Roel Smolders

Applicability of non-invasively collected matrices for human biomonitoring

With its inclusion under Action 3 in the Environment and Health Action Plan 2004–2010 of the European Commission, human biomonitoring is currently receiving an increasing amount of attention from the scientific community as a tool to better quantify human exposure to, and health effects of, environmental stressors. Despite the policy support, however, there are still several issues that restrict the routine application of human biomonitoring data in environmental health impact assessment. One of the main issues is the obvious need to routinely collect human samples for large-scale surveys. Particularly the collection of invasive samples from susceptible populations may suffer from ethical and practical limitations. Children, pregnant women, elderly, or chronically-ill people are among those that would benefit the most from non-invasive, repeated or routine sampling. Therefore, the use of non-invasively collected matrices for human biomonitoring should be promoted as an ethically appropriate, cost-efficient and toxicologically relevant alternative for many biomarkers that are currently determined in invasively collected matrices. This review illustrates that several non-invasively collected matrices are widely used that can be an valuable addition to, or alternative for, invasively collected matrices such as peripheral blood sampling. Moreover, a well-informed choice of matrix can provide an added value for human biomonitoring, as different non-invasively collected matrices can offer opportunities to study additional aspects of exposure to and effects from environmental contaminants, such as repeated sampling, historical overview of exposure, mother-child transfer of substances, or monitoring of substances with short biological half-lives.

A Conceptual Framework for Using Mussels as Biomonitors in Whole Effluent Toxicity

As a main source of direct and continuous input of pollutants in the aquatic ecosystem, studying the effects of effluents on receiving ecosystems has a high ecological relevance. While ecological risk assessment procedures are usually based on a chemical-based single component approach, their application for complex mixtures and effluents is less straightforward. A chemical-based approach has to rely on the knowledge of what chemicals are present in effluents, their potential toxicity, how all of these individual chemicals interact and what their individual and combined contribution to the mixture is. Whole effluent toxicity (WET) testing, however, is an integrative tool that measures the toxic effect of an effluent as a whole and accounts for uncharacterized sources of toxicity and for interactions. This paper addresses the use of transplanted bivalves, i.e., caged mussels, as a biomonitoring tool in WET testing with special reference to field situations in both freshwater and marine environments. We indicate how endpoints at different levels of biological organization within exposed mussels can give an integrative overview of effects. Finally, we will provide a framework for future research using mussels and discuss a multitude of instream responses for routine, efficient and cost-effective active biomonitoring applications.

Sources of Variability in Biomarker Concentrations

Human biomonitoring has become a primary tool for chemical exposure characterization in a wide variety of contexts: population monitoring and characterization at a national level, assessment and description of cohort exposures, and individual exposure assessments in the context of epidemiological research into potential adverse health effects of chemical exposures. The accurate use of biomonitoring as an exposure characterization tool requires understanding of factors, apart from external exposure level, that influence variation in biomarker concentrations. This review provides an overview of factors that might influence inter- and intraindividual variation in biomarker concentrations apart from external exposure magnitude. These factors include characteristics of the specific chemical of interest, characteristics of the likely route(s) and frequency of exposure, and physiological characteristics of the biomonitoring matrix (typically, blood or urine). Intraindividual variation in biomarker concentrations may be markedly affected by the relationship between the elimination half-life and the intervals between exposure events, as well as by variation in characteristics of the biomonitored media such as blood lipid content or urinary flow rate. Variation across individuals may occur due to differences in time of sampling relative to exposure events, physiological differences influencing urinary flow or creatinine excretion rates or blood characteristics, and interindividual differences in metabolic rate or other factors influencing the absorption or excretion rate of a compound. Awareness of these factors can assist researchers in improving the design and interpretation of biomonitoring studies.

A Review on the Practical Application of Human Biomonitoring in Integrated Environmental Health Impact Assessment

Environmental health sciences focus on the link between the presence of contaminants in the environment and their relation with possible adverse health effects. Within this context, human biomonitoring (HBM) data have proven to be a valuable addition to, or have even surpassed, estimates of exposure based on environmental measures. Probably the main achievement of HBM data is that it provides an integrated overview of the pollutant dose any constituent is exposed to and incorporates bioaccumulation, excretion, half-life, and other potentially critical toxicokinetic parameters. In an integrated environmental health impact assessment framework, HBM serves as a pivotal point between environment and health, on the one hand leaning on environmental data to provide information on sources and pathways of exposure, and on the other hand clarifying hypotheses on the relationship between internal dose and prevalence of disease clusters. This study reflects the work performed in the INTARESE project (Integrated Assessment of Health Risk of Environmental Stressors in Europe). Because it was perceived that there was an overall lack of knowledge on the general methodology and potential application of HBM data in integrated environmental health impact assessment, an extensive review of literature was performed on past and current developments, potential, and applicability of HBM within the context of integrated environmental health impact assessment. This study covers three main topics that provide guidance for improved interpretation and application of HBM data: (1) sample collection and storage, (2) sample measurement, and (3) data interpretation. These main issues were discussed for 15 of the most common or relevant (classes of) chemicals. For more detailed information, the reader is pointed to the unabridged review (INTARESE, 2007), and consultation is available through the INTARESE web site (www.intarese.org).

Biomonitoring and biomarkers to unravel the risks from prenatal environmental exposures for later health outcomes

An increasing number of studies have addressed the concern that environmental pollutants may contribute to the early origin of diseases. Epidemiologic studies suggest that prenatal exposure to air pollutants, several food contaminants, and chemicals present in consumer products are associated with nongenetically transmitted adverse health effects, which manifest after birth. Changes in neurobehavior, sexual development, the prevalence of asthma and allergy, and growth curves have been shown to be associated with pollutant exposure at early life stages. This review focuses on human molecular epidemiologic studies that contribute knowledge by introducing biomarker measurements to obtain a mechanistic understanding of the relation between early life exposures and health outcome. It has been hypothesized that subtle effects induced by pollutant exposure during development can lead to functional deficits and altered programming, which leads to increased disease or dysfunction risk later in life. Biomarker analysis may provide sensitive tools to trace these subtle changes and obtain mechanistic insight about the causal pathway between external exposure and health effects in human population studies. Biomarkers of exposure can be measured in mothers before conception, during pregnancy, or after birth. Different biological tissues-such as peripheral or cord blood samples, hair samples, meconium, and urine-provide specific information that reflects the actual dose during pregnancy or at birth. Biomarkers of effect may include changes in hormone concentrations, oxidative stress variables, changes in gene expression levels, and epigenetic changes.

Availability and comparability of human biomonitoring data across Europe: a case-study on blood-lead levels.

Recently, it has become clear that the complexity of environmental health issues requires an approach that takes into account the complexities, interdependencies and uncertainties of the real world. An urgent issue that has surfaced is the need for accurate tools to better describe exposure characterization to environmental chemicals. By including human biomonitoring (HBM) data, a greater precision in exposure and associated risk estimates and more accurate dose-response relationships may be achieved. A restricting issue still is the availability of reliable and comparable HBM data. The aim of the current study was twofold: (1) to find out whether it is practically feasible to collect raw, individual HBM data across Europe; and (2) to evaluate the comparability and use of these HBM data for environmental health impact assessment at a European scale. Blood-lead (B-Pb) was selected as the chemical of choice because of its long history as an environmental pollutant in HBM programs and its known public health relevance. Through literature search and identification of HBM experts across Europe, HBM programs that measured B-Pb were identified and asked to share individual data on age, gender and B-Pb levels. Following this request, more than 20,000 individual data points from 8 European countries were collected. Analysing these data made clear that it is difficult to use disparate data collections because of the inherent variability with respect to the gender and age of participants and calendar-years sampled. When these confounders were taken however, there was no additional variability in B-Pb distributions among different countries. It was concluded that while it is possible to collect HBM data from different sources across Europe, the need to get data from comparable (sub-)populations is essential for appropriate use and interpretation of HBM data for environmental health impact assessment.

Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 1: Metals

The aim of the current HBM-study is to further the understanding of the impact of inter- and intra-individual variability in HBM surveys as it may have implications for the design and interpretation of the study outcomes. As spot samples only provide a snapshot in time of the concentrations of chemicals in an individual, it remains unclear to what extent intra-individual variability plays a role in the overall variability of population-wide HBM surveys. The current paper describes the results of an intensive biomonitoring study, in which all individual urine samples of 8 individuals were collected over a 6-day sampling period (a total of 352 unique samples). By analyzing different metals (As, Cd, Mn, Ni) in each individual sample, inter- and intra-individual variability for these four metals could be determined, and the relationships between exposure, internal dose, and sampling protocol assessed. Although the range of biomarker values for different metals was well within the normal range reported in large-scale population surveys, large intra-individual differences over a 6-day period could also be observed. Typically, measured biomarker values span at least an order of magnitude within an individual, and more if specific exposure episodes could be identified. Fish consumption for example caused a twenty- to thirty-fold increase in urinary As-levels over a period of 2-6h. Intra-class correlation coefficients (ICC) were typically low for uncorrected biomarker values (between 0.104 and 0.460 for the 4 metals), but improved when corrected for creatinine or specific gravity (SG). The results show that even though urine is a preferred matrix for HBM studies, there are certain methodological issues that need to be taken into account in the interpretation of urinary biomarker data, related to the intrinsic variability of the urination process itself, the relationship between exposure events and biomarker quantification, and the timing of sampling. When setting up HBM-projects, this expected relationship between individual exposure episode and urinary biomarker concentration needs to be taken into account.

Framework for the development and application of environmental biological monitoring guidance values

Human biomonitoring (HBM) is widely recognised as a useful tool to aid assessment of exposure to chemical substances, but our ability to detect hazardous substances (or their metabolites and health effects) often exceeds our understanding of their biological relevance. There are only a few established frameworks for developing and using occupational and environmental biological guidance values (BGVs), mostly for data-rich substances that have been in use for some time. BGVs for new substances and those with unknown dose-response relationships are difficult to derive. An accepted framework based on current scientific knowledge and best practice is therefore urgently needed to help scientists, regulators, and stakeholders to design appropriate HBM studies, interpret HBM data (both for groups and individuals) understand the limitations and to take appropriate action when required. The development and application of such a tool is described here. We derived a conceptual framework that was refined by consultation with an advisory group and workshop. The resulting framework comprised four levels defined by increasing data, with increasing confidence for human health risk assessment. Available data were used for 12 chemicals with expert judgement to illustrate the utility of the framework.

Cellular Energy Allocation in Hediste diversicolor Exposed to Sediment Contaminants

Environmental contaminants released into water tend to accumulate in sediment, leading to exposure for sediment-dwelling organisms. This study aimed to clarify whether chronic (56 d) exposure to a mixture of environmentally relevant concentrations of contaminants (tributyltin [TBT] and perfluorononanoic acid [PFNA]) spiked in clean sediment would affect the sediment-dwelling polychaete Hediste diversicolor. Endpoints were burial time, biomass change, and cellular energy allocation (CEA). Sediments were spiked with these two contaminants to produce different levels of contamination. Chemical analyses of the sediment following the exposure indicated that the spiking procedure was only partially successful and treatments were grouped into four categories according to contaminant concentrations: “background,” “low,” “moderate,” and “high.” No significant differences were found between treatments with respect to burial time, biomass change, or energy storage fractions (proteins, lipids, carbohydrates) in the polychaetes. A significant increase in cellular respiration was found for polychaetes in “moderate” and “high” treatment groups compared to the “background” treatment group. This resulted in significantly lower cellular energy allocation values for “moderate” and “high” treatment groups compared to “background.” Although the effects were not marked, the results show that sediment-dwelling organisms may be affected following chronic exposure to environmental contaminants. There is a need to clarify whether chronic exposures exert a negative effect on sediment-dwelling organisms.

Human biomonitoring and the INSPIRE directive: spatial data as link for environment and health research.

Recently, there has been a rapid gain of interest in the availability, applicability, and integration of different types of spatial data for environment and health issues. The INSPIRE Directive (Directive 2007/2/EC) aims at providing better and easily accessible spatial information in Europe for the formulation and implementation of community policy on the environment by triggering the creation of a European spatial information infrastructure that delivers integrated spatial information services to potential users. Human biomonitoring (HBM) significantly contributes to the already existing data on environment and health because of its specific nature of providing information on the internal dose of chemicals rather than their mere presence in different environmental compartments. However, due to the intrinsic nature of HBM data, a number of issues need to be dealt with if HBM data are to be used to its full capacity in a geographic information systems (GIS) environment and within the INSPIRE directive. The current article highlights some of these issues, and discusses a number of options to improve the geographical relevance of HBM data for their optimal use within the INSPIRE Directive framework. The main aim of this publication is to illustrate that HBM has a significant contribution to make to the INSPIRE Directive, although some kind of data aggregation will be necessary to protect individual privacy. If HBM data wants to have a significant contribution to spatial information used to assist policymaking and on the surveillance or tracking of the direct or indirect impact of such policies, the HBM data need to be compatible with other data collected within the other themes of the INSPIRE Directive.