Editorial

4 pages, 189 KiB

Open AccessEditorial

The Recent Progress in Nanotoxicology and Nanosafety from the Point of View of Both Toxicology and Ecotoxicology

by Yuan-Hua Wu, Sheng-Yow Ho, Bour-Jr Wang and Ying-Jan Wang

Int. J. Mol. Sci. 2020, 21(12), 4209; https://doi.org/10.3390/ijms21124209 - 12 Jun 2020

Cited by 4 | Viewed by 1887

This editorial aims to summarize the 14 scientific papers contributed to the Special Issue “Nanotoxicology and nanosafety 2.0 from the point of view of both toxicology and ecotoxicology”. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

Research

Jump to: Editorial, Review

20 pages, 5166 KiB

Open AccessArticle

The Effect of the Chorion on Size-Dependent Acute Toxicity and Underlying Mechanisms of Amine-Modified Silver Nanoparticles in Zebrafish Embryos

by Zi-Yu Chen, Nian-Jhen Li, Fong-Yu Cheng, Jian-Feng Hsueh, Chiao-Ching Huang, Fu-I Lu, Tzu-Fun Fu, Shian-Jang Yan, Yu-Hsuan Lee and Ying-Jan Wang

Int. J. Mol. Sci. 2020, 21(8), 2864; https://doi.org/10.3390/ijms21082864 - 20 Apr 2020

Cited by 46 | Viewed by 4683

Abstract

As the worldwide application of nanomaterials in commercial products increases every year, various nanoparticles from industry might present possible risks to aquatic systems and human health. Presently, there are many unknowns about the toxic effects of nanomaterials, especially because the unique physicochemical properties [...] Read more.

As the worldwide application of nanomaterials in commercial products increases every year, various nanoparticles from industry might present possible risks to aquatic systems and human health. Presently, there are many unknowns about the toxic effects of nanomaterials, especially because the unique physicochemical properties of nanomaterials affect functional and toxic reactions. In our research, we sought to identify the targets and mechanisms for the deleterious effects of two different sizes (~10 and ~50 nm) of amine-modified silver nanoparticles (AgNPs) in a zebrafish embryo model. Fluorescently labeled AgNPs were taken up into embryos via the chorion. The larger-sized AgNPs (LAS) were distributed throughout developing zebrafish tissues to a greater extent than small-sized AgNPs (SAS), which led to an enlarged chorion pore size. Time-course survivorship revealed dose- and particle size-responsive effects, and consequently triggered abnormal phenotypes. LAS exposure led to lysosomal activity changes and higher number of apoptotic cells distributed among the developmental organs of the zebrafish embryo. Overall, AgNPs of ~50 nm in diameter exhibited different behavior from the ~10-nm-diameter AgNPs. The specific toxic effects caused by these differences in nanoscale particle size may result from the different mechanisms, which remain to be further investigated in a follow-up study. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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22 pages, 8422 KiB

Open AccessArticle

Cytotoxicity of NiO and Ni(OH)₂ Nanoparticles Is Mediated by Oxidative Stress-Induced Cell Death and Suppression of Cell Proliferation

by Melissa H. Cambre, Natalie J. Holl, Bolin Wang, Lucas Harper, Han-Jung Lee, Charles C. Chusuei, Fang Y.S. Hou, Ethan T. Williams, Jerry D. Argo, Raja R. Pandey and Yue-Wern Huang

Int. J. Mol. Sci. 2020, 21(7), 2355; https://doi.org/10.3390/ijms21072355 - 28 Mar 2020

Cited by 19 | Viewed by 3091

Abstract

The use of nanomaterial-based products continues to grow with advancing technology. Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that products containing them do not impose harmful effects to human or environmental health. In this study, we evaluated the comparative [...] Read more.

The use of nanomaterial-based products continues to grow with advancing technology. Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that products containing them do not impose harmful effects to human or environmental health. In this study, we evaluated the comparative cytotoxicity between nickel oxide (NiO) and nickel hydroxide (Ni(OH)₂) in human bronchoalveolar carcinoma (A549) and human hepatocellular carcinoma (HepG2) cell lines. Cellular viability studies revealed cell line-specific cytotoxicity in which nickel NPs were toxic to A549 cells but relatively nontoxic to HepG2 cells. Time-, concentration-, and particle-specific cytotoxicity was observed in A549 cells. NP-induced oxidative stress triggered dissipation of mitochondrial membrane potential and induction of caspase-3 enzyme activity. The subsequent apoptotic events led to reduction in cell number. In addition to cell death, suppression of cell proliferation played an essential role in regulating cell number. Collectively, the observed cell viability is a function of cell death and suppression of proliferation. Physical and chemical properties of NPs such as total surface area and metal dissolution are in agreement with the observed differential cytotoxicity. Understanding the properties of NPs is essential in informing the design of safer materials. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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17 pages, 5514 KiB

Open AccessArticle

Differential Cytotoxicity Induced by Transition Metal Oxide Nanoparticles is a Function of Cell Killing and Suppression of Cell Proliferation

by Larry M. Tolliver, Natalie J. Holl, Fang Yao Stephen Hou, Han-Jung Lee, Melissa H. Cambre and Yue-Wern Huang

Int. J. Mol. Sci. 2020, 21(5), 1731; https://doi.org/10.3390/ijms21051731 - 03 Mar 2020

Cited by 14 | Viewed by 2957

Abstract

The application of nanoparticles (NPs) in industry is on the rise, along with the potential for human exposure. While the toxicity of microscale equivalents has been studied, nanoscale materials exhibit different properties and bodily uptake, which limits the prediction ability of microscale models. [...] Read more.

The application of nanoparticles (NPs) in industry is on the rise, along with the potential for human exposure. While the toxicity of microscale equivalents has been studied, nanoscale materials exhibit different properties and bodily uptake, which limits the prediction ability of microscale models. Here, we examine the cytotoxicity of seven transition metal oxide NPs in the fourth period of the periodic table of the chemical elements. We hypothesized that NP-mediated cytotoxicity is a function of cell killing and suppression of cell proliferation. To test our hypothesis, transition metal oxide NPs were tested in a human lung cancer cell model (A549). Cells were exposed to a series of concentrations of TiO₂, Cr₂O₃, Mn₂O₃, Fe₂O₃, NiO, CuO, or ZnO for either 24 or 48 h. All NPs aside from Cr₂O₃ and Fe₂O₃ showed a time- and dose-dependent decrease in viability. All NPs significantly inhibited cellular proliferation. The trend of cytotoxicity was in parallel with that of proliferative inhibition. Toxicity was ranked according to severity of cellular responses, revealing a strong correlation between viability, proliferation, and apoptosis. Cell cycle alteration was observed in the most toxic NPs, which may have contributed to promoting apoptosis and suppressing cell division rate. Collectively, our data support the hypothesis that cell killing and cell proliferative inhibition are essential independent variables in NP-mediated cytotoxicity. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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11 pages, 2225 KiB

Open AccessArticle

Evaluation of the Genotoxic and Oxidative Damage Potential of Silver Nanoparticles in Human NCM460 and HCT116 Cells

by Mingxi Jia, Wenjing Zhang, Taojin He, Meng Shu, Jing Deng, Jianhui Wang, Wen Li, Jie Bai, Qinlu Lin, Feijun Luo, Wenhua Zhou and Xiaoxi Zeng

Int. J. Mol. Sci. 2020, 21(5), 1618; https://doi.org/10.3390/ijms21051618 - 27 Feb 2020

Cited by 38 | Viewed by 4651

Abstract

Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles. Despite the many benefits of nano-Ag, more and more research indicates that it may have potential [...] Read more.

Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles. Despite the many benefits of nano-Ag, more and more research indicates that it may have potential biotoxic effects. Studies have shown that people who ingest nanoparticles by mouth have the highest uptake in the intestinal tract, and that the colon area is the most vulnerable to damage and causes the disease. In this study, we examined the toxic effects of different concentrations of Ag-NPs on normal human colon cells (NCM460) and human colon cancer cells (HCT116). As the concentration of nanoparticles increased, the activity of the two colon cells decreased and intracellular reactive oxygen species (ROS) increased. RT-qPCR and Western-blot analyses showed that Ag NPs can promote the increase in P38 protein phosphorylation levels in two colon cells and promote the expression of P53 and Bax. The analysis also showed that Ag NPs can promote the down-regulation of Bcl-2, leading to an increased Bax/Bcl-2 ratio and activation of P21, further accelerating cell death. This study showed that a low concentration of nano Ag has no obvious toxic effect on colon cells, while nano Ag with concentrations higher than 15 μg/mL will cause oxidative damage to colon cells. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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29 pages, 7384 KiB

Open AccessArticle

Nanoplastics Cause Neurobehavioral Impairments, Reproductive and Oxidative Damages, and Biomarker Responses in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure

by Sreeja Sarasamma, Gilbert Audira, Petrus Siregar, Nemi Malhotra, Yu-Heng Lai, Sung-Tzu Liang, Jung-Ren Chen, Kelvin H.-C. Chen and Chung-Der Hsiao

Int. J. Mol. Sci. 2020, 21(4), 1410; https://doi.org/10.3390/ijms21041410 - 19 Feb 2020

Cited by 216 | Viewed by 13100

Abstract

Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than macroplastics, as the former can permeate biological membranes. The toxicity of microplastic exposure on humans and aquatic organisms [...] Read more.

Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than macroplastics, as the former can permeate biological membranes. The toxicity of microplastic exposure on humans and aquatic organisms has been documented, but the toxicity and behavioral changes of nanoplastics (NPs) in mammals are scarce. In spite of their small size, nanoplastics have an enormous surface area, which bears the potential to bind even bigger amounts of toxic compounds in comparison to microplastics. Here, we used polystyrene nanoplastics (PS-NPs) (diameter size at ~70 nm) to investigate the neurobehavioral alterations, tissue distribution, accumulation, and specific health risk of nanoplastics in adult zebrafish. The results demonstrated that PS-NPs accumulated in gonads, intestine, liver, and brain with a tissue distribution pattern that was greatly dependent on the size and shape of the NPs particle. Importantly, an analysis of multiple behavior endpoints and different biochemical biomarkers evidenced that PS-NPs exposure induced disturbance of lipid and energy metabolism as well as oxidative stress and tissue accumulation. Pronounced behavior alterations in their locomotion activity, aggressiveness, shoal formation, and predator avoidance behavior were exhibited by the high concentration of the PS-NPs group, along with the dysregulated circadian rhythm locomotion activity after its chronic exposure. Moreover, several important neurotransmitter biomarkers for neurotoxicity investigation were significantly altered after one week of PS-NPs exposure and these significant changes may indicate the potential toxicity from PS-NPs exposure. In addition, after ~1-month incubation, the fluorescence spectroscopy results revealed the accumulation and distribution of PS-NPs across zebrafish tissues, especially in gonads, which would possibly further affect fish reproductive function. Overall, our results provided new evidence for the adverse consequences of PS-NPs-induced behavioral dysregulation and changes at the molecular level that eventually reduce the survival fitness of zebrafish in the ecosystem. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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14 pages, 2767 KiB

Open AccessArticle

The Vitamin A and D Exposure of Cells Affects the Intracellular Uptake of Aluminum Nanomaterials and Its Agglomeration Behavior: A Chemo-Analytic Investigation

by Fabian L. Kriegel, Benjamin-Christoph Krause, Philipp Reichardt, Ajay Vikram Singh, Jutta Tentschert, Peter Laux, Harald Jungnickel and Andreas Luch

Int. J. Mol. Sci. 2020, 21(4), 1278; https://doi.org/10.3390/ijms21041278 - 14 Feb 2020

Cited by 11 | Viewed by 3932

Abstract

Aluminum (Al) is extensively used for the production of different consumer products, agents, as well as pharmaceuticals. Studies that demonstrate neurotoxicity and a possible link to Alzheimer’s disease trigger concern about potential health risks due to high Al intake. Al in cosmetic products [...] Read more.

Aluminum (Al) is extensively used for the production of different consumer products, agents, as well as pharmaceuticals. Studies that demonstrate neurotoxicity and a possible link to Alzheimer’s disease trigger concern about potential health risks due to high Al intake. Al in cosmetic products raises the question whether a possible interaction between Al and retinol (vitamin A) and cholecalciferol (vitamin D3) metabolism might exist. Understanding the uptake mechanisms of ionic or elemental Al and Al nanomaterials (Al NMs) in combination with bioactive substances are important for the assessment of possible health risk associated. Therefore, we studied the uptake and distribution of Al oxide (Al₂O₃) and metallic Al⁰ NMs in the human keratinocyte cell line HaCaT. Possible alterations of the metabolic pattern upon application of the two Al species together with vitamin A or D3 were investigated. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging and inductively coupled plasma mass spectrometry (ICP-MS) were applied to quantify the cellular uptake of Al NMs. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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16 pages, 4628 KiB

Open AccessArticle

Manifestation of Systemic Toxicity in Rats after a Short-Time Inhalation of Lead Oxide Nanoparticles

by Marina P. Sutunkova, Svetlana N. Solovyeva, Ivan N. Chernyshov, Svetlana V. Klinova, Vladimir B. Gurvich, Vladimir Ya. Shur, Ekaterina V. Shishkina, Ilya V. Zubarev, Larisa I. Privalova and Boris A. Katsnelson

Int. J. Mol. Sci. 2020, 21(3), 690; https://doi.org/10.3390/ijms21030690 - 21 Jan 2020

Cited by 19 | Viewed by 2552

Abstract

Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m³ during 5 days for 4 h a day in a nose-only setup. A control group of rats [...] Read more.

Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m³ during 5 days for 4 h a day in a nose-only setup. A control group of rats were sham-exposed in parallel under similar conditions. Even this short-time exposure of a relatively low level was associated with nanoparticles retention demonstrable by transmission electron microscopy in the lungs and the olfactory brain. Some impairments were found in the organism’s status in the exposed group, some of which might be considered lead-specific toxicological outcomes (in particular, increase in reticulocytes proportion, in δ-aminolevulinic acid (δ-ALA) urine excretion, and the arterial hypertension’s development). Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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17 pages, 4160 KiB

Open AccessArticle

Fate Determination of ZnO in Commercial Foods and Human Intestinal Cells

by Ye-Rin Jeon, Jin Yu and Soo-Jin Choi

Int. J. Mol. Sci. 2020, 21(2), 433; https://doi.org/10.3390/ijms21020433 - 09 Jan 2020

Cited by 24 | Viewed by 3066

Abstract

(1) Background: Zinc oxide (ZnO) particles are widely used as zinc (Zn) fortifiers, because Zn is essential for various cellular functions. Nanotechnology developments may lead to production of nano-sized ZnO, although nanoparticles (NPs) are not intended to be used as food additives. Current [...] Read more.

(1) Background: Zinc oxide (ZnO) particles are widely used as zinc (Zn) fortifiers, because Zn is essential for various cellular functions. Nanotechnology developments may lead to production of nano-sized ZnO, although nanoparticles (NPs) are not intended to be used as food additives. Current regulations do not specify the size distribution of NPs. Moreover, ZnO is easily dissolved into Zn ions under acidic conditions. However, the fate of ZnO in commercial foods or during intestinal transit is still poorly understood. (2) Methods: We established surfactant-based cloud point extraction (CPE) for ZnO NP detection as intact particle forms using pristine ZnO-NP-spiked powdered or liquid foods. The fate determination and dissolution characterization of ZnO were carried out in commercial foods and human intestinal cells using in vitro intestinal transport and ex vivo small intestine absorption models. (3) Results: The results demonstrated that the CPE can effectively separate ZnO particles and Zn ions in food matrices and cells. The major fate of ZnO in powdered foods was in particle form, in contrast to its ionic fate in liquid beverages. The fate of ZnO was closely related to the extent of its dissolution in food or biomatrices. ZnO NPs were internalized into cells in both particle and ion form, but dissolved into ions with time, probably forming a Zn–ligand complex. ZnO was transported through intestinal barriers and absorbed in the small intestine primarily as Zn ions, but a small amount of ZnO was absorbed as particles. (4) Conclusion: The fate of ZnO is highly dependent on food matrix type, showing particle and ionic fates in powdered foods and liquid beverages, respectively. The major intracellular and intestinal absorption fates of ZnO NPs were Zn ions, but a small portion of ZnO particle fate was also observed after intestinal transit. These findings suggest that the toxicity of ZnO is mainly related to the Zn ion, but potential toxicity resulting from ZnO particles cannot be completely excluded. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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28 pages, 11329 KiB

Open AccessArticle

Neuron-Like Cells Generated from Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells as a New In Vitro Model for Neuronal Toxicity Screening: Using Magnetite Nanoparticles as an Example

by Uliana De Simone, Arsenio Spinillo, Francesca Caloni, Laura Gribaldo and Teresa Coccini

Int. J. Mol. Sci. 2020, 21(1), 271; https://doi.org/10.3390/ijms21010271 - 31 Dec 2019

Cited by 15 | Viewed by 3991

Abstract

The wide employment of iron nanoparticles in environmental and occupational settings underlines their potential to enter the brain. Human cell-based systems are recommended as relevant models to reduce uncertainty and to improve prediction of human toxicity. This study aimed at demonstrating the in [...] Read more.

The wide employment of iron nanoparticles in environmental and occupational settings underlines their potential to enter the brain. Human cell-based systems are recommended as relevant models to reduce uncertainty and to improve prediction of human toxicity. This study aimed at demonstrating the in vitro differentiation of the human umbilical cord lining-derived-mesenchymal stem cells (hCL-MSCs) into neuron-like cells (hNLCs) and the benefit of using them as an ideal primary cell source of human origin for the neuronal toxicity of Fe₃O₄NPs (magnetite-nanoparticles). Neuron-like phenotype was confirmed by: live morphology; Nissl body staining; protein expression of different neuronal-specific markers (immunofluorescent staining), at different maturation stages (i.e., day-3-early and day-8-full differentiated), namely β-tubulin III, MAP-2, enolase (NSE), glial protein, and almost no nestin and SOX-2 expression. Synaptic makers (SYN, GAP43, and PSD95) were also expressed. Fe₃O₄NPs determined a concentration- and time-dependent reduction of hNLCs viability (by ATP and the Trypan Blue test). Cell density decreased (20–50%) and apoptotic effects were detected at ≥10 μg/mL in both types of differentiated hNLCs. Three-day-differentiated hNLCs were more susceptible (toxicity appeared early and lasted for up to 48 h) than 8-day-differentiated cells (delayed effects). The study demonstrated that (i) hCL-MSCs easily differentiated into neuronal-like cells; (ii) the hNCLs susceptibility to Fe₃O₄NPs; and (iii) human primary cultures of neurons are new in vitro model for NP evaluation. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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23 pages, 4347 KiB

Open AccessArticle

Behavioral Impairments and Oxidative Stress in the Brain, Muscle, and Gill Caused by Chronic Exposure of C₇₀ Nanoparticles on Adult Zebrafish

by Sreeja Sarasamma, Gilbert Audira, Prabu Samikannu, Stevhen Juniardi, Petrus Siregar, Erwei Hao, Jung-Ren Chen and Chung-Der Hsiao

Int. J. Mol. Sci. 2019, 20(22), 5795; https://doi.org/10.3390/ijms20225795 - 18 Nov 2019

Cited by 24 | Viewed by 4209

Abstract

There is an imperative need to develop efficient whole-animal-based testing assays to determine the potential toxicity of engineered nanomaterials. While previous studies have demonstrated toxicity in lung and skin cells after C₇₀ nanoparticles (NPs) exposure, the potential detrimental role of C₇₀ [...] Read more.

There is an imperative need to develop efficient whole-animal-based testing assays to determine the potential toxicity of engineered nanomaterials. While previous studies have demonstrated toxicity in lung and skin cells after C₇₀ nanoparticles (NPs) exposure, the potential detrimental role of C₇₀ NPs in neurobehavior is largely unaddressed. Here, we evaluated the chronic effects of C₇₀ NPs exposure on behavior and alterations in biochemical responses in adult zebrafish. Two different exposure doses were used for this experiment: low dose (0.5 ppm) and high dose (1.5 ppm). Behavioral tests were performed after two weeks of exposure of C₇₀ NPs. We found decreased locomotion, exploration, mirror biting, social interaction, and shoaling activities, as well as anxiety elevation and circadian rhythm locomotor activity impairment after ~2 weeks in the C₇₀ NP-exposed fish. The results of biochemical assays reveal that following exposure of zebrafish to 1.5 ppm of C₇₀ NPs, the activity of superoxide dismutase (SOD) in the brain and muscle tissues increased significantly. In addition, the concentration of reactive oxygen species (ROS) also increased from 2.95 ± 0.12 U/ug to 8.46 ± 0.25 U/ug and from 0.90 ± 0.03 U/ug to 3.53 ± 0.64 U/ug in the muscle and brain tissues, respectively. Furthermore, an increased level of cortisol was also observed in muscle and brain tissues, ranging from 17.95 ± 0.90 pg/ug to 23.95 ± 0.66 pg/ug and from 3.47 ± 0.13 pg/ug to 4.91 ± 0.51 pg/ug, respectively. Increment of Hif1-α level was also observed in both tissues. The elevation was ranging from 11.65 ± 0.54 pg/ug to 18.45 ± 1.00 pg/ug in the muscle tissue and from 4.26 ± 0.11 pg/ug to 6.86 ± 0.37 pg/ug in the brain tissue. Moreover, the content of DNA damage and inflammatory markers such as ssDNA, TNF-α, and IL-1β were also increased substantially in the brain tissues. Significant changes in several biomarker levels, including catalase and malondialdehyde (MDA), were also observed in the gill tissues. Finally, we used a neurophenomic approach with a particular focus on environmental influences, which can also be easily adapted for other aquatic fish species, to assess the toxicity of metal and carbon-based nanoparticles. In summary, this is the first study to illustrate the adult zebrafish toxicity and the alterations in several neurobehavior parameters after zebrafish exposure to environmentally relevant amounts of C₇₀ NPs. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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14 pages, 2955 KiB

Open AccessArticle

Role of Autophagy in Zinc Oxide Nanoparticles-Induced Apoptosis of Mouse LEYDIG Cells

by Jingcao Shen, Dan Yang, Xingfan Zhou, Yuqian Wang, Shichuan Tang, Hong Yin, Jinglei Wang, Rui Chen and Jiaxiang Chen

Int. J. Mol. Sci. 2019, 20(16), 4042; https://doi.org/10.3390/ijms20164042 - 19 Aug 2019

Cited by 64 | Viewed by 4442

Abstract

Zinc oxide nanoparticles (ZnO NPs) have shown adverse health impact on the human male reproductive system, with evidence of inducing apoptosis. However, whether or not ZnO NPs could promote autophagy, and the possible role of autophagy in the progress of apoptosis, remain unclear. [...] Read more.

Zinc oxide nanoparticles (ZnO NPs) have shown adverse health impact on the human male reproductive system, with evidence of inducing apoptosis. However, whether or not ZnO NPs could promote autophagy, and the possible role of autophagy in the progress of apoptosis, remain unclear. In the current study, in vitro and in vivo toxicological responses of ZnO NPs were explored by using a mouse model and mouse Leydig cell line. It was found that intragastrical exposure of ZnO NPs to mice for 28 days at the concentrations of 100, 200, and 400 mg/kg/day disrupted the seminiferous epithelium of the testis and decreased the sperm density in the epididymis. Furthermore, serum testosterone levels were markedly reduced. The induction of apoptosis and autophagy in the testis tissues was disclosed by up-regulating the protein levels of cleaved Caspase-8, cleaved Caspase-3, Bax, LC3-II, Atg 5, and Beclin 1, accompanied by down-regulation of Bcl 2. In vitro tests showed that ZnO NPs could induce apoptosis and autophagy with the generation of oxidative stress. Specific inhibition of autophagy pathway significantly decreased the cell viability and up-regulated the apoptosis level in mouse Leydig TM3 cells. In summary, ZnO NPs can induce apoptosis and autophagy via oxidative stress, and autophagy might play a protective role in ZnO NPs-induced apoptosis of mouse Leydig cells. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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Review

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19 pages, 626 KiB

Open AccessReview

A Review on the Environmental Fate Models for Predicting the Distribution of Engineered Nanomaterials in Surface Waters

by Edward Suhendra, Chih-Hua Chang, Wen-Che Hou and Yi-Chin Hsieh

Int. J. Mol. Sci. 2020, 21(12), 4554; https://doi.org/10.3390/ijms21124554 - 26 Jun 2020

Cited by 22 | Viewed by 4401

Abstract

Exposure assessment is a key component in the risk assessment of engineered nanomaterials (ENMs). While direct and quantitative measurements of ENMs in complex environmental matrices remain challenging, environmental fate models (EFMs) can be used alternatively for estimating ENMs’ distributions in the environment. This [...] Read more.

Exposure assessment is a key component in the risk assessment of engineered nanomaterials (ENMs). While direct and quantitative measurements of ENMs in complex environmental matrices remain challenging, environmental fate models (EFMs) can be used alternatively for estimating ENMs’ distributions in the environment. This review describes and assesses the development and capability of EFMs, focusing on surface waters. Our review finds that current engineered nanomaterial (ENM) exposure models can be largely classified into three types: material flow analysis models (MFAMs), multimedia compartmental models (MCMs), and spatial river/watershed models (SRWMs). MFAMs, which is already used to derive predicted environmental concentrations (PECs), can be used to estimate the releases of ENMs as inputs to EFMs. Both MCMs and SRWMs belong to EFMs. MCMs are spatially and/or temporally averaged models, which describe ENM fate processes as intermedia transfer of well-mixed environmental compartments. SRWMs are spatiotemporally resolved models, which consider the variability in watershed and/or stream hydrology, morphology, and sediment transport of river networks. As the foundation of EFMs, we also review the existing and emerging ENM fate processes and their inclusion in recent EFMs. We find that while ENM fate processes, such as heteroaggregation and dissolution, are commonly included in current EFMs, few models consider photoreaction and sulfidation, evaluation of the relative importance of fate processes, and the fate of weathered/transformed ENMs. We conclude the review by identifying the opportunities and challenges in using EFMs for ENMs. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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24 pages, 1911 KiB

Open AccessReview

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

by Rong-Jane Chen, Yu-Ying Chen, Mei-Yi Liao, Yu-Hsuan Lee, Zi-Yu Chen, Shian-Jang Yan, Ya-Ling Yeh, Li-Xing Yang, Yen-Ling Lee, Yuan-Hua Wu and Ying-Jan Wang

Int. J. Mol. Sci. 2020, 21(7), 2387; https://doi.org/10.3390/ijms21072387 - 30 Mar 2020

Cited by 47 | Viewed by 5258

Abstract

Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a [...] Read more.

Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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31 pages, 749 KiB

Open AccessReview

Health Impact of Silver Nanoparticles: A Review of the Biodistribution and Toxicity Following Various Routes of Exposure

by Zannatul Ferdous and Abderrahim Nemmar

Int. J. Mol. Sci. 2020, 21(7), 2375; https://doi.org/10.3390/ijms21072375 - 30 Mar 2020

Cited by 540 | Viewed by 15586

Abstract

Engineered nanomaterials (ENMs) have gained huge importance in technological advancements over the past few years. Among the various ENMs, silver nanoparticles (AgNPs) have become one of the most explored nanotechnology-derived nanostructures and have been intensively investigated for their unique physicochemical properties. The widespread [...] Read more.

Engineered nanomaterials (ENMs) have gained huge importance in technological advancements over the past few years. Among the various ENMs, silver nanoparticles (AgNPs) have become one of the most explored nanotechnology-derived nanostructures and have been intensively investigated for their unique physicochemical properties. The widespread commercial and biomedical application of nanosilver include its use as a catalyst and an optical receptor in cosmetics, electronics and textile engineering, as a bactericidal agent, and in wound dressings, surgical instruments, and disinfectants. This, in turn, has increased the potential for interactions of AgNPs with terrestrial and aquatic environments, as well as potential exposure and toxicity to human health. In the present review, after giving an overview of ENMs, we discuss the current advances on the physiochemical properties of AgNPs with specific emphasis on biodistribution and both in vitro and in vivo toxicity following various routes of exposure. Most in vitro studies have demonstrated the size-, dose- and coating-dependent cellular uptake of AgNPs. Following NPs exposure, in vivo biodistribution studies have reported Ag accumulation and toxicity to local as well as distant organs. Though there has been an increase in the number of studies in this area, more investigations are required to understand the mechanisms of toxicity following various modes of exposure to AgNPs. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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14 pages, 2094 KiB

Open AccessReview

Potent Impact of Plastic Nanomaterials and Micromaterials on the Food Chain and Human Health

by Yung-Li Wang, Yu-Hsuan Lee, I-Jen Chiu, Yuh-Feng Lin and Hui-Wen Chiu

Int. J. Mol. Sci. 2020, 21(5), 1727; https://doi.org/10.3390/ijms21051727 - 03 Mar 2020

Cited by 105 | Viewed by 14860

Abstract

Plastic products are inexpensive, convenient, and are have many applications in daily life. We overuse plastic-related products and ineffectively recycle plastic that is difficult to degrade. Plastic debris can be fragmented into smaller pieces by many physical and chemical processes. Plastic debris that [...] Read more.

Plastic products are inexpensive, convenient, and are have many applications in daily life. We overuse plastic-related products and ineffectively recycle plastic that is difficult to degrade. Plastic debris can be fragmented into smaller pieces by many physical and chemical processes. Plastic debris that is fragmented into microplastics or nanoplastics has unclear effects on organismal systems. Recently, this debris was shown to affect biota and to be gradually spreading through the food chain. In addition, studies have indicated that workers in plastic-related industries develop many kinds of cancer because of chronic exposure to high levels of airborne microplastics. Microplastics and nanoplastics are everywhere now, contaminating our water, air, and food chain. In this review, we introduce a classification of plastic polymers, define microplastics and nanoplastics, identify plastics that contaminate food, describe the damage and diseases caused by microplastics and nanoplastics, and the molecular and cellular mechanisms of this damage and disease as well as solutions for their amelioration. Thus, we expect to contribute to the understanding of the effects of microplastics and nanoplastics on cellular and molecular mechanisms and the ways that the uptake of microplastics and nanoplastics are potentially dangerous to our biota. After understanding the issues, we can focus on how to handle the problems caused by plastic overuse. Full article

(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)

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