Tritium: Its relevance, sources and impacts on non-human biota.

Tritium (3H) is a radioactive isotope of hydrogen that is abundantly released from nuclear industries. It is extremely mobile in the environment and in all biological systems, representing an increasing concern for the health of both humans and non-human biota (NHB). The present review examines the sources and characteristics of tritium in the environment, and evaluates available information pertaining to its biological effects at different levels of biological organisation in NHB. Despite an increasing number of publications in the tritium radiobiology field, there exists a significant disparity between data available for the different taxonomic groups and species, and observations are heavily biased towards marine bivalves, fish and mammals (rodents). Further limitations relate to the scarcity of information in the field relative to the laboratory, and lack of studies that employ forms of tritium other than tritiated water (HTO). Within these constraints, different responses to HTO exposure, from molecular to behavioural, have been reported during early life stages, but the potential transgenerational effects are unclear. The application of rapidly developing "omics" techniques could help to fill these knowledge gaps and further elucidate the relationships between molecular and organismal level responses through the development of radiation specific adverse outcome pathways (AOPs). The use of a greater diversity of keystone species and exposures to multiple stressors, elucidating other novel effects (e.g., by-stander, germ-line, transgenerational and epigenetic effects) offers opportunities to improve environmental risk assessments for the radionuclide. These could be combined with artificial intelligence (AI) including machine learning (ML) and ecosystem-based approaches.

Tritiated Steel Micro-Particles: Computational Dosimetry and Prediction of Radiation-Induced DNA Damage for In Vitro Cell Culture Exposures.

Biological effects of radioactive particles can be experimentally investigated in vitro as a function of particle concentration, specific activity and exposure time. However, a careful dosimetric analysis is needed to elucidate the role of radiation emitted by radioactive products in inducing cyto- and geno-toxicity: the quantification of radiation dose is essential to eventually inform dose-risk correlations. This is even more fundamental when radioactive particles are short-range emitters and when they have a chemical speciation that might further concur to the heterogeneity of energy deposition at the cellular and sub-cellular level. To this aim, we need to use computational models. In this work, we made use of a Monte Carlo radiation transport code to perform a computational dosimetric reconstruction for in vitro exposure of cells to tritiated steel particles of micrometric size. Particles of this kind have been identified as worth of attention in nuclear power industry and research: tritium easily permeates in steel elements of nuclear reactor machinery, and mechanical operations on these elements (e.g., sawing) during decommissioning of old facilities can result in particle dispersion, leading to human exposure via inhalation. Considering the software replica of a representative in vitro setup to study the effect of such particles, we therefore modelled the radiation field due to the presence of particles in proximity of cells. We developed a computational approach to reconstruct the dose range to individual cell nuclei in contact with a particle, as well as the fraction of "hit" cells and the average dose for the whole cell population, as a function of particle concentration in the culture medium. The dosimetric analysis also provided the basis to make predictions on tritium-induced DNA damage: we estimated the dose-dependent expected yield of DNA double strand breaks due to tritiated steel particle radiation, as an indicator of their expected biological effectiveness.

Cyto-Genotoxicity of Tritiated Stainless Steel and Cement Particles in Human Lung Cell Models.

During the decommissioning of nuclear facilities, the tritiated materials must be removed. These operations generate tritiated steel and cement particles that could be accidentally inhaled by workers. Thus, the consequences of human exposure by inhalation to these particles in terms of radiotoxicology were investigated. Their cyto-genotoxicity was studied using two human lung models: the BEAS-2B cell line and the 3D MucilAirTM model. Exposures of the BEAS-2B cell line to particles (2 and 24 h) did not induce significant cytotoxicity. Nevertheless, DNA damage occurred upon exposure to tritiated and non-tritiated particles, as observed by alkaline comet assay. Tritiated particles only induced cytostasis; however, both induced a significant increase in centromere negative micronuclei. Particles were also assessed for their effects on epithelial integrity and metabolic activity using the MucilAirTM model in a 14-day kinetic mode. No effect was noted. Tritium transfer through the epithelium was observed without intracellular accumulation. Overall, tritiated and non-tritiated stainless steel and cement particles were associated with moderate toxicity. However, these particles induce DNA lesions and chromosome breakage to which tritium seems to contribute. These data should help in a better management of the risk related to the inhalation of these types of particles.

The METREPOL criteria-are they still relevant?

The medical management of radiation accidents manual on the acute radiation syndrome proposed a successful strategic approach to diagnosing and treating acute radiation syndrome: the response category concept. Based on clinical and laboratory parameters, this approach aimed to assess damage to critical organ systems as a function of time, categorising different therapeutical approaches. After 20 years of its publication, the following paper attempts to provide a broad overview of this important document and tries to respond if proposed criteria are still relevant for the medical management of radiation-induced injuries. In addition, a critical analysis of its limitations and perspectives is proposed.

Basic concepts of radiation emergency medicine.

Nuclear and radiological accidents are not frequent but may lead to major consequences in the population. For the health systems, the need to handle a large number of victims will probably remain as an exception. However, a high number of affected victims can be expected in some terrorist scenarios. In addition, medical accidents in radiotherapy, fluoroscopy and diagnostic radiology have increased the number of patients with severe radiation injuries considerably, especially in developed countries. Given the increased use of ionising radiation for industrial and medical purposes and new technological applications emerging, the number of accidents may increase in the future. Consequently, the early identification and adequate management of these emergencies is a priority, as well as the need for medical preparedness, requiring knowledge about various emergency scenarios and planning appropriate responses to them before they occur. Unfortunately, medical professionals have a substantial knowledge gap in identifying and treating injured persons affected by ionising radiation. As managing radiation accidents is a very challenging process, exercises must be carried out to organise a well-trained multidisciplinary group of professionals to manage any radiation accident properly. Efforts on a continuously updated guidance system should be developed. In addition, new approaches to foster sustainable interdisciplinary and international cooperative networks on radiation injuries are necessary. Lessons learned from past nuclear and radiological emergencies have significantly contributed to strengthening scientific knowledge and increasing the available medical information on the effects of ionising radiation in the human body. In this context, radiation emergency medicine has emerged as a discipline that contributes to the diagnosis, treatment, medical follow-up and prognosis of persons affected by radiation injuries in a nuclear or a radiological emergency. In this paper, we review some relevant concepts related to the medical preparedness and multidisciplinary response required to attend to persons affected by these emergencies.

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects.

Tritium has been receiving worldwide attention, particularly because of its production and use in existing fission reactors and future nuclear fusion technologies, leading to an increased risk of release in the environment. Linking human health effects to low-dose tritium exposures presents a challenge for many reasons. Among these: biological effects strongly depend on the speciation of tritiated products and exposure pathway; large dosimetric uncertainties may exist; measurements using in vitro cell cultures generally lack a description of effects at the tissue level, while large-scale animal studies might be ethically questionable and too highly demanding in terms of resources. In this context, three-dimensional models of the human airway epithelium are a powerful tool to investigate potential toxicity induced upon inhalation of radioactive products in controlled physiological conditions. In this study we exposed such a model to tritiated water (HTO) for 24 h, with a range of activity levels (up to ∼33 kBq µl-1 cm-2). After the exposures, we measured cell viability, integrity of epithelial layer and pro-inflammatory response at different post-exposure time-points. We also quantified tritium absorption and performed dosimetric estimates considering HTO passage through the epithelial layer, leading to reconstructed upper limits for the dose to the tissue of less than 50 cGy cumulative dose for the highest activity. Upon exposure to the highest activity, cell viability was not decreased; however, we observed a small effect on epithelial integrity and an inflammatory response persisting after seven days. These results represent a reference condition and will guide future experiments using human airway epithelium to investigate the effects of other peculiar tritiated products.

In Vitro Analysis of the Effects of ITER-Like Tungsten Nanoparticles: Cytotoxicity and Epigenotoxicity in BEAS-2B Cells.

Tungsten was chosen as a wall component to interact with the plasma generated by the International Thermonuclear Experimental fusion Reactor (ITER). Nevertheless, during plasma operation tritiated tungsten nanoparticles (W-NPs) will be formed and potentially released into the environment following a Loss-Of-Vacuum-Accident, causing occupational or accidental exposure. We therefore investigated, in the bronchial human-derived BEAS-2B cell line, the cytotoxic and epigenotoxic effects of two types of ITER-like W-NPs (plasma sputtering or laser ablation), in their pristine, hydrogenated, and tritiated forms. Long exposures (24 h) induced significant cytotoxicity, especially for the hydrogenated ones. Plasma W-NPs impaired cytostasis more severely than the laser ones and both types and forms of W-NPs induced significant micronuclei formation, as shown by cytokinesis-block micronucleus assay. Single DNA strand breaks, potentially triggered by oxidative stress, occurred upon exposure to W-NPs and independently of their form, as observed by alkaline comet assay. After 24 h it was shown that more than 50% of W was dissolved via oxidative dissolution. Overall, our results indicate that W-NPs can affect the in vitro viability of BEAS-2B cells and induce epigenotoxic alterations. We could not observe significant differences between plasma and laser W-NPs so their toxicity might not be triggered by the synthesis method.

Uranium in drinking-water: a unique case of guideline value increases and discrepancies between chemical and radiochemical guidelines.

BACKGROUND: Uranium represents a unique case for an element naturally present in the environment, as its chemical guideline value in drinking water significantly increased from 2 µg/L in 1998 up to 15 µg/L in 2004 and then to 30 µg/L in 2011, to date corresponding to a multiplication factor of 15 within a period of just 13 years. OBJECTIVES: In this commentary we summarize the evolution of uranium guideline values in drinking-water based on both radiological and chemical aspects, emphasizing the benefit of human studies and their contribution to recent recommendations. We also propose a simpler and better consistency between radiological and chemical values. DISCUSSION: The current chemical guideline value of 30 µg/L is still designated as provisional because of scientific uncertainties regarding uranium toxicity. During the same period, the radiological guideline for (238)U increased from 4 Bq/L to 10 Bq/L while that for (234)U decreased from 4 Bq/L to 1 Bq/L. These discrepancies are discussed here, and a value of 1 Bq/L for all uranium isotopes is proposed to be more consistent with the current chemical value of 30 µg/L. CONCLUSION: Continuous progress in the domains of toxicology and speciation should enable a better interpretation of the biological effects of uranium in correlation with epidemiological human studies. This will certainly aid future proposals for uranium guideline values.