REPORT OF THE
UNITED NATIONSSCIENTIFIC COMMITTEE
ON THE.
..
EFFECTS OF.·ATOMIC·. RADIATION-

1

I'' . -.~-=- .
.

.., . -·.. -

·~

·.

.

... .

·-

.
--·-- ......

GENERAL ASSEMBLY

OFFICIAL RECORDS : NINETEENTH SESSIONSUPPLEMENT No. 14 CA/ 5814)
~·=-•

)?~

--

~~·

-.. .

if?. 'f.J) ·- f-c • (_I: : :1.; .· .
":.

UNITED NATIONSNew York, 1964.) b.)"f

NOTE
Throughout the present report, references to the annexes are indicated by aletter immediately followed by a number: the letter denotes the relevant annex andthe number the paragraph therein. Within each annex, references to its scientificbibliography are indicated by numbers.
Symbols of United Nations documents are composed of capital letters combinedwith figures. Mention of such a symbol indicates a reference to a United Nations
document.

ANNEX B

RADIATION CARCINOGENESIS IN MAN

CONTENTSParagraphs

I. INTRODUCTION

Paragraphs

IV. NECK TUMOURS (EXCLUDING THYROID) AFTER

1-20

THERAPEUTIC IRRADIATION , •. , ...••• , ..••.•••..• 122-125

II. LEUKAEMIA • . . • • • . • • . • • • . . • • . • • • • • . . • . . • . • . • • 21-89
Leukaemia in Japanese A-bomb survivors . • • • • •Leukaemia in early post-detonation entrants in
Hiroshima . . . . • . . . • . . . . . . . . . . • . . • . . . • • . • . . •Leukaemia in American radiologists . . • . • . • . • . •Leukaemia in ankylosing spondylitis patients . . • •Leukaemia in children irradiated therapeuticallyfor "enlarged thymus" • . . . . . . • • . . • • • • . • • • . . .
Leukaemia in children irradiated in utero • • . . • •Leukaemia in other groups medically irradiatedfrom external sources • • • • • • . • • • • • . • • • • • • • . • •Leukaemia after 11a1 therapy • • . . . • • • • . . • • • . • . . •Leukaemia in polycythemia vera patients treatedwith P 32 • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •Leukaemia and environmental radiation e."<posure

21-33

V. SKIN TUMOURS AFTER THERAPEUTIC IRRADIATION. 126-129

34-36

VI. BONE TUMOURS .•.••....•.••....•.•.•.•..••.. 130-145

37-39
40-55

Bone tumours after therapeutic irradiation ....• 130-131
Bone tumours in persons with radium body burdens •••.......•.••.••.••••.•••••••••...••.• 132-145

56-61
62-73

VII. THORIUM-RELATED NEOPLASMS •••..•••••••••... 146-151
VIII. LUNG CANCER IN MINERS ....................... 152-174

74-81
82-85

IX. OVER-ALL INCIDENCE OF NEOPLAS~!S AFTER TOTALBODY IRRADIATION •...••••••..•.•••.•.....•...• 175-193
Japanese A-bomb survivors •...•..•............ 175-180
Populations exposed to high levels of environmental radiation ••.••..•••.••..............•
181
Children exposed iii utero to diagnostic irradiation 182-193

86-87
88-89

Ill. THYROID NEOPLASMS ••••.••••.•. , . , , •..•. , . .. . 90-121
Thyroid carcinoma in Japanese A-bomb survivors 90-100

Pag1

Thyroid neoplasms in patients therapeutically irradiated from external sources .............. 101-119
Thyroid neoplasms in patients given I131 •••••••• 120-121

TABLES ••..•.••••.....••.•••••......••.......
REFERENCES •..•..••...••••••••.••.•••..•..•..

100
107

tural and functional changes which appear to be similarin nature.

I. Introduction

1. The purpose of this survey is to review data on
the risk of induction of cancer by ionizing radiations
in man, with emphasis on information either new or
not discussed in detail in the 1962 report of the Committeea to the General Assembly. 1 •b

5. Among the mechanisms likely to be of importance,
which include systemic as well as local factors, are(a) direct cellular injuries, including changes in genes
and chromosomes; ( b) promotion of growth and development of cells with malignant potential through local
injurious effects on related cellular systems and stroma;( c) complex perturbations of cellular and tissue homeostasis; ( d) systemic influences and effects on distanttissues and cells which may result in altered immunological mechanisms, endocrine disturbances, and changes inmetabolism and nutrition.

2. Most of the information available on tumour induction by radiation in man and experimental animals
comes from studies of the effects of high doses of radiation, that is, doses of hundreds of rads and greater.
From these data it is known that ionizing radiation inhigh doses may cause or contribute to the induction ofcancer in widely diverse types of mammalian tissues,
though the susceptibility of the different tissues varies
greatly with genetic and physiological factors.

6. Radio-biological investigations suggest that relatively large doses of radiation are usually required tocause severe systemic effects or produce observablechanges in tissue structure and function. Such highdose effects may play a major role in the production of
the neoplasms that are superimposed on chronic radiation-induced tissue changes. However, in so far as cancer may result from low doses of ionizing radiation,
the major mechanisms would presumably be more consistent with the production of malignancy as a resultof mutations, of chromosomal injuries or possibly ofchanges enhancing the susceptibility of cells to transformation by viruses.

3. Few data are available at low doses of radiation(doses of the order of 10 rads and Jess), and the extent
to which radiation has a general carcinogenic effect at
low doses is a matter of speculation.
4. The mechanisms of carcinogenesis in general are
not well understood. However, the evidence is that theneoplastic change occurs at the cellular level and is frequently associated with observable modifications in cellstructure (particularly chromosomal constitution) andfunction. A variety of carcinogens, including chemicals
and viruses as well as ionizing radiations, produce struc-

7. Radiation-induced tumours are indistinguishable
in general from cancers arising from other causes. Furthermore, as noted above, there may be common basic
mechanisms. These two considerations affect both thetype of statistical data that can be obtained in clinical• Official Records of the General Assembly, Seventeenth Ses~
sion, Suf>/1/ement No. 16 (A/5216); hereinafter referred to as
the "1962 report".
b Superscripts refer to the corresponding entries in the bibliography at the end of the present annex.

81and experimental studies and the interpretation of suchdata.
8. When similar basic mechanisms are involved in
the production of radiation-induced and other cancers,
the effect of radiation may be either (a) to advance intime the control curve of age distribution of tumoursor ( b) to multiply by some factor the age-dependent
incidence. When similar mechanisms are not involved,
the effect of radiation may be to produce an additional
incidence unrelated to the control age incidence. The
yield of tumours, in any given interval after the exposure, will be determined by which of these processes
or by what combination of them operates and by possible changes in survival time occasioned by the irradiation.
9. Most of the data available in man, and even inexperimental animals, are confined to a limited periodof time following irradiation. Any attempt to estimate
the total lifetime incidence of tumours is likely to involve extrapolation.
10. In making risk estimates for human populations,the difficulties of epidemiological studies must be borne·in mind. There is the possibility of large variation insusceptibility in the population because of differencesin genetic, physiological and environmental factors.
Thus the dose-effect relationship observed in a study ofa whole population does not necessarily apply to individuals or to subgroups of the population. When isolated risk estimates are derived from irradiated subjects
highly selected for one reason or another and are applied to the general population, this should be done withgreat caution.
11. In many instances it has been necessary to perform dose determinations long after the irradiation,and since it may be impossible to reproduce the conditions
existing at the time of the original irradiation, many ofthe dose estimates necessarily have a wide margin of
uncertainty.
12. In addition, there are problems of terminology andstatement of dose. When the body is irradiated non-uniformly (because of limited field size, limited penetrationof the radiation, or non-uniform distribution of radio·
active nuclides within the body) the irradiation cannot
be unambiguously specified by a single number but onlyin terms of dose distribution. To provide a basis for aparticular risk estimate, one must, however, select asingle value of a quantity that characterizes the irradiation, even though such a value may be of limited accuracy
or significance.
13. The physical quantities most commonly determined for external irradiation are either kerma or exposure in free air, 2 since measurements are frequently
performed with devices of minimal mass and without
the use of phantoms. Because of the complexity of thephysical interactions, there may be a considerable difference between the quantities thus determined and theabsorbed dose in the tissues of interest.
14. All empirical risk estimates are valid only forthe conditions of irradiation under which they wereobtained. Thus, a risk estimate valid for a certain dosedelivered in a single exposure probably is not valid forthe same dose delivered over a long period of time.
15. For estimation of risk as a function of dose one
requires ideally a dose-effect curve established over awide range of doses. Hmvever, in man, information isscanty and when available refers only to a limited dose

range. Within this range and within the limitations described above estimates of risk can be made. Outside
this dose range it is necessary to make assumptions as
to the nature of the underlying dose-effect relationship.
16. One such assumption relates to "threshold dose".
For certain types of radiation-induced cancer there may
be a threshold dose, but this can be established only froman understanding of the mechanisms. Even statisticalstudies of cancer incidence in large irradiated populations cannot unequivocally establish the existence of athreshold. In general, therefore, for the estimation ofrisk at low doses it has to be accepted that there is a
finite risk of cancer induction, however small, even at
the lowest doses.
17. In most cases in which extrapolation to low doses
has been attempted a linear relationship between doseand effect has been assumed. A discussion of the useof the linear hypothesis can be found in the 1962 report. It should be noted that the assumption of linearity
is the only one which allows the use of mean doses in
estimating risks. In general, the assumption of a linear
dose-incidence relationship at low-dose levels is likely
to result in an over-estimate of the degree of risk.
18. This is, in general, likely to be true because mosth.'1lown dose-response curves tend to be sigmoid or linear
at their lower ends, and because, on theoretical grounds,
single-event changes may be expected to predominate
at very low doses. Assurance that linear extrapolations
are likely to over-estimate the risk is greatest when observation includes the region of rapidly increasing response with increasing dose.
19. An estimate based on the relative increases overthe "natural" incidence will be influenced to a large extent by the natural incidence, which in some cases (forexample, thyroid or bone cancer) is very low. Absoluterisk estimates are a measure of the susceptibilities ofdifferent tissues to the induction of cancer by radiation.
20. In this report risk estimates of cancer induction
will be presented either in relative terms, as increase
relative to natural incidence, or in absolute terms, expressed as the number of cases per unit time and unit
dose in a population of given size, for example as number X lQ-6 per year per rad. It must be emphasizedthat these estimates of risk are reliable only in the rangeof doses, usually high, for which information is available. The use of the estimate at doses outside the observed range may be very much in error, and in the lowdose range where a linear extrapolation to zero doseis used, it can in most cases only be taken as an indication of the upper limit of risk.

II. Leukaemia
LEUKAEMIA IN JAPANESE A-DOMD SURVIVORS

21. The most informative data that are available on
the relationship between radiation exposure and leukaemia in man are those obtained from the studies ofthe survivors of the atomic bombing in Hiroshima andNagasaki. Even in these studies there are great uncertainties in dosimetry, in the size and characteristics of
exposed populations. and in the leukaemia incidence
data. Furthermore, the incidence is being observed ina population of survivors, therefore of individuals
heavily selected at least at the high dose levels.
22. Some studies have been done on an "open population" in which there may be little accounting for migra-

82

table I and figure 1. Estimates of relative risk are given
in table II.
24. In table I and figure 1 it can be seen that there
was a sharp increase in the reported leukaemia incidence
in the exposed (within 5,000 metres) after 1946, reaching a peak eleven times higher than in the non-exposed(beyond 5,000 metres) in 1951. From 1952 to 1959 theincidence in the exposed fluctuated below this peak;from 1960 to 1962 it fluctuated within a still lower range.
25. Brill et al. 1 have summarized and compared previously reported findings on leukaemia in atomic bomb
survivors in Hiroshima and Nagasaki, as obtained fromthe ABCC Master Sample or "closed population", up
to 1958. Table III presents incidence by distance fromthe hypocentre for the 89 confirmed leukaemia cases in
Hiroshima and the 60 confirmed leukaemia cases in
Nagasaki during the twelve-year period 1947-1958.

tion of persons both non-exposed and exposed. To attempt to circumvent the uncertainties that arise in thefollow-up of such an "open population", the Atomic
Bomb Casualty Commission (ABCC) created the Master Sample, a "closed population" matched by age andsex in segments of the population proximally exposed( 0-2.000 metres from hypocentre), distally exposed(2,000-10.000 metres), and non-exposed (beyond
10,000 metres).
23. Watanabe 6 has reported the incidence of leukaemia among Hiroshima survivors ("open population"), including all leukaemia cases for the seventeen
years 1946-1962. Recomputations of these data to obtain the leukaemia incidence in the total population, inthe non-exposed population (beyond 5,000 metres, presumably including post-detonation entrants), and in the
exposed population (within 5,000 metres) are given in
20

Exf;osed Coses(wilhin S,OOOm)

15

I..

0

~
I..

8.
It')

0

.,
.,
I..

a..
UI

10

Ill

0

u
0

·e.,
0

.>I.
:>

"

..J

..:~
... ...

5

Non-exposed Coses_./·.._..
.... .. ......··....
.. ··... :·..·..··r- •.- • ...····-·-·•'•:,... --:-"' .- • ··•••. ~···All
\ .....~·-- ..... .,,,,.. ···.:·..
~···..
,-if":. . -

•

.

• ••

Japan

· .··.·.;. ..... --·--·r... . .

••••

~··
0 ....___._~...._~..___.~......~....___.~......~....___.~_._~......~...___.~...._~....___,

1945

l955

1950

1960

Figure 1. Leukaemia cases in Hiroshima, 1946-1962 (modified from Watanabe 8 )83

26. The incidence of leukaemia was greatly increased
among survivors exposed within 1,500 metres from the
hypocentre. Between 2,000 and 10,000 metres the average yearly incidence in Hiroshima (28/10°/y) was regarded by Brill et al. as not significantly greater thanthat expected in Japan where leukaemia rates are reported to be 20-30/106/y. Nor is the incidence significantly different from the average yearly incidence in the
non-exposed Hiroshima population during the same
period of time, as deduced from Watanabe's figures.
The elevated leukaemia incidence (37 /10°/y) in those
exposed between 2,000 and 10,000 metres in Nagasaki(table III) is significantly ( P < 0.05) higher than expected on the basis of the frequency obtaining in the] apanese population.
27. Brill et al.1 also analysed relations between radiation dose corrected for shielding (among those persons
for whom knowledge permitted individual dose corrections) and average incidence of confirmed leukaemia
during the nine-year period 1950-1958 in the Master
Sample in Hiroshima and Nagasaki. Figures 2 and 3
provide a general guide to neutron and gamma radiation
doses according to distance from hypocentre in Hiroshima and Nagasaki. Figures for attenuation of dose byshielding were based on the average attenuation factors
observed during test explosions in the Nevada Desert. 8
For individuals who had been located in the open no
attenuation factor for shielding was applied. For thosepartly shielded a 15 per cent attenuation of the air dose
was assumed for gamma radiation and 25 per cent forneutrons. For persons inside houses of light Japanesestyle construction an attenuation of 30 per cent of the

NEUTRON AND GAMMADOSES 1.'I NAGASAKI
2

5

2

2
ia-''----.1.....--..L....---L---.U..~-....._

0

500

1000

1500

2000

2500

_ _....._,_J
3000

HORIZONTAL DISTANCE FROM GROUND ZERO (Metres)

Figure 3. Estimates of neutron and gamma air doses in Nagasaki
as a function of horizontal distance from ground zero (modified from York3)
5

NEUTRON AND GAMMADOSES IN HIROSHIMA

air dose was assumed for gamma radiation and of 50
per cent for neutrons. Persons located in other shielding
categories were not taken into account because the corresponding attenuation factors were not known. This
resulted in further reduction of the sample and of thenumber of leukaemia cases. Gamma and neutron estimates were added in a 1 :1 ratio, assuming an RBE of
1 for neutrons. If the RBE were in actual fact higher
than 1, then using a 1 :1 ratio, as is done here, would
yield a higher estimate of risk of leukaemia per unit dose,at least in Hiroshima.
28. Table IV presents data on confirmed leukaemia
incidence according to absorbed dose as obtained bythese procedures for 51 cases in Hiroshima ancl 25 casesin Nagasaki during the nine-year period 1950-1958. The
yearly leukaemia incidence according to dose is showngraphically in figure 4.
29. For Hiroshima the relation of dose to annual
leukaemia incidence in the nine-year period 1950-1958
can be described by a straight line over the dose rangeof about 100-900 rads. Between 10 and 100 rads theincidences in each dose group, though consistent withthe same straight line, do not differ significantly fromone another.
30. The data indicate that at least in the range between
100 and 900 rads the average rate of increase of theincidence with dose \Vas 1.1 cases/10 6 /y/rad at Hiroshima and 1.6 cases/10"/y/rad at Nagasaki, or between
1 and 2 cases/106 /y/rad in both cities. Since in Nagasaki the exposed population was smaller and the casesof leukaemia fewer, the estimate for that city is statistically less reliable. However, the major cause of uncer-

2

5

Ul

5

Cl

~

:=

2

t:l

~ i.o

FIRST COLLISIONNEUTRON DOSE--~""\

Cl
5

10·• L - - - - - ' - - - - ' - - - 1 - - - . l . - - . . . l . . . l . l . . . . l . . . . - 1 - - . I
500
1000
ISOO
ZCOO
2500
3000

?

HORIZO?-;TAL DISTANCE FROM GROUND ZERO (Metres)

Figure 2. Estimates of neutron and gamma air doses in Hiroshima as a function of horizontal distance from ground zero(modified from York3)84

of additional cases, a distinction of practical as well as
theoretical importance. 135

Leukaemia incidence, 10-S/YearIOOOr------..----800

LEUKADIIA IN EARLY POST-DETONATIO'.S'ENTRANTS 1::-; HIROSHnfA

600

34. The data from the report of \Vatanabe 6 on leukaemia cases developing between 1950 and 1962 (thirteen
years) in persons entering Hiroshima soon after thedetonation have been recomputed and presented in table
V. Although the incidence was higher than expected fromdata on non-exposed persons, the difference between theearliest entrants and later entrants was not statisticallysignificant.
35. Estimates of radiation e.xposure from fall-out andfrom neutron-induced radio-activity have been published•·~ (figure S), but their reliability cannot be
assessed .
3?. The locations of the early post-detonation entrants
durmg the first days after entry are not known. In viewof the extensive destruction and the long-lasting firestorm near the hypocentre which broke out within a few
hours of the explosion, it has been considered probablethat very few persons might have been close to the hypocentre for substantial periods of time during the first day
after detonation.

-400
200
0 ~~~:...i.,.~.·~·......

.J
..

;w
.;.
· . . ..:...:.·
•

100

200

3000

'.2000

1000

.·..
.··
..
..·
...... 'I'..

NAGASAKI •• •••l . .·

I_ I t····0Utf~...... .-.SP,91'!.
0

200

400

Figure 4. Average incidence of confirmed leukaemia in the mas·
ter s~mple, _Pr?per plus resei:ve, 1950-1958, light shielding, byrelative radiation dose (modified from Brill et al.1)

LEUKAEMIA IN AMERICAN RADIOLOGISTS

37. Earlier studies, already discussed in the 1962
report, are summarized in table VI. Since the 1962
report Lewis 9 has reviewed the 425 death certificates ofregistered specialists in radiology dying between the agesof thirty-five and seventy-four during the fourteen-year
period 1948-1961. In table VII the observed numbers ofdeaths for which the main cause was leukaemia or a
related disease are compared with the corresponding
exp.ested nu?lber~ calcul.ated by applying to the numberof hvmg rad1olog1sts at nsk the death rates (standardized
with respect to sex, race, age and year of death) due toeach relevant cause. The estimated number of male radiologists, thirty-five to seventy-four years of age, increased
from 2.167 in 1948 to 4,713 in 1961; in the fourteen-year
period the number of man years at risk at these ages was
47,348. The mortality ratio for leukaemia was 3.0, with
1~ cases observed among the radiologists as comparedwith 4.02 cases expected. The average annual incidence of death from leukaemia in radiologists during
these four~ee!1 years was 253/106/y, as compared with an
expected mc1dence of 85/106 /y, giving an excess incidence of 168/l{)G/y. About 4.4 of the twelve leukaemia
deaths in the group of radiologists were expected to beof the lymphocytic type (predominantly chronic), but?nly 1 case of lymphocytic leukaemia was observed. andit was of the acute type. Therefore, all 12 cases of leukaemia in the radiologists were of types J...11own to be
increased by irradiation.
·
38. Based on the risk estimates from Hiroshima theexcess leukaemia incidence observed in the radiolo~sts
would result from a single acute whole body exposure ofabout 100 rads. Little is known about the ma!!Tlitude anddistribution of the dose received by the early ;:,diologists,
but the evidence available indicates that doses far inexcess of 100 rads were received chronically O\'er
periods of up to forty years, and this would suggest that
long-term radiation exposure is less effective than shortterm exposure in inducing leukaemia.
39. For Hodgkin's disease, lymphosarcoma, andlymphoblastoma, the observed numbers of deaths amongt~inty affecting both estimates probably lies in the limita-

tions of the dosimetry rather than in the inherent
variability of the data.
31. In both Hiroshima and Nagasaki taken together
there is moderate correlation between year of onset ofl~~kaemia and distance from the hypocentre. In bothcities the group with symptoms of radiation sickness
was closer to the hypocentre and had a significantly incre~se.d leukaemia incidence over the group without
radiation symptoms.
32. The predilection of the various types of leukaemia
for specific age groups does not appear to have beenmarkedly altered as a result of irradiation. The rarityof chronic lymphocytic leukaemia in Japan was confirmed. The types of leukaemia observed to be increased
most in survivors under I.SOO metres were chronic
granulocytic and acute leukaemia. The acute leukaemias
occurred predominantly in people under ten years of aae
at the time of exposure. There is normally a stro~g
pred!lection for this type in the young. In the Japanesesurvivors, although chronic granulocytic leukaemia has
occurred predominantly in the middle age groups. it has
also been seen with increased frequency in children.
Ac1;.1te leukaemias:-including granulocytic, myelomonocyt1c and unclassified types-also have occurred withincreased frequency.
33. The incidence of leukaemia of various haematologic ty~s has ~arie~ sxste_matically in relatic;in ~o ;..geat the time of .1rrad.1at1on,' so that the age-mc1clence
curves for the 1rrad1ated and control populations arenearly paralleJ.1 3 G Because the natural incidence of certain types varies with age by as much as an order ofmagnitude or more, the numbers of cases of induced
leukaemia of these types have varied correspondinaly
with age at the time of irradiation. A given amount"'ofradiation may thus be inferred to have increased theprobability of .the disease by a given percentage of thenatural age-ad1usted rate rather than by a given number
85

200

SOIL: 0.028 % Mn {w/w)} ACTIVATION
0.89 % Na {w/w)
ANALYSIS(6 SAMPLES)

e::

z

w

0::

:::>
V')
0

a.

x

w

300

400

500

600

700

GROUND RANGE (Metres)"ll = Time of detonation.

Figure 5. Neutron-induced ground activity-Hiroshima (modified from Borg and Conard5)

radiologists were in reasonable agreement with the
expected numbers (table VII). On the other hand, inthe population at risk there were five deaths from multiple myeloma where one was expected, and four deaths
from aplastic anaemia where 0.2 was expected. Vlhile theincreased incidence of aplastic anaemia was not surprising, the association of multiple myeloma with radiation
had not been substantiated before.

the patients given multiple courses had been followed fora longer period. Young men were given, on the average,
more courses of treatment than older men. The patients
included boys of fourteen years of age to men well overfifty-five years of age.
43. In over 90 per cent of the patients the radiation
fields were confined to limited areas of the body which
included the affected joints. Fields with generous margins were used over the spine, sometimes including thepelvis and other joint areas. Details of X-ray exposure
were obtained from a sample of approximately one inevery si..x of the patients ( 1,878 men). Both exposures tospinal bone marrow (roentgens) and whole body integral
exposures (megagramme-roentgens) were estimated.
The spinal exposure was estimated in two different
forms: as mean exposure to the marrow throughout thewhole length of the spine, and as maximum e.xposure at apoint in the spinal marrow. Finally, the mean spinal
marrow exposure was estimated separately for thosepatients receiving only spinal irradiation. Eighteen of
the 37 leukaemia cases were patients receiving only spinal
irradiation.
44. Since the patients did not receive all their radiation
treatment on one occasion . and since the proportions ofpatients given various exposures did not remain constantthroughout the period under review, it is not possible
to measure the incidence of leukaemia in relation to thesize of the exposure simply by relating the numbers ofpatients with leukaemia following a given exposure to
the estimated total numbers of patients given the same
exposure. Court Brown and Doll met this difficulty by
estimating the population at risk for each level of exposure from the sum of the number of years the pacients
sur;ived after receiving an individual exposure andbefore receiving additional radiation treatment which
would place them in the next, arbitrarily defined, exposure category.

LEUKAEMIA IN ANKYLOSING SPONDYLITIS PATIENTS

40. There have been no new data on leukaemia incidence in relation to dose in patients X-irradiated therapeutically for presumed ankylosing spondylitis since
Court Brown and Doll 12 • 13 in England studied the caserecords of 13,352 patients treated in 81 treatment
centres from 1January1935 to 31December1954. Only
cases of leukaemia found before 1955 were consideredin the analysis. This study was discussed in the 1962
report. However, for purposes of comparison with studies of dose-incidence relations in other irradiated populations. it is discussed here also in somewhat modified
form.
41. In the evaluation of the dose-incidence relationship, the cases used included 32 with an establisheddiagnosis ("A" series) and 5 probable cases ("B"series). Since only 1 certain case of leukaemia was recognized among the 2,065 irradiated women (total incidence 48/105 ) , the analysis was confined to men, and the
population at risk was defined as the 11,287 males in the
study series.
42. The patients had been subjected to total cumulative
exposures ranging from 112 R to more than 3.000 R infrom one course of fractionated exposures (over abouta month) to eight courses of therapy with separations by
as many as eight years. The majority of patients given
only one course had been treated since 1950, and most of86

45. The accuracy of this method depends much on thelimits of latent period for the radiation-induced leukaemia. On the basis of 10 cases receiving only one courseof treatment it appeared that the latent period would be
seldom less than two years, more frequently of the orderof three to five years, and less commonly, lo!1ger. However, in their analysis the authors postulated that leukaemia was equally likely to appear at any time after
irradiation with the exception of the first year. Sincemany patients were treated during the last few years of
the study, the study may be incomplete with respect torecording the total incidence of leukaemia.
46, The incidence of leukaemia in irradiated spondylitics increased with age from 11/104 /y in those less thantwenty-five years of age to 56/10•/y in those fifty-fiveyears of age or older, consistent with the age-dependent
increase in incidence of comparable forms of leukaemia
in the general population of England and Wales. 136 The
excess of leukaemia, which was of the order of a tenfold
increase in the "natural" age-adjusted rate, was present
irrespective of the age at which radio-therapy was started
but was slightly greater when treatment was begun late
in life. For a given exposure, therefore, at least five times
as many cases of leukaemia were induced in the elderlygroup as in the young group, although the natural agedependent rate was increased by a similar, or only slightly
different, percentage in both groups. The greater increasein the elderly cannot be ascribed to differences in exposure because there was a tendency to give older patients
less radiation treatment rather than more.
47. A significant excess of deaths from all types ofleukaemia occurred in the irradiated spondylitics, ascompared with the expected numbers in a non-spondylitic, non-irradiated population, with ratios of 4.6 forlymphocytic, 6.1 for myelocytic, 11.8 for monocytic, and52.4 for other and unspecified leukaemia.
48. Since adequate data are not available on the incidence of leukaemia in male spondylitics not treated byirradiation nor in non-spondylitics receiving spinal
irradiation, the expected rates of leukaemia used in thisstudy were those for the general male population of
Britain standardized for age.
49. A certain possibility of error exists in the use ofthis control population in view of the fact that an association between leukaemia and rheumatic diseases has been
observed.15 Also, the existence of hereditary factors inankylosing spondylitis and rheumatoid arthritis has beenreported. 14 Another cause of concem is the possibility
that some of the other forms of therapy used for ank")'losing spondylitis may also be leukaemogenic. Agents
such as antipyrine, gold salts, and phenylbutazone havebeen known to depress the bone marrow activity. 16 Bean 17
has reported the development of leukaemia in six nonirradiated patients who had received phenylbutazone.
Three of these had ankylosing spondylitis.
50. In the survey of Court Brown and Doll 13 the caserecords did not provide enough detail for a special studyof the use of drugs. These authors pointed out that butazolidine could hardly have played any part in the development of the cases of aplastic anaemia found, as it was
not in general use until 1952. The authors indicated thatgold had been used for many years, as had many types ofanalgesics, including amidopyrine. That drugs werelargely responsible for the development of leukaemia did
not seem reasonable to the authors, but decisive data were
not provided in their report.
51. The numbers of men receiving various exposuresof radiation to spine alone or spine plus extraspinal re-gions, given in terms of mean exposures to spinal marrow, and the numbers of man years at risk at twelve
levels of estimated exposures. are given in table VIII.
The exposures are the total exposures received less thosereceived in the twelve months preceding the diagnosis ofleukaemia. The data on the leukaemia patients are summarized in table IX, along with the crude and standardized incidence rates.
52. The annual leukaemia incidence increased from
O.S/10'1/y in the standard control population to i2/l04 /yfollowing an exposure of 2,250 R or more. Below 500 R
2 of the 4 cases of leukaemia were lymphatic.
53. The mean exposure received by the spinal marrow
was believed by Court Brown and Doll to be the mostsatisfactory measure of radiation exposure under theconditions of the investigations. However, they pointed
out that it failed to take into account the considerable
exposure to the extraspinal marrow in some of the patients. Therefore, they considered separately the patients
who received treatments to the spine and sacro-iliac
regions only. These data are given in table X.
54. Patients whose treatment was initially confined tothe spine and sacro-iliac joints but who subsequently
received e..xtraspinal (including wide field) irradiation
were included in the group only for that part of their
Ii fe between initial treatment and the first extraspinal
treatment. Although this improved the accuracy of dose
estimates, the data became limited in value because of
the consequent reduction in the number of leukaemia
cases.
55. A regression line fitted through the incidences
observed at exposures in the range bef:iNeen approximately 300 and 1,500 R to the spine, has a slope of
0.5 /10 5 /y/R. Extrapolation of the line below 300 R is
not warranted. It will be recalled that the straight line
describing the relation between dose and incidence ofleukaemia in the Hiroshima population of survivors to
the A-bomb explosion has a slope between 1 and 2/10 6/y/rad in the range from 100 to 900 rads. The characteristics of the irradiated population and the conditions ofirradiation in Hiroshima were very different from thoseobtaining in the spondylitics. Not only had the Hiroshima
survivors received an instantaneous burst of radiation
while the spondylitics had received several courses oftreatment, but most of the Hiroshima survivors had presumably been exposed to whole body irradiation, whereas
in the spondylitics only parts of the body (probably involving one-third to one-half of the bone marrow) were
irradiated. The similarity of the two slopes suggests thata common risk estimate may apply to both populations.
LEUKAEMIA IN CHILDREN IRRADIATED
THERAPEUTICALLY FOR "ENLARGED THY:l.n;s''56. There have been a number of epidemiologic
studies of the incidence of leukaemia in children who
received therapeutic X-irradiation during childhood forbenign conditions. 1 8-2 6 These studies have been discussed
in the 1962 report. Among these studies, those by Hempelmann and his colleagues are the largest and the only
ones which have shown an increased incidence of leukaemia.
57. The most recent reports on the Hempelmann survey are those by Pifer et a!. 21 and by Toyooka et al. 28 • 29
The numbers of leukaemia cases observed, of cases
expected in infants treated with X-rays for "thymic enlargement", and of sibling controls in both Series (Iand II), are given in table XL All children were con87

mates. Polhemus and Koch 35 used children attending thesame hospital during the same period (consecutive surgical admissions) matched for age, socio-economic andgeographic factors. In Kjeldsberg's study30 the controls
were healthy children born at a time different from thatof the leukaemic children and therefore not experiencing
the same likelihood of antenatal X-ray examination. In
the study by Murray et al. 21 there were three control
groups-children dying of non-malignant disease during
the same period, siblings, and live siblings of the deceased
controls. Finally, Lewis 31 used as controls all of thechildren born at the hospital in which the leukaemic
children had died.
65. Court Brown et al., 35 in an extensive prospective
study of women who were irradiated during pregnancy
between 1945 and 1956, found that among 39,166 liveborn children who had received antenatal irradiation,nine had died of leukaemia before the end of 1958. The
expected number was 10.5. None of the children of the
750 women irradiated in the first three months of pregnancy had developed leukaemia during an averagefollow-up of over si.x years. No correlation was foundbetween incidence of leukaemia and the amount of antenatal exposure.
66. MacMahon 39• 40 designed an extensive prospective
study to examine this problem by a method which utilized
objective evidence of intra-uterine X-ray irradiation. The
study population consisted of 734,243 children born in,and discharged alive from, any of thirty-seven largematernity hospitals in the north-east United States in theyears 1947-1954. The frequency of intra-uterine X-ray
irradiation in the population was estimated by review of
the records of a 1 per cent systematic sample. Abdominalor pelvic X-rays were recorded in 370 ( 10.6 per cent) of
the 7,242 single pregnancies in the sample. Children
dying of leukaemia before the end of 1960 were identified by review of death and birth certificates. After correction for indirect associations with birth order andother complicating variables, it was estimated that leukaemia mortality was about 40 per cent higher in the
X-rayed than in the non-X-rayed members of the study
population, giving a relative risk of 1.4, with 95 per centconfidence limits 1.0 and 2.0.
67. No estimates of dose were obtained in any of thesestudies. However, in MacMahon's study, X-ray cases
were divided into three categories ranked in order ofprobable (relative) dose, according to the probable numbers of films involved in the diagnostic procedures.
Although there was a minor trend toward higher cancer
risk in the more heavily exposed categories. it was far
from significant. It was shown that neither the higher
risk of leukaemia in first births nor the higher frequency
of pre-natal X-ray in first births e.-..;:plained the association
between X-ray irradiation and increased leukaemia incidence. It remains to be demonstrated whether or not theassociation between irradiation and leukaemia explains
the high frequency of leukaemia in first births. The ratioof mortality in first-born to that in later-born was as
great in the separate X-ray categories ( 1.5 in the
X-rayed, 1.3 in the non-X-rayed) as in the combined
data, 1.4. The birth-order differential was also as greatamong children in specific relatiYe dose categories (pelvimetry) as in the total.
68. The report 30 which included deaths to the end of1960 of children born during the years 1947-1954. dealt
with children predominantly O\'er fiye years of age andshowed a higher frequency of intra-uterine X-irradiationin cases of leukaemia and cancer deaths, as comparedsidered to have been at risk from birth until 31 December
1960, or until death.
58. In Series I most of the children were treated between 1926 and 1946, and treatment techniques and reasons for treatment varied greatly. In Series II the children were treated between 1940 and 1957, and treatment
methods were more uniform. Many of the children irradiated in the earlier years were given relatively large
doses to large areas, and posterior as well as anterior
positioning of ports was often involved. The children
more recently irradiated were usually given smaller doses
to relatively small areas, with anterior positioning ofports. In Series II the X-ray energies, the numbers oftreatments and the total period of treatment were usuallyless than in Series I.
59. The 6 cases of leukaemia observed in Series I included four lymphocytic and two acute undifferentiatedtypes. The data do not make it possible to study the regression of incidence with dose.
60. These data are inadequate to distinguish between
the influence of (a) the irradiation and ( b) the condition,so-called "thymic enlargement", or the underlying basis
for the diagnosis which served as the indication fortherapy. Conti et al. 22 reported no cases of leukaemia ina group of 1.564 children and 96 per cent with no evidence at treatment of the condition called ''thymic enlargement". Eighty-eight per cent of the children weretreated through relatively small ports with exposures of
75 to 300 R, averaging 150 R, to the thymic region, and12 per cent of them received 200 to 450 R. One case was
expected. These children (90 per cent) were studied
from eleven to eighteen years after the therapy.
61. Murray et al. 21 found 2 cases of leukaemia inseventy-five children treated for pertussis, 1 case in
1,073 persons treated to the head and neck mainly for
lymphoid hyperplasia of the nasopharynx, and no leukaemia deaths in 2,460 children treated with superficial
X-rays for benign skin lesions.
LEUKAEMIA IN CHILDREN IRRADIATED in utero

62. Several retrospective studies of children irradiated in utero have been carried out and their results are
summarized in table XII.
63. In the retrospective study by Stewart et af. 30-32 of
the incidence (mothers' memory) of pre-natal abdominal
diagnostic irradiation among mothers of 780 children
dying under ten years of age of leukaemia (during theyears 1953-1955) and mothers of 1,638 control live children matched for age, sex, and location, there was a
relative risk for leukaemia of about 1.83. Excessive maternal age was also related to an increased risk of leukaemia and an increased incidence of Down's syndrome.
The incidence of post-natal diagnostic or therapeutic exposure was almost twice as high in the leukaemic children
as in the control group for the first three years of life,
and the frequency of post-natal acute pulmonary infec·
tions and severe injuries was also significantly increased
in children who subsequently died of leukaemia.
64. The controls in these retrospective studies varied
considerably. Stewart et al. 32 used live children matched
for age, sex and location. Ford et al. 33 used children
dying under ten years of age of causes other than cancer
during the same period of time as the treated children.
Here, the infom1ation about radiation exposure during
the last trimester of pregnancy was obtained from obstetricians and hospital records. Kaplana. employed twocontrol groups-closest siblings and most habitual play-88with the 1 per cent sample of the population. It is ot
interest that an earlier report;' 0 which included only
deaths prior to 1958, showed little or no difference infrequency of intra-uterine irradiation between the twogroups. It is possible that differences in young children
have been similarly under-estimated in some other studies
as a result of insufficient follow-up time for a significant
portion of the population. The small relative risk and theoccurrence of the pea.I.;: risk after five years of age are two
characteristics of the association which may go far
towards reconciling this view with the negative results
reported in a number of surveys.
69. Wise 41 has studied first-born children who had
died of leukaemia during the period 1953-1955. In agroup of 306 such cases ten birth cohorts were represented ( 1945-1954), and in nine of these the mean age
at death of cases with a history of pre-natal irradiation
was four months greater than the mean age at death of
the non-X-rayed cases. Only two cohorts had been followed from birth to one year of age (1953-1954), andonly one had been followed from birth to two years ofage (1953).
70. Stewart and Hewitt,•: studying 628 children born
between 1952 and 1956 who died of leukaemia andlymphosarcoma before the age of five years, found thatthe percentage of X-rayed cases varied significantly withage at death and increased from a~e zero to. age ~o~r.
Assuming that none of the leukaemia cases dymg w1thm
about fourteen months after e..'Cposure, i.e., before theage of one year were radio-genie, these authors also suggested that radio-genie cases had a different age distribution than spontaneous cases, and that, over this age
range, the radio-genie cases had a tendency to develop
later than "spontaneous" cases. The proportion of controls X-rayed (8.3 per cent) was almost the same as thatfor the youngest-"spontaneous"-leukaemia cases(8.5 per cent), and according to this hypothesis the"e.."<tra" X-rayed cases in the older age groups are attributable to the intra-uterine exposures.
71. According to MacMahon 43 the probability of deathfrom leukaemia for white children in the United States
up to the age of ten years is 46 per 10 5 persons. Assumingthat 10 per cent of these children were X-rayed in utero,and that the X-rayed have a 40 per cent higher risk than
the non-X-rayed, it follows that the over-all risk of
46/105 is made up of a risk of 62/10 5 for the 10 per cent
X-rayed and 44/10 5 for the 90 per cent not X-rayed. The
difference, 18/1~, is the e.."<cess risk in the irradiatedchildren. This would be compatible with extrapolated
estimates from post-natal irradiated groups of 2 cases
per million per rad per year only if the foetal dose received was 9 rads. This is probably at least twice theaverage dose received.
72. While individual studies of the incidence of leukaemia in children irradiated in utero have yielded different risk estimates, these are of different reliability on
purely statistical grounds as indicated by their confidence
limits. As discussed later in this annex, it has beenshown10 s that there is no inconsistency in the findings ofeleven surveys, five of which involved small samples withlarge sampling variabilit~ e::nd gave. estima.tes ?f relath:erisks less than one. The JOmt maximum hkehhood estimate of the relative risk from all these surveys was infact found to be 1.4 with 95 per cent confidence limits
1.2 and 1.6.
73. Although accurate estimates of doses are not available it seems difficult to avoid the conclusion that irradiation' of foetal tissue gives rise to a greater risk per unit

dose than post-natal irradiation, possibly by a factor as
high as 5. As in all cases of irradiation for medical reasons, there is no way to separate the leukaemogenic effectof radiation from other possible aetiologic factors connected with the reasons that had prompted the irradiation.
LEUKAEMIA IN OTHER GROUPS MEDICALLY IRRADIATED
FROM EXTERNAL SOURCES

74. Simon et al. 44 found, in 71,582 patients treated byradium therapy for carcinoma of the cervix in large
treatment centres throughout the world. an incidenceof between 6.2 and 11.6 cases of leukaemia per 105 persons. Comparing this to the British death rate of 5.8/10 6for leukaemia in women fifty-five years old and the incidence of 9.0/105 for a similar group in the UnitedStates, they concluded that the incidence was not increased by radium treatment. However, since 25 percent of the patients did not survive one year and since
60 per cent did not survive five years, the population atrisk was greatly reduced before the greatest incidenceof radiation-related leukaemia, if it occurred, would
have been expected.
75. Faber45 • 48 , in a study of cases of leukaemia reported in the Danish Cancer Registry during the years
1940 to 1954, found that 34.8 per cent of the 442 acuteleukaemia cases, 32.6 per cent of the 307 chronic granulocytic leukaemics, 17.7 per cent of the 861 chronic
lymphocytic leukaemics, and 21.3 ~r cent of. the 3~5
non-leukaemic controls used, had a history of diagnostic
or therapeutic X-irradiation. The period between irradiation and development of the disease ranged from ten
to sixty months for the acute cases and from ten to one
hundred and forty months for the chronic granulocytic
cases with no notable peak in the distribution. The relative risks and their 95 per cent confidence limits are:
2.0 (1.7-2.7) for acute leukaemia, 1.8 (1.3-2.5) for
chronic granulocytic leukaemia, 0.8 ( 0.6-1.1) for
chronic lymphocytic leukaemia. From the limits it canbe concluded that only for acute and chronic granulocytic
types was there a significant increase in risk. The doses
received and the reasons of irradiation are not known.
76. Neumann41 reported that from 1954 to 1960, 10
fatal cases of leukaemia were recorded in Stuttgart
among tuberculosis patients over fourteen years of age
in a sample equivalent to 91,549 person-years, and 5.86
cases were expected in a corresponding sample of thegeneral population of Stuttgart in the same period. This
gives a relative risk for leukaemia of 10/5.86 or 1.7 forthe tuberculous patients who presumably were e.."<posed
more frequently to chest roentgenography than were
control subjects. However, this does not differ significantly from unity, and in the ten tuberculous patients
who died of leukaemia the exposure was slightly lo\verthan that for the whole sample of tuberculous subjects.
77. Stewart et al."' 8 in the United Kingdom made aretrospective survey of possible association between exposure to diagnostic or therapeutic X-irradiation andthe subsequent development of leukaemia in adults. The
frequency of irradiation appeared to be the same in theso-called L group (512 lymphatic leukaemia and lymphosarcoma cases), in a group of 951 cases with tumoursof various sites, and in a group of 974 apparently
healthy controls. In the so-called M group ( 511 myeloid
and monocvtic leukaemia cases) the frequency of irradiation of Chest or abdomen was higher and that of thelimbs not different from controls. To obtain risk estimates these authors compared frequency of trunk irradiation in their M series with the frequency of trunk
89

irradiation among all other groups pooled together(standard group), disregarding limb irradiation because
the frequency of limb irradiation was not higher thanin control groups.
78. In the standard group during the last ten years
prior to the survey, 29 patients reported therapeutic irradiation, 1,025 reported diagnostic irradiation, and 1,323
reported no exposure. In the M group ( myeloid andmonocytic leukaemia) the corresponding figures were:
24 with therapeutic irradiation, 243 with diagnostic irradiation, and 244 with no exposure. The relative risksof leukaemia were 4.5 (95 per cent confidence limits:
8.0-2.5) for therapeutic irradiation of trunk and 1.2( 1.4-1.0) for diagnostic irradiation of trunk.

79. Gunz and Atkinson, 0 in a retrospective study in
New Zealand, found that 47 of 590 leukaemia patients
had received prior X-ray and/or radio-isotope (various)
therapy for a variety of malignant or benign conditions,as compared with 38 of 712 non-diseased controls, giving a relative risk of 1.5 (1.0-1.9). They also found that
7 of 122 cases of myclomatosis (5.7 per cent) had previously been irradiated therapeutically (relative risk 1. L
limits 1.7-0.7). Prior radiation therapy was found in 25of the 355 acute leukaemia cases (relative risk of 1.3,
limits 2.1-0.8), 9 of the 78 chronic granulocytic leukaemias (relative risk 2.3, limits 5.0-1.0), and 13 of the
157 chronic lymphocytic cases (relative risk 1.5, limits
2.9-0.8).
80. In the same study the frequency of diagnostic
irradiations received in the previous ten years was also
investigated. Significant differences in the frequency of
diagnostic irradiation among the various groups wereapparent. No conclusion can be drawn with regard to
the relative risks involved because the effect of diagnostic doses cannot be separated from that of the presumably much higher therapeutic doses received by a fraction of the same sample.
81. While therefore there is evidence that, as expected, therapeutic irradiation in adults may give rise
to a detectable increase of risk of leukaemia, the question of the effect of diagnostic irradiation remains open.
The results of Stewart et al." 8 are open to question as
they barely reach statistical significance, because in thatstudy leukaemics showed not only higher frequency ofirradiation but also a different distribution, compared tocontrols, of diseases that might themselves lead to anincreased risk of leukaemia, and because irradiations of
the limbs, though they must have involved substantial
doses to the bone marrow, were disregarded. More intensive investigations and better dosimetry are required
before meaningful estimates of risk from diagnostic
irradiation of adults can be obtained.
LEUKAEMIA AFTER l1 81 THERAPY

82. Pochin,~ 0 in a study of an estimated 59,000 patients (estimated 221,900 patient-years at risk) treated
for thyrotoxicosis with radio-iodine for the twenty years
preceding mid-1960 in the main clinics of the United
Kingdom, Canada and Austria. and in a number ofclinics in the United States, collected 8 published cases
anc;I 10 others, as well as 1 case of lymphosarcoma. He
estimated from the appropriate national leukaemia rates
an expected number of 21 -+- 5 cases of leukaemia and~oncluded that presently available evidence, while givm~ no support to the possibility of leukaemia induction.
neither excluded such induction nor made it possible toset any upper limit to the actual frequency. The averagefollow-up time in this study was about 3.8 years after
therapy.
83. Wald et al.. 16 in their 1962 review, listed 2 additional cases of leukaemia and 1 of lymphoblastoma. Of
the total of 20 cases there were 19 in which the type ofleukaemia was known and 15 were acute. This proportion was higher than anticipated in a normal populationof the same age and sex distribution. About 20 per cent
only of the patients treated were males, but over 70 per
cent of the cases of leukaemia occurred in males. Eight ofthe 20 cases were diagnosed in less than two years after
therapy, and only 5 were diagnosed more than four
years after therapy. The mean age of this population
was higher than that of hyperthyroid patients in general,
probably reflecting the conservative use of P 31 in theyoung.
84. Werner et al. 51 in 1961 further analysed the data
for the patients in the United States (collected by
Werner and included in Pochin's report). In this series
there were 10 leukaemia cases among 32,000 thyrotoxicosis patients treated with P 31 with an averagefollow-up time of 4.44 years. An incidence of 13.8 cases
was expected. There \Vere significantly fewer chronic
cases (3 as opposed to 9 expected). For males there
was a significant e.xcess of acute cases ( 6 to 1), while
for females there was a significant deficit of total cases(2 to 10) and of chronic cases (1to6).
85. No information is available on the incidence ofleukaemia in thyrotoxic patients not treated with radiation which would make it possible to distinguish the
influence of the disease itself on leukaemia incidence
from that of !131 •LEUKAEJ\IIA IN POLYCYTHEMIA VERA PATIE!\TS
TREATED WITH P32

86. Wald et aJ. 16 in 1962 reviewed 1,238 cases of polycythemia vera cases treated with P32 • Among these there
had been 41 deaths (3.3 per cent) from acute leukaemia.
Since nearly 75 per cent of the patients in the combinedseries reviewed (observation periods ranging from sevento eighteen years) were still alive at the time the reports
were made, complete ascertainment of leukaemia incidence has yet to be made. In the absence of adequate
information on leukaemia incidence in polycythemia vera
patients not treated with radiation, it is not possible todistinguish the influence of P 32 from that of the disease.
Prior to the advent of radio-phosphorus, as well as since,
X-ray therapy has also been used frequently. There issome evidence among patients not treated with radiation
si:ggesting that the condition of polycythemia may predispose to leukaemia or may be a condition closely related to leukaemia.
87. The general concept of myelo-proliferative dise<l:ses developed by Dameshek 52 would suggest that t11e
stimulus producing an increased incidence of one formof this general type of disorder, e.g. myeloid leukaemia,
m!g~t well ~~ capable of the initiation of closely related
chmcal entities such as polycythemia vera, erythremic
myelosis, and myelo-sclerosis. Yamazaki et al.Z 3 found18 cases of polycythemia vera among Hiroshima atomic
bomb survivors (22 per cent of the 81 cases reported in
all of Japan since 1950). It should also be recalled that
Lewis 0 found an increased incidence of multiple myeloma in United States radiologists.
LEUKAEMIA AND E!\VIRONMENTAL RADIATION EXPOSURE

88. Craig and Seidman 5 • have reported that the incidence of leukaemia in the one hundred and sixty-three90metropolitan areas of the United States bears no demonstrable relationship to differences in the amountsof cosmic radiations received.
89. Court Brown and Doll,5 5 in a study of the four
principal cities of Scotland, five rural areas, and the restof Scotland found that, from 1939 to 1956, leukaemia
mortality was highest in Aberdeen (mainly excess ofacute and chronic myeloid) and in Edinburgh (mainly
excess of chronic lymphocytic leukaemia). The average
gamma radiation backgrow1d in Aberdeen was 90 mrads
per year and in Edinburgh 57 mrads per year. It wasthought that the excess leukaemia mortality found waspartly the result of better case finding in the large cities.

examinations are considered, a different distribution isseen. All 4 cases diagnosed at other hospitals are in theproximal exposed group, and their eliniination irom theanalysis results in a distribution that does not departsignificantly from chance (P>0.30). Fourteen of the
21 cases occurred within 1,399 metres, a significant increase compared with those at greater distances.
94. According to Socolow et al., 56 although the overall incidence of thyroid cancer in the Adult Health Study
may not depart greatly from that cited by others forJapan, the age distribution differed significantly in thatthe cases in the A-bomb survivors were younger. Of
the 21 cases, 8 were diagnosed in the group under theage of thirty-five years. At the time of exposure thesepatients ranged in age from six to twenty years. The
latent period after exposure can only be defined as lessthan thirteen or fifteen years owing to the fact that allcases in this study were diagnosed between 1956 and1961. Among cases occurring in the younger age groups,
over 80 per cent were e.'\:posed within 1,400 metres,
whereas in older age groups fewer than 50 per cent weresimilarly exposed.
95. From the available information it is difficult todefine a pertinent population base for these cases or toevaluate the general significance of identified cases.
However, if the findings were representative of theincidence in the total exposed and non-exposed populations in this study, the incidence of thyroid carcinoma
in the exposed would be 19/14,970 or 0.13 per cent, andin the non-exposed 2/4,992 or 0.04 per cent.
%. In 1964 Zeldis et al. 57 reviewed thyroid lesions
in autopsy and surgical pathology specimens in Hiroshima A-bomb survivors. From 1 January 1948 to 30
December 1960, thyroid specimens were available in
1,253 of a total of 1,535 adult autopsy cases e.xamined
at ABCC. For the same period, a total of 342 surgical:hyroid specimens, representing 301 cases, were assembled from all pathology departments in Hiroshima.
However, for analysis of the surgical thyroid specimens,
it proved impossible to define a pertinent population basefor the entire series or to evaluate the general significance of identified cases in the face of the known occultcharacter of many thyroid lesions. Therefore, analysis
was made simply of diagnoses in those 70 of the surgicalcases which fell into two e.'\:posure groups (within 1,399
metres and between 1,400 and 1,999 metres). TableXIII gives the incidence of thyroid cancer and thyroid
adenoma in the autopsies and in the 70 surgical thyroid
specimens according to distance from hypocentre.
97. The incidence of thyroid carcinoma in the totalof 1,253 autopsy cases, in the entire exposed group, orin the group exposed between 2,000 and 9,000 metres,
is about 3 per cent, or only about 1.15 times the incidence in the non-exposed. The incidence in the nonexposed is 1.7 times that in the group exposed between
1,400 and 1,999 metres. The incidence in the group
exposed within 1,400 metres is about twice that in the
non-exposed group. The incidence of thyroid adenoma
is more than doubled in the most proximally exposedgroup and slightly increased in other exposure groups.
98. In the surgical specimens, the incidence of thyroid
carcinoma in the group exposed within 1,400 metreswas 3.75 times that in the 1,400-1.999 metres group.
However. the incidence of thyroid adenoma was 2.6
times greater in the latter group than in the formergroup.
99. The increased incidence of thyroid carcinoma in
the autopsy cases in the group exposed within 1,400

m. Thyroid neoplasms
THYROID CARCINO:'.l!A IN JAPANESE A-BOMB SURVIVORS

90. Socolow et al. 56 have reviewed the cases of carcinoma of the thyroid that were detected through routine
medical examination, between 1 July 1958 and 1 July
1961, in matched groups of exposed and non-exposed
subjects included in the long-term medical investigations (Adult Health Study) of the Atomic Bomb Casualty Commission (ABCC). The sample used in the
Adult Health Study consisted of four components balanced for age and sex: group 1 (proximal), exposed
within 2,000 metres of the hypocentre (reported acuteradiation symptoms); group 2 (proximal). exposed
within 2,000 metres (reported no acute radiation symptoms) ; group 3 (distal) exposed 3,000 to 3,499 metres;
and group 4 (non-exposed), beyond 10,000 metres or
not in the city at the time of the bombing. The review bySocolow ~t al. includes 10,780 subjects in Hiroshima and4,589 in Nagasaki.
91. During the three-year period of this study 355
patients were found to have enlarged thyroid glands in
Hiroshima and Nagasaki. Biopsies were recommended
in 114 cases in Hiroshima and 17 in Nagasaki, corresponding to 37 and 38 per cent, respectively, of patientswith thyroid enlargement. Seventy biopsies were performed, 64 in Hiroshima and 6 in Nagasaki. While
there was a random distribution of three types of thyroid enlargement among the four component groups in
Nagasaki, single nodules were diagnosed more often
among patients of exposure group 1 in Hiroshima.
Biopsy was recommended in about 80 per cent of caseswith single nodules, 50 per cent with multi-nodular
glands and 3 per cent of cases with diffuse goitre. That
there was some degree of uniformity of sampling issuggested by the fact that the percentages of patientswith single nodules of the thyroid who were biopsied
were fairly constant (range 42-45 per cent) within thefour exposure groups in Hiroshima. A similar analysis
cannot be made in Nagasaki in view of the smaller number of cases and fewer biopsies performed.
92. Twenty-one patients with histologically confirmed
thyroid carcinomas were seen. Seventeen cases werediagnosed as a result of a routine Adult Health Study
medical examination and 4 cases were diagnosed elsewhere just before the inception of the current study
in July 1958.
93. In Hiroshima, exposure group 1 contained 10of the 18 thyroid cancer cases seen in that city, a finding which is moderately significant (O.OS>P>0.02).
When the figures for both cities are combined, 10 of
the 21 cases fall within group 1, a distribution of doubtful significance (O.lO>P>0.05). However, if only the
17 cases diagnosed as a result of the Adult Health Study91

metres was found not to be statistically significant(P = 0.07), but the increased incidence in the thyroid
cancers in the surgical specimen groups exposed within
1,400 metres was found to be statistically significant. 5 ;100. Taken together, both surveys suggest that theincidence of thyroid carcinoma has been increasing in
the irradiated population of Hiroshima and Nagasaki,
the incidence varying inversely with distance from the
hypocentre. Difficulties of ascertainment, due to the factthat the incidence of carcinoma of the thyroid is difficult
to record, and the fact that the latent periods are long,
make it difficult to set up the surveys that would benecessary to obtain information on the dose-effect re·lationship and therefore on the risk of induction.
THYROID NEOPLASMS IN PATIENTS THERAPEUTICALLYIRRADIATED FROM EXTERNAL SOURCES

101. Takahashi et al., 58 in a retrospective survey ofhuman cancer in relation to medical exposure in certain
hospitals up to 1962 in Japan, found 638 cases of thyroid
cancer, of which 29 ( 4.55 per cent) had histories oftherapeutic irradiation with the thyroid within the radiation beam. In control groups of similar age distribution,
9 of 1,535 (0.59 per cent) received irradiation to thisneck region. The difference was significant at the 1 percent level.
102. However, the control group in this study is insufficiently characterized to permit adequate interpretation of the results with respect to the influence of factors other than radiation in the results. The study does
not distinguish between (a) effects of radiation, and( b) effects of the conditions which prompted the irradiation, on the occurrence of neoplasms after irradiation.
Furthermore, it is not clear how far back in time thesurvey of irradiation went. It should be noted also thatthe data indicate an average dose of 14 rads in thecontrols.
103. Neglecting these reservations, it is possible tocompare the proportion of irradiated subjects among
patients developing thyroid cancer and among healthy
controls. The relative risk estimate so obtained amounts
to 8.4 with 95 per cent confidence limits 14.8 and 4.8,
respectively. Dividing the estimate by the excess radiation ( 160 R) received on the average by thyroid cancer
patients compared to healthy controls gives a relativerisk per R of approximately 5 per cent. In table XIV
are given the proportions of patients with and without
thyroid cancer, according to the estimated exposure.

patients follO\ved ten years or longer after treatment,
and 1 case among the toxic goitre patients.
106. Data on ages at irradiation and at operation forthyroid cancer, and approximate doses, for the 7 cancer
cases in the tuberculous adenitis group are given in table
XV. Five of the 7 cases were four to eighteen years ofage at the time of irradiation, and the others were twentythree and thirty-four years of age, respectively. Five of
these 7 cancer cases were among 54 patients who hadreceived exposures between SOO R and 1,000 R, and 2of the cases were among 66 patients who had received
exposures of 1,000 R or more. The one patient who
developed thyroid cancer after irradiation for toxic
goitre had received an exposure of about 2,000 R at
sixteen years of age.
107. In the prospective survey by De Lawter andWinship 74 of adult patients X-irradiated for hyperthyroidism or other benign diseases of thyroid, there
was no evidence of thyroid cancer in any of the 222
patients followed for an average of 22.S years.
108. In a retrospective survey of 286 cases of thyroid
cancer, Winship and Rosvoll 70 found that 80 per centof the 286 cancer cases had received prior therapeutic
irradiation to head or neck during infancy or childhood,mostly for "enlarged thymus", others for hypertrophic
tonsils and adenoids, and some for other benign diseases. The exposures ranged from 180 R to 6,000 R withan average of 600 R. The latent periods averaged 8.6
years, were often less than five years, and in 12 cases
there were thyroid tumours at birth which later proved
to be carcinoma.
109. In the prospective survey of Pifer et al. 21 (seetables XI and XVI and paragraphs 57 and 58 for description of survey) of infants X-irradiated therapeutically for "thymic enlargement", 8 cases of thyroid
cancer were found in Series I among patients followedfrom thirteen to thirty-four years, as compared with
0.09 case expected on the basis of the "natural" incidence. The relative risk was 88.9. In Series I, 21 casesof thyroid adenoma were found, and 0.9 was expected,
with a ratio of 23.3. The mean exposure for Series I
was 329 R.
110. In Series II, with patients followed only fromthree to twenty years, only 1 case of thyroid carcinoma
was found, and 0.01 case was expected. The mean exposure for Series II was 126 R.
111. The 9 cases of thyroid carcinoma in the twoseries combined were associated with cumulative exposures ranging from 156 R to 1,092 R, with a mean of
598 R. Seven of these cases had been irradiated withcombined anterior and posterior port arrangements, 1
anteriorly only, and in 1 case the port arrangement had
not been ascertained. The 21 cases of thyroid adenoma
were associated with cumulative e.xposures ranging from
144 R to 756 R, with a mean of 372 R. The percentagesof these adenoma cases in the various exposure positions \Yere similar to those for the carcinoma cases.

104. In many prospective surveys18128- 29 • 60 • 61 and innumerous retrospective surveys, 63 - 73 therapeutic irradiation of children has been associated with a subsequent
increase in incidence of thyroid tumours. In some prospective studies 22 • 62 this association has not been found.
A number of surveys of thyroid cancer incidence following therapeutic irradiation for benign conditions are
summarized in table XVI.
105. In 1962 Hanford et al. 59 reported the results of astudy of 458 patients who had received therapeutic irradiation for non-malignant disease of the cervical region (thyroid included). Of these patients. 431 patients
comprised three main treatment groups, including 43
treated as infants for "enlarged thymus", 92 children
and adults treated for toxic goitre. and 296 children andadults treated for tuberculous adenitis. Eight cases ofthyroid cancer were found where ,...., 0.1 case was expected, 7 of them among the 162 tuberculous adenitis

112. Toyooka et al.,=s in analysing the data of Piferet al.. 21 found that the incidence of thyroid tumours wasconsiderably higher when a dose was given half anteriorly and half posteriorly than when the same dose
was given from an anterior approach only. Including
additional thyroid neoplasms found between 1960 and
1964, it was found that 29 of the total of 34 thyroid
tumour cases (malignant and benign) occurred among
472 children treated by combined anterior and posterior92

is valid for acute e..xposure of children only in an estimated e..xposure range of 100 to 300 roentgens.
118. Analogous joint estimates had been obtained by
Beach and Dolphin138 through a different method of
estimation and on the basis of more limited and partly
different data. Their risk estimate (35 cases/106 /rad)is a lifetime risk estimate. Assuming that the period ofrisk for cancer of the thyroid is between fifteen andtwenty years, Beach and Dolphin's estimate is slightly
higher than the one given in the previous paragraph.
Differences in method and in material can easily accountfor the discrepancy.
119. The validity of an estimate of risk such as is
given here is limited, like all empirical estimates, to therange of e..xposures from which it has been derived-in
the present case between 100 and 300 R. It also suffersfrom the fact that the results were obtained in children
irradiated for medical reasons and may therefore be different from the estimate that would apply to a random
sample of the population. Finally, the uncertainties in
dosimetry are high. Doses have probably been overestimated, thus slightly lowering the risk estimate.

approaches, whereas only 5 of the tumour cases developed in the 2,111 children treated anteriorly only.
113. Attempts to demonstrate a dose dependence forthese major positional groups were unsuccessful. A decision cannot now be made as to whether the high tumour
incidence in children treated anteriorly and posteriorly
was a consequence of port position, of statistical variation, or of other factors. The possibility has been demonstrated that the posterior approach. with its attendantdifficulties, could have resulted in e..'(posure of larger
regions of the neck and head, including the pituitary
gland, than was the case when the anterior approach
alone was used. In this connexion, there is uncertainty
in this and other surveys of children irradiated for"thymic enlargement" as to the extent of the inclusionof the thyroid gland in the radiation beam in many of thepatients. 0 f importance in this study are the facts thatmany of the older children (irradiated in earlier years)
were given relatively large doses to relatively large areas,
often with posterior as \veil as anterior position of ports,
and with greater X-ray energies, numbers of treatments
and total periods of treatment, as compared with younger
children (more recently irradiated).
114. Toyooka et al., 29 in a report of clinical aspectsof these thyroid tumour cases, indicated an equal se..x
distribution of adenomas, but a greater frequency ofcarcinomas in females. The mean exposure in carcinoma
cases was almost three times that for the entire group,and the mean e..xposure for adenoma cases was almost
double that for the whole group. The average latent
periods were 16.3 years for carcinomas and 18.2 years
for adenomas. There was no relation between latent
period and exposure.
115. Saenger et al. 21 reported a prospective study of
1,644 patients under sixteen years of age who had received X-ray therapy to the head, neck or chest during
the period 1932-1950 for benign conditions, and of 3,777
untreated siblings. Irradiation for "thymic enlargement"
accounted for 33 per cent and irradiation for cervicaladenitis for 26.9 per cent. Twenty-one per cent of thesample received radiation therapy for two or more presumably unrelated conditions. Exposures ranged from< 50 R to 5,000 R, with 62 per cent receiving less than
400 Rand 72.5 per cent receiving less than 600 R. Elevencases of thyroid cancer were found among previously
treated cases who were under twenty-three years of age
at the time of cancer development, and 0.12 case was
expected, giving a relative risk of about 91.
116. No one of the surveys on the incidence of thyroid
cancer among irradiated subjects makes it possible toobtain dose-effect regression. Because of the small number of cases in any individual survey only one point of
the dose-response curve can be determined from each ofthem. Crude risk estimates, however, can be obtained
for a number of surveys by determining the slope ofthe straight line connecting the origin with the points
obtained when the observed incidences (cases per manyear) are plotted against exposures. The risk estimates
are summarized in table XVI.
117. A single straight line can be fitted through theincidences observed in surveys of children when plottedagainst exposures. Its slope indicates that the rate ofincrease of the incidence with exposure is 0.9 cases/108/y/R. Taking into account the statistical uncertainty ofthe data and the probably larger uncertainties of thedosimetry, it appears that the joint risk estimate may be
between 0.5 and 1.5 cases/108/y/R. The estimate is basedon an average follow-up time of about sixteen years and

THYROID NEOPLASMS IN PATIENTS GIVEN!1 31120. In 1962 Sheline et al. 15 reported on a group of
256 patients with diffuse hyperthyroidism (non-nodular
thyrotoxicosis) treated with P 31 between 1946 and 1953.
Eight patients ( 3.12 per cent) developed multiple nodules
in the thyroid glands between five and eleven years after
therapy and then had surgery. The nodules occurred in
six of eighteen patients ( 33.3 per cent) under 20 yearsof age at the time of treatment. and in two of 238 adultpatients (0.84 per cent). The ages at time of treatmentin these tumour cases ranged from 2.66 to 29 years. Oneof the children showed evidence of thyroid carcinoma oflow grade malignancy.
121. Aside from the above case, no association between P 31 treatment for thyrotoxicosis and thyroid cancer has been reported.
IY. Neck tumours (excluding thyroid) after
therapeutic irradiation

122. Takahashi et al.. 58 in their retrospective surveyof human cancer in relation to medical exposure in Japan,
found 906 cases of cancer of the neck (excluding thyroid
cancer), namely, cancer of the pharynx, larynx, root of
tongue, cervical oesophagus, parotid gland, etc. Of these,
eleven (1.21 per cent) had histories of therapeutic irradiation of the neck. compared with a control irradiation
frequency of 8 out of 1,770 (0.45 per cent). The difference was significant at the 5 per cent level and gave an
over-all relative risk of 2.7.
123. In table XVII are presented the relative risk
values for neck cancer at various ranges of estimatedexposure. The relative risk is only 1.22 at the 500-2.000
R range and increases to 4.41 for the 6,000-8.000 R
range. The risk of radiation-induced cancers of the neckother than thyroid cancers seems to be less than that forradiation-induced thyroid cancer.
124. These data suggest that relatively large exposures
are required to cause substantial increase in incidence ofneck cancers other than thyroid cancer. This is in accord
with the observation by Goolden 78 in his review ofpharyngeal and laryngeal cancers following radiotherapy (which in 75 per cent of patients was given forthyrotoxicosis) that few cases did not show signs of93

(Series II) children so treated (from 1940 to 1957)
with exposures in the same range but with a mean of
126 R. The relative risks are 7.5 for Series I and 7.7 forSeries II, representing increases per R in the vicinity of
2.0 and 5.3 per cent, respectively. However, it should be
noted that all of the 6 cases of osteochondroma given
both anterior and posterior treatments (Series I) occurred within the tissues in the primary X-ray beam,
whereas 4 of the 5 cases of osteochondroma observed inchildren irradiated anteriorly (Series I and II) arose intissues outside the primary beam. In the sibling control
groups, 1 case was observed in Series I ( 1.53 e..xpected),
and no case was found in Series II ( 0.66 case expected).

severe radiation damage to the skin or subcutaneous tissues long preceding the appearance of the cancer. It
should be noted that the severity of skin changes depends
on a number of radiological and temporal factors.
125. Pifer et al., 21 in their study of 1,451 children
treated for thymic enlargement between 1926 and 1946
with exposures averaging 329 R found 3 cases ofsalivary gland cancer up to 1960, compared with 0.05
case expected, and compared with 0.09 case expected in
2,073 sibling controls and none observed.
V. Skin tumours after therapeutic irradiation

126. Takahashi et al., 58 in their survey of human cancer in relation to medical exposure in Japan noted theincrease in relative risk of skin cancer with the exposure
received (table XVIII). As in the case of thyroid canc:er,
though the rising trend is apparent, limits are very wide
owing to the paucity of cases.
127. The over-all relative risk was 6.0, with limits
16.3 and 2.2. With an average e..xcess radiation of 240 R
in the cancer group the relative risk per roentgen is 2.6
per cent. Most instances of radio-therapy probably involved fractionated exposures and these risk estimates
may not apply to single e..xposures.
128. Clinical and occupational experience suggeststhat the risk of cancer of the skin is low and thatradiation-induced skin lesions usually precede the development of cancer. It may well be, however, that, as
the observations are not based on well designed surveys,
radiation-induced cancers are recognized as such mainly
because of the existence of previous lesions.

BONE TUMOURS IN PERSONS WITH RADIUM
BODY BURDENS

132. Hasterlik et al. 82 • 88 have extended and confirmed
the results of earlier surveys which indicated a strong
correlation between the frequency of development ofbone tumours and the skeletal content of radium. They
reported a study of 264 persons sought out and measured
for radium content in the Chicago area who had been
formerly employed in the radium watch dial industry(219) or as radium chemists ( 4), or who had received
radium as a form of medical therapy (41). With respect
to watch dial painters, this study concerned itself almost
exclusively with those women whose occupational history
antedated 1925. Detailed radiographic studies of theentire skeleton were completed in 236 of the 264 persons.
Of the 264 persons measured for radium, there were
23 (8.7 per cent) with a body burden of< 0.001 µ.Ci
Ram, 36 (13.6percent) with0.001-0.01µ.Ci,102 (38.4
per cent) with 0.01- 0.1 µ.Ci, 62 (23.5 per cent) with
0.1- 1.0 µ.Ci, and 41 ( 15.5 per cent) with > 1 µ.Ci. The
frequencies of different body burdens and the numberof cases of bone malignancy are given in table XIX.
133. Three of the 61 radiographed persons (including 43 dial painters) in the 0.1 to 1.0 µ.Ci range ( 4.9
per cent) revealed malignant neoplasms of or associatedwith the skeleton. Of the 40 radiographed persons (including 19 dial painters) containing above 1 µ.Ci, 14(35 per cent) had such malignant neoplasms. Of the 17
neoplasms, 12 were bone sarcomas ( 0.45 to 6.8 µ.Ci),and the others were epithelial and other neoplasms of
mastoid and paranasal sinuses ( 0.89 to 4.7 µ.Ci). The
bone sarcoma case at 0.45 µ.Ci, however, was found to
be a person with an exceptionally rapid metabolism andtherefore a higher original burden than this figure would
indicate. 8 •134. Analvses of these data suffer from the fact thatthe determin"'ations of radium content of the body havebeen done at least thirty-six years after the acquisitionof the radio-active material. At the present time. theextrapolation of these burdens of radium to radium
burdens at early times is difficult and carries large factorsof uncertainty. The dial painters may. in addition. havebeen e..xposed to substantial gamma doses over the periodof their employment at this work. Furthermore. there isgreat uncertainty as to the relevant radiation dose andits target in terms of production of osteosarcoma, e.g.
integration of radiation doses to whole skeleton. to someunit volume of bone, etc. The radiation doses to different
units or components of bone vary greatly.

129. Two studies have shown the occurrence of skincancer in 10 per cent71 and 28 per cent, 78 respectively, of
patients with chronic radiation dermatitis. Since thelatent period may vary from three to as long as fortyeight years or more, 7 g those percentages may reflect incomplete ascertainment. The dependence of the frequency and seriousness of radiation dermatitis on dose
has not been studied quantitatively and would in any casecomplicate the establishment of dose-effect relationships
for cancer of the skin. No increase in incidence of skincancer has been noted yet among the survivors of Hiroshima and Nagasaki.
VI. Bone tumours
BONE TUMOURS AFTER THERAPEUTIC IRRADIATION

130. Most of the few cases of bone sarcoma that havebeen reported after radiation therapy have arisen in areasof bone containing previously either a benign tumour orchronic osteomyelitis. 80 In some instances, however, thesite of origin was normal prior to irradiation. Reports ofradiation-induced osteogenic sarcoma have in some cases
indicated substantial radiation damage of bone and/o:marrow persisting before cancer development, while inother cases this has not been detected. The lowest exposure thought to have caused an osteogenic sarcoma81
is, at the present time, about 3 ,OOO R. Most other reported
cases have received larger exposures, usually between
4,000 and 7.500 R, sometimes greater.
131. However, Pifer et al. 21 found 9 osteochondroma
cases ( 1.2 e..xpected) up to 1960 in 1,451 (Series I)
children treated for thymic enlargement (from 1926
to 1946) with exposures averaging 329 R, and 2 case>of osteochondroma (0.26 expected) up to 1960 in 1,358

135. However, tentative and very rough estimates ofrelationships between incidence and body burden havebeen drawn by Hasterlik82 who analyzed data in twobody burden ranges. In the range of 1 to 10 µ.Ci there was94142. Because many of these patients are e-"Xposed to
substantial amounts of mesothorium (Ram) the total
radiation from decay of the mesothorium chain has been
estimated and the equivalent in terms of radiation fromRa 226 has been used, the data being expressed in µ.Ci
minimum pure radium equivalent (MPRE).
143. In December 1963 Evans et a/.m reported on
237 subjects (of the more than 350 under study) who
had had radiological examinations. Of these, 76 cases
showed radiological abnormalities associated with bodyburdens ranging from 0.23 to 44.0 µ.Ci minimum pureradium equivalent (lv!PRE). Excluding dental abnormalities, which were almost universal in these 76 cases,
there were 18 persons with no evidence of abnormality
or disease (including body burdens as high as about
3 µ.Ci MPRE), 19 cases of spontaneous fracture ( 0.6
to 20.0 µ.Ci), 23 cases of osteogenic sarcoma ( 0.6 to 24.0µ.Ci), 8 cases of cancer of the paranasal sinus or mastoid( 1.0 to 10.0 µ.Ci), and 3 cases of osteomyelitis of mandible or maxilla (15.0 to 44.0 µ.Ci).
144. More recently, Maletskos et al. 1 " 8 summarized theresults of the same survey covering 361 subjects (88males and 273 females) with skeletal burdens of Ra226
and Ra 228 • Two-thirds of the subjects were dial painters, some of whom had received Ra 2 ~ 6 alone and othersa mixture of Ra226 and Ra 228 • The remainder werepersons contaminated as a result of laboratory work or
by ingestion or injection of the radio-active materials.
l'.fost of the cases studied earlier (before 1957) came toattention because of the symptoms they developed, while
the majority of cases studied more recently were investigated after being found by search. There were 299
found by search and 62 by symptoms. The main exposure period of the dial painters was from 1918 to 1925,
although a few started as early as 1915. Fourteen of thecases had originally been e-xamined by Martland. 129-131
145. With regard to the data of Maletskos et al.,mone of the authors has stated ;86 "At the present stageof the statistical study of these data ... , no clinicallysignificant signs or symptoms are seen with residual or
terminal body burdens of <0.5 µ.Ci Ra (MPRE). Withhigher residual body burdens, beginning in the neighbourhood of 1 µ.Ci Ra and e--..::tending to about 25 µ.Ci Ra, thefraction of the total number of cases which involve eitherof these types of malignancies ( osteogenic sarcomas
and carcinomas of the paranasal sinuses and mastoids)
amounts to roughly ~-" This statement need not betaken to be in conflict with reports of radiographicallyobserved changes in fine structure of bone such as appear
in table XXII associated with burdens below 0.1 µ.Ci.
Data on the percentages of subjects in various body burden ranges showing osteogenic sarcomas or cancers ofparanasal sinuses or mastoid are not yet available forpublication.

a total of 41 persons with about 1,300 man years irradiation experience and 14 cases of malignancy. The riskof malignancy per man year of exposure in this groupis therefore about 1.06 X 10-2 • In the group of 62 persons (2,200 man years irradiation experience) in the
0.1 to 1.0 µ.Ci body burden range, with 3 cancer cases,
the risk is about 1.34 X 10-3 •136. On the basis of the assumed initial intake ofradium, it can be calculated that the risks of developmentof bone tumours in the two groups are 22 and 33 X 10-6
cases per year per microcurie intake. respectively. The
selection of midpoints in the two content ranges for thesecalculations involves certain assumptions concerning the
distribution of patients with different body burdens
within the two ranges.
137. Assuming as the Committee did in the past thatthe cells lining bone surfaces are those that give rise tomalignancies when irradiated, crude estimates of risk
per unit dose can be obtained from these data and may betaken to be about 4 cases/1()6/y/rad. or a figure of
the same order of magnitude as that for leukaemia andthyroid cancer following irradiation from e--..::ternalsources. However, comparison of the figures may bequite misleading in this case. since it is not known how
much of the dose that is delivered over several decades
is, in fact, responsible for the induction. Also, the doses
are average values to the cells lining bone surfaces anddo not take account of the highly inhomogeneous distribution of the absorbed dose. Furthermore, the estimateof risk of bone tumour is based on experience within two
broad dose ranges only and therefore gives no information on the shape of the dose incidence relationship noron the effects of lower doses. It may be noted that thegeneral incidence of primary bone tumours is reported
to be about 10 cases/10°/y and may, in fact, be somewhat lower.
138. In these studies 82 only 2 of the 264 patients
showed (by X-ray spectroscopy) evidence of the presence of mesothorium as well as of Ra 220 • This situation
is in contrast to the patients studied by other groups in
the United States, since the dial painters in other groups
ingested paints containing varying mixtures of Ram,
radio-thorium, and/or mesothorium. In the study by
Hasterlik et al., most of the dial painters were unselectedcases but several of the other subjects were not.
139. Aside from the study described above, Hasterlik
et al. 83 have found 2 cases (death certificates) of acute
myeloid leukaemia in radium patients, one of which was
confirmed by their study of the original blood smear
made shortly before the patient's death in 1931.
140. Barrer et al. 121 have given a preliminary summaryof the data from the first 150 cases studied in a large
survey in the State of New Jersey, United States. Three(2 per cent) developed osteogenic sarcomas, associatedwith body burdens of 0.6, 0.9, and 1.67 µ.Ci Ra 2:?S. Therewas 1 case of chronic myelogenous leukaemia associatedwith a body burden of < 0.0042 µ.Ci Ra 226 • Of 190
death certificates for deceased radium cases, 64 (33.7
per cent) made mention of malignancies, of which 16
cases were of bone and periosteum (8.4 per cent) and3 were tumours of the nose and of the paranasal sinuses(1.5 per cent).
141. At the Massachusetts Institute of Technology8 5
there have been studies of persons with skeletal burdensof radium or radium-mesothorium mixtures resulting
from occupation (dial painters, chemists, physicists).
from parenteral injection of radium solutions and fromingestion of radium or radium-mesothorium mi-xtures.

VII. Tlioriurn-rclated neoplasms

146. Thorium dioxide in a colloidal suspension.
known as Thorotrast. \Vas widely used in diagnostic
radiology between 1928 and 1945, primarily for thevisualization of the liver, spleen. cerebral arteries andcavities of the body. The thorium dioxide content ofThorotrast is usually about 25 per cent by weight. but
may vary considerably. After intracavitary or extravascular injection, Thorotrast remains largely at theplace of injection and may be carcinogenic there. After
intravascular injection, the thorium dioxide particles
are deposited in phagocytic cells of the reticulo-endo95

is absorbed to variable degrees by the particles or particulate agglomerations of origin themselves. It should
also be mentioned that irritation of tissues by the particles, apart from effects of radiation, cannot be discounted as a factor in the pathogenesis of tumours. Data
from experimental mammals, 133 using non-radio-active
zirconium hydroxide in colloidal suspension, give some
support to that view.
151. According to Wald et al., 1 fl various case reports
and follow-up studies have resulted in the accumulationof about ten instances of leukaemia follo\ving thorium
injection. In 6 cases for which detailed data were available, the latent period was 12 -+- 7 years. A causal relationship has not been established between leukaemia andThorotrast injection.

thelial system, and by this means they are concentrated
in liver and spleen. Immediately a redistribution begins
which continues slowly for years and results in changeof position of the particles in the organs of concentrationand in increasing amounts in the connective tissues ofthe body.
147. In 1962 Dahlgren 88 reviewed the literature on tumours following administration of Thorotrast. He listed
68 cases of malignant tumours that had been reported,
including 3 sarcomas at the site of extravascularly deposited Thorotrast (volume injected 20 ml in 1 case,unknown in 2 cases) with latent periods of six to twentyfive years; 26 carcinomas and sarcomas in a variety oforgans (kidney, breast, eyelid, maxillary sinus, bronchi,
peritoneum, ovary, seminal vesicle) after deposition of
Thorotrast in natural cavities (volume injected known
in 4 cases, 10, 24, 30 and 30 ml, respectively) with latent
periods ranging from ten to thirty-five years; 33 malignant tumours (sarcomas and carcinomas) of liver andbile-ducts after systemic injection of Thorotrast (volume
injected J...-nown in 12 cases: 3 cases at 20, 34 and 70 ml,
respectively; 5 cases at 75 ml; and 4 cases at 80 ml) withlatent periods ranging from three to twenty-four years;
and 6 cases of malignant tumours in various organs(colon, lung, spleen, kidney) after systemic injectionof Thorotrast (only one !mown injected volume, 15 ml)with latent periods ranging from thirteen to twenty-four
years. The mean latent period for the total cases is 17.7
years, with mean latent periods in the four subgroups
above ranging from 16.7 to 18.3 years.
148. In 1963 Blomberg et al. 89 reported a study ofpatients who had received Thorotrast injections in cerebral angiography during the years 1932-1947. They
found 6 cases of primary malignant liver tumours ( 5hepatic cancers and 1 haemangio-endothelioma) in 908
patients (about 0.66 per cent). Information on theamount of Thorotrast injected was available for 436 of
the patients and for 3 of the 6 cases of liver cancer. The
413 patients who had received less than 30 ml showedno tumours of liver, while 18 patients receiving between
30 and 40 ml showed 1 case of liver cancer and 2 among
5 patients receiving more than 40 ml had liver cancers.
Of the remaining 3 patients who had received more than
40 ml, 2 died during the first year after the injection andthe fifth patient was not traced. The latent periods forthe 6 liver cancer cases found in this study ranged fromnineteen to twenty-seven years, and the longest observation period was twenty-nine years. Blomberg et al. 89
indicate that the order of magnitude of the mean alpharadiation doses to the liver and the spleen after intravascular injection may be hundreds of rads per year.
149. According to Looney, 91 the accumulated mean
radiation dose to the liver in Thorotrast-injected patients who developed Kupffer cell sarcoma of the liver(mean latent period 15 ± 7 years) was of the order of
1,000 to 1.500 rads. The estimated accumulated dose to
the liver of one patient who developed an hepatic tumour
only three years after 20 ml of Thorotrast was about
100 rads.
150. However, it should be emphasized that there areenormous difficulties involved in attempts to determine
dose parameters and the doses relevant to cancer incidence for thorium dioxide. After intravascular injection.
the distribution of the material, and therefore of theradiation as well. is extremely non-uniform and changes
with time. The radiation, consisting of alpha-, beta-, andgamma radiation in the ratio 90:9:1, 132 is confined largely
to a very short radius from the particles of origin and

VIII. Lung cancer in miners

152. A review of earlier studies of lung cancer related
to radiation in miners has been published by Stewart
and Simpson. 92
153. In 1926 Rostoski et al. 93 reported that in miners(pitchblende) in the Schneeberg region of Saxony,
dying between 1921 and 1926, about 50 per cent had
carcinoma of the lung, with the majority originating inlarge bronchi, while the incidence of lung carcinoma inthe control groups \Vas not noteworthy.
154. Pirchan and Sikl94 found that about 50 per centof the miners (pitchblende) of Jachymov, dying in 1929
and 1930, also had carcinoma of the lung. Observationsof these miners up to 1939 confirmed earlier findings.
155. Although these mines contain several potentiallycarcinogenic materials including arsenic and cobalt, theseelements are also found in many mines where there is no
particularly high incidence of carcinoma of the lung.
Radium itself. as a constituent of the airborne dust in
the mines, has been suspect, but measurements of theradium content of the lungs of deceased miners haveshown no substantial difference from that in the average
human of middle age. Silicosis and silicotuberculosis
have been considered as contributing causes since at
Jachymov nearly half the miners died of either silicosis,
tuberculosis, or a combination of the two, and pneumoconiosis was often found at autopsy in the Schneeberg
miners as well.
156. The opinion is now generally held that airborneradon in the mines may probably be the most essential
factor in the production of lung cancer. The J achymov
and Schneeberg mines have radio-active air and radioactive ore in common.
157. According to Bale95 the major portion of theradiation dose from Rnm stems from the decay of theshort-lived daughters (RaA. through RaC') that are
carried by the atmosphere in varying degrees of equilibrium with the radon parent and are trapped in thelungs. Radon itself and the daughter products of its
decay while in the lungs contribute only about one partin a thousand of the total dose to the bronchial epithelium.
158. Chamberlain and Dyson 96 concluded from experiments that the major portion of the radiation doseto the trachea and large bronchi was attributable to thefraction of RaA preformed in the inhaled atmosphereand unattached to dust or condensation nuclei.
159. Evans and Goodman 97 summarized data on theradon content of the air in the Schneeberg and J achymov
96

mines and concluded that the average radon concentration to which the miners had been exposed was about
2.9 X 10-9 Ci/l. They concluded also that prolonged
breathing of an atmosphere containing about 10-9 Ci/lof radon may have been responsible for the increase in
the incidence of lung cancer observed in the Schneeberg
and J achymov miners.
160. In 1945 Mitchell 98 considered it possible that the
average radon concentration was higher in the years
before the hazard was recognized and regarded a levelof about 1.5 X 10-8 Cijl as a reasonable estimate ofaverage concentration.
161. Assuming a linear relationship between concentration of Rnm and duration of exposure and the lungcancer incidence, and using the Schneeberg and Jachymov experience, Evans and Goodman 9 ' in 1940, andMitchell98 in 1945 suggested MPC (ma.'<imum permissible concentration) values for human exposure to airborne Rn~z= and daughters of 10-11 Cijl and 5 X 10-11
Cijl, respectively. From the literature Mitchell concluded that the approximate SO per cent incidence oflung carcinoma in the J achymov miners was associatedwith employment of the order of ten years and exposure
during working hours to a concentration of radon notless than 2.5 X 10-S Cijl. To reduce the incidence of lungcarcinoma to about that of the community as a whole,i.e., to the order of 0.1 per cent for ten years, the concentration of radon in the air would have to be reduced
to 5 X 10-11 Cijl.
162. Sikl99 in 1950 stated that in his experience theaverage duration of exposure associated with carcinomaof the lung was seventeen years, the shortest thirteen
years.
163. Jacoe 100 in 1953 in his search for airborne radonin tunnels and non-uranium mines in Colorado, mostly
in areas of little air movement, found a range of concentration from zero (instrumental) to one reading of
2.1 X 10-9 Cijl. Most of the samples were in the rangeof 5 X 10-10 to 10-11 Cijl.
164. Harris101 in his examination of atmospheresin zinc, iron and talc mines in New York, where ventilation was low, found radon concentrations ranging
from 4 X 10-11 to 10-12 Ci/l.
165. Oosthuizen et al. 102 in their measurements ofradon concentrations in the air of the gold mines of theEast, Central and West Rand, South Africa, found inareas where the uranium content of the ore was too low
for economic extraction, average radon atmospheric concentrations in the range from 2.5 X 10-11 Ci/l, to 5 X
10-11 Cijl, with measured values as high as 2 X 10-10 to
3 X 10-1 ° Cijl. In mining areas where the extraction of
uranium was economic, radon concentrations in themines were in the range from 10-10 to S X 10-1° Cifl.
These authors reported that the incidence of lung cancer in a large group of underground workers was investigated in two independent surveys, and in each theincidence was similar to that observed in a comparable
age group of the population at large.
166. Yourt103 found in dead-end drifts in a number of
non-uranium hard-rock mines (gold mines) in Northern
Ontario radon concentrations with a median in therange of 1.2 X 10-11 to 1.5 X 10-11 Cifl.
167. No gross excess of lung cancer has been notedin the miners employed in non-uranium mines in Colorado, New York State or northern Ontario. However,there apparently has not been a study carried out to detect small significant increases in incidence.

168. Earlier calculations of radiation dose received
by the bronchi of the J achymov miners were made by
Mitchell. 98 who concluded that the epithelial cells of themain bronchi received about 0.13 rad of alpha radiationin eight hours of exposure, and by Evans, 10 • who calculated that the total dose to the bronchus during theduration of underground exposure (average seventeen
years) amounted to about 600 rads.
169. Later, Bale, 95 taking into account the short-lived
daughter products preformed in the radon-containing
atmosphere, calculated the dose rate to the epithelial layerof bronchial tissue from l0-1 ° Ci Rn 222/l, l0-1 ° Ci RaA/1
and 5 X 10-11 Ci RaC'/l as being LO rad/40-hour week.
In comparison with previous calculations of the dosefrom the same radon concentration, this value is about
2,000 times that predicted by Evans and Goodman 9 ' in
1940, about 300 times that predicted by Mitchell98 in
194S, and about 100 times that predicted by Evans1 CH
in 1950.
170. De Villiers and Windish105 reported that 23 of
the Sl deaths ( 45 per cent) among miners with one ormore years of underground experience in the fluorspar
mining community of St. Lawrence, Newfoundland,
during the ten-year period 1952-1961 were due to primary lung cancer, chiefly near the hilum of the lungs.
A shift in the average age at death of the lung cancer
cases to involve younger age groups, and an association
between age at entry into risk and age at death, werealso observed. The number of deaths expected as aresult of malignant neoplasms of trachea, bronchus andlung among the total of 71 deaths from all causes in all
St. Lawrence miners during 1952-1960, based on 157
such deaths among 15,264 deaths (less those among St.
Lawrence miners) from all causes in males of Newfoundland, was 0.73. The 21 observed cases among the
71 miners dying of all causes was 28.8 times this expected
number. The ratios for the four ten-year age groups
between 2S and 64, inclusive, were 43.2 (25 to 34 years),
10.6 (35 to 44 years), 16.0 (4S to 54 years), and 8.0(SS to 64 years). Considerable numbers of deaths fromtuberculosis and pneumoconiosis were also found.
171. The most outstanding environmental finding in
the mines at St. Lawrence has been the discovery ofconcentrations of radon and daughters in air, well ine.'Ccess of suggested MPC levels. On the basis of theseconcentrations and other considerations, it was suggested that underground workers were probably exposed
to an average potential alpha energy to complete decayof between 2.5 and 10 times the. previously suggested
working level of 1.3 X 105 Mev per litre of air for a
forty-hour working week. m These levels were measured
in mines in which no radio-active ore bodies had beenfound. The mine water was regarded as the source ofthe radon.
172. The more important findings relating to St. Lawrence, J achymov and Schneeberg, and to the uranium
mines of South Africa and the United States, are compared in table XX which gives data on radio-activity invarious mines and the associated incidence of lung cancer. The incidence of lung cancer at St. Lawrence as apercentage of miner deaths ranges between 33.3 per cent
(23 of 69 underground miner deaths 1933-1961) and45.1 per cent (23 of 51 underground miner deaths 19S21961).
173. Wagoner et al. 125 reported recently on a studyof the cancer mortality pattern of a group of UnitedStates uranium miners and millers for the thirteen-year
period 19S0-1962 and compared their age-race-cause97

March 1960). Neoplasms diagnosed prior to the beginning of these studies were eliminated, and analyses werebased on the more restricted, but known, Life-Span
Study population rather than on the total city population.
178. In table XXI are shown crude incidence rates
and age-sex-adjusted rates of malignancies (excluding
leukaemia) per 100,000 persons. The indicated excess ofmalignancies in the most proximally exposed group in
Hiroshima is not so large as that previously reported ona city-wide basis by Harada and Ishida,106 but thegradient of incidence with exposure distance is statistically significant. In Nagasaki, with a considerably
smaller number of collected cases, variations with exposure distance are not significant. For reasons not understood, the incidence in the non-exposed group in Nagasaki (particularly in males) is significantly greater thanin exposed groups.
179. Figures now available137 allow some comparison
to be made between the number of cases of leukaemia
and that of all other forms of cancer which may havebeen induced by radiation. During the years 1950-1959,
36 more deaths from leukaemia (standard error 6.4)
occurred amongst the groups of people who had been
exposed within 1,400 m of the hypocentre at Hiroshima
and Nagasaki than was to be e>..-pected from the mortality
amongst those exposed to lower doses of radiation at
between 1,400 and 2,000 m. During the same period, 30
more deaths from other forms of malignant disease(standard error 13.6) occurred in the fonner group thanwere expected on the basis of mortality in the lattergroup. In this comparison, therefore, the number ofdeaths from all malignancies other than leukaemia, inexcess of those in the comparison population, \Vas 0.8(standard error 0.4) times the excess number of deaths
f ram leukaemia occurring in the same population andduring the same period.
180. It seems probable that the mean latency forradiation-induced leukaemia is less than that for otherforms of radiation-induced malignancy for which information is available and, therefore, that within the periodof this survey ( e."(tending to thirteen years after irradiation) the proportion detected of all deaths that would
finally occur would be greater for leukaemia than forother malignancies. For this reason the value of the ratio
may be expected to rise somewhat in coming years andcannot yet be assessed accurately. Moreover, these data
are based on mortality statistics and not on morbidity
records, and so may not accurately reflect even the present
incidence of disease. It already seems evident, however,that leukaemia (in acute forms and the chronic myeloidform), which normally accounts for only 2 per cent of
all deaths from malignant disease, is increased in its
incidence by radiation received under these circumstances, by a much larger factor than is the total of allother forms of malignant disease.

specific mortality experience with that of the generalmale population of the Colorado Plateau area. Amongwhite uranium millers. total- and cause-specific mortality did not differ significantly from that expected.
Among \vhite uranium miners, 218 deaths were observed
as compared with 148.7 expected ( P < 0.01). Categories in which death significantly exceeded that expected were: (a) respiratory neoplasms among uranium
miners with five or more years underground experience( 11 observed as compared with 1.1 expected or a relativerisk of 10); (b) "all other causes", in the same groupof miners, a reflection of pulmonary fibrosis and its complications: and ( c) accidents, particularly in mines,
regardless of type of employment or duration of underground mining experience. The tenfold increase in respiratory cancer was not attributable to age. smoking,heredity, urbanization, self-selection, diagnostic accuracy, or prior hard-rock mining or other ore constituent,
including silica dust. The evidence presently available
implicates airborne radiation in the genesis of this increase in respiratory cancer.
174. The data available in miners from Jachymov,
Schneeberg, the Colorado Plateau and the St. Lawrence
region strongly suggest that cancer of the lung can be
induced by inhaled radon and its daughters. Risk estimates cannot, hmvever, be obtained from these groups
because only the relative frequency of lung cancer among
all cases of death is kna\vn, rather than the mortality
from lung cancer in the population of miners.
IX. Over·all incidence of neoplasms after
total-body irradiation
JAPANESE A-BOMB SURVIVORS

175. The 1962 report discussed the report of Harada
and Ishida106 on the incidence of neoplasms among survivors of the Hiroshima A-bomb during the period April
1957-December 1958. The data were obtained from thetumour registry and were not based on the Atom Bomb
Casualty Commission (ABCC) closed sample. The incidence of neoplasms varied inversely with distance fromhypocentre. The "doubling dose" for cancer incidence
was estimated as having been received at about 1,300
metres from hypocentre, where the dose was approximately 400 rads. 8176. Studies of the mortality of A-bomb survivors recently reported10 • show that in a subsample of 20,000
persons (ABCC Medical Subsample, Selection I, 19501958) there is thus far no evidence of a higher generalmortality in the more heavily irradiated groups. Whenmortality from specific causes was studied, the wellknown leukaemogenic properties of radiation wereclearly reflected, but for no other causes were radiation
effects seen. In this study the non-exposed group wasdeemed unsatisfactory as a control, at least for theperiods in question, since it was characterized by abnormally low mortality in relation to both the exposed
survivors and the Japanese population generally, anddeaths from tuberculosis and cancer were notably deficient. Therefore, the control of this study relied on comparison oi persons exposed at different distances fromthe hypocentre.
177. Zeldis et al. 51 reported recently on the Hiroshima and ~agasaki tumour registry study of cancer
incidence covering a further twelve months in Hiroshima
in addition to the twenty months already reported byHarada and Ishida106 (May 1957-December 1959), andon the first thirty-six months in Nagasaki (April 1958-

POPULATIONS EXPOSED TO HIGH LEVELS OF
EXVIROKMENTAL RADIATIOK

181. Gianferrari et al. 111 made a survey of births,
deaths and other relevant variables in some communitiesof the Cerva Valley, Italy, where the background radiation is higher than normal (aYerage total exposure of
gamma radiation 15 R per thirty years), and in a nearby
area similar geographically, socially and eco::iomically
except for one-fifth ( 3 R per thirty years) of the background radiation level. The average uranium content(as U 30s) in various alimentary sources in the respective low background and high background areas was:98

soil 1.0, 20.8 mg/kg; drinking water 0.06, 0.24 µg/l;
vegetables 0.3 17.7 mg/kg; and fodder 0.4, 18.4 mg/kg.
In the high radiation area the observed proportion ofdeaths from cancer was higher than expected in every
age group. However, the increase was statistically significant only in the sixty-one to eighty-year age group.
CHILDREN EXPOSED in utero TO DIAGNOSTIC IRRADIATIO:-<

182. In the first reports of the retrospective study
by Stewart et al. 30 • 31 of the relationship of pre-natal
diagnostic X-ray exposure to subsequent developmentof leukaemia and other malignancies in children dying
under ten years of age, it was found that more of themothers of children dying of cancer had received abdominal X-ray e."'<amination during the relevant pregnancy than had mothers of control (living) children.
Of the twenty mothers X-rayed in the first half of pregnancy. eighteen were mothers of children dying of cancer and only two were controls. The ratio of foetal
irradiation in cancer cases to controls was 1.7 for deaths
up to the age of four years and 2.5 for deaths from fiveto nine years of age.
183. The frequency of viral infections and threatened abortions was also significantly higher among themothers of the dead children. X-ray exposures in infancy, acute pulmonary infections and severe injuries
were three post-natal events significantly increased inchildren who subsequently died of leukaemia. Excessive
maternal age was related to increased incidence of
Down's syndrome and increased risk of leukaemia.
184. l\Iore recently, in an extension of the survey,
Stewart32 concluded that most childhood cancers andleukaemias were pre-zygotically determined, that the
recent increase in incidence of childhood leukaemia wasdue to the pre-zygotic form, and that the ma.ximum incidence of that form occurred earlier than the maximum
incidence of pre-natal leukaemias.
185. Madiahon's prospective study3 9 of this problem
utilized a study population of 73,243 children born inthe years 1947-1954 and the frequency of intra-uterine
X-ray exposure estimated from a 1 per cent systematic
sample. Abdominal or pelvic X-rays were recorded in
770 ( 10.6 per cent) of the 7,242 single pregnancies inthe sample, and a total of 584 children born in the study
sample who subsequently died of cancer before the endof 1960 were identified. There were 85 ( 15.3 per cent)of the 556 cancer deaths born of "single pregnancies"
which had maternal abdominal or pelvic X-ray recorded,
as compared with 770 of the 7,242 ( 10.6 per cent) single
pregnancies in the whole 1 per cent samples ( P < 0.05).
After correction for indirect associations with birth orderand other complicating variables, it was estimated thatcancer mortality was about 40 per cent higher in the
X-rayed than in the non-X-rayed members of the study
population. This relationship held for each of the threemajor diagnostic categories: leukaemia, neoplasms ofthe central nervous system, and other neoplasms.
186. The excess cancer mortality in the X-rayedgroup was most marked at ages five to seven years, atwhich time the relative risk was 2.0. The excess risk
was apparently exhausted by age eight years. A trend
toward higher mortality in the more heavily exposedchildren was small and not statistically significant. No

99signific~nt variation with stage of pregnancy at exposure
was evident.
_187. The n;ost important determinant of the amountot. pre-I?atal X-ray e."'<posure appeared to be birth order.
First births had three times as many exposures, andgr.eate~ doses, than later births. There was little changewith birth order after the first birth.
188. In MacMahon's study the ratio of 556 cancer
deaths in 7.242 sample births indicates a total cancer
oortality rate of 76.8/10~ single live births. Since inboth the zero ~o four and the five to nine-year age
groups for Umted States children born in 1950. leukaemia accounts for about half of all deaths, he recrarded
it as likely that the probabilities of dying fro~ anyneop~astic disease during these age intervals were approximately double the values for leukaemia. Applying
the.se probabilities to the population of his study, heestu~1ated that the study population would be e.'<pected
to yield 388 cancer deaths in the first five years of lifeand 246 in the second five years (total 634). The observed numbers were 352 and 197. respectively (total
549). Eighteen other cancer deaths occurred at age ten
years or older.
189. A deficit of 20 per cent of the expected deaths
for the five to nine-year age group can be accounted forto some extent because the population has so far been
followed for only three-fourths of tlie person-years
necessary for complete ascertainment.
190. Using an indirect method of standardization.
MacMahon calculated that the cancer mortality rate in
the X-rayed population, adjusted for the several variables, was 10.31 per 10,000 live births. Using this value,
he obtained a relative risk for all cancers of 10.31/7.8
or 1.42, compared to that of 1.52 without adjustment.
191. MacMahon, in estimating relative risk for malignancy from Stewart's data, e."'<cluding twins and taking
into account Stewart's figure of 1.16 as the measure ofbias in mothers reporting, and including all abdominal
X-ray during the relevant pregnancy, derived a figureof 1.65, not very different from that derived in his study.
192. Stewart's data, however, indicate no appreciable
decline in relative risk even at the highest ages included,
whereas Madfahon's data show no increased risk after
the age of seven years.
193. Recently, MacMahon and Hutchison 108 reviewed
eleven published studies (to September 1, 1962) on thequestion of relative risk of malignant disease in children
from exposure to X-ray in iitero. The relative risks infive of these studies 21 • 3 11-39 • 109 were less than one and insix studies 31 • 33- 35• 39• 110 were greater than one. H~wever.
in view of the great overlap in the confidence limits ofall eleven studies, they tested the possibility that all
studies were consistent with a single risk value andfound the maximum likelihood estimate of this common
risk value by computing the weighted mean of the elevenobserved relative risks. They concluded that there was
no inconsistency in the findings of the eleven studies.
and that the five studies reporting relative risks lessthan one all involved small samples with large e.xpected
sampling variability. The maximum likelihood estimateof the risk involved is 1.40, and the true value may be
expected to be within the range of 1.20 to 1.64
(P = 0.05).

TABLE I.

INCIDENCE OF LEUKAEMIA I:S HIROSHIYA (1946-1962)(Computed.from data of Watanabe 5)
Non-e:ic/xJUd populalio~ Hiroshima•

Total population Hiroshima

Ezposed Population Hiroshima(wiJhin 5,000 melres)

01isel year

Persons
number

Cases
Na.

Cases
io-•

Persons
numbu

Cases
No.

Cases

PersotJJ

JO-'

11umbu1946 .•.........
1947 •..........
1948 ...........
1949 •..........
1950 •..........
1951. ..........
1952 ...........
1953 ...........
1954 ...........
1955 ...........
1956 ...........
1957 .••........
1958 ...........
1959 ...........
1960 ...........
1961 •..........
1962 ...........

171,204
222,434
246,134
262,832
285,712b
297,758
321,973
339,432
361,367
360,808
382,011396,730
412,707426,564
431,285b459,301
479,379

2
6
15
21
13
20
17
22
17
22
18
17
21
26
15
22
14

1.17
2.70
6.09
7.99
4.55
6.75
5.28
6.48
4.70
6.10
4.71
4.29
5.09
6.10
3.48
4.79
2.92

72,135
123,607
147,548
164,498
187,610b
199,898
224,355
242,055
264,232
263,915
285,360
300,321316,539
330,638
335,601h
363,859
384,000

1
l

i
10
10
11
10
6

1.38
0.81
2.71
5.47
0.53
1.50
3.56
2.48
1.51
3.03
1.75
2.33
3.16
3.02
3.28
2.75
1.56

99,06998,827
98,58698,334
98,102b97,86097,61897,377
97,13596,89396,651
96,40996,16895,926
95,684b95,442
95,379TOTALS

288

83.19

TOTALS

104

40.83

TOTALS

4
9
1

3
8

6
4
8

5

fuuss
Cases

Cases
No.

Cases
JO-'

Jo-•

1

9
16
13
14
13
10
11
16
4
12
8

1.01
5.06
11.16
12.20
12.23
17.37
9.22
16.43
13.38
14.45
13.45
10.37
11.44
16.84
4.18
12.63
8.42

0.00
4.25
8.45
6.73
11.70
15.87
5.66
13.95
11.87
11.42
11.70
8.04
8.28
13.82
0.90
9.88
6.86

184

189.84149.38

5
11
12
12

17

• Non-exposed population presumably includes early entrants after detonation.
b Figure from census for year indicated.

TABLE II.

RISK OF LEUKAEMIA IN HIROSHIYA A-BOMB SURVIVORS'(1946-196Z, open population)},{ etres fromhypoeenlre

Estimated
dost range•(rad)E:zposed
population

Uukaemiocases

Cases J0- 1
exposedRalio loexpeeted
in&ilkn.&eb

0-1,500
1,500-5,000
0-5,000> 10,000-200
200- < 1> 10,000- < 1

11,83987,23099,069

127
57
184

1,072
65
186

26.0
1.6
4.5

• Without correction for attenuation by shielding.
b The expected incidence is that observed in the period 1946-1962 in the population beyond
5,000 m., namely 41 X 10--.

TABLE Ill. AVERAGE INCIDENCE OF CONFIRMED LEUKAEMIA IN RESIDENTS OF HIROSHIMA AND
NAGASAKI IN 12 YEARS (1947-1958) BY CITY OF EXPOSURE AND DISTANCE FROY HYPOCE!'/TRE.
ABCC MASTER SAMPLE(Modified from Brill et al.7)
Nagasaki

Hiroshima

Distance(metres)dose (rad)•0-999 m.
(1,400- > 10,000) .
1,000-1,499 m.
(200-1,400) .......
1,500-1, 999 m.
(30-200) ..........
2,000-9,999 m.
( < 1-30) ........

TOTAL

Xo.
leukaemia'ases!:~i;f20

14,638

1,366

3

5,330

563

39

126,446308

20

37,758530

9214,62942

344,19768

21

747,82728

34925,65337

89

1,103,540

81

60

1,012,938

59• Uncorrected for shielding.

100

No.
leulraemia
cases!:~i;l

J947-J958

Casts JO-•Man-yal riskJ9./7-J958

Cases JO-'Man-yal risk

LeMkaemia dealhs
all Japan
Cases J<r'

1.07
1.19
1.37
1.47
1.58
1.67
1.91
2.12
2.28
2.41
2.44
2.65
2.67
2.80

TABLE IV. LEUKAEllIA INCIDE!'CE IS ABCC !\!ASTER SAYPLE L.'i 9 YEARS (1950-1958) BY
RADIATION DOSE (CORRECTED FOR LIGHT SHIELDING) IN HIROSHIMA AND NAGASAKI(Modified from Brill et al.7)
HiroshimaNo.

J.!an-yleukaemia
at risk
casts
19SO-J9S8

Dose i7I rads

> 1,280 ..........
641-1,280 .........
321-640 ..........
161-320 ..........
81-160 ..........
41-80 ...........
21-40 ...........
0-20b ..........
TOTAL

NagasakiCases JO-• Ratio loNo.
Jfon-y<ZPtcltd leukaemia
at rislr
iuidtnu•
'asu

1,561
1,000
656
320
188
61
41
22

78
50
33
16

2
12

3,204
9,999
7,623
21,88837,27848,79848,402547,83951

725,031

70

3.5

5

10
5

7
7
3

!i~i~1

1950-1958

0

1
9

0
2,237
979
624
473
0
100
41

25

262,188

95

2
4
6
0

9

~~isl ineider.ce•

387
1,341
2,043
6,408
12,681
11,565
9,981
217,7823

32
1

Cases I0- 1 Rlllio toe:rpa:ed

112
49
31

_?•..

5
2
4.8

• The expected incidence is the estimated yearly incidence in Ja pan in the period 1950-1958,
namely 2 X 10-5,b Includes A-bomb survivors exposed between 2,000 and 10,000 metres.

TABLE V.

INCIDENCE OF LEUKAEMIA (1950-1962) AMONG EARLY ENTRA."iTS INTO
HIROS!UMA AFTER A-BOMB EXPLOSION(Modified from Watanabet)

Population .•..••.••.......•..
No. of leukaemias developed ....
Incidence per 100,000 per year".

Cases entered
within J days

Cases en/Ped
J-7 days aftc

Cases entced
7-14 days after

25,79927
8.05

11,001
5
3.50

7,326
7

Cases entced
trithin Z flleelrs

44,126
39

7.35

6.79

•Average yearly incidence of leukaemia for 13 years (1950-1962) in non-exposed population(beyond 5,000 metres) in Hiroshima, computed from data of Watanabe,• was 2.34 X 10-1•

TABLE VI.

Ouu1>ati011

Time

Radiologist ..............•.....•

1929-43

INCIDENCE OF DEATH FROM LEUKAEMIA IN PHYSICIANS U

Plaee

Leu-

Total
.Uaths•kamlill.Uaths]Ju:idcnu

8' Non-radiologist. •...•••.•.•..• 1929-43

USA
USA

175
50,1608
221

All physicians ..................

1933--42

USA

26,788

143

4.57%
0.443
0.533

Radiologist .••.....•..•. - •...•..

1938-42

USA

95

5

5.303

All specialists ••......•..•...•.
All physicians ...•....•••....•

1938-42
1938-42

USA
USA

2,029
12,419

19
62

0.943
0.503

Radiologist .....................
Non-radiologist .....•.....•...

USA
USA

124
15,637

6
113

4.843
0.723

All physicians ..................

1944-48
1944-48
1947-51

USA

11,481133

1.203Radiologist •.•...........••..•..
All physicians ................

1949-58
1949-58

USA
USA

296
23,39311
221

Radiologist .....................

1897-56

G. Brit.

463

3

3.713
0.77%
0.653

205
34,626

8
158

3.90%
0.443

Ratio ofintiden£e.r
Generalradiologists: population
all physician: iJu:idenu

Marchm
10.3:1
0.393
10.6:1

Radiologist •....................
Non-radiologist ....•....•.•..•
Radiologist .•.........•....••.•.

1938-42
1938-42
1952-55

Eire
USA
USA

.Marchw

0.523

Non-radiologist ....••.•.•...••

1952-55

USA

1930-54
1930-54
1930-54

USA
USA
USA

1.003
3.65%
2.333
0.633

• With known diagnosis.

101

Peller and PickW
Cronkitetn

4.8:1
Court Brownm
li1rich119
Melville in Schwartz
and Uptonm

3.6:1
Radiologist .....•..•.....•....•.
Non-radiologist with X-ray .....
Non-radiologist without X-ray ..

Henshaw and Hawkins118
Dublin and Spiegelman117

6.7:1

3.573

USA

Rtf<rt1"1

0.393(1950)\Varrenw

TABLE VII. MORTALITY AMONG RADIOLOGISTS: DEATHS ATTRIBUTED TO CASCERS OF THE LYMPHATIC AND BLOOD-FORMING TISSUES AND FROM APLASTIC A."'AEMlA. 0!--1.Y DEATHS OCCURRISG
BETWEEN THE AGES OF 35 AND 74, IKCLUSIVE, L"' THE 14-YEAR PERIOD, 1948 TO 1961, ARE
INCLUDED 9
1"!er·
xalional

Number of deaths~

Principal
diseaurubric200 .......•. Lym phosarcoma
201 .•....•.. Hodgkin's disease202, 205 ..... Lymphoblastoma
203 ••....... Multiple myeloma
204 ...•..•.• Leukaemia
292.4 .•.•.... Aplastic anaemia

Mortality

00.

Ez.

Strt'edPeeled

P•

4b
1
1

2.4
1.6
0.38
1.01
4.02
0.23

> .05
> .05
> .05

5
12
4

95%

ratio
(.M.R.)

Confidence
Ji.R.

1.7

0.5 to 4.3
0.02 to 3.5
0.07 to 14.6
1.6 to 11.6
1.5 ro 5.2
4.7 to 44.5

0.6
2.6
5.0
3.0
17.0

.004
.001
.0001

• Probability that the observed number of deaths, or a larger number, would occur by chance.
b Includes two deaths from lymphosarcoma, one from reticulum cell sarcoma, and one frommalignant lymphoma.

TABLE VIII. NUMBER OF MEN RECEIVING THERAPEUTIC RADIATION TO THE SPINAL MARROW BY 31/12/54, A.'ffi
MAN•YEARS AT RISK FOLLOWING EACH LEVEL OF EXPOSURE THROUGHOUT THE PERIOD OF OBSERVATION: STUDY SERIES
Mean ezPOSIU< toNo.ofmt11

spinal(roentgen)

exposedby Jl/JZ/5·1"'"'"°"'

Less than 250 ••••........•
25()-499 ••••••.••.........
500-749 .•..•.............
750-999 ..•.•..•..........
1,000-1,249 ••...•......••.
1,250-1,499 •••......•....•
1,500-1,749 ............. ..

Mean czj>OsMre tospinal rr.arrow(re><ntgen)iVo. of man-)lta.r.s
at risk follorDing

exposure

1,153
1,708
1,912
2,268
2,124
938
500

8,184
10,33910,126
11,654
10,6325,098
2,437

No. of ,,,,,,,.,'<arsat risk follo-J>ing
ezposu.reNo. of men

e:cpostd
by JI/IZ/54

1,750-1,999 ...............
2,000-2,249 ...............
2,250-2,499 .......•.......
2,500-2,749 ...............
2,750 or more• .............

305
172
118
44
45

1,550
939
509
283
151

TOTAL

11,287

61,902•Average exposure-3,043 R.

TABLE IX. THE NUMBERS OF PATIENTS WHO DEVELOPED LEUKAEbUA, AND THE CRUDE AND STA.>ID..\RDIZED INCIDENCE Ii.ATES,AFTER. DIFFERENT MEAN EXPOSURES TO THE SPINAL KAR.R.OW: MALE "A" AND "B" CASES, EXCLUDING CO-EXISTENT CASES U
Mean exposure lo spinal marrow (R)Lest

11ia ..
O•

No. of men developing leukaemia"A" cases .....•.......•.•..•"A" and "B" ca..ses ...........

zso

ZSO49950<>749

750999

1
1

2
3

6
6

3
.;

1,()()0- J,ZSO1,Z49
1,499

7
8

2
3

Z,750
1,50<>- J,750- Z,000- Z,250J,749
1,999
Z,Z49
Z,499

3
3

1
1

2
2

Z,50<>Z,749

3
4

07'

mort

Total

32
37

Crude incidence per 10,000 men per
year"A" and "B" cases ...........

0.49

2.16

4.59

6.99

12.18

63.65

5.98

Standardized incidence per 10,000
men per year
"A" and "B" cases ...........

0.49

1.98

4.66

7.21

14.44

i2.16

5.98

•The rate given for "zero" therapeutic exposure is the corresponding rate among men of the same agHistribution and observed
over the same period, calculated from the mortality from leukaemia experienced by the whole male population of Britain.

102

TABLE X. THE INCIDENCE OF LEUKAEMIA •.\FTER DIFFERENT MEA."' EXPOSURES TO THE SPINAL MARROW:
11
MALE "A" AND B" CASES GIVEN ONLY SPL......\L IRRADIATION, EXCLUDING COEXISTENT CASES u

Jiea11 e:::posure lo spinal marrow (R)
Less
than
0

zso

zso-

SOO7-19

750-

-199

999

1,000l,Z-19

l,ZSO1,199

J,5001,749

J,750J,999

Z,000
or mare•

Total

566

679

40,247

No. of man-years at risk following
exposure .....................

5,404

7,673

6,573

8,262

7,411

2,782

897

No. of men developing leukaemia
1'A'' cases ..................
"A" and "B" cases .........

0
0

2
2

4
4

3
3

4

0
0

2
2

Crude incidence per 10,000 men
per year"A" and "B" cases .........

5

17
18

0.49

1.53

4.72

6.75b

8.12•

4.47

Standardized incidence per 10,000
men per year"..~"and 11 B" cases ......... 0.49

1.44

4.83

6.82b

8.70'

4.47

•For the group receivin,g 1,500 R or more the crude incidence
is 18.68; standardized incidence 19.86. For the group receiving
1,750 R or more the crude incidence is 16.0i; standardized
incidence 16.82.

•Average exposure, 2,290 R.

b For the group receiving 1,000-1,499 R the crude incidence is

4.91; standardized incidence 5.06. For the group receiving 1,0001,749 R the crude incidence is 6.31; standardized incidence 6.82.

TABLE Xl. OBSERVED A."'D EXPECTED NUMBERS OF LEUKAEMIA CASES IN
CHILDREN IRRADIATED FOR "THYYIC ENLARGEMENT"(Modified from Pifer et al.!l)Series I
TreatedSeries group

Number of persons........................
Average age (yrs.) at observation ... , . . . . . . .
Leukaemia cases (total)....................
Cases expected• (local) ............. , . • . . . •Ratio obs./expected. . . . . . . . . . . . . . . . . . . . . . .
Mean exposure (R) for cases..... . . . . . . . . . . .

1,451
18.5
6
0.96
6.25
336
(15<H84)329
l\foan exposure for series. . . . . . . . . . . . . . . . . . .
Cases < 200 R...........................
4
Cases> 200 R...........................
2

Series II

Siblings

Trealtd

Siblin1s

2,073

1,358
8.1
0
0.51

2,256

0
1.27

1

0.87
1.15

126
0
0

•Cases expected on the basis of records for upstate New York, the area in which the children
were treated.

TABLE XII. RELATIVE LEUKAEMIA RISK IN RETROSPECTIVE STl,;DIES OF CHILDREN
DYING OF LEUK.AEMI.>. AFTER DIAGNOSTIC IRRADIATION in utero

A1e (Jiears)
Years ofof lndlaemus kati:fOT
atkalhlndlaemics&/erenu

Stewartn ..................

< 10

1953-55

Ford et al." ..............•.

< 10

1951-55

Kaplan 14 ••••••••••••••••••

1955-56

Kaplanu ........ , .........

1955-56

Polhemus and Koch

1950-57

35 •••••••

Kjeldsbergae, ..............

?

1946-56

Murray et al.n •. ...........

< 20

1940-57

Murray et az.11 .. .......•...

< 20

1940-57

Murray et al.21 . .•....••..•.

< 20

1940-57

103

Percent41e of mothas
rtuiring abdaminali"adiaJ;o,. during Prefn41")'
Leukanr.i&s

ConJTols

96/780(12.3%)
20/70(28.6%)
37/150(24.7%)
34/125(27.2%)
72/251(28.7%)

117 /1,638(7.1 %)
48/247(19.4%)
24/150(16.0%)
27/125(21.6%)
58/251(23.1 %)
8/55
(14.5%)
3/65(4.6%)
7/93(7.53)
2/82(2.4%)

5/55(9.1 %)
3/65(4.6%)
3/65{4.6%)
3/65(4.63)

Relalive risk,
95% limils
in llraeluts

1.8 (2.4-1.4)

1.7 (2.9-0.8)
1. 7 (3. 7-1.0)
1.4 (2.5-0. 7)
1.3 (2.0-0.9)
0.6 (2.0-0.2)
1.0 (12.0-0.6)
0.6 (2.4-0.1)
1.9 (40.0-1.1)

TABLE XIII. THYROID TL'YOURS IN AUTOPSIES AND SURGICAL THYROID SPECIMENSIN ]APA.."'°ESE A-BOMB SURVIVORS ACCORDING TO DISTANCE FROM HYPOCENTRE(Hiroshima ABCC, 1948-1960£7)
Metres from hypocenlre< I ,4()()

J,400-1,999

Z,000-9,999

Non-uJ>o.ud!\umber of autopsies .........•...
No. and per cent carcinoma ...... .
No. and per cent adenoma ....... .

124
7 (5.63)
9 (7.23)188
3 (1.63)
7 (3.73)397
12 (3.03)
l 8 (4.53)

544
15 (2.73)
15 (2.73)

Number of surgical specimens ..... .
No. and per cent carcinoma ...... .
No. and per cent adenoma ....... .

35
15 (42.83)
5 (11.13)

35
4 (11.4%)
10 (28.6%)

TABLE X!\T, RELATIVE RISKS FOR THYROID CANCER AT VARIOUS EXPOSURE
LEVELS AFTER THERAPEL71C IRRADIATION (EXTERXAL SOURCES) TO NECK REGION(Computed from data. of Takahashi et al. OS)
Proportiunof thyroid

cancer casa

'7cEstimated exposure (roentgen)

0....................................

500-2,000................................
2,000-4,000................................
4,00H,000................................

'7c

95.45
(609)
0.94
(6)
2.04

99.43
(4,044)

(13)

(10)

0.78
0.47

0.05
(2)
0.02

(3)

(1)

(5)

6,000-8,000................................

Proportio11of <onlrols

8,000-10,000...............................

0.16> 10,000.................................

0.16
(1)

0.25
(10)
0.25

Rdaliot risk.
953 limits in
brtukets

4.0 (l.2-13.2)
8.6 (4.3-15.4)
16.6 (3.1-89.0)
19.9 (2.0--200.0)(1)

TABLE XV. AGES AT IRRADIATION AND AT OPERATION, LATE:-<T INTERVAL, A..'\D THYROID EXPOSURE
IN 7 CASES OF THYROID CANCER FOLLOWING RADIO-THERAPY FOR TUBERCULOUS ADENITIS u
Age atirradiation

Age al cancer
opera1io11

lnlm'al

years

years

:,•ears

ApP,.oxinralc exposure (roentgen)

7........................

4
9
15
18
18
23
34

17
27
26
45
42
40
44

13
18
11
27•
24
17
10

1,500 (rt. lobe) 1,000 (isthmus)
700 (both lobes)
500--700 (rt. lobe)
500 + (over 8 years)
650 (rt. lobe)
1,000 (each lobe)
700 (rt. lobe)~feans. . . . . . . . . . . . . . . . . . .

1 7.3

34.4

17.1

Cases

!........................
2... .. .... .... .. . . ... . . . .

3........................
4 ........................
5 ........................

6........................

•From first radiation treatment.

104

TABLE XVI.

THYROID CA."!CER FOLLOWI!-iG THERAPEUTIC IRRADIATION

J,fan-7

Conti:: .......................•.•......•De Lawter" ...............••............
Hanford" ...........•...................
Latourett~ ......•......................
Pifer27 , Series I .•........................
Pifer2'1, Series II ........................ .
Saengeru .............................. .
Simpson'°•'. ............................ .

Children
AdultsChildren, Adults
ChildrenChildrenChildrenChildrenChildren

Arera.re•=/HJSUT•

al risk(r~lzen)

Casts

CastsX
10.../ylUsk estimate(cX 10-•fy/R)

21,896
5,000
5,711
15,13026,843
11,00024,871
18,829

168
2,100
900b
214
329
126
330
52()d

0
0
8
1
8
1
11
10

0
0
1,400
66
298
91
442
531

o.o (0.0-1.1)'
0.0 (0.0-0.03)
1.6 (0. 7-3.1)
0.3 (0.01-1.7)
0.9 (0.4-1.8)
0.7 (0.01-4.0)
1.3 (0.9-2.3)
1.0 (0.5-1.9)

e Partly overlaps Pifer's Series I.

• In brackets, approximate 953 confidence limits of the estimate.
b Mean exposure to largest group (653).

d Mean exposure to cases developing cancer.

TABLE XVII. RELATIVE RISKS FOR NECK CANCER (EXCLUDING THYROID) AT VARIOUS EXPOSURE
LEVELS AFTER THERAPEUTIC IRRADIATION (EXTERNAL SOURCES) TO NECK REGION(Computed from data of Takahashi et al.")Proportion a/cancer ea.us

Proportion of
C011trols

98.79
(895)
0.33

99.43
(4,044)
0.25
(10)

3

Estimated e:>:PGSUTes (roenlten)

0.....................................
500-2,000...... . . . . . . . . . . . . . . . . . . . . . . . . . . .

(3)2,000-4,000.................................
4,000-6,000.................................
6,000-8,000.................................

3

Relatire risk,
953 limits inlwacktls

1.5 (0.4-16.0)

0.66

0.25

2.7 (0.9-7.0)

(6)

0.11

(10)
0.05

2.2 (0.2-24.0)

(1)

(2)

0.11

0.02

(1)

(1)

4.5 (0.3-74.0)

TABLE XVlII. RELATIVE RISKS FOR SKIN CA.'<CER AT VARIOUS EXPOSURE
LEVELS AFTER THERAPEUTIC IRRADIATION (EXTERNAL SOUltCES)(Computed from data of Takahashi et al. 68 )Proportion ofeancer cases

Propor lion ofcontrols

95.45
(294)
0.97

(4,044)3

E.stimaled e:i:posures (rotnlgen)

0....................................
500-2,000... . . . . . . . . . . . . . • . . . . . . . . . . . . . . .

0.65
(2)

(2)

0.65

0.02

(2)

(1)

0.97
(3)

4,000-6,000................................
6,000-8,000................................
8,000-10,000...............................

0.97> 10,000.................................

0.32

(3)
(1)

105

lwackels

99.43
0.25
(10)
0.25
(10)
0.05

(3)

2,000-4,000................................

3

Relative risk,
95% limits in

4.1 (1.2-9.6)
4.1 (1.2-9.6)
13. 7 (1.8-100.0)
27.4 (2.5-300.0)

TABLE X!X. LONG-TEIUI EFFECTS OF RADIUM DEPOSITION IN YAN (CORRELATION OF
CLINICAL AND RADIOGRAPHIC FI?>'DINGS WITH CURRENT BODY BURDE:SS OF Ra!24)
Hasterlik et al.82

Bod;y conlenl CPC>)

Numberradio17aphed<0.001 ....••....•.......•.
0.001-0.01 .•.••.•...........
0.01-0.1 .............•......
0.1-1.0 .••.....•.........•••> 1.0 •...•...........•.....
TOTAL

Radiocraphic changes in skeleton attribtllabk to radium deposition
N011e

Minimal

Mild

17
28
90
61
40

14
28
80
25
1

3
0
8
13
2

0
0
1

9

9•

5

236

148

26

15

Moderate Ad•anud0
0
1

Malic11a..:

4

0
0
0
5b
28°

3
14

14

33

17

• MsTh present in two cases.
b Severe tooth changes only in one case.
• Based on film taken elsewhere in two cases.

TABLE XX.

CoYPARISON OF ST. LAWREXCE, jACID"YOV AND ScBNEEBERG, CoLoRADo PLATEAU AND SoUTH AFRICA DATA m
Fluorspar Mi11es

Uranium MiMs

J (J(;h;ymm I'>' Schnetba-t

St. U1"Ttnce
Non·workinc

area.sWorkint
areas

Abandonedmi~

Workint
min.e

Colorado Platea"
Workinc
minL.sSouth Africa
Worki11g
mines

Radon (picocuries per litre)
Average ............... .
Range ....•.•......•...

270-25,00Qa

5-1,510?-59,000

2,900?-18,000

70-59,000

25-500

Radon daughters (multiples of
1.3 X 1O' Mev per litre per
working week)
Average ............... .
Range ••.......•..••.••

53
4.2-193

2.5-lOb
0-12

Gamma radiation (mR/h) ....
Incidence of lung cancer as %of miner deaths •••..••....

0.03-0.50
33 (1933-1961)45 (1952-1961)

43 (1875-1939)•
52 {1921-1939) 0

11.4d

3.5•

Duration of underground exposure (years)
Average and range ....•.

12.5 (5.5-21.3)

17 {13-23) 1

7, 8, 9, 10, 12

17 .3 (3-30)b

Induction period (years)
Average and range •....•

19.1 (11.5-25.0)

25 {15-43) 1

Age at death (years)
Average and range •...•.

46.8 (33.56)

55 (37-69)•

50 (40-67) 1• Calculated on basis of highest radon daughter concentration
found.
b Estimated.
•After Lorenz {1944).1!:
d Miners with 3 or more years underground experience--5
cases-Archer and others (1962).w

58.2 (45-73)• Based on an autopsy series-23 cases among 650 autopsiesOosthuizen and others (1958).un
1 Nine cases-Pirchan and Sikl (1932).94•Thirteen cases-Rostoski and others (1926)," as quoted by
Lorenz {1944).w
h Based on 14 of 23 cases reported by Oosthuizen and others(1958).102

TABLE XXI. INCIDENCE OF MALIGNANT NEOPLASMS EXCLUDING LEUKAEMIA, HIROSHIMAAND NAGASAKI TCldOUR REGISTRIES, 1957-1959 (SEXES AND AGES COYBI.SED) 17
Distance from h;ypoce1flre ;,. metres

Hiroshima (32 months)
No. of cases ...•..................
Crude rate per 1os ..................
Age- and sex-adjusted rate ...........
Nagasaki (30 months)
No. of cases ......................
Crude rate per 105 ..................
Age- and sex-adjusted rate .•.........

500-1,499

1,500-Z,499

Z,500-9,999.Von-ezposed

Total

79
978.1
953.3

183
829.2
819.7

151
773.4
758.6

120
625.1
650.1

533
774.0
7i4.0

19
635.9
846.4

47
608.1
667.1

29
475.5
600

36
697.l
915.2

131
596.0
735.4

106

REFERENCES
1. United Nations Scientific Committee on the Effectsof Atomic Radiation, Report of the United Nations
Scientific Committee on the Effects of Atomic
Radiation. General Assembly document Suppl. No.
16 (A/5216), 1962.
2. International Commission on Radiological Units
and Measurements, Radiation quantities and units.
Report lOa. National Bureau of Standards Handbook 84, Washington. D.C., 1962.

3. York, E. N., In communication from M. Morgan,
AFSWC, to G. S. Hurst, ORNL, ORNL-CF-5711-44 ( 1957). Graphs reprinted in paper by R. H.
Ritchie and G. S. Hurst, "Penetration of weaponsradiation: Application to the Hiroshima-Nagasaki
studies''. Health Physics 1: 390-404 ( 1959).
4. Arakawa, E. T., Residual radiation in Hiroshima
and Nagasaki. Atomic Bomb Casualty Commission
Technical Report 02-62 ( 1962) .
5. Borg, D. C., R. A. Conard, Activation analysis of
Hiroshima soil samples with estimations of residual
activity following atom bomb detonation in August
1945. Report BNL-7976 (1961).
6. vVatanabe, S., Leukaemias in Hiroshima during
the years from 1946 to 1962. Personal communication.
7. Brill, A. B., M. Tomanaga, R. M. Heyssel, Leukemia in man following e..'Cposure to ionizing radiation. A summary of the findings in Hiroshima andNagasaki, and a comparison with other humane..xperience. Annals Internal Med. 56: 590-609(1962).
8. Ritchie, R.H., G. S. Hurst, Penetration of weaponsradiation: Application to the Hiroshima-Nagasaki
studies. Health Physics 1 : 390-404 ( 1959).
9. Lewis, E. B., Leukemia, multiple myeloma, andaplastic anemia in American radiologists. Science
142: 1492-1494 (1963).
10. Lewis, E. B., Leukemia and ionizing radiation.
Science 125: 965-975 ( 1957).
11. Braestrup, C. B., Past and present radiation e..xposure to radiologists from the point of view oflife expectancy. Amer. J. Roentgenol. 78: 988-992(1957).
12. Court Brown, W. M., Nuclear and allied radiationand the incidence of leukaemia in man. Brit. Med.
Bull. 14: 168-173 (1958).
13. Court Brown, W. M., R. Doll, Leukaemia andaplastic anaemia in patients irradiated for ankylosing spondylitis. Med. Res. Council Spee. Report
295, HMSO, London, 1957; v.e. United Natiou
document A/AC.82/GjR.105.
14. O'Connell, D., Heredity in ankylosing spondylitis.
Annals Internal Med. 50: 1115-1121 (1959).
15. Abbatt, J. D., A. J. Lea, Leukaemogens. Lancet ii:
880-883 (1958).

107

16. Wal~, N., G_. E. T?oma Jr., G. Brown Jr., Hematolog1c marnfestatlons of radiation e..xposure inman. Progress in Hematology 3: 1-52 (1962).
17. Bean, R. H. D., Phenylbutazone and leukaemia.
Brit. Med. J. ii: 1552-1555 ( 1960).
18. Sjmpson, C. L., L. H. Hempelmann, L. 11. Fuller,
Neoplasia in children treated with X-rays in infancy for thymic enlargement. Radiology 64: 840845 (1955).
19. Hempe~m~nn, L. H., Epidemiological studies ofleukem1a m persons exposed to ionizing radiation.
Cancer Res. 20: 18-27 (1960).
20. Murray, R. W., L. H. Hempelmann, A review of
the tumor incidence in children irradiated forbenign conditions, pp. 282-293 in Radioactivity inMan. G. R. Meneely, ed., Charles C. Thomas
Springfield, Ill., 1961.
'
21. Murray, R., P. Heckel, L. H. Hempelmann, Leuk~mia in children e..xposed to ionizing radiation.
New Eng. J. Med. 261: 585-589 (1959).
22. Conti, E. A., G. D. Patton, J. E. Conti, et al., Present health of children given X-ray treatment to theanterior mediastinum in infancy. Radiology 74:
386-391 ( 1960).
23. Latourette, H. B., F. J. Hodges, Incidence of neoplasia after irradiation of thymic region. Amer. J.
Roentgenol. 82: 667-677 (1959).
24. Saenger, E. L., F. N. Silverman, T. D. Sterling,
et al., Neoplasia following therapeutic irradiation
for benign conditions in childhood. Radiology 74:
889-904 ( 1960).
25. Snegireff, L. S., The elusiveness of neoplasia following roentgen therapy in childhood. Radiology
72: 508-517 (1959).
26. Moloney, W. C., Discussion of paper by C. L.
Simpson, pp. 344-345 in Radiation Biology andCancer. University of Texas Press, Austin, Texas
1%~'
27. Pifer, J. W., E.T. Toyooka, R. W. Murray, et al.,Neoplasms in children treated with X-rays forthymic enlargement. I. Neoplasms and mortality.
J. Nat'l. Cancer Inst. 31: 1333-1356 (1963); v.e.
United Nations document A/AC.82/G/L.891.
28. Toyooka, E.T., J. W. Pifer, S. L. Crump, et al.,Neoplasms in children treated with X-rays forthymic enlargement. II. Tumor incidence as afunction of radiation factors. J. Nat'l. Cancer Inst.
31: 1357-1377 (1963); v.e. United Nations document A/AC.82/GjL.891/Add.1.
29. Toyooka, E. T., J. W. Pifer, L. H. Hempelmann,
Neoplasms in children treated with X-rays forthymic enlargement. III. Clinical description ofcases. J. Nat'!. Cancer Inst. 31: 1379-1405 (1963);
v.e. United Nations documentA/AC.82/GjL.891/
Add.2.

30. Stewart, A., J. Webb, D. Giles, et al., Malignant
disease in childhood and diagnostic irradiation inutero. Lancet ii: 447-only (1956).
31. Stewart, A., J. Webb, D. Hewitt, A survey of childhood malignancies. Brit. Med. J. i: 1495-1508(1958).
32. Stewart, A. M., Aetiology of childhood malignancies. Congenitally determined leukaemias. Brit.
Med. J. i: 452-460 (1961).
33. Ford, D. D., J. C. S. Paterson, W. L. Trueting,Fetal exposure to diagnostic X-rays and leukemia
and other malignant diseases in childhood. J. Nat'!.
Cancer Inst. 22: 1093-1104 (1959).
34. Kaplan, H. S., An evaluation of the somatic andgenetic hazards of the medical uses of radiation.
Amer. J. Roentgenol. 80: 6%-706 (1958).
35. Polhemus, D. W., R. Koch, Leukemia and medical
radiation. Pediatrics 23: 453-461 (1959).
36. Kjeldsberg, H., Radioah."tiv bestraling og leukemifrekvens hos barn. T. norske Laegenforen. 77:
1052-1053 (1957).
37. Lewis, T. L. T., Leukaemia in childhood after
antenatal exposure to X-rays. Brit. Med. J. ii:
1551-1552 (1960).
38. Court Brown, W. M., R. Doll, A. B. Hill, Incidenceof leukaemia after exposure to diagnostic radiationin 1etero. Brit. Med. J. ii: 1539-1545 ( 1960).
39. MacMahon, B.. Prenatal X-ray exposure andchildhood cancer. J. Nat'l. Cancer Inst. 28: 11731191 (1962).
40. MacMahon, B., Paper read at Am. Pub. Health
Assoc. 1958.
41. Wise, },if. E., Irradiation and leukaemia. Brit. Med.
J. ii: 48-49 (1961).
42. Stewart, A., D. Hewitt, Oxford survey of childhood cancers. Monthly Bull. of Ministry of Health
22: 182-192 (1963).
43. MacMahon, B., Statement in Hearings on Fallout,
Radiation Standards, and Countermeasures. partII, pp. 594-601. Congress of the United States,
88th Congress, lst session, August 20, 21, 22, and27, 1963; v.e. United Nations document A/AC.82/
GjL.888.
44. Simon, N., M. Brucer, R. Hayes, Radiation andleukemia in carcinoma of the cervix. Radiology 74:905-911 ( 1960).
45. f6.ber, M., Cited in paper by \Vaid et al., reference
46. Faber, M., Radiation-induced leukemia in Denmark, pp. 397-404 in Advances in Radiobiology. G.
C. de Hevesy, A. G. Forssberg and J. D. Abbatt,eds., Charles C. Thomas, Springfield, Ill., 1957.
47. Neumann, G., Roentgen diagnosis and incidence ofleukemia. Deut. Med. Wochschr. 87: 90-94(1962).
48. Stewart, A., \V. Pennybacker, R. Barber. Adult
leukaemias and diagnostic X rays. Brit. Med. J. ii:
882-890 (1962).
49. Gunz. F. W., H. R. Atkinson, Medical radiations
and leukaemia: A retrospective survey. Brit. Med.
J. i: 389-393 (1964).
108

50. Pochin, E. E., Leukaemia following radioiodine
treatment of thyrotoxicosis. Brit Med. J. ii: 15451550 ( 1960).
51. Werner, S. C., A. M. Gittelsohn, A. B. Brill, Leukemia following radioiodine therapy of hyperthyroidism. J. Am. Med. Assoc. 177 : 646-648(1961).
.
52. Dameshek, W., F. Gunz, Leukemia. Chapter 12.
Grune and Stratton, Inc., N.Y.., 1958.
53. Yamazaki, K., S. Kurita, A. Hoshino. Statisticalobservations on polycythemia vera in j apan, p. 80
in Abstracts of VIII Int'l. Congr. Hemat., Tokyo,
1960.
54. Craig, L., H. Seidman, Leukemia and lymphoma
mortality in relation to cosmic radiation. Blood 17:
319-327 (1961).
55. Court Brown, W. M., R. Doll, Geographical variations in leukaemia mortality in relation to background radiation. Proc. Roy. Soc. Med. 53: 762763 (1%0).
56. Socolow, E. L., A. Hashizume, S. Nerushi, et al.,Thyroid carcinoma in man after exposure to ionizing radiation: A summary of the findings in Hiroshima and Nagasaki. New England J. Med. 268 :
406-410 (1963 ).
57. Zeldis, L. J., S. Jablon, M. Ishida, Current statusof ABCC-NIH studies of carcinogenesis in Hiroshima and Nagasaki, pp. 225-240 in Physical Factors and Modification of Radiation Injury. H. E.
Whipple and L. D. Hamilton, eds., Annals of N.Y.
Acad. Sci., vol. 114 (1964).
58. Takahashi, ?·•. T. Kitabataki, M. Wakabayashi,
et al., A stat1st1cal study on human cancer inducedby medical exposures. To be published in Nippon
Acta Radiologica.
59. Hanford,). M., E. H. Quimby, V. K. Frantz .
Cancer ansmg many years after radiation therapy
incidence after irradiation of benign lesions in th~
neck. J. Am. Med. Assoc. 181: 404-410 (1962).
60. ~impson, C. L., L. H. Hempelmann, The associat10n of tumors and roentgen-ray treatment of
thorax in infancy. Cancer 10: 42-56 ( 1957).
61. Ne~man, C. _G. H., Long-term follow-up of 32
pabents irradiated for thymic enlargement in infancy. Brit. Med. J. i: 34-36 ( 1%0).
62. ~arl~n~, L. H., Cancer of the thyroid and previous
irradiation. Surg. Gynec. Obstet. 112: 564-566(1961).
63. Clark, D. E., Association of irradiation with cancer of the thyroid in children and adolescents. J.
Am. Med. Assoc. 159: 1007-1009 (1955).
64. Clark, D. E., The association of irradiation withcancer of the thyroid in children and adolescents.
Proc. Int. Conf. Peaceful Uses of Atomic Energy
11: 146-148 ( 1956).
65. Duffy, B. J. Jr., P. J. Fitzgerald. Thyroid cancer
in childhood and adolescence : A reoort on 28 cases.
Cancer 3: 1018-1032 (1950).
66. ~aventos, A .. R. C. Hom Jr., I. S. Ravdin, Carcinoma of the thyroid in youth: A second look ten
years later. J. Clin. Endocrinol. Metab. 22: 886891 (1962).
67. Wilson, E. H., S. P. Asper Jr., The role of X-ray
therapy to the neck region in the production of-·
thyroid cancer m young people: A report of 37
cases. Arch. Int. Med. (Chic.) 105: 244-251(1960).
68. Wilson, G. M., R. Kilpatrick, H. Ecker, et al.,Thyroid neoplasms following irradiation. Brit.
Med. J. ii: 929-934 ( 1958).
69. Winship, T., R. V. Rosvoll, Childhood thyroid carcinoma. Cancer 14: 734-743 (1961).
70. Winship, T., R. V. Rosvoll, A study of thyroid
cancer in children. Am. J. Surg. 102: 747-752(1961).
71. Goolden, A. W. G., Carcinoma of the thyroid following irradiation. Brit. Med. J. ii: 954-955(1958).
72. Uhlmann, E. M., Cancer of the thyroid and irradiation. J. Am. Med. Assoc. 161: 504-507 (1956).
73. Raventos, A .. D. 0. Duszynski, Thyroid carcinoma
following irradiation for medulloblastoma. Amer.
J. Roentgenol. 89: 175-181 (1%3).
74. DeLawter, D. S., T. Winship, A follow-up studyof adults treated with roentgen rays for thyroid
disease. Cancer 16: 1028-1031 ( 1963).
75. Sheline, G. E., S. Lindsay, K. R. McCormack,
et al., Thyroid nodules occurring late after treatment of thyrotoxicosis with radioiodine. J. Clin.
Endocrinol. Metab. 22 : 8-18 ( 1962).
76. Goolden, A. W. G., Radiation cancer-A review
with special reference to radiation tumours in thepharynx, larynx and thyroid. Brit. J. Radio!. 30:
626-640 (1957).
77. Saunders, T. S., H. Montgomery, Chronic roentgen and radium dermatitis. J. Am. Med. Assoc.
100: 23-28 ( 1938).
78. Teloh, H. A., M. L. Mason, M. C. Wheelock, A
histopathologic study of radiation injuries of theskin. Surg. Gynec. and Obst. 90: 335-348 (1950).
79. Glucksmann, A., L. F. Lamerton, W. V. Mayneord, Carcinogenic effects of radiation, pp. 497539 in Cancer, vol. 1. R. 'vV. Raven ed., Butterworth and Co., Ltd., London. 1957.
80. Bloch, C., Postradiation osteogenic sarcoma. Report of a case and review of literature. Am. J.
Roentgenol. 87: 1157-1162 (1962).
81. Jones, A., Irradiation sarcoma. Brit. J. Radio!. 26 :273-284 ( 1953).
82. Hasterlik, R. J., A. J. Finkel, C. E. Miller, Thelate effects of radium deposition in man, pp. 943946 in Radiation Standards, Including Fallout,part II. Congress of the United States, 87th Congress, 2nd session. Also statement by R. J. Hasterlik in part I. pp. 325-333; v.e. United Nations document A/AC.82/GjL.813.
83. Hasterlik, R. J., A. J. Finkel, C. E. Miller, The
cancer hazards of industrial and accidental e.xposure to radioactive isotopes, pp. 832-837 in Unusual Forms and Aspects of Cancer in Man. H. E.
Whipple and N. H. Moss_. eds., Annals N.Y. Acad.
Sci., vol. 114 (1964).
84. Lucas, H .. R. E. Rowland, C. E. Miller, et al., An
unusual case of radium toxicity. Amer. J. Roentgenol. 90: 1042-1051 (1963).
85. Evans, R. D., Radium and mesothorium poison109

ing. Annual Progress Report, USAEC :N-Y0-9505(1%3).
86. Evans, R. D., Personal communication via A.
Brues.
87. Henle, C.. L. Barrer, H. Fisher, et al., Some results of chronic internal irradiation in humans.
Laval Medical 34: 184-188 ( 1963).
88. Dahlgren, S., Tumours following administrationof thorotrast. Special publication from the Department of Pathology, Karolinska Institute, Stockholm, December 1962.
89. Blomberg, R., L. E. Larsson, B. Lindell, et al.,Late effects of thorotrast in cerebral angiography.
Acta Radiologica 1: 996-1006 ( 1963).
90. Lindell, B., Statement made during discussions ofradiation and cancer at the XIIIth Session of the
UNSCEAR. Geneva, 1964.
91. Looney, vV. B., Tumor induction in man following
radium and thorium ( thorotrast) administration.
A brief summary prepared for the present document.
92. Stewart, C. G., S. D. Simpson. The hazards ofinhaling radon-222 and its short-lived daughters:
consideration of proposed maximum permissible
concentrations in air. pp. 333-355 in Radiological
Health and Safety in Mining and Milling of Nuclear Materials, vol. I. IAEA, Vienna, 1964.
93. Rostoski, 0., E. Saupe, G. Schmorl, Die Bergkrankheit der Erzbergleute in Schneeberg in
Sachsen ("Schneeberger Lungenkrebs"). Ztschr.
Krebsforsch. 23: 360-384 (1926).
94. Pirchan, A., H. Sikl, Cancer of the lung in minersof Jachymov (Joachimsthal): report of cases observed in 1929-1930. Amer. J. Cancer 16: 681-722(1932).
95. Bale, W. F., Hazards associated with radon andthoron. Unpublished memorandum, 14 March
1951.
96. Chamberlain, A. C., E. D. Dyson, The dose to thetrachea and bronchi from the decay products ofradon and thoron. Brit. J. Radio!. 29: 317-325(1956).
97. Evans, R. D., C. Goodman. Determination of thethoron content of air and its bearing on lung cancer hazards in industry. J. Ind. Hyg. and Toxicol.
23 : 89-99 ( 1940) .
98. Mitchell, J. S., Memorandum on some aspects ofthe biological action of radiations, with specialreference to tolerance problems. l\Iontreal Laboratory report HI-17 (1945).
99. Sikl, H., The present status of knowledge about
Jachymov disease (cancer of the lungs in theminers of the radium mines). Unio Internat. Contra Cancrum 6: 1366-1375 (1950).
100. Jacoe, P. W., The occurrence of radon in nonuranium mines in Colorado. Arch. Ind. Hyg. andOcc. Med. 8: 118-124 ( 1953).
101. Harris, S. J., Radon levels found in mines in New
York State. Arch. Ind. Hyg. and Occ. Med. 10:
54-60 ( 1954).
102. Oosthuizen, S. F., W. G. Pyne-1\Iercier, T. Fichardt. et al., Experience in radiological protection inSouth Africa, Proc. 2nd Int. Conf. Peaceful Usesof Atomic Energy 21: 25-32 (1958).

103. Y ourt, G. R., Personal communication to Stewart
and Simpson, reference 92.
104. Evans, RD., Quantitative aspects of radiation carcinogenesis in humans. Unio Intemat. Contra Cancrum 6 : 1229-1237 (1950).
105. de Villiers, A. J., J . P. Windish, Lung cancer in afluorspar mining community. I. Radiation, dust andmortality ex perience. Brit. J. Ind. Med. 21: 94-108(1964).
106. Harada, T., M. Ishida, Neoplasms among A-bomb
survivors in H iroshima: First report of the research committee on tumor statistics, Hiroshima
City 1'.fedical Assoc., Hiroshima, Japan. J. Nat'!.
Cancer Inst. 25: 1253-1264 (1960).
107. Beebe, G. W., M. Ishida, S. Jablon, Studies of themortality of A-bomb survivors. l. Plan of study
and mortality in the medical subsample (selection1), 1950-1958. Rad. Res. 16: 253-280 (1962).
108. Maci\1ahon, B., G. B. Hutchison, Prenatal X-ray
and childhood cancer: a review. Paper read at the
VIIIth Infl. Cancer Congr., Moscow, 1962. To be
published in Acta Unio lnternat. Contra Cancrum.
Abstract and table in Hearings of Joint U.S. Congressional Committee on Atomic Energy, part 2,
1963.
109. Wells, J., C. M. Steer, Relationship of leukemia inchildren to abdominal irradiation. Am. J . Obs. Gyn.
81: 1059-1063 (1961).
110. Ager, E. A., L. M. Schuman, H. M . Wallace, et aJ.,
An epidemiologic study of childhood leukemia.
Minnesota Med. Bull. 33: 253-275 ( 1962).
111. Gianferrari, L., A. Serra, G. Morganti, et al., Mortality from cancer in an area of high backgroundradiation. Bull. World Health Organ. 26: 696-697(1962).
112. Schwartz, E. E., A. C. Upton, Factors influencing
the incidence of leukemia: Special consideration of
the role of ionizing radiation. Blood 13 : 845-864(1958) .
113. Court Brown, W. M. , R. Doll, Expectation of lifeand mortality from cancer among British radiologists. Brit. Med. J. ii: 181-187 ( 1958).
114. March, H. C., Leukemia in radiologists. Radiology
43: 275-278 (1944).
115. March, H . C., Leukemia in radiologists in a 20year period. Amer. J. Med. Sci. 220: 282-286(1950).
116. Henshaw. P. S., J. W . Hawkins, Incidence of leukemia in physicians. J. Nat'!. Cancer Inst. 4: 339346 (1944).
117. Dublin, L., M. Spiegelman, Mortality of medical
specialists 1938-1942. J. Amer. Med. Assoc. 137:
1519-1524 (1948).
118. Peller, S., P. Pick, Leukemia in American physicians. Acta Unio lntemat. Contra Cancrum 11:
292-294 ( 1955).
119. Ulrich, H., The incidence of leukemia in radiologists. New England J. Med. 334: 45-46 (1946).
120. Warren , S., Longevity and causes of death from
irradiation in physicians. J. Amer. Med. Assoc.
162: 464-468 (1956) .
121. Cronkite, E. P ., W. Moloney, V. P . Bond, Radiation leukemogenesis: An analysis of the problem.
Amer. J. .Med. 28: 673-682 (1960).
110122. Lorenz, E., Rad ioactivity and lung cancer: A critical review of lung cancer in the miners of Schneeberg and Joachimstal. J. Nat'!. Cancer Inst. 5:
1-15 (1944).
123. Archer, V. B., H. J. Magnuson, D. A. Holaday,
et aJ. . Hazards to health in uranium mining andmilling. J. Occ. Med. 4: 55-60 (1962).
124. Evans, R. D ., J.E. Gary, S. D. Clark, Radium andmesothorium poisoning in human beings. Paperand exhibit presented at the American Medical
Association meetings, Portland, Oregon, December
1963.
125. Wagoner, J. K., V. E. Archer, B. E. Carroll, et al.,Cancer mortality patterns among U.S. uranium
miners and millers, 1950 through 1962. J. Nat'!.
Cancer Inst. 32: 787-801 (1964).
126. Court Brown, W. M., R. Doll, Radiation and leukaemia. Lancet i: 162-163 ( 1958).
127. Barrer, A. L ., H. W. Fisher, C. B. Henle, et al.,Epidemiological follow-up of New Jersey radiumcases. 1. Report of a Medical Study Group (July
1963) . 2. Resume of findings from individual casestudies. Progress report July 1963. USAEC report
NY0-10604 (1964).
128. Maletskos, C. J. , A. G. Braun, M. M . Shanahan,
et al., Quantitative evaluation of dose response relationships in human beings with skeletal burdensof Ra~ 26 and Ra 2 z8 • In press.
129. Aub, J. C., R. D. Evans. L. H. Hempelmann, et al.,The main effects of internally deposited radioactive materials in man. Medicine 31: 221-329(1952) .
130. Martland , H . S., Occupational poisoning in manufacture of luminous watch dials. J. Am. Med.
Assoc. 92: 466-only ( 1929).
131. Martland, H. S., The occurrence of malignancy inradioactive persons. Am. J. Cancer 15: 112-193(1931).
132. Johansen (1954), Cited by Dahlgren in reference

88.
133. Benstead, J. P. M ., J . 0 . Crookall, A comparison
between the late effects of thorotrast and a nonradioactive zirconium hydroxide sol in mice. Brit.
J. Cancer 17 (1): 62-69 (1963) .
134. Holaday, D. A ., D. E. Rushing, R D. Coleman,
et al., Control of radon and daughters in uranium
mines and calculations on biological effects. U.S.
Public Health Service Pub!. 494 (1957).
135. Upton, A. C., Comparative aspects of carcinogenesis by ionizing radiation, pp. 221-239 iti Controlof Cell Division and Cancer Induction, National
Cancer Institute Monograph, No. 14 ( 1964) .
136. Doll , R., The age factor in the susceptibility of
man and animals to radiation. Brit. J . Radio!. 35 :31-36 (1962) .
137. Jablon , S., M. Ishida, G. W. Beebe, Studies of themortality of A-bomb survivors. 2. Mortality inselections I and II, 1950-1959. Rad. Res. 21:
423-445 ( 1964).
138. Beach . S. A., G. W. Dolphin, A study of the relationship between X-ray dose delivered to thethyroids of children and the subsequent development of malignant tumours. Physics in Med. andBiol. 6: 583-598 (1962).