Framework for Risk Assessment Flashcards
Risk Assessment Framework
5
- Problem Formulation
- Hazard Identification
- Dose-Response Assessment
- Exposure Assessment
- Risk Characterization
PHEDR
What is the main goal of problem formulation?
to figure out the technical and analytical approach
Subgoals of problem formulation
Goals:
1. Identify issues to be assessed
1. Identify goals, breadth, depth, and focus of risk assessment (like scope & limitations)
1. Establishes who the decision maker, stakeholders, risk assessor are
what, so what, who
Differentiate
Problem Formulation - Outputs
2
Conceptual model
* Taken from literature
* environmental stressors, pathways, sources, populations at risk, potential adverse effects
Analysis plan
* how to locate pollution data
* What chemicals of concern
* How to assess & measure doses, exposures
* what risk metrics to use
* Other technical requirements
Importance of Problem Formulation 3
- Ensure commitment of stakeholders & decision makers
-
Better chance of finding acceptable policy solution
* Stakeholders & DMs should be in process from very beginning — some sort of ownership on the decision - Save time and resources
Explain the main challenge of Problem Formulation
- Need to balance extensive dialogue & practical efficiency
- Can take away time
Hazard Identification - Goal
to understand the extent of harm caused by a specific hazard
Hazard Identification - 4 subgoals
- determine adverse effects related to exposure
- do an RRL - choose from data & evaluate supporting scientific evidence (maganda ba)
- produce a list of potential toxic effects - so people know wtf is going on
- establish causation - describe nature & strength
List
Hazard Identification - Sources of Evidence
4
- Epidemiology
- Toxicology
- In-vitro studies
- In-silico studies
Describe
Epidemiology as a Source of Evidence for Hazard Identification
- observational human studies
- Mostly observational, about correlations
* No controlling of variables/experimenting
Toxicology as a Source of Evidence for Hazard Identification
experimental animal evidence
* More definitive causation
* Arguments surrounding testing on animals
* Concerned w/ symptoms & doses
* we shifted towards this bc it’s unethical to do it on humans
In-vitro studies as a Source of Evidence for Hazard Identification
in-vitro studies – cell-based studies
* Eg. Ivermectin – tested on a petri dish
* Principle of emergent property: cell acting different outside of its system
* Works well for dermal absorption properties – Estee Lauder is leaning more towards in-vitro testing now
Define
Principle of emergent property
cell acting different outside of its system
it gains the property when it works with other components in a system, however the property does not manifest when the cell is by itself.
In silico stu stud as a Source of Evidence for Hazard Identification
computer modelling
* How a variant can mutate
* How substances will be stored, excreted etc. in & from body
Note Garbage in, garbage out – data should be quality to get quality conclusions
* Eg. MMDA claimed to have models that helped in their decision making, & their outputs were always crap – maam questions the data of MMDA
* Still needs data from other fields
What is assessed during Hazard Identification?
5
- Contaminants, its degradation products, and metabolites
- Determinants of toxicity
- Adverse health effects – typically broad
- Characterization based on effects, target organs, and mode of action
- Weight of evidence analysis
wadcc
List
Determinants of hazards’ toxicity
6
- Level, frequency, and duration of dose/exposure
- Demographic of exposed populations
- Routes of exposure
- Absorption and metabolism of contaminants
- Physical form of contaminant
- Presence of other contaminants (synergistic or additive effects)
Describe
Adverse health effects
- usually broad
Includes
1. Overt diseases (cancer, birth defects)
1. More subtle biological effects (alterations in gene expression)
1. Upstream effects - effects that can play an early role leading to disease
Define
Upstream effect
effects that can play an early role in leading to disease
Biological endpoint
- A direct marker of disease progression;
- Describes health effects (or probability of health effects) from exposure to a hazard
Define
mode of action
how substance affects the target cell or organs
Define
Weight of evidence analysis
judgment on whether the body of evidence available supports the conclusion that a substance is a hazard to humans
- Assess which ones to follow/not follow
- Look at methodology & method of analysis
- Ex. cigarettes: tobacco is organic, formaldehyde is preservative, tar is carcinogen, nicotine is stimulant
Importance of Hazard Identification
- High quality scientific studies = best evidence
- Human data is the gold standard
- Use of Epidemiological studies
- Use of Toxicological studies
Issue w/ High quality scientific studies
best evidence, BUT
1. Not always available
2. Design and methodological limitations
Issue w/ Human data
1. Use of Epidemiological studies
1. Use of Toxicological studies
Studies examine occupational populations not representative of general population
aka, Done on healthier humans
Issue w/ Use of Epidemiological studies
- Limited by uncertainties on amount and duration of exposure;
- Presence of potential confounders
Issue w/ Use of Toxicological studies
Challenge of determining relevance to humans
List
Dose-Response Assessment Goals
2
- Characterize relationship between dose & adverse effect
- To estimate toxicity values, the dose makes the poison
*
Define adverse effects
likelihood/severity
How do we characterize dose & adverse effect?
Mathematical models: Dose-Response Relationship
For each adverse effect
To pinpoint with effect will come out first
Explain
The dose makes the poison, and provide examples
Impt to estimate toxicity values bc everything can be poison given the right amount
Ex
* rashes from sun poisoning
* too much oxygen → go blind
* too much water → ??? i forgot
Differentiate
Carcinogen vs noncarcinogen
Carcinogens
* Mode are assumed to have no threshold
* aka all levels have some risk
* Ex. asbestos, PAHs
Noncarcinogens
* act in relation to a threshold
* low levels may occur without adverse effects
* Some concentrations will be okay, /then/ adverse effects happen
* Ex. pollen, dust, asthma
Both
* after biological threshold, ↑ exposure = ↑ severity of adverse effect
How do we estimate toxicity values?
At what dose makes adverse effects start
T/F
We are 100% sure that noncarcinogens are noncarcinogens
F
* we are never really sure until someone gets cancer!
Which thresholds exist for carcinogens? How are they used?
- Model is fit to available data → derive slope of dose response curve
- Cancer slope factor (CSF) or unit cancer risk (UCR) is derived from slope
- With exposure data, CSF is used to characterize risk
Which thresholds exist for noncarcinogens? How are they used?
- NOAEL: no observed adverse effect level or
- LOAEL: lowest observed adverse effect
NOAEL & LOAEL are used as a point of departure (POD) for extrapolation for reference dose (RfD)
* Used with exposure data to characterize risk
Define
RfD
reference dose
* dose without risk if chemical exposure occurs over a human lifetime
What is the value for Uncertainty Factors Values
Value of 10 for interspecies & intraspecies extrapolation
Differentiate
Interspecies vs Intraspecies extrapolation
Interspecies
* NOAEL from animal studies
* We favor some animals over others bc of extrapolation factor
* Farther it is = more extrapolation
Intraspecies extrapolation
* accounts for natural variability in response in human populations
What is an additonal factor for sensitive/vulnerable populations
RfD = (NOAEL / uncertainty factors)
RfD: reference dose
What are the issues with thresholds for carcinogens & noncarcinogens?
Scientific evidence suggests contrary shit:
* Noncarcinogens do not always have a threshold
* Carcinogens may have a threshold
“Carcinogenicity” determined to vary widely
What is a possible solution for issues regarding thresholds for carcinogens & noncarcinogens?
Use benchmark dose (BMD) to replace NOAEL/LOAEL
* BMD: estimate of dose at which a specific increase in adverse effect (aka BMR) is apparent
* BMR: benchmark response
List
Important threshold variables (carcinogens & noncarcinogens)
2 carci+ 4 non + bonus 2
CSF - cancer slope factor
UCR - unit cancer risk
NOAEL - no observed adverse effect level
LOAEL - lowest observed adverse effect level
POD - point of departure
RfD - reference dose
New:
BMD - benchmark dose
BMR - benchmark response
Define
Exposure assessment
to identify actual or likely exposure/dose in a given population
List
Goals for Exposure Assessment
3
(1) Calculate and estimate potential exposures
(2) Determine concentration of substance of interest
(3) Describes substance and exposed population
How does Exposure Assessment calculate and estimate potential exposures?
- identifies heaviest/most likely exposure pathway
- Informs you for management strategies
Which aspects of the substance are described whe doing an Exposure Assessment?
- magnitude
- duration
- timing
- route of exposure
Which aspects of the **exposed population **are described whe doing an Exposure Assessment?
- size
- nature
- categories
Differentiate
Exposure vs Dose
Exposure: chemical contact on outer boundary of the person
Dose: amount of chemical taken in the body
Note:
* Sometimes dose < exposure
* Not likely na dose = exposure
List
Categories for Identifying Information
4
- Characterizing exposure setting
- Identify exposure pathways
- Quantify exposure (magnitude, frequency, duration)
- Quantify potential human intake
T/F
Our main exposure pathways are the dermal, mucosal pathways, as well as our private parts
Private parts not really
How do we quantify exposure?
3
- magnitude
- frequency
- duration
Unit for quantifying potential human intake
unit body weight per unit time
mg/kg-BW/day
- mg/kg - unit
- BW - body weight
- /day - Per unit time
Differentiate
2 types of exposure
Acute: bursts
* relatively short period of time
Chronic: Tends to be continuous
* long periods of time, pwede pang lifetime
List
Exposure Characterization Methods (Exposure Assessment)
6
- Direct/Indirect measurements
- Surveys
- Biomonitoring
- Modeling
- Average Daily Dose (ADD)
- Lifetime Average Daily Dose (LADD)
DBSMAL
Differentiate
Direct vs Indirect measurements
Direct: directly measure
* Actual frequency, intensity, and/or duration
Indirect: use an indirect metric
* Sampling air, water, soil, or food products
* number of headaches from fumes
What kinds of surveys show Exposure Characterization Methods?
What issues arise from surveys?
- actual/hypothetical habits involving a particular exposure pathway
- Problem: people overreport or underreport – produces uncertainty
How is biomonitoring an Exposure Characterization Method?
- we take Biological samples/biomarkers (Blood, hair, urine, fecal matter, etc)
- also measure concentrations of substances or metabolites (But metabolites dont stay in the body for a long time)
How is Modelling an Exposure Characterization Method?
- Math modeling can estimate hypothetical exposure
- Ex. COVID particles travelling in a bus wow p6)
Identify & Differentiate
ADD vs LADD
Average Daily Dose (ADD)
* Estimate of average daily dose level
* acute/subchronic/chronic?
* For non-cancer endpoints
Lifetime Average Daily Dose (LADD)
* Estimate of average daily over a person’s lifetime
* Lifetime exposure for both cancer and non-cancer endpoints
We are obsessed w/ lifetime exposures lol (ex. Blue light exposure)
Explain
“Without exposure, there is no risk”
Risk will always be present, but our exposures vary.
* Variability across popu = diff exposures (individuals, geography, and time)
* Substances move across the environment
So, we use exposure defaults
Define
Exposure Defaults
Why do we use them, when exposures vary?
assumptions about common exposure patterns
* Ex. an average adult drinks 2L water per day and breathes 22 cu. meters of air per day
* We make the generalization so that it’s easier for policy
Define
Risk Characterization
To synthesize the risk for a specific population
List
Goals of Risk Characterization
3
- Make judgement on risk to population
- Characterize uncertainty
- Synthesize risk for a particular health effect from a particular substance.
Note
* Respond to original problem formulated
* Allow for separation of policy judgements from scientific findings.
List
Methods of Risk Characterization
- Population cancer risk
- Bright Line
- Hazard Index
- Margin of Exposure
Explain
population cancer risk
Population cancer risk = CSF x LADD (Cancer Slope Factor, Lifetime Average Daily Dose)
[All are acceptable] Risk of:
* 1 in 1000000
* 1 in 100000
* 1 in 10000
Siyempre u want 1 in 1M but the others are fine; depends on manager
Explain
Bright LIne
Standard intended to be clear and prevent subjective interpretation
Usually uses calculated RfD to guide risk management
< RfD is usually acceptable
Explain
Hazard Index
What values are below and above concern?
Relationship bet. actual pop exposure and an established RfD
More specific way to compute acceptable risk (compared to just < RfD)
HI < 1 - below RfD; low risk
HI > 1 - above RfD; concern
What is a risk manager’s job?
- be a technical expert
- must write v good executive summary (what politicians usually read)
Explain
Margin of Exposure
What values are below and above concern?
Compares exposure to a NOAEL or BMDL
* MOE > 100 - relatively low risk
* MOE = 1 - risk level is of concern
How does risk characterization help understand the greater risk of the most highly exposed?
- usually on a normal distribution graph
For avg population (mean or median of exposure distribution)
For individuals at highest end of exposure distribution (90th/ 95th/ 99th percentiles) - at greater risk (aka need to consider them the most)
