A new inventory from PARC provides an overview of the physiologically based kinetic (PBK) models assessing the internal exposure in humans during life concerning five groups of chemicals: bisphenols, metals, mycotoxins, perfluorinated compounds, and pesticides.

Twenty-one European institutes from ten countries have joined forces, under PARC, to develop a strategy and tools for more efficient chemical risk assessment across the lifespan. These will contribute to the necessary policy-making actions for human-life protection, especially regarding the vulnerable populations such as pregnant women and foetuses, newborns, young children and elderly.  To this end, a new publication with an inventory of the available mathematical models used for the assessment of lifetime internal exposure to prioritised substances is now on line.  

Human biomonitoring - physiologically basedkinetic (PBK) models

Humans are daily exposed to numerous substances. To monitor these exposures and potential early effects caused by these substances in the body, we conduct human biomonitoring (HBM) surveys collecting biological samples like blood or urine to measure the levels of specific substances. The measurement considers all possible sources of exposure, regardless of how the substances entered the body, the environment of exposure (such as home or work), and the activities or products consumed.  

In conjunction with HBM data and exposure information, toxicokinetic (TK) modelling can establish a link between external and internal exposure (forward dosimetry) or internal to external exposure (reverse dosimetry) over time. One specific type of TK model, known as PBK models (also called PBTK or PBPK), is crucial in risk assessment and gaining popularity in regulatory applications. These models quantitatively describe the processes of absorption, distribution, metabolism, and excretion of substances in the human body. They divide the body into compartments representing organs connected by blood. PBK models help determine the effective and bioavailable concentration at the target site, improving our understanding of the relationship between exposure and adverse effects.

PARC addresses limitations on existing PBK models  

The PARC project focuses on refining and developing PBK models for human risk assessment. The goal is to address the sensitivities between sub-group populations by considering factors such as the evolution of physiological and biochemical processes throughout life (e.g., placental transfer, blood-brain barrier, etc.), diversity in exposure routes, interpretation of biomonitoring data (e.g., concentrations of parent compounds or metabolites in blood, urine, or other biological matrices), and kinetic of mixtures. In this way, PARC builds upon recommendations and lessons learnt from the EU funded HBM4EU project ↗. It emphasises the limited toxicokinetic information on absorption and metabolism data when it comes to inhalation exposure (important for occupational settings) and dermal exposure routes (important for assessing exposure to cosmetics and consumer products) for a high number of chemicals prioritised by PARC, including metals, PFAS, and pesticides). It also highlighted that models and parameter data are lacking for vulnerable populations such as pregnant women and foetuses, newborns, young children or the elderly. This underscores the need for further research and development in these areas to enhance our understanding and assessment of potential risks associated with exposure to these chemicals.

European Agencies in synergy

In collaboration with ongoing efforts at the European Food Safety Authority (EFSA ↗) and the European Chemicals Agency (ECHA ↗), the project developed practical tools, models, methods, and a general strategy to enhance the use of PBK models for comprehensive risk assessment across the lifespan.

This PARC project will propose a coherent implementation of these models and provide training on PBK model usage to evaluate lifetime internal exposures. This will empower end-users, including PARC data owners, EFSA panels/ECHA working groups, national risk assessment experts and other relevant stakeholders such as those from the chemical industry.