To Örebro University

Metal additive manufacturing (AM) relies on alloy feedstock powders that may come into contact with the workers' skin during handling, yet skin-relevant data on metal release and biological reactivity remain limited. Here, we assessed the cutaneous bioactivity of the fine particle fraction of four gas-atomized Fe-based AM powders (316L stainless steel, Fe-powder A, and tooling steels B and C). Powders were sieved to <10 mu m and characterized by scanning electron microscopy and X-ray photoelectron spectroscopy before and after incubation in artificial sweat (ASW). Metal biodissolution was quantified in ASW and keratinocyte culture medium using atomic absorption spectrophotometry. Cellular responses were evaluated in HaCaT keratinocytes using Cell Painting-based phenomics and multiplex cytokine/chemokine profiling and in an ex vivo full-thickness human skin explant model, including superficial barrier disruption, IL-8/CXCL8 quantification, and histological assessment. ASW exposure induced marked shifts in the outermost surface composition across powders, indicating sweat-driven surface transformation. Biodissolution was low and medium-dependent, with Fe dominating the release in ASW, and with an overall metal release remaining limited in cell culture medium. In HaCaT cells, MCP-1/CCL2, IL-6, and IL-8/CXCL8 were quantifiable but showed no significant changes following powder exposure. Cell Painting revealed subtle, shared phenotypic signatures, primarily involving mitochondrial-associated features, without evidence of broad cellular stress. In the ex vivo skin model, AM powders did not increase IL-8/CXCL8 secretion, the particles remained localized to the skin surface without detectable penetration, and coexposure with Staphylococcus epidermidis did not enhance bacterial colonization or induce inflammation. To the best of our knowledge, this is the first study that applies a human skin explant model to evaluate dermal responses to metal AM powders. Overall, the tested AM powders showed low short-term cutaneous reactivity under skin-relevant conditions, providing human-relevant evidence to inform occupational risk assessment in AM environments.

Perfluorohexyloctane (F6H8) is a semifluorinated alkane recently approved for ophthalmic treatment of dry eye disease. Although considered locally safe for topical use, its structural similarity to persistent per- and polyfluoroalkyl substances (PFAS) raises concerns about systemic accumulation and long-term toxicity. To investigate potential hepatic effects, we examined the metabolic impact of F6H8 exposure in human HepaRG hepatocytes across a broad concentration range representing short- and long-term exposure scenarios. Combined targeted and untargeted metabolic profiling by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) was performed on intracellular extracts and extracellular media. F6H8 induced pronounced, concentration-dependent metabolic alterations, many of which exhibited non-monotonic responses. Low concentrations primarily affected amino acid, fatty acid, and lipid metabolism, while central carbon metabolism was disrupted only at the highest exposures. Notably, a putative biotransformation product, perfluorohexyloctanoic acid, was detected, suggesting metabolic persistence and conversion to a PFAS-like structure. This metabolite showed strong associations with cellular metabolic profiles and elicited metabolic changes that only partially overlapped with those induced by the parent compound, indicating distinct biological activity following biotransformation. These findings indicate that F6H8 elicits broad metabolic reprogramming and may not be metabolically inert as previously assumed. Given its clinical use and structural similarity to persistent fluorochemicals, the results highlight the need for comprehensive, long-term safety assessment of F6H8 and related semifluorinated alkanes.

Perfluorohexyloctane (F6H8) is a semifluorinated alkane increasingly used in medical applications. Emerging evidence, however, indicates that this compound can persist in biological systems and influence cellular processes. These observations suggest that the exceptional stability of F6H8, while beneficial for medical performance, may also have implications for long-term biological and health outcomes.

This study applied a virtual effect-directed analysis (vEDA) approach, integrating effect-based analysis and chemical screening, to identify bioactive compounds in rubber infill from artificial turf. Bioreporter assays targeting diverse toxicological endpoints were selected to detect a wide range of potential endocrine-disrupting and genotoxic compounds. Of 21 samples, all except one showed aryl-hydrocarbon receptor (AhR) activity (14-31,400 ng benzo[a]pyrene equivalents/g), four induced p53 activity (0.04-0.86 µg actinomycin D equivalents/g) and two showed estrogen receptor α (ERα) activity (530 and 1020 pg estradiol equivalents/g). Chemical analysis quantified up to 87 polycyclic aromatic compounds (PAC) and gas chromatography high-resolution mass spectrometry-based suspect screening yielded 281 tentative identifications. Annotation with bioassay activity data from databases and predictive models revealed 29 AhR-, 32 ERα- and 18 p53-active compounds. Univariate analysis was used to prioritize compounds for further chemical and toxicological confirmation. Eighteen AhR agonists were confirmed, contributing 0-98% to the observed AhR activity in the samples. Phenylamine additives, detected at high concentrations, exhibited low AhR activating potency and contributed < 1%. In contrast, methylated chrysene isomers elicited relatively high potencies and contributed substantially (≤65%) to the observed AhR activity. N-Isopropyl-N'-phenyl-p-phenylenediamine (IPPD) was confirmed as p53 active and explained ∼50% of the observed activity in the most p53-active sample. Styrene-butadiene rubber (SBR) showed higher AhR- and p53 activities and concentrations of quantified compounds than the alternative materials. The study highlights differences in chemical hazards among rubber infill materials and demonstrates the utility of vEDA as an early-warning tool for identifying compounds of concern.

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.