Understanding Risk Analysis and Management

Objectives for the Lecture

• Recognize the main aspects of risk analysis.
• Key step is to identify the steps in the risk assessment process.
• Need a framework for risk-based decision making.
• Need methods to identify hazards.
• Establish dose-response assessment to assess exposure, and to characterize the risks.
• Important to analyze the factors affecting risk perception.

Risk Analysis

• A process consisting of three components: risk assessment, risk management and risk communication.

Key Terms

• Hazard: capability of a substance to cause an adverse effect.
• Risk: probability that the hazard will occur under specific exposure conditions.
• Risk assessment: the process by which hazard, exposure, and risk are determined.
• Risk management: the process of weighing policy alternatives and selecting the most appropriate regulatory action based on the results of risk assessment and social, economic, and political concerns.

Risk Assessment vs. Risk Management

• "Risk Assessment "asks how risky a situation is.
• "Risk Management" asks what should be done about it.
• Risk management should not influence the processes and assumptions made in risk assessment but the two elements depend on each other.
• Risk assessment is a systematic scientific evaluation of potential adverse health effects resulting from exposures to hazardous agents or situations.
• Risk management is the process by which policy actions are chosen to control hazards identified in the risk assessment stage of the framework.

Risk Assessment vs. Risk Management Stages

• Enhanced problem formulation and scoping: available risk-management options are identified during this first step, and the problem is clearly defined.
• Planning and assessment: risk-assessment tools are used to determine risks under existing conditions and under potential risk-management options.
• Risk management: risk and non-risk information are integrated to inform choices among options.

Objectives of Risk Assessment

• Important to protect human, animal, and ecological health.
• Weigh potential dangers against useful benefits for society.
• Define acceptable levels of contaminants in food, water, and the environment.
• Aids in making informed choices on program activities.
• Evaluates how much risk remains after control measures are applied.

Risk Assessment Steps

• Involves a structured process entailing hazard identification, dose-response assessment, exposure assessment, and risk characterization.
• Hazard Identification: characterizing the innate adverse toxic effects of agents.
• Dose-response assessment: characterizing the relation between doses and incidences of adverse effects in exposed populations.
• Exposure assessment: measurement or estimation of the intensity, frequency, and duration of human exposures to agents.
• Risk characterization: estimating the incidence of health effects under the various conditions of human exposure.

Hazard Identification

• Identification of the type and nature of adverse effects that an agent has an inherent capacity to cause in an organism, system, or (sub)population.
• Important to evaluate the weight of evidence for adverse health effects, based on an assessment of all available data on toxicity and mode of action.
• Gathering and evaluating data on the types of health effects or disease that may be produced by a chemical and exposure conditions under which environmental damage, injury or disease will be produced.
• Critical, is the likelihood of harm due to exposure that distinguishes risk from hazard

Hazard Identification Considerations

• This investigates what kind of harm an agent can cause.
• Includes the type of toxicity, target organs/systems, and mechanism of toxicity
• The key questions focus on when and how the harm occurs, examining route of exposure, dose, duration, and population sensitivity.
• Address two questions: the nature of any health hazard to humans that an agent may pose and the circumstances under which an identified hazard may be expressed.

Hazard Identification - Gathering Data

• Considers human epidemiology data, various types of animal testing data, and in vitro methods when gathering data.
• Animal Bioassays are a crucial component of hazard identification, despite costing millions of ollars and taking years to complete.
• Considers the chemical's structure, solubility, stability, pH sensitivity, volatility, and chemical reactivity to assess hazard potential (Structure-Activity Relationships).

Hazard Identification - In Vitro and Short-Term Tests

• Ranging from bacterial mutation assays performed entirely in vitro to more elaborate short-term tests, such as skin painting studies in mice or altered rat liver foci assays conducted in vivo.
• These tests are important as a quick screening for potential hazards before long-term studies, help identify mechanisms of toxicity, and reduce reliance on animal testing.

Hazard Identification - Epidemiologic Data

• Provides direct evidence of how an agent affects human health.
• Involves well-conducted epidemiologic studies in which a positive association between exposure and disease has been observed
• Can also involve known or presumed exposures, comparing exposed with nonexposed individuals, or with known cases, compared with persons lacking the particular diagnosis
• Includes the evaluation of strength of association, consistency of observations, specificity, appropriateness of temporal relationship, biological plausibility, and verification.

Hazard Identification - Alternative Sources of Data

• Quantitative Structure-Activity Relationships (QSARs) use computer models to assess large groups of chemicals based on structure and known effects of similar compounds.
• Read-across relies on existing information about similar chemicals to infer properties of the chemical of interest.
• Adverse Outcome Pathways (AOPs) use in vitro methods to evaluate changes in normal cellular signaling pathways, moving away from high-dose studies in laboratory animals.

Adverse Outcome Pathways (AOPs)

• The AOPs are made up of specific elements:
• The first is the interaction between the toxic substance and an organism.
• Key events that characterize the progression of the toxicity.
• Adverse outcomes that occur at individual or population levels.

Assessing Toxicity Testing Needs

• Involves a step-wise approach

Assessment - Dose-Response Assessment

• Characterization of the relationship between the dose of an agent and the incidence of adverse effects in an exposed population.
• A qualitative and quantitative description of the inherent properties of an agent or situation having the potential to cause adverse effects.
• Critical is the first adverse effect observed as the dose or exposure is increased (at the lowest level of exposure).
• Can use either threshold and nonthreshold approaches

Assessment - Threshold Approaches

• In cases where the toxic effect is assumed to have a threshold, hazard characterization usually results in the establishment of health-based guidance values.
• The Acceptable Daily Intake (ADI) applies to additives or residues.
• Acceptable Daily Intake is for substances that are intentionally added to food, like additives
• The Tolerable Daily Intake (TDI) is for contaminants.
• Tolerable Daily Intake is for substances that are not intentionally added, but still end up in food

Health-Based Guidance Values

• Calculating health values starts with the NOAEL values.
• These are divided by uncertainty factors which have parameters in relevance of animal response to human risk.
• The goal is to arrive at a value more comparable to a NOAEL.

The Benchmark Dose Method

• Addresses many limitations of the NOAEL method.
• Less dependent on dose selection and accounts form the shape of the dose-response curve.
• Estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality.

Assessment - Nonthreshold Approaches

• Estimates of risk if there is not a threshold for carcinogenicity
• Carcinogen (Cancer) Risk Assessment involves two steps:
• Perform qualitative evaluation of to it's carcinogenic risk to humans based on the weight of evidence.
• Quantitate the risk for those substances classified as definite or probable human carcinogens.

Risk assessment - Exposure Assessment

• Main objectives of exposure assessment are to determine source, type, magnitude, and duration of contact with the chemical(s) of interest .
• Critical element of the risk assessment process, as hazard does not occur in the absence of exposure.

Exposure Assessment goals

• The key is to determine the type and amount of total exposure.
• Important to consider potential human exposure and how a dose may be reaching target tissues.
• To know what exposure pathways are for the risk scenario under development.
• The methods may be: -- Point estimate -- Stochastic

Exposure assessment

• Takes into consideration to occurrence and concentration of the chemical in diet.
• Important the consumption patterns, and the likelihood of consumers eating large amounts of foods chemical is present.
• Using what ingredients are available and the body weight is how to approach the exposure.

Risk Characterization

• Combines all information to predict the frequency and severity of adverse effects in a population that is exposed to the substance.
• In short, risk characterization tells you how likely and how severe the effects of a substance might be in the real world.
• Considers the conclusions from hazard assessment, the dose-response, and exposure assessment.
• Used to predict what the frequency and severity of effects may be what exposed populations.

Risk Characterization: Considerations

• This estimates the ration of exposure to hazard or of hazard to exposure.
• Hazard Quotient (HQ) can be useful in those equations.
• HQ< 1: is a high risk.
• HQ > 1: may suggest the need to refine the risk assessment or a risk management consideration.

Risk Characterization: The Margin of Exposure (MOE)

• The MOE is used when considering the presence in food and feed of chemical substances when deemed inappropriate or unfeasible.
• This can be used for 2 main situations for it's assessment:
• Substances in which, as a result of effects, there's no toxicological data.
• Can be for substances that are both Gentoxic and carcinogenic - risk management actions are less of high risk

Explore the core components of risk analysis, including risk assessment, management, and communication. Learn to identify hazards, assess exposure, and understand factors influencing risk perception. Grasp the distinction between risk assessment and risk management for informed decision-making.