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Risk Assessment
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Types Of Risk Assessment Human Health Risk Assessment - The
characterization of the probability of
potentially adverse health effects from humanexposures to environmental hazards.
Ecological Risk Assessment A process thatestimates the likelihood of undesirableecological effects occurring as a result ofhuman activities.
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Problems With Risk
AssessmentsA basic problem with both human and
ecological risk assessments is the
sparseness and uncertainty of thescientific data. Also -
Variability within dose-response curves
Extrapolation of animal data to humans Extrapolation from high-dose to low-
dose effects
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Four Steps To A Risk
Assessment Document Hazard Identification
Dose-Response Assessment Exposure Assessment
Risk Characterization
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Hazard Identification Hazard identification involves gathering and
evaluating toxicity data on the types of health
injury or disease that may be produced by achemical and the conditions of exposureunder which injury or disease is produced.
The subset of chemicals selected for thestudy is termed chemicals ofpotentialconcern.
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Hazard Identification Data Data from acute, subchronic, and chronic
dose-response studies are used.
a H.R.A. would have a priority ranking of studiesthat would involve humans and other mammals.
an E.R.A. would use different species in differenttropic levels; the test species selected are
generally representative of naturally occurringspecies with practical considerations such as easeof culture, sensitivity, availability, and existingdatabases also involved.
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Dose-Response Assessment The dose-response assessment involves
describing the quantitative relationshipbetween the amount of exposure to achemical and the extent of toxic injuryor disease.
The description is different for non-carcinogenic versus carcinogenic effects.
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Non-Carcinogenic Effects Allowable Daily Intake - The US Food and
Drug Administration, the World Health
Organization, and the Consumer ProductSafety Commission use theAllowable DailyIntake (ADI) to calculate permissiblechronic exposure levels. The ADI is determined by applying safety factors
to the highest dose in chronic human or animalstudies that has been demonstrated not to causetoxicity.
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Non-Carcinogenic Effects -
Continued Reference Dose - The US EnvironmentalProtection Agency has slightly modified the
ADI. For the EPA, the acceptable safety levelis known as the Reference Dose (RfD)
an estimate of a daily exposure level for humanpopulations, including sensitive subpopulations,
that is likely to be without an appreciable risk ofdeleterious health effects during a lifetime
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Non-Carcinogenic Effects -
Continued The position of the EPA is that humans
are as sensitive as the most sensitivetest species unless other data areavailable.
RfD = NOAEL or LOAEL
UF1 x UF2 x Ufx
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Non-Carcinogenic Effects -
Continued Safety/Uncertainty Factors
x10 Human Variability
x10 Extrapolation from animals to humans
x10 Use of less than chronic data
x10 Use of LOAEL instead ofNOAEL
x10 Incomplete database
x0.1 to 10 MF Modifying Factors
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Non-Carcinogenic Effects -
Continued Minimum Risk Levels (MRLs), used byATSDR, are similar to the EPA's
Reference Dose (RfD) and ReferenceConcentration (RfC).An MRL is an estimate of the daily human
exposure to a hazardous substance that is
likely to be without appreciable risk ofadverse noncancer health effects over aspecified duration of exposure.
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Non-Carcinogenic Effects
Continued 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 likelyto occur in humans.
For an E.R.A. chief measurement endpointsare mortality, growth and development, and
reproduction. In E.R.A.s one must sometimesextrapolate effects from a surrogate speciesto the species of interest, or from acute datato chronic data.
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Carcinogenic Effects Mathematical models are used to
extrapolate from the high doses used inanimal experiments to the low doses towhich humans are normally exposed ina chronic setting.
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Carcinogenic Effects -
Continued
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Carcinogenic Effects -
Continued
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Carcinogenic Effects -
Continued The key risk assessmentparameter derived
from the carcinogen risk assessmentprocess
is the slope factor. The slope factor is atoxicity value that quantitatively defines therelationship between dose and response.
= a plausible upper bound estimate of the
probability that an individual will develop cancer ifexposure is to a chemical for a lifetime of 70years.
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Carcinogenic Effects -
Continued Slope Factor = a plausible upper-bound
estimate of the probability of aresponse per unit intake of chemicalover a lifetime
Risk per unit dose
Units of Risk (mg/kg-day)-1
Symbol for Slope Factor = q1*
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Cancer Assessment Categories
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Exposure Assessment
Exposure assessment involvesdescribing the nature and size ofvarious populations exposed to achemical agent, and the magnitude andduration of their exposures.
Without exposure there can be no toxicity.
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Steps In Exposure Assessment Characterization of exposure setting
Identification of exposure pathways Quantification of exposure
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Characterize The Exposure
Setting 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?
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Identification of Exposure
Pathways Contaminated groundwater ingestion
(drinking water), dermal contact (bathing),and inhalation of volatile organic compounds(showering)
Surface water and sediments incidentalingestion and dermal absorption ofcontaminants (people in bodies of water)
Contaminated food ingestion ofcontaminated fish tissue, vegetables and fruitgrown in contaminated soil or covered withcontaminated dust, meat, and dairyproducts
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Identification of Exposure
Pathways Surface soils ingestion and dermal
absorption of contaminants by childrenplaying in dirt
Fugitive dust and VOC emissions inhalationby 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 toxiclipophilic contaminants
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Exposure Pathways -
ContinuedAll potential exposure pathways are
considered with an analysis of
the contaminants released
the fate and transport of the contaminants
the population exposed to the
contaminants
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Quantification of Exposure General statement
[ ] Of Chemical x Intake x Retention Factorx Length of Exposure
For Noncarcinogens
Maximum Daily Dose (MDD)
For Carcinogens Lifetime Average Daily Dose (LADD)
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Lifetime Average Daily Dose = [ ] OfThe Chemical x Contact Rate x
ContactFraction x Exposure Duration
________________________________
Body Weight x Lifetime
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LADD Calculation Example
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LADD Calculation Example -
Continued
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ImportantNote to Calculation
of LADD Be aware of the units used for
consumption of the chemical (How
often the chemical is obtained).You may need to back calculate the
number to mg/kg/day averaged over 70years (a lifetime) If the units are already in mg/kg/day, then no
back calculation is needed, if units aremg/kg/month, then you only need to calculateback from months to days.
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Risk Characterization Exposure Assessments and ToxicityAssessments are integrated to give aprobability of a negative effect.
Risk characterization is conducted forindividual chemicals and then summed for
mixtures of chemicals Additivity isassummed.
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Risk Characterization -
Continued For Noncarcinogenic chemicals
The Maximum Daily Dose is compared to
the RfD. If MDD is < RfD, then noproblem- except when dealing withmultiple chemicals.
For ecological issues Estimated Environmental [ ]/Toxic Endpoint [ ]
= Quotient, Quotients approaching orexceeding 1.0 represent increasing risk
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Risk Characterization -
Continued For Carcinogenic Chemicals
You determine the upper confidence Limit
on Risk
UCL Risk = Slope Factor x LADD
Units for Slope Factor are (mg/kg/day)-1
Units for LADD are mg/kg/day
Therefore units cancel and you get a unit-lessnumber
This unit-less number represents the increase in thenumber of cancer cases per year due to chemical
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Risk Characterization -
ContinuedVirtually Safe Dose
This was initially defined (1961) as 1 extra
cancer death per 100 million peopleexposed
Found unenforceable byFDA in 1977
Currently the EPA uses 1 extra cancer
death per 1 million people exposed. California uses 1 extra death per 100,000people exposed (Proposition 65)