RISK ASSESSMENT
DR. LYNN CRISANTA R. PANGANIBAN
Professor, Department of Pharmacology & Toxicology
UP College of Medicine
Consultant, National Poison Management & Control Center
UP College of Medicine – Philippine General Hospital
Email: ldpanganiban@[Link]
OBJECTIVES
✓ to discuss the concepts and methods of health risk
assessment
✓ to know the components and key issues in conducting
the risk assessment process
RISK ASSESSMENT
RISK ASSESSMENT
✓ Systematic, scientific characterization of potential adverse health effects
resulting from human exposures to hazardous agents
✓ Qualitative/quantitative estimates of the likelihood of adverse effects from
exposures to specified health hazards
OBJECTIVES OF RISK ASSESSMENT
OBJECTIVES OF RISK ASSESSMENT
✓ Balance risks and benefits
✓ Set target levels of risk
✓ Set priorities for program activities
✓ Estimate residual risks and extent of risk reduction after steps are taken to reduce risks
COMPONENTS OF RISK ASSESSMENT
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
Source: WHO Human Health Risk Assessment Toolkit: Chemical Hazards (2010)
HAZARD IDENTIFICATION
COMPONENTS OF
RISK ASSESSMENT Process of determining whether an agent or activity
can cause an increase in the incidence of an adverse
health condition
✓ HAZARD IDENTIFICATION
Is the identity of the chemical or activity
✓ HAZARD CHARACTERIZATION known?
✓ EXPOSURE ASSESSMENT
Is the chemical or activity potentially
✓ RISK CHARACTERIZATION hazardous to humans?
HAZARD IDENTIFICATION
COMPONENTS OF
Toxic Agent?
RISK ASSESSMENT
Physicochemical characteristics?
✓ HAZARD IDENTIFICATION
Mechanism of action?
✓ HAZARD CHARACTERIZATION
Absorption, Distribution, Metabolism
✓ EXPOSURE ASSESSMENT and Excretion?
✓ RISK CHARACTERIZATION Life cycle of the product
HAZARD IDENTIFICATION
COMPONENTS OF
RISK ASSESSMENT Toxic endpoint?
✓ HAZARD IDENTIFICATION
Population at risk?
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT KEY ISSUE:
✓ RISK CHARACTERIZATION SOURCES OF DATA
HAZARD IDENTIFICATION
Roadmap for Hazard Identification
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
Source: WHO Human Health Risk Assessment Toolkit: Chemical Hazards (2010)
HAZARD CHARACTERIZATION
Process of characterizing the relationship between the
COMPONENTS OF dose of an agent administered or received and the
RISK ASSESSMENT incidence of an adverse effect in exposed populations
What properties of the chemical have the potential
✓ HAZARD IDENTIFICATION to cause adverse health effects?
✓ HAZARD CHARACTERIZATION Do guidance or guideline values from international
organizations exist for the chemical?
✓ EXPOSURE ASSESSMENT
What assumptions about exposure and dose are
incorporated into guidance/guideline values for the
✓ RISK CHARACTERIZATION chemical?
Do these assumptions reflect conditions specific to
the local population?
HAZARD CHARACTERIZATION
COMPONENTS OF
RISK ASSESSMENT
1.
✓ HAZARD IDENTIFICATION 1 Guidance values
5
✓ HAZARD CHARACTERIZATION Guideline values
✓ EXPOSURE ASSESSMENT REFERENCE DOSE
✓ RISK CHARACTERIZATION TOLERABLE DAILY INTAKE
CANCER SLOPE FACTOR /
CANCER POTENCY SLOPE
HAZARD CHARACTERIZATION
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION KEY ISSUE:
✓ Quality of experimental studies
✓ EXPOSURE ASSESSMENT
✓ Long latency of disease
✓ RISK CHARACTERIZATION ✓ Sources of data
HAZARD CHARACTERIZATION
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
Threshold Dose
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION NOEL = No observable effect level
NOAEL = No observable adverse effect level
LOEL = Lowest observable effect level
LOAEL = Lowest observable adverse effect level
BMD = Bench mark dose
BMDL = Benchmark dose lower bound
HAZARD CHARACTERIZATION
COMPONENTS OF REFERENCE DOSE
RISK ASSESSMENT Reference Dose (RfD) – an estimate of a daily exposure to
the human population that is likely to be without
✓ HAZARD IDENTIFICATION
appreciable risk of deleterious effects during a lifetime
✓ HAZARD CHARACTERIZATION
𝑵𝑶𝑨𝑬𝑳 (𝒐𝒓 𝑳𝑶𝑨𝑬𝑳 𝒐𝒓 𝑩𝑴𝑫)
𝑹𝒇𝑫 =
✓ EXPOSURE ASSESSMENT 𝑼𝑭 𝒙 𝑴𝑭
where:
✓ RISK CHARACTERIZATION NOAEL – No observable adverse effect level
LOAEL – Lowest observable adverse effect level
BMD - Benchmark dose
UF – Uncertainty factor
MF – Modifying factor
HAZARD CHARACTERIZATION
UNCERTAINTY FACTORS AND MODIFYING FACTORS
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
HAZARD CHARACTERIZATION
CANCER POTENCY SLOPE (CPS)
COMPONENTS OF
RISK ASSESSMENT
Cancer
Y2
20/100
✓ HAZARD IDENTIFICATION population
✓ HAZARD CHARACTERIZATION Y1
X1 X2
𝑦 6 mg/kg/day
✓ EXPOSURE ASSESSMENT 𝐶𝑃𝑆 = Dosage
𝑋
✓ RISK CHARACTERIZATION 20/100
𝐶𝑃𝑆 =
6𝑚𝑔/𝑘𝑔
𝐶𝑃𝑆 = 3 per 100/mg/kg/day
HAZARD CHARACTERIZATION
Roadmap for Hazard Characterization
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
Source: WHO Human Health Risk Assessment Toolkit: Chemical Hazards (2010)
EXPOSURE ASSESSMENT
Process of measuring or estimating the
COMPONENTS OF intensity, frequency and duration of the human
RISK ASSESSMENT exposure to a toxic agent; also describes the
nature and size of exposed population and the
✓ HAZARD IDENTIFICATION route, timing of exposure relative to life span
✓ HAZARD CHARACTERIZATION How are humans or non target organisms
exposed to the hazard, and what is the
✓ EXPOSURE ASSESSMENT magnitude and duration of their exposure?
✓ RISK CHARACTERIZATION In what ways could people come into contact
with the chemical?
EXPOSURE ASSESSMENT
COMPONENTS OF
RISK ASSESSMENT EXPOSURE PATHWAY
✓ HAZARD IDENTIFICATION EXPOSURE ROUTE
✓ HAZARD CHARACTERIZATION
RANGE OF EXPOSURE
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION QUANTIFYING EXPOSURE
EXPOSURE ASSESSMENT
COMPONENTS OF EXPOSURE PATHWAY
RISK ASSESSMENT
Site Conceptual Model of Exposure Pathway
✓ HAZARD IDENTIFICATION Environmental fate and transport
✓ HAZARD CHARACTERIZATION Exposure route
Source of the toxic agent
✓ EXPOSURE ASSESSMENT Exposure site
Potential exposed population
✓ RISK CHARACTERIZATION
Source: ATSDR-Public Health Assessment Guidance Manual, 2005
update: [Link]
EXPOSURE ASSESSMENT
COMPONENTS OF EXPOSURE ROUTE
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
Route of exposure can be an important consideration in
the potential for adverse effects of exposure to an agent
Damalas CA (2016)
EXPOSURE ASSESSMENT
COMPONENTS OF RANGE OF EXPOSURE
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
EXPOSURE ASSESSMENT
COMPONENTS OF QUANTIFYING EXPOSURE
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
Point of Contact Measurement
✓ HAZARD CHARACTERIZATION
Scenario Evaluation
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION Reconstruction
EXPOSURE ASSESSMENT
Point of Contact Measurement
COMPONENTS OF
RISK ASSESSMENT ✓ Measuring the amount of a chemical at the point of
contact with people or the environment
✓ HAZARD IDENTIFICATION ➢ Usually reported as a concentration
✓ Whether measured or modeled, in the field or in a
✓ HAZARD CHARACTERIZATION controlled setting, exposure concentrations always
represent a certain time and location
✓ EXPOSURE ASSESSMENT ✓ Important to understand the spatial and temporal
dimensions of an exposure concentration in
comparison to the corresponding dimensions of the
✓ RISK CHARACTERIZATION assessment question
• Instantaneous or very short term
• Integrated over time
• Time series
• Discrete
From material developed by Dr. David Macintosh for the APEC Introductory level training on risk assessment and risk management (2012)
EXPOSURE ASSESSMENT
Scenario Evaluation
COMPONENTS OF
RISK ASSESSMENT ✓ Exposure requires that a hazardous agent and a person
are present in the same location at the same time
✓ HAZARD IDENTIFICATION ✓ Scenario evaluation refers to combining separate
analyses of concentrations and time-location patterns
✓ HAZARD CHARACTERIZATION ✓ Concentrations and time-location patterns can be
determined from measurements or models
✓ EXPOSURE ASSESSMENT ✓ Exposure can be quantified in several different forms
➢ Time-weighted average concentration
✓ RISK CHARACTERIZATION ➢ Cumulative concentration (concentration x time)
➢ Intake rate
✓ These terms are often synonyms for exposure: exposure
concentration, exposure dose, potential dose,
administered dose
From material developed by Dr. David Macintosh for the APEC Introductory level training on risk assessment and risk management (2012)
EXPOSURE ASSESSMENT
Scenario Evaluation
COMPONENTS OF (Intake Rate/Exposure Rate)
RISK ASSESSMENT
✓ Average daily dose (ADD) is a common dose metric.
✓ HAZARD IDENTIFICATION
Average Daily Dose =
concentration x contact rate/factor x exposure duration/frequency
✓ HAZARD CHARACTERIZATION body weight x averaging time
✓ EXPOSURE ASSESSMENT Concentration = amount of chemical/mass or volume of the media
Contact = mass or volume of the media in contact with the body
✓ RISK CHARACTERIZATION rate/factor
Exposure = period of time over which the person is in contact with
duration the chemical
Averaging time = period of time over which the exposure is relevant for
health risk characterization
EXPOSURE ASSESSMENT
Scenario Evaluation
COMPONENTS OF (Intake Rate/Exposure Rate)
RISK ASSESSMENT
✓ Average daily dose (ADD) is a common dose metric.
✓ HAZARD IDENTIFICATION
Average Daily Dose =
concentration x contact rate/factor x exposure duration/frequency
✓ HAZARD CHARACTERIZATION body weight x averaging time
✓ EXPOSURE ASSESSMENT ✓ For non-carcinogenic endpoints: Period
Average Daily Dose
(Averaging time is exposure duration)
✓ RISK CHARACTERIZATION
✓ For carcinogenic endpoints: Lifetime
Average Daily Dose
(Averaging time is length of a typical lifetime)
EXPOSURE ASSESSMENT
Reconstruction
COMPONENTS OF
RISK ASSESSMENT ✓ Estimate exposure from body burden and dose
after the exposure has taken place
✓ HAZARD IDENTIFICATION
➢ External Dose: Concentrations in environmental
media (air, water, soil, produce)
✓ HAZARD CHARACTERIZATION
➢ Internal Dose: Concentrations in biologic fluids
(biomarkers of exposures)
✓ EXPOSURE ASSESSMENT
• Recent exposures: Blood, urine, exhaled breath,
saliva
✓ RISK CHARACTERIZATION
• Past exposures: Blood, urine, hair, nails, adipose
tissues, breast milk
EXPOSURE ASSESSMENT
COMPONENTS OF 1. Source of pollutant: water, soil, marine products, air
RISK ASSESSMENT 2. Concentration of chemical at the source
3. Duration of human exposure
✓ HAZARD IDENTIFICATION
4. Frequency of human exposure
✓ HAZARD CHARACTERIZATION 5. Route of human exposure
6. Dosage of human exposure
✓ EXPOSURE ASSESSMENT Exposure is expressed in
7. Population involved unit / kg body weight
/ day
✓ RISK CHARACTERIZATION
KEY ISSUE: Availability and capability of laboratories
to measure environmental and biological samples
EXPOSURE ASSESSMENT Harmonization Project Document No. 8
Roadmap for Exposure Assessment
indoor air, lake water, river water and outdoor soil. These concentrations can be determined
from a measurement campaign or a modelling effort.
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
Source: WHO Human Health Risk Assessment Toolkit: Chemical Hazards (2010) Figure 5: Generic road map for exposure assessment in the context of the Toolkit.
RISK CHARACTERIZATION
COMPONENTS OF Process of estimating the incidence of a health
effect under the various conditions of human
RISK ASSESSMENT exposure described in the exposure evaluation;
it is performed by combining the hazard
✓ HAZARD IDENTIFICATION characterization and exposure evaluation data
✓ HAZARD CHARACTERIZATION
What is the risk for the exposed populations?
✓ EXPOSURE ASSESSMENT
How does the estimated exposure compare
✓ RISK CHARACTERIZATION with guidance/guideline values for the
chemical?
RISK CHARACTERIZATION
Health Protective Guidance Levels
COMPONENTS OF Human, Non-
Cancer
Human, Cancer Ecological
RISK ASSESSMENT Convention Exposure below Probability of a Exposure
threshold for tumor is concentration
adverse effect acceptably low below threshold
for adverse effect
✓ HAZARD IDENTIFICATION
Hazard ADI, TDI, RfD, Cancer slope Predicted No
Characterization RfC, BMD, etc. factor (CSF) Effect
✓ HAZARD CHARACTERIZATION Input Concentration
(PNEC)
✓ EXPOSURE ASSESSMENT Exposure Input Period average Lifetime average Predicted
daily dose daily dose environmental
(PADD) (LADD) concentration
✓ RISK CHARACTERIZATION (PEC)
Risk Metric Hazard Quotient Excess Lifetime Hazard Quotient
(HQ) Cancer Risk (HQ)
(ELCR)
Calculation HQ = PADD/ADI ELCR = LADD x HQ = PEC/PNEC
(or other) CSF
From material developed by Dr. David Macintosh for the APEC Introductory level training on risk assessment and risk management (2012)
RISK CHARACTERIZATION
Characterization of Non-Cancer Risk
COMPONENTS OF
RISK ASSESSMENT
Hazard Quotient (HQ)
✓ HAZARD IDENTIFICATION ✓ A metric for evaluating the risk associated with exposure
to chemicals that may cause (non-cancer) effects
✓ HAZARD CHARACTERIZATION ✓ Calculated as the ratio of average daily to a guideline
value
✓ EXPOSURE ASSESSMENT HQ = Period Average Daily Dose
✓ Guideline values / Guidance Value
reference doses for a HQ < 1 The chemical exposure is
✓ RISK CHARACTERIZATION wide range of less than the benchmark;
chemicals are available unlikely to result in adverse
from international and effect
national resources HQ > 1 The exposure is greater
than the benchmark;
potential risk
From material developed by Dr. David Macintosh for the APEC Introductory level training on risk assessment and risk management (2012)
RISK CHARACTERIZATION
Characterization of Cancer Risk
COMPONENTS OF
RISK ASSESSMENT
Excess Lifetime Cancer Risk (ELCR)
✓ HAZARD IDENTIFICATION ✓ A metric for quantifying risk associated with exposure to
chemicals that may cause cancer
✓ HAZARD CHARACTERIZATION ✓ Calculated as the product of dose and the cancer slope
factor
✓ EXPOSURE ASSESSMENT
✓ Information on carcinogenicity of chemicals is available
from international and national resources
✓ RISK CHARACTERIZATION
From material developed by Dr. David Macintosh for the APEC Introductory level training on risk assessment and risk management (2012)
RISK CHARACTERIZATION
Characterization of Cancer Risk
COMPONENTS OF
RISK ASSESSMENT
ELCR = Lifetime Average Daily Dose x Cancer Slope Factor
✓ HAZARD IDENTIFICATION
ELCR < 10-6 Excess lifetime cancer risk less than 1 in a million is
✓ HAZARD CHARACTERIZATION typically considered de minimus or negligible
ELCR > 10-4 Excess lifetime cancer risk greater than 1 in ten
thousand is a common benchmark for gathering
✓ EXPOSURE ASSESSMENT additional information or relaxing conservative
assumptions that may be used in a screening
✓ RISK CHARACTERIZATION analysis
From material developed by Dr. David Macintosh for the APEC Introductory level training on risk assessment and risk management (2012)
RISK CHARACTERIZATION
Roadmap for Risk Characterization
COMPONENTS OF
RISK ASSESSMENT
✓ HAZARD IDENTIFICATION
✓ HAZARD CHARACTERIZATION
✓ EXPOSURE ASSESSMENT
✓ RISK CHARACTERIZATION
Source: WHO Human Health Risk Assessment Toolkit: Chemical Hazards (2010)
RISK ASSESSMENT
Risk characterization
Exposure Assessment
Hazard ID
KEY ISSUE
Hazard Characterization
“The relationship between components of the risk assessment paradigm is only
as stable as any “leg” that supports the overall risk characterization. If any
component is weak or missing, then the over all characterization is unstable.”
TAKE HOME POINTS
✓ Risk assessment is a systematic, scientific characterization of potential
adverse health effects resulting from human exposures to hazardous agents.
✓ Components of risk assessment process are: hazard identification, hazard
characterization, exposure assessment and risk characterization.
✓ The relationship between components of the risk assessment paradigm is
only as stable as any “leg” that supports the overall risk characterization. If
any component is weak or missing, then the over all characterization is
unstable.
END
THANK YOU!
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