02307 - Toxicological Chemistry

Academic Year 2020/2021

  • Docente: Alberto Leoni
  • Credits: 8
  • SSD: CHIM/08
  • Language: Italian
  • Moduli: Rita Morigi (Modulo 1) Rita Morigi (Modulo 2) Alberto Leoni (Modulo 3)
  • Teaching Mode: Traditional lectures (Modulo 1) Traditional lectures (Modulo 2) Traditional lectures (Modulo 3)
  • Campus: Bologna
  • Corso: First cycle degree programme (L) in Applied Pharmaceutical Sciences (cod. 8518)

Learning outcomes

At the end of the course the student has the basic knowledge of the mechanisms of action and of the chemical-toxicological aspects of molecules harmful to health. In particular, the student is able to: - understand the mechanisms of action at the molecular level, - know the chemical-toxicological aspects of pollutants of interest

Course contents

1 (5 CFU). Teacher: Prof. Rita Morigi

Definition of toxic substance. Classification of toxic effects. Factors that influence toxic effects. Chemical-physical properties of toxic substances. Volatility and vapor pressure. Solubility. Persistence, bioaccumulation and biomagnification. Absorption. Transdermal route. Via inhalation. Oral. Biochemical mechanisms of toxicity. Electrophilic species. Nucleophilous species. Oxidation-reductive reagents. Radical species. Interference with enzymatic activities. Intermolecular forces and the concept of covalent and non-covalent interaction between two molecules.

Biotransformation of xenobiotics. The phases of biotransformation of xenobiotics. Xenobiotic biotransformation sites. Organs and tissues Cellular localization. Phase I biotransformations and their enzymes. Oxidation reactions catalysed by CYP. Oxidation reactions catalyzed by CYP and / or FMO. Other reactions catalyzed by CYP. Oxidation reactions catalysed by peroxidases. Dehydrogenase / reductase catalyzed reactions. Hydrolysis reactions and their enzymes. Phase II biotransformations and their enzymes. Conjugation with glucuronic acid. Conjugation with sulfonate. Conjugation with acetyl. Conjugation with glutathione. Conjugation with amino acids. Conjugation with methyl. Factors influencing biotransformations. Influence of extrinsic factors on biotransformations. Influence of intrinsic factors on biotransformations.

Principles of chemical carcinogenesis. Cancer: general aspects. Stages of carcinogenesis: initiation, promotion, progression. Genotoxic chemical carcinogens. Molecular mechanisms of genotoxic chemical carcinogens. Classes of genotoxic carcinogens. Non-genotoxic carcinogens (epigenetics).

Risk factors and legislative aspects of toxic chemical compounds. REACH (Registration, Evaluation, and Authorization of Chemicals). SVHC substances. CLP (Classification, Labeling, and Packaging). Classification of substances and mixtures.

Metals and metalloids. Factors that influence toxicity. Mechanisms of toxicity. Main metals and metalloids of toxicological interest. Arsenic. Cadmium. Chrome. Mercury. Lead. Aluminum. Nickel. Selenium.

Inorganic compounds. Inorganic carbon compounds. Carbon monoxide. Cyanide. Cyanogens, cyanamides and cyanates. Inorganic nitrogen compounds. Ammonia. Hydrazine. Nitrogen oxides. Nitric acid. Nitrites and nitrates. Inorganic compounds of halogens. Hydrogen halides. Interhalogens and halogen oxides. Hypochlorous acid and hypochlorite. Perchlorate. Nitrogen compounds of halogens. Inorganic silicon compounds. Silica. Asbestos. Silanes. Inorganic phosphorus compounds. Phosphine. Diphosphorus pentoxide. Phosphorus halides. Inorganic sulfur compounds. Hydrogen sulphide. Sulfur dioxide and sulphites. Sulfuric acid. Carbon disulfide. Halogenated sulphides.

Organoazotate compounds. Aliphatic and aromatic amines. Nitriles, nitroderivatives and isocyanates. Heterocyclic amines. Azocompounds, toxicokinetics and toxicodynamics. N-nitrosamines, uses and sources of exposure, toxicokinetics and toxicodynamics.

Pesticides. Insecticides. Organochlorine insecticides. Carbamates. Insecticides of natural origin: pyrethroids, neonicotinoids, macrocyclic lactones. Herbicides. Fungicides.

Compounds used in sports doping. Anabolic agents. Endogenous androgenic anabolic steroids. Exogenous androgenic anabolic steroids. SARMs. Peptide hormones, growth factors and related compounds. Erythropoietin and analogues. Gonadotropins. Corticotropin. Growth hormone, GH. Insulin. Hormonal modulators. Aromatase inhibitors. SERMs and other estrogenic modulators. Agents active on myostatin function. PPAR-delta receptor agonists and protein-kinase activators. Drug abuse for doping purposes. Beta-adrenergic agonists. Diuretics and doping masking agents. Stimulants, narcotics, cannabinoids.

Radionuclides and contrast media. Radiation and radioactivity. Radon. Radio. Iodinated contrast agents containing gadolinium.

Module 2 (3CFU). Teacher: Prof. Alberto Leoni

Hydrocarbons. Saturated aliphatic hydrocarbons. Short-chain saturated aliphatic hydrocarbons, longer chain (> C5). Non-aromatic unsaturated aliphatic hydrocarbons. Ethylene. Butadiene. Aromatic hydrocarbons. Benzene. Toluene. Xylene. Polycyclic aromatic hydrocarbons. Chemical-physical characteristics. Sources of exposure. Toxicocinetics. Toxicodynamics.

Organo-oxygenated compounds. Alcohols and phenols. Methanol. Ethanol. Ethylene glycol. Upper alcohols. Phenols. Structure and chemical-physical characteristics. Exposure sources and scenarios. Toxicokinetics and toxicodynamics. Aldehydes and ketones. Formaldehyde. Carbonyl derivatives α, β unsaturated. Acrolein. 4-Hydroxy-2-nonenal (HNE). Acrylamide. Foreign. Phthalates.

Organohalogen compounds. Alkyl halides. Carbon tetrachloride, chloroform, dichloromethane. Polychlorinated paraffins. Hydrochlorofluorocarbons. Perfluoroalkyls. Alkenyl halides. Vinyl chloride. Trichlorethylene. Aryl halides. Chlorobenzene. Hexachlorobenzene. Polychlorinated biphenyls (PCBs). Polychlorinated dibenzofurans and dibenzodioxins.

Drugs of abuse. Classification of drugs of abuse. Drugs with a depressive action on the Central Nervous System. Drugs with a stimulating action on the Central Nervous System. Psychotropic drugs (psychedelic). Cannabinols.

Readings/Bibliography

Stanley E. Manahan, Toxicological Chemistry and Biochemistry, Lewis Publisher, Third Edition 2003.

C. Marzano, C. Medana. Toxicological chemistry. Piccin. 2018

Slides and lecture notes.

Teaching methods

The course includes theoretical frontal activity.

Assessment methods

The exam consists of an oral interview. The test has the objective of verifying the acquisition of the knowledge foreseen according to what is detailed in the objectives of the course and it will be considered overcome by the correct answer to various questions relating to the topics covered, including the illustration of the formula and the molecular toxicity mechanism of the different xenobiotics. Exam registration is done through Almaesami. The dates of appeal of the two modules are the same. The oral exam on each module can be taken according to the scheduled appeals even on different dates. The order of oral tests can be chosen by the student. The final grade is calculated as a weighted average of the scores shown in the oral tests of the individual modules. The minimum grade to pass the test is 18/30.

Teaching tools

All the topics of the course are carried out through the use of Powerpoint presentations. Up-to-date teaching material is provided in class, also available via username and password at Teaching On Line (IOL)- University of Bologna.

Office hours

See the website of Alberto Leoni

See the website of Rita Morigi

See the website of Rita Morigi

SDGs

Good health and well-being Climate Action

This teaching activity contributes to the achievement of the Sustainable Development Goals of the UN 2030 Agenda.