29.11.2012 1 MASARYK UNIVERSITY Brno – Czech Republic RECETOX HUMAN HEALTH RISK ASSESSMENT Pavel Čupr, Ondřej Mikeš RISK ASSESSMENT METHODOLOGY Human health risk assessment is the PROCESS to estimate the probability of adverse health effects in humans who may be exposed to chemicals in contaminated environmental media - food, drinking water, sediments, soil, air - inhalation….), - for actual time or in the future (prospective estimation) or retrospective assessment (in the past…). WHY we are doing RA? – We must interpret all measured Concentrations - CONTAMINATION 29.11.2012 2 RISK ASSESSMENT METHODOLOGY Risk Assessment Process (U.S. EPA approach) Hazard Identification Exposure Assessment Toxicity Assessment Risk Characterization 4 Main parts of this methodology 29.11.2012 3 RISK ASSESSMENT METHODOLOGY Advantage of this approach Probability Of Cancer and Noncancer RISK ASSESSMENT Propabilistic approch Step 1:Hazard Identification • Collected database about chemical concentration – obtained by sampling – Or by modeling work • Info about toxicity of these chemicals • Develop model of how chemical may move through environment – Conceptual Site Model is used to organize information regarding chemicals and potential transport to organisms © Vermont DPS, 2000 AFCEE, 2002 The first step in the RA is the Hazard identification. The hazard identification defines the problem, explicitly identifies the components like: 29.11.2012 4 Step 2: Exposure Assessment The exposure assessment attempts to quantify the exposure of the receptor (selected population) to chemicals via a given pathway. The daily intake of a contaminant via individual pathways can then be summed to estimate the total daily intake TDI (mg/kg/day). Exposure via individual exposure pathways can be calculated using contaminant concentrations in environmental samples (water, diet, sediments, soils, air..) and human behavior information (=exposure parameters = from exposure surveys). Alternatively, total exposure (POPs,…) can be estimated by collecting human tissue samples for chemical analysis (i.e., blood and breast milk samples). Step 2: Exposure Assessment • Who is Exposed? – Adult, Child, Special Populations • How Are They Exposed? – Ingestion, Inhalation, Skin Contact • What is the Concentration of Chemical to Which They are Exposed? – ppm in Water or Soil • How Often Are They Exposed? – Days per year, Number of years Prediction of Exposure scenarios 29.11.2012 5 Putting it all together. . . – exposure parameters ATBW EDEFCRC daykgmgCDIDoseIntake × ××× =− )/( • Intake Equation for Drinking Water Example C= Chemical Concentration (Obtain from sampling) CR= Contact Rate (2 liters water/day) EF= Exposure Frequency (350 days/year) ED= Exposure Duration (30 years) BW=Body Weight (70 kg.) AT= Averaging Time (10,950 days) Step 3: Toxicity assessment / Dose-Response Curve relationship Dose – Chemical concentration per unit body weight Response – Level of measured adverse effect Noncancer risks (noncancer chemicals) - to quantify the Reference Dose – Chemical concentration per unit body weight without significant biolog. effects (http://www.epa.gov/iris/rfd.htm) The toxicity assessment attempts - to quantify the sensitivity of the receptor to the chemical hazard (STRESOR). - to use Dose/response relationship 29.11.2012 6 Uncertainty Factors (UFs): (conditions for using of UF and MF) - Use a 10-fold factor when extrapolating from valid experimental results in studies using prolonged exposure to average healthy humans. This factor is intended to account for the variation in sensitivity among the members of the human population and is referenced as "10H". - Use an additional 10-fold factor when extrapolating from valid results of long-term studies on experimental animals when results of studies of human exposure are not available or are inadequate. This factor is intended to account for the uncertainty involved in extrapolating from animal data to humans and is referenced as "10A". - Use an additional 10-fold factor when extrapolating from less than chronic results on experimental animals when there are no useful long-term human data. This factor is intended to account for the uncertainty involved in extrapolat- ing from less than chronic NOAELs to chronic NOAELs and is referenced as "10S". - Use an additional 10-fold factor when deriving an RfD from a LOAEL, instead of a NOAEL. This factor is intended to account for the uncertainty involved in extrapolating from LOAELs to NOAELs and is referenced as "10L". Modifying Factor (MF): Use professional judgment to determine the MF, which is an additional uncertainty factor that is greater than zero and less than or equal to 10. The magnitude of the MF depends upon the professional assessment of scientific uncertainties of the study and data base not explicitly treated above; e.g., the completeness of the overall data base and the number of species tested. The default value for the MF is 1. http://www.epa.gov/iris/rfd.htm …. Chemical 1 Chemical 2 Chemical 3 … Total RISK (aditive sum of individual Chemical- risks) RISK ASSESSMENT METHODOLOGY – noncancer risk Internal dose Chronic Daily Intake Noncancer RISK ASSESSMENT RfD – reflect the worst type of health outcomes from this chemical RfD = TDI Tolerable daily intake (RfD is only for noncancer chemicals!!) ….. …… Exposure scenario models [C] concentrations RISK = CDI / RfD Noncancer RISK > 1 Significant risk 29.11.2012 7 Gama-HCH 7 PCBs DDT DDE DDD Total RISK (aditive sum of individual Chemical-risks) = expressed as a probability of health effects Internal dose Chronic Daily Intake RISK - probability of an individual developing cancer over a lifetime as a result of exposure to the potential carcinogen Acceptable RISK = 1.10-6 (probability of carcinogenesis for 1 person per million) Cancer RISK - probabilistic approach Beta-HCH Alpha-HCH Exposure scenario models [C] concentrations Cancer RISK = 1 - exp (-CDI * SF) SF – SLOPE FACTOR DOSE DESE – RESPONSE relationship EXTRAPOLATION TO LOW DOSE P RISK Relevant to Cancer risks (cancer chemicals) !!! Databases of these RISK INDEXES - WEB RISK ASSESSMENT METHODOLOGY – cancer risk RISK > 1.10-6 Significant risk Gama-HCH 7 PCBs DDT DDE DDD Total RISK (aditive sum of individual Chemical- risks) = expressed as a probability of health effects RISK = 1 - exp (-CDI * SF) RISK ASSESSMENT METHODOLOGY Internal dose Chronic Daily Intake Cancer and Noncancer RISK ASSESSMENT -U.S. EPA probabilistic approach Beta-HCH Alpha-HCH physiologically based pharmacokinetic (PBPK) model Exposure scenario models [C] concentrations RISK = CDI / Rfd Cancer Noncancer 29.11.2012 8 Step 4: Risk Characterization The risk characterization combines the information obtained on toxicity with the calculated exposure to provide an estimate of risk. Purdue 1997 RISK = CDI / RfDNoncancer RISK > 1 Significant risk Cancer RISK = 1 - exp (-CDI * SF) RISK > 1.10-6 Significant risk GIS HCB Gama-HCH Beta- HCH Alpha-HCH 7 PCBs DDT, DDD DDE Total RISK (sum of individual Chemical-risks) All chemicals Togeother = expressed as a probability of health effects RISK = 1 - exp (-CDI * SF) ……… RISK ASSESSMENT METHODOLOGY Spatial distribution of these both RISKs Advantage – This RA allow us to realize the Exposure scenario models in future RISK = CDI / Rfd Cancer Noncancer 29.11.2012 9 Predicted level of toxicant in people Metabolism Accumulation Excretion Lung, intestine, and skin absorption rates Genetic predisposition Personal habits Lifestyle Overall health Nutritional health Food pesticide levels Soil/dust levels Water pollutant levels Air pollutant levels !!Emphasize!! Chemical stress is only ONE of all stresors and relevant PREDICTORS for final Human Health RISKs!! RISK ASSESSMENT METHODOLOGY 1) TGD - Technical Guidance Document on Risk Assessment EC (European Commission 2003): EC (European Commission 2003): Technical Guidance Document on Risk Assessment (Edition 2). Part II. Chapter 2 Risk Assessment for Human Health. (EUR 20418 EN/1). http://ecb.jrc.ec.europa.eu/home.php?CONTENU=/DOCUMENTS/TECHNICAL_GUIDANCE_DOC UMENT/EDITION_2/ , Institute for Health and Consumer Protection. European Chemicals Bureau. Detail description of Risk assessment method: 2) Quantitative Environmental Risk Analysis for Human Health – detail description of Risk assessment method with many exercises - case studies. (Robert A. Fjeld et al., 2007) Robert A. Fjeld; Norman A. Eisenberg; Compton, K. L. Eds.) (2007): Quantitative Environmental Risk Analysis for Human Health. Chapter 9 Exposure Assessment, chapter 10 Basic Human Toxicology, chapter 11 Dose–Response and Risk Characterization, (pp 199-314). John Wiley & Sons, Inc. Hoboken, New Jersey. 3) Risk Assessment Guidance for Superfund, (U.S. EPA) Part A (1989) Part B (1991) Part C (1991) Part D (2001) Part E (2004) Part F (2009) 29.11.2012 10 http://www.epa.gov/reg3hwmd/risk/index.htm RISK ASSESSMENT METHODOLOGY Source of important toxicological indexis: RfD, Slope Factor… Where we can get these informations SOURCEs ? DATABASES? IRIS http://www.epa.gov/iris 309–00–2 example: (CAS, chemicals.. 29.11.2012 11 http://toxnet.nlm.nih.gov/ http://www.inchem.org/ 29.11.2012 12 23 Thank you for your attentionThank you for your attention