A biochemical-based model for the dosimetry of dietary organically bound tritium--Part 1: Physiological criteria.

In this paper the physiological criteria for a novel form of model are described whose biokinetics are governed by the overall metabolic reactions of the principal nutrients: carbohydrates, fats, and proteins. The biokinetics of a particular element are based primarily on the oxidation of glucose, fatty acids, and amino acids and the formation of water, carbon dioxide, and urea. The compartmental models proposed follow the pathways of the major elements including hydrogen and, hence, tritium. The parameters for two models of differing complexity--called the HCNO-S and HCNO-C models--were evaluated here on the basis of biochemical reactions; the results of compartmental analysis are reported in an accompanying paper. The simpler form of the HCNO model has single compartments representing the principal nutrients. The more complex model includes compartments representing the longer-term retention of carbohydrates as glycogen, fats as adipose tissue, and proteins in bone and soft tissues. The pool sizes and hydrogen transfer rates are estimated. The incorporation of biochemical reactions and important metabolic parameters serve to give the models a greater semblance of physiological merit than those currently available. For example, ingestion of carbohydrates results in a respiratory quotient of 1.0 and 100% of the hydrogen content oxidized to water, which are the same as values published in the literature. This form of metabolic model enables development of models for other isotopes, besides 3H, of the major elements of the body, e.g., 14C, 15N, 18O.

A biochemical-based model for the dosimetry of dietary organically bound tritium--Part 2: Dosimetric evaluation.

In this paper the dosimetry for a novel form of physiological model, whose biokinetics are governed by the overall metabolic reactions of the principal nutrients carbohydrates, fats and proteins, is evaluated by compartmental analysis. Two models of differing complexity, called the HCNO-S and HCNO-C models, were developed from parameters evaluated in an accompanying paper. The simpler form has single compartments representing the principal nutrients. The more complex model includes compartments representing the longer-term retention of carbohydrates as glycogen, fats as adipose tissue, and proteins in bone and soft tissues. The effective doses for various tritiated intakes are the same, or similar, as calculated by the two HCNO models, except for tritiated protein. The dose coefficient for an intake of tritiated water is approximately 8% greater than that recommended by the ICRP when the tritium body burden is considered as a homogenous pool. However, when the composition of individual organs is taken into account, the dose coefficient for an HTO intake is approximately 22% greater than the ICRP value. The HCNO-C dose coefficient for OBT in a normal diet is 5.0 x 10(-11) Sv Bq(-1), which is 1.2-fold greater than the ICRP dose coefficient for an OBT intake. The HCNO-C composition model gave organ and tissue doses with the largest range for a tritiated Reference Man dietary intake, the highest dose (red marrow, then breast) being around three-fold the lowest. A property of the HCNO models, important for bioassay analyses, is that a major part (> 90%) of an OBT intake is oxidized and excreted as HTO, which is physiologically more accurate than the current ICRP OBT model. The effective dose of specific tritiated foods, e.g., rice and wheat, was evaluated on the basis of their constituents.

Review of the ICRP tritium and 14C internal dosimetry models and their implementation in the Genmod-PC code.

Biokinetic models for tritium and 14C compounds, as described by various ICRP publications, have been incorporated into the Genmod-PC internal dosimetry code. This work reviews the models for tritium and 14C labeled compounds that the ICRP has formulated over several decades. The ICRP dosimetry prescribed for hydrogen and carbon radionuclides is fundamentally different from that recommended for other elements in that it is based on retention functions for whole body activity instead of compartmental biokinetic models. The ICRP recommends dosimetric methods for tritium and 14C compounds, ten of which are coded in Genmod-PC as compartmental models, namely, five tritium compounds, e.g., tritiated water, tritium gas, and five 14C compounds, e.g., carbon dioxide, carbon-labeled methane. The values of the Genmod-PC calculated dose coefficients were compared with the ICRP's values. It is shown how the dose coefficients for intakes of tritium and 14C compounds are affected by different interpretations of the methods recommended by the ICRP for two of the three classes of vapors and gases. Some aspects of the ICRP models, such as the percent oxidized, would benefit from reconsideration so as to produce tritium and 14C biokinetics that are less dependent on the radionuclide.

Influence of gender differences in the carbon pool on dose factors for intakes of tritium and 14C-labeled compounds.

The ICRP's biokinetic models for five tritium-labeled and five 14C-labeled compounds (not including radiopharmaceutical compounds and excepting carbon monoxide) incorporate a compartment representing the body carbon pool. Using the ICRP models, as coded into the Genmod-PC internal dosimetry code, higher dose coefficients are calculated for females than for ICRP's Reference Man. The ICRP's committed effective dose coefficients for the ingestion of tritiated water and organically bound tritium by the adult male are 1.8 x 10(-11) and 4.2 x 10(-11) Sv Bq(-1), respectively. Using the Genmod-PC code, the corresponding dose coefficients for the adult female are 2.2 x 10(-11) and 6.2 x 10(-11) Sv Bq(-1), which are 25% and 46% greater than the adult male's. Similarly, the ICRP's dose coefficient is 5.8 x 10(-10) Sv Bq(-11) for an intake of organically bound 14C by the adult male, and the estimated dose coefficient using Genmod is 54% greater for the adult female. The carbon retention half-time for an average adult female is calculated as 51 d and that for an average adult male, 38 d; the latter is similar to the carbon half-time of 40 d recommended by International Commission on Radiological Protection (ICRP). The longer turnover time of whole body carbon in females is one factor that causes the dose coefficients for females to be higher than those of males; a second factor is the smaller whole body mass of ICRP's Reference Woman compared to Reference Man.

Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice.

To help resolve uncertainties as to the most appropriate weighting factor for tritium beta rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium beta rays compared to X rays ranged from 1.0 +/- 0.5 to 1.3 +/- 0.3. A best estimate of the RBE for this experiment was about 1.2 +/- 0.3. A wR value of 1 would thus appear to be more appropriate than a wR of 2 for tritium beta rays.

Comparison of the ICRP and MIRD models for Fe metabolism in man.

A task group of the Medical Internal Radiation Dose (MIRD) Committee has recently published a model of Fe metabolism in man. This model was developed to calculate doses from radioiron injected for medical diagnostic purposes. It is a compartment model with recirculating Fe exchanging between plasma and extracellular fluids, tissue storage compartments, bone marrow and red blood cells (RBC). It is a first order model with the exception of Fe in the RBC compartment, which is assumed to retain Fe for 120 days, at which time the Fe returns to the extracellular fluid compartment. By contrast, the International Commission on Radiological Protection (ICRP) model is a "once through" first order compartment model, with the compartments represented by organs (spleen, liver and other soft tissue) rather than physiological compartments as in the MIRD model. Both of these models have been implemented in the computer code GENMOD which contains the ICRP recommended lung and gastrointestinal tract models and which is used at the Chalk River Nuclear Laboratories to calculate doses, excretion rates, derived investigation levels, etc. The results of calculations using these models have been compared to see if the much less sophisticated ICRP model was adequate for radiation protection purposes. It was found that the effective dose per unit intake of radioiron was higher for the MIRD model and urinary excretion rates following an exposure were considerably different. It is concluded that the ICRP model should not be used in dosimetry calculations, or for comparing monitoring results to model calculations.