8. Risk Assessment Flashcards
What is risk?
Risk is the probability of an adverse outcome under specified conditions.
What is risk assessment?
Risk assessment is the systematic scientific characterization of potential adverse effects of exposure on the environment or human health.
What is risk management?
Risk management is the process by which policy actions are chosen to control hazards.
how is risk defined as an equation?
Risk = Exposure + Hazard
Something may be hazardous but if you’re not exposed to it in significant amounts then it is not a risk.
Describe the relationship between NOAEL and level of exposure.
The NOAEL is the greatest concentration or amount of a substance at which no detectable adverse effects occur in an exposed population. So if you’re exposed to a toxicant, and your exposure does not surpass the NOAEL, then you are safe. If you are exposed to a toxicant where your exposure is so high that the exposure dose surpasses the NOAEL, then you have a risk.
What is the chemicals management plan (CMP)?
It was a plan created by the government of Canada. The CMP builds on previous initiatives to protect human health and the environment by assessing chemicals used in Canada and by taking action on chemicals found to be harmful. The assessment of chemicals is done under the jurisdiction of the CMP.
What is the Canadian Environmental Protection Act (CEPA)?
The Canadian Environmental Protection Act, 1999 (CEPA) is the cornerstone of Canada’s regulatory system for controlling exposure to toxic substances. CEPA requires that all substances used in Canada be assessed for environmental and human health impacts.
What is significant about how the CEPA deals with controlling toxic substances?
A substance is toxic if it is entering or may enter the environment in a quantity or concentration or under conditions that:
(a) have or may have an immediate or longterm harmful effect on the environment or its biological diversity;
(b) constitute or may constitute a danger to the environment on which life depends; or
(c) constitute or may constitute a danger in Canada to human life or health.
They include “may have” because if there is some evidence but there is doubt or theres correlation but not causation, it can still fall under this act.
What are the principal components of risk assessment?
- Exposure assessment: who is exposed, at what dose, through which route, how often, or for how long? Can be predicted, measured directly (ex: blood), or measured indirectly (ex: environment).
- Hazard assessment: what type of adverse health effects may occur after exposure to a chemical?
- Dose response assessment: What are the health effects at different exposures?
- Risk characterization: a numerical assessment of risk, identification of key uncertainties.
What do you do with exposure data and hazard assessment (toxicity data)?
Once we have the hazard assessment and exposure data we want to see where we lie in terms of the concentrations that we are consuming.
How is a dose response assessment used?
It is used to determine what a safe level of exposure is.
Combine the information from hazard characterization and exposure assessment to form a conclusion about the nature and magnitude of risk, and, if indicated, implement additional risk management measures.
What is a NOAEL, LOAEL, BMD10, LD50, reference dose, an acceptable daily intake, and a point of departure? Where do we get these values from?
- NOAEL: No observed adverse effect level
- LOAEL: Lowest observed adverse effect level
- BMD10: Benchmark dose 10% response
- Reference dose (RfD) – estimate of a dose without an appreciable adverse effect (calculated dose we think is safe)
- Acceptable daily intake (ADI) (same as RfD but for food)
- Point of Departure (POD) – often the NOAEL,
LOAEL or BMD (what you used to calculate your RfD)
All of these values are measure on the dose response curve or from the values obtained from the dose-response curve.
What is a margin of exposure (MOE)? How is it calculated?
- A MOE is calculated to figure out if a certain toxicant needs to be regulated.
- Common practice is to characterize the ‘distance’ between expected exposures and the level of exposures associated with harm, assuming there is a threshold (if there’s no threshold there’s no safe level).
- MOE = Hazard critical effect level (point of departure) / estimate of exposure
- > the “hazard critical effect level” is whatever is most sensitive to the exposure and the “estimate of exposure” is how much exposure there is.
What does a high or low MOE mean?
– High MOE is good (there is a big gap which means no one is exposed to the amount that causes harm).
– Low MOE is potentially of concern (because some of the population would potentially be exposed)
– Less than 1 means some are exposed above a level associated with potential for harm
What does it mean if a dose response curve has a threshold or no threshold?
If there is a threshold then it means that there is a safe level of exposure. If there is no threshold then there is no safe level of exposure because it is toxic as soon as there is a concentration of substance.
When following the CEPA, what are the 6 categories that we need to consider in a risk assessment in order to determine risk?
- Exposure
- Health effects
- Receptor (mechanism of action in body or environment)
- Persistance
- Bioaccumulation
- Toxicity
What is the CMP categorization process? What is it used for?
When the CMP first started, groups and people nominated chemicals they thought were a concern. Out of that list, they prioritized chemicals to make a domestic substances list (DSL). The list was very big and they had to prioritize. The risks could be for health or for environment.
- For the health list, they prioritized the chemicals with the greatest potential for human exposure.
- For environmental chemicals, they have to be persistant OR bioaccumulative. Then, for further analysis by health canada they had to be persistant OR bioaccumulative AND inherently toxic to humans. For further analysis by environment canada they had to be persistant OR bioaccumulative AND inherently toxic to non-human organisms.
What is the “weighing of evidence” according to the CEPA?
It’s when you put your evidence together so you can decide what you’re confident in.
You can have really reliable studies that have weak signals (more reliable). You can also have low quality studies that have strong signals (makes you doubt the evidence but the studies that are available show a strong effect).
You have to combine the data from all the studies that were done (in vitro studies, animal studies, human studies, mechanistic studies). You then have to look at the relevance lens and the specific context of the current question in order to weigh the evidence.
What makes evidence be considered good or bad quality?
Whether or not the data is consistent across species or target organs.
What is the qualitative assessment of hazard information?
- You assess the consistency of the data you have: Whether or not the data is consistent across species or target organs.
- You weigh your evidence: You have to combine the data from all the studies that were done (in vitro studies, animal studies, human studies, mechanistic studies). You have to look at the quality and quantity of the data, the relevance of the data, and the specific context of the current question in order to weigh the evidence.
- You also have to look at the mode of action information which gives you key events and processes that the chemical effects. It can also allow for the development of adverse outcome pathways (AOPs). This is important because if you know the mechanism, you can look for other chemicals that do the same thing and see if they’re also toxic. It helps make biological sense and helps group things.
What is an adverse outcome pathway?
According to the OECD: AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on mechanistic reasoning.
**a different definition from google:
An adverse outcome pathway (AOP) is a model that identifies the sequence of molecular and cellular events required to produce a toxic effect when an organism is exposed to a substance.
The OECD is pushing for AOP’s to be made but they are very expensive and hard to make.
What is uncertainty?
Uncertainty is a lack of precise knowledge as to what the truth is.
- can be reduced through additional investigation
- uncertainty factors are used to account for experimental inadequacies e.g. intraspecies or interspecies differences, short versus chronic exposures, inadequate numbers of animals.
What are different examples of things in a study that can cause uncertainty?
– Human relevance of a tumour in an animal study
– Casual interpretation from conflicting evidence (one study says yes and another one says no)
– Shape of Dose-Response at Low Doses (If you don’t have a lot of dose groups)
– Representativeness of Historical data (Maybe the rat strain you’re using has changed over the years…check historical data to see if what you observed has happened in other rats of this strain. Maybe you don’t have access to all the historical data.)
– Extent of extremes in exposure due to human behaviour
– Number of tons of product in commerce (depending on the requirements of different countries, people might have to declare the volume of the product they make and sometimes they don’t. If it’s a high production product they will most likely have to declare how much they’re making to the government but we don’t necessarily know how much is in commerce.)
What are different examples of variability in a study (NOT TO BE CONFUSED WITH UNCERTAINTY)?
– Bodyweights – Consumption Rates of Food and Water – Ventilation Rates of Homes – Frequency of exercise – Immune status – Genetic variability – Physical location – Windspeeds, wind directions – Cooking methods
