The Human Plutonium Injection Experiments

“late” data (80, 300, 400, 500, and

10,000 days) to obtain the exponent for

the second power-function term for uri-

nary excretion.  (The 1600-day data

were analytically suspect and were dis-

carded; those data, and data from the

workers in the same time frame, were

influential in Langham’s extension of

his power function to 1750 days.)  Fix-

ing the slope (in a log-log plot) for the

late data meant the early data would not

have undue influence.  Once the slopes

in the two regions were fixed, the coef-

ficients of the two power terms were

found from a weighted nonlinear least

squares fit, using the medians (rather

than the raw data or the means) to cut

down on any undue influence from out-

liers.  A similar analysis was done for

fecal excretion, although Moss and Ti-

etjen did not have to constrain the data.

The final results are:

Y

u

5

0.4132 X

2

1.0615

1

0.0187 X

2

0.3217

,

Y

f

5

1.1481 X

2

1.4400

1

0.0058 X

2

0.2039

.

The dependence of the excretion func-

tion on two power terms is obvious in

the log-log plot of the data (Figure 6),

which has two distinct regions of dif-

ferent slopes.  The second region is es-

pecially obvious because of the data at

10,000 days, which has less scatter be-

cause of improved analytical methods.

However, the corrected data around day

80 and days 300 to 500, when plotted

on an individual basis for each patient,

also strongly indicate the different slope

of the second region, despite the much

greater scatter of those data evident in

the figure.  

Excretion of plutonium. The equa-

tions have allowed new estimates to be

made of the amount of plutonium that

would be excreted over the long term

(see Table 3), and it turns out that this

is more than twice the amount of what

had been estimated earlier with Lang-

ham’s single-term power function.  For

example, after 10,000 days (27.4 years),

a total of 32.0 percent of internal pluto-

nium will have been excreted compared

to the 12.1 per cent estimated from

Langham’s function.  This fact helps

explain why body-burden values de-

rived from autopsy studies of plutonium

workers tend to be less than that previ-

ously estimated from the urine data.

However, because 68.0 per cent of the

plutonium remains (versus 88.9 per

cent), the conclusion about removing

workers from further exposure once

they have reached the maximum per-

missible limit remains as true today as

it was in 1945.  

On the other hand, the implications for

dose estimates are significant.  After

fifty years, almost half the plutonium

will have been excreted.  Thus, the re-

sults of a tissue analysis on a worker

that died 50 years after his exposure

would extrapolate to an initial body

burden almost twice that estimated

from the Langham function.  The in-

crease in body burden translates, in

turn, to an increase in the radiation

dose to the person over the rest of his

life.

Two physiological regions. Physical-

ly, the importance of a two-term power

function is that it likely corresponds to

two different physiological processes.

Moss and Tietjen believe that for the

The Human Plutonium Injection Experiments

220

Los Alamos Science Number 23  1995

1

10

100

1000

10000

Days after injection

0.0001

0.001

0.01

0.1

1.0

Per cent of injected dose excreted

Pu from blood reservoir

Pu from bone reservoir

Langham model

Figure 6.  A Re-analysis of the Plutonium Urinary Excretion Data

The data are the median values for urinary excretion in the human injection studies

after rejection of suspect data and correction for chemical yield.  The solid curve repre-

sents the two-term power function that results when the slope of the curve determined

from the early data (5 through 15 days) is used to fix the exponent of the first term of

the function and the late data are used to determine the exponent of the second term.

The curve shows two distinct regions that probably correspond to an early release of

plutonium from a blood reservoir followed by a slower release from a bone reservoir.

The original Langham power-function model is also shown (dashed line); the apparent

poor fit is, of course, a result of the recent adjustments of the data.

Table 3.  10,000-day Excretion of Plutonium

Moss-Tietjen function

Langham function

Urinary excretion:

17.4 %

7.8 %

Fecal excretion:

14.6 %

4.3 %

Total excreted:

32.0 %

12.1 %

Amount remaining:

68.0 %

88.9 %

---

first couple of weeks, most of the ex-

creted plutonium is coming from a

blood reservoir.  For later times, the

plutonium is being released more slow-

ly from a bone reservoir with some

contribution from the liver.  Such be-

havior had been postulated in 1972 by

Betsy Stover from an analysis of long-

term plutonium excretion in dogs, and

Langham had conjectured about this

type of physiological change as well.

However, the human data did not ap-

pear, until recently, to follow the same

pattern.  Now, the dog and human data

are consistent.

These results form an interesting con-

trast with radium.  After intake, radium

is almost immediately deposited in the

bone.  To be excreted, it has to be me-

tabolized and returned to the blood.  So

there is only one region, and the excre-

tion rate, although initially very high,

drops off in a log-log plot with no ap-

parent changes in slope.  A single-term

power function is adequate to describe

the full excretion behavior for radium.

Although our two-term power function

fits the general trend of the initial ex-

cretion of plutonium, there has always

been some variability in the first four

days, which, as it turns out, has a phys-

iological basis.  Typically, there is an

increase in the excretion rate at about

four days (Figure 7) corresponding to a

turnover in red blood cells.  Soluble

plutonium has been shown to combine

with the iron-transport protein in the

blood, transferrin, where it is incorpo-

rated into developing red blood cells.

However, after four days, cataboliza-

tion, or destruction, of about 10 per

cent of the developing red blood cells,

including all those containing plutoni-

um rather than iron, are released back

into the blood, which increases the

amount available for excretion.  Such a

peak in the excretion data cannot, of

course, be modeled with simple, one-

or two-term power functions.  But rec-

ognizing why a peak occurs at the four-

day mark is a satisfying check of our

understanding of the metabolism of plu-

tonium in humans.  Perhaps more im-

portant, though, noting the existence of

the peak in most of the original human

excretion curves helps substantiate the

sensitivity and, thus, the importance

and relevance of that fifty-year-old

data.

Additionally, the iron-transport bound

plutonium that is released back into the

blood is not incorporated into mature

red blood cells.  Some fraction of this

plutonium is excreted and the rest is re-

deposited in tissue.  A cycle of this sort

continues on and on, which gradually

brings small amounts of plutonium into

the blood to be excreted.

Implications of the Plutonium

Injection Studies

In the years that have passed since the

human plutonium injection studies, the

data have been endlessly analyzed, dis-

cussed, and re-analyzed by the commu-

nity of health physicists concerned with

the protection of plutonium workers.

What has been learned and what impact

has this knowledge had on health pro-

tection for plutonium workers?

The determination of a radiation dose

to workers from plutonium (or the toxic

dose from any material, for that matter)

requires a biokinetic model that de-

scribes, in mathematical terms, how a

known intake of plutonium translates to

a time-dependent distribution of pluto-

nium throughout the body.  For exam-

ple, an inhalation exposure to plutoni-

um dust would need expressions that

describe, as a function of time, the frac-

tion of plutonium retained by the lung,

the fraction that enters the bloodstream,

the fraction that is coughed up, swal-

lowed, and passed through the gastroin-

testinal tract, the fraction in the blood

that goes to various organs, such as the

liver and bone, the fraction of plutoni-

um that is filtered out by the kidneys

and excreted, and so forth.  The human

plutonium injection studies coupled

with autopsy results yielded consider-

able data that were applicable to the

calculation of the time-dependent distri-

The Human Plutonium Injection Experiments

Number 23  1995  Los Alamos Science  

221

1

2

3

5

7

10

Days after injection

0.01

0.1

1.0

Per cent of injected dose excreted

Pu-239 in man (CHI-3)

Iron-59 in man (normalized)

Feedback from catabolized precursor blood cells

Figure 7.  The Four-day Peak for Red Blood Cells

Many of the urinary excretion curves for the human plutonium injection studies show a

small peak around day 4 (the blue curve above uses the excretion data of CHI-3).  This

peak corresponds to the release of plutonium back into the blood when about 10 per

cent of newly forming red blood cells, which started their life cycle at the time of the

injection, are destroyed (catabolized).  A similar peak is observed in studies with iron-

59 in man (red curve), as well as for plutonium-239 in dogs (not shown).

---