Basics of Risk Assessment

Transcription

1 Basics of Risk Assessment Christopher J. Portier, Ph.D. Director National Center for Environmental Health Agency for Toxic Substances and Disease Registry International Conference on EMF and Health Brussels, Belgium November 16, 2011 National Center for Environmental Health Agency for Toxic Substances and Disease Registry

2 Risk Assessment in the Federal Government Managing the Process (NRC, 1983) RESEARCH RISK ASSESSMENT RISK MANAGEMENT Laboratory and field observations of adverse health effects and exposures to particular agents Hazard Identification (Does the agent cause the adverse effect?) Development of regulatory options Information on extrapolation methods for high to low dose and animal to human Field measurements, estimated exposures, characterization of population Dose-Response Assessment (What is the relationship between dose and incidence in humans?) Exposure Assessment (What exposures are currently experienced or anticipated under different conditions?) Risk Characterization (What is the estimated incidence of the adverse effect in a given population?) Evaluation of public health, economic, social, political consequences of regulatory options Agency decisions and actions

3 Science Research Test Hypotheses Interpretation Risk Assessment Policy Evaluation Characterization Communication TRANSLATION Cost Assessment Economics Research Test Hypotheses Interpretation Risk Management Society Decision Cost/Benefit Set Priority Manage

4 Human Systems Gohlke and Portier (2006)

5 Understanding Environment and Human Disease Human Clinical Laboratory Epidemiology Animal Models Tissue Cultures Molecular Biology Cell Cultures Gohlke and Portier (2006) Boverhof and Zacharewski (Tox. Sci., 2006)

6 Mevissen and Portier, 2011

7 Mevissen and Portier, 2011

8 Mevissen and Portier, 2011

9 IARC Use of Evidence EVIDENCE IN EXPERIMENTAL ANIMALS Sufficient Limited Inadequate ESLC Sufficient Group 1 EVIDENCE IN HUMANS Limited Inadequate Group 2A Group 2B Group 2B (exceptionally, Group 2A) Group 3 ESLC Group 4 Modified from Vincent Cogliano, IARC

10 Systematic Reviews Courtesy of M. Wolfe, NTP

11 Track and document study selection Table format Total studies identified 199 Exclusion reason no data on relevant health outcomes and exposure 33 review or commentary 12 relevant endpoints but assessed at <1 yr 6 primarily mechanistic or other "supportive" 51 Other 4 Studies included 93 Listing of citations of excluded articles Not included, no data on relevant health outcomes and exposure "Itai-itai byo" and other views on cadmium. Food Cosmet Toxicol 1972; 10(2): [Preventive medicine possible only by overcoming current vices]. Zahnarztl Mitt 1979; 69(12): New studies: pills don''t increase diabetes danger; smoking multiplies pill-associated stroke risk. Fam Plann Perspect 1979; 11(2): Nonpharmacological approaches to the control of high blood pressure. Final report of the Subcommittee on Nonpharmacological Therapy of the 1984 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 1986; 8(5): The Surgeon General''s 1990 Report on The Health Benefits of Smoking Cessation. Executive Summary. MMWR Recomm Rep 1990; 39(RR-12): i-xv, 1-12 Courtesy of M. Wolfe, NTP

12 Display data in summary tables Courtesy of M. Wolfe, NTP

13 Manhattan plot style graphic showing the environmentwide association with Type II Diabetes Patel et al., PLOS One, 2010

14 Identifying Important Disease Pathways Human Genetics + Human Disease Identify Pathways Related to Human Disease New omics & HTS Predict Data Chemical-Gene- Disease Interactome Sets of Pathways High Throughput High Content Chemical-Specific Data Predict Risks Fingerprint Toxicants Develop Screens Set Priorities Develop Hypotheses

15 Gohlke et al. (BMC Systems Biology, 20

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17 P-Values for Each Study

18 Recommending a Standard Response NOAEL LOAEL Statistically Significantly Different From Control Dose

19 Added Risk Benchmark Dose (BMD) Method BMR Benchmark Response (10%, 5%, 1%) 95% CI BMDL BMD Exposure

20 Added Risk BMR Benchmark Dose (BMD) Method Benchmark Response (10%, 5%, 1%) Modifying/Uncertainty Factors 95% CI MRL Exposure BMDL BMD

21 Evaluating Dose-Response Patterns Methylene Chloride Naphthalene 1,4-Dichlorobenzene 1,2,3-Trichloropropane Propylene glycol mono-t-butyl ether

22 Questions? CDC_DrCPortier For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA Telephone, CDC-INFO ( )/TTY: Web: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Environmental Health Agency for Toxic Substances and Disease Registry

23 Science and the Risk Decision Process Sparse and Infrequent Observations Decision to Delay Decision Observational Error Theoretical Misunderstanding Oversimplified Biological Models Incorrect Interpretation of Observations Prepublication Leaks Politics Stakeholder Pressure Decision Media Further Misunderstanding Scientific Basis For Decision Scientific Publication Controversy Further Refinements of Unimportant Details Confusion Coincidental Agreement Between Theory and Observations Black Box Mathematical Models Unrealistic Assumptions Computer Coding Errors Crude Diagnostic Tools

24 This paper was produced for a meeting organized by Health & Consumers DG and represents the views of its author on the subject. These views have not been adopted or in any way approved by the Commission and should not be relied upon as a statement of the Commission's or Health & Consumers DG's views. The European Commission does not guarantee the accuracy of the data included in this paper, nor does it accept responsibility for any use made thereof.