94276 - Human Toxicology

Learning outcomes

At the end of the course the student will acquire knowledge of basis and human toxicology and of the evaluation of toxicity of chemical substances towards men. The student is expected to be able to: 1. assess genotoxicity of a chemical substance; 2. assess the persistence and excrection of chemicals in the human body.

Course contents

The course includes the modules: - Principles of Toxicological Assessment - Genotoxicity Assessment - Toxicokinetics and toxicogenetics

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.

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.

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.

Readings/Bibliography

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.

Teaching methods

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

Assessment methods

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.

Office hours

See the website of Vera Linda Ribeiro Marques