Risk Assessment

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Risk Assessment

• Textbook Chapter 14.1 - 14.3
• Toxicology Tutor. Part1
  http//www.sis.nlm.nih.gov/Tox/ToxTuto
  r.html
• Risk Assessmemt
• Exposure Standards
• Includes short quiz segments

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Other useful Web sites

• USEPA reference doses RfD Integrated Risk
  Information System (IRIS)
• http//cfpub.epa.gov/ncea/iris/index.cfm?fuseactio
  niris.showSubstanceList
• National Primary Drinking Water Standard
  (Maximum Contaminant Level) http//www.epa.gov/sa
  fewater/mcl.html
• Minnesota Health Risk Limits for drinking water
  http//www.health.state.mn.us/divs/eh/groundwater/
  hrltable.html
• MPCA-Risk-Based Guidance for the Soil - Human
  Health Pathway. http//www.pca.state.mn.us/cleanup
  /riskbasedoc.html

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• National Center for Environmental Risk Assessment
  (NCEA)
• http//cfpub.epa.gov/ncea/
• Superfund Soil Screen Guidance (SSL)
• http//www.epa.gov/superfund/health/conmedia/soil/
  index.htm

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Risk Assessment

• The scientific estimation of a hazard
• Governmental Agencies involved in risk
  assessment
• Federal
• Food and Drug administration (FDA)
• Occupational Health and Safety Administration
  (OSHA)
• EPA
• State
• MPCA
• MDA

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Risk assessment and safe levels in groundwater

• Used in determination Maximum Contaminant Levels
  in groundwater
• US health standards
• Used in determination of state Health Risk Limits
  
• These are state guidance values for ground water.
  

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Risk assessment and food safety

• Determination of pesticide residue in food
• The concept of safe food basket. Consider all
  food sources of a pesticide.

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Risk assessment is used in environmental cleanup

• It is used in the process of determining the
  remediation goals (RG) in remediation of
  contaminated sites.
• A risk assessment is part of the Remedial
  Investigation (RI) and Feasibility Study (FS) to
  determine alternative remedies. After the risk
  assessment is complete

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• A remedial investigation is conducted to
  determine if cleanup is needed.
• A feasibility study determines alternative
  remedies and estimates costs of alternatives,
• This is a discussion document brought before
  regulators and responsible parties (RPs).

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Basic Risk Assessment Terms

• Hazard
• Capability of a substance to cause an adverse
  effect such as injury, disease, or death.
• Risk
• Probability that a hazard will occur under
  specific conditions.
• Risk Assessment
• The process by which hazard, risk, and exposure
  are determined.

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Lifetime Mortality Risk
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Risk Assessment Management

• A risk assessment
• Describes the magnitude and probability of an
  adverse health effect from exposure to a
  contaminant. (Also applies ecological risk
  assessment)
• Risk management -- the eventual outcome of risk
  assessment
• The process of weighing policy alternatives and
  selecting the most appropriate action based on
  the results of risk assessment and social,
  political, and economic concerns.

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Traditional Risk Assessment

• Four main components if little or nothing is
  known about the hazard and risk
• 1. Hazard identification
• Identification of hazardous substances and the
  toxic effects.
• What is the chemical, or chemicals, that are
  hazardous and what is the health or ecological
  harm?
• Is the chemical a carcinogen?

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• In the case of most cleanup sites this involves
  the discovery of significant concentrations of
  substances with known toxicity.
• If hazard is not known this is can be difficult
• This has proved to be a very difficult step in
  the determination of the risk of deformed frogs
  in Minnesota.

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Traditional Risk Assessment (cont.)

• 2. Exposure assessment
• Determine the pathways and rate of uptake. What
  are the receptors?
• 3. Dose/response assessment
• Determination of the mathematical relationship
  between concentration and response using the
  principles of toxicology. (See last section on
  Toxicology)
• 4. Risk characterization
• What is the impact of the hazard.

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Risk assessment is used for risk management

• Risk Management
• Communicate risk to individuals , groups, and
  institutions.
• Propose remedies and choose the best remedy.

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1. Hazard identification

• What is the chemical, or chemicals, that are
  hazardous and what is the health or ecological
  response.
• If the chemicals involved are well studeid this
  may be just chemical analysis of the media in
  question.
• Is the chemical a carcinogen?
• Carcinogens are treated differently than non
  carcinogens.

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Hazard identification Identification of
Carcinogens

• A complex process involving animal studies etc.
  (see textbook)
• A known human carcinogen
• B1 probable human carcinogen sufficient animal
  evidence, limited human evidence
• B2 probable human carcinogen sufficient animal
  evidence, no or inadequate human evidence
• C possible human carcinogen limited animal
  data
• D not classifiable no or inadequate cancer
  studies
• E evidence of that the compound is not
  carcinogenic

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2. Exposure assessment

• Exposure pathway and quantity.
• EPA has tabulated standard default exposure
  factors. Contact Rates (CR) Table 14.4
• EF and ED are eh defaults used for exposure which
  we will use for calculation cancer risk

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MPCA scenarios

• Acute Noncancer Exposure Scenario - Evaluation of
  a young child (e.g., 1 - 2 years old) for single
  event or several exposure events over a short
  period of time (e.g., ingestion of a bolus of
  soil). (10 g bolus)
• Subchronic Noncancer Exposure Scenario -
  Evaluation of a young child for short-term (e.g.,
  several weeks to several months) exposure due to
  higher exposure potential (e.g., increased soil
  contact during summer months).
• Chronic Noncancer Exposure Scenario - Evaluation
  of a young child experiencing the reasonable
  maximum soil-related exposure in a residential
  setting.
• Chronic Cancer Exposure Scenario - Evaluation of
  a individual lt 1 year to 33 years old. The
  exposure would be age-adjusted to incorporate the
  different exposure experiences (e.g., higher
  exposure as a child).

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Bioconcentration factors

• For some types of hazards bioconcentration is
  important in human health and ecosystem exposure.
• E.g. The bioconcentration of DDT in fish tissue
  is very important in determining the risk of DDT
  to eagles and other fish eating animals.
• E.g. The bioconcentration of methyl mercury in
  fish tissue is important in determining the
  ecological in human health risks of mercury.
• Factor (conc. in fish tissue)/ (conc. in
  water)

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Bio concentration in fish tissue (concentration
relative to the concentration in water)
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3. Dose response

• Non linear response for non carcinogens.
• At concentrations below the threshold excretion
  or detoxification is equal to or greater than
  intake rate.
• Linear response for carcinogens.
• E.g. No threshold level. Any concentration is
  assumed to increase risk.

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Dose Estimates Toxic Effects(from lab or
epidemiological data)

• NOAEL -- No observed adverse effect level
  highest data point at which no observed
  adverse/toxic effect.
• LOAEL -- Low observed adverse effect level
  lowest point at which an observed effect.

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Reference Doses for Noncarcinogenic Response

• Definition of RfD
• Reference dose RfD the maximum daily dose of a
  compound (mg/kg/day) to which even the most
  sensitive members of a population can be exposed
  for a lifetime without adverse health effects.

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• RfD NOAEL/VF
• VF is an uncertainty factor (UF in IRIS),
  usually 10 or greater. IRIS also includes a
  modifying factor (MF VF2) for such factors as
  incomplete databases. Much of the time MF 1.

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Reference Doses for Noncarcinogenic Response
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Source of RfD values

• Integrated Risk Information System (IRIS)
  http//cfpub.epa.gov/ncea/iris/index.cfm?fuseactio
  niris.showSubstanceList
• Compare to ATSDR non-enforceable (guidance
  values) Minimal Risk Levels
• http//www.atsdr.cdc.gov/mrls.html

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Cancer Risk Dose ResponseLinear extrapolation of
excess cancer
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Cancer risk

• The linear model at low risk is quite
  conservative (most risk assessors consider it to
  be very protective).
• Textbook shows other models but we will not deal
  with them.

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4. Characterization of Risk b Carcinogenic Risk

• Risk at less that 10-2 is usually calculated
  using slope factor (potency factor, PF, in the
  book), which is derived from linear dose-response
  plots.
• Assume linear response with zero excess cancer
  only at zero exposure.
• PF SF (slope factor) can be called the
  plausible upper bound estimate of the probability
  of a response per unit intake of a chemical over
  a lifetime.

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Life-time excess risk for carcinogensRisk over
background

• Seek to reduce excess risk to less than 1 in
  10,000
• The usual goal is to attain excess risk of less
  than one in hundred thousand (10-5).
• Impossible to determine experimentally either
  from epidemiological or animal data.
• Population sizes too small.
• For some types cancer the the background
  incidence of cancers may already be quite high.
• Must extrapolate from animal or epidemiological
  data at much higher concentrations
• What functional relationship should be used?
• Usually use linear model.

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Carcinogenic response, Lifetime Avg. Daily Dose
(Fig. 14.5)
Potency slope
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Cancer Risk Plot (Cont.)

• The x-axis is called AD average daily dose.
  This is the same as the CDI chronic daily
  intake when expressed per unit body weight and
  applied over a lifetime. We can use the equation
  and correct for actual exposure
• Incremental lifetime risk (CDI)(PF)
• CDI mg/(kg)(d)
• For cancer risk this is the chronic daily intake
  for a life-time. It is adjusted based on the
  default exposure compared to life-time of 70 yr
  (365 days/yr.) used for the calculation of the PF
  slope. EPA default exposures given in Table
  14.4)

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EPA - Contact Rate default assumptions (Table
14.4)
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CDI, eqn. 14.7

• CDI (C x CR x EF x ED) /(BW) (AT)
• C concentration in soil, water, etc
• CR Contact rate, quantity of soil, water, etc.
  consumed. Also, called IR ingestion rate, L/d
  or mg/d, etc
• EF exposure frequency (days / year)
• ED exposure durations (years)
• AT Life-time contact x actual years
• (70 yr) (365 d/yr) 25,550 d
• BW body wt. in kg.

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Also can be written as
The second term corrects for the difference
between the assumed exposure and a lifetime
exposure (70 years, in days)
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In class exercises

• What is the cancer risk of arsenic at 5 ppm in
  soils on a residential site
• 5 ppm is the new (2006) SRV.
• Slope 1.5 per mg/(kg)(day) Note the per
  language. (From IRIS slope for solid ingestion)
• Daily intake ?
• Assume average daily dose of 100 mg of soils per
  day for a 70 kg adult

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Answer

• First calculate the dose (AD CDI) in mg/(kg)(d)
• (mg of As per kg of body weight)
• Concentration is mg of As/ kg of soil
• As C 5 mg/kg
• CR 100 mg/d of soil per day for and adult
• 100 mg/d of soil 1 x 10-4 kg of soil per day
• CDI (5)(1 x 10-4 ) (70) (350)(30)
  (70)(365) 
• CDI (7.1 X 10-6)(0 .410)
• CDI (3 x 10-6 )mg/(kg)(d)

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• Risk CDI x PF
• (PF is slope)
• (3 x 10-6 )1.5 4.5 x 10-6  ( This a
  ratio with no units)
• Below 10-5 so is OK.
• Note MPCA just lowered the SRV for As to 5 mg/kg
  based on non cancerous acute exposure for small
  children CDI x slope
• (well see this later)

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4. Risk Characterizationb. Noncancer Risk

• Risk f(dose response)(CDI - RfD)
• CDI Chronic daily intake (for chronic
  exposure).
• Book uses PF f(dose response)
• This is confusing because this not the cancer
  risk slope and the function is really not linear
• The CDI is also different. It is usually the
  chronic intake but it does not assume a lifetime
  exposure. Risk is generally not not assumed to
  increase with very, very long times. We will not
  correct for the difference in EF and a 365 day
  year (too small).
• For non cancerous contaminants the risk is zero
  if the CDI RfD.

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Risk management goal non cancer risk

• Reduce risk to zero
• CDI must not exceed the RfD
• Then the maximum allowable CDI is the RfD.
• 0 f(dose response)(CDI - RfD)
• when CDI RfD

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Reference concentration (RfC)

• Reference concentration
• RfC C when CDI RfD
• Risk assessors use RfC for values for soils but
  then can include an additional safety factor.
  See MPCA Soil Reference Values (SRV).
• Refer to MPCA-risk-assessment for soils Guidance
  Document on the course web site and associated
  Tier 2 Excel spreadsheet for SRVs.

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Relating CDI to concentrations in soil water and
air

• CDI (C x CR) /(BW )
• C concentration
• CR contact rate
• Mass or volume of exposure to medium per unit
  time. E.g. mg per day of soil ingestion intake.
• BW body weight

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Max. allowable C when CDI RfD

• RfD (C x CR) /(BW )
• If you what to calculate RfC
• RfD (RfC x CR)/BW
• Then
• RfC (RfD x BW)/CR

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In class exercise

• What is the upper limit for soil Cd concentration
  in soil that can be tolerated by a 20 kg child if
  the only intake of Cd is soil ingestion. Assume
  bioavailabilty in soils is the same as for a pure
  salt. (Bioavailability is a current area of
  study)
• Use the RfD value of 0.001 mg/kg/d (oral -
  in food, chronic) from IRIS
• Water RfD 1 E-4 mg/kg/d
• Calculate the max allowable concentration in
  soils.

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EPA - Contact Rate default assumptions (Table
14.4)
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Answer

• Assume Soil food
• RfD 0.001 mg/kg/d
• RfD (C x CR) /(BW )
• Assume CR 200 mg/d of soil
• RfC (RfD x BW)/CR
• Problem, CR is in mg of soil and we need
  results in concentration per kg of soil.
• CR 200 mg/d 2 x 10-4 kg/d

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• Then RfC 1 x 10-3mg/kg/d (20 kg)(2 x 10-4
  kg/d)
• 0.001mg/kg/d (C)(0.0002 kg/d)/(20kg)
• RfC 100 mg/kg
• MPCA SRV 25 mg/kg
• This includes reduction by an additional factor

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• Note To do a risk assessment for a site
  containing more than one toxic contaminant you
  must consider all of the contaminants.
• We will consider this later.

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In Class exercise

• Estimate the RfD for cyanide (CN-) used in the
  calculation of the current MCL for drinking
  water. MCL 200 ppb (Nerve damage or thyroid
  problems).
• Assume 20 kg child

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Answer

• RfD (C x CR) /(BW )
• C RfC MCL
• CR 2 L/d
• ((.2 mg/L)2 L/d)/ 20kg
• 0.020 mg/kg/d
• This is the value in IRIS

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Reference Concentrations (allowable limits) for
different exposure scenarios

• Different for different land use scenarios
  because the CR is different
• Residential use requires the lowest soil
  concentrations because the exposure is greatest .
  This is the unrestricted level of cleanup.

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Compare to cancer risk for As to non risk
assumptions

• Acute, 10 kg child, single dose
• Ingestion of a single 10 g bolus of soil
• ATSDR
• Provisional Oral Acute 0.005 mg/kg/day RfD
  
• UF 10 Gastro. Final 09/00
• Calculate
• Note day not needed for single dose
• (Mass of soil) (RfC)/BW RfD
• 10 g .010 kg
• (RfC) (BW)(RfD/(Mass of soil)
• ((10)(0.005))/0.01 5 mg/kg in soil
• Cancer risk is 4.5 x 10-6

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Compare Chronic Risk

• Assume soil intake for a child 200 mg/d of
• IRIS Chronic 0.0003 mg/kg/day
• (RfC) (BW)(RfD/(CR)
• ((10)(0.0003)/.0002 15 mg/kg of As in soil
• The 2006 residential SRV was set based on the
  acute exposure of a child.
• 5 mg/kg is an average soil concentration in
  Minnesota.
• Industrial land use yields 20 mg/kg based on
  cancer risk to workers

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Quantifying Non Cancer Risks when several
hazardous substances are present

• Noncancer hazard quotient for systemic toxic
  response
• HQ E/RfD
• where E exposure level (intake) CDI
• HQ is not a probability
• Hazard index HQ1 HQ2 . . . HQn
• If HQ gt 1, may be concern concern increases as
  HQ increases.
• Remediation usually seeks to reduce HI to less
  than 1 for each target organ. Also use HQ for
  systemic toxins.
• For most toxins MPCA uses 0.2 HQ for each
  element or compound.

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Alternative way to calculate HQ

• Also
• HQ C/RfC

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Risk for multiple toxins affecting the same organ

• Can treat this separately and add up the HQ
  values for each organ toxin.
• The MPCA Soil Reference Value worksheet limits
  most elements to HQ lt 0.2. Some like lead, HQ
  1
• The sum of HI for each organ toxin must must be lt
  1.0
• See Tier 2 SRV worksheet

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Quantify cancer risk when several hazardous
substances are present

• Sum the excess risk for all cancers
• Usually must be below 10-5

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Risk Assessment at Contaminated Sites

• Human health risk.
• Ecological risk.
• For major contaminated sites, e.g cleanup of
  National Priority List (NPL) (CERCLA) sites,
  both types of a risk assessment must be done.
  NPL sites are Super Fund sites (e.g. TCAAP).

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Risk Assessment at Contaminated Sites (cont.)

• Exposure assessment and risk characterization
  elements of traditional risk assessment are
  expanded and hazard identification is contracted
  
• 1. Data Collection
• 2. Data Evaluation
• 3. Exposure Assessment
• 4. Toxicity Assessment
• 5. Risk Characterization
• This is an example of of risk based assessment
  for Risk Based Corrective Action (RBCA).

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Risk Assessment at Contaminated Sites (cont.)

• Hazard identification and dose/response data
  mostly from existing data.
• Exposure assessment uses different scenarios for
  land use.
• Toxicity assessment done to get the most current
  data and guidance.
• Likely do not need new data for human health risk
  but may need new data for ecological risk (eco
  risk is not as well understood)

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Risk Assessment at Contaminated Sites (cont.)

• For any chemical risk to exist three elements
  must be present
• A chemical source exceeding safe exposure
  concentrations
• A completed pathway for the chemical to enter a
  receptor and
• A human or ecological receptor available for
  chemical contact.
• If any one of these elements is absent, exposure
  pathways are incomplete and there is no risk.

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1. Data Collection

• Sampling of environmental media
• Goal is to characterize contaminants, exposures,
  and exposed populations, and to determine which
  risks need to be eliminated (develop a list of
  contaminants of concern (COCs))
• For contaminants that are also found in nature
  (e.g. metals) the preliminary list of COCs
  usually includes all found above background in
  the area.
• Want data that can be used to assess risk with a
  known degree of confidence.

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2. Data Evaluation

• What contamination is present, and at what
  levels?
• Are site concentrations sufficiently different
  from background?
• Are all exposure pathways identified?
• Are all pathways fully characterized?

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3. Exposure Assessment

• Exposure assessment aims to estimate the COCs
  present or migrating from a site.
• Include an estimate of reasonable maximum
  exposure the highest exposure that is
  reasonably expected to occur at a site - for the
  most vulnerable receptors.
• E.g. Hg - fetuses and small children Al in acid
  lake water - fish fry.

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Pathway Processes

• Transport (movement within a particular medium
  air, water, soil)
• Transformation (any process that changes the
  physical or chemical structure of a compound
• Cross-media transfer

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3. Quantifying Exposure

• Exposure concentrations
• Monitoring data (current locations at specific
  points)
• Modeling (future or distant concentrations)
• E.G. BIOSCREEN
• Other considerations (e.g., steady-state vs.
  non-steady, or number and type of fate processes)
• Chemical intake (mass per unit body weight)
• exposure scenario
• mode of contact

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Exposure to contaminated soils

• Direct risk by dermal contact, inhalation, and
  ingestion.
• See the MPCA-risk-assessment for soils Guidance
  Document on the course web site and associated
  Tier 2 Soil risk Excel spreadsheet. (Soil
  Reference Values)
• Leaching of mobile contaminants to ground water.
• Define Soil Leaching Values
• Concentration limits for risk to ground water

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4. Toxicity Assessment

• Gather toxicity information
• Identify exposure periods
• Determine toxicity values (slopes) for
  carcinogens
• Determine RfD values for non carcinogens
• Summarize toxicity information

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5. Risk Characterization

• Gather and integrate exposure and toxicity
  information
• Quantify pathway risks
• Combine pathway risks (multiple chemicals)
• Summarize and present risks
• Report HQ values and excess cancer risk.

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Summarize Present Results

• Place the estimates of risk in context with what
  is known and/or unknown about site
• Describe exposed population
• Describe uncertainties and confidence in results
• Describe major factors driving site risks e.g.,
  substances, pathways

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Risk Management at Contaminated Site

• Define remedial goals (RG values) to reduce
  concentration of COCs such that
• risk of excess cancer is in the range of 10-5 to
  10-6.
• Limit the Hazard Index for non carcinogens (by
  target organ) to lt1
• See the MPCA-risk-assessment for soils Guidance
  Document on the course web site and associated
  Tier 2 soil Excel spreadsheet.
• For MPCA SRV for residential scenario HQ values
  are mostly limited to lt 0.2. (extra safety
  factor)

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Risk Management at Contaminated Site (cont.)

• Because of different exposure scenarios RG values
  are lower for residential land (unrestricted) use
  compared to industrial land use
• For many contaminants in ground water the cleanup
  goals are defined by the maximum contaminant
  levels (MCL) in the Clean Water Act or State
  Health Risk Levels (HRL).

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Process of Ecological Risk Assessment, Fig. 14-8
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Stressor and Endpoints

• Stressor - the toxin or other stress on the
  system
• E.g. Cd, phosphate, or heat load in stream from a
  power plant.
• Endpoints.
• Assessment Endpoints- defined by assessment of
  health of the system.
• Measurement endpoints.
• Quantitative data
• From knowledge of exposure assessment
• May requires phyolgenetic extrapolation to
  transfer toxicity data form on e species to
  another

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Summary

• Steps for traditional risk assessment
• 1. Hazard identification
• 2. Exposure assessment
• 3. Dose/response assessment
• 4. Risk characterization
• The results of risk assessment can be used for
  risk management.
• Eg. to decide on cleanup goals.

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• Characterization of non cancerous risk is in
  relation to a reference dose. Any dose greater
  than the RfD produces risk.
• Characterization of cancer risk does not involve
  a threshold. Risk is only zero at zero dose.
• Dose response usually linear (use slope factor)
• Risk is calculated as excess lifetime risk with
  respect background.
• Want to reduce excess risk to 10-5 or smaller.

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• For major environmental contamination sites both
  both ecological risk and human risk must be
  considered.
• Define remedial goals to
• Reduce reduce non-cancerous risk to a value of
• Hazard Index lt 1 (might be limited to organ
  toxicity)
• Reduce life time excess cancer risk to less
  that 10-5
• Some concentration goals defined in rules. like
  MCL values in water and lead in soil.

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Daily assignment for Wed. Oct 17

• Assuming a 10 kg child and the EPA reference dose
  for oral Cd (see IRIS-EPA web site on links
  page), a hazard quotient for soil Cd of 1 and
  the EPA default consumption rate, what is a safe
  limit for the concentration of Cd in water based
  on non cancer risk.

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Non cancer Answer

• RfD 5 E-4 mg/kg-day
• Assuming a HQ of 1, max. dose is 5 x 10-4
  mg/kg-day.
• For a 10 kg child this is
• (10kg)5 x 10-4 mg/kg-day 5 x 10-3mg/day
• Mass of soil 200 mg/d 2 x 10-4 kg/d
• Allowed soils Conc. (5 x 10-3mg/day)/2 x 10-4
  kg/d
• 25 mg/kg

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Daily assignment for Wed Oct 18.

• 7 contaminants were found in soilsbrownfields
  site. Antimony 12 mg/kg, Cd 20 mg/kg, Cu
  550, Selenium 150, Thallium 2.5, tin 7000
  and Naphthalene 9. Assuming this site will be
  used for houses in the future, will cleanup be
  needed. The decision will be made based on the
  Hazard Index (HI values for ) for each individual
  element or organ system . Use the SRV work sheet.
  Justify

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Answer

• FIX this.
• RfD 5E-4 mg/kg-day
• Cd Soil conc. 20 mg/kg
• Mass of soil ingested 200 mg/d .0002 kg/d
• Dose of V (500mg/kg)(.0002 kg/d)/10kg
• 0.01 mg/kg/d
• HQ 0.01/.009 1.11
• Sb
• RfD 4E-4 mg/kg-day
• Dose of Sb (100mg/kg)(.0002 kg/d)/10kg
• 0.002 mg/kg/d
• HQ 0.002/.0004 5

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Daily assignment for wed. Oct. 15

• An epidemiological study of workers exposed to 20
  mg of compound X per day for 25 years produced a
  frequency of pancreatic cancer of I in 100. What
  is the daily exposure for the same length of
  length of time that will increase the existing
  incidence of a cancer by 1 in a million. Assume
  a linear response as for the graph in the
  lecture. Hint first draw the response graph and
  write an equation for the line. Then solve for
  1 x 10-6 incidence.

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