For many chemicals, the health impacts associated with exposure and the most likely exposure pathways remain unknown. The impacts of human exposure to mixtures of chemicals are also poorly understood, particularly in the most vulnerable individuals. Such knowledge is critical to informing policy makers and the public (under the pillar on science to policy) regarding the most scientifically sound interpretation of exposure levels (under the pillar on a European human biomonitoring platform).
Under HBM4EU, we will combine health information with the results of human biomonitoring in order to inform our understanding of exposure-response relationships. Using modelling tools we will relate internal exposure with environmental sources and identify the most likely exposure pathways to support public and individual actions.
We will assess the potential health impacts of chemical exposures in different age groups and across genders, taking into account other factors such as socio-economic status, lifestyle, diet and environmental conditions. We will generate and assess the evidence for a causal link between chemicals and health impacts and identify the most suitable markers of such effects.
We will also the investigate the effects of exposure to mixtures of chemicals, and will use cutting edge technologies to search for emerging substances in human matrices that may serve as early warnings of future concern.
Human biomonitoring and health studies have a lot of similarities in terms of the infrastructure and procedures required for their implementation. This Work Package will develop guidelines and standardized operating protocols (SOPs) on how to combine human biomonitoring and health studies in a cost-effective manner. The guidelines and SOPs will incorporate lessons learnt from experiences with combining these two types of studies.
Feasibility studies will be conducted on the integration of human biomonitoring and health studies, in order to identify both synergies and obstacles that can emerge during the preparation and implementation of fieldwork studies in different settings and across national infrastructures. We will host a workshop to explore the synergies and obstacles related to the combination of HBM and health studies will be organized.
Partners in this Work Package will gather information about existing biological samples that have been collected and stored for future use in health studies and that may be used for human biomonitoring. We will develop criteria to guide the use of these kinds of samples in human biomonitoring. We will also investigate the legal and technical options for recording links between human biomonitoring studies, health studies and administrative registers, such as causes of death register, cancer register and hospitalizations.
The main objectives of this Work Package is to link human biomonitoring data to exposure. Our work will link data from human biomonitoring, environmental monitoring and external exposure modelling. This will support a more effective interpretation of human biomonitoring data in elucidating chemical exposure and supporting both chemical risk assessment and management.
Our work will help to determine the external exposure levels for the HBM4EU priority substances, starting from human biomonitoring data and using a reverse dosimetry approach. This will contribute to the identification of exposure levels in Europe that are above health-relevant values. Available physiology-based toxicokinetic (PBTK) models will be reviewed and analysed to properly parameterize a generic PBTK modelling platform for the priority substances, both individually and in combination. Both the biochemical interactions between components of chemical mixtures to which the EU population may be exposed, as well as changes in absorption, distribution, metabolism and excretion (ADME) properties and internal exposure processes with age and gender will be taken into account.
This new knowledge will allow the HBM4EU team to assess newly proposed regulatory thresholds and to determine which exposure pathway(s) and route(s) contribute more to the overall exposure burden.
Existing exposure-related and ancillary data for HBM4EU priority substances and state of the art exposure models will be collated and adapted to estimate regional differences in exposure. Exposure models will be coupled to PBTK to effectively translate the estimated exposure levels into internal and biologically effective dose at target tissues and candidate biomonitoring matrices.
Work Package partners will collect, organize and store available scientific data on the effect of exposures on health outcomes using mechanistic information. This work will produce new knowledge on the connection between chemical exposures and health, using data from human cohorts, occupational studies, hot spots and other epidemiological studies.
We will identify knowledge gaps in exposure-health outcome relationships that can be answered either by experimental in-vitro or in-vivo studies, or by epidemiological or health studies. Our work aims to validate plausible pathways of toxicity and link them with adverse outcome pathways (AOPs) though a joint analysis of the metabolic and gene regulatory pathways in human samples.
Our work will describe the links between exposures to HBM4EU priority substances identified within HMB4EU and human health outcomes using two complementary approaches, namely by developing AOPs and by exploiting cohort studies. The results emerging from this Work Package will play an essential role in the establishment associations between exposure and adverse health outcomes that are based on an understanding of mechanisms of action.
Implementing human biomonitoring programmes involves the identification and quantification of pollutants in human biological matrices, by analysing biomarkers of exposure, and the assessment of biological changes which occur as a result of exposure, by analysing biomarkers of effect. Biomarkers of effect and exposure are crucial for the assessment of exposure-effect relationships. Biomarkers of effect reflect any accurately reproducibly and quantifiable change that provides an objective measure of health status or disease after exposure.
Our work will provide the tools to understand the impact of environmental exposures on human health, through the identification and validation of specific biomarkers of effect. For this purpose, HBM4EU partners will create an inventory of existing biomarkers of human health effects, based on the scientific literature, and will classify these biomarkers according to their relevance, level of validation, applicability to human biomonitoring studies, and adverse outcome pathways (AOPs).
We will focus on the HBM4EU prioritized substances, including mixtures, and will explore biomarkers of effect related to neurological development, reproductive diseases, endocrine diseases, obesity and metabolic diseases and allergies, among other clinically-relevant outcomes. As a proof of concept, partners will explore specific biomarkers of effect in available human samples from on-going European human cohort studies, and will develop and implement new biomarkers of effect, if needed.
One of the main objectives of this Work Package is to develop summary indicators to describe the exposure and body burden of chemical mixtures, with an emphasis on defining priority mixtures and identifying the drivers of mixture toxicity.
We will re-evaluate existing human biomonitoring data on mixtures, as well as collecting new human biomonitoring data on mixtures, with the aim of identifying real-life exposure patterns to mixtures.
Practical approaches to identify and assess the potential health risks and impacts of mixtures will be further developed and applied. Policy makers, stakeholders and the public at large will be kept informed about the exposure of the European population to mixture and the associated health risks.
Current human biomonitoring programmes are primarily based on the targeted analysis of chemicals that are known to be hazardous to human health. Such efforts are limited in their capability to detect and identify emerging chemicals, for which appropriate biomarkers are not in place and exposure trends are not established.
This Work Package addresses the issue of emerging substances, through the development and application of “suspect screening” approaches for the identification and monitoring of already known emerging chemicals that are not yet routinely measured, as well as non-targeted profiling approaches for revealing unknown chemicals that are potentially hazardous.
The work aims to anticipate emerging risks in the broader perspective of work towards a sustainable chemicals agenda, generating exploratory human data that might guide future priority setting for human biomonitoring programmes. Based on the latest cutting-edge technologies and integrated methodological approaches, the goal of this work is to respond to the need for early signals of the presence of chemicals in humans. This knowledge can support a policy agenda that aims to identify early warnings.