Transcript Risk Assessment for Air Toxics

Risk Assessment for Air
Toxics: The 4 Basic Steps
NESCAUM Health Effects Workshop
Bordentown, NJ
July 30, 2008
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The Air Toxics Risk Assessment Process
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The General Four Step Risk Assessment Process
Risk Assessment
1. Exposure
Assessment
Risk Management
Statutory and legal
Considerations
Public Health
Considerations
4. Risk
Characterization
Toxicity Assessment
2. Hazard ID
3. Dose-Response
Assessment
Social
Factors
Risk Management
Decision
Risk
Management
Options
Economic
Factors
Political
Considerations
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The General Air Toxics Risk Assessment Process
Planning and Scoping
Exposure Assessment
Toxicity Assessment
Is a chemical
toxic?
Who is exposed?
What chemicals are they exposed to?
How does the exposure occur?
What is the
relationship
between the dose
of a chemical
and the response
that results?
Risk Characterization
What is the likelihood that the exposure will result in
an adverse health effect?
How sure are we our answers are correct?
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The Detailed Air Toxics Risk Assessment Process
Planning and Scoping
Exposure Assessment
Toxicity Assessment
FATE AND TRANSPORT ANALYSIS
Hazard Identification
SOURCE IDENTIFICATION
Chemical
Release
Measures of
Exposure
SOURCES
CHEMICAL
CONCENTRATIONS
Air, Soil, Water, Food
(monitor/model)
POPULATION CHARACTERISTICS
Dose/
Response
Assessment
Y
X
Risk Characterization
EXPOSURE
information
DOSE/RESPONSE
information
Quantitative and Qualitative Expressions of Risk/Uncertainty
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Toxicity Assessment Focus
Planning and Scoping
Exposure Assessment
Toxicity Assessment
Hazard Identification
Dose/
Response
Assessment
Y
X
Risk Characterization
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Step A - Hazard Identification
• Is exposure to a
chemical causally
linked to particular
health effects?
• Is the effect of
practical significance?
• What is the nature and
strength of the
evidence of
causation?
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Hazard ID can consider both….
Biological Effects
• Lethality (LD50, LC50)
• Impairment of normal
biological function
(e.g., liver damage)
• Heritable genetic
change
• Increases/decreases in
species population size
or range
• Health/productivity of
ecosystems
• Etc.
Non-Biological Effects
•
•
•
Reduced visibility from
airborne particulates
Damage to historic
structures by air
pollutants
Climate change from
global warming
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Numerous Biologic Endpoints
Cancer
Non-Cancer

Multiple Adverse Endpoints
• Mutations
• DNA damage
• Etc.
 Uncontrolled
Growth of Cells
Interaction with
HAP
• Reproductive,developme
ntal, neurological
disorders
• Immunologic effects
• Acute effects (edema,
CNS depression)
• Various other systemic
effects (e.g., liver,
kidney, lung damage)
NASA Graphic
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Hazard Identification
Where do we get our information?
Data on adverse biologic effects
usually generated through…
• Epidemiological studies
• In-vitro assays (i.e., test
tube)
Human
Epidemiological
Studies
• In vivo biologic assays
• Structure-activity
relationships (SAR)
Laboratory Animal
Experiments
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Step B – Dose/Response Assessment
• Now that we’ve
established that a
chemical is toxic…
• We need to understand
how much dose gives
how much response
(how potent is the
chemical?)
• Some of our Hazard ID
information may help
us answer that
question
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Dose-Response Curves
• Response patterns show how the compound
affects exposed organisms
• Patterns can differ from one health endpoint
to another
• Patterns can differ between populations (e.g.
animals to humans, different life stages)
R
R
D
D
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Dose-Response - Noncancer
EPA assumes…
• There is a threshold below which no observable
adverse effect will occur (there is a toxicity threshold)
• We usually don’t know exactly where that point is
from our lab animal data, so…
• We use our animal data, in conjunction with a series
of uncertainty factors, to estimate a “safe” or
“reference” exposure for humans
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% Animals Responding
Dose-Response - Noncancer
Liver Toxicity
(Critical Effect)
Tremors
Apply
Uncertainty
Factors
Enzyme
Change
Weight Decrease
Human
RfC
NOEL
NOAEL
LOAEL
Concentration
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= Observed Animal Data
Inhalation RFC
NOAEL or LOAEL ( HEC)
RfC (mg/m ) 
UF 1 x UF 2 ... x UFi
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Uncertainty Factor Criteria
• Extrapolating from animal data
• Sensitive human populations
• Subchronic NOAEL instead of
chronic NOAEL
• LOAEL used instead of NOAEL
• Uncertainties in the database for
the chemical
UF
10, 3, or 1
10, 3, or 1
10, 3, or 1
10, 3, or 1
10, 3, or 1
*HEC = human equivalent concentration
**RfD (Oral) calculated similarly (usually in mg/kg-d)
***Some RfCs developed in the past may have employed a
modifying factor (MF) to account for overall quality of the tox
database
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Dose-Response - Cancer
Unless we have data that indicates otherwise,
we assume …
• There is no exposure which is without cancer risk
(a non-threshold response)
• Even very low doses are not risk free
• We know the lowest exposure from our lab animal
experiments, but how do we extrapolate to the
very low concentrations people are more likely to
experience?
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Response (Tumor or Nontumor Data)
Dose-Response - Cancer
Upper 95%
Confidence
Limit on Dose
Potency = the slope of
the linear default line
x
Empirical
Range of
Observation
Environmental
Exposure Levels
Of Interest
Central
Estimate
x
10%
Linear
Default
Range of
Extrapolation
0%
LEC10
EC10
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Exposure Concentration
Inhalation Unit Risk
IUR (risk per ug/m3) =
Slope of the line from the
point of departure to zero
• The IUR is the unitless upper bound estimate
of the probability of tumor formation per unit
concentration of chemical
• Measures of potency for ingestion are
developed in a similar fashion, but are…
• In units of (risk per mg/kg-d)
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In Summary …
Cancer Risk
• Nonthreshold
(generally)
• Slope Factors
• Inhalation Unit
Risk
• Oral Potency
Factor
Non-Cancer Hazard
• Threshold
(generally)
• Reference Values
• RfC (inhalation)
• RfD (oral)
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Sources of Toxicity Data
There are many choices
•
•
•
•
•
•
•
EPA IRIS database
California Hotspots program
ATSDR MRLs
NCEA provisional values
EPA HEAST
Open literature
Etc.
Which value should we use?
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Sources of Toxicity Data
For air toxics risk assessments…
OAQPS has developed and
maintains a list of
recommended chronic toxicity
values for each of the HAPs
• Inhalation IURs and RfCs
• Oral slope factors and RfDs
http://www.epa.gov/ttn/atw/toxsource/summary.html
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The General Risk Assessment Process
Let’s restate this 4-step process with a
simple mathematical formula…
RISK =
f [(Measure of Exposure), (Measure of Toxicity)]
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The Risk Assessment Continuum:
Tiered Approaches to the Process
Complete study-specific data, no assumptions; higher cost, lower uncertainty
Add uncertainty/variability analysis
More refined exposure assessment
More refined dispersion & exposure modeling
Simple dispersion model
Lookup Table
No data, all assumptions; lower cost, high uncertainty
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The General Four Step Risk Assessment Process
Risk Assessment
1. Exposure
Assessment
Risk Management
Statutory and legal
Considerations
Public Health
Considerations
4. Risk
Characterization
Toxicity Assessment
2. Hazard ID
3. Dose-Response
Assessment
Social
Factors
Risk Management
Decision
Risk
Management
Options
Economic
Factors
Political
Considerations
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Questions?
• Contact
Heidi Hales
VT DEC/NESCAUM
[email protected]
802-241-3848
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