web di Maria Isabel Rodrigues Correia