94192 - Drugs Production Labs Sustainability

Learning outcomes

At the end of the course the student is aware of the environmental risks associated with the activities of a chemical-pharmaceutical laboratory and therefore, in projection, of the activities related to the production process of the drug. It acquires regulatory skills necessary for the greener design and management of future corporate work activities or at research institutes where it will operate, with reference to the national and European regulatory framework. The student knows the criteria for identifying the compounds with the greatest environmental impact and is able to propose alternative and greener methods based on the case studies dealt with.

Course contents

Theoretical lessons

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

Main classes of pollutants. General information on pollutants (production, distribution, sampling. The quality of the data in the analytical laboratory according to European standards.

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.

Waste management. Regulations: Legislative Decree 152/2006 and subsequent amendments. Waste categories. WEEE. Waste disposal, MUD and SISTRI.

The environmental impact assessment (V.I.A.). EIA, SEA procedures and AIA integrated environmental authorization. WORK ENVIRONMENT Legislative Decree 81/08 Protection of health and safety in the workplace.

Green Economy. The "Green Paper" of the European Commission on integrated product policy; notes on the environmental legislation and policies of the European Community. Sustainability and the UN objectives for sustainable development. The technical standard (ISO, UNI, EN standard). Introduction to the main standards: ISO 9001, ISO 14001, ISO 17025.

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.

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.

Laboratory experiences

- Collection of data relating to waste produced by different laboratories during normal teaching activities. This work, organized in a team, aims at the preliminary assessment of the type of chemical products and the environmental impact on the basis of the quantities and related disposal costs.

- Extraction of apigenin from the dried flower heads of Matricaria recutica with natural deep solvent.

- Synthesis of Nifedipine in deep euptetic solvent - Application of Suzuki's reaction with green catalysts to the synthesis of diaryls.

Readings/Bibliography

S.E. Manahan. Chimica dell'ambiente, Piccin, Padova, 2000

C. Baird, M. Cann. Chimica Ambientale, Zanichelli, Bologna, 2006

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

C. Marzano, C. Medana. Chimica tossicologica. Piccin. 2018

Slides and lecture notes.

Teaching methods

The course includes lectures and laboratory exercises, both of which are mandatory attendance. The laboratory exercises are carried out by the students individually. The student is supported by the teacher and tutor in carrying out laboratory experiences in order to achieve greater practical autonomy. The laboratory activity is carried out with the assistance of laboratory technicians in order to sensitize students to operate in compliance with safety standards. Seminars and expert interventions in the topics covered in the course are scheduled within the theoretical lessons.

Assessment methods

The final verification of the course is aimed at ascertaining the achievement of the didactic objectives. Registration for the exam is done through AlmaEsami: https://almaesami.unibo.it/almaesami/welcome.htm. Verification of learning is carried out through an oral test consisting of a discussion of an alternative method for carrying out an experience of the teaching laboratories chosen by the student developed according to the topics covered during the course.

Teaching tools

The lessons will be carried out with the support of common audiovisual media such as a projector-PC system. The slides presented during the lectures are made available to students on the online teaching site (IOL) https://iol.unibo.it/, username and password are reserved only for students enrolled at the University of Bologna. Practical exercises will be carried out by students in single-place teaching laboratories, specially equipped with the necessary instruments and (reactive) materials

Office hours

See the website of Alberto Leoni