Brief historical background of toxicology and achievements. The areas of toxicology. Basic terminology in toxicology.
Dose-response relationship in toxicology. Receptor analysis.
Absorption of a xenobiotic: exposition route of chemicals, absorption by gastrointestinal and respiratory tract, absorption through the skin. Distribution and storage of toxicant in the tissues. Urinary and faecal and respiratory excretion. Toxicokinetic/pharmacokinetic models; definition of distribution volume, clearance, biodisposition. Toxicokinetic of multiple administrations.
Biotransformation of xenobiotics: Reactions of oxidation and reduction (phase 1; reactions catalyzed by cytochrome P450. Biochemical and molecular features of cytochrome P450. Phase 1 metabolic reactions catalyzed by enzymes different from P450. Conjugation reactions (phase 2).
Toxic activation. Reactive metabolites and covalent binding to macromolecules. Halogenated hydrocarbons activated by reduction, halothane and congeners. Activation of aliphatic and aromatic compounds; toxicity of benzene and hexane. Activation of phenolic compounds and amino toxicity of p-acetamolo. Activation of xenobiotics after conjugation reactions.
Direct toxic actions: step 1: interactions of chemical compounds with the target molecules, step 2, cytotoxicity, tissue injury and repair mechanisms. Lipid peroxidation, damage of redox systems. Damage of calcium homeostasis, step 3 tissue damage. Examples of interaction of xenobiotics with the immune system, respiratory, nervous and gastrointestinal and hepatic impairment.
Test of acute, subacute and chronic toxicity and interpretation of results. Classification of the chemical compounds according to their toxicity. Endpoints of toxicity tests. Threshold dose level and the No Observed Adverse Effect Level (NOAEL, LOAEL). Estimating the Acceptable Daily Intake (ADI). Risk assessment of carcinogenic compounds. Risk phrases according to EEC regulations.
Genotoxicity. Reaction of the chemical compounds with the genetic material. Chemical mutagenesis. Mutagenesis tests in prokaryotic organisms. Mutagenesis tests in eukaryotic organisms and mammalian cells. Mutagenesis tests in vivo.
Chemical carcinogenesis. Control of cellular functions. Activation of proto-oncogenes. Model multi-stage of chemical carcinogenesis. Meccansimo of action and evaluation of carcinogenic risk. Test of carcinogenesis in vivo, chronic test and short-term tests.
Teratogenesis and reproductive toxicology teratogenesis test in vivo.
Pharmacogenetics and Pharmacogenomics. Assessment of toxicity in biotechnological material, NBE and GMOs.