Development of Metabolic Model of Tritium in the Human Body
Tsuyoshi MASUDA, Kensaku MATSUSHITA, Yasuhiro TAKO, Shun’ichi HISAMATSU
Department of Radioecology
Abstract
In the radiation safety assessment for nuclear facilities including the first commercial spent nuclear
fuel reprocessing plant in Rokkasho, Japan, the internal dose of the public due to tritium has been estimatedusing the dose conversion factors based on the ICRP metabolic model of hydrogen in the human body. TheICRP metabolic model is very simple and is comprised of a free water tritium (FWT) compartment andorganically bound tritium (OBT) compartment having biological half-lives of 10 and 40 d, respectively.
Although the biological half-life of tritium water (HTO) in the human body was examined in several
cases such as accidental intakes or experimental administrations, actual data on the metabolism of OBT arequite limited. The objective of this research program is to establish experimentally the metabolism of tritium
including OBT in the human body for more realistic dose estimation. In the present experiment, the stable
isotope of hydrogen, deuterium (D), was used as a substitute for tritium.
Until FY 2013, D-labeled glucose, palmitic acid, and leucine were administered to volunteers as
representative of carbohydrates, lipids, and proteins, respectively, followed by measuring the D/H ratio in
their urine. A model for metabolism of each compound was constructed by using the urine D/H data. The
model had a compartment of free water D (FWD) and two compartments of organically bound D (OBD1 andOBD2), which are separately connected to the FWD compartment. The OBD1 and OBD2 represent thecompartments having fast and slow rates of degradation to the FWD, respectively. The parameters in themodel were determined by a least square fitting method using the measured data. By combining the models
for those compounds as representative of three major nutrients, we could predict the metabolism of D infoods from their proportion of the three major nutrients.
In FY 2014, D-labeled soybean was prepared and administered to volunteers. The urine excretion of D
from the volunteers was measured to verify the prediction with the combined model and composition of
three major nutrients in soybean. After soybean plants were exposed to 20% D2O as soil water andatmospheric moisture for 3 weeks, soybeans were harvested and lyophilized. The dried soybeans weresoaked in tap water to remove exchangeable OBD, and then lyophilized again. Volunteers were administered
8.5 to 11 g of lyophilized D-labeled soybean during lunches of four successive days. After the firstadministration, their urine samples were collected for up to 16 weeks for analysis of D concentrations withmass spectrometers. The first morning urine samples for 7 d before the administration were also collectedand used as control samples of each volunteer. All processes of the experiment were approved by the IES
Review Board for Human Subject Experiments, and written informed consents were obtained from allvolunteers.
The estimated concentrations of FWD in urine by the combined model and the proportion of the threemajor nutrients of soybean, agreed relatively well with the observed values throughout the experimentalperiod. We constructed a metabolic model of D-labeled soybean directly from the measured data andcalculated cumulative D-burden after single D-labeled soybean ingestion for 50 y. The cumulative D-burden

obtained was 1.6 times smaller than the prediction by the combined model. On the other hand, thecumulative dose for 50 y after single dietary reference intakes for Japanese by the combined model was 1.3
times larger than the prediction by the ICRP model for OBT. Judging from the error in the soybean case, it
was considered that the prediction by the combined model was roughly consistent with the ICRP model.

f1(mol D mol-1 H)

Ｑ
1-f

FWD concentration

1-dd

OBD2

OBD1

FWD

100
10
10.1050100Time (d)Fig. 3 An example of the typical time course ofFig. 1 Structure of the metabolic model for ingested

concentrations of free water deuterium in urinedeuterium.

samples after the first administration of deuterium

Q: mass of administered deuterium. OBD1, OBD2,labeled soybean. The solid line shows theFWD: compartment of deuterium. f1, d:estimation by the model shown in Fig. 1.

distribution factor. kn: elimination rate constant.
M: mass of deuterium in each compartment.

C modeldLdP

L modelP model

Observed FWD concentration(mol D mol-1 H)

dC60

y = 0.9565x
R² = 0.9154

40200Fig. 2 Structure of the combined metabolic model for

0204060

Estimated FWD concentration(mol D mol-1 H）

ingested deuterium in foods.
C model, L model, P model: submodel (Fig. 1) ofFig. 4 Estimated and observed concentrations of freeingested deuterium in carbohydrates, lipids, andwater deuterium in urine samples of all the maleproteins, respectively. dc, dL, dP: proportion ofvolunteers.

carbohydrates, lipids, and proteins in food,respectively.