Risk Assessment

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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 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.

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Problems With Risk Assessments

• 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 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 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.

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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 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.

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Dose-Response Assessment

• 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.
• 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 Product Safety Commission use
  the Allowable Daily Intake (ADI) to calculate
  permissible chronic exposure levels.
• 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.

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Non-Carcinogenic Effects - Continued

• 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)
• 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

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Non-Carcinogenic Effects - Continued

• 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

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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 of NOAEL
• x10 Incomplete database
• x0.1 to 10 MF Modifying Factors

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Non-Carcinogenic Effects - Continued

• Minimum Risk Levels (MRLs), used by ATSDR, are
  similar to the EPA's Reference Dose (RfD) and
  Reference Concentration (RfC).
• 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.

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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
  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.

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Carcinogenic Effects

• 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.

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Carcinogenic Effects - Continued
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Carcinogenic Effects - Continued
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Carcinogenic Effects - Continued

• 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.
• 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.

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Carcinogenic Effects - Continued

• Slope Factor a plausible upper-bound estimate
  of the probability of a response per unit intake
  of chemical over 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 involves describing the
  nature and size of various populations exposed to
  a chemical agent, and the magnitude and duration
  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 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

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Identification of Exposure Pathways

• 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

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Exposure Pathways - Continued

• All 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 Factor x
  Length of Exposure
• For Noncarcinogens
• Maximum Daily Dose (MDD)
• For Carcinogens
• Lifetime Average Daily Dose (LADD)

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Lifetime Average Daily Dose

• Of The Chemical x Contact Rate x Contact
  Fraction 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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Important Note 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 70 years (a lifetime)
• 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.

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Risk Characterization

• Exposure Assessments and Toxicity Assessments are
  integrated to give a probability of a negative
  effect.
• Risk characterization is conducted for individual
  chemicals and then summed for mixtures of
  chemicals Additivity is assummed.

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Risk Characterization - Continued

• For Noncarcinogenic chemicals
• The Maximum Daily Dose is compared to the RfD.
  If MDD is lt RfD, then no problem- except when
  dealing with multiple chemicals.
• For ecological issues
• Estimated Environmental /Toxic Endpoint
  Quotient, Quotients approaching or exceeding 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-less
  number
• This unit-less number represents the increase in
  the number of cancer cases per year due to
  chemical

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Risk Characterization - Continued

• Virtually Safe Dose
• 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)