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2. Emerging Issues in Industrial Hygiene – The Impact of Biomonitoring Data Sol Bobst, PhD Senior Scientist Center for Toxicology & Mechanistic Biology EXPONENT, Inc. Houston, Texas sbobst@exponent.com Tel: 832-325-5714 GSM: 281-686-6363 FAX: 832-325-5799

3. Biomonitoring Overview • What is it? • Intended Uses • Interpretation • TLV / BEI Evaluation Process • Resources • Acknowledgements

4. What is Biomonitoring? • “Biomonitoring,” is defined in the environmental public health field as the assessment of human exposure to an environmental chemical via the measurement of that chemical, its metabolites, or reaction product(s) in human blood, milk, urine, saliva, adipose, or other tissue in individuals (in a population). Needham: Int J Hyg Env Health, 2006

5. Why is it important to the Practice of Industrial Hygiene? • Identification • Evaluation • Control

6. Current Consensus • Biomonitoring Data are being generated and published faster than regulators and professionals can analyze and interpret them. • There is a need for well defined guidelines for interpreting biomonitoring data. • There is a need to understand how biomonitoring data should be utilized in a risk evaluation framework for regulators and industrial stakeholders. • There is a need to clearly communicate that biomonitoring data do not substantiate a human health risk and disease.

7. Intended Uses for Biomonitoring • Provide a metric of exposure for use in risk assessment. • Monitor/Idenitfy exposure trends within a population. • Use available tools to provide the basis for more effective design of approved studies / risk assessments.

8. Use in Risk Assessment • Establish & Characterize Exposure / Trends. • Investigate “linkages” between exposure and adverse health effects. • Facilitate Risk Management. • ECOTOC Document 44, November 2005

9. The Challenge • The Production of Biomonitoring Data, or utility of a Biomonitoring Study, often does not address all of the requirements for rigorous and effective risk evaluation. • What does the data mean? How is it useful? What is inappropriate interpretation?

10. Issues in Biomonitoring • Data Quality • Interpretation • Ethics • Transperency • Biomonitoring vs. Biomarkers

11. Data Quality • Requirements – Must address intended use, but also evaluate potential use • Methodology, Study Design, Calibrations • Technical Quality

12. Interpretation of Biomonitoring • Analytical Integrity • Standardized Methodology, • (local vs. international standards) • Recovery, Reproducibility • Accounting for false positives/contamination

13. Ability to Describe Exposure Requires Toxicokinetics • Routes of Exposure • Endogenous Contribution • Pharmacokinetics/Pharmacodynamics of Absorption, Distribution, Metabolism, Excretion • Genotoxic Effects • Forward or Reverse Extrapolation of Dose

14. Exposure – Effect Continuum

15. Benefits of Including Biomonitoring Evaluation into Industrial HSE Policy • Enhance Risk Management. • Case by Case evaluation of chemical specific Biomonitoring can result in effective guidance for data development of: • Animal testing • Methodologies for assessing human exposure • IH sampling. • Save Time, Resources, Money.

16. Shift in Focus • From External Exposure Concentrations to Internal Dose Estimation. • Future Regulatory Decisions may set exposure guidelines (EPA, OSHA, TCEQ) based on BEI(s), or Biomonitoring / Biomarker indices.

17. Biomonitoring Interpretation in Industrial Hygiene • ACGIH • Process for Evaluating TLV/BEI • Opportunity for Involvement • http://www.acgih.org/TLV/

18. Interpretation • Define Limitations • Example – One Person – One Blood Sample – One Test!!!!! • NHANES Study, CDC • Account for Variability – Population Context • Age, Gender, Sample Volume, Geographical Location of Sample

19. Biomarker Evaluation is an Important Step in Interpreting Biomonitoring Data • Biomarker vs. Biomonitoring Data • Biomonitoring: Arsenic in Hair (Chemical in Fluid/Tissue/Matrix) • Biomarker: DNA Adduct (Metric of Metabolism / Biological Mechanism) • Measure of Chemical Metabolite in Biological Fluid/Tissue. • Accurate Metric for Understanding External Exposure.

20. Biomarker Evaluation is an Important Stepin Interpreting Biomonitoring Data

21. Feedback • What Concerns or Issues in Biomonitoring are important to you?

22. Public Resources for Biomonitoring • ECOTOC Report • NAS Report • Other

23. ECETOC Report(European Centre for Ecotoxicology & Toxicology of Chemicals) • Guidance for the Interpretation of Biomonitoring Data, Document No. 44, Brussels, November 2005. • Establishes Framework for evaluating biomonitoring data for risk assessment. • More Detailed Guidelines on Interpretation • Examples: Parabens, Hexachlorobutadiene

24. NAS Report • Human Biomonitoring for Environmental Chemicals (NRC – NAS 2006). • Conclusions: • There is a need for a consistent rationale for selecting chemicals for study based on exposure and public-health concerns. • Appropriate Statistical Principles Need to be Applied when sampling populations. • Recommend that biomonitoring program sponsors require planning for communication and evaluation. for any applied use.

25. Other • Biomonitoring.info – Environmental Health Research Foundation http://biomonitoringinfo.org/ • CDC – National Biomonitoring Program: http://www.cdc.gov/biomonitoring/

26. Acknowledgements • Exponent Biomonitoring Team • Angelina Duggan • Elizabeth Anderson • Ben Thomas • Louis Bloemen • Sanjeev Saraf • Martin Barrie

27. References • Guidance for the Interpretation of Biomonitoring Data, Document No. 44, Brussels, November 2005, ECOTOC. • Needham, Calafat, Barr “Uses and issues in biomonitoring” Int J Hyg Environ Health 2007 May;210(3-4):229-38. Epub 2006 Dec 8. • Albertini , Bird , Doerrer, Needham, Robison, Sheldon, Zenick. “The use of biomonitoring data in exposure and human health risk assessments.”Environ Health Perspect. 2006 Nov;114(11):1755-62. • Doerrer “Integration of human biomonitoring exposure data into risk assessment: HSEI intiatives and perspectives Int J Hyg Environ Health 2007 210; 247-251

28. Report Website Links • NAS Biomonitoring Report - http://books.nap.edu/openbook.php?isbn=0309102723 • ECETOC Report -http://www.ecetoc.org/docsharenoframe/netservices/documents/viewpaperpublication.aspx?PortalSource=718&DocID=1058