Cefic-lri Programme | European Chemical Industry Council

D2.2-VITO: Generation and Application of a Model to Determine Intra- and Inter-individual Variation in Biomarkers

Principal Investigator

Prof. Greet Schoeters
Flemish Institute for Technologic Research (VITO)
Boeretang 200
2400 Mol
Tel: + 32 14 335200
Fax: + 32 14 580523


Dr. Elly Den Hond, Eva Govarts, Flemish Institute for Technologic Research (VITO)
í…se Marie Hansen, National Research Centre for the Working Environment, Denmark
Prof. Lisbeth E. Knudsen, Marie Pedersen, Line Mathiesen, Ann Dyreborg Larsen, University of Copenhagen, Institute of Public Health, Department of Environmental Health, Denmark
Liesbeth Bruckers, Hasselt University, Center for Statistics, Diepenbeek, Belgium


Biomarkers which reflect levels of pollutants in the human body offer a unique opportunity to investigate impact of environmental pollution on humans. Biomarker levels in the general population are influenced by genetic, physiological and external factors. Knowledge on which factors are important may help to prioritise risk management measures. This information is also crucial for comparison biomarker values among different populations.

This project aimed to analyze systematically human biomarker data from large environmental health programs which have been running over the last years in Belgium and in Denmark to attain more insight in inter-individual variability of biomarkers. The databases contained data from the general population and from exposed workers. Different age groups were included and information on covariates such as gender, body composition, occupational exposure, smoking behavior, nutrition and other life style factors was available.
The project focused on urinary 1-hydroxypyrene. This urinary metabolite of pyrene is a widely used marker for exposure to polyaromatic hydrocarbons (PAHs). PAH are non-persistent compounds to which the general population is exposed through different sources (traffic, cooking, heating, food,…). Although pyrene is not carcinogenic, some 4 to 7-ring PAH are. Urinary 1-hydroxypyrene is a biomarker with a relatively short half-life (18-20 hours).

As a second marker of exposure to PAHs, DNA adducts were studied. This is a biomarker of effective dose. As a third marker, serum levels of marker PCBs were investigated. These compounds are persistent and accumulate in body fat. PCBs have endocrine properties and are suspect to interfere with early development. Exposure of the general population occurs mainly through food.

One of the major goals of the project was to develop a strategy to describe biomarker data to get clear information on levels and ranges in the general population. It dealt with biomarker values below the limits of detection (LOD), outliers, missing values, detection and quantification of significant covariates by multivariate regression models. The multiple linear regression model allowed to identify the major determinants of variability and to quantify their importance. It was found that, for 1-hydroxypyrene, in adolescents, 2.5% of the variability was explained by biological factors and 2.3% by life style factors. In adults, respective data were 8.5% and 15.7%. Further, in adolescents, 36% of the variability in serum levels of marker PCBs is explained by biological factors, 14% by local factors and 1% by food consumption, and in adults, 31% by biological factors, 3% by local factors and 4% by food consumption. It was shown that the approach which has been developed can be extrapolated to other biomarkers in different matrices (PCBs in cord blood) or to other chlorinated substances (e.g. HCB, p,p’-DDE in serum).

Related Publications

E Govats, E Den Hond, G Schoeters, L Bruckers (2010) Determinants of Serum PCBs in Adolescents and Adults: Regression Tree Analysis and Linear Regression Analysis, Human and Ecological Risk Assessment: An International Journal, 16:5, 1115-1132.

E Den Hond, E Govarts, L Bruckers, G Schoeters, Determinants of polychlorinated aromatic hydrocarbons in serum in three age classes – methodological implications for biomonitoringEnvironmental Health Perspectives, submitted.

í…M Hansen, L Mathiesen, M Pedersen, LE Knudsen, Urinary 1-hydroxypyrene (1-HP) in environmental and occupational studies – a review, International Journal of Hygiene and Environmental Health 2008, in press.

í…M Hansen, L Mathiesen, M Pedersen, LE Knudsen, Biomarkers of environmental and occupational PAH exposure. Focus on 1-hydroxypyrene in urine, in: Environmental impact of polycyclic aromatic hydrocarbons, Editor Chimezie Anyakora, 2007, pp 99-134.

LE Knudsen, í…M Hansen, Biomarkí¸rer, biomonitoring og biobanker som redskab i eksponeringsvurdering, Miljí¸ og sundhed 2007, suppl. 7, 28-37.

Timeline: March 2006 > February 2008

LRI funding: €248,000

Cefic-Lri Programme Responsible Care

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