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ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs – Threshold Doses for Tissue Reactions in a Radiation Protection Context

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TLDR
Estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence are provided and it appears that the rate of dose delivery does not modify the low incidence for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease.
Abstract
This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

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References
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Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003

TL;DR: Doses above 0.5 Gy are associated with an elevated risk of both stroke and heart disease, but the degree of risk at lower doses is unclear, and mis diagnosis of cancers as circulatory diseases could not account for the associations seen.
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Developmental kinetics, turnover and stimulatory capacity of thymic epithelial cells

TL;DR: In this article, the authors used single-cell analysis of stromal cells to analyze extensive changes in the number and composition of thymic stroma throughout life, revealing a surprisingly dynamic population.
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Treatment volume and tissue tolerance

TL;DR: T tentative conclusions were drawn regarding the influence on "tolerance" doses of tissue organization and the volume of an organ irradiated and sigmoid dose response curves, which are sensitive to small increases in "biologically effective" dose.
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Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies.

TL;DR: The most promising current strategies to limit or prevent anthracycline‐induced cardiotoxicity, as well as possible strategies to prevent existing cardiomyopathy from worsening are summarised.
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Consequential late effects in normal tissues

TL;DR: In tissues with a consequential component of the late sequelae, amelioration of the acute response to irradiation may be a useful approach to minimize late side effects of effective radiation therapy.
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