To Örebro University

The rapid rise of 3D printing, both in industrial and home settings, presents emerging health and environmental risks. While 3D printing enhances sustainability by reducing waste and optimizing resource use, its impact on human health remains poorly understood. The use of metals and polymers linked to health risks, coupled with the release of inhalable particles and volatile organic compounds, raises concerns about respiratory and systemic effects. The absence of clear guidelines creates high public demand for information and limits safe implementation, particularly in schools and homes where millions of 3D printers are expected by 2030. Additionally, improper disposal of 3D printing polymer materials may exacerbate plastic pollution. This article proposes the perspective of a structured risk assessment framework set on particle emissions from industrial 3D printing. It will offer a practical tool to bridge current knowledge gaps and to inform safe practice and policy development, because immediate action is necessary to balance innovation with safety.

As the volume of plastic waste from electrical and electronic equipment (WEEE) continues to rise, a significant portion is disposed of in the environment, with only a small fraction being recycled. Both disposal and recycling pose unknown health risks that require immediate attention. Existing knowledge of WEEE plastic toxicity is limited and mostly relies on epidemiological data and association studies, with few insights into the underlying toxicity mechanisms. Therefore, this study aimed to perform comprehensive chemical screening and mechanistic toxicological assessment of WEEE plastic-associated chemicals. Chemical analysis, utilizing suspect screening based on high-resolution mass spectrometry, along with quantitative target chemical analysis, unveiled numerous hazardous compounds including polyaromatic compounds, organophosphate flame retardants, phthalates, benzotriazoles, etc. Toxicity endpoints included perturbation of morphological phenotypes using the Cell Painting approach, inflammatory response, oxidative stress, and endocrine disruption. Results demonstrated that WEEE plastic chemicals altered the phenotypes of the cytoskeleton, endoplasmic reticulum, and mitochondria in a dose-dependent manner. In addition, WEEE chemicals induced inflammatory responses in resting macrophages and altered inflammatory responses in lipopolysaccharide-primed macrophages. Furthermore, WEEE chemicals activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, indicating oxidative stress, and the aryl hydrocarbon receptor (AhR). Endocrine disruption was also observed through the activation of estrogenic receptor-α (ER-α) and the induction of anti-androgenic activity. The findings show that WEEE plastic-associated chemicals exert effects in multiple subcellular sites, via different receptors and mechanisms. Thus, an integrated approach employing both chemical and toxicological methods is essential for comprehensive assessment of the toxicity mechanisms and cumulative chemical burden of WEEE plastic-associated chemicals.

Existing research has proven difficult to understand the interplay between upstream signalinge vents during NLRP3 inflammasome activation. Additionally, events downstream of inflammasome complex formation such as cytokine release and pyroptosis can exhibit variation, further complicating matters. Cell Painting has emerged as a prominent tool for unbiased evaluation of the effect of perturbations on cell morphological phenotypes. Using this technique, phenotypic fingerprints can be generated that reveal connections between phenotypes and possible modes of action. To the best of our knowledge, this was the first study that utilized Cell Painting on human THP-1 macrophages to generate phenotypic fingerprints in response to different endogenous and exogenous NLRP3 inflammasome triggers, and to identify phenotypic features specific to NLRP3 inflammasome complex formation. Our results demonstrated that not only can Cell Painting generate morphological fingerprints that are NLRP3 trigger-specific, but it can identify cellular fingerprints associated with NLRP3 inflammasome activation.

This popular science report presents a short summary of the most important findings and suggestions regarding environment, health and safety (EHS) issues for users of Additive Manufacturing (AM), also known as industrial 3D-printing. The report is based on three different parts of a project (HÄMAT 1-3) that was carried out over the years 2017 - 2024, involving an interdisciplinary network consisting of universities, companies, research institutes as well as non-governmental organizations (HÄMAT websites). The project has been funded by Vinnova and was coordinated by Swerim. The main aim of HÄMAT was to study EHS issues and thereby provide guidance for a well-designed and safe work environment upon establishing this new promising technology. 

The environmental fragmentation of plastics generates a mixture of plastic particles of various sizes, which frequently co-occur with other mobile and persistent environmental pollutants. Despite the prevalence of such scenarios, the interaction between micro- and nanoplastics (MNPs) and their combined effects with environmental pollutants, such as highly toxic hexavalent chromium (Cr(VI)), remain almost entirely unexplored in mammalian species. This study demonstrated that nanoplastic and microplastic particles co-aggregate and together influence Cr bioaccumulation patterns and related physiological alterations in rats. Following a four-week repeated intragastric exposure of Wistar rats to MNPs and Cr(VI), either alone or in combination, MNPs significantly enhanced Cr bioaccumulation in the liver, heart, brain, and skin. Under co-exposure conditions, Cr(VI) was the primary driver of cellular effects observed in the blood, including shifts in immune cell subpopulations (e.g., neutrophils, lymphocytes) and alterations in red blood cell indices, while serum biochemistry reflected limited physiological stress. MNPs per se decreased creatine kinase activity and increased cholesterol levels. In summary, polystyrene MNPs increase Cr(VI) distribution and bioavailability, but co-exposure does not uniformly exacerbate toxicity. Instead, their interaction may selectively alter physiological responses, emphasizing the need for a deeper understanding of their combined effects and potential health risks.

Per- and polyfluoroalkyl substances and nanoplastics frequently co-occur in environmental matrices, yet the effects of co-exposure on cellular responses upon ingestion are poorly understood. Here, we exposed human intestinal Caco-2 cells to perfluorooctanesulfonic acid, nanoplastics, and their combination. Cell painting-based phenomics was used to map phenotypic alterations across subcellular structures, and untargeted metabolomics using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was employed to assess metabolic changes. Results show that perfluorooctanesulfonic acid predominantly affected the actin cytoskeleton, Golgi apparatus, and plasma membrane, while nanoplastics primarily targeted mitochondria. Combined exposure disrupted the endoplasmic reticulum, RNA, and mitochondria. Perfluorooctanesulfonic acid reduced levels of carnitines, free fatty acids, nucleotides, and sugars, whereas nanoplastics inhibited ceramides, triglycerides, sphingomyelins, and additional free fatty acids. Combined exposure produced a metabolic profile resembling that of nanoplastics, with specific differences attributed to perfluorooctanesulfonic acid. Overall, nanoplastics appear as the main drivers of the co-exposure effects.

Metal additive manufacturing (AM), also known as industrial 3D printing, has revolutionized modern industry, enabling the creation of complex, high-performance components across sectors such as aerospace, automotive, and biomedicine. While the printing process itself is often well-contained, a critical and understudied phase – post-processing – has emerged as a source of potentially hazardous airborne particulate matter. These emissions may pose health risks to workers, particularly through interaction with the immune system, which serves as the body's first line of defense and a sentinel of environmental stressors. Yet, limited data exist on the physicochemical properties and immunotoxicological impact of these particles. This study aimed to assess the immunological consequences of particle emissions released during the post-processing of metallic AM alloys, using a human macrophage model and a multi-omics framework.

Airborne particles were collected directly from an operational AM facility using a cascade impactor, separating them into five size fractions, ranging from coarse (>2.5 μm) to nanoscale (<250 nm). A comprehensive physicochemical characterization was performed using scanning electron microscopy with energy-dispersive spectroscopy and X-ray photoelectron spectroscopy. The emitted particles were highly heterogeneous, with irregular, sharp morphologies, and exhibited increased surface oxidation compared to virgin feedstock powders. Functional toxicological assessments were performed in human macrophages, including transmission electron microscopy to evaluate particle uptake. Macrophages, both resting and lipopolysaccharide-primed, displayed potent and dose-dependent inflammatory responses, as seen by elevated secretion of several cytokines (e.g., IL-1β, IL-6). RNA sequencing revealed profound alterations in macrophage gene expression, including dysregulation of NF-κB signaling, cellular senescence, and lipid metabolism pathways. Gene set enrichment analysis indicated broader perturbations in immune regulation and macrophage homeostasis. Non-targeted metabolomics demonstrated significant changes in intracellular metabolic profiles. Specifically, there was an upregulation of numerous lipids and a suppression of several metabolites involved in immunomodulation and cellular energy homeostasis, including tryptophan, NAD, and phenylalanine. Integrated multi-omics analysis revealed a coordinated crosstalk between transcriptional and metabolic responses, pointing to an acute and multifaceted inflammatory reprogramming of macrophages in response to post-processing AM particles.

In conclusion, this study provides the first integrative multi-omics characterization of human immune cell responses to airborne particulate emissions from metal AM post-processing. These results not only advance the field of nanosafety in industrial AM environments but also underscore the urgent need for targeted risk mitigation strategies during post-processing.

The innate immune system is the first player involved in the recognition/interaction with nanomaterials. Still, it is not the only system involved. The co-evolution of the microbiota with the innate immune system built an interdependence regulating immune homeostasis that is poorly studied. Herein, the simultaneous interaction of iron-oxide nanoparticles (Fe-oxide NPs), immune cells, and the microbiota associated with the blood of the sea urchin Paracentrotus lividus was explored by using a microbiota/immune cell model in vitro-ex vivo and a battery of complementary tools, including Raman spectroscopy, 16S Next-Generation Sequencing, high-content imaging, NanoString nCounter. Our findings highlight the P. lividus immune cells and microbiota dynamics in response to Fe-oxide NPs, including i) morphological rearrangement and immune cell health status maintenance (intracellular trafficking increasing, no phenotypic alterations or caspase 3/7 activation), ii) transcriptomic reprogramming in immune cells (Smad6, Lmo2, Univin, suPaxB, Frizzled-7, Fgfr2, Gp96 upregulation), iii) immune signaling unchanged (e.g., P-p38 MAPK, P-ERK, TLR4, IL-6 protein level unchanged), iv) enrichment in extracellular vesicle released in the co-culture medium, and v) a shift in the composition of microbial groups mainly in favor of Gram-positive bacteria (e.g., Firmicutes, Actinobacteria),. Our findings suggest that Fe-oxide NPs induce a multilevel immune cell-microbiota response restoring homeostasis.

Chromium (cr) toxicity, even at low concentrations, poses a significant health threat to various environmental species. Cr is found in the environment in two oxidation states that differ in their bioavailability and toxicity. While cr(iii) is essential for glucose metabolism, the oxyanion chromate cr(vi) is mostly of anthropogenic origin, toxic, and carcinogenic. The sources of cr in the environment are multiple, including geochemical processes, disposal of industrial waste, and industrial wastewater. Cr pollution may consequently impact the health of numerous plant and animal species. Despite that, the number of published studies on cr toxicity across environmental species remained mainly unchanged over the past two decades. The presence of cr in the environment affects several plant physiological processes, including germination or photosynthesis, and consequently impacts growth, and lowers agricultural production and quality. Recent research has also reported the toxic effects of cr in different aquatic and terrestrial organisms. whereas some species showed sensitivity, others exhibited tolerance. Hence, this review discusses the understanding of the ecotoxicological effect of cr on different plant and animal groups and serves as a concise source of consolidated information and a valuable reference for researchers and policymakers in an understanding of cr toxicity. Future directions should focus on expanding research efforts to understand the mechanisms underlying species-specific responses to cr pollution.