Action B4

Exposure assessment (AUTH)

The  objectives of this action are:

  • to apply a detailed multimedia model for the environmental contaminants capturing various exposure pathways and routes at different geographical scales in order to permit the appropriate analysis of environmental monitoring data;
  • to apply an exposure model to derive individual exposure taking into account time activity diaries and lifestyle
  • to develop a lifetime generic PBTK model in: (a) forward mode to assess the internal doses of chemicals in the target tissues and (b) backward mode to reconstruct chemical exposure from HBM data

 

The expected results are:

  • Environmental burden for the chemicals contaminants capturing the various exposure pathways and routes.
  • Exposure scenarios and quantitative exposure estimates for the population as a whole and for specific population sub-groups
  • Biology-based modeling system to interpret biomonitoring data with regard to their use for health impact assessment

Action B.4 is divided into four inter-related tasks, focusing respectively on the application of multimedia modeling to assess environmental concentrations of the selected chemicals in the different environmental media  starting from environmental monitoring values, on the application of models for exposure assessment for total populations and for targeted population sub-groups  and on the development of a lifetime generic PBTK model both in the forward mode to estimate the concentration of chemicals in the target tissues and in backward mode (reverse dosimetry) to reconstruct exposure estimates from biomonitoring data.

Task 4.1 Environmental modeling (AUTH)

 

The aim of this task is the application of multimedia models for families of environmental toxicants for which neurotoxicity or carcinogenicity has been established (i.e. heavy metals, selected organic substances such as PCBs and PBDEs).

Task 4.2 Exposure modeling (CSIC)

 

An already developed exposure modeling framework will be applied and further refined based on information on environmental media concentrations (from Task 2.1 – data collection), or alternatively from the environmental burdens derived from Task 4.1 – environmental modeling. In addition data from exposure factor databases, and time activity diaries and dietary habits for the populations and selected subgroups of interest will be used to derive exposure levels for the population and vulnerable groups.

Task 4.3 Development of a lifetime generic PBTK model incorporating mixtures interaction (AUTH)

 

The aim of this task is to develop a generic PBTK model which will incorporate advanced characteristics including lifespan evolution in physiology, from the moment of conception till 80 years of life-time; detailed description of pregnancy (mother-foetus interaction) and lactation (toxicants concentration in milk) periods; detailed compartmental description of human anatomy and receptor binding; detailed description of inhalation, dermal and oral routes of exposure; interaction of mixtures at the level of metabolism

The generic character of the model will be ensured by the capability of assessing new chemicals or chemicals with limited information. In this case, the model will be linked to quantitative structure-activity relationships (QSARs), so as to calculate chemical-specific input parameters of PBTK models.

Task 4.4 Reverse dosimetry (AUTH)

 

This task entails the application of reverse dosimetry techniques to assimilate human biomonitoring data and their translation into intake distribution. The main aim is to identify the specific input distributions that best explain the observed outputs (i.e. biomonitoring data) while minimizing an appropriate metric of error.

The generic PBTK model using a computational inference engine for inverse modelling optimization and Bayesian-based hierarchical population modelling for extrapolation of single individual samples to population-relevant exposure estimates will be the crux of our approach.