A comparison of the chemo- and radiotoxicity of thorium and uranium at different enrichment grades.

Uranium and thorium are heavy metals, and all of their isotopes are radioactive, so it is impossible to study chemical effects entirely independent of the radiation effects. In the present study, we tried to compare the chemo- and radiotoxicity of both metals, taking into account deterministic radiation damages reflected by acute radiation sickness and stochastic radiation damages leading to long-term health impairments (e.g., tumor induction). We made at first a literature search on acute median lethal doses that may be expected to be caused by chemical effects, as even acute radiation sickness as a manifestation of acute radiotoxicity occurs with latency. By simulations based on the biokinetic models of the International Commission on Radiological Protection and using the Integrated Modules for Bioassay Analysis software, we determined the amounts of uranium at different enrichment grades and thorium-232 leading to a short-term red bone marrow equivalent dose of 3.5 Sv considered to cause 50% lethality in humans. Different intake pathways for incorporation were considered, and values were compared to the mean lethal doses by chemotoxicity. To assess stochastic radiotoxicity, we calculated the uranium and thorium amounts leading to a committed effective dose of 200 mSv that is often considered critical. Mean lethal values for uranium and thorium are in the same order of magnitude so that the data do not give evidence for substantial differences in acute chemical toxicity. When comparing radiotoxicity, the reference units (activity in Bq or weight in g) must always be taken into account. The mean lethal equivalent dose to the red bone marrow of 3.5 Sv is reached by lower activities of thorium compared to uranium in soluble compounds. However, for uranium as well as thorium-232, acute radiation sickness is expected only after incorporation of amounts exceeding the mean lethal doses by chemotoxicity. Thus, acute radiation sickness is not a relevant clinical issue for either metal. Concerning stochastic radiation damages, thorium-232 is more radiotoxic than uranium if incorporating the same activities. Using weight units for comparison show that for soluble compounds, thorium-232 is more radiotoxic than low-enriched uranium in the case of ingestion but even more toxic than high-enriched uranium after inhalation or intravenous administration. For insoluble compounds, the situation differs as the stochastic radiotoxicity of thorium-232 ranges between depleted and natural uranium. For acute effects, the chemotoxicity of uranium, even at high enrichment grades, as well as thorium-232 exceeds deterministic radiotoxicity. Simulations show that thorium-232 is more radiotoxic than uranium expressed in activity units. If the comparison is based on weight units, the rankings depend on the uranium enrichment grades and the route of intake.

Thorium promotes lung, liver and kidney damage in BALB/c mouse via alterations in antioxidant systems.

Thorium (232Th), long lived (14.05 billion years) most stable thorium isotope, is thrice naturally abundant than uranium. 232Th occurs as rocky deposits and black monazite sands on the earth's crust geographically distributed in coastal South India and other places globally. Monazite sand comprises of cerium and large quantities of radioactive thorium. The environmental hazard lies in monazite rich area being termed as High Background Radiation Area (HBRA). In this study, we mimicked the HBRA under controlled chamber conditions using thorium oxalate as a thorium source for BALB/c mice exposure. Furthermore, sequential radio-disintegration of 232 Th leads to thoron (220Rn), the noble gas and other daughter products/progeny predominantly via alpha decay/emissions. Such progeny tend to attach to aerosol and dust particles having potential inhalation hazard followed by alpha emissions and damages that we evaluated in mouse lung tissues post thoron inhalation. Secondly, along with the radio disintegration and alpha emission, high energy gamma is also generated that can travel to various distant organs through the systemic circulation, as significant findings of our study as damages to the liver and kidney. The mechanistic findings include the damages to the hematological, immunological and cellular antioxidant systems along with activation of canonical NF-κß pathway via double stranded DNA damage.

Role of calcium ion channels and cytoskeletal proteins in Thorium-232 induced toxicity in normal human liver cells (WRL 68) and its validation in swiss mice.

Hepatic disorders reported in humans exposed to Thorium-232 (Th-232) rationalizes the present study investigating the toxicological response of normal human liver cells (WRL 68) and its validation in Swiss mice. Cell count analysis of WRL 68 cells-treated with Th-nitrate (1-200 µM) estimated IC50 of ∼24 µM (at 24 h) and 35 µM (at 48 h). Analysis of cell viability (trypan blue assay) showed the IC50 of ∼172 µM. Phase contrast bright-field microscopy revealed Th-induced morphological changes and cell-released microvesicle-like structures in extracellular space. Th-estimation by ICP-MS (Inductively-coupled plasma mass-spectrometry) showed uptake of Th by cells as a function of concentration and incubation time. Employing DTPA as a chelating agent in cell harvesting solution, cell-internalized/strongly-bound Th was estimated to be ∼42% of total incubated Th. Th-uptake studies in the presence of ion-channel specific inhibitors (e.g. nifedipine, thapsigargin) revealed the role of plasma membrane calcium channels and cytoplasmic calcium in modulating the Th-uptake. Transmission electron microscopy of Th-treated cells showed cell-derived extracellular vesicles, alterations in the shape and size of nucleus and mitochondria as well as cytoplasmic inclusions. The order of Th accumulation in various sub-cellular protein fractions was found to be as cytoskeleton (43%) > cytoplasmic (15%) > chromatin (7%) > nuclear (5%) & membrane (5%). Immunofluorescence analysis of WRL 68 cells showed that Th significantly altered the expression of cytoskeleton proteins (F-actin and keratin), which was further validated in liver tissues of Swiss mice administered with Th-232. Findings herein highlight the role of calcium channels and cytoskeleton in Th-induced toxicity. Keywords: Thorium toxicity; Liver cells; Calcium channels; Sub-cellular targets, Cytoskeleton; Swiss Mice.

Phytotoxicity mechanism of the natural radionuclide thorium in Vicia faba.

Elucidation of the phytotoxic mechanisms of thorium (Th) is important for controlling Th accumulation in crops and improving the efficiency of phytoremediation. Here, we analyzed the subcellular distribution of Th in Vicia faba seedlings and the toxic reaction of seedlings to Th (5-40 µmol·L-1) at the subcellular and cellular levels. Increasing the phosphate level in the culture medium from 0.01 to 0.1 mmol·L-1 decreased the Th accumulation by the roots by 47-57%. Th was mainly distributed in the root cell walls (94-96%) and existed mainly in the form of residue (92-94%). Th accumulation in the root was similar to the changes observed for P, Ni, Cu, and Fe. High concentrations of Th (40 µmol·L-1) induced abnormal root growth and leaf photosynthetic metabolism. At the cellular level, Th (40 µmol·L-1) induced root edge cell death and inhibited root respiration and cell mitosis. SOD, POD and CAT activities were involved in the regulation of reactive oxygen species accumulation in the roots. Untargeted metabolomics identified 580 and 262 differentially expressed metabolites in roots and leaves. At the metabolic level, its toxicological mechanism involved a severe inhibition of the expression of nucleotides in roots and leaves.

Quantitative encapsulation and retention of 227Th and decay daughters in core-shell lanthanum phosphate nanoparticles.

Targeted alpha therapy (TAT) offers great promise for treating recalcitrant tumors and micrometastatic cancers. One drawback of TAT is the potential damage to normal tissues and organs due to the relocation of decay daughters from the treatment site. The present study evaluates La(227Th)PO4 core (C) and core +2 shells (C2S) nanoparticles (NPs) as a delivery platform of 227Th to minimize systemic distribution of decay daughters, 223Ra and 211Pb. In vitro retention of decay daughters within La(227Th)PO4 C NPs was influenced by the concentration of reagents used during synthesis, in which the leakage of 223Ra was between 0.4 ± 0.2% and 20.3 ± 1.1% in deionized water. Deposition of two nonradioactive LaPO4 shells onto La(227Th)PO4 C NPs increased the retention of decay daughters to >99.75%. The toxicity of the nonradioactive LaPO4 C and C2S NP delivery platforms was examined in a mammalian breast cancer cell line, BT-474. No significant decrease in cell viability was observed for a monolayer of BT-474 cells for NP concentrations below 233.9 µg mL-1, however cell viability decreased below 60% when BT-474 spheroids were incubated with either LaPO4 C or C2S NPs at concentrations exceeding 29.2 µg mL-1. La(227Th)PO4 C2S NPs exhibit a high encapsulation and in vitro retention of radionuclides with limited contribution to cellular cytotoxicity for TAT applications.

Living near an active U.S. military base in Iraq is associated with significantly higher hair thorium and increased likelihood of congenital anomalies in infants and children.

In Iraq, war contamination is the result of dispensed bombs, bullets, detonation of chemical and conventional weapons, and burn-pit emissions by US bases. Increases in congenital anomalies were reported from Iraqi cities post-2003. These cities were heavily bombed and encircled by US bases with burn-pits. Thorium is a radioactive compound and a direct depleted-uranium decay-product. Radioactive materials, including depleted uranium, are routinely stored in US bases and they have been shown to leak into the environment. We conducted a case-control study to investigate associations of residential proximity to Tallil Air Base, a US military base near Nasiriyah, as well as levels of uranium and thorium in hair and deciduous teeth with congenital anomalies. The study was based on a sample of 19 cases and 10 controls who were recruited during late Summer and early Fall of 2016. We developed mixed effects logistic regression models with village as the random effect, congenital anomaly as the outcome and distance to the US base and hair metal levels (one at a time) as the predictor variable, controlling for child's age, sex and paternal education. We also explored the mediation of the association between proximity to the base and congenital anomalies by hair metal levels. We found an inverse association between distance to Tallil Air Base and risk of congenital anomalies and hair levels of thorium and uranium. The results of our mediation analyses were less conclusive. Larger studies are necessary to understand the scope of war contamination and its impact on congenital anomalies in Iraq.

Thorium exerts hazardous effects on some neurotransmitters and thyroid hormones in adult male rats.

Assessment of the hazardous effects of thorium, a naturally radioactive element, on the nervous and endocrine systems, which are intimately involved in maintaining homeostasis, is important. In the present study, rats were divided into control and thorium groups and were decapitated after 2, 4, and 6 weeks. We observed that intraperitoneally injected thorium (6.3 mg/kg body weight) crossed the blood-brain barrier and was localized in the cerebellum, cerebral cortex, and hypothalamus of the rats in the given order. Thorium administration significantly decreased the GSH level and increased MDA, NO, and Fe3+ levels. Furthermore, thorium administration decreased NE and DA levels and induced fluctuations in 5-HT level. Thorium administration also increased serum TSH level, which in turn increased T4 and T3 levels. Together, these results indicate that thorium administration stimulates TSH secretion, which significantly increases T4 and T3 secretion from the thyroid gland. Moreover, these results indicate that thorium administration exerts hazardous effects on the neuroendocrine axis.

Evaluation of the effect of three constituent metals of monazita on the radiosensibility of human osteoblasts.

Thorium has gained notoriety in recent years, as a potential source of nuclear energy, substituting uranium in power plants. Monazite is an important source of thorium, as well of uranium and rare earths elements. Workers involved in the extraction and manipulation of this mineral are occupationally exposed to a range of metal mixtures containing thorium and to ionizing radiation. As an osteotropic substance, thorium is mostly deposited in bone tissue and may interfere in cellular radiosensitivity. A human osteoblast cell line was used to evaluate the effects of thorium (Th), cerium (Ce) and lanthanum (La) on cell radiosensivity, using proliferation as indicator. Assays were performed using cell cultures exposed to metals alone and metals combined with ionizing radiation. No stimulus of proliferation was observed when samples were exposed to metals or radiation alone. On the other hand, the metals were able to influence cell radiosensivity, in a concentration-dependent manner when metals and radiation were applied simultaneously. Samples irradiated and exposed to metals combinations revealed an interaction between them in all the tested arrangements (Th-Ce, Th-La, Th-Ce-La). All interactions proved to be of the antagonist type relative to the proliferation indicator, with a higher degree seen for the Th-Ce association. Such results showed the possibility that metal mixtures together with radiation may produce combined effects on osteoblasts, through modifications on the degree of radiosensivity. The results indicate the possibility of an enhancement in occupational risk for workers that manipulate monazite byproducts. Thus, the development of risk assessment models that include the evaluation of mixtures and their cytotoxic and radiotoxic effects on tissues and organs must be highlighted.

Frequency of micronuclei among persons resident in the vicinity of a mineral sand processing factory in Pulmoddai, Sri Lanka.

Lanka Mineral Sands Ltd (LMS), a government-owned company, has been mining mineral sands including monazite which contains thorium (Th) at Pulmoddai, Sri Lanka since 1957. Th emits alpha particles on decay and gamma rays are emitted by the daughter products. The cytokinesis-blocked micronucleus (MN) assay is popular for large scale radiation exposure studies as it is an easy, fast and reliable method of biodosimetry. The objective of the study was to determine the frequency of micronuclei among persons residing in the vicinity of LMS. A cross-sectional study was conducted from November 2012 to September 2016 among persons 35-45 years of age to evaluate the frequency of micronuclei in peripheral blood lymphocytes. Fifty-three employees of LMS factory, 25 residents within 5 km from LMS, 25 residents 20-25 km from LMS and 29 residents from >50 km away from LMS were included in the study. The highest median frequency of micronuclei per 1000 binucleated (BN) cells was in the group residing within 5 km from LMS with a median (IQ range) of 0.67 (0.17-2.17). The median (IQ range) of MN frequency of employees of LMS, residents 20-25 km from LMS and residents >50 km from LMS were 0.66 (0.16-1.16), 0.33 (0.00-0.67) and 0.33 (0.33-0.67), respectively. There was no significant difference in the MN frequency between employees of LMS and the group residing within 5 km from LMS. Being a resident of Pulmoddai and being exposed to X-rays were significant predictors of MN frequency. Persons residing within 5 km from LMS had a higher risk of MN formation irrespective of being employed at LMS.

The hematological and biochemical changes in rats exposed to britholite mineral.

The present study was to investigate the alteration of biochemical and hematological parameters on the rats exposed to natural radiation caused by britholite mineral (REE, Ca, Na)5 [(Si,P)O4]3(OH,F) within 15 days. Britholite was collected from Kuluncak mining area, Malatya, bearing radioactive 232Th isotope (average 2.68% ThO2), which is rare earth elements found high amounts. Britholite is toxic for the living animal and human and emits the radiation to natural surroundings about 0.8R/h due to its radioactive 232Th properties. In this study, animals were divided to two groups, one groups exposed to 232Th, the other group was served as control group. All animals were fed with same food and water during the experimental study (15 days). After 15 days, the hematologic and biochemical parameters (Na, K, Ca, P, Cl, Mg, glucose, cholesterol, HDL, LDL, albumin, Uric acid, AST, ALT, total protein, Fe, urea and creatine level and hormonal parameters (TSH, T3 and T4)) were analyzed The levels of serum triglyceride in the ionizing radiation group generated by 232Th isotope (p < 0.05) statistically significantly increased compared with control group value. Lymphocytes, TSH, T3 and T4 decreased in the ionizing radiation group generated by 232Th isotope while neutrophils increased in the ionizing radiation group generated by 232Th isotope. The rats exposed to ionizing radiation generated by 232Th isotope caused significant changes in the hematological and biochemical parameters and the most significantly alteration was observed in the thyroid hormonal levels, which might be due to high radiation doses within short time. These results should be kept in mind to maintain healthy life in people who lives in britholite mineral vicinity.

Influence of Speciation of Thorium on Toxic Effects to Green Algae Chlorella pyrenoidosa.

Thorium (Th) is a natural radioactive element present in the environment and has the potential to be used as a nuclear fuel. Relatively little is known about the influence and toxicity of Th in the environment. In the present study, the toxicity of Th to the green algae Chlorella pyrenoidosa (C. pyrenoidosa) was evaluated by algal growth inhibition, biochemical assays and morphologic observations. In the cultural medium (OECD TG 201), Th(NO3)4 was transformed to amorphous precipitation of Th(OH)4 due to hydrolysis. Th was toxic to C. pyrenoidosa, with a 96 h half maximum effective concentration (EC50) of 10.4 µM. Scanning electron microscopy shows that Th-containing aggregates were attached onto the surface of the algal cells, and transmission electron microscopy indicates the internalization of nano-sized Th precipitates and ultrastructural alterations of the algal cells. The heteroagglomeration between Th(OH)4 precipitation and alga cells and enhanced oxidative stress might play important roles in the toxicity of Th. To our knowledge, this is the first report of the toxicity of Th to algae with its chemical species in the exposure medium. This finding provides useful information on understanding the fate and toxicity of Th in the aquatic environment.

[Impact of Radioactive Elements on Microbial Complexes in Cryogenic Soils of Yakutia].

It has been found that microorganisms in cryogenic soils of Yakutia are resistant to the long-term impact of cesium and thorium. The number of microorganisms in the studied ecological-trophic groups does not depend on the concentrations of radioactive elements. Differences in the number of microorganisms are determined by the physicochemical conditions that are created in different horizons of the soils studied. The long-term impact of radiation (for 36 and 66 years) on microorganisms inhabiting the permafrost soils of Yakutia has developed their adaptive capacity to high concentrations of these radioactive elements.

Subcellular distribution and chemical forms of thorium in Brassica juncea var. foliosa.

Brassica juncea var. foliosa (B. juncea var. foliosa) is a promising species for thorium (Th) phytoextraction due to its large biomass, fast growth rate and high tolerance toward Th. To further understand the mechanisms of Th tolerance, the present study investigated the subcellular distribution and chemical forms of Th found in B. juncea var. foliosa Our results indicated that in both roots and leaves, Th contents in different parts of the cells follow the order of cell wall > membranes and soluble fraction > organelles. In particular, Transmission Electron Microscope (TEM) analysis showed that Th was abundantly located in cell walls of the roots. Additionally, when plants were exposed to different concentrations of Th, we have found that Th existed in B. juncea var. foliosa with different chemical forms. Much of the Th extracted by 2% acetic acid (HAc), 1 M NaCl and HCl in roots with the percentage distribution varied from 47.2% to 62.5%, while in leaves, most of the Th was in the form of residue and the subdominant amount of Th was extracted by HCl, followed by 2% HAc. This suggested that Th compartmentation in cytosol and integration with phosphate or proteins in cell wall might be responsible for the tolerance of B. juncea var. foliosa to the stress of Th.

The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology.

Due to increasing use of lanthanides/actinides in nuclear and civil applications, understanding the impact of these metal ions on human health and environment is a growing concern. Hemoglobin (Hb), which occurs in all the kingdom of living organism, is the most abundant protein in human blood. In present study, effect of lanthanides and actinides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] on the structure and function of Hb has been investigated. Results showed that these metal ions, except Ce(IV) interacted with carbonyl and amide groups of Hb, which resulted in the loss of its alpha-helix conformation. However, beyond 75µM, these ions affected heme moiety. Metal-heme interaction was found to affect oxygen-binding of Hb, which seems to be governed by their closeness with the charge-to-ionic-radius ratio of iron(III). Consistently, Ce(IV) being closest to iron(III), exhibited a greater effect on heme. Binding constant and binding stoichiometry of Th(IV) were higher than that of U(VI). Experiments using aquatic midge Chironomus (possessing human homologous Hb) and human blood, further validated metal-Hb interaction and associated toxicity. Thus, present study provides a biochemical basis to understand the actinide/lanthanide-induced interference in heme, which may have significant implications for the medical and environmental management of lanthanides/actinides toxicity.

Effect of Uranium and Thorium Radionuclides on Biochemical Characteristics of Duschekia fruticosa in "Soil-Plant" System.

The biochemical characteristics of Duschekiafruticosa, grown for a long time under a variety of exposure doses of natural background radiation (up to 150 µR/h) was studied. Uranium was found to make the dominant contribution to the y-background exposure doses. The pH-values and the content of organic matter in soils within the surveyed territory remained unchanged. Accumulation of radionuclides of uranium and thorium in the "soil-plant" system was studied. It is shown for the D. fruticosa that U and Th uptake decreased with y-background increasing. Study of anti-free radical and anti-peroxide cells' protection system indicated a balanced activity of prooxidant-antioxidant systems in the cells of the D. fruticosa leaves. The combined effect of incorporated uranium and thorium is accompanied by a significant increase in chlorophyll content in D. fruticosa.

Transfer Rates of ²³8U and ²³²Th for E. globulus, A. mearnsii, H. filipendula and Hazardous Effects of the Usage of Medicinal Plants From Around Gold Mine Dump Environs.

Medicinal plant consumption can be a source of human exposure to radioactive elements such as (238)U and (232)Th, which can lead to internal radiation doses. The uptake of (238)U and (232)Th from soils to the leaf samples of three different medicinal plant species (Eucalyptus globulus, Acacia mearnsii and Hyparrhenia filipendula) from the purlieu of the Princess gold mine dump, an abandoned contaminated tailings storage site (TSS), located at longitude 27°55'00″E and latitude 26°09'30″S in Davidsonville (Roodepoort, west of Johannesburg, South Africa) was measured. This was done using ICP-MS spectrometry and substantial differences were observed in the soil-plant transfer factor (TF) values between these radionuclides. The plant species E. globulus exhibited the highest uptake of (238)U, with an average TF of 3.97, while that of H. filipendula was 0.01 and the lowest TF of 0.15 × 10(-2) was measured for A. mearnsii. However, in the case of (232)Th, the highest average TF was observed for A. mearnsii (0.29), followed by E. globulus (0.10) and lowest was measured for H. filipendula (0.27 × 10(-2)). The ratio of TF average value i.e., (238)U to (232)Th in the soil-plant leaves was 38.05 for E. globulus, 0.01 for A. mearnsii and 4.38 for H. filipendula.

Determination of (238)U, (232)Th and (40)K activity concentrations in riverbank soil along the Chao Phraya river basin in Thailand.

The activity concentrations of (238)U, (232)Th and (40)K in riverbank soil along the Chao Phraya river basin was determined through gamma-ray spectrometry measurements made using a hyper-pure germanium detector in a low background configuration. The ranges of activity concentrations of (238)U, (232)Th and (40)K were found to be 13.9 â†” 76.8, 12.9 â†” 142.9 and 178.4 â†” 810.7 Bq kg(-1), respectively. The anthropogenic radionuclide, (137)Cs, was not observed in statistically significant amounts above the background level in the current study. The absorbed gamma dose rate in air at 1 m above the ground surface, the outdoor annual effective dose equivalent, the values of the radium equivalent activity and the external hazard index associated with all the soil samples in the present work were evaluated. The results indicate that the radiation hazard from primordial radionuclides in all soil samples from the area studied in this current work is not significant.

Modification of catalase and MAPK in Vicia faba cultivated in soil with high natural radioactivity and treated with a static magnetic field.

The effects of a static magnetic field (SMF) and high natural radioactivity (HR) on catalase and MAPK genes in Vicia faba were investigated. Soil samples with high natural radioactivity were collected from Ramsar in north Iran where the annual radiation absorbed dose from background radiation is higher than 20mSv/year. The specific activity of the radionuclides of (232)Th, (236)Ra, and (40)K was measured using gamma spectrometry. The seeds were planted either in the soil with high natural radioactivity or in the control soils and were then exposed to a SMF of 30mT for 8 days; 8h/day. Levels of expression of catalase and MAPK genes, catalase activity and H2O2 content were evaluated. The results demonstrated significant differences in the expression of catalase and MAPK genes in SMF- and HR-treated plants compared to the controls. An increase in catalase activity was accompanied by increased expression of its gene and accumulation of H2O2. Relative expression of the MAPK gene in treated plants, however, was lower than those of the controls. The results suggest that the response of V. faba plants to SMF and HR may be mediated by modification of catalase and MAPK.

The role of chemical interactions between thorium, cerium, and lanthanum in lymphocyte toxicity.

Thorium, cerium, and lanthanum are metals present in several types of minerals, the most common of which is monazite. Cerium and lanthanum are elements in the lanthanides series. Thorium, an actinide metal, is a hazardous element due to its radioactive characteristics. There is a lack of information describing the possible chemical interactions among these elements and the effects they may have on humans. Toxicological analyses were performed using cell viability, cell death, and DNA damage assays. Chemical interactions were evaluated based on the Loewe additivity model. The results indicate that thorium and cerium individually have no toxic effects on lymphocytes. However, thorium associated with lanthanum increases the toxicity of this element, thereby reducing the viability of lymphocytes at low concentrations of metals in the mixture.