This report is the first in a series of reports replacing Publications 30 and 68 to provide revised dose coefficients for occupational intakes of radionuclides by inhalation and ingestion. The revised dose coefficients have been calculated using the Human Alimentary Tract Model (Publication 100) and a revision of the Human Respiratory Tract Model (Publication 66) that takes account of more recent data. In addition, information is provided on absorption into blood following inhalation and ingestion of different chemical forms of elements and their radioisotopes. In selected cases, it is judged that the data are sufficient to make material-specific recommendations. Revisions have been made to many of the models that describe the systemic biokinetics of radionuclides absorbed into blood, making them more physiologically realistic representations of uptake and retention in organs and tissues, and excretion. The reports in this series provide data for the interpretation of bioassay measurements as well as dose coefficients, replacing Publications 54 and 78. In assessing bioassay data such as measurements of whole-body or organ content, or urinary excretion, assumptions have to be made about the exposure scenario, including the pattern and mode of radionuclide intake, physical and chemical characteristics of the material involved, and the elapsed time between the exposure(s) and measurement. This report provides some guidance on monitoring programmes and data interpretation.

https://journals.sagepub.com/doi/pdf/10.1177/0146645315577539

ICRP Publication 130: Occupational Intakes of Radionuclides: Part 1.

The mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co3O4). This study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry. Our study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity. Cobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity.

/pdf/low-solubility-particles-and-a-trojan-horse-type-mechanism-1a9p00hnw0.pdf

Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells

The biokinetics of inorganic cobalt in the human body.

Better information is available now on long-term particle retention in the human lungs than there was in 1994, when the human respiratory tract model (HRTM) was adopted by the International Commission on Radiological Protection (ICRP). Three recent studies are especially useful because they provide such information for groups of people who inhaled very similar aerosols. For all three the HRTM significantly underestimates lung retention of insoluble material. The purpose of this work was to improve the modelling of long-term retention in the deep lung. A simple physiologically based model developed to predict lung and lymph node particle retention in coal miners was found to represent lung retention in these studies adequately. Instead of the three alveolar-interstitial (AI) compartments in the HRTM, it has an alveolar compartment which clears to the bronchial tree and to a second compartment, representing the interstitium, which clears only to lymph nodes. The main difference from the HRTM AI model is that a significant fraction of the AI deposit is sequestered in the interstitium. To obtain default parameter values for general use, the model was fitted to data from the three recent studies, and also the experimental data used in development of the HRTM to define particle transport from the AI region for the first year after intake. The result of the analysis is that about 40% of the AI deposit of insoluble particles is sequestered in the interstitium and the remaining fraction is cleared to the ciliated airways with a half-time of about 300 days. For some long-lived radionuclides in relatively insoluble form (type S), this increased retention increases the lung dose per unit intake by 50-100% compared to the HRTM value.

https://iopscience.iop.org/article/10.1088/0952-4746/30/3/005/pdf

Modelling particle retention in the alveolar–interstitial region of the human lungs

The ICRP Task Group on Internal Dosimetry is developing new Occupational Intakes of Radionuclides (OIR) documents Application of the Human Respiratory Tract Model (HRTM) requires a review of the lung-to-blood absorption characteristics of inhaled compounds of importance in radiological protection Where appropriate, material-specific absorption parameter values will be given, and for other compounds, assignments to default Types will be made on current information Publication of the OIR provides an opportunity for updating the HRTM in the light of experience and new information The main possibilities under consideration relate to the two main clearance pathways Recent studies provide important new data on rates of particle transport from the nasal passages, bronchial tree (slow phase) and alveolar region The review of absorption rates provides a database of parameter values from which consideration can be given to deriving typical values for default Types F, M and S materials, and element-specific rapid dissolution rates

/pdf/updating-the-icrp-human-respiratory-tract-model-49oyzfukyb.pdf

Updating the ICRP human respiratory tract model

Intakes and doses are assessed for seven workers who accidentally inhaled particles containing Co in the same incident. Comprehensive whole body data to 15 y, and some early urine and fecal data, are available for each individual. The biokinetic and dosimetric models currently recommended by ICRP have been used to assess these cases. It was not possible to obtain good fits to the data using the ICRP models with their default parameter values. However, good fits to all the measurement data were obtained by varying parameter values following a procedure similar to that recommended in recently developed guidelines for assessment of internal doses from monitoring data. It was found that retention in the lungs was much longer than predicted by the ICRP Human Respiratory Tract Model, and so for each case it was necessary to reduce the particle transport clearance of material from the deep lungs. This reduction in lung clearance rates, and the use of specific AMAD values, were the dominating factors in changing assessed doses from those calculated using ICRP default values.

M. Gerondal

Papers

Assessment of intakes and doses to workers followed for 15 years after accidental inhalation of 60CO.