The European COPHES/DEMOCOPHES project: Towards transnational comparability and reliability of human biomonitoring results

Abstract

COPHES/DEMOCOPHES has its origins in the European Environment and Health Action Plan of 2004 to “develop a coherent approach on human biomonitoring (HBM) in Europe”. Within this twin-project it was targeted to collect specimens from 120 mother–child-pairs in each of the 17 participating European countries. These specimens were investigated for six biomarkers (mercury in hair; creatinine, cotinine, cadmium, phthalate metabolites and bisphenol A in urine). The results for mercury in hair are described in a separate paper. Each participating member state was requested to contract laboratories, for capacity building reasons ideally within its borders, carrying out the chemical analyses. To ensure comparability of analytical data a Quality Assurance Unit (QAU) was established which provided the participating laboratories with standard operating procedures (SOP) and with control material. This material was specially prepared from native, non-spiked, pooled urine samples and was tested for homogeneity and stability. Four external quality assessment exercises were carried out. Highly esteemed laboratories from all over the world served as reference laboratories. Web conferences after each external quality assessment exercise functioned as a new and effective tool to improve analytical performance, to build capacity and to educate less experienced laboratories. Of the 38 laboratories participating in the quality assurance exercises 14 laboratories qualified for cadmium, 14 for creatinine, 9 for cotinine, 7 for phthalate metabolites and 5 for bisphenol A in urine. In the last of the four external quality assessment exercises the laboratories that qualified for DEMOCOPHES performed the determinations in urine with relative standard deviations (low/high concentration) of 18.0/2.1% for cotinine, 14.8/5.1% for cadmium, 4.7/3.4% for creatinine. Relative standard deviations for the newly emerging biomarkers were higher, with values between 13.5 and 20.5% for bisphenol A and between 18.9 and 45.3% for the phthalate metabolites. Plausibility control of the HBM results of all participating countries disclosed analytical shortcomings in the determination of Cd when using certain ICP/MS methods. Results were corrected by reanalyzes. The COPHES/DEMOCOPHES project for the first time succeeded in performing a harmonized pan-European HBM project. All data raised have to be regarded as utmost reliable according to the highest international state of the art, since highly renowned laboratories functioned as reference laboratories. The procedure described here, that has shown its success, can be used as a blueprint for future transnational, multicentre HBM projects.

Introduction

Human biomonitoring (HBM) surveys have been established in many European countries, such as e.g. Austria, Belgium (Flanders), Czech Republic, France, Germany, Slovenia and Spain (Castano et al., 2012, Cerná et al., 2012, Fréry, 2010, Hohenblum et al., 2012, Kolossa-Gehring et al., 2012, Perharic and Vracko, 2012, Schoeters et al., 2012). However, all these activities have been focused on a certain country or region, and on different sets of analytical parameters. They have been or are carried out for various purposes and are based on different populations, different protocols and recruitment strategies and analysis is performed in many different analytical labs. This non-uniformity makes it difficult to compare HBM data among countries and across Europe.

HBM, as a tool for exposure assessment of hazardous substances in the general population, has increasingly gained recognition by both politicians and the general public over the last two decades (Angerer et al., 2006, Angerer et al., 2007). The demand for HBM data, comparable between study populations and across national (European) borders, constantly increased over the years.

Action three of the “European Environment and Health Action Plan 2004–2010” (Directorate-General for Health & Consumers, 2012) of the European Commission envisaged the development of a coherent approach to HBM in Europe in close cooperation with the member states of the European Union (EU). Consequently, a twin project was launched in 2009: the Consortium to Perform Human Biomonitoring on a European Scale (COPHES), funded by the European Seventh Framework Programme (FP7), and DEMOCOPHES, the pilot study to test the feasibility, funded by the Directorate-General for the Environment (DG ENV) of the European Commission with co-founding from the participating countries (Joas et al., 2012).

The three most important aims of COPHES/DEMOCOPHES were (a) to generate comparable HBM data across Europe, (b) to establish a European HBM network with a sufficient number of laboratories in the EU member states, able to perform HBM (capacity building) and (c) to develop biomarkers and analytical methods for new or emerging environmental pollutants (phthalates and bisphenol A).

Achieving comparable HBM data is a prerequisite for European-wide political activities in the field of environmental medicine. Capacity building for laboratories was necessary because the development of a “coherent approach on HBM in Europe” cannot be based on only a few highly specialized laboratories, which were known in Europe at the beginning of this project. The development of biomarkers for newly emerging pollutants is an on-going necessity in HBM, which should be considered in new HBM projects.

The desired comparability of HBM results and capacity building of qualified laboratories within the EU can only be achieved by harmonization and standardization of both, the pre-analytical (sampling, storage, etc.) and the analytical phase. Furthermore an extensive internal and external quality assurance programme within the analytical phase was necessary to guarantee the reliability and comparability of analytical data. To achieve all these aims we could rely on 30 years of experience with the German External Quality Assessment Scheme (G-EQUAS) and with the elaboration of analytical procedures for HBM (Angerer et al., 1993, Schaller et al., 1987, Schaller et al., 2001, Taylor et al., 2007). This publication is focused on quality assurance measures and on the results for all urinary compounds. A further paper will deal with mercury in hair, because this biological matrix has distinct requirements.