Developing a Selection Framework for Zinc Ion-Based Biomaterial Design: Guided by the Biosafety Assessment of ZIF-8 and ZnO.

In recent years, nanomaterials have gained widespread use in the biomedical field, with ZIF-8 and ZnO emerging as promising candidates due to their remarkable performance in osteogenesis, angiogenesis, and antimicrobial therapy. However, before advancing these nanomaterials for clinical applications, it is imperative to evaluate their biocompatibility. In particular, comparing nanomaterials with similar biomedical functions is crucial for identifying the most suitable nanomaterials for further development and market entry. Our study aimed to compare the biocompatibility of nano-ZIF-8 and nano-ZnO under the same conditions. We found that nano-ZIF-8 exhibited lower toxicity both in vitro and in vivo compared to nano-ZnO. To gain insights into the underlying mechanisms responsible for this difference, we conducted further experiments to investigate lysosome damage, mitochondrial change, and the occurrence of ferroptosis. Additionally, we performed transcriptome sequencing to analyze the expression of relevant genes, thereby providing robust validation for our findings. In summary, our study highlighted the importance of evaluating nanomaterials with similar biomedical effects. Through this comparative study, we have not only shed light on the superior biocompatibility of nano-ZIF-8 over nano-ZnO, but also contributed valuable insights and methodological references for future material screening endeavors. Ultimately, our study served as a stepping stone toward the development of safer and more effective nanomaterials for various biomedical applications.

Paradoxical effects of nanomaterials on plants: Phytohormonal perspective exposes hidden risks amidst potential benefits.

The rapid growth of nanotechnology has led to the production of a significant amount of engineered nanomaterials (NMs), raising concerns about their impact on various domains. This study investigates the negative interactions between NMs and phytohormones in plants, revealing the changes in signaling crosstalk, integrated responses and ecological repercussions caused by NM pollution. Phytohormones, which include auxins, cytokinins, gibberellins, abscisic acid, ethylene, jasmonic acid, salicylic acid and brassinosteroids are essential for plant growth, development, and stress responses. This review examines the intricate relationships between NMs and phytohormones, highlighting disruptions in signaling crosstalk, integrated responses, and ecological consequences in plants due to NM pollution. Various studies demonstrate that exposure to NMs can lead to alterations in gene expression, enzyme functions, and ultimately affect plant growth and stress tolerance. Exposure to NMs has the capacity to affect plant phytohormone reactions by changing their levels, biosynthesis, and signaling mechanisms, indicating a complex interrelation between NMs and phytohormone pathways. The complexity of the relationships between NMs and phytohormones necessitates further research, utilizing modern molecular techniques, to unravel the intricate molecular mechanisms and develop strategies to mitigate the ecological consequences of NM pollution. This review provides valuable insights for researchers and environmentalists concerned about the disruptive effects of NMs on regulating phytohormone networks in plants.

Nanomaterials-induced programmed cell death: Focus on mitochondria.

Nanomaterials are widely utilized in several domains, such as everyday life, societal manufacturing, and biomedical applications, which expand the potential for nanomaterials to penetrate biological barriers and interact with cells. Multiple studies have concentrated on the particular or improper utilization of nanomaterials, resulting in cellular death. The primary mode of cell death caused by nanotoxicity is programmable cell death, which includes apoptosis, ferroptosis, necroptosis, and pyroptosis. Based on our prior publications and latest research, mitochondria have a vital function in facilitating programmed cell death caused by nanomaterials, as well as initiating or transmitting death signal pathways associated with it. Therefore, this review takes mitochondria as the focal point to investigate the internal molecular mechanism of nanomaterial-induced programmed cell death, with the aim of identifying potential targets for prevention and treatment in related studies.

Molecular dynamics simulations suggest the potential toxicity of fluorinated graphene to HP35 protein via unfolding the α-helix structure.

Fluorinated graphene, a two-dimensional nanomaterial composed of three atomic layers, a central carbon layer sandwiched between two layers of fluorine atoms, has attracted considerable attention across various fields, particularly for its potential use in biomedical applications. Nonetheless, scant effort has been devoted to assessing the potential toxicological implications of this nanomaterial. In this study, we scrutinize the potential impact of fluorinated graphene on a protein model, HP35 by utilizing extensive molecular dynamics (MD) simulation methods. Our MD results elucidate that upon adsorption to the nanomaterial, HP35 undergoes a denaturation process initiated by the unraveling of the second helix of the protein and the loss of the proteins hydrophobic core. In detail, substantial alterations in various structural features of HP35 ensue, including alterations in hydrogen bonding, Q value, and RMSD. Subsequent analyses underscore that hydrophobic and van der Waals interactions (predominant), alongside electrostatic energy (subordinate), exert influence over the adsorption of HP35 on the fluorinated graphene surface. Mechanistic scrutiny attests that the unrestrained lateral mobility of HP35 on the fluorinated graphene nanomaterial primarily causes the exposure of HP35's hydrophobic core, resulting in the eventual structural denaturation of HP35. A trend in the features of 2D nanostructures is proposed that may facilitate the denaturation process. Our findings not only substantiate the potential toxicity of fluorinated graphene but also unveil the underlying molecular mechanism, which thereby holds significance for the prospective utilization of such nanomaterials in the field of biomedicine.

Unveiling key mechanisms: Transcriptomic meta-analysis of diverse nanomaterial applications addressing biotic and abiotic stresses in Arabidopsis Thaliana.

The potential applications of nanomaterials in agriculture for alleviating diverse biotic and abiotic stresses have garnered significant attention. The reported mechanisms encompass promoting plant growth and development, alleviating oxidative stress, inducing defense responses, modulating plant-microbe interactions, and more. However, individual studies may not fully uncover the common pathways or distinguish the effects of different nanostructures. We examined Arabidopsis thaliana transcriptomes exposed to biotic, abiotic, and metal or carbon-based nanomaterials, utilizing 24 microarray chipsets and 17 RNA-seq sets. The results showed that: 1) from the perspective of different nanostructures, all metal nanomaterials relieved biotic/abiotic stresses via boosting metal homeostasis, particularly zinc and iron. Carbon nanomaterials induce hormone-related immune responses in the presence of both biotic and abiotic stressors. 2) Considering the distinct features of various nanostructures, metal nanomaterials displayed unique characteristics in seed priming for combating abiotic stresses. In contrast, carbon nanomaterials exhibited attractive features in alleviating water deprivation and acting as signaling amplifiers during biotic stress. 3) For shared pathway analysis, response to hypoxia emerges as the predominant and widely shared regulatory mechanism governing diverse stress responses, including those induced by nanomaterials. By deciphering shared and specific pathways and responses, this research opens new avenues for precision nano-agriculture, offering innovative strategies to optimize plant resilience, improve stress management, and advance sustainable crop production practices.

MoS2 2D materials induce spinal cord neuroinflammation and neurotoxicity affecting locomotor performance in zebrafish.

MoS2 nanosheets belong to an emerging family of nanomaterials named bidimensional transition metal dichalcogenides (2D TMDCs). The use of such promising materials, featuring outstanding chemical and physical properties, is expected to increase in several fields of science and technology, with an enhanced risk of environmental dispersion and associated wildlife and human exposures. In this framework, the assessment of MoS2 nanosheets toxicity is instrumental to safe industrial developments. Currently, the impact of the nanomaterial on the nervous tissue is unexplored. In this work, we use as in vivo experimental model the early-stage zebrafish, to investigate whether mechano-chemically exfoliated MoS2 nanosheets reach and affect, when added in the behavioral ambient, the nervous system. By high throughput screening of zebrafish larvae locomotor behavioral changes upon exposure to MoS2 nanosheets and whole organism live imaging of spinal neuronal and glial cell calcium activity, we report that sub-acute and prolonged ambient exposures to MoS2 nanosheets elicit locomotor abnormalities, dependent on dose and observation time. While 25 µg mL-1 concentration treatments exerted transient effects, 50 µg mL-1 ones induced long-lasting changes, correlated to neuroinflammation-driven alterations in the spinal cord, such as astrogliosis, glial intracellular calcium dysregulation, neuronal hyperactivity and motor axons retraction. By combining integrated technological approaches to zebrafish, we described that MoS2 2D nanomaterials can reach, upon water (i.e. ambient) exposure, the nervous system of larvae, resulting in a direct neurological damage.

Biomarkers of exposure and effect in human biomonitoring of metal-based nanomaterials: their use in primary prevention and health surveillance.

Metal-based nanomaterials (MNMs) have gained particular interest in nanotechnology industry. They are used in various industrial processes, in biomedical applications or to improve functional properties of several consumer products. The widescale use of MNMs in the global consumer market has resulted in increases in the likelihood of exposure and risks to human beings. Human exposure to MNMs and assessment of their potential health effects through the concomitant application of biomarkers of exposure and effect of the most commonly used MNMs were reviewed in this paper. In particular, interactions of MNMs with biological systems and the nanobiomonitoring as a prevention tool to detect the early damage caused by MNMs as well as related topics like the influence of some physicochemical features of MNMs and availability of analytical approaches for MNMs testing in human samples were summarized in this review. The studies collected and discussed seek to increase the current knowledge on the internal dose exposure and health effects of MNMs, highlighting the advantages in using biomarkers in primary prevention and health surveillance.

Adapting the in vitro micronucleus assay (OECD Test Guideline No. 487) for testing of manufactured nanomaterials: recommendations for best practices.

The current Organisation for Economic Co-Operation and Development test guideline number 487 (OECD TG No. 487) provides instruction on how to conduct the in vitro micronucleus assay. This assay is one of the gold standard approaches for measuring the mutagenicity of test items; however, it is directed at testing low molecular weight molecules and may not be appropriate for particulate materials (e.g. engineered nanoparticles [ENPs]). This study aimed to adapt the in vitro micronucleus assay for ENP testing and underpins the development of an OECD guidance document. A harmonized, nano-specific protocol was generated and evaluated by two independent laboratories. Cell lines utilized were human lymphoblastoid (TK6) cells, human liver hepatocytes (HepG2) cells, Chinese hamster lung fibroblast (V79) cells, whole blood, and buffy coat cells from healthy human volunteers. These cells were exposed to reference ENPs from the Joint Research Council (JRC): SiO2 (RLS-0102), Au5nm and Au30nm (RLS-03, RLS-010), CeO2 (NM212), and BaSO4 (NM220). Tungsten carbide-cobalt (WC/Co) was used as a trial particulate positive control. The chemical controls were positive in all cell cultures, but WC/Co was only positive in TK6 and buffy coat cells. In TK6 cells, mutagenicity was observed for SiO2- and both Au types. In HepG2 cells, Au5nm and SiO2 showed sub-two-fold increases in micronuclei. In V79 cells, whole blood, and buffy coat cells, no genotoxicity was detected with the test materials. The data confirmed that ENPs could be tested with the harmonized protocol, additionally, concordant data were observed across the two laboratories with V79 cells. WC/Co may be a suitable particulate positive control in the in vitro micronucleus assay when using TK6 and buffy coat cells. Detailed recommendations are therefore provided to adapt OECD TG No. 487 for testing ENP.

Safe and sustainable by design Ag nanomaterials: A case study to evaluate the bio-reactivity in the environment using a soil model invertebrate.

Safe-and-sustainable-by-design (SSbD) nanomaterials (NMs) or NM-containing products are a priority. Silver (Ag) NMs have a vast array of applications, including biomedical and other products, even as nanopesticides. Thus, their release to the environment is expected to increase. The aim of the present study was to assess the ecotoxicity of the SSbD Ag NM to the soil model species Enchytraeus crypticus (Oligochaeta). The Ag NM tested consists in a SSbD Ag with biomedical applications, a hydroxyethyl cellulose (HEC) coated Ag NMs (AgHEC) and its toxicity was compared to the naked Ag NMs (Ag-Sigma), an Ag-based biomedical product (PLLA-Ag: Poly l-Lactide microfibers doped with Ag), and AgNO3. Effects were assessed both in soil and aqueous media, following the standard OECD guideline in soil (28 days) and the OECD extension (56 days), and short-term pulse (5 days) in aqueous media: reconstituted water (ISO water) and soil:water (S:W) extracts, followed by a 21-days recovery period in soil. Ag materials were thoroughly characterized as synthesized and during the test in media and animals. Results in S:W showed AgHEC was more toxic than Ag-Sigma (ca. 150 times) and PLLA-Ag (ca. 2.5 times), associated with a higher Ag uptake. Higher toxicity was related to a smaller hydrodynamic size and higher suspension stability, which in turn resulted in a higher bioavailability of Ag NMs and released ions, particularly in S:W. Toxicity was correlated with the main physicochemical features, providing useful prediction of AgNMs bioactivity. The ability to test E. crypticus in a range of media with different and/or increasing complexity (water, S:W extracts, soil) provided an excellent source to interpret results and is here recommended.

Ecotoxicity and trophic transfer of metallic nanomaterials in aquatic ecosystems.

Metallic nanomaterials (MNMs) possess unique properties that have led to their widespread application in fields such as electronics and medicine. However, concerns about their interactions with environmental factors and potential toxicity to aquatic life have emerged. There is growing evidence suggesting MNMs can have detrimental effects on aquatic ecosystems, and are potential for bioaccumulation and biomagnification in the food chain, posing risks to higher trophic levels and potentially humans. While many studies have focused on the general ecotoxicity of MNMs, fewer have delved into their trophic transfer within aquatic food chains. This review highlights the ecotoxicological effects of MNMs on aquatic systems via waterborne exposure or dietary exposure, emphasizing their accumulation and transformation across the food web. Biomagnification factor (BMF), the ratio of the contaminant concentration in predator to that in prey, was used to evaluate the biomagnification due to the complex nature of aquatic food chains. However, most current studies have BMF values of less than 1 indicating no biomagnification. Factors influencing MNM toxicity in aquatic environments include nanomaterial properties, ion variations, light, dissolved oxygen, and pH. The multifaceted interactions of these variables with MNM toxicity remain to be fully elucidated. We conclude with recommendations for future research directions to mitigate the adverse effects of MNMs in aquatic ecosystems and advocate for a cautious approach to the production and application of MNMs.

Comparative toxicological analysis of two pristine carbon nanomaterials (graphene oxide and aminated graphene oxide) and their corresponding degraded forms using human in vitro models.

Despite the wide application of graphene-based materials, the information of the toxicity associated to some specific derivatives such as aminated graphene oxide is scarce. Likewise, most of these studies analyse the pristine materials, while the available data regarding the harmful effects of degraded forms is very limited. In this work, the toxicity of graphene oxide (GO), aminated graphene oxide (GO-NH2), and their respective degraded forms (dGO and dGO-NH2) obtained after being submitted to high-intensity sonication was evaluated applying in vitro assays in different models of human exposure. Viability and ROS assays were performed on A549 and HT29 cells, while their skin irritation potential was tested on a reconstructed human epidermis model. The obtained results showed that GO-NH2 and dGO-NH2 substantially decrease cell viability in the lung and gastrointestinal models, being this reduction slightly higher in the cells exposed to the degraded forms. In contrast, this parameter was not affected by GO and dGO which, conversely, showed the ability to induce higher levels of ROS than the pristine and degraded aminated forms. Furthermore, none of the materials is skin irritant. Altogether, these results provide new insights about the potential harmful effects of the selected graphene-based nanomaterials in comparison with their degraded counterparts.

Nanotoxicity of two-dimensional nanomaterials on human skin and the structural evolution of keratin protein.

Two-dimensional (2D) materials have been increasingly widely used in biomedical and cosmetical products nowadays, yet their safe usage in human body and environment necessitates a comprehensive understanding of their nanotoxicity. In this work, the effect of pristine graphene and graphene oxide (GO) on the adsorption and conformational changes of skin keratin using molecular dynamics simulations. It is found that skin keratin can be absorbed through various noncovalent driving forces, such as van der Waals (vdW) and electrostatics. In the case of GO, the oxygen-containing groups prevent tighter contact between skin keratin and the graphene basal plane through steric effects and electrostatic repulsion. On the other hand, electrostatic attraction and hydrogen bonding enhance their binding affinity to positively charged residues such as lysine and arginine. The secondary structure of skin keratin is better preserved in GO system, suggesting that GO has good biocompatibility. The charged groups on GO surface perform as the hydrogen bond acceptors, which is like to the natural receptors of keratin in this physiological environment. This work contributes to a better knowledge of the nanotoxicity of cutting-edge 2D materials on human health, thereby advancing their potential biological applications.

A comparison of dermal toxicity models; assessing suitability for safe(r)-by-design decision-making and for screening nanomaterial hazards.

The objective of Safe-by-Design (SbD) is to support the development of safer products and production processes, and enable safe use throughout a materials' life cycle; an intervention at an early stage of innovation can greatly benefit industry by reducing costs associated with the development of products later found to elicit harmful effects. Early hazard screening can support this process, and is needed for all of the expected nanomaterial exposure routes, including inhalation, ingestion and dermal. In this study, we compare in vitro and ex vivo cell models that represent dermal exposures (including HaCaT cells, primary keratinocytes, and reconstructed human epidermis (RhE)), and when possible consider these in the context of regulatory accepted OECD TG for in vitro dermal irritation. Various benchmark nanomaterials were used to assess markers of cell stress in each cell model. In addition, we evaluated different dosing strategies that have been used when applying the OECD TG for dermal irritation in assessment of nanomaterials, and how inconsistencies in the approach used can have considerable impact of the conclusions made. Although we could not demonstrate alignment of all models used, there was an indication that the simpler in vitro cell model aligned more closely with RhE tissue than ex vivo primary keratinocytes, supporting the use of HaCaT cells for screening of dermal toxicity of nanomaterials and in early-stage SbD decision-making.

Potential Biosafety of Mxenes: Stability, Biodegradability, Toxicity and Biocompatibility.

MXenes are two-dimensional nanomaterials with unique properties that are widely used in various fields of research, mostly in the field of energy. Fewer publications are devoted to MXene application in biomedicine and the question is: are MXenes safe for use in biological systems? The sharp edges of MXenes provide the structure of "nanoknives" which cause damage in direct physical contact with cells. This is effectively used for antibacterial research. However, on the other hand, most studies in cultured cells and rodents report that they do not cause obvious signs of cytotoxicity and are fully biocompatible. The aim of our review was to consider whether MXenes can really be considered non-toxic and biocompatible. Often the last two concepts are confused. We first reviewed aspects such as the stability and biodegradation of MXenes, and then analyzed the mechanisms of toxicity and their consequences for bacteria, cultured cells, and rodents, with subsequent conclusions regarding their biocompatibility.

Harmonization Risks and Rewards: Nano-QSAR for Agricultural Nanomaterials.

This comprehensive review explores the emerging landscape of Nano-QSAR (quantitative structure-activity relationship) for assessing the risk and potency of nanomaterials in agricultural settings. The paper begins with an introduction to Nano-QSAR, providing background and rationale, and explicitly states the hypotheses guiding the review. The study navigates through various dimensions of nanomaterial applications in agriculture, encompassing their diverse properties, types, and associated challenges. Delving into the principles of QSAR in nanotoxicology, this article elucidates its application in evaluating the safety of nanomaterials, while addressing the unique limitations posed by these materials. The narrative then transitions to the progression of Nano-QSAR in the context of agricultural nanomaterials, exemplified by insightful case studies that highlight both the strengths and the limitations inherent in this methodology. Emerging prospects and hurdles tied to Nano-QSAR in agriculture are rigorously examined, casting light on important pathways forward, existing constraints, and avenues for research enhancement. Culminating in a synthesis of key insights, the review underscores the significance of Nano-QSAR in shaping the future of nanoenabled agriculture. It provides strategic guidance to steer forthcoming research endeavors in this dynamic field.

An overview on dispersion procedures and testing methods for the ecotoxicity testing of nanomaterials in the marine environment.

Considerable efforts have been devoted to develop or adapt existing guidelines and protocols, to obtain robust and reproducible results from (eco)toxicological assays on engineered nanomaterials (NMs). However, while many studies investigated adverse effects of NMs on freshwater species, less attention was posed to the marine environment, a major sink for these contaminants. This review discusses the procedures used to assess the ecotoxicity of NMs in the marine environment, focusing on the use of protocols and methods for preparing NMs dispersions and on the NMs physicochemical characterization in exposure media. To this purpose, a critical analysis of the literature since 2010 was carried out, based on the publication of the first NMs dispersion protocols. Among the 89 selected studies, only <5 % followed a standardized dispersion protocol combined with NMs characterization in ecotoxicological media, while more than half used a non-standardized dispersion method but performed NMs characterization. In the remaining studies, only partial or no information on dispersion procedures or on physicochemical characterization was provided. This literature review also highlighted that metal oxides NMs were the most studied (42 %), but with an increasing interest in last years towards nanoplastics (14 %) and multicomponent nanomaterials (MCNMs, 7 %), in line with the growing attention on these emerging contaminants. For all these NMs, primary producers as algae and bacteria were the most studied groups of marine species, in addition to mollusca, while organisms at higher trophic levels were less represented, likely due to challenges in evaluating adverse effects on more complex organisms. Thus, despite the wide use of NMs in different applications, standard dispersion protocols are not often used for ecotoxicity testing with marine species. However, the efforts to characterize NMs in ecotoxicological media recognize the importance of following conditions that are as standardized as possible to support the ecological hazard assessment of NMs.

Computational Assessment of the Biocompatibility of Two-Dimensional g-C3N3 Toward Lipid Membranes.

One of the most recent additions to the family of two-dimensional (2D) materials, graphitic C3N3 (g-C3N3), has been considered a viable contender for biomedical applications, although its potential toxicity remains elusive. We perform all-atom molecular dynamics simulations to decipher the interactions between model lipid membranes and g-C3N3 as a first step toward exploring the cytotoxicity induced at the nanoscale. We show that g-C3N3 can easily insert into the cellular membranes following a multistage mechanism consisting of simultaneous desolvation of the 2D material along with enrichment of nanomaterial-lipid interactions. Free energy calculations indicate that g-C3N3 is more stable in a membrane-bound state compared to an aqueous solution; however, the insertion of the material does not disturb the structural integrity of lipid membranes. After being inserted into a membrane, g-C3N3 is unlikely to be released into the cellular environment and is incapable of extracting lipid molecules from the membrane. The nature of interaction between the 2D material and membranes is found to be independent of the nanomaterial size. Also, the performance of g-C3N3 toward biomolecular delivery is shown to be significantly improved compared to the state-of-the-art 2D materials graphene and hexagonal boron nitride (h-BN). It is revealed that, the affinity of g-C3N3 toward lipid membranes is weaker compared to the nanotoxic graphene and h-BN, while being marginally higher than h2D-C2N, which in turn, increases the biocompatibility of the material, thereby brightening its future as a noncytotoxic material for forthcoming biomedical applications.

Zebrafish Insights into Nanomaterial Toxicity: A Focused Exploration on Metallic, Metal Oxide, Semiconductor, and Mixed-Metal Nanoparticles.

Nanomaterials are widely used in various fields, and ongoing research is focused on developing safe and sustainable nanomaterials. Using zebrafish as a model organism for studying the potentially toxic effects of nanomaterials highlights the importance of developing safe and sustainable nanomaterials. Studies conducted on nanomaterials and their toxicity and potential risks to human and environmental health are vital in biomedical sciences. In the present review, we discuss the potential toxicity of nanomaterials (inorganic and organic) and exposure risks based on size, shape, and concentration. The review further explores various types of nanomaterials and their impacts on zebrafish at different levels, indicating that exposure to nanomaterials can lead to developmental defects, changes in gene expressions, and various toxicities. The review also covers the importance of considering natural organic matter and chorion membranes in standardized nanotoxicity testing. While some nanomaterials are biologically compatible, metal and semiconductor nanomaterials that enter the water environment can increase toxicity to aquatic creatures and can potentially accumulate in the human body. Further investigations are necessary to assess the safety of nanomaterials and their impacts on the environment and human health.

Cytotoxicity prediction of nano metal oxides on different lung cells via Nano-QSAR.

In recent years, nanomaterials have found extensive applications across diverse domains owing to their distinctive physical and chemical characteristics. It is of great importance in theoretical and practical terms to carry out the relationship between structural characteristics of nanomaterials and different cytotoxicity and to achieve practical assessment and prediction of cytotoxicity. This study investigated the intrinsic quantitative constitutive relationships between the cytotoxicity of nano-metal oxides on human normal lung epithelial cells and human lung adenocarcinoma cells. We first employed quasi-SMILES-based nanostructural descriptors by selecting the five physicochemical properties that are most closely related to the cytotoxicity of nanometal oxides, then established SMILES-based descriptors that can effectively describe and characterize the molecular structure of nanometal oxides, and then built the corresponding Nano-Quantitative Structure-Activity Relationship (Nano-QSAR) prediction models, finally, combined with the theory of reactive oxygen species (ROS) biotoxicity, to reveal the mechanism of toxicity and differences between the two cell types. The established model can efficiently and accurately predict the properties of targets, reveal the corresponding toxicity mechanisms, and guide the safe design, synthesis, and application of nanometal oxides.

An integrated approach to occupational health risk assessment of manufacturing nanomaterials using Pythagorean Fuzzy AHP and Fuzzy Inference System.

Nanomaterials (NMs) have the potential to be hazardous owing to their unique physico-chemical properties. Therefore, the need for Health Risk Assessment (HRA) of NMs is expanding. In this study, a novel HRA was developed by the Pythagorean Fuzzy Health Risk Assessment (PFHRA) approach. Risk is considered to be the outcome of parameters including Occurrence Likelihood (OL), Potential Exposure (PE) and Toxic Effects (TE). In our proposed method, priority weights of sub-factors in Pythagorean Fuzzy-Analytical Hierarchical Process (PF-AHP) were determined by pairwise comparison based on expert judgment. After determining parameter scores, both RM and risk class (i.e., negligible, minor, major and critical) were reported as Fuzzy Inference System (FIS) output. Ultimately, a risk management strategy is presented for NMs manufacturing workplaces. This proposed method provides experts with more flexibility to express their opinions. The PFHRA approach was applied for two scenarios. The production scenario for SiNPs can create minor (5%) and major (95%) occupational health risks; the production scenario for ZnONPs can create minor (100%) concerns. However, the production SiNPs and ZnONPs utilizing the CB Nanotool technique had a major and minor risk class, respectively. The results of the present study confirmed the reliability and applicability of this approach.