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Introduction to course Tuesday December 6 09.00 Herman Autrup Professor, PhD, Fellow ATS Human Health and Ecological Risk Assessment and Risk Management INTERNATIONAL FACULTY: Herman Autrup, Professor School of Public Health University of Århus Denmark Len Ritter, Professor Canadian Network of Toxicology Centres, University of Guelph, Canada Martin van den Berg, Professor Institute of Risk Asssessment Sciences, University of Utrecht, The Netherlands Mary E. Meek, McLaughlin Center for population Health Risk Assessment, Ottowa, Canada LECTURES: Give the theoretical background for risk assessment General human and ecotoxicology Tools used in risk assessments Animal studies Human studies Exposure assessment Mode of Action Standard setting Management and communication
Introduction to course Tuesday December 6 09.00 Herman Autrup Professor, PhD, Fellow ATS Human Health and Ecological Risk Assessment and Risk Management 1 Course Coordinator: Khunying Mathuros Ruchirawat Objectives: Give an introduction to the assessment of risk of chemicals to human health and well-being and the environment, and present the newest concepts in the evaluation of risks Format: Lectures including case studies, and risk assessment exercise, special feature Presentation of IPCS/WHO Risk Assessment Toolkit Teaching material: Hand-outs of power-point presentations, and additional material provided by the lecturers 2 INTERNATIONAL FACULTY: Herman Autrup, Professor School of Public Health University of Århus Denmark Len Ritter, Professor Canadian Network of Toxicology Centres, University of Guelph, Canada Martin van den Berg, Professor Institute of Risk Asssessment Sciences, University of Utrecht, The Netherlands Mary E. Meek, McLaughlin Center for population Health Risk Assessment, Ottowa, Canada Kerstin Gutschmidt, WHO, Geneva 3 LECTURES: Give the theoretical background for risk assessment General human and eco-toxicology Tools used in risk assessments Animal studies Human studies Exposure assessment Mode of Action Standard setting Management and communication 4 RISK ASSESSMENT EXERCISE Flameretardents – PBDE Mercury Arsenic Water disinfection Parabenes Benzen 5 Friday, December 16 Presentation of Risk Assessment Exercise – 30 min each group, allow 5 min for questioning and discussion Examination for graduate students: January - 6 hrs written examination, questions prepared by all the international faculty - members 6 ??? 7 Toxic Effects of Chemicals Tuesday December 6 09.15 Herman Autrup, Professor, PhD 8 GENEREL INTRODUCTION TOXICOLOGICAL PARADIGME MECHANISTIC TOXICOLOGY DESCRIPTIVE TOXICOLOGY RISK ASSESSMENT STRUCTURE OF LECTURE 9 LIVING IN A CHEMICAL WORLD Man-made and natural Approx 60.000 chemicals in use Only 1500 chemicals account for 95% of the production (HPV) Covers 11 mill different products 10 [...]... discipline, as the earliest humans had to recognize which plants were safe to eat • Humans are exposed to chemicals both deliberately and inadvertently Most exposure of humans to chemicals is via naturally occurring compounds consumed in the diet from food plants TOXICOLOGY AFFECTS US EVERYDAY California Wants to Serve a Warning With Fries (NY Times, Sept 21, 2005) Fish-mercury risk underestimated (CNN.com,... Exposure: Diet and water Macrophage engulfed particles Factors controlling uptake: Lipid solubility Degree of ionization Size of molecule Transport via blood and lymph to liver Dose depends on level of contaminants in source pH Risk assessment: How much is taken up – dose – default 100% 23 UNBORN CHILD - PLACENTA • Lipid solubility • Molecule size • Ionisation 24 UPTAKE-DISTRIBUTION 25 Local and Systemic... AND TIMING DIFFERENTIATES A POISON FROM A REMEDY 19 Modification of Paracelcus TOXICOLOGICAL PARADIGM Toxicokinetics What We do to the Chemical Exposure Toxicodynamics What the Chemical Does to Us Internal Dose Absorption Distribution Metabolism Excretion Storage Biologically Effective Dose Early Biological Effect Altered Structure & Function Disease Susceptibility and Modifying Factors (Genetics and. .. products Workplace – production of chemical and manufacturing of product General environment – indirect exposure Misuse of chemicals 13 WHAT IS TOXICOLOGY? • Toxicology helps create a safer world • Definition: The study of the negative effects of chemical and physical agents on living organisms • Modern toxicology uses chemicals as tools to understand molecular/cellular biology Toxicology is the... DOSE 29 TOXICOKINETIC MODELLING 30 CELL RESPONSE TO STRESS AND INJURY Normal cell (homeostasis) Stress Increased demand Cell injury Cell injury Adaptation Inability to adapt Cell death 31 MECHANISTIC TOXICOLOGY Focuses on how • Chemicals produce adverse effects • Biological systems protect themselves against adverse effects Involves • Cellular and Molecular Biology • Chemistry, often xenobiotic metabolism... Transcriptomics - RNA mRNA Protein Metabolic product Proteomics Proteins Metabolic product Metabonomics – metabilites Biochemical or 33 physiological response GENOMICS IN TOXICOLOGY • Comprehensive understanding of the mechanism of action of toxicants • Identification of biomarkers of exposure • Development of comprehensive screening tools to identify potential toxicants • Extrapolation of mechanisms between . Fellow ATS Human Health and Ecological Risk Assessment and Risk Management 1 Course Coordinator: Khunying Mathuros Ruchirawat Objectives: Give an introduction to the assessment of risk of chemicals. assessment General human and eco-toxicology Tools used in risk assessments Animal studies Human studies Exposure assessment Mode of Action Standard setting Management and communication 4 RISK ASSESSMENT. of chemicals to human health and well-being and the environment, and present the newest concepts in the evaluation of risks Format: Lectures including case studies, and risk assessment exercise,