In 2003 the European Commission (EC) announced its Environment and Health Strategy. This strategy contained many aspects of research and development addressing key priorities in the developing field of environmental public health. This led to the European Union (EU) Environ- ment and Health Action Plan and included an action to develop a coherent approach to humanbiomonitoring. The EC, supported by a multidisciplinary working group of Member States representatives (Implementation Group on HumanBiomonitoring) and by an Expert team to Sup- port BIOmonitoring (ESBIO) is preparing an EU Pilot Project. The Pilot study has been delayed and it is hoped it will be launched by the end of 2008.
Action 1 (Develop environmental health indicators) and Action 2 (Develop integrated monitoring of the environ- ment, including food, to allow the determination of rele- vant human exposure) of the European Environment and Health Action Plan 2004–2010, concerns the health of the environment and integrated monitoring of environmen- tal contamination leading to human exposure, i.e. exter- nal human exposure. Action 3, currently underway, focuses on internal human exposure or human biomoni- toring. In the third action, the European Commission commits itself 'to develop in close cooperation with the Mem- ber States a coherent approach to HumanBiomonitoring in Europe and to launch an EU Pilot Project to test out the feasi- bility of such a coordinated approach'. For this reason, an Expert team to Support BIOmonitoring (ESBIO) together with the Implementation Group (IG) of the European HBM has been preparing implementation of an EU pilot project, which was launched in the spring 2007. The back- ground and rationale for the EU Pilot Project and the Dan- ish proposal of a conceptual framework for a national HBM program (cf. Figure 1) are presented in this paper. The proposed framework builds on the principles and experience gained from scientific work at national and EU level, e.g. NoMiracle, as well as environment and human health indicator reporting within the area of cumulative risk from exposure [7,13-19].
Action-plan: interpreting results for policy making Together with medical and environmental scientific experts and policy makers, social scientists worked on the preparation of an action-plan for the interpretation and policy measures with regard to the humanbiomonitoring results [33,34]. In the beginning the discussions in the working group mainly focussed on environmental and medical scientific interpretation of the monitoring data. Consultation of scientific experts as well as desk research was considered to provide the necessary knowledge and answers. Later on in the conceptual process other ele- ments were introduced by the social scientists: comple- mentary assessment criteria, complementary assessment methods and involvement of other actors in the process. In three successive analytical phases, the human biomon- itoring results are assessed on different aspects. The first phase focuses on the question: how severe are specific results with regard to public health risks? To a large extent in this phase the discussion focuses on reference values for interpreting the data. This is quite problematic since knowledge of these issues is still rather limited. Only with regard to lead (international) norms are available. There- fore an average reference value per pollutant or health effect is used to decide which humanbiomonitoring results are relatively high. A comparison is also done with research outcomes from other studies e.g. from abroad. The second phase focuses on the question: what are the causes for a specific monitoring result? For example, causes may be environmentally related or life style related. In the third and final phase the focus is on the question: can we identify a (local) source for the pollution? At first the action-plan was thought of as a merely scien- tific quest: with the right group of experts the interpreta- tion with regard to policy priorities will follow automatically. While trying to build bridges towards pol- icy interpretation though, the limitations of an exclusively scientific endeavour were clearly evident: no scientist or group of scientists dared to claim that they possessed the necessary and overarching knowledge for answering diffi- cult questions – questions e.g. on policy priorities when factors other than (medical and environmental) scientific ones also had to be taken into account (economics, social preferences, feasibility of policy measures; issues intro- duced by the social scientists). The social scientists there- fore proposed the formation of a jury that will judge relevant data and knowledge in order to give advice to the government.
Exposure characterizations are a critical component of hu- man health risk assessments, providing key insights on the environmental determinants of health at the local, regional, national, and global scales. Contaminant exposure is spatially and temporally dependent and can be influenced by natural and anthropogenic factors that impact air and water quality as well as the integrity of locally-harvested food sources. In remote subarctic Indigenous (First Na- tions, Métis and Inuit) communities of the Northwest Ter- ritories (NT), Canada, the ongoing reliance on country foods (e.g., locally-harvested land mammals, fish, birds and plants) may influence people’s exposure to environmental contaminants, potentially causing significant differences in exposure profiles relative to the general population of Canada. Country food consumption in First Nations peo- ples has been associated with improved nutrition, food se- curity, and lower rates of chronic disease [1–3]; however, such foods can also pose potential risks via exposure to contaminants such as mercury and cadmium. Humanbiomonitoring is a validated method used in studies to quantify environmental exposure to both natural and an- thropogenic chemicals and contaminants. For example, a humanbiomonitoring approach is employed within the Canadian Health Measures Survey (CHMS) to characterize profiles of exposure in the Canadian population [4 – 7]. Due likely to logistical issues such as low density population in the region, and expense, neither the Health Canadian Mea- sures Survey nor the First Nation Biomonitoring Initiative sampled communities of the Northwest Territories. To ad- dress these concerns, our team has been conducting an ongoing multi-year contaminant biomonitoring study to investigate current levels of contaminant exposure among participating Dene First Nations communities of the Canadian subarctic.
Based on information from the desk research (with the exception of most policy aspects and research aspects, where the process involved mainly asking questions) the experts were asked to assess the cases with respect to the different sub criteria on a qualitative response scale of 7 items, resulting in rankings of hotspot cases. For example regarding the importance of humanbiomonitoring: Very important - Important - Fairly important - Fairly unim- portant - Unimportant - Very unimportant - Do not know We also asked them to explain their arguments and any type of assessment uncertainty. Furthermore the experts were asked to give weights to the (relative importance of ) respective sub criteria. In a multi-criteria analysis the combination of individual expert rankings and weightings resulted in overall expert group consensus rankings regarding the priority of hotspot cases (Table 4). The overview of consensus rankings presents us a rather mixed picture. No hotspot case clearly scored high on all criteria. Several score high on one or two criteria but con- siderably lower on other: e.g. Mortality Dendermonde and Shredder Menen. Only one case scores consistently (rather low) on all criteria: Chipboard plants. Based on
Food is often a major source of human exposure to a wide range of hazardous substances, such as industrial chemicals, natural substances and trace elements. To estimate the levels of those substances which consumers are exposed to through the diet, calculations based on the food content and consumers' self-reported food intake are traditionally used. However, this method is not sufficient since it might have low reliability and does not consider factors as for example uptake or metabolism of the contaminant. Therefore, as a complement, the Swedish National Food Agency (NFA) applies humanbiomonitoring (HBM) to measure the body burden of contaminants, i.e. assessing the internal exposure. HBM is the only tool that integrates exposure from different sources, traces the availability of the food contaminants with potential threats to human health and allows assessment of health- and nutritional status . Moreover, it can demonstrate the temporal trends and population distribution of exposure, identify vulnerable groups and possible emerging risks, as well as be used to following-up risk reducing or preventive actions. Together with
Some of the points made are: (1) There is not a single generic bioethical analysis applicable to the use of humanbiomonitoring data, each specific use requires a separate deliberation; (2) Using unidentified, population-based biomonitoring information for risk assessment or population surveillance raises fewer bioethical concerns than personally identified biomonitoring information such as employed in health screening; (3) Companies should proactively apply normative bioethical principles when considering the disposition of products and by-products in the environment and humans; (4) There is a need for more engagement by scholars on the bioethical issues raised by the use of biomarkers of exposure; (5) Though our scientific knowledge of biology will continue to increase, there will always be a role for methods or frameworks to resolve substantive disagreements in the meaning of this data that are matters of belief rather than knowledge.
While heavy metal concentrations in adults were similar between central and peripheral areas, some differences appeared in children that might be seen as the conse- quence of the pollution from the plants. In the central area, the higher lead concentrations seen in children but not in adults could be due to the higher gastro-intestinal absorption of lead in children (40–50 %) than in adults (3–10 %). Moreover, the time spent outdoors was signifi- cantly associated with higher blood lead levels in chil- dren living at proximity of the plants. This could result from specific behavior of children, in particular hand-to- mouth activity. Nevertheless, all the blood lead values observed in children in Ath were below the value of 100 μg/l, which is the level of concern used until re- cently [37, 38]. Among studied children, three had blood lead values exceeding the more stringent threshold of 50 μg/l. But even this threshold cannot ensure absence of toxicity, as no safe lead-exposure threshold can be identified to date and more and more studies report health effects at low blood lead levels. Low-level expos- ure to lead during early childhood is associated with lower neuropsychological development through the first 7 years of live, with delayed puberty, and with a lower intelligence quotient (IQ) [3, 39–41]. Moreover, the stee- pest declines in IQ occur at blood levels <100 μg/l . Nevertheless, in our study, we have not observed associ- ation between blood lead concentrations and behavioral score. We cannot exclude that this was a consequence of the limited number of observations. Given the recent findings about health effects at low blood lead levels, the German HumanBiomonitoring Commission suspended their HBM value of 100 μg/l for lead in blood and set a reference value of 35 μg/l [42, 43]. In the United States, the Center for Disease Control and Prevention (CDC) also recommended to replace the blood lead “level of concern” of 100 μg/l and recommended the use of 50 μg/l as new reference value .
The Flemish Environment and Health Study (FLEHS), a humanbiomonitoring programme involving newborns, adolescents and adults in Flanders (the northern part of Belgium) , faces the same challenges. Participants with lower SES, defined in terms of educational attain- ment, household income or ethnic background, are sys- tematically underrepresented in the study samples. For example, of the respondents in the combined samples of the FLEHS II studies of mothers and adults (20–40 years of age) in 2008 (n = 459), 5.1% were in the low educational attainment group (had not completed secondary educa- tion), compared to 14.7% in the general Flemish popula- tion (25–34 years of age). 3.9% of respondents had a foreign origin (a parent not born in Belgium), compared to 15% of the general Flemish population. Social scientists from the FLEHS research team have begun to explore this participation bias. To address the issue of social inclusion in the study, we designed, implemented and evaluated a targeted recruitment strategy nested in the FLEHS III mother-newborn study of 2014. This article describes the process and the outcome of this targeted approach, which aimed to increase the participation rate of socially disad- vantaged pregnant women and obtain a study sample that was more representative of the social and ethnic diversity of the Flemish population.
Proxy monitoring: while it is the intention of the steps outlined in the current document to convert HBM data into risk management and policy making options, the most efficient way of controlling human dose may not be by controlling human exposure, but by monitoring and controlling a specific, main, exposure route and setting limits for a proxy. This approach may be seen as a combi- nation of awareness raising, controlling substance expo- sure and increased monitoring efforts, but generally involves ecosurveillance (or ecological biomonitoring) instead of humanbiomonitoring. For a number of well- studied chemicals such as cadmium or methylmercury, there are well-defined exposure sources that have a major contribution to the total dose. If more detailed informa- tion is needed on the spatial or temporal evolution of these compounds, an ecological biomonitoring network may be better suited to gather this information than a HBM network. Using animals or plants as a proxy for human exposure can alleviate some of the more troubling features of HBM, such as ethical issues, selecting repre- sentative subpopulations, correcting for confounding fac- tors or statistical power requirements. For example, the use of lichens for monitoring of PCDD/Fs  or mosses for heavy metal monitoring  are documented in liter- ature. HBM surveys have extensively documented that fish and seafood are a major source of methylmercury uptake in humans [16,17]. Hence, improved mercury monitoring may benefit from more detailed information on methyl- mercury content in seafood rather than providing addi- tional data in human tissues, certainly if this type of data is directly fed into other policy options for risk reduction such as "controlling substance exposure" or "raising awareness" [77,78]. It needs to be stressed however that the use of proxy monitoring as a substitute for HBM is only valid if uptake routes are well understood. As already mentioned earlier, ecosurveillance data may in any cir- cumstance be useful for the identification of potential (local) sources (step 3).
Environmental sciences – such as environmental chemis- try and engineering – focus on exposure. Key practices of knowledge generation include developing monitoring systems of emission sources, modelling distribution pat- terns and pathways of environmental chemicals including their migration and uptake. In the thought style of envi- ronmental science, risk assessments model the dynamics of chemicals in environmental compartments, estimate exposure and doses at individual and collective levels; indicators are developed, monitored and related to regu- latory frameworks with exposure limits that are based on toxicologic and epidemiologic assessments. Assessments from an environmental science perspective can include both human and ecosystem exposures. Different from epidemiological surveillance, this kind of monitoring does not necessarily imply immediate synthesis with health data and aetiologic hypotheses testing; rather it aims at precautionary risk management and exposure reduction.
whats_in_your_blood/index.cfm. The goal of these sur- veys was not to prove a scientific hypothesis, but to raise awareness of the general public about the extent of chem- ical pollution in Europe and to show how essential a strong European chemical regulation is. The results have shown that persons tested are 'contaminated' with a cock- tail of persistent, bio-accumulative and toxic man-made chemicals. Although the study was conducted in full respect of the rights of each participant, questions were brought up about the exact procedures to follow, on which it seemed difficult to get consistent answers. According to the protocol of the Convention on Human Rights and Biomedicine (ref , article 7), every "research" project has to be submitted to an independent research ethics committee and approval of an ethics com- mittee has to be required before the start of the project. In the case of WWF the question was raised weather such a campaign had to be considered a "research" project or not, since its purpose is not primarily to produce knowl- edge but to raise awareness. Furthermore, only very few samples were collected in a large number of countries (13 families from 12 EU countries) http://assets.panda.org/ downloads/generationsx.pdf and it was unclear whether ethical approvals were required in each country.
Family members have a certain period sharing similar environmental conditions, including indoor dust, contact with consumer products containing PFCs, as well as die- tary intake of foods and drinking water, leading to simi- lar exposure to PFOS and PFOA. Hence, significant cor- relations of exposure to PFOS and PFOA among family members were observed. However, lack of correlation of serum PFOS concentrations between father and mother, son, or daughter, suggested more unidentified factors affecting the body load of PFOS than PFOA, possibly relating to both the exposure routes and accumulation and elimination in human bodies of PFOS. Larger vari- ability in serum PFOS levels of fathers than the mothers and offspring support the hypothesis (Figure 2). Further, the results illustrated that potential sources of PFOS might exist in some working environment and make a larger difference of exposure of the fathers with different occupation, although the subjects in the present study were recruited from those without known occupational exposure to fluorine chemicals. Therefore, exposure to PFOS from different working environment need to be further studied.
Biomonitoring, the determination of chemical substances in human body fluids or tissues, is more and more frequently applied. At the same time detection limits are decreasing steadily. As a consequence, many data with potential relevance for public health are generated although they need not necessarily allow interpretation in term of health relevance. The European Centre of Ecotoxicology and Toxicology of Chemicals (ECETOC) formed a dedicated task force to build a framework for the interpretation of biomonitoring data. The framework that was developed evaluates biomonitoring data based on their analytical integrity, their ability to describe dose (toxicokinetics), their ability to relate to effects, and an overall evaluation and weight of evidence analysis. This framework was subsequently evaluated with a number of case studies and was shown to provide a rational basis to advance discussions on humanbiomonitoring allowing better use and application of this type of data in human health risk assessment.
During the past 30 years, biomarker-based approaches have been used in the area of humanbiomonitoring with the expectation of refining exposure assessment, providing tools for the detection of disease-related changes and their association with environmental and genetic factors and, thereby, facilitating an improved understanding of the eti- ology of human disease [1, 2]. The National Institute of Environmental Health Sciences (NIEHS) in the USA, for example, has prioritized research focusing on the devel- opment of markers sensitive to environmental exposure, early (preclinical) biological response, and genetic sus- ceptibility as one of its strategic plans for 2006–2011 . In biomonitoring environmental toxicants, each bio- marker and the associations among the biomarkers of exposure, effect, response and susceptibility have the potential to provide a better understanding of the biological relevance of the markers themselves. Exposure biomarkers, such as hydroxylated metabolites of toxicants in urine, are used to indicate the internal dose received and to help estimate the exposure amounts of toxicants that have gained entry into the body . Effect biomarkers are measured as the forms that interact with critical targets, such as DNA- and hemoglobin-adducts or cytogenic alterations [for example, chromosomal aberrations (CAs), micronuclei (MN), sister chromatid exchange (SCE), comet/single-cell gel electrophoresis assay, among others]. Susceptibility biomarkers include genetic variations on metabolic enzymes, such as cytochrome P450s (CYPs). Figure 1 summarizes the relations among these biomarkers in terms of risk assessment, which is the ultimate goal of biomonitoring.
Studies dedicated to fundamental processes which occur in a human body under influence exerted by various environmental factors are among priority issues in contemporary scientific research. Human biological monitoring (HBM) data of give true information about overall contents of hazardous substances in a body or about their biological impacts at various introductions into it as well as about individual differences in exposure levels, metabolism and excretion speed . Humanbiomonitoring data are the most important for assessing impacts on health in case of biologically accumulating or persistent contaminants. The report issued by WHO European Regional Office  gives a review on concepts and sphere of HBM techniques application and presents the results of the latest international and national research over the last 15 years; it also describes trends in distribution of specific contaminants, and lists priority issues of environmental protection and health protection basing on HBM data analysis. Toxic mercury (organic and non-organic compounds), cadmium, lead, and arsenic are the most strictly controlled among all elements. The authors of the report highlight that HBM data on East European region are insufficient; as for data on the Russian Federation, they are represented only by overall mercury content in hair and urine, lead content in umbilical blood, and cadmium and arsenic content (in mothers' urine). These data were obtained during pilot testing which took place in maternity hospitals in Moscow region [2, 3].
Although no official opinions from national ethics bodies have been stated in regard to humanbiomonitoring , all Portuguese public health institutions have an ethics committee to which research and surveillance projects using a HBM approach have to be submitted prior to their commencement, as any project involving data and sample collection. All study protocols mentioned were approved by the University of Lisbon, Faculty of Medicine Ethics Committee. In addition, projects where recruitment involved collaborations with other health institutes were also approved by their respective ethics committees, as was the case of Dr Alfredo da Costa Maternity where preg- nant women are recruited in Lisbon and Dona Estefânia Hospital where children were formerly recruited, and all the hospitals and maternities collaborating with FEXHE- BIO's aims of determining foetal exposure to lead. Appraisals from health ethics committees are not legally binding  but it is accepted practice to conform to the recommendations made.
The successful completion of the DEMOCOPHES project and the complements from other exposure stud- ies in Europe illustrate the feasibility and usefulness of biological monitoring approaches, in particular when relying on hair samples that may be easily obtained, stored and transported. While such studies have become a routine function in the United States through the National Health And Nutrition Examination Survey , and the biomonitoring reports from the Centers for Disease Control and Prevention have become key resources for research on human exposures to environmental chemicals, Europe has lagged behind. Following international policy decisions to decrease global mercury pollution, such humanbiomonitoring studies will be crucial to monitor the effects of the interventions.