risk assessment lecture

8/8/2019 Risk Assessment Lecture

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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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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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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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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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Continued


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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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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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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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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)

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