Section 6: Key Points

What We've Covered
This section made the following main points:
  • A hazard is the capability of a substance to cause an adverse effect.
    A risk is the probability that the hazard will occur under specific conditions.
  • Risk assessment is the process of determining hazard, exposure, and risk.
    Risk management is the process of weighing policy alternatives and deciding on the most appropriate regulatory action.
  • There are four basic steps to risk assessment:
    1. Hazard Identification
      • Identify or develop information suggesting or confirming whether a chemical poses a potential hazard to humans.
      • (Quantitative) Structure Activity, or (Q)SAR methods, including computer models, help consider closely related chemicals as a group or category.
      • Read-across involves estimating what a chemical may be like, including the presence or absence of certain properties or activities, based on one or more other chemicals.
      • Adverse Outcome Pathways (AOPs) involve in vitro methods that evaluate changes in normal cellular signaling pathways.
      • Other emerging methods include (Quantitative) in vitro to in vivo extrapolation, or (Q)IVIVE, Integrated Testing Strategies, and Integrated Approaches to Testing and Assessment (IATA).
    2. Dose-Response Assessment
      • Carcinogenic (cancer) risk assessment involves two steps:
        1. Perform qualitative evaluation of all epidemiology studies, animal bioassay data, and biological activity.
        2. Quantitation of the risk for substances classified as definite or probably human carcinogens.
      • Non-carcinogenic risk assessment includes:
        • Acceptable Daily Intake (ADI), which divides the NOAEL by uncertainty/safety factors.
        • Reference Dose (RfD), which divides the NOAEL or LOAEL by uncertainty/safety factors.
        • Benchmark Dose Method (BMD), which extrapolates data to determine a point of departure (POD) that accounts for study quality.
        • Assessments for noncancer toxicity effects, acute or short-term exposures, and occupational exposures.
    3. Exposure Assessment
      • People are exposed to mixtures of hundreds of chemicals in everyday life.
      • An exposure pathway describes the:
        • Route a substance takes from its source to its endpoint.
        • How people can be exposed to the substance.
      • The three steps of exposure assessment are to:
        1. Characterize the point of exposure setting and exposure scenario.
        2. Identify exposure pathways.
        3. Quantify the exposure.
      • Exposure models are commonly used because actual exposure measurements are often not available.
    4. Risk Characterization
      • This final phase predicts the frequency and severity of effects in exposed populations.
      • Biological and statistical uncertainties are described.
      • For carcinogenic risks, the probability of a person developing cancer over a lifetime is estimated by multiplying the cancer slope factor for the substance by the chronic, 70-year average daily intake.
      • For noncarcinogenic effects, the exposure level is compared with an ADI, RfD, or MRL derived for similar exposure periods.