PřF:CB040 Special Toxicology - Course Information

CB040 Special Toxicology

Extent and Intensity

2/0/0. 2 credit(s) (fasci plus compl plus > 4). Recommended Type of Completion: zk (examination). Other types of completion: k (colloquium).

Teacher(s)

prof. Ing. Jiří Matoušek, DrSc. (lecturer)
prof. RNDr. Jakub Hofman, Ph.D. (assistant)

Guaranteed by

prof. RNDr. Ivan Holoubek, CSc.
RECETOX – Faculty of Science
Contact Person: prof. RNDr. Jakub Hofman, Ph.D.

Timetable

Mon 15:00–16:50 409-stara KAM1

Prerequisites

General toxicology knowledge

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Macromolecular Chemistry (programme PřF, D-CH) (2)

Course objectives

At the end of the course, students should be able to:
- interpret basic concepts of general and special toxicology
- describe main entry routes of poison into organism and their impact on toxicity
- define main phases of poison´s interaction with organism including dose – effect relationships
- discuss membrane transport mechanisms
- define interactions of poison on molecular, cellular and organ levels
- characterise individual phases and reactions of metabolic transformations of xenobiotics
- conclude methods of experimental toxicology and their application in chemical safety
- recognise actual and potential carcinogens and mutagens
- gain overview on toxicology of main types of inorganic and organic compounds
- discuss toxicological problems of pharmaceuticals including addiction and drug abuse
- define toxicological problems of agrochemicals, mainly pesticides
- define toxicological problems of organic colorants and products of technical chemistry
- be oriented in toxicological literature and to use international toxicological databases accessible on-line
- define toxicological problems of the main groups of chemical warfare agents
- know principles of first aid at intoxications by main types of chemicals

Syllabus

• ***** Introduction, course aims and contents. Position of toxicology in the system of sciences on the edge of chemistry and biology. Classification of toxicology. General toxicology. Basic conceptions. Poison (toxicant, toxic agent). Toxicity, types and factors influencing toxicity. Interaction of poison with living organism, basic steps of interactions on molecular, cellular and organ level (penetration, resorption, distribution, transport to target site, interaction with receptors, metabolisation, elimination, excretion). Dose-effects relationships.
• ***** Specifics of interacting poison with organism depending on the route of entry. Penetration through respiration system (resorption of vapours, gases and solid particles through mucous membranes of laryngopharynx, resorption in tracheae and lungs). Penetration at oral intoxication (Resorption in gastrointestinal tract). Penetration at percutaneous intoxication. Other routes of entry. Distribution of poison in organism (dynamics of distribution in blood, mechanisms of bonding with plasma proteins, distribution in tissues).
• ***** Interactions of poison on cellular level. Transport mechanisms through membranes (diffusion, electro-diffusion, other passive and active transport mechanisms). Interference with cellular functions (synthesis of macromolecular compounds, transport mechanisms and membrane permeability, cellular energetic metabolism, cellular cycle, genetic information). Interactions of poison on molecular level. Receptor theory and its modern interpretations.
• ***** Biotransformation of poison, effect on toxicity (activation, detoxification), localisation of biotransformation processes in organs. First stage of biotransformation. Oxidative reactions (epoxidation and hydroxylation on aromatic ring, hydroxylation of aliphatic and alicyclic compounds, oxidation of alcohols, aldehydes and ketones, O-, N- and S-dealkylation, N-oxidation, sulphoxidation, oxidative deamination and desulphuration). Reductive reactions (Reduction of carbonyl groups, organic sulphoxides, bisulphides, N-oxides, aromatic nitro- and azo-compounds, reductive dehalogenation, aromatic dehydroxylation etc.). Hydrolytic reactions (hydrolysis of esters, amides, halogenides of acids, hydratation of epoxides).Enzymic systems of the 1st stage of biotransformation (monooxygenases, cytochrome P-450, NADPH-cytochromreductases, microsomal N-oxidases, flavin monooxygenases, enzymes catalysing reductive and hydrolytic reactions, other enzymic systems.
• ***** Second stage of biotransformation. Formation of conjugated metabolite from primary metabolite and active conjugation agent, or from activated primary metabolite and amino acid. Formation of O-, N-, S- glucuronides; sulphates, acylation, mercapturate and methylation conjugation. Mechanisms of peptide conjugation. Enzymic systems of the 2nd stage of biotransformation} enzymic systems for glucuronides, sulphates, mercapturates, enzymic systems of acylation and methylation, other enzymic systems).
• ***** Affected sites by poisons in organism, target organs and systems.
• ***** Elimination and excretion of toxicants and metabolites. Elimination through kidney (glomerular filtration, tubular absorption, tubular secretion), excretion by urine, elimination through liver, elimination to stomach and intestines, excretion by faeces, elimination to breast milk, saliva, excretion through lungs. ***** Experimental toxicology. Experimental animals, application techniques (i.v., i.m., i.p., s.c., p.o., inhalation). Tests for acute toxicity (oral, inhalation, percutaneous, acute irritancy and sensitisation. Testing for subacute, subchronic and chronic toxicity (including neurotoxicity, mutagenicity and carcinogenicity). Toxicometrics (ED50, LD50, EC50, LC50 and like) including statistical evaluation. Test methods for chemical compounds and formulations according to binding legal norms of the Czech Republic. EU classification of acute toxic poisons.
• ***** Genetic toxicology. Molecular mechanisms of mutagenesis, mechanisms of mutagenesis on cellular level. Chemical mutagenesis and carcinogenesis. Proven and potential chemical carcinogens, activities involving carcinogenic risk. Tests for mutagenicity and carcinogenicity.
• ***** Toxicology of inorganic chemicals (hydrogen, acids, bases, beryllium, strontium, barium, radium, boranes, salts of indium and thallium, carbon monoxide and dioxide, hydrogen cyanide, hydrogen sulphide, carbon sulphide, phosgene, silicon oxide, silicates, compounds of nitrogen, phosphorus, arsenic, antimony and bismuth, oxygen, compounds of sulphur, selenium, halogens, heavy metals and their compounds).
• ***** Toxicology of organic chemicals (aliphatic and aromatic hydrocarbons, alcohols and phenols, aldehydes and ketones, organic acids, esters of inorganic and organic acids, ethers, nitro- and nitroso compounds, aliphatic and aromatic amines, halogenated hydrocarbons, pohyhalogenated biphenyls, polyhalogenated dibenzodioxins and dibenzofurans.
• ***** Toxicology of pharmaceuticals. Narcotics, hypnotics, psychopharmaceuticals (stimulants, thymoleptics, anxiolytics, dysphorics, neuroleptics, hallucinogens), analgetics, antipyrhetics, antirheumatics, cardiaca, laxanthia, diuretics, antihistaminics, antidiabetics, tuberculostatics, antibiotics, cytostatics. Drug abuse and drug addiction (Basic types of toxicomania).
• ***** Toxicology of organic colorants (dyes and organic pigments) and precursors (raw materials and end-products). Toxicology of polymeric materials and paints. Toxicology of other important products of industrial and applied chemistry. Chemical safety. Toxicological information databases of WHO, UNEP, ILO, EU, EPA, ATSDR et al.
• ***** Toxicology of agrochemicals. Plant nutrition and protection. Herbicides and phytotoxic agents (based on inorganic chemicals, chlorinated phenoxyacetic acids, other herbicides). Insecticides (chlorinated hydrocarbons, organic phosphates, carbamates, other insecticides). Acaricides, fungicides, molluscicides, rodenticides etc.
• ***** Toxicology of chemical warfare agents. Development and present state of chemical warfare and chemical disarmament. Basic groups of chemical warfare agents. Irritants and incapacitants, lung injurants, generally toxic (blood) agents, vesicants, nerve agents. Fundamentals of protection, detoxification, prophylactics, first aid and therapy of intoxication, medical evacuation system in protection of troops and population against chemical warfare agents and highly toxic chemicals.

Literature

• MATOUŠEK J., LINHART P.: CBRN: Chemické zbraně. SPBI, Ostrava 2005.
• WIRTH W., GLOXHUBER C.: Toxicology. G. Thieme Verlag, Stuttgart – New York 1985.
• Databáze IPCS-INCHEM (WHO, ILO, FAO, UNEP, EU), EPA, ASTDR, OPCW aj. podle aktualizace
• Právní normy ČR o nebezpečných chemických látkách, zejména Zákon č 356/2003 Sb o chemických látkách a chemických přípravcích, Zákon č. 59/2006 Sb. o prevenci závažných havárií (ve znění pozdějších předpisů) a další navazující nařízení a vyhlášky
• WHO, UNEP, ILO: Guidelines on the Prevention of Toxic Exposures. WHO, Geneva 1985
• MATRKA, Miroslav and Vlastimil RUSEK. Průmyslová toxikologie : úvod do obecné a speciální toxikologie [Matrka, 1998]. 3. opr. vyd. Pardubice: Vysoká škola chemicko-technologická, 1998, 157 s. ISBN 80-7194-131-X. info
• Základy obecné a speciální toxikologie. Edited by Karel Picka - Jiří Matoušek. 1. vyd. Ostrava: Vysoká škola báňská - Technická univerzita Ostrava, 1996, 103 s. ISBN 80-85368-91-9. info
• MARHOLD, Josef V. Přehled průmyslové toxikologie : organické látky. 1. vyd. Praha: Avicenum, 1986, s. i-x. info
• MARHOLD, Josef V. Přehled průmyslové toxikologie : organické látky. 1. vyd. Praha: Avicenum, 1986, xxx, 760. info

Teaching methods

Lectures utilising audiovisual means (mainly over-head projection) are interactive. Students are frequently asked to express their views on tabled problems in order to support development of their critical thinking. They are also stimulated to discuss and pose questions on the lecture´s topics. Main stress is laid on toxicological mechanisms and updated practice in applying gained knowledge for chemical safety as well as health and environmental protection considering their future employment.

Assessment methods

Attending lectures is not obligatory (pursuant to the Study Order) but strongly recommended justified with the effect of the above mentioned teaching methods for implementing course objectives not to speak on the impossibility to gain practical experience from literary sources. During the lectures, the understanding of topics from previous lectures is verified. Final assessment proceeds as individual oral exam with 4 extensive questions that need comprehensive structured answer, and a couple of smaller additional questions to verify depth of knowledge and skill required according to the course objectives, mainly ability of applications for practical solving model toxicological problems one can meet in chemical, food and other relevant industrial branches, agriculture, transport, and services as well as at extraordinary events of technological and natural origin or in armed conflicts.

Language of instruction

Czech

Further comments (probably available only in Czech)

Study Materials
The course can also be completed outside the examination period.
The course is taught annually.

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