THE RISK ASSESSMENT introduction2010

THE RISK ASSESSMENT PROCESS Tueday December 6 2011 Herman Autrup 1 HAZARD is the inherent capacity of a substance or a mixture to cause adverse effects in man or the environmnet under the condition of exposure RISK is the probability of an adverse effect on man or the environmnet occuring as a results of a given exposure to a chemical or mixture HAZARD vs RISK 2 EXPOSURE HAZARDRISK RISK RISK ASSESSMENT PARADIGME Public, NGO Scientific panels Myndigheder 3 4 EFFECT ASSESSMENT Hazard identification Human and ecological Dose-respons assessment EXPOSURE ASSESSMENT Workers Consumers In-direct via environment RISK CHARACTERIZATION RISK ASSESSMENT 5 RISK ASSESSMENT  Systematic, scientific characterization of potential adverse human or ecological exposure to hazardous agents or activities  Considers relationship between exposure and responses, including variation in susceptibility and attendents uncertainties Is a process of evaluation, including the identification of the attendant uncertainties, of the likelihood and severy of an adverse effect following exposure underdefined condition to a risk source 6 7 8 IMPROVEMENT OF EXPOSURE INFORMATION 9 • Identification of relevant structural characteristics and potential mechanism or mode of action of a target chemical • Identification of other chemicals that have the same structural characteristics and/or mechanism or mode of action • Use of existing experimental data to fill the data gap(s). FILLING THE DATA GAPS 10 [...]... (effect) assessment • Determine No Observed Adverse Effects Level (NOAEL) 28 HUMAN HEALTH EFFECTS DATA Relevance, complexicity, costs humans animal experiments in vitro tests (Q)SAR uncertainty WHAT IS EXPOSURE ASSESSMENT? • EXPOSURE is the contact of a chemical, physical, or biological substance with the outer boundary of an organism • EXPOSURE ASSESSMENT is the determination or estimation of the magnitude,... CYCLE OF A CHEMICAL 11 RISK= HAZARD x EXPOSURE Hazard (high concern) x Exposure (minimal) = low risk Hazard (low concern) x Exposure (high) = low risk Hazard (moderate concern) x exposure (high)= Potential for risk exists 12 RISK SOURCES  Air (indoor/ambient)  Drinking water  Food  Soil  Consumer products  Waste Integrated exposure over all routes – allocation of fraction 13 RISK SOURCES – CHEMICALS... EXPOSURE ASSESSMENT - CRITICAL ISSUES • EXPOSURE ASSESSMENT MUST CONSIDER TIME SCALE RELATED TO TOXICOLOGICAL EFFECT • PEAK EXPOSURES; AVERAGE EXPOSURE • CRITICAL WINDOWS OF EXPOSURE (e.g REPRODUCTIVE EFFECTS) • PERSISTENCE • BIOACCUMULATION 32 RISK CHARACTERIZATION INTEGRATION OF EXPOSURE DATA and DOSE RESPONS SUSCEPTIBLE POPULATION – CHILDREN, ELDERLY 33 RISK CHARACTERIZATION the estimation of the incidence... Route of exposure and test duration  Integrity of study 22 RELEVANCE OF THE DATA • Appropriate species tested – Most similar toxicokinetics and toxicodynamics to man – Most sensitive animal species • The route of exposure (duration) is relevant for the population and exposure scenario • Proper identification and representativeness of the substance – Significant impurities described • Species-specific effects/responses... drugs (contaminants) Can be found in many different environments - air, water, soil 14 RISK SOURCES - EXPOSURE  Home – use of products  Workplace – production of chemical and manufacturing of product  General environment – indirect exposure  Transit – accidents  Misuse of chemicals Risk scenarios for all exposures 15 RISK SOURCES - AIR  Particles  Classical pollutants criteria pollutants  Inorganic... effect in 50% of the test population (labelling of chemical) CHRONIC TOX: NOEL = No observed effect level (acceptable intake levels, TDI) LOEL = Lowest observed effect level NOAEL = No observed adverse effect level BMD10 = Dose at which 10% of animals is affected DNEL = Derived no effect level 27 HUMAN HEALTH EFFECT ASSESSMENT • Identify effects of concern • Quality and relevance of the data • Relevance... CHARACTERIZATION the estimation of the incidence and severity of the adverse affect likely to occur in a human population (or environmental compartment) due to actual or predicted exposure to a substance  comparing a no effect concentration to an exposure value (thresholded)  determine exposure levels for acceptable risk (non thresholded) 34 THE USE OF UNCERTAINTY OR SAFETY FACTORS species differences... Inorganic compounds  Volatile organic compounds  Aerosol National air quality standards based upon WHO guidance values 16 RISK SOURCE - DRINKING WATER  Pesticides  Detergents  Disinfection by products  Natural compounds /geogenic compounds Water framework directives 17 RISK SOURCES - FOOD  Natural toxins - aflatoxin  Food additives - flavours  Food contaminants - dioxins  Compounds produced... epidemiological studies • Case reports • Controlled studies in human volunteers  Ethical considerations! 24 DOSE-RESPONSE - EFFECT ASSESSMENT • CONSIDERATION OF TOXIC EFFECTS AT VARIOUS DOSE LEVELS • EFFECTS: GRADED AND MEASURED RESPONSE: QUANTAL AND COUNTED • SHAPE OF THE DOSE-RESPONSE CURVE • ESSENTIALITY CONSIDERATIONS • NO(A)EL DERIVATION vs PROBABILISTIC APPROACHES 25 DOSE-RESPONSE CURVE Response...  Ecological cycling PBT and vPBT compounds CMR compounds – carcinogenic, mutagenic, reprotoxic 19 HAZARD IDENTIFICATION  To identify if a particular chemical has the potential to cause adverse effects  Qualitative decision reflecting the presence of a hazard  Animal studies, epidemiological data, alternative methods, in silico (QSAR)  OECD Guidelines, GLP principle  Weight of evidence 20 HAZARD . exposure RISK is the probability of an adverse effect on man or the environmnet occuring as a results of a given exposure to a chemical or mixture HAZARD vs RISK 2 EXPOSURE HAZARDRISK RISK RISK ASSESSMENT. panels Myndigheder 3 4 EFFECT ASSESSMENT Hazard identification Human and ecological Dose-respons assessment EXPOSURE ASSESSMENT Workers Consumers In-direct via environment RISK CHARACTERIZATION RISK ASSESSMENT 5 RISK ASSESSMENT. THE RISK ASSESSMENT PROCESS Tueday December 6 2011 Herman Autrup 1 HAZARD is the inherent capacity of a substance or a mixture to cause adverse effects in man or the environmnet under the