Biomonitoring: Uncertainties and Future Research Directions Linda - - PowerPoint PPT Presentation

April 16, 2009

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Linda Sheldon, PhD, Marsha Morgan, PhD and Jon Sobus, PhD National Exposure Research Laboratory, RTP, NC

Biomonitoring: Uncertainties and Future Research Directions

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Biomonitoring can provide us with:

– A running log of past exposures – An indication of future health effects – A means to identify and minimize risk

Why biomonitoring?

– Many chemicals measurable at trace levels – Readily available, high quality data (e.g., NHANES)

The Potential: The Present: But How do we use it ?

– A coordinated research program is needed

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Key Questions for Public Health Protection

Exposures Health Effects

?

How do we reduce risk? Is there a risk?

Exposure-Effect Continuum

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Exposures Health Effects But currently we have few models or approaches to interpret/link data to understand risk Key link between exposures and health effects

Biomonitoring

Biomarkers

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Biomonitoring data (only)

• Surveillance tool
• Identifies trends over time
• Answers question about exposure:

– What are we exposed to? – Who is exposed?

• Does not answer all questions:

– Where does exposure occur? – When does exposure occur? – How does exposure occur? – Why are people affected differently?

What can we do now?

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20 40 60 80 100 120

Aggregate intake

• f Bisphenol-A

Excreted Bisphenol-A

Exposure and Biomonitoring data

ng/kg/day

90% 8% 1% 1%

Major Route: Dietary Ingestion Major Source: Solid Food (CTEPP study)

Children

• Answers a lot more questions about

exposure and potential health risks: – What are we exposed to? – Who is exposed? – Where does exposure occur? – When does exposure occur? – How does exposure occur? – Why are people affected differently?

Dietary Indirect Inhalation Dermal

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Uncertainties and data gaps – both understanding processes and the linkages exposure data

Exposures

?

Health Effects Biomarkers

biomarker data toxicokinetic data models toxicodynamic data

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Exposure data

• Needs

– Source data (allows us to identify major sources of chemical exposure)

• Data on activities and product use
• Levels of chemicals and their degradates in environmental media

(e.g., air, water, food, soil, and dust)

• Temporal variability of environmental levels of chemicals

– Route data (allows us to identify important routes of exposure)

• Intake of chemicals and their degradates by the inhalation, ingestion,

and dermal routes

– Human activity pattern data (allows us to estimate frequency, magnitude and duration of exposure)

• Timing, duration, and frequency of human contact
• Limitations (must have linked exposure/biomonitoring studies)

– Too few exposure data are available in biomonitoring studies (e.g., NHANES) – Few standardized collection methods exist for exposure data comparisons

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Toxicokinetic and Toxicodynamic Data

• Needs

– Rate data:

• absorption, distribution, metabolism, and elimination
• interperson and intraperson variability
• route-specific rate estimates (i.e., dermal, inhalation, ingestion)

– Dose models:

• Toxicokinetic models
• Physiologically-based toxicokinetic models

– Dose-response models:

• Toxicodynamic models
• Physiologically-based toxicodynamic models
• Limitations

– Few dose/dose-response models exist – Dependence on animal data (interspecies uncertainty)

c5

Slide 9 c5 Linda: We have shown in the biomonitoring chapter that few biomarkers meet these critieria (based on the NHANES data). You may want to address this current limitation here.

ctsuser, 3/10/2009

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Biomarkers

• Needs

– Good biomarkers

• Sensitivity: vary with respect to exposure
• Specificity: reflect exposure to a specific chemical and a specific scenario
• Validity: indicate an underlying exposure event
• Biological relevance: relate to the potential health effect or linked sets fo

biomarkers

• Practicality: easy to obtain, store and analyze

– Data on temporal variability

• Changes in biomarker levels over time

– Metabolite profiles in biological media

• Limitations

– Few biomarkers meet all of these criteria

c1

Slide 10 c1 Linda: We have shown in the biomonitoring chapter that few biomarkers meet these critieria (based on the NHANES data). You may want to address this current limitation here.

ctsuser, 3/10/2009

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Biomarker Monitoring Approaches

• Issue – Biomarker concentrations vary with time, need to account for that
• Needs

– Understand variability in exposure and biomarker measurements – Reliable sampling methods - estimate urinary output not just concentrations

• Limittations

– Few data on the variability of chemicals and their degradates in biological media – Few standard collection protocols exist for biomonitoring data comparisons

0.00E+00 2.00E-07 4.00E-07 6.00E-07 8.00E-07 1.00E-06 20 40 60 80 100 time (h) U ER (m icrog/h) 1 2 3 C

• nc (m

icrog/L)

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Future Research Directions

• Incorporate biomonitoring into Risk Assessment/Risk Management

framework

• Refine predictive exposure and dose models
• Conduct linked exposure-biomarker studies
• Develop ‘gold standard’ biomarkers
• Understand temporal variability of biomarkers
• Validate useful surrogate biomarkers
• Identify key variables to improve the interpretation & use of

biomonitoring data (e.g., NHANES)