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Background Human exposure to micro- and nanoplastic particles (MNPs) is inevitable but human health risk assessment remains challenging for several reasons. MNPs are complex mixtures of particles derived from different polymer types, which may contain plenty of additives and/or contaminants. MNPs cover broad size distributions and often have irregular shapes and morphologies. Moreover, several of their properties change over time due to aging/ weathering. Case-by-case assessment of each MNP type does not seem feasible, more straightforward methodologies are needed. However, conceptual approaches for human health risk assessment are rare, reliable methods for exposure and hazard assessment are largely missing, and meaningful data is scarce. Methods Here we reviewed the state-of-the-art concerning risk assessment of chemicals with a specific focus on polymers as well as on (nano-)particles and fibres. For this purpose, we broadly screened relevant knowledge including guidance documents, standards, scientific publications, publicly available reports. We identified several suitable concepts such as: (i) polymers of low concern (PLC), (ii) poorly soluble low toxicity particles (PSLT) and (iii) fibre pathogenicity paradigm (FPP). We also aimed to identify promising methods, which may serve as a reasonable starting point for a test strategy. Results and conclusion Here, we propose a state-of-the-art modular risk assessment framework for MNPs, focusing primarily on inhalation as a key exposure route for humans that combines several integrated approaches to testing and assessment (IATAs). The framework starts with basic physicochemical characterisation (step 1), followed by assessing the potential for inhalative exposure (step 2) and includes several modules for toxicological assessment (step 3). We provide guidance on how to apply the framework and suggest suitable methods for characterization of physicochemical properties, exposure and hazard assessment. We put special emphasis on new approach methodologies (NAMs) and included grouping, where adequate. The framework has been improved in several iterative cycles by taking into account expert feedback and is currently being tested in several case studies. Overall, it can be regarded as an important step forward to tackle human health risk assessment.
Background Human exposure to micro- and nanoplastic particles (MNPs) is inevitable but human health risk assessment remains challenging for several reasons. MNPs are complex mixtures of particles derived from different polymer types, which may contain plenty of additives and/or contaminants. MNPs cover broad size distributions and often have irregular shapes and morphologies. Moreover, several of their properties change over time due to aging/ weathering. Case-by-case assessment of each MNP type does not seem feasible, more straightforward methodologies are needed. However, conceptual approaches for human health risk assessment are rare, reliable methods for exposure and hazard assessment are largely missing, and meaningful data is scarce. Methods Here we reviewed the state-of-the-art concerning risk assessment of chemicals with a specific focus on polymers as well as on (nano-)particles and fibres. For this purpose, we broadly screened relevant knowledge including guidance documents, standards, scientific publications, publicly available reports. We identified several suitable concepts such as: (i) polymers of low concern (PLC), (ii) poorly soluble low toxicity particles (PSLT) and (iii) fibre pathogenicity paradigm (FPP). We also aimed to identify promising methods, which may serve as a reasonable starting point for a test strategy. Results and conclusion Here, we propose a state-of-the-art modular risk assessment framework for MNPs, focusing primarily on inhalation as a key exposure route for humans that combines several integrated approaches to testing and assessment (IATAs). The framework starts with basic physicochemical characterisation (step 1), followed by assessing the potential for inhalative exposure (step 2) and includes several modules for toxicological assessment (step 3). We provide guidance on how to apply the framework and suggest suitable methods for characterization of physicochemical properties, exposure and hazard assessment. We put special emphasis on new approach methodologies (NAMs) and included grouping, where adequate. The framework has been improved in several iterative cycles by taking into account expert feedback and is currently being tested in several case studies. Overall, it can be regarded as an important step forward to tackle human health risk assessment.
Assessing the pharmacokinetics of monoclonal antibodies (mAbs) in relevant animal models is essential for designing improved formulations and developing mAb delivery platforms. We have established the pig, a large natural host animal for influenza with many similarities to humans, as a robust model for testing the therapeutic efficacy of anti-influenza mAbs and evaluating mAb delivery platforms. Here, we compared the pharmacokinetic characteristics of two anti-influenza hemagglutinin mAbs, human 2-12C and porcine pb27, in Göttingen minipigs and Landrace × Large White outbred pigs. Minipigs offer the advantage of a more stable weight, whereas outbred pigs are more readily available but exhibit rapid growth. Outbred pigs and minipigs showed similar pharmacokinetics and a similar porcine pb27 half-life (half-life of 15.7 days for outbred pigs and 16.6 days for minipigs). In contrast, the half-life of human 2-12C was more rapid in two of the minipigs but not in the outbred pigs, correlating with the development of antidrug antibodies in the two minipigs. Our results demonstrate that both outbred pigs and minipigs are appropriate models for pharmacokinetic studies and the evaluation of mAb delivery platforms, potentially bridging the gap between small animals and human trials.
Mycotoxins are among the most concerning natural toxic food contaminants. Over the years, significant efforts have been made to characterize the risk associated with their exposure. However, assessing their toxicity has so far been elusive due to the lack of adequate models that closely mimic the physiological conditions of human cells in vivo. Here, we present the SpheroFlow Device (SFD), an efficient microfluidic platform designed, manufactured, and validated to evaluate mycotoxin-induced cytotoxicity under dynamic and continuous exposure in 3D culture settings. In the present study, we integrated human neuroblastoma SH-SY5Y spheroids into the SFD to assess the acute toxicity induced by the mycotoxins ochratoxin A (OTA) and patulin (PAT). The developed system enabled qualitative and quantitative measurements of concentration–response relationships and provided accurate control over the culture microenvironment. Our findings show that by enhancing 3D culture model by applying dynamic flow, SH-SY5Y spheroids exhibited different sensitivities to OTA and PAT compared to conventional static SH-SY5Y spheroids, confirming the critical role of culture models in mycotoxin toxicity assessment. This is the first study assessing the neurotoxicity of OTA and PAT on 3D neuroblastoma spheroids considering the contribution of fluid flow.
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