Toxicity of mixtures of zinc oxide and graphene oxide nanoparticles to aquatic organisms of different trophic level: particles outperform dissolved ions

Concomitant releases of various engineered nanoparticles (NPs) into the environment have resulted in concerns regarding their combined toxicity to aquatic organisms. It is however, still elusive to distinguish the contribution to toxicity of components in NP mixtures. In the present study, we quantitatively evaluated the relative contribution of NPs in their particulate form (NP_(particle)) and of dissolved ions released from NPs (NP_(ion)) to the combined toxicity of binary mixtures of ZnO NPs and graphene oxide nanoplatelets (GO NPs) to three aquatic organisms of different trophic levels, including an alga species (Scenedesmus obliquus), a cladoceran species (Daphnia magna), and a freshwater fish larva (Danio rerio). Our results revealed that the effects of ZnO NPs and GO NPs were additive to S. obliquus and D. magna but antagonistic to D. rerio. The relative contribution to toxicity (RCT) of the mixture components to S. obliquus decreased in the order of RCT_{GO NP(particle)} >?RCT_{ZnO NP(particle)}?>?RCT_{ZnO NP(ion)}, while the RCT of the mixture components to D. magna and D. rerio decreased in the order of RCT_{ZnO NP(particle)}?>?RCT_{GO NP(particle)}?>?RCT_{ZnO NP(ion)}. This finding also implies that the suspended particles rather than the dissolved Zn-ions dictated the combined toxicity of binary mixtures of ZnO NPs and GO NPs to the aquatic organisms of different trophic level. The alleviation of the contribution to toxicity of the ionic form of ZnO NPs was caused by the adsorption of the dissolved ions on GO NPs. Furthermore, the ZnO NP_(particle) and GO NP_(particle) displayed a different contribution to the observed mixture toxicity, dependent on the trophic level of the aquatic organisms tested. The difference of the contributions between the two particulate forms was mainly associated with differences in the intracellular accumulation of reactive oxygen species. Our findings highlight the important role of particles in the ecological impact of multi-nanomaterial systems.     

Effect of size and shape on toxicity of zinc oxide (ZnO) nanomaterials in human peripheral blood lymphocytes

The multi-industrial applications of zinc oxide nanomaterials (ZnO NMs) lead to increasing exposure to humans. Though the ZnO nanoparticles (NPs) toxicity had been evaluated previously, toxicity of other forms of ZnO nanomaterials has not been evaluated. In this study, cytotoxicity and genotoxicity of four different types of ZnO NMs were evaluated using human peripheral blood lymphocytes (HPBL). In addition, the effect of anti-oxidants on ZnO NMs induced toxicity was also evaluated. Our results suggest that, size and shape of the nanomaterials have profound effects on their toxicity. The NPs and nanorods (NRs) possessed higher level of oxidative potential and ROS generation capacity than microparticles (MPs) and microrods (MRs). In contrast, MPs and MRs possessed higher level of lipid peroxidation capacity. The smaller NPs are more genotoxic while larger MPs and MRs were more cytotoxic in nature. Treatment with vitamin C or Quercetin significantly reduces the genotoxicity associated with ZnO NMs. The influence of size and shape in mediating NMs toxicity should be taken into account and the possible supplementation of anti-oxidants might mitigate the toxicity.     

Toxicity of zinc oxide (ZnO) nanoparticles on human bronchial epithelial cells (BEAS-2B) is accentuated by oxidative stress

Although several studies reported that cytotoxic effects of various nanoparticles are partially due to induction of oxidative stress, it is unclear how oxidative state of the cell per se could influence its sensitivity to cytotoxic nanoparticles. This is of clinical significance because certain pathological conditions such as inflammation is associated with elevated oxidative stress and this may alter sensitivity of cells and tissues to cytotoxic nanoparticles. Hence, this study investigated how initial exposure of BEAS-2B human bronchial epithelial cells to oxidative stress influences subsequent response to cytotoxic challenge with zinc oxide (ZnO) nanoparticles (≈10 nm). Oxidative stress was induced by exposing BEAS-2B cells to 5 and 10 μM of H₂O₂ for 45 min in PBS (with Ca²⁺). Subsequently, the H₂O₂ solutions were washed off and the cells were exposed to varying concentrations (5–25 μg/ml) of ZnO nanoparticles in culture media for 24 h, followed by cell viability assessment with the WST-8 assay. The results demonstrated that initial transient exposure of cells to oxidative stress accentuated cytotoxicity of ZnO nanoparticles. In the negative control unexposed to H₂O₂, >99% of cells remained viable up to a ZnO nanoparticle concentration of 10 μg/ml, but displayed a steep decrease in viability above 10 μg/ml ZnO. By contrast, cells that were initially exposed to 5 and 10 μM of H₂O₂, displayed a sharp drop in viability even at concentrations below 10 μg/ml ZnO. At 10 μg/ml ZnO, cells initially exposed to 10 μM H₂O₂ displayed a viability of 40.6 ± 2.0%, which is significantly lower than the corresponding values of 72.8 ± 2.0% and 99.9 ± 1.1% obtained for initial exposure to 5 μM H₂O₂ and the negative control, respectively. Hence, initial exposure of BEAS-2B cells to oxidative stress sensitized their subsequent response to cytotoxic challenge with ZnO nanoparticles.     

Antimicrobial activity of zinc oxide (ZnO) nanoparticle against Klebsiella pneumoniae

Context: Zinc oxide nanoparticles (ZnO Nps) have potential application in piezoelectric nanogenerator and in biotechnology.

Objective: The antibacterial activity of ZnO Nps on Klebsiella pneumoniae (ATCC 70068) and mode of action of ZnO Nps was investigated.

Methods: ZnO Nps was synthesized by a precipitation method and characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) methods. In vitro susceptibility of K. pnumoniae of the ZnO Nps was detected using the disk diffusion method, and the minimum inhibitory concentration (MIC) value was determined using the serial dilution method. The chemical and physical interaction between the cell envelope of K. pneumonia and ZnO Nps was investigated. The effect of ZnO Nps on the cytotoxic activities of K. pneumonia was investigated using a HEp-2 cell line.

Results: The MIC of ZnO Nps was found in 40?µg/ml. The standard growth curve showed that ZnO Nps of 0.75?mM inhibited K. pneumoniae after 4?h. The interaction with outer membrane protein (OMP) and lipoploysacharride (LPS) residues showed modulation in ～66?kDa and ～29?kDa proteins with the use of increasing concentrations of ZnO Nps. The amount of nucleic acid and protein released from the cells increased with the ZnO Nps concentration used. Importantly, the OD of the ZnO Nps-treated cells decreased within 30?min of incubation in the presence of SDS. ZnO Nps-treated K. pneumoniae were five-fold less infectious in the HEp-2 cell line at doses between 0.50 and 0.75?mM.

Discussion: These results suggest the potential antibacterial use of ZnO Nps against K. pneumoniae infections.     

Effect of poly (ethylene oxide)‐poly (propylene oxide)‐poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2)

Objectives Intestinal toxicity and low levels of systemic drug exposure are among the major problems associated with tumour therapy. We have developed poly (ethylene oxide)‐poly (propylene oxide)‐poly (ethylene oxide) (PEO‐PPO‐PEO) micelles loaded with irinotecan hydrochloride (CPT‐11) hoping to decrease CPT‐11‐induced intestinal toxicity while increasing its systemic exposure. In addition, we have investigated the potential involvement of breast cancer resistance protein (BCRP) in biliary excretion, pharmacokinetics, and intestinal toxicity of CPT‐11. Methods PEO‐PPO‐PEO micelles were prepared using PEO₂₀‐PPO₇₀‐PEO₂₀ and lecithin. The effect of PEO‐PPO‐PEO micelles on BCRP‐mediated cellular accumulation and transport efflux of CPT‐11 was evaluated in MDCKII/BCRP cells. The biliary excretion, intestinal damage, and pharmacokinetic study of CPT‐11‐loaded PEO‐PPO‐PEO micelles were investigated in rats. Key findings The obtained micelles could effectively inhibit BCRP‐mediated CPT‐11 efflux in MDCKII/BCRP cells, and significantly decrease the drug biliary excretion in rats. Moreover, intestinal toxicity, assessed by microscopic examination of pathological damage, was ameliorated in rats injected with PEO‐PPO‐PEO micelles compared with rats injected with CPT‐11 alone. Treatment with PEO‐PPO‐PEO micelles resulted in prolonged circulation time in blood and increased bioavailability of CPT‐11 and SN‐38 (7‐ethyl‐10‐hydroxycamptothecin). Conclusions PEO‐PPO‐PEO micelles were identified as promising carriers able to reduce intestinal toxicity and increase antitumour therapeutic effect of CPT‐11. The study indicated a potential involvement of BCRP in CPT‐11 pharmacokinetics and CPT‐11‐induced intestinal toxicity.     

思密达与氧化锌联用治疗尿布皮炎49例疗效观察

目的:对照观察思密达与氧化锌联用和单用氧化锌、皮炎平及达克宁霜对尿布皮炎的治疗效果。方法:把收住院和门诊诊治的病例随机分为四级,经常规处理后,治疗组以思密达与氧化锌联用,对照组分别以氧化锌、皮炎平及达克宁霜治疗,一个疗程后现察疗效。结果:治疗组效果明显优于三个对照组(P＜O．01)。结论:思密达与氧化锌联用治疗尿布皮炎是一种较为理想的方法。     

Cytotoxic, genotoxic and pro-inflammatory effects of zinc oxide nanoparticles in human nasal mucosa cells in vitro

Despite increasing application of zinc oxide nanoparticles (ZnO-NPs) for industrial porpuses, data about potential toxic properties is contradictory. The current study focused on the cyto- and genotoxicity of ZnO-NPs in comparison to ZnO powder in primary human nasal mucosa cells cultured in the air-liquid interface. Additionally, IL-8 secretion as a marker for pro-inflammatory effects was measured. Particle morphology and intracellular distribution were evaluated by transmission electron microscopy (TEM). ZnO-NPs were transferred into the cytoplasm in 10% of the cells, whereas an intranuclear distribution could only be observed in 1.5%. While no cyto- or genotoxicity could be seen for ZnO powder in the dimethylthiazolyl-diphenyl-tetrazolium-bromide (MTT) test, the trypan blue exclusion test, and the single-cell microgel electrophoresis (comet) assay, cytotoxic effects were shown at a ZnO-NP concentration of 50 μg/ml (P < 0.01). A significant enhancement in DNA damage was observed starting from ZnO-NP concentrations of 10 μg/ml (P < 0.05) in comparison to the control. IL-8 secretion into the basolateral culture medium was increased at ZnO-NP concentrations of 5 μg/ml (P < 0.05), as shown by ELISA. Our data indicates cyto- and genotoxic properties as well as a pro-inflammatory potential of ZnO-NPs in nasal mucosa cells. Thus, caution should be taken concerning their industrial and dermatological application. Additionally, further investigation on repetitive NP exposure is needed to estimate the impact of repair mechanisms.     

四逆汤对失血性休克家兔一氧化氮（NO）和一氧化氮合酶（NOS）的影响

目的：探讨中药四逆汤对失血性休克家兔一氧化氮的影响。方法：采用动物分组对照实验，测量不同状态下动物血浆一氧化氮和一氧化氮合酶(NOS)的变化。结果：与休克前比较，休克组的家兔血浆一氧化氮水平各时段均明显提高(P＜0．01)，而治疗组仅在治疗后30min家兔一氧化氮及NOS水平明显提高(P＜0．01)，其他时段与休克前比较，未见显著差异(P＜0．01)，且休克后lh、4h、8h休克组一氧化氮水平显著高于治疗组(P＜0．01)。经药物治疗的失血性休克家兔血浆一氧化氮水平明显降低。     

The effects of baicalein or baicalin on the colloidal stability of ZnO nanoparticles (NPs) and toxicity of NPs to Caco-2 cells

Recent study suggested that the presence of phytochemicals in food could interact with nanoparticles (NPs) and consequently reduce the toxicity of NPs, which has been attributed to the antioxidant properties of phytochemicals. In this study, we investigated the interactions between ZnO NPs and two flavonoids baicalein (Ba) or baicalin (Bn) as well as the influence of the interactions on the toxicity of ZnO NPs to Caco-2 cells. The antioxidant properties of Ba and Bn were confirmed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, with Ba being stronger. However, the presence of Ba or Bn did not significantly affect cytotoxicity, intracellular superoxide or release of inflammatory cytokines of Caco-2 cells after ZnO NP exposure. When Ba was present, the cellular viability of Caco-2 cells after exposure to ZnO NPs was slightly increased, associated with a modest decrease of intracellular Zn ions, but these effects were not statistically different. Ba was more effective than Bn at changing the hydrodynamic sizes, Zeta potential and UV–Vis spectra of ZnO NPs, which indicated that Ba might increase the colloidal stability of NPs. Taken together, the results of the present study indicated that the anti-oxidative phytochemical Ba might only modestly protected Caco-2 cells from the exposure to ZnO NPs associated with an insignificant reduction of the accumulation of intracellular Zn ions. These results also indicated that when assessing the combined effects of NPs and phytochemicals to cells lining gastrointestinal tract, it might be necessary to evaluate the changes of colloidal stability of NPs altered by phytochemicals.     

Different modes of synergistic toxicities between metam/copper (II) and metam/zinc (II) in HepG2 cells: apoptosis vs. necrosis

Both metam sodium and copper/zinc‐containing compounds are widely used as fungicides. They therefore may co‐occur in the biosphere. Despite certain studies of individual toxicity for either metam or copper (II)/zinc (II), their synergistic toxicity has not been examined. In this paper, a remarkable synergistic toxicity was observed in HepG2 cells when metam and copper (II)/zinc (II) at non‐toxic and sub‐toxic levels were combined. Unexpectedly, cell death modes between metam/copper (II) and metam/zinc (II) were different: For metam/copper (II), apoptosis was evident from morphological characteristics including cytoplasm‐chromatin condensation, phosphatidylserine (PS) exposure, SubG₀/G₁ DNA fragmentation, mitochondrial membrane potential decrease, pro/anti‐apoptotic protein activation, and cytochrome c release; for metam/zinc (II), necrosis was evident from organelle swelling and uncontrolled collapse. To our knowledge, this work first not only demonstrates the synergistic toxicities of metam and both copper (II)/zinc (II), but also verifies the different modes of apoptosis/necrosis between metam/copper (II) and metam/zinc (II). © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1964–1973, 2016.     

Toxicity of ZnO nanoparticles (NPs) with or without hydrophobic surface coating to THP-1 macrophages: interactions with BSA or oleate-BSA

It is recently shown that biological macromolecules in food could interact with nanoparticles (NPs) and consequently change the biological effects of NPs. In this study, the interactions between ZnO NPs with or without hydrophobic surface coating and bovine serum albumin (BSA) or oleate (OA) complexed to BSA (OA-BSA) were assessed. Atomic force microscope (AFM) showed topographic changes of both types of NPs by BSA or OA-BSA, which could indicate the formation of protein corona. ZnO NPs showed negative Zeta potential, which was slightly decreased by BSA or OA-BSA, with OA-BSA being more effective. The UV–Vis was increased, whereas the fluorescence and synchronous fluorescence was decreased by the presence of ZnO NPs. Exposure to both types of ZnO NPs was associated with cytotoxicity to THP-1 macrophages, which was equally mitigated by BSA or OA-BSA associated with decreased cellular Zn elements. Exposure to ZnO NPs was associated with decreased release of cytokines, which was not affected by BSA or OA-BSA. In combination, the results from this study suggested that both BSA and OA-BSA could be adsorbed to ZnO NPs regardless of hydrophobic surface coating, which reduced the cytotoxicity of NPs to macrophages probably due to reduced association between NPs and cells. BSA and OA-BSA equally protected THP-1 macrophages from ZnO NP exposure, which might indicate that complexation to OA did not compromise the cytoprotective effects of BSA. These data might also indicate the complex interaction between NPs and biological macromolecules as food components, which should be considered for future nanotoxicological studies.     

ACE活性和eNOS含量与妊高征相关性研究

目的:探讨胎盘组织一氧化氮合酶含量和血清中血管紧张素转化酶(ACE)活性改变在妊高征发生、发展中的作用。方法:选择轻、中、重度妊高征病人各10例为实验组,正常妊娠妇女30例为对照组,用马尿酸微量比色法检测血清中ACE活性,采用免疫组化ABC法分析妊高征胎盘组织中内皮型一氧化氮合酶(eNOS)含量的变化情况。结果:1妊高征组ACE活性明显高于对照组;2妊高征患者胎盘中eNOS含量显著低于正常足月孕者(P<0.05),且轻度妊高征患者胎盘eNOS含量显著高于中度及重度患者(P<0.05)。结论:血清ACE活性升高与妊高征的发生、发展密切相关。正常足月孕胎盘和妊高征患者胎盘绒毛血管内皮细胞中均存在eNOS抗原,妊高征患者胎盘中含量的减少与其发病有关。     

Accumulation and toxicity of CuO and ZnO nanoparticles through waterborne and dietary exposure of goldfish (Carassius auratus)

Dietary and waterborne exposure to copper oxide (CuO) and zinc oxide (ZnO) nanoparticles (NPs) was conducted using a simplified model of an aquatic food chain consisting of zooplankton (Artemia salina) and goldfish (Carassius auratus) to determine bioaccumulation, toxic effects, and particle transport through trophic levels. Artemia contaminated with NPs were used as food in dietary exposure. Fish were exposed to suspensions of the NPs in waterborne exposure. ICP‐MS analysis showed that accumulation primarily occurred in the intestine, followed by the gills and liver. Dietary uptake was lower, but was found to be a potential pathway for transport of NPs to higher organisms. Waterborne exposure resulted in about a 10‐fold higher accumulation in the intestine. The heart, brain, and muscle tissue had no significant Cu or Zn. However, concentrations in muscle increased with NP concentration, which was ascribed to bioaccumulation of Cu and Zn released from NPs. Free Cu concentration in the medium was always higher than that of Zn, indicating CuO NPs dissolved more readily. ZnO NPs were relatively benign, even in waterborne exposure (p ≥ 0.05). In contrast, CuO NPs were toxic. Malondialdehyde levels in the liver and gills increased substantially (p < 0.05). Despite lower Cu accumulation, the liver exhibited significant oxidative stress, which could be from chronic exposure to Cu ions. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 119–128, 2015.     

Toxicity of ZnO nanoparticles (NPs) to THP-1 macrophages: interactions with saturated or unsaturated free fatty acids

In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA.     

Extracellular signal-regulated kinase (ERK) and nitric oxide synthase mediate intrathecal morphine-induced nociceptive behavior

Intrathecal (i.t.) administration of morphine at a high dose of 60nmol into the spinal lumbar space in mice produces a severe hindlimb scratching followed by biting and licking. Nitric oxide (NO) is thought to play an important role in signal transduction pathways that enhance nociceptive transmission in the spinal cord. The present study was designed to determine whether high-dose i.t. morphine could influence the activation of the extracellular signal-regulated kinase (ERK), a mitogen-activated protein (MAP) kinase in neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) activation. Both 7-NI and TRIM, selective inhibitors of nNOS, resulted in a dose-dependent inhibition of high-dose i.t. morphine-induced behavior. The selective iNOS inhibitor W1400 in relatively large doses inhibited in a non dose-dependent manner. The i.t. injection of morphine evoked a definite activation of ERK in the lumbar dorsal spinal cord. Behavioral experiments showed that U0126 (0.5-2.5nmol), a MAP kinase-ERK inhibitor, dose-dependently attenuated the behavioral response to i.t. morphine. In mice treated with high-dose morphine, 7-NI was very effective in blocking ERK activation, whereas W1400 had no effect. Taken together, these results suggest that the behavioral response to high-dose i.t. morphine may be triggered by the nNOS-ERK pathway in the dorsal spinal cord.     

热毒清对内毒素性发热家兔体温及血浆NO的影响

目的观察热毒清对内毒素性发热家兔的体温以及血浆NO水平的影响,并比较不同剂量的药效。方法采用内毒素注射的方法制成发热家兔模型60只,随机分为6组,阿司匹林组(A组),热毒清高剂量组(B组),热毒清中剂量组(C组),热毒清低剂量组(D组),双黄连口服液组(E组),对照组(F组),每组10只,观察比较各组体温变化。结果与对照组比较,热毒清中剂量组及热毒清高剂量组对发热家兔的体温有明显的降温作用,且比阿司匹林组作用持续时间延长;热毒清低剂量组及双黄连组对发热家兔的体温无明显的降温作用。结论热毒清高剂量及热毒清中剂量能够降低内毒素性发热家兔的体温,改善症状和体征,降低血浆NO水平。作用机理可能是调控细胞因子网络,抑制循环血中NO的产生。     

超临界二氧化碳制备布地奈德-聚氧乙烯固体分散体及体外评价

本文以水难溶性药物布地奈德为模型药物，研究超临界流体技术制备布地奈德-聚氧乙烯固体分散体的方法及其影响因素。采用超临界二氧化碳静态法制备布地奈德-聚氧乙烯固体分散体，用粉末X射线衍射法、差示扫描量热法、溶解度法和体外溶出实验进行固体分散体的物相鉴别。在40 ℃，20 MPa条件下，布地奈德-聚氧乙烯N750(1∶10)是形成固体分散体的最佳条件，布地奈德与聚氧乙烯载体形成氢键，以无定形状态存在于载体中，溶解度和体外溶出速率显著提高。超临界流体技术是制备固体分散体的一种可行方法。     

Short-term evaluation of hepatic toxicity of titanium dioxide nanofiber (TDNF)

Various in vitro and in vivo studies have shown titanium dioxide nanoparticles (TDNPs) increase the production of reactive oxygen species and change the expression of genes and proteins involved in the inflammatory response and cell division. Although, the cytotoxicity of TDNPs has been shown to be largely dependent on the characteristics of the particles including shape and surface area. This present study investigates the effects of titanium dioxide nanofibers (TDNFs) with a diameter of 300–800?nm, on the histopathology of liver tissue, changes in feed efficiency and liver weights, changes in hepatic gene expression, and serum biochemical parameters in male Sprague-Dawley rats. Male Sprague-Dawley rats were fed concentrations of 0?ppm, 40?ppm, and 60?ppm TDNF by oral gavage for two weeks. Selected inflammatory response, oxidative stress, and regulatory cell cycle genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Differences in gene expression compared to the 0?ppm group were observed in genes Gnat3, IghA, IL-1β, p21, p53, and TNF-α. Histopathology, body and liver weights, and feed efficiency showed no significant differences. Albumin levels in all groups were not significantly higher than the reference range while ALT levels for all groups were high compared to the reference value. Currently, the results suggest TDNF does not exhibit significant hepatic toxicity. This may be explained by the rutile crystalline structure of the nanofibers, the lower concentration or the short duration of exposure toxic used during experimentation.     

Biodegradability of poly(γ-benzyl L-glutamate)/poly(ethylene oxide) /poly(γ-benzyl L-glutamate) block copolymer in mice

Biodegradability of poly(γ-benzyl L-glutamate)/poly(ethylene oxide)/poly(γ-benzyl L-glutamate) block copolymer (GEG) having different content of poly(ethylene oxide) (PEO) were examined using magnetite as a tracer in mice. GEG microspheres containing magnetite were injected into mice through tail vein. Biodegradability and tissue distribution of microspheres were examined by analyzing the amount of magnetite in the microspheres recollected from mice organs after specific time interval. The results showed that GEG microsphere of high content of PEO was degraded more rapidly than those of low content of PEO in the mice organs.     

Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment.

Methods: Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C?×?T protocol). The dose is expressed as 6?h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2?mg/m³ CuO NPs, with a primary particle size of 10 9.2–14?nm and an MMAD of 1.5?μm.

Results: Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4?mg/m³. After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2?mg/m³. The olfactory epithelium in the nose degenerated 24?h after exposure to 6.3 and 13.2?mg/m³, but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver.

Conclusion: A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period.