Tritium Metabolism in the Human Body
Tshuyoshi 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 experiment, the stable isotope ofhydrogen, deuterium (D), was used as a substitute for tritium.
In FY 2013, volunteers were administered with 4 g of D-labeled and 0.4 g of 13C-labeled leucine or 1
g of D-labeled and 0.1 g of 13C-labeled alanine during lunches of four successive days. After the firstadministration, their urine and breath samples were collected for up to 16 weeks for analysis of D and 13C,
respectively, with mass spectrometers. All procedures of the experiment were approved by the IES Review
Board for Human Subject Experiments, and written informed consents were obtained from all volunteers.
The D/H ratio data obtained for the urine samples were used to construct a model of metabolism of D
ingested as leucine or alanine. The model had a compartment of free water D (FWD) and two compartmentsof organically bound D (OBD1 and OBD2), which are separately connected to the FWD compartment. The
OBD1 and OBD2 represent the compartments having fast and slow rates of degradation to the FWD,respectively. The dividing ratio of ingested OBD to OBD1, transfer rate constant between thosecompartments, and the excreting rate constant of FWD compartment were determined by a least square
fitting method using the measured data. The excreting rate constant of D from the FWD was 7.6×10-2 d-1
for leucine and was 8.2×10-2 d-1 for alanine, which were comparable with that of the ICRP metabolic model,
7.1×10-2 d-1. Although the degradation rate constants of OBD1 and OBD2 were not substantially different
between leucine and alanine (7.1-7.8×10-3 d-1 and 7.6-8.2×10-2 d-1), the dividing ratio for ingested OBD tothe OBD1 having the fast degradation rate was smaller for leucine (5.2×10-1) than for alanine (9.0×10 -1).
Thus the cumulative exposure of the human body to D calculated by the model after a single oral intake
during 50 y, which corresponds to the committed dose for tritium, was larger in leucine than alanine.
We calculated the cumulative exposure after a single oral intake of various compounds labeled by D or
13
C by using the model constructed in the present study and the model constructed previous to FY 2013. The
obtained results were compared with the cumulative exposure by ICRP metabolic model for tritium. The
comparison showed that our model for 13C gave lower exposure than that of ICRP model, while higher
exposure are obtained by our model for tritium than the ICRP one, showing the necessity for the furtherstudy.

Table 1
Subject group

Dose of labeled compounds and isotopes

Chemical formula of labeled

Dose to subjects (g person-1)

compoundLabeledcompoundD

13

Leucine-administeredgroup(CD3)2CDCD2CD(NH2)COOH(13CH2)213CH13CH213CH(NH2)13COOH

1.00.10.14
000.057

Alanine-administeredgroup

CD3CD(NH2)COOH

1.00.086

0CH313CH(NH2)13COOH

0.100.042

13Table 2B Alanine group parameters in the modelParameter
Valuef1
1.0±0.0d0.90±0.0534±16
k1
k20.0071±0.0026
k30.082±0.007*: Each value is the mean±standard deviation.

CTable 2A Leucine group parameters in the model*
ParameterValue
f1
0.97 ± 0.05
d0.52 ± 0.07
7.8 ± 3.8
k1
k20.0078 ± 0.0056
k30.076 ± 0.021*: Each value is the mean±standard deviation.

AlanineLeucine

dC concentrationin breath (atom % )

1-f1

f1

131-dOBD2

OBD1݇ଵ ‫ܯ‬ை஻஽భ ሺ‫ݐ‬ሻConcentration of D in urine-1(mol D mol H)݇ଶ ‫ܯ‬ை஻஽మ ሺ‫ݐ‬ሻFWD݇ଷ ‫ܯ‬ு஽ை ሺ‫ݐ‬ሻFig. 1 Three-compartment model of metabolism of D
ingested as amino acid
FWD, OBD1, OBD2: compartment names, MFWD(t),MOBD1(t), M OBD2(t): D amounts in each compartment(g). k1 to k3: transfer rate constants.

Time after administration (d)Fig. 2 Concentration of 13C in breath CO2 and D in urine waterOpen circle: concentration after administration. Solid line:
estimated values by the model.
10.00

Ratio

1.00
0.10
MF

LeucineM

F

Alanine

MFHDOM

FGlucoseM

F

Palmitic acid AverageFig. 3 Ratio of cumulative exposure to D or 13C for 50 y after single dose by present three-compartment model to that by the ICRPmodel.
Cumulative exposure is the area under the retention curve of D and 13C. Results reported through 2013 are included. M, male. F, female. Openbar, D. Filled bar, 13C. The average was obtained by the assumption of representing Leucine F, Glucose F, and Palmitic acid F as protein,carbohydrate, and fat in the diet of Japanese given by the Standard Table of Food Composition in Japan (5th revised edition), respectively.