Risk Assessment

Dr. Imran
 Risk Assessment
▸ Risk assessment is a formalized process for
characterizing and estimating the magnitude of
the harm resulting from some condition usually
Definitions

one or more hazardous substance in the

environment.

▸ PCCRARM also defined “the process of

identifying, evaluating, selecting and
implementing actions to reduce risk to human
o health and ecosystem”.
Environmental risk assessment
o Refers to human health risk
o Ecological risk assessment
o Refers to damage to natural or artificial
ecosystem, wildlife species
3
▸ Environmental ▸ Ecological risk
risk assessment
▹ Ecotoxicology
assessment ▹ Used in probability of
▹ Environmental extinction of species or
toxicology population due to
▹ Exposure assessment chance or pollution.
▹ Used in sediments
quality standard,
comparison of
alternative remediation
strategies, to establish
▸ Protection of health & well being of
no effect concentration
which can inform
ecological system
cleanup level
▹ Safe drinking water
▹ Clean air
▹ Fertile land for agriculture
▹ Erosion control
▹ Stabilization of coastal environment
▹ Unpolluted water for fisheries
▹ Places for recreation
4
▸ Hazard Identification
▸ Dose Response Assessment
▸ Exposure Assessment
▸ Risk Characterization
Four Step
Approach

▸ Hazard Identification
▹ Identifying a toxic substance or mixture naming one or more endpoints
(e.g., lung cancer, neurotoxicity) which are of concern
▹ List of the chemicals (usually from 129 priority pollutants) that have
been identified in the soil
▹ Based of their quantity, mobility, coherence with health reports or
actual exposure assessment few of chemicals were selected
 ▸ Dose Response Assessment

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▹ Dose response curve can be constructed for the endpoints of
the concern or whether specific threshold have been
determined.

▹ Unfortunately for many compounds the only dose response

data are from previous old studies that used dosing level
Four Step
appropriate for determining LD50, but not appropriate for
Approach
low dose extrapolation.

▸ Exposure Assessment
▹ Must take into account the measured or estimated
concentrations of a substance (air, water, food, soil) and all
applicable routs of exposure (inhalation, ingestion, skin
absorption).

▹ Exposure assessment must incorporate estimates of

bioavailability and increasingly rely on physiologically based
PK models to provide the estimates of internal dose, the dose
actually delivered to the target organ.
6 Four Step
Approach
▸ Risk Characterization
▹ It involves a quantitative estimate of the exposure level at
which a --------- level of excess risk exists.

▸ Model of Risk Characterization

▹ The one --------- assume a linear relationship between the
dose and the outcome, starting at the smallest dose above
zero (i.e., no thresholfd) with the slope of line determined
wit available studies.

▸ Multistage ▸ LNT Model

▹ Which emphasis
Model mutational events,
▹ Understanding of involved in initiation
chemical rather than promotion
carcinogenesis as
process involving
initiation and
 ▸ Slope factor

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▹ Carcinogen Assessment Group of EPA has prepared a cancer
potency estimates referred to as slop factor for a number of
common carcinogens using the linearized Multistage Model,
which is considered as most generally applicable
extrapolate approach for chemical carcinogens.
Four Step
Approach

▸ Dose Distribution Model

▹ Give higher estimate of the dose and are considered less
protective of the public health, although future research
may validate their use for some substances.
 ▸ Slope factor
▹ Regulatory agencies provides a rationale for setting
enforceable standard for toxic chemicals in
● Air
● Water
Application of the
Risk Assessment
● Soil
● Food
● Consumer products
● Wastes including hazardous waste

▸ Amendments to Clear Air Act 1990

▹ Veterinary application
▹ Terrorism and Preparedness
▹ Military Application
▹ Future land use of contaminated sites
▹ Energy and Transportation
 ▸ Veterinary Application
▹ Risk assessment is required mainly for risk to the human
consumer of the plants and animals, but it also applied to
the animal health.
Application of the
Risk Assessment
▹ Risk assessment has been applied to several others major;

● Live stock disease (bovine

spongiform encephalopathy)
● …………. Movements
● West Neil virus
● Mosquitoes born blue tongue
disease of livestock
● Likelihood rabies entering in
Britain
● Gill disease in salmon farming
 ▸ Terrorism and Preparedness
▹ Since 2001 the USA has focussed heavily on all
aspects of terrorisms and preparedness for both
natural, non-natural and deliberate disaster.
Application of the

● Estimating the likelihood and magnitude of

Risk Assessment
terrorist events
● Design and vulnerability of infrastructure
● Food supply
● Drinking water
● Consequences of infectious disease
● Industrial chemical hazards

▸ Terrorism and Preparedness

▹ National Security & Preparedness policy including
● Detainment versus rights
● Vaccination versus individual liberty
● Redundancy versus cost containment
 ▸ Military Application

▹ Risk assessment was first applied in Prussian Army

Application of the

soldiers which were injured by horses

Risk Assessment
▹ Swine flu virus (H1N1) identification

▹ Risk assessment has been applied to excess injury

rates
○ Among occupying forces
○ Formal international peacekeepers
○ Forced anthrax vaccination
○ Psychiatric hospitalization
○ Exposure to chemicals
 ▸ Future Land Use of Contaminated
Sites
▹ Economic and demographic factors dictating the
reuse and redevelopment of formal industrial &
Application of the
Risk Assessment
agriculture sites
▹ Cleaning decision and goals linked with future land
use
○ Ecological vs human health
○ Workers vs public health
○ Dollar cost effectively

▸ Risks associated with community urban air

pollution are an example.
▸ Risks associated with rapid industrialization
and urbanization, but also have to deal with
threats to their immediate environment like
 ▸ Energy and Transportation
▹ Fossil fuel offers a very fertile area for risk assessment&
risk balancing internationally, once the energy crises
recognized.
Application of the

▹ Restriction in nuclear plants for the generation, fossil

Risk Assessment
fuel may increase the reactiveness of nuclear energy in
future
▹ Balancing the hazards of handling, transportation, &
storing nuclear waste against the social, economic &
health consequences of other fuel is important.
▹ The main man-made global contribution to
environmental exposure has come from radioactive
fallout from the testing of nuclear weapons in the
atmosphere, since 1950.
▹ Some potential sources of exposure have raised public
concern, such as lost medical or industrial radiation
sources, deliberate contamination of items such as
foodstuffs with radioactive materials, by using
conventional explosives.
 ▸ Estimate the risk associated with variety of hazards and

Balancing Risk & Cost

prioritize, starting with those that pose with greatest risk
with greatest number
▸ Based on acceptable risk to decide whether take part in
action or not
▸ Cost benefit analysis in terms of lives, health or
environmental quality
▸ Risk-Risk Balancing (lowest risk)
▸ Remediation workers at hazardous sites face the risk beyond
those related to chemical, biological or radiological and
workers risk is used to balance by the risk reduction of costly
cleanups.
▸ Risk assessment can be used in applications for hazardous
facilities such as nuclear plants, liquified natural gas depot,
municipal solid waste incineration and hazardous waste sites.
▸ Risk analysis has an important role in many Government
decisions, like management of dioxin contaminated soil and
 ▸ Balancing Benefit & Risk of Fish
Consumption
▹ Main contaminant of the fish are methylmercury, PCBs &
Dioxin.
Balancing Risk &

○ Adult population
○ Pregnant women & young children
▹ High end fish eaters , the people who reject red meat,
recreational anglers, subsistence fishing
Cost

▸ EPA uses 19 kg/year average fish consumption

for general population & 55 kg/year as
▸subsistence
Environmental Equity
consumption level..
▹ Most hazardous workplace or community exposure are
not distributed uniformly
▹ A low socioeconomic person is more likely to
encounter such hazardous in their work or home
 ▸ Environmental Risk Assessment is to
identify
▹ Whether a particular exposure level of an agent is
acceptable or whether a target population can continue
Acceptable Risk

the exposure level without unacceptability

consequences.

▹ Identify the level of harm at society level

▹ Unacceptability to one person, may be proactive

challenge to another

▹ Acceptable risk is human value & social decision rather

scientific one.

▹ Risk is acceptable or not, it is necessary to define an end

point.

▹ Communication challenge
 ▸ Shortening of Life
consequences considered by
● Cancer versus other causes

approximately declining
▸ Injury or Illness leading to disability
Spectrum of adverse

risk assessors in ● Acute vs chronic

order of severity
● Permanent vs temporary disability
● Serious vs minor disability
▸ Illness or injury temporary disability followed by
recover
● Chronic vs acute
● Serious vs minor disability
▸ Physical discomfort without disability
▸ Psychological disorder with behavioural
consequences
● Post traumatic stress disorder
● Anxiety reaction
● Stress reaction
● Chronic frustration or anger
 ▸ Group I
● Known human carcinogen;

Carcinogen Classification
○ Adequate evidence in human
▸ Group 2A
● Probable human carcinogen;
○ Limited evidence in human, but sufficient animal
evidence
▸ Group 2B
IARC

● Possible human carcinogen;

○ Limited evidence in human and less than sufficient
in animals
▸ Group 3
● Not classifiable;
○ Evidence of carcinogenicity is limited in human as
well as in experimental animals
▸ Group 4
● Probably not carcinogenic in humans;
○ Evidence suggested not a carcinogenic in human
and animals
▸ EPA uses the similar categories, but they labelled A, B1, B2 C,
 ▸ Risk assessment based on animal toxicology

Interspecies Extrapolation ▸ Evolutionary resemblance among animals, their

common derivations, their protein structure provides
the basis for the principal of animal extrapolation to
human

▸ Presence of enzyme and consequent metabolism vary

not only among species, but among strains of a species
between sexes

▸ Toxic substance produce the same effect

● Bladder cancer or leukaemia

▸ Substance may be a carcinogen in one species but not

in other,
 ▸ Animal toxicological data

Interspecies Extrapolation ▸ Drawback

● Whether the human is more or less susptible to
the agent than the experimental animal

▸ Safety factor of 10 assumes that human are more than

10 times more sensitive

▸ 2, 3, 7, 8-TCDD (Dioxin), Guinea pigs are 100 times

more sensitive than rats
 ▸ Toxic substance produce their effects at the molecular
and cellular level can help to clarify the risk approach
Interpreting the model
● 95% confidence limit calculation, to ensure
protectiveness of public health as a “upper
bound” to risk estimate
● Establish a science policy decision using a no-
threshold model in cancer risk assessment
● While no-threshold model is used for genotoxic
carcinogens, but not necessary for other
carcinogens such as promoters

▸ Lineralized Multistage Model

● Two stage process of carcinogenesis, recognizing
that a single hit may not be sufficient to cause
cancer.
● Dose estimated by linearized multistage model is
intermediate between the doses generated by the
other two models.
 ▸ Highest dose known to produce no effect (NOAEL)

Risk Assessment for non-

carcinogens end points
▸ Control dose has no effect, the lowest dose known to
produce an adverse effect (LOAEL)
▸ Benchmark dose
● Is the lower confidence limit on a dose which
produces an effect in some percent of test
animals
▸ NOEL & NOAEL
● NOAEL is dose at which there was no biologically
or statistically significant adverse effect
● NOEL there may be a measurable effects that are
known to have adverse consequences
● It is sensitive to the doses chosen for the study
▸ LOAEL
● Some studies even the lowest dose induced a
significant adverse effect, treat LOAEL different
from NOAEL, incorporating 10X uncertainty
 ▸ Reference Dose or Acceptable Daily Intake
● Daily dose express usually in ug/kg/day that one

Risk Assessment for non-

carcinogens end points
could be exposed to every day (usually for a 50
years life-time) without experiencing any adverse
effect

▸ Safety Factor or Uncertainty Factor

● it is a factor used by risk assessors to derive a

reference dose that is considered safe or below
which an adverse effect is unlikely to occur

○ To use animal data to protect human, UF 10

○ To protect the most sensitive human individuals,
UF10
○ To calculate chronic or lifetime RfD from a study
using only a subacute or acute exposure, UF10
○ If the RfD is based on an LOAEL rather than on
NOAEL, UF10
 ▸ Reference Dose or Acceptable Daily Intake
● Daily dose express usually in ug/kg/day that one

Risk Assessment for non-

carcinogens end points
could be exposed to every day (usually for a 50
years life-time) without experiencing any adverse
effect

▸ Safety Factor or Uncertainty Factor

● it is a factor used by risk assessors to derive a

reference dose that is considered safe or below
which an adverse effect is unlikely to occur

○ To use animal data to protect human, UF 10

○ To protect the most sensitive human individuals,
UF10
○ To calculate chronic or lifetime RfD from a study
using only a subacute or acute exposure, UF10
○ If the RfD is based on an LOAEL rather than on
NOAEL, UF10
 ▸ Epidemiology & Toxicology provide information for risk
assessment
Information used in risk ● Epidemiological studies often lack power and
characterization insisting on a 0.05 level of significance
introduces a strong bias against findings
association between exposure and outcome.

● Toxicological studies have advantages in terms of

accuracy of exposure and dose measurement but
there are uncertainties on converting animal
doses to to human exposure
 ▸ Risk assessment focusses the life time exposure and
life time risk
Dose duration and risk
● Radiation risk assessment are more likely to
apportion risk over time, recognizing that the
childhood exposure has different impact from
adult exposure

● Relation between dose and duration is

complicated.

● Peak doses may exceed threshold, which are

never achieved by small daily doses, even over a
longer period of time

● Age is a major variable influencing susceptibility

& response
 ▸ The MTD is the highest dose “that does not alter the
animal’ longevity or wellbeing: from unrelated effects.
Maximally tolerated dose
▸ Extreme Value Theorem

■ Extreme value is a branch of the statistics focussing

on extreme deviation form the median of probability
distribution.
● Useful for evaluating highly unusual events such as 100
years flood.
● Extreme value approaches could be applied to estimate
risk to the most highly sensitive individuals, who may
much more than 10 times as susceptible as the median
of the population.
 ▸ Uncertainty permeates the risk assessment process,
even the mechanism by which agent produce s diseas
is well documented.

■ Uncertainty is introduced in the dose response data

from animal studies, the exposure assessment & the
Uncertainty

risk estimation process.

■ Uncertainty introduced by inadequate date vs

methodology from inherent variability among
individuals

■ Epidemiological and Toxicological research are

helpful to reduce the uncertainty.
 ▸ Published animal research
▸ Endpoint in human
▸ Controversy has been caused by the uncertainties involved in
extrapolating from animals to people.
Limitation of Risk
Assessment ▸ Spares human studies-rely on animal models
▸ Inadequate human exposure data
▸ Cancer risk assessment-type of model used
▸ Risk estimate on collective exposure are not easily translated
into individual risk
▸ Ignorance of dose aspect, peak exposure and duration
▸ Debate of acceptable risk level
 ▸ Goal of risk perception research is to understand how
individuals appreciate risk, how they make their risk-
taking and risk binding decision and how to bring their
understanding specific into congruence with actual
level of risk.
Risk Perception
Acceptable or Reduces Unacceptable or Increases
Apparent Riskiness Apparent Riskiness
Assumed voluntarily or self imposed Borne involuntarily or imposed by others

Adverse effects immediate Outcome delayed

Alternatives not available, a necessity Alternatives available, a luxury

Risk certain Risk uncertain

Occupational exposure Community exposure

Familiar hazard Feared or “dread” hazard

Consequences reversible Consequences irreversible

Some benefits gain from assuming risk No apparent benefits to person at risk

Hazards associated with perceived good Someone else profits “my expense”
 ▸ Impart information to the public as well as to
individuals
Risk Communication ▸ Unpleasant news
▸ Risk Communication Model
■ Risk communication one way path between
the expert and the public
■ “Convergence Model”

▸ Risk Comparison
■ Is an approach to communicating risk by
contrasting unfamiliar risk with familiar ones.
● Driving so many miles in the car
● Radiation risk of transcontinental air flight
● Lung cancer risk from smoking
 Media Coverage of Risk

■ Newspaper and television coverage exaggerate the

Risk Communication hazards of everyday life

■ Media are an important source of hazard and risk

information for many people

■ Environmental news coverage can be improved if a

dialogue between toxicologists, risk assessors and
reports can be developed