Biomonitoring: Uncertainties and Future Research Directions Linda Sheldon, PhD, Marsha Morgan, PhD and Jon Sobus, PhD National Exposure Research Laboratory, RTP, NC Photo image area measures 2” H x 6.93” W and can be masked by a collage strip of one, two or three images. The photo image area is located 3.19” from left and 3.81” from top of page. Each image used in collage should be reduced or cropped to a maximum of 2” high, stroked with a 1.5 pt white frame and positioned edge-to-edge with accompanying images. Office of Research and Development April 16, 2009 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Title Master to change>
Why biomonitoring? The Present: – Many chemicals measurable at trace levels – Readily available, high quality data (e.g., NHANES) But How do we use it ? – A coordinated research program is needed The Potential: Biomonitoring can provide us with: – A running log of past exposures – An indication of future health effects – A means to identify and minimize risk Office of Research and Development 1 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
Key Questions for Public Health Protection Is there a risk? ? Health Effects Exposures How do we reduce risk? Exposure-Effect Continuum Office of Research and Development 2 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
Biomonitoring Key link between exposures and health effects Biomarkers Health Effects Exposures But currently we have few models or approaches to interpret/link data to understand risk Office of Research and Development 3 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
What can we do now? 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? United States Environmental Protection Agency Office of Research and Development 4 Office of Research and Development | Full Name of Lab, Center, Office, Division or Staff goes here. <Click here to change> Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
(CTEPP study) Children 120 100 Exposure and 80 ng/kg/day Biomonitoring data 60 40 • Answers a lot more questions about 20 exposure and potential health risks: 0 – What are we exposed to? Aggregate intake Excreted – Who is exposed? of Bisphenol-A Bisphenol-A – Where does exposure occur? 8% 1% – When does exposure occur? 1% Dietary – How does exposure occur? Indirect – Why are people affected differently? Inhalation Dermal 90% Major Route: Dietary Ingestion Major Source: Solid Food Office of Research and Development 5 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
Uncertainties and data gaps – both understanding processes and the linkages models ? Health Effects Exposures Biomarkers exposure data toxicokinetic data biomarker data toxicodynamic data Office of Research and Development 6 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
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 Office of Research and Development 7 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
c5 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) Office of Research and Development 8 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
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
c1 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 Office of Research and Development 9 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
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
Biomarker Monitoring Approaches • Issue – Biomarker concentrations vary with time, need to account for that 1.00E-06 3 8.00E-07 icrog/L) icrog/h) 2 6.00E-07 onc (m (m 4.00E-07 ER 1 U C 2.00E-07 0.00E+00 0 0 20 40 60 80 100 • Needs time (h) – 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 Office of Research and Development 10 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
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) Office of Research and Development 11 Full Name of Lab, Center, Office, Division or Staff goes here. <Go to View, Master, Slide Master to change>
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