Toxicological inhalation studies in rats to substantiate grouping of zinc oxide nanoforms.

BACKGROUND: Significant variations exist in the forms of ZnO, making it impossible to test all forms in in vivo inhalation studies. Hence, grouping and read-across is a common approach under REACH to evaluate the toxicological profile of familiar substances. The objective of this paper is to investigate the potential role of dissolution, size, or coating in grouping ZnO (nano)forms for the purpose of hazard assessment. We performed a 90-day inhalation study (OECD test guideline no. (TG) 413) in rats combined with a reproduction/developmental (neuro)toxicity screening test (TG 421/424/426) with coated and uncoated ZnO nanoforms in comparison with microscale ZnO particles and soluble zinc sulfate. In addition, genotoxicity in the nasal cavity, lungs, liver, and bone marrow was examined via comet assay (TG 489) after 14-day inhalation exposure. RESULTS: ZnO nanoparticles caused local toxicity in the respiratory tract. Systemic effects that were not related to the local irritation were not observed. There was no indication of impaired fertility, developmental toxicity, or developmental neurotoxicity. No indication for genotoxicity of any of the test substances was observed. Local effects were similar across the different ZnO test substances and were reversible after the end of the exposure. CONCLUSION: With exception of local toxicity, this study could not confirm the occasional findings in some of the previous studies regarding the above-mentioned toxicological endpoints. The two representative ZnO nanoforms and the microscale particles showed similar local effects. The ZnO nanoforms most likely exhibit their effects by zinc ions as no particles could be detected after the end of the exposure, and exposure to rapidly soluble zinc sulfate had similar effects. Obviously, material differences between the ZnO particles do not substantially alter their toxicokinetics and toxicodynamics. The grouping of ZnO nanoforms into a set of similar nanoforms is justified by these observations.

Immunological, histological and immunohistochemical alternations induced by zinc oxide nanoparticles and mureer plant in spleen albino rats with the prospective anti-inflammatory action of gallic acid.

The current study was proposed to evaluate the mortal impacts of either alone or mixed treatments of zinc oxide nanoparticles (ZnO NPs) and mureer or Senecio glaucus L. plant (SP) on spleen tissue via immunological and histological studies and to estimate the likely immunomodulatory effect of gallic acid (GA) for 30 days in rats. Rats were classified into eight groups with orally treated: Control, GA (100mg/kg), ZnO NPs (150mg/kg), SP (400mg/kg), GA+ZnO NPs (100,150mg/kg), GA+SP (100,400mg/kg), ZnONPs+SP (150,400mg/kg) and GA+ZnONPs+SP (100,150,400mg/kg). Interleukin-6 (IL-6) level was measured using an enzyme-linked immunoassay (ELISA). Also, the pro-apoptotic protein (caspase-3) expression was estimated using an immunohistochemistry assay. Our data revealed that ZnO NPs and SP triggered a significant increase in the levels of IL-6 and total lipids (TL) and the activity of lactate dehydrogenase (LDH), (p<0.001). Furthermore, they overexpressed caspase-3 and caused lymphoid depletion. They revealed that the immunotoxic outcome of mixed treatment was more than the outcome of the alone treatment. However, GA restored the spleen damage from these adverse results. Finally, this study indicated that ZnO NPs and SP might be immunotoxic and splenotoxic agents; however, GA may be displayed as an anti-inflammatory and splenic-protective agent.

Combined effects of organic and mineral UV-filters on the lugworm Arenicola marina.

Pollution from personal care products, such as UV-filters like avobenzone and nano-zinc oxide (nZnO), poses a growing threat to marine ecosystems. To better understand this hazard, especially for lesser-studied sediment-dwelling marine organisms, we investigated the physiological impacts of simultaneous exposure to nZnO and avobenzone on the lugworm Arenicola marina. Lugworms were exposed to nZnO, avobenzone, or their combination for three weeks. We assessed pollutant-induced metabolic changes by measuring key metabolic intermediates in the body wall and coelomic fluid, and oxidative stress by analyzing antioxidant levels and oxidative lesions in proteins and lipids of the body wall. Exposure to UV filters resulted in shifts in the concentrations of Krebs' cycle and urea cycle intermediates, as well as alterations in certain amino acids in the body wall and coelomic fluid of the lugworms. Pathway enrichment analyses revealed that nZnO induced more pronounced metabolic shifts compared to avobenzone or their combination. Exposure to avobenzone or nZnO alone prompted an increase in tissue antioxidant capacity, indicating a compensatory response to restore redox balance, which effectively prevented oxidative damage to proteins or lipids. However, co-exposure to nZnO and avobenzone suppressed superoxide dismutase and lead to accumulation of lipid peroxides and methionine sulfoxide, indicating oxidative stress and damage to lipids and proteins. Our findings highlight oxidative stress as a significant mechanism of toxicity for both nZnO and avobenzone, especially when combined, and underscores the importance of further investigating the fitness implications of oxidative stress induced by these common UV filters in benthic marine organisms.

Mixture toxicity study of two metal oxide nanoparticles and chlorpyrifos on Eisenia andrei earthworms.

Co-exposure soil studies of pollutants are necessary for an appropriate ecological risk assessment. Here, we examined the effects of two-component mixtures of metal oxide nanoparticles (ZnO NPs or goethite NPs) with the insecticide chlorpyrifos (CPF) under laboratory conditions in short-term artificial soil assays using Eisenia andrei earthworms. We characterized NPs and their mixtures by scanning electron microscopy, atomic force microscopy, dynamic light scattering and zeta potential, and evaluated effects on metal accumulation, oxidative stress enzymes, and neurotoxicity related biomarkers in single and combined toxicity assays. Exposure to ZnO NPs increased Zn levels compared to control in single and combined exposure (ZnO NPs + CPF) at 72 h and 7 days, respectively. In contrast, there was no indication of Fe increase in organisms exposed to goethite NPs. One of the most notable effects on oxidative stress biomarkers was produced by single exposure to goethite NPs, showing that the worms were more sensitive to goethite NPs than to ZnO NPs. Acetylcholinesterase and carboxylesterase activities indicated that ZnO NPs alone were not neurotoxic to earthworms, but similar degrees of inhibition were observed after single CPF and ZnO NPs + CPF exposure. Differences between single and combined exposure were found for catalase and superoxide dismutase (goethite NPs) and for glutathione S-transferase (ZnO NPs) activities, mostly at 72 h. These findings suggest a necessity to evaluate mixtures of NPs with co-existing contaminants in soil, and that the nature of metal oxide NPs and exposure time are relevant factors to be considered when assessing combined toxicity, as it may have an impact on ecotoxicological risk assessment.

Nonphytotoxic and pH-responsive ZnO-ZIF­8 loaded with honokiol as a "nanoweapon" effectively controls the soil-borne bacterial pathogen Ralstonia solanacearum.

The development of intelligently released and environmentally safe nanocarriers not only aligns with the sustainable agricultural strategy but also offers a potential solution for controlling severe soil-borne bacterial diseases. Herein, the core-shell structured nanocarrier loaded with honokiol bactericide (honokiol@ZnO-ZIF-8) was synthesized via a one-pot method for the targeted control of Ralstonia solanacearum, the causative agent of tobacco bacterial wilt disease. Results indicated that honokiol@ZnO-ZIF-8 nanoparticles induced bacterial cell membrane and DNA damage through the production of excessive reactive oxygen species (ROS), thereby reducing bacterial cell viability and ultimately leading to bacterial death. Additionally, the dissociation mechanism of the nanocarriers was elucidated for the first time through thermodynamic computational simulation. The nanocarriers dissociate primarily due to H+ attacking the N atom on imidazole, causing the rupture of the Zn-N bond under acidic conditions and at room temperature. Furthermore, honokiol@ZnO-ZIF-8 exhibited potent inhibitory effects against other prominent Solanaceae pathogenic bacteria (Pseudomonas syringae pv. tabaci), demonstrating its broad-spectrum antibacterial activity. Biosafety assessment results indicated that honokiol@ZnO-ZIF-8 exhibited non-phytotoxicity towards tobacco and tomato plants, with its predominant accumulation in the roots and no translocation to aboveground tissues within a short period. This study provides potential application value for the intelligent release of green pesticides. ENVIRONMENT IMPLICATION: The indiscriminate use of agrochemicals poses a significant threat to environmental, ecological security, and sustainable development. Slow-release pesticides offer a green and durable strategy for crop disease control. In this study, we developed a non-phytotoxic and pH-responsive honokiol@ZnO-ZIF-8 nano-bactericide based on the pathogenesis of Ralstonia solanacearum. Thermodynamic simulation revealed the dissociation mechanism of ZIF-8, with different acidity controlling the dissociation rate. This provides a theoretical basis for on-demand pesticide release while reducing residue in the. Our findings provide strong evidence for effective soil-borne bacterial disease control and on-demand pesticide release.

Insights into the alleviation of cadmium toxicity in rice by nano-zinc and Serendipita indica: Modulation of stress-responsive gene expression and antioxidant defense system activation.

The adversities of cadmium (Cd) contamination are quite distinguished among other heavy metals (HMs), and so is the efficacy of zinc (Zn) nutrition in mitigating Cd toxicity. Rice (Oryza sativa) crop, known for its ability to absorb HMs, inadvertently facilitates the bioaccumulation of Cd, posing a significant risk to both the plant itself and to humans consuming its edible parts, and damaging the environment as well. The use of nanoparticles, such as nano-zinc oxide (nZnO), to improve the nutritional quality of crops and combat the harmful effects of HMs, have gained substantial attention among scientists and farmers. While previous studies have explored the individual effects of nZnO or Serendipita indica (referred to as S.i) on Cd toxicity, the synergistic action of these two agents has not been thoroughly investigated. Therefore, the gift of nature, i.e., S. indica, was incorporated alongside nZnO (50 mg L-1) against Cd stress (15 µM L-1) and their alliance manifested as phenotypic level modifications in two rice genotypes (Heizhan43; Hz43 and Yinni801; Yi801). Antioxidant activities were enhanced, specifically peroxidase (61.5 and 122.5% in Yi801 and Hz43 roots, respectively), leading to a significant decrease in oxidative burst; moreover, Cd translocation was reduced (85% for Yi801 and 65.5% for Hz43 compared to Cd alone treatment). Microstructural study showed a decrease in number of vacuoles and starch granules with ameliorative treatments. Overall, plants treated with nZnO displayed gene expression pattern (particularly of ZIP genes), different from the ones with alone or combined S.i and Cd. Inferentially, the integration of nZnO and S.i holds great promise as an effective strategy for alleviating Cd toxicity in rice plants. By immobilizing Cd ions in the soil and promoting their detoxification, this novel approach contributes to environmental restoration and ensures food safety worldwide.

Lipidomics Analysis Unravels Aberrant Lipid Species and Pathways Induced by Zinc Oxide Nanoparticles in Kidney Cells.

Zinc oxide nanoparticles (ZnO NPs) are widely used in versatile applications, from high technology to household products. While numerous studies have examined the toxic gene profile of ZnO NPs across various tissues, the specific lipid species associated with adverse effects and potential biomarkers remain elusive. In this study, we conducted a liquid chromatography-mass spectrometry based lipidomics analysis to uncover potential lipid biomarkers in human kidney cells following treatment with ZnO NPs. Furthermore, we employed lipid pathway enrichment analysis (LIPEA) to elucidate altered lipid-related signaling pathways. Our results demonstrate that ZnO NPs induce cytotoxicity in renal epithelial cells and modulate lipid species; we identified 64 lipids with a fold change (FC) > 2 and p < 0.01 with corrected p < 0.05 in HK2 cells post-treatment with ZnO NPs. Notably, the altered lipids between control HK2 cells and those treated with ZnO NPs were associated with the sphingolipid, autophagy, and glycerophospholipid pathways. This study unveils novel potential lipid biomarkers of ZnO NP nanotoxicity, representing the first lipidomic profiling of ZnO NPs in human renal epithelial cells.

Ecotoxicity of doped zinc oxide nanoparticles: Perspectives on environmental safety.

Studies on the ecotoxicity of doped zinc oxide nanoparticles (ZnO NPs) are recent, with the first publications starting in 2010. In this sense, this is the first study that comprehensively reviews the ecotoxicological effects of ZnO NPs doped with lanthanide elements to fill this literature gap. This research explores a multifaceted question at the intersection of nanotechnology, toxicology, and environmental science. Different types of dopants commonly used for ZnO doping were investigated in this review, focusing on the ecotoxicological effects of lanthanides as dopants. Bacteria were the main class of organisms used in ecotoxicological studies, since antimicrobial activity of these nanomaterials is extensively explored to combat the imminent problem of resistant bacteria, in addition to enabling the safe use of these nanomaterials for biomedical applications. Doping appears to exhibit greater efficacy when compared to undoped ZnO NPs in terms of antimicrobial effects; however, it cannot be said that it has no impact on non-target organisms. An extensive examination of the literature also establishes the importance and need to evaluate the effects of doped ZnO NPs on organisms from different environmental compartments in order to identify their potential impacts. We underscore the dearth of research information regarding the environmental toxicity/ecotoxicity of doped ZnO nanoparticles across various ecological levels, thereby limiting the extrapolation of findings to humans or other complex models. Therefore, we emphasize the urgency of a multi-parameter assessment for the development of sanitary and environmentally safe nanotechnologies.

Metal nanoparticle-induced effects on green toads (Amphibia, Anura) under climate change: conservation implications.

The toxicity of aluminum oxide (Al2O3), copper oxide (CuO), iron oxide (Fe3O4), nickel oxide (NiO), zinc oxide (ZnO), and titanium dioxide (TiO2) nanoparticles (NPs) on amphibians and their interaction with high temperatures, remain unknown. In this study, we investigated the survival, developmental, behavioral, and histological reactions of Bufotes viridis embryos and larvae exposed to different NPs for a duration of 10 days, using lethal concentrations (LC25%, LC50%, and LC75% mg/L) under both ambient (AT: 18 °C) and high (HT: 21 °C) temperatures. Based on LC, NiONPs > ZnONPs > CuONPs > Al2O3NPs > TiO2NPs > Fe3O4NPs showed the highest mortality at AT. A similar pattern was observed at HT, although mortality occurred at lower concentrations and Fe3O4NPs were more toxic than TiO2NPs. The results indicated that increasing concentrations of NPs significantly reduced hatching rates, except for TiO2NPs. Survival rates decreased, abnormality rates increased, and developmental processes slowed down, particularly for NiONPs and ZnONPs, under HT conditions. However, exposure to low concentrations of Fe3O4NPs for up to 7 days, CuONPs for up to 72 h, and NiO, ZnONPs, and TiO2NPs for up to 96 h did not have a negative impact on survival compared with the control group under AT. In behavioral tests with larvae, NPs generally induced hypoactivity at AT and hyperactivity at HT. Histological findings revealed liver and internal gill tissue lesions, and an increase in the number of melanomacrophage centers at HT. These results suggest that global warming may exacerbate the toxicity of metal oxide NPs to amphibians, emphasizing the need for further research and conservation efforts in this context.

Physiological and molecular mechanisms of ZnO quantum dots mitigating cadmium stress in Salvia miltiorrhiza.

This study delved into the physiological and molecular mechanisms underlying the mitigation of cadmium (Cd) stress in the model medicinal plant Salvia miltiorrhiza through the application of ZnO quantum dots (ZnO QDs, 3.84 nm). A pot experiment was conducted, wherein S. miltiorrhiza was subjected to Cd stress for six weeks with foliar application of 100 mg/L ZnO QDs. Physiological analyses demonstrated that compared to Cd stress alone, ZnO QDs improved biomass, reduced Cd accumulation, increased the content of photosynthetic pigments (chlorophyll and carotenoids), and enhanced the levels of essential nutrient elements (Ca, Mn, and Cu) under Cd stress. Furthermore, ZnO QDs significantly lowered Cd-induced reactive oxygen species (ROS) content, including H2O2, O2-, and MDA, while enhancing the activity of antioxidant enzymes (SOD, POD, APX, and GSH-PX). Additionally, ZnO QDs promoted the biosynthesis of primary and secondary metabolites, such as total protein, soluble sugars, terpenoids, and phenols, thereby mitigating Cd stress in S. miltiorrhiza. At the molecular level, ZnO QDs were found to activate the expression of stress signal transduction-related genes, subsequently regulating the expression of downstream target genes associated with metal transport, cell wall synthesis, and secondary metabolite synthesis via transcription factors. This activation mechanism contributed to enhancing Cd tolerance in S. miltiorrhiza. In summary, these findings shed light on the mechanisms underlying the mitigation of Cd stress by ZnO QDs, offering a potential nanomaterial-based strategy for enhancing Cd tolerance in medicinal plants.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles induce mitochondrial permeability and cardiac damage after oral exposure in rats.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are found in diverse products for human use. E171 is used as whitening agent in food and cosmetics, and ZnO NPs in food packaging. Their potential multi-organ toxicity has raised concerns on their safety. Since mitochondrial dysfunction is a key aspect of cardio-pathologies, here, we evaluate the effect of chronic exposure to E171 and ZnO NPs in rats on cardiac mitochondria. Changes in cardiac electrophysiology and body weight were measured. E171 reduced body weight more than 10% after 5 weeks. Both E171 and ZnO NPs increased systolic blood pressure (SBP) from 110-120 to 120-140 mmHg after 45 days of treatment. Both NPs altered the mitochondrial permeability transition pore (mPTP), reducing calcium requirement for permeability by 60% and 93% in E171- and ZnO NPs-exposed rats, respectively. Treatments also affected conformational state of adenine nucleotide translocase (ANT). E171 reduced the binding of EMA to Cys 159 in 30% and ZnO NPs in 57%. Mitochondrial aconitase activity was reduced by roughly 50% with both NPs, indicating oxidative stress. Transmission electron microscopy (TEM) revealed changes in mitochondrial morphology including sarcomere discontinuity, edema, and hypertrophy in rats exposed to both NPs. In conclusion, chronic oral exposure to NPs induces functional and morphological damage in cardiac mitochondria, with ZnO NPs being more toxic than E171, possibly due to their dissociation in free Zn2+ ion form. Therefore, chronic intake of these food additives could increase risk of cardiovascular disease.

Enhanced visible light driven photodegradation of rifampicin and Cr(VI) reduction activity of ultra-thin ZnO nanosheets/CuCo2S4QDs: A mechanistic insights, degradation pathway and toxicity assessment.

In this study, we focused on fabrication of porous ultra-thin ZnO nanosheet (PUNs)/CuCo2S4 quantum dots (CCS QDs) for visible light-driven photodegradation of rifampicin (RIF) and Cr(VI) reduction. The morphology, structural, optical and textural properties of fabricated photocatalyst were critically analyzed with different analytical and spectroscopic techniques. An exceptionally high RIF degradation (99.97%) and maximum hexavalent Cr(VI) reduction (96.17%) under visible light was achieved at 10 wt% CCS QDs loaded ZnO, which is 213% and 517% greater than bare ZnO PUNs. This enhancement attributed to the improved visible light absorption, interfacial synergistic effect, and high surface-rich active sites. Extremely high generation of ●OH attributed to the spin-orbit coupling in ZnO PUNs@CCS QDs and the existence of oxygen vacancies. Besides, the ZnOPUNs@CCS QDs, forming Z-scheme heterojunctions, enhanced the separation of photogenerated charge carriers. We investigated the influencing factors such as pH, inorganic ions, catalyst dosage and drug dosage on the degradation process. More impressively, a stable performance of ZnO PUNs@CCS QDs obtained even after six consecutive degradation (85.9%) and Cr(VI) reduction (67.7%) cycles. Furthermore, the toxicity of intermediates produced during the photodegradation process were assessed using ECOSAR program. This work provides a new strategy for ZnO-based photocatalysis as a promising candidate for the treatment of various contaminants present in water bodies.

Zinc oxide nanoparticles exacerbate skin epithelial cell damage by upregulating pro-inflammatory cytokines and exosome secretion in M1 macrophages following UVB irradiation-induced skin injury.

BACKGROUND: Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs. RESULTS: We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release. However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. CONCLUSIONS: Our findings propose a new concept for ZnONP-induced skin toxicity mechanisms and the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.

Screening of low-toxic zinc oxide nanomaterials and study the apoptosis mechanism of NSC-34 cells.

With the increasing application of ZnO nanomaterials (ZnO-NMts) in the biomedical field, it is crucial to assess their potential risks to humans and the environment. Therefore, this study aimed to screen for ZnO-NMts with low toxicity and establish safe exposure limits, and investigate their mechanisms of action. The study synthesized 0D ZnO nanoparticles (ZnO NPs) and 3D ZnO nanoflowers (ZnO Nfs) with different morphologies using a hydrothermal approach for comparative research. The ZnO-NMts were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Mouse brain neuronal cells (NSC-34) were incubated with ZnO NMts for 6, 12, and 24 h, and the cell morphology was observed using TEM. The toxic effects of ZnO Nfs on NSC-34 cells were studied using CCK-8 cell viability detection, reactive oxygen species (ROS) measurement, caspase-3 activity detection, Annexin V-FITC/PI apoptosis assay, and mitochondrial membrane potential (Δφm) measurement. The results of the research showed that ZnO-NMts caused cytoplasmic vacuolization and nuclear pyknosis. After incubating cells with 12.5 µg mL-1 ZnO-NMts for 12 h, ZnO NRfs exhibited the least toxicity and ROS levels. Additionally, there was a significant increase in caspase-3 activity, depolarization of mitochondrial membrane potential (Δφm), and the highest rate of early apoptosis.This study successfully identified ZnO NRfs with the lowest toxicity and determined the safe exposure limit to be < 12.5 µg mL-1 (12 h). These findings will contribute to the clinical use of ZnO NRfs with low toxicity and provide a foundation for further research on their potential applications in brain disease treatment.

Exposure to zinc oxide nanoparticles induced reproductive toxicities in male Sprague Dawley rats.

BACKGROUND: This research delves into the reproductive toxicology of zinc oxide nanoparticles (ZnO-NPs) in male Sprague Dawley rats. It specifically examines the repercussions of Zn accumulation in the testes, alterations in testosterone levels, and histopathological changes in the gonadal tissues. AIMS: The primary objective of this study is to elucidate the extent of reproductive toxicity induced by ZnO-NPs in male Sprague Dawley rats. The investigation aims to contribute to a deeper understanding of the potential endocrine and reproductive disruptions caused by ZnO-NPs exposure. METHODS: Characterization techniques including SEM-EDX and XRD affirmed the characteristic nature of ZnO-NPs. Twenty-five healthy post weaning rats (200-250 g) were intraperitoneally exposed to different concentrations of ZnO-NPs @ 10 or 20 or 30 mg/kg BW for 28 days on alternate days. RESULTS: Results showed significant dose dependent decline in the body weight and testicular somatic index of rats. It also showed significant dose dependent accumulation of Zn in testis with increasing dose of ZnO-NPs. Conversely, serum testosterone level and sperm count were reduced with increasing dose of ZnO-NPs. Histological results showed dose dependent abnormalities i.e., vacuolization, edema, hemorrhage, destruction of seminiferous tubules, loss of germ cells and necrosis in rat testis. CONCLUSION: The findings of this study clearly indicate that high doses of zinc oxide nanoparticles (ZnO-NPs) can adversely affect the structural integrity and functional efficacy of the male reproductive system. Given these results, it becomes crucial to implement stringent precautionary measures in the utilization of ZnO-NPs, particularly in cosmetics and other relevant sectors. Such measures are imperative to mitigate the toxicological impact of ZnO-NPs on the male reproductive system and potentially on other related physiological functions. This study underscores the need for regulatory vigilance and safety assessments in the application of nanotechnology to safeguard human health.

Doping zinc oxide and titanium dioxide nanoparticles with gold induces additional oxidative stress, membrane damage, and neurotoxicity in Mytilus galloprovincialis: Results from a laboratory bioassay.

BACKGROUND: While previous studies have provided insights into the effects of zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles (NPs) on aquatic organisms, there is still a substantial amount of information lacking about the possible effects of their doped counterparts. The goal of the current work was to address this gap by examining Mytilus galloprovincialis reaction to exposure to doped and undoped nanoparticles. METHODS: Two concentrations (50 or 100 µg/L) of undoped ZnO and TiO2 NPs, as well as their gold (Au) doped counterparts, were applied on mussels for 14 days, and the effects on biomarkers activities in digestive glands and gills were assessed by spectrophotometry. RESULTS: The NPs were quasi-spherical in shape (below 100 nm), stable in seawater, and with no aggregation for both doped and undoped forms. Analytical results using inductively coupled plasma atomic emission spectroscopy indicated the uptake of NPs in mussels. Furthermore, it was found that biometal dyshomeostasis could occur following NP treatment and that doping the NPs aggravated this response. At the biochemical level, exposure to undoped NPs caused membrane damage, neurotoxic effect, and changes in the activities in the gills and digestive glands of superoxide dismutase, catalase, and glutathione-S-transferase, in a concentration and organ-dependent manner. CONCLUSION: Doping ZnO NPs and TiO2NPs with Au induced additional oxidative stress, membrane damage, and neurotoxicity in mussels.

A critical review on fate, behavior, and ecotoxicological impact of zinc oxide nanoparticles on algae.

The rapid inclusion of zinc oxide nanoparticles (ZnO NPs) in nanotechnology-based products over the last decade has generated a new threat in the apprehension of the environment. The massive use of zinc nanosized products will certainly be disposed of and be released, eventually entering the aquatic ecosystem, posing severe environmental hazards. Moreover, nanosized ZnO particles owing the larger surface area per volume exhibit different chemical interactions within the aquatic ecosystem. They undergo diverse potential transformations because of their unique physiochemical properties and the feature of receiving medium. Therefore, assessment of their impact is critical not only for scavenging the present situation but also for preventing unintended environmental hazards. Algae being a primary producer of the aquatic ecosystem help assess the risk of massive NPs usage in environmental health. Because of their nutritional needs and position at the base of aquatic food webs, algal indicators exhibit relatively unique information concerning ecosystem conditions. Moreover, algae are presently the most vital part of the circular economy. Hence, it is imperative to understand the physiologic, metabolic, and morphologic changes brought by the ZnO NPs to the algal cells along with the development of the mechanism imparting toxicity mechanism. We also need to develop an appropriate scientific strategy in the innovation process to restrain the exposure of NPs at safer levels. This review provides the details of ZnO NP interaction with algae. Moreover, their impact, mechanism, and factors affecting toxicity to the algae are discussed.

Integrative chemical, physiological, and metabolomics analyses reveal nanospecific phytotoxicity of metal nanoparticles.

The increasing application of metal nanoparticles (NPs) via agrochemicals and sewage sludge results in non-negligible phytotoxicological risks. Herein, the potential phytotoxicity of ZnO and CuO NPs on wheat was determined using integrative chemical, physiological, and metabolomics analyses, in comparison to Zn2+ and Cu2+. It was found that ZnO or CuO NPs had a stronger inhibitory effect on wheat growth than Zn2+ or Cu2+. After exposure to ZnO or CuO NPs, wheat seedlings accumulated significantly higher levels of Zn or Cu than the corresponding Zn2+ or Cu2+ treatments, indicating the active uptake of NPs via wheat root. TEM analysis further confirmed the intake of NPs. Moreover, ZnO or CuO NPs exposure altered micronutrients (Fe, Mn, Cu, and Zn) accumulation in the tissues and decreased the activities of antioxidant enzymes. The metabolomics analysis identified 312, 357, 145, and 188 significantly changed metabolites (SCMs) in wheat root exposed to ZnO NPs, CuO NPs, Zn2+, and Cu2+, respectively. Most SCMs were nano-specific to ZnO (80%) and CuO NPs (58%), suggesting greater metabolic reprogramming by NPs than metal ions. Overall, nanospecific toxicity dominated the phytotoxicity of ZnO and CuO NPs, and our results provide a molecular perspective on the phytotoxicity of metal oxide NPs.

Toxicological assessment of divalent ion-modified ZnO nanomaterials through artificial intelligence and in vivo study.

The nanotechnology-driven industrial revolution widely relies on metal oxide-based nanomaterial (NM). Zinc oxide (ZnO) production has rapidly increased globally due to its outstanding physical and chemical properties and versatile applications in industries including cement, rubber, paints, cosmetics, and more. Nevertheless, releasing Zn2+ ions into the environment can profoundly impact living systems and affect water-based ecosystems, including biological ones. In aquatic environments, Zn2+ ions can change water properties, directly influencing underwater ecosystems, especially fish populations. These ions can accumulate in fish tissues when fish are exposed to contaminated water and pose health risks to humans who consume them, leading to symptoms such as nausea, vomiting, and even organ damage. To address this issue, safety of ZnO NMs should be enhanced without altering their nanoscale properties, thus preventing toxic-related problems. In this study, an eco-friendly precipitation method was employed to prepare ZnO NMs. These NMs were found to reduce ZnO toxicity levels by incorporating elements such as Mg, Ca, Sr, and Ba. Structural, morphological, and optical properties of synthesized NMs were thoroughly investigated. In vitro tests demonstrated potential antioxidative properties of NMs with significant effects on free radical scavenging activities. In vivo, toxicity tests were conducted using Oreochromis mossambicus fish and male Swiss Albino mice to compare toxicities of different ZnO NMs. Fish and mice exposed to these NMs exhibited biochemical changes and histological abnormalities. Notably, ZnCaO NMs demonstrated lower toxicity to fish and mice than other ZnO NMs. This was attributed to its Ca2+ ions, which could enhance body growth metabolism compared to other metals, thus improving material safety. Furthermore, whether nanomaterials' surface roughness might contribute to their increased toxicity in biological systems was investigated utilizing computer vision (CV)-based AI tools to obtain SEM images of NMs, providing valuable image-based surface morphology data that could be correlated with relevant toxicology studies.