TOSSICOLOGIA GENERALE ED AMBIENTALE

Academic Year 2024/2025 - Teacher: SANTINA CHIECHIO

Expected 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
  • Explain the concepts of risk assessment and risk management.
  • Describe the toxicity of the main environmental pollutants 

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. Santina Chiechio

Required Prerequisites

Basic knowledge of anatomy, physiology, and biochemistry.

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.

MAJOR ENVIRONMENTAL POLLUTANTS - Pesticides. Polycyclic aromatic hydrocarbons. Dioxins. Phthalates

Textbook Information

  1. Casaret and Doull's TOXICOLOGY: The Basic Science of Poisons, Ed. McGraw-Hill

Course Planning

 SubjectsText References
1PRINCIPI GENERALI DI TOSSICOLOGIA; TOSSICOLOGIA PREDITTIVA E VALUTAZIONE DEL RISCHIO; TOSSICOCINETICA; TOSSICODINAMICA; MECCANISMI MOLECOLARI E CELLULARI DI TOSSICITA'1-2
2Fattori che influenzano la risposta ai tossici. 1,2
3Esposizione ad agenti tossici: vie e siti, durata e frequenza dell'esposizione. 2
4Tossicità acuta, subcronica e cronica. Valutazione del rischio. Soglia di tossicità, effetti privi di soglia. LOEL, LOAEL, NOEL, NOAEL, NEL.2
5Relazione dose-effetto. Curve dose-risposta. Margine di sicurezza, ADI. 1
6Membrane cellulari, trasporto passivo, filtrazione, trasporto attivo, diffusione facilitata. 1-2
7Assorbimento attraverso il tratto gastrointestinale. Assorbimento attraverso i polmoni (gas e vapori, aerosol). Assorbimento attraverso la pelle. 1-2
8Distribuzione, siti di deposito. Barriera ematoencefalica, placenta. Volume apparente di distribuzione. Clearance. Emivita. 1-2
9Escrezione: urinaria, attraverso le feci, la bile, intestinale, aria espirata, liquido cerebrospinale, latte, sudore, saliva e capelli. 1-2
10Conseguenze 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
12nterazioni tra sostanze chimiche (effetto additivo, sinergismo, potenziamento, antagonismo, tolleranza). Analisi delle curve dose-risposta. 2
13Principali classi di recettori e meccanismi di trasduzione del segnale. Interazione con bersagli funzionali. 1-2
14Principali sistemi neurotrasmettitoriali. 3
15Alterazioni morfologiche funzionali e biochimiche prodotte da xenobiotici. Meccanismi generali di danno cellulare. Radicali liberi.1
16Meccanismi 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 Santina Chiechio.

 

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.