Mobilization and health risk assessment of fertilizer induced uranium in coastal groundwater.

Uranium (U) in groundwater is hazardous to human health, especially if it is present in drinking water. The semiarid regions of southern India chiefly depend on groundwater for drinking purposes. In this regard, a comprehensive sampling strategy was adopted to collect groundwater representing different lithologies of the region. The samples were collected in two different seasons and analysed for major and minor ions along with total U in the groundwater. Two samples during pre monsoon (PRM) and seven samples during post monsoon (POM) had U > 30 µgL-1, which is above the World Health Organization's provisional guideline value. The high concentration of U (188 µgL-1) was observed in the alluvial formation though a few samples showed the release of U near the pink granite (39 µgL-1) and the concentration was low in the lateritic formation (10 µgL-1). The uranyl carbonato complexes UO2(CO3)22- and UO2(CO3)34- were associated with high pH which facilitated the transport of U into groundwater especially during POM. U3O8 is the major form observed in groundwater compared to either UO2 or UO3 in the both seasons. The uranium oxides were observed to be more prevalent at the neutral pH. Though U concentration increases with pH, it is mainly governed by the redox conditions. The principal component analysis (PCA) analysis also suggested redox conditions in groundwater to be the major process facilitating the U release mechanism regardless of the season. The POM season has an additional source of U in groundwater due to the application of nitrogenous fertilizers in the alluvium region. Furthermore, redox mobilization factor was predominantly observed near the coastal region and in the agricultural regions. The process of infiltration of the fertilizer-induced U was enhanced by the agricultural runoff into the surface water bodies in the region. Health risk assessment was also carried out by determining annual effective dose rate, cancer mortality risk, lifetime average daily dose and hazard quotient to assess the portability of groundwater in the study area. Artificial recharge technique and reducing the usage of chemical based fertilizers for irrigation are suggested as sustainable plans to safeguard the vulnerable water resource in this region.

Waterborne uranium causes toxic effect and thyroid disruption in zebrafish larvae.

Uranium is a radioactive element that is widely present in aquatic environment. However, limited knowledge is available about the effect of uranium on thyroid system, which plays a key role in the development of animals. In this study, zebrafish embryos were exposed to different environmentally relevant concentrations of uranium (2, 20 and 100 µg/L) for 120 h. The bioaccumulation, developmental toxicities, changes of thyroid hormones (THs) and key genes related to the hypothalamic-pituitary-thyroid (HPT) axis in larvae were analyzed after exposure. Results showed that uranium could bioaccumulate in zebrafish larvae, with the bioconcentration factors ranging from 49.6 to 523. Consequently, significant developmental toxicities and changes in locomotor activities were observed with a concentration-dependent manner. The levels of triiodothyronine (T3) levels in larvae were substantially decreased, whereas those of thyroxine (T4) were increased in fish bodies. The levels of THs were regulated by the negative feedback loops through HPT axis related genes, most of which (NIS, Deio1, Deio2, TRα, TSHß and UGT1ab) were significantly depressed after exposure to uranium. Our results suggest the potential toxicities and thyroid disruption of uranium on zebrafish, which would provide baseline data set for better understanding the impact of waterborne uranium on aquatic organisms and the associated mechanisms. This study also highlights the key role of thyroid disruption in the ecological risk assessment of uranium pollution.

Elemental and radionuclide exposures and uptakes by small rodents, invertebrates, and vegetation at active and post-production uranium mines in the Grand Canyon watershed.

The effects of breccia pipe uranium mining in the Grand Canyon watershed (Arizona) on ecological and cultural resources are largely unknown. We characterized the exposure of biota to uranium and co-occurring ore body elements during active ore production and at a site where ore production had recently concluded. Our results indicate that biota have taken up uranium and other elements (e.g., arsenic, cadmium, copper, molybdenum, uranium) from exposure to ore and surficial contamination, like blowing dust. Results indicate the potential for prolonged exposure to elements and radionuclides upon conclusion of active ore production. Mean radium-226 in deer mice was up to 4 times greater than uranium-234 and uranium-238 in those same samples; this may indicate a potential for, but does not necessarily imply, radium-226 toxicity. Soil screening benchmarks for uranium and molybdenum and other toxicity thresholds for arsenic, copper, selenium, uranium (e.g., growth effects) were exceeded in vegetation, invertebrates, and rodents (Peromyscus spp., Thomomys bottae, Tamias dorsalis, Dipodomys deserti). However, the prevalence and severity of microscopic lesions in rodent tissues (as direct evidence of biological effects of uptake and exposure) could not be definitively linked to mining. Our data indicate that land managers might consider factors like species, seasonal changes in environmental concentrations, and bioavailability, when determining mine permitting and remediation in the Grand Canyon watershed. Ultimately, our results will be useful for site-specific ecological risk analysis and can support future decisions regarding the mineral extraction withdrawal in the Grand Canyon watershed and elsewhere.

Screening of potential uranium protein targets in fish ovaries after chronic waterborne exposure: Differences and similarities between roach and zebrafish.

Concentration of uranium (U), a naturally encountered radioactive element in earth's crust, can be enhanced in freshwater ecosystems (µg.L-1 - mg.L-1) due to various anthropogenic activities. The consequent aquatic organism exposure to U leads to its accumulation in all organs, particularly in the gonad, and in subcellular fractions (mainly the cytosol); then it is known to affect fish at several biological levels, and more particularly, at a reproduction endpoint, with a decrease in the total number of eggs, spawn events and larvae survival. The understanding of U reprotoxicity requires the fine knowledge of its speciation at molecular level, i.e., its interaction with cytosolic biomolecules. In this study, we focus on the U-protein interactions in gonads. A non-denaturating extraction protocol combined with size exclusion chromatography (SEC) allowed the separation of metal-protein complexes in ovaries of U-contaminated wild roaches before their elemental detection (ICP MS). This enables unprecedented information to be obtained about U distribution in ovaries of autochthonous fish, Rutilus rutilus, which is different in some points from that obtained in the model species, Danio rerio under controlled laboratory conditions at a similar concentration level. Finally, the ability to transpose results from model to autochthonous fish was briefly discussed.

Survival and Reproductive Effects in the Aquatic Invertebrate Ceriodaphnia dubia Exposed to Uranium Spiked Site Water Collected from Two Creeks in the Yukon, Canada.

This study evaluates aqueous uranium (U) toxicity in Ceriodaphnia dubia exposed to surface water collected from two creeks located in U-rich areas of Yukon, Canada. Water for toxicity testing was collected at two times of the year to represent water quality characteristics generally observed during open-water (high flows) and winter baseflow water (low flows) seasons. Collected water was transferred to the toxicological laboratory and spiked with U to achieve nominal concentrations of 50, 150, 350, 500, 650, 800, and 1000 µg U/L. Toxicity endpoints included lethal concentrations (LC50) for survival, in addition to no observed effect concentration (NOEC) and lowest observed effect concentration (LOEC) for reproduction. All derived toxicity endpoints were significantly higher than applicable Canadian water-quality guidelines for U (15 µg/L [Chronic] and 33 µg/L [Acute]). No effects on C. dubia survival were observed at LC50 concentrations > 799 µg U/L. Derived NOEC (381 µg U/L) and LOEC (524 µg U/L) values also were significantly above chronic water quality guidelines. The differences noted in the toxicity response between seasons were mainly due to the presence of toxicity ameliorating factors for U (i.e., dissolved organic carbon). These results highlight the high conservatism in applicable water-quality guidelines and the crucial need to consider site-specific water characteristics when deriving environmentally relevant, yet protective thresholds for uranium in aquatic environments.

Age-dependent ingestion and inhalation doses due to intake of uranium and radon in water samples of Shiwalik Himalayas of Jammu and Kashmir, India.

The research work involved the ingestion and inhalation doses due to the intake of radon and uranium through water samples used by the inhabitants, measured in the villages of the Shiwalik Himalayas of Jammu and Kashmir, India. The uranium concentration in collected water samples was assessed by LED fluorimetric technique. All values of doses were found to be below the proposed limit of 100 µSv year-1 for all age categories except for infants due to the high-dose conversion factor. The annual effective doses for the various body organs due to the intake of radon was also calculated and found the maximum dose for lungs than other organs. The concentration of radon in water samples was assessed by Smart Rn Duo portable monitor and compared with RAD7. Statistical analysis was carried out and the Shapiro and Wilk (Biometrika, 52(3/4), 591-611, 1965) test has been also used for the distribution of the data. The physicochemical parameters were also measured in the collected water samples.

Integrating laboratory and field studies to assess impacts of discharge from a uranium mine and validate a water quality guideline value for magnesium.

Magnesium (Mg) is a primary contaminant in mine water discharges from the Ranger Uranium Mine (north Australia). Site-specific water quality guideline values (WQGVs) for Mg have been derived from laboratory and field studies. Contaminated groundwater with elevated electrical conductivity and metals (Mg, Mn, U, SO4 , and Ca) was detected flowing from the mine site into adjacent surface waters. This provided an opportunity to investigate the protectiveness of the Mg WQGV by conducting an integrated laboratory and field study. A direct toxicity assessment (DTA) of the groundwater was conducted with local tropical freshwater species: duckweed (Lemna aequinoctialis), green hydra (Hydra viridissima), and the aquatic snail Amerianna cumingi. An in situ toxicity assessment was carried out in the creek receiving diluted groundwater by use of the same species of snail, to aid interpretation of laboratory-derived data. The toxicity of the contaminated groundwater was higher than Mg-only toxicity testing for H. viridissima, with other elevated metals and major ions contributing to toxicity. However, for duckweed and snail, the contaminated groundwater was less toxic than the Mg-only testing. In situ snail monitoring supported laboratory exposures, showing no effect on reproduction of A. cumingi exposed to an average of approximately 5 mg/L Mg; however, a very small effect was noted closer to the groundwater source, probably associated with other contaminants. The minimal toxicity observed for L. aequinoctialis and A. cumingi, despite the elevated Mg, can be explained by the high calcium (Ca) concentration of the water and the potential amelioration of metal toxicity. The extent of Ca amelioration of Mg toxicity was organism dependent. This study affirms the proposed environmental rehabilitation standard of 3 mg/L Mg for surface waters with a Ca concentration typical of water from this mine site. Integr Environ Assess Manag 2019;15:64-76. © 2018 SETAC.

Decontamination of radioactive wastewater: State of the art and challenges forward.

Radioactive substances have been widely used in many industrial sectors, e.g. nuclear power station, biomedical engineering, etc. With increasing applications of nuclear technology, more and more radioactive wastewater is being generated via different channels, which indeed is posing an emerging challenge and threat to the environment and human health. Given such a situation, this review attempts to offer a holistic view with regard to the state of the art of technology for decontamination of radioactive wastewater as well as shed lights on the challenges forward. Different from reclamation of other types of wastewaters, the most challenging issue in decontamination of radioactive wastewater is the effective stabilization and solidification of soluble radioactive nuclides present in wastewater, which are critical for final disposal. Moreover, the potential risk of human exposure to wastewater radiation needs to be carefully assessed, and this issue should also be taken into consideration in the selection, design and operation of the radioactive wastewater treatment process. These clearly differentiate the treatment principle of radioactive wastewater from those of traditional industrial and municipal wastewaters. Lastly, the challenges from the perspectives of technology development, environmental and human health impacts and possible solutions forward are also elucidated.

Accumulation and effects of uranium on aquatic macrophyte Nymphaea tetragona Georgi: Potential application to phytoremediation and environmental monitoring.

This study analyzed the ability of Nymphaea tetragona Georgi (N. tetragona) to accumulate water-borne uranium and any effects this could exert on this plant species. In accumulation experiments, N. tetragona was exposed (21 d) to different concentrations of uranium (0-55 mg L-1) and the content of uranium was determined in water and plant tissues (leaves, submerged position and plant) to determine the translocation factor (TF) and bioconcentration factor (BCF). The content of uranium in the plant and plant tissues showed concentration-dependent uptake, leaves were the predominant tissue for uranium accumulation, and TF and BCF values were both affected by the concentration of uranium in the water. In this research, the uranium content and BCF value in the leaves of N. tetragona were upto 3446 ±â€¯155 mg kg-1 and 73 ±â€¯3, respectively. In physiological experiments, uranium treatment boosted the activity of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in the leaves, and increasing uranium concentrations aggravated damage to the cell membrane system. Uranium contamination significantly inhibited the content of soluble protein, as well as chlorophyll-a, chlorophyll-b and carotene in the leaves, indicating the structure and function of chloroplast were destroyed, reducing the photosynthetic performance of plants. These results indicate that the macrophyte N. tetragona can accumulate uranium while showing a stress response via metabolic mechanisms under uranium exposure, and it may be a suitable bioremediation candidate for aquatic marine contamination.

Life history traits and genotoxic effects on Daphnia magna exposed to waterborne uranium and to a uranium mine effluent - A transgenerational study.

Assessing the impact of uranium mining industry on aquatic ecosystems near mining areas is critical to ensure the long-term health and sustainability of ecosystem services. As so, a transgenerational study with Daphnia magna has been conducted to perceive to what extent intermittent discharges of uranium mine effluents into watercourses may impact the DNA integrity and life history traits of cladocerans. Organisms were exposed for 48 h to a 2% dilution of an uranium mine effluent (UME) and to a corresponding dose of waterborne uranium (WU) that, according to our preliminary studies, induces significant DNA damage in daphnids. After exposure, organisms were transferred to clean medium, where three successive generations were monitored for genotoxicity and other effects at the individual and population level. Despite some differences between WU and UME data, our results revealed that the negative impacts of the short-term exposure gradually disappeared after placing the organisms in clean medium. These results suggest that, under intermittent stress, daphnids are able to recover, since after the 3rd brood release, DNA damage (measured as DNA strand breaks) is no longer observed and has no significant impact on the detectable life traits of offspring. Although our results indicate that populations of D. magna are not affected by intermittent and highly diluted discharges from uranium mining, aquatic systems under this kind of pressure should not be seen as hazardous-free. Future studies in this field are recommended and these should consider radionuclides in the water column, their accumulation in the sediments and also multiple life stages.

Toxicokinetic and toxicodynamic of depleted uranium in the zebrafish, Danio rerio.

This study investigated the accumulation pattern and biological effects (genotoxicity and histopathology) to adult zebrafish (male and female) exposed to a nominal waterborne concentration of 20 µg L-1 of depleted uranium (DU) for 28 days followed by 27 days of depuration. Accumulation pattern showed that (i) DU accumulated in brain, (ii) levels in digestive tract were higher than those measured in gills and (iii) levels remained high in kidney, brain and ovary despite the 27 days of depuration period. Genotoxicity, assessed by comet assay, was significant not only during DU exposure, but also during depuration phase. Gonads, in particular the testes, were more sensitive than gills. The histology of gonads indicated severe biological damages in males. This study improved knowledge of ecotoxic profile of uranium, for which a large range of biological effects has already been demonstrated.

Uranium (238U) bioaccumulation and its persuaded alterations on hematological, serological and histological parameters in freshwater fish Pangasius sutchi.

The early biomarkers for the hematological, serological and histological alterations due to the effect of ½ and » LC50 of 238U in different organs in freshwater fish Pangasius sutchi for water-borne 238U accumulation was investigated. The toxicological data due to 238U accumulation on the hematological parameters such as hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and hematocrit (Hct) to evaluate the oxygen carrying capacity has been indicated as the secondary response of the organisms. The biomarkers of liver damage were determined as by Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), Alkaline Phosphatase (ALP), γ-Glutamyl Transferase (γ-GT). Similarly, the renal biomarkers of kidney damage were accessed by creatinine, uric acid, triglycerides, and cholesterol. The decrease in hemoglobin in the experimental group due to disturbed synthesis of hemoglobin was directly proportional to the concentration and exposure duration of 238U. The histological studies proved that liver and gills are the target organ for 238U toxicity. The extensive histological lesions were observed in various tissues due to oxidative stress by the accumulation of 238U, and the 238U toxicity in the organs was in the order of Gills

Zebrafish exposure to environmentally relevant concentration of depleted uranium impairs progeny development at the molecular and histological levels.

Uranium is an actinide naturally found in the environment. Anthropogenic activities lead to the release of increasing amounts of uranium and depleted uranium (DU) in the environment, posing potential risks to aquatic organisms due to radiological and chemical toxicity of this radionucleide. Although environmental contaminations with high levels of uranium have already been observed, chronic exposures of non-human species to levels close to the environmental quality standards remain scarcely characterized. The present study focused on the identification of the molecular pathways impacted by a chronic exposure of zebrafish to 20 µg/L of DU during 10 days. The transcriptomic effects were evaluated by the use of the mRNAseq analysis in three organs of adult zebrafish, the brain the testis and the ovaries, and two developmental stages of the adult fish progeny, two-cells embryo and four-days larvae. The results highlight generic effects on the cell adhesion process, but also specific transcriptomic responses depending on the organ or the developmental stage investigated. The analysis of the transgenerational effects of DU-exposure on the four-day zebrafish larvae demonstrate an induction of genes involved in oxidative response (cat, mpx, sod1 and sod2), a decrease of expression of the two hatching enzymes (he1a and he1b), the deregulation of the expression of gene coding for the ATPase complex and the induction of cellular stress. Electron microscopy analysis of skeletal muscles on the four-days larvae highlights significant histological impacts on the ultrastructure of both the mitochondria and the myofibres. In addition, the comparison with the transcriptomic data obtained for the acetylcholine esterase mutant reveals the induction of protein-chaperons in the skeletal muscles of the progeny of fish chronically exposed to DU, pointing towards long lasting effects of this chemical in the muscles. The results presented in this study support the hypothesis that a chronic parental exposure to an environmentally relevant concentration of DU could impair the progeny development with significant effects observed both at the molecular level and on the histological ultrastructure of organs. This study provides a comprehensive transcriptomic dataset useful for ecotoxicological studies on other fish species at the molecular level. It also provides a key DU responsive gene, egr1, which may be a candidate biomarker for monitoring aquatic pollution by heavy metals.

Recent aspects of uranium toxicology in medical geology.

Uranium (U) is a chemo-toxic, radiotoxic and even a carcinogenic element. Due to its radioactivity, the effects of U on humans health have been extensively investigated. Prolonged U exposure may cause kidney disease and cancer. The geological distribution of U radionuclides is still a great concern for human health. Uranium in groundwater, frequently used as drinking water, and general environmental pollution with U raise concerns about the potential public health problem in several areas of Asia. The particular paleo-geological hallmark of India and other Southern Asiatic regions enhances the risk of U pollution in rural and urban communities. This paper highlights different health and environmental aspects of U as well as uptake and intake. It discusses levels of U in soil and water and the related health issues. Also described are different issues of U pollution, such as U and fertilizers, occupational exposure in miners, use and hazards of U in weapons (depleted U), U and plutonium as catalysts in the reaction between DNA and H2O2, and recycling of U from groundwater to surface soils in irrigation. For use in medical geology and U research, large databases and data warehouses are currently available in Europe and the United States.

Uranium (238U)-induced ROS and cell cycle perturbations, antioxidant responses and erythrocyte nuclear abnormalities in the freshwater iridescent shark fish Pangasius sutchi.

The strategic plan of this study is to analyze any possible radiological impact on aquatic organisms from forthcoming uranium mining facilities around the Nagarjuna Sagar Dam in the future. The predominantly consumed and dominant fish species Pangasius sutchi, which is available year-round at Nagarjuna Sagar Dam, was selected for the study. To comprehend the outcome and to understand the mode of action of 238U, the fish species Pangasius sutchi was exposed to » and ½ of the LC50 doses of waterborne 238U in a static system in duplicate for 21 days. Blood and organs, including the gills, liver, brain and muscles, were collected at different time periods-0h, 24h, 48h, 72h, 96h, 7, days 14days and 21 days-using ICP-MS to determine the toxic effects of uranium and the accumulation of 238U concentrations. The bioaccumulation of 238U in P. sutchi tissues was dependent on exposure time and concentration. The accumulation of uranium was, in order of magnitude, measured as gills>liver>brain>tissue, with the highest accumulation in the gills. It was observed that exposure to 238U significantly reduced antioxidant enzymes such as superoxide dismutase, catalase, and lipid peroxidase. The analysis of DNA fragmentation by comet assay and cell viability by flow cytometry was performed at different time intervals. DNA histograms by flow cytometry analysis revealed an increase in the G2/M phase and the S phase. The long-term 238U exposure studies in fish showed increasing micronucleus frequencies in erythrocytes with greater exposure time. The higher the concentration of 238U is, the greater is the effect observed, suggesting a close relationship between accumulation and toxicity. A possible ROS-mediated 238U toxicity mechanism and antioxidant responses have been proposed.

Epigenetic, histopathological and transcriptomic effects following exposure to depleted uranium in adult zebrafish and their progeny.

This study investigated the effects of adult zebrafish exposure to a nominal concentration of 20µgL-1 of depleted uranium (DU) for six days upon DNA methylation, gene expression and the appearance of histopathological damage in their progeny. In the embryos at the 2-8 cell stage, the parental exposure induced significant DU accumulation, with levels seven times higher than those measured in the control embryos, but in larvae 96h post-fertilisation (hpf), uranium concentration had already returned to a level identical to that of the control larvae. A significant two-fold increase in the global level of DNA methylation was observed in embryos as early as the prim5 (24 hpf) stage and was still maintained at the 96 hpf stage despite the fact that DU had already been depurated at the later stage. RNA sequencing analysis indicated an impact of parental exposure upon the total RNAs transmitted from the mother to eggs, and the up-regulated genes were those associated with post-traductional protein modification and trafficking and cellular signalling pathways, whereas the down-regulated genes concerned the translational process, cell cycle regulation and several cell signalling pathways. Alterations of photoreceptor cells and the axon-axon junctions between photoreceptors were observed in the eyes of adult fish exposed for 10days to DU. Actin and myosin filament disorganisation was observed in the skeletal muscles of 96 hpf larvae, at a stage when the maternally transmitted DU had already been excreted. These data reveal the extreme sensitivity of zebrafish embryos to DU transmitted through the oocyte by exposed females.

Proteome changes in rat serum after a chronic ingestion of enriched uranium: Toward a biological signature of internal contamination and radiological effect.

The civilian and military use of uranium results in an increased risk of human exposure. The toxicity of uranium results from both its chemical and radiological properties that vary with isotopic composition. Validated biomarkers of health effects associated with exposure to uranium are neither sensitive nor specific to uranium radiotoxicity and/or radiological effect. This study aimed at investigating if serum proteins could be useful as biomarkers of both uranium exposure and radiological effect. Male Sprague-Dawley rats were chronically exposed through drinking water to low levels (40mg/L, corresponding to 1mg of uranium per animal per day) of either 4% (235)U-enriched uranium (EU) or 12% EU during 6 weeks. A proteomics approach based on two-dimensional electrophoresis (2D-DIGE) and mass spectrometry (MS) was used to establish protein expression profiles that could be relevant for discriminating between groups, and to identify some differentially expressed proteins following uranium ingestion. It demonstrated that the expressions of 174 protein spots over 1045 quantified spots were altered after uranium exposure (p<0.05). Using both inferential and non-supervised multivariate statistics, we show sets of spots features that lead to a clear discrimination between controls and EU exposed groups on the one hand (21 spots), and between 4% EU and 12% EU on the other hand (7 spots), showing that investigation of the serum proteome may possibly be of relevance to address both uranium contamination and radiological effect. Finally, using bioinformatics tools, pathway analyses of differentially expressed MS-identified proteins find that acute phase, inflammatory and immune responses as well as oxidative stress are likely involved in the response to contamination, suggesting a physiological perturbation, but that does not necessarily lead to a toxic effect.

Hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to gamma radiation and depleted uranium singly and in combination.

Radionuclides are a special group of substances posing both radiological and chemical hazards to organisms. As a preliminary approach to understand the combined effects of radionuclides, exposure studies were designed using gamma radiation (Gamma) and depleted uranium (DU) as stressors, representing a combination of radiological (radiation) and chemical (metal) exposure. Juvenile Atlantic salmon (Salmo salar) were exposed to 70mGy external Gamma dose delivered over the first 5h of a 48h period (14mGy/h), 0.25mg/L DU were exposed continuously for 48h and the combination of the two stressors (Combi). Water and tissue concentrations of U were determined to assess the exposure quality and DU bioaccumulation. Hepatic gene expression changes were determined using microarrays in combination with quantitative real-time reverse transcription polymerase chain reaction (qPCR). Effects at the higher physiological levels were determined as plasma glucose (general stress) and hepatic histological changes. The results show that bioaccumulation of DU was observed after both single DU and the combined exposure. Global transcriptional analysis showed that 3122, 2303 and 3460 differentially expressed genes (DEGs) were significantly regulated by exposure to gamma, DU and Combi, respectively. Among these, 349 genes were commonly regulated by all treatments, while the majority was found to be treatment-specific. Functional analysis of DEGs revealed that the stressors displayed similar mode of action (MoA) across treatments such as induction of oxidative stress, DNA damage and disturbance of oxidative phosphorylation, but also stressor-specific mechanisms such as cellular stress and injury, metabolic disorder, programmed cell death, immune response. No changes in plasma glucose level as an indicator of general stress and hepatic histological changes were observed. Although no direct linkage was successfully established between molecular responses and adverse effects at the organism level, the study has enhanced the understanding of the MoA of single radionuclides and mixtures of these.

Increasing uranium exposure durations to the aquatic snail Amerianna cumingi does not result in lower toxicity estimates.

Reproductive inhibition (egg production) of the aquatic snail Amerianna cumingi over 4 d has been used to derive toxicity estimates for toxicants of concern in tropical Australia. Toxicity estimates from this test have been used as chronic data points in species sensitivity distributions (SSDs) for deriving site-specific guideline values. However, revised guidance for the Australian and New Zealand Water Quality Guidelines advises that test durations for adult macroinvertebrates should be ≥14 d to be considered chronic. Hence, to strengthen the data set underpinning the site-specific guideline value for uranium (U) in Magela Creek, which receives water from the Ranger Uranium Mine in northern Australia, the toxicity of U to A. cumingi was compared after 4 d, 9 d, and 14 d. Daily U concentrations were measured because of expected U loss during testing, providing extensive chemical analyses of the U exposure during the toxicity tests. Comparison of the U concentrations causing 50% reproductive inhibition (IC50) after 4 d, 9 d, and 14 d showed no difference in toxicity (4 d IC50 = 161 µg L-1 , confidence interval = 133-195; 9-d IC50 = 151 µg L-1 , confidence interval = 127-180; 14-d IC50 = 153 µg L-1 , confidence interval = 29-180). The present study provides evidence that test durations of <14 d are suitable for assessing chronic toxicity to U for this species and supports the use of the 4-d toxicity estimate in the SSD for U. Environ Toxicol Chem 2016;35:2851-2858. © 2016 Commonwealth of Australia.

Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish.

We examined the effects of chronic exposure to different concentrations (2 and 20 µg L(-)(1)) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5'-CCGG-3') and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 µg L(-)(1) DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 µg L(-)(1) DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 µg L(-)(1) DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects.