J. D. Harrison

Systematic Review and Meta-analysis of Circulatory Disease from Exposure to Low-Level Ionizing Radiation and Estimates of Potential Population Mortality Risks

Background: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels. Objectives: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures. Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms “radiation” AND “heart” AND “disease,” OR “radiation” AND “stroke,” OR “radiation” AND “circulatory” AND “disease.” Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries. Results: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia. Conclusions: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).

ICRP Publication 119: Compendium of Dose Coefficients Based on ICRP Publication 60:

This report is a compilation of dose coefficients for intakes of radionuclides by workers and members of the public, and conversion coefficients for use in occupational radiological protection against external radiation from Publications 68, 72, and 74 (ICRP, 1994b, 1996a,b). It serves as a comprehensive reference for dose coefficients based on the primary radiation protection guidance given in the Publication 60 recommendations (ICRP, 1991). The coefficients tabulated in this publication will be superseded in due course by values based on the Publication 103 recommendations (ICRP, 2007).

Polonium-210 as a poison

The death of Alexander Litvinenko on 23 November 2006 has brought into focus scientific judgements concerning the radiotoxicity of polonium-210 ((210)Po). This paper does not consider the specific radiological circumstances surrounding the tragic death of Mr Litvinenko; rather, it provides an evaluation of published human and animal data and models developed for the estimation of alpha radiation doses from (210)Po and the induction of potentially fatal damage to different organs and tissues. Although uncertainties have not been addressed comprehensively, the reliability of key assumptions is considered. Concentrating on the possibility of intake by ingestion, the use of biokinetic and dosimetric models to estimate organ and tissue doses from (210)Po is examined and model predictions of the time-course of dose delivery are illustrated. Estimates are made of doses required to cause fatal damage, taking account of the possible effects of dose protraction and the relative biological effectiveness (RBE) of alpha particles compared to gamma and x-rays. Comparison of LD(50) values (dose to cause death for 50% of people) for different tissues with the possible accumulation of dose to these tissues suggests that bone marrow failure is likely to be an important component of multiple contributory causes of death occurring within a few weeks of an intake by ingestion. Animal data on the effects of (210)Po provide good confirmatory evidence of intakes and doses required to cause death within about 3 weeks. The conclusion is reached that 0.1-0.3 GBq or more absorbed to blood of an adult male is likely to be fatal within 1 month. This corresponds to ingestion of 1-3 GBq or more, assuming 10% absorption to blood. Well-characterised reductions in white cell counts would be observed. Bone marrow failure is likely to be compounded by damage caused by higher doses to other organs, including kidneys and liver. Even if the bone marrow could be rescued, damage to other organs can be expected to prove fatal.

Radiation doses and risks from internal emitters.

This review updates material prepared for the UK Government Committee Examining Radiation Risks from Internal Emitters (CERRIE) and also refers to the new recommendations of the International Commission on Radiological Protection (ICRP) and other recent developments. Two conclusions from CERRIE were that ICRP should clarify and elaborate its advice on the use of its dose quantities, equivalent and effective dose, and that more attention should be paid to uncertainties in dose and risk estimates and their implications. The new ICRP recommendations provide explanations of the calculation and intended purpose of the protection quantities, but further advice on their use would be helpful. The new recommendations refer to the importance of understanding uncertainties in estimates of dose and risk, although methods for doing this are not suggested. Dose coefficients (Sv per Bq intake) for the inhalation or ingestion of radionuclides are published as reference values without uncertainty. The primary purpose of equivalent and effective dose is to enable the summation of doses from different radionuclides and from external sources for comparison with dose limits, constraints and reference levels that relate to stochastic risks of whole-body radiation exposure. Doses are calculated using defined biokinetic and dosimetric models, including reference anatomical data for the organs and tissues of the human body. Radiation weighting factors are used to adjust for the different effectiveness of different radiation types, per unit absorbed dose (Gy), in causing stochastic effects at low doses and dose rates. Tissue weighting factors are used to take account of the contribution of individual organs and tissues to overall detriment from cancer and hereditary effects, providing a simple set of rounded values chosen on the basis of age- and sex-averaged values of relative detriment. While the definition of absorbed dose has the scientific rigour required of a basic physical quantity, the same is not true of the ICRP protection quantities equivalent and effective dose (i.e. those measured in sieverts). The ICRP quantities are intended for practical application in radiological protection and the choice of radiation and tissue weighting factors used in their calculation involves simplifying assumptions regarded as acceptable for this purpose. Best estimates of doses and risks to individuals and specific population groups may be calculated using ICRP biokinetic and dosimetric approaches, but would require the use of best available information on RBE and age-, sex- and population-specific risk factors. Consideration of uncertainties is important in applications such as the assessment of the probability of cancer causation for an individual and in estimating doses in epidemiological studies. While the ICRP system of protection does not take explicit account of uncertainties, an understanding of the various contributions to uncertainty can be seen to be of value when making judgments on the optimisation of protection.

Lack of detectable transmissible chromosomal instability after in vivo or in vitro exposure of mouse bone marrow cells to 224Ra alpha particles.

Abstract Bouffler, S. D., Haines, J. W., Edwards, A. A., Harrison, J. D. and Cox, R. Lack of Detectable Transmissible Chromosomal Instability after In Vivo or In Vitro Exposure of Mouse Bone Marrow Cells to 224Ra Alpha Particles. Several studies over recent years have highlighted the possibility that radiation can induce transmissible genomic instability. Most of these involve in vitro irradiation and usually in vitro culture. Here it is reported that the short-half-life bone-seeking α-particle emitter 224Ra did not induce excess transmissible chromosomal instability in CBA/H mouse bone marrow cells in a 100-day period after in vivo or in vitro exposure. Similarly, no excess transmissible chromosomal instability could be detected after in vivo whole-body X irradiation. It was noted, however, that short-term culture of murine bone marrow cells elevated yields of aberrations, as did transplantation of untreated marrow into radiation-ablated hosts. These findings emphasize the sensitivity of murine hemopoietic tissue to experimental manipulation and reinforce the importance of appropriate concurrent control experiments in any investigation of transmissible genomic instability.

An image-based skeletal tissue model for the ICRP reference newborn

Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set-both male and female-that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in mineral bone composition may have significant dosimetric implications when considering localized marrow dosimetry for radionuclides that target mineral bone in the newborn child.

Dose to red bone marrow of infants, children and adults from radiation of natural origin

Natural radiation sources contribute much the largest part of the radiation exposure of the average person. This paper examines doses from natural radiation to the red bone marrow, the tissue in which leukaemia is considered to originate, with particular emphasis on doses to children. The most significant contributions are from x-rays and gamma rays, radionuclides in food and inhalation of isotopes of radon and their decay products. External radiation sources and radionuclides other than radon dominate marrow doses at all ages. The variation with age of the various components of marrow dose is considered, including doses received in utero and in each year up to the age of 15. Doses in utero include contributions resulting from the ingestion of radionuclides by the mother and placental transfer to the foetus. Postnatal doses include those from radionuclides in breast-milk and from radionuclides ingested in other foods. Doses are somewhat higher in the first year of life and there is a general slow decline from the second year of life onwards. The low linear energy transfer (LET) component of absorbed dose to the red bone marrow is much larger than the high LET component. However, because of the higher radiation weighting factor for the latter it contributes about 40% of the equivalent dose incurred up to the age of 15.

Plutonium worker dosimetry

Epidemiological studies of the relationship between risk and internal exposure to plutonium are clearly reliant on the dose estimates used. The International Commission on Radiological Protection (ICRP) is currently reviewing the latest scientific information available on biokinetic models and dosimetry, and it is likely that a number of changes to the existing models will be recommended. The effect of certain changes, particularly to the ICRP model of the respiratory tract, has been investigated for inhaled forms of 239Pu and uncertainties have also been assessed. Notable effects of possible changes to respiratory tract model assumptions are (1) a reduction in the absorbed dose to target cells in the airways, if changes under consideration are made to the slow clearing fraction and (2) a doubling of absorbed dose to the alveolar region for insoluble forms, if evidence of longer retention times is taken into account. An important factor influencing doses for moderately soluble forms of 239Pu is the extent of binding of dissolved plutonium to lung tissues and assumptions regarding the extent of binding in the airways. Uncertainty analyses have been performed with prior distributions chosen for application in epidemiological studies. The resulting distributions for dose per unit intake were lognormal with geometric standard deviations of 2.3 and 2.6 for nitrates and oxides, respectively. The wide ranges were due largely to consideration of results for a range of experimental data for the solubility of different forms of nitrate and oxides. The medians of these distributions were a factor of three times higher than calculated using current default ICRP parameter values. For nitrates, this was due to the assumption of a bound fraction, and for oxides due mainly to the assumption of slower alveolar clearance. This study highlights areas where more research is needed to reduce biokinetic uncertainties, including more accurate determination of particle transport rates and long-term dissolution for plutonium compounds, a re-evaluation of long-term binding of dissolved plutonium, and further consideration of modeling for plutonium absorbed to blood from the lungs.

In utero and neonatal sensitivity of ApcMin/+ mice to radiation-induced intestinal neoplasia

Purpose: To assess the sensitivity of ApcMin/+ mice (adenomatous polyposis coli Apc, multiple intestinal neoplasia, Min) to the development of intestinal adenomas after x-irradiation in utero, as neonates, or as young adults. Materials and methods: CHB6 ApcMin/+ mice were exposed to an acute dose of 2 Gy x-rays either in utero on day 7 or 14 post-conception, as 2-day or 10-day neonates or as 35-day young adults. Tumour identification and counting was performed 200 – 214 days later. Results: Irradiation as 10-day-old neonates resulted in a significantly greater overall tumour incidence (average of about 130 tumours per animal) than irradiation as 35-day-old young adults (about 70 tumours). Irradiation as 2-day-old neonates resulted in an intermediate incidence (about 85 tumours). In contrast, the greatest tumour incidence observed after in utero irradiation of ApcMin/+ mice, of about 44 tumours per animal after 2 Gy irradiation at 14 days post-conception, was significantly lower than the incidence in irradiated adults. Tumour incidences after irradiation as 7-day embryos was not significantly raised above numbers in unirradiated controls (about 30 tumours). These tumour numbers include cystic crypts, largely radiation-induced, which were classed as early stage microadenomas on the basis of loss of wild-type Apc+ and expression of beta-catenin. Conclusions: The sensitivity of ApcMin/+ mice to the induction of intestinal tumours by radiation was shown to be in the order: 10 d neonates >2 d neonates >35 d young adults >14 d fetus >7 d embryo.

Doses from the consumption of Cardiff Bay flounder containing organically bound tritium

ICRP dose coefficients for the ingestion of organically bound tritium (OBT) by adults and children are intended for general application to unspecified forms in diet and may not be applicable to intakes of a specific form of OBT. To obtain information relating to OBT in fish from Cardiff Bay, the retention of tritium in adult rats was determined after administration as either tritiated water (HTO) or dried flounder flesh containing OBT. Two components of retention were obtained in each case. The first component, attributable to tritium equilibrating with body water, had a half-time of retention of 3 days in each case, and accounted for 97% of the intake as HTO and 70% after intake of OBT in flounder. Results were consistent with rapid catabolism of a large proportion of flounder OBT to HTO. The second component of retention, attributable to OBT in rat tissues, accounted for 3% of tritium intake as HTO and 30% after intake as flounder OBT; the half-times of retention were 10 days and 25 days, respectively. The results obtained after administration as HTO are consistent with published animal data and correlate with the ICRP assumptions for adult man of half-times of 10 days for 97% behaving as HTO in body tissues and 40 days for 3% incorporated into OBT in body tissues. The results obtained after administration of flounder OBT suggest that appropriate assumptions for retention in adult man are 70% with a 10 day half-time and 30% with a 100 day half-time. These assumptions result in an ingestion dose coefficient of 6 x 10(-11) Sv Bq(-1). This compares with the ICRP value for OBT ingestion by adults of 4.2 x 10(-11) Sv Bq(-1), based on half-times of 10 days and 40 days applied to equal proportions of retained tritium. It is proposed that a dose coefficient of 6 x 10(-11) Sv Bq(-1) should be applied to tritium in flounders from Cardiff Bay. It is further proposed that this dose coefficient should be applied to all ingestion intakes by adults relating to this source of exposure, unless specific information is available showing that a significant proportion of the intake is HTO. The same proposals apply to dose coefficients derived here for flounder OBT consumption by children.