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This study assessed the oxidative stress impacts of Ag NPs and ZnO NPs and their mixtures in zebrafish (Danio rerio). Zebrafish were exposed to sublethal concentrations of each NP and a mixture for 28 days followed by a 28-day recovery period (without NP exposure) and measurements made on hepatic levels of antioxidant enzymes (CAT, SOD, and GPx), MDA levels, expression of the genes for the Hsp70 and Hsp90, and MT, blood biochemical parameters (total protein, globulin, albumin, AST, ALT, ALP, and LDH), and genotoxicity in erythrocytes (via measurement of micronuclei (MN) and nuclear (NA) abnormalities). There was a tendency for an increase in the variation in the responses of antioxidant defense systems and there were higher MDA levels with increasing exposure concentration of Ag NPs and with increasing exposure time. Total protein, globulin, and albumin decreased during the exposure period, especially on the days of 28. Moreover, levels of AST and LDH increased significantly in the NPs co-exposure treatments, while levels of ALT and ALP significantly decreased. The highest expression levels for these genes occurred on day 14 and in the NPs co-exposure treatments. For exposure to both NPs individually and as a mixture, the frequency of MN and other NA were significantly increased (p < 0.05). During the recovery periods, most of the effects seen were reduced, most notably in the individual NPs treatments. The overall results suggest that the toxic effects of Ag NPs and ZnO NPs in combination significantly increase their toxicity in zebrafish., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest related to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Gold nanoparticles (AuNPs) are widely used in biomedicine and their specific properties including, size, geometrics, and surface coating, will affect their fate and behaviour in biological systems. These properties are well studied for their intended biological targets, but there is a lack of understanding on the mechanisms by which AuNPs interact in non-target organisms when they enter the environment. We investigated the effects of size and surface chemistry of AuNPs on their bioavailability, tissue distribution and potential toxicity using zebrafish (Danio rerio) as an experimental model. Larval zebrafish were exposed to fluorescently tagged AuNPs of different sizes (10-100 nm) and surface modifications (TNFα, NHS/PAMAM and PEG), and uptake, tissue distribution and depuration rates were measured using selective-plane illumination microscopy (SPIM). The gut and pronephric tubules were found to contain detectable levels of AuNPs, and the concentration-dependent accumulation was related to the particle size. Surface addition of PEG and TNFα appeared to enhance particle accumulation in the pronephric tubules compared to uncoated particles. Depuration studies showed a gradual removal of particles from the gut and pronephric tubules, although fluorescence indicating the presence of the AuNPs remained in the pronephros 96 h after exposure. Toxicity assessment using two transgenic zebrafish reporter lines, however, revealed no AuNP-related renal injury or cellular oxidative stress. Collectively, our data show that AuNPs used in medical applications across the size range 40-80 nm, are bioavailable to larval zebrafish and some may persist in renal tissue, although their presence did not result in measurable toxicity with respect to pronephric organ function or cellular oxidative stress for short term exposures., Competing Interests: Declaration of Competing Interest SFO is an employee and shareholder of AstraZeneca PLC. All other authors declare no potentially competing interests., (Copyright © 2023. Published by Elsevier Inc.)

We assessed the acute toxicity effects (96 h) of silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) and chronic (28 d) exposure to Ag NPs, including in combination with ZnO NPs. In the chronic studies, we further assessed the toxicokinetics and bioaccumulation of Ag and the resulting histopathological effects in the gill, intestine, and liver of zebrafish. Co-exposures with ZnO NPs reduced the toxicity of Ag NPs for acute (lethality) but enhanced the toxicity effects (tissue histopathology) for chronic exposures. The histological lesions for both NPs exposures in the gill included necrosis and fusion of lamellae, for the intestine necrosis and degeneration, and in the liver, mainly necrosis. The severity of the histological lesions induced by the Ag NPs was related to the amount of accumulated Ag in the zebrafish organs. The Ag accumulation in different organs was higher in the presence of ZnO NPs in the order of the gill > intestine > liver. Depuration kinetics illustrated the lowest half-life for Ag occurred in the gill and for the combined exposure of Ag with ZnO NPs. Our findings illustrate that in addition to tissue, time, and exposure concentration dependencies, the Ag NPs toxicity can also be influenced by the co-exposure to other NPs (here ZnO NPs), emphasizing the need for more combination exposure effects studies for NPs to more fully understand their potential environmental health risks., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Zinc oxide nanoparticles (ZnO NPs) and multi-layer graphenes (MLGs) are widely used, and due to the lack of appropriate wastewater treatment may end up in the aquatic environment, with unknown consequences to biota. The main purpose of this study was to assess the acute toxicity, histopathological and behavioural changes caused by the exposure of ZnO NPs and MLGs, alone and combined, to the blackfish Capoeta fusca. The estimated mean 96 h-LC 50 for ZnO NPs was 4.9 mg L -1 and 68.4 mg L -1 for MLGs. In combination, MLGs increased the acute toxicity of the ZnO NPs. The effects of the different NPs on the gills included hyperplasia, aneurisms, and fusion of the lamellae. In the intestine, exposure to the NPs resulted in an increase in the number and swelling of goblet cells and tissue degeneration. Loss of balance, restlessness, erratic and abnormal swimming patterns were the most common behavioural changes seen in the ZnO NPs' exposed blackfish. In contrast with the acute toxicity findings, MLGs decreased the histopathological and behavioural effects of the ZnO NPs on both gills and intestinal tissues as well as fish behaviour. Our experimental results illustrated insights into the simultaneous exposure assessment of metal-based NPs and carbon nanomaterials, although further research is needed on the interactions exposure of these substances to interpreting the toxicological effects of metal-based nanomaterials seen in exposed organisms., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is a global research interest in metal nanoparticles (MNPs) due to their diverse applications, rapidly increasing use, and increased presence in the aquatic environment. Currently, most MNPs in the environment are at levels unlikely to cause overt toxicity. Sub-lethal effects that MNPs may induce, notable immunotoxicity, could however have significant health implications. Thus, deciphering the immunological interactions of MNPs with aquatic organisms constitutes a much-needed area of research. In this article, we critically assess the evidence for immunotoxic effects of MNPs in bivalves and fish, as key wildlife sentinels with widely differing ecological niches that are used as models in ecotoxicology. The first part of this review details the properties, fate, and fundamental physicochemical behavior of MNPs in the aquatic ecosystem. We then consider the toxicokinetics of MNP uptake, accumulation, and deposition in fish and bivalves. The main body of the review then focuses on immune reactions in response to MNPs exposure in bivalves and fish illustrating their immunotoxic potential. Finally, we identify major knowledge gaps in our current understanding of the implications of MNPs exposure for immunological functions and the associated health consequences for bivalves and fish, as well as the general lessons learned on the immunotoxic properties of the emerging class of nanoparticulate contaminants in fish and bivalves.

Silver nanoparticles (AgNPs) are increasingly used in a wide range of products and as a consequence, the environmental concentration will inevitably increase in the near future. Many aquatic organisms have been shown to be sensitive to the toxic effects of silver, including oxidative stress mechanisms. In this study, we assessed the ability of silymarin (Silybum marianum) to counter the oxidative effects of AgNPs in Nile tilapia (Oreochromis niloticus). Fish were fed on the diets supplemented with 50 or 200 mg kg -1 of free or nanoencapsulated silymarin for 50 days. Subsequently, they were exposed via the water to three concentrations (0.05, 0.1, and 0.5 mg L -1 ) of AgNPs for 24 h, and the effects of this exposure assessed on blood plasma and liver oxidative status. Growth performance and most body indices measured were not affected by any of the experimental diets. There were no effects of free silymarin (FS) or nanoencapsulated silymarin (NS) on levels of plasma aspartate aminotransferase (AST), alanine transaminase (ALT), or on the total protein (TP). In contrast, malondialdehyde (MDA) content, glutathione peroxidase (GPx) activity, and plasma glucose (GLU) were all affected by the high dietary FS and NS treatments compared with controls. Prior to the AgNPs exposure, the levels of SOD and GPx activity were higher and MDA levels lower in the silymarin treatment groups compared to controls. Exposure to AgNPs resulted in a reduction in the levels of GPx and SOD activity and an increase in the level of MDA that was dependent on the exposure concentrations of AgNPs. Based on GPx, MDA, and GLU indices, both forms of silymarin decreased the toxicity of AgNPs, but NS supplementation was the most effective. Thus, we show dietary silymarin supplementation can reduce AgNP toxicity and nanoencapsulation increases its efficacy as an antioxidant.

In this study, we investigated the bioaccumulation and toxicokinetics of zinc oxide nanoparticles (ZnO NPs) alone and in the presence of graphene nanosheets (GNs) in the blackfish (Capoeta fusca). Blackfish were exposed via water to two ZnO NPs concentrations alone or as a combination with GNs and uptake of Zn into the gills, intestine, liver, and kidney was assessed at 7, 14 and 28 d. Zn elimination from these tissues was then assessed after a further 7, 14 and 28 d in clean water for both ZnO NPs concentrations and combined ZnO NPs/GN exposures. In the body tissues analyzed of exposed fish, the highest amounts of Zn occurred in the intestine and the lowest amount in the liver. Zn levels in blackfish after 28 d of exposure were higher in all treatment groups compared to those on 7 d (p < 0.05). For both ZnO NPs exposure concentrations, the highest amount of Zn was eliminated from the intestine, followed by the gills. Furthermore, elimination kinetics for both ZnO NPs concentrations alone and in combination with GNs showed that the shortest half-life for Zn is occurring in the intestine. Moreover, uptake rates of Zn in fish exposed to ZnO NPs + GNs followed the same pattern observed for the ZnO NP, with intestine and gills having the highest levels followed by kidney and liver. Thus, we show accumulation and elimination of Zn from ZnO NPs in blackfish depends on the tissue, exposure concentration and duration, and is dependent on the presence of GNs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

The relative importance of ingestion and transdermal uptake of nanomaterials is poorly understood, particularly in sediment dwelling organisms, where diet has the potential to contribute significantly to particle accumulation. In aquatic sediments, nanoparticles may partition to bind with the solid fraction of sediment, be freely mobile in the pore water or, for certain metal/metal oxides, undergo dissolution, each of which could influence the route of nanoparticle uptake. Here, we used the freshwater worm Lumbriculus variegatus as a model species. We took advantage of its unique feeding and non-feeding life-stages to assess the contribution of dietary and transdermal uptake in the bioaccumulation of cerium oxide nanoparticles (CeO 2 NP) and soluble Ce(III)NO 3 . Distribution of cerium between the solid, colloidal and soluble fractions in the sediments was determined through sediment separations using micro and ultrafiltration techniques. We assessed particles of differing sizes (10, 28 and 615 nm CeO 2 ) and stabilizing surfactants (10 nm electrostatic Citrate-CeO 2 and steric stabilized PEG-CeO 2 ). Soluble Ce(III)NO 3 , was found to accumulate readily across the skin of the worms whilst nanoparticles were not. Sediments reduced the uptake of Ce III by limiting the presence of dissolved species of cerium in the pore waters. Neither particle size nor the coatings studied altered the distribution of nanoparticles between solid and colloidal fractions of the sediment, with ∼99% associated to the solid phase. Any uptake of CeO 2 nanoparticles into worms was only through ingestion. Stabilized 10 nm particles were retained even after gut clearance, indicating that these particles may translocate across the gut wall.

Some nanoparticles (NPs) may induce adverse health effects in exposed organisms, but to date the evidence for this in wildlife is very limited. Silver nanoparticles (AgNPs) can be toxic to aquatic organisms, including fish, at concentrations relevant for some environmental exposures. We applied whole mount in-situ hybridisation (WISH) in zebrafish embryos and larvae for a suite of genes involved with detoxifying processes and oxidative stress, including metallothionein (mt2), glutathionine S-transferase pi (gstp), glutathionine S-transferase mu (gstm1), haem oxygenase (hmox1) and ferritin heavy chain 1 (fth1) to identify potential target tissues and effect mechanisms of AgNPs compared with a bulk counterpart and ionic silver (AgNO3). AgNPs caused upregulation in the expression of mt2, gstp and gstm1 and down regulation of expression of both hmox1 and fth1 and there were both life stage and tissue-specific responses. Responding tissues included olfactory bulbs, lateral line neuromasts and ionocytes in the skin with the potential for effects on olfaction, behaviour and maintenance of ion balance. Silver ions induced similar gene responses and affected the same target tissues as AgNPs. AgNPs invoked levels of target gene responses more similar to silver treatments compared to coated AgNPs indicating the responses seen were due to released silver ions. In the Nrf2 zebrafish mutant, expression of mt2 (24 hpf) and gstp (3 dpf) were either non-detectable or were at lower levels compared with wild type zebrafish for exposures to AgNPs, indicating that these gene responses are controlled through the Nrf2-Keap pathway.

Copper nanoparticles (CuNPs) are used extensively in a wide range of products and the potential for toxicological impacts in the aquatic environment is of high concern. In this study, the fate and the acute toxicity of spherical 50nm copper nanoparticles was assessed in juvenile rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas) and zebrafish (Danio rerio) for in vivo aqueous exposures following standardized OECD 203 guideline tests. The fate of the CuNPs in the aqueous media was temperature dependent. At the higher study temperature (26±1°C), there was both an enhanced particle aggregation and higher rate of dissolution compared with that at the lower study temperature (15±1°C). 96h LC50s of the CuNPs were 0.68±0.15, 0.28±0.04 and 0.22±0.08mg Cu/L for rainbow trout, fathead minnow and zebrafish, respectively. The 96h lowest-observed-effect concentration (LOEC) for the CuNPs were 0.17, 0.023 and <0.023mg/L for rainbow trout, fathead minnow, and zebrafish respectively, and are below the predicted environmental concentration of CuNPs for some aquatic environments suggesting a possible ecotoxicological risk to fish. Soluble copper was one of main drivers for the acute toxicity of the copper nanoparticles suspensions. Both CuNPs suspension and copper nitrate caused damage to gill filaments and gill pavement cells, with differences in sensitivity for these effects between the fish species studied. We show therefore common toxicological effects of CuNPs in different fish species but with differences in sensitivity with implications for hazard extrapolation between fish species., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Increasing use of metal and metal oxide nanoparticles [Me(O)NPs] in products means many will inevitably find their way into marine systems. Their likely fate here is sedimentation following hetero-aggregation with natural organic matter and/or free anions, putting benthic, sediment-dwelling and filter feeding organisms most at risk. In marine systems, Me(O)NPs can absorb to micro-organisms with potential for trophic transfer following consumption. Filter feeders, especially bivalves, accumulate Me(O)NPs through trapping them in mucus prior to ingestion. Benthic in-fauna may directly ingest sedimented Me(O)NPs. In fish, uptake is principally via the gut following drinking, whilst Me(O)NPs caught in gill mucus may affect respiratory processes and ion transport. Currently, environmentally-realistic Me(O)NP concentrations are unlikely to cause significant adverse acute health problems, however sub-lethal effects e.g. oxidative stresses have been noted in many organisms, often deriving from dissolution of Ag, Cu or Zn ions, and this could result in chronic health impacts., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Manufactured metal (oxide) nanoparticles are entering the aquatic environment with little understanding on their potential health impacts for exposed organisms. Adopting an integrative approach, we investigated effects of particle size and coating on biological responses for two of the most commonly used metal (oxide) nanoscale particles, silver (Ag) and titanium dioxide (TiO₂) in zebrafish embryos. Titanium dioxide nanoparticles (nominally, 4 nm, 10 nm, 30 nm and 134 nm) had little or no toxicity on the endpoints measured. Ag both in nano form (10 nm and 35 nm) and its larger counterpart (600-1600 nm) induced dose-dependent lethality and morphological defects, occurring predominantly during gastrula stage. Of the silver material tested 10 nm nanoparticles appeared to be the most toxic. Coating Ag nanoparticles with citrate or fulvic acid decreased toxicity significantly. In situ hybridisation analysis identified the yolk syncytial layer (YSL) as a target tissue for Ag-nano toxicity where there was a significant induction of the heavy metal stress response gene, metallothionein 2 (Mt2) at sub-lethal exposures. Coherent Anti-stroke Raman Scattering (CARS) microscopy provided no evidence for silver particles crossing the chorionic membrane in exposed embryos. Collectively, our data suggest that silver ions play a major role in the toxicity of Ag nanoparticles.

Silver nanoparticles cause toxicity in exposed organisms and are an environmental health concern. The mechanisms of silver nanoparticle toxicity, however, remain unclear. We examined the effects of exposure to silver in nano-, bulk-, and ionic forms on zebrafish embryos (Danio rerio) using a Next Generation Sequencing approach in an Illumina platform (High-Throughput SuperSAGE). Significant alterations in gene expression were found for all treatments and many of the gene pathways affected, most notably those associated with oxidative phosphorylation and protein synthesis, overlapped strongly between the three treatments indicating similar mechanisms of toxicity for the three forms of silver studied. Changes in oxidative phosphorylation indicated a down-regulation of this pathway at 24 h of exposure, but with a recovery at 48 h. This finding was consistent with a dose-dependent decrease in oxygen consumption at 24 h, but not at 48 h, following exposure to silver ions. Overall, our data provide support for the hypothesis that the toxicity caused by silver nanoparticles is principally associated with bioavailable silver ions in exposed zebrafish embryos. These findings are important in the evaluation of the risk that silver particles may pose to exposed vertebrate organisms.

Zinc oxide nanoparticles (ZnO NPs) are widely used in commercial products and knowledge of their environmental fate is a priority for ecological protection. Here we synthesized model ZnO NPs that were made from and thus labeled with the stable isotope (68)Zn and this enables highly sensitive and selective detection of labeled components against high natural Zn background levels. We combine high precision stable isotope measurements and novel bioimaging techniques to characterize parallel water-borne exposures of the common mudshrimp Corophium volutator to (68)ZnO NPs, bulk (68)ZnO, and soluble (68)ZnCl(2) in the presence of sediment. C. volutator is an important component of coastal ecosystems where river-borne NPs will accumulate and is used on a routine basis for toxicity assessments. Our results demonstrate that ionic Zn from ZnO NPs is bioavailable to C. volutator and that Zn uptake is active. Bioavailability appears to be governed primarily by the dissolved Zn content of the water, whereby Zn uptake occurs via the aqueous phase and/or the ingestion of sediment particles with adsorbed Zn from dissolution of ZnO particles. The high sorption capacity of sediments for Zn thus enhances the potential for trophic transfer of Zn derived from readily soluble ZnO NPs. The uncertainties of our isotopic data are too large, however, to conclusively rule out any additional direct uptake route of ZnO NPs by C. volutator.

We studied the effects of ZnO nanoparticles [ZnO NPs, primary particle size 35 ± 10 nm (circular diameter, TEM)], bulk [160 ± 81 nm (circular diameter, TEM)], and Zn ions (from ZnCl(2)) on mortality, growth, and reproductive endpoints in the sediment dwelling marine amphipod Corophium volutator over a complete lifecycle (100 days). ZnO NPs were characterized by size, aggregation, morphology, dissolution, and surface properties. ZnO NPs underwent aggregation and partial dissolution in the seawater exposure medium, resulting in a size distribution that ranged in size from discrete nanoparticles to the largest aggregate of several micrometers. Exposure via water to all forms of zinc in the range of 0.2-1.0 mg L(-1) delayed growth and affected the reproductive outcome of the exposed populations. STEM-EDX analysis was used to characterize insoluble zinc precipitates (sphaerites) of high sulfur content, which accumulated in the hepatopancreas following exposures. The elemental composition of the sphaerites did not differ for ZnO NP, Zn(2+), and bulk ZnO exposed organisms. These results provide an illustration of the comparable toxicity of Zn in bulk, soluble, and nanoscale forms on critical lifecycle parameters in a sediment dwelling organism.

This review summarises and evaluates the present knowledge on the behaviour, the biological effects and the routes of uptake of silver nanoparticles (Ag NPs) to organisms, with considerations on the nanoparticle physicochemistry in the ecotoxicity testing systems used. Different types of Ag NP syntheses, characterisation techniques and predicted current and future concentrations in the environment are also outlined. Rapid progress in this area has been made over the last few years, but there is still a critical lack of understanding of the need for characterisation and synthesis in environmental and ecotoxicological studies. Concentration and form of nanomaterials in the environment are difficult to quantify and methodological progress is needed, although sophisticated exposure models show that predicted environmental concentrations (PECs) for Ag NPs in different environmental compartments are at the range of ng L(-1) to mg kg(-1). The ecotoxicological literature shows that concentrations of Ag NPs below the current and future PECs, as low as just a few ng L(-1), can affect prokaryotes, invertebrates and fish indicating a significant potential, though poorly characterised, risk to the environment. Mechanisms of toxicity are still poorly understood although it seems clear that in some cases nanoscale specific properties may cause biouptake and toxicity over and above that caused by the dissolved Ag ion. This review concludes with a set of recommendations for the advancement of understanding of the role of nanoscale silver in environmental and ecotoxicological research., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Despite increasing application of silver nanoparticles (NPs) in industry and consumer products, there is still little known about their potential toxicity, particularly to organisms in aquatic environments. To investigate the fate and effects of silver NPs in fish, rainbow trout (Oncorhynchus mykiss) were exposed via the water to commercial silver particles of three nominal sizes: 10 nm (N(10)), 35 nm (N(35)), and 600-1600 nm (N(Bulk)), and to silver nitrate for 10 days. Uptake into the gills, liver, and kidneys was quantified by inductively coupled plasma-optical emission spectrometry, and levels of lipid peroxidation in gills, liver, and blood were determined by measurements of thiobarbituric acid reactive substances. Expression of a suite of genes, namely cyp1a2, cyp3a45, hsp70a, gpx, and g6pd, known to be involved in a range of toxicological response to xenobiotics was analyzed in the gills and liver using real-time PCR. Uptake of silver particles from the water into the tissues of exposed fish was low but nevertheless occurred for current estimated environmental exposures. Of the silver particles tested, N(10) were found to be the most highly concentrated within gill tissues and N(10) and N(Bulk) were the most highly concentrated in liver. There were no effects on lipid peroxidation in any of the tissues analyzed for any of the silver particles tested, and this is likely due to the low uptake rates. However, exposure to N(10) particles was found to induce expression of cyp1a2 in the gills, suggesting a possible increase in oxidative metabolism in this tissue.

Nanoparticles (NPs) are reported to be a potential environmental health hazard. For organisms living in the aquatic environment, there is uncertainty on exposure because of a lack of understanding and data regarding the fate, behavior, and bioavailability of the nanomaterials in the water column. This paper reports on a series of integrative biological and physicochemical studies on the uptake of unmodified commercial nanoscale metal oxides, zinc oxide (ZnO), cerium dioxide (CeO(2)), and titanium dioxide (TiO(2)), from the water and diet to determine their potential ecotoxicological impacts on fish as a function of concentration. Particle characterizations were performed and tissue concentrations were measured by a wide range of analytical methods. Definitive uptake from the water column and localization of TiO(2) NPs in gills was demonstrated for the first time by use of coherent anti-Stokes Raman scattering (CARS) microscopy. Significant uptake of nanomaterials was found only for cerium in the liver of zebrafish exposed via the water and ionic titanium in the gut of trout exposed via the diet. For the aqueous exposures undertaken, formation of large NP aggregates (up to 3 mum) occurred and it is likely that this resulted in limited bioavailability of the unmodified metal oxide NPs in fish.

The aim of this project was to compare cerium oxide and silver particles of different sizes for their potential for uptake by aquatic species, human exposure via ingestion of contaminated food sources and to assess their resultant toxicity. The results demonstrate the potential for uptake of nano and larger particles by fish via the gastrointestinal tract, and by human intestinal epithelial cells, therefore suggesting that ingestion is a viable route of uptake into different organism types. A consistency was also shown in the sensitivity of aquatic, fish cell and human cell models to Ag and CeO2 particles of different sizes; with the observed sensitivity sequence from highest to lowest as: nano-Ag > micro Ag > nano CeO2 = micro CeO2. Such consistency suggests that further studies might allow extrapolation of results between different models and species.

Our recent work suggests limited uptake of unstabilized metal oxide nanoparticles via water into fish, however, some other studies have indicated such exposures can induce oxidative stress. To investigate tissue distribution and toxicity of titanium dioxide (TiO(2)) nanoparticles that may enter into fish, we conducted a series of injection studies. Rainbow trout (Oncorhynchus mykiss) were intravenously injected with 100 microg TiO(2) nanoparticles and the content of titanium in blood, brain, gills, liver, and kidney quantified at time points between 6 h and 90 days using inductively coupled plasma optical emission spectroscopy. Injected Ti was concentrated in the kidneys and remained there up to 21 days, however, there was evidence of clearance of TiO(2) at 90 days. Ti accumulation in the liver was 15 times lower than in the kidney with no apparent clearance. Using TEM we showed nanoparticles were localized in tissue vesicles surrounding the kidney tubules. In a second injection study, rainbow trout were injected with 100 microg TiO(2) and plasma samples from individual fish analyzed for total protein and creatinine content at time points between 6 h and 21 days to assess for possible effects on kidney function. No effect of TiO(2) on total plasma protein content or creatinine concentrations were found indicating that neither urine production nor glomerular filtration rate were affected. We conclude that in trout upon a single high dose exposure of TiO(2) nanoparticles via the bloodstream, TiO(2) accumulates in the kidneys but has minimal effect on kidney function.