Action B5

Environment-wide association studies (ISS)

The final aim of this Action is twofold:

  • to provide a methodology for interpreting through advanced statistical tools the HBM data collected in Action B.2 and/or collected through targeted filed campaigns in Action B.3 in order to quantify health effects attributable to the exposure scenarios identified;
  • to validate the population exposure scenarios derived in Action B.4 through the use of biomonitoring data.

Toxicokinetic modelling will be used to translate external exposure into internal dose and biologically effective dose as it relates to toxic effects, taking into account the toxicokinetic aspects of exposure patterns, exposure routes (e.g. absorption, distribution, metabolism), accumulation and elimination and inter-individual variation. Integrating exposure modelling and biomonitoring through the use of toxicokinetic models provides an opportunity to validate model predictions and to interpret biomonitoring data with regard to exposure routes and sources, as well as health outcomes.

The expected results are:

  • Validation of the exposure estimates derived in Action B.4 (Exposure assessment) with the use of human biomonitoring data and biology-based models (reverse dosimetry)
  • Quantitative assessment of health impact to the population and specific sub-groups due to exposure to selected chemicals through advanced statistical analysis (multivariate regression analysis)

The Action 5 is split into two main tasks: the first comprises the forward use of physiology-based toxicokinetic models to assess internal exposure to associated to external exposure results gathered from Action B.4 as well as their backward use to reconstruct the exposure patterns of the local population to the selected chemicals based on biomonitoring data; the second regards the use of exposure and epidemiological data with PBTK models and HBM data through the application of advanced statistical tools to interpret the biomonitoring data collected in Actions B.2 or measured in Action B.3 towards a more precise assessment of the health impact associable to environmental burden in the areas of interest to the project.

Task 5.1: Data assimilation by linking biomarker data to exposure burden from multiple routes and comparing them to Biomonitoring Equivalents (ISS)

 

This task focuses on exposure reconstruction, which stands for the re-assessment of the external exposure that is consistent with the measured biomonitoring data. Here, the method and iterative algorithm for exposure reconstruction developed in Task B.4.4 – “reverse dosimetry” will be applied on the HBM datasets collated from the combination of data collected from Actions B.2 – Data collection and management and B.3 – “Targeted measurement campaigns to fill the data gaps”. The objective is to estimate the chemical exposure profiles of the populations and sub-groups of population of interest in the four demonstration sites of the project.

Task 5.2: Link with Health Observations (ISS)

 

The overall objective of this task is the quantitative estimation of the effect on human health due to exposure to selected chemicals using the results derived from the application of PBTK model and /or biomonitoring data collected in Action B.2 – “Data collection and management” or collected through targeted field campaigns executed in Action B.3 – “Targeted measurement campaigns to fill the data gaps”. Internal doses will be coupled to health impacts on the local population through advanced statistical methods to derive the dose – response functions which account for differences in exposure patterns, susceptibility differences and inter-individual variation (due to lifestyle, age, sex or physiological status) in health response.