General toxicology
Academic Year 2023/2024 - Teacher: SANTINA CHIECHIOExpected Learning Outcomes
- To provide students with basic knowledge of toxicology.
- To present the main classes of potentially toxic substances.
- To provide pharmacokinetic and pharmacodynamic concepts that characterize the toxicological profile and mechanism of action of xenobiotics.
Course Structure
Face-to-face lectures
In case of mixed or remote mode, due to the pandemic situation, necessary changes can be introduced, in order to accomplish the planned program as reported in the syllabus.
schedule: https://www.dsf.unict.it/courses/l-29_sfa/lectures-schedule
Information for students with disabilities and/or SLD: In order to guarantee equal opportunities and in compliance with regulations in force, interested students can ask for a personal interview in order to plan any compensatory and/or dispensatory measures, based on the didactic objectives and specific needs. It is also possible to contact our Department CInAP referent, Prof. Teresa Musumeci
Required Prerequisites
Attendance of Lessons
Mandatory attendance
according to the rules of the teaching regulations of the Degree Course in CTF,
as indicated in the following link: http://www.dsf.unict.it/corsi/lm-13_ctf/regolamento-didattico
Detailed Course Content
Principles of toxicology
Pharmacokinetic and pharmacodynamic concepts that characterize the toxicological profile and mechanism of action of xenobiotics.
GENERAL PRINCIPLES OF TOXICOLOGY - Areas of toxicology. Classification of toxic agents. Classification of toxic effects. Allergic reactions, idiosyncrasy; immediate and delayed toxicity reversible, irreversible, local, and systemic toxicity. Factors influencing the response to toxins.
PREDICTIVE TOXICOLOGY AND RISK ASSESSMENT - Exposure to toxic agents: routes and sites, duration and frequency of exposure. Acute, subchronic, and chronic toxicity. Risk assessment. Toxicity threshold, effects without a threshold. LOEL, LOAEL, NOEL, NOAEL, NEL. Dose-response relationship. Dose-response curves. Margin of safety, ADI.
TOXICOKINETICS: ABSORPTION, DISTRIBUTION, METABOLISM, AND ELIMINATION OF TOXIC SUBSTANCES - Cell membranes, passive transport, filtration, active transport, facilitated diffusion. Absorption through the gastrointestinal tract. Absorption through the lungs (gases and vapors, aerosols). Absorption through the skin. Distribution, deposition sites. Blood-brain barrier, placenta. Apparent volume of distribution. Clearance. Half-life. Excretion: urinary, fecal, biliary, intestinal, cerebrospinal fluid, milk, sweat, saliva, and hair. Toxicological consequences of xenobiotic biotransformation. The cytochrome P450 system. Production of toxic metabolites through phase I and phase II metabolic reactions. Induction and inhibition of metabolism.
TOXICODYNAMICS: TOXIC-RECEPTOR INTERACTION - General information on receptors. Chemical bonds involved in ligand/receptor binding. Binding studies. Characteristics of the interaction. Reversible and irreversible interactions. Interactions between chemicals (additive effect, synergy, potentiation, antagonism, tolerance). Analysis of dose-response curves. Major classes of receptors and signal transduction mechanisms. Interaction with functional targets.
MOLECULAR AND CELLULAR MECHANISMS OF TOXICITY - Major neurotransmitter systems. Morphological, functional, and biochemical alterations produced by xenobiotics. General mechanisms of cell damage. Free radicals. Mechanisms of toxicity: genotoxicity, mutagenesis, carcinogenesis, and teratogenesis.
Textbook Information
- Casaret and Doull's TOXICOLOGY: The Basic Science of Poisons, Ed. McGraw-Hill
Course Planning
| Subjects | Text References | |
|---|---|---|
| 1 | PRINCIPI GENERALI DI TOSSICOLOGIA; TOSSICOLOGIA PREDITTIVA E VALUTAZIONE DEL RISCHIO; TOSSICOCINETICA; TOSSICODINAMICA; MECCANISMI MOLECOLARI E CELLULARI DI TOSSICITA' | 1-3 |
| 2 | Fattori che influenzano la risposta ai tossici. | 1,2 |
| 3 | Esposizione ad agenti tossici: vie e siti, durata e frequenza dell'esposizione. | 2 |
| 4 | Tossicità acuta, subcronica e cronica. Valutazione del rischio. Soglia di tossicità, effetti privi di soglia. LOEL, LOAEL, NOEL, NOAEL, NEL. | 2 |
| 5 | Relazione dose-effetto. Curve dose-risposta. Margine di sicurezza, ADI. | 1 |
| 6 | Membrane cellulari, trasporto passivo, filtrazione, trasporto attivo, diffusione facilitata. | 1-2 |
| 7 | Assorbimento attraverso il tratto gastrointestinale. Assorbimento attraverso i polmoni (gas e vapori, aerosol). Assorbimento attraverso la pelle. | 1-2 |
| 8 | Distribuzione, siti di deposito. Barriera ematoencefalica, placenta. Volume apparente di distribuzione. Clearance. Emivita. | 1-2 |
| 9 | Escrezione: urinaria, attraverso le feci, la bile, intestinale, aria espirata, liquido cerebrospinale, latte, sudore, saliva e capelli. | 1-2 |
| 10 | Conseguenze tossicologiche delle biotrasformazioni degli xexobiotici. Il sistema del citocromo p450. Produzione di metaboliti tossici attraverso reazioni metaboliche di fase I e reazioni metaboliche di fase II. Induzione ed inibizione metabolica. | 1,2,3 |
| 11 | INTERAZIONE TOSSICO RECETTORE; Generalità sul recettore. Legami chimici coinvolti nel legame ligando/recettore. Studi di binding. Caratteristiche dell’interazione. Interazioni reversibili e irreversibili. | 3 |
| 12 | nterazioni tra sostanze chimiche (effetto additivo, sinergismo, potenziamento, antagonismo, tolleranza). Analisi delle curve dose-risposta. | 2 |
| 13 | Principali classi di recettori e meccanismi di trasduzione del segnale. Interazione con bersagli funzionali. | 3 |
| 14 | Principali sistemi neurotrasmettitoriali. | 3 |
| 15 | Alterazioni morfologiche funzionali e biochimiche prodotte da xenobiotici. Meccanismi generali di danno cellulare. Radicali liberi. | 1 |
| 16 | Meccanismi di tossicitá: genotossicitá, mutagenesi, cancerogenesi e teratogenesi. | 1 |
Learning Assessment
Learning Assessment Procedures
The examination is conducted through an oral test.
Schedule: https://www.dsf.unict.it/courses/l-29_sfa/exams-calendar
Information for students with disabilities and/or learning disorders (DSA):
In order to ensure equal opportunities and compliance with current laws, interested students can request a personal interview to plan any compensatory and/or dispensatory measures based on their educational objectives and specific needs.
It is also possible to contact the CInAP (Center for Active and Participatory Integration - Services for Disabilities and/or DSA) faculty coordinator in our department, Professor Teresa Musumeci.
Examples of frequently asked questions and / or exercises
Describe the main mechanisms of toxicity.
Describe the primary pathways of exposure to xenobiotics.
Risk assessment.
Interaction between xenobiotics and biological targets.
Metabolic interactions.