Transcript Risk Assessment Types Of Risk Assessment   Human Health Risk Assessment - The characterization of the probability of potentially adverse health effects from human exposures.

Risk Assessment
Types Of Risk Assessment
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Human Health Risk Assessment - The
characterization of the probability of
potentially adverse health effects from human
exposures to environmental hazards.
Ecological Risk Assessment – A process that
estimates the likelihood of undesirable
ecological effects occurring as a result of
human activities.
Problems With Risk
Assessments
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A basic problem with both human and
ecological risk assessments is the
sparseness and uncertainty of the
scientific data. Also Variability within dose-response curves
Extrapolation of animal data to humans
Extrapolation from high-dose to lowdose effects
Four Steps To A Risk
Assessment Document
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Hazard Identification
Dose-Response Assessment
Exposure Assessment
Risk Characterization
Hazard Identification
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Hazard identification involves gathering and
evaluating toxicity data on the types of health
injury or disease that may be produced by a
chemical and the conditions of exposure
under which injury or disease is produced.
The subset of chemicals selected for the
study is termed “chemicals of potential
concern”.
Hazard Identification – Data
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Data from acute, subchronic, and chronic
dose-response studies are used.
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a H.R.A. would have a priority ranking of studies
that would involve humans and other mammals.
an E.R.A. would use different species in different
tropic levels; the test species selected are
generally representative of naturally occurring
species with practical considerations such as ease
of culture, sensitivity, availability, and existing
databases also involved.
Dose-Response Assessment
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The dose-response assessment involves
describing the quantitative relationship
between the amount of exposure to a
chemical and the extent of toxic injury
or disease.
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The description is different for noncarcinogenic versus carcinogenic effects.
Non-Carcinogenic Effects
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Allowable Daily Intake - The US Food and
Drug Administration, the World Health
Organization, and the Consumer Product
Safety Commission use the Allowable Daily
Intake (ADI) to calculate permissible
chronic exposure levels.
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The ADI is determined by applying safety factors
to the highest dose in chronic human or animal
studies that has been demonstrated not to cause
toxicity.
Non-Carcinogenic Effects Continued
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Reference Dose - The US Environmental
Protection Agency has slightly modified the
ADI. For the EPA, the acceptable safety level
is known as the Reference Dose (RfD)
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an estimate of a daily exposure level for human
populations, including sensitive subpopulations,
that is likely to be without an appreciable risk of
deleterious health effects during a lifetime
Non-Carcinogenic Effects Continued
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The position of the EPA is that humans
are as sensitive as the most sensitive
test species unless other data are
available.
RfD = NOAEL or LOAEL
UF1 x UF2 … x Ufx
Non-Carcinogenic Effects Continued
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Safety/Uncertainty Factors
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x10 Human Variability
x10 Extrapolation from animals to humans
x10 Use of less than chronic data
x10 Use of LOAEL instead of NOAEL
x10 Incomplete database
x0.1 to 10 MF Modifying Factors
Non-Carcinogenic Effects Continued
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Minimum Risk Levels (MRLs), used by
ATSDR, are similar to the EPA's
Reference Dose (RfD) and Reference
Concentration (RfC).
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An MRL is an estimate of the daily human
exposure to a hazardous substance that is
likely to be without appreciable risk of
adverse noncancer health effects over a
specified duration of exposure.
Non-Carcinogenic Effects
Continued
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For a H.R.A. any toxic effect can be used for
the NOAEL or LOAEL so long as it is the most
sensitive toxic effect and it is considered likely
to occur in humans.
For an E.R.A. chief measurement endpoints
are mortality, growth and development, and
reproduction. In E.R.A.s one must sometimes
extrapolate effects from a surrogate species
to the species of interest, or from acute data
to chronic data.
Carcinogenic Effects
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Mathematical models are used to
extrapolate from the high doses used in
animal experiments to the low doses to
which humans are normally exposed in
a chronic setting.
Carcinogenic Effects Continued
Carcinogenic Effects Continued
Carcinogenic Effects Continued
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The key risk assessment parameter derived
from the carcinogen risk assessment process
is the “slope factor”. The slope factor is a
toxicity value that quantitatively defines the
relationship between dose and response.
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= a plausible upper bound estimate of the
probability that an individual will develop cancer if
exposure is to a chemical for a lifetime of 70
years.
Carcinogenic Effects Continued
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Slope Factor = a plausible upper-bound
estimate of the probability of a
response per unit intake of chemical
over a lifetime
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Risk per unit dose
Units of Risk (mg/kg-day)-1
Symbol for Slope Factor = q1*
Cancer Assessment Categories
Exposure Assessment
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Exposure assessment involves
describing the nature and size of
various populations exposed to a
chemical agent, and the magnitude and
duration of their exposures.
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Without exposure there can be no toxicity.
Steps In Exposure Assessment
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Characterization of exposure setting
Identification of exposure pathways
Quantification of exposure
Characterize The Exposure
Setting
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What are the situations which could
lead to exposure?
What would lead to high exposure,
medium exposure, and low exposure?
Describe the situations for the various
exposure scenarios.
Who are the people / animals exposed?
Identification of Exposure
Pathways
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Contaminated groundwater – ingestion
(drinking water), dermal contact (bathing),
and inhalation of volatile organic compounds
(showering)
Surface water and sediments – incidental
ingestion and dermal absorption of
contaminants (people in bodies of water)
Contaminated food – ingestion of
contaminated fish tissue, vegetables and fruit
grown in contaminated soil or covered with
contaminated dust, meat, and dairy products
Identification of Exposure
Pathways
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Surface soils – ingestion and dermal
absorption of contaminants by children
playing in dirt
Fugitive dust and VOC emissions – inhalation
by nearby residents or onsite workers
Subsurface soil and air-borne contaminants –
future land-use conditions during construction
activities
Contaminated breast milk – nursing infants
whose mothers were exposed to highly toxic
lipophilic contaminants
Exposure Pathways Continued
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All potential exposure pathways are
considered with an analysis of
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the contaminants released
the fate and transport of the contaminants
the population exposed to the
contaminants
Quantification of Exposure
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General statement
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For Noncarcinogens
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[ ] Of Chemical x Intake x Retention Factor
x Length of Exposure
Maximum Daily Dose (MDD)
For Carcinogens
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Lifetime Average Daily Dose (LADD)
Lifetime Average Daily Dose
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= [ ] Of The Chemical x Contact Rate x
Contact Fraction x Exposure Duration
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Body Weight x Lifetime
LADD Calculation Example
LADD Calculation Example Continued
Important Note to Calculation
of LADD
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Be aware of the units used for
consumption of the chemical (How
often the chemical is obtained).
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You may need to back calculate the
number to mg/kg/day averaged over 70
years (a lifetime)
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If the units are already in mg/kg/day, then no
back calculation is needed, if units are
mg/kg/month, then you only need to calculate
back from months to days.
Risk Characterization
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Exposure Assessments and Toxicity
Assessments are integrated to give a
probability of a negative effect.
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Risk characterization is conducted for
individual chemicals and then summed for
mixtures of chemicals – Additivity is
assummed.
Risk Characterization Continued
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For Noncarcinogenic chemicals –
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The Maximum Daily Dose is compared to
the RfD. If MDD is < RfD, then no
problem- except when dealing with
multiple chemicals.
For ecological issues –
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Estimated Environmental [ ]/Toxic Endpoint [ ]
= Quotient, Quotients approaching or
exceeding 1.0 represent increasing risk
Risk Characterization Continued
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For Carcinogenic Chemicals –
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You determine the “upper confidence Limit
on Risk”
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UCL Risk = Slope Factor x LADD
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Units for Slope Factor are (mg/kg/day)-1
Units for LADD are mg/kg/day
Therefore units cancel and you get a unit-less
number
This unit-less number represents the increase in the
number of cancer cases per year due to chemical
Risk Characterization Continued
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Virtually Safe Dose –
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This was initially defined (1961) as 1 extra
cancer death per 100 million people
exposed
Found unenforceable by FDA in 1977
Currently the EPA uses 1 extra cancer
death per 1 million people exposed.
California uses 1 extra death per 100,000
people exposed (Proposition 65)