A pilot study on the feasibility of European harmonized human biomonitoring: Strategies towards a common approach, challenges and opportunities.

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother-child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).(1) Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop, linking biomonitoring surveys with health examination surveys and with research, and coping with the diverse implementations of EU regulations and international guidelines with respect to ethics and privacy.

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making.

Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

[Ethical considerations on the planning, assessment and management of biological monitoring data]. / Aspetti etici sull'impostazione, valutazione e gestione dei test di monitoraggio biologico.

If a society aims at preserving its socio-ethical values, practices concerning the planning, assessment and management of biomonitoring tests in occupational health surveillance and research should not conflict with these values. Protecting both health and employment of every candidate or employee must be the aim of the occupational health physician. For assessing ethical acceptability of occupational health surveillance practices, their accuracy, relevance, need or necessity, and consequences must first be analysed. This analysis must constitute the basis for any societal democratic decision making process, which cannot be substituted for simply by individual informed consent. A physician trained in occupational health is the professionalism required for doing the testing and assuring the protection of the confidentiality of medical data, in accordance with strict legal and deontological rules. In biological monitoring studies and, in general, in any occupational health research settings, however, the principle of individual, really informed consent must be used, whenever possible. This may also considerably contribute to the committment of study subjects to the research goals. On the other hand, this committment would also contribute to promoting impartial research which is needed to improve the knowledge in occupational health and to increase health protection and prevention.

Current scientific, ethical and social issues of biomonitoring in the European Union.

Occupational health regulations and practices in EU Member States have been directed, to a large extent, by the principle of social protection, aiming to protect both the health and the employment of every (candidate) worker. Medical and biomonitoring practices have played a major role in identifying health problems at work and also in establishing preventive measures. Lately, a new tendency is occurring that reduces health protection to compliance with a limited set of standards for workplaces and individuals. According to this approach, 'predictive' medical tests might be used for the selection of the fittest workers. At a time when the labor market is evolving towards less stable forms of work, such a 'standardization approach' may lead to an unequal occupational health policy: the better off being more protected, the more exposed being less protected and the more susceptible being excluded. Instead, biomonitoring tools should only be developed as part of medical surveillance and used for those who need it most.

Individual susceptibility and prevention of occupational diseases: scientific and ethical issues.

Genetic testing of employees is controversial; objections have been raised with regard to privacy, right to work, and the relevance of the tests. A study is being conducted on "the ethical, social, and scientific problems related to the application of genetic screening and genetic monitoring for employees in the context of a European approach to health and safety at work." A conceptual model is proposed of the complex interactions between exposure, acquired and inherited susceptibility, and risk for disease. The validity of tests for determining genotype and phenotype and their relevance for disease must be evaluated critically to provide an objective basis for ethical discussions. The acceptability of such tests is related to a number of issues, which are identified and discussed.