https://stacks.cdc.gov/view/cdc/37676/cdc_37676_DS1.pdf

Toxicological Profile for Lead

Influence of particle size on regional lung deposition - What evidence is there?

Recent epidemiological studies of the association between lung cancer and exposure to radon and its decay products are reviewed. Particular emphasis is given to pooled case-control studies of residential exposures, and to cohorts of underground miners exposed to relatively low levels of radon. The residential and miner epidemiological studies provide consistent estimates of the risk of lung cancer, with significant associations observed at average annual concentrations of approximately 200 Bq/m³ and cumulative occupational levels of approximately 50 working level months (WLM), respectively. Based on recent results from combined analyses of epidemiological studies of miners, a lifetime excess absolute risk of 5 × 10⁻⁴ per WLM [14 × 10⁻⁵ per (mJh/m³)] should now be used as the nominal probability coefficient for radon- and radon-progeny-induced lung cancer, replacing the previous Publication 65 (ICRP, 1993) value of 2.8 × 10⁻⁴ per WLM [8 × 10⁻⁵ per (mJh/m³)]. Current knowledge of radon-associated risks for organs other than the lungs does not justify the selection of a detriment coefficient different from the fatality coefficient for radon-induced lung cancer. Publication 65 (ICRP, 2003) recommended that doses from radon and its progeny should be calculated using a dose conversion convention based on epidemiological data. It is now concluded that radon and its progeny should be treated in the same way as other radionuclides within the ICRP system of protection; that is, doses from radon and its progeny should be calculated using ICRP biokinetic and dosimetric models. ICRP will provide dose coefficients per unit exposure to radon and its progeny for different reference conditions of domestic and occupational exposure, with specified equilibrium factors and aerosol characteristics.

https://journals.sagepub.com/doi/pdf/10.1016/j.icrp.2011.08.011

Lung Cancer Risk from Radon and Progeny and Statement on Radon

In this Review, the authors examine the aetiological, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, the clinical outcomes with targeted therapies, and strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as 'druggable' targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours.

/pdf/tyrosine-kinase-gene-rearrangements-in-epithelial-4egyukubom.pdf

Tyrosine kinase gene rearrangements in epithelial malignancies

– The 2007 Recommendations of the International Commission on Radiological Protection (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979, 1980, 1981, 1988) and Publication 68 (ICRP, 1994). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1988a, 1997b) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2, Task Group 21 on Internal Dosimetry, and Task Group 4 on Dose Calculations. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 has been issued (ICRP, 2015), and describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), this current publication and upcoming publications in the OIR series (Parts 4 and 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic model; and data on monitoring techniques for the radioisotopes encountered most commonly in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv Bq−1 intake) for inhalation and ingestion, tables of committed effective dose per content (Sv Bq−1 measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The electronic annex that accompanies the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This third publication in the series provides the above data for the following elements: ruthenium (Ru), antimony (Sb), tellurium (Te), iodine (I), caesium (Cs), barium (Ba), iridium (Ir), lead (Pb), bismuth (Bi), polonium (Po), radon (Rn), radium (Ra), thorium (Th), and uranium (U).

ICRP Publication 137: Occupational Intakes of Radionuclides: Part 3.

IMBA (Integrated Modules for Bioassay Analysis) is a suite of software modules that implement the current ICRP biokinetic and dosimetric models for estimation of intakes and doses. The IMBA modules have gone through extensive quality assurance, and are now used for routine formal dose assessment by Approved Dosimetry Services throughout the UK. HPA has continued to develop the IMBA modules. In addition, several projects, sponsored by organisations both in the USA and in Canada, have resulted in the development of customised user-friendly interfaces (IMBA Expert™ ‘editions’). These enable users not only to use the standard ICRP models, but also to change many of the parameter values from ICRP defaults, and to apply sophisticated data handling techniques to internal dose calculations. These include: fitting measurement data with the maximum likelihood method; using multiple chronic and acute intakes; and dealing with different data types, such as urine, faces and whole body simultaneously. These interfaces were improved further as a result of user-feedback, and a general ‘off-the-shelf’ product, IMBA Professional, was developed and made available in January 2004. A new version, IMBA Professional Plus, was released in April 2005, which is both faster and more powerful than previous software. The aim of this paper is to describe the capabilities of IMBA Professional Plus, and the mathematical methods used.

IMBA Professional Plus: a flexible approach to internal dosimetry.

A parameter uncertainty analysis has been performed to derive the probability distribution of the weighted equivalent dose to lung for an adult (w lung H lung ) per unit exposure to radon progeny in the home. The analysis was performed using the ICRP Publication 66 human respiratory tract model (HRTM) with tissue weighting factor for the lung, w lung = 0.12 and the radiation weighting factor for alpha particles, w R = 20. It is assumed that the HRTM is a realistic representation of the physical and biological processes, and that the parameter values are uncertain. The parameter probability distributions used in the analysis were based on a combination of experimental results and expert judgement from several prominent European scientists. The assignment of the probability distributions describing the uncertainty in the values of the assigned fractions (A BB , A bb , A AI ) of the tissue weighting factor proved difficult in practice due to lack of quantitative data. Because of this several distributions were considered. The results of the analysis give a mean value of w lang H lung per unit exposure to radon progeny in the home of 15 mSv per working level month (WLM) for a population. For a given radon gas concentration, the mean value of w lung H lung per unit exposure is 13 mSv per 200 Bq.m -3 .y of 222 Rn. Parameters characterising the distributions of w lung H lung per unit exposure are given. If the ICRP weighting factors are fixed at their default values (A BB , A bb , A AI = 0.333, 0.333, 0.333; w lung = 0.12; and w r = 20) then on the basis of this uncertainty analysis it is extremely unlikely (P 0.0007) that a value of H w /P p for exposure in the home is as lots as 4 mSv per WLM, the value determined with the epidemiological approach. Even when the uncertainties in the A BB , A bb , A AI values are included then this probability is predicted to be between 0.01 to 0.08 depending upon the distribution assumed for describing the uncertainties in the A BB , A bb , A AI values. Thus, it is concluded that the uncertainties in the HRTM parameters considered in this study cannot totally account for the discrepancy between the dosimetric and epidemiological approaches.

Uncertainty Analysis of the Weighted Equivalent Lung Dose per Unit Exposure to Radon Progeny in the Home

The European project Alpha-Risk aims to quantify the cancer and non-cancer risks associated with multiple chronic radiation exposures by epidemiological studies, organ dose calculation and risk assessment. In the framework of this project, mathematical models have been applied to the organ dosimetry of uranium miners who are internally exposed to radon and its progeny as well as to long-lived radionuclides present in the uranium ore. This paper describes the methodology and the dosimetric models used to calculate the absorbed doses to specific organs arising from exposure to radon and its progeny in the uranium mines. The results of dose calculations are also presented.

Dosimetric models used in the Alpha-Risk project to quantify exposure of uranium miners to radon gas and its progeny.

Epidemiological studies on uranium miners are being carried out to quantify the risk of cancer based on organ dose calculations. Mathematical models have been applied to calculate the annual absorbed doses to regions of the lung, red bone marrow, liver, kidney and stomach for each individual miner arising from exposure to radon gas, radon progeny and long-lived radionuclides (LLR) present in the uranium ore dust and to external gamma radiation. The methodology and dosimetric models used to calculate these organ doses are described and the resulting doses for unit exposure to each source (radon gas, radon progeny and LLR) are presented. The results of dosimetric calculations for a typical German miner are also given. For this miner, the absorbed dose to the central regions of the lung is dominated by the dose arising from exposure to radon progeny, whereas the absorbed dose to the red bone marrow is dominated by the external gamma dose. The uncertainties in the absorbed dose to regions of the lung arising from unit exposure to radon progeny are also discussed. These dose estimates are being used in epidemiological studies of cancer in uranium miners.

Dosimetric calculations for uranium miners for epidemiological studies.

Doses from intakes of radionuclides cannot be measured but must be assessed from monitoring, such as whole body counting or urinary excretion measurements. Such assessments require application of a biokinetic model and estimation of the exposure time, material properties, etc. Because of the variety of parameters involved, the results of such assessments may vary over a wide range, according to the skill and the experience of the assessor. The need for harmonisation of assessment procedures has been recognised in a research project carried out under the EU 5 th Framework Programme. The aim of the project IDEAS (partly funded by the European Commission under contract No. FIKR-CT2001-00160) was to develop general guidelines for assessments of intakes and internal doses from individual monitoring data. The IDEAS project started in October 2001 and ended in June 2005. To ensure that the guidelines are applicable to a wide range of practical situations, a database was compiled of cases of internal contamination that include monitoring data suitable for assessment. About 50 cases from the database were analized by different assessors, the results were collated, and differences in assumptions identified, with their effects on the assessed doses. From the results, and other investigations, draft guidelines were prepared, to provide a systematic procedure for estimating the required parameter values that are not part of the measurement data. A virtual workshop was held on the Internet, open to internal dosimetry professionals, to discuss the draft guidelines, which were revised accordingly. In collaboration with the IAEA, an intercomparison exercise on internal dose assessment was then conducted, which was also open to all involved in internal dosimetry. Six cases were developed and circulated with a copy of the revised guidelines, which participants were encouraged to follow, to test their applicability and effectiveness. The results were collated and a Workshop held to discuss the results with the participants. The guidelines were refined on the basis of the experience and discussion. The guidelines are based on a general philosophy of: • Harmonisation: by following the Guidelines any two assessors should obtain the same estimate of dose from a given data set. • Accuracy: the "best" estimate of dose should be obtained from the available data. • Proportionality: the effort applied to the evaluation should be proportionate to the dose - the lower the dose, the simpler the process should be. Following these principles, the Guidelines use the following "Levels of task" to structure the approach to an evaluation: Level 0: Annual dose 6 mSv). The guidelines provide: • Background information about the biokinetic models and the corresponding bioassay functions for the interpretation of monitoring data. • Detailed information about the handling and evaluation of monitoring data. • A structured approach to dose assessment consisting of a step-by-step procedure described in well-defined flowcharts with accompanying explanatory text.

/pdf/general-guidelines-for-the-estimation-of-committed-effective-3ueauhnvh5.pdf

General guidelines for the estimation of committed effective dose from incorporation monitoring data : (Project IDEAS - EU contract no. FIKR-CT2001-00160)

J. W. Marsh

Papers

IMBA Professional Plus: a flexible approach to internal dosimetry.

Uncertainty Analysis of the Weighted Equivalent Lung Dose per Unit Exposure to Radon Progeny in the Home

Dosimetric models used in the Alpha-Risk project to quantify exposure of uranium miners to radon gas and its progeny.

Dosimetric calculations for uranium miners for epidemiological studies.

General guidelines for the estimation of committed effective dose from incorporation monitoring data : (Project IDEAS - EU contract no. FIKR-CT2001-00160)