Periodic Reporting for period 3 - PlasticsFatE (Plastics fate and effects in the human body)
Okres sprawozdawczy: 2024-04-01 do 2025-03-31
Due to their unique properties, plastics are widely used and found everywhere. In the environment, plastics degrade slowly to micro-plastics (MP) (< 5 mm) and nano-plastics (NP) (< 1 um). MP are also added, e.g. to cosmetics or released from textiles or tyre wear, and make up a complex mixture of polymers and associated chemicals (AC) added to improve their performance or adsorbed from the environment in concentrations much higher than the surroundings. There is strong evidence that humans are exposed to micro- and nano-plastics (MNP) through diet, drinking water or inhalation. However, our present understanding of the extent of human exposure to MNP is still poor, which is why scientifically sound data on exposure, fate and effects of MNP in humans is urgently needed. One challenge in assessing the impact of MNP and AC on human health is to make sure that our measurement and testing methods are capable of producing reliable data. Despite progress in measuring plastic particles in environmental media, reliable measurements and toxicity testing of these particles in the human body, in food, drinking water or air is still scarce. This is even more the case for NP particles that may enter human cells. The lack of robust scientific data and methodologies hampers the development of standards and test guidelines for science-based risk assessment and the implementation of relevant policies and regulations. PlasticsFatE will address these challenges by implementing a comprehensive measurement and testing program (“test the test”) to establish validated methods and robust data on human exposure, fate and hazard of MNP.
A test materials strategy has been established covering relevant polymer particles (such as PE, PET, PP, PS) and made available for method testing and validation. We have continued to focus on organizing the supply of test materials and supporting material characterization for exposure, fate and hazard assessment. Tasks included the selection and characterization of additional MNPs (in particular of sub-micro- and nanosized as well as fiber materials), evaluation of analytical techniques, physicochemical material characterization for exposure and hazard testing, and method validation. Collaborative efforts led to the development of protocols for sample preparation and purification, and analytical techniques suitable for MNP identification, detection and measurement. Additionally, in vitro digestion models and leaching approaches were established to simulate MNP translocation and bio-transformation in the gut, and the leaching of additives from NP particles and how this may change the overall toxicity. Also, inter-laboratory comparison studies (ILS) have been implemented to ensure method accuracy and reliability for particle detection and size measurement.
We have also delivered significant achievements in the development and validation of computational models for understanding MNP fate and behaviour after ingestion and inhalation. Studies on bottled water, food (still ongoing), indoor/outdoor air and personal care products provided valuable insights into real human exposure levels. Investigations into MNP effects on the human gut microbiome and chronic ingestion studies have been started. Close collaboration across the project facilitated the validation of human tissue digestion and exposure monitoring and biomonitoring protocols. Furthermore, a quality assurance/quality control document was drafted to ensure a high data quality and methodological consistency in MNP research.
Substantial progress was made in toxicity testing of MNPs, focusing on cell viability, cellular uptake, barrier integrity, and immunotoxic effects. Studies encompassed a wide range of in vitro models simulating acute and sub-acute exposure scenarios, human tissues and organs. Investigations into particle transport across biological barriers and bioaccumulation studies provided valuable insights. Collaborative efforts are ongoing to establish inter-laboratory comparisons of in vitro and in vivo studies also by engaging in CUSP meetings to facilitate knowledge exchange.
Work progress has also been made to enhance human health risk assessment for MNPs and associated chemicals through an Integrated Approach to Testing and Assessment (IATA). We are developing decision support systems and prospective risk assessment tools to guide regulatory decision-making. Ambitious publications are planned to address risk assessment approaches and regulatory gaps, with a focus on supporting relevant EU policies and regulations.
We are also testing critical methodologies and strategies developed in the project through a number of case studies. Activities included method validation for occupational exposure monitoring and human biomonitoring, investigation of MNP surfaces to serve as potential vectors for pathogens and contaminants, and preliminary studies on long-term effects of MNPs through uptake in the lung and the food-web. Regular coordination meetings are organised across WPs to ensure feedback and method improvement and standardization.
All project findings achieved so far have been actively disseminated, to engage stakeholders, and shape policy discourse, also within CUSP. Efforts included the development of dissemination plans, web portals, training workshops, and policy recommendations. Collaborative engagement across sectors significantly enhanced PlasticsFatE's visibility and influence, contributing to broader efforts addressing MNP-related challenges.
We have also delivered significant achievements in the development and validation of computational models for understanding MNP fate and behaviour after ingestion and inhalation. Studies on bottled water, food (still ongoing), indoor/outdoor air and personal care products provided valuable insights into real human exposure levels. Investigations into MNP effects on the human gut microbiome and chronic ingestion studies have been started. Close collaboration across the project facilitated the validation of human tissue digestion and exposure monitoring and biomonitoring protocols. Furthermore, a quality assurance/quality control document was drafted to ensure a high data quality and methodological consistency in MNP research.
Substantial progress was made in toxicity testing of MNPs, focusing on cell viability, cellular uptake, barrier integrity, and immunotoxic effects. Studies encompassed a wide range of in vitro models simulating acute and sub-acute exposure scenarios, human tissues and organs. Investigations into particle transport across biological barriers and bioaccumulation studies provided valuable insights. Collaborative efforts are ongoing to establish inter-laboratory comparisons of in vitro and in vivo studies also by engaging in CUSP meetings to facilitate knowledge exchange.
Work progress has also been made to enhance human health risk assessment for MNPs and associated chemicals through an Integrated Approach to Testing and Assessment (IATA). We are developing decision support systems and prospective risk assessment tools to guide regulatory decision-making. Ambitious publications are planned to address risk assessment approaches and regulatory gaps, with a focus on supporting relevant EU policies and regulations.
We are also testing critical methodologies and strategies developed in the project through a number of case studies. Activities included method validation for occupational exposure monitoring and human biomonitoring, investigation of MNP surfaces to serve as potential vectors for pathogens and contaminants, and preliminary studies on long-term effects of MNPs through uptake in the lung and the food-web. Regular coordination meetings are organised across WPs to ensure feedback and method improvement and standardization.
All project findings achieved so far have been actively disseminated, to engage stakeholders, and shape policy discourse, also within CUSP. Efforts included the development of dissemination plans, web portals, training workshops, and policy recommendations. Collaborative engagement across sectors significantly enhanced PlasticsFatE's visibility and influence, contributing to broader efforts addressing MNP-related challenges.
For the first time, the applicability of suitable measurement and testing methods will be examined and validated for a variety of relevant MNPs based on well-characterized test and reference materials and interlaboratory comparisons studies. The resulting physicochemical characterization and toxicity data will be integrated into a newly developed human and environmental risk assessment strategy, to reliably assess true hazard and exposure to these particles and associated additives and contaminants in food, drinks, air and personal care products (PCP), and their fate and effects in the human body. This will be a milestone in our current understanding of the complex interaction between MNP particles and human health but also in the development of new standards (within VAMAS/TWA 45 or ISO/TC 147/SC2-JWG-1) that can support the implementation of EU policies (such as the EU plastics strategy) and regulations (such as REACH). New exposure, fate and toxicokinetic models and advanced in vitro 2D/3D co-culture cell and in vivo models as well as new MNP-specific biomarkers and toxicity endpoints were used and provided new insight into the mode of action that steer the behavior and effects of MNP particles in human cells, fluids and tissues and may lead to oxidative stress, toxicity, or (chronic) inflammation. More work will be devoted in the final year to elucidate long-term effects and the still unknown role of chemicals associated with MNP by using more realistic (aged) MNP particles, exposure times, doses and concentrations, and analytical methods (such as HPLC or ICP/MS) and co-exposure experiments to assess also combined effects of MNP and chemical contaminants leaching from these polymers in the human body.