TY - JOUR AB - Concepts of similarity, such as grouping, categorization, and read-across, enable a fast comparative screening of hazard, reducing animal testing. These concepts are established primarily for molecular substances. We demonstrate the development of multi-dimensional similarity assessment methods that can be applied to multicomponent nanomaterials (MCNMs) for the case of core-shell quantum dots (QDs). The term ‘multicomponent’ refers to their structural composition, which consists of up to four different heavy metals (cadmium, zinc, copper, indium) in different mass percentages, with different morphologies and surface chemistries. The development of concepts of similarity is also motivated by the increased need for comparison of innovative against conventional materials in the safe and sustainable by design (SSbD) context. This case study thus considers the industrial need for an informed balance of functionality and safety: we propose two different approaches to compare and rank the case study materials amongst themselves and against well-known benchmark materials, here ZnO NM110, BaSO4 NM220, TiO2 NM105, and CuO. Relative differences in the sample set are calibrated against the biologically relevant range. The choice of properties that are subjected to similarity assessment is guided by the integrated approaches to testing and assessment (IATA) for the inhalation hazard of simple nanomaterials, which recommends characterizing QDs by (i) dynamic dissolution in lung simulant fluids and (ii) the surface reactivity in the abiotic ferric reducing ability of serum (FRAS) assay. In addition, the similarity of fluorescence spectra was assessed as a measure of the QD performance for the intended functionality as a color converter. We applied two approaches to evaluate the data matrix: in the first approach, specific descriptors for each assay (i.e., leachable mass (%) and mass based biological oxidative damage (mBOD)) were selected based on expert knowledge and used as input data for generation of similarity matrices. The second approach introduces the possibility of evaluating multidimensional raw data by a meaningful similarity analysis, without the need for predefined descriptors. We discuss the strengths and weaknesses of each of the two approaches. We anticipate that the similarity assessment approach is transferable to the assessment of further advanced materials (AdMa) that are composed of multiple components. AU - Di Battista, V.* AU - Sanchez-Lievanos, K.R.* AU - Jeliazkova, N.* AU - Murphy, F.* AU - Tsiliki, G.* AU - Zabeo, A.* AU - Gajewicz-Skretna, A.* AU - Mikołajczyk, A.* AU - Hristozov, D.* AU - Stone, V.* AU - Schmid, O. AU - Hunt, N.* AU - Oomen, A.G.* AU - Wohlleben, W.* C1 - 69840 C2 - 55274 CY - Thomas Graham House, Science Park, Milton Rd, Cambridge Cb4 0wf, Cambs, England SP - 924-941 TI - Similarity of multicomponent nanomaterials in a safer-by-design context: The case of core-shell quantum dots. JO - Environ. Sci.-Nano VL - 11 PB - Royal Soc Chemistry PY - 2024 SN - 2051-8153 ER - TY - JOUR AB - Advanced materials are rapidly being developed in different material categories. They share little commonalities apart from their novelty, which raises concerns that these materials may fall into a regulatory gap with potentially inappropriate risk management. But how to assess materials that are still under development? Here we present the Advanced Materials Earliest Assessment (AMEA) approach to fill this gap by proposing simple assessment steps and guidance for design rules meant to be applied by innovators in early material development phases (ideation, business case and lab phases). AMEA provides a structured approach to exploit the available knowledge at each phase, starting from the intended product, application and global region, starting also from the conventional material in the same application, of which the sustainability benefits and sustainability challenges often constitute the motivation for advanced material development. During the lab phase, AMEA recommends focusing on acquisition of data with discriminating power, and triggers more requirements and/or specific testing methods depending on the positioning of the material with respect to the three dimensions “nano-enabled?”, “advanced?”, and “containing particles?” The methodological part can be amended for other material classes without relevance of nanostructures. Similarity and ranking approaches compare material versions synthesized in lab phases against each other and the conventional material in terms of performance, lifecycle emissions/exposures and hazards. AMEA prioritizes the discriminating power of specific data to refine the design targets instead of using generic assumptions with high uncertainties. It is the entry point of the HARMLESS decision support system covering the ensuing pilot and launch phases of innovation management to fulfill safe-and-sustainable-by-design material development. AU - Wohlleben, W.* AU - Persson, M.* AU - Suarez-Merino, B.* AU - Baun, A.* AU - Di Battista, V.* AU - Dekkers, S.* AU - van Someren, E.P.* AU - Broßell, D.* AU - Stahlmecke, B.* AU - Wiemann, M.* AU - Schmid, O. AU - Haase, A.* C1 - 70854 C2 - 55732 CY - Thomas Graham House, Science Park, Milton Rd, Cambridge Cb4 0wf, Cambs, England TI - Advanced materials earliest assessment (AMEA). JO - Environ. Sci.-Nano PB - Royal Soc Chemistry PY - 2024 SN - 2051-8153 ER - TY - JOUR AB - In recent years, the interest in quantum dots (QDs) has spread across different branches of biology and medicine thanks to their photophysical properties, which make them excellent candidates for use in bioimaging, drug delivery, theranostic applications and, more recently, gene therapy. With the continuous expansion of applications, QD-mediated cellular responses have become of concern. The immune system and the liver have been confirmed to be important targets, and both are sensitive to cadmium sulfide quantum dots (CdS QDs). Here, the effect on mRNA has been studied by whole-transcriptome analysis in human HepG2 cells (as a model of liver cells) and THP-1 macrophage-like cells, and the mechanisms of mRNA regulation by miRNAs during exposure to Cd as CdS QDs or Cd(ii) (as CdSO4 8/3-hydrate) are discussed. CdS QD exposure induced modulation of the transcriptome of hepatocytes activating RAS signaling and increasing intracellular calcium, which results in the activation of the apoptotic pathway. CdS QDs also affect macrophages inducing production of TNFα and other cytokines and hindering the autophagic process. The results obtained in vitro on mRNA regulation are partially consistent with those hypothesized after in silico analysis of a wide range of miRNAs regulated in the same conditions. AU - Paesano, L.* AU - Vogli, M. AU - Marmiroli, M.* AU - Bianchi, M.G.* AU - Bussolati, O.* AU - Zappettini, A.* AU - Marmiroli, N.* C1 - 68574 C2 - 53567 CY - Thomas Graham House, Science Park, Milton Rd, Cambridge Cb4 0wf, Cambs, England SP - 1177-1189 TI - Cellular mechanisms of transcriptional regulation of human cell lines exposed to cadmium-based quantum dots. JO - Environ. Sci.-Nano VL - 10 IS - 4 PB - Royal Soc Chemistry PY - 2023 SN - 2051-8153 ER - TY - JOUR AB - The potential toxicity of nano-TiO2 (nTiO2) in the next generation of organisms is important for the environmental toxicological profile of nTiO2. nTiO 2 has been shown to disrupt maternal thyroid hormone metabolism, whereas the effects of prenatal exposure to nTiO2 on the transplacental transfer of thyroid hormones (THs) to the fetus have not been clarified. In this study, pregnant SD rats at gestation days (GDs) 0–17 were daily orally administered with 6.17, 12.34, 61.70, and 308.50 mg kg−1 of nTiO2 (29.6 ± 8.1 nm). Results showed that nTiO2 exposure could inhibit the development of rat placenta and fetus at GD 18. Notably, THs (T3 and T4) were highly accumulated (increased by 19–90%) in the placenta. The retention of placental THs may be related to the down-regulation of TH transporters. nTiO2 could induce oxidative stress on the maternal liver where TH transporters are produced. Genes encoding for TH transporters were mostly down-regulated by 29–65% and a decreased abundance of these transporters in the placenta was observed. An increased concentration of titanium can be observed in the placenta and fetus and subsequently the vascularization of labyrinth tissue was impaired. These findings imply that prenatal exposure to nTiO2 in rats at levels converted from the human daily dietary level might restrict the transplacental transfer of THs and compromise placental function, thus inhibiting fetal growth and development, which could have implications for human health and safety. AU - Chen, F.* AU - Wang, C.* AU - Yue, L.* AU - Tang, J.* AU - Du, H.* AU - Wu, Y.* AU - Schröder, P. AU - Wang, Z.* AU - Xing, B.* C1 - 64960 C2 - 52233 SP - 2351-2362 TI - Nano-TiO2 retarded fetal development by inhibiting transplacental transfer of thyroid hormones in rats. JO - Environ. Sci.-Nano VL - 9 IS - 7 PY - 2022 SN - 2051-8153 ER - TY - JOUR AB - Nanomaterials can induce plant tolerance to abiotic environmental stresses, whereas the sensing mechanism and the resulting response at the cellular level need further exploration. Bright Yellow 2 tobacco (Nicotiana tabacum L.) suspension-cultured cells challenged with 100 mM NaCl were exposed to increasing doses (0.05, 0.1, and 0.5 mg L−1) of nano-CeO2 (nCeO2) or nitrogen-doped carbon dots (N-CDs). nCeO2 at 0.1 mg L−1 or N-CDs at 0.5 mg L−1 were optimal for alleviating salt stress and nCeO2 wassuperior to N-CDs. Notably, the expression of genes (IPUT1, SOS3, SOS2, and SOS1) involved in Na+-GIPC perception-Na+-extrusion was stimulated (5.3-fold) after nCeO2 exposure for 4 h, and NHX1 encoding Na+ vacuolar sequestration was induced by 7.8-fold after N-CDs treatment for 6 h. Subsequently, the net Ca2+ influx and Na+ efflux were strongly promoted by 293.6% and 191.3% after incubation with nCeO2, while no obvious Na+ extrusion but the transient K+ influx (by 3.0-fold) was observed for N-CDs. The downstream metabolic modifications in fatty acids, or amino acids and carbohydrates could favor the adaptation to salt stress. This work reveals the specific nanomaterial-induced early cell perception and signaling cascade, contributing to the nano-based agricultural practices for combating salt stress. AU - Chen, F.* AU - Zhu, L.* AU - Tang, J.* AU - Wang, C.* AU - Yue, L.* AU - Schröder, P. AU - Wang, Z.* C1 - 66311 C2 - 52776 SP - 4018 –4026 TI - Nanomaterial-modulated cellular sodium extrusion and vacuolar sequestration for salt tolerance. JO - Environ. Sci.-Nano VL - 9 PY - 2022 SN - 2051-8153 ER -