Exposure Assessment, George Gray

Center for Risk Science and Public Health

Exposure Assessment

George Gray

Center for Risk Science and Public Health Department of Environmental and Occupational Health

Milken Institute School of Public Health


Exposure and Risk

•  “Exposure” is used to describe the extent of contact with the proposed causative agent (or its proxy) in a risk relationship

•  Examples

Risk Exposure Measure Lung cancer from cigarette smoking

Pack-years of exposure

Automobile road fatalities Vehicle Miles Traveled (VMT)

Workplace injuries Working days


Critical Point – Exposure Measure Units

•  Exposure needs to be measured or modeled in units that match with risk relationship

•  Good: Exposure = Tcp = annual minutes on phone while driving

•  Bad: Incremental Cancer Risk = Cancer Slope Factor (mg/kg/day)-1 x Ingestion (mg/kg/day)

Exposure = ppm benzene in air

Cohen, JT and Graham, JD (2003) A Revised Economic Analysis of Restrictions on the Use of Cell Phones While Driving. Risk Analysis 23: 5-17


The Risk Assessment Paradigm

Exposure Assessment asks the questions:

•  To how much of the substance of concern are people exposed?

•  What are the sources of exposure?

•  What are the pathways of exposure?

•  What is the appropriate measure of dose?


Exposed Populations

•  Individuals •  Populations •  Sensitive Subpopulations


Exposure Assessment


Exposure Media and Routes

Air

Soil

Water

Diet

Ingestion

Inhalation

Dermal Contact


Exposure Pathways

•  Examples (not exhaustive!): •  Ingestion of soil, water, food, or particles •  Inhalation of air or particles •  Dermal contact with soil, sediment, water or air

Air

Soil

Water

Diet

Ingestion

Inhalation

Dermal Contact


Making Equivalent Doses

X

X X X X

X

500 mg Drug X

Mouse = 0.07 kg Human = 70 kg

500 mg/0.07 kg = 7,143 mg/kg 500 mg/70 kg = 7.143 mg/kg

7,143 mg/kg Drug X

mg/kg is common way to make doses equivalent across species


ADD: average daily dose C: concentration IR: intake rate T: time (duration of exposure) AF: absorption (bioavailability) factor BW: body weight AT: averaging time Units: typically mg pollutant /kgbody weight /d

Generic Average Daily Dose Equation


Aggregate Exposure

•  Sometimes there may be several sources of exposure to a single compound

•  Ex/ Benzene in air •  Workplace •  Automobile refueling and driving (gasoline) •  Personal habits (cigarette smoke)

•  Which belong in (or out) depend on the scope of RIA and options considered


Exposure Assessment

Exposures can be either measured or modeled (or combination of the two)

•  Measured •  more precise (sampling!) •  more expensive, not always methods •  can’t be used to predict future risk

•  Modeled •  estimate concentrations, exposures or doses •  require many assumptions •  models imprecise and rarely validated •  allow better incorporation of time in exposure

estimates


Estimating Exposure: Pesticide Residues on Food

•  Goal is understanding of amount of pesticides “on the dinner plate”

•  3 Ways used to estimate pesticide residues on food •  theoretical maximum residue contribution •  farm gate data •  residue monitoring

•  Residue estimates combined with consumption data to estimate exposure


Theoretical Maximum Residue Contribution

•  Assume every acre of a crop has pesticide at maximum allowable level (tolerance level)

•  Assume level does not decrease with time, processing, storage, or cooking

•  Considered upper bound on true level of consumer exposure to pesticide residue on food


Farm Gate Data

•  Derived from field trials of pesticide use •  Measure level of pesticide on crop at

“farm gate” - after treatment at highest allowable level with minimum preharvest interval

•  May be adjusted with experimentally determined processing, washing, or cooking factors and estimates of percentage of crop treated


Residue Monitoring

•  Based on measurements of pesticide residues on food as purchased at grocery store

•  Reflects normal preparation (washing, cooking, etc.)

•  Reflects actual agricultural practices such as pesticide application rates, different preharvest intervals, and the effects of time and storage


Does The Choice Matter?

Example: Chlorothalonil (Bravo®) on Celery

chlorothalonil (ppm) % of tolerance •  TMRC 15.0 100.0

•  Field Data 4.1 27.1

•  Residue Monitoring 0.8 0.12

Source: Gary L. Eilrich (1991) Tracking the Fate of Residues from the Farm Gate to the Table, in Pesticides and Food Safety (Tweedy, B.G., Dishburger, H.J., Ballantine, L.G., and McCarthy, J. eds.) American Chemical Society, Washington, D.C.


Quantitative Approaches

•  Point Estimates (for either individuals or populations)

•  Central Tendency

•  Extrema (“Reasonable Maximally Exposed”)

•  Bounding Point Estimates

•  Interval Estimates

•  Distributional Estimates


Point Estimation

•  Example: Inhalation of fine particulate matter (PM) in ambient air for a city of 1M •  Ambient concentration: 50 µg/m3

•  Average inhalation rate: 15 m3/d •  Average body weight: 70 kg

•  Average daily dose (ADD): 10.7 µg/kg/d


Interval Estimation

•  Same Example:

•  Ambient concentration: 50 µg/m3

•  Inhalation rate range: 2 m3/d – 44 m3/d •  Body weight range: 1 kg - 650 kg

•  Minimum Possible Dose: 0.2 µg/kg/d •  Maximum Possible Dose: 2,200 µg/kg/d •  Dose based on midpoints: 3.5 µg/kg/d

•  Now What?


Uncertainty & Variability

•  Variability •  “…represents heterogeneity or diversity in a well-

characterized population which is usually not reducible through further measurement or study.”

•  Uncertainty •  “…represents ignorance about a poorly characterized

phenomenon which is sometimes reducible through further measurement or study.”


Distribution of Body Weight


Distribution of Inhalation Rate


Distributional Approach

•  Same Example:

•  Treat BW, InhR as variable •  BW ~ LogNormal(mean = 70kg, GSD = 1.29) •  InhR ~ LogNormal(mean = 15m3/d, GSD = 1.9)


Distributional Result (n=1000)

Median = 7.8

Mean = 10.0

95%ile = 26.2


Standardized Exposure Factors

•  Examine a regulatory risk assessment and you will find a large set of standardized assumptions for estimating exposure. •  Body weight: 70 kg •  Lifetime: 75 yrs •  Daily breathing rate: 20 m3/d •  Water intake: 2 L/d

•  Why do these exist? •  Is the use of these factors good or bad?


Final Thoughts

•  To be useful, an estimate of exposure or any other element of a risk assessment requires a description of uncertainty •  “Usually, exposure assessments will contain less

uncertainty than other steps in a risk assessment, especially the dose response portion” -- Dennis Paustenbach, Human and Ecological Risk Assessment

•  Precision required of exposure estimates depends on precision required in output (risk estimate) and the precision available in other inputs.

Exposure Assessment, George Gray

Government & Nonprofit

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