Risk Assessment
PRESENTATION WEEK 3
Risk Assessment and Management
Risk assessment is the systematic scientific
characterization of potential adverse health effects
resulting from human exposures to hazardous agents
or situations.
Risk is defined as the probability of an adverse
outcome under specified conditions.
Risk management refers to the process by which
policy actions are chosen to control hazards.
Risk Assessment and Management
FIGURE 4–1 Risk assessment/risk management
Risk Assessment and Management Formulating
FIGURE 4–2 Risk management framework for environmental health from the U.S.
Commission on Risk Assessment and Risk Management.
Risk Assessment and
Management
Formulating
Absorption
Distribution
Metabolism, and
Elimination
(ADME)
FIGURE 4–3 Toxicology paradigm.
Hazard Identification-Assessing Toxicity of
Chemicals
Structure Activity Relationships (SAR)
In vitro or short term studies, in vivo animal bioassays,
Information from human epidemiologic studies
SAR
Chemical’s structure and properties
solubility, stability, volatility
pH sensitivity, electrophilicity
chemical reactivity
FIGURE 4–4 Adverse outcome pathways (AOPs) and biomarkers link responses and
describe disease pathogenesis.
Hazard Identification-Assessing Toxicity of
Chemicals
In Vitro and Short-term Animal Bioassays (chemicals that cause
Tests (faster less tumors in animals can cause tumors in
expensive) humans -“precautionary principle”)
bacterial mutation assays; Standard Cancer Bioassays
skin
cell painting studies Include testing in two species and both
in mice; sexes, with 50 animals per dose group
altered
and near life time exposure.
rat liver foci
Transgenic mouse models have been
assays;
developed as possible alternatives to the
developmental, standard 2-year cancer bioassay
reproductive, neuro, and Improve the prediction of cancer risk to
immunotoxicity. humans.
Hazard Identification-Assessing Toxicity of
Chemicals
Epidemiologic Data in Risk Assessment
Positive association between exposure and disease has
been observed
However, other factors may interfere in accurate
assessment: Life style choices (smoking, diet), number of
people and who impacted
Cross sectional studies
Cohort studies
Case–control studies
Hazard Identification-Assessing Toxicity of
Chemicals
Cross-sectional studies Case Control Study
are observational studies that analyze A study that compares two groups
data from a population at a single point in of people: those with the disease
time. or condition under study (cases)
They are often used to measure the and a very similar group of people
prevalence of health outcomes, who do not have the disease or
understand determinants of health, and condition (controls). Researchers
A cohortfeatures
describe study isofaatype of
population. study the medical and lifestyle
epidemiological study in which a group of histories of the people in each
people with a common characteristic is group to learn what factors may be
followed over time to find how many associated with the disease or
reach a certain health outcome of condition. For example, one group
interest (disease, condition, event, death, may have been exposed to a
or a change in health status or behavior). particular substance that the other
was not. Also called retrospective
Hazard Identification-Assessing Toxicity of
Chemicals
Hazard Identification-Dose Response
Dose–response assessment
LD50 (dose producing 50% lethality)
Exposure assessment LC50 (concentration producing 50%
lethality)
Variation in susceptibility ED10 (dose producing 10% response)
NOAEL (No observed adverse effect level”)
Characterization of uncertainty
LOAEL (Lowest observed adverse effect
level)
Hazard Identification-Dose Response
FIGURE 4–5 Dose – response curve.
dose below which no additional increase in response is
observed.
Threshold Approach
LOAEL (Lowest observed adverse effect level)
NOAEL (No observed adverse effect level”)
Dose near the lower end of the dose–response range
Nonthreshold Approach
Hazard Identification-Dose Response
Uncertainty Factor (UF)
Modifying actors (MF)
Reference Dose
UF: when insufficient data are
available to support the use of
Acceptable chemical-specific and species-specific
Daily extrapolation factors.
Intake MF: The five main factors that modify
toxicity are the form of the chemical,
the dose received, the route of
exposure, the degree of absorption,
and factors relating to the recipient
Reference Dose - RfD
A reference dose RfD is the The EPA defines an oral reference dose
United States Environmental Protect (abbreviated RfD) as:
ion
Agency's maximum acceptable [A]n estimate, with uncertainty spanning
oral dose of a toxic substance. perhaps an order of magnitude, of a daily
oral exposure to the human population
Reference doses are most (including sensitive subgroups) that is likely
commonly determined for pesticides to be without an appreciable risk of
. deleterious effects during a lifetime
Uncertainity Factor
Uncertainty Factor The general formula for
deriving the RfD is:
Pertaining to a substance, it is a
factor used by risk RfD = NOAEL or LOAEL
assessors to derive a UF1 x UF2 x ..
reference dose that is
considered safe or below
which an adverse effect is
unlikely to occur
Hazard Identification-Dose Response
FIGURE 4–6 Toxicokinetic (TK) and toxicodynamic (TD)
considerations
inherent in interspecies and inter-individual extrapolations.
Hazard Identification-Dose Response
Models Derived from Mechanistic Assumptions
Example: Radiation Research
One hit model
Multi-hit model
Considerations
Time to tumor formation
Physiologically based toxicokinetic modeling
Biologically Based Dose–Response (BBDR) modeling.
Risk Characterization
Variation in Susceptibility
INFORMATION RESOURCES
Toxicology Data Network ( OXNE ) National Library o Medicine
([Link] provides
World Health Organization
([Link] ([Link]
International Agency for Research on Cancer (IARC)
National Institute of Environmental Health Sciences (NIEHS)
National Toxicology Program ([Link]
RISK PERCEPTION AND COMPARATIVE ANALYSES OF
RISK
Most likely to
provoke calls for
government
regulation.
FIGURE 4–7 Perceptions of risk
illustrated using a “risk space”
axis diagram.