Levels of naturally occurring radioisotopes in local and imported bottled drinking water available in Québec City, Canada.

Consumption of local and imported bottled water in Canada has greatly increased during the past three decades. While the presence of natural radioactivity is often overlooked when dealing with the water quality of these bottled products, it could contribute substantially to the uptake of radionuclides especially when sourced from regions with higher radioactivity levels compared to where it is consumed. In this study, the activity of several naturally occurring radionuclides (i.e., 210Po, 226,228Ra, 230,232Th, 234,235,238U) were measured in bottled water available in Québec, Canada after sample pretreatment and analysis by either radiometric or mass spectrometry approaches. 230,232Th and 228Ra concentrations were below minimum detectable activity levels in all samples tested. Analytical results for 234U, 235U, 238U, and 226Ra showed concentrations that ranged from 0.38 to 115 mBq/L, (2.2-313) x 10-2 mBq/L, 0.48-58.4 mBq/L, and 1.1-550 mBq/L, respectively. 210Po was detected in only 5 samples and its activity ranged from 2 to 26 mBq/L. To determine variability in activity within brands, the same brands of bottled water were purchased during two consecutive years and analyzed. The possible radiological impact of the consumption of these types of water was assessed based on different drinking habit scenarios. Some of the imported water brands showed higher activity concentrations than local sources or tap water, suggesting that individuals drinking predominantly imported bottled water would receive a higher radiation dose than those who drink mainly local water.

Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice.

Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated dose, dose rate and time-dependent effects in a dose range of 0.005 to 2 Gy on immune parameters after whole body irradiation (IR) using a pro-inflammatory (ApoE-/-) and a wild type mouse model. Long-term effects on spleen function (proliferation, monocyte expression) were analyzed 3 months, and short-term effects on immune plasma parameters (IL6, IL10, IL12p70, KC, MCP1, INFγ, TGFß, fibrinogen, sICAM, sVCAM, sE-selectin/CD62) were analyzed 1, 7 and 28 days after Co60 γ-irradiation (IR) at low dose rate (LDR, 0.001 Gy/day) and at high dose rate (HDR). In vitro measurements of murine monocyte (WEHI-274.1) adhesion and cytokine release (KC, MCP1, IL6, TGFß) after low-dose IR (150 kV X-ray unit) of murine endothelial cell (EC) lines (H5V, mlEND1, bEND3) supplement the data. RT-PCR revealed significant reduction of Ki67 and CD68 expression in the spleen of ApoE-/- mice after 0.025 to 2 Gy exposure at HDR, but only after 2 Gy at LDR. Plasma levels in wild type mice, showed non-linear time-dependent induction of proinflammatory cytokines and reduction of TGFß at doses as low as 0.005 Gy at both dose rates, whereas sICAM and fibrinogen levels changed in a dose rate-specific manner. In ApoE-/- mice, levels of sICAM increased and fibrinogen decreased at both dose rates, whereas TGFß increased mainly at HDR. Non-irradiated plasma samples revealed significant age-related enhancement of cytokines and adhesion molecules except for sICAM. In vitro data indicate that endothelial cells may contribute to systemic IR effects and confirm changes of adhesion properties suggested by altered sICAM plasma levels. The differential immunomodulatory effects shown here provide insights in inflammatory changes occurring at doses far below standard anti-inflammatory therapy and are of particular importance after diagnostic and chronic environmental exposures.

Thresholds for carcinogens.

Current regulatory cancer risk assessment principles and practices assume a linear dose-response relationship-the linear no-threshold (LNT) model-that theoretically estimates cancer risks occurring following low doses of carcinogens by linearly extrapolating downward from experimentally determined risks at high doses. The two-year rodent bioassays serve as experimental vehicles to determine the high-dose cancer risks in animals and then to predict, by extrapolation, the number of carcinogen-induced tumors (tumor incidence) that will arise during the lifespans of humans who are exposed to environmental carcinogens at doses typically orders of magnitude below those applied in the rodent assays. An integrated toxicological analysis is conducted herein to reconsider an alternative and once-promising approach, tumor latency, for estimating carcinogen-induced cancer risks at low doses. Tumor latency measures time-to-tumor following exposure to a carcinogen, instead of tumor incidence. Evidence for and against the concept of carcinogen-induced tumor latency is presented, discussed, and then examined with respect to its relationship to dose, dose rates, and the dose-related concepts of initiation, tumor promotion, tumor regression, tumor incidence, and hormesis. Considerable experimental evidence indicates: (1) tumor latency (time-to-tumor) is inversely related to the dose of carcinogens and (2) lower doses of carcinogens display quantifiably discrete latency thresholds below which the promotion and, consequently, the progression and growth of tumors are delayed or prevented during a normal lifespan. Besides reconciling well with the concept of tumor promotion, such latency thresholds also reconcile favorably with the existence of thresholds for tumor incidence, the stochastic processes of tumor initiation, and the compensatory repair mechanisms of hormesis. Most importantly, this analysis and the arguments presented herein provide sound theoretical, experimental, and mechanistic rationales for rethinking the foundational premises of low-dose linearity and updating the current practices of cancer risk assessment to include the concept of carcinogen thresholds.

Relative Biological Effectiveness and Non-Poissonian Distribution of Dicentric Chromosome Aberrations following Californium-252 Neutron Exposures of Human Peripheral Blood Lymphocytes.

Cells exposed to fast neutrons often exhibit a non-Poisson distribution of chromosome aberrations due to the high ionization density of the secondary reaction products. However, it is unknown whether lymphocytes exposed to californium-252 (252Cf) spectrum neutrons, of mean energy 2.1 MeV, demonstrate this same dispersion effect at low doses. Furthermore, there is no consensus regarding the relative biological effectiveness (RBE) of 252Cf neutrons. Dicentric and ring chromosome formations were assessed in human peripheral blood lymphocytes irradiated at doses of 12-135 mGy. The number of aberrations observed were tested for adherence to a Poisson distribution and the maximum low-dose relative biological effectiveness (RBEM) was also assessed. When 252Cf-irradiated lymphocytes were examined along with previously published cesium-137 (137Cs) data, RBEM values of 15.0 ± 2.2 and 25.7 ± 3.8 were found for the neutron-plus-photon and neutron-only dose components, respectively. Four of the five dose points were found to exhibit the expected, or close to the expected non-Poisson over-dispersion of aberrations. Thus, even at low doses of 252Cf fast neutrons, when sufficient lymphocyte nuclei are scored, chromosome aberration clustering can be observed.

Relative Biological Effectiveness and Non-Poissonian Distribution of Dicentric Chromosome Aberrations after Californium-252 Neutron Exposures of Human Peripheral Blood Lymphocytes.

Cells exposed to fast neutrons often exhibit a non-Poisson distribution of chromosome aberrations due to the high ionization density of the secondary reaction products. However, it is unknown whether lymphocytes exposed to californium-252 (252Cf) spectrum neutrons, of mean energy 2.1 MeV, demonstrate this same dispersion effect at low doses. Furthermore, there is no consensus regarding the relative biological effectiveness (RBE) of 252Cf neutrons. Dicentric and ring chromosome formation was assessed in human peripheral blood lymphocytes irradiated at doses of 12-135 mGy. The number of aberrations observed were tested for adherence to a Poisson distribution and the maximum low-dose relative biological effectiveness (RBEM) was also assessed. When 252Cf-irradiated lymphocytes were examined along with previously published cesium-137 (137Cs) data, RBEM values of 15.0 ± 2.2 and 25.7 ± 3.8 were found for the neutron-plus-photon and neutron-only dose components, respectively. Four of the five dose points were found to exhibit the expected, or close to the expected non-Poisson over-dispersion of aberrations. Thus, even at low doses of 252Cf fast neutrons, when enough lymphocyte nuclei are scored, chromosome aberration clustering can be observed.

Administration of lower doses of radium-224 to ankylosing spondylitis patients results in no evidence of significant overall detriment.

The use of low doses of radium-224 (224Ra) chloride for the treatment of ankylosing spondylitis was stopped following the discovery that patients treated with it had a higher than control incidence of leukaemia and other cancers. This was so even though the treatment resulted in decreased pain and increased mobility-both of which are associated with decreased mortality. It was decided to re-analyze the epidemiological data looking at all causes of death. The risk of leukaemia, solid cancer, death from non-cancer causes and from all causes in a study populations of men that received either the typical dose of 5.6 to 11.1 MBq of 224Ra, any dose of 224Ra or no radium were compared using the Cox proportional hazard model. For patients that received the typical dose of 224Ra agreed with the excess cancer was similar to that reported in previous studies. In contrast, these patients were less likely to die from non-cancer diseases and from all causes of death than the control patients. No excess mortality was also found in the population of all males that received the radionuclide. It is concluded that 224Ra treatment administered at low doses to patients with ankylosing spondylitis did not impact mortality from all causes. The study demonstrates the need to consider all causes of death and longevity when assessing health impacts following irradiation.

A Nontarget Mechanism to Explain Carcinogenesis Following α-Irradiation.

This commentary highlights the published data on the metabolic processes that lead to the development of cancer following intakes of asbestos and chemical agents. Following exposure to both, the key initiating event is cell injury leading to cell death that may further lead to inflammation, fibrosis, and cancer. Since α-particle transits also kill cells, it is suggested that cell death and inflammation will also trigger carcinogenesis within tissues irradiated by these particles. Such an explanation would be consistent with the inflammation and fibrosis seen in tumor-bearing tissues irradiated by radon-222, radium-226, thorium-232, plutonium-239, and other α-emitting radionuclides. It would also provide an explanation for dose-related changes in latency and in the similar dose-responses for the same tissue in differently sized species.

In vivo animal studies help achieve international consensus on standards and guidelines for health risk estimates for chronic exposure to low levels of tritium in drinking water.

Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta-emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explores the gaps in this knowledge and provides recommendations on the best ways forward for improving our understanding of the health effects of low-level exposure to it. Linking health effects specifically to tritium exposure is challenging in epidemiological studies due to high uncertainty in tritium dosimetry and often suboptimal cohort sizes. We therefore argued that limits for tritium in drinking water should be based on evidence derived from controlled in vivo animal tritium toxicity studies that use realistically low levels of tritium. This article presents one such mouse study, undertaken within an international collaboration, and discusses the implications of its main findings, such as the similarity of the biokinetics of tritiated water (HTO) and organically bound tritium (OBT) and the higher biological effectiveness of OBT. This discussion is consistent with the position expressed in this article that in vivo animal tritium toxicity studies carried out within large, multi-partner collaborations allow evaluation of a great variety of health-related endpoints and essential to the development of international consensus on the regulation of tritium levels in the environment. Environ. Mol. Mutagen. 59:586-594, 2018. © 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Tritium ( 3 H) Retention In Mice: Administered As HTO, DTO or as 3 H-Labeled Amino-Acids.

The objective of this study was to compare the biokinetics of injected H-labeled light (HTO) and heavy (DTO) water in CBA/CaJ mice and to compare the organ distribution and/or body content of H administered by chronic ingestion for 1 mo to C57Bl/6J mice, as either H-labeled water or H-labeled amino acids (glycine, alanine and proline). HTO and DTO were administered to CBA/CaJ mice by single intraperitoneal injection and body retention was determined for up to 384 h post-injection. Tritium-labeled water or H-labeled amino acids were given to C57Bl/6J mice ad libitum for 30 d in drinking water. Body content and organ distribution of H during the period of administration and subsequent to administration was determined by liquid scintillation counting. No differences were found between the biokinetics of HTO and DTO, indicating that data generated using HTO can be used to help assess the consequences of H releases from heavy water reactors. The results for H-water showed that the concentration of radionuclide in the mice reached a peak after about 10 d and dropped rapidly after the cessation of H administration. The maximum concentration reached was only 50% of that in the water consumed, indicating that mice receive a significant fraction of their water from respiration. Contrary to the findings of others, the pattern of H retention following the administration of a cocktail of the labeled amino acids was very little different from that found for the water. This is consistent with the suggestion that most of the ingested amino acids were rapidly metabolized, releasing water and carbon dioxide.

Evaluation of Apoptosis with 99mTc-rhAnnexin V-128 and Inflammation with 18F-FDG in a Low-Dose Irradiation Model of Atherosclerosis in Apolipoprotein E-Deficient Mice.

Low-dose radiation in apolipoprotein E-deficient (ApoE-/-) mice has a protective effect with less subsequent atherosclerosis. Inflammation and apoptosis play major roles in the development of atherosclerosis. We evaluated the temporal pattern of the development of histologic atherosclerosis, inflammation with 18F-FDG, and apoptosis with 99mTc-rhAnnexin V-128 at 3 time points. METHODS: ApoE-/- mice were fed a high-fat diet, exposed to low-dose 60Co γ-radiation of 25 mGy at 2 mo of age, and evaluated within 1 wk (2-mo group), 1 mo (3-mo group), and 2 mo (4-mo group) from the time of radiation. Mice were divided into 3 subgroups and each received 18F-FDG, 99mTc-rhAnnexin V-128, or no radiotracer for autoradiography. Mice underwent euthanasia and aortic root dissection. The extent of atherosclerosis was determined by en face and Oil red O imaging. Aortic arch inflammation (18F-FDG) and apoptosis (99mTc-rhAnnexin V-128) were determined with digital autoradiography. Aortic sinus sections were stained with Sudan IV for assessment of lesion area and stage, antiCD68 antibody for inflammation and anti-cleaved-caspase 3 antibody for apoptosis. RESULTS: The extent of aortic atherosclerosis increased from 2 to 3 mo and from 3 to 4 mo. Inflammation (CD68) decreased and apoptosis (anti-cleaved-caspase 3 antibody) increased in aortic sinus slices measured as percentage of lesion by 4 mo. With increasing lesion stage, lesion inflammation decreased and lesion apoptosis increased. Aortic arch inflammation (18F-FDG uptake) did not differ over time and did not correlate with average lesion stage. However, aortic arch apoptosis (99mTc-rhAnnexin V-128) increased significantly by 4 mo and correlated with average lesion stage. There were no differences between the treatment subgroups (18F-FDG, 99mTc-rhAnnexin V-128, or no radiotracer). CONCLUSION: The temporal pattern of development of inflammation and apoptosis differ during the development of atherosclerosis in ApoE-/- mice treated with low-dose radiation. Advanced lesions are characterized by increased apoptosis and either less or similar amounts of inflammation, shown on immunohistochemistry and autoradiography. Treatment with radiotracers had no significant effects on extent of atherosclerosis, inflammation, or apoptosis.

Correction: Low-Dose Irradiation Affects Expression of Inflammatory Markers in the Heart of ApoE -/- Mice.

[This corrects the article DOI: 10.1371/journal.pone.0119661.].

Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1ß, TGFß, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention of radiation related, long-term side effects but also give important implications for low dose anti-inflammatory radiotherapy.

Further evaluations of the toxicity of irradiated advanced heavy water reactor fuels.

The neutron economy and online refueling capability of heavy water moderated reactors enable them to use many different fuel types, such as low enriched uranium, plutonium mixed with uranium, or plutonium and/or U mixed with thorium, in addition to their traditional natural uranium fuel. However, the toxicity and radiological protection methods for fuels other than natural uranium are not well established. A previous paper by the current authors compared the composition and toxicity of irradiated natural uranium to that of three potential advanced heavy water fuels not containing plutonium, and this work uses the same method to compare irradiated natural uranium to three other fuels that do contain plutonium in their initial composition. All three of the new fuels are assumed to incorporate plutonium isotopes characteristic of those that would be recovered from light water reactor fuel via reprocessing. The first fuel investigated is a homogeneous thorium-plutonium fuel designed for a once-through fuel cycle without reprocessing. The second fuel is a heterogeneous thorium-plutonium-U bundle, with graded enrichments of U in different parts of a single fuel assembly. This fuel is assumed to be part of a recycling scenario in which U from previously irradiated fuel is recovered. The third fuel is one in which plutonium and Am are mixed with natural uranium. Each of these fuels, because of the presence of plutonium in the initial composition, is determined to be considerably more radiotoxic than is standard natural uranium. Canadian nuclear safety regulations require that techniques be available for the measurement of 1 mSv of committed effective dose after exposure to irradiated fuel. For natural uranium fuel, the isotope Pu is a significant contributor to the committed effective dose after exposure, and thermal ionization mass spectrometry is sensitive enough that the amount of Pu excreted in urine is sufficient to estimate internal doses, from all isotopes, as low as 1 mSv. In addition, if this method is extended so that Pu is also measured, then the combined amount of Pu and Pu is sufficiently high in the thorium-plutonium fuel that a committed effective dose of 1 mSv would be measurable. However, the fraction of Pu and Pu in the other two fuels is sufficiently low that a 1 mSv dose would remain below the detection limit using this technique. Thus new methods, such as fecal measurements of Pu (or other alpha emitters), will be required to measure exposure to these new fuels.

Relative toxicity of (45)Ca beta-particles and (242)Cm alpha-particles following their intravenous injection into mice as radiolabelled FAP.

PURPOSE: To determine the relative toxicity of alpha- and beta-radiations under conditions of controlled temporal and spatial dose distribution. METHODS: Fused aluminosilicate particles were radiolabelled with either (45)Ca (a beta-emitter) or (242)Cm (an alpha-emitter). These were injected into CBA/Ca mice to give lifespan, whole-body doses of approximately 0.5, 1.0 or 1.5 Gy. Most animals were entered into a lifespan toxicity study, but some were killed for radiochemical analysis and autoradiography. RESULTS: Twenty-seven tumour types were identified. The most common malignant tumours were: Mammary carcinoma; liver carcinoma; malignant lymphoma; uterine histiocytic sarcoma. Excess relative risk (strictly hazard ratio) was higher for radiation-induced carcinomas than for sarcomas. The carcinomas, but not sarcomas showed a reduction in relative risk at the highest radiation dose employed. This reduction was most easily attributed to a systemic effect. The highest relative toxicity measured was for liver carcinoma (5.9, 95% confidence intervals [CI] 2.4, 14) and the lowest for uterine carcinoma (0.6, CI 0.03, 9.7). Overall, the excess relative risk ratio for SURVIVAL WAS 1.9 (CI 1.1, 3.2), FOR ALL CARCINOMA WAS 2.3 (CI 1.7, 3.0) AND FOR ALL SARCOMA WAS 2.7 (CI 0.72, 10). CONCLUSIONS: The 10-fold variability in the observed toxicity ratio for different tumour endpoints shows that tissue sensitivity is a more important determinant of relative toxicity than radiation quality. The use of single radiation-weighting (w(R)) factors for radiation risk prediction and for radiological protection dosimetry is inconsistent with scientific observation.

Introduction to arsenic contamination and health risk assessment with special reference to Bangladesh.

The problem of arsenic contamination in the Bengal River Basin illustrates a classic conundrum in environmental health, namely, that development projects can have double effects: on one hand development of tube wells eliminated bacterial pathogens and on the other it exposed the population to poisoning from arsenic. Thus, in future development projects the full health risk of a project must be considered during the planning, implementation, and decommissioning phases (Caussy 2003b; Caussy et al. 2003b). If such a holistic approach would have been followed, the mass contamination in the Bengal River Basin, in which millions of people were and are exposed to unsafe levels of arsenic, could have been averted. Although definite knowledge gaps in applying risk assessment steps for arsenic contamination exist, arsenic clearly poses a serious health problem and economic consequences to the affected population of the Bengal River Basin. It is binding on the international community to alleviate the problem through remediation measures to reduce arsenic exposure. One Environmental Sustainability Millennium development goal is to increase the proportion of population with sustainable access to an improved water source (Bartram et al. 2005). Providing water with safe levels of arsenic to affected communities of the Bengal River Basin will directly contribute to improved community health.

Tritium in well waters, streams and atomic lakes in the East Kazakhstan Oblast of the Semipalatinsk Nuclear Test Site.

The concentration of tritium has been determined in well waters, streams and atomic lakes in the Sarzhal, Tel'kem, Balapan and Degelen Mountains areas of the Semipalatinsk Test Site. The data show that levels of tritium in domestic well waters within the settlement of Sarzhal are extremely low at the present time with a median value of 4.4 Bq dm(-3) (95% confidence interval:4.1-4.7 Bq dm(-3)). These levels are only marginally above the background tritium content in surface waters globally. Levels in the atomic craters at Tel'kem 1 and Tel'kem 2 are between one and two orders of magnitude higher, while the level in Lake Balapan is approximately 12,600 Bq dm(-3). Significantly, levels in streams and test-tunnel waters sourced in the Degelen Mountains, the site of approximately 215 underground nuclear tests, are a further order of magnitude higher, being in the range 133,000--235,500 Bq dm(-3). No evidence was adduced which indicates that domestic wells in Sarzhal are contaminated by tritium-rich waters sourced in the Degelen massif, suggesting that the latter are not connected hydrologically to the near-surface groundwater recharging the Sarzhal wells. Annual doses to humans arising from the ingestion of tritium in these well waters are very low at the present time and are of no radiological significance.