1. ‘DOSE’-‘OUTCOME’ IN GENERAL Relationship between a measured outcome associated with a measured dose –‘outcome’ = level of biological response or prevalence of a disease. –‘dose’ = defined here as what drives the outcome Concepts of no-observed-adverse- effect-level (NOAEL) and lowest- observed-adverse-effect-level (LOAEL).

2. ‘DOSE’-‘OUTCOME’ CURVE Curve for an individual (hypothetical) Curve for a population Curve for an animal ‘model’ Uncertainty and the usefulness of the NOAEL concept

3. EXTRAPOLATION OF DOSE- OUTCOME DATA: OPTIONS Extrapolation of available data to a threshold –most substances producing systemic toxic effects Extrapolation to origin - no threshold –for carcinogens

4. TYPES OF DOSE-OUTCOME DOSE CARCINOGENNON- CARCINOGEN data extrapolate data end here OUTCOME

5. EXTRAPOLATION OVER WIDE RANGES: A PROBLEM?? (e.g., asbestos) 1010 -1 10 -3 10 -5 10 -1 10 -4 10 -7 Lifetime risk of lung cancer or mesothelioma Respirable asbestos fiber concentration (fibers/cm 3 ) Actual data from occupational epidemiology Range of interest for the whole population

6. STANDARDS SETTING limitUse of dose-outcome information to develop a level of exposure (a limit) below which the risk of the health outcome in question is “acceptable” uncertaintyAcknowledgement of uncertainty safety factorsApplication of safety factors moral/ethicalThe moral/ethical dimension??

7. HAZARD AND RISK HAZARDHAZARD, the intrinsic property of an agent that reflects its potential to cause harm. RISKRISK, the probability of actual harm under the conditions that the agent is encountered.

8. EHS 507 Risk Assessment & Management Science “Objective” Policy “Subjective” Dose-Response Assessment Exposure Assessment Risk Characterization Risk Management Hazard Identification

9. POSSSIBLE SOURCES OF DATA ON WHICH TO BASE DOSE- RESPONSE ASSESSMENT NEEDED FOR RISK ASSESSMENT EpidemiologicEpidemiologic studies (i.e., observational studies of exposed human populations) Human Experimental Studies AnimalAnimal studies In vitroIn vitro studies