Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Pooled biological specimens for human biomonitoring of environmental chemicals: Opportunities and limitations

Journal of Exposure Science & Environmental Epidemiology volume 24, pages 225–232 (2014)Cite this article

Subjects

Abstract

Biomonitoring has become the “gold standard” in assessing chemical exposures, and has an important role in risk assessment. The pooling of biological specimens—combining multiple individual specimens into a single sample—can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends or to identify susceptible populations in a cost-effective manner. Pooled samples provide an estimate of central tendency and may also reveal information about variation within the population. The development of a pooling strategy requires careful consideration of the type and number of samples collected, the number of pools required and the number of specimens to combine per pool in order to maximise the type and robustness of the data. Creative pooling strategies can be used to explore exposure–outcome associations, and extrapolation from other larger studies can be useful in identifying elevated exposures in specific individuals. The use of pooled specimens is advantageous as it saves significantly on analytical costs, may reduce the time and resources required for recruitment and, in certain circumstances, allows quantification of samples approaching the limit of detection. In addition, the use of pooled samples can provide population estimates while avoiding ethical difficulties that may be associated with reporting individual results.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Cohen Hubal EA, Richard A, Aylward L, Edwards S, Gallagher J, Goldsmith M-R et al. Advancing exposure characterization for chemical evaluation and risk assessment. J Toxicol Environ Health B Crit Rev 2010; 13: 299–313.

    Article  CAS  Google Scholar 

  2. Sexton K, Needham L, Pirkle J . Human biomonitoring of environmental chemicals. Am Sci 2004; 92: 38–45.

    Article  Google Scholar 

  3. National Research Council. Human Biomonitoring for Environmental Chemicals. National Academy Press: Washington, DC, USA. 2006 Available from http://www.nap.edu/catalog.php?record_id=11700, Accessed 25 September 2012.

  4. Angerer J, Ewers U, Wilhelm M . Human biomonitoring: state of the art. Int J Hyg Environ Health 2007; 210: 201–228.

    Article  CAS  Google Scholar 

  5. Kolossa-Gehring M, Becker K, Conrad A, Schroter-Kermani C, Schulz C, Seiwert M . Environmental surveys, specimen bank and health related environmental monitoring in Germany. Int J Hyg Environ Health 2012; 215: 120–126.

    Article  CAS  Google Scholar 

  6. World Health Organisation Biomonitoring of human milk for persistent organic pollutants (POPs) in food safety. 2009. Available from http://www.who.int/foodsafety/chem/pops_biomonitoring/en/index.html, Accessed 8 January 2013.

  7. World Health Organisation. Fourth WHO-Coordinated Survey of Human Milk for Persistent Organic Pollutants in Cooperation with UNEP. Guidelines for Developing a National Protocol 2007. Food Safety, Foodborne Diseases and Zoonoses Department, World Health Organisation: Geneva, Switzerland.

  8. United Nations Environment Program. Draft implementation plan for the global monitoring plan for the first effectiveness evaluation. 2007. UNEP/POPs/COP.3/23/Rev.1. Available from http://chm.pops.int, Accessed 18 February 2013.

  9. Stockholm Convention Global monitoring plan overview. 2008. Available from http://chm.pops.int/Implementation/GlobalMonitoringPlan/Overview/tabid/83/Default.aspx, Accessed 18 February 2013.

  10. Global monitoring plan for persistent organic pollutants under the stockholm convention article 16 on effectiveness evaluation. First regional monitoring report, Western Europe and other groups (WEOG) region. 2008. Available from http://chm.pops.int/Programmes/Global%20Monitoring%20Plan/Monitoring%20Reports/tabid/525/language/en-US/Default.aspx, Accessed 18 February 2013.

  11. Caudill SP . Characterizing populations of individuals using pooled samples. J Exposure Sci Environ Epidemiol 2010; 20: 29–37.

    Article  Google Scholar 

  12. Schisterman EF, Vexler A . To pool or not to pool, from whether to when: applications of pooling to biospecimens subject to a limit of detection. Paediatr Perinat Epidemiol 2008; 22: 486–496.

    Article  Google Scholar 

  13. Schisterman EF, Vexler A, Mumford SL, Perkins NJ . Hybrid pooled-unpooled design for cost-efficient measurement of biomarkers. Stat Med 2010; 29: 597–613.

    PubMed  PubMed Central  Google Scholar 

  14. Mary-Huard T . Biases induced by pooling samples in microarray experiments. Bioinformatics 2007; 23: i313–i318.

    Article  CAS  Google Scholar 

  15. Angerer J, Aylward LL, Hays SM, Heinzow B, Wilhelm M . Human biomonitoring assessment values: approaches and data requirements. Int J Hyg Environ Health 2011; 214: 348–360.

    Article  CAS  Google Scholar 

  16. Caldwell KL, Mortensen ME, Jones RL, Caudill SP, Osterloh JD . Total blood mercury concentrations in the U.S. population: 1999–2006. Int J Hyg Environ Health 2009; 212: 588–598.

    Article  CAS  Google Scholar 

  17. Patterson DG, Jr ., Hampton L, Lapeza CR, Jr ., Belser WT, Green V, Alexander L et al. High-resolution gas chromatographic/high-resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal Chem 1987; 59: 2000–2005.

    Article  CAS  Google Scholar 

  18. Caudill SP . Use of pooled samples from the National Health and Nutrition Examination Survey. Stat Med 2012; 31: 3269–3277.

    Article  Google Scholar 

  19. Galea S, Tracy M . Participation rates in epidemiologic studies. Ann Epidemiol 2007; 17: 643–653.

    Article  Google Scholar 

  20. O'Neill MS, Jerrett M, Kawachi I, Levy JI, Cohen AJ, Gouveia N et al. Health, wealth, and air pollution: advancing theory and methods. Environ Health Perspect 2003; 111: 1861–1870.

    Article  Google Scholar 

  21. Goldman LR, Anton-Culver H, Kharrazi M, Blake E . Banking of human tissue for biomonitoring and exposure assessment: utility for environmental epidemiology and surveillance. Environ Health Perspect 1995; 103: 31–34.

    PubMed  PubMed Central  Google Scholar 

  22. Chaix B, Gustafsson S, Jerrett M, Kristersson H, Lithman T, Boalt A et al. Children's exposure to nitrogen dioxide in Sweden: investigating environmental injustice in an egalitarian country. J Epidemiol Community Health 2006; 60: 234–241.

    Article  Google Scholar 

  23. Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL . Urinary concentrations of triclosan in the U.S. population: 2003–2004. Environ Health Perspect 2008; 116: 303–307.

    Article  CAS  Google Scholar 

  24. Toms LML, Sjödin A, Harden F, Hobson P, Jones R, Edenfield E et al. Serum polybrominated diphenyl ether (PBDE) levels are higher in children (2–5 years of age) than in infants and adults. Environ Health Perspect 2009; 117: 1461–1465.

    Article  CAS  Google Scholar 

  25. Harden FA, Müller JF, Toms LML, Gaus C, Moore M, Päpke O et al. Dioxins in the Australian population: levels in blood. National Dioxins Program Technical Report No. 9, 2004. Australian Government Department of the Environment and Heritage: Canberra, Australia, 119 pp.

  26. Faraggi D, Reiser B, Schisterman EF . ROC curve analysis for biomarkers based on pooled assessments. Stat Med 2003; 22: 2515–2527.

    Article  Google Scholar 

  27. Health Canada Report on human biomonitoring of environmental chemicals in Canada. Results of the Canadian Health Measures Survey cycle 1 (2007–2009) 2010, 1–283, Available from http://www.hc-sc.gc.ca/, Accessed 21 May 2013.

  28. Rawn DF, Ryan JJ, Sadler AR, Sun WF, Haines D, Macey K et al. PCDD/F and PCB concentrations in sera from the Canadian health measures survey (CHMS) from 2007–2009. Environ Int 2012; 47: 48–55.

    Article  CAS  Google Scholar 

  29. Becker K, Seiwert M, Angerer J, Kolossa-Gehring M, Hoppe HW, Ball M et al. GerES IV pilot study: assessment of the exposure of German children to organophosphorus and pyrethroid pesticides. Int J Hyg Environ Health 2006; 209: 221–233.

    Article  CAS  Google Scholar 

  30. Mumford SL, Schisterman EF, Vexler A, Liu A . Pooling biospecimens and limits of detection: effects on ROC curve analysis. Biostatistics 2006; 7: 585–598.

    Article  Google Scholar 

  31. Vexler A, Liu A, Schisterman EF . Efficient design and analysis of biospecimens with measurements subject to detection limit. Biom J 2006; 48: 780–791.

    Article  Google Scholar 

  32. Bignert A . Some Consequences Using Pooled Samples Versus Individual Samples and Pooled Samples with Various Relation Between Sampling Error and Uncertainty due to Chemical Analysis. Swedish Museum of Natural History: Stockholm, Sweden. 2008.

    Google Scholar 

  33. Morello-Frosch R, Brody JG, Brown P, Altman RG, Rudel RA, Perez C . Toxic ignorance and right-to-know in biomonitoring results communication: a survey of scientists and study participants. Environ Health 2009; 8: 6.

    Article  Google Scholar 

  34. Harrison M . Applying bioethical principles to human biomonitoring. Environ Health 2008; 7 (Suppl 1): S8.

    Article  Google Scholar 

  35. Bauer S . Societal and ethical issues in human biomonitoring–a view from science studies. Environ Health 2008; 7 (Suppl 1): S10.

    Article  Google Scholar 

  36. Oleskey C, Fleischman A, Goldman L, Hirschhorn K, Landrigan PJ, Lappe M et al. Pesticide testing in humans: ethics and public policy. Environ Health Perspect 2004; 112: 914–919.

    Article  Google Scholar 

  37. Aylward LL, Kirman CR, Schoeny R, Portier CJ, Hays SM . Evaluation of biomonitoring data from the CDC national exposure report in a risk assessment context: perspectives across chemicals. Environ Health Perspect 2012; 121: 287–294.

    Article  Google Scholar 

  38. European Food Safety Authority. Opinion of the scientific panel on food additives, flavourings, processing aids and materials in contact with food. On request from the commission related to 2,2-bis(hydroxyphenol)propane (bisphenol A). Question number EFSA-Q-2005-100. Adopted on 29 November 2006. EFSA J 2006; 428: 1–75.

    Google Scholar 

  39. Centers for Disease Control and Prevention. Fourth National Report on Human Exposures to Environmental Chemicals. Centers for Disease Control and Prevention, Department of Health and Human Services: Altanta, GA, USA. 2009.

  40. Devers KJ, Frankel RM . Study design in qualitative research–2: Sampling and data collection strategies. Educ Health (Abingdon, England) 2000; 13: 263–271.

    Article  CAS  Google Scholar 

  41. Ferriby L, Knutsen J, Harris M, Unice K, Scott P, Nony P . Evaluation of PCDD/F and dioxin-like PCB serum concentration data from the 2001–2002 National Health and Nutrition Examination Survey of the United States population. J Exposure Sci Environ Epidemiol 2007; 17: 358–371.

    Article  CAS  Google Scholar 

  42. Calafat AM, Wong LY, Ye X, Reidy JA, Needham LL . Concentrations of the sunscreen agent benzophenone-3 in residents of the United States: National Health and Nutrition Examination Survey 2003–2004. Environ Health Perspect 2008; 116: 893–897.

    Article  CAS  Google Scholar 

  43. Thompson J, Toms LML, Eaglesham G, Hobson P, Mueller JF . Comparison of PFOS and PFOA serum concentrations in people undergoing regular venesections and in the broader community. Organohalogen Compounds 2010; 72: 826–829.

    Google Scholar 

  44. Rappaport SM . Implications of the exposome for exposure science. J Expos Sci Environ Epidemiol 2011; 21: 5–9.

    Article  CAS  Google Scholar 

  45. Aylward LL, Toms LML, Mueller JF . Estimation of reference values for dioxin, furan, and PCB congener concentrations for the Australian population. Organohalogen Compounds 2012; 74: 752–755.

    Google Scholar 

  46. Toms LML, Mueller JF . Chemical monitoring initiative: Australian human blood sample collection and chemical testing. Final report. A consultancy funded by the Australian Government Department of the Environment, Water, Heritage and the Arts: Australia. 2010.

    Google Scholar 

  47. Aylward L, Toms LML, Mueller JF . Evaluation of serum dioxin concentrations in Australian Vietnam veterans with diabetes mellitus. Organohalogen Compounds 2009; 71: 200–204.

    Google Scholar 

  48. Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey Dataset 2003–2004. Centers for Disease Control and Prevention, Department of Health and Human Services: Altanta, GA, USA. 2004.

  49. Koizumi A, Harada K, Inoue K, Hitomi T, Yang H-R, Moon C-S et al. Past, present, and future of environmental specimen banks. Environ Health Prev Med 2009; 14: 307–318.

    Article  Google Scholar 

  50. Wiesmuller GA, Eckard R, Dobler L, Gunsel A, Oganowski M, Schroter-Kermani C et al. The environmental specimen bank for human tissues as part of the German environmental specimen bank. Int J Hyg Environ Health 2007; 210: 299–305.

    Article  Google Scholar 

  51. Wise SA, Koster BJ . Considerations in the design of an environmental specimen bank: experiences of the national biomonitoring specimen bank program. Environ Health Perspect 1995; 103: 61–67.

    PubMed  PubMed Central  Google Scholar 

  52. Needham LL, Calafat AM, Barr DB . Uses and issues of biomonitoring. Int J Hyg Environ Health 2007; 210: 229–238.

    Article  CAS  Google Scholar 

  53. Hays SM, Becker RA, Leung HW, Aylward LL, Pyatt DW . Biomonitoring equivalents: a screening approach for interpreting biomonitoring results from a public health risk perspective. Regul Toxicol Pharmacol 2007; 47: 96–109.

    Article  CAS  Google Scholar 

  54. Reigard R, Roberts J Recognition and management of pesticide poisonings. EPA #735-r-98-003. 5th edition. Available from http://www.epa.gov/oppfead1/safety/healthcare/handbook/handbook.htm, Accessed 18 September 2012.

  55. Esteban M, Castaño A . Non-invasive matrices in human biomonitoring: A review. Environ Int 2009; 35: 438–449.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Entox is a joint venture of the University of Queensland and the Queensland Department of Health. ALH receives an APA scholarship. LMLT is funded by an ARC DECRA (DE120100161). JFM is funded through an ARC Future Fellowship. MM is funded by the INTERFLAME project, supported by the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement 295138.

Author information

Authors and Affiliations

  1. National Research Centre for Environmental Toxicology (Entox), University of Queensland, Brisbane, Queensland, Australia

    Amy L Heffernan & Jochen F Mueller

  2. Summit Toxicology, LLP, Falls Church, Virginia, USA

    Lesa L Aylward

  3. School of Clinical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia

    Leisa-Maree L Toms

  4. Children’s Health and Environment Program, Queensland Children’s Medical Research Institute, University of Queensland, Herston, Queensland, Australia

    Peter D Sly

  5. Department of Applied Environmental Science, Stockholm University, Stockholm, Sweden

    Matthew Macleod

Authors
  1. Amy L Heffernan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lesa L Aylward
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leisa-Maree L Toms
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter D Sly
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew Macleod
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jochen F Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amy L Heffernan.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heffernan, A., Aylward, L., Toms, LM. et al. Pooled biological specimens for human biomonitoring of environmental chemicals: Opportunities and limitations. J Expo Sci Environ Epidemiol 24, 225–232 (2014). https://doi.org/10.1038/jes.2013.76

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jes.2013.76

Keywords

This article is cited by

Search

Advanced search

Quick links