[en] The apparent dose-response relationship between amount of exposure to acute radiation and level of mortality in humans is affected by uncertainties in the dose values. It is apparent that one of the greatest concerns regarding the human data from Hiroshima and Nagasaki is the unexpectedly shallow slope of the dose response curve. This may be partially explained by uncertainty in the dose estimates. Some potential effects of dose uncertainty on the apparent dose-response relationship are demonstrated

[en] Many radiation-induced lethality experiments that have been published for various mammalian species have been compiled into a database suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behavior within each experiment, etc. The data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Also, photon source energy, exposure geometry, and body weight considerations were used to select studies where the dose to hematopoietic marrow was nearly uniform, i.e., < +- 20%. The data base reflects 13 mammalian test species ranging from mouse to cattle. Some 211 studies were compiled but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to practical human exposures. Of the 105 studies, 70 were for various rodent species, and 35 were for nonrodent groups ranging from standard laboratory primates (body weight ∼5 kg) to cattle (body weight 375 kg). This paper considers seven different dose-response models which are tested for validity against those 105 studies. The dose-response models included: a right-skewed extreme value, a left-skewed extreme value model, log-logistic, log-probit, logistic, probit, and Weibull models. In general, the log transformed models did not improve model performance and the extreme value models did not seem consistent with the preponderance of the data. Overall, the probit and the logistic models seemed preferable over the Weibull model. 30 refs., 8 tabs

[en] Our recent work in the comparison of parametric models for use in animal radiation mortality studies is reviewed, along with predictions of lethal doses for man based on these models. 1 ref., 1 tab

[en] Based upon an extensive data base including 100 separate animal studies, an estimate of the mortality dose-response relationship due to continuous photon radiation is predicted for 70 kg man. The model used in this prediction exercise includes fixed terms accounting for effects of body weight and dose rate, and random terms accounting for inter- and intra-species variation and experimental error. Point predictions and 95% prediction intervals are given for the LD₀₅, LD₁₀, LD₂₅, LD₅₀, LD₇₅, LD₉₀, and LD₉₅, for dose rates ranging from 1 to 50 R/min. 6 refs., 5 tabs

[en] Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between ∼ 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is ''critical'' to hematopoietic recovery does not resemble stem-like cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD₅₀ and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients

[en] This paper reviews new estimates of the LD₅₀ in man by Mole and by Rotblat, the biological processes contributing to hematologic death, the collection of animal experiments dealing with hematologic death, and the use of regression analysis to make new estimates of human mortality based on all relevant animal studies. Regression analysis of animal mortality data has shown that mortality is dependent strongly on dose rate, species, body weight, and time interval over which the exposure is delivered. The model has predicted human LD₅₀s of 194, 250, 310, and 360 rad to marrow when the exposure time is a minute, an hour, a day, and a week, respectively

[en] This paper reviews new estimates of the L₅₀ in man by Mole and by Rotblat, the biological processes contributing to hematologic death, the collection of animal experiments dealing with hematologic death, and the use of regression analysis to make new estimates of human mortality based on all relevant animal studies. Regression analysis of animal mortality data has shown that mortality is dependent strongly on dose rate, species, body weight, and time interval over which the exposure is delivered. The model has predicted human LD₅₀s of 194, 250, 310, and 360 rad to marrow when the exposure time is a minute, an hour, a day, and a week, respectively

[en] The scientific basis for compensation of persons developing cancer who have a documented history of exposure to radiation or other carcinogens is an important legal issue. The measure Relative Attributable Risk (RAR) has been proposed as a basis for determining eligibility for compensation. The purpose of this report is to present results of an analysis of the magnitude and sources of uncertainty in the RAR measure. The range of 1/10⁶/rad-year to 6/10⁶/rad-year was chosen as a reasonable range of excess-risk estimates for thyroid cancer based on published estimates. The use of such a range in risk estimates produces very wide variability in RAR estimates. Uncertainty in underlying incidence levels and in dosimetry are other major factors contributing to large variability in estimated RAR levels

[en] Isotope dilution analysis (IDA) has been historically used in situations where separation of an analyte from its matrix is difficult or imprecise. A requirement of IDA is that analyte mass be either measured or inferred for the determination of specific activity or its equivalent. Thus, two measurements are necessary: one of activity and one of mass, and the latter requirement frequently limits the sensitivity potentially available from IDA. Methods to circumvent the problem have been described, but these are usually subject to other constraints. For example, in substoichiometric IDA, equal amounts of analyte are isolated and counted before and after dilution, but the isolation of exactly equal quantities of material is usually difficult. This paper describes the principle of a new technique that couples IDA with carbon 14 to high-performance liquid chromatography (HPLC). It removes the need for a direct mass measurement and thereby greatly improves the sensitivity of IDA while retaining its high selectivity. Viewed from the chromatographic perspective, it offers a sensitive, analyte-specific procedure for indirect detection

[en] Studies conducted during the 1950s and 1960s of radiation-induced mortality to diverse animal species under various exposure protocols were compiled into a mortality data base. Some 24 variables were extracted and recomputed from each of the published studies, which were collected from a variety of available sources, primarily journal articles. Two features of this compilation effort are (1) an attempt to give an estimate of the uniform dose received by the bone marrow in each treatment so that interspecies differences due to body size were minimized and (2) a recomputation of the LD₅₀ where sufficient experimental data are available. Exposure rates varied in magnitude from about 10^-2 to 10³ R/min. This report describes the data base, the sources of data, and the data-handling techniques; presents a bibliography of studies compiled; and tabulates data from each study. 103 refs., 44 tabs