Health effects triggered by tritium: how do we get public understanding based on scientifically supported evidence?

The Commission for 'Corresponding to Radiation Disaster of the Japanese Radiation Research Society' formulated a description of potential health effects triggered by tritium. This was in response to the issue of discharging water containing tritium filtered by the Advanced Liquid Processing System (ALPS), generated and stored in Fukushima Daiichi Nuclear Power Station after the accident. In this review article, the contents of the description, originally provided in Japanese, which gives clear and detailed explanation about potential health effects triggered by tritium based on reliable scientific evidence in an understandable way for the public, were summarized. Then, additional information about biochemical or environmental behavior of organically bound tritium (OBT) were summarized in order to help scientists who communicate with general public.

Epidemiological Study of Mortality Among Workers Exposed to Tritium in France.

Workers of the Commissariat for Atomic Energy and Alternative Energy (CEA) may be potentially exposed to tritium over long periods. We aimed to assess the effect of tritium exposure on mortality in a cohort of employees followed by radiotoxicological monitoring. A total of 1,746 employees who worked for at least six months at one of three CEA centers were included between 1962 and 2011 (median follow-up 29.6 years). The cumulative dose of tritium was based on the quantification of tritium present from urinary excretion monitoring data from the beginning of occupational exposure to the end of such exposure or December 2011. Mortality was first compared to that in the French population using the standardized mortality ratio (SMR). Then, mortality risk ratios (RRs) per category of cumulative dose of tritium were estimated using categorical Poisson models adjusted for age at the onset of exposure, age, calendar period, sex, smoking, employment status, CEA center, and taking into account the number of person-years. The main causes of mortality were tumors (48%) and cardiovascular diseases (20%). The comparison of mortality within the cohort to that in the French population highlighted a lower rate for all-cause mortality and that due to cancer, related to the healthy worker effect bias. The regression model showed no effect of cumulative dose on all-cause mortality. The risk of death for most malignancies was positive, but not significant for the higher classes of doses relative to the reference class. The highest risk (not significant) was present for the class of higher doses for tumors of the larynx, trachea, bronchi and lung. The risk was significant for the higher doses for tumors of the pancreas and bladder (based on a limited number of cases: five and six deaths, respectively). Significantly more smokers died from tumors of the respiratory system than non-smokers, as expected. We were unable to show an effect of cumulative tritium dose due to the small size of the cohort and the low exposure level. However, our study underlines the need to continue following tritium-exposed workers and conducting multicenter studies.

Estimation of radiation dose from ingested tritium in humans by administration of deuterium-labelled compounds and food.

Radiation doses from organically bound tritium (OBT) in foods have been a major concern near nuclear facilities. The current dose coefficient for OBT is calculated using a standard model from the International Commission on Radiological Protection, in which some biokinetic values are not based on human metabolic data. Here, the biokinetics of ingested OBT, and radiation doses from them, were estimated by administering labelled compounds and foods to volunteers, using a deuterium (D) tracer as a substitute for tritium. After the administration of D-labelled glucose, alanine, palmitic acid, or soybean, the D/H ratios in urine were measured for up to 119 days, and the biokinetic parameter values were determined for OBT metabolism. The slow degradation rates of OBT could not be obtained, in many volunteers administered glucose and alanine. The estimated committed effective dose for 1 Bq of tritium in palmitic acid varied from 3.2 × 10-11 to 3.5 × 10-10 Sv Bq-1 among volunteers and, for those administered soybean, it varied from 1.9 × 10-11 to 1.8 × 10-10 Sv Bq-1. These results suggest that OBT, present in some ingested ingredients, gives higher doses than the current dose coefficient value of 4.2 × 10-11 Sv Bq-1.

Prolonged effect associated with inflammatory response observed after exposure to low dose of tritium ß-rays.

Background: The value of relative biological effectiveness of tritium increases at low dose domain, which results in the suspicion of weighting factor of 1 for tritium after low dose exposure. Thus, present study was carried out to analyze the differences in the cellular responses at early and late period between low dose of tritium ß-rays and γ-rays radiation.Methods: MCF-10A cells were exposed to low dose of tritium ß-rays or γ-rays, then cellular behaviors, such as DNA double strand breaks (DSBs), apoptosis, reactive oxygen species (ROS) level and inflammatory relevant gene expression were analyzed at early and late period post-irradiation.Results: At early period the elimination of DSB foci produced by HTO is longer than γ-rays. High ROS level and a continual change of cell cycle distribution are observed in HTO radiation group. Based on the results of RNA sequencing, Ingenuity Pathway Analysis (IPA) indicates TNFR1 signaling and production of nitric oxide and ROS are activated as an acute response at 24 h post radiation. Moreover, it also shows a disturbance in cholesterol biosynthesis. The results of 30 days point that there is a lasting active inflammatory response, accompanying with a persistent high expression of relevant cytokines, such as TNF and IL1R.Conclusion: Compared to an acute response induced by γ-rays, a persistent inflammatory response exists in HTO-irradiated cells when cultured for 30 days, which might be related to accumulation of tritium in the form of organically bound tritium (OBT) in cellular DNA or lipids.

Estimation of Biological Effects of Tritium.

Nuclear fusion technology is expected to create new energy in the future. However, nuclear fusion requires a large amount of tritium as a fuel, leading to concern about the exposure of radiation workers to tritium beta radiation. Furthermore, countermeasures for tritium-polluted water produced in decommissioning of the reactor at Fukushima Daiichi Nuclear Power Station may potentially cause health problems in radiation workers. Although, internal exposure to tritium at a low dose/low dose rate can be assumed, biological effect of tritium exposure is not negligible, because tritiated water (HTO) intake to the body via the mouth/inhalation/skin would lead to homogeneous distribution throughout the whole body. Furthermore, organically-bound tritium (OBT) stays in the body as parts of the molecules that comprise living organisms resulting in long-term exposure, and the chemical form of tritium should be considered. To evaluate the biological effect of tritium, the effect should be compared with that of other radiation types. Many studies have examined the relative biological effectiveness (RBE) of tritium. Hence, we report the RBE, which was obtained with radiation carcinogenesis classified as a stochastic effect, and serves as a reference for cancer risk. We also introduce the outline of the tritium experiment and the principle of a recently developed animal experimental system using transgenic mouse to detect the biological influence of radiation exposure at a low dose/low dose rate.

The risk of leukaemia in young children from exposure to tritium and carbon-14 in the discharges of German nuclear power stations and in the fallout from atmospheric nuclear weapons testing.

Towards the end of 2007, the results were published from a case-control study (the "KiKK Study") of cancer in young children, diagnosed <5 years of age during 1980-2003 while resident near nuclear power stations in western Germany. The study found a tendency for cases of leukaemia to live closer to the nearest nuclear power station than their matched controls, producing an odds ratio that was raised to a statistically significant extent for residence within 5 km of a nuclear power station. The findings of the study received much publicity, but a detailed radiological risk assessment demonstrated that the radiation doses received by young children from discharges of radioactive material from the nuclear reactors were much lower than those received from natural background radiation and far too small to be responsible for the statistical association reported in the KiKK Study. This has led to speculation that conventional radiological risk assessments have grossly underestimated the risk of leukaemia in young children posed by exposure to man-made radionuclides, and particular attention has been drawn to the possible role of tritium and carbon-14 discharges in this supposedly severe underestimation of risk. Both (3)H and (14)C are generated naturally in the upper atmosphere, and substantial increases in these radionuclides in the environment occurred as a result of their production by atmospheric testing of nuclear weapons during the late 1950s and early 1960s. If the leukaemogenic effect of these radionuclides has been seriously underestimated to the degree necessary to explain the KiKK Study findings, then a pronounced increase in the worldwide incidence of leukaemia among young children should have followed the notably elevated exposure to (3)H and (14)C from nuclear weapons testing fallout. To investigate this hypothesis, the time series of incidence rates of leukaemia among young children <5 years of age at diagnosis has been examined from ten cancer registries from three continents and both hemispheres, which include registration data from the early 1960s or before. No evidence of a markedly increased risk of leukaemia in young children following the peak of above-ground nuclear weapons testing, or that incidence rates are related to level of exposure to fallout, is apparent from these registration rates, providing strong grounds for discounting the idea that the risk of leukaemia in young children from (3)H or (14)C (or any other radionuclide present in both nuclear weapons testing fallout and discharges from nuclear installations) has been grossly underestimated and that such exposure can account for the findings of the KiKK Study.

Determination and maintenance of DE minimis risk for migration of residual tritium (3H) from the 1969 Project Rulison nuclear test to nearby hydraulically fractured natural gas wells.

The Project Rulison underground nuclear test was a proof-of-concept experiment that was conducted under the Plowshare Program in 1969 in the Williams Fork Formation of the Piceance Basin in west-central Colorado. Today, commercial production of natural gas is possible from low permeability, natural gas bearing formations like that of the Williams Fork Formation using modern hydraulic fracturing techniques. With natural gas exploration and production active in the Project Rulison area, this human health risk assessment was performed in order to add a human health perspective for site stewardship. Tritium (H) is the radionuclide of concern with respect to potential induced migration from the test cavity leading to subsequent exposure during gas-flaring activities. This analysis assumes gas flaring would occur for up to 30 d and produce atmospheric H activity concentrations either as low as 2.2 × 10 Bq m (6 × 10 pCi m) from the minimum detectable activity concentration in produced water or as high as 20.7 Bq m (560 pCi m), which equals the highest atmospheric measurement reported during gas-flaring operations conducted at the time of Project Rulison. The lifetime morbidity (fatal and nonfatal) cancer risks calculated for adults (residents and workers) and children (residents) from inhalation and dermal exposures to such activity concentrations are all below 1 × 10 and considered de minimis. The implications for monitoring production water for conforming health-protective, risk-based action levels also are examined.

Determination of in vitro lung solubility and intake-to-dose conversion factor for tritiated lanthanum nickel aluminum alloy.

A sample of tritiated lanthanum nickel aluminum alloy (LaNi4.25Al0.75 or LANA.75) similar to that used at the Savannah River Site Tritium Facilities was analyzed to estimate the particle size distribution of this metal tritide powder and the rate at which this material dissolves in the human respiratory tract after it is inhaled. This information is used to calculate the committed effective dose received by a worker after inhaling the material. These doses, which were calculated using the same methodology given in the U.S. Department of Energy Tritium Handbook, are presented as inhalation intake-to-dose conversion factors (DCF). The DCF for this metal tritide was determined to be 9.4 × 10 Sv Bq, which is less than the DCF for tritiated water. Therefore, the radiation worker bioassay programs designed for tritiated water are adequate to monitor for intakes of this material.

Quick management of accidental tritium exposure cases.

Removal half-life (RHL) of tritium is one of the best means for optimising medical treatment, reduction of committed effective dose (CED) and quick/easy handling of a large group of workers for medical treatment reference. The removal of tritium from the body depends on age, temperature, relative humidity and daily rainfall; so tritium removal rate, its follow-up and proper data analysis and recording are the best techniques for management of accidental acute tritium exposed cases. The decision of referring for medical treatment or medical intervention (MI) would be based on workers' tritium RHL history taken from their bodies at the facilities. The workers with tritium intake up to 1 ALI shall not be considered for medical treatment as it is a derived limit of annual total effective dose. The short-term MI may be considered for tritium intake of 1-10 ALI; however, if the results show intake ≥100 ALI, extended strong medical/therapeutic intervention may be recommended based on the severity of exposure for maximum CED reduction requirements and annual total effective dose limit. The methodology is very useful for pressurized heavy water reactors (PHWRs) which are mainly operated by Canada and India and future fusion reactor technologies. Proper management will optimise the cases for medical treatment and enhance public acceptance of nuclear fission and fusion reactor technologies.

A comparison of the mutagenic and apoptotic effects of tritiated water and acute or chronic caesium-137 gamma exposure on spleen T lymphocytes on normal and p53-deficient mice.

PURPOSE: This study was carried out to compare the mutagenic effects on spleen T lymphocytes of mice exposed to tritiated water (HTO) and chronic or acute (137)Cs gamma irradiation. MATERIALS AND METHODS: p53 wild type (p53(+/+)) and p53 null type (p53(-/-)) mice were exposed to a total dose of 3 Gy of HTO, chronic (137)Cs and acute (137)Cs. RESULTS: In spontaneous T-cell receptor (TCR) variant fractions and fractions following exposure to HTO, chronic (137)Cs and acute (137)Cs, TCR variant fractions in p53(+/+) mice were 5.9 x 10(-4), 9.8 x 10(-4), 6.4 x 10(-4) and 20.1 x 10(-4), respectively. In contrast, those fractions were increased in p53(-/-) mice to 11.2 x 10(-4), 18.8 x 10(-4), 15.7 x 10(-4) and 31.3 x 10(-4), respectively. The frequency of apoptotic cells of the spleen 12 h after HTO injection increased to 5.0% in p53(+/+) mice, but did not increase at all in p53(-/-) mice. CONCLUSIONS: When compared on the basis of induced TCR variant fractions in p53(-/-) mice, HTO (7.6 x 10(-4)) was 1.7 times more mutagenic than chronic (137)Cs (4.5 x 10(-4)), but 2.6 times less mutagenic than acute (137)Cs gamma irradiation (20.1 x 10(-4)).

[Cytogenetic examination of nuclear specialists exposed to chronic beta-radiation of tritium].

For the first time the cytogenetic examination of the group of nuclear specialists (79 persons) chronically exposed to tritium beta-radiation for a long period was carried out. The frequencies of unstable (conventional method) and stable (FISH-method) chromosome aberrations have been analyzed. 50 years after the beginning of working under the conditions of the increased radiation level the differences (in comparison with control values) were revealed for all cytogenetic parameters. The frequency of the radiation-specific markers (dicentrics and centric rings) exceeds more than 2-fold the control level. A significant but poor correlation between the frequency of unstable aberrations and the total absorbed dose (during the whole working period) was revealed. A retrospective estimation of irradiation doses for 14 nuclear workers was made by the frequency of stable chromosome aberrations. The obtained dose values ranged from 110 to 1250 mSv.

The hazards of tritium--revisited.

Tritium (3H) is the radioactive isotope of hydrogen, with a half-life of 12.3 years. It is created naturally in the atmosphere, and in higher annual rates in nuclear reactors and in nuclear weapon tests. This article surveys the properties of tritium, its biokinetics and its biological effectiveness. The safety levels of tritium have been a subject of dispute for many years, as many scientists consider that its doses and risks, as promulgated by the International Commission on Radiological Protection are, too low and should be at least doubled. Recent reports and evidence of increased cancer risks near nuclear installations that release tritium are discussed; these are of interest in view of new proposals to expand civil nuclear power.

Systematic review of experimental studies on the relative biological effectiveness of tritium.

Tritium ((3)H) is a radioactive isotope of hydrogen. A number of factors combine to create a good deal of interest in tritium doses, both to workers and to members of the public. Tritium is ubiquitous in environmental and biological systems and is very mobile due to its occurrence as water. In this study we systematically review experimental data relating to tritium exposure with a view to assessing its low dose limiting relative biological effectiveness (RBE(max)). Interpretation of published experimental studies is complicated by the fact that the reference radiations varied, and doses and dose rates were frequently much higher than those normally received by humans. The four available animal carcinogenicity studies gave RBE values of about 2.5 with chronically-delivered gamma-ray reference, and about 1.2 with chronically-delivered X-ray reference. However, because of problems associated with the design and interpretation of the experiments, we do not consider that these RBE values should be taken to apply to the induction of cancer at low doses (i.e. they should not be interpreted as RBE(max)). Combining the six studies with chronic gamma-ray reference, with adequate quantitative data that examined endpoints apart from cell survival and related endpoints, yields an aggregate RBE estimate of 2.19 (95% CI 2.04, 2.33); the analogous combined RBE estimate using the three studies with chronic X-ray reference groups is 1.17 (95% CI 0.96, 1.39). Again, problems with the design, in particular the range of doses used in some of these studies, mean that these RBE values should also probably not be interpreted as RBE(max).

Leukemia mortality among workers at the Savannah River Site.

The authors investigated associations between ionizing radiation and leukemia mortality among workers at the Savannah River Site (South Carolina). A total of 18,883 workers hired between 1950 and 1986 were followed through 2002 to ascertain causes of death. Estimates of radiation doses from external sources and internal tritium uptakes were derived from dosimetry records through 1999. Radiation dose-mortality trends were evaluated for leukemia, leukemia excluding chronic lymphocytic leukemia, and myeloid leukemia. A positive association was observed between leukemia mortality and radiation dose under a 3-year lag assumption (excess relative rate/10 mSv = 0.04, 90% confidence interval: -0.00, 0.12). The association was of larger magnitude for leukemia excluding chronic lymphocytic leukemia (excess relative rate/10 mSv = 0.08, 90% confidence interval: 0.01, 0.20) and myeloid leukemia (excess relative rate/10 mSv = 0.12, 90% confidence interval: 0.02, 0.35). Compared with males, females had less complete dosimetry information; when analyses were restricted to males, the estimated association for each cause of death increased slightly in magnitude and goodness of fit. Exposures accrued 3-15 years prior were more strongly related to leukemia than exposures in the more distant past. This study provides evidence of positive associations between radiation dose and leukemia mortality among Savannah River Site workers. The temporal patterns of association appear consistent with those in studies of populations exposed at higher dose rates.

Effect of pre-exposure to beta rays of tritium on some biochemical parameters measured in organs of rats subsequently irradiated with fast neutrons.

The experiment examined biological responses produced by combined sequential exposure to low-level tritium contamination, followed by challenging irradiation with fast neutrons. Modifications of endogenous antioxidant potential of different organs in rats were discussed in relation to tissue radiosensitivity. Rats pre-contaminated to 7 cGy and 35 cGy have been additionally irradiated to 1 Gy with fast neutrons. Lipid peroxide level was determined in liver, kidney, small intestine, spleen, bone marrow, and plasma. Reduced glutathione (GSH) level and glucose-6-phosphate dehydrogenase (G6PDH) activity were determined in erythrocytes. An in vitro thymidine uptake assay was performed in isolated bone marrow cells. The lipid peroxide level decreased significantly only in liver and kidney from rats pre-exposed to 35 cGy. For small intestine and spleen, tissues of comparatively higher radiosensitivity, no induced radioprotection was observed, as reflected in the homeostasis of the lipid peroxides. The same behavior was observed in bone marrow, the most radiosensitive tissue studied. However, the bone marrow thymidine-incorporation assay revealed a possible adaptive-type reaction in rats pre-exposed to 35 cGy. We conclude that for radiosensitive tissues pre-exposure to chronic low doses of low linear energy transfer (LET) irradiation has no protective effect on their antioxidant status, whereas a protective effect is observed in radioresistent tissues.

Radiation protection by cysteamine against the lethal effects of intracellularly localized Auger electron, alpha- and beta-particle emitting radionuclides.

The mechanisms by which DNA-incorporated radionuclides impart lethal damage to mammalian cells were investigated by examining the capacity of cysteamine (MEA) to protect against lethal damage to V79 cells caused by unbound tritium (3H2O), DNA-incorporated 131/125I-iododeoxyuridine (IdU) and the alpha-particle emitter 210Po-citrate. Radiolabeled cells were maintained at 10.5 degrees C for 72 h in the absence or presence of MEA (0.65-2.6 mM) and the surviving fraction was determined. Protection against lethal damage caused by 3H2O, 131IdU or 125IdU and 210Po-citrate depended on the concentration of MEA with maximum protection at 1.3-1.9 mM. The dose modification factors obtained at 1.3 mM for the radiochemicals were 2.5 +/- 0.3, 1.8 +/- 0.2, 1.7 +/- 0.1 and 1.4 +/- 0.1, respectively. MEA provides more protection against indirect than direct effects of ionizing radiation, and indirect effects play a role in the radiotoxicity of Auger electron emitters incorporated into the DNA of mammalian cells.

Leukaemia in the vicinity of two tritium-releasing nuclear facilities: a comparison of the Kruemmel Site, Germany, and the Savannah River Site, South Carolina, USA.

In 1991, an increased rate of childhood leukaemia was reported from the small northern German community of Elbmarsch, which is located on the banks of the River Elbe opposite the Kruemmel nuclear power plant. Owing to the fact that the increase occurred six years after the start-up of the plant, radioactive discharges were suspected as being implicated in the development of the cases. Previous investigations have failed to identify any exposure which might be associated with the cluster. Nonetheless, concern regarding the increased tritium burden in the environment remains. To further assess the impact of tritium releases to the environment upon population cancer rates, the releases and leukaemia rates at the Savannah River site, USA, were compared with the Kruemmel site. Based on the data from 1991 to 1995, the incidence of childhood leukaemia in the vicinity of the Savannah River site was non-significantly less than expected compared with the significantly higher than expected rates close to the German plant. In contrast, tritium releases from the Savannah River site exceed those from the Kruemmel site by several orders of magnitude. The results of this observational study suggest that factors other than environmental tritium releases are associated with the increased number of leukaemia cases near the Kruemmel site.

Effects of prenatal low-dose beta radiation from tritiated water on learning and memory in rats and their possible mechanisms.

Pregnant adult Wistar rats were randomly divided into four groups. Three of these groups were irradiated with beta rays by a single intraperitoneal injection of tritiated water ((3)H(2)O) administered on the 13th day of gestation. The doses absorbed by their offspring were estimated to be 4.6, 9.2 and 27.3 cGy. The influence of radiation on the postnatal learning ability and memory behavior and on brain development of the offspring was investigated. The number of pyramidal cells (in areas CA1, CA2, CA3 and CA4) and neurons in the hippocampus of the offspring was also measured. In addition, the Ca(++) conductance of hippocampal pyramidal cells cultured in vitro was observed. The results showed that an exposure to 4.6 cGy could prolong avoidance response time significantly and decrease the number of hippocampal pyramidal cells in the CA1 area compared to controls. An exposure to 9.2 cGy significantly decreased the establishment of conditioned reflexes and the number of hippocampal pyramidal cells in the CA3 area. This exposure also induced the degeneration and malformation of hippocampal neurons cultured in vitro, in addition to decreasing the number of hippocampal neurons observed on each culture day. A dose of 27.3 cGy significantly decreased brain and body weights and the maximum electric conductance of Ca(++) in hippocampal pyramidal neurons. In general, dose-dependent effects were observed for most of the parameters assessed in the present study. Possible mechanisms are discussed.