8. Risk Assessment

Question 1

What is risk?

Answer 1

Risk is the probability of an adverse outcome under specified conditions.

Question 2

What is risk assessment?

Answer 2

Risk assessment is the systematic scientific characterization of potential adverse effects of exposure on the environment or human health.

Question 3

What is risk management?

Answer 3

Risk management is the process by which policy actions are chosen to control hazards.

Question 4

how is risk defined as an equation?

Answer 4

Risk = Exposure + Hazard

Something may be hazardous but if you’re not exposed to it in significant amounts then it is not a risk.

Question 5

Describe the relationship between NOAEL and level of exposure.

Answer 5

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.

Question 6

What is the chemicals management plan (CMP)?

Answer 6

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.

Question 7

What is the Canadian Environmental Protection Act (CEPA)?

Answer 7

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.

Question 8

What is significant about how the CEPA deals with controlling toxic substances?

Answer 8

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.

Question 9

What are the principal components of risk assessment?

Answer 9

1. 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).
2. Hazard assessment: what type of adverse health effects may occur after exposure to a chemical?
3. Dose response assessment: What are the health effects at different exposures?
4. Risk characterization: a numerical assessment of risk, identification of key uncertainties.

Question 10

What do you do with exposure data and hazard assessment (toxicity data)?

Answer 10

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.

Question 11

How is a dose response assessment used?

Answer 11

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.

Question 12

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?

Answer 12

1. NOAEL: No observed adverse effect level
2. LOAEL: Lowest observed adverse effect level
3. BMD10: Benchmark dose 10% response
4. Reference dose (RfD) – estimate of a dose without an appreciable adverse effect (calculated dose we think is safe)
5. Acceptable daily intake (ADI) (same as RfD but for food)
6. 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.

Question 13

What is a margin of exposure (MOE)? How is it calculated?

Answer 13

• 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.

Question 14

What does a high or low MOE mean?

Answer 14

– 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

Question 15

What does it mean if a dose response curve has a threshold or no threshold?

Answer 15

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.

Question 16

When following the CEPA, what are the 6 categories that we need to consider in a risk assessment in order to determine risk?

Answer 16

1. Exposure
2. Health effects
3. Receptor (mechanism of action in body or environment)
4. Persistance
5. Bioaccumulation
6. Toxicity

Question 17

What is the CMP categorization process? What is it used for?

Answer 17

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.

Question 18

What is the “weighing of evidence” according to the CEPA?

Answer 18

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.

Question 19

What makes evidence be considered good or bad quality?

Answer 19

Whether or not the data is consistent across species or target organs.

Question 20

What is the qualitative assessment of hazard information?

Answer 20

1. You assess the consistency of the data you have: Whether or not the data is consistent across species or target organs.
2. 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.
3. 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.

Question 21

What is an adverse outcome pathway?

Answer 21

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.

Question 22

What is uncertainty?

Answer 22

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.

Question 23

What are different examples of things in a study that can cause uncertainty?

Answer 23

– 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.)

Question 24

What are different examples of variability in a study (NOT TO BE CONFUSED WITH UNCERTAINTY)?

Answer 24

– 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

Question 25

How do you calculate the RfD or the ADI? What are some uncertainty factors?

Answer 25

ADI = NOAEL (experimental dose) / safety factors
RfD = NOAEL or LOAEL / Uncertainty factors

uncertainty factors:

• human variability
• Extrapolation from animals to humans
• Use of less than chronic data (study was short term, 14-28 days)
• Use of LOAEL instead of NOAEL
• Modifying factor (anything else… ex: only toxic in women? people metabolize differently?? etc.)

Question 26

What is the precautionary principle of the CEPA?

Answer 26

Precaution: where you THINK there’s a danger and you don’t have scientific certainty, you can still act. You can use the precautionary principle to regulate a substance even if you’re not 100% sure but you’re worried there is a danger. Based on assumptions.

Question 27

What is BPA and what is it used for? Is it manufactured in Canada?

Answer 27

• Bisphenol A (BPA) is used to make polycarbonate plastic (recycle symbol 7 PC*) and epoxy resin linings of food and beverage cans.
  BPA has wide application in consumer products:
  – Re-useable containers, medical devices (ex: IV tubing), dental sealants, sports helmets, protective coatings (common in tin cans), adhesives
  – It is a high volume product with a global production at 3 billion kg/y (2003)
• It’s not manufactured in canada but it is imported.

Question 28

What are the BPA exposure assessment findings?

Answer 28

1. Exposure assessment:
   possible sources of exposure were identified: dietary intake, environmental media, other (dental materials, consumer products).

Question 29

What early research needs were identified for BPA’s?

Answer 29

2. Early research needs were identified (what they were missing information about):
   – Health Canada’s study of baby bottles and bottle liners
   – Health Canada’s study of BPA in house dust

They can then do studies to fill these needs.

Question 30

What was the exposure estimate summary for BPA’s?

Answer 30

3. Exposure estimate summary:
   they separated out infants (0-18 months) and general population and looked for the maximum exposure range of BPA’s per day for the groups. For infants they considered exposures from baby bottles, infant formula, and environmental media. For the general pop. they considered exposures from canned food, polycarbonate bottles, and environmental media.

Question 31

In the health effects assessment on BPA’s, what toxicological endpoints were assessed? What did the data suggest?

Answer 31

endpoints that were assessed:

1. Carcinogenicity and genotoxicity
2. Reproductive and developmental toxicity
3. Developmental neurotoxicity

The data suggested:
Rodent data suggest effects on neurobehavioural development at levels below the established NOAELs for systemic and reproductive and developmental toxicity. So basically the reproductive and developmental toxicity had a higher NOAEL than developmental neurotoxicity, meaning that developmental neurotoxicity is the critical endpoint (affected at lowest dose).

Question 32

What was selected as the critical endpoint in the health effects assessment on BPA’s? What were the effects on the critical endpoint? What doses was it affected at?

Answer 32

What was selected & effect:
•Developmental Neurotoxicity: several rodent studies suggestive of alterations in receptor function, behaviour and brain function

What doses:
•Though limited, key findings in the dataset are suggestive of effects at low doses ranging from 10 to 100 μg/kg-bw per day.
bw = bodyweight
•Some concern supported by conclusions on developmental neurotoxicity identified by expert panel assessments.

Question 33

Which dataset was the margin of exposure for BPA’s calculated for and why?

Answer 33

It was calculated based on the neurotoxicity dataset because it was the risk that was closest to the amount of exposure that we have. (it was also the critical endpoint)

Question 34

What did the risk assessment on BPA’s conclude?

Answer 34

Based on the information available ….it is proposed that bisphenol A be considered as a substance that may be entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health. It is therefore proposed that bisphenol A does meet the criteria in paragraphs 64(a) and 64(c) of CEPA 1999.

(It met the criteria that have to be satisfied under the CEPA in order to suggest that regulations may be required).

Question 35

What happens once a risk is identified?

Answer 35

You have to manage the risk.

Question 36

What was the risk management goal for BPA’s once the risk was identified?

Answer 36

The Risk Management goal (2010) was to minimize exposure to infants from polycarbonate baby bottles and canned infant formula. Recent data indicate a 96% decrease in the exposure of bottle-fed infants to BPA. The remaining low exposure is mainly due to house dust.
This shows that they decided that the critical population was babies and they therefore regulated the products used for babies.

Furthermore, Public awareness has also allowed for a decrease in BPA in dust and stuff because companies will cater towards what people want. Ex: buying things that say BPA free!

Question 37

What was done after the publication of the final BPA assessment and risk management?

Answer 37

New bisphenols were flagged and there was more information gathering done on certain bisphenols. They found many more and they wanted to see if it was possible to group these chemicals into categories or not so they could assess the chemicals without having data for them. They wanted to use interpolation, extrapolation, or read-across in order to assess the bisphenols in the group.

Question 38

What was done about BPA analogues in Canada?

Answer 38

They wanted to know what the effects of BPA substitutes or alternatives are on humans now that BPAs are being used less. So they’re continuing to look at it.

Question 39

What are SDG’s? What organization are they a part of?

Answer 39

SDG’s are sustainable development goals that are identified by the united nations. There are different SDG’s for example:

• climate action
• no poverty
• gender equality
• good health and well being
  etc. .

Question 40

What are the SDG’s related to health and the environment?

Answer 40

1. safe occupational environment
2. Safe indoor and outdoor environment
3. Safe consumer products
4. Safe food and drinking water
5. Lower risks of chemical emergencies
6. Reduced generation of hazardous waste

Question 41

What are the SDG’s related to hazardous chemicals?

Answer 41

• *idk how detailed we need to know this…it was on a picture on the slide
  1. good health and well-being: reduce the number of deaths and illnesses due to hazardous chemicals and air, water, and soil pollution and contamination
  2. Clean water and sanitation: improve water quality by reducing pollution, eliminating, dumping, and minimizing release of hazardous chemicals and materials.
  3. Responsible production and consumption: achieve the environmentally sound management of chemicals and all wastes throughout their life cycle and significantly reduce their release to air, water, and soil to reduce their adverse impacts on human health and the environment.

Question 42

Do all countries have legislation for chemical safety?

Answer 42

No… Canada, europe, USA does… other countries have it in development or don’t have any at all.

Question 43

What is the OECD trying to do to get a concerted approach to chemicals and hazardous waste around the world?

Answer 43

They’re trying to design studies that will satisfy various agencies around the world so that different countries will believe the data and think that it is true (so we can share credible data with each other). It is called the cooperative chemicals assessment program where they are writing the guidelines together with other agencies.
Includes: Europe, Japan, Canada, and US.