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Regulatory Toxicology

Regulatory Toxicology. Chapter 10. Safety evaluation & Risk Assessment. Chapter 10. Safety Evaluation. Part 1. 混合. Risk Assessment. Part 2. Introduction and Definitions. Section 1. Historical context.

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Regulatory Toxicology

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  1. Regulatory Toxicology Chapter 10 Toxicology - Chaper 10

  2. Safety evaluation& Risk Assessment Chapter 10 Toxicology - Chaper 10

  3. Safety Evaluation Part 1 Toxicology - Chaper 10

  4. Toxicology - Chaper 10

  5. Toxicology - Chaper 10

  6. Toxicology - Chaper 10

  7. 混合 Toxicology - Chaper 10

  8. Toxicology - Chaper 10

  9. Toxicology - Chaper 10

  10. Toxicology - Chaper 10

  11. Toxicology - Chaper 10

  12. Toxicology - Chaper 10

  13. Toxicology - Chaper 10

  14. Toxicology - Chaper 10

  15. Risk Assessment Part 2 Toxicology - Chaper 10

  16. Introduction and Definitions Section 1 Toxicology - Chaper 10

  17. Historical context • Advance in analytical chemistry forced the regulatory agencies to develop “tolerance levels ” such as thresholds limit values and acceptable daily intakes. • “nondetects” are not equivalent to “not present”. There is no “absolute safe”. Toxicology - Chaper 10

  18. Historical context • During 20 years before 1990, only 7 substances (vinyl chloride, asbestos, benzene, radionuclides, mercury, arsenic, beryllium) had been regulated under the basis of no-effect level widely agreed as safe at that time. • Replacement of “safety levels” with “acceptable risk levels ”. Toxicology - Chaper 10

  19. Historical context • NRC(1983): Risk Assessment in the Federal Government: managing the process. • NAS(1994): Science and Judgment in Risk Assessment • Presidential/Congresssional Commission on Risk Assessment and Risk Management (1997) Toxicology - Chaper 10

  20. Definitions • Risk – The probability of an adverse outcome to the human health. • Hazard – Intrinsic toxic properties of environmental agents. • Risk assessment – The systematic characterization of potential adverse health effects resulting from human exposure to hazardous agents or situations. Toxicology - Chaper 10

  21. Definitions • Risk characterization – The combination of qualitative and quantitative analysis of risk. • Risk management – The process by which policy actions are chosen to control hazards identified in risk assessment. • Risk communication – The challenging process of making risk assessment and management information comprehensible to community groups and “stakeholders”. Toxicology - Chaper 10

  22. Toxicology - Chaper 10

  23. Key steps of risk assessment Section 2 Toxicology - Chaper 10

  24. Key Steps • Hazard identification • Dose-response assessment • Human exposure assessment • Risk characterization Toxicology - Chaper 10

  25. Risk Perception • Knowledge • Life experience • Psychological factors • Political factors • Social and economical factors Toxicology - Chaper 10

  26. Hazard identification • Assessing toxicity of chemicals • Structure / activity relationship • In vitro and short-term tests • Animal bioassays • Use of epidemiologic data • Mechanistic considerations Toxicology - Chaper 10

  27. Dose-response assessment • Needs for extrapolations • Threshold approaches: non-carcinogenic chemicals, system toxicants • Nonthreshold approaches: carcinogenic chemicals, ionizing irradiation • Models derived from mechanistic assumptions Toxicology - Chaper 10

  28. Toxicology - Chaper 10

  29. Toxicology - Chaper 10

  30. Toxicology - Chaper 10

  31. Human exposure assessment • To determine exposure pathways • To quantify pathway-specific exposure • To calculate overall exposures • Point estimation method • Probabilistic method Toxicology - Chaper 10

  32. Risk characterization • Noncancer risk calculation • NOAEL or LOAEL • RfD or RfC • Cancer risk calculation • Radiation risk factor • Carcinogenic potency factor Toxicology - Chaper 10

  33. Noncancer Risk Assessment • Identify critical effect. • Identify NOAEL or LOAEL for the critical effect. • Apply UFs to the NOAEL or LOAEL to derive RfD or RfC. Toxicology - Chaper 10

  34. As Defined by EPA RfD or RfCis ... an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily (for RfD) or continuous (for RfC) exposure to the human population (includingsensitive subgroups) that islikely to be withoutan appreciable risk of deleterious effects during a lifetime. Toxicology - Chaper 10

  35. Toxicology - Chaper 10

  36. Uncertainty analysis factors *uncertainty 10 individual difference 10 or 3 difference between animal and human 10 or less extrapolation from sub- to chronic 10 or less extrapolation from LOAEL to NOAEL 10 or less data quality * These factors are as used by the U.S. EPA. Other health organizations use similar factors. In EPA, the maximum UF for any given database is 3,000. Databases weaker than this are judged too uncertain to estimate RfD/RfCs. Toxicology - Chaper 10

  37. Framework of risk assessment / management Section 3 Toxicology - Chaper 10

  38. Toxicology - Chaper 10

  39. Risk assessment is a challenging area in toxicology Toxicology - Chaper 10

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