Health risk assessment exam preparation

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Exam 2024

  1. What is the overarching goal of health risk assessment of chemicals? Include in your answer one example of what the conclusions from a health risk assessment can be used for. (2p)

    The overarching goal of health risk assessment of chemicals is to evaluate the likelihood that exposure to a chemical may cause adverse health effects in humans, under specific conditions of use or exposure. The aim is to provide a scientific basis for decision-making to protect public health.

    Example of use:
    The conclusions from a health risk assessment can be used to establish regulatory limits—such as occupational exposure limits or maximum contaminant levels in drinking water—to ensure that chemical exposures remain within safe bounds.

Answered by ChatGPT.

  1. Name the three main steps of a health risk assessment and briefly explain (1-2 sentences), in your own words, what is done in each step. (6p)

    The three main steps of a health risk assessment are:

    1. Exposure assessment:
      This step investigates where and how people might be exposed to the chemical, including the sources, routes (such as inhalation or ingestion), levels of exposure, and which groups are most highly exposed.
    2. Hazard assessment:
      In this step, the harmful effects of the chemical are identified (hazard identification), such as which organs are affected and what the critical effects are. The relationship between dose and response is characterized, accounting for differences between species, individual variability, and setting health-based guidance values (hazard characterization).
    3. Risk characterization:
      This final step integrates information from exposure and hazard assessments to determine if there is a health risk, to whom the risk applies, and evaluates the margins of safety.

Answered by ChatGPT based on information of slide.

  1. Adversity is a central concept in health risk assessment, especially for determining the critical effect on which to base the assessment.
    a) In your own words, describe what is meant by an adverse health effect according to the WHO definition. (2p)
    b) What can be considered adverse is to some extent subjective. Nevertheless, there are some health hazards that are commonly agreed to be of high concern in the regulatory setting, for example that require harmonized classification under the CLP, name 2 such health hazards. (2p)

    a) An adverse health effect is a change in an organism’s body or function—such as its growth, development, physiology, or lifespan—that reduces its ability to function normally or cope with additional stress, or makes it more likely to be harmed by other environmental factors. Deciding whether an effect is truly adverse requires expert judgment.
    b) Two health hazards that are commonly considered of high concern and require harmonized classification under the CLP are:

    Carcinogenicity (causing cancer)

    Reproductive toxicity (causing harm to fertility or unborn children)

    Answered by ChatGPT and a) is answered with slide provided.

  2. The no observed adverse effect level (NOAEL) has traditionally been used as point of departure, e.g. for calculating health-based guidance values. What is NOT true about the NOAEL? Circle one option (1p):

  • The NOAEL is dependent on dose selection and study design.
  • Studies with low power (e.g. small group sizes) lead to higher NOAELs.
  • The NOAEL is the dose-level where there is complete absence of any adverse effect.
  • The true effect size at a NOAEL remains unknown.

Answered myself.

  1. The benchmark dose (BMD) approach is another way to establish a point of departure.
    a) Briefly describe the main principles of the benchmark dose (BMD) approach, include an explanation of the BMD, BMDL and BMDU, and the BMR. (3p)
    b) Name one advantage of the Benchmark dose (BMD) approach over the NOAEL approach for determining a point of departure for health risk assessment. (1p)
    c) Name one advantage of the NOAEL approach over the BMD approach for determining a point of departure for health risk assessment. (1p)

a) The benchmark dose (BMD) approach involves modeling the dose-response data to estimate the dose that produces a predefined level of effect, called the benchmark response (BMR), compared to controls.

BMR (Benchmark response): a predefined level of response compared with response in untreated animals (considered adverse)

BMD (Benchmark dose): the dose resulting in the predefined BMR

BMDL (Benchmark dose lower confidence limit): the statistical lower confidence limit of the BMD

BMDU (Benchmark dose upper confidence limit): the statistical upper confidence limit of the

BMD

b) The BMD approach makes use of the entire dose-response dataset, allowing for interpolation between doses and providing a more statistically robust and informative point of departure that reflects data variability and uncertainty (via confidence intervals).

c) The NOAEL approach is easier to calculate, more straightforward to standardize, and is traditionally more familiar and easier to understand for regulators and risk assessors.

a) comes from slides, b) and c) answered by ChatGPT based on slides.

  1. Animal toxicity studies are often considered the most informative type of data for health risk assessment.
    a) What are two main purposes of in vivo testing in animals, in the context of chemical risk assessment? (2p)
    b) Briefly describe two limitations of using animal data for health risk assessment. You may consider both scientific and ethical aspects. (2p)
    c) Regulatory health risk assessment often requires that toxicity tests are conducted in accordance with standardised and internationally validated test guidelines, for example the OECD test guidelines. Why? (1p)

a)

  1. To identify potential adverse health effects and target organs caused by chemical exposure under controlled conditions.

  2. To determine dose-response relationships and establish safe exposure levels that can be used for human risk assessment.

b)

Scientific limitation: Differences in physiology and metabolism between animals and humans mean that results from animal studies may not always accurately predict human responses.

Ethical limitation: Animal testing raises ethical concerns due to the potential pain, suffering, or harm caused to animals.

c) Because standardised and internationally validated guidelines ensure the reliability, reproducibility, and comparability of results, and help meet legislated requirements for risk management and mitigation.

Answered by ChatGPT

  1. Human data from epidemiological studies may also be available for use in health risk assessment of chemicals. Briefly describe one strength and one limitation of using human epidemiological data for health risk assessment. (2p)

    Strength:
    Epidemiological studies provide direct evidence of health effects in humans, reflecting real-world exposures and population variability.

    Limitation:
    Epidemiological studies often face challenges such as confounding factors, exposure misclassification, and difficulty in establishing a clear cause-and-effect relationship between the chemical and the observed health effects.

Answered by ChatGPT

  1. You have heard about New Approach Methodologies (NAMs) and developments towards using more NAM data in (regulatory) risk assessment in several lectures and from the agencies that we visited.
    a) What are NAMs? (1p)
    b) What type of data do NAMs generally contribute to health risk assessment currently? (1p)
    c) Briefly describe one challenge for implementing NAM-based risk assessment of chemicals. (2p)
    d) How can AOPs be helpful when using NAM data in health risk assessment? (1p)

    a) NAMs (New Approach Methodologies) refer to innovative scientific methods and technologies—including in vitro, in silico, and other non-animal approaches—developed to provide information on chemical safety, often as alternatives or supplements to traditional animal testing.

    b) NAMs mainly provide mechanistic and biological data, such as information on molecular, cellular, or pathway-level effects (e.g., in vitro bioactivity, computational modeling), rather than direct evidence of adverse health effects in whole organisms.

    c) One challenge is the limited ability of many NAMs to predict complex adverse outcomes in whole humans, especially for endpoints like chronic toxicity or systemic effects. There is often uncertainty about how to extrapolate results from NAMs to real-world human exposures and health outcomes, making regulatory acceptance more difficult.

    d) AOPs (Adverse Outcome Pathways) provide a structured framework linking molecular and cellular effects (often measured by NAMs) to adverse health outcomes in humans, helping to interpret NAM data in the context of risk assessment and regulatory decision-making.

Answered by ChatGPT

  1. The NOAEL for the pesticide X is 0.5 mg/kg bw/day. The reasonable worst-case exposure to X as residues in food in the general population is 1 µg/kg bw/day.
    a) Calculate the Tolerably Daily Intake (TDI) for X, show your calculation. You may use the default assessment factor. (2p)
    b) Is the risk for the general population acceptable or unacceptable? Motivate your answer. (2p)
    c) What variabilities is the default assessment factor supposed to account for? (2p)
    d) Briefly describe one direct and one indirect method for exposure assessment you could use to assess the exposure of X in the general population. (2p)

a) Default assessment factor (AF) = 100

TDI=NOAEL/AF=0.5mg/kg bw/day / 100 = 0.005mg/kgbw/day = 5μg/kgbw/day

b) MOE = NOAEL / Exposure = 0.5 mg/kg bw/day / 0.001 mg/kg bw/day = 500

Default Assessment Factor (AF) = 100

Since MOE (500) > AF (100), the risk is acceptable.

c) The default assessment factor (100) accounts for:

  • Interspecies differences (animal to human, ×10):
    including toxicokinetics (×4.0) and toxicodynamics (×2.5).
  • Inter-individual differences (between humans, ×10):
    including toxicokinetics (×3.2) and toxicodynamics (×3.2).

d) Direct method:
Biological monitoring—measuring levels of X in human blood or urine to assess actual body burden.

Indirect method:
Questionnaire/interview—collecting information about people’s food consumption habits and potential sources of X exposure through surveys or diaries.

Answered by ChatGPT with slides provided.

  1. Chemical mixture “M” consists of 4 known components listed below with their respective TDIs and exposure levels. As you notice, the exposure to each individual component is below their respective TDI.
    a) Calculate the Hazard Index of mixture M. Show your calculation. (2p)
    b) Is the health risk acceptable or not acceptable? Motivate your answer. (2p)
    c) This is a common default model for mixture risk assessment, what is it called? (1p)

    Component TDI (µg/kg bw) Exposure level (µg/kg bw)
    1 10 2
    2 2 1
    3 20 4
    4 100 40

    a) HI= Exp 1/TDI 1 + Exp 2/TDI 2 + Exp 3/TDI 3 + Exp 4/TDI 4 = 2/10 + 1/2 + 4/20 + 40/100 = 1.3
    b) Since HI = 1.3 > 1,
    the health risk is NOT acceptable.
    Motivation:
    Although exposure to each individual component is below its TDI, the combined exposures exceed the acceptable limit for the mixture, indicating a potential health risk.

    c) Dose Addition

Answered by ChatGPT with slides provided.

  1. You are working as an expert on a panel that has been asked to conduct a risk assessment of Substance Y, a plastic chemical used in many applications, such as building materials and toys. Toddlers are the most highly exposed population group with an estimated average exposure of 5 µg/kg bw/day and a highest worst-case exposure of 10 µg/kg bw/day. In adult males and females, the average exposure is 1 µg/kg bw/day and highest worst-case exposure is 5 µg/kg bw/day. The main exposure route is orally. Y is not very volatile and is not absorbed through the skin to a large extent. The panel is considering the following toxicity data:
    ― Several studies in rats and mice conducted according to OECD test guidelines have reported effects of Y in fetuses, such as high frequency of malformations, primarily of the brain, skeleton and eyes after oral exposure to pregnant females. The NOAEL from these studies is 10 µg/kg bw/day.
    ― Two reproductive toxicity studies conducted according to OECD test guidelines exist but did not report any effects on fertility or development. However, there are several research studies (not conducted according to test guidelines) that report reduced anogenital distance (AGD) and reduced fertility in male offspring. A NOAEL cannot be established from these studies and the LOAEL for these effects is 10 µg/kg bw/day.
    ― A recent developmental neurotoxicity study in rats is available that was very well conducted, although not strictly according to OECD test guidelines. In this study, oral exposure of dams to Y during pregnancy and lactation until weaning caused hyperactivity in their offspring with a NOAEL 5 µg/kg body weight and day.
    a) What would you select as the critical effect and point of departure (PoD) for the risk assessment? Motivate your answer. (3p)
    b) Calculate relevant margin(s) of exposure (MOE), motivate your choice of exposure level(s) for the calculations. (2p)
    c) Is the MOE sufficient? Motivate your answer. (2p)

    a) Critical effect: Developmental neurotoxicity (hyperactivity in offspring).

    PoD: NOAEL = 5 µg/kg bw/day (from the most sensitive, well-conducted study).

    Motivation:

    • It represents the most sensitive adverse outcome (developmental neurotoxicity).
    • The study is recent and of high quality, even though not strictly OECD compliant.

    b) Calculate MOE (using worst-case exposure): MOE = PoD / Exposure = 5 / 10 = 0.5
    I use the worst-case exposure (10 µg/kg bw/day for toddlers) to be conservative and to protect sensitive groups.

    c) No, the MOE is not sufficient. The required MOE is at least 100 to account for differences between animals and humans and variability among humans. Here, the MOE is only 0.5, which is much lower than 100, so the risk is not acceptable.

Answered by ChatGPT

  1. Risk assessment requires expert judgement. This means that some risk assessment judgements are influenced by the risk assessor’s expertise, experience and other potential interests. Give two examples of choices or decisions made in a risk assessment that may be influenced by expert judgment. (2p)

    1. Selecting the critical effect and point of departure (PoD):
      Experts decide which study or health effect is most relevant for setting health-based guidance values.

    2. Determining appropriate assessment factors:
      Experts choose how large assessment factors should be to account for uncertainties or data gaps in the risk assessment.

Answered by ChatGPT

  1. Risk assessors and risk managers (for example authorities) often have to communicate health risks from chemicals.
    a) Give two examples of factors (such as a specific behaviour or approach) that promote good and efficient risk communication. (2p)
    b) Why is it critical to be truthful, open and show good will when communicating risk to the public? (1p)

    a)

    1. Clear and simple language: Avoiding technical jargon helps the public understand the information.
    2. Two-way communication: Listening to concerns and feedback from the audience builds trust and addresses misunderstandings.

    b)
    Because it builds public trust, encourages cooperation, and ensures credibility—people are more likely to follow advice if they believe the information is honest and transparent.