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HBM4-VITO:Understanding inter- and intra-individual variability in HBM spot samples

Principal Investigator

Dr. Ir. Roel Smolders
Boeretang 200, 2400 Mol, Belgium
Tel: +32 14 33 51 59
Fax: + 32 14 58 05 23


Nicholas Warren, Louise Bowers, Kevin McNally, Richard Cotton, John Cocker, Katherine Jones, HSL, UK
Sean Hays, Lesa Aylward, Chris Kirman, Summit Toxicology, L.L.P., USA
Len Levy, Ruth Bevan, Lini Ashdown, Institute of Environment and Health (IEH), Cranfield University, UK
Greet Schoeters, Elly den Hond, VITO, BE
Holger M. Koch, Jürgen Angerer, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr-Universität Bochum (IPA), DE


In many large-scale human biomonitoring (HBM) surveys, single samples of blood, urine or other bodily matrices are collected from large numbers of individuals recruited from the general population. These HBM surveys aim to obtain information on the distribution of exposures in the population, the comparison of different subgroups or the identification of high exposure groups. Biomarker data are also related to potential exposure sources and exposure pathways, other studies attempt to correlate biomarkers with biological effect and health data. The single sample analyses capture the variability of internal dose in the population, without however disentangling the variability due to variation between individuals or within an individual. It is often not documented to what extend the individual variability fluctuates compared to the between-subject variability. This may lead to misclassification of individuals with high/low exposures and is of particular concern if the exposure pattern is discontinuous and the compounds have a short half life in the biological matrix.

Using a combination of existing biomarker data, toxicokinetic modelling and newly generated biomarker analysis tailored to this problem, the project will determine the most important drivers affecting the representativeness of single biomarker samples for assessing an individual’s internal dose, and will, if necessary, identify which aspects of HBM survey sampling need to be improved in order to better understand the relationship between inter-and intra-individual variation in biomarker values.

The objectives of this project are threefold:

  1. To identify the key determinants influencing how representative a spot sample is of longer-term average biomarker levels within individuals;
  2. Development of an easy to use software tool to assist interpretation of studies utilising single human biomonitoring samples in terms of exposure; and
  3. Where appropriate, to propose alternative sampling schemes that provide more representative measures of longer term average exposures for individuals and populations.

Related Publications

Understanding inter- and intra-individual variability in human biomonitoring spot samples, HBM4-VITO Executive Summary 2014.

Lesa L. Aylward , Sean M. Hays , Roel Smolders , Holger M. Koch , John Cocker , Kate Jones , Nicholas Warren , Len Levy & Ruth Bevan (2014). Sources of Variability in Biomarker Concentrations, Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 17:1, 45-61



Understanding inter- and intra-individual variability in HBM spot samples by Smolders R., Warren N., McNally K., Cocker J., Aylward L., Hays S., Kirman C., Levy L., Bevan R., Koch HM., Angerer J. and Schoeters G., presented at the 14th Cefic-LRI Annual Workshop 2012



HBM4: Representativeness of a single biomonitoring sample, by Roel Smolders, presented at the 16th Cefic-LRI Annual Workshop 2014


Timeline: January 2012 > December 2013

LRI funding: € 224,450


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