OVERVIEW

Toxicology is a science that helps us understand the harmful effects of agents, or situations, can have on human and animal health, and on the environment. Toxicology tries to understand and identify the dose and through what mechanism the substances are hazard.

AIMS AND CONTENT

LEARNING OUTCOMES

The aims of the Toxicology module, is to provide the knowledge about the interactions between xenobiotics and humans and about the onset of toxic effects. The basic knowledge of modern toxicology will be provided, dealing with exposure and mechanisms by which xenobiotics penetrate the human body and the way in which they are metabolized and excreted. Some toxicity tests and methods for toxicological risk assessment will be illustrated. The main toxicity factors and target molecules of toxic substances, as well as the most recurrent toxicity mechanisms such as the production of radicals, alteration in the homeostasis of calcium, mitochondrial damage, embryonic toxicity and genotoxicity, will be investigated. Organ toxicity, such as neurotoxicity and blood toxicity, will also be addressed. Finally, the toxicity of metals, drugs and dopping will be explored too.

AIMS AND LEARNING OUTCOMES

The Toxicology module wants the students will acquire the basic knowledge of toxicology, the toxicokinetics and toxicodynamics, and will learn the fundamental concepts related to the evaluation of toxicity in human.

The teacher intends to work on basic functional alphabetic, personal and social skills.

At the end of the module, the students will have to:

- remember the biochemical and physiological effects of xenobiotics and their molecular mechanisms, the toxicokinetic properties (time-action) of the xenobiotics, including the absorption, distribution, metabolism and excretion;

- remember the most recurring mechanisms of action of toxic agents, the kinetic parameters, the metabolization reactions, the routes of exposure and elimination of xenobiotics and their metabolites, the factors that influence distribution in the body for the treated xenobiotics during the lessons, the main factors of toxicity and the target molecules of toxic agents;

- remember toxicity tests and their interpretation, organ-specific toxicity, embryotoxicity and teratogenicity and the effects on human health for different xenobiotics;

- demonstrate ability to use data deriving from toxicological tests in order to evaluate the safety and classify the chemical substances;

- demonstrate ability to use the various descriptors of acute and chronic toxicity;

- analysis of dose-response curves; to identify threshold dose; graphically describe the hormesis; to elaborate a log-probit transform and comparison of curves and xenobiotics as regards potency, efficacy, target compartment.

TEACHING METHODS

The didactic modality foresees frontal lessons with insights related to the program.  Specific topics will be introduced through icebreaker activities. Peer education, peer evaluation methods and the flipped classroom could also be used to allow students to actively learn and acquire the ability to communicate effectively using appropriate terms; these activities could be carried out in pairs, in groups or alone, and may require the creation of a final presentation to the class. The student would receive feedback from the teacher and/or from the other classmates, and a debate could be sparked in the classroom.

To improve the ability to use data deriving from toxicological tests for safety evaluation, exercises will be carried out using data present in the literature; similarly, specific activities will be carried out to improve the ability to analyze and describe dose-response relationships, to evaluate the safety and classification of chemical substances, to identify threshold doses, to graphically describe the hormesis. Activities will be proposed to elaborate a log-probit transformation and to compare curves and xenobiotics as regards potency, efficacy, and target, and to use the acute and chronic toxicity descriptors.

To facilitate the achievement of learning outcomes, attendance of lessons is recommended.

SYLLABUS/CONTENT

An introduction to the general principles of toxicology. Definition and aims of toxicology; toxicological responses: allergic reaction, idiosyncrasy, tolerance; local / systemic effects; acute / chronic effects.

Exposure route, frequency and duration of the exposure; dose-response relationships; threshold dose; hormesis; IT, log-probit transform and curve comparison; power and effectiveness

Toxicological risk and prevention: management of the toxicological data. Toxicological risk assessment for xenobiotics: hazard identification and risk characterization. Toxicity test: acute, subchronic and chronic tests.

Quantitative parameters (DL50, NOAEL, LOAEL, ADI, DNEL). Classification of chemicals. Toxicological test. Factors that influence the response to toxicological agents: individual variability, gender, age, intra-specie and inter-specie variability.

Toxicokinetics: absorption, biotransformation (phase I and II reactions: enzymes, cofactors), distribution and elimination of xenobiotics. Quantitative parameters: Vd, half-life, clearence. Induction and inhibition of CYP450.

Toxicodynamics: release from the exposure site and interaction with functional targets. Main molecular and cellular mechanisms of toxicity. Repair systems.

Carcinogenesis and chemical carcinogens: genotoxic and epigenetic substances

Developmental toxicology: teratogenic substances, mechanisms and kinetics; endocrine disruptors.

Organ toxicity: liver, kidneys, nervous system.

Toxicological agents: pesticides, metals, toxicological substances from plants, fungi and algae, bacterial and animal compounds; alcohol, drugs, drugs of abuse. Doping agents.

RECOMMENDED READING/BIBLIOGRAPHY

Casarett & Doull Elementi di Tossicologia (a cura di Patrizia Hrelia, Giorgio Cantelli Forti). Casa Editrice Ambrosiana.  2013

Casarett and Doull’s Tossicologia: I fondamenti dell’azione delle sostanze tossiche - Ed. EMSI, 2010

Galli C.L. – Corsini E. – Marinovich M.: Tossicologia - Ed. Piccin, 2008

TEACHERS AND EXAM BOARD

Exam Board

CHIARA CERVETTO (President)

MASSIMO GRILLI

MANUELA MARCOLI (President Substitute)

GUIDO MAURA (Substitute)

MARCO MILANESE (Substitute)

ANNA MARIA PITTALUGA (Substitute)

LESSONS

LESSONS START

For lessons start and timetable go to the link: https://easyacademy.unige.it/portalestudenti/

Please check the module Aulaweb page for timetable updates dependent on the sanitary and epidemic situation.

Class schedule

TOXICOLOGY

EXAMS

EXAM DESCRIPTION

To assess student’s achievement of learning, the examination will be an oral exam (30 minutes) in presence of the Commission consisting of at least of two professors (or sometimes in presence of the lecturer and an expert subject designated by the CCS).

ASSESSMENT METHODS

The Commission will verify the achievement of educational objectives with high accuracy by collecting information about the nature and extent of learning outcomes, capacity, as well as, connection and reasoning within the topics of the module. 
About the toxicokinetics: the student will have to know the kinetic properties (time-action) of toxic substances, also considering absorption, distribution, metabolism and excretion. 
As regards the mechanistic aspects: the student will have to know the molecular targets and the effects deriving from their interactions with the xenobiotic, as well as the main ways in which some xenobiotics induce cytotoxicity and cell death, genotoxicity and embryonic toxicity. 
As regards the achievement of the educational objectives on the dose-response curves: the student will have to be confident with the topic and able to describe gradual and quantal curves, the hormesis and probit transformation, identifying significant points of the curves. 
The Commission will also evaluate the student on the toxicity tests explained during the lessons, on drug addiction and doping, and on toxicological effects due to metals and contaminants.
If the students don't achieve minimal educational objectives, the commission will invite them to improve their knowledge, using supplemental explanations by contacting the lecturer.

Exam schedule