Nanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken... Show moreNanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken embryos. We injected the embryos in the vitelline vein at stages 18–19. We injected polystyrene nanoparticles (PS-NPs) tagged with europium- or fluorescence. Their biodistribution was tracked using inductively-coupled plasma mass spectrometry on tissue lysates, paraffin histology, and vibratome sections analysed by machine learning algorithms. PS-NPs were found at high levels in the heart, liver and kidneys. Furthermore, PS-NPs crossed the endocardium of the heart at sites of epithelial-mesenchymal transformation; they also crossed the liver endothelium. Finally, we detected PS-NPs in the allantoic fluid, consistent with their being excreted by the kidneys. Our study shows the power of the chicken embryo model for analysing the biodistribution of nanoplastics in embryos. Such experiments are difficult or impossible in mammalian embryos. These findings are a major advance in our understanding of the biodistribution and tissue-specific accumulation of PS-NPs in developing animals. Show less
Schmeisser, S.; Miccoli, A.; Bergen, M. von; Berggren, E.; Braeuning, A.; Busch, W.; ... ; Tralau, T. 2023
The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for... Show moreThe predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of "New Approach Methodologies" (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure-activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today's regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free "Next Generation Risk Assessment" (NGRA). Show less
Food security and sustainable development of agriculture has been a key challenge for decades. To support this, nanotechnology in the agricultural sectors increases productivity and food security,... Show moreFood security and sustainable development of agriculture has been a key challenge for decades. To support this, nanotechnology in the agricultural sectors increases productivity and food security, while leaving complex environmental negative impacts including pollution of the human food chains by nanoparticles. Here we model the effects of silver nanoparticles (Ag-NPs) in a food chain consisting of soil-grown lettuce Lactuca sativa and snail Achatina fulica. Soil-grown lettuce were exposed to sulfurized Ag-NPs via root or metallic Ag-NPs via leaves before fed to snails. We discover an important biomagnification of silver in snails sourced from plant root uptake, with trophic transfer factors of 2.0–5.9 in soft tissues. NPs shifts from original size (55–68 nm) toward much smaller size (17–26 nm) in snails. Trophic transfer of Ag-NPs reprograms the global metabolic profile by down-regulating or up-regulating metabolites for up to 0.25- or 4.20- fold, respectively, relative to the control. These metabolites control osmoregulation, phospholipid, energy, and amino acid metabolism in snails, reflecting molecular pathways of biomagnification and pontential adverse biological effects on lower trophic levels. Consumption of these Ag-NP contaminated snails causes non-carcinogenic effects on human health. Global public health risks decrease by 72% under foliar Ag-NP application in agriculture or through a reduction in the consumption of snails sourced from root application. The latter strategy is at the expense of domestic economic losses in food security of $177.3 and $58.3 million annually for countries such as Nigeria and Cameroon. Foliar Ag-NP application in nano-agriculture has lower hazard quotient risks on public health than root application to ensure global food safety, as brought forward by the United Nations Sustainable Development Goals. Show less
Wang, M.R.; Rücklin, M.; Poelmann, R.E.; Mooij, C.L. de; Fokkema, M.; Lamers, G.E.M.; ... ; Richardson, M.K. 2023
Nanomaterials are widespread in the human environment as pollutants, and are being actively developed for use in human medicine. We have investigated how the size and dose of polystyrene... Show moreNanomaterials are widespread in the human environment as pollutants, and are being actively developed for use in human medicine. We have investigated how the size and dose of polystyrene nanoparticles affects malformations in chicken embryos, and have characterized the mechanisms by which they interfere with normal development. We find that nanoplastics can cross the embryonic gut wall. When injected into the vitelline vein, nanoplastics become distributed in the circulation to multiple organs. We find that the exposure of embryos to polystyrene nanoparticles produces malformations that are far more serious and extensive than has been previously reported. These malformations include major congenital heart defects that impair cardiac function. We show that the mechanism of toxicity is the selective binding of polystyrene nanoplastics nanoparticles to neural crest cells, leading to the death and impaired migration of those cells. Consistent with our new model, most of the malformations seen in this study are in organs that depend for their normal development on neural crest cells. These results are a matter of concern given the large and growing burden of nanoplastics in the environment. Our findings suggest that nanoplastics may pose a health risk to the developing embryo. Show less
Wang, M.; Rücklin, M.; Poelmann, R.E.; Mooij, C.L. de; Fokkema, M.; Lamers, G.E.M.; ... ; Richardson, M.K. 2023
Nanomaterials are widespread in the human environment as pollutants, and are being actively developed for use in human medicine. We have investigated how the size and dose of polystyrene... Show moreNanomaterials are widespread in the human environment as pollutants, and are being actively developed for use in human medicine. We have investigated how the size and dose of polystyrene nanoparticles affects malformations in chicken embryos, and have characterized the mechanisms by which they interfere with normal development. We find that nanoplastics can cross the embryonic gut wall. When injected into the vitelline vein, nanoplastics become distributed in the circulation to multiple organs. We find that the exposure of embryos to polystyrene nanoparticles produces malformations that are far more serious and extensive than has been previously reported. These malformations include major congenital heart defects that impair cardiac function. We show that the mechanism of toxicity is the selective binding of polystyrene nanoplastics nanoparticles to neural crest cells, leading to the death and impaired migration of those cells. Consistent with our new model, most of the malformations seen in this study are in organs that depend for their normal development on neural crest cells. These results are a matter of concern given the large and growing burden of nanoplastics in the environment. Our findings suggest that nanoplastics may pose a health risk to the developing embryo. Show less
Toxicity of ZnO nanoparticles (NPs) are often related to the release of Zn2+ ions due to their dissolution. Studies also suggest that the toxicity of ZnO NPs cannot be solely explained by the... Show moreToxicity of ZnO nanoparticles (NPs) are often related to the release of Zn2+ ions due to their dissolution. Studies also suggest that the toxicity of ZnO NPs cannot be solely explained by the release of Zn2+ ions; however, there is a lack of direct evidence of ZnO particulate effects. This study compared the acute toxicity of ZnO NPs and ZnSO4 following intranasal exposure using a combination of metallomics and metabolomics approaches. Significant accumulation of Zn in the liver was only found in the ZnO NP treatment, with 29% of the newly accumulated Zn in the form of ZnO as revealed by X-ray fine structure spectroscopy (XAFS). This is the first direct evidence suggesting the persistence of ZnO NPs in liver upon intranasal exposure. Although both ZnO NPs and ZnSO4 altered the metabolite profiles, with some overlaps and considerable specificity, of both liver and plasma samples, more and distinct metabolites in the liver and opposite effects in the plasma were altered by ZnO NPs compared with ZnSO4, consistent with no accumulation of Zn detected in liver from ZnSO4. Specifically, a large number of antioxidant-related compounds and energetic substrates were exclusively elevated in the liver of ZnO NP-treated animals. These findings provided direct evidence that persistence of ZnO NPs induced particle-specific effects on the antioxidant systems and energy metabolism pathways. Show less
The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife... Show moreThe number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, "Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment" was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages:• We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures.• Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors.• Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps.• A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. Show less
Lu, T.; Zhu, Y.; Ke, M.; Peijnenburg, W.J.G.M.; Zhang, M.; Wang, T.; ... ; Qian, H. 2019
Ciprofloxacin (CIP), one of the most frequently detected antibiotics in water systems, has become an aquatic contaminant because of improper disposal and excretion by humans and animals. It is... Show moreCiprofloxacin (CIP), one of the most frequently detected antibiotics in water systems, has become an aquatic contaminant because of improper disposal and excretion by humans and animals. It is still unknown how trace amounts of CIP affect the aquatic microbial community diversity and function. We therefore investigated the effects of CIP on the structure and function of freshwater microbial communities via 16S/18S rRNA gene sequencing and metatranscriptomic analyses. CIP treatment (7 μg/L) did not significantly alter the physical and chemical condition of the water body as well as the composition of the main species in the community, but slightly increased the relative abundance of cyanobacteria and decreased the relative abundance of eukaryotes. Metatranscriptomic results showed that bacteria enhanced their phosphorus transport and photosynthesis after CIP exposure. The replication, transcription, translation and cell proliferation were all suppressed in eukaryotes, while the bacteria were not affected in any of these aspects. This interesting phenomenon was the exact opposite to both the antibacterial property of CIP and its safety for eukaryotes. We hypothesize that reciprocal and antagonistic interactions in the microcosm both contribute to this result: cyanobacteria may enhance their tolerance to CIP through benefiting from cross-feeding and some secreted substances that withstand bacterial CIP stress would also affect eukaryotic growth. The present study thus indicates that a detailed assessment of the aquatic ecotoxicity of CIP is essential, as the effects of CIP are much more complicated in microbial communities than in monocultures. CIP will continue to be an environmental contaminant due to its wide usage and production and more attention should be given to the negative effects of antibiotics as well as other bioactive pollutants on aquatic environments. Show less
Bopp, S.K.; Barouki, R.; Brack, W.; Dalla Costa, S.; Dorne, J.C.M.; Drakvik, P.E.; ... ; Gils, J. van 2018
Humans and wildlife are exposed to an intractably large number of different combinations of chemicals via food, water, air, consumer products, and other media and sources. This raises concerns... Show moreHumans and wildlife are exposed to an intractably large number of different combinations of chemicals via food, water, air, consumer products, and other media and sources. This raises concerns about their impact on public and environmental health. The risk assessment of chemicals for regulatory purposes mainly relies on the assessment of individual chemicals. If exposure to multiple chemicals is considered in a legislative framework, it is usually limited to chemicals falling within this framework and co-exposure to chemicals that are covered by a different regulatory framework is often neglected. Methodologies and guidance for assessing risks from combined exposure to multiple chemicals have been developed for different regulatory sectors, however, a harmonised, consistent approach for performing mixture risk assessments and management across different regulatory sectors is lacking. At the time of this publication, several EU research projects are running, funded by the current European Research and Innovation Programme Horizon 2020 or the Seventh Framework Programme. They aim at addressing knowledge gaps and developing methodologies to better assess chemical mixtures, by generating and making available internal and external exposure data, developing models for exposure assessment, developing tools for in silico and in vitro effect assessment to be applied in a tiered framework and for grouping of chemicals, as well as developing joint epidemiological-toxicological approaches for mixture risk assessment and for prioritising mixtures of concern. The projects EDC-MixRisk, EuroMix, EUToxRisk, HBM4EU and SOLUTIONS have started an exchange between the consortia, European Commission Services and EU Agencies, in order to identify where new methodologies have become available and where remaining gaps need to be further addressed. This paper maps how the different projects contribute to the data needs and assessment methodologies and identifies remaining challenges to be further addressed for the assessment of chemical mixtures. Show less
