Knowledge and understanding: the student will acquire the theoretical skills useful for:

1) relate the toxic action of substances to their physico-chemical properties;

2) relate the toxicokinetic and toxicodynamic of xenobiotics to their toxicological profile;

3) correlate the chemical structure of substances with their molecular and cellular mechanisms of toxicity;
4) associate the risk factors of toxic compounds with their evaluation and regulation under the current legislative requirements;

5) relate their toxicological potential to environmental pollution (air, soil, food, etc.).

 

Applying knowledge and understanding. The student will be able to use the knowledge acquired in the context of toxicological chemistry to evaluate analysis protocols in in environmental and food matrices.

Making judgements: The student will be able to interpret the literature experimental results relating to the analysis of toxicological compounds.

Communication skills: At the end of the course the student will be able to relate the acquire knowledge with appropriate terminology for a correct scientific presentation focused on toxicological studies.

Learning skills: The student will develop theoretical skills useful for being able to update and expand his knowledge to face new toxicological problems.

 

The course comprises 70 hours of lectures supported by PowerPoint slides. Students will be involved and invited to actively participate, also through the in-depth study of specific topics of interest to them.

The basic knowledge required for admission to the course is Inorganic and Organic Chemistry, Physics and Biology. In addition, a school level knowledge of Anatomy and Physiology is required.

Classroom attendance is compulsory. The maximum limit of absences allowed is 30%, as stated in the teaching regulations of the degree course, which can be consulted on the website of the Department of Pharmaceutical and Health Sciences.

The calendar of lectures is published on the website http://www.dsf.unict.it/corsi/l-29_sfa/orario-delle-lezioni 

GENERAL PART

Definition of toxic substance. Classification of toxic effects. Factors influencing toxic effects. Chemical and physical properties of toxic substances. Volatility and vapor pressure. Solubility. Persistence, bioaccumulation, and biomagnification. Absorption. Transdermal route. Inhalation route. Oral route. Biochemical mechanisms of toxicity. Electrophilic species. Nucleophilic species. Oxidoreductive reagents. Radical species. Interference with enzymatic activities. Intermolecular forces and the concept of covalent and noncovalent interaction between two molecules.

Biotransformation of xenobiotics. The steps in the biotransformation of xenobiotics. The sites of biotransformation of xenobiotics. Organs and tissues. Cellular localization. Phase I biotransformations and their enzymes. CYP-catalysed oxidation reactions. Oxidation reactions catalysed by CYP and/or FMO. Other reactions catalysed by CYP. Oxidation reactions catalysed by peroxidases. Reactions catalysed by dehydrogenases/reductases. 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 (epigenetic) carcinogens.

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

SPECIAL PART

Metals and metalloids. Factors influencing toxicity. Mechanisms of toxicity. Principal metals and metalloids of toxicological interest. Arsenic. Cadmium. Chromium. Mercury. Lead. Aluminium. 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 halogen compounds. 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. Phosphorus pentoxide. Phosphorus halides. Inorganic sulphur compounds. Hydrogen sulphide. Sulphur dioxide and sulphites. Sulphuric acid. Carbon disulphide. Halogenated sulphides.

Hydrocarbons. Saturated aliphatic hydrocarbons. Saturated aliphatic short-chain hydrocarbons, longer chain (>C5). Non-aromatic unsaturated aliphatic hydrocarbons. Ethylene. Butadiene. Aromatic hydrocarbons. Benzene. Toluene. Xylene. Polycyclic aromatic hydrocarbons. Chemical and physical characteristics. Sources of exposure. Toxicokinetic. Toxicodynamic.

Organooxygen compounds. Alcohols and phenols. Methanol. Ethanol. Ethylene glycol. Higher alcohols. Phenols. Structure and chemical-physical characteristics. Sources and exposure scenarios. Toxicokinetic and toxicodynamic. Aldehydes and ketones. Formaldehyde. α,β-unsaturated carbonyl derivatives. Acrolein. 4-Hydroxy-2-nonenal (HNE). Acrylamide. Esters. Phthalates.

Organonitrogen compounds. Aliphatic and aromatic amines. Nitriles, nitroderivatives and isocyanates. Heterocyclic amines. Azocompounds, toxicokinetic and toxicodynamic. N-nitrosamines, uses and sources of exposure, toxicokinetic and toxicodynamic.

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

SPECIFIC TOPICS

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

Chemical warfare agents. Organophosphate volatile agents.

Compounds used in sports doping. Anabolic agents. Endogenous androgenic anabolic steroids. Exogenous anabolic androgenic steroids. SARMs. Peptide hormones, growth factors and related compounds. Erythropoietin and analogues. Gonadotropins. Corticotropin. Growth hormone, GH. Insulin. Hormone modulators. Aromatase inhibitors. SERMs and other oestrogenic 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.

Drugs of abuse. Classification of drugs of abuse. Drugs with depressant action on the central nervous system. Drugs with stimulant action on the Central Nervous System. Drugs with psychotropic activity (psychedelics). Cannabinols.

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

Natural toxic products. Toxic substances from bacteria, fungi (mycotoxins, fungi toxins), protozoa. Toxic substances from plants. Poisons and toxins of animal origin: insects, fish, reptiles, and amphibians.  

1. C. Marzano, C. Medana. Chimica tossicologica. Piccin. 2018
2. Stanley E. Manahan, Toxicological Chemistry and Biochemistry, Lewis Publisher, Third Edition 2003.
3. Teaching material provided by the teacher available on Studium.

Describe the main categories of toxic elements.

Define and distinguish the two main phases of biochemical transformations that xenobiotics may undergo in the body.

Explain the correlation between alkylating agents and carcinogenesis.

List the active species produced by ionising radiation.

Mercury and its absorption through the pulmonary route.

Main toxic effects of beryllium and latency period in beryllium poisoning.

Main toxic chemical reactions involving organohalide compounds.