C10 : A Tiered Strategy to Assess Microplastic Inhalation

Description

The LRI C10 project aims to develop better tools for the identification of the inhalation toxicity of microplastics of different origin/with different properties.

Humans are ubiquitously exposed to microplastics; this includes a diverse class of compounds/particles but also very different routes of exposure i.e. drinking water, food, and air pollution. The concentration of nano- and microplastic particles (NMPs) in the environment is increasing in parallel to global plastic production and increasing use of plastic materials. NMPs are detectable in numerous aquatic organisms and also in human biomonitoring samples. Thus, there is agreement on the issue that humans ingest and inhale microplastics which pose a possible risk for human health.

However, so far, human risk assessment is lacking a standardized approach due to the following reasons:

• Limited availability of appropriate reference materials
• Analytical challenges in the detection and dose definition
• Missing information about relevant phys-chem properties of test materials

Missing of standardized testing conditions (particle sizes, time lines, appropriate cell systems for in-vitro testing and application, dose response, relevant endpoints and time lines for in vivo studies)

In general, comprehensive experimental data of particle properties and particle-bio interactions are needed to perform a high-quality risk management in the case of adverse health effects on human. Data on the fate of particles in the body upon inhalation, dosimetry and dose-metrics as well as biodissolution are decisive factors to achieve an improved risk assessment.

The state of the art characterization of micro- and nanoplastics separately and after cellular uptake with respect to the application of correlative measurement techniques is yet limited because of the difficulty to find the same particles and cells in different instruments. In this project existing and new algorithms will be further developed and integrated in microscopy and spectroscopy workflows for automatic relocalization, detection, and measurement of identical objects.

Objectives

Obj. 1:  Identify the most relevant molecular descriptors, particle morphology descriptors, as well as particle interaction descriptors that determine inhalation toxicity

Obj. 2: . Identify existing schemes for particle dosimetry and assessment and transfer concepts of analogy from other solid inhalable particles to microplastics,

Obj. 3:   Set-up a tiered testing approach starting with in vitro testing that relies on state-of the art methodology and uses cell lines that are relevant and -if possible- standardised and predictive. Refine testing according to exposure considerations and test systems of different complexity and, finally derive conditions and input parameters for in vivo testing

Obj. 4:   Rank microplastic properties (phys-chem parameters, distribution and dose knowledge and biological effect profiles) by their relevance for human risk assessment, most specifically human hazard by inhalation.

Obj. 5:   Based on the ranking, provide recommendations for subsequent confirmatory in vivo studies

Obj. 6:   Provide the information to and interact with parallel work on especially concerning the science-based group ranges (in the relevant descriptor) that support adequate binning ranges in the model (by the same descriptors).