LEARNING OUTCOMES

The Toxicology module aims at providing students with the basic knowledge regarding the interactions between xenobiotics and living organisms and the mechanisms through which such interactions can lead to harmful effects.

AIMS AND LEARNING OUTCOMES

The module of Toxicology will provide students with a solid knowledge of toxicodynamics and toxicokinetics, organ toxicity, toxicity tests and risk assessment. Toxicokinetics refers to all the biological processes underlying absorption, distribution, metabolism and excretion of toxicants. Its primary objective is to analyse the systemic exposure to toxicants achieved in laboratory animals and its relationship to dose level and time-course of the toxic effects. Toxicodynamics is the study of the effects of toxicants or their metabolites on living systems, with a special focus on the cellular and molecular mechanisms of their biological actions.  Organ toxicity is the study of the effects of toxicant exposure at the level of the different organs and tissues. Finally, toxicity tests and risk assessment describe the in vitro and in vivo tests to assess the toxic effects of new chemical entities that are necessary for evaluating risks for human health and safety.

TEACHING METHODS

Traditional lectures during which all the course topics will be illustrated in great details. The teaching materials used during the lectures will be available for students on the website of AulaWeb.

SYLLABUS/CONTENT

Introduction to Toxicology. Definition of toxic agent. General and specialist areas of toxicology. Local or systemic toxicity, immediate and delayed toxicity, reversible or irreversible toxicity.

Toxicokinetics. Factors influencing toxicity: absorbed dose, route of exposure, duration and frequency of exposure, toxification and detoxification processes, elimination rate.

Toxicodynamics. Reaction with the biological target: target attributes, types of reaction with the target, effects on the target. Major cellular toxicity mechanisms: structural damage or dysfunction. Oxidative stress, mitochondrial toxicity, alteration of calcium homeostasis. Methods for the measurement of free radicals, of oxidative stress of phospholipids, proteins and DNA, of intracellular calcium. Cell death: necrosis, apoptosis, necroptosis and autophagy. Cellular and tissue repair mechanisms. Genotoxicity, chemical carcinogenesis and developmental toxicity. 

Drug interactions. Introduction. Pharmacokinetic and pharmacodynamic mechanisms of interaction. Drug-drug, drug-herb and drug-food interactions. Consultation databases.

Organ toxicity. Neurotoxicity: neuronopathies, axonopathies, myelinopathies, neurotransmission toxicity. Glutamate excitotoxicity: toxic effects of monosodium glutamate and of natural occuring agonists of glutamate receptors. Glutamate excitotoxicity and its role in acute and chronic disorders of the central nervous system (cerebral ischemia, Parkinson's disease, Huntington's Chorea, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuroAIDS). Adult neurogenesis: a mechanism of cell replacement and neurorepair.

Natural toxins. Molecular targets, mechanisms of action and their use in pharmaco-toxicological studies.

Toxicity tests and risk assessment. Acute toxicity test and determination of the LD50. Therapeutic index and certain safety factor. Subacute, subchronic and chronic toxicity tests. Short and long-term carcinogenesis tests. Genotoxicity tests. Developmental toxicity test. Risk assessment methods.

Laboratory exercises. Superfused synaptosomes and gliosomes for the study of neurotoxin effects. Measurement of intracellular calcium with spectrophotofluorimetric techniques. Intracerebral microdialysis to study the effects of xenobiotics in vivo.

RECOMMENDED READING/BIBLIOGRAPHY

Galli, Corsini, Marinovich. Tossicologia. Ed. Piccin; Greim, Deml. Tossicologia. Ed. Zanichelli; Klaasen , Watkins III.  Casarett & Doull's. Elementi di Tossicologia. Ed. Ambrosiana; Cantelli Forti, Galli, Hrelia, Marinovich. Tossicologia molecolare e cellulare. Ed. UTET.