REPORT OF THE
UNITED NATIONSSCIENTIFIC COMMITTEE
ON THE
EFFECTS OF ATOMIC RADIATIONGENERAL ASSEMBLY
OFFICIAL RECORDS : THIRTEENTH SESSIONSUPPLEMENT No. 17 (A/3838)

New York, 1958

UNITED NATIONSREPORT OF THE
UNITED NATIONSSCIENTIFIC COI\IMITTEE
ON THE
EFFECTS OF ATOMIC RADIATIONNOTE
Throughout this report and its annexes cross-references are denoted by a letter
followed by a number: the Jetter refers to the relevant technical annex (see Tableof Contents) and the number is that of the relevant paragraph. \Vithin each technicalannex, references are made to its individual scientific bibliography by a number
without any preceding letter.
Symbols of United Nations documents are composed of capital letters combined with figures. Mention of such a symbol indicates a reference to a United
Nations document.

TABLE OF CONTENTS
ChapterPage

I.

INTRODUCTIOl"

II.

GENERAL • • • • • • • • • • • • • • • • • • . • • • • • • • • • • • • • • • • • • • • • • • • • • • ••• •••••••••• •. •••••••• . ••••• •. • •. •• •••. •••III.

PHYSICAL DATAIV.
V.

FUNDAMENTAL RADIOBIOLOGY

VI.
VII.

•• ••• •• •••••••••••••••• •••• •••• •••••• . . ••••••••••• ••••• ••••• •• ••• •••••SOMATIC EFFECTS OF RADIATION •••••••.•••••••••• , • • • • • • • • •GENETIC EFFECTS OF RADIATION . • • • • • • • • • • • • • • . • • • • • • • • • • •STJM).!ARY AND CONCLUSIONS • • • • • • • • • • • • • • • • • • • • • • • • • • • • . •

1
3
8
17
22
30
36

Anne.res

A.
B.

C.
D.
E.
F.
G.
H.
I.

DEFINITIONS OF QUANTITIES, UNI:'S AND SY1tBOLS • • • . • • • • • . • •RADIATION FRO}!: NATl:J'RAL SOURCES •••••.••••••.••• , • • • • • • •MAN-:MADE SOURCES (Other than environmental contamination).
ENVIRONMENTAL CONTA.MlNATION • • • • • • . • • • • • • • • • • . • • • • • • •METHODS OF MEASUREMENT • • • • • • • • • • • • • • • . • • • • • • • • • • • • • • .

FUNDAMENTAL RADIOBIOLOGY • • • • • • • • • • • • • • • . • • • • • • • • • • • • • •MAMMALIAN SOMATIC EFFECTS • • • • • • • • • • • • • • • • • • • • • • • • • • • •THE GENETIC EFFECTS OF RADIATION . • • • • • . • • • • • • • • • • • • . • • •LIST OF REPORTS SUBMITTED TO THE COMMITTEE . • • • • • • • • • • • • •

47
49
60

98
124
127
153
172
205

Appendix

227~L"'P ..•......••.................................•........ at end of Report
LIST OF SCIENTIFIC EXPERTS ••••••••••••• , • • • • • • • • • . . • • • • • .

iii

Chapter I

INTRODUCTION
1. Living beings have alwavs been exposed to ionizing
radiation from various natural sources. Nevertheless,the discovery of X-rays by Roentgen in 1895, and ofradioactivity in uranium salts by Becquerel in 1896,
brought, in addition to very great benefits, unforeseen
hazards. Considerable damage resulted until the firstmeasures of precaution were adopted. Indeed, within
only five years, 170 cases of radiation injury wererecorded.
2. The medical use of X-rays increased considerably
during the First World War; this increased the incidence of over-exposure. By 1922 about 100 radiologists
had died from its effects. The discovery of radioactivity
was followed by a rapid development in knowledge of thecharacteristics and properties of radioactive substances,
their separation and their applications, so that the hazard
became extended to those undertaking chemical workwith radioactive materials.

United Kingdom of Great Britain and i'iorthern Irelandand the United States of America.
6. The terms of reference of the Committee were set
out in paragraph 2 of the above-mentioned resolution
by which the General Assembly requested the Committee:" (a) To receive and assemble in an appropriate anduseful form the following radiological information
furnished by States Members of the United Nations
or members of the specialized agencies :" ( i) Reports on observed levels of ionizing
radiation and radioactivity in the environment;" (ii) Reports on scientific observations and e.."periments relevant to the effects of ionizing
radiation upon man and his environment
already under way or later undertaken bynational scientific bodies or by authorities
of national Governments ;"(b) To recommend uniform standards \vith respect to procedures for sample collection and instrumentation, and radiation counting procedures to be
used in analyses of samples;"(c) To compile and assemble in an integrated
manner the various reports, referred to in sub-paragraph (a) ( i) above, on observed radiological levels ;"(d) To review and collate national reports,
referred in sub-paragraph (a) (ii) above, evaluatingeach report to determine its usefulness for the purposes of the Committee;"(e) To make yearly progress reports and todevelop by 1 July 1958, or earlier if the assembled
facts warrant, a summary of the reports received onradiation levels and radiation effects on man and his
environment together with the evaluations provided
for in sub-paragraph ( d) above and indications ofresearch projects which might require further study;"(f) To transmit from time to time, as it deems
appropriate, the documents and evaluations referred
to above to the Secretary-General for publication anddissemination to States Members of the United Nations or members of the specialized agencies."

3. As exposure of human beings and of animals led
progressively to knowledge of the gross effects of radiation, national and international conferences were held todiscuss possible methods of protection against the radiations emitted by X-ray tubes and radium. The year 1921
marks the birth of national organizations for radiologicalprotection and the publication of their first recommendations. International action was first taken during theSecond International Congress of Radiology, which met
at Stockholm in 1928; there. the International Commission on Radiological Protection was established,members of which were elected according to theirrecognized ability in this field, independent of theirnationality.
4. Progress in experimental physics since the beginning of the twentieth century has also brought about
new sources of radiation such as man-made radioactivitv
and powerful accelerators. Following the discovery of
nuclear fission in 1939 and its applications, radiation
hazards and protection problems increased very extensively and the atomic explosions in Hiroshima andNagasaki caused many human deaths from radiation.
The contamination of the environment by explosions of
nuclear weapons. the discharge of radioactive wastes
arising from nuclear reactors, and the increasing use of
X-rays and of radioisotopes for medical and industrial
purposes e..""Ctend the problem to whole populations andalso raise new international questions. In 1955, theGeneral Assembly of the United Nations decided toinclude in the agenda of its tenth session an item entitled"Effects of atomic radiations".

SESSIONS OF THE Cm.IllllTTEE Al\1) PROGRESS REPORTS

7. The first session of the Committee was held from
14 to 23 11.farch 1956 and the second session from 22
October to 2 November 1956. A first yearly progr~ss
report was submitted to the General Assembly at its
eleventh session (A/3365) and covered those two firstsessions. The second yearly progress report of the Co_mmittee to the General Assembly at its twelfth ses.s1on(A/3659) dealt with the third session of th.e Comrrnttee
held from 8 to 18 April 1957. The text or the prese_nt
report was drafted by the Committee in the course of its

Co::.-.sTITUTION OF THE CoMMITTEE
5. The General Assembly, as a result of debates heldin the First Committee from 31 October to 10 November
1955. adopted resolution 913 (X) on 3 December 1955
and thereby established a Scientific Committee consistingof Argentina, Australia, Belgium, Brazil, Canada,
Czechoslovakia, Egypt*, France, India, Japan, Mex.ico,
Sweden, the Union of Soviet Socialist Republics, the*Now in the United Arab Republic.

1

mittee, the large body of information submitted byGovernments.

fourth session held from 27 January to 28 February
1958, and finally approved at the fifth session held from
9 June to 13 June 1958.

Co-OPERATION WITH GOVERNMENTS,
ORGANIZATION OF THE WORK OF THE COMMITTEESPECIALIZED AGENCIES AND INDIVIDUALS

8. At its first session, the Committee elected Dr. C. E.
Eddy of Australia as its Chairman and Professor Carlos
Chagas of Brazil as its Vice-Chairman. Following theuntimely death of Dr. Eddy, the Committee, at its second
session, elected Professor Chagas as its Chairman andProfessor Zenon Bacq of Belgium as its Vice-Chairman.
At the third session, Professor Bacq and Dr. E. A.
Watkinson of Canada were elected respectively Chairman and Vice-Chairman of the Committee and also
served through the fourth session. During the fifthsession, Professor Rolf Sievert of Sweden and Dr.
V. R. Khanolkar of India were elected, respectively,
Chairman and Vice-Chairman of the Committee.
9. The Committee, in the course of its first session,
decided to examine the matters falling within its field ofcompetence under the following five main headings :" (a) Genetics;" ( b) The effects of irradiation by internally absorbed isotopes and the effects of e..xternal radiation ;" ( c) Natural radiation levels ;" ( d) Exposures during medical procedures andoccupational exposure ;" ( e) Environmental contamination".
10. The Scientific Committee, as a working procedure,
used informal ad hoe groups formed by specialists inthe various fields. The composition of these groups
fluctuated from time to time according to the specificarea under examination. The method of work consistedof full and unrecorded discussions centred on a blackboard. During the meetings of these groups and in theplenary meetings of the Committee, information submitted by Governments was discussed and evaluated.

12. States Members of the United Nations and members of the specialized agencies were invited to submit
certain classes of information to the Committee. These
reports are listed in annex I of the present report.
13. In appropriate fields, the Committee had the benefit of the valuable co-operation of the Food and Agriculture Organization of the United Nations, the United
Nations Educational, Scientific and Cultural Organization, the World Health Organization, the \Vorld
Meteorological Organization, the International Commission on Radiological Protection and the International
Commission on Radiological Units and Measurements.
14. The Committee must also express its appreciation
to the many individual scientists not directly connectedwith national delegations whose voluntary co-operationand good will contributed in no small measure to the
preparation of the report.
PREPARATION OF THE REPORT

15. At the opening of its fourth session, the Committee had before it a first draft of its report to theGeneral Assembly (A/AC.82/R.61 and addenda), prepared in accordance with the decisions taken at its third
session, along with a revised version of that draft(A/AC.82/DRAFT 2 and addenda), both prepared in
the Secretariat in co-operation with groups of delegatesnominated by the Committee.
16. On 13 June 1958, the Committee approved thepresent report and decided to transmit it to the Secretary-General of the United Nations for publication anddissemination to States Members of the United Nations
or members of the specialized agencies. Copies of thereport were also made available to the secretariat of theSecond United Nations International Conference on thePeaceful Uses of Atomic Energy.
17. This comprehensive report presents a survey ofthe subject based upon the information received and theconclusions reached by the Committee in the light ofcurrent scientific knowledge. It is recognized that, as
knowledge in this field increases, modifications andamplifications of this report will become necessary.

SCIENTIFIC STAFF

11. The Committee, at its first session, requested theSecretary-General to arrange for a number of scientists
to be added temporarily to the Secretariat on a basis ofrotation in order to prepare scientific data for the meetings of the Committee. Accordingly, a small scientificstaff was recruited and was responsible for presenting,in a form suitable for the consideration of the Com-

2

Chapter II

GENERAL
I. INTRODUCTION
1. The radiations to which human beings are exposedfrom natural and man-made sources are similar in their
physical nature and in the quality of their biologicaleffects. Radiation from both these sources must be taken
into account when assessing the present and future
effects upon man and his environment.
2. Although there e.xists a large body of information
concerning the effects of irradiation, it is apparent that
our knmded_ge is still insufficient. It is in no way c0111parable: f?r mstance, to our knowledge of the physics ofthe rad1atl?ns then:selves, nor, on the biological side, toour experience \V1th many diseases. We have someknowledge of the biological effects caused by exposure
to large doses of radiation, but we know very little about
the possible effects on man of intermittent small doses?r o~ low l_evels of continuous irradiation. Knowledge
m this area is most urgently needed, and the lack of it has
been of the greatest concern to this Committee.

range than alpha rays and, because of their much greater
speed, they produce much less dense ionization. Few
isotopes emit beta particles of maximum range greaterthan 2.0 cm and none of range greater than 8 cm in tissue.

Gamma rays
8. Gamma rays are electromagnetic radiations emitted
by the nuclei of some radioactive isotopes; they haveenergies which are characteristic of the radioisotope bywhich they are emitted. Since they are not charged
particles they ionize matter indirectly through ejection ofhigh speed electrons from the material in which they areabsorbed. The energy of these electrons is then dissipated by interaction with the medium. Because theattenuation of the primary gamma rays is relatively
small, these electrons may be ejected at a considerable
depth in tissue ; each electron then dissipates its energy
within a short distance (from less than a millimetre to afew centimetres depending on its energy) of its pointof origin. No definite range can be given for gamma
rays since they penetrate any thickness of matter butwith progressively decreasing intensity.
9. Low energy gamma rays are absorbed more readily
than those of high energy and for them heavy elements
are more effective absorbers than those of low atomic
number. For higher energies, however, the attenuation
depends almost entirely on mass per unit area and ispractically independent of the kind of material.

II. BASIC PHYSICAL CONCEPTS
3. The radiations with which the Committee is concerned include X-rays, neutrons, protons, cosmic rays
and the radiations (a-, [3-, y-rays) emitted by radioactive materials. All of these radiations produce biological effects by means of the same physical process,namely ~nergy transfer. Radiation passing throughmatter without energy transfer produces no effect.
4. The biological effect of a given type of radiation
depends upon the energy absorbed in the tissue. For
this rea~on, radiation dose is defined in terms of energy
absorpt10n. Whatever the type of radiation, much of theenergy transferred is dissipated in ionization. Radiation
comprising charged particles produces ionization directly. Other types of radiation produce ionization indirectly, by ejection of charged particles.
5. The ratio between the energy absorbed and thetotal ionization produced is almost independent of thekind and energy of particles producing the ionization;
therefore, ionization is used as a measure of radiation
exposure.
Types of radiation
Alpha rays
6. Alpha rays are helium nuclei emitted with definite'.lld char~cteristic energy by the nuclei of some radioisotopes m the process of radioactive disintegration.
Because of their relatively small velocity, and because
they art; char~ed, they produce very dense ionization
along '".1th their paths, and their range or penetration in
m!itter 1s consequently small. Practically none is knownwith a range greater than 0.1 mm in tissue.

X-rays
10. X-rays are also electromagnetic radiations and,
therefore, interact with matter and produce biologicaleffects in the same manner as gamma rays. They differ
only in the fact that the emission process is an e.xtranuclear rather than a nuclear phenomenon. In practice,most X-rays are produced by the retardation of previously accelerated electrons in the anode of an X-ray
tttbe. The energy of X-rays and. therefore, their penetrating power is determined by the voltage applied to thetube. The X-rays used for diagnostic medical procedures
are less energetic and less penetrating than most gamma
rays but it is possible to generate X-rays which are morepenetrating than gamma rays from any radioactive
nuclei.
Neutrons
11. Neutrons are normal constituents of atomic nuclei,
from which they are ejected during processes such as
fission. Because they are uncharged, they cannot produce
ionization directly.
12. Fast neutrons lose energy mainly by collision with
the nuclei of light atoms, especially those of hydrogen(protons). These nuclei recoil and, being charged, produce ions as they dissipate the energy transferred fromthe neutron. Because they are heavier. the recoil nuclei
do not move as fast as electrons of the same energy.
Therefore, they give rise to a more dense ionization thanbeta rays or electrons ejected during the absorption ofBeta rays
7. Beta rays are high speed electrons emitted by the
nuclei of certain radioactive isotopes. Being charged
particles they produce ionization directly in matter
through which they pass. They have a much greater3rintegration of the induced radioisotopes.

X-rays and gamma rays. The transmission of energy
from fast neutrons to recoil nuclei can take place at aconsiderable depth in tissue; like X-rays and gamma
rays, fast neutrons have no definite range.
13. Slow neutrons have no definite range either. Theyinteract with matter mainly by nuclear reactions which
result in an immediate emission of charged particles or
gamma rays during the creation of isotopes. some ofwhich are radioactive. The surrounding medium is
ionized by these particles or gamma rays as well as by thedelayed radiation emitted during the subsequent disTABLE l.
Radiation

Cosmic rays
14. Cosmic rays are an extremely penetrating groupof radiations that originate from heavy particles comingfrom extra-terrestrial sources. The primary component
is absorbed in the high atmosphere, giving rise to various
types of radiation, each producing ionization in its own
characteristic manner.
15. Some of the principal characteristics of the above
radiations are summarized in table I.

PRINCIPAL CHARACTERISTICS OF VARIOUS RADIATIONS
Principal source

Typical enugy

Penell'ation

Radioactive nuclei
Radioactive nuclei
Radioactive nuclei

A few Mcv"
A few Kev• to several Mev
A few Kev to several Mev

Very easily absorbed
Easily absorbed
Relatively penetrating

X-ray tube
Nuclear fission andtransmutation
Extra-terrestrial

A few Kev to several Mev
Up to several Mevb

As for gamma rays
In general very
penetrating
Very penetrating

Nature of radiation

Alpha (a:) ....... High speed helium nuclei
Beta (ft) ........ High speed electrons
Gamma (-y) ..••. Electromagnetic radiation(photons)
X-rays .......... Identical with gamma
Neutrons ....... Uncharged particles
Cosmic ..........Mixture

a For explanation, see paragraph 17.
b "Thermal neutrons" have very low energies,

May exceed many thousand
Mev

corresponding to a velocity which is the same as that of the molecules in air ofnormal temperature.

nuclei disintegrate is proportional to the number ofatoms present ; the fraction decaying per unit time isconstant and characteristic of the particular radioactive
element. It is convenient to specify this characteristic bystating the ''half-life" of the radioisotope, i.e., the time inwhich the number of radioactive atoms will decrease tohalf its value. Starting with any given activity, after
one half-life 50 per cent of the activity remains, after
two half-lives 25 per cent remains and so on. The halflives of different radioactive isotopes range from thousand millions of years (e.g. uranium-238) down to asmall fraction of a second (e.g. radium C'). It is
important to note that isotopes of very long half-lives
show only a slight radioactivity per unit mass (e.g. 1
curie of uranium-238 weighs 3 tons \vhilst 1 curie ofradium-226 weighs only 1 gram).
19. The half-lives and other characteristics of someof the radioactive isotopes with which this report willdeal are given in table II.

Symbols and units of measurements
16. The quantities and units used in this report havebeen defined by international bodies; the current definitions are quoted in annex A. A further description is
given in the following text. The nomenclature in thisreport, with a few exceptions, follows the system prepared by the International Union of Pure and Applied
Physics.
The electron-volt
17. The energy of ionizing radiation is usually
measured in electron-volt ( ev) or in the multiple unitsof one thousand electron-volt (Kev) or one million
electron-volt (Mev.). One electron-volt is the energy
equal to that ga'.ned by an electron when it is accelerated
through a potential difference of one volt and is equal
to 1.6 x 10-12 erg.
Half-life of radioactive isotopes
18. For a given radioactive isotope, the rate at which
TABLE II.

PHYSICAL DATA FOR SOME RADIOACTIVE ISOTOPES

Isotope
Types of radiation

CH

Carbon-14
Potassium-40
Radium-226

K40
Ra226b

Decaying to:Rn222
p 0 21s
Pb214
Bi214
p 0 2u
Pb2to
Bi210
Po~lo

Sr9o

Radon (gas)Radium A
Radium B
Radium C
Radium C'
Radium D
Radium E
Radium F (polonium)
Strontium-90

(3
(3

'Y

a

(,.)

a
a
(3
(3

'Y
'Y

a
(3
(3

'Y

a

('Y)

{3

APJrro:timale half-life•

5,600 years
1.3 x 109 years
1,600 years
3.8 days
3 minutes
2i minutes
20 minutes
0.00015 seconds
22 years
5 days140 days
28 years

Decaying to:

ygo
Cs137
IISI

Yttrium-90
Caesium-13i
Iodine-131

f3
(3

f3

•The duration of exposure from isotopes within the body
qepends not only on the radioactive half-life but also on thetime of retention in the body, and in some instances this is much
shorter than the radioactive half-life, e.g. for Caesium-137: half-

64 hours
30 years
8 dayslife 30 years, half period of retention 140 davs.
b Thorium-232 and its decay products are 'also of interest; thedetails about the corresponding series of radioactive isotopes
will be found in annex B.

4

hn

'Y
'Y

The activity of a radioactive sample
20. The activity of a radioactive sample is the numberof disintegrations occurring per unit time. The unit bywhich it may be expressed is the curie ( c). One curiecorresponds to 3.7 x 101° disintegrations per second. The
denominations millicurie (me), microcurie ( µc) andmicromicrocurie (µµc), correspond to 3.7 x 10', 3.7 x
10 4 and 0.037 disintegrations per second ( dps), respectively. It is convenient to remember that lµµc is approximately two (2.22) disintegrations per minute ( dpm).

been used: 1 for X-rays, gamma rays and beta rays,
and 10 for alpha rays.
Significant dose for e·valttationof a specific biological risk
26. Any specific biological effect of irradiation mustbe evaluated from physical factors such as the distribution of tissue_ dos~ (expressed in rem) in space and timeand fro~ b10log1cal factors ~uch as _radiosensitivity,
latent penod, recovery and repair. The simplest situationis that in which a dose-effect relation for a biologicaleffect is known, making it possible for the probabilitv ordegree of this effect to be calculated. Whether the effecteventually may manifest itself in the form of deleterious
consequences, however, depends on individual circumstances such as expectation of life, or, in the case ofgenetic injury, expectation of children. For this reason,
the potential effect indicated by a direct application ofan assumed dose-effect relation must be weighted according to these individual circumstances.
27. In the case of genetic injury, there is evidence thatthe relevant tissue dose is the accumulated dose to the
gonads and that the dose-effect relation is linear. In thiscase it is proper to weight directly the individual gonaddose instead of the possible potential effect, using as
weighting factor the future number of such children to
be conceived by the irradiated individual. On this basis,a genetically significant dose can be defined as the dose
which, if received by every member of the population,
would be e..xpected to produce the same total genetic
injury to the population as do the actual doses received
by the various individuals.

Radiation dose
21. The radiation dose in any material is the energy
absorbed per unit mass of the material. Sometimes it isuseful to describe exposure to radiation without reference to any actual material present. This can be donewith the help of a reference substance, which is usually
air because the absorbed energy can be evaluated fromthe measurable ionizations produced by the radiation.*
The rad22. The rad is the unit of dose in the sense of absorbed
energy. One rad is equal to an energy absorption of
100 ergs per gram of irradiated material at the pointof interest. As defined, it is applicable to any ionizing
radiation provided the energy deposited is measured(or calculated) in the material actually irradiated. The
tissue dose in rads is the primary determinant of biological effect.
The roentgen
23. The roentgen is the unit in which e."'<posures to
X-rays or gamma rays are e..xpressed. It is defined andmeasured in terms of the ionization which they produce
in air under specific conditions. It is thus a unit ofe.xposure and not of absorbed energy. As defined, itcannot be applied to radiations other than X-rays or
gamma rays.

Ill. BASIC BIOLOGICAL CONCEPTS

28. A living cell is a highly complex entity, all parts ofwhich are involved in its normal functioning. Radiation

may induce alterations at random in any part of thiscomple."'< mechanism, and this may have harmful consequences ranging from inhibition of cell division to
impaired function or cell death. Cells of a particular
type are arranged as tissues, many of which form different organs. Some tissues are more sensitive to radiation
than others : among these are tissues of the gonads, theskin, the intestines, the eye, and the blood-forming
tissues present in the bone marrow, spleen, lymph nodes
and elsewhere in the body.
29. The biological effects of radiations are complex
because many different constituents of the intricate
cellular mechanism and subsequent regulation of thewhole organism are affected. The interpretation of actual
damage is further complicated by interrelations of cells
in the tissues. by repair processes and other regulatory
reactions. There are two modes of tissue repair: recovery of the damaged cells and replacement of injured
o:ies by others. An important feature of radiation action
is damage to the recovery or repair mechanism itself, ineither cells or whole organisms.
30. For practical purposes it is important to consider
separately radiation injury to two categories of cells,
namely, those concerned with the maintenance andintegrity of the individual (such as cells in bone marrow,blood, liver or nervous system) and those concerned withthe maintenance and integrity of the genetic informationthat is handed on from generation to generation ( reproductive cells of gonads). Correspondingly, we shallspeak of somatic effects (limited to the irradiated organism itself), and of genetic effects (limited to its descendants).

Relative biological effectiveness (REE)
24. The relative biological effectiveness of the energy
delivered to tissue by an ionizing radiation depends upon
the type of radiation, the particular biological process
and the rate and level of exposure. The REE appears tobe associated primarily with the linear energy transfer
along the path of the ionizing particle. Conventionally,
X-rays and gamma rays of certain energies are used as
reference radiation. If, for certain processes, the REEof alpha rays is taken to be 10, this implies that, forthese processes, an alpha ray dose of one-tenth rad willproduce the same degree of biological effect as an X-ray
dose of one rad, even though the energy absorption is
only one-tenth as great. A more detailed discussion on
this subject is presented in annex A.
The rem
25. It is convenient to have a unit of dose biologicallyequivalent to the rad, i.e. taking RBE into account. This
unit is the rem, defined by the relation
Dose in rem = Dose in rad x RBE
In this report. tissue doses are generally expressed inrem. In the calculations, conventional REE-values have

* The concepts introduced here as "dose" and "exposure" aremore fully described by the International Commission on Radiological Units and Measurements in recommendations publishedin 1956, where they are referred to as "absorbed dose" and"exposure dose" respectively. See annex A.

5

shortening of life-span and malignant tumours. Examples of the local effect of prolonged external irradiation are late skin changes (including dermatitis, atrophyand skin cancer). An example of chronic internal irradiation is the well-known case of dial painters who accidentally ingested small amounts of luminous paints
containing radium, and some of whom later developed
severe diseases, including tumours of bone. If somecharacteristic effect appears after an exposure-free interval or latent period of several months or years, it istermed a delayed effect (and leukemia or cancer may
develop in this way). Among the survivors of atomic
bomb explosions in Hiroshima and Nagasaki, the development of leukemia has been significantly more frequent
during the years since the e.xplosions than among a nonexposed population.

31. Certain factors may influence the biological effects
of exposure to ionizing radiation. i\mong the physicalfactors are the type of radiation (such as X-rays, alpha,beta or gamma radiation), its energy, the size of dose,its distribution in time (whether given during a short ora long period, or repeatedly), its spatial distribution(involving the whole or only part of the body) ar:d theorigin of the radiation (from outside or from wi~n thebody). Biological factors which affect the scnsitlVltY. of
a tissue to radiation include its degree of oxygenat10n
and water content, its blood supply and metabolic state,
and various constitutional states of the body as a whole.
32. External radiation refers to radiation reaching
the body from sources outs~de i~. Interna~ rad~ation isthat which comes from radioactive materials mcorporated within the body following their ingestion, inhalation or injection. Both act in basically the same way, butinternal radiation exposure is often distributed more
irregularly. since rad_ioa~tive materials may b~ conce~­
trated mainly in certam t1s~ues or organ~, and s1~ce radiation may only penetrate tor a short distance trom thesites of concentration in the body.
33. v\Then radioactive elements are taken up by thebody, they may accumulate particularly in one tissue ororgan which then becomes the most severely injured byirradiation. A critical organ is defined as that organ the
injury of which causes the greatest damage to the body.
The critical organ is usually the one which accumulates
the greatest concentration of the radioactive material,
but this is not always the case, since some organs are
more sensitive to radiation. and some are more essential
to the well-being of the body than others. The toxicity
of radioactive isotopes is determined not only by thecharacteristics of the radiation of the nuclide. Various
factors-physical (size of particles), chemical (watersolubility of material, metabolic affinity of the element),
ecological (balance of calcium, iodine) and physiological(mode of intake, metabolic conditions of the organism)-may affect the degree of absorption, the pattern of
distribution and the metabolic fate of the radioisotopes
in the body. All these factors may influence the extent
of injury.

Genetic effects
35. Genes are the entities which determine heritablecharacters. The genes are located at specific points-loci-in a certain definite sequence in threadlike structures,the chromosotn.es within the cell nucleus. whose number
is characteristic of the species. Each individual inherits
one set of chromosomes through the sperm from thefather and another set through the egg from the mother,so that most cells of a man contain hvo sets of chromosomes. At formation of gametes (sperm or egg) thetwo sets are reduced by a special process to one complete
set in which each chromosome or any given part of it
may have come originally from either the mother or thefather at random.
36. Both genes and chromosomes are particularly
vulnerable to the effects of radiation. Therefore. e..'\:posure to radiation is expected to increase the numberof random and rare heritable changes beyond that which
naturally takes place in cells. These changes are known
as mutations: they usually give rise to unfavorable genes
which play a part in causing defects and diseases in man.
Only the frequency of the mutational changes is alteredby changed radiation exposure : the severity of t11e effects
of any individual change is unaffected by dose.
37. The existence of a given gene is only recognizable
when alternative forms of it occur which have different
effects. The normal form A of a gene together with somemutant for A' may both be present in a population. An
individual may then be characterized by any of thethree combinations AA, AA', or A'A'. These individuals
are said to be homozygous for A, heterozygous for A andA', and homozygous for A' respectively. AA and A'A'
will differ; but t11e behaviour of AA' depends upon therelation between A and A'. If AA' behaves like AA, A'
is recessive to A. If it behaves like A'A', A' is dominant
to A. Intermediate conditions are quite usual and thisrelation is known as partial dominance.
38. The genetic constitution of an individual is derived almost equally from each of the two parents. In
hun1an populations, however, matings are influenced bya wide variety of geographic, social. economic and religious factors as well as physical and mental characteristics. Knowledge of these factors is of value for anunderstanding of genetic changes from generation to
generation. Although the true situation is very comple..-x..
it is often a permissible approximation to regard matings
as taking place at random in a human population. One
consequence of this continual intermingling of genes ineach generation is that the total of genes in the population
really behaves in some respects as a single pool. to which
mutation adds new genes, favourable and unfavourable.
\Vhen a e;ene is recessive, so that its effects shmv only if

Somatic effects
34. Depending upon the factors mentioned, thesomatic effects of a given dose may be manifested invarious ways. If a single large dose of over 600 rem ofpenetrating radiation is delivered to the whole humanbody or to a large part of it in a matter of minutes, it willcause death in a matter of days or weeks. The signs andsymptoms associated with such exposures are known a:.
the acute radiation syndrome. If, however, such a doseis delivered to a limited part of the body, as for instanceto the hand. generally only a local reaction such as skinerythema will be evident. Moreover. if a dose of wholebody irradiation, which would rapidiy have caused deathif given as a single dose, is divided into small fractions
which are delivered over a period of months or years,
with exposure-free intervals between them, immediate
death does. n?t occur but a pattern of chronic injury may
result. Tlus is due to the fact that the body is able, tosome extent, to recover in the inten·als between exposures. However. chronic exposure. despite apparent
recovery, may have permanent pathological effects, andthe ensuing illnesses may develop after long latent
periods. Chronic irradiation may cause severe damage tothe blood-forming tissues causing leukemia or hvpo·
plastic anaemia. It may also cause fibrotic and scle~oticchanges in tissues. a diminished resistance to infection,62. No effect is manifested until the dose exceeds acertain value, the threshold dose for that effect. Therefore, doses up to this limit \vill have no effect.
The graphical illustration of both types is shown infigure 1.

an individual receiYes copies of it from both parents,
single copies of it in one individual are then unnoticed
even although two copies may have serious consequences.
Such a gene may come to be carried by many individuals
through the population before an appreciable numberof them are affected by having received two copies of it.
By contrast, a dominant gene is able to affect individuals
who have received only a single copy of it and will usuallyexert its effects on the more immediate descendants of
the individual in whom it originated. Hence, an unfavorable dominant gene usually persists through fewer
generations and spreads to a smaller fraction of the
population before elimination than does a recessive gene
having similar unfavourable consequences.

JQQ; .---.--r~-.---.--r---r---r-..........--.-"""T-il""--r

-

. 1-.

z

w
0

a::
w

a... 50
l-

o

w
LI..

Biological consequences of radiation
39. The e.'Xtent of biological effect from increased
radiation is primarily determined by the quantitative
relation between radiation dose and its effect. In principle, many basic types of such relation exist, but only
two will be discussed here :1. The effect is directly proportional to dose andthe frequency increases linearly with increasing dose.
Therefore, any dose, no matter how small, will havean effect.

u..

LrJ

DOSE {RELATIVE UNITS)
Figure 1. A pictorial representation of the difference between
a threshold and a non-threshold situation. Dose increases to theright. Note that the non-threshold line is a straight line; it neednot be. (Modified from Langham and Anderson, United
Nations document A/AC.82/G/R.130, U.S.A. Congressional
Hearings on Radiation, June 1957, part 2, page 1363.)

7

rChapter III

PHYSICAL DATA
6. As the genetic effect of exposure is assumed to be a
linear function of gonad dose, it is possible to weight theindividual doses directly, the weighting factor being thefuture number of children to be e..'l\:pected by each individual subsequent to the exposure. A weighted genetically significant dose is accordingly defined in chapter
II (paragraph 27).
7. According to one hypothesis, the induction of leukemia is also a linear function of dose. The appropriate
weighting factor is not known but as a first approximation the various contributions to marrow exposure may
be compared without weighting. Another hypothesis assumes a threshold for the induction of leukernia ; in thiscase a per capita marrow dose has no meaning but theindividual marrow doses become determining factors.

I. INTRODUCTION
1. In estimating doses to which populations are exposed, the Committee has classified the sources into three
categories :(a) Natural ;( b) Man-made (except environmental contamination) ;( c) Environmental contamination.
The relative risks from different radiation sources, ingeneral, increase with the radiation doses from thesources. It is therefore useful to compare the doses fromvarious man-made sources with those from the natural
sources to which the human race has always been
exposed.
2. In this report, consideration has been given to
those sources which are contributing to the populationdose at the present time, together with some estimates of
future e..xposure from environmental contamination. In
the future, various man-made sources may increase inrelative importance ; the radioactive waste of atomic
industry, nuclear reactor accidents and the use of isotopes in medicine, research and industry may well become problems.

III. METHODS OF :\IEAS"URDfENT
8. The ultimate purpose of radiological measurementsof concern to the Committee is the estimation of tissue
dose from natural sources, man-made sources and environmental contamination. In some cases, however,measurements of radioactivity are also of primary concern. It is emphasized that new and improved methods
are constantly being developed.
9. It is customary to classify measurements of thisnature into categories relating to the method used, i.e.
direct or indirect. Direct exposure measurements arethose made with ionization chambers or instruments
calibrated in terms of air ionization. Indirect methods
are those where dose is calculated from activity measurement. The rates of e..xposure from medical and industrial
practice and from terrestrial and cosmic radiation are
sufficiently high to allow direct measurement. Exposure
rates from other sources are low and the dose must
usually be estimated indirectly by activity measurement
and subsequent calculation.
10. A survey of the methods of measurements \vhich
have been found to be valuable in relation to the workof the Committee is given in annex E.

II. DOSE ESTIMATES REQUIRED FOR EVALUATION
OF BIOLOGICAL RISKS

3. A quantitative estimation of the total deleterious
irradiation effects in a general population must be based
upon information as to the extent of the likely biologicaleffects as estimated from assumed dose-effect relationships and also upon individual weighting factors appropriate for the deleterious consequences as discussed inchapter II, paragraphs 26 and 27.
4. Only in the case of a linear dose-effect relation
with no threshold value of the dose is it relevant to add
the dose contributions from various sources. This canbe done in the case of genetic injury and, according to
one hypothesis, also in the case of a possible inductionof leukemia.
5. In order to meet the requirements of subsequent
chapters which are concerned with biological consequences, it has been necessary to estimate the following
doses:(a) For evaluation of genetic injury: the dose to the
gonads.
( b) For evaluation of possible induction of leukemia :the. mean marrow dose (averaged overall 1,500 g ofactive marrow).
For most uniform exposure of the whole body. the listed
gonad doses are very close to the mean whole body dose.
The significance of partial exposure of the body (as inmedical practice) is difficult to eYaluate. but a usefulindex of risk seems to be the significance of each corresponding exposure of marrow as e.."pressed by themean marrow dose.

IV. NATURAL SOURCES OF RADIATION
11. Man is exposed to radiations from : (a) externalsources, namely cosmic rays and terrestrial radiations
from radioactivity in the ground, the air and building
construction materials, and ( b) internal sources suchas the radioisotopes potassium-40 and carbon-14 which
are normal body constituents, radium and thorium deposited in bone and radon, thoron and its disintegration
products in solution in blood and tissues.
External natural sources
12. The penetration of the cosmic radiation at sea
leYel is so great that the dose rate of all organs of thehuman body is practically uniform and equal to the dose
rate in air. This dose rate is of the order of 30 mrem peryear.
13. The variation of cosmic ray intensitv with altitude
and geographical location is known. The·altitude effect8

dose rate is 2 mrem per year. This rate is substantially
increased in areas of high natural radioactivity and in
badly ventilated buildings constructed of materials containing radioactive elements. The osteocyte dose fromthis source is negligible. Radium is taken up from theenvironment and is deposited together with calcium inbone structure. The average osteocyte dose from radium
is in the range of 38 mrem per year, but it may be tentimes larger in some geographical areas. With a random
distribution of the radium in the bone, the average marrow dose will be 2 to 5 per cent of the osteocyte dose.
20. From the above-mentioned figures, the total soft
tissue dose from natural internal sources is computed
to be 23 rnrem per year, the osteocyte dose is in the rangeof 50 mrem per year, dependent on the radium content
of the bone, and the marrow dose is approximately 15
mrem per year.
Summary
21. Estimates of doses which arise from natural
sources are given in table I.

is the more important: from sea level to 3,000 m the dose
rate increases by a factor of approximately 3. At sea
level the range of variation with latitude is 14 per cent;at an altitude of 4,000m it increases to 33 per cent.
There are also small longitudinal and temporal variations. Cosmic ray intensity is only slightly reduced eveninside massive stone buildings.
14. Radiations from the ground arise from radioactive elements in rocks and soil. The concentrations ofthese radioactive elements (uranium, thorium and theirdecay products, and potassium) vary widely with geological conditions and are generally higher in granitic
rocks than in sedimentary formations or soil. Areasrich in some of these radioactive elements (e.g. monazite
sand areas as in Kerala, India and Guarapari, Brazil)show exceptionally high radiation intensitiesB~ 7 • The
radiations from the radioactive elements contained insome building-construction materials (masonry) often
more than compensate for the shielding effect of thebuilding, so that indoor e.."<posures are frequently higher
than those out of doors.
15. On account of the penetrating character of theseradiations, the gonad, osteocyte and marrow doses may
be considered to be approximately the same. Taking into
account the shielding factors and time spent in buildings,
it is estimated that radiations from the ground and frombuilding-construction materials contribute in the rangeof 50 mrem per year to the gonad doseB-' 0 • This range
is representative for the major part of the population in
the areas for which values have been reported. In highactivity areas, such as those mentioned above, the dose
may range up to 830 mrem per yearn 27 •16. Radon and thoron diffuse from the earth andbuilding materials and constitute a minor e..xternal radiation source from which the gonad dose is approximately
1 mrem per year in normal circumstances. High concentratiom of radon and of its decay products have been
observed in ill-ventilated rooms of masonry buildings incertain areas. Under these conditions slightly enhanced,
but still small, gonad doses may arise.
17. Thus, gonad. osteocyte and marrow doses from all
external sources are usually of the order of 75 mrem peryear, but may range up to 190 mrem per year with local
conditions in many countries, whilst in the high activity
areas they may range up to 830 mrem per yearB 27 •TABLE I.

ANNUAL DOSES FROM NATURAL
RADIATION SOURCESa
Annual dose~~~~~~~~~~~--']

SourceMean ma.TTOV

Gonad~

Osletxyle ~(mrem)(mrtm)(mrtm)~

Cosmic rays ...........
Terrestrial radiation ....
Atmospheric radiation ..

28
47
2

28
47
2

28
47
2

Internal
K-40 .................

19

11

11

1.6

1.6

External

C-14 .......•.........
Rn-Tn ................
Ra ...................

2

Approximate totals

100

1.6

2
38

0.5

130

95

• The totals in the table are for "normal" natural radiation
intensities; in certain areas the values range up to ten times
higher than those given.

22. Detailed considerations of natural radiation
sources are to be found in anne..x B, including more
complete data for different areas.

V. MAN-YA.DE SOURCES( e%cept environmental contamination)
23. At the present time radiation exposures fromman-made sources ( e..xcluding environmental contamination) arise principally from:(a) Medical uses of X-rays and radioactive materials,( b) Industrial and research uses of X-rays and radioactive materials, and( c) Other sources such as luminous dials of watches,
television sets and shoe-fitting fluoroscopes.
Medical ttses of X-rays and radioactive materials
24. Medical uses of X-rays and radioactive materials
are:(a) Diagnostic uses of X-rays,(b) Use of X-rays and external radioactive sources
for radiotherapy, and( c) Use of radioactive isotopes as internal sources
for diagnosis and therapy.
.
This section deals only with the e..xposure of patients.
Occupational e..xposure from medical uses of X-rays ;indradioactive materials is treated in paragraphs 34-3_,_

Internal natiiral sources
18. Some of the normal constituents of the humanbody are radioactive. The specific activity of potassium40 is about 10-0 curies per gram of natural potassium;
carbon-14, formed by interaction of cosmic rays withthe air, has an equilibrium concentration of about 7.10-12
curies per gram of carbon, corresponding to the specificactivity of the carbon of the atmospheric carbon dioxide.
The specific activity is constant and therefore the dosefrom these radioactive isotopes is determined solely by
the potassium and carbon content of the tissues. Softtissues of the body receive a dose of about 20 mrem
per year from internal potassium-40 and of 1-2 mrem per
year from carbon-14. The bone (marrow excluded)contains less potassium than soft tissues, and the osteocyte dose from potassium-40 is of the order of 10 mrem
per year; bone doses from carbon-14 are similar to soft
tissue doses from the same isotope.
19. Soft tissues receive a dose from radon. thoron
and their disintegration products taken in from the atmosphere and dissolved and retained in the tissues ; the9

mendations of the International Commission on Radiological Protection and are collected and further elaborated in the report of the joint study group of the ICRPIICRU (See annex C).The annual genetically significant
dose that may be achieved with good practice v..-ithout
detriment to diagnostic information has been estimatedto be 15 mrem for Sweden.

Diagnostic uses of X-rays
25. The diagnostic use of X-1:a~'S has beei: of greatvalue in the development of medicme. The wide use. ofthese methods in some countries and their increasmg
application in mwy oth~r~ make it imp?rtant _to c?nsider
any risks tha_t such radiat10n may ~ntail. ~st1?1at1ons of
the contribut10n to the annual genetically significant dosefrom diagnostic X-ray procedures have been made f~rsome countries in which however. the use of X-rays 1s
extensive. In some of these countries this contribution
seems to be about equal to that from natural sources.
A detailed discussion on the values, which are presented
in table II. is given in annex C. It should be noticed that
all estimates of the genetically significant dose dependon assumptions as to. the averag:e ch_ild ~pectancy ofvarious groups of patients of which little is yet known.

Radiotherapy
29. The contribution from radiotherapy in Englandand Wales has been estimated to be appreciably less thanthat from diagnostic procedures but greater than thatfrom any other man-made contribution. In the UnitedStates, the annual genetically significant gonad dose fromradiotherapy has been estimated at roughly 10 mrem.
This estimate is based on what appear to be rather conservative figures for the number of treatments per year
contributing to the genetically significant dose. Publisheddata for Australia and Denmark estimate a contribution
to the genetically significant dose from radiotherapy of
28 mrem per year and 1 mrem per year respectively.
30. The estimated values are not strictly comparable,
since different assumptions have been made in each. In
the United States estimate all treatment of malignant
conditions was disregarded because:(a) A high percentage of patients were above theaverage age of child-bearing, and(b) For many, the prognosis was bad, so that the
chance of subsequent parenthood was small.
In the published estimate for Australia, simplifying
assumptions were made as to the area of field treated
and the dose delivered in the treatment of malignant,pre-malignant and non-malignant conditions. In addition,
it was assumed that a normal child expectancy existed
for all surviving patients not assumed to be sterilized
by the irradiation. In the Danish survey it was assumed
that the patients treated for malignant conditions had
one-fifth the child e>..-pectancy of normal individuals. In
the summary table (table III) the range of values isquoted.
31. In considering induction of somatic injuries, thedose from some treatments. such as those of skin cancer
and of various benign conditions, should be included in
the population average, since prognosis is relatively good
and the patients are not ruled out on the age factor.
Hence. it appears that radiotherapy may give a contribution to marrow exposure of higher relative significancethan the contribution to the exposure of the gonads. No
estimates of the per capita mean marrow dose (fromradiotherapy) were available to the Committee.

TABLE II. ESTIMATED LEVELS OF GONAD EXPOSURE
FRO:l.1 DIAGNOSTIC X-RAY PROCEDURES
A11nual gemtically signi}ieant dost (mrem)&timaUd minimum

Denmark ................. .
England and Wales ........ .
France ......... ············
Sweden ................... .
U.S.A ..................... .

Probable value

17

23
57

38
150 ± 10050 ± 30~~~~~~~~~~~-

A11n1tal per capifo gonad dost (mrem) •Austria ................... .
Japan .................... .

16-24
10-30

a The per capita gonad dose has been found to differ but little
from the genetically significant dose in countries for which bothhave been estimated.

26. More than 80 per cent of the genetically significant
dose from diagnostic X-ray exposure is contributed bysix or seven procedures (those involving the region of
L11e lower abdomen and pelvis) during which the gonads
are usually in the primary field. However, these procedures constitute only about 10 per cent of all examinations.
27. For countries with an extensive use of X-rays,
the average annual marrow dose of the population canbe estimated to range beyond 100 mrem per person.
This figure is very close to the per capita marrow closefrom natural radiation. X-ray examinations of thegastro-intestinal tract and of the chest (including mass
chest X-ray sun eys) give the highest contributions to
the average marrow dose. A comparison between dosecontribution is relevant only if a linear dose-effect relationship can be assumed. The average marrow dose per
examination varies within the range 1-1,000 mrem fordifferent types of examinations, and the individual doses
may show a large variation around each average. This
will mean the existence of some heavily exposed individuals who, in the case of a non-linear dose-effectrelationship. may run a much higher risk than is indicated by the dose figures. All figures mentioned aboverefer to the mean dose in the whole mass of active
marrow, of which only a small fraction may actually be
exposed. The e..xposed marrow may in extreme cases
receive very high doses, especially in the case of fluoroscopy where the dose-~ate in the irradiated marrow may
be several rem per minute.
28. The data submitted from several countries indicate that it may be possible to reduce the diagnostic
exposure considerably by careful attention to techniques.
Valuable precautions are described in the current recom1

Medical uses of radioactive isotopes (internal
administration)
32. The principal contributions to the population dosefrom the medical use of radioisotopes arise from theuse of iodine-131 and phosphorus-32. which are mostwidely employed. While considerable quantities of gold198 are used, the biological significance of exposure fromthis source is negligible since gold-198 is generally limited
to palliative treatment of incurable conditions. Other
radioisotopes are used in Yery small quantities and almost entirely for diagnostic purposes.
33. Estimates of the average gonad dose resulting
from the use of iodine-131 and phosphorus-32 can bebased upon information about either treatments or radioisotope shipments. the first approach being more accurate
and preferable. From the report of the ICRP /ICRU
10

tests are fission products. There are also some formedby neutron induction and some residual fissionable
material.
Fall-out mechanisms
40.. Fission prodll:cts injected. into the stratosphereconstitute a reservoir from which they fall onto thewhole of the earth's surface over a period of many years(stratospheric fall-out). Fission products not pen~trat­
ing into the stratosphere may be transported over long
distances in the troposphere by air currents but are
deposited on the earth's surface by rainfall and sedimentation over a period of a few months (troposphericfall-out). Because of the gradual deposition of iall-out
from the stratosphere, most of the resulting irradiationof man arises from radioactive isotopes of long half-lifesuch as strontium-90 and caesium-137. In contrast. theearlier deposition of tropospheric fall-out makes it neccessary also to consider the doses from radioisotopes ofmuch shorter half-life such as strontium-89, zirconium95 and ruthenium-103 and 106, iodine-131, barium-140
and cerium-144.
41. Near the test site there is an early deposition ofradioisotopes which is influenced by various meteorological and testing conditions and which may involve a
special hazard to any individual in this area of immediate
local fall-out.
42. Meteorological conditions and the predominantoccurrence of nuclear tests in the northern hemispherecause a non-uniform deposition of the longer-lived isotopes over the globe, as a result of v,·hich countries between 30° and 50° North experience a deposition ofthese about three times as great as the world-wide average. Countries in the southern hemisphere and in thetropical belt have smaller deposits with a maximum
between 30° and 50° South, of the order of the worldwide average valueD 1 s. In some countries. troposphericfall-out increases the deposition of the longer-lived isotopes strontium-90 by a small amount. Local meteorological and climatic factors influence the e.xtent and modeof the deposition in a particular locality.

joint study group and other information available to theCommittee it seems likely that the genetically significant
dose is lower than 1 mrem per year, even in the countries
for which the highest figures can be e.xpected.

l ndustrial and research uses of X-rays andradioactive materials
Ocrnpational exposure
34. Industrial, medical, atomic energy and research
workers are subject to radiation exposure resulting fromtheir occupation; they may also inhale or ingest radioactive material. Exposure of atomic energy workers is
in all countries estimated to contribute less than 1 mrem
per year to the genetically significant dose received by
the population. The e.xposure of medical, industrial andresearch workers is less accurately known but probably
adds at the present time less than 1 mrem to the annual
genetically significant dose even in technologically advanced countries.
35. The Committee notes that systematic measurement
and recording oi the exposures of medical, industrial
and research workers is desirable since some individual
doses are likely to be relatively high.
Other sources of radiation
36. Watches and clocks with radioactively luminous
dials give an annual genetically significant dose of about
1 mrem. X-rays from television receivers contribute lessthan 1 mrem. X-rays from shoe-fitting fluoroscopes contribute still less, as they expose a relatively small numberof individuals. but might be an important hazard to thee.xposed individuals.
Summary
37. The doses from the principal man-made sources
other than environmental contamination are summarizedin table III and are appropriate for countries with anextensive use of these sources.
TABLE III.

&...."NUAL DOSES FROM l\lAN-lllADE
SOURCES OF RADIATION.Measured contamination of air and ground bystrontium-90 and caesimn-137
43. Results of measurements of strontium-90 andcaesium-137 concentrations in different materials are
given in annex D. These show an average air concentration at ground level of strontium-90 of the order of 10-19
to 10-11 c/l in 1956-1957D1 0-11• Values for strontium-90
deposited on the ground at the middle of 1957 wereabout 8mcjkm2 in Japan, 8mcjkm 2 in the United Kingdom, 4-2lmcjkm 2 in the United States and 3-12 mcjkm 2
in the Soviet Union, in the northern hemisphere, andabout 4mc/km 2 in Argentina, in the southern hemisphere. At the middle of 1957 a caesium-137 deposit ofabout 6mc/km 2 was measured in Japan and Sweden(tables XV, XVI and XVIII annex D).

(except environmental contamination)a
Ann11al Dose

Source~nelicaUy siV1ifica11t

dose (mrem)

Medical (exposure ofpatients)(a) Diagnostic ....•.
(b) Therapy ....... .
(c) Internal. ...... .
Occupational

20-1501- 30
Less than 1Less than 2

Pu capita mean marrmo
dose (mrem)

Ranges beyond 100
No estimate madeLess than 10

1-3•For countries having an extensive use of the radiation
sources listed and reporting data to the Committee.

VI. ENVIRONMENTAL CONTA)!!::\ATION
38. Radioactive contamination of man's environment
occurs as a result of nuclear explosions and may also
arise from radioactive waste disposal and accidents involving dispersion of radioactivity. At the present time
the radiation doses from these last two sources are negligible, but in the future they might become appreciable.

Uptake of radioisotopes
44. Radioisotopes enter the human body by inhaJation of airborne material and more particularly by m·gestion following (a) uptake by and deposition O?
vegetation, (b) transfer through animals. (c) contamination of water supplies. In this respect strontium-90,
caesium-137 and iodine-131 are of special importance.
The particulate nature of fall-out and t.1-1e occurrenceof single particles with an activity higher thai: tfie average might result in the intake. by a single indn.,dual, of
an amount of radioactive material exceeding that ea!-

Radioactive fall-out
39. Most of the radioactive isotopes which cause theenvironmental contamination following nuclear weapon
11culated on the assumption of i:illf~rm distribution of
the fall-out deposit. The relative importanc~ of ~evarious modes of intake must, however, be considered massessing the significance of this.

reached throughout the chain and also that some of thefirst steps may be more dependent on fall-out rate thanon the accumulated deposit of strontium-90. Dietary
habits in different countries also vary considerably. Thus
milk is by far the most important contributor of calcium
to the human diet in some parts oi the world, whereas,in other parts, leaf vegetables and cere<:1s .are .the mostimportant contributors. It follows that it is di~cult to
calculate with accuracy the transfer of strontmm-90
from soil through the food-chain to human bone b~t information on concentrations in foods and human tissues
is available from direct measurements.

Doses from external sources
45. For the computation of dose from fc;ll·ol!t deposit
many factors besides the deposition of rad1oact!ve materials should be considered, such as the weathe:mg; effecton the deposit, leaching through soil and shieldi_ng bybuildings. Taking into account the fall-out. i:iatenal ~e­posited up to 1958 and excluding the _addi~o.nal radioactive material to fall from the reservoir ex1stmg at thattime gonad doses of the order of 1 to 20 mrem havebeen' computed for a 30-year period. The wid7 range ~fthese estimates is largely accounted for by regi?nal variations. The computations have be~n made u~m~ a reduction factor of 10 for attenuation and shielding ofbuildings, and for weathering e~ects. Values sugge;ted
for this factor in reports submitted to the C<;>mmittee
range, however, from 3 to 21. It should be poi_nted outthat the gonad dose from external gamma radiation fr~m
fall-out deposit is in most cases ~n;iall compared 'Yith
the gonad dose from fall-out radioisotopes taken mto
the body»2 0-25 •Strontium-90 in foodstuffs
50. Concentrations of strontium-90 in various foodstuffs differ for different countries. Expressed in micromicrocuries strontium-90 per gram calcium,* the rangesof average concentrations in milk fr.om ~fferent locations were in 1955 about 1.9 to 7.2, m 19:>6 1.2 to 8.8,
and in 1957 2.7 to 16. In 1956, white rice in Japan
contained 36 to 62 S.U. while frozen vegetables in the
United States in 1956-1957 contained about 9 S.U.,
ranging from 1 to 29 S.U.DtB-4 9
Strontiimi-90 in man
51. Mean levels of strontium-90 measured in thebones of children under the age of 5 years (excluding
stillborn) were, expressed in strontium units, 1.5 (Canada. May 1956 to May 1957) 1.15 (United Kingdom,1957). 0.67 (United States, July 1956 to June 1957),
and 2.3 (USSR, second half of 1957). The range ofvalues is typified by the interquartile values for t~e
United Kingdom measurements, 0.7 to 1.8 S.U., ~bilethe data for the United States show an approximate
gaussian distribution with a standard deviation of about
40 per cent. The age group .of 0. to 5. years repres~nts a
population that spent all its ltfe m. a .cont;mmat!!denvironment where the level of contammahon ot the diet
was increasing. The quoted strontium-90 concentrations
contribute an average dose of about 2 to 6 mrem per
year to the bone cells ( osteocytes) or a mean bone marrow dose of 0.7 to 2 mrem per year. A marrow cellwhich is almost enclosed by bone would receive a dose
which may be equal to that in compact bone. The maximum marrow dose received by these cells could differ bya factor of about 5 from the quoted mean marrow levels.
52. The strontium-90 content in bone of the full-term
foetus is found to be less than that in bones of childrenof under 5 years of age. This is typified by results fromthe United Kingdom where the mean level for stillborns
was about 0.55 S.U. in 1957 (42 samples). The strontium-90 concentration in the latter part of the foetal
life is directly correlated with the strontium-90 concentration in the mother's blood and this concentration
will increase as the contamination of food increases. 0 ~s-a 7

Doses from internal sources of stratospheric origi11
46 Radioactive materials entering the human bodydeliv~r a dose closely related to the time during which
they are retained by the bod_y. Th~s means that many_of
the radioisotopes produced m fission do not pres~t ~n­ternal radiation hazards since they do not enter significantly into metabolic processes. Therefore, attention. has
been centred on radioisotopes which are potentiallyhazardous by reason of some or all .of the follow!ng
factors : ( 1) high fission yield, ( 2) fairly long physi~alhalf-life, ( 3) efficient tr:insfer thr~ugh the food-chamto the human diet, ( 4) high absorptt0n ?Y the J;>ody ~nd( 5) long biological retention time. Special con.s1derat~on
has been given to elements that concentrate m specifictissues even though they do not h.ave. all the ~aracter­istics discussed. Using these cntena, the. importantradioisotopes should be expected to be strontmm-90 andcaesium-137. Other long-lived radioisotopes are considered relatively unimportant ~s internal .hazards as
their incorporation in the.bo~y 1s poo~. Iod!ne-131, although of short half-life, is given consid~rat1on becauseof its selective concentration in the thyr01d gland.
47. In addition to fission products and neutron-induced activities some of the residual fissionable material
will also be distributed by m~teorological con.di~ions andcan be hazardous since it consists of alpha-em1ttmg boneseekers. However, absorption by the body is so very lowthat there is at present no evidence of any uptake ofthese materials in human tissues.
Strontium-90 in food-chains
48. Since strontium and calcium are chemically similar strontium-90 follows calcium through the foodch~ns from the environment to man and is eventually
incorporated with ~t in ?one .. It has b<:en found that, inthe different steps m this chain, there 1s some degree of
discrimination against strontium. This depends upon
differences in the utilization of the two elements invarious biological processes. DsHs
49. Computations on the transfer of strontium-90
from fall-out to human bone are complicated by thepossibility that equilibrium conditions have not yet been

Caesimn-13i in man
53. The contamination of food sources by caesium137 has been found to be rather more dependent atpresent on fall-out rate than upon the accumulated deposit. Caesium-137 concentrations are often e..xpressedby the caesium-137 /potassium ratio. Some evidence
exists, however, that the metabolism and routes of entry
into the human body of these two elements are to somedegree different and th;;i.t a biological meaning similar to* 1 micromicrocurie strontium-90 per gram calcium is called
1 strontium unit, or 1 S.U.

12

that of the strontium-90/ calcium ratios should not be
implied. Because of the short biological half-life of
caesium-137 (about 140 days), the level of this isotope
in the human body must approach equilibrium with theenvironment relatively quickly.Dss-io
54. i\Ieasurements of caesium-137 in humans in thenorth temperate zone showed a range of 25 to 70,uµ.c pergram of potassium during 1957, corresponding to agonad dose of about 1 mrem per year (ranging fromabout 0.5 to 2 mrem per year). On the assumption thatthe caesium concentration is the same in the marrow as
in other soft tissue, the average marrow dose is computed as about 1 mrem per year.D• 5 - 75

dose from strontium-90. Barium-140. in the amounts
that C?rrespond to the mean residence time of the tropos~hen_c fall-out. (two to four \Veek) gives a dose contnbut10n that is less than 10 per cent of that fromstron ti um-89. Dso-sa
61. Measurement of iodine-131 is of interest becauseof the selective conc~ntration ?f iodine by the thyroid
gland of m_an and ~mmals. It is not possible to state a
representative thyroid dose. Measurements in the UnitedStates for the period of 1955 to 1956 show that excluding areas immediately adjacent to test-sites th~ annual
thyroid dose in man averaged about 5 mre~. Doses togonads and other soft tissue from iodine-131 are negligible. DSHO
62. Dose contributions from short-lived activities are
dependent on .fa!J-out ~ate. In c~ses wher~ the dependence on deposit is dominant, as ror strontmm-90 in theequilibrium that will eventually be reached if tests continue. contributions from short-lived activities will be
negligible.
Future doses from stratospheric fall-out
63. Prediction of future levels of stratospheric fallout requires information on the processes connectedwith the injection of long-lived radioisotopes into thestratosphere and the chain of events that occur between
injection of the radioactive material and its appearance
as fall-out on the ground. Available information would
allow at most a short-term extrapolation.
64. The extrapolation over a short period is, however,insufficient for evaluation of the biological hazards fromstratospheric fall-out. For the purpose of a biologicalassessment it is necessary to extend the calculation overperiods much longer than those considered, and many
arbitrary assumptions have to be introduced. This makes
the estimated values a matter of speculation; and it is,furthermore, very difficult to give any indication as tothe degree of uncertainty. Detailed discussion on theprediction of future fall-out levels for certain hypothetical conditions is given in annex D, paragraphs 94110.
65. Table IV gives 30- and 70-year doses calculatedon the basis of e.xtrapolated values of stratospheric fallout rate and deposit in hypothetical cases. The figuresin the table include the e.xternal exposure from thedeposit of stratospheric fall-out. Taking into accountshielding effects of buildings and weathering effects on
the deposit, external contribution from the stratosphericfall-out is expected to contribute about 20 to 40 per centof the gonad dose.
66. It should be emphasized that the figures for doses
from stratospheric fall-out are computed from population weighted world-wide average estimates of fall-out
rate and deposit. Therefore, regional dose levels differing by a factor of about one-fifth to two can be expected,
depending mainly upon latitude.D18 In some areas of theworld the tropospheric fall-out may tend to raise theupper limit of this range, especially in the vicinity oftest sites.
67. For the calculations of future fall-out rates anddeposits two assumptions are used: (a) the rate of fallout of strontium-90 will remain in the future at theconstant value observed for the last four years. or ( b)the rate of injection of strontium-90 into the stratosphere will remain in the future at a value equal to themean value for the years 1954 to 1958 inclusive. Thissecond assumption gives a value for the fall-01;1t rate anddeposit at equilibrium about a factor of 2 higher thanthat calculated by using the first assumption.

Doses from sources of tropospheric origin
55. Fall-out from the troposphere consists mainly of
short-lived isotopes. The dose contributions therefore
depend to a great extent on fall-out rate rather thanon total deposit. Since the mean residence time in the
troposphere is relatively short there would be no further
exposure from these isotopes shortly after tests were
stopped.
56. Tropospheric fall-out occurs predominantly in thelatitudes in which tests are conducted and the zones
mostly affected are determined by the predominant
weather conditions in those latitudes. Caused mainlyby the distribution of test-sites, the world-wide distribution of tropospheric fall-out follows roughly the patternof the stratospheric fall-out. The doses from tropospheric fall-out, therefore, are likely to vary with geographic location roughly in the same manner as doses
from stratospheric fall-out.
External sources
57. The tropospheric material has an observed mean
residence time of two to four weeks and although it isdeposited intermittently during the year, a certain deposit of short-lived activities is built-up and maintained.
The reported values indicate that a level of short-lived
radioactivity maintained at about 50 to 200 mc/km 2 •Allowing a factor of 10 for shielding and weathering,
this gives annual gonad and mean bone marrow doses ofthe order of 0.25 to 1 mrem. Locally, even at distancesof several thousand kilometres from test-sites, levels of
the same order as from the natural radiation background(2 mrem/week), however, have been observed for a
few days after tests.Drs
Internal sources
58. The air concentration of fission products atground level has been reported to be around 10-15 c/lduring 1957. Assuming that this material has the same
composition as the fall-out, the annual doses resulting
from inhalation can be computed to be of the order of
0.1 mrem or less, except for a thyroid dose of about 0.6
mrem. If the material is insoluble, an annual lung doseof about 1.5 mrem may be expected. 079
59. Dose contributions from short-lived activities canbe introduced through food-chains when the food has notbeen stored for a long time. Storage of food reduces theactivity of short-lived isotopes, which makes it very
difficult, if not impossible, to give world-wide averageannual doses from tropospheric material.
60. Strontium-89/strontium-90 activity ratios in milk
have been reported as fluctuating in the range 1 to 25(Canada, Nonvay, United Kingdom, United States),
the values largely depending on whether the cows wereon pasture. The strontium-89 may thus give rise to abone dose ranging from about 1 to 20 per cent of the13TABLE IV.

ESTIMATED DOSES FROM STR...\TOSPHERIC FALL-OUTa(Computed from population weighted world-wide average values of stratospheric fall-out rate and depositb)
Per capita mean marrow dose:

Gt1'tlically significant dost:.Maximum for any 30-year Ptriod (rem)DUS,\.faximum for any 70.ytar period (rem)DI!•
Eslimatt for countries

Estimates for countries
deriving most of dietar:Y
calcium from rice 0

dtriving most of dietary
talcium from milkc\Veapon tests cease at end of 1958...
Weapon tests continue until equilibrium is reached in about a hundredyears .......................... .

~6

0.010

Assumptio11 ad Assumptio11 b•

0.10

0.045
.4.ssumplioua•Assumption bd

Assumption ad

Assrm:ptiot: b"

1.3

2.8

7.5

17

Estimattd perce?1tages of tr.e maximum doses for coniinued wtaPon tests
Assumption bd
Assumption a•

Weapon tests cease
1958............................
22
10
1968............................
45
33
1978............................
63•55
1988............................
72
62
Weapon tests continue..............
100
100
a The methods used for calculation of these doses are given inparagraphs 91 to 126 of annex D.
h Regional values may differ by a factor of about 1/5 to 2
from the estimated population weighted world-wide averagevalues because of the latitudinal variation of fall-out rate anddeposit. In some areas of the world the tropospheric fall-out may
tend to raise the upper limit of this range, especially in thevicinity of test sites.
•The extent to which these estimates apply to populations ofdifferent dietary habits and to those living in areas of differing

13

24
34

42

Assumption b4

6
16
26
35
100

100
soil conditions is discussed in parap-aph 69.
d Assumption a is that the injection rate is such as to maintaina constant fall-out rate of strontium-90 and caesium-137, whereas
assumption b is that weapon tests equivalent in release andstratospheric injection of fission products to the whole sequenceof weapon tests from the beginning of 1954 to the end of 1958
will be repeated at constant rate. This second assumption v.'111
give an equilibrium value for the fall-out rate and deposit
approximately a factor of 2 higher than that calculated by using
the first assumption.

68. The caesium-137 taken into the human body has
been considered to be the main radiation source to the
gonads and it has been assumed that the human burdenof caesium-137 is a quantity dependent on fall-out rate
only. The body burden of caesium-137 resulting froma certain value of fa11-out rate has been found to vary bya factor of 2 owing to differences in dietary habits.
69. For the bone-marrow dose calculations, relationships between the bone content of strontium-90 and theaccumulated deposit have been used. These relationships,
which are discussed in detail in annex D to this report,
depend on the soil characteristics and the dietary habitsin the areas considered. The diet and soil characteristics
used in the computations correspond to available datafrom the United States, the United Kingdom and fromJapan for the two types of main calcium sources mentioned in the table, namely milk and rice. In actual practice populations do not subsist entirely on either milk or
rice, and these calculations should, therefore, be accepted
as approximations. Large local variations are possible :for example, variations by a factor of about 3 are indicated for the Japanese data, because of variations in soil
characteristics. Application of these :figures to othercountries of apparently similar diets also implies uncertainties.D:nG-1 ~ 1Radioactive waste
70. Another aspect of environmental contamination isrelated to the disposal of radioactive wastes from atomic
energy plants. This includes problems such as the ultimate disposal of fission products from spent fuel elements. the release of low-level wastes from the normal
operation of reactors and chemical processing plants,
and the possibility of accidents. The Committee has not
giYen any detailed consideration to the technical aspectsof these problems, but from information available it isclear that there is no genernl population hazard from thiscause at the present time. The Committee realizes thatthese problems may become of importance in the future
and considers that the release oi radioactive wastes
should be made a matter of international co-ordination
and agreement.
V1I. S'C':M~IARY A!'D CO!\CLl:SIONs
The 'oucco; of rndiation to which mankind "

LI.

o~

Assumption a•

exposed include natural sources, medical, industrial andresearch uses of radiation, environmental contamination
due to nuclear explosions and release of radioactive wastefrom atomic energy plants and miscellaneous sources
such as luminous dials of watches, television sets andshoe-fitting fluoroscopes. Medical, industrial and research uses of radiation expose only a fraction of the
population, whilst natural sources and environmental
contamination expose the whole population to a moreor less uniform level. Average doses to the populationfrom all these sources are, however, of significance withregard to the genetic effect and possibly with regard tosome somatic effects.
72. The exposure from these sources is summarizedin table V, which gives the genetically significant
dose and the per capita mean marrow dose. The genetically significant dose has been calculated for a 30-year
period and the marrow dose for a 70-year period. Thesefigures are relevant to the genetic burden and the possible induction of leukemia respectively. The contribution from occupational exposure is at present small compared to that from the other sources of radiation. Although immense quantities of radioactive materials will
be produced in the future use of nuclear reactors, theexposure from this source is at present negligible andcould in the future be maintained at very low levels byappropriate procedures.
73. Comments on each of the sections of table V aregiven in the follmving paragraphs, together '\vith somequalifications regarding the applicability of the Yarious.figures. Under the appropriate headings, indications for
future fields of investigation are also outlined.
Natural sources
74. Exposure of the human population from natural
sources is fairly uniform oYer the earth and a representative figure- is quoted in the table. However, areas
in several countries show dose levels considerably inexcess of those given in the table. '.lfore data are needed
concerning exceptionally large local variations of exposure from natural sources. These data can be of value
in radiobiological research only if good demographic
data foe the population in the am' exi't.

14

TABLE

v. EsTnIATED DOSE FRmr DIFFERENT RADIOACTIVE SOURCES( Compttted from world-wide averages)

SourceGe11tti<ally rignificam dose:
lla:tim11rnfOT a11y JO-year teriod (rem)Dns

Natural sources ................... .

3

Man-made sources (except environmental contamination and occupational exposure)" .........•.......

0.5-5

Occupational exposureb ............ .

Less than 0.06

Ranges beyond 7
0.1--0.2

Environmental contamination
hypothetical cases)•· d&timaus for countries
deri11int most of dietarycalcium from milk•

Estf"}ates for cour.:ri.:sdert~1~g 7n':_Jt of ditlG1j•

0.16

0.96

0.010

Weapon tests cease at end of 1958 ...

Weapon tests continue until equilibrium is reached in about a hundredyearss ..............•...........

. Per capita nuan manO"~ dosl:
J1a:t:mumfor any 70-ycar period (rem)Dl!l

Assumption at

Assumption bi.Assumption at

Assumption b'

0.060

0.12

1.3

2.8

c.clc:u.m Jrom ri&e•

7.5

17

E.stirnaud Perccntozes of the maximum doses for continued 111capon tests

Weapon tests cease
1958..... .. .. .. .. . . .. . . . .. ... .. .
1968............................
1978............................
1988............................
Weapon tests continue..............

A.m•rnPtion at

Assumplion bi

Assumption at

Assumpti<m bi

17
42
64
79
100

9
33
56

13
24
34
42
100

6
16
26

67
100

35
100

•For countries having an extensive use of the radiation sources
listed and reporting data to the Committee.
b Doses for certain technologically highly developed countries
only.
• Regional values may differ by a factor of about 1/5 to 2
from the estimated population weighted world-wide averagevalues because of the latitudinal variation of fall-out rate anddeposit. In some areas of the world, the tropospheric fall-out
may tend to raise the upper limit of this range, especially in thevicmity of test sites.
d Computed from population weighted world-wide average ofstratospheric fall-out rate and deposit,•The extent to which these estimates apply to populations ofdifferent dietary habits and to those living in areas of differingsoil conditions is discussed in paragraph 69.
1 Assumption a is that the injection rate is such as to maintaina constant fall-out rate of strontium-90 and caesium-137, whereas
assumption b is that weapon tests equivalent in release and?tratospheric injection of fission products ro the whole sequenceof. weapon tests from the beginnmg of 1954 to the end of 1958\\'.ill be repea_t~d .at constant rate. This second assumption will
give ai:i eqmhbnum value ~or the fall-out rate and de~sit
approximately a factor of 2 higher than that calculated by usmg
the first assumption.
s The values for the 30-year doses have been corrected fortropospheric fall-out in accordance with paragraph 57, using avalue of 0.5 mrem/year for the period of testing.

Man-made sources (except environmental
contamination)
75. The doses shown under the heading "man-madesources" in the table result mainly from medical diagnostic X-ray procedures. The figures, which containlarge uncertainties. refer to countries in which those
procedures are now widely applied, and in these countries increasing use may be largely compensated forby improvements in technique. Although these figures
are not at present representative for many countries
with less extensive medical facilities, the use of X-raysin these countries can be e.xpected to increase greatly
in the next few decades. The diagnostic use of X-rays is
an indispensable medical aid, and therefore a continuing
exposure to mankind from this source will necessarily
be incurred.
76. In addition to the diagnostic X-ray procedures,radiotherapy and the medical use of radioisotopes contribute to the population exposure in certain countries
with e.xtensive medical facilities. The per capita dosefrom radiotherapy may amount to 20 per cent of thatfrom diagnostic X-ray procedures. However, the significance of the radiotherapeutic contribution depends on
the life expectancy of the patients. The genetically significant dose from the medical use of radioisotopes isless than 1 per cent of that from diagnostic X-ray
exposure.
77. As medical practice varies considerably, not only
from country to country but also from hospital to hos-

pita! within the same country, it is very difficult to state
the average practice within a general population. Recommendations with regard to suitable sampling proceduresfor estimating the genetically significant dose have been
given by the ICRP/ICRU Study Group (cf. annex C).
78. It seems likely that the present exposure per examination during diagnostic procedures can be reduced
considerably, without detriment to their value, by adopting methods of the type recommended by the International Commission on Radiological Protection. Futuretechnical improvements in X-ray equipment and auxiliary devices may also result in reduced exposure per
examination, if their use does not invite more extensive
examinations.
79. A reduction in dose might be achieved by a further
consideration by the medical profession of the circumstances in which X-ray diagnosis is appropriate. This
could be facilitated by statistical information on theimportance of each e.....amination class for the reductionof any specified morbidity. Administrative co-ordination
between authorities who require that certain examinations be made in the routine health surveillance of whole
populations or special groups, such as school-children,
students, employees, could well be improved.
80. ·whilst much of the foregoing discussion relates
to population exposures, it must be noted that high individual doses may be incurred during particular X-ray
diagnostic procedures especially where poor techniques
are used.
15

81. Although the occupational exposure is at presentof little significance for the whole population, the doseto individuals may involve special exposure problems andshould be checked by the complementary techniques ofsite and personal monitoring.
82. A number of sources of radiation, such as luminous watches, television sets, shoe-fitting machines, contribute to the population dose by an amount of the orderof 1 per cent of the total contribution from man-madesources.

report is able to give valuable information for the near
future, but the doses given for the 30-year and 70-year
periods in tables IV and V in this chapter involve extrapolations over such an extended period that they must
be considered as speculative. The figures in the table are
population weighted world-wide averages. Countries between 30° and 50° North e.."perience levels nearly afactor of 2 higher than the population weighted worldwide average, whilst countries in the southern hemisphereand those in the tropical belt experience smaller doses.

Environmental contamination
83. The Committee has received extensive information on the strontium-90 and caesium-137 concentrations
in soil, plants. animal and human foods and in humanbeings. However, there are many countries from which
no data have been submitted. The information so far
received, whilst not sufficiently extensive to give a comprehensive world-wide picture, does enable useful conclusions to be drawn.
84. Levels of strontium-90 and caesium-137 vary withgeographical location. In addition, other factors such as
agricultural conditions and practices, especially of soil
and water management, living and dietary habits andfood technology will influence the level of these isotopes
in man. Because of these factors. caution is necessary
in applying data obtained in one area to an estimation of
the contamination of the diet in another area.
85. There are at present no practical methods of preventing the entry of these radioisotopes into the humanbody once they have been released into the environment.
86. The model used in calculating the doses from environmental contamination as set out in annex D of this

87. Adequate knowledge on the altitude and latitude
distribution of fission products in the stratosphere and of
injection rates is required to decrease our uncertainty
in the prediction of future doses from fall-out. A better
understanding of fall-out phenomena would be achieved
if nations co-ordinated sampling and measurement programmes and exchanged data on methods and results.
Biological sampling should be co-ordinated with fall-out
sampling procedures.

88. In order to interpret information from biologicalsampling, it is important to consider data concerningsoil conditions and pertinent agricultural procedures,such as fertilizer practices, depth of ploughing. and also
food technology. The dietary habits in a given area
should determine the nature and scope of the sampling
programme.
89. The Committee has given initial consideration, in
co-operation with UNESCO, FAO, and WHO, to thepotential environmental contamination in relation to thedisposal of radioactive wastes from atomic energy plants
and considers that this subject should be made a matterof international co-ordination and agreement.

16

Chapter IV
FUNDA~IENTAL

RADIOBIOLOGY

1. The radiation effects in man, the major object of
this report, are a particular case of what is known tooccur in other organisms. It is generally accepted thatradiation damage has its origin in individual cells, whichhave either been killed or impaired in function. A great
deal of knowledge of fundamental importance has beenobtained by the experimental study of unicellular andmulticellular organisms. Despite this, we do not yet
understand how radiations act on living cells: the problem is very comple..x and its solution requires fundamental knowledge which does not exist as yet.

inhibition of respiration and of protein synthesis maylead to the inhibition of specific functions such as those
involved in. immunological or secretary processes.
5. On the other hand, radiation may affect cell constituents which are so specific that only one or two arelikely to e..xist in each cell. This is the case for individual
genes which e..xpress themselves in specific hereditary
attributes. It is believed that they are composed of very
specific desoxyribonuncleic acids (DNA)-perhaps
associated with components like proteins. In a gamete(sperm or egg) there is only one gene of each kind; after
fertilization the growing embryo and adult organism
have two series of such units in every cell. Genes are concerned, through very complex series of biochemical
processes, with the formation of cellular enzymes responsible for carrying out metabolic processes and ofother constituents of the organized cellular structures.
Thus, if a gene is altered (as occurs in most mutations)a whole chain of reactions may be interrupted at one
link, and important cellular constituents or building
blocks may fail to be formed. Of course, besides thegenes there may be other vulnerable constituents but at
the present time the genetic material is one of the mostradiosensitive known when the consequences of its
damage are observed.
6. A major characteristic of radiation damage is that
it is not a single effect-many constituents of a cell aredamaged more or less simultaneously and at random. It
is the interplay of the activity of the remaining nonaffected constituents with that of the affected ones which
will determine the final outcome. This intricacy makes
the problem very difficult, and an identical response ineach case need not be e..'tpected. Fsz-as
7. Effects similar to the ones produced by ionizing
radiation have been found to occur in cells treated withultraviolet light or with various radiomimetic chemicals.
In attempting to understand the sequence of events,
studies with these agents which act often more specifically on well-defined biochemical systems are sometimesof much greater value than those of ionizing radiation.
8. The chemical constitution of most cellular structures is only very crudely known, but is of great importance for the understanding of the mechanism of theinitial action of radiation. Furthermore, trace amountsof many elements such as calcium are present in chromosomes and other structures. As these may be replaced byradioactive atoms, this substitution might have consequences which are at present unsuspected. That could
well be the case with strontium-90 if it replaced calcium
in chromosomes.F1 5-16

l. THE SEQUENCE OF EVENTS
2. The succession of events which takes place between
the time of irradiation and the appearance of the recognizable effects is very intricate. The energy of theradiation dissipated in form of ionisation and e..xcitationis "immediately" used in chemical reactions. The firststep or succession of steps probably takes place in an
extremely short time (which may be as short as 10-aseconds). As many as several hundred of these primarybiophysical events may occur inside one mammalian cell
submitted to an irradiation of 1 rad, but these primary
events may not all result in biological effects.

II. DIRECT AND INDIRECT EFFECTS
3. There are two possible ways of considering theeffects of radiation which are in no way mutually exclusive and may very well complement each other. The
primary event may act directly on some essential molecular structures of cells (direct effects) or it may decompose water or common organic molecules into highly
reactive radicals (indirect effects). \Vhen water-themost abundant constituent of cells-is decomposed, theindirect effect is due to free hydroxyl radicals, hydrogenatoms or perhydroxyl radicals which are in turn capableof acting on the cellular constituents. The relative contribution of each of these two possible mechanisms isdependent upon the conditions of irradiation, but it isas yet unknown in detail. Both mechanisms are believed
to mduce rather similar changes in biological structures
and they lead to the formation of long-lived organic
radicals which have been detected after the irradiationof many organic compounds and of some living systems. Fl-:, F11-u, Fs1

III. SPECIFIC CELLULAR CONSTITUENTS
4. Some of these primary events will have no biological. effect. The alteration they produce may berever~1ble or they may affect one of many identical cell
constituents and so be of no consequence. Some cellularfunctions like respiration or protein synthesis are notusually ~~aged immedia~ely, because, it is believed,these a.ctiVItles. take place m cellular structures ( mitochondna or m1crosome) which are numerous and may
also be.les~ v.ulnerable. However, the factors responsible
for mamtammg these stntctures may have been impaired
and delayed effects may then be observed. The secondary

IV. MORPHOLOGICAL DAMAGE
9. After irradiation of cells. both nucleus and cytoplasm may be found to be damaged when observed underthe microscope. If chromosomes are broken. the bro~enends mav reconstitute norm:illy (restitutions) or giveabnormai .rearrangements. Some of the latter are presumably invisible in the microscope, although the order17

of genes on the ch<;>mosom~s, ~hich appears essential for
their correct genetic functtomng, may have been altered.
Another visible sign of damage to the cell is an increasein size of both nucleus and cytoplasm. This increase isdue in part to changes in permeability and osmotic relationship, and, in part, to continued synthetic activity.
Furthermore, abnormal vacuoles are sometimes visible,
and the particles (mitochondria) on which respiratory
enzymes are organized have sometimes been found to bemorphologically altered.
10. Nucleus and cytoplasm are very closely interdependent parts of the cell in normal circumstances and analteration in either part will affect the other, as.has b~en
shown in experiments with unicellular organisms hke
amoeba or egg cells. It is generally believed that mostgenetic damage needs to be initiated inside or in theimmediate neighbourhood of the gene itself. H~we:rer.
in some instances, chemicals can become mutagemc atter
irradiation. Fa6-8a

divisions has taken place. Chromosome damage is one
known cause of delayed death of cells, but on the other
hand, cytoplasmic damage might also be lethal. It istherefore impossible in most cases to establish the exact
origin of cell death.Fm-1 0•
Other damage
14. Besides mutations, delay or blocking of mitosis,
or death, other effects may be obsen•ed. Exchange ofions or of organic substances between the cell and its
environment. cellular movement, or the storage of chemical energy which will be used in various synthetic
reactions may all be interfered with, but such effects
have usually been demonstrated only after relatively highdosages of radiation. It should be stated that the available
methods of analysis are still very crude and it is quitepossible that many specific effects have so far remained
undetected.FDr-101, F10;-112

VI. BIOLOGICAL EFFECTS IN TISSUES

V. BIOLOGICAL DAMAGE TO INDIVIDUAL CELLSAND IN HIGHER ORGANISMS

15. In higher organisms, all the forms of damage

Retardation of cell division
11. Any detectable biological damage must originate
in some biochemical change, but the exact sequence of
events from the biochemical to the biological is still unknown. The biological damage seems to follow a constantpattern in micro-organisms, protozoa or cultures ofmammalian cells. If the cells are preparing to divide,
irradiation retards the process of division (mitosis).
While this retardation is often associated with an inhibition of the synthesis of the genetically important DNA,
instances are known where this does not necessarily
occur. In these cases, other cellular structures or biochemical mechanisms which are important for cell
division, may have been interfered with, but further
understanding would only be possible with a fuller
knovdedge of normal mechanisms of mitosis. Following
the retardation. cell division is resumed in a seemingly
normal fashion but permanent damage has usually supervened and the cell dies after one or more division
cycles. F91-92

described for individual cells occur and these may affectboth the tissues, if local damage is considered, and theorganism as a whole. Our understanding of the underlying mechanisms is complicated by the fact that all
tissues live in very close contact with each other. Furthermore, tissues are interconnected by blood and thenervous system; radiation damage to one tissue may well
be intensified or compensated for by the activity ofothers. It is one of the objects of radiobiology to clarify
these processes.
Cellular differentiation
16. A cellular process which is very sensitive to radiation is that of cellular differentiation in which embryoniccells, apparently all identical during the first few division
cycles, change into the fully specialized tissue cells of
the adult. A relatively small number of the cells ofdifferentiating embryos will give rise to specific organsof the adult. If some of these stem cells are killed, delayed in development or made functionally inactive, important malformations of these organs can occur.
17. Some cells remain undifferentiated during development and are present in tissues throughout adult life.
Their differentiation leads to the continuous formationof blood cells or to the renewal of skin and intestinal
epithelium and to the maturation of gametes. Duringcertain stages of this differentiation these cells become
more sensitive to radiation and may be killed or theirdifferentiation may be impaired; this will produce conditions such as anaemia, leucopenia, skin and intestinal
atrophy and also sterility. However, some undifferentiated cells may remain undamaged and initiate therecovery of the affected tissues. On the other hand,certain damaged cells may sun'ive and develop into
malignancies (leukemia, skin tumors, or osteosarcoma
when bone is irradiated).FJ. 13-122

Mutation
12. Another frequently observed cellular alteration ismutation, which leads to the interruption of one or more
important biochemical steps (such as the synthesis of
an indispensable enzyme or of cellular constituent). In
micro-organisms this will lead to lethal damage if thecompound previously synthesized by the enzyme is not
supplied to the progeny cells or if it belongs to an essential cellular component. When the cells of the germ lineof multicellular organisms are irradiated, similar mutations occur ·which can be observed in the offspring.
Somatic cells are also known to undergo mutations which
may express themselves by somatic changes or damage.
It takes a short time for a mutation to become established.
Experimental evidence presented shows that, during thistime, the process can be modified to some extent. It isbelieved, however, that once the process is completed,it cannot be reversed except by a new mutation (reverse
mutation) .F9s-sG, Fua-120

Latent period
18. Somatic effects appear after a certain latent period.
For the effects discussed in the previous paragraph thelatent period depends on the time the cells take todifferentiate and on the length of their normal life. In
the case of leucopenia, anaemia or intestinal damage, thelatency is usually from one to several days, whereas in
the case of cataract, or of leukemia or other malignancies,
it may last for many years.

Lethal effects
13. Cell division is often irreversibly blocked and thismay be associated with major visible chromosome damage resulting in unequal distribution of nuclear material
between daughter cells. Sometimes the block in cell
division only occurs after a certain number of these18

LComparative radiosensitivity in living orga11i.sms
19. ·when the survival of different animal species
after irradiation with the same dose is compared, it has
been found that their radiosensitivity varies widely. It
may take several hundred thousand rem to kill 50 per
cent of individuals in a population of bacteria or protozoa but the dose necessary to kill 50 per cent of manycold-blooded vertebrates is several thousand rem and in
the case of mammals it is only of a few hundred rem.
20. The variation of radiosensitivity in mammals is
less marked when compared at the cellular level (as intissue cultures). The histopathological changes in corresponding organs of species having strikingly different
radiosensitivity, such as in guinea pigs and rabbits, havebeen found to be nearly the same. This indicates that theintervention of other mechanisms, e.g. those of neurohumoral regulations. influences the radioresistance of
the whole organism.F1 3s-Hs
Adaptation to radiation
21. The possibility of an acquired radioresistance ofcells or of organisms has been suggested. The data now
available show no acquired radioresistance of normal
cells. even after a great number of heavily irradiatedgenerations. The special case of the apparent radioresistance in vivo of tumours recurring after radio therapy isprobably related to a change in the tissues around thetumour and to polyploidy of the tumour cells, but does
not seem to be related to the selection of a more resistantgenetic material in these cells. A second special case isfound in the hereditary changes to radiation resistance inbacteria; these changes are now believed to be spontaneously occurring mutations which can be selected bymeans of irradiation rather than induced by irradiation.
At present, there is no evidence of biological adaptation
to ionizing radiations.F14s-151
Secondary damage
22. Irradiated cells are known to give rise to unusual
products which may arise either from chemical reactions
during irradiation (as in the case of small amounts ofperoxides) or from cellular damage (in which caseenzymes may be released in abnormal concentration in
the blood stream) or as the result of some abnormality
in cellular metabolism. In complex organisms these products may be the cause of secondary damage far awayfrom the site of irradiation as has been observed in a
few instances; nucleic acid metabolism can be impaired
in a tumour which was shielded during irradiation; andwhen non-irradiated thymus cells are grafted on a totally
irradiated host, these thymus cells may become tumorous. Fl53-153

VII. BIOLOGICAL EFFECT ON POPULATIONS
23. The effects of radiation will be reflected in theindividual and at the end in the population. The increaseof radiation will cause an increase in the load of mutations. Although we have some knowledge of particular
probl~s, we still do not have a satisfactory theory of the?yn:im1c of mutations in the population and therefore itis difficult to predict the consequences of this increase in
the mutation rate. Nevertheless certain effects on therel~tionship between various sp:cies in biological populations cannot be excluded a priori.
. 24. PopuI<:tions. of ~iving organisms commonly live
m close relationship with each other and in many cases
may even become interdependent. Many instances are
known of specific micro-organisms living in mutually19

advantageous symbiosis with plants or animals. An
equilibrium between mutation, adaptation and selectionof these species has become established during the longprocess of evolution. Increased irradiation would increase the mutation rate of these species and, in the caseof micro-organisms which usually divide very rapidly
and are haploid cells, consequent shift in equilibriummight conceivably cause severe repercussions throughout whole populations. Consequences to humanity could
be very serious, if a species with important economic
implications were eliminated. So far, attention has notbeen given to such possible effects on populations oforganisms.

VIII. DOSE-EFFECT RELATIONSHIP
25. For an estimation of radiation hazards, it is ofprime importance to have information on the dose-effectrelationship at low doses. The data so far available point
to the fact that at low dose the amount of gene.tic damageis related linearly to the increase in radiation, thus
supporting the assumption that natural radiation contributes to natural mutations. This linear relationshiphas been found to be true for all experiments so far
performed on viruses, micro-organisms, multicellularplants and animals.
These results further indicate that, as dosage is decreased, the number of individuals affected becomes
smaller but the consequences to each of those affected
remain the same.
A certain number of somatic effects are also related
linearly to dose. For instance, the birthweight of miceborn from embryos irradiated in utero decreases proportionately with exposure, and it is possible that theinduction of leukemia in man is linearly related to thedose of radiation received.
Threshold dose
26. In many other instances of somatic effects no response has been so far observed below a certain dose,the "threshold dose" for that effect. One must distinguish between at least two notions of threshold. The
appearance of a threshold may be e.xplainable in physicalterms in the sense that more than one primary event isneeded to produce the effect; and the sigmoid dose effectcurves obtained for certain types of chromosome aberrations and for the killing of mammalian cells in tissue
cultures probably illustrate this phenomenon. This stateof affairs, which holds for some unicellular organisms,
is generally further complicated in higher organisms by
the fact that different physiological conditions come intoplay. In mammals, for example, it may happen that
before the primary effects become apparent as functionalor morphological changes, some recovery processes orphysiological events prevent or retard the appearance ofthe final biological effect. The threshold for skin erythema, for instance, is higher for a fractionated dose,
because recovery is taking place between the successive
irradiations.
27. The dose-effect relationship is not necessarily
identical for similar effects when different species are
considered. For instance, tumours can be induced inmice if they are exposed to a dose of radiation above acertain threshold. The time it takes for the tumour toappear and the longevity of the animal have to be ta}cen
into consideration and the existence of a linear relationship for similar tumours in man cannot be ruled out.
28. As a result of technical improvement and of new
experimental approaches, the value of the observedfore, unwise to transpose results from experimental
animals to human beings, unless there is general agreement between results throughout a wide range of organisms and preferably not before the relevant fundamental
mechanisms are fully understood.Fm-135

threshold has been reduced in certain instances. Thisis one of the reasons why maximum permissable doses
have steadily decreased over the last twenty-five years,
another reason being that genetic effects for which there
is no threshold are now being taken into considerationand that the number of exposed people is continuously
increasing. Fs-n

Physical and chemical factors
Type of radiation
35. Radiations of various types usually produce similar biological responses, but they may differ in effectiveness: densely ionizing particles (a rays, neutrons whichgive recoil protons) have a higher efficiency in producing most forms of cellular damage than radiation( y-, X-rays) giving lower ionic densities. Cellular damage resulting from several simultaneous ionizations
within a given structure will have a higher probability ofoocurring when the density of ionization is high. On thecontrary, if only one ionization is needed, densely ionizing radiation will be less efficient because many ionizations will be wasted. This pattern in energy distribution
in the cell may affect the final response. For example,
neutrons are more effective in producing lethal effects
and in decreasing the life-span of mammals. The influence of the pattern of energy distribution may also differ
with the conditions of irradiation. The response to thesparsely ionizing X- and y-rays is considerably reduced
in anoxic conditions. This is not so for densely ionizing
radiations. Anoxic conditions exist in the lens of the eye
and this explains why neutrons produce cataract much
more readily than X-rays, an unforeseen finding which
was not understood until the oxygen effect for various
types of radiation was studied in full detail. Our lackof understanding of many mechanisms of radiation
damage should therefore call for great caution whenhuman beings are exposed. F<-T

Stimulating effects
29. In some experiments it has been claimed that low
irradiation stimulates certain biological functions s~chas protein synthesis, increase in size or even the life
span. These effects when further studied, have generally
been found to be the consequence of damage done elsewhere in the cells or organisms. ~·m
IX. VARIABLES IN RADIOBIOLOGICAL PROCESSES
Biological factors
Cell division
30. It has been known for more than a half century
that dividing cells are more sensitive (sometimes asmuch as one thousand times more) than resting ones.
It is this radiosensitivity of dividing cells which makes
radiotherapy of value in the selective destruction ofsome malignant tumours, in which cell division is oftenmuch more frequent than in surrounding normal tissues.
This increased sensitivity of dividing cells exists usuallyfor lethal effects, chromosome aberrations, inhibition ofmitosis and mutations. The most striking exception tothis phenomenon is the high sensitivity of the nondividing lymphocytes.
Aget;
31. It has to be pointed out that very little is known
about the processes involved in ageing of cells; methodsof determining cellular age would be of considerable help
in many radiobiological problems. However, in mice it
has been found that soon after birth the radiosensitivity
to killing falls progressively and then remains at aminimum until the latter part of the normal life-span,
during which it increases strikingly. Birds, on the other
hand, have a much more constant radiosensivitity
throughout their adult life.

Time distribution of dose
36. In general, a dose which is lethal when given in ashort time may produce effects which are difficult to
detect when it is spread out over a lifetime. However, insome cases, the same over-all dose given in a short ora long time gives the same response ; this is true for
effects of the genetic material (induction of mutation)or for the formation of bacteriophage in a lysogenic
bacteria.Fi 2 -u

Physiological conditions
32. Dehydration usually increases the radioresistanceof cells. Starvation, chronic anaemia and manv otherabnormal conditions may influence the susceptibility of
mammals to radiation. The first two factors are believedto increase the radiosensitivity of mice; more information on this subject would be of great help in attempts topredict the sensitivity of humans living under various
conditions.

Oxygen37. By reducing the oxygen concentration inside cells
during irradiation with X or y rays one may diminish
by a factor of 3 to S the cell sensitivity to lethal effects,
to chromosome damage and to some of the associatedmutations as well as to some biochemical effects of radiation. The effect of oxygen is perhaps related to theformation of a perhydroxyl radical and of hydrogen
peroxide, in addition to the other radicals arising fromthe decomposition of water. Several other hypotheses to
explain the oxygen effects have been proposed and haveto be kept in mind.
38. However, the presence of oxygen favours someof the cellular processes following irradiation. such as
the rejoining and rearrangement of chromosome breaks
which are dependent on respiration. The presence ofoxygen during irradiation appears also to affect cellularfunctions necessary for recovery. The influence ofoxygen is therefore \'ery complex since it can affecteither the primary events or the processes of recovery.
39. The effect of oxygen has so far been observed tobe negligible in the case of densely ionizing radiation
like alpha rays, neutrons or slow electrons.F1 3 6 - 131

Genetic strain
33. The sensitivity of bacteria of similar species butof different strains to killing may vary by a factor ofseveral-fold. In higher organisms, this factor has beenstudied in a few cases: in mice, for example, the variation of the dose needed to produce lethal effect does notappear to vary by more than about 25-30 per cent between the most and least sensitive strains.
Species difference
34.' Many reactions to radiation differ widely fromone species to another, as can be observed by the variation of threshold values for a similar effect. It is, there-

20Temperature
40. It has been shown in isolated systems (enzymes,
bacteriophage) that a decrease of temperature during
irradiation reduces its effect. In living organisms, a lowtemperature may also affect the bio-physical processes
which take place during irradiation. The change of temperature may also influence the biological expression of
the primary lesion or the recoyery mechanism. Irradiation at low temperature may either decrease or increase
genetic effects as observed by mutations or chromosome
aberrations. On the other hand, when vertebrates areirradiated and kept thereafter at low temperatures, aradiation effect does not become expressed until thetemperature is increased to normal levels. Neverthelessthe final radiation damage is the same.

:=it~d animal is cai;iable of reducing the mortality: them;ected ce~ls substi~ute !?r the ones killed by irradiation.
The pract1ca_I apphcab1hty to human beings of bonemarrow gratts depends on an understandina of theimnmnological d~fen~e mechanisms by which ~1ammals
destroy any foreign ti~sue grafted upon them. Intensive
fundamental and applied research is needed.
45. It is possible to combine the effects of chemical
protectors and of recovery factors. \Vhen this is done for
mice, they have a still better chance of sun+:ina thanif either treatment is applied independently. Ho~;evereven when chemical protectors and recovery factors ar~applied simultaneously, considerable cellular damage
may persist and it frequently becomes expressed as atumour at a later stage.F173- 15 •X. PROTECTION
41. The possibility of altering both the direct andindirect effects of radiation experimentally gives someprospect of interfering with the initial steps of radiation
damage. A variety of chemical protectors have beenfound, but to be effective, they must be present during
radiation. Among these cysteamine and AET* havebeen used successfully both in vitro and in vivo. It has
been found possible to counteract the induction of many
chemical and biochemical effects and to reduce chromosome aberrations and some mutations, as well as toincrease considerably the survival of cells and tissues.
Although the bulk of experiments on the survival of
mammals has been done with mice and rats, successful
e..xperiments with AET have been reported on a small
number of dogs and monkeys.
42. The mode of action of these chemical protectors
is in no way certain and several hypotheses have been
put forward: they may, as in 1Jitro, act by ''neutralizing"
the free radicals or reducing the oxygen tension, butthere is not always a correlation between the e..xistence ofan oxygen effect and the possibility of chemical protection. These agents may also protect sensitive biologicalsites directly by preventing radicals from attacking themor they might stabilize the sensitive biological structures.
Prospects of using chemical protectors adequately inman still await the discovery of substances which are
sufficiently nontoxic to be used in effective concentration.F42-41, F1s9-169

XII. CONCLUSIONS
46. In this chapter an attempt h~s bee~ n;ade to pointout the fundamental problems ot radiob10logy, theirpresent status and their relevance to the practical humanhazards of today.
47. In order to estimate the hazards to human beings,
it is necessary to take into account the cumulative effectsof radiation in each individual, although the averagehazard often seems statistically very small. _l\n understanding of the basic mechanisms by which the damageis produced may be the only way of making any rational
assessment of the damage produced at very low doses.
While the physical events are more or less understoodon the basis of our knowledge of modern physics orphysical chemistry. the unknowns on the biological side
are still enormous. The need for fundamental researchis therefore very great. The only way of meeting thischallenge is by the training of scientists in the different
disciplines that biological research demands.
48. The lack of fundamental knowledge of normal
cell stmcture and function is in our opinion the major
factor limiting progress in radiobiology. Further research is urgently needed in general biology taken in its
widest possible sense.
49. The major problems on which radiobiological research is needed include:(a) The nature of the primary damage to cellular
structures and the pathways of expression of thisdamage.
( b) The dose-effect relationships at low dosages.
( c) The mechanisms of chemical protection andrecovery.
Other fields whose importance is still undetermined may
become soon of very great interest, as e.g. the mode ofaction of radionuclides at the cellular level (paragraph 8).
50. Despite the benefits brought to mankind by theproper use of ionizing radiations in medicine, the evidence points to the fact that these radiations are harmful
and that their effects are frequently cumulative. Evenvery small doses may occasionally have highly deleteri~us
biological consequences. It is also known that radiosensitivity tends to increase with the degree of _comple..xity of the organisms. In addi~on to these. establishedfacts. problems no less compelling have ansen (paragraphs 8, 23) and it is possible that they have _not yet
received sufficient attention. These problems will haveto be reckoned with before one can obtain a completely
accurate estimate of radiation hazards. In the light ofthese considerations there is an imperative need forkeeping the radiation level as low as feasible.

XL RECOVERY
43. Many approaches have been used to modify radiation damage after it is established. Not enough is known
about the mechanisms which lead to this damage. andabout natural processes of recovery, to make any rational attempt to influence them. In the case of unicellularorganisms it has been found possible to alter the sequenceof events with the aid of physical or chemical agents
applied after irradiation. Most effects of ultra-violet
radiation can be counteracted by subsequent treatment
with visible light (photo-reactivation). Formation ofbacteriophage in lysogenic bacteria by ultra-violet or
X-rays can be greatly reduced by the action of added
catalase ( catalase reactivation).
44. In the case of mammals, it has been found possible~o reJ?lace d~aged cells by grafting normal ones to theirradiated animals. It has been clearly shown in micethat the injection of bone marrow into a lethally irradi-* S-2-aminoethylisothiuronium Br. HBr. Recently it was
found that a re-arrangement occurs in organism to 2-mercap·
toethylguanidine HBr (see F 163).
21

Chapter V

SOMATIC EFFECTS OF RADL,\TION
such instances, the dose of radiation absorbed is largely
confined to certain organs. The ability of an organ toabsorb a specific isotope from the blood depends on its
stage of development and varies from time to time withchanges in its metabolic state. For instance, in the earlystages of human development, the precursors of bone
do not selectively absorb strontium. Later on, however,during bone growth, strontium is rapidly absorbed. Stilllater, when growth has ceased, the rate of uptake
decreases.

1. The effects of ionizing radiations on man and animals have been obsen•ed for many years. These observations have shown that all mammalian cells are vulnerable
to this type of injury; they have also demonstrated thattissues and people can, to a very large extent, recoverfrom radiation injury even after severe damage. The
clinical manifestations of radiation injury are the endresult of the biophysical effects and of the biochemical
reactions through which radiations produce effects on themolecular and cellular level and of a variety of local andsystemic physiological and regulatory factors which
determine the course and eventual outcome of any injury
to the human body. In analysing the action of radiationon the body. it is necessary to consider the physicalfactors of exposure as well as the relevant biologicalfactors.

Concept of sensitivity
6. Originally, investigators were struck by the rapidand dramatic morphological changes which they observedin the blood-forming organs, the skin. the intestines andthe gonads, and therefore classified these organs as"radiosensitive". The greater doses required to produce
equally obvious changes in the blood vessels, the lensand nervous system led to an intermediate classification
for these tissues or organs. Finally, muscles and connective tissues were classified as "radio-resistant".
7. In the light of our present knowledge, such asimple classification is no longer adequate, and in somerespects may be misleading. There are several major
factors that enter into the estimation of sensitivity. In
general, the estimate will depend on the nature andfunctional or metabolic state of the biological system
under investigation. ]\fore specifically, and perhaps more
importantly, however, it will also depend on the particular part of the system investigated and on the sensitivityof the methods employed for this purpose. Thus, anorgan e.""amined with the microscope will appear to be
more sensitive than when examined with the naked eye.
Similiarly, an organ e.xamined with the most refined
physiological techniques may prove to be much moresensitive tl1an when examined by classical morphologicalmethods. It is apparent that as our method of observation
changes, the observed sensitivity of the biological system
will also change.

l. PHYSICAL FACTORS
2. The principal physical factor determining the biological effect of ionizing radiation is the dose, defined inchapter II. If the dose is expressed in rem, the influenceof the type of radiation (linear energy transfer) is taken
into account. The dose of radiation absorbed in allorgans must be known. Furthermore, since there may
be important differences between the doses absorbed
in various organs or even locally within a single organ,
the distribution of dose is an important consideration.
3. In the case of external sources of radiation. suchdifferences may result from the following factors : theradiation beam may be directed at only one part of the
body (e.g. the hand). The radiation beam may be attenuated as it passes through the body (e.g. X-rays) or may
not even penetrate below the surface (e.g. alpha particles). The radiation (e.g. X-rays) may be absorbed
quite differently by tissues of different chemical composition (bone, muscle).
4. The distribution in time of the radiation exposuremust also be considered. The same dose may be received:(a) quickly, in one exposure (e.g. 10 minutes); (b)slowly and continuously over an extended period (e.g.
5 years); or (c) fractionally (e.g. 1 single dose eachyear for 10 years). Extending the over-all exposure
time as in ( b) and ( c) greatly reduces the amount ofsomatic damage with the exception of those changes
where a linear dose-effect relationship may apply.
Factors of importance in determining the duration of
exposure from a radioactive isotope and its daughter
products are their _Physical half-lives, the type andenergy of the radiations emitted, the time of retention
and the rate of excretion from the body.
5. In the case of radioactive isotopes that enter the
body, the dose distribution is determined by the capacityof the various organs to absorb the isotope from theblood. Certain isotopes such as sodium remain in thefluids of the body and thus travel through the wholebody. Other isotopes are taken rapidly from the bloodby a particular organ. as in the case of iodine concentration in the thyroid gland, or strontium in bone. In

Relation bet-..ueen dose and effect
8. For the scientific study of radiation effects it isnecessary to k'TIOW quantitatively the relation between
magnitude or frequency of biological effects and radiation dose, i.e. the dose-effect relationship. Various relations are theoretically possible; two general types will
be mentioned here. First, the effect may be direct proportion to the dose. Thus any dose. no matter how small,will have some effect, although after a small dose thesomatic effect may be minute. Secondly. there may bea threshold dose below which no effect occurs. In thecase of mice of a typical strain. for e.'\:ample, there is a
threshold dose of about 400 rem (whole-body exposure
to X-rays) below which practically no acute deaths
occur. Above this threshold. the number of deaths increases rapidly with the dose, reaching 100 per cent\Vithin two weeks after exposure to twice this dose. It
may be assumed that intermediate relations e.xist, represented by a curved line, showing extremelv lit:de effect

22

.,,

at lmv dose, thus indicating an "apparent" threshold.
9. All studies of the dose-effect relationship are complicated by the unavoidable presence of natural radiations. In man, the annual dose from natural radiations
is about 100 mrem. It is assumed that a certain amount ofgenetic damage (some natural mutations) in man iscaused by these radiations. It is conceivable that analogous changes may occur in somatic cells and that suchchanges, being cumulative with age, may have adverse
influences. However, there is at present no evidence forsuch an assumption. It is conceivable that noxious agents,
such as carcinogenic compounds, bacteria, parasites andvirsuses, in our environment may potentiate the effectsof radiations.
10. The interpretation of the dose-effect relationshipfollowing multiple e.."posures is more complex than in
the case of a single e.."posure; such an interpretation musttake into account a variety of biological factors, recovery
and sensitization. for instance. These factors, which arevariable, may act separately or in conjunction with eachother. The injury may build up in simple proportion to
the exposure or it may not increase because the tissues
are able to recover before the ne..'Ct exposure occurs.
However, repeated exposures would act to diminish thephysiologic reserve of the irradiated tissue, and eventually a state can be reached in which repair no longer
balances injury. Moreover, previ.ously irradiated organisms may show modifications in radiosensitivity. However. such modifications have not been sufficiently
studied.
11. Although a characteristic dose-effect cun•e may
be associated with each somatic effect, the curve will be
subject to certain variations which stem from constitutional differences in the populations of animals or humanbeings. Other factors which have an influence on radiation reactions are sex and age. For certain effects,
infants and children react more quickly and with greater
severity than adults. During senescence, resistance toradiation declines. Even within groups of individuals
homogeneous in age and se..\., individual variations occur
as a result of differences in genetic constitution andindividual history.

the functional responses. Many of the former can beproduced by a number of other aaents and some of thetransient functional responses to low levels of radiation
have been compared to the non-specific alterations associated with the stress-syndrome which can also be elicitedby a variety of agents.
15. Radiation injuries have no pathognomonic features which distinguish them from other injuries.
but with experience and with a history of radiation ex~
posure, it is possible to recognize patterns of chanaes
which are fairly distinctive. Just as mutations produ~edby irradiation do not differ in kind from those which
occur spontaneously, in the same way, exposure ofsomatic cells to ionizing radiations has not created new
types of diseases. \Vhat has been observed is that theincidence of certain types of diseases has been increased
by such exposures.
16. It has been observed that, after acute lethal or
sublethal irradiation. mammals become susceptible toinfection and. indeed, often die because their natural
defence mechanisms have been impaired. These mechanisms are comple..x. but they are chiefly dependent on
three main functions : (a) natural barriers to invadingorganisms; ( b) cellular defence-mechanisms (phagocytosis), and ( c) humoral-defence mechanisms (antibodies). All three of these functions may be severely
affected by a large single exposure. but the e..'Ctent of
impairment from small doses is not knmvn.
17. Disturbances of immunological mechanisms canbe produced by external and internal radiation. In thelatter case, disturbances may occur when the cells of thereticulo-endothelial system have incorporated radioactive material. This may inhibit the immunological
functions of the cells.
18. Exposure to ionizing radiation can lead to theformation of pathologic metabolic products in the tissues,
as is known to occur in some other types of injury, e.g ..
thermal bums. It is possible that these products may
play a part in the or_igin of a r:umber of secondary radiation effects. There is some evidence for the presence of
certain toxic products in blood coming from irradiatedorgans of experimental animals and in the lymph withdrawn from the thoracic duct of these animals. The
chemical nature of these substances. normally boundand inactive within the cell. is not known as yet. but
some of them are histamine-like substances.
19. Certain types of radiation injury ~eq11ire months
or years to make their appearance. This is true whether
or not acute manifestations of injury ·were observed at
the time of e..;;:posure. Delayed injuries of th_i~ type c:refrequently the result of metabolic and nutnt10nal disturbances in irradiated organs. When the blood supplyof the organ has also been impaire_d. ~he ~istu_rbances ~reincreased and lead to marked dimmubon rn function
accompanied by heightened liability to injury and totumour formation. Such changes are readily obse:ved
in the skin and can occur in any organ that has received
a sufficiently high dose, either in one brief expos11re orover an e..'Ctended period of time.

II. GENERAL PATHOLOGY
12. Analysis of the biological action of radiations on
multicellular organisms has shown that the sequence of
events generally begins with the local damage at theplace of the primary biophysical event. Such damage
usuallv involves cellular and extracellular structures ofdiverse origin and function, and it may range from thealmost imperceptible to the very gross. The former may
appear as a transitory change, such as an alteration in
the permeability of a membrane or an interruption in thesecretory activity of a cell, whereas in the latter case theinjury will be quite apparent. as in the case of a radiation
burn, for instance.
13. Injury, no matter what its cause. brings into playa number of well-known co-ordinated physiologicalevents that are concerned with defence and repair andwith maintenance of the integrity of the organism as awhole. Radiation injury follows this universal biologicallaw of reaction to injury, although radiations can modify
these reactions to some e.."tent. It is clear that, without
repair, we could not use radiations in the treatment ofmalignant diseases.
14. It is important to remember that radiations do
not produce effects that are specific or novel in character.
This is true of the morphological changes as -.,vell as ofIII. SPECIAL PATHOLOGY
20. Clinical observations on large numb~rs of humanbeings and numerous studi~s on a great variety '?f experimental animals have provided much valuab_le mformation on many types of radiation injury in vano_us organs.
In general. these lesions are the result of relatn:ely large
doses of the order of 100 r. and greater, delivered to23

deep-seated cancers. and most of our knowledge concerning the effects on the skin has been obtained fromobservations of the results of therapeutic irradiation
with X-rays. Diagnostic procedures rarely lead to obsen•able changes and then only in the case of prolonged
or repeated exposures. Contamination of the skin withradioactive material can also produce severe lesions inthe skin if the radiation dose is sufficiently great, as has
been observed among Japanese fishermen and inhabitants of the Marshall Islands exposed to immediate andlocal fall-out in 1954.
26. Depending on the size of the field irradiated andon the dose absorbed, changes can be obsen•ed ranging
from transient erythema, changes in pigmentation, andtemporary loss of hair to severe necrosis and ulceration.
Among the early radiologists, chronic radiation dermatitis of the hands and face was a common condition, andcancer often occurred in the damaged skin. This was
the form of radiation-induced tumour first to be described in man.

small parts of the body, but the effects of small doses
have also been extensively studied.
The blood-forming organs
21. The tissues producing the formed elements of theblood (red cells, white cells and platelets) are widelydistributed throughout the body; they are found principally in the bone marrow, the lymph nodes, the spleen,
the thymus (in children) and in the foetal liver. The
widespread distribution of these tissues makes it very
difficult to irradiate any part of the body without exposing part of this system.
22. The majority of the cells composing the bloodforming organs are known to react promptly and to
relatively small single doses of radiation. Of the whitecells, the lymphocytes are the most sensitive and their
response as measured in the circulating blood is a mostsensitive indicator of whole-body exposure to radiationin man. Under special conditions of clinical investigation, a temporary drop in lymphocytes has been reported
after a single dose of 250 mrem. After repeated doses ofa few roentgens, changes in the morphology of lymphocytes (bilobed) have been reported to be more readily
detected than a mere reduction in number. It has been
established that the blood-forming organs of children are
more sensitive than those of adults.
23. Chronic or repeated exposures at low dose levels
will impair production of white cells and red cells, but
this impairment may not become apparent or detectable
for some years. For these reasons, blood examinations
are not as sensitive or as reliable a diagnostic procedure
as was previously thought. Radiologists and others who,in the past, have been exposed almost daily for many
years to relatively low levels of radiation have shown
reduced numbers of white cells (leucopenia) and of
red cells (anaemia). Among the delayed effects ofradiation exposure of the blood-forming organs, leukemia is the most serious condition. An increased incidence of the disease has been reported among the following five groups of people exposed to radiations : ( 1)radiologists; (2) atomic bomb survivors of Hiroshima
and N agasal.:i ; ( 3) patients with severe arthritis of thespine who were treated with X-rays for this condition;.( 4) children who had been treated with X-rays inmfancy to reduce the size of the thymus gland: and( 5) a group of children who were exposed when stillin utero during diagnostic X-ray examinations of themother. In two of these five groups, it has been possible
to make estimates of the degree of exposure and to relatethem to the incidence of leukemia. These data are disc.ussed in detail in appendix G. Finally, it must be mentioned that leukemia can also be induced in certain
species of experimental animals by exposure to radiations. Lab~ratory mice. which are especially susceptible
to one particular tvpe of leukemia. have been intensively'·
studied.

Gastro-intestinal tract
27. The gastro-intestinal tract is relatively easily affected by radiations, and radiologists have learned toexercise particular care when administering radiation
to the abdomen. Changes can range from interferencewith physiological functions such as intestinal mobility
and secretion of digestive juices to denudation and ulceration of the mucosa! lining. Relatively large doses ofradiation can cause transient and even permanent depression or cessation of acid and pepsin secretion in thestomach, for instance. Ulcerations produced by radiation
may lead to local infection and bacteriaemia. These areoften produced by bacteria that normally live in the intact
intestinal tract without causing harm. Injury by irradiation can thus adversely affect the delicate balance thatexists in nature between host and parasite. Denudation
may also result in intractable loss of body fluid throughthe impaired intestinal mucosa. The dose levels required
to produce these serious effects have a high threshold.
This type of injury to the small and large intestines plays
an important and often crucial role in the outcome of
the acute radiation syndrome which will be describedlater.
28. The passage of ingested radioactive materials
through the intestinal tract might produce similar injury,
especially when such material is insoluble and when it
remains for prolonged periods in certain portions of theintestinal tract where for physiological reasons it moves
slowly and in concentrated form, as it would do in thecolon. No such injury has been described in humanbeings, but experiments with animals have shown thatsuch lesions can be produced by feeding very large
amounts of insoluble radioactive materials.
Nervous system
29. In the past, when morphological criteria wereused almost exclusively for the classification of organs
according to their radiosensitivity, the central and peripheral nervous system were regarded as belonging to
the more resistant organs. While it is still generally truethat considerable doses are required to produce morphological alterations in nervous tissue, it has become apparent in recent years that functional changes can be
elicited with much smaller and often very low doses andthat such changes may be of great significance.
30. Among these changes one may mention: decreasein excitability, the induction of an imbalance between

Skin
24. Of all the organs in the human body, the skin is
the most frequently exposed. and it probably has been
the most frequently damaged, as all external radiations
m.ust pass t_hrough it be!ore reaching other structures.
Smee the discovery of. X-rays. therefore, skin changes
have been very promment and they have been very
carefully analysed. In fact, for a long time, skin reactions ( erythema) served as a quantitative measure ofradiation dose in man.
25. Until relatively recently, reactions in the skin havebeen a severe limiting factor in radiation therapy of24the processes of excitation and inhibition. and changes
in conditioned reflexes. Modifications of the electroencephalogram have been described at very _low doses.
Changes of a transitory character are seen m cases ofwhole-body exposure to doses of several tens of roentgens. Irradiation of animals with 300 !o 400 r produc~schanges in the electro-encephalogram ot about one week s
duration. In cases of exposure to 800-900 r, changes start
immediately after irradiation and persist up to the timeof death.

Vascular system
34. Functional and morphological abnormalities inblood and lymphatic vessels have been observed in many
irradiated organs, ranging from transient changes inpermeability to necrosis and rupture with haemorrhage
into the extra-vascular spaces. Changes in the vascularand lymphatic system play an important part in thepathogenesis of many acute and delayed types of radiation damage, as for example in the skin. Erythema of
the skin is primarily due to changes in blood vessels,
and chronic skin lesions are .i:sually accompanied byprominent vascular abnormalities such as dilated orcompletely obliterated blood and lymphatic channels.
Lesions in blood vessels are likely to produce impairment of arterial and venous blood flow through theaffected parts of an organ. Thus they can cause secondary metabolic changes due to diminished blood supply.

Bone
31. Many lesions of bone have been described inhuman beings and e..-x:perimental animals following exposure to radiations from external and internal sources.
Damage has ~anged from temporary inhibi!ions of ~onegrowth in children and young amm;4s with rela_ttvely
small doses (of the order of 100 r) to bone necrosis andfractures following exposure in radiotherapy to doses
greater than 1000 r. It i~ important to emph~size thatthe growing bones of children and young ammals aremuch more vulnerable than those of mature and older
individuals. Skeletal development in childhood can bearrested temporarily by moderate doses. The maj?rityof the bone abnormalities reported has resulted eitJ:er
from large doses used in radiotherapy or from dep~sitsof radioactive materials such as radium and mesothonumin bone. With both types of e..xposure, malignant tumours
have been observed to develop either in bone itself or instructures adjacent to bone. Bone-seeking radio:active
materials such as radio-strontium are at present incorporated at greater concentrations in the growing b_?~esof children than in the bones of adults. Such deposit10n
is likely to occur in the areas of most ~ctive. bone growth( epiphyses). Studies of bones following smgle or _multiple doses of radio-strontium in experimental ammals
have shown that severe lesions and tumours are most
likely to arise in these particular areas.

Eyes
35. Acute conjunctivitis and keratitis have been observed following exposure with relatively large doses ofa few hundred r. The sensitivity of the retina can beused as a detecting procedure of the effect of radia~ion
upon the human body. However, apart from tJ:~ retma,
perhaps the lens has proved to be the most sensitive partof the eye. Lens opacities (cataracts) ha".e been reporte_d
to occur following whole-body and part1al body irradiation in man and in experimental animals. Cataracts area characteristically late effect of radiation. In mai:i. t~eminimal single dose required for cataract production isestimated to be near 200 rad of X and gamma rays. By
a single e..xposure to radiations from atomic bomb explosions. cataract cases have been reported to be one of thelate effects. Neutrons are more effective in inducing
cataracts and several such instances have been observed
amona physicists in recent years. Cataracts have also
been ~bserved in e..-x:perimental animals (dogs) several
years after the administration of radio-strontium.

Gonads
32. The ovaries and testes are more sens1hve thanmany other organs to damage by radiation. Temporarychanges in fertility can be produced. in either s':-"'· bysingle exposures (30 r in the male and 300 r m thefemale) or through the cumulative effects of repeatedexposures of a few roentgens. Eggs and sperm during
development are more susceptible to damage than whenmature. The minimal sterilizing dose is less for men
than for women. Functional changes in the gonads as aresult of exposure to small doses can be observed more
readily in \Vomen by irregularities or temporary suppression of ovulation and menstruation. Temporary
sterility as evidenced by suppression of mensti:uation
may last from a month to a year or so, depending on
the dose.
33. In the mouse. chronic irradiation with multiple
doses is more effective in producing abnormalities suchas changes in the oestrus cycle than is a single exposure.
Under chronic irradiation with gamma rays and fastneutrons, fertility of male mice is affected earlier thanfemale fertility: these changes preceded other deviations
from normal. Neutrons are more effective in producingchanges in the gonads than X or gamma rays. Various
types of benign and malignant tumours have been observed in the ovaries of mice following single andrepeated e.."'Cposures to external irradiation. Such tumours
are the result not only of the local action of the radiations on the ovaries but also of hormonal disturbances
created in the animal as a whole.

Lungs
36. When heavily irradiated, th~ lungs show slowly
dev-eloping, progressive changes which have been known
as radiation pneumonitis. The rich vascular system of
the lungs is susceptible to rad~ation injury. and d_elayc:dchanges have been observed m blood vessels. Fibrosis
and cancer of the lung have been described in miners ofradioactive ores, but many other factors ha~e undoubtedly played an important part in the production. of these
diseases. However, radiation from radon and its decay
products deposited in the lungs o~ miners undou~te~yaugmented the effects of other nox10us agents. Radiation
pneumonitis and cancer of the.lung h_ave been p~odu~edin experimental animals by mhalation of radioacttvematerials such as plutonium and cerium.
Endocrine organs
37. Functional disturbances of organs with internal
secretion have not received as much attention as thoseof other organs. However, the role of the adrenal carte~in the "alarm-reaction" and in the "stress-syn~o1?ehas been investigated \~ith regard to i;ij'!ry by radiadtion,and it has been established that rad1at10n can pro uce
certain non-specific effects which are mediated throughthe adrenal gland (lymphopenia, for instance) ~d th~~they are identical with those produced ~y other stress fagents. This emphasizes the non-spec1fi~ character osome effects of radiation. Effects of this type can beobtained with a few hundred roentgens of X-rays, and
it is possible that other endocrine processes also con-25

cemed with regulatory functions in the body can likewise be aifected by such doses. These are matters which
require much further investigation.
38. Of all the glands with internal secretion, thethyroid gland is the one that has been studied most thoroughly in man, especially in connexion with radioactive
iodine, which is selectively concentrated in this organ.
The effects of radiation from radioactive iodine upon
the thyroid gland in hyperthyroidism have been of great
benefit in the treatment of this disease. Corollary studies
have also thrown much light on the early functional
effects that radiation may have on this organ and on themorphological alterations that follow later, including thecomplete destruction of the gland. Endocrinologicalstudies have demonstrated that it is relatively easy to
disturb certain sensitive hormonal equilibria existingin the body.
Embryonic development
39. Radiation has long been known to be harmful toembryos. Malformations have been observed in children
who had been exposed to X-rays or other ionizing radiations while they were developing in the uterus. Our
knowledge of these effects is based on what happens after
accidental exposure of human embryos coupled withextensive experiments with laboratory mammals. In rats
and mice, 200 r of conventional X-rays (250 J...-v) given
to the pregnant mother will selectively destroy specificprimitive cells in the embryo at certain stages; this willinterfere with subsequent developmental processes. The
kind of malformation which results depends upon thephase of embryological development going on at thetime of irradiation. In the laboratory it is possible toproduce virtually at will a whole series of malformationsof the nervous system, skeleton, eye and other organs byproperly timing the radiation. In general, a critical period
exists for the induction of any particular malformation.
40. The dose of radiation is also an important determinant because some developmental processes are
more sensitive than others to disturbances produced byradiation. After low doses (25 to 50 r) only certain abnormalities may occur at given stages, whereas 400 r is
so damaging that the embryo usually becames extremely
malformed or it may even be killed at once. In general,the malformative processes that result from radiation ofdeyel?ping mammals can be explained by embryologic
pnnc1ples worked out for other vertebrates.
41. Although human data on the results of exposureof embry? and foetus are meagre and fragmentary, there
are ~uffic1ent experimental quantitative data to provide
a guide for avoiding clinical hazards. The lowest dose of
conventi.onal X-rays (250 J...-v) that will produce visible
destruction of embryonal cells in such animals is 30 r
and doses of 25 r are capable of causing deviations ofskele~al development in mice with certain predisposing
genetic backgrounds. In laboratory mammals some of
the gro~sest m~lformations follow radiation given in
the e~rher sormt~ stages, o.r period of early organogenes1~ b1;1t so?1~ tissues contmue to be highly susceptible
to radiation m1ury throughout intra-utenne life andinto the newborn period. For e..'i:ample the retina of theeye and the brain are particularly vclnerable to malformation. If one makes inferences about man from theresults of exp.e~imental _work ~n animals in an attempt
to assess the nsh: to the 1oetus, 1t can be stated that partsof the human brain are probably susceptible to considerable injury until the last months of gestation and that loss
?f sing!~ developing neuro?s is possible well into early
infant life. Among the children who were e..xposed iniitero to radiations from atomic bombs. some cases of microcephaly with mental retardation have been obseryed.
42. It has been demonstrated in experimental animals
that soluble radioactive materials when ingested by themother can be transferred through the placenta to theembryo and growing foetus. Radio-strontium and othersubstances which may pass through the placental barrier
can become fixed in the skeleton or in other organs andproduce damage. In the very early stages of embryogenesis, radiation e..xposure of this type can involve allcells of the growing embryo and resemble whole-body
exposure, whereas in later stages of development it will
resemble partial body exposure through fixation of material in specific organs.
Whole body irradiation: single dose
Acute radiat·ion syndrome
43. Clinical studies on people injured by exposure to
nuclear radiations from e.xplosions of nuclear weapons
and from similar exposures in laboratory accidents haveadded much to our knowledge of the acute and subacuteeffects of whole-body radiation in human beings in andbelow the lethal range. The median lethal dose for man
is considered to be approximately 300-500 rem. Thisdose will produce an acute illness, fatal within thirty to
sixty days to 50 per cent of the people thus exposed. A
few additional people will die after this period. The
following is a synopsis of the most important clinicalsymptoms and of the course of the illness following such
an e..xposure.
44. The earliest symptoms are nausea and vomiting
and sometimes diarrhoea; these may appear within anhour after exposure and can last as long as two days.
They are accompanied by a feeling of great prostrationand fatigue, by hyper-excitability of reflexes and othersymptoms attributable to disturbances of the somaticand autonomic nervous system. This first phase, afteran exposure to about 400 rem, is followed by a periodof subjective \vell-being, although tissue-damage progresses. Characteristic changes in the white blood cells
begin very early; usually they are already present on
the first day. An early and rapid fall occurs in thelymphocytes. The granulocytes, after a transient initial
increase, also rapidly fall below normal levels. In the
fatally injured, all types of white blood cells continue todecrease to extremely low levels. A similar, though lesssevere and somewhat delayed, fall will be seen in the red
blood cells, causing progressive anaemia. There is atendency to bleeding. This is due to a reduction in thenumber of platelets, as well as to an increased permeability of blood vessels. Anaemia and leucopenia may
be severe at death.
45. At the height of the illness, usually during thesecond and third \Veek, the fully developed radiation
syndrome is characterized by a sustained high fever andextreme exhaustion; there is loss of weight, reddeningof the skin ( erythema) and loss of hair and there are
haemorrhages in the skin, and ulceration of the mouth.
throat and intestines. Loss of protective function of themucosa of the mouth and intestinal tract combined withsevere impairment of white blood cell production andof other immunological functions make irradiated individuals susceptible to infections from bacteria normallyresiding in the individual and usually harmless. Infections of this kind have frequently been the cause of death.
46. It is apparent that initial injury leads to comple."(chains of events inYolving practically all organs of the
body and may seriously interfere with the balanced in-26

terplay between them ( homeostasis). Apart from cellular
damage, general reactions of the vascular and nervous
systems, marked alterations in fluid and electrolyte balance and ot.1-1er metabolic changes play an important andoften decisive role in the pathogenesis of this illness.
47. Survivors of injury of this magnitude recoverslowly and require a prolonged period of convalescence.
Disturbances in the blood-forming organs and in the
gonads are the last to disappear and some of the changes
in the bone marrow and in the circulating white cells
may persist for many months. The patterns of recovery
from massive radiation injury of this kind clearly demonstrate that radiation, in addition to producing damage,
temporarily inhibits the mechanisms of repair. Interference with reaction to injury is an important factor andits significance may be equal to that of the primarysensitivity of cells.
48. When the dose of a single whole-body exposure
is reduced, illness of the type described above is correspondingly less severe and fewer symptoms are observed. It has been suggested that. with a dose of 100
rem, not more than 15 per cent of those e.xposed would
be affected and that illness would be of short durationand comparatively mild. At low dose levels (beti.•;een 25
and 50 rem) significant findings may be restricted almost
entirely to the blood; these will be difficult to detect
without special methods.
Possible delayed effects
49. It is a peculiar and striking characteristic of radiation injury that although apparent recovery occurs
among surviviors after e.xposure to a large single doseof about 400 rem. certain delayed effects may be observedin the years following e.xposure and recovery. Latechanges have now been observed in survivors of a large
dose of radiation to the whole body and they include
the following: loss of hair, changes in te.-x:ture and pigmentation of hair, cataracts, impaired spermiogenesis,
anaemia and leucopenia and leukemia. It has been said
that there is also, in man, a non-specific increase in themortality rate (shortening of the normal life-spanthrough diseases other than leukcmia) but there is as
yet no definite evidence for this from studies of atomic
bomb survivors in Japan or of comparable groups.
SO. 'Whole-body irradiation may, by randomly producing non-specific tissue changes, adversely influence
all those disorders which commonly affect human beings
and which ordinarily increase with age.
Shortening of the life span
51. All the major delayed effects discussed above willtend to diminish the average life-span. In addition, radiation may have the effect of accelerating the sequenceof changes which constitute the "normal" process ofageing. Experiments on animals have demonstrated thatwhole-body exposure to doses that cause no early deaths
and relatively few acute symptoms can, nevertheless,shorten the average life-span. and it is possible that thesame may be true for man, although specific human evidence of this point is difficult to obtain. Observationsin the United States on radiologists and others using
X-rays, d~ring the past twenty years or so, have thus
far established an increased incidence of leukemia inthis populc:tion, and have suggested further that there
may be an mcreased total rate from other "non-specific"
causes. Preliminary results of a survey of radiologists
in the United Kingdom, however, show no evidence ofshortening of life-span in this group as compared withother medical groups and control populations. The datafrom man _and from labora~ory e.-x:perimentation relating
to shortening and lengtheruna of the life-span are dealt
with in annex G.
!>
Cancer
. 52. Within a decade following the discovery of X-rays
it became apparent that exposure to radiation carried
with it the risk of malignant disease. The first evidence
wa~ t!iat of. cancer of the skin developing in severe~ad1ahon les1o~s of persons expos~d occupationally orm the course ot treatment. It has smce been found thatradiations of various types, external and internal haveinduced or help ~o induce ti:mours in the blood-fo~mingorgans ( leukerma), the skm and subcutaneous tissue.
the skeleton (sarcoma of ~one. in radium f!Oisoning), thelung (cancer of the lung m mmers of radioactive ores),the thyroid and liver, for instance. Parallel experimentswith animals have emphasized the general susceptibilityof most tissues of the higher species to cancer inducedby radiation.
53. In common with ultra violet rays and with a great
variety of chemical agents known to produce cancer,
exposure to ionizing radiation is followed by a long induction period before the appearances of malignant
growths. In man, the induction period for cancer is often
of ten to twenty years duration and it may be evenlonger. For leukemia the induction period appears tobe shorter, and the disease more commonly develops
between five and ten years after a single irradiation. It
is impossible to estimate the induction time of tumours
which occur "spontaneously" in man since their causes
are unknown; but the common increase in cancer incidence during later life may indicate that long induction
periods are characteristic for human tumours.
54. This induction period is characterized by generaltissue changes as outlined earlier, such as destructionof cells followed by compensatory proliferation of new
cells and deterioration in the nourishment of tissue due
to defects in its blood supply. In the course of thesechanges, a general derangement occurs in the architecture of the affected tissue. Although the majority ofradiation-induced tumours have originated in tissues soaltered, the reasons for the increased frequency of cancer in such situations are unknown. Clinical experiencesuggests that malignant tumours are an infrequent andnot an invariable or inevitable result of severe radiation
exposure.
55. In certain cases, it has been shown that tumour
induction occurs through the mediation of specific physiological or endocrine responses of the whole organism,
rather than by specific radiation action on the cell. Suchmechanisms are responsible for the induction by irradiation of tumours of the ovary and pituitary in mice. As
another example, it has been shown that unirradiatedthymic cells introduced into an irradiated host may
become the origin of malignant tumours. Such indirect
physiological mechanisms have not been demonstrated
in man, but it is possible that they exist.
56. Clinical and experimental evidence show that
where the total body is irradiated, leukemia is the m?st
probable end-result among the various for~s of m~1g­
nant disease. Leukemia has been the predommant finding
among the groups of radiologists studied. Although therelatively soft X-rays to which these me~ w~re presumably largely exposed produce more !omzat10n ~n somecalcium-rich areas than in the soft tissues, no mcreasein bone tumour incidence has been noted.

tumours were attributable to a natural radiation level of
9 rem per 70-year human life-time, and if it were assumed further that the natural frequency of thesetumours is between 5 and 10 cases per million individuals per year, and that the increment from added
radiation is a linear function of the response and that
there is no threshold, then the increment from an addition of one rem per 70 years would be one-ninetieth of
the natural incidence. Thus, in 70 years to an assumed
350 to 700 cases per million of population. an additional 4-8 cases would be added. This may be taken as
the worst case; if a threshold exists for the induction ofbone tumours which is higher than the assumed total
radiation, then the increment would be zero. More complex mechanisms of cancer formation would be expected
to lead to intermediate values.
61. In attempting similar predictions in the case ofleukemia, it also seems reasonable to assume that not all
leukemia is due to natural radiation, since there areother known causes in the environment and since humanobservations at high irradiation doses indicate a lower
slope to the dose-incidence curve. Assuming that theincreased incidence per rem would be 1.5 per 1 million
per year for the rest of the lives of the exposed individuals, and considering the two limiting mechanisms
as discussed in the preceding paragraph, we can derive
the number of cases added to the natural incidence by 1
rem per 70 years (for a population of mean age 35) as
1.5 x 35, or 52 induced cases per million persons per
70 years (that is about 150,000 cases per 70 years in aworld population of 3 thousand million), in the upper
limiting case, and zero in the lower limiting case. The
upper value would represent an increment to the natural
leukemia incidence which is estimated at 1,400 to 3,500
per million per 70 years (or within the limits of fourand ten million in the total population of the world).
These are theoretical computations, and it is difficult
to estimate the relative importance of radiation andother environmental factors in tumour induction in man.

57. When the skeleton is selectively irradiated byradioelements such as radium, an increase in bonetumours is a prominent result. This is borne out by
clinical studies of many persons who, twenty-five tothirty-five years ago, accidentally ingested radium in theprocess of painting watch dials or received it orally or
by injection during inappropriate medical treatment.
Cases are recorded in which tumours have arisen inpatients who, after twenty or more years, retained between one-half and one microcurie of radium in thewhole skeleton, implying an original intake of about
one hundred times that amount: this delivered a total
average dose to bones of about 2000 rads. Since most of
this radiation was delivered by alpha particles, the average dose in rems would be considerably higher. However,some patients with a total radium burden of more than
10 microcuries after more than twenty years have notdeveloped tumours although such individuals invariably
show a sequence of destructive and proliferative changes
in bone similar to those observed at the sites of originof malignant tumours induced by radiation.
58. From experiments with animals it is clear that
other radioelements which are deposited in the skeleton,
e.g. plutonium, strontium-89 and -90 and various rareearth elements can likewise produce bone tumours andother tissue changes which have been observed in radium
poisoning in man. While no such cases are recorded inhuman beings, this may be attributed to the fact that
there have been no comparable human exposures to theseradioelements. Experimental data suggest that bonetumour incidence can adequately be approximated on
the basis of the dose in rems to the osteocytes. Experiments with mice suggest that ten microcuries of strontium-90 in the skeleton are equivalent in carcinogenic
effect to not more than one microcurie of radium. In the
one series of animal experiments which was designed
to determine the dose-effect relationship for radiostrontium and bone tumour, the relationship appeared
to be sigmoid: however, there is as yet no critical discrimination between interpretations in terms of a sigmoid. a linear, or a strictly threshold relationship.
5?. Since tumours induced by radiations in man andvanou~ animals ha".e arisen almost exclusively in damaged hssue, and smce experiments have shown that
there are t:;vels of radiation below which no increase in
the normal 'biological background" of tumour incidence
can be detected, it has been believed that there is a minimum (threshold) dose of radiation causing the inductionof tu~ours. Such thresholds vary from organ to organ:md with. the age of the organism. Owing to limitations
m expenmental methods, including the lapse of time
~efor~ tumours appear after application of cancermducmg agents and owing to the "biological background''of ~p<?ntaneous tumours, and the physical backgroundradiation. the possibility remains that there may not bea true thres?~Id. !he situation would then be analogous
to that obta1mng m the case of genetic changes.
60. In accordance with the latter concept, it has beensuggest~d that the tu~our ~ay have its origin througha ~utat1onal change m a smgle somatic cell ; or alternatively, th:it the somatic mutation may be one of theevents leadmg t? tumour development. In its simplest
form,. the somatic ~uta~on theory would postulate thateach mcrement or radiation above the natural background would carry with it a proportional probabilityof . tumour development (linear response). An upper
estimate of the eff~ct of radiation in causing tumoursof ?one can be obtained by the following consideration.
If 1t were assumed that 10 per cent of all primary bone

IV. SuM MARY AND coNcLusroNs
62. A large body of knowledge has accumulated during the last sixty years on the somatic effects of ionizing
radiations on man and animals. This knowledge has comefrom numerous observations on human beings and fromextensive experimentation with laboratory animals. In
both cases, the effects of external and internal radiation
have been studied and, although many of these effects
are far from being understood in all details, our knowledge is sufficient to provide a general picture of theevents that occur after human beings and animals havebeen exposed to ionizing radiations of all kinds. In general, the effects following exposure to relatively large
doses are well known, whereas the effects of small doses
are not understood nearly as 'veil.
63. All types of ionizing radiations produce similar
biological effects; these are usually not distinguishable
from other pathological conditions. Some radiations,such as neutrons and alpha rays, are more efficient inproducing certain types of somatic effects. Physical factors of exposure such as dose. dose rates and dose
distribution are as important in determining the natureand extent of the biological effects as are the age andsex of the individual exposed and the part of the bodythat has suffered e.xposure. Radioactive isotopes produce
harmful effects in those organs in which they are selectively retained. The extent of these effects depends on
the physical characteristics of the isotopes, such as thehalf-life, and the type and energy of the radiations

28

emitted, as well as on the time of retention in a particularorgan and the sensitivity of that particular organ toradiation injury. Absorption of measurable quantities
of radioactive materials in human beings and animals has
been demonstrated in recent years. Strontium-90, having
a half-life of 28 years and being deposited selectively inbone, may be cited as an example to which particularattention must be given.
64. Exposure to relatively large doses of e..'Cternal orinternal irradiation produces a variety of characteristic
and well-known somatic effects which may occur either
immediately or with a delay of a few days to several
years. Certain organs, such as the blood-forming organs,the skin and the gonads, are particularly vulnerable toinjury by ionizing radiations. Many of the acute effects,
such as erythema of the skin and radiation sickness
following whole-body e..xposure, have characteristic
threshold doses. Similar thresholds e..xist for acute bloodand bone disorders following ingestion of large amountsof radium and other radioactive materials.
65. The tissues of the embryo and foetus are among
the most sensitive to radiation. Malformations and otherpathological conditions have been observed following
exposure of pregnant women to accidental and therapeutic irradiation and to diagnostic procedures, e.g. pelvimetry. Experimental work has demonstrated thatradioactive materials, such as strontium and other soluble radionuclides circulating in the blood of the mother.
can be absorbed and deposited in foetal organs such as
the skeleton, where they may produce lesions.
66. As the dose of radiation is reduced below theamounts giving rise to acute functional or morphologicalalterations, the reactions of the organism become moredifficult to detect immediately and the effects may be
progressively delayed in time. Thresholds are not easily
revealed under these conditions of e..xposure; in fact, forsome of the most delayed phenomena, it is uncertain
whether they e..'Cist.
67. It is a very characteristic feature of radiation injury that delayed reactions may occur many months or
years following exposure. The morphological and functional alterations which occur during the long periodsof latency are poorly understood. It has been shown thateven after such periods acute manifestations of somaticeffects may develop. Among the late effects, leukemia,bone cancer and other malignant changes are worthy ofmention. It has been demonstrated that whole-body exposure can shorten the average life span of e..xperimental
animals, and it is possible that the same may be true forman.

68. Sm:i-11 doses o_f radiation given repeatedly can havea cumulative effect m thos; cases in which the processesof recovery a;i? co.mpensat1on are limited. It is not !mown~hether sens1t1~at10? occurs. The existence of adaptation
m the broad b1olog1cal sense of the term has not been
proven.
. ~9: In vi~w _of the present tendency of the levels of
1o~zmg. radiations to increase gradually, as a result ofvano~s !nfluences, and on a_ccount of the life span ofman, 1t 1s felt that along with measurements of theselevels there should be continuing research on all aspectsof the somatic effects of radiation. To ensure a thoroughexamin~tion of all relevant factors, the Committee points
out the importance of :(a) Demographic studies of populations living inareas that differ in natural radiation levels with referenceto effects perhaps ~ttributable to these levels or to otherenvironmental variables which might produce similareffects;( b) Systematic studies, on a wide scale, of groups of
persons who have received radiation for medical purposes;( c) Continued and expanded e..xperimental work on awide range of experimental organisms regarding the latesorr.atic effects of small amounts of external and internalradiation with particular emphasis on dose-effect relationships;( d) The development of methods to serve as sensitive
indicators of damage produced by e.xposure to small
amounts of radiation ;( e) Expanded clinical and experimental studies on
the nature of cancer and leukemia in conne.xion withradiation exposure, and on the basic cellular biologicalproblems which may have bearing upon this;(f) Increased opportunities for exchange of e..'Cperience among e..'Cperts engaged in all of these fields ofresearch.
70. It can be anticipated that research in all of thesefields will greatly benefit mankind. This will come about
not only through a better understanding of the effectsof ionizing radiations, but also through increased lmowledge of malignant diseases and of the ageing process.
At the present time, due to the fact that threshold doses
for the delayed somatic effects of radiation are not
e..xactly knO\vn, it must be recognized that the exposureof human populations to increasing levels of ionizing
radiations may cause considerable and widespread
somatic damage.

29

Chapter VI

GENETIC EFFECTS OF RADIATION
them.m The effects of these small changes range fromtrivial variation or slight detriment to disturbances having serious effects on reproduction or even survival.

1. The inherited characteristics of man distinguishhim from other species and in part determine the natureof each one of us. They have been accumulated overmany generations. Experimental work on many organisms has shown that ionizing radiation can cause mutations. which are permanent, and for the most partdeleterious, changes in the inherited characters. It therefore cannot be doubted that exposure of the germ cellsof human beings to such radiations will occasionallycause similar changes and so, over many generations,affect individual descendants in populations yet unborn
and never themselves exposed.
2. While some hazards are implicit in almost all technological advances, it must be remembered that inherited
changes are an inescapable consequence of the irradiationof human populations, and that they affect at random
persons who can seldom, if ever, be individually identified. They therefore pose ethical and legal problems
which should be of special concern to Governments.
This chapter is concerned both with mutation, especiallyin man, and with the consequences that can be expectedfrom an increase in this process brought about by small
general increases in the radiation exposure of humanpopulations. Certain technical terms employed have already been described (chapter II, paragraphs 35-38).

Natural mutations
5. By natural mutations are meant those which result
from conditions beyond our control in normal life, suchas natural sources of radiation, thermal agitation andchemical processes within cells. Experimental studies ofnatural mutations in a wide range of organisms from theunice11ular forms to the higher plants, insects and mammals, have indicated that mutation at any one specificgene locus is a very rare event.ru 3 There is, however,a considerable variation in rates of mutation between
various loci as well as between various organisms. m 4 - 28
The estimates of frequencies of appearance of new mutant genes for the mouse and for the fruit fly Drosophila
mostly range between lQ-5 and 10-s per locus per tested
gamete but, because natural mutation is a rare event,they are subject to large sampling errors and perhaps tosome bias in respect of the group for which estimates
are available. Frequencies as low as 10-9 per locus percell have been observed in bacteria. In man, test matingscannot be employed to associate a given mutation with a
specific locus and special methods, either direct or indirect, must be used to analyze the available material.
6. The direct methodHa 0 is restricted to the study ofmutations to dominant genes, that is. to genes which are
manifested in heterozygotes, and in a modified form to
the study of mutations of genes located upon the chromosomes which determine sex. It is based upon direct countsof the number of sporadic and inherited cases of thecondition under investigation. For single clinical entities
the estimated frequencies of appearance of new dominant mutant genes mostly range between 4 x 10-e and 40
x 10-6 per gamete. These values are supported by calculations using the indirect approach. It must, however, beremembered that a single clinical entity may be affectedby mutation of any one of many genes.
7. The mutation rates for clinical entities due to recessive genes cannot be estimated by direct counting, but
can nonetheless be calculated by an indirect method.H 31
This is based upon the hypothesis that there is in the
population under study a genetic equilibrium at which
as many new forms of genes are produced by mutations
as are eliminated by subsequent failures of reproduction.
An attempt is then made to estimate this last number.
However, a possible slight advantage or disadvantage
in heterozygotes may grossly affect the figures, which
for this and other reasons are very uncertain indeed. Hs 2
To improve the accuracy of the estimates more information is needed about such selective pressures.

I. MUTATION
General
3. Some facts about mutation have been so widelyconfirmed by experiments in other organisms that one;an have every confidence in applying them to mutationm man as well:(a) Mutations, once completed, are irreparable. The
altered or mutant genes can be changed only by further
mutational processes.
( b) Mutations arise at random in this sense: they
are not brought about by that particular aspect of theenvironment toward which the mutant organism willsubsequently show an altered response.
. (c) The great majority of observed effects of mutations are harmful. The combinations of genes naturally
pre~ent in the individuals of a species have been selected
durmg very many generations; any random change has,
therefore, little chance to be of immediate benefit.
4. Mutations may be roughly classified according towh~ther they are structural changes involving whole
regions of the chromosomes, or whether they are so~11ed point mutations. which apparently involve only
smgle genes.H 2 The mam problem for man is the effectof irradiation upon the cells of the germ-line from which
eggs and sperm are later produced. In experimental
studies of animals, gross chromosomal changes are more
rarely observed among offspring conceived long after
such irradiations than are point mutations : they are also
comparatively rare at low doses. Hence. the mutations
which are transmitted to future generations are principally the apparent gene mutations-point mutations andthose minor re-arrangements and losses that behave like

Radiation-induced mittat-ions
8. AH the kinds of ionizing radiations v>'hich havebeen tested e..'Cperimentally upon living organisms areable to induce mutations which are transmissible to theprogeny, if energy is absorbed in the cells oi the germ
line.

30

averaged over a large class of human genes, in so far
as it can be estimated, can be taken as a representative
figure for the large classes of genes which together
determine broad categories of damage in populations.He~
14. Any estimate in man of induced mutation rates oi
individual genes re~uires extremely difficult studies ofvery large numbers. 46 - 58 In fact, completed surveys ofthe progeny of irradiated parents have failed to demonstate unequivocal changes, or increases in any clinicalentities investigated.H 5 o-si This very failure provides
some reason to suppose that the rep;esentative doublingdose for human genes does not he below 10 rad.H;i
However, in these surveys, small changes are rather
consistently observed to occ:urH~o-~ 1 in the directions expected to result from increased mutation rates. Taken
together, these observed marginal changes do seem toestablish the occurrence of phenomena expected to result
from increased mutation: moreover, it seems somewhat
unlikely that they would have been observed if the representative doubling dose for human genes e..'Cceeded 100
rad. The Committee therefore accepts as reasonably
probable that the representative doubling dose for humangenes lies in the range 10 to 100 rad, but for purposesof calculation the £eometric mean (about 30 rad) is aconvenient figure. 73 The representative doubling dosefor human gene mutations cannot in any event lie below
about 3 rad, the magnitude of the genetically significant
dose delivered in most areas by natural sources ofradiation. H72
15. Any further narrowing of the limits upon thequantitative relations between dose and mutation in man,here expressed through the representative doubling dose,can come only from comparative surveys of the offspringof special irradiated and control groups. The phenomenon which comes closest to being established is a shift
in the se..'C ratio at birth an1ong the progeny of irradiatedparents.H5° To clarify this phenomenon and its interpretation, experiments on animals, especially mammals, areurgently needed in parallel with the continuation ande.."ttension of surveys relevant to radiation-induced
genetic injury to man.
16. There is another approach to expressing the overall quantitative relation between radiation exposure andinduced mutation in man. It is to ask the question: what
total number of mutations is produced by a given exposure of a set of human genes to radiation? Because no
direct observations of radiation-induced mutations in
man have been made, an answer to this question can
only be estimated by the very uncertain procedure ofanalogy with other species.nu

9. It is of basic importance for any discussion of thegenetic effects of radiation to establish the relationshipbenveen frequency of induced mutation and dose, andespecially whether this relationship is linear at the lower
dose levels. The Committee emphasizes that there is atpresent no known threshold of radiation e..xposure below
which genetic damage does not occur. The experimental
foundation for a linear dose relationship is fairly wellestablished at moderate doses but is increasingly meagre
at lower doses, terminating in one experiment upon
Drosophila sperm at 25 rad.Hl 0 Experiments alreadyplanned or under way in the United Kingdom and in
the United States will together test linearity over therange of doses from 37.5 to 600 rad for spermatogonial
irradiation of the mouse.Rn However, the range from 5
rad to 25 rad is of primary concern in discussing humanhazards. If methods can be found in any organism totest linearity in the above range of doses, especially forgonial irradiation, this test should be carried out. In themeantime, it is prudent to assume at least as much hazard
as is implied by a linear relation between mutation andgonad dose, as has been done in the present report.
10. In organisms other than man it has been confirmed that the mutational effect of a given dose is independent of its rate of delivery over a wide range. Moreover, it has been shown that there is no recovery frommutational damage with time in the mouse for periods up
to two years after irradiation. The range of times investigated experimentally does not extend nearly as far
as the breeding period of some thirty years involved in
the chronic irradiation of human populations. N evertheless, in the absence of evidence to the contrary, theCommittee accepts the conclusion that the mutational
effects of small doses of radiation delivered to the cellsof the human germ line over long periods of time are
cumulative. Hence, any irradiation of whole populations
must be considered as having genetic consequences.
11. In a number of organisms there is good reason tobelieve that the radiation-induced mutational event is
not completed at the moment of irradiation, but throughsubsequent physiological processes which may occupy
some tens of minutes or even a period of hours. Asidefrom possible prevention beforehand, the opportunity
to effect repair may therefore exist for a limited period
after irradiation.H 12- 13 The Committee considers thatinvestigations directed towards the understanding andthe possible eventual establishment of such opportunities
should be actively pursued and supported.

12. The balance of evidence at present available suggests that mutations induced by ionizing radiations arein general similar in kind and effect to those of natural
origin.Bio In the present report it has therefore been
assumed that this is so. Nevertheless, the Committee
recognizes that further research is needed before wecan be sure that radiation-induced mutations are notsometimes different qualitatively from those of spontaneous origin, and possibly more severe in their effects.H11,1s!I. ESTIMATES OF THE EFFECTS OF IRRADIATION
17. It would be desirable to estimate the genetic effects of exposure to radiation in terms of ''social consequences". However, such consequences are so diversein their effects on the individual, on his family and on
the community as to be impossible to express numerically.
It is possible, however, to measure a number of components. the most satisfactory of which is, at present. thenumber of people more or less seriously a:ffect.ed byhereditary defects. An alternative measure, more direct~yrelated to the total mutation rate, can be expressed interms of reductions in the capacities of individuals tosurvive and reproduce.Raz
18. Even complete knowledge of the dose-mutatio?
relations in man would not suffice to make useful estImates of the social consequences (in th~ sense of thepreceding paragraph) resulting from a given exposure

13. It will be seen below that, in order to estimate thehazards which arise from the irradiation of human populations, it is convenient to speak of the dose which would
produce in a generation as many additional mutations
as al~eady oc~ur ?aturally. called the "doubling dose" .H02
Particularly m VIew of the current acceptance of a linear
relati~nship between dose and frequency of induced~utation, the Committee accepts the validity and practical usefulness of the concept of a representative doubling dose; that is, it accepts that a mean value properly31

means clear. In some, the environment of the embryoin the uterus appears to be of importance in determining
whether they are expressed and there is some evidence
to suggest that many genes modifying the process in acomplex manner are involved. The cleft palate syndromes
constitute a good example of this class. Such traits areconcentrated in families, but seldom to any e."'\:tent explicable by genetic theory based upon any simple
mechanism.
22. The remaining 2 per cent fall into two groups ofunequal size.Hoo Those of the smaller group do appear infamilies in the proportions to be expected from a simple
theory of recessive gene transmission, but the over-all
frequency of appearance, taken in association with extreme negative selection due to the severity of the traits,
is too high to be explained entirely by a balance between
mutation and selection-that is. unless mutation rates are
postulated which are many times greater than thoseestimated either for dominant mutations in man or forgenes studied experimentally in animals. An excellent
example is fibrocystic disease of the pancreas. It may be
noted here that many estimates of mutation rates to recessive genes would be very high if they were to be
calculated on the assumption of a balance between mutation and selection against the traits concerned. Those of
the larger group are illnesses, individually common andsevere, which have been attributed by some to simple
mutants modified in some way in their expression, but
for which the extent and manner of genetic influence is
uncertain and hard to determine. The best e.xamples ofthis class are diabetes mellitus and schizophrenia. If theobserved high frequencies of such traits are assumed
to be due to a balance of mutation with selection, it isnecessary to postulate mutation rates which seem quite
unreasonably high: this is true especially if some degreeof expression of the trait is common in heterozygotes.
23. Only in respect of the strictly limited category of
traits first mentioned above (those determined by single
genes), is it possible to predict with any assurance theeffect of a given increment in the mutation rate.H92 For
all the other traits mentioned, any increment in mutation
would eventually be reflected in some equal or lesser
increment of trait frequency.H 92 Thus, a category of
traits affecting some 1 per cent of all live births would be
expected eventually to increase in direct proportion withany change in mutation rate maintained over sufficiently
long periods. The remaining classes of traits discussed
above, affecting some 3 per cent of all live births, would
also be expected to increase but this increase would beless than proportional to the change in mutation rate,
although the precise extent of it cannot at present be
estimated. A permanent doubling of the mutation rate
might therefore result eventually in an increase in thepresent 4 per cent of live births affected by something
more than 1 per cent and less than 4 per cent : that is,
the proportion affected would rise to between 5 per centand 8 per cent.
24. The total number of individuals who will ultimately be affected by a given small increase of the mutation rate during just one generation is also calculable:
it is equal to the exi:ra number who would be affected inevery generation under conditions of equilibrium with amutation rate permanently increased to the same extent.
However, the affected individuals making up this total
number would be distributed in an unknown mannerover many generations subsequent to that in which thetemporary increase of mutation rate occurred.
25. These considerations do not take into account theeffects of mutation on the so-called "biometrical" char-of a population to radiation. Indeed, such estimates cannot be made with any given degree of completeness before the science of human genetics is equally complete.
In the present state of knowledge, the Committee haschosen to approach the problem by inquiring successively
as to: (a) the magnitude of the social consequences now
laid upon human populations by unfavourable genes;( b) the proportion of this due to continually occurring
gene mutation: and ( c) the inerease in gene mutation
rates, expressed as a fraction of the natural rates, thatcan be expected from a given addition to the naturalradiation exposure. Under certain assumptions thesequantities may be multiplied together to yield a measureof the social burden resulting from a given population
exposure.Hsa These assumptions are :Hss
( i) That the part of the present genetic social burden
due to recurrent mutation is related to the present naturalrate of occurrence of mutations, through a balance between production and elimination of unfavourable mutant genes. In fact, the current rate of elimination ofsuch genes must, through their present number anddistribution, be related in a complex manner to the history of mutation and elimination in the population.
(ii) That the future environment will be sufficiently
similar to the present one for the manifestation of themutation to be generally the same then as now : in particular, that the relationship between the social consequences and the elimination of the mutant gene will not
be significantly affected.
(iii) That the gene mutations brought about by
irradiation are qualitatively the same as those of natural
origin.
The Committee considers that assumptions ( i) and (ii)are reasonable and accepts '(iii) as an approximation.

III. THE SOCIAL BURDEN CONFERRED UPON POPUU.TIONSBY THE PRESENCE OF UNFAVOURABLE GENES, AND
THE EFFECTS OF INCREASED EXPOSURE TO RADIATION

19. One of the tasks of human genetics is to extend
our knowledge of the part played by genetic factors inheal~ and disease. This task is largely achieved by highly
specialized examinations of affected individuals andtheir families and by studies of the children of closely
related parents,· of twins, and of whole populations.
.;\ll research in this wide field is highly relevant to the
problems discussed in the present report.
Genetic morbidity due to specific traits118 B- 9 •. 20. It is estimated that about 4 per cent of liveborn
infants suffer or will suffer from detectable genetic traits~f importance. However, it is only under certain conditions that the relationship between changes in mutation
rate and changes in trait frequencies can be predicted.
?pecifically, it must be known that the trait frequency
is lar~ely determined by a balance between mutation andselec~1?n against the trait concerned: in general. thisc?nd1t10n can be satisfied only for traits determined bysimple genetic mechanisms, and usually by single mutant genes. In the liveborn, the total frequency of traits
thought to satisfy both these criteria is probably not
mo.re than 1 per cent of all live births, including sometraits whose effects are sma11.n 9 o Most of the mutant
gern:s concemed are dominant, although some are recessive.

21. In addition to these traits, there is a considerable
numb.er, affecting about 1 per cent of all live births,n9 ogenetically determined by mechanisms which are by no32
L•. . . . . . . . . .

-acters considered m paragraph 27 and the succeeding
paragraphs: moreover, they disregard the existence of alarger class oi mutations to genes with relatively small
effects known to occur in experimentally irradiated organisms. Such mutant genes, having individually lessadverse effects upon survival and reproduction, would
be expected to spread to more members of a population
than those considered here, and might indeed constitutethe major element in the over-all social consequencesof a prolonged increase in mutation rate.
26. On the preceding basis, a simple calculation of
the numbers of affected individuals can be madeH 92 fora steady population of 1 million persons per generationand for each rad of continuous genetically significant
e.xposure per generation. After reaching equilibrium(i.e. after many generations), the number of individual
defects attributable to this one rad per generation would
probably lie between 100 and 4,000 in each generationof a million persons, i.e. an increase in the number ofaffected persons of between 0.01 per cent and 0.40 per
cent of the population. If the one rad dose were applied
only once, to a single generation, a total number of individuals with defects between 100 and 4,000 would be
expected, but they would occur spread out in an unknown
manner over many subsequent generations. Much of thegenetic damage occasioned by mutation takes a considerable time to appear in the form of affected individuals.
If it is supposed that the world's population will bestabilized at 5 x 109 in the interim before current mutation is so e.xpressed, and that the world population below
the mean age of breeding is then about 2.5 x 109 , thepreceding figures become respectively 250,000 and 10
million in each generation after equilibrium is reachedand 250,000 and 10 million total, but spread out in a~unk"Ilown manner over a long period subsequent to theirradiation. These calculations would apply to each radfrom any source of irradiation affecting the whole population of the earth.

changes and possible over-all survival and reproductive
advantage of heteroz)'.gotes may be decisive, the mutation:ate ~y be comparatively unimportant. It must be borne
m. mmd that. a r~ther small number of genes, each maintame~ at a high trequency by a balance between different
selectwe forces, m.ay. ,~·ell have as large an influence on
the mean and vanab1hty of the population as would amuch larger number of genes each maintained at al?wer frequen9' by a balance between recurrent mutat10n and selection.
lntelligenceH 102

29. Intelligence is the character of greatest humanconcern. It is a biometrical character in so far as it ismeasured by the standard intelligence quotient. An increased mutation rate among the genes ordinarily determining the genetic variability of the intelligence quotient
would tend to increase that variability. This would
theoretically lead to an increase in the numbers of persons with high and with low intelligence quotients, although not necessarily equally. At the same time, by
analogy with genes whose effects are large enough to be
individually detectable and which are commonly foundto interfere in a destructive manner with the biologicalstructures or mechanisms primarily affected by them, it
would be e.xpected that new mutations would, in general,be such as to diminish the average intelligence quotient.
Thus the most probable effect of an increased mutation
rate would be to lower the average intelligence quotient,although there is not sufficient experimental basis for any
judgement as to the amount of any such lowering.
Life spanH1oa

30. Correlations between relatives and studies of twins
strongly suggest a considerable degree of genetic control
over the life-span in man, so that mutation would be e.xpected to have some effect upon it. A shortening of thelife-span has been observed in the immediate offspringof male mice irradiated with fast neutrons. It is imperative that these studies be continued and extended, foruntil human data are available we must rely on resultsfrom experiments on animals. However, man and mouseare sufficiently different for quantitative e.xtrapolation
between the two species to be particularly uncertain. By
analogy with the results on mice, a decrease in life-spanin subsequent generations would be expected following
an increase in mutation rate, but the amount of any suchdecrease is very uncertain. It should be understood thatsome of the factors that reduce life-span are the specificgenetic diseases and abnormalities discussed earlier.

Biometrical characters11 9 s- 1 os

27. Some human characteristics show a type of genetically controlled \--ariation somewhat different from the
all-or-none control by specific genes so far considered in!his rep~rt.. These characters can generally be measured
m quantitative terms, and are therefore termed biometrical. They are determined by genes just like those previously discussed except that their effects are so small, or
related to each other and to the environment in such acomplex m~m;1er, .that the effects of individual genes
c31nnot be d1st1~g~ushed, and can only be studied collectively by statisucal methods. Consequently. little ish."tlo~vn experimentally of their mutations or other behav10ur. Yet they are known to exert considerable
eff~ts on such important characters as life-span. birthwe1ght, stature and intelligence. Both the average value
an? the extent .of variations of such characters in a population m~y be influenced by its genetic constitution: andchan_ges m both must be considered in relation to reproductive fitness as well as to their social consequences.
28. There are two questions of basic knowledge thatare largely unanswered: (a) the extent to which the
population average is determined by recurrent mutation
rather than solely by a balance between selective forces
H99-100. of th e genetic. component of'. .<:nd ( b) !he f ract10n
vanab1lity that is due to recurrent mutation H97- 9 s The
possibility cannot be excluded that for some charactersthe mutation rate is the primary factor in determining the
average and t~e var.iability of the population. On theother hand, smce influences such as environmental

Gmeral fertilityns 2 , 10•

31. With appropriate corrections for changes in population size, each unfavourable gene that arises by mutation in a population will be balanced by the elimination
in a subsequent generation of a copy descended from it;otherwise the frequency of the mutant gene in the population would increase cumulatively. The means by whichthese eliminations are brought about is the reduced effective fertility of individuals. This can be thought of asa reduction in the chance that individuals, starting at thetime of fertilization of the egg, will complete normal
reproductive cycles. Thus, in a population in genetic
equilibrium-that is, one in which the appearance ofunfavourable genes by mutation is exactly balanced byelimination-the total of reductions in fertility could be
estimated to a first approximation if all unfavourable
mutations could be detected and counted.
32. Many calculations have been made concerning the033Areas of uncertainty
36. The chief uncertainties associated with an attempt
to assess the consequences of a given increase in radiation centre around the following:(a) The dose required to double the mutation rate, is,for the present, believed to be reliable only within a tenfold range.
(b) Any assessment of the present extent of hereditary defects in the population simply in terms of affected
people is admittedly an incomplete measure of "social
consequences", which can in any case vary from country
to country with the social environment.
( c) The proportion of the hereditary defects which
is maintained by recurrent mutation is not at all certain.
In the absence of adequate and appropriate observations
on the workings of selection pressures in man, present
opinions have had to be based on essentially crude
criteria.
(d) The possible extent to which irradiation would
affect human biometrical characters, their range andmode of variation, is at present largely a matter of
speculation.
( e) The effect of a future environment on the magnitude of the "social burden" is not known. Improvements in social, medical, and biological procedures which
can be brought to bear on human populations might
lessen the effects of some of the deleterious changes.
However, such influences could also operate in the opposite direction. Therefore, we cannot predict how futurechanges in environment will interact with any hereditaryalterations so as to influence the general and the individual states of health in future human populations.

possibility of general reduced fertili~ as a consequenceof increased mutation rate. In the light of these, theCommittee considers that the human race appears tohave sufficient reserve capacity for breeding to n:Cl:ke
the possibility of its slow extinction by reduced fert1~1tyof genetic origin due to doubling of the normal mutatwn
rate by any mutagenic agent seem very remote.Hios
Pool of unfavourable recessive geneSH1 os-ios
33. Although not directly related to the social burdencaused by mutation, the attempt tp n:e~sure. the total ofunfavourable recessive genes per md1v1dual m the population is of great interest.H106 This can be done, because
matings occur between related individuals. such . ascousins. There is a predictable chance that the offsprmg
of such a mating will receive two identical copies of thesame gene from a common ancestor, one copy throughthe mother and one through the father. If the gene has avisible effect and is recessive, it will show up in thesehomozygous progeny more often than in the population
at large. In this way, it has been estimated that eachindividual in the general poulation carries on the average
about one or at most three unfavourable recessive genesof a kind giving rise, when homozygous, to some specificdetectable clinical entity.H101
34. It is also possible to estimate the over-all effect of
unfavourable recessive genes by examining the vitalstatistics of cousin marriages. Although the available
data are somewhat limited and inconsistent, it appears
that the average individual may well contain a numberof unfavourable recessive genes having a total effectequivalent to that of 3 to 5 genes, each of which would,
if homozygous, cause failure to survive to maturity.R107
Comparison of these two estimates, the specific and thegeneral, can in principle give some indication of the
proportion of the total unfavourable effect of recessive
genes upon reproduction and survival that is mediatedthrough specific clinical entities detectable at the present
time. Because the specific conditions studied have aneffect less extreme than total failure to reproduce, this
proportion may perhaps lie in the neighbourhood of
one-third or one-tenth.H 1 o1

Indications for research
37. Although much is known, quantitative estimatesof the mutational consequences of genetically significant
irradiation of human populations remain subject to grave
limitations, especially in the areas just outlined. Theselimitations underlie several of the recommendations forgenetical research made by a study group of the World
Health Organization in a report submitted to this Committee and now published. The Committee draws theattention of the General Assembly to these recommendations, and, in particular, to the following areas ofresearch:(a) Studies of children whose parents hai;e received
substantial radiation exposure, together with investigations of natural mutation rates in man;( b) Studies of the reproductive patterns both ofdiverse human populations and of carriers of detrimental genes ;( c) Studies relevant to the genetics of biometricalcharacters in man. such as intelligence or life-span, andof balanced selective systems in general ;(d) Any other studies which shed light on induced or
natural mutation rates in man or in cells of humantissues;( e) Studies on the production by ionizing radiation,
especially at low doses. of mutations and related eventsin a variety of materials but particularly in the cells of
mammals;(f) Studies of the effects of irradiation on whole
populations ;(g) Studies of the mutation event itself, including
the time and manner in which the mutational process canbe influenced;

SUMMARY

Conclusions
35. It is accepted that radiation-induced mutations are,in general, harmful and increase in direct proportion to
the genetically significant exposure, even at very low
dose levels; and that a dose of between 10 and 100
rads per generation would probably be required to
double the natural mutation rate in human populations.
.t\bout 4 per cent of all births are affected with hereditarydisorders, some one-quarter of which appear to be atle~st la~gely ~etermin~d by single gene differences. On
this basis, an mcrease m the mutation rate would eventually result in a directly proportional increase in a partof this 4 per cent, amounting to more than one quarterbut less than the whole of it. In addition, there would besome changes in other hereditary characteristics of a lesssharply defined nature, but the probable extent of thesea.nd their importai:ice cannot be assessed at the present
tune. The Conumttee concludes from the foregoing
genetic facts that C..'\.posures to ionizing radiation should
be reduced wherever possible, and that medical and industrial procedures tending to increase radiation levels
to whic.li human populations might be exposed should be
carefully weighed as to such benefits or hazards as each
may have.

34

petent specialists become available, and collaboration
with human geneticists by agencies dealing with vitalstatistics, public health, and demography with a view tomaking their data more accessible and suitable for genetic analyses. The lin~s of research pursued must,however, cover a very wide range; experimentation on anriety of plants and animals is essential and is complementary to work on man.

(Ii) Comparative studies of the mutations which
occur naturally and those which are induced by different
ionizing radiations.
38. Certain measures would expedite the needed research on human populations: e:-.1:ended support of thee.xisting research institutes for human genetics, to makepossible the undertaking of long-term research programmes, development of new research centres as corn-

35

Chapter VII

SUMMARY AND CONCLUSIONS
l. LEVELS OF RADIATION

1. In estimating the possible hazards of ionizing radiation, it is clearly necessary to know both the levels ofsuch radiation received by man and his environment
from various sources, and the present and future effects
likelv to be produced thereby. It is of particular importance to assess the effects of radioactive fall-out from
nuclear weapons, since this source of general environmental contamination is of recent origin, has been of uncertain significance, and has led to concern in the minds
of many people. All sources of radi<l;tion must, ~oweyer,
be reviewed for a complete evaluat10n of the s1tuatwn.

7. Table I summarizes our estimates of the averageamounts of radiation likely to be received by populations
during specified periods, and gives the basis for a comparison between the amounts received from natural andartificial sources. The method of calculation is describedin chapter III, the averaging periods of 30 and 70 years
being used as relevant respectively to transmissible
genetic changes and to somatic injury during the lifetimeof an individual. The estimates for medical e..xaminations
and occupational exposures are based upon the present
situation in certain countries with developed facilities,
rather than on a forecasted world average. The values
quoted for various hypothetical future circumstances are
not intended as predictions, but are calculations based onassumptions discussed in chapter III, and the values andranges are subject to all the uncertainties outlined there.

2. The Committee, aware of the complexity of thistask, knows that our present information about radiationlevels and effects is inadequate for an accurate evaluationof all hazards, and that many of the estimates will necessarily be approximate or tentative.
3. The physical characteristics of ionizing radiation,and the amounts of human exposures to it, are at present
more accurately known than its biological consequences,
especially where small doses and dose rates are concerned. In the present chapter, therefore, we review firstthe amounts of radiation received by man, both in regard
to the exposure of individuals and of whole populations,and in respect to present and possible future levels. We
then attempt to estimate the biological effects of varying
amounts of radiation of different types, and to evaluate
the hazard resulting from certain sources of particularsignificance.

Radiation from natural sources

8. The radiation received by man from natural
sources varies somewhat from place to place according
to the local radioactivity of the earth's surface; and thatof only occasional populated areas exceeds the average
by a factor of 10. Studies on populations living in theseareas are of extreme interest for the development of ourknowledge on the effects of small doses of radiation. The
contribution from cosmic rays differs at different altitudes and geomagnetic latitudes. That from the normal
radioactive potassium and carbon content of the body isabout the same in different people, but the radiation due
to radium. thorium and their decay products varies considerably. The radioactivity of the masonry used forsome types of dwelling may appreciably increase theradiation e..xposure of the occupants. The variations inlevels of irradiation from natural sources are discussed
in chapter III; the magnitude of these variations, as well
as of the average level, is informative in making comparisons with exposures due to artificial sources. Harmful effects attributable to radiation from natural sources
are not known with any certainty, but it seems likely thatsome genetic, and possibly some somatic, injury is causedin this way.

4. The relevant physical data refer to the world's
population as a whole, as well as to individuals andgroups of people receiving relatively higher e..xposures
because of their occupation or place of living. These exposures may involve the whole body uniformly, or may
be greater for certain organs or tissues, as when radioactive material is selectively concentrated in them.

IL

5. Tissues of the embryo, of the bone and bone marrow, and of the gonads are of particular importance.
Irradiation of the embryo (and of the foetus) may lead
to abnormalities of development or may prove fatal. Irradiation of bone marrow and of bone may give rise toleukemia and to bone tumours, and these tissues are subjected to higher doses than other tissues of the body byradioactive materials such as strontium-90 and radium
which become concentrated in bone. Irradiation of the
gonads is able to bring about changes in the hereditarymaterial; and these may be transmitted to subsequent
generations if the irradiation is received before or during
the years of reproductive activity.
6. As with any scientific assessment, the conclusionsof this report must be subject to revision in the light ofadvancing knowledge; and the Committee hopes that thereport itself, after submission to the General Assembly,
will assist this advance by stimulating critical discussion
amongst scientists. In view of the complex nature of thesubject, individual sentences or assessments may easily
be misunderstood unless related to the context of thereport as a whole.

Exposure diee to medical procedz,res

9. It is useful to estimate this exposure, appropriately
averaged over whole populations, since the genetic, andperhaps some somatic, effects of these procedures will
depend upon this average value. In the countries withextensive medical facilities where its magnitude has been
estimated, the radiation given for medical purposes
makes the largest artificial contribution to the irradiationof the population, but no data are available for countries\Vith fe\ver such facilities. The reported values of genetically significant doses are of the same order as the doses
from natural sources. Among medical procedures, thecontribution from diagnostic X-ray examinations greatly
exceeds that from radiotherapy and radioisotope applications, the latter making only a small contribution; and36

TABLEI.

EsTnIATED DOSE FROM DIFFERENT RADIOACTIVE SOURCES(Computed from world-wide averages)
SourceGe,,,,:icaUy •icnificanl dos•
Maximum .far any JO-year period (r<m)DIU. Per ea.pita mean mana:D dose
.l!a:smum for '"'Y 7~ar period (r<m)D:!l3

7

Man-made sources (except environmental contamination and occupational
exposure)" ....................... .

0.5-5

Occupational exposureb •..............

Less than 0.06

Ranges beyond 7
0.1-0.2

Natural sources ..................... .

E.stimaJu for counlries

Environmental contamination(hypothetical cases)c. d"riring 11'.0St of dfrtary
cakiumfrom milk<\Veapon tests cease at end of 1958 ..

Weapon tests continue until equilibrium is reached in about a hundredyears• ....................... .

0.16

0.010

0.96

.-tssumplion at

Anumptian bi

Assumplion al

Assumption bi

Assumptiosc alAssumpticm bt

0.060

0.12

1.3

2.8

7.5

17

Estimated peranlaits of t/ie maximum doses for continued weapon tests

Weapon tests cease1958 ......................... .
1968 ......................... .
1978 ......................... .
1988 ......................... .
\Veapon tests continue ........... .

Assumption at

Assumption bi

Assumptian atAssumption b'

17
42
64
79
100

9
33
56
67
100

13
24
34
42
100

6
16
26
35
100

•For countries having an extensive use of the radiation sources
listed and reporting data to the Committee.
b Doses for certain technologically highly developed countries
only.
•Computed from population weighted world-wide average ofstratospheric fall-out rate and deposit.
d Regional values may differ by a factor of about U to 2 fromthe estimated population weighted world-wide average values
because of the latitudinal variation of fall-out rate and deposit.
In some areas of the world the tropospheric fall-out may tend toraise the upper limit of this range, especially in the Vicinity oftest sires.
•The extent to which these estimates apply to populations ofdifferent dietary habits and to those living in areas of differingsoil conditions is discussed in paragraph 69 of chapter Ill.
1 Assumption a is that the injection rate is such as to maintain aconstant fall-out rate of strontium-90 and caesium-13i, whereas
assumption bis that weapon tests equivalent in release and stratospheric injection of fission products to the whole sequence ofweapon tests from the beginning of 1954 to the end of 1958 will
be repeated at constant rate. This second assumption will givean equilibrium value for the fall-out rate and deposit approxi·
mately a factor of 2 higher than that calculated by using the first
assumption.
•The values for the 30-year doses have been corrected for tropospheric fall-out in accordance with paragraph 57 of chapter Ill,using a value of 0.5 mrem/year for the period of testing.

80 to 90 per cent of the total diagnostic dose to the gonads
is due to relatively few types of examination of theabdomen and pelvis.
10. Most of these values are preliminary estimates,
and further investigations are needed, for which procedures have been suggested by the International Commissions on Radiological Protection and on Radiological
Units and :Measurements in a report prepared at therequest of this Committee and submitted to it in document A/AC.82/G/R.117.
11. The significant dose to bone and bone marrowfrom medical procedures has been less closel;y studied
than the genetically significant dose, although 1t may beof importance if bone tumours or leukemia are inducedby radiation at low dose levels. Although individual marrow exposures vary very \videly, the average is unlikely
to differ greatly from that received by the marrow fromall natural sources.
12. The contribution made by medical procedures tothe radiation exposure of populations has only lately
been estimated and has increased very rapidly in somecountries in recent years, so that it is difficult to evaluate
such genetic and somatic effects as are associated with anincreasing employment of radiological procedures inmedicine. No information is yet available for predictionof the future trend of medical e."{posures. It is expectedthat improvements in equipment and techniques may
considerably reduce individual exposures, but the evere."{panding use of X-rays may well increase the world
population dose. Precautions of the type described by theInternational Commissions on Radiological Protection
and on Radiological Units and Measurements shouldmake possible such reduction of exposure to radiation
as is without detriment to the medical value of theseprocedures.
Occupational exposure
13. At present, the exposure to ionizing radiation received occupationally forms only a small contribution to
the total irradiation of the population as a whole, amounting to about 2 per cent of that from natural sources incountries in which occupational e.xposure is probably
largest. With an increasing use of nuclear reactors, _ofradioactive materials and probably of medical and industrial radiological procedures, this is clearly a figu~ewhich should be kept under close review. Although thissource does not appear likely to make a substantial ~on­tribution to the total radiation e.'Cposure of populationsin the immediate future, the occupational C;xposure ~fsome individuals may represent a large fract10n of their
total radiation exposure.

37

ried several times around the world. This troposphericfall-out consists of a mixture of radioactive materials,
most of which are short-lived isotopes. At the present
time, the tropospheric fall-out is deposited intermittently
during the year and a certain deposit of short-lived
activities is built up and maintained. When appropriate
factors for shielding and weathering effects are included,
the gonad and average marrow dose from this deposit,
as an external source, is calculated to be about 0.5 mrem
per year.
20. Transient increases of the doses from tropospheric fall-out have been observed in limited areas
shortly after weapon tests. These transient increases may
give rise for a few days to dose rates of the order of
those from natural sources.
21. The radioisotopes of tropospheric fall-out may betaken up into the body by inhalation and ingestion. Since
the radioisotopes of principal concern are short-lived,
storage of the contaminated food products reduces thedose which they contribute. The gonad dose over thewhole population from inhaled and ingested troposphericmaterial is negligible as compared with the contribution
from this material as an external source. The averagebone marrow dose from internal sources is about 0.2
mrem per year.
22. Increases in radioactivity of the thyroid glandhave been found during periods of several weeks or a
few months following weapon tests. In human thyroids
a dose from iodine-131 of about 5 mrem per year has
been estimated for 1955-1956 in the United States excluding areas immediately adjacent to weapon test sites.
Doses of this order are unlikely to cause detectabledamage or functional change in the gland.
23. Irradiation of bone may result from incorporationof intermediate and short-lived fission products. Although these materials do not cause prolonged irradiation, they may become selectively concentrated into thoseareas of bone in which active growth is taking place atthe time, and so cause more intense radiation locallythan if the same amounts of these materials were distributed throughout the whole skeleton.
24. The Committee has insufficient information on
local variations and temporary increases of troposphericfall-out in populated areas at different distances from
weapon test sites, and emphasizes the lack of further
data which would permit evaluation of the biological significance of this source of environmental contamination.

14. Since 1928, the International Commission on
Radiological Protection has recommended "maximum
permissible doses" for those who are occupationally exposed to radiation, ~nd has proposed appropriate methods of measurement. Their present recommendations,which have recently been reviewed in the light of progress
in radiobiological knowledge and which propose reductions in dose levels, may not be final but are at present
widely accepted as a sound basis for the protection of
those exposed occupationally to ionizing radiation.

t

I

Radioactive wastes
15. The discharge of radioactive waste in countries
with nuclear reactors has not Jed to appreciable radiation
exposure of populations, and only small proportions of
the wastes produced need to be discharged. The likely
future extension in the use of such reactors, however,and the possibility of accidental releases of fission products, clearly require that this subject be kept underreview. It is important that work should be actively
continued on methods of minimizing environmental contamination from these causes.
Radiation from fall-out
16. Fall-out from nuclear weapon tests causes radiation exposure in several ways (chapter III). Exposureof the world population results from the slow fall-out
of fission products which have been distributed in thestratosphere. Exposures also result from any fall-out
from the radioactive "cloud" which passes through thetroposphere without having reached the higher stratosphere, and from the fall-out which may occur in areas
adjacent to weapon tests or within some thousand kilometres of them.

17. We also consider the ways in ,.,·hich fall-out
material causes irradiation to different parts of the body,to people on different diets or under different agricultural
conditions, and to people of different ages: and thechange in the amounts of radiation that would result
from altered or unaltered rates of injection of radioactive materials into the stratosphere.
Fall-out adjacent to tests
18. The early fall-out of radioactive materials near tothe sites of nuclear explosions, which is influenced byvarious meteorological and testing conditions, may cause
high radiation exposure to individuals within these areas.
The amount of such radiation exposures varies veryg~catly with the weapon tested, with the height of firing,with the distance from the point of explosion, with thedirection of winds at various altitudes and with thechance occurrence of rainfall through radioactive material in the early hours after the test. Therefore, at present, these doses cannot in general be calculated. Undervery special conditions, high radiation exposure anddeleterious effects have been reported, as in the cases ofthe Marshall Islanders and the crew of a Japanese fishing vessel. Not enough information is available as to thegeneral circumstances in which such local deposition
may occur, and the extent and duration of the exposuresliable to be involved.

W orl.d-'Wide fall-out from the stratosphere
25. Radioactive materials injected into the stratosphere, especially by high-yield nuclear explosions, constitute a reservoir from which they fall onto the wholeof the earth's surface for many years. The rate of fallout varies with latitude and is greater in the northernhemisphere, where most of the tests are carried out.
\Vithin any given small area, fall-out rate may also varywith local meteorological conditions. The figures given
in table I are computed from world-wide average deposits from stratospheric fall-out. The radiation due tostratospheric fall-out from weapons exploded so far willcontribute a 30-year gonad dose of 10 mrem, and a 70year per capita mean marrow dose of 160 mrem and 960
mrem for two populations deriving most of their dietarycalcium from milk and rice respectively.
26. Owing to the relatively gradual fall-out from thestratosphere, most of the subsequent radiation is due to
two radioactive isotopes of slow decay, other fission

Fall-out from the troposphere
19. Radioactive materials injected into the atmosphere
below the tropopause (at about 14 km) are brought down
to the earth's surface bv rainfall and sedimentation. This
process takes a few months during which they are car-38

of ~etary_ calcium and strontium-90, and where low
calcmm soils are frequent. These two estimates demons~rate the pre~ent range i;if known dietary contaminations. They will be used m an attempt to estimate thehazard of radiation from fall-out in paragraph 57 below,
effects
when the nature and frequency of the bioloaical0of radiation have been considered.

products already having largely undergone decay. These
two radioactive isotopes are caesium-137 and strontium90. The physical properties and chemical behaviour of
the two differ.
27. Caesium-137 is responsible for most of the gonad
radiation from fall-out noted in table I. 'When it is taken
into the body, it becomes distributed more or less evenly
throughout the tissues, causing uniform irradiation of
the whole body; and when present in the surroundings,
its penetrating gamma radiations cause a similarly uni~
form irradiation of tissues.
~8.

33. It is evident that the radiation exposures fromfall-out which are most likely to be of significance are:(a) ~ose fr<;>m short-lived fission products andradioactive material due to local or tropospheric fall-out :( b) Those of the gonads and other organs from
caesium-137 due to stratospheric fall-out;(c) Those of bone and adjacent tissue from strontium-90 which also comes largely from the stratosphere.
The relative importance of these contributions varies
from region to region.

Strontium-90, on the other hand, is not a gamma-~1tter _and does not contribute significantly to the irradi-

at10n ot any part of the body from without. However,?n being taken into the body, it becomes incorporated
m bone because of its chemical similarity to the normal
element calcium. This similarity with
calcmm and selective concentration in bone raises problems which do not occur with caesium-137.

bon~-forming

I!. BIOLOGICAL EFFECTS OF RADIATION
34. The biological effects of ionizing radiation are
exhibited in different ways according to whether isolated
cells, tissues, organs or organisms are examined. In
passing from unicellular to higher organisms, the primary physicochemical consequences of radiation become
increasingly influenced by secondary effects due to thereactions of the organism to the primary events. Detailed
knowledge of these reactions is needed for a full understanding of the results and mode of action of radiation.
The following paragraphs deal first with the cellulareffects of radiation : then with the somatic effects on theirradiated individual and with the genetic effects on hisprogeny.

29. The average concentration of strontium-90 in thebones of children, in whom new bone is continuously
being formed. is higher than in adults whose bones werelargely formed before the environment, and consequently the food supply, became contaminated withstrontium-90. The highest concentrations of strontium90 in bone have in fact been observed in children from a
few months to five years old. The bone marrow exposures from fall-out given in table I are due to thestrontium-90 content of bone and refer to the concentrations estimated for children of these ages. The corresponding exposures of bone cells from fall-out are, on
the average . about three times the values for bone marrow. Marrow cells almost enclosed by bone would receive
doses similar to those in compact bone. The maximum
marrow dose could differ by a factor of about 5 fromthe average level.

35. The effects of ionizing radiations on living matterare extremely complicated, and their exact mechanisms
are still largely unknown. The initial disturbance is associated with ionization (and excitation) of molecules
which lead to alterations in their properties. Many functions of the cell are thus affected by radiation, and, although some specific effe~ts may be caused by one or a
few events in the cell, many are probably the combined
result of numerous such events.

30. The radiostrontium concentration in bone is also
affected by dietary habit and by the ratio of the amountsof strontium-90 to calcium in the diet. At present thisratio differs in various dietary constituents : it is higher
in brown rice than in white . somewhat higher in many
vegetables than in milk products, higher in rain-water
than in river water, and lower in sea fish than in freshwater fish.

36. The minimum doses causing certain detectablebiological effects differ very much in different organisms,
but for most mammals they are of about the same magnitude. so that the results of ex:periments on such animals
can, as a first approximation, be applied to man. The
sensitivity of different tissues to radiation varies considerably, however. Our knowledge of the biologicaleffects of low radiation levels is meagre because of experimental difficulties and the lengthy obsenrations necessary to obtain results in this field. At present, opinions
as to the possible effects of low radiation levels must be
based only on extrapolations from experience with highdoses and dose rates.

31. Agricultural conditions may also affect the content
of strontium-90 in the diet, since the available calciumof the soil will. within certain limits, influence the ratioof strontium-90 to calcium in crops derived from thesoil. The distribution of soils which are highly deficientin calcium and their utilization require further study.
More work is also needed to understand the distributionof strontium-90 in the soil, its chemical availability toplants and uptake through their roots, its behaviour
un~er ploughing a;id the leaching of it from soil by theact10n of water, smce the figures in table I for futures~rontium-~O levels In bo~e are calculated on the assumpt10n that this matenal will not be leached from soil andthis assumption may lead to unduly high values. 'Effects of radiations on man
37. Man may prove to be unusually vulnerable toionizing radiations. including continuous exposure at
low levels. on account of his known sensitivity to radiation, his long life, and the long interval betw-een conception and the end of the period of reproduction.

32. Bone marrow exposures from fall-out are given intable I for two conditions: one based on observations in
the Unit~d S.tates of -~merica and the United Kingdom,
where milk 1,s the mam source b~th of dietary calcium
and of strontmm-90, and where soil calcium contents arecommonly high; and the other based upon data from
J~pan where milk products are much less used and where
nee and other vegetable products form the main source

38. Embryonic cells are especially sensitive to radiation, and some evidence suggests that exposure of tJ;efoetus to small doses of radiation may result in leukem1aduring childhood. Irradiation of pregnant mammals has
shown that doses exceeding 25 rem to the foetus daring
39

certain stages of its developmen~ can cause abnormalities

grafting of blood-forming tissue has so far been successful only in small mammals irradiated with a lethal doseto the whole body, and no attempt to apply this treatment
to irradiated man has yet been reported.

in some organs. Some embryomc cells (neuroblasts) of

'
I
il
I

!I

I

,I

I'

certain species cultivated in vitro respond to doses as
small as 1 rad. If these results should be applicable to
man and since they relate to the development of thebrain, the opinion seems justified that even a very small
dose to the human foetus may involve some risk of
injurious effects if received during a critical period ofpregnancy. Radiostrontium must be expected to enter
foetal bone when calcification starts in the second trime.ster of pregnancy, and so cause irradiation ?f ~headjacent developing nen•ous system and hypophysis withe.xposures ranging up to that occurring in the bone. The
uptake of radiostrontium in foetal bone tissue is, however, at present very small, contributing less ra~ation
than 1 per cent of that due to natural sources; but if thepresent rate of test explosions is continued, it will rise
ultimately to some 10 per cent of that due to natural
sources.

45. Prevention of the effects of radiation is renderedmore difficult, and complete protection against it impossible, because changes which already occur during theirradiation lead to later damage. The discovery of chemical protectors, although important theoretically, has not
yet yielded methods which appreciably reduce radiation
damage in man. At present. effective protection fromexternal radiation sources can only be achieved by adequate shielding or by keeping at a safe distance from thesource. Much work is in progress on the effect of certain(chelating) agents in discharging from the body radioisotopes incorporated there, and so diminishing exposure
to internal irradiation.
46. Morphologically recognizable damage may be induced by total or partial, continuous or intermittent
irradiations much in e.iccess of the currently accepted"maximum permissible levels" of occupational exposure.
Such damage includes leucopenia, anemia and leukemia.
Other pathological conditions such as cataract, carcinomaof the thyroid, and bone sarcoma are known to have resulted from partial body irradiations, but with rather
high doses involving hundreds or even thousands of rem
given to these organs.
47. The shortening of the life-span in small rodents
exposed to large doses has suggested the possibility thatcertain degenerative processes may be aggravated bycontinued e.icposure to low radiation levels. Such ashortening has also been inferred from an analysis of the
published death rates of United States radiologists compared with those of certain other groups of medical men.
However, studies in the United Kingdom have failed todemonstrate such an effect.

39. Children are regarded as being more sensitive toradiation than adults, although there is little direct evidence on this subject, except for an indication thatcancer of the thyroid may result from doses of a few
hundred rad which do not induce this change in adults.
40. In human adults it is difficult to detect the effectof a single exposure to less than 25 to 50 rem, or of continuing exposure to levels below 100 times the naturallevels. The first sign of radiation damage to the bloodforming tissues seems to be a drop in the number oflymphocytes and platelets and the appearance of abnormalities such as bilobed lymphocytes.
41. Rapid but transient disturbances have been observed in mammals after exposure to a single dose of
25 to 200 mrem. Appropriate biochemical and physiological techniques have, however, only recently been
applied to the study of irradiated organisms, and have
not yet given a clear picture of what happens to organisms irradiated with small doses or dose rates. Too few
mammalian species have hitherto been studied in thisrespect, and there is a clear need to widen this basis,from \vhich inferences can be drawn concerning man.

48. Present uncertainty about the effects of low doselevels makes it imperative that as much relevant information as possible be collected about groups of persons
chronically exposed at these levels and for whom adequate control groups exist, for instance, certain populations in areas of high natural radiation and workers inuranium mines.

42. Processes of repair play an important role in the
final outcome of radiation damage. They are one causeof the existence of a threshold dose (or dose rate)characterized by the fact that this dose or greater ones
produce a particular biological effect which does notappear when the dose is less than the threshold. In thelatter case, physicochemical events have cx:curred. but
recovery processes have prevented the final appearanceof the biological damage. Threshold doses are found forsome somatic effects, such as erythema of skin. Other
forms of radiation damage to cells, tissues or organisms,
however, appear to be cumulative; for instance, mutational damage, once established, is not repaired.

49. Exposure of gonads to even the smallest doses ofionizing radiations can give rise to mutant genes whichaccumulate, are transmissible to the progeny and areconsidered to be. in general, harmful to the human race.
As the persons who will be affected will belong to future
generations, it is important to minimize undue exposuresof populations to such radiation and so to safeguard thewell-being of those who are still unborn.
50. The present assumption of the strictly cumulative
effect of radiation in inducing mutations in man is based
upon some theoretical considerations and a limited
amount of experimental data obtained by e.xposure ofexperimental organisms to relatively high dose levels.
This assumption underlies all present assessments of themutational consequences of irradiation. Therefore, extension of the experimental data to the lowest practicable
dose levels is needed.

43. Damaged cells or tissues may be eliminated andreplaced by regenerated normal cells. this process being
most active in embryos and young animals and in certain
tissues of the adult. The affected cells may also re-establish apparently normal biochemical functions. During
the process of regeneration of tissues damaged by radiation, malignant tumours may be induced.

51. The knowledge that man's actions can impair his
genetic inheritance, and the cumulative effect of ionizing
radiation in causing such impairment, clearly emphasize
the responsibilities of the present generation, particularly
in view of the social consequences laid on human populations by unfavourable genes.

44. The power of repair differs considerably in different organisms and types of cells, and varies to a highdegree with the physiological conditions. No chemicaltreatment has yet been discovered \Vhich will induce or
accelerate recovery from radiation damage in man. The
40

( b) Both natural radiation and r~diation from fall-possibility cannot be excluded that our present estimates
exaggerate the hazards of chronic e.~posure to low levelsof radiation. Only further intensive research can establish the true position.**
57. Any present attempt to evaluate the effects ofsources of radiation to which the world population is
exposed can produce only tentative estimates with wide
margins of uncertainty. Estimates are given in chapter
III for the radiation exposure of populations from such
sources, and in chapters V and VI for the likely somaticand genetic effects of given exposures. On the basis ofthese, the Committee has tried to evaluate the possible
effect of natural and of fall-out radiation in causing leukemia, tumours of bone and major genetic defects (tableII) since these are conditions which may possibly be induced by irradiation at low dose levels. The methods ofcalculation, and the main sources of uncertainty in theseestimates, are described in chapters III, V and VI, where
factors of correction are also given for the different estimates corresponding to differences in the assumptions on
which the calculations are based. It will be evident thatthe estimates indicate only the order of magnitude of thefrequency with which effects may be produced, and that
our ignorance as to whether thresholds e.'<ist for the
induction of leukemia or bone tumours by radiation
cause the greatest uncertainty in the estimates.
Indications for research
58. This report presents evidence both of the increasing levels of radiation exposure, and of our uncertainties as to the nature and extent of the effects ofradiation on man, particularly when received at low dose
rates over long periods. It is most important, therefore,that scientific research and the collection of informationon the effects of radiation should be actively continued
and developed so that the uncertainties in all branches ofradiobiology are reduced or removed.

out inYolve the whole world population to a greater. or
lesser extent, whereas only a fraction of the population
receive medical or occupational exposure. However, ~heirradiation of any groups of people, before_ and durmg
the reproductive age, will contribute genetic effects towhole populations in so far as the gonads are exposed.
( c) Because of the delay with which_ the s?ma?ceffects of radiation may appear, and with which its
genetic effects may be manifested, the full _extent of thedamage is not immediately apparent. It 1.s. therefore,
important to consider the speed with. which levels of
exposure could be altered by human act10n.
It is clear that medical and occupational ~xposure, a~dthe testing of nuclear weapons, ~a~ be mfluenced :>yhuman action and that natural rad1at10n and the fall-out
of radioactiv~ material already injected into the stratosphere, cannot.
56. Present knowledge concerning long-ter~ _effects
and their correlation with the amounts of radiation received does not permit us to evaluate with any precisio.n
the possible consequence to man. of e~p9sure to low radiation levels. Many effects of 1rrad1at1on are delayed;often they cannot be distinguished from effects of otheragents; many will only develop once a. threshold dose has
been exceeded; some may be cumulauve an? others not:and individuals in large populations, or part1cul~r grou~ssuch as children and foetuses may have special sens1tivitv. These facts render it very difficult to accumulatereliable information about the correlation between small
doses and their effects either in individuals or in large
populations. £yen a slow rise in the environmental radioactivity in the world, whether from weapon tests or any
other sources, might eventually cause appreciabl_e dan:iageto large populations before it could be defini~ely_1dentified
as due to irradiation. Appearance and elimmatton of adverse genetic effects would be very slow ; and, as theradioactive contamination accumulated, it might so act
as to increase the likelihood of somatic injury in individuals due to the additional exposure. Such a situation
requires that mankind proceed with great caution in viewof a possible underestimation. At the same time, the
TABLE

l I.

**The maximum permissible levels of exposure and maximum permissible body burdens of radioactive isotopes recommended in 1954-1955 by the International Commission on
Radiological Protection as applying in the case of occupational
exposure must not be misinterpreted to apply in the case of
exposure of whole populations.

ESTHL.\.TES OF CERTAIN POSSIBLE ANNUAL CONSEQUENCES OF RADL.\TION RECEIVED BY
WORLD POPULATION FROM CERTAIN SOURCES
Souru of radiaJion
World population

1JSsumed

Un millions)Ltukemia
If threshold 0 rem .....•.......... 13,000
5,000
If threshold 400 rem .............. 3,000
5,000
Major Genetic Defe.ctse . . . . . . . . . . . . . . 5,000

Fall-oulfram toeapcm tests

Z.oalural 0<currmu
assumed per ~~arNatural radiation

Tests

stoppint
in 1958

150,000
250,000
150,000
250,000
700,000 to 3,000,000

15,00025,000ObOb
25,000 to 1,000,000

Jn equilibrium
after prolonged

ccmliJ<ua1ion of tests

400 to 2000•
5,000 to 60,000
0d500 to 40,000

difficulties. If it were assumed that 5 to 10 cases per million
normally occurred per year, and that 10 per cent of these were
induced by natural radiation the followinf figures could be calculated from the 70-year osteocyte doses i a non-threshold hvpothesis were assumed:'
For tests stopping in 1958 and world population 3,000 million,
70 to 900 per year (as the maximum rate).
In equilibrium after prolonged continuation of tests and world
population 5 ,OOO million, 1,000 to 25,000 per vear (as the continuing rate).
•
If a threshold of 400 rem were assumed, the incidences would
be zero unless individual osteocyte doses exceeded the mean value
by a factor of SO to 500 in the case of tests stopping in 1958 andby a factor of 5 to 60 in equilibrium after prolonged continuationof tests.

• !\Iaximum rate during peak period. An estimated total ofless than 25,000 to 150,000 would ultimately occur.
b Unless individual bone marrow dose exceeds mean value by
a factor of 60.
c Unless individual bone marrow dose exceeds mean value by
a factor of 80 to 500.
d Unless individual bone marrow dose exceeds mean value by
a facto~ of 5 to 60.
° Conditions which are at least a serious handicap to thoseaffected, as listed in table Xl of annex H.
r A total of 2,500 to 100,000 would occur over subsequent years.
!\ OTEs.-The methods of estimating incidences of leukemia
and major genetic ct.efects are described in annex D, paras. 127
to 130.
:rhe quantitat: .e evaluation of an increase in incidence ofprimary bone tumour attributable to radiation presents great42

involve national and international decisions which lie
outside the scope of its work.*t

52. Besides increasing the incidence of easily discernible disorders, many of them serious but each comparatively rare, increased mutation may affect certain
universal and important "biometrical'' characters suchas intelligence or life-span. In this way, it is possible that
continued small genetically significant exposures of a
population may affect, not only a correspondingly small
number of individuals seriously. but also most of its
members to a correspondingly small extent. While lesseasy to detect, this second kind of effect on a population
could also be serious. Unfortunately, the great majorityof the genes affecting the ·'biometrical'' characters are
not individually detectable and so can only be studied
collectively and with difficulty. In consequence, far lessis known about them than about genes responsible forindividually detectable changes and very little indeed
about their response to irradiation, even in the beststudied experimental organisms. Hence it is impossible,
at the present time, to estimate with any assurance theeffect upon biometrical characters of any given level ofirradiation of human populations. Much further researchthroughout this field is therefore needed.

55. Certain general conclusions emerge clearly fromthe foregoing part of this report:(a) Even the smallest amounts of radiation are liable
to cause deleterious genetic, and perhaps also somatic,
effects.
*The USSR submitted a draft proposal for paragraph 54
which, as amended by Czechoslovakia with the agreement of
the USSR, read as follows :"The scientific information received by the Committee indicates that the genetic effects of radiation must be considered
reactions for which there is no threshold. This means that
any increase in the exposure of the human organism to radiation will lead to an increase in the incidence of hereditarydiseases. According to one body of scientific opinion, malignant
neoplasms and also leukemias are diseases the incidence of
which may increase as the level of radiation rises. These data,
together with the fact that there is very little likelihood thatthe human organism can adapt itself to conditions of increased
environmental radiation, indicate that any increase in the radiation dose above the natural radiation level must be considered
undesirable for mankind. Efforts should accordingly be madeto improve the physical basis and the technique of the medical
use of radiation by formulating more precise indications forthe use of radiation and by eliminating adverse side effects.
It is also essential to develop, on the basis of broad international co-operation among scientists, research on the improvement of protection and safety techniques in atomic industry
and in science and technology. The physical and biological
data presented in the report make it plain that efforts should
be made to eliminate the uncontrolled source of radiation, i.e.,
to end experimental nuclear and thermonuclear explosions,and enable the Committee to draw the conclusion that there
should be an immediate cessation of test explosions of nuclear
weapons."
This proposal was rejected by the following roll-call vote:
In favo11r: Czechoslovakia, Union of Soviet Socialist Republics, United Arab Republic.
Against: Argentina, Australia, Brazil, Canada, France, Japan,
Mexico, Sweden, United Kingdom of Great Britain and Northern Ireland, United States of America.
Abstaining: Belgium (Chairman}, India.
The above te-"<t e-xpresses the dissenting view of Czechoslovakia, the United Arab Republic and the USSR to the wordingof paragraph 54, which was approved by a majority of theCommittee.
t India also submitted a draft proposal for paragraph 54
which, with amendments accepted by India, read as follows:"The exposure of mankind to ionizing radiation at present
arises mainly from natural sources, from medical and industrial procedures, and from environmental contamination due
to nuclear explosions. The industrial, research and medical
applications expose only part of the population while natural
sources and environmental sources expose the whole population. The artificial sources to which man is exposed during
his work in industry and in scientific research are of value inscience and technology. Their use is controllable, and exposures can be reduced by perfecting protection and safety
techniques. All applications of X-rays and radioactive isotopes
used in medicine for diagnostic purposes and for radiation
therapy are for the benefit of mankind and can be controlled.
Radioactive contamination of the environment resulting from
explosions of nuclear weapons constitutes a growing increment to world-wide radiation levels. This involves new andlargely unknown hazards to present and future populations;these hazards, by their very nature, are beyond the controlof the exposed persons. The physical and biological data contained in the report lead to the conclusion that it is undesir~ble
to allow any general rise in the level of world-wide ~ntamu:_ia­tion because of its harmful effects and that any activity which
produces such a rise should be avoided. Nuclear tests are themain source at present which produce such a rise."This proposal was rejected by the following roll-call vote:
In favo11r: Brazil, Frarice, India, Japan, United States ofAmerica.
Against: Argentina, Australia, Mexico, Sweden, United
Kingdom of Great Britain and Northern Ireland.
Abstai11ing: Belgium (Chairman}, Canada, Czechosloyakia,
Union of Soviet Socialist Republics, United Arab Republic.

53. The Committee emphasizes the urgent necessity
for well-planned investigations which may lead to abetter understanding of the mechanism of mutation andthe eventual possibility of controlling this process. Moreinformation is needed on the effect of radiation in inducing mutations in man. Indeed, even the dose required to
double the normal mutation rate in man is not knownwith any accuracy. There is also need for a much closer
co-operation between geneticists and demographers in
elucidating the nature of the complex process of humanselection. Many important subjects of relevant geneticalresearch have been reviewed by a study group of theWorld Health Organization in their report "Effects ofRadiation upon Human Heredity", document A/AC.82/
GjR.58.

III. GENERAL CONCLUSIONS
54. The e..xposure of mankind to ionizing radiation atpresent arises mainly from natural sources, from medical
and industrial procedures, and from environmental contamination due to nuclear e..xplosions. The industrial,
research and medical applications expose only part ofthe population while natural sources and environmental
sources expose the whole population. The artificial
sources to which man is exposed during his work inindustry and in scientific research are of value in scienceand technology. Their use is controllable, and exposures
can be reduced by perfecting protection and safety techniques. All applications of X-rays and radioactive isotopes used in medicine for diagnostic purposes and forradiation therapy are for the benefit of mankind and canbe controlled. Radioactive contamination of the environment resulting from explosions of nuclear weapons constitutes a growing increment to world-wide radiationlevels. This involves new and largely unknown hazards
to present and future populations : these hazards, by theirvery nature, are beyond the control of the e..xposed persons. The Committee concludes that all steps designed tominimize irradiation of human populations will act tothe benefit of human health. Such steps include the avoid:i-nce of unnecessary exposure resulting from medical,
mdustrial and other procedures for peaceful uses on the
one hand and the cessation of contamination of the environment by e..xplosions of nuclear weapons on theother. The Committee is aware that considerations involving effective control of all these sources of radiation

41

59. Our knowledge of radiation and of its hazards is
not however static; although still limited, it has been expanding rapidly. In recent years, considerable and sometimes spectacular advances have been made in our
understanding of many of these matters. In the light ofgeneral scientific experience, the Committee confidently
expects that continuing research on an increasing scale
will furnish the knowledge urgently needed to master
those risks which we know to be associated with thedevelopment and scope of the uses of nuclear energy for
the welfare of mankind.

experimental nuclear explosions require further investigation. In particular, more evidence is required on the
behaviour of fission products in the stratosphere. Collation of information is needed to determine the patternand e.xtent of global fall-out on land and oceans. Far
more e..xtensive information is needed as to the mechanisms whereby fission products, particularly strontium-90
and caesium-137, reach food-chains and enter the human
body, as well as the concentration of those materials inhuman tissues, particularly under the conditions where
this is likely to be greatest.

Indications for research into radiation levels
60. The doses received by both individuals and whole
populations from various sources are not yet adequately
known. Consequently,(a) The range of tissue dose rates due to naturalradioactivity, particularly in heavily populated areas withadequate demographic records , as well as the variations
in content of natural radioactive substances in humanbeings need further e..'{amination;( b) Fuller information is required as to the e.xposureof various populations to radiation during industrial procedures and during medical procedures, especially in so
far as this involves children or foetuses and exposure of
the bone marrow or gonads. It would be valuable if thesefurther investigations could provide ( i) a more representative estimate for some countries already studied,(ii) a fuller study of the dosage associated with thevaried extent of medical facilities in different countries,(iii) clearer estimates of the radiation given to different
tissues, including bone, (iv) the contribution from radiotherapy and ( v) a continuing study of future developments and of changes in the medical radiation e..xposure;( c) More extensive research is required on the fateof industrial radioactive effluents of various types and on
the prevention of radiation exposures of populations
from this source;( d) Many factors which determine the distributionof local, tropospheric and stratospheric fall-out froml11dicati01zs for research into biological effects

61. Information concerning the biological effects ofirradiation of man is derived from experimental biology,
and from clinical observations and statistical surveys.
(a) All advance in radiobiology depends upon progress in general cellular biology, and requires intensive
study of the fields concerned.
( b) Fundamental biological knowledge is required forour understanding and control of the way in which radiation influences cells and their hereditary material, andhow it brings about carcinogenesis. Further studies ofthese phenomena are needed, and form the only satisfactory basis for measures which could be adopted toprevent or cure the harmful effects of radiation.
(c) To identify any occasional harmful effects of low
doses and dose rates requires systematic and long-term
observation and the recording of relevant facts , especially concerning the frequency of certain somatic disorders and the genetic structure of populations. It is atask to which this Committee urgently draws the atten tion of demographers and medical statisticians, especiallyin regard to possible correlation of certain diseases withhigh natural or artificial radiation e..'{posure.
Training for research
62. The advance of research in all these fields depends
upon appropriate training of scientific workers.

tofirst page43

ANNEXES

Annex A

DEFINITIONS O F QU-mITIES, UNITS AND SYMBOLS
1. The 1956 report of the International Colnmission
on Radiological Units and n/leasurementsl gives thefollowing definitions of quantities and units used inradiological physics.*"1.1 Absorbed dose of any ionizing radiation is theenergy imparted to matter by ionizing particles perunit mass of irradiated material at the place of interest.
"1.2 The unit of absorbed dose is the rad. One radis 100 ergs/g.
"1.3 Integral absorbed dose in a certain region isthe energy imparted to matter by ionizing particles inthat region.
" 1 . 4 - ~ h eunit of integral absorbed dose is the granrrod. One gram rad is 100 ergs.
"1.5 Absorbed dose rate is the absorbed dose perunit time.
"1.6 The unit of absorbed dose rate is the rad perunit time.
"1.7 Exposure dose of X - or garttnta radiation ata certain place is a measure of the radiation that isbased upon its ability to produce ionization.
"1.8 The unit of exposure dose of X- or gamma
radiation is the roetttgen ( r ) . One roentgen is an exposure dose of X- or gamma radiation such that theassociated corpuscular emission per 0.001293 g of air
produces, in air, ions carrying 1 electrostatic unit ofquantity of electricity of either sign.
"1.9 Exposure dose rate is the exposure dose perunit time.
"1.10 The unit of exposure dose rate is the roenfgett
per unit titne.
"1.11 Intetlsity of radiation (radiant energy flax
density) at a given place is the energy per unit timeentering a small sphere of unit cross-sectional area
centred at that place.
"1.12 The unit of intensity of radiation may be erg
per square centimeter second, or watt per square centimeter.

"1.13 The unit of quantity of radioactive material,
evaluated according to its radioactivity, is the czrrie(c). One curie is a quantity of a radioactive nuclide
in which the number of disintegrations per second is
3.700 x 1O1O.
"1.14 Specific gatiznta-ray emission (specific gamma-ray output) of a radioactive nuclide is the esposure dose rate produced by the unfiltered gamma
rays from a point source of a defined quanttty of that
nuclide at a defined distance.
"1.15 The unit of specific gamma-ray emission is
the roentgen per ttzilluurie hour (r/mch) at 1 cm.
"1.16 Linear elrergy transfer ( L E T ) is the linear
rate of loss of energy (locally absorbed) by an ionizing particle traversing a material medium.
"1.17 Linear energy transfer may be conveniently
expressed in kilo electron volts per murort ( k e ~ / ~ ) .
"1.18 Mass stopping power is the loss of energy
per unit mass per unit area by an ionizing particle
traversing a material medium.
"1.19 Mass stopping power may be conveniently expressed in kilo electro~zvolts per ,dlligram per squareceltti~neter(kev cm2/mg) ."2. The RBE symbol is described in the I.C.R.U. report, in the follo\ving way:
"2.1 RBE (relative biological effectiveness) isused to compare the effectiveness of absorbed doseof radiation delivered in different ways. I t has beencommonly represented by the symbol 7. It signifies
that m rads delivered by a particular irradiation procedure produces a biological response identical withthat produced by rn? rads delivered by a different
procedure.
The statement that 'the RBE of a radiation relative to y radiation is 10' signifies that m rads of aradiation produces a particular biological response in
the same degree as 10m rads of y radiation. This
statement may be further summarized as 7 a = 10.

*Symbols and nomenclature. There are numerous national
and international bodies that have reached varying degrees of
acceptance of the use of symbols and units f o r physical quantities. However, there is no universal acceptance of any one setof recommendations. I t is suggested that each country modify
the symbols used herein, in accordance with its own practices.
Thus one may write: kev, keV, or Kev; "C or C"; rad perunit time, rad per time, or rad divided by time: rad/sec, rad/s,
or rad-s-I ; etc. The most generally accepted system of symbols
and units may be that contained in document U I P 6 (1955)
prepared by the International Union of Pure and Applied Phys~cs.These are in fairly close a reement wid1 the recommendations of the International ~tanfardizationOrganization project
ISO/'TC 12, the ConfCrence GCneralc de Poids et Mesures,
Union Internationale de Chimie Pure et AppliquCe, and theInternational Elcctrotechnical Committee.
NOTE:Throughout this report and its annexes cross-refercenes are denoted by a letter followed by a number : the letterrefers to the relevant technical annex (see Table of Contents)
and the number is that of the relevant paragraph. Within eachtechnical annex, references are made to its individual scientificbibliography by a number without any preceding letter.

The concept of RBE has a limited usefulness because the biological effectiveness of any radiation depends on many factors. Thus the RBE of two
radiations cannot in general be expressed by a single
factor but varies with many subsidiary factors, suchas the type and degree of biological damage (and hencewith the absorbed dose), the absorbed dose rate, thefractionation, the oxygen tension, the pHt and thetemperature.
"2.2 RBE dose is equal numerically to the productof the dose in rads and an agreed conventional valueof the RBE with respect to a particular form of radlation effect. The standard of cornpailson is X- or
gamma radiation having a LET in water of 3 kev/cc
delivered at a rate of about 10 rad/min.
same"2.3 The unit of RBE is the refit. It has
inherent looseness as the RBE and in adbtlon assumes conventional and not necessarily measuredYvalues of RBE. I t is therefore recommended that its
use be restricted to statements relating to radiation
protection. For esample the statement might be made:The permissible weekly whole body RBE dose is
0.3 rem regardless of the type of radiation to which aperson is exposed.
Should occasion arise when results have been evaluated with other than agreed conventional values ofRBE, the values used should be clearly stated.
I n the case of mixed radiations the RBE dose isassumed to be equal to the sum of the products of theabsorbed dose of each radiation and its RBE :RBE dose in rerns = L [(absorbed dose in rads) x
RBE] ."REFEREXCE
1. International Commission on Radiological Units
and Measurements (ICRU) : Report oi the ICRU,
1956. U.S. National Bureau of Standards, Handbook 62,
IVashington 1957.

Annex B

RADIATION FROM NATURAL SOURCES

Paragraph

I. Cosairc IUYS ....................................... 2-7
Absorption in air .................................. 3-4
Variations .......................................
Variations with altitude

5-6............................ 7111. NATURAL
RADIOACTIVE ISOTOPES IN THE E N V I R O N ~ I E N T
Uranium and thorium .............................. 10-11
Radium ......................................... 12
Radon .......................................... 13
Thoron .......................................... 14
Particle-borne radioisotopes in the atmosphere ........ 15
Potassium ....................................... 16
Carbon-14 ....................................... 17
Tritium ......................................... 18
IV. IRRADIATIONFROM EXTERNAL SOURCES
Calculated values for gamma-ray intensities. ........... 19
Measured total outdoor radiation.. ................... 20
External irradiation in buildings. .................... 21-22
Special areas ...............'...................... 23-24
Summary of irradiation by external sources ........... 25
Gonad and bone doses .............................. 26-27
V. INTERNALWIOACTIVE
SOURCESRadioactive substances in the body ................... 28
Carbon-14 ....................................... 29
Potassium-40 .....................................30-3 1
Radium ......................................... 32
Particulate air-borne activity ........................ 33

VI. IRBU)IATIONFROM INTERNAL SOURCES.. ................ 34-39
Conclusion................................................. 40

References

1. A distinguishing characteristic of irradiation by
natural sources is that the entire population of the world
is =posed to it and that it remains relatively constant in
time, while varying from place to place with local geological conditions. The various natural sources include :(a) External sources of extra-terrestrial origin(cosmic rays) and external sources of terrestrial origin,
i.e. the radioactive isotopes present in the crust of theearth and in air.
( b ) Internal sources, i.e. the radioisotopes K40 and
C14 which exist as a small percentage of these elements
and are normal constituents of the body, and other isotopes such as Razz=,ThZJ2and their decay products thatare taken up from the environment.

protons, 20 per cent of alpha particles, 0.78 per cent of
C, N, 0 nuclei and 0.22 per cent of nuclei with Z> lo.'*
The energy of the primary particles is very high andvalues up to 1019eV have been reported.

I. COS>~IC
RAYS
2. The pimalycomponent of cosmic rays is the radiation incident
theof theof theearth. I t
composed of 79 per cent (in number) of*NOTE:Throughout this report and its annexes cross-references are denoted by a letter followed by a number: the letter(s= Table of C o n t a t r )refem to the relevant technicaland the number is that of the relevant paragraph. Withip
technical annex, references are made to its individual sclenMc
bibliography by a number without any preceding letter.

Absorption in air

3. The primary particles lose energy in their passage
through matter by ionization, radiation, and nuclear interactions and thus produce new groups of rays. Thissecondary radiation, still very energetic, is composed ?felectrons, photons, neutrons and mesons. The composltion of the radiation changes with altitude.

4. The radiation a t sea level is composed of mesons(-80 per cent) which constitute the secondary hardcomponent, electrons (-20 per cent), which constitutethe secondary soft component, and some primary protons (-0.05 per cent)? T h e average mass absorption
coefficient of the soft component a t sea level has beenreported to be 8.5 s 10-scmvg (E. Regener, quoted by
Hess3).

TABLE
11.13

6. Different authors give different values for cosmic
ray intensities at sea level (table I ) even at comparable
latitudes. There are indicationsG17that the most reliable
figure for the intensity a t the middle latitudes (-SO0)
and a t sea level is 1.9 - 1.96 ion-pairs/cma.sec, which
gives a soft tissue and gonad dose of .= 28 mrad/year.
OF COSMIC IUYSTABLEI. INTENSITYAND DOSES TO
THE SOFT TISSUES AND G 0 N N ) S I N
VARIOUS REGIONS NEAR SEA LEVEL

Place ofcbservat~a

Geomagnetic
l a f i t d c in
dcgrccs

Ionization in
ion pairs per
cma -see

Dose to flusoft
tissues and gonads
i n fnrad/sear
Ref.

Great Britain.. .

55' N 1.92

28

8

United States. ..

41' N 1.96

29

6

Austria*. ......

48' N 1.928

9France .........

4g0N 1.66 !Hard 1.15
\Soft 0.51

2410........

25' N 2.35 Hard 1.76
{Soft 0.59

34

11

20
28

12

Japan.

.kgentinas..... 23' 15' S 1.4
52' 42' S

1.9
--

a

Measured by counters.

Variafio~rwith altitude

7. The ionization in ion pairs/cms.sec and corresponding dose rates in air at N T P are given in tzble I1 forcertain locations. The table shoivs that an increase inaltitude iroin 0 m to 3.000 m gives an approximately
threefold increase in intensity. while the latitude variation even at 3,000 m is only 50 per cent. Neher's data
for sea level intensity, on which table I 1 is based, are30 per cent higher tha? those of other observers. Therefore, the values glren In this table may be considered as
upper limits.

Darc raie
mrad/ycar

Intensify
ion p a i r s / m 3 .su
Alli:r&m

0 .........

.......

1500 .,
3050..
4580 .........
6100 .........

.......

5. The intensity of cosmic rays increases verystrongly .with altitude in consequence of decreased atmosphenc absorption, and increases with increasing geomagnetic latitude in consequence of the effect of theearth's magnetic field. The latitude effect is confined tolatitudes between O0 and approximately 5S0 (apparently
at all altitudes). Small, short-lived changes of intensity
in time are produced by solar flares (up to 12 percent)'e6. Temperature changes in the upper layers of theatmosphere, local increases in pressure, air fronts andother factors also produce negligible temporary variations in intensity. but they are not significant from thepoint of view of the external irradiation of the organism.

COSMIC R ~ YINTESSITIESAND DOSE RATES

A1 5Oelafiftrde

Ncor
EgiraforA1 50'
latitudeh'car
Eguabr

2.8
4.5
8.8
18
34

2.4
3.0
6.1
12
23

41

33
44
89
175
340

66
128
263
500

8. Naturally occurring radioactive isotopes such as
HS, C 4 , K40, Rbs7, ThC9' and U2Ssand the decay products of the last tcvo isotopes are widely distributed inrodcs and soils and in the air. Physical characteristics
of some isotopes are given in tables IIIa and IIIb. The
data given in these tables may be found in many textbooks, but they are included here because they illustrate
the relative importance of different radioactive elements
and are used in calculations later on. The dose rate for anelement at given concentration is determined from decay,
yield and energy of its radiation. Shielding factors areassessed in the light of the penetrating power of theradiation. The relative contribution of the decay products of radium and thorium to total doses can be calculated, and the deviation from the theoretical equilibrium
concentration of the decay products of radium in bones,
caused by partial diffusion of radon, can be taken into
account.
9. Some of the isotopes listed in the tables viz. K40,
ThZ3', U23B,
have half-lives comparable to the geologicalage of the earth, estimated at 4 x 10"ears, and for thisreason are still present in nature. Other isotopes, in spiteof their short half-lives, are also present today, because
they are decay products of long-lived isotopes like RaZ",
or because they are produced from atmospheric nuclei
by cosmic rays, like C14 and H3.
111. NATURAL
RADIOACTIVE

ISOTOPES I N
THE EXVIRONMENTUranilit~tand Thorium

10. Naturally radioactive elements are widely distributed over the earth's surface. Thorium-bearing minerals
are found in the United States (Rodry hfountains area
and the Carolinas), in India (Kerala coast), in Brazil(coastal region of Espirito Santo), on Taiwan and inother parts of the world. Uranium has been found inlarge quantities in the United States (in brown coaldeposits, petroleun~beds. and the phosphatic rocks of
Florida), the Belgian Congo. Ontario and Sasltatchewan
in Canada, Fergana in the USSR. Czechoslovakia andSouth -Africa and other areas. For fuller information on
the distribution of uranium aid thorium. see ICerr.15
11. Radioactive elements are more commonly associated with certain types of rock than with others. Acidigneous rocks are richer in them than basalts. Shales,in particular, which contain organic substances. are more
highly radioactive than other sedimentary rocks (table
IV). Potassium. thorium and radium show a tendency
to concentrate in rocks \\-ith a high silicon content(table V) . Tables IV. V and VI contain data on concentrations of radioactive elements in rocks.

TABLEIIIa. DATAOX PARTICLE RADIATION FROM CERTAIN
NATUMLLY OCCURRING RADI0.4CTIVE ISOTOPES-

IsolopeNcnu

SymbolEtiergy

B
B
4

B

0.018
0.155
1.3
4.78
5.49
6.00
0.7
3.15
7.68
0.027

..........
.........
.........

B

1.17

P

5.30
3.98
0.05
0.4-2.2
5.4
5.6
6.28
6.77
0.34
0.58
6.05
2.25
8.78
1.79

.......

....... Thorium C
Potll.. ....... Thorium C'
Bill".

a
P

a

B

B
a

P

j3

B
P

a
P

a

B
B
a

B
(I

....... Thorium C"

B

12.26
5,600
1.3 r 109
1,600
3.825
3.05
26.8
19.7
1.5-10-4
22
5.O
138
1.39.1010
6.7
6.1
1.9
3.64
54.5
0.158
10.6

K4o.. ........... Potassium-40
Pb314.. .......... Radium B
BP13.. .......... Radium C

AcB8. ...........

Pb"'.

...........

bfesothorium I1

Thorium B

Bi'J12.. .......... Thorium C

TI?ba.. ...........

Thorium C' '

years
years
years
years
days
min
min
min
sec

years
days
days
years

Yea
hours
years
days
sec
sec

hours

60.5

min

3.10J
3.1

sec

TABLEI1 Ib. DATAON GAMMA RADIATION FROM
NATURkL RADIOISOTOPES~~.

Radiooclios
half-Lijc(Ales)

Hz.. ......... TritiumC". ......... Carbon-14
K40
Potassium-40
Razz6
Radium
Ra22z
Radon
Pdla.. ....... Radium A
PPlc.. ....... Radium B
Bi214. ........ Radium C
Pdl4,. ....... Radium C'
PbZ'O.. ....... Radium D
Biz10 ......... RadiumE
Po210......... Polonium
ThB' ......... Thorium
Ram.. ....... hlesothorium I
Acza..
h,Iesothorium I1
ThzB......... Radiothorium
Rat%......... Thorium X
RnB0 ......... Thoron
Pozls.. ....... Thorium A
mu......... Thorium B

TP..

RodiafionminT - ~ B L EIV.

~ D I U V THORIUbI,
AND POTASSIU3f COXTESTSIN VARIOUS R O C K S ~ ~Ram, g/grlO"

Trpc of rockTh-, g/gxlOd

K'e. g / g x I P

Igneous rocks:
Mean value's ................
Granifes:
North America, Greenland.. ...
Finland.. ....................
Alps ........................
Basalfs:
North America, Greenland.. ...
Great Britain, Germany, Franceand Hungary ...............
Seditnenfary rocks:
approx. 0.3
Sandstone. ..................
Limestone. .................. up to 1.5 (117).Uum shales in Sweden. ........ up to 120 (6017)

TABLE
V.

drinking water is in most cases mainly due to Ra'26. The
radium content of water sources is determined by theextent to which the water is enriched by the leaching ofrocks. Water containing calcium, barium and stablestrontium is particularly likely to be enriched withradium. This is one of the reasons for the wide variations in the radium content of water. The concentration
varies between wide limits and characteristic values are
given in table VII.

~ D I U L ITHORIUbI,
AND POTASSIUbf
CONTESTS IN SILICEOUS ROCESIO

Igneous rocks:
Acid rocks>65% SiOz
Granites.. ....... 3.1
Young granites(Maxlevel) ...... 6.5(Granodiorite) 2.7
Intermediate rocks
65-55% SiOt...(Diorite) ...... 1.4
Basic roch
<55% SiOl(Gabbro) ..... 0.87
mrabusic locks:...(Peridotite) ... 0.52

...

20

3.4

59
18

5.1
2.5

6

1.i
Oceo n...

5.1

Rivers in U.S.A.
Average. .........................
Mississippi ........................

0.7

23

-

I

AND POTASSIUhf CONTENTS IN
VARIOUS R O C K S ~ ~Igneous.. ............
Sedinunhry rocks:
Sandstones.. ........
Shdes.. ............
Limestones ..........

7 x 10-17
1-3x 10-15

Public water sufiWics*
Sweden (tap water). ...............
U.S.A. (tap water)
Average for 41 towns... .........
hlaximum Uoliet, Ill.) ..........
USSR mean value (fresh water). .....
Austria, Bad Gastein (tap aater) ....
Germany, Frankfurt-am->lain (tapwater). .........................

TABLEVI. AVERAGER4DIUh1, URANIUM, THORIUM

Type d r o d.............................

Ram.

Pa, Thn:.

K.

g/grIO"c/gxlQ

1/tx1@

c/c~IO1

1.3

4.0

12

2.6

0.71
1.08
0.42

1.2
1.2
1.3

6
10
1.3

1.1

Springs in special areas
Boulder, Col., U.S.A.. ..............
Hot Springs. Japan.. ...............
Jdchymov (Joachirnstal),
Czechoslovakia. .................
Bad Gastein, Austria.. .............
France. ...........................

2.7
0.27

Radiac trt
12. The radium concentration in rocks has been ioundto vaCY between lo-" and lo-'' gram of radium pergram of rock." The average radium content in the soil
is estimated at 2 x lo-'' gram of radium per gram of
the radi~unconcentration in the soil in various
parts o i the United States has been iound by measurementZ3 to vary between 0.9 and 8.0 x 10-l9gram ofradium per gram oi soil. Tables IV to VI show radium
concentrations in various minerals. The radioactivity offresh surface water is sometimes due to radon in higher
concentration than that corresponding to the radium contration. and it should be not~cedthat many old data on
natural ra,jioactiri~ of ,vater refer to radon and not
radium concentration. The natural radioactivity ofsomemeasurements of the Ra"6 content in foodstuffs
are given in table ~ 1 1 1 .

TABLEvI I 1. R A E COXTESTS~IX FOODSTUFFS~~
Rn contort in gFoodE
of food x IOU

Wheat.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
20-26
Potatoes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
67-123
Milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . O.O375/millilitre
Meat ....................................
8.0

52

Radon13. RnZ"?,an isotope of the gaseous element radon anda decay product of Ra?26 in the uranium series, accumulates in the soil in areas where uranium-bearing minerals
are present, and diffuses into the air. The average radon
concentration in the soil is of the order of lV13 curie/gramJ1. The rate of injection into the atmosphere isapproximately 4.3 s l@1° curies per hour per square
metre of the surface (in the neighbourhood of Leningrad, USSRzB).Seasonal changes occur in the rate of
injection. The radon content of the air at ground level
depends to a considerable =tent on meteorological conditions. The average "equivalent" concentration of radon
with its decay products in the air is approximately
1-3 x 10-l3 c/l (see table XIa). In areas with higher
radioactivity (granite and other areas) the radon content may be higher than the concentrations given above
by several iactors of ten.
Thoron14. Thoron (Rn2=O) another isotope of radon is adecay product of Th23zand also diffuses from the groundinto the air. As for radon, the concentration in air
depends to a considerable extent upon meteorologicalconditions. The average concentration in air is approximately 0.5 x lV13 c/l (see table XIa) but in areas withhigher radioactivity it may be higher by several factorsof ten.

activity of ocean water is mainly due to K40 with aconcentration of 3-5 x 10-l3 c/cm3.
17. The carbon isotope C4is formed in the atmosphere as a result of nuclear reactions between cosmic
rays and atmospheric nuclei. -ill the carbonaceous substances taking part in carbon exchange with the atmosphere have a constant equilibrium concentration of C 4
equal to 7.21 x lV1' c per g of carbon,=;corresponding
to a distintegration rate of 0.27 dps per g of carbon.
Rocks in which such exchange cannot take place have adepending on their geologlower specific activity of C4,
ical age. Ancient carbonaceous rocks (marble and others)of geological age greater than the half-life of carbon1'
do not as a rule contain this isotope. Observation has
shown, however, that the concentration of C1' in nature
has been increasing recently owing to contributions froma new source, namely, the explosion of nuclear~eapons.~~~~'

Tritittm
18. Tritium (H3) has always been present in naturesince it is formed in the atmosphere by the action ofcosmic rays. The total quantity of tritium is at an equilibrium level equal to the rate of formation multiplied by
the mean radioactive lifetime. The aqueous componentof the cells of the htin~anbody probably has a tritium
concentration equal to the one observed in foodstuffs
and drinking water. The natural atomic concentration oftritium in the hydrogen of river waterJg is 5 x 1V18.
Such a tritium concentration may be calculated to result
mrad/year to soft tissues.
in a dose rate of 1.8 x

Particle-borne radioisotopes in the atmosphere
15. I n addition to radon and thoron, the atmosphere
contains their solid decay products, mainly Ra B, Ra C
and T h B, which attach themselves to small particles andthus constitute the natural particulate air-borne activity.
IV. IRRADIATIONFROM EXTERNAL SOURCES
The distribution of the aerosol-borne activity according
Calcrtlated vdrtes for ganznta-ray intensities
to particle size is shown in table IX1'. The particulate
activity can be collected by special filters or by electro19. The gamma radiation over rocks and soils constatic precipitation. Long-lived material that remains
taining known amounts of radioactive materials u-as firstafter the decay of Th B (10.6 h half-life) constitutes
calculated by Hess40 Later, Hultqvist17 calculated charonly a very minor part of the total activity. Concentraacteristic radiation values for minerals with the concentions vary widely with local and meteorological factors.
trations of radioactive materials given in table IV.
Extensive reference to data on radon equivalent content
Hultqvist developed simple numerical espressions forin both indoors and outdoors air is given by H u l t q ~ i s t , ~ ~the gamma-ray dose, corrected for the scattered raand a summary of some typical values has been given by
diation. If his formulae are used to estimate the contriLowder and(see also table XIa). The particlebution to the dose rate (D, rad/year) from various conborne radioactivity is relevant to internal irradiation
centrations of radioactive materials in the ground (s, gresulting from inhalation, since the particles, but not the
per g ) , the following expressions are obtained:
gases, accumulate in the respiratory tract.

TABLE
=.I7

DISTRIBUTIONO F RADIOACTIVITYACCORDING TO PARTICLE Dl-ULETER
Dose rates calculated from Hultqvist's equations ( 1)using the data of table VI are given in table X.

TABLE
X. DOSE RATES OF EXTERN.=

G-?iSlX-

Ra, U,IRRXDWTION FROM TBE ELEMENTS
T h A h 3 K C O N T A I 3 m I S ROC=

Potassiicnt
16. Potassium is relatively abundant in nature. Its
radioactive isotope KO' constitutes 0.0119 per cent of
the total amount of potassium and contributes 32
p-dps per g H and 3.+-dps per g K. The potassium
content of various rocks has been given in tables IV-VI.
T h e potassium concentration in the soil varies between
and 3 x 1V2g of potassium per g of soil. The radio-

Dose role in mrad/yrara frm

Type of rock

Ro-

Uxr

Th"'

K'"

Igneous rocks.. ......

24

25.8

36.8

34-6

13
20

7.7
7.7
8.4

18.4

14.6

30.6
4

36

Sedimentary rocks:

Sandstones. .......
Shales .............
Limestones. .......

7.7

3.6

Calculated from equations (1) and the data in table VI.

DOSERATES OF EXTERNAL GAMMAIRRADL4TION OUT OF DOORS I N
VrlRIOUS COUNTRIESTABLEXIV. DOSERATE OF EXTERNAL GAMMA

TABLE
XI.

IRRADIATION INSIDE BUILDINGS LV AUSTRIA%
T 9 c of building

Dose raftmrad/war.-

COUW

Great Britain.. ..
France..........

United Statess.. .
Austria
Sweden6 ........

.........

48
45-90
180-350
50-160588560-12050

Comment-.

~ e f .

41
10

Granites and shales
For 19 inhabited localities

a Values obtained by subtraction of 28 mrad/year for cosmic
raps.

OF RADOS AXD
TABLE
XIa. CONCEXTRATIONSTHORON LN EQUILIBRIU3l WITH THEIR DECAY PRODUCTSPRESENT IN THE AIR IN VARIOUS REGIONS A h D
CORRESPONDING CALCULATED DOSES
Aonopc conunlrafion
in c/l r 10"
Place of obsmvalion

Czechoslovakia. ...
Great Britain.. ....
Japan .............
FranceAustria.. .........
Sweden..

............

.........
USSR .............

Rn

8.0
3.0
1-2.5
2.0
1-3
1.0
1.0

Dare inmrad/yeor

Tn

Rn

0.6

11
4.3
1.4-3.5
2.8
1.4-4.3
1.4
1.4

0.5

Tn

F&f.

0.8

28
32
11
34
35
36
26

0.7

Arwage cnctnlrolionin -,c/Z- -r1-0-"
d i & d (oulcr walls).....................

57
112
202

48
99
158

' Using table VI of ref. 17 and excluding cosmic rays (1.9
ion-pairs/cms-sec).
TABLE
OF ExTERh.AL GILMh*
1RR.ADLkTION INSIDE BUILDINGS IN GREATB R I T - ~ I N ~ 'r w a r~~ of gBuildinrc

S%s mcmurcd

Local
gommorays Mcan(a) Aberdeen, Laboratory. ....
(b) .4berden, bell tower. .....
(c) Aberdeen, entrance hall.. ..
2. Concrete or (a) Aberdeen, rooms on various
brickfloors..................
(b) Leeds, rooms in hospitalbuilding ...............
(c) Leeds, single storey
laboratory .............
(d) Leeds.variousrcamsin house
1. All granite

107
99
101

102

73
81

Tn

Rn

Tn

0.0276
0.091

7.5
13

0.4
1.3

0.095926.4

1.35.;, ,,,

Mean dare r&. in mrad/year*

49
Brick
104
Light-weight concrete.. .... I 72
(containing alum shale)

Dose rotr. mrad/ymr*

22. ~h~ gamma radiation from radioactive Inaterial
in thebe calculated by Hultqvist's relations'yDRn= 14.2 X 1 @ 2 X C R n mrad/year. . . ...(2)DTn= 14.0 X 101'X CTnmrad/year
where C is the concentration of radon and thoron incuries per litre of air. Values corresponding to the concentrations of columns 2 and 3 of table XIa are given
in columns 4 alld 5.

C e ~ ~ ~ e o f r Highcstreadingwn:
Larrstreadinp

wood ....................

85-12875-86

a Table W,of ref. 17 was used, the calculation being madeaccording to equation (2).

DOSERATES OF EXTERNAL GAMMAIRRADIATION IN SWEDISH
B U I L D I N G S ~ ~l4
,
*d.%)

Rn

Wood ................. 0.527
Brick.. ................ 0.909
Light-weight concrete(containing alum shale) 1.86

TABLE
XII.

(-

5444

TABLE
XV. DOSERATE OF EXTERNAL G ~ I M A
IRRADIATION FROM Rn AND Tn PRESENTIN THE AIR JXSWEDISHBUILDINGS

Measttred total outdoor radiafiott
20. Total gamma ray and cosmic ray intensities havebeen measured by various authors using ionizationchambers. The experimental dose rates are given intable X I and may be compared with calculated values.
w h e r e necessary, gamma ray figures in table X I havebeen obtained by subtracting an average value of 28
mrad/year for cosmic rays.

Building maferial

All granite. .....................
Brick (brick or concrete). .........

Exfer?zal irradiatiorr in buildings
21. External irradiation by gamma rays is greater
inside buildings of brick, concrete, shales and othermaterials than out of doors because of the radioactive
elements contained in these materials. Some increase in
the dose may be produced by the accumulation of radonor thoron as a result of poor ventilation in the buildings.
On the other hand, the buildings reduce the dose of
external irradiation by absorbing .the radiation fromsources outside the buildings. Tables XII, XI11 andX I V indicate the dose rates of external gamma irradiation inside buildings, table XV the dose rate from radon
and thoron present in the air in buildings (without
ventilation).

34
35
36

Stockholm street
Igneous rocks
Clay

Dose raft. mrad/ycar

Wooden house.. .................

I

Special areas
23. Much higher values of the external radiation havebeen found in some areas where the thorium content in
the soil is particularly ligh.
24. The region of Kerala (India), which is approximately 100 k m 5 n area (about 200 krn long and several
hundred metres wide) has a population of about 100,000.
y-lle available measurements+~have been made in ten
villages of the intensity of the radiation inside buiMingsof three types constructed of various materials typical of
the region. The basic materials are brick and cement( A ) , clay ( B ) and wood (C). The results of the measurements and corresponding calculated doses are given
in tables XVII and XVIIa. The mean \-alue of the individual dose is 1,300 mrad/year, calculated from theequation
P,
A

D='

78

x,

ZP,
r

80
57

where P, is the population in village r and X, is themean value of the dose in village r.
54

TABLEXVI. EXTERXALIRRADIATION I N SPECIAL .~REXS
Geology

Location

Area.-

Monazitesand
alluvial
deposits

Brazil States ofSequence oI inter50,000
Average 500 42
Rio de Janeiro
mittent coastal
peak values
and Espirito
strips each sev1,000
Sanco (Outdoor) eral km long andseveral hundred
metres wide
htineralized Brazil States ofApproximately 6
Pasture land,
Average 1,600 42
Minas Gerais
volcanic
k m l in a dozen
scattered farms, peak values
intrusives
and Goias
scattered places
1 village with
12,000(Outdoor)
350 inhabitants

TABLE
XVII. DOSESOF EXTERNAL GAMMA IRRADIATION INSIDEBUILDINGS AT TEN INHABITED LOCALITIES IN THE I<EKUREGION INDIA)^^
Name a/ village

Area o j oillolc
in 1,000
No. ojppulation
sq. metres(in thousands)

No. ofhouses'EsLd

Mean daseralc
mrod/ycar

1. Kadiapattam.. ....
2. Manavalakuruchi .
3. IvIuttam.. .........
4. Midalarn.. ........
5. Viligem.. ........
6. Karamanal.. ......
7. ICavalen~..
8. Kullatoor.. ........
9. Vettoor. ..........
10. Varkala.. .........

.

........

TABLE
XVIIa. DOSESOF ESTERNAL G A 3 l l L - I R L T I O N INSIDE BUILDINGS OF VARIOUS TYPES IN THE K E K ~ WREGION INDIA)^^
KO. o jh c sPnccnIa;e of tala1
irumber of h c s inthr repion

Brick.. .............
Cement. ............

73

Type B. Clay.. ..............
TypeC. Wood ...............
Bamboo. ............
Palm.. ..............

62

Type of hmrse andbuilding materialType A.

TABLE
XVIII.

52

Dose. mrad/yeu
Maximum
oolrrcMinimum
value

15

2,890

66

60
25

3,150

105

3,950

145

MEAN \r.4LUES OF DOSES OF ESTER-VAL IRRADIATIONFROM VARIOUS SOURCES OF RrlDIAiTION

Sourca of rodiolion

Dosc rak. w a d / y e a r.Wear > a l u

Extreme d u e s

1. Cosmic rays.. ...................

28

20-34

Table I

Ordinary regions:
2. Gamma rays over rocks.. .........
3. Gamma rays out of doors.. .......
4. Gamma rays fro111aerial sources.. .

73
70
3

25-1 20
48-1601.4-1 1

Table X
Table XI
Table XIa

265

180-350

Table XI

131-2,814

Table XVIIActicc regions:
5. Gamma rays, granitic regions inFrance ..........................
6. Gamma rays, monazite region,
Kerala in India. .................

1,270'--a- -By subtraction of cosmic ray dose of 28 rnrad/year from total.

food and water and is present with its decay products
Suntttzary o j irradiation by externd sorircesinthe body. Radioactive material from the atmosphere
25. An approximate estimate of the level of esternal
entersthe respiratory tract by inhalation and some airirradiation from natural sources can be made from theborne
particulatematerial is retained.
above material. The measured doses out-of-doors invarious regions give a mean dose equal to 70 n~rad/year
Carbori-14(excluding highly radioactive regions). On the other
29.
The
total
carboncontent of the body is approxihand, a value for the mean dose over rocks of 73 mrad/
mately
18
per
cent
or
12.6
kg for a total body weight ofyear may be derived by calculation from the mean :oncentrations of radioactive elements in the most w~dely 70 kg. Therefore, the amount of CI4 for a total bodyweight of 70 kg is of the order o i 0.1 mc.
distributed rocks (Table X). Thus in normal regions
the mean dose can be estimated at approximately 70
Poiassiunt-40
mrad/year. Summary data on external irradiation are
30.
The
total
potassiumcontent of the body has been
given in Table XVIII, column 3 of which indicates
given as 0.185 per cent or 130 g by Sievert,* as the avermean doses, column 4 the spread of typical values, andage value of a series of observations by several authors.
column 5 of the reference to the data used in estimating
While individual values range between 0.12 and 0.35
the mean level of irradiation.
per cent, the majority of results group together rather
closely around the average value given above.
Gortad atld bone doses
31. The concentration of radioactive potassium in
26. I n calculating the doses to the gonads and bones' ~givenvarious organs, according to Forbes and L e w i ~ ,isfrom external gamma irradiation, a coefficient (shielding
in table XXI.
factor) must be introduced to allow for the partial absorption of gamma radiation by outer tissues. Spiers3'
PoT.%ssIU&~
COYTENT OF VARIOUS
TABLE=I.
gives the following estimates for the gonads :ORGANS OF M . ~ N ~ ~TABLEXIX. GONADALSHIELDING FACTOR FOR
G.%3IV%R4YS IN THREE POSITIONS:HORIZOSTAL, SITTIXG A h 9 STAhmING
Shielding falor

Fcmok

PodionAonagc

.\4&

Awagc

0.67
Horizontal. ........... 0.52
0.56
0.70
0.70
Sitting.. ............. 0.58
0.72Standing.. ............ 0.59
Mean factor for both sews: 0.63
The mean shielding factor in the case of bones will alsolbe taken
here to be 0.63

27. Estimated aggregate values can now be given for
the gonad and bone doses from natural sources of radiation--cosmic rays and radioactive elements. The populations are subdivided into three groups according tolevel of irradiation: people living in normal regions i.e. regions where the level of irradiation is not morethan 100 mrad/j-ear; population groups living in active
regions with a higher level of irradiation, up to 500
mrad/year ; and lastly, persons living in regions with ahigh level of irradiation-over 500 mrad/year. Such adivision is artificial, but is useful in considering the biological effects of irradiation.

TABLE
X X . MEAN DOSE TO GONADS AND BONESFROM NATUIUL EXTERNAL SOURCES I N NORhML
REGIONS AND blORE ACTIVE REGIONS
RegionPopulationin millions

Aggrceolr mean dose
mrcm/ycar'

1. Normal regions. .............. 2,500
2. Granitic regions in France.. ....
7
0.1
3. Lfonazite region, Kerala in India
4. Monazite region Brazil. .......
0.05

-

75
190
830
315

Using a shielding factor of 0.63 for -,-rays and a dose rare of
28 mrem/year due to cosmic rays.

V. IXTERK-AL
R~\DIOACTIVE SOURCES

Radioactive nrbsta~~ces
itt the body
28. The radioactire isotopes e4and K40 are normal
constituents of the human body. Ra2?=is taken up from

Pcrccnlogc of l o w
body w i g h t

Orgon

Skin .......................
Skeleton. ...................
Tibia. .....................
hiusdes ....................
Nervous system. ............
Liver. .....................
Heart. .....................
Lungs. .....................
Kidneys. ...................
G.I. tract. ..................
Adipose tissue. ..............
Remainder. .................
Total body weight: 73 kg
-

6.5
13.4
1.4
39.6
2.1
2.3
0.6
2.2
0.4
1.5
21.4
6.4

-~

Radiut~t
32. Radium, like calcium, is selectively incorporated
in bone. As the amount of radium daily ingested in foodhas been estimatedd6 to be around 1.6 x 1@l2 g, theuptake through drinking water is significant only if theradium concentration in the water is at least 10-l6 g
Ra2'e/cm3. Consumption of such water may result in an
increased body burden of radium, but, as the concentration is normally lower, the body content of radium isbelieved to depend in most cases on the radium content
of the food. The following figures have been reported
for the total radium content in the human body: 1.6 x
l@1°g47.3.3 x
gZ7,and 0.4--3.7 x lV1°g4=.Muth2'(table XXII) has recently published values of radium
concentrations in different tissues which seem to indicatethat a substa~ltialproportion of the radium burden islocated in soft tissues. These values have not yet been
confirmed in other laboratories.

TABLE
XXII.

&UIIUM CONTEST IY lT-4RIOUS

TISSUES~

Tirs;rc

Number ofmmpks& confcnl per E of unfrc&d lirsu8

Jfinimum toluc .Mean ualxe Maximum valuc--

Bones ...........
Lungs...........
Liver ...........
Spleen ..........
Muscles.. .......
Testicles ........

6
4
4
3
2
28

4.9
1.6
0.4
1.8

9.7
2.3
3.4
4.6
1.3
0.6

16
3.5
11
7.4

Particztlafe air-borrre activity
33. Because the disintegration products of radon andthoron are present in the air attached to the particles ofaerosols, the amount of radioactive air-borne material
retained in the respiratory tract depends upon the filtering properties of this tract for particles of ditierent sizes.
Figure 1 shows some characteristic average retention
values for particles of different sizes taken from a graphgiven by Hultqvist (ref. 17: p. 46). Virtually all theactivity is concentrated in particles of no more than
0.04 microns in diameter and up to about 70 per cent ofsuch particles will be retained in the lungs according to
the graph.

of the distribution of radium in the orgmism, but thishas not yet been confirmed by other researchers. The
local distribution of radium in bone tissue is of considerable importance in estimating osteocyte doses40*50
and it is generally studied by radioautography but at thelevel of the natural concentration of radium in the bones,
this method does not yield reliable results :the data published on radium distribution have been obtained withrelatively large concentrations of radium. The question
therefore arises whether a similar picture of radium
distribution in bone tissue would be obtained with small
concentrations. There is as yet no satisfactory answer
to this question and it is accordingly assumed here thatwhen radium is present in natural concentrations in nonactive regions, its distribution in bone tissue is uniform.
36. As the range of alpha-particles in the tissues isapprosimately of the same order as the diameter of thecavities in bone tissue. the relationship between alphaparticle range and cavity size must be taken into accountin calculating the dose. According to Spiers40 this may
be reduced to introducing into the equation for calculating the dose a geometric factor having different values
for bones of differing structure. Spiers (op. cit) expresses the equation for calculating the bone dose in thecase of alpha particles from radium in the bones in thefollowing form (in which 50 per cent of the energy isassumed to come from disintegration products) :D = 1.78 s 10" Pm mrad/year
is the mean geometric factor, m the radium
where
content in the bones in grams of radium per gram ofbone.
37. For a body burden of lVIO g RaZZa,which isaverage for normal (non-active) regions, the numericalFigure 1 Approximate "median curve" for the alveolar retenvalue of the osteocyte dose is thention The broken line refers to that magnitude range for which
D = 38 mrem/year
no experimental investigations are available. (Reproduced from
Hultqvist, ref. 17, page 46.)
= 1.48, using an RBE = 10. The mean dosewhere
to the bone marrow is largely due to the /3 activity of theradium decay products, and may be estimated to beapprosimately
0.5 mrem/year
34. The dose rates from potassium and carbon are
Dg = 0.5 mrern/year
approsimately uniform over the body and are calculated from the known concentration of these elements
38. The dose of irradiation by radon and thoron andand the specific energies of their radiations. Calculated
their distintegration products is considerably greater (asdose rates are given in table XXIII,using the following
compared with external irradiation) if these substancesparameters :are taken up into the organism with inhaled air. In thiscase the lungs are the critical organ. Assuming, in acKCO:energy of quanta E y = 1.5 Mev, 0.1 quantum
cordance with the data given above, that 60 per cent ofper disintegration, average energy of /3 particles EB =the aerosol particles carrying the radioactivity of the dis0.6 Mev, 50 per cent of the energy of the gamma quantaintegration
products of Rn and T n are retained in theis absorbed by the tissues ;tissues and that the volume of the lungs is 3,000 cmS
C4:average energy of /3 particles EB= 0.067 Mev.
and their weight 800 g, the numerical value of the lungfromdose can be calculated, according to Hultqvi~t?~*'~
35. In calculating the doses of irradiation from rathe following equations :dium taken up into the organism, only the alpha-particle
DRn= 5.0 X I@' CRn mrem/year
energy is taken into account as a rulet and all the radium.......(3)is assumed to be in the bones. Figures published reDTn= 66.5 X 101' CTn mrem/year
centlyn ,(table XXII) present a rather different picture

I

RADIOACTIVITYOF TI-IEBODY AND TISSUE DOSESFROM Kt0 .4&P C14 (standard man, 70 k g )TABLEXXIII.
Elcmcnl

Weigh1 in
pcrcenhgc

K ...........

0.20

K4o.. ........ 2.38.10-5............ 18.0.......... 2.8-10."

C
C"

a

Wright in E

140
1.66.10-2

12,6001.96-10-8

Activity inRadiolion cxricr x 10'b a d dorc. 0sk dasc
mrad/yca?
mrodiyeor

r

10.4
1.15

16.5
2.3

9.0'
2.3

4

9.0

1.6

1.6

15

Using the potassium content in the bones according to Table XXI.

TABLEXXIV.

DOSESTO LUNGS FROM R4DON AND TIIORON IN THE AIR(based on measuremeltts carried out i n Sweden)
Dose in mrcm/year:fiRn

OvlnruoU
librium

Assum- Withrn;
Mihequrlion
librium JW rec

Wood. .............. 0.527 0.537
Brick.. ............. 0.909 0.913
Light weight concrete(contain.alum shale) 1.86 1.86

Assumin;equvrr:rtt~

39. Aggregate figures for internal irradiation give thefollowing dose rates: gonads 20 ~nrem/year and osteocytes 50 mrem/year.

40. Since the data given in the text relate to individual inhabited regions and are naturally far fromcomplete, it may be asked whether they can be considered representative for the whole population of theworld. As far as the level of irradiation from sources
such as cosmic rays and radioactive elements that are
constituents of the body (potassium and carbon) is concerned, the answer is in the affirmative. In the case ofother sources of external and internal irradiation present
in the soil, water and air are capable of being taken up
into the organism, the level of irradiation depends on thegeological features of the region concerned and therefore
varies considerably from one place to another. In thiscase, only a very approximate estimate of the mean levelof irradiation is possible. The results of such an approximation are given in table XXV.

TABLEXXV. DOSESOF EXTERNAL AND INTERNALIRRADIATION FROM NATURAL SOURCES OF RADIATION
Dose mrem/yrar
o!hnsofl tissues* T o bones

irradiation:
Cosmic rays.. .............. 28
Gamma rays out-of-doors. ... 47

28
47

Commcnl

At sea level

Internal irradiulion:......................

K4Q..

19

...................... 1.6
Ra'm ......................
?
Cl4..

Total irradiadon from all sources 95

11
1.6
38

1 25

I

With
run-

1
rium

I

rqui-

I?

R'ifh

zz

lia

'&*
rium lion

263 73453 128

185 52605 173

0.0959 0.461

where C is the radon or thoron concentration in curies/
litre. The results of measurements carried out in three
types of buildings in Sweden are given in table XXIV ;the doses were calculated from equations (3) and (4).

Inadidion

IWscc

0.0278 0.136
0.0910 0.450

where C is the radon or thoron concentration in curies/
litre, and radioactive equilibrium is assumed. In anothercase-that of ventilated buildings, where the air in theofbuilding is renewed every seventeen minutes, i.e.
the air is renewed per second-Hultqvist obtained thefollowing equations :TOgonads andWill:senlibtion

At sea level--* Including bone muro\t- since the conuiburion from Ra inbone does not esceed about 0.5 rnrenl per year.

REFERENCES
1. Rossi, B., High energy particles, Prentice Hall. New
York, p. 520 (1952).
2. Rossi, B., High energy particles, Prentice Hall, New
York, p. 8 ( 1952).
3. Hess, V. F. and Vancour, R. P., J. Atm. Terrest.
Phys. 1, 13 (1950), UN document A/AC.82/G/
R102. Radiological Data, submitted by Austria.
4. Wilson, J. A. (Editor), Progress in cosmic physics,
Amsterdam, ( 1952).
5. UN document A/AC.82/G/R.15, Information submitted by Sweden, (1956).
6. Hess. V. F. and O'Donnell, C. A., Journal of gphysical research, 56, No. 4: p. 557 (1951).
7. Hess, V. F., Arch. Met. Geophys. Biol. A, 3, pp.
56-63 (1950).
8. U N document A/AC.82/G/R.2, Information submitted by the United Kingdom, (1956).
9. UN document A/AC.82/G/R.102. Information submitted by Austria, (1957).
10. UN document A/AC.82/G/R.179, Information submitted by France, (1958).
11. UN document A/AC.82/G/R.70, Information submitted by Japan, (1957).
12. U N document A/AC.82/G/R.81, Information submitted by Argentina, (1957).
13. Libby, W. F., Science, 122,57 (1955).
14. Hultqvist, B., in UN document A/AC.82/G/R.l5.
Also published in Kungl. Svenska Vetenskapsakademiens Handlingar, Vol. 6, Ser. 4, No. 3 ( 1956).
15. Kerr, P. F., International Conference on PeacefulUses of Atomic Energy, Geneva, 6,s-59 (1955).
16. Faul, H. (Editor), Nuclear geology, New York,(1954).
17. HultGist, B., Kungl. Svenska Vetenskapsakademiens Handlingar, Vol. 6, Ser. 4, No. 3 (1956).
18. Rankama, K. and Sahama, T. C., Geochemistry.
University of Chicago Press (1950).
19. Hikschfelder, J. O., Magee, J. L. and Hull, M. H.,
Phps. Rev. 73, 852 (1948) ; Holmes. A. Radioactivitat und geologie. Verhandl. Naturforsch. Ges.,
Basel. XLI, pp. 136-185 (1930).
20. Kaye. G. and Laby, T. H., Phys. and Chem. Constants, Longmans Green Co., N.Y.. (1948).
21. Leipunsky. 0. I.. Atomic Energy. 12 Val. 111, p.
530, (1957).
22. Cowan. F. P., Everyday radiation, Physics Today
5, KO. 1010 (1952).
23. UN document A/AC.82/G/R.55, Lowder, W. M.,
and Solon, L. R.. Background radiation, p. 13.

21. UN document A/AC.82/G/R.lj, Sievert, R. M.,
Measurements of low-level radioactivity, pa_rticulady the -1 radiation from living subjects, (1936).
25. U N document L4/AC.82/G/R.95, Lough, S. Allan,
Deputy Director, The radium content of soil, water,iood and hurnms. Reported values, ( 1957).
26. U N document A/AC.82/G/R.39, Information submitted by the USSR, Content of natural radioactive
su6stances in the atmosphere and in water in the
territory of the USSR, (1956).
27. Muth, H.. Schramb, A.. Xurand, K., and Mantue,
H. J., Brit. J. Radiobiology, Suppl. No. 7 (1957).
28. UN document A/AC.82/G/R.1T1 Information submitted by Czechoslovakia.
29. UN document A/AC.82/G/R.19, Information submitted by Austria.
30. Fritsch. A., Puiset. I. and Coursajet, J., J. Radiol.
Electr. et bled. Nuclhaire (in press).
31. Eisenbud, M. and Harley, J., Science 117, 141(1953).
32. UN document A/AC.82/G/R.2, Information submitted by the United Kingdom, The hazards to menof nuclear and allied radiations.
33. U N document A/AC.82/G/R.70, Information submitted by Japan, Radiological data in Japan.
34. Solon, L. K.. Lowder. W. M., Zila, A. V., Devine,
H. D., Blatz, M. and Eisenbud, M., External environmental radiation in U.S.A., U.S.A.E.C. Healthand Safety Laboratory, N.Y. (1958).
35. U N document A/AC.82/G/R.102, Information submitted by Austria, Radiological data.
36. Sievert, R. h4. and Hultqvist, B., Variations innatural radiation in Sweden. Acta Radiogica, Vol.
37, F. 3-4 (1952).
37. Anderson, E. C. and Libby, W. F., Phys. Rev., 81,
64 (1951).

38. Rafter, T. A. and Fergusson, G. J., N.Z.J. Scienceand Tech. B38,871 (1957).
39. Anderson. E. C., Ann. Rev. of Nucl. Science, 2,
63: (1953).
40. Hess. V. F.. in Ergebnisse der Kosmischen Physik,Vol. 11. 95-149. Akademische Verlagsgesellschait,
Leipzig, ( 1934). Cf. R. Nuhleisen :Atmospharische
Elektrizitat. Handbuck der Physik, Vol. 48 ( 1957).
41. Spiers. F. W. and Griffith, H. D., Brit. J. Radiol.
N.S. 29,175 (1956).
42. UK document A/AC.82/G/R34. Roser, R. X. andCullen. T. L., Intensity levels of natural radioactivity in selected areas in Brazil.
43. U N document A/-AC.82/G/R 166 (1958). Bharatwal, D. S. and Vaze, G. H., Ileasurernents on theradiation fields in the monazite areas of Kerala inIndia.
44. Sievert, R. M., Intern. Conf. Peaceful Uses ofAtomic Energy, Geneva 13, 187 (1956) and UN
document A/AC.82/G/R.15 ( 1956).
45. Forbes, G. B. and Lewis, A. M.. J. Chem. Invest.
35, No. 6 (1956).
46. Hursh, J. B., The tzafural radioactivity of man, Proc.
Bio-assay and Anal. Chem. Meeting. National Lead
CO., Ohio, October 6-7, (1955), pp. 110-123.
47. Hursh. J. B. and Gates, A. A.. Nucleonics. 7, NO. 1,
46 (1950).
48. Stehney, A. F. and Lucas, H. F., International Conference on the Peaceful Uses of Atomic Energy,
Geneva 1 1 , 4 9 ( 1956).
49. Spiers, F. W., The Brit. J. of Radiology, Vol.
XXVI, No. 306 ( 1953).
,
M.,
50. U N ddcument A / A c ; ~ ~ / G / R . ~ ~Hindmarsh,
Larnerton, L. F., Owen, hf., Spiers, F. W., Vaughan,J., The relative hazards of SrS0and Ra2=''.

Annex C

MAN-RPADE SOURCES(Other than environmental contamination)

Paragraph
I. INTRODUCTION.............................................

1

11. MEDICALUSES OF X-RAYSB ~ ' DRADIOACTIVE MATERIALS ..........
The genetically significant dose ..............................
Calculations ............................................
Statistical data .........................................
Exposure of the bone marrow ...............................
Diagnostic uses of X-rays ..................................
Estimates of the genetically significant dose ................
Estimates of bone marrow dose ..........................
Accuracy of estimates ...................................
Reduction of gonadal dose ................................
Radiotherapy .............................................
Genetically significant dose ...............................
Bone marrow dose ......................................
Internally administered radioisotopes ........................

.....................................
........................................

Occupational exposure
72
Medical workers
73
Atomic energy workers .................................. 77
Industrial and research workers ........................... 80
Summary .............................................. 82
IV. OTHERMAN-MADE SOLTRCES OF RADIATION ...................... 84

APPE~-DICESI-X :DATAFOR EVALUATIONDIAGNOSTIC

OF THE GENETICALLY SIGNIFICANTDOSE FROMX-RAY
EXPOSURE

I. Australia
11. Austria
111. Denmark
IV.England and Wales
V. France
VI. Japan
VII. New Zealand
VIII. Noway
IX. Sweden
X. United States of America
DATAON DI-&GNOSTIC X-RAYEXPOSUBE: C O N M DOSE FOR EXAMINATIONFOR THE 31OST IIIPORTAXT E X P O S t . CLASSES

1. The various estimates of genetically significant
dose which have been available to the Committee are
discussed in this annex, and some preliminary estimatesof mean marrow doses are also given. The presentation follows, as far as possible, the scheme given inchapter 111.

11. MEDICALUSES OF X-RAYS
AND RADIOACTIVE NATERIALS

2. Medical uses of X-rays and radioactive materials
are responsible for the largest man-made =posures ofmany populations at the present time, the doses possibly
ranging up to more than 100 per cent of the dose due
to natural sources in some of the countries for which
estimates have been made.
3. The medical exposure is mainly an exposure ofpatients undergoing diagnostic examinations or radiation therapy. It is also an occupational =posure, fromwhich, however, the dose to the population as a whole iscomparatively very small. This occupational exposure istreated separately in paragraphs 72-83.
4. In view of the importance of the medical exposure,
the Committee invited the International Commission on
Radiological Protection (ICRP) and the International
Commission on Radiological Units and h,Ieasurements(ICRU)"(a) T o consider and discuss the question of how
to arrive at reliable data indicating the doses to different parts of the body (particularly the gonads) received by indi~idualsand, in the aggregate, by large
population groups due to medical uses of ionizing
radiations and"(b) T o examine what recording system, if any, isat present feasible for the determination of the relevant dose values."
The two Commissions formed a joint study group to
consider and prepare a report1 for the Committee on
these problems.* The following is the summary of theirreport.**" I . Prelintinary cottsiderations" ( a ) The principal objective has been to recommend methods for the evaluation of the geneticallysignificant annual gonad dose, G,, which arises frommedical uses of ionizing radiation.
" (b) It is assumed that the magnitude of the significant gonad dose due to natural background may betaken as a standard of reference and that 25 per centof this dose is the greatest absolute accuracy which
need be aimed at for an initial determination.
"(c) While not always yielding values strictly interms of G, as defined in paragraph 4 (of the
ICRP/U Study Group report), the preliminary sur-

* N ~ EThroughout:
this report and its annexes cross-reierences are denoted by a letter followed by a number: the letterrefers to the relevant technical annex (see Table of Contents)
and the number is that of the relevant paragraph. Within eachtechnical annex. references are made to its individual scientificbibliography by a number without any preceding letter.
**The references to pages in the Joint Study Group report
have been omitted here.

veys which have already been conducted have yieldedvalues of G, of the order of 100 mrad (probablevalue) and 50 mrad (minimum value) for the U.S.A.
and of the order of 2010 mrad (minimum values)for Denmark, Sweden and the United Kingdom(England and Wales).
"(d) These surveys show at present that diagnosis
makes a much larger contribution than therapy, andthat some 85 per cent of the diagnostic dose arises
from 6 or 7 types of examination, constituting only
about 10 per cent of all examinations of the types
listed.;"(e) It follows that, as regards dosimetry, those
6 or 7 types call for special consideration in future
surveys.

"2. Recont~~tendatio?ls"(a) It is recommended that the basic studies becontinued and extended, making use of suitable ionization dosemeters in order to obtain data that may
be used in the preparation of standard tables whichgive the average gonad dose in mrad corresponding
to each type of diagnostic and therapeutic use of ionizing radiation. Special attention should be paid to thesix or seven types of diagnostic examinations which
account for 85 per cent of the gonad dose.
"(b) I t is recommended that in all countries theanalysis of film records, together with the results of
2 ( a ) above, be used as a first approximation to G,.
If the dose so calculated exceeds a few per cent of
natural background. a detailed analysis is recommended.
"(6) It is recommended that where required, themore detailed analysis should be obtained by meansof a sampling programme, operated through personal
contact between trained surveyors and both medical
institutions and radiation practitioners, and that dataobtained from this sampling programme should be
used for the determination of G,.
"(d) It is recommended that prior to initiating themain sampling programme (referred to in 2 (c)above), a number of presurveys should be conductedin order to obtain information useful in planning andconducting the programme.
" (e) I t is recommended that in preparation for themain sampling programme, careful planning and instructional programmes should be initiated by aproperly selected group of medical physicists. healthphysicists, radiologists, statisticians, biometricians,
and surveyors. Appropriate dosemeters should .bemade available to the surveyors who should be instructed in their use.
" ( f ) I t is suggested that surveys will result in
improved practices with a consequent reduction in
exposure. This is likely to be a most important consequence of all surveys, and specific suggestions are
made for the reduction of gonad dose due to diagnostic
procedures.

t The list referred to here excludes dental examinations andmass miniature radiography.

"3. Not recrmt)iaelrded"The systematic recording and registration of theradiation received by every member of the population
is not recommended."/

5. The ICRP/ICRU Joint Study Group was mainly
concerned with how the genetically significant doseshould be assessed. This problem is discussed in further
detail in this report. As the scheme of computation iscommon for all types of exposure, it is presented separately, before the various classes of exposure are
discussed.

The gei~eticallysigtlificant dose

Cdculations
6. A general definition of genetically significant dose
has been given in chapter 11. Approximations must be
made to calculate this dose, the most obvious being consideration of groups rather than individuals. It is convenient to start with the approximate definition*

where D= (annual) genetically significant dose,

Nlk= (annual) number of individuals of age

class k, subjected to class j exposure,
Nk =total number of individuals of age-class k
wjk=future number of children expected by an
exposed individual of age-class k subsequent to a class j exposure,
wk =future number of children expected by anaverage individual of age-class k,
dlk =gonad dose per class j exposure of an individual of age-class k,(F) and (Ail) denote "female" and "male" respectively.
7. For the practical work, Equation (1) can be simplified considerably, the iirst step being to replace thedenominator by W O N where
,

and

1

..

w =-

2 w; N;

expressed by the present specific annual birth rate.
This makes i t possible to calculate, by summation, thetotal future expected number of children of an individual of any age, and hence also the mean for any
age-group. If significantly less than unity, the probability of an individual of age a to reach age t should
also be considered. This gives

w;= 2 c;1-8

at P; (t)

(4)

where
wl

=expected future number of children of anindividual of age a. With kno~vledgeof
the function nri of age, the average w;
for any age-group k can be calculated,=age-specificannual birth rate, i.e., annualc',expected number of children of an individual of age-group t,=number of years included in age-group t,At
P i (t) =probability of an individual of age a toreach age (group) t.

10. I t must be noted that c; may have a tendency
to change considerably before an average individual ofa specified age has reached the age-group in question.
-4s it is, however, difficult to predict the values for the
future, c; has been assumed not to vary with time.
11. We= wi+, is the number of children expected by
the average individual during his whole life. The range
of w' is normally 0.8-2, and the range of W' is 2-4
for most developed countries. The ratio IV/w ranges
from 1.5 to 3.
12. The female and the male contribution to thegenetically significant dose can both be written

13. If the gonad dose due to an examination of typej is nearly uniform for all age-classes k, thenapproximately for all k, and Equation (5) reduces to-. (3)k

In the last expression, * denotes the sex. N is the tota
number of individuals of the population. I t should benoticed that w.N is about twice the future numberof children expected by the present population eventhough the value of w may be as low as 0.8.
8. -4s equation (1) has w* in both the numerator
and denominator, the numerical value of w has nodirect relevance, and all terms can be expressed byhelp of the ratio w , ~ / w . For understanding of thedemographic background, however, it is valuable torealize that m must be calculated from the sum of the
age-group products \\.;:N,
for a population. whichmeans that an assumption has to be made regarding
the expected fzctitre number of children (w;) of anindividual in any specified age-group.
9. The assumption could be that the average individual?\i~ill have a future annual child-expectancy* T h e degree of approximation involved in the use of equation(1) depends on the definition of classes j. In theory, there need
be no approximation since the classes may be made so restrictive as to include only one individual per class.

where D; is the contribution from type j examinationof the specified sex to the genetically significant dose.
This again can be written as

which is the expression that has been used for presentation of the data in most of appendices I-X.
14. The necessary information to make it possible
to calculate D; by help of Equation (8) is:=the mean gonad dose per individual
undergoing class j examination,(b) N;/N = the relative frequency of class j examination, i.e., the number of examinations per capita, per year,(a) d;

(G) w;/w =the relative child-expectancy of theaverage'lass jexamination.
T h e formula is applicable also to foetal exposure(w, =W) which must not be overlooked.

administered radioisotopes.
In collecting these data, examinations and treatments
should be classified by(i) radiological type ;(ii) anatomical part ;(iii) age and sex of patient:(iv) disease (for therapy and radioisotopes, at least).
F,, (;I, (;;I(i;;), the classifications recommended
by the ICRP/ICRU Study Group1 should be used.

15. Often dl varies considerably from hospital tohospital. hIost of the uncertainty in estimates of Dl
is probably due to the difficult);of estimating a reliableaverage of d l for a population.
16. If there are no data On the child-ex~ectmc~
ofthe parients*
estimate
D; may be
made, under the assumption that the child-expectancy
is not influenced by the nature of the condition forwhich the patient is examined. w; can then be calculated from the age-distribution of the patients andthe normal child-expectancy for each age-group,

20. The dassification of examinations suggested by
the ICRP/ICRU Joint Study Group' has been slightly
rearranged, for the purposes of this report, to comprisel. Hip and femur (upper third)
2. Femur (middle and lower third)
3. Pelvic region
2 . .
4. LumbosacralNikw--r nrn Nn ,~r W;'
1(9)5. Lumbar spineN;
Ni
6. Dorsal spine
7. Urography (descending [intravenous] pyelowhere w* can be taken from Equation (4). If w;/w is
not given in the primary material, it may be recalcuPP~Y
lated from N;/N, d' and this approximation of D;, but
8. Retrograde (ascending) pyelography
will in that case reflect only variations in the age9. Urethrocystography (bladder examinations, q s distribution of the patients examined and not indicate
tography, urethrography)
any dependence of child expectation on type of examination.
10. Pelvimetry
11. Hysterosalpingography
17. I n the case where the age-distribution in an
12. Obstetrical abdomen
examination class is not known, a yet more simplified
13. Abdomen (pancreas, spleen, liver, pneumoperiassumption must be used, namely
toneum, general =aminations of the urinary
w;=\V* for all persons below mean age of childbearing
tract)
14. Lower gastrointestinal tract (small intestine, apw; = O for all persons above mean age of childpendix, colon, "barium enema")bearing
15. Upper gastrointestinal tract (pharynx, oesoIf n is the total number in the population below thephagus, stomach, "barium swallow and meal")mean age of child-bearing. it follows from Equation (3)16. Gall bladder fcholeqstography)that
17. Chest (heart, cardiac angiography, aorta, respiran*(10)
tory system, lungs)
N
18. Thorax (sternum. ribs, shoulder, clavicle)
which is also, indirectly, a definition of the "mean age
19. Upper limb (hand, forearm, upper arm)of child-bearing". Equation (8) reduces approxileg and foot20. hwermately to
21. Head (skull, cervical spine)
N n;~;="-l.d,=-.-.
(11)
22. Dentaln N
n23. Mass miniature radiography (photofluoroscopy)
Statistical data
21. For countries where a large part of the radiological work is done in private offices, much of it perhaps
18. The scheme of calculation presented in paraby "on-radiologists, it is very difficult to determine thegraphs 6-17 is the one that has been followed by theCommittee in evaluating
data on gonad a- total number of CXaminationS per year, and Still moredifficult to establish the number of ~~iUninati0nSof eachposure. The difficulty of applying any standardized
type or the age and sex distribution of the patients exmethod of calculation to a large amount of heterogeneous
information from various countries
the im- amined. Film consumption provides some check on total
volume of radiography, but none at all on fluoroscopy.
portance of carefully planning any survey of -posure
Underthese circumstances it appears that a rather carelevels which is to yield a statistically useful result.
fully organized survey along the lines suggested by the
19. ~ ~ ~ r o ~ rmeasuresi a t e should be taken to deterICRP/ICRU study Group is required to obtain themine more accurately the frequency of each type ofn,cessary data. ~t is important to specify whether aexamination or treatment. The data available at theor a figure for film cont,td number ofpresent time are particularly scarce or unreliable withsumption in a country, in fact includes all practrces.
regard to the following :Special care should be given the resent at ion of dental( a ) Diagnostic examinations by non-radiologists (byand mass chest examinations.
radiographic and fluoroscopic methods but pamcularlypart of thediag22. F~~countries
by the k n e r ) in countries where these constitute an
nosticis \\..here thebymajor
govemen:al!nStlNappreciable part of the total radiological practice.
tions and a high percentage of the examnatlons Is( b ) X-ray treatment.
carried out in hospitals, it is probable that the total
number of procedures is known fairly accurately and( c ) Diagnostic and therapeutic uses of internally-'

w*=-,.w'

6329. According to another hypothesis, there is a threshold dose ior the induction of leukemia; in this case a
per capita marrow dose has no relevance but the individual marrow doses become the determining factors. As
the relevant dose may then well be the maximum doseto the marrow. wherever it occurs. the mean dose will
not give a measure o i the possible risk.
30. As the evaluation of the significance of a marrow
exposure may involve the number of "years-at-risk",
the mean life-expectancy of each dass of patients should
be studied.
31. More extensive measurements of the marrow dose
resulting from diagnostic and therapeutic proceduresshould be made.

that sampling of representative hospitals is satisfactoryfor determining the number oi examinations of eachtype carried out.
23. All iniormation on the number of films, views
taken, size of fields and radiographic factors used for an"average" examination are helpful for calculation ofdose in the absence of measurements, or as a check onmeasured values. Measurements performed by specialists give, however, more reliable results than any calculations.
21. The gonad dose per examination should be determined more carefully for those exposure classes inwhich the doses are expected to have the greatest genetic
significance. The dose should be investigated in a mannerthat permits the assessments of an average for a whole
population. The doses received by children require particular attention since few data are available. In any
estimates of genetically significant doses, at least children and adults should be treated separately and, when
the inaccuracy in other factors has been reduced suficiently. it may be desirable to classify adults on the basisof size as well.
25. Foetal exposure has a special genetic significancebecause of the comparatively high relative child-expectancy, which in the case of the foetus becomes W/w(stillborns neglected).
26. The difference between the mean child-expectancyof each class of patients and the-mean child-expectancyof the same age and sex group in the population should
be determined with regard to its correlation with :( a ) type of diagnostic examination ;( b ) disease treated and type of treatment.
The correlation with type of diagnostic examination
may prove to be small but there is at present no evidence.
In therapy, the dependence on disease treated is obvious
but must be determined quantitatively to permit accurate
estimation of the genetically significant dose.

32. The weight and distribution of active marrow at
different ages should be determined.
Diagi~osticuses of X-rays
33. It has been estimated that 75 to 90 per cent of thetotal dose from medical uses of ionizing radiations resultsfrom the diagnostic uses of X-rays.'
Estbmtes of the genetically significant dose
34. It should be noticed that almost all estimates of
the genetically significant dose from diagnostic exposure
have been made under the assumption that the childexpectancy of the patients is not influenced by the natureof the condition for which they were examined. This
assumption has not yet been supported by any evidence.
35. The Committee has considered data on gonad exposure from diagnostic X-ray procedures in Australia.*
Austria? Denmark,' England and Wales5 F r a n ~ e , ~and U.S.A.l0 Some authors
J a ~ a nN
, ~~ n v a y Swedeng,~
have reported all data needed for an estimate of thegenetically significant dose (with the exception stated inparagraph 34), while others have given less complete
information. Because of the different procedures of
estimates and bemuse of the difference in diaenostic
practice, the data are not strictly comparable. ~ G v e v e r ,as far as practicable the material is presented in thisaccording to the same uniform scheme, following
the procedure given in paragraphs 6-26.
36. The material from the various countries is presented separately in appendices 1-10. as it has beenfound difficult to make a step by step comparison of
the data. So far as possible the anatomical classificationof examinations recommended by the ICRP/ICRU
Study Group1 has been used. When the original report
differs from this classification, the authors' own terms
have been used. within quotation marks, following thenumber of the most closely related standard class. For
uniformity of presentation, the data are recorded interms of equation (8).

Exposure of the botle marrow
27. ~ c c o r d i nto~ one h~potllesis.the possible adiation induction of leukemia is a linear function of dose.
The same dose to different individuals will probably
entail different degrees of risk for the subsequent
occurrence of the disease, depending upon the age at
the time of exposure and other unknown factors. As theappropriate weighting procedure is not ]inown, the various contributions to marrow exposure must. at present,pe compared without weighting, and the per capita dosein a population is taken as approximately determining
the total number of cases of leukemia t.0 be expectedduring the years following a certain =posure.
28. For the linear dose-effect relationship the relevant
dose is assumed to be the mean marrow dose, averaged
over the whole mass of active marrow (ca. 1,500 g inan adult). The active marrow is taken to be distributed
approximately as follows :Spinal column ........... -40 per centRibs and sternum ......... . 2j ""Pelvis ................... . I j
S ~ ~ ....................
l l
10 " "
Other (e.g. in extremities.
etc.) .................. .10
Infants and children have a wide distribution of active
marrow throughout the skeleton. making estimates ofthe mean dose difficult, especially as the distribution isdependent on age.
(I..

37. The procedure by kvhich Dj was estimated foreach countv is indicated in the introduction to each setof tables. Values of dl for some of the more important
examinations are collected in appendix XI.
38. The most obvious feature of the detailed results
has already been pointed out by the ICRP/ICRU Study
Group1 and by others. namely that about 85 per cent of
the genetically significant dose results from s i s o r seyen
anatomical types of examinations (those in the reglonof the lower abdomen and pelvis). during which the
gonads are usually in the primary beam. although these
constitute less than 10 per cent of the total number of
examinations.

,A

dc

64

39. Data from countries for which it has been possible
to calculate both the per capita gonad dose and thegenetically significant dose indicate that. at present. thesedoses are almost the same. This is, of course, a mere
coincidence and is true only for the total of all contributions. The relative contribution from the various exposure dasses is quite different in the two cases. For
example, while both the annual per capita gonad dose
and the annual genetically significant dose in the British
minimum estimate (see appendix I V ) are 23 mrem,
the corresponding contributions for an esamination 01

Yeur ofst&

CantryPop@tion
at !rm of
study
(N)

Annual number of examinations Conper ccrpifa of falal popu&fion s u m plion o j d n n n d*R
X-ray
genetiPopulolion
Expccrcd Relative
jlmsally
undcr
number child Radiogof
expect- raphy
Anmnal signiffman
Meanchild chrldrm ancy (except -F
numbermnl
agc ojchild
ctpcclafter dental & Flu*>Ipndose A
bearingawy
birth
mass or+
Mass
.D
(Di)
(*R+*F)(n)((m) ( W / m ) m m y ) nopy nrrwys D e d d(mem) (mcm)id,';;;

Aumalia.. ...... 19551957
Austria.. . . ..... 1955-195

9,500,000
6,974,000 3,095,000
Denmark........ 1956-1957 4,450,000 (1,610,000) 0.92
England di Wales. 1955
44,440,000 (18,700,000) 0.93
Fnnce.. ...... . 195i
42,000,000 19,000,000
Japan..... ...... 19%
90,000,000 55,000,000
New Zesland.. .. 1957
2,221,000 (1,160,000) 1.71
Norway ......... 1956
3,400,000!.heden......... 1955
7,178,000 (2,980,000) 0.91
U.S.A.. . ..
1955-1956 162,000,000 81,700,000.

......

a group with a low child-expectancy such as "female
bladder". are 0.26 and 0.08 mrem, and the contributions
from a high child-expectancy group such as .'ioetal exposure in pelvimetrv" are 1.4 and 3.4 mrem res~ectivelv.
- 40.
the' available data have beenAcollect;din table 1, w h i h gives a comparison the frequency of
es-nations
and the level exposure in various countries. The per ,-@ita number of radiographic e d a i n a tions reported by Martin in Australia is unusually highand is the lnain source for the high estimate o i thegenetically significant dose in this country.

2.54
2.20
3.28
2.19

2.25
2.76
2.36
2.21
1.55
1.92
2.4l
1.98

-.

0.48
0.19 no data
0.067 0.31 O.OOi5 na data
0.23-*
0.23 no data
0.30 -*
0.076 0.0?1
0.15 0.62c 0.50° no data
0.25 0.04 0.26 no data
0.34 -- 0.09
0.24
0.15
0.31
0.14 (0.3b)10.25 0.08 0.13 0.4 (1.2b)-.

160 (?ad) 330(5gd)
1.0
0.86

17d
23d
57d

7jd
75d
75d

Pn
capifadace(mrcm)

Dl/f

150 (2Sd)
16-24
17d

Zd

6jd

23d
5Td
10-30

1.1
1.0
38
115
36
0.68 141 (50") 430 (150d) 210 (75d)170

Fluoroscopy is generally performed only in connexion withradiography.
b Number of films.
26,000,000 fluoroscopic examinations per year in France include 19,000,000 mass surveys on the population under age 30.

In addition, 2,000,000 photofluoroscopic examinations are performed annually, so the total number of mass survey euarnlnations is likely to exceed 21,000,000 per year.

Estimates of bone marrow dose
41. The reports on the dose resulting from the treatment of Atzkylositlg Sporzdylitis provide the best basis atpresent for evaluation of a possible risk for radiation-induced leukemia." A discussion on the interpretation ofthis material is given in chapter V. It should be noticed
that some references to marrow dose in literature referto the mean spi~ralmarrow dose instead of the averageover the whole mass of active marrow. The latter doseis only about 40 per cent of the mean dose in the spine
marrow if other marrow than the spinal has not been
exposed.
42. Few measurements of the dose resulting fromdiagnostic X-ray exposure of the bone marrow havebeen published. The annual mean marrow dose fromdiagnostic X-ray exposure in Australia has been estimated to be about 100 mrem per capita.lz An attempt
has been made here to make another estimate based upona good current practice and an average frequency of examinations in the same countries which have reported
data on gonad exposure.
43. A representative number of examinations of eachtype N,, has accordingly been taken from the data on thegenetically significant dose, and the mean marrow dose,
averaged over the whole active marrow dose, has been
calculated from available information on number of films
per examination, size of films, skin dose per film, percentage depth dose, etc. Since the estimate at best is only
a very preliminary one, it has been considered justifiable to make several simplifying assumptions.
44. All estimates have been based on "standard man"as defined by the ICRP?3 It has been assumed that the
total weight of active marrow is 1,500 grams and that
it is distributed as follows: spinal column, 40 per cent;ribs and sternum, 25 per cent; pelvis, 15 per cent ; skull,
10 per cent ;other, 10 per cent. No estimates for children
have been attempted ;this would be more difficult becauseof the wide distribution of active marrow throughout
the skeleton of a child and the dependence of this distribution on age.

d Minimum estimate.

45. The number of films per examination have been
determined from manuals of radiology"*15 and frompublished reports on radiographic techniques. The number of films assumed per esamination range from one to
five (including spot films), depending on the anatomicalpart ; the average is 2.6 as compared with an average of3 assumed by Laughlin and Pullman.l0 In most cases,
Webster and Merrill's1° values of skin dose have beenused. These are considerably lower than many of the
published values (e.g. Ritter, Warren and PendergrassL7) but are not as low as those of Ardran andCrooks.18 They are probably fairly representative of thebest present-day radiological practice but may be ?Ppreciably lower than the skin doses in average pracace-

46. The half-value layer of the incident radiation has
been assumed to be 3.0 mm of aluminium in all cases,
corresponding to an effective voltage of 33.6 kV- The
position of the marrow for each view has been determined from "A Cross-Section Anatomy" by Eycleshymer and Schoemakerle and the amount of marrow
included in the field estimated from reproductions
typical radiographs as found in manuals of radlographlcoftechniques.15'16 The percentage depth dose at the level
the marrow has been determined in each case fro111
depth dose tables published by Johns, Epp and Fedorul<,?O
their values being corrected for differences in focusskin distance and for shielding of marrow by the surrounding bone.. The absorption coefficient assumed forbone is not too Important since, for the quality of radiation used. the reduction in dose due to bone shielding isprobably less than 20 per cent in every case. No correction has been made for the fact that the marrow islocated in a trabecular bone structure since it has been
estimatedz1that the increase in marrow dose due to proximity of bone is not inore than 5 to 15 per cent for radiation of diagnostic quality.

47. The product of the skin dose, the corrected percentage depth dose and the fraction of active marrowassumed to be in the field gives the contribution to themean marrow dose for each location of marrow. Calculation of dose by this method gives values somewhat
lower than measurements of marrow dose reported byJones and Ellis2' but are not in serious disagreement.
The calulated doses are in good agreement with somepreliminary measurements by Laughlin et al.'? of thedose received by the marrow of the vertebral column
during a photoffuorographic chest examination.

48. The estimates of mean marrow dose from fluoroscopic procedures are much more uncertain than thosefrom radiography. Skin dose rates of 5 r per minute and
10 r per minute have been assumed for radiologists andnon-radiologists respectively, and the total time of fluoroscopy taken to be two to five minutes depending on ex-

amination. For a country, such as the United States,
where the number of examinations by non-radiologists
is high, the annual contribution from these examinations
to the per capita mean marrow dose can be estimated tobe between 10 and 20 mrem. In the examinations madeby radiologists the fluoroscopic contribution to the percapita mean marrow dose is less important although theindividual dose from this practice in =treme cases may
be very high.
49. From the mean marrow dose. calculated under
the simplified assumptions specified above, a per ca.pita
marrow dose from each type of examination has been
estimated, assuming an average frequency of each examination fairly representative for countries such as theUnited Kingdom, the United States and Sweden. The
breakdown of the total by type of examination is given
in table 11.
50. It is apparent from the table that the highest contribution to the per capita mean marrow dose comes fromexaminations of the gastro-intestinal tract and that mass
chest X-ray surveys are of relatively much greater importance here than they are in the case of geneticallysignificant dose. The sum of the contributions in thetable is approximately 45 mrem/year and after allowancefor the contribution from fluoroscopy, the per capita
mean marrow dose might be of the order of 50-100 mrem
per year, somewhat lower than the Australian estimate"and current British estimateP3.
51. The mean marrow dose per examination in mass
chest X-ray procedures has been measured by several
investigators, who report doses between 70and 120 mrem

TABLE
11. ANNUALPER CAPIT.4 MEAN LIARROW DOSE FROM DIAGNOSTIC
X - R A Y EXPOSURE (EXCLUDLVG FLUOROSCOPY)(Figures based upon an assumed average practice, cf. text)
manow

N o . exom.
9erl.OW(mrcm)

IOU
pop.

Mcon

dmc

No.

vim5

Eraminolion

1. Lower femur.. ....... 1 AP
2. Hip and femur.. ..... 1 -4P
3. Pelvis.. ............. 1 . w
4. Lumbe-sacral. ....... 1 AP
5. Lumbar spine.. ...... 1 AP
6. Dorsal spine. ........ 1 AP
7. Inuav. pyelography.. 5 l\P
2 AP
8. Retrog. pyelography.
1 AP
9. Urethrocystography..
10. Pelvimetry ........... 1 AP
11. Salpingography....... 3 AP
12. Abdomen (obstetrical) 1 AP
13. Abdomen..
1 AP
14. Lower G.1 ............ 2 -4P
15. Upper G.I.. .......... 1 -4P
16. Cholecystography..
4 PA
17. Chest.. ............. 1 PA
18. (a) Ribs and sternum. 1 PA(b) Shoulder.. ....... 1 P-4
19. Arm.. .............. 1
20. Foot.. .............. 1
21. (a) Skull.. .......... 1 AP(b) Cervical spine. . . . 1 r\P
22. Dental.. ............ 1
23. Mass min.b.. ........ 1 P-4.
.
.

..........

...

dAnnuol W~$itomMOW

daw(mrcm)+ 1 LAT+ 1 LAT+ 1 L.4T + 2 OBL+ 2 LAT+ 1 LAT + 1 OBL+ 1 LAT + 2 OBL+ 1 outlet + 2 LAT+ 3 PA+ 2 PA + 1 L-AT
+ 1 L.4T+ 1 LAT+ 1 L.4T+ 1 PA + 2 LAT+ 1 PA + 2 L.4T

" -4merican practice including about 100 examinations per year per 1,000 of total population gives a mean marrow dose of 8 mrem per cafifu and year. Britlsh practice involves only
20 examinations per year per 1,000 of total population, which corresponds to less than
0.4 mrem #r caPi!u and year. The asumptions on location of active marrow make estimatesfor shvll esDosure verv uncertain.
b See disiussion in text, paragraphs 51-52.

66

for good practice, with examinations involving only apostero-anterior vie^.^^*^^*^^-^^ In some countries lateralviews are taken in addition to the postero-anterior view.'3
Although the doses reported per examination might beconsidered as low estimates for the current practice,there are indications that it may be possible to reduce thisexposure considerably in the future.
52. The relatively high per capita mean marrow dosefrom mass chest X-ray examinations is due to the highirequency of this examination. Assuming 10 per centof the population examined each year the annual per
capita mean marrow dose from this type of examination
would be 10 mrem; however, certain regions report ashigh frequency as one examination per capita per year
which would result in the ten-fold per capita dose.
53. I n countries where fluoroscopy has not been replaced by photofluoroscopy for mass s u r v e y ~the, ~ annual
per capita mean marrow dose probably results to a highdegree irom these surveys and may considerably exceed
100 mrem.

Accuracy of estintutes
54. The Committee is in agreement with the suggestion of the ICRP/ICRU Study Group1 that since theaccuracy in estimating the annual genetically significant
dose to a "normal" population due to natural sources isabout r 25 mrem, the same absolute accuracy is satisfactory for a first estimate. at least, of the genetically significant dose due to medical sources. This means an accuracy of e 25 per cent for e.g. the United States andabout & 100 per cent for countries such as Denmarkand Sweden. I t is stated by Osborn and S m i t h w a t theestimate for the United Kingdom may be out by a factorof 2 to 10 and there is a factor of nearly 3 between theminimum and probable doses estimated for the UnitedStates.lo It is evident that the accuracy desired for evena first estimate has not yet been obtained: the eventual
objective should be to reduce the absolute uncertainty ofthe estimate well below that of the baclcground dose.
55. It is convenient to discuss the inaccuracies in theestimates which have been made of the genetically significant dose in terms of equation (8). As pointed out inparagraphs 21-22, the total number of examinations is
not very accurately known in countries where a largepart of the radiological work is done in private offices andeven by non-radiologists.
56. Estimation of the factor w,/w in equation (8)depends. as has already been said, on trvo considerations : (a)the age and sex distribution of patients receiving each type of examination and ( b ) the difference
between the child-bearing expectancies of class jk andclass k as a whole. There does not appear to be any
evidence on the latter point. However, for most typesof diagnostic examination wj, may not differ greatly
from wk. Further, it is only for the six or seven examinations which make the largest contributions that a difference between w,r and wkcan affect appreciably the estimate of genetically significant dose.
57. The determination of the distribution of the total
number of examinations on various exposure classes andon age and sex groups must be made by sampling procedures. This is difficult to carry out satisfactorily unlessa high percentage of the examinations are made out at a
relatively small number of hospitals.
58. The same difficulty is related to the estimate of arepresentative average gonad dose per examination. As
the gonad dose per examination varies from hospital

to hospital it is very f i c u l t to give an average with agood accuracy. This is probably the main source of uncertainty to the calculated genetically significant dose andthe per capita mean marrow dose. Values o i the gonaddose per examination as measured in various countries
are collected by type of -amination in appendis XI.
59. Another source of uncertain5 in the per capita
mean marrow dose is the scant information on the distribution of active marrow.

Redrrctioft of gonadal dose

60. From an international point of view, the mostserious criticism is the fact that to date, estimates areavailable for only six or seven countries. Fortunately,
the have been made for some of the countries in which
medical exposures may be expected to be highest.
that
61. It has been demonstrated1*g*13*1~~~8f2*2~a6*a1
gonad doses can be reduced very decidedly by improved
techniques (e.g., by a factor of 50 to 100) for some cuaminations of males. The greatest attention must be
paid. of course, to the six or seven esaminations which
contribute the largest significant doses. Methods havebeen pointed out by the ICRP.'J3
62. The following is quoted from the report of the
ICRP/ICRU Joint Study Group :l" 1. Currettt Recomniendations"Equipmeat for fluoroscopy"The fixed total filter equivalent value should be atleast 2 mm aluminium, and should be based on thevalue obtained at the highest voltage of the X-ray
apparatus.
"The use of a timer to measure the fluoroscopy timeis recommended.
"Procedure for fltcoroscop y"Before a fluoroscopic examination is begun, theeyes must be sufficiently dark-adapted. In order towork with the lowest possible dose-rate, the adaptation period should be at least 10 minutes. A smaller
time may be used if there has been preliminary
adaptation using red goggles.
"Eqrtipnzeltt for radiography" A total filter of at least 2 mm aluminium should
be used.
"An automatic switch should be incorporated.
"Other types of diagnostic work
"Dental radiography"Fluoroscopy is strongly deprecated.
"klobile diag,rostic equipment"All transportable equipment should be provided
with cones or with other restricting devices so that thesmallest anode s k i distance is normally at least 30 cm(12 in.).
"It should be noted that damage has occurred toworkers and patients from contact radiography.
"At least 1.5 mm aluminium equivalent should be
provided as a fixed total filter.
"Fluoroscopy should be used only if the eqtlipmel?t
meets the requirements recommended for fluoroscoPlc
equipment.
"Protection of patients"General rules"By X-ray protection of the patient it is meant thatthe radiation exposure of the patient should be-reduced as much as is compatible with successful dlag-

nostic investigation or therapeutic treatment. In thecase of non-malignant diseases, therapeutic treatment
shall be employed with caution. I n all therapeutic anddiagnostic exposures, the integral dose should be kept
as low as possible in order to protect the patient asmuch as possible from the radiation. Moreover, forthis purpose, the tube-current, or the mAs value, andthe number of examinations should be kept to a minimum. An automatic timer should indicate the lengthof the diagnostic or therapeutic exposure. In all diagnostic investigations, the beam that strikes the patient
should have a cross-section no larger than is essential
for the investigation. This is of articular importancein fluoroscopy. In all irradiations the gonads should beprotected as much as possible by collimation of thebeam or by protective screens. I n the case of children,
it is important, in view of the little known action ofradiation on
tissues, to be cautious about repeating diagnostic examinations and to avoid too frequent systematic esarninatiorls of the whole of thebody.
"Exposzire ijt diag,rostic CZa?71i?Zati0lls"For ease and clarity in the consideration of
exposures received in diagnostic work, it is recommended that tables be set up giving doses for radiograpy and fluoroscopy of lung, stomach, intestines, etc,
Integral dose should also be taken into account as it
gives a much clearer picture of the true exposure.
Special attention should be given to the possible hazards to pneumothoras patients who. as a result of themany screenings after each inflation, may receive large
doses. The screenings should be replaced in part byradiographs.
"Radiation certificate"In view of the continually increasing medical andtechnical use of ionizing radiation, it is desirable toaccumulate information regarding the doses received
both by individuals and by the population as a whole.
As far as the indiyidual is concerned, the information
could be obtained by the introduction of a certificate
in which are recorded details of all radiation exposure(medical and occupational) received through life.
Probably it is impracticable to introduce such a certificate at preset, but it is recommended that all radiologists and dentists keep records of the doses given,and the field sizes and radiation qualities used. in all
diagnostic procedures. ( I t is presumed that suchrecords are already available in the case of therapeutic
procedures.)"2. Reco?nmendaiions regardi?lg the followi~zg
items are tcitder consideration" ( a ) The provision of specially designed protective devices for the gonads of patients.
" ( b ) Additional recommendations regarding minimum film-focus distances.
" ( c ) Increasing the protective requirements fordiagnostic and therapeutic tube housings.
"(d) Improvements in beam collimation.
" ( e ) The pro~isionof permanent filters of at least
2 mm A1 equivalent on all diagnostic X-ray tubes.
"(f) The ad\-antages of using high voltage techniques for diagnostic J\-ork.
(6') The provisionercposure counters on all
diagnostic equipment.
''(12) The use of image intensifiers to reduce thedose to the patient, and consequently to the operator,"

rather than as a means of permitting more extensive
and prolonged fluoroscopy than hitherto.''63. It is improbable that there will be great improvement in accuracy of estimation of gonad doses until therange of actual doses is reduced appreciably by conscientious adherence to procedures as have been recommended by the ICRP. In this connexion it is probablethat the "feedback" suggested by the ICRP/ICRU
Study Group is already operating, i.e., the attention toestimation of the genetically significant dose is already
reducing the dose.
64. Reduction o i gonad dose may also be obtained in
the future by means of improved radiological equipment
and supplies, e.g., faster films. faster screens, etc. The
advantage to be gained by increased use of image amplifiers has already been pointed out by the ICRP/ICRU.l
65. Finally, reduction in gonad dose can be achievedby a reconsideration by the medical profession of thecircumstances under which X-ray diagnosis is appropriate. This could be facilitated bv statistical informationon the significance of each aimination class for the
reduction of any specified morbidity. When medical
decision has been taken, administrative co-ordination
should be improved between authorities who require thatcertain examinations be made in the routine health surveillance of whole populations or special groups such as
school-children, students, employees, immigrants.
66. The tables in appendix XI point to the possibilityof carrying out some examinations at much lower gonad
exposure levels than are likely to be obtained in the
average case at present. The annual genetically significant dose that may be achievable without detriment todiagnostic information has been estimated to be less than
30 mrem for AustraliaZand 15 mrem for S ~ e d e n . ~Radiotherapy
Geiietically signijica~ztdose
67. S. H. Clark3' has estimated the genetically significant dose due to radiotherapy in the United States as
about 10 mrem per year. This figure, quoted by Laughlin
and P ~ l l m a n , is
' ~based on the assumption that treatmentof malignant conditions are not genetically significant.
I t may hence be an under-estimate. For Australia,
Martin2t3=reports an estimate of the contribution to thegenetically significant dose from radiotherapy as 28
mrem per year, assuming a normal child-espectancy ?fall surviving patients that were not assumed to be stenlized by the irradiation. Surrey by Purser and Quistss
yields an estimate of 1 mrem per capita gonad dose per
year in Denmark. I n the Danish survey it was found that
22 per cent of the genetically significant dose resulted
from treatment of malignant conditions, assuming thatthe patients treated for malignancies have one-fifth thechild-expectancy of normal individuals.
Bone nzarrow dose
68. I t does not appear possible to estimate T%-itbany
certainty even the order of magnitude of the per capita
mean marrow dose, due to radiotherapy, from the data
at present available to the Committee.
I~zfer?zallyad?riinistered radioisotopes
69. The principal contributions to the population dosefrom &e medical use of radioisotopes arise from the useof 113'and P3'which are most widely em~loved.Whileconsiderable quantities of -qu19Sare ;sed.-thG biologicalsignificance of esposure from this course is negligible

75. The age-distribution of the workers is usuallysuch that about 50 per cent are under the mean age o iHence. the genetically significant dose
~hild-bearing.~*'.~~
is approximately equal to the per capita dose. Averageannual doses ranging from 500 - 5,000 mrem have beenreported to the Committee as resulting from occupational medical exposure,~7*iciebut this esposure does
not refer to all installations shown in table 111. F o r
example, the exposure oi dentists or their assistants is
usually very
and most radiotherapy with X-rays
can be carried out under conditions ensuring good proAnnual average doses of up
tection of the pers~nnel.'~to 5,000 mrem refer to less than 0.2 persons per 1,000of the total population and result therefore in a percapita dose of less than 1 mrem per year, mostly from
X-ray diagnostic ~ o r k . ~ ~ * ' ~76. Medical radioisotope work is usually performed
with little exposure of the pers~nnel.'~An important
exception is the work with implantation of radium applicators and needles where the personnel may at present
be exposed to considerably more than 100 mrern per
week.so.66.~: This cuposure, however, involves only avery small group of people.

since A U ~ ~ generallyVSlimited to palliative treatment
of incurable conditions. Other radioisotopes are usedin very small quantities and aln~ostentirely for diagnostic purposes.
70. Estimates of the per capita gonad dose resulting
from the use of 1131 and P3Qan be based upon information about either treatments or radioisotope shipments, the first approach being more accurate and preferable.3i~39.40From the report of the ICRP/ICRU
Joint Study Group1 and other information available to~ ' ~ likely that the geneticallythe C ~ m r n i t t e e , ~it~seems
significant dose is lower than 1 mrem per year, evenin the countries ior which the highest figures can be
expected.
71. Some experience on the effects of ingesting radioactive substances relates to the early period when thehazard was not realized. The work with radioactive luminous materials was early recognized as hazardous if
not properly conducted:' but radioactive contrast media
such as Thorotrast were being used occasionally in
X-ray diagnostic work until a few years ago. The highretention of the radioactive material in the liver and thespleen resulted in rather high exposure, with dose-ratesof the order of 0.3 rem per day during periods ofyear^.'^*'^

Atontic erlergy workers
77. More complete and more accurate data are available for this group than for any other occupationally=posed group, since in countries in which atomic energy
establishments are operated, monitoring procedures havebeen set up to cover exposed personnel.
78. The contribution from =posure of atomic energy
worlters to the genetically significant dose to the population is about 0.1 mrem per year or less in countries forwhich it has been estimated.4i~46*51~s2
However, since thenumber of atomic energy workers is =petted to increasein the near future, this figure may increase in proportion.
79. The figures in table I V have been taken from a report of the United States Atomic Energy Commissiot~.~~111. IXDUSTRIAL
ASD RESEARCHUSES OF X-UYS ASD
RADIOACTIVE bf ATERIALS

Occtrpaiional exposure
72. The exposure from industrial and research usesof X-rays and radioactive materials is mainly an occupational one. The estent to which non-occupationally
exposed individuals are esposed depends upon the degree of environmental contamination. The latter problem
is treated in annes D.

T;IBLEIV. EXPOSURE
OF ATOMIC ESERGYPERSONNEL IN THE UNITEDSTATESOF AMERICA

Medical workers
73. The countries reporting on the number of persons
in medical radiologicalhave presented
figures ranging from 0.17-4.69 per 1.000 of the total
population. Ilowever, in many cases it is not clear what
has been meant by "medical worker".

( a ) Exposure of A.E.C. contracfor persotrnel
to penetrating radialion (1955)
Annual dose (mrcm)

0- 1,000
1,000- 5,000
5 , ~ 1 0 , ~ 0
10,0~15,000>15,000

74. The following table shows the extent of X-ray
work in New Zealand's and Swedeni' and gives anidea of the relative number of various installations incountries with =tensive medical facilities.

I957

Type of inrfdlalion

0.14
0.02
0.24

0.15
0.01
0.40

0.46
0.03
0.93

0.02

-

-

-

TOTAL
ALDICAL
0.42
Shoefitting ............... 0.03
Veterinary.. ............. 0.01
Industrial. .............. 0.003
Research and educational.. 0.01

Year

1.42

0.004
0.02
0.03

iiighest dose
(repn)

1947 .................... 23.5
1918.. .................. 20.3
1949 .................... 13.6
1950 ....................
9.0
1951 ....................
7.1
1952 .................... 15.7
1953 .................... 12.9
1954.. .................. 27.8
1955.. .................. 17.9

-

0.56

94.2
5.2
0.5
<0.1
<0.01

100.0

(b) Highest accumulated yearly doses lo individual
A.E.C. contractor employees during routine operations(accidents excluded)

Sxeden. 1955

Number of
Number of
Number ofpzaqils per
planls pcr crposcd vurfins~.ooOofI , W ofpcr 1.000 of
totai$opulalM; total poprrbfion foldpopulalron

Diagnostic.. .............
Therapy ................
Dental.. ................
Chiropractors andnaturopathic...........

Pnrrnlage

56,708
3,157
285
41
3
60,194

TABLE
111. N U A ~ B E
O FRX-RAY IXSTALLATIONS,
bz ~ ~ n d .

N u n k of rorkus

0.01
0.06
0.02

69

Average of 10
highest dosu
(rent)

5.2
1.2
2.6
2.2
1.8
2.9
3.4
3.9
4.1

Itdustrial and researclt workers
80. The information on exposure of industrial andresearch workers is less complete than the information
on exposure of the other occupational group^.^^'"^^'^*^^
As is evident from the relation between the number of
persons and number of plants in table 111, the concept"research worker" is not well defined. If the exposure
is assumed to be equal to that in the group of medical
workers, the contribution to the population dose is lower,
because of the smaller number of workers. Industrial
yradiography is one of the main sources of exposureof this81. A speaal occupational problem is the exposure ofworkers in mining and milling radioactive materials suchas uraniurn.*8*54 If not properly conducted, this work
may involve considerable hazard to the workers.

82. From the information surveyed above, it appears
that the contribution from occupational exposure to thegenetically significant dose is less than 2 mrem per year

for most countries. Despite the fact that this contribution is relatively small and the corresponding contribution to doses significant for somatic injury is also small,the exposure of radiation workers merits special attention for two reasons : ( a ) there n4l be a considerable
increase in the near future in the number of atomic
energy employees in many countries, and ( b ) individual
exposures may be high even though the contribution to
the mean dose of the population is small.
83. Methods for reducing the occupational exposure
have been pointed out by ICRPISand ILO.SS
IV. OTHER
MAN-MADE SOURCES OF RADIATION
81. Watches and clocks with radioactive luminous
dials give an annual genetically significant dose of about
1 mrem.46*"X-rays from television receivers contributeless than 1 mre~n.'~X-rays from shoe-fitting fluoroscopes contribute still less, as they normally expose a
relatively small number of i n d i ~ i d u a l s . ~(However,~~'~~~~
they might be an important hazard to the exposed individuals, see reference 64.)

DATA FOR EVALUATION OF THE GENETICALLY SIGNIFICANT DOSE
F'RORl DIAGNOSTIC X-R4Y EXPOSURE

APPENDIXIAUSTRALIA
The data on gonad exposure in Australia have beentaken from papers by Martin21S6.The author has rear-

ranged his material for the purpose of this report.
Martin's estimate of the annual genetically significant
dose is unusually high. This is mainly due to the highper capita number of examinations, which the author
has assumed to be 60 per cent higher than the number
for England and Wales (cf. paragraph 40).

(See Appendix I. Table I on page 71.)

. . . . .

6 : : : :- ZQ s a s s

E?

o

0 h

=-23

I

ci +

-000
dInM-In
GOOmd

n99994q?8a2

ooooeoooooc

~8

c c

.B::::.-c .. .. L =e
Y

.

.

.

.

C

.

.

.

.

5 : ;gzKKo e ~ g g''02 $
~ ~ g

<uhEX

.

3

--

-

AFJPEXDIX
I1
AUSTRIAThe data submitted by 4ustriaS do not permit a presentation according to Equation (8). The folloiving
information is giv& :I

d , fmrcm)(A) Radiography:
Pelvis, hips. lumbar_spine - 6 . &-Abdomen, colon, genitoun'nary
Pelvimetry, obstetrics.,..............

7.5

40-240 (AP) 6-24 (-4P)
20-80 (Lat) 8-30 (Lat)
6,000,- 0.75 -- 200 (AP)- - - 1,000 (Lat)
Other classic techniques. . 52
60

12,000-i

10Tomography.. .........
0.152
2
Other special techniques..
O.i5
Dental.. ............... not known
10-10010-1002
1
Mass surveys.. .........
7.5(B) FIuuroscopy:
hlass surveys.. ......... negligible310
not h o n n not knouvn
Other examinations..

-

...

-

From the above data, the per capita gonad dose fromdiagnostic X-ray exposure is estimated to be 16-25 mrem
per year.
APPENDIX
I11
i ':rDENMARKThe pritnary ntaterialIt

1. The following estimate of the genetically significant dose from diagnostic X-ray procedures in Denmarkis based upon data published by Hammer-Jacobsen.' The
author assumes the annual number of examinations in
Denrnarlc to be 1,000,000 plus 1,000,000 mass chest

photofluoroscopies. The data are assumed to be representative for 1956 (the dose-measurements were madeduring September 1956-February 1957).
2. The examinations cover the total practice withradiography and fluoroscopy combined. However. thedistribution of examinations with respect to type andsex is as observed in one hospital in which about 5 percent of the total number of examinations are performed.
3. The author estimates a per capifa dose of 26 mremfrom the above data, but considers that this may be aminimum estimate.
4. No data on foetal exposure are given. The author
estimates the foetal contribution to the total per capita
dose in proportion to the relation foetal/female contribution given by Osborn and S ~ n i t h . ~Presentation of the nratmial for this report
5. The Danish data include values for Nj and dl inall cases needed for an estimate of Dj.
6. No values for w,/w are given. The values for wj/w
presented in the table for England and Wales have beenused as substitutes in the first approximation. This gives
female and male contributions of 5 and 8 mrem to thegenetically significant dose, as compared to the author's
per capita doses of 7 and 15 mrem respectively.
7. If the foetal contribution is taken in proportion to
the female contribution and the ratio 72.2 per cent fromthe British report is used, the foetal value will be 4 mrem.
This seems, however, to be a low value, as a back calculation by help of the known value of wj/w for the
foetus, implies a foetal dose of, e.g., less than 500 mrem
per examination from pelvimetry, whereas other countries report values ranging from 2,500-4,500 mrem.

DATAFOR EVALUATION OF THE GENETICALLY SIGNIFICANT DOSE FROM DIAGSOSTIC X-RAY EXPOSURE
APPEXDIX111. TABLEI.
DENMARK
Molu

Fcmoks

No.

T>*c of crominolion

1.OW

N I/N

dl
mrcm

wj/w

Di

mrrm

1.000

NI/N

dl
mrcm

Tot&
=i/m

Dj
mrcm

Di

wrm

Dl

b n ccnl

0.7
0.09
2.2
911
2.5
54
1. Hip and femur.. ................
4.3
3.25
1.7
0.6
0.7
0.00
2.
"Knee and aus". ..............
0.9
0.13
2.5
527
0.7
195
3. Pelvic region. ...................
97
4*(~umbarspine. ..................
3.1
206
0.6
0.42
4.3
5.
2.2
20
6. Dorsal spine.. ...................
1.1
14
0.7
0.01
4.3
948
4.3
525
0.8
1.81
7. Intraven. pyelography.. ..........
0.9
2,400
0.4
1,060
0.8
0.34
8. Retrograde pyelography ..........
"Urethrocystography" .........
0.0
430
0.00
0.4
3,450n
0.3
0.04
0.4
4,720
0.4
406
9.( "Cptogr. dur. micturition*'. . . .
0.9
1.51............. 2.2564
10. Pelvimetry.. .....,
1.1
0.18
0.9
183
11. Hysterosalpingography ...........
1.8
0.64
2.0
177
12. Obstetrical abdomen. ............
0.4
567
0.4
19
0.6
0.02
13.
"Abdomen, A. P., urin.". .......
0.2
0.02
4.3
37
4.3
19
"Bariumenema". .............
14.
0.4
0.02
7.4
19
7.2
8.4
15. "Barium swallow and meal". ....
0.2
0.01
2.0
1.7
4.0
14.5
16. "Gall bladder". ...............
1.3
0.00
34.6
0.33
0.07
"Chest" ...................... 36.0
34
0.5
0.01
4.5
"Chest, special". ..............
3.8
5.0
0.20
0.7
0.00
2.2
2.0
0.03
"Shoulder" ....................
18ll.1 "Ribs and sternum". ...........
0.2
0.15
0.4
0.00
0.4
0.45
19.
".km and hand". .............
5.8
0.05
1.1
0.00
9.4
0.24
20.
"Foot" ........................
2.9
0.6
1.0
0.00
4.7
3.25
"I-Iead". ...................... 14.8
0.2
1.5
0.00
17.5
0.8
21.{ "Teeth" ......................
1.0
0.00
1.8
4.4
1.3
0.8
0.5
0.00
3.8
1.6
"Cervical spine". ..............
4.0
0.17
0.5
0.00
22. Dental.. . . . . . . . . . . . . . . . . . . . . . . .
23. hiass min. radiography. .......... 110
0.15
1.3
0.02
110
0.25
SLT-TOTALS 5.25
Allo\x-ance for foetal exposure, assumed to be 72.2% of female contribution. .................

-

-

-

-

The dose 3,450 mrem for m2les in item 9 is an average of dose measurements from 7 male adults urethrog-raphygraphy2 male adults cystopphy.

++ 1 boy urethro--APPENDIXIV
E N G L A N D A N D WALES
The pri?nary ntaterial
1. The Committee has not received material uponwhich it can base an estimate of the probable geneticallysignificant dose for England and Wales. I t is, however,possible to give a lower limit under certain assumptions.
The primary figures (for radiography and fluoroscopy
combined) have been taken from a report by Osborn
and Smith (1956).5 These authors have used values forthe gonad dose per examination published by Stanford
and Vance (1956).5* They computed the product N;
w; d; using the follotving statistics:( a ) The total number of diagnostic =aminations per
year based on official figures.
( b ) The distribution of examination with respect totype, age and sex in what was believed to be a representative sample of hospitals.
(c) The child-expectancy derived from official statistics and assumed not to be influenced by the natureof the condition for which the patient was esamined(except in the case of hysterosalpi~gograph~).

2. An estensive British survey of the diagnostic e s posure in the United Kingdom is at present being made,5B
but no data are a~ailablefor this report.
Presentation of the material for this report*
3. After division by wN the values reported by
Osborn and Smith may be taken as approsirnate lower
limits of the contributions to the genetically significant
dose for England and Wales. The values of w,/w foreach examination class have been caIculated from the
known values of Nj/N, dj and the approximation of
Dj, and should depend only upon the age-distribution
within the class following the assumption under 1. ( c )above.
*These calculations are based on available figures which insome cases have been "rounded off" in publication. The results
are therefore approximate and, although adequate for thepresent purpose, are less accurate than could be derived from
calcul~tionsbased on the original data.

NUMBEROF E-WIINATIONS PER 1,000 OF TOTAL POPULATION(1000 N;/N)

ENGU~
AND WALESAPPENDIXIV. TABLEI.
Exam.
No.

Fcmalcs( d l ages)

Malet(all n;u)

ForlJ g o M d r

1.
2.
"Hip and femur".
3. Pelvis .............................
4.
5.
"Lumbar spine". ................

................

6.
7.

8.

"Thoraac spine". ................
"Pyelography" ...................

.......................
......................

9.
"Bladder"10. Pelvimetry..
11. Salpingography ....................
12.
13.
"Abdomen with obstetric".
14.
"Barium enema".. ...............
15.
"Barium swallow and meal". ......
16. Cholecystography
17. Chest.. ...........................
shoulder". ...
18. "Ribs and sternum
19.
m..... .........................
20. Lowerleg .........................
21.
"Mead
cervical spine". .........
22. Dental ............................
23. Llasssurveys ......................
24. Others.. ..........................

.......

..................

+

.-

+

Including 1.91 obstetrical.
Including alloa-ance for possible pregnancy in non-obstetric abdominal examinations.
Large film.
G Sial film.
6 t h exam. a t hospitals.

RELATIVECHILD EXPECTANCY(.r;/rv>
APPENDIX

IV. TABLE11.

ENGLAND
AND WALES

Exam.
No.

Females(all ores)

1.
2. "Hip and femur". ................
0.75
3. Pelvis.. ...........................
0.93
4.
5. "Lumbar spine". ................
0.63
6. "Thoracic spine". ................
0.67
7.
8. "Pyelography".. .................
0.81
9. "Bladder" .......................
0.30
10. Pelvimetry.. ......................
0.94
11. Salpingography ....................
1.07
12.
13. "Abdomen with obstetric". .......
1.08
14. "Barium enema". ................
0.22
15. "Barium swallow and meal". ......
0.40
16. Cholecystography.. ................
0.16
17. Chest .............................
1.3/0.50
18. "Ribs and sternum
shoulder".
0.38/0.67
19.Arm ..............................
1.1
20. Lower Leg. .......................
0.98
21. "Headcervical spine". .........
1.5/0.52
22. Dental.. .......................... 0.53/1.0
23. hfass surveys.. ....................
1.32
24. Others.. ..........................

+

...

+

Maks
(all ages)

Foctd goMdr

1.13
0.56

2.36

0.83
0.80

u

0.53
0.23

u

-

-

1.54
0.58
0.43
0.28
1.3/0.85
0.74/0.88
1.5
1.2
1.6/1.1
0.37/0.87
0.88

2.36

u

CI

Y

u

U
Y
U
C

Y

u
a
Y
C
U

(See footnotes to table I).

GONAD DOSE PER EXAMINATION(d; in mrad or mrem)
APPENDIXIV. TABLE
111.
ENGLAND
AND WALES
Fcmalcs(all ogrs)

&am.

No.

1.
2. "Hip and femur".. ...............
. 3. Pelvis.. ..........................
4.
5. "Lumbar spine". ................
6. "Thoracic spine". ................
7.
8. "Pyelography" ...................
9. "Bladder" .......................
10. Pelvimetry ........................
1 1. Salpingography ....................
12.
13. "Abdomen with obstetric". .......
14. "Barium enema". ................
15. "Barium swallow and meal". ......
16. Cholecystography ..................
17. Chest .............................
18. "Ribs and sternum shoulder". ...
19. Arm.. ............................
20. Lower leg.. .......................
21. "Headcervical spine". .........
22. Dental.. ..........................
23. Mass surveys.. ....................
24. Others.. ..........................

++(See footnotes to table I).

Mnks(all arcs)

F&ANNUALGENETICALLY SIGNIFICANT DOSE
(D; in mrem)
APPENDIX IV. TABLEIV.
ENGLAND
AND LVALES
Fmdes(all ages)(aU arcs)

0.82
0.51

4.18
1.60

2.34
0.02

0.56
0.03

8. "Pyelography"............... 2.33
9. "Bladder".. ................. 0.08
10. Pelvimetry. ................... 0.65
1 1. Salpingography ................ 0.24
12.
13. "Abdomen with obstetric". ....
14. "Barium enema". ............
15. "Barium swallow and meal". ..
16. Cholecystography..............
17. Chest.. .......................
18. "Ribs and sternum - shoulder"
19. Arm ..........................
20. Lower leg. ....................
2 1.
"Head cervical spine". .....
22. Dental.. ......................
23. Mass surveys.. ................
2 4 Others.. ......................

0.67
0.02

Pn vnl

M&s
Foc!d

T d

aftold1.

2. "Hip and femur".. ...........
3. Pelvis. ........................
4.
5. "Lumbar spine" ..............
6. "Thoracic spine". ............
7.

-

+

TOTAL

The pritnary material
1. The estimate presented here is based upon datasubmitted by Reboul and Istin." The authors assume theannual number of radiographic examinations in France
to be 5,000,000 plus 1,300,000examinations of employees
and militaries. The distribution on various types of
examinations is studied on 18.889 cases. The data are
assumed to be representative for 1957.
2. The authors point out that the foetal exposure due
to pelvimetry and obstetrical examinations is lower inFrance than in other countries, due to the low frequencyof these examinations.
3. 28,000,000 flrtoroscopies are performed annually,
19,000.000 of which are examinations of patients underage 30, mostly in mass chest examinations. There are
only 2,000,000 photofluoroscopies per year. The gonaddose from photofluoroscopy has been estimated by
Turpin, Dupire, Jammet and Leje~ne.~O
4. The authors consider their values to be minimum
estimates.

Presel~tationof tlre material for this report
5. The French data include values of N, for the wholematerial, and the corresponding values of dl in mostcases. Where the dose is not reported, an average dose,
likely to be representative, has been used. These values
are indicated with an asterisk in the table.

6. Values for the relative child =pectancy (wj/w)
cannot be derived from the French data. However, anapproximate figure can be calculated from the inf ormation on the fraction of patients under age 30, for eachtype of examination. The approximate figures differ
little from the values of wj/w presented in the table
for England and Wales. Therefore, the British values
may be regarded as fairly representative also for the
French material, and they have accordingly been usedin the calculations.

7. The contribution from radiography, 27 mrem, ismost likely a very low estimate. An interesting featureof the French material is the remarkably high contribution of fllcoroscopy used in mass survey exa~ninatw~rs.
Because of the uncertainty with regard to average mewing time and other factors determining the dose per=amination, the total value 57 mrem must be considered
uncertain by at least a factor of two.

DATAFOR EVALUATION O F T H E GENETICALLY SIGNIFIC-U'T DOSE FROM DIriGNOSTIC X - K ~ PEXPOSURE
A.

L ' ~ ~ l J - 4 ~ COXTRIBUTION FROM j,000,000 RnDIOGR4PHIC EXAhlIXATIOXS(foetal exposure escluded)

APPESDIXV. TABLE
I.

FUNCE
Fcmclcs

No.

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

lo00
NI/X

E x a m i d i o n s i d s i n ; radiography"Membres inf. 1/3 sup.". ............
"Bassin" (items 10 and 12 excluded)"Colonnes lombaires" ...............

di
mrem

w w

Males

Djw)

wen:

loo0

Ni/N

di

mrcm

Told
wi/w

D
mrcm

Dj

mrcm

Percent

1.59. . 3.30
2.43"Colonnes dorsales". ................ 1.70
"Urographies".. .................... 1.38
"Urhtho-Cysto" (not ind. item 11).
0.25

...

"Pelvimetries". ..................... 0.038"Hy~terogra~hies".................. 0.46
"Grossesses". ...................... 0.26.. 0.043............... 0.046........................... 0.28....................... 2.28..................... 0.5 1....................... 3.1 7
16. "Veeicules". ....................... 1.97........................ 20.7....................... 0.042................... 0.1 2................... 1.07
1.50........ 1.93.............. 2.41.......................... 2.57................... 0.94
22. 23. "Radiophotographies". ............. .240
TOTALS

B. ADDITIOS.~LCONTRIBUTION FROU 1 , 3 0 0 , 0 0 0 RADIOGRAPHIC EXAMINATIOKS OF EMPLOYEES AND MILITARIESContribution estimated in ~ r o ~ o r t i oton number of examinations, photofluoroscopy excluded. ............

5.2

19.3

0.2
0.4
27

0.7
1.5
100

C. ALLO\VANCEFOR FOETAL EXPOSURE
Estimate from British values in proportion to the frequency of esaminations
U X . : Dj (mrcm)

10. "Pelvimetries" ................................ 3.47
12. "Grossesses". . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.73

U.K.:1000 S J NFrance: 1000 N I / N

0.58
1.94

0.038
0.26

T0r.u R4DIOGRAPEY:

D. COXTRIBUTION
FROM FLUOROSCOPY
19,000,000 esaminations under zge 30, with an average gonad dose of 30 mrem per esam. (mostly mass surveys)
1000 h',/N

23.

"Examens syst6matiques". ........................

452

dl (ivrcm)

30

wdw

2.21
TOTALDL4GP;OSTIC:

30
57

APPESDIXV I
JAPANThe data submitted by Japan7 do not permit a presentation according to Equation (8). The following
information is given :TyPo ojercminc!ion

lOC4 Nj/Ndi (mrem)(A) Radiography:
Chest, large film. ............ 109
Chest, tomography. ......... 57
Abdomen ................... 68
Mass surveys. .............. 260
Others ..................... 46( B ) Ruoroscopy:
Chest.. .................... 18-4bdomen ...................
22

were children. The age-distribution in the various typesof examinations is based upon a materid of 39,315
examinations.
3. The total number of =aminations for 1955 was
found to be 1.910,000. The annual increase during theperiod 1915-1931 was 15.5 per cent. The number ofmass miniature radiographs during 1955 was estimatedat 1,000,000.

4. In addition to the actually occurring doses, theauthor presents "possible" values iound after simple
measures to reduce the gonad exposure. If the indications for pelvimetry and obstetric =aminations are mademore restrictive, the achievable annual genetically significant dose that would result is estimated to be 15 mrem
instead of the value of 38 mrern found for 1955.
Preselttatio~tof the ntaterial for this report

From the above data, the per capita gonad dose from- 30
diagnostic X-ray e~posureis estimated to be
mrem per year.

5.
the original paper thesignificant
do, ,as calculated for each su; as an average dose per
productive eamete. The sum of these doses was taken
io espress "the radiation burden to the zygote. The
figures in the following table have been recalculated by
the author to conform with the presentation in thisreport.

APPENDIXVIINEW ZEALAND
1. No typosure data have been submitted from New
Zealand. but it has been re~ortedthat an extensive survey of 'diagnostic expos&e has been initiated. New
Zealand has full records of all diagnostic X-ray plants
in the countrv and a svstem of medical services that
permits a qu&titative issessment of virtually all diagnostic X-ray work done.
2. D~~~on the number of maminations have beenreported45to the Committee and are presented in table I
in the main text of annex C. A characteristic feature is
the high annual number of dental(0.24
per capita). 95 per cent of these are made on school
children between the ages of 12 and 16.
3. The frequency of mass miniature chest -amination (with an annual number of 0.09 per capita) is
reported together with the information that 23 per centof all notified cases of pulmonary tuberculosis are discovered by mass X-ray surveys, with a case yield of
about 1.8 per 1.000 examinations.

APPENDIXXU N I T E D STATES O F AMERICA
The pritrtary material

1. The estimate of the genetically significant dose for
the United States of America is based upon a surveyof literature up to about the middle of 1956, reported
by L u ~ h l i nand Pullmanlo. In the report, which is only
preliminary~the authors have computed the probableannual gonad dose per person up to age 30 years. They
also give a ~ ~ t i n i f ~ t estimate.
zrt~z
2. The most characteristic feature of these data isthat the surveyors have listed radiography and fluoroscopy separately and, in the case of fluoroscopy, also
separated radiologists' examinations from those of nonradiologists.
3. The primary material of the Laughlin-Pullman
report is shown in the tables I to VI, with regard to
the estimate of the probable dose. The probable percapita gonad dose Up to age 30 is found to be about
140 = 100 mrem. The minimum estimate is 50 i 30
mrem.

APPEXDIXV I I INORWAYme data submitted by ~~~~~~6 do not permit any
estimate of the genetically significant dose. ~~~~d doses
have been measured by Koren and M a ~ d a l ;their~~annual consumption of X-ray films is 1.1 per capita, thevalues are included in the tables in appendix XI. As thecontribution from diagnostic X-ray procedures to thegenetically significant dose is likely to be high enough towarrant more detailed analysis, which is reported to beplanned.

Preserztatiort of the rrraterial for this report
4. AS nothing is h-own about the actual child-espectancy of patients undergoing X-ray e.aminations, thefirst approximation has been to assume that it is not
influenced by the nature of the condition for which thepatient was esarnined. The value of w,/w for each ex*ination class would then depend only upon the age-dlstribution within the class. With this assumption, theannual gonad dose per person up to age 30 years may
be taken as an approximate figure for the annual genetically significant dose. w , l w has been calculated frpm
the known valuesof N,/N, d j and this approximah~nof D ~~t. has been necessary to assume that the dose per
czsarnination is the same for the two age-groups "12-29
years" and "over 12". Tables VII to XVI give the final
presentation of the material.

APPENDIXI X
SWEDEN
Tlre prittzary ntoterkl
The estimate of the genetically significant dosefrom diagnostic X-ray procedures in Sweden is baseda report by L a r s s ~ n The. ~ data are representative
for 1955.
2. Dose measurements were performed on 1.957 patients in 17 X-ray departments. Of the patients, 394'.

77

APPI':NL)IXIX.

DATAFOR EVALUATIONTAIILEI.

OF TIIE GENETICALLY

---

1.WO

0.14
Oa008
0.21

2GO
35
200

0.11
0.021
0.10

0.12
0.040
0.30

2.47

0.31

490

1.06

011

0.28

0.2

om40

0.020

926

1.40

0.22

1840
1080

0.11
0.28

0.011
<0.0006

'

2000

1.12

0.0036

"

285
1160
1620
20
16.8

0.M4
0.84
0.13
0.060

<OMH)6
0.030
0.10
0.17
0.017

4.1

0.003

2.2

2.4

0.6

0.008

4.4

<Ob <0.0064<(0.05227

6.8........... 2,04'~nlrnrcnoluumgn1,hy''.

I

400
1
280

................... 1.3 0.10................. 0.84 0.71............. 3.8 025. 3.6 0.42......... 0.20 028
10. Pdvimetry ................. 0.59 0.44
fl.30b
11. IIyslcr~lpingogrnyhy...... 1.2
12. Obaktrical nbdomcn ......... 0.59 0.44
13. "Abdomen sway" ..... ... 2.4
0.30
0.20
14. "Coluu" ................. 4.8037
16. "8tomach" ........... .... 17.1
10. Cholooys~rn~~liy........... 8.6 0.36
Chest". ..... ........ ... 41.0
0.37

I"laser lag, ~ U U
fore, nnc~

39.6

0.41

22. Don ....................... 128

0.41

21.

D;
(mrm)

G/w

0. Urclhrocyalqrnyhy:::d;(mrcm)

N;/N

j1Tl~orni~wino"

8.

1.m

(mrm)

) . ' L u m b a r n n d a l spine"

;:

D;

d;
(mrw)

1. "11i11"
2. "l~am~~r"
3. Pclvicmgion..
6.

Fminls dildrrn

NSN w'dw

Tws ofaantination

upper nrm. 1111nd.fool"..

X-RI\YEXPOSURE-

Fernole adultr

Nu.

SIGNIFICANT DOSE FROM DIAGNOSTIC

<<I

1.43

*

'

0.31

'

445
(910) d
1240

.

0.034

'

"
'
"

'

105

<<I

0.086
0.00
0.044
0.0007
0.013

<<Om7

* A correction of the normal anc-apccific ehilcl-upcctnncy has been mode hcre.
b Every three wornen arc crpected t o have n child nubsequently.
111nll cawo of foctr~lexDmure except pelvilaetry nnd obstetric111 nbdo~nen.1l1efoetrll co~ltributionhne h e ndcrivcd from the assumption that 5.6 pcr cent of tllc won~enin fcrtilc nuee wcrc pregnant.
d lrlcl~iclingtwo ~ ~ ~ l i 0 g r 0 1 over1 h 8 tile t r i ~ o n c .

NUMBEROF FEJI-LE

UNDER AGE 30 PER 1000 OF TOTAL POPULATIOS(1000n ,(')/N)

E-WMATIONSA P P E ~ I X.
X TABLEI.

USA
Radiography

Fluoroscopy

Exam.

No.

1.
2.
3'
4.
5.
6.
7.

8.

9.
10.
11.
12.
14.
13.
15.
16.
17.
18.
19.
20.
21.
22.
23.

2.54*

. "Skeleton-pelvic region". ............

2.810

0.35b

0.50'

1.11
0.71
2.26
0.08
0.62

0.301

0.28'

0.40b

,

1 "Pyelography". .....................

"Urinary tract". ....................
Pelvimetry.. ..........................
Salpingography.. ......................
Abdomen (obstetrical). .................

1"Abdomen and colon". ...............

-

Stomach and upper G.I.. ...............
"Gall bladder". .....................
Chest (lungs, heart, oesophagus). ........

(3.6)

3.26
3.53
0.81
9.5

" S k e l e t o n ~ t r e m i t i e sand chestp'. ....

(2.8)

3.26

}

(1.0)
(1.0)

Head.. ...............................
2.17
(2.0)
275'
Dental ...............................
35*.e
Mass surveys.. ........................(all age4 (0-29): 20.4

Pelvis and hips.
Heart.

b Lumbar spine.

--b Including 1/3 of all examinations of age-group under 2 years.
i Including 0.10 from chiropractors.

Including 0.09 from chiropractors.
d Each film counted as one examination.

(Figures in brackets b e bctn drrwcd by an arbitrary split of a$gure for a larger group o j examination-classes.)Children under 10 years.

FEMALEGONAD DOSE PER EXAMINATION(d,(q in mrem)
APPENDIX
X. TABLE
11.

USA
ibdiography

Flvorascopy

i b d i d o g u k andna-radidogists

Exam.

NO.

0-1 1

I

"Skeleton--pelvic region". ............

Radi&isls

12-29

0-11

Non+didonnsis
12-29

0-1 1

12-29

1

) "Pyelography". .....................
.....................

"Urinary tract".
Pelvimetry ............................
Salpingography ........................
Abdomen (obstetrical). .................

1
I

\

20.
21.
22.
23.

J

"Abdomen and colon". ...............
Stomach and upper G.I..
"Gall bladder". .....................
Chest (lungs, heart, oesophagus). ........

...............

"Skeleton-xtremities

and chest".

....

.

.

Head.. ...............................
(60)
Dental ................................
4.
Mass surveys.. ........................(all ages 0-29) :* See footnotes to table I.

0.2
2'
3

5

(30)

be looO

b The dose from chiropracto~has been a ~ ~ ~ m e d

USA
--

-

Radwgrrphy
Erarr..

NO.
1.

i!
5.
6.
7.

1

I

+I I

) "Abdomen and colon". ...............

::: }

0-11

12-29

G11

12-29

5.6b

0.7.

2.6b

1.0

-

0.1.

0.5.

0.6s

1.7.

2.6
1.5

5.3
3.2

0.8
0.2

1.P
0.4

O.0ls

0.01.

(0.04)

0.03

Chest (iungs, heart, oesophagus). ........

(0.4)

....

(0.03)

0.00(0.01)

0.00

0.00
1.10.129.5(0.01)

0.00

2.5

6

4aSkeleton-extrernitiesand chest".

(1.1)
(0.7)

2.6
1.4
11.2
1.6
0.3
3.2
2.1
0.3
0.01

Stomach and upper G.I.. ...............
"GaU bladder". .....................

20.
21.
22.
23.

12-29

&-on-radidopitlr

2.5.

" ~ h l e t o n - p l v i c region".. ...........

"Urinary tract". .....................
Pelvimetry.. ..........................
Salpingography. .......................
Abdomen (obstetrical). .................

13.
14.
15.
16.
17.

&dioloeOfs

non-mdiulogisls

1 "Pyelography". .....................

9.
10.
11.
12.

Flroroscopy

Radwlopis!~andHead.. ...............................
(0.02)
Dental.. ..............................
0.3'
hlass surveys.
(all ages 0-29):
TOTAL 6.5.........................

b Induding 0.2

See footnotes to table I.

4

9from chiropractors.

NUMBEROF HALE EXAblINATIONS UNDER AGE 30, PER 1,000 O F TOTAL POPUIATION(1,000 nlM/N)
APPENDIXX. TABLE
117

No.

:

1

E: j
3.

7.

8.

13'
14.
15.
16.
17.
18.

-

"Skeleton-pelvic

region". ............

"Skeleron-estremities and chest". ....

&I 1

12-29

0.40h

0.5ji

1.24

-

0.341

0.31'

8.99
1.19

2.02
2.43

0.44
0.29

0.53
0.67

0.25.

0.51.

(0.69)

1.60

-

-

(4.1)
(3.2)

3.63

(1.1)

0.10'

0.79

3.63
3.93
0.91
10.6

(1 .I)

0.05'

Head.. ...............................
(2.2)
2.42
Dental ................................
33**=
1724
Mass surveys.. ........................(all ages 0-29): 16.7

Pelvis and hips.
b Lumbar spine.

Including 0.09 from chiropractors.
d Each film cwnred as one exam.
Children under 10 5-ears.
Geni to-urinary region.
f

12-29

3.11°

"Pyelography" ......................

Stomach and upper G.I.. ...............
"Gall bladder". .....................
Chest (lungs, heart, oesophagus). ........

1

0-1 1

0.45b

} "Abdomen and colon". . . . . . . . . . . . .
I

12-29

2.85.

"Urinary tract". .....................
Pelvimetry ............................
Sal pingography .. :. ....................
Abdomen (obstetrical). .................

9.
10.
11.
12.

20.
21.
22.
23.

0-1 1

USA

u Heart.

b Including 1/3 of d l exams. of age-group under 2 years.

Including 0.1 1 from chiropractors.
(Figrrres i n brackets have been derived by an arbitrary split of a
j'igirre for a larger group o j cxan;inafionclasses.)

&IALE GONAD DOSE PER EX4JIINATIOS(dl in mrem)

APPENDIXX. TABLE
V

USA
Radiography

h%.
NO.

1. '
2.
3.
4.
5.
6. ,

0-1 1

region". ............

I "Pyelography". .....................
"Urinary tract". .....................
Pelvimeuy.. ..........................
Salpingography ........................
Abdomen (obsteuical) ..................
"Abdomen and colon". ...............

1

12-29

Noa-raddcgists
0-11

12-29

2,000b2,000.

6,000'

2,000

2,O0OB

6,000.

2,o0Ob6,000"

750
500

750
500

2,000
600

750
500

20b

20a

(40)

10

300

-

-

-

Stomach and upper G.I.. ...............
"Gall bladder". .....................
Chest (lungs, heart, oesophagus). ........

(120)

200
200
10
1.2

and chesty*.....

(120)

1.O

(40)

5

0.6
8.
1

(a)

5

: ]

20.
21.
22.
23.

0-11

2,0ooa

9.
10.
11.
12.
14.
Is.
15.
16.
17.

Radido~~s:~

12-29

1,100*"Skeleton-pelvic

7.

8s

Fluoroscopy&d~ologirfsand
non-rad;ologirts

dSkeleton-ruemities

(750)
(750)

Head .................................
(120)
Dental ................................
12.
&lass surveys. ....................... ..(all ages 0-29):

See footnotes to table I.

The dose from chiropractors has k e n assumed to be 2,000
rnrem/exam.

ANNUAL MALE GONAD DOSE PER PERSON UNDER AGE 30n,(M)(1.98 X

X dlMin mrem)

APPENDIX X. TABLE
VI.

USA
Radiograph3
Radiologists andnon-radiologists

Exam.
No.

Fluorarcopr
Rodiologisis'"
Urinary tract". .....................
Pelvimetry ............................
Salpingography ........................
Abdomen (obsteuical). .................
"Abdomen and colon". ...............

)
I

a

(1.6)

Stomach and upper G.I.. ...............
"Gall bladder" ......................
Chesr (lungs, heart, oesophagus). ........

(1.6)

and chest". ....

(0.8)

"Skeleton-xtremities
J

-

(1.o)

Head. ................................
(0.5)
Dental.. ..............................
0.8%
Mass surveys.. ........................ (all ages 0-29) :T0r.u.
14.5

See footnotes to table I.

b Including 0.4 from chiropractors.

81

Nan-radidogisls!A

NUMBEROF FEMALE EXA~~INATIONSPER 1000 OF TOTAL POPULATION(1,OOO.Nj(F)/N)
APPE~PIXX. TABLE
VII.
Flrcoaos~Rndiograflhy
Radidogisis andeon-radidogirts
Exam.
No.

0-1 1

"Skeleton-pelvic

USA

Rodidopitts

O m 12

1&*on-radiokuirfs

Oon 12I

Own 1213-11{

region". ............

,"Urinary tract". .....................
Pelvimetry ............................
Salpingography ........................
Abdomen (obstetrical). .................

} "Abdomen and colon". ...............
stomach and upper G.I.. ...............
"Gall bladder". .....................
Chest (lungs, heart, oesophagus). ........

I

1 "Skeleton-extremities and chest". ....

20.
21.
22.
23.

J

-

(1.0)
(1.0)
(3.6)
(2.8)

Head.. ...............................
(2.0)
Dental ................................
35
hiass surveys.. ........................ (All ages)

9.1
515
61

FEMALEGONAD DOSE PER EXAMINATION(djcF)in rnrem)

USA

APPE~IS
X. TABLE
VIII.
--

Rndionafhy
Exam.
No.

1.
2.
3'
4.
5.
6.

0-11

Radidorisls

O w It.

0-11'

Na-rndidozislro w 12'0-11

ODIr 12.

1,000

2,600b500" S k e l e t o n l v i c region". ............

1,000
1,300

7.

"Pyelography" ......................
8.
9.
"Urinary tract". .....................
10. Pelvimetry.. ...........................
11. Salpingography .........................
12. Abdomen (obstetrical). ..................

}

13'"Abdomen and colon". ...............
14.
15. Stomach and upper G. I.. ................
16.
"Gall bladder". .......................
17. Chest (lungs, heart, oesophagus). .........

:: }

20.
21.
22.
23.

Flnaorwpy

Rodidogish andnon-radidogists"Skeleton-xtremities

-

1,200

-

1,000
2,500
10,000
260

(550)
(350)
(60)

500
300
200
0.3

(60)
(60)

0.5
0.2

1,000

3,000

1,000

3,000

1,500

750

1,500
750

1,000
500

1,500
350

15

15

(30)

10

(30)
(30)

5
5

and chest". ....

Head. .................................
Dental .................................
Mass surveys.. .........................

-

4

7

(All ages)

I t has been assumed that the dose in the age-group over 12
years is the same zj in the age-group 12-29.

3

b

i

Weighted average including chiropractors' contribution.

RELATIVEFEMALE CHILD EXPECTANCY(n~l'F)/w)

APPEXDIXX. TABLEIX.

USA
Radiologish andmn-radidogisfs

Exam.
xo.

0-1 1

Over 12Rodidogisls
0-11

Non-rodidogisls

OoerIZ

0-11

Over 12/ 1~Pyelography17......................

"Urinary tract". .....................
Pelvimetry .............................
Salpingography .........................
Abdomen (obstetrical). ..................

I

-

-

...............

1.98
1.98

.........

1.98

....

1.98

"Abdomen and colon".
Stomach and upper G. I.. ................
"Gall bladder". .......................
Chest (lungs, heart, oesophagus).

I"Skeleton-extremities and chest".

Head.. ................................
Dental.. ...............................
Mass surveys.. .........................

1.98
1.98
(All ages):

Figures back-calculated from tables 11, 111 and VII.

F E J CONTRIBUTION~
TO THE AXNUAL GEKETICALLY SIGNIFICmT(D1(qin mrem)a
APPE,VDISX. T-~BLE
X.

No.

5.
6.

I

0-1 1

"Slteleton-pelvic

region".

}}......................

...............

"Abdomen and colon".
13.
14.
15. Stomach and upper G. I.. ................
16.
"Gall bladder". .......................
17. Chest (lungs, heart, oesophagus). .........

f:

20.
21.
22.
23.

1

"Skeleton-xtremities

and chest". ....

Head.. ................................
Dental .................................
Mass surv~ys...........................

Rndidogists
0-11

OorrIZ

Non-rodidogists
0-11

Ooa 1 2

0.7

2.6

2.5

5.6
1.0

......................

1

OFn I.?

............

7'"Pyelography"
8.
9.
"Urinary tract".
10. Pelvimetry.. ...........................
11. Salpingography .........................
17. Abdomen (obstetrical). ..................

USA
Fluoroswpy

Radiography

Rndidogisis andnon-mdidogists
Exam.

DOSE

2.6
1.4
11.2
1.6
0.3

0.1

0.5

0.6

1.7

2.6
1.5

5.3
3.2

0.8
0.2

1.4
0.4

(0.4)

3.2
2.1
0.3
0.01

0.01

0.01

(0.04)

0.03

(0.3)

0.00

(0.01)

0.00

0.00
1.1
0.1
29.5

(0.01)

0.00

2.5

6

-

(1.1)
(0.7)

(0.2)
0.3
()\I1ages):
TOTAL
6.5

Figures identical with those in table 111.

83

4

9

NUMBEROF K4LE EXUIINATIONS PER 1000 OF TOTAL POPULkTION(l,OOO.N,'"'/N)
APPENDIXX. TABLE
XI.
Radiography

Fluoroscopy

Radido ists andnon-rutdolists
a m .

No.

0-1 1

1. '
2.
3. ,
4.
5.
6.

USA

Rodidoyirls

Ouer 120-11

Non-rodidogisls

&e?It

0-11

Oon12

\

2.85
,#

Skeleton-pelvic region". ............
1

0.45

7.

8. ] "Pyelography". .....................
9.
"Urinary tract". ....................
10. Pelvimetry .............................
11. Salpingography .........................
12. Abdomen (obstetrical). ..................
13.
"Abdomen and colon". ...............
14.
15. Stomach and upper G. I.. ................
16.
"Gall bladder" ........................
17. Chest (lungs, heart, oesophagus). .........

(4.1)

and chcst". .....

(3.2)

)

:;: }

20.
21.
22.
23.

"Skeleton-xtremities

-

-

-

(1.1)
(1.1)

Head.. ...............................
(2.2)
33
Dental ................................
Mass surveys.. ........................ (..211 ages):

7.0
10.3
580
69

MALE GONAD DOSE PER EXUILWATION(dt(lf)in mrem)
APPESDIS X. TABLE
XII.

USA
Radiography

Eiom.

KO.

0-1 I

1.
2.
3.
4.
5.
6.
7.
8.

-)

9.
10.
11.
12.

"Urinary tract". .....................
Pelvimetry ............................
Salpingography.. ......................
Abdomen (obstetrical).. ................

20.
21.

22.
23.

&r

Radiologists
12.

.Volt-radidogisls
0-11

Oon 12-

2,000

2,000

5,200'~

2,OOo
300

2,000

6,000

2,000
600

750
500

(40)

10

bll

OWlZ.

1,100

, "Skeleton-pelvic

1
: }
14.
1315.
16.
17.

FIuor05~0pu

Radidogisls andnon-radidogislr

region". ............
2,ooo"Pyelography " ......................

"Abdomen and colon". ...............

Stomach and upper G. I.. ...............
"Gall bladder". ......................
Chest (lungs, heart, oesophagus).. .......

-

-

-

-

(750)
(750)

200

(120)

200
10
1.2

~iSkeleton-extrerniriesand chest". .....

(1 20)

1.O

Head.. ...............................
Dental ................................
Mass surveys ..........................

(120)
12
(All ages):

0.6
8
1

* I t has been assumed that the dose in the age-group over 12
years is the same as in the age-group 12-29.

5(a)b Weighted average including chiropractors' contributions.

5

REL~TIVEMALE CHILD EXPECT-a-CY(\V~(~~)/W)~
APPENDIXUSA

X. TABLE
XIII.
Rodiogmghy

Erom.
.No.

0-11

6.
7.
8.
9.
10.
11.
12.
14.
13*
15.
16.
17.

h e r I.?

Raddogisu&I1

OIKl12Na-rudXo&u
0-11

Orcr I t

1.98

0.57

1.98

0.18

'

1.
2.
3'
4.

5.

FIiullosm~y

Radidoguh andnon-radiologisfs

1.98. "Skeletonpelvic region". ............

0.55
1.98

,
"P~elography". .....................
''Urinary tract".
Pelvimetry ............................
Salpingography.
Abdomen (obstetrical). .................

0.47.....................
.......................

1

-

-

"Abdomen and colon". ...............
Stomach and upper G. I...
"Gall bladder".
Chest (lungs, heart, oesophagus). ........

:;: }"Skeleton-rtremities

-

1.98

0.50

1.98

0.58

1.98

0.4

1.98

0.59

1.98

0.4

1.98

0.51
0.6
0.6

1.98

0.6

1.98

0.4

1.98

1

1.98

0.4

1.98
1.98
(-411 ages)

0.6
0.6
0.7

1.98

0.4

and chest1*.

Dental ................................
Mass surveys.. ........................

0.62

1.98

..............
......................

....
Head.. ...............................

20.
21.
22.
23.

1.98

0.5

Figures back-calculated from tables V, VI and XI.

MALE CO~TRIBUTION TO THE ANNUAL GESETICALLY SIGNIFICANT DOSE
in rnrern).
APPENDIXX. TABLE
XIV.
Radidogisb andnon-radiologists

Erom.
No.

0-1 1

.....................

.......................

"Urinary tract".
Pelvimetry ............................
Salpingography ........................
Abdomen (obstetrical). .................

} "Abdomen and colon". ...............

I...............

Stomach and upper G. I..
"Gall bladder". ......................
Chest (lungs, heart, oesophagus). ........
1

19.
20.
21.
22.
23.

} "Skeleton-extremities and chest". ....
Head .................................
Dental ................................
blass surveys.. ........................

(0.8)

(0.5)
0.8
(All ages)
TOTAL 14.5

Figures identical with those in table VI.

Om I 2RodidogisIr
0-11

OanJ2

USA

Kon-rdidogisit
0-11

&uIP

FOETALEXPOSURE
USA

APPE~TDIX
X. TABLE
XV.
Es'zm.

di

ntrcm

No.

1.
2.

314.

dh*Nd-V
r1.000(back-2fZalcd)

Di
mrem.

'

:

5.
6.
7.
8.
9.
10.
11.
12.

8

icS*eleton--plvic region". "Pyelography" ..............................

,"Urinary tract". ............................
Pelvimetry.. ................................. 4,000
Salpingography ...............................
Abdomen (obstetrical). ........................
400) "Abdomen and colon". ......................

Stomach and upper G.I.. .......................
"Gall bladder". .............................
Chest(lungs,heart,oesophagus)................

15.
16.
17.

:: }

20.
21.
22.
23.
24.

"Sbleton-tremities

0.3

and chest". . . . . . . . . . . . . .

Head ........................................
Dental .......................................
Masssurveys .................................
Others .......................................

TOTAL

a

1/0.67 of the figures given by Laughlin and Pullman.

GENETICALLYSIGNIFICANT DOSE (Dj IN LIREM); SUMXL4RY TABLE
APPENDIXX. TABLE
XVI.
Exam.
No.

Childre8) "Pyelography". ..................

\

i9:
20.
21.
22.
23.

-

"Abdomen and colon". ............
Stomach and upper G.I.. ............
"Gall bladder". ..................
Chest (lungs, heart, oesophagus). .....

5.5

1

Mole
adt~lrs

FoetalTold

PCTcent

2.2"Urinary tract". .................
Pelvimeby .........................
Salpingography .....................
Abdomen (obstetrical). ..............

1FcnalcadrJls

USA

9.3

1.5

.

1.1

0.0

0.0

1.1

0.8

Head.. ............................
Dental.. ..........................
Rlass surveys. ......................

0.7
1.1

0.0

0.0
2.7
0.0

0.7
4.9
0.1
141

0.5
3.5
0.1
100

"Skeleton-estremities and chest".

*

TOTAL35.2
Included in adult figures.

1.1
0.1
44. i

40.7

20.7

DATA ON DIAGNOSTIC X-RAY EXPOSURE: GONAD DOSE PER EX4i)lINATIONFOR THE MOST DIPORTAIYT EXPOSURE CLASSESAPPENDIXXI
The tables I to XIV have been taken from the reportof the ICRp/ICRU Joint Study Group. They shoxv
estimates of various authors of the gonad doses due togiven types of examinations. The wide variations prob-

ably result from different techniques rather than fromuncertainty in measurements. Hence the lower values
indicate what levels may be achieved with good practice.
Further details and references are given in the I C R ~ICRU Study Group report.

3feanucRrfncncc

Tcchnirol dolo

HammerJacobsen(1957)
Denmark'

62-64 kv,
400-450 mi\s
F F D = 100 cm
2 films per
examination

LarssonSweden960-70 kv,
200-500 m ~ s
3 films per
examination

mrnls madeonA{&

Frnrolr

Patients:
12 male9 female567(20-3600)

53(30-100)

Patients:
19 male18 female1150(1 00-2600)

205(75450)

480
840
2100
650-2000

270
420
900
600-1000Years:
0- 2
2- 7
7-1 2
12-30

Laughlin and
Pullman(1957)U.S.A.10
Stanford andVancc 11955). , 68 kv. 200 m ~ s
U.S.A.@F F D = 90 cm

Technical dala

Measitremcntrmodc
onHammerJacobsen(1957)
Denmark4

Patients:
7 male4 female

Koren andiLIaudalNorwap62 kv, 250 mAS
F F D = 100 cm
2 films per
examination

Phantom

50-78 kv, 80 m ~ sPatients:
6 male2 femaleLailghlin and
Pullman(1 957)
U.S.A.10-

Patients

5840 kv, 250 m,ks
F F D = 100 cm
2 films per
examination

LarssonSweden9

CoMd do- pa cxaminalion (wad)' :Rcmmkr

Gonad dore pcr cxaminafwn (mrad)
Rnnurkr

Years:
12-30

M&

F

d

1650

300

=

Teclt~ticoldata

Measurcmn:ls
ma& 011

Denmark'

60-63 kv,200-360 mas
F F D = 100 cm
1-2 films per examination

Patients:
7 male1 female

Koren and Maudal
Norway@70 kv. 250 mAS
FFD = 100 c n ~Phantom

LarssonSu-edens

59-64 LT, 500 mu
F F D = 100 cm
1 film per examination

Patients:
16 male20 fema!e

65 kv, 100 m.u
F F D = 90 cm

Patients

Reference

Hammer-Jacobsen(1957)

Gonad dare n jVm(mra8

Remarks

Ma&

F e d

Gonad datc pn uaminaIion

had)

Molr

Fcmak

567
(50-2500)

70

1100

210

Laughlin and
Pullman (1957)
U.S.A.10
Stanford and V a n e(1955)

U.K.s'65 kv, 100 m4s
FFD = 90 cm,
no extra hlter
65 kv, 100 m s
FFD = 90 cm,

ArdranandCrooks

AP

1100

Normaltechnique

2000<3mmAl-filter

210

670

(1957)

U.KY

75 kv, 80 me
FFD = 110 cm,
3 mrn Al-filter.
The same, but testes,covered with lead

* Measurement made on hantom.

t Atomic Energy ~ e s e a r c Establishment.
i'AERE'I
technique

480
20

80,

TABLEIV. LUMBARSPINE
Rcfermce

Hammer-Jacobsen(1 957)
Denmark'
Koren and Maudal
Norwaybs

Afeasnrenunfs

Technical da~amodcan65-84 kv, 1250 AS
FFD = 100 cm
3 films per examination

Patients:
22 male22 femaleI

Phantom

68h,310 rnAs
FFD = 100 cm
75 kv, 500 n u s
FFD = 90 cm

LarssonSweden965-70 kv, 500 m4s
FFD = 90-100 un
4 films per examination

Patients:
12 male7 femaleLaughlin and
Pullman (1957)
U.S.A.10

1

72 kv, 500 m s
FFD = 90 cmt

120 kv, 20 mas
FFD = 90 cm
120 kv, 60 rnis
FFD = 90 cm

Ardran and Crooks(1 957)
UK26

1

F~

68 kv, 200 m.u
FFD = 90 cm,
no extra filter
68 kv, 200 m s
FFD = 90 cm,
4 3 mm Al-filter
75 kv, 80 m ~ s
FFD = 110 cm
3 mm -4l-filter
The same, but testes,covered with lead

Measurement made on phantom.

t Atomic Energy Research Establishment.

,a[&prmolr104(10-400)222(20-600)

AP

4.5

60

4.5

60

Lat.

6

91

6

91

375

680

(68-1 180)

(490-860)

2700
900

900
1050
2190

Lumbarspine andlumbo-sacral
regionAP.I
Lat

Patients

Gonad dnrc pn r x a m i n a f i a

bra4

uolc

Years:
0- 2
2- 7
7-1 2

'68 kv, 200 m s
FFD = 90 cni
Stanford and Vance(1955)U.K.m

G o n a d ( 2 r flm

RcnuubNormaltechnique

2400

24

227

24

227

26.6

86

26-6

86

6

40

6

40

7

16

7

16

24
6-0

'AERE'ttechnique

1.0
0.5

95'

Gonad dart per $Zm

Technical &&Mcasurcmc~rfr
made onP-kt

61-65 Lv,3300-4300 m.u
FFD = 130-143 cm
16 films per esamination

Patients:
50 male50 female

AdultsAdults65-73 kv, 650-1700 mas
FFD = 130-143 cm
6 films per examination

Patients:
14 male8 female

Chiddenunder
15 years

Cord dare pa cxcrr.;naiion

hod)

Male

(mod)

Fcmak

Mole

Fern&

1820
(935-2680)

L~ammer-Jacobsen(1957)
Denmark4

LeFebvre and Serra(1957)

FranceLarssonSweden9I

Children:
3 months
3 >.ears
6 years

10 films
12 films
16 films

Patients

66120 kv, 95 n w
12-26 films pere-samination

Patients:
25 male17 female

Hospital
1790(141-21 60)

55 h-,
250-270 m s
5-1 1 fdms per
examination

Patients:
10 maleHospital
21300(22*-2500)

12-30 years
PyeloDP~Y

100-2000

200-1200

486

1290

Laughlin and
Pullman (1957)
US.A.10
Stanford and Vance(1955)

U.K.58
Ardran and Crooks(1957)

U.K.5

72 lw, 100 nus
FFD = 90 cm
6 films per examination
75 LC,80 m u
FFD = 110 cm
3 mm Al added

Patients
Male :
patients
Female:phantom

0.5*

95With lead rubber over the scrotum.

t Doses reduced to 1-3% by shielding of scrotum.

TABLE
VI.
Rcjercncc

HammerJacobxn(1957)
Denmark4
Laughlin and
Pullman(1957)U.S.A.10

RETROGRADEPYELOGRAPHY
Measrut

Technical datam n l s majc

63-67 kv, 4000 mas
FFD = 130--143 cm
7 films per
examination

Patients:
8 male9 femaleon

Rrmarks

12-30
Yea=
Pyelography

Gonad dose per eramination (n~od)'

Mole

Femak

100-2000

200-1200

TABLE
VII. URETHROCYSTOGRAPHY'71 kv, 3285 mAs

HammerJacobsen(1957)
Denmark4

Koren andblaudalNonvayBS

FFD = 137 cm
6 films per
examination

Patients:
7 maleUrethrography

4209(2700-8400)

63-87 kv,
2000-2850 mAS
FFD = 100-130 an
5 films per
examination

Patients:
2 male2 female

Cystography

5261(3500-7000)

Urethrocyst*' 102-109 kv,

357-476 AS
FFD =!W cm
9 films per
examination

Patients:
9 male9 femaleduringmicturition
A dults

7841
669(2400-17200) (200-1500)

79-86 kv,
256-341 AS
FFD =90 cm
8 films per,examination

Patients:
6 male5 female

Under 152314
(200-4700)

75 kv, 200 mAS
100 kv, 500 m ~ s
FFD =60 cm
1 +4 films per
examination

Phantom

80-100 kv

Patients:
26 maleHospital 1
16 female

100-200 mAS
5-15 films per,examination
Radiography
Laughlin and
Pullman(1957)
U.S.klo

460(350-560)

Fluoroscopy
iPatients:
5 maleWP~Y

205(120-330)

AP
Lat.

Hospital 2

4100
1000
(1000-1 1000) (550-1650)
760(320-1240)

Years:
12-30

100-300

200-1oOO

Years:
0-1 2
12-30

500-2000
500-6000

500-1000
500-3000

HammerJacobsen(1957)
Denmark'

Koren andhlaudalNomap

Gonad datep n flm

Gonad dose
pn cxuminalim

Tcrhnical
da!aLfcasurcmrnrs madeon

Remarks'81-85 Lv,
1354 mhs
FFD-100 cm
2-3 films per
examination

15 patients

A P f Lat.

738
(400-1400)

84-92 I;v,
1250 mAs_
FFD -97 cm
3-4 films per,examination

4 patients

Stereoscopic
APfLat.

906
K(650-1300)

II

Phantom

2 films: 90 LT
640 AS
1 film: 90 h i
95 AS
FFD = 90-100 cm-12 patients

Rrfhcra(mad)(m+ad)

fmak

fmak

,

LarssonSweden978 kv, 310 mas
FFD = 100 an

85 kv, 500 mAS
FFD = 90 cm

AP

!-86

86

Lat.

76

76

3
merentprojections

Laughlin and
Pullman(1957)U.S.A.10
Stanford and
120 kv,100 mAS
Vance (1955) 120 kv, 50 m ~ s
U.K.a
FFD =90 cm

Patients

AP
Lat.

240
840

TABLE
IX. SALPINGOGRAPHY

Hammer69 kv.
Jacobsen (1957) 1259 m u
Denmark'
FFD = 100 cm
2-7 films per examination
LarssonSweden9Laughlin and
Pullman (1957)
U.S.A.10

65-90 kv,
120-150 mAs
6-11 films per examination

7 patients
32 patients

TABLE
X. ABDOJIEW
Refntncc

Technirol &laII63-70 kv,600 mAs

FFD = 100-143 cm

HammerJacobsen(1957)
DenmarF

1 film per
examination

71 kv, 750 m&
FFD=100 cm
1-2 films per
examination

Koren and
Maudal
Norwap80 kv. 180 mas
F F D = 100 cm
3 films per
examination

LarssonSweden9

Female 4-13 films
per examination.
Male 3-7 films per
examination. Sometimes fluoroscopy,
1 -5-2 min.

Laughlin and
Pullman
1957)
U.S.A.10

Abdomen and colon
radiography

Stanford andVance (1955)

1

U.K.s
Ardran andCrooks(1957)
U.K.5

72 kv, 100 m4s
F F D =90 cm
80 kv, 150 mAs
F F D =90 cm

Measuremcnfs madeonRemorL

Patients:
5 male4 femalei\PPatients:
21 female

Gonad dose ficr examination (%rod)
JfoL

F e d

Obstetric

Phantom

Patients:
7 male7 femaleYears:
0- 2
2- 7
7-1 2
12-30

Patients

75 kv, 60 n ~ ~ s Male:patients
FFD-110 cm
Female:3 mm Al-filter
phantom
addedWith lead rubber protection.

TABLE
XI.
Technical data

Rcjc~cna

BARIUMENEUMCCMKC~ntsnurdc
an

LeFebvre andSerra (1957)
France15 films
7 films
9 films

Patients

LarssonSweden9

About 10 films:
mean fluoroscopy
time 7 min.

Patients:
31 male15 female

I

Children:
3 months
3 years
6 years

Abdomen& colon12-30 years

Radiography

Laughlin and
Pullman(1957)
U.SA.10

Gonad dare pn examinolia (mrad)
Remarks

Mak

Fcmak

450
700
900

400
455
800

255
(52485)2065(1075-2920)

140-200

420-500

0-750

420-1500

420-750

420-1500

Lower
4

G.I.T.

Fluoroscopy

13-30 years

I

Lower

G.I.T.

Fluoroscopy

Stanford andFluoroscopy:
Vance (1955) 50 kv, 2 ma
U.K.5J
3 min.

ChildrenPatients

40

20

TABLE
XII. BARIUM SWALLOW AND MEAL
Mconur-mcnls madeonChildren:
3 months
3 years
6 years

Conad dose pa exambarion (mrad)

Mlc

FrmoIr

220
496
220

20 films
16 films
20 films

Patients'75 kv, 6 0 m ~ s
F F D =60 cm
12 films per
examillation

Phantom

2 -9

144

Fluoroscopy:
70 LT, 3 mA, 3 min.
,FSD a 4 0 cm

Phantom

1.2

45

12.5
(2.7-29)(8.5-55)

4.3(2-1-13-6)

31(7.8-78)

60-200200-300

12-30 years

0-500

200-750

Upper
G.I.T.
Children

200-500

200-750

20

9LeFebvre andSerra (1957)
FranceKoren and
Maudal
Norwa?

Remarks

80-110 LC
40-80 mAs
10-15 films
Mean fluoroscopy
time 7 min.

Sweden9

Patients:
25 male25 female

Hospital 1

Patients:
25 male25 female

Hospital 2

I

33

Stomachh upper

G.I.T.

Radiography

12-30 years

Laughlin and
Pullman(1957)U.S.A.~"

Upper<

G.I.T.

FluoroscopyiStanford andVance (1955)

U.K.s

Fluoroscopy
70 L.-, 2 m a 3 min.

Patients

Fluoroscopy with
Ardran andimage intensifier
Crooks (1957) 75 L.-, 0.5 m a
U.IC.2j
5 min. 5 mm
-41-filter addedMale:patients
Female:phantom

Tcchn~cddata

mnlr ma&d.leasurc-

WncnccKoren and
Maudal
NorwapLarssonSweden980 hr,125 n u s
F F D = 1 0 0 cm
5 films per
examination'60-80 Lv
35-200 mAs
4-6 films perc examination.
Fluoroscopy
80 kv,3 mA,,1.2-2-5 min.

on

Phantom

70 kv, 150 mAS
F F D = 90 cm
3 films per
esamination

A fak

Female

6.i

260

3.1
(1 -3-6.5)

19(10-41)

Patients:
26 male25 female

Hospital 1

Patients:
16 maleHospital 2

7.1(4.3-11)

12-30
years

0-1 0

75-2001.8

15.6

Laughlin and
PullmanStanford andVance (1955)
U.KJE

Gonad dare p n uaminufion (tpzad)

RcmarbPatients

TABLE
XIV. CHEST-

Technical daIa

kftonrem~l;~~ra& onRernorh

G01:ad dose 9crJTlm(mrad)
liak

LeFebvre and Serra(195 7)
FrancePa tients

I

Children:
3 months

80 kv, 27 mas

Koren and Maudal
Nom~i?

FFD = 150 cm

5-5 films per esamination

Laughiin and
Pullman (1957)
U.S.A.10& fluoroscopy
70-80 kv,
2-2 -5m4
1-3 minI

Female

Jfak

FmaL

5

PA

<1

1-0

<1

1.0

Lat.

<1

1-5

<1

1-5

1-6
(0.9-2-7)

4-6(2-6-10.8)

0-450
0-5
0-1 -2

0-240
0-5
0-0-3

0-40

0-30

Patients:
78 male22 femaleYears:
0- 2
2-12
12-30

Radiography

Fluoroscopy

Sanford and V a n e(1955)(mrad)

Phantom

95 kv,60 m a s(FFD = 150 cm

LarssonSweden9G a a d darr per cxaminaiion

68 kv

Patients'Radiography
FFD = 180 cm
3 mm AI-filter added.

Male:patients
Female:phantom' Fluoroscopy with image
intensifier
75 kv, 0 . 5 m.4
3 min., 5 mm
\Al-filter addedMale:patients
Female:phantom

PA

0.36

0 -07

0.36

0 -07

PA

0-01

0.02

0.01

0 -02

3.0

3-0

U.K.a

Ardran and Crooks(1957)

U.K."

1. International Commission on Radiological protection (ICRP) and International Commission on
Radiological Units and Measurements (ICRU),
Joint Study Group report on Exposure of man toionizing radiation arising from ntedical procedures.
Physics in Medicine and Biology, 2, 107-151(1957). See also UN document A/AC.82/G/R117.
2. Martin, J. H. : T h e contribution t o the gene ~rraterialof the population front the medical use of ionizing
radiations. Medical Journal of Australia, in print.
3. Austria: Report to the United Nations ScientificCommittee on the Effects of Atomic Radiation, on
radiological data, UN document A/AC.82/G/R.102.
4. Hammer-Jacobsen, E.: Gonadedoser i diagnostisk
radiologi (Gonad doses in diagnostic radiology).
Ugeslcrift for Laeger (Denmark), 119, 279-290(1957), see also UN document A/AC.82/G/R.221.
5. Osborn, S. B. and Smith, E. E.: T h e geneticallysignificattt dose frowt the diagnostic use of X-rays
i n England and PVales. The Lancet, 16 June, 949953 (1956). See also UIU document A/AC.82/
G B . 5 1.
6. Reboul, J. and Istin, J.: Doses gonades en radiodiagnostic. Bordeaux (1958) U N document A/
AC.82/G/R.194).
7. japan :Report to the United Nations Scientific Committee on the Effects of Atomic Radiation, on radiological data, UN document A/AC.82/G/R.70.

8. Nonvay: Report to the United Nations ScientificCommittee on the Effects of Atomic Radiation, on
radiological data, U N document A/AC.S2/G/R. 106
and i4/AC.S2/G/R.106/Add.1.
9. Larsson, L.-E.:
Radiation doses to the gonads o fpatients irt Swedish roetttgcn diagnostics. Acta
radiologica, Supplement No. 157 (1958), see also
UN document A/AC.82/G/R.182.
10. Laughlin, J. S. and Pullman, I. : Gonadal dose produced by the medical use of X-rays, U N document
A/AC.82/G/R.f 4.
11. Court-Brown, W. M. and Doll, R.: Leukwmia andapEartic anae?nia in patients irradiated for ankylosing spondylitis. Medical Research Council (U.K.)
Special Report Series. No. 295 (1957). See also
UN document A/AC.82/G/R.105.

12. Martin, J. H.: An estitttate of the potential leukae?nogenic factor i n the diagnostic w e of X-rays.
Medical Journal of Australia, in print.
13. International Commission on Radiological Protection (ICRP) :Recomtraendations, revised 1 December 1954. Brit. J. Radiol. Suppl. 6 (1955).
14. Clark, K. C.: Positioning i,t radiograplty. 7th ed.,Grune and Stratton Inc., New York and London( 1956).

15. Sante. L. R. :Manz~alof roentgenological techliiques,
15th ed. revised, Edwards Bros. Inc., Ann -Arbor( 1946).
: -ti;

16. Webster. E. W. and hilerril, 0. E.: Measltrefiletztsof gonadal dose i n radiographic examinatiotls, New
England Journal of Medicine, 257,811-819 (1957).
17. Ritter, V. IV., Warren, S. R. and Pendergrass,
E. P. : Roentgen doses during diagnostic procedz~res.
Radiology, 59, 238-249 ( 1952).
18. Ardran, G. M. and Crooks, H. E.: A corrtparisorrof radiographic teclzrriqz~eswith special referewe
to dosage. Brit. J. Radiol., 26, 352-357 (1953).
19. Ecyleshym, A. C. and Schoemaker, D. M.: A
cross-sectiotz anatotny. Appleton-Century Crofts
Inc., New York (1938).
20. Johns, H. E., Epp, E. R and Fedoruk, S. 0.:
Depth dose data, 75 k V p to 140 kVp. Brit. J. Radiol.,
26,32-37 (1953).
21. Jones, D. E. A. and Ellis, R. E. : T h e nteastcrelltent
of the dose-corrtribrctions frorlt the mairr treatment
fields. Appendix B to ref. 28.
22. Laughlin, J. S., Meurk, hi. L., Pullman, I. andSherman, R. S.: Bone, shirt and gonadal doses i nroutine diagnostic procedures. American Journal of
Roentgenology, 78, 961-982 ( 1957).
23. Lorentzon, L:Smne notes on skin doses arrd bonemarrtnu doses irr nmss rnitriature radiography. UN
document A/AC.82/G/R. 176.
24. Martin, J. H.: Radiation doses to the gonads i ndiagnostic radiology and their rclation to the longternz getretic Imard. Medical Journal of Australia,
2,806410 (1955).
25. Ardran, G. M. and Crooks, H. E.: Gonad rdiationdose frorrr diagnostic procedures. Brit. J. Radiol.,
30,295-297 ( 1957).
26. Ardran, G. M. : Dose reduction i n diagnostic radiology. Brit. J. Radiol., 30, 436-438 (1957).
27. Christensen, H.: Patienters udsaetteke for ioniserende strrOInitrg (The exposure of patients to ionizing radiation). Ugeskrift for Laeger (Denmark),
119.290-295 (1957).
28. Martin, J. H. :Radiation doses received by the skirtof a patient during routitre diagnostic X-ray examinations, Brit. J. Radiol., 20, 279-283 (1947).
29. Tubiana, hi. :Doses recues par les organes genitaux
au cours des examerrs radiographiques efectuhs
chez l'enfant. U N document A/AC.82/G/R.186.
30. Camerman, J. : Examens radiographiques ct danger
des radiatiorrs. Journal Belge de Radiologie, 39,
165-178 (1956).
31. Bacq, 2. M. :D u danger des examens radioscopiqxes
pour les trtalades (see also discussion followingtext). Journal Belge de Radiologie, 39, 687-695(1956).
32. BaiIy, N. A. : Patient exposure to ionizing radiation
irr dental radiography. Radiology, 69,42-45 (1957).
33. Trout, E. D.. Kelley. J. P., Cathery, G. : T h e w e offilters to cortfroi radiation exposure to the patient
in diagnostic roerttgertolo y. American Journal of
Roentgenology, 67. 946-9 2 ( 1952).
34. -4rdran, G. M. and Kemp, F. H.: Protection of themale gonads in diagnostic procedures. Brit. J.
Radiol. 30, 280 (1957).
35. Etter, L. E.: Radiation dose reduction by higher

4

voltage dental roentgenography. Journ. Amer.
Dental Association. j3.305-309 (1956).
36. Martin, J. H.: Necessity and fjzeatls of protectirtg
patients i n diagnostic and therapeutic radiology.
Proceedings of the College of Radiologists of Australasia. 1, 103-112 (1957).
37. Clark, S. H.: Genetic radiation exposures i n thefield of medicine. Bulletin of the Atomic Scientists,
12, 14-18 (1956).
38. Purser, P. R. and Quist, C. F.: An estinrate o f thegenetic dose from radiotherapy. Acta. radiol. 48,
267-272 ( 1957).
39. Chmberlain, R. H. : Gonadal radiation itt the genetically significant portion of the population derived
frotn the radioactive isotope procedures i n nzedicine.
Hearings before the special sub-committee onradiation of the Joint Committee on Atomic Energy,
U.S. Congress, Part 1, 885-888 (1957). See also
U N document A/AC.82/G/R 130.
40. Johns, H. E. and Taylor, R. hi. :Dose fronz unsealed
radio-nrcclides. U N document A/AC.82/G/R.129.
41. International Labour Office: Code of practice forradiatiotz protection i n lutitinizing zuork. Geneva(1957).
42. Hursh, J. B.. Steadman, L. T., Looney, W. B. and
Colodzin, hl. : T h e excretion of thorium and thorium
daughters after Thorotrast ad~nirzistratio~t.Acta
radiol., 47, 482-498 (1957).
43. Rotblat, J. and Ward, G.: The radioactivity fromThorotrast and its retention in tissue. Physics in
Medicine and Biology, 1, 125-137 (1956).
44. Service dJhygi2ne atomique et de radio-pathologie
du C.E.A. : Etude de l'irradiation professionelle en
France en 1955. U N document A/AC.82/G/R.16,
Part 111.4.
45. New Zealand: Report to the United Nations Scientific Committee on the Effects of Atomic Radiation.
on radiological data, UN document A / A C . ~ Z ~G/R185.
46. Medical Research Council (U.K.) : T h e hazards totnan of nuclear atdallied radiations, London ( 1956).
See also U N document A/AC.82/G/FL2.
47. Swedish government official report : StrrSIskydd(Radiation protection), Statens Offentliga Utredningar 1956:38, Stockholme ( 1956).
48. Australia: Report to the United Nations ScientificCommittee on the Effects of Atomic Radiation, on
radiological data, U N document A/AC.82/G/R.29.
49. Larrson, L. E. :Radiation doses to pafients and persottnel in jrrodern roentgen diagnostic work, Acta
radiologica, 46, 680-689 ( 1956).
50. Mayneord, W. V. :Some problems of radiation protection. Brit. J. Radiol., 24, 525-537 (1951).
51. U.S. Atomic Energy Commission : Occupationalradiation exposures i n U.S. atomic energy projects.
U N document A/AC.82/G/R.71.
52. Boulenger, R.: Doses wtoyenrres regues par le personnel d u C.E.N. Mol de 1954 d 1957. U N document
A/AC.82/G/R.210.
.53. New Zealand: Report to the United Nations Scientific Committee on the Effects of Atomic Radiation,
on radiological data UN document A/AC.~Z/
G/R.107.

Belgium : Rapport sur la protection salzitaire daru
Pexploitatioiz des r~tineraist~ranif2resau Kafanga,
UN document A/AC.82/G/R. 116.
International Labour Office : General code of practice for i~zdustrial radiation protection, Geneva(1957).
Libby, W. F.: Dosages fro~it nattwal radioactivity
atzd costtzic rays, Science, 122, 57-58 (1955). See
also UN document A/AC.82/G/R. 109.
Dyson, E. D. : Shoe-fittitig X-ray fitcoroscopesradiation nz earzcrenzertts and hazards. British hledical Journal, 2,269-272 ( 1956).
Stanford, R. W. and Vance, J.: The qttaniity ofradiation received by the reproductive organs ofpatients during routine diagnostic X-ray examinations. Brit. J. Radiol., 28,266-273 (1955).
Spiers, F. W.: Meancrement of the gorurdal dose
i n the medical use of X-~ays. Physics in Medicine
and Biology, 2, 152-156 (1957).
Turpin, R., Mille M. Dupire, Jammet, H. and
Lejeune, J.: Etude de la dose/gonade, lors desexantens radio-photographiques systemutiqtces. UN
document A/AC.82/G/8.2 11.

Hammer-Jacobsen, E. : Gonad dose ntearurements
irt Den~ttark,U N document A/AC,82/G@219.
Hammer- Jacobsen, E. :Risk of parentl~oodand ksk
of subseqztettt pareittlzood, Denmark 1955 and 1956,
UN document A/AC.82/G/R.220.
Verbal commtrnication by the delegation of theUnited Kingdom.
Kopp, H.: Stdlebeskadigelse fordrsaget af pedoskop. Overvejelser over foragelse af den totale
gonadestr2ledosis fra pedoskoper (Radiation damage from pedoscopes. Increase of total gonad dosefrom ped&cope) .'ugeskrif t for ~aege; 119, 766770 (1957).
Koren, K. and Maudal, S.: Gonad doses received
during the nredical application of roentgen radiation.
Acta radiol., 48, 273-279 (1957).
Numpar, J. :Physical aspects of protection irt roentge?t and radircrrt therapy. Acta radiol. et cancerol.
F~hemoslovenica,4, 152 (1949).
Hansen. P. B. and Madsen, C. B.: Tolerance dose
problent in radiological work. Acta radiol., 34, 519528 (1950).

Annex D

ENVIRONMENTAL CONTAMINATIONTABLEOF CONTENTS

Paragraph

I. ~ I O A C T I V EFALL-OUT ....................................

1
Fall-out mechanisms ..................................... 6
Measurement of fall-out ................................. 9
Airborne activity ..................................... 10
Fall-out deposit ....................................... 12

I1. COMPUTATION
OF EXTERXAL DOSE FROM FALL-OUT
DEPOSIT ...... 20
I11. SrDO
AS A N INTERNAL SOURCE ............................... 36
Evaluation of SPOas an internal hazard .................... 28
S P Oin soil ............................................. 29
SrDO
in food-chains ...................................... 33
Discrimination factors .................................. 34
The soil-vegetation step in food-chains ...................... 37
Concentration of SrsOin foodstuffs ........................ 48
Calcium sources in diet .................................. 50
Stable strontium sources in diet ........................... 52
Daily intake of S P Oin man ............................... 53
SrPOin human bone ...................................... 55
The importance of the stable strontium determination ....... 56
SrsOdistribution in different bones of the skeleton .......... 57
Uniformity of SroOdistribution in bone ................... 58
The problem of computing skeleton dose from SPO......... 63
Concentrations of S P Oin man ........................... 66.

I V Csla7AS AN INTERNAL SOURCE ............................... 68
bllethods for measureme~tof concentrations of CslJ7 ......... 71
Concentrations of CslB7ill foodstuffs ....................... 73
Daily intake ofin man .............................. 74
Concentrations of CslS7in man ............................ 75
Dose rate from C 3 in a n ......................... 76.

V DOSESFROM TROPOSPHERIC FALL-OUT ........................ 77
External sources ........................................ 78
Internal sources ......................................... 79
S e e and Ba140 as internal sources ....................... 80
1131as an internal source ............................... 84................ 91\TI ESTIMATION
OF DOSES FROM FUTURE FALL-OUT
Estimation of fall-out rate and deposit in the future ......... 94
Case 1 : Tests stop at the end of 1958 .................... 102
Case 2 : Tests continue ................................ 103
Values of F, (0) and F d (0) ............................ 107
Methods for dose estimations ............................. 111
External irradiation of gonads caused by CslS7............. 113
Internal irradiation of gonads caused by.............. 114
Total irradiation of gonads cause by Csla7 ................. 115
Internal irradiation of bone marrow caused by SrsO........ 116
Estimated doses ........................................ 124
T'II . CALCULATION
OF BIOLOGICAL EFFECTS ........................ 127
Leukemia. assuming a linear dose response relationship andno threshold ........................................... 128
Leukemia. assuming a threshold of 400 rem ................. 129
Major genetic defects ................................... 130
VIII XOTEo x I K F O R ~ A T I O S D O C U ~ I E N T.......................... 131
REFERE:;CES
TABLES.

.

98

I. ~ I O A C T ~ TFALL-OUT,
1. I n a nuclear explosion, several hundred radioactive
tsotopes are produced from fission. With exception of asmall number of isotopes they have short half-lives anddecay rapidly. In addition to fission products and residual fissionable material? a number of neutron-induced
radioisotopes are produced. Their nature depend on thesurrounding materials. Also, most of the radioisotopes
formed by neutron-induction have short half-lives,
usually less than a few hours.

2. The radioisotopes formed in a nuclear explosion
are distributed by rneteorologicai processes and eventually reach the surface of h e earth. They enter thehuman body in el-era1 ways : first, by direct inhalationof airborne material ; second, through uptake and deposition on vegetation eaten by humans; third, by transfer
through animals and, fourth, by contamination of water
3. I n addition to considering the esposure from material taken into the body, it is necessary to consider external radiation exposure. Except at the immediate siteof the explosion, external radiation from airborne material is negligible in comparison with the external radiation from fission products deposited on the ground. The
external radiation from deposited fission products depends mainly on their activity, half-lives and gamma
emission characteristics.

4, Materials entering the human body deliver a dose
which is closely related to the time they are retained by
the body. This means that many of the isotopes producedin fission do not present radiabon hazards since they do
not enter significantly into metabolic processes. Attention has therefore been centred on isotopes which arepotentially hazardous by reason of: (1) high fission
yield, (2) fairly long physical half-life, (3) high absorption by the body and (4) long biological retention time.
Special consideration is given to elements that concentrate in specific tissues, even though they do not have all
the characteristics described. Using these criteria, themost important isotopes would be expected to be SrWand CsZ3;.

5. I n addition to the fission products and certain
neutron-induced activities, some of the residual fissionable material, such as isotopes of uranium and plutonium, will also be distributed by meteorological processes and can be hazardous since they are alpha emittingbone seekers. However. the absorption by the body isvery low and at present there is no evidence of any
uptake o i these materials in human tissues.

7. The heat of the fireball from explosions in the
kiloton* range is dissipated quite rapidly and the fission
products do not normally rise above the tropopause. The
radioactive cloud from an explosion may travel manytimes around the earth and. during this time, the tropospheric fall-out is deposited at latitudes fairlp close tothat of the =plosion. The relative magnitude o i the contribution of the stratospheric and tropospheric components to the deposit therefore is different for difierent
localities. Half the radioactive material in the tropos,here is removed by deposition, mainly through rainfall, in about three weeks' and the deposition is effectively complete within three months. This deposit consists mainly of isotopes of fairly short half-life. A t thepresent time the tropospheric fall-out is deposited intermittently during the year and a certain deposit of shortlived activities is built up and maintained. Isotopes of
special concern for this report are Srso, ZP5, Ru103,
RulOa, Ba140and Ce144.
8. If the fireball touches or comes dose to the groundin a nuclear explosion, there will be a local fall-out that
constitutes a significant fraction of the total activity
produced. This type of fall-out consists of radioactivity
erried down by relatively large particles and in addition
to fission products, contains shortlived isotopes producedby neutron induction in the material from the grounddrawn into the fireball. This annex is concerned mainlywith stratospheric and tropospheric fall-out.
Mcaslcreritent of fall-out
9. Measurements have been undertaken to determine
ccncentrations of radioactivity due to fall-out in air, soil
and biological material, especially foodstuffs and humanbone. Emphasis has been placed on a determination of
the world-wide distribution of SPO.A survey of methods
which have been found to be valuable in relation to thework of this Committee is given in annex E, and all
relevant data from fall-out measurements that are submitted to this Committee are collected in tables X I V to
XX and in the map at the end of the volume.

Airborjre activity
10. Air samples can be obtained by filtration of air orby electrostatic precipitation. Studies of vertical distribution of fission products in the atmosphere have been
made using filters carried by aircrafts or balloons. The
samples are cou~ltedfor total beta activity after decay ofnatural radioactivity o r analysed for individual nuclides
after radiochemical separation. One cause of uncertainty
in the measurement of airborne activity at high altitude
is in many cases the insufficient knowledge of the-.collec..
tion efficiency for this particulate activity.

-_-

6. The fireball from a nuclear explosion in the megaton* range cools so slowly that a major part of the fission
products enter the stratosphere, where they become
widely distributed. From this reservoir, the fission products fall onto the earth's surface over a period of many
years (stratospheric fall-out) . These fission products
therefore consist mainly oi long-lived isotopes. The
mechanism of transfer from the stratosphere to thetroposphere is not completely understood.
NOTE:Throughout this report and its annexes cross-reier-.

ences a r e denoted by a letter followed by a number : the letterrefers to the relevant technical annex (see Table of Contents)
and the number is that of the relevant paragraph. Within eachtechnical annex, references are made to its individual scientificbibliography by a number without any preceding letter.

11. hleasurements at ground level in 1956-1957 show
a concentration of S P Ofrom 10-l9 to lV17 c/l of airZJ.
For altitudes up to about 10,000 metres, the amount ?ffission products per kg of air increases slowly with a h tude, but the rate of increase is much greater above thet r ~ p o p a u s e ? . At
~ ~ ~the. present time there are too few
data available to permit a complete inventory of tile
stratospheric content.
a* I n a nuclear explosion the total energy release is compared''with the energy release by T N T (trinitro!oluene)
hen it3
cuplodes. Thus a 1 kiloton nuclear explosion 1s one ~vhlchPtoduces the same energy as the explosion of 1 kiloton (10' tor?s)of TNT, namely of about 10" calories. A 1 megaton e ~ p l o s t msimilarly would correspond to the explosion of 1 megaton
I(10' tons) of TNT.

Fall-out deposit
12. Fall-out deposit measurements are necessary toestimate the external irradiation of man and the amountof specific isotopes likely to enter the biological foodchains and so eventually the body.
13. Many countries are measuring fall-out rate andaccumulated deposit. At present, there are available tothis Committee results from about 350 stations. However, large areas of the earth are not covered by thesurvey and not all the stations and laboratories operate at
the same technical level. The results received by theCommittee, however, allow a number of useful calculations to be made.
14. Soil analysisD?B and various types of collectors,
are used for studying fall-out deposit. Table I gives
some technical information on these collectors. The
agreement between results obtained by different methodsof collection is reasonably good.
15. The location of sampling stations is of the utmost
importance in obtaining representative samples. The location of new stations should be determined in consultation with meteo<ologists to assure a representative collection of prec~pitation (especially in areas wheresnow-fall is important).
16. With daily collection on gummed film or gauze,
the amount of long-lived nuclides in the samples is generally very low ;and, owing to the large soluble iraction,
the washing effect of rainfall is considerable. For thesereasons the radiochemical determination of SreOin thesesamples is talueless. The S P Ocontent can, however, becomputed by measuring the total beta activity of thesamples and following its decay (assuming that all theactivity originated in a single test).8 However, in thepresent situation. with stratospheric mixture of materials from different tests, this computational method isunreliable unless it is repeatedly calibrated against radiochemical determinations on samples collected by the pot
m e t h ~ d . ~A* lmore~ refined method for the con~putation,
taking into account the stratospheric reservoir, has recently been worked out, but this method is based on datathat are not generally available.1° The advantages of thegauze or gummed film is that they allow a daily surveyof fall-out at many different stations.
17. Results reported to the Committee up to March
1958 are shown in tables XIV, X V and XVII and in

Evaporalia sarn$lirrg
worn pol cdkcfion)

Lfcfhod

Collection.. .............. Rain water and dust
Area, approx. range in m'.. 0.05 to 17
T i e of collection..
1 to 30 days or during
precipitation, also 3months' samples
Sample preparation andevaluation.. ........... The water is evaporated and the residue
mounted for counting or first ashed orradio-chemically analysed.

.......

Efficiency of collectionin per cent.. ...........

100'

Assumed 100 per cent effective.
Determined by measurement of effluent water.
The pot collection method is used as reference.

the map at the end of the volunle where the fall-out
deposit at 1 July 1957 is plotted.
18. The world-wide fall-out rate and deposit of SrQO
is uneven and there are variations with latitude whichshow maxima in the region between 30° and 50' Northand South, with a minimum near equator, as shown by
the curve on figure 1. This curve, showing the fall-out
rate during 1956 and 1957, is based on data obtained byradiochemical analysis. Data from soil analysis" andfrom gummed film measurementsx0 give the same overall picture ior fall-out deposit, although the peak in thenorthern hemisphere seems to be somewhat broader. The
computation of a world-wide average of fall-out rate anddeposit is rendered difficult by the existence of large
It is dear, however,areas not covered by surveys.D103-10athat the southern hemisphere has accumulated deposits
that are lower than the average, while areas in thenorthern hemisphere (Japan, the United Kingdom, theUnited States) have deposits of about three times theworld average.lO-l5It should further be pointed out thatthe large deviations from the average are towards thelow side.
19. It has been reported that the fall-out rate in somecountries shows seasonal variations,I3 apparently correlated with the known ozone fluctuations. This is, however, not supported by data from other countries.
11. COMPUTATION
OF EXTERNAL DOSE

OM

FALL-OUT DEPOSIT

20. The fall-out deposit contains gamma-emitters andis therefore an external source of radiation. The composition of the fission products and the corresponding
gamma intensities change with time after an explosion.
In the tropospheric component there is a large numberof short-lived gamma-emitting isotopes and in the stratospheric component Cs13' is predominant.
21. It is impossible to make direct measurement of thevery low exposure rate from fall-out except at areas
close to test sites. Therefore, more indirect methods must
be used.
22. T o compute the exposure rate from deposited
fission products, it is customary to assume that they are
uniformly distributed over an infinite plane. The exposure rate from primary radiation is approximately
Independent of the distance above the ground, provided

Fi:trafion and ion crckangc

Rain water and dust
0.07 to 3.1
4 to 30 days or during precipitation

The water is passed throughpaper, pulp, paper filter,
anion exchanger and cationexchanger. The paper
and the exchangers are
separately ashed andm o ~ n t e dfor counting.

GvrnmrdBm

Dust
0.1
1 day

The gummed film isashed and the residue mounted onplanchet or sealed
between plastic
films for counting.

Gaurr

Dust
0.3
1 &Y

The gauze isashed and
subsequently
treated as thegummed film.

NorthLatitudeSouth

Figtire I. Veteorological factors for the different places of observation have not been taken into account

this does not exceed a few metres. One gets the eupression :1 = c X Ey X FdT(t)
(1)
where
I is the exposure rate (mrad/year)
mrad.Am2c = 0.1
year.mcMev
Ey is the average gamma energy emitted per disintegration ( Mev)
FdT(t) is the total activity of the deposit (mc/km2)
This formula can be used for individual y--emitterssuch as CslS7, or for mixtures if E7 and FdT(t) are
known.
23. Two computation methods for the exposure ratefrom composite fall-out deposits have been used. One
computation is based on measurements of total betaactivity of daily gummed film or rainwater samples.16
This method has been shown to be reasonable at present
even though the radioactive fall-out now is a misturefrom several explosions.'0

24. The other method talces into account that the exposure is derived from two components: (1) a "fresh"
component of tropospheric origin and (2) a "long-lived"
component (CslS7)mainly of stratospheric origin.17 It isshown that the 30-year dose** can be expressed withreasonable accuracy as :D30 = aAt
b-40135(2)
where a and b are constants, A, is the total beta activity(mc/km2) and A',,,,
is the activity of Cs13; (mc/km").
The values of the constants depend on the collection time
and the time before the beta counting is done.
25. Values obtained for the infinite plane 30-year
exposure due to fall-out deposited up to the end of 1957
are shown in table XIV and are of the order of 10 to
180 mr. The dose delivered to the gonad and bone marrow must be computed taking into account shielding,weathering and leaching factors. The shielding factor
accounts for the reduced dose rate during the time thepopulation spend indoors where the dose rate from fallput deposit is reduced. whereas the weathering and leachlng factors account for movement of the depos~ted
gamma-emitting isotopes from the upper layers oi theearth's surface, for esanlple to lower layers of the soil.
Taking all these effects into account, composite reduction
factors ranging from 3 to 21 have been used in reports
received by the C ~ m m i t t e e . ~Using~ ~ ~ an. ~average~ . ~ ~ reduction factor of 10, the 30-year genetically s i ~ i f i c a n t** The 30-year dose, which is approsirnately .+e geneticallysigcificant dose, is the dose received by an in&vldual for the
first 30 years of his life.

+dose would be about 1 to 18 mrem. It should be emphasized that this is only the dose from what is alreadydeposited. and that the total dose from what has been
injected into the atmosphere \\;ill be higher, as discussed
in paragraphs 94 to 115. Including the tropospheric component, the total dose from the external component ill
be of the same order of magnitude as the dose from fallout isotopes taken up by the body.
111. SroOAS AN IXTERXAL RADIATION SOURCE
26. Among the f d - o u t isotopes, SrnOis of particclarinterest on account of the biological hazard that thisisotope presents. Strontium is an element of the alkalineearth group, and its chemical properties are m many
ways similar to those of calcium. barium and radium.
Thus SrgOco-precipitates with calcium as phosphate or
carbonate, and is included in the bone structure. Once
included, SrnOmay remain in the bone structure formany years. the exact time not being knotvn.ls The
osteocyte and bone marrow cells will be irradiated by rhe,8 particles from SrSnand its daughter product Yon.The
ultimate question to be answered is the size o i bone andbone marrow doses delivered by these isotopes.
27. To evaluate the present hazard from SrgOthe concentration in the bone must be deternlined. For hazard in
the future, however, the change in this concentration,
together with the concentration of SroOin different f o ~ d stuffs, should be determined. Of course, SroOprimarily
follows stable strontium through the food-chain, i.e.,
irom the deposit on the ground, through uptake by plants
and transfer through animals. For practical reasons,however. it is the calcium contributors to the national
diet that are mostly studied.

Evaluation of SPOas apt interjral hazard
28. A Sr" programme should attempt to take up thefollowing problems :( a ) Amount of SPOso far deposited ;( b ) Amount of SrgOto be deposited :(c) Rate of deposition of SroO:(d) -4s a result of (a), ( b ) and ( c ) :Eventual total accumulation of SroOon the ground :(e) Kinetics of strontium in the biological cycle :( f ) Present bone level of SreO;(g) Future bone level of SrsO.
TOthis end, the determination of SroOin the follo~vingmaterials is needed :(a) Human bone:(27) Components of the human f ood-chains ;(c) Fall-out materials (collected by the pot method) ;(d) Air (atmosphere and stratosphere) :(e) Soils, grazing grounds and waters.
The determinations oi stable calcium and strontium inthe above-mentioned materials are of importance since
their concentration is of value in interpreting the SrcO
results.

Country .........................
Period of measurement.. .......:..
SrgOin mc/km2. ..................
- -Japan28January-May 1957
2.5-6.3

SPOitt soil
29. Soil analysis is useful for the determination of
accumulated SreO,as soil can be considered as a primarycollector. For determination of fall-out rate, however,this method is not sufficiently accurate. In addition, thesoil anal 4 s has little value for the direct estimation ofpresent .$roo hazard owing to the difficulty of estimating
the relative importance of the uptake of S P Oin plantsfrom soil and from foliage retention, that is, fromuptake of SreOdeposited directly on the leaves.
30. The extraction of Sr" from the soil for analysis
is difficult and many techniques are used, such as alkaline
fusion. acid leaching, ammonium acetate leaching andelectrodioipsis. The large amount of soil needed foranalysis makes the alkaline fusion impracticable and theacid leaching method is very much preferred.E13

31. The upper 5 an of the soil retain at present about
70-80 per cent o i the deposited SrnO,the exact d u evarying somewhat with the type of soi1.12J0-23The total
amount of SrnO,as determined in different countries. isgiven in table 11. Wlere only the upper 5 un of the soil\$-as analysed, a factor of 1/0.7 has been used to calculate
the total amount. The numbers given are the averageand the range of reported values. The values are in
reasonable agreement with values for total deposit of
SrnOobtained by other methods of m e a s ~ r e m e n t . ~ * " J ~ ~ ' ~32. For the study of the behaviour of Sr90 in foodchains, it is useful to express the SreOconcentration in
activity per gram of available calcium.** The amountof calcium per kg of soil is extremely variable : for example, different areas in the United Kingdom show arange from 0.1 to 150 g calciumhg soil,*? although asmall part only of the calcium is likely to be labile andavailable to plants in soils with the higher concentrations.
Also, the available fraction of calcium is very variable :for example, in two different localities in the UnitedStates 3 and 42 per cent respectively of the calcium isa ~ a i l a b l eThe
. ~ ~ availability to plants may also vary if its
chemical form in the soil changes with time or under
different conditions. Similarly the chemical form of
stable strontium will influence its availability to plants.
St-goill food-chains

33. From the environment to the human skeleton,
strontium follows a long path accompanying calcium.
The problems to be considered are the transfer of SrnO
and stable strontium in food-chains 2nd the transferfrom soil to plant.

Discrintirurtion factors
34. The chemical similarities between strontium andcalcium make the use of Sroo/calcium ratio convenient
for following SroO irom the environment to ltuman** For concentrations of Sr" the unit 1 micro-microcnrie( ~ p c )SrgOper gram calcium is used (1 strontium unit, 1 S.U.).

Stvedeng
Mid-1956
1.2%(0.6-2.0)

U E ; ~m.

US-ATO. M

July i957

October 1957
9.7
(3.2-13)

5.3(3.5-14.5)

USSR5
February-July 1957
6.0
(3.0-12)--&Thesepreliminary data are probably too lo\\-, as an ammonium acetzte leaching rnethod was used for the extraction of Sr'"
irom soil.

I

!
1
1

I

Alan. .........

Double tracer witheach meal

4 patients, 9 to 73

Diet + bone

0.54 (0.50-0.62)

29

Man. ......... Korrral mised

Stable Sr/Ca ratio
in diet and bone

Average adult dietin U.K.

Diec + bone

0.25

30

&Ian. ......... Kormal mised

Stable Sr/Ca ratio
in diet and bone

Average diet in
CanadaDiet -+ bone

0.5

Man. ......... Kormal mixed

Stable Sr/Ca ratios

1 normalDiet + bone

0.21

31

Man.. ........

Non-milk

Double traccr witheach meal

4 patients

Diet + bone0.44 (0.374.51)

29

Man.. ........ Non-milk

Double tracer,
single dose

2 pztients

Diet -, bone

0.35 (0.25,0.45)

32

M a n . ......... Normal mixed

S F / & ratio in dietand boneIndirect calculation

Diet + bone

0.25

33

Man. .........

Stable Sr/Ca ratio
in diet and bone(disregarding
marine contribution to diet)

Average Japanesediet and averagebone concentration

Diet + bone

0.17

34

Sheep. ........ Grass from uncultivated pasture

Stable Sr/Ca ratio
in grass and bone

6 animals

Diet --t bone

0.24 (0.15-0.31)

22

Sheep. ........ Grass from uncultivated pasture

SrgQ/Ca r a t i o in
grass and bone

6 animals

Diet + bone

0.23 (0.09-0.42)

22

Goat.. ........ Kon-milk

Double tracer, daily
dose

2 animals

Diet + bone

0.23

35

Rat. .........-

Double t r a c e r indietary

Diet + bone

0 . 5 7 f 0.02

28

R a t . . ......... Son-milk

Double t r a c e r indietary

Diet -t bone

0.2i+0.01

28

Rat. ..........

Non-milk

Lifetime feeding ofradiostrontium/
Ca

Diet + bone

0.28

27

Rat. .......... Non-milk

Stable Sr/Ca ratios

Diet + bone

0.27

27

Mouse.. .......

Non-milk

Stable Sr/Ca ratios

Diet -r bone

0.35

27

Guinea pig.. ... Non-milk

Stable Sr/Ca ratios

Diet + bone

0.22

27

Jack rabbit.. ... Xatural (on desert)

Stable Sr/Ca ratios

Diet -t bone

0.20

27

Cottontail rabbit Natural (on desert)
Kangaroo rat.. . Natural (on desert)
Con.. .........

Stable Sr/Ca ratios
Stable Sr/Ca ratios
Radiostrontium andradioiaicium a tdifferent times
SreQ asssy of Wisconsin milkshed,
1953
SPO assay of Wisconsin milkshed,
1955

Diet + bone
Diet + bone
Diet + milk

SrO'J assay in U.K.,
1955
Double tracer, daily
dose 2 animals 13
days
Double t r a c e r indietary
Double t r a c e r indietary

Diet + milk

Cow. .........
Cow. ..........
Cow. ..........
Goat. .........
Rat. ..........
Rabbit. .......

years old

Diet + milk

Diet + milk

Diet --+ milk

Plasma + foetus
Plasma -t foetus" -uthou h some of the following discrimination factors are

determined as DF (diet-blmd), they have been ~ r i t t e n

103

is very nearDF (diet --, bone), as DF (blood + bone)unity.,s. s,SU:b The range or mean f standard error is given where avai4b1e.

bones. However, the chemical behaviours of strontium
and calcium are not identical and, therefore, their utilization varies in biological processes such as assimilationand milk secretion. For example, cows utilize calciuiii
more efficientlythan strontium in producing milk. To express quantitatively the preferential utilization of one ofthese elements in a given process, the following nomenclature is proposed :Discrimination factor' D F (prmurmr+smple) =Sr/Ca ratio in sample
S r / 6 ratio in precursor
This discrimination between strontium and calcium iscaused by several physiological factors among which themost important are: referential absorption of calcium
from the gastrointestinal tract; preferential urinary excretion of strontium; preferential secretion of calcium
from blood into milk and preferential transfer of calcium across the placental barrier. The quantitative evaluation of the contributions of these physiologicalprocesses has been made under certain conditions.'*
I t is possible to define an over-all discrimination factor
for a given food-chain as the product of the discrimination factors for each step of the chain. under the condition that there is no additional entrance of strontium or
calcium from other sourres into any of the intermediate
steps. For example, in the chain: soil + grass + cow's
milk + human bone, the over-all discrimination factoris :DF (soil+bone) = D F (soil+grass) X D F (grass+aw's milk)
X D F (COW'S milkjhuman bone).
35. Various methods have been described for measuring- the discrimination factors :(a) By measuring the stable strontium/calcium ratio
in precursor and in sample ;25(b) By measuring the radiostrontium/calcium ratio,
for e-xarnple Srg0/calcium in precursor and in sample inequilibrium, either under field condition^^^*^^ or in dietary experiments :?'(c) By double tracer esperiments, for example, using
Ca4"nd Sra5.28

36. I n the case of SrOOtransfer from fall-out deposit
to human bone, the problem is complicated a t present by
the possibility that.the human bone may often not be in
equilibrium with the environment. The discrimination
factors obtained by technique ( a , ) give inherently theequilibrium value and this technique is therefore very
important for the evaluation of future risk. For thisreason, the determination of stable strontium and calcium in the steps of the food-chains is fundamental.
I t is important, however, that the subjects have lived ona diet with a constant stable strontium/calcium ratio andthat the entire diet is analysed. Some values for discrimination factors are summarized in table I11 and in paragraph 47.
Tlte soil-vegetation step in food-cha.i)ts

37. I t is very diliicult to compute an over-all discrimination factor for the soil-vegetation step. The plants
receive S P from soil through the roots and also directlyfrom iall-out deposited on the leaves and the concentration may not be uniform throughout the plant.19*20With
information available at present it is difficult to estimate
f A system of nomenclature has been earlier proposed" : inthis system the term "Observed Ratio" ( O R ) was proposed forthe over-all discriminztion between a precursor and sample andthe term "Discrimination Factor" was used to denote the discrimination that is produced by a given physiological process.

the relative importance of the two routes of entry as:( a ) The accumulated deposit is at present increasing,whereas the fall-out rate has been zpproximately constant for the last four years.D10'(b) The mechanism of deposition (dry fall-out, continuous slow precipitation, heavy showers) may change
the efiiciency of foliar retention.
(c) The type and condition of the foliage may change
the efficiency for retention of direct deposit.
(d) There are great differences in the growing
periods and, therefore, in the exposure time of different
plants.
(e) The accumulation of fission products at the stemsof plants may irlfluence the relative significance of thetwo factors, as this accumulation will depend on the fallout rate for some previous years.D4i( f ) There are indications that in soils with low available calcium contents, the root uptake of S F 0 is more
important than in soils with more available calcium.DH( g ) The depth of the root penetration, the soil type,the water supply and the depth oi ploughing may change
the root uptake.
38. For the indirect evaluation of the relative importance of the hvo components, both stable strontium andcalcium data are useful. A possible approach is based on
the measurement of the specific activity of SPOin plantand in soil (ppc SPo/g stable strontium). As the S P O
retained by the foliage- is carrier-free the ratio:
specific activity of SrsOin soil
specific activity of S P Oin plant
gives the fraction of the total SI- in the plant that comesfrom soil. If the specific activity of the soil is computedfrom the total strontium content and not from theamount of strontium available to the plant, this fraction
will represent a lower limit, and the available strontium
may in certain circumstances represent a small proportion only of the total strontium.
39. An experiment has been reported on the direct
determination of the surface contamination of grain of
the 1956 harvest in the Soviet Union. The grain waswashed with 0.5 per cent hydrochloric acid and water.
which removed at least 50 per cent of the total Srm."

40. Another approach to the problem depends on a
direct correlation of the rate of deposition of SrgO,theaccumulated deposit and the SroOcontent in any particular food. This has been attempted for milk's in the following way, taking yearly averages to avoid seasonal
effects, and assuming that the S P in milk comes fromthe following sources :(a) Uptake by vegetation through the roots, assumed
to be proportional to the accumulated deposit in soil (Fd,in mc/kmg, the value at the beginning of the one-year
period) :( b ) Direct deposits on leaves, assumed to be proportional to the fall-out deposit in a one-year period (fd, in
mc/km9).
The average S t 9 0 level in milk in a one-year period Csf
is then given by:(3)
Chl = a,l(Fd
1/2fd) b d dwhere ah, and bhl are proportionality constants.

++

41. Using data from Perry, N. Y., U.S.A., a set GI
constants ax and bhl can be computed. The values for
Fd and Jd are estimated from New York City pot data
corrected by a factor derived from gummed film datafrom places near Perry and in New York City.

Pi. Y., U. S. A.
TABLE
IV. Sr90 DATA FROM PERRY,

status of the soil as well as upon the type o i plant, conditions of culture and the rate and quantity of SrsOfallSrlC in
Periodmi,r,s.o.
sf;dd$~:;$
out. It should be emphasized, however, that the SrS0
uptake of plants from soil is effected not only by the
April 1954-3Iarch 1955 1.20
0.89
2.30
absolute quantity of calcium present. but also by the
2.78
Jan. 1955-Dec. 1955. . 1.89
2.16
degree of saturation of the colloidal complex o i the soil
Oct. 1955-Sept. 1956.. 2.86
4.57
3.36
July1956-June1957..
3.91
7.48
3.58
by calcium and other cations. such as magnesium, potassium and sodium. and this varies materially from one
From these data one calculates the constants: a\r = 0.34 S.U.
soil to a n ~ t h e r . ' ~km2/mc and b~ = 0.23 S.U. km2/mc.*
45. In the important case of rice, the outer layers of
the grain become contaminated by carrier-free Sr90
42. I n the milk from the four one-year periods, thedeposited on them from fall-out occurring during a very
derived from foliar retention are 43,
fractions of SrQO
35, 27 and 21 per cent respectively of the total SrgO short period before the harvest. The kernel of the grain
has an S P Ouptake which appears to be more dependent
content. These fractions need not necessarily be measupon accumulated deposit than upon rate of fall-out ;?aures of the foliar retention of the plants, as the relative
this will be accentuated by the shortness of the growing
contribution may have been altered by factors such as
period, by the ploughing of each season's straw into thewashing of the grass by rain, and differences in chemical
upper soil layers and also by the formation of a root mat
form of the Sfl0 that the plants had obtained from theunder certain conditions of growth. The SrgOcontent of
two origins. I t is likely also that values of a, .may vary
white rice is thus mainly dependent on root uptake,with time if the chemical state of radiostrontlum in thewhereas that of brown rice, from which the outer layers
soil changes progressively.
have not been removed, is at present more dependent on
43. T o determine the root uptake directly, crop essurface contamination.
periments have been performed in the United Kingdom
46. To distinguish between the amount of S P Oreachwith Spa tracerag6With the conditions of soil and cultiing plants through their roots, as compared with thatvation in that country, concentration of 1.1 S.U. in grasscoming from foliar absorption or uptak'e from the stem
was found for an accumulated level of 1mc/krn2 frombase, is important for predicting their relative sign&root uptake alone."&This corresponds to a milk concencance under future conditions. If, in the future, the accutration of about 0.15 S.U.? derived by using the appromulated deposit of SraOin the soil has increased conpriate discrimination factor from table III.D3GThesiderably relative to the fall-out rate. the relative uptake
constant ah* in equation (3) should thus have a valueof SrsOfrom the soil is likely to become much greaterof about 0.15 S.U. km2/mc for the United Kingdom
th,m that by other routes, especially for soil of very low
as derived from experiments lasting for one year withcalcium content. Forecasts of plant contamination under
S P s well equilibrated with soil. Experiments also indisuch future conditions can, therefore, only be based adecate a Ioliar retention ranging up to 90 per cent of thequately upon that component of present uptake which
total herbage contamination.
depends on the accumulated deposit of SrgO.
44. For other food materials and crops. a method
47. From the preceding paragraphs it may be deduced
similar to that given in paragraph 40 is applicable withthat an evaluation of a generally valid discrimination
three provisions :factor that includes the step from soil is very difficult at( a ) The relevant period during which the fall-out isbest. For defined conditions, however, some values haveaveraged should in some cases be limited to the growing
been reported. Thus DF <soil+diet) has been estimatedperiod of the plant if this is much shorter than one year,
as 0.5, based on values tor stable strontium/calcium
although the fall-out duiing this period may correlate
ratiosin average Japanese soil and diet.s4 Data obtainedwith the annual fall-out rate.
+,I,~)
mayintheUnited States indicated that DF( b ) Some plants have leaves at the base of the stem,
be about unity.46 A general approach, by using stable
or a horizontal mat of roots, which may persist for sevstrontium/calcium ratios in average rock and soil anderal years and prevent the SrS0 fall-out from passing
in human bones, has given the value 0.07 k 0.01 forto the soil. If the growing parts of the plant derive SrS0
DF (soil + human bone),*7 although this value will vary acfrom such a persistent stem base or root mat, the approcording to the type of diet.
priate averaging period for the fall-out rate may need
to be several years. Since, at the present time, the fallConce~ztrationsof Sfl0itz foodstuffs
out deposited during the last four years is nearly equal
38. Data submitted to the Committee on concentrato the total fall-out deposit. the formula given above may
tions of SrsO in different foodstuffs are collected in
fail to distinguish between uptake from a stem base ortable XVI. The data show a wide range, caused both byroot mat on the one .hand and from the accumulated
geographic and seasonal effects. Only selected data aredeposit present in the soil on the other.
thesefore meaningful if one wants to examine the in( c ) The uptake of Sr9@fromthe soil is likely to becreaseof the concentration with time. Some such data
Influenced somewhat by the amount of available calcium
for milk are collected in table V. Analysis has sholm
In the soil. There are indications that in soils which arethat dried and fluid milk and cream and skimmed mi&very deficient in available calcium, the root uptake offrom the same whole mill; sample have the same SrsO/S P o may be greater than from high total calcium soils.22 calcium
ratio.48
and that on such soils the possible formation of root mats
49. Cereals and vegetables, as a rule, show higher conflay also enhance the uptake. The foliar uptalce of SrsO
centrations of Sr90 than milk and milk products, as
1s not, however. influenced in this way by soil calcium.
shown in table VI.
The proportions of S P Otaken up through leaves andthrough roots will therefore depend on the calcium
Calciiir~zsozcrces itz diet=esgiven in reference 43 were calculated using experi50. If the dietary habits of a population are k n o \ ~ nmental data from a shorter period. They differ byiabout 10 per
cent from the values above.
with respect to the main sources of calicum and also the&$;fzizs,

1
1

conceatration of Sr" in the var-ious foodstuffs, the daily
uptdie of SP" from vegetation to human bone can b?
computed, using discrimination factors for the different
steps in the food-chains as given in table III.D3B
Table VII, submitted by the Food and Agriculture Organization in consultation with the World HealthOrganization, gives some data on dietary habits in different countries. Additional data from some of these countries support the values. 2313013415* It should be pointed outthat there are only a few countries from which suitabledata were a ~ a i l a b l e . ~ ~TABLE
V. AVERAGE
CONCE~TRATIOS OF Sr90 IN MEE(IN S.U.) I N SOME SELECTED AREAS
Canada6 stations*. ...................
U.K.
Somersetb.
U.S..4.
Perry, N. Y. (Jan.-Dec.). ......
(Apr.-Dec.). ...... 1.1
New York City (Jan.-Dec.) ....
Uune-Dec.).. .. 1.4
Stzte College, Miss. (hfay-Sept.)
Columbus. \iiisc. (Jan.-Oct.). ..
(Mayact.) ...
Mandan, No. Dak. (Jan~Dec.)(May-Dec.) .

...................

.

5.0

6.2 48,49

4.1 4.4

5.1 22,30

1.9 3.3 3.9
2.2 3.7 4.0
2.7
4.5
3.7
5.0
3.8 4.8
3.7 4.2
2.6 4.0 5.3
9.2 16
7.2 9.1 22

Stable sfrorttizt?nsources in diet
52. Some data on the content of stable strontium invarious types of food are also available and are summarized in table VIII.

TABLE
VI 11. AVER~GE
STABLE STROh'TIUM CONTENT92

IN VARIOUS TYPES OF FOODS

92

Cereals and vegetables.. ............
Milk and milk products .............
Marine fish.. ......................
Fresh water fish.. ..................

92
92
92

COXCENTRATIONSOF S F xx (S.U.)
CEREALS AND VEGETABLES

Japan
Rice, white.. .... 49 (36,62)
Rice, brown.. ... 154 (81-250)
Wheat, flour.. ...
Wheat, brown.
Soviet Union
Wheat and rye. . 69 (28-140)
United Kingdom
Vegetables. .....
United States
Different cereals.
14 (4-38)
Vegetables*. ....
8 (1-29)

..

IX

23
53
162 (153,170)

TABLEIX. AVER~GE
DAILY INTAKE OF CALCIUM,
STABLE STRONTICYI AND Sr90 IN ADULTDIET M USITEDKINGDOBI~~

1 1 (6-35)

9 (1-23)

30

FOO~

33q

Milk ...........
Flour and bread*.A11 other foods..

Per tapila avcrogc daily inlckc, m; calciirm

84

52
109
264
53
56
370

510
5 70
i 80
20
32
2 60
585

.S!ublc strmliunr:+toke, M / ~ C Y

SrW intake

667
332
200
1199

193
714
526
1433

3.64
0.66
2.35
6.65

F W / ~ ~ Y* Fortified with mineral calcium.

54. Wide variation czn be expected because of different food habits and living conditions. as illustrated by
con~putationsirom Japan?' They show that whereas the
majority of the population have an average daily intake
of 3.3 to 5.8 ppc SrQO
per day, there is a substantial number of people, who either eat unpolished brown rice ordrink and prepare food with unfiltered rainwater, xvhich
may cause a daily intake of 23 to 26 ppc SreOper day.
Sfd0it! Izlcirrarr bone
55. The nleasurements of SrgO concentrations inhuman bone give the data that are most needed for theestimation of present risks f r o 3 fall-out. The interpretation of bone SreOresults is complicated by four irnportant facrors, which \\-ill be discussed in the following
paragraphs.

IS THE A V E R ~ G E DIETS OF A FEWSELECTED C O ~ - T R I E S ~ ~Ccrcals. lr~eloblcs, Alilk oad nrilk
LIC.
prodrrcls

CaIcium inlakc,
mg/dcy

TOTAL

TABLE
'1711. SOMEPRINCIPAL SOURCES OF CALCIW~

Argentina ...........
Australia ............
Canada.. ...........
Japan ..............
Ph~hppincs..........
Union of South .Africa
United Kingdom.. ...

22,23
20, 22,48
23
23

Daily intake of SrOOiw ntnn
53. Daily intake of Srs"as been reported from someplaces. Table IX shows data from the United Kingdom,
together with data on stable calcium and strontium
intake.

* The samples were frozen vegetables from food plants.

Cou~~try

2
0.3
3
1

These data show that the stable strontium/calcium ratioof certain foods may be up to ten times higher than inmilk and milk products. Therefore milk may not be themain source of stable strontium in diet although it may
be the main source of calcium (see table IX).

* hlonthly data for each station are compared with data fromthe same month in the two years, altogether 57 values used.
b Median values.

TABLE
171.

in the different countries. The main contribution to thehuman diets vary widely from one country to another,uld there are wide variations within the same country inaccordance with many general and local differences ix1
food supplies, dietary habits and economic conditions.51
Milk and milk products are the major source o i calcium
intake in most Western countries (giving about 70-85
per cent of the total calcium), whereas they plzy a very
minor role in nlost of the countries in Asia and Africa,
where other foods such as cereals, vegetables and also
fish and marine products are the principal sources ofcalcium in the average diets. Moreover, certain foods
not originally rich in calcium are fortified by mineral
calcium in many countries.

Fish and maritic
pr,,,l,

12
106

-

7
12

51. The data in table VII should only be taken to
indicate the order of magnitude of the calciuill supplies106( 1 ) L)ue to lag in contamination of calcium sources
human bone is not yet in equilibrium with thewith SrgO,
environment. T o correlate the SrSOcontent of humanbone with the contamination level of the environment
and to predict future risks, it is necessary to know how
close the system bone-environment is to equilibrium. For
this purpose stable stronti~immeasurements are veiyuseful.
(2) If SrS0were unevenly distributed in the humanskeleton the measurement of a single bone \\-ould not be
representative of the average skeleton value.
( 3 ) Uneven distribution of SPO within the bonewould also make the relevant dose computation dific~dt.
(4) The average Sr90 content of bone may also varywith age.

The importo?tce of the stable stro)ztitrnz deterncilzation
56. Using the stable strontium/calci~im ratios in different steps of the food-chains and in bone, it is possible
to determine the discrimination factorsDS5and computethe equilibrium concentration in bone. The determination of stable strontium in bone can be done by spectographf7vS3*j4or by activation
The reported
values diifer somewhat, and this may partly be =plainedby a small but significant difference observed from one
100 pglocality to the next.47 An average of 450
strontium/gram calcium has been found using 756 samples from all over the world." Investigations in Canada
and the United Kingdom have given average values from
290 to 370 pg strontium/gram calcium using a limited
number of samples (16 to 35).2"40150 Young children
apparently have somewhat lower strontium concentrations in bone than a d ~ l t s , which* ~ ~ ~should~
be expected
as a result of foetal discrimination against strontium.3s

trations in young children may be in equilibrium with
their current diet, although the amount of boae contaminated at this concentration may well be only afraction of the whole skeleton. Correction for non-unidistribution is not, however, required if
fornlity of SrDO
the concentration in young children is used as an indication of the masimunl concentrations being reached in
new bone deposited in older children or adults.
(b) Any change in source of calcium intake may involve an alteration of Srw level in this intake and thus
in bone that is currently being formed. An important
instance arises in young clilidren. whose bone calcium
will have been derived from three different sources :(i) From the mother during gestation ;(ii) From the mother's milk during maternal
feeding ;(iii) From the subsecluent dietary sources.

60. Some indication may be given as to the importanceof these factors. Calcium derived during gestat:ion appears at present to be somewhat lower in SrgOlevels(about one half) than the dlild's subsequent diet, since
the level in the bones of stillborn children is rather lessthan in children 1 to 2 years old (table X). The SPO
content of the bones of a child o i 2 years would be only
slightly lowered for this reason since at this age only
about 15-20 per cent of the bone calcium and associatedSrgOwill have been derived during g e s t a t i ~ n . ~ ~+SrO0 d,istribzctiotz in diferent botles of the skeletopc
57. The problem of non-uniformity in the distribution of stable strontium in different bones in the skeletonof man has also been investigated by stable strontium
measurements. It seems that there is a uniform clistribution,4i*5awhich should mean that the distribution of S P O
should also be uniform when the skeleton has reachedequilibrium with a contaminated environment. This has
been confirmed for goats fed by Ca4%nd Sf19 over an
extended period,s6 and by measurements on the distribution of SrBOin cow's bones." In man, hon~ever,there
are experiments showing non-uniformity by single injections of double tracers arid also in the SPOdistribution at present in a d ~ l t s . ~ ~ J ~Uniformity of SrgOdistn'brrtioa in bone
58. I t seems clear that SroOwould be distributed uniformly with calcium throughout the bones of a child
whose calcium intake had been contaminated with SrgO
at constant concentration during the whole of its life
since, in these circumstances, all bone formed would bederived from calcium of equal SraOcontent.
59. Non-uniform deposition would arise frotll two
main causes :(a) A progressive change in the SroOcontaminationof dietary sources will lead to a corresponding change.
in S P Olevel of new deposits of bone, which contain themost sensitive cells. With rising dietary levels, the bone
. concentrations in young children will indicate the current:' dietary conditions. Much of the bone of older children
and of adults will, however, be contaminated at lower- levels corresponding to the lower levels in diets ofearlier years. In this sense, the maximtun bone concen-

61. Maternal milk contains about 40 per cent of thelevel of SrgOin the diet of the mother.93 Since about 25
per cent or less of the bone of a 2-year-old child. previously breastfed for half a year, will have been derived
from maternal milk, this factor would only lower the
average bone S P O level by about 15 per cent or lessfrom an equilibrium condition with the diet.58

62. Thus the highest radiation doses delivered to bonefrom radiostrontium are likely to be those in the newbone, that is at present being laid down in children
aged over 1 year. If the concentration remains constant,the absolute quantity of strontium in the body increases
with the size of the skeleton up to 30 years, and on theassumption of a linear dose effect relationship, theprobability of somatic mutation in bone-marrow cells
increases with the size of the skeleton.
The probletn of computing skeletolr dose from SrOO
63. As a first approximation, SrgOwill be considered
to be uniformly distributed in the skeleton and it will
be assumed that the whole radiated energy is absorbedby the bone. The mean particle energy of the pair S P O
and YgOis 1.13 MevSS,so that a skeleton containing Ig
calcium per 7g bone will receive an average dose rate incompact bone of 2.7 mrem/year per strontium unit.''I n the skeleton about 10 to 13 per cent is spongious bone.
having a dose rate of about 0.9 mrem/year per strontium
unit. The average dose rate to the compact and spongious
bone of 2.5 mrenl/year will be used in the follow~ng
calc~1ations.~~~~~
64. The bone marrow dose from Sfl0 deposited in thebone will be lower than the bone dose, depending on thesize of the marrow cavity. A calculation of a mean marrow dose is therefore a very complex p r ~ b l e r n . ~ "I n- ~ ~the following it will be assumed that 1 strontium unit willcause a mean bone marrow dose rate of 1 rnrem/yyar.
The true value of the mean marrow dose** mtght
P$The computation of the mean marrow dose is difficult andapproximate only.

1TABLEX.

- ~ V E R ~ G CONCENTRATIONEO F SrgOI N MAN (STRONTIUM UXITS)'
Canada*Unikd Iiingdum'l+Fnilcd Stalc+I'.b

Age Group19561957

1956

1957

1955-1956

19361957

Stillborn to 1 month.. .......................
I month to 1 year.. .........................
1 year to 5 years.. ..........................
5 years to 20 years. .........................
More than 20 years. ........................

0.7 (3)
1.6 (2)2.1 (1)0.1 (1)0.4 (3)0.44 (5)0 2 0 (11)0.83 (13)0.25 (12)0.11 (5)0.55 (42)
1.1 (19)
1.2 (17)0.45 (19)0.1 (1)0.56 (10)0.26 (17)0.07 (137)0.67 (30)0.54 (32)0.07 (62)" T h e number of samples in each age group is given inparentheses.

Including a few data from North America outside the UnitedStates.
-4ge group 0 to 5 years.

however, be as low as 0.5 or as high as 2 mrem/year
per strontium unit."
65. It should be emphasized that bone marrow cells
which are almost surrounded by bone will receive doses
which may be qua1 to those in compact bone. Taking
into account all causes for non-uniformity, i.e. the nonunifornl deposition in the mineralized zones, the variation in bone layer widths and geometrical factors(comers), the bone marrow level is probably five times
the figures quoted above.

gamma-emitting daughter product, BalS', which can be
determined using gamma-spectroscopy, as can
The large difference in energy of the gamma rays emitted from Cs13' (0.66 Mev) and K40 (1.46 blev) makes
the discrimination adequate even ~vithcrystal detectorsof low energy resolution. Radiochemical methods arealso in use ior separation of caesium from othermaterial.E15
72. The present burden of Cs137in man can be determined in vivo with whole body spectrometry o r gamma
spectro~copy.~'~Large liquid scintillators have the advantage of being geometrically efficient, but the energy
resolution is relatively poor. Sodium iodide crystals
have good energy resolution, but even with the largest
crystals available, the counting rate is not as high aswith the large liquid scintillators. To obtain the masimum of information, both types of counter seemConcentratiorr of SF0 in l r m z
66. The knowledge of average values is not sufficient
for risk evaluation and individual data are extremely
useful. I t is emphasized that data on bone concentrations
should be accompanied by the following information:( a ) Date of death or biopsy ;( b ) Age at death or biopsy;(c) Precise origin :(d) I n case of children : methods of feeding.
67. Not all the data obtained so far include complete
information, and further studies are required. Table X
gives some of the bone concentrations measured in different countries (see also table XVII).
.

IV. &I3'-4s A N IKTERXAL SOURCE

68. The similarity behveen the nature of the precursors, half-lives and fission ~ie'ldsof SroOand CS'~'suggests that the distribution of these two isotopes issimilar in fall-out. On the other hand, their different
chemical properties make their behavour in food-chains
and in the body different.
69. Cs13' is poorly taken up from soil by
Therefore, the contamination of food sources should
depend largely on fall-out rate. The biological half-lifeof caesium is comparatively short (about 140 days inmanas and 20 days in cowa6), thus indicating that thelevel of the isotope in the human body will approach
equilibrium with the environment relatively quickly.
70. Cs13' concentrations are often expressed by the
C~'~'/potassium ratio. Some evidence exists. however,that the metabolism and routes of entry into the humanbody of these elements are to some degree different. For
example, in man, the biological half-life of potassium(35 days)6i is apparently shorter than that of caesium.
An analogy of Srso/calcium ratios should therefore not
be implied.

Concentration of Cs'$' i n foodstr~fs
73. As in the case of SrBOit should be possible torelate the Cs13' burden in man to the concentration in
the diet. In some areas (i.e. the United States), milk
contributes about 50 per cent of the human uptakea5and can therefore be used for comparative purposes.
During 1956-1957, milk in different countries showeda general CS'~' concentration of 20 to 70 ppc Csla7/g
p ~ t a s s i u m . " ~ ~ The~ ' ~wide~ ~ 'range~ ~ ~is~partly~ ~ caused
by variation ~irithgeo raphic locality. Measurement ofrice in Japan 1956-195 showed a concentration of about
50,upc CsIS7/g potassium.

5

Daily intake of C.P7 in nrart
74. Estimations of daily intake of Cs13' have been
made for Japan and the United States, giving about 30
to 50 ppc C ~ ' ~ ~ / d a yBecause. * ~ ~ ~of~the short biologicalhalf-life for Csla7,variations in the diet will change theCs13' level in man rapidly. With the constant concentration in the diet, the equilibrium burden in man isreached in about two years.
Concentrations of Csl$' in mart
75. The measurements of CslS7in man show a rangeof 25 to 70 ppc
potassium in the north temperatezone during 1956-1957 with an average of about 35 ppc
shortly after
Cs137/g p o t a s s i ~ m .During~ ~ ~ ~ periods~
tests, a slight increase has been o b s e n ~ e d .Concentra~~tions in the diet and in man are apparently rather similar,
which is unespected because oi the longer biologicalhalf-life of caesium as compared to potassium.G5

AfctJtod~for J~teanirenterztof corlcerztratio~rsof CsJJ7
Dose rate frofrt CsJS7in ltzail
71. bleasurements of concentrations of CsX3'can bemade without radiochemical separations. Cs137 has a
76. Since the average potassium content of a standard man (70 kg body weight) is about 150 g,67*60*i0*Higher mean marrow doses are possible and higher doses
the average
gonad dose rate amounts to about
in small foci of bone can be expected.

to the mean residence time of the tropospheric fall-out
1 mrem/year (ranging from about 0.5 to 2 mrern/year) .G5( 3 weeks), gives a dose contribution that is less than
Uniform distribution of caesium in soft tissue is assumed as is indicated by stable caesium n~easurements.~~ 10 per cent of the dose from SF9.
83. Data from measurements in Canada. show thepresence of Srs9in bone from man and animds, as given
77. Fall-out from the troposphere consists mainly of
in table XI.
short-lived isotopes and the dose contributions are thereTABLEXI. CONCESTR~TIOSSOF SrS9 AND Sr9O
fore primarily dependent on fall-out rate rather thar.
ET B O S E ~ ~on accumulated deposit. The latitudes where the tropob p c per g calcium)
spheric fall-out is deposited are mainly determined by
the latitude of the test sites. The doses from tropospheric
Sainpk aitd do& of death
A cc
SrSQ
Srgo
fall-out material vary with geographic location rough!y
Human
bone
in the same manner as the dose from stratospheric
December 1956.. ...... 5 months
5.110.6
1.8rt0.2
fall-out.
December 1956.. ...... 10 months
3.7*0.4
1.4k0.2
November 1956.. ...... 22 months
5.7i0.3
3.8=0.2
External Soilrces
Cow bone
78. The tropospheric material has an observed mean
October 1956.. ........ Foetal
144
8.6
residence time of two to four weeks1 and although it is
October 1956.. ........ 3 weeks
28.3
5.3
deposited intermittently during the year. a certain deOctober 1956.. ........ 4 weeks
43.4
5.1
posit of short-lived activities is built up and maintained.
October 1956.. ........ 6 years
15.6
8.1
The reported values indicate that a level of short-lived
October 1956.. ........ 13 years
18.7
3.8
radioactivity is maintained at about 50 to 200/mc/km2
lugust 1956.. ........ Old
6.3
3.3(See table XIV). Allowing a factor of 10 for shielding
August 1956.. ........ Old
8.4
6.9
and weathering and assuming an average y-energy ofabout 0.5 &Ievl6,the annual gonad and mean bone mar1"'
art ifztertzal source
row dose should be of the order of 0.25 to l mrem/84.
bIeasurementsof 113' are oi interest because ofyear.D"the selective concentration of iodine by the thyroid
Infernal Sources
glands of mm. and animals. The nonnal human thyroid
weighs 20-35 g and contains about 10 to 15 mg of stable
79. The air concentration of fission products at
iodine. All soft tissue has small amounts of stable iodine
ground level has been reported to be about 10-'5c/l
and blood plasma contains about 0.05 pg/a3.i5 The
during 1956 to 1957 (See table XVI). Assuming that
effective half-life of Il3' in the body is very close to thethis material has the same composition as the fall-out,radioactive half-life, 8 days.='
the annual dose resulting from inhalation has been computed'? using data for retention, volume of inhaled air,85, Since 1954, many laboratories have measured
weight of critical organs, etc., based on 1.C.R.P.activities offrom fall-out in human and cattle
criteria.Bi The annual doses, according to the calculathyroid^.^^-^^ The thyroid samples obtained from autoptions, are :sies are counted with scintillation counters calibrated
against 1131standards. In some cases the results are
Whole body dose .................. 0.2 mremcorrected using values from muscle measurements toLung dose (if material soluble) ..... 0.1 mrem
eliminate the K40 and CslJ7contributions.
(if material insoluble) ... 1.5 mrem
Thyroid dose ..................... 0.6 mrem
86. Apparently the cattle contamination is from two
Bone dose (Sre9,SrnO,Bal*) ........ 0.15 mremsources : inhalation and feeding on contaminated pasAverage bone marrow dose (SPg, SrgO,
tures. Restllts obtained by feeding cattle on fresh fodder
Bal'O) ......................... 0.05 mrem
or with barn fodder during the same periods suggest
Average gut dose .................. 0.03 mremthat 70 per cent of the IIS1 uptake is from intestinal
a b s o r p t i ~ nbut
. ~ ~there are other experiments that indiSflo and Bawo as intertral sotrrces
cate both higheP1 (up to 95 per cent) and lowerTi per80. Dose contribution from short-lived activities cancentage from this route of entry.
be introduced through food-chains when the food has not
87. Results of measurements of the IIS1content inbeen stored for a long time. Storage of food reduces thecattlethyroids from various laboratories show a large
activity of short-lived isotopes, which makes it very
spread of values. Neglecting high values from areas neardifficult. if not impossible, to give world-wide average
test sites, average results for cattle from difierent geoannual doses from tropospheric material.
graphical locations are comparable. and are of the order
81. I t has been reported that SP9/Sreo activity ratiosof 1 to 100 ppc/g thyroid for the period May 1955 to thein milk show fluctuations in the range 1 to 25.20*22*48*'0~
end of 1956.m1T8O n account of the short half-life, IX3'
is*74 There are marked seasonal variations, largely deconcentrations in thyroids vary with time as related topendent on whether the cows were on pasture. Thus theweapon test^.'^^^^
average S P 9 concentration in milk has been reported as
88. 1131activities in human thyroids are lower than
3 to 12 ppc SP9/g calcium in January to April.
in those of cattle from the same area and show A s s
whereas it was of the order of 100 to 150 ppc SPs/g
spread in the values. Considering only the IIS1actlvlhes
calcium in September and October in Canada in bothfrom a group of barn-fed cattle and correcting for dif1956 and 1957. The SroOconcentration was all the time
ferent respiratory volumes, values similar to those ofof the order or' 4 to 8 ppc SPo/g calci~m.'~*'~
11unlan thyroids are obtained.80 This supports the idea
83. computation of the relative doses from the twothat the human 1131intake is through inhalation. I nisotopes, using the range of values observed in milk forsome areas of the United States away from test sites. thethe Srs9/Srg0ratios, show that the doses from S P W v e1131 concentrations in human thyroids averaged aboutrise to a bone dose ranging from about 1 to 20 per cent
4 ppc/g thyroid during May 1955.'O The human thyroidsof that from SPO.f Ball0 in the amount that corresponds
measured were mostly from adults (more than 50 Yearsold). but a few samples from persons of different agesiA biological half-life of strontium of 11 years is used?'
-

b

i

-

suggested that the 1131activity increased slightly withage.8o The human thyroid concentrations also vary withtime according to weapon test periods. I t is therefore
difficult to estimate the integral thyroid dose over a
period of time.
89. Considering the linear dimensions of the normal
thyroid gland, it can be computed that the gamma contribution to the average thyroid dose is about 10 per centof the beta contribution.82 Integrating the data for theUnited States, excluding areas immediately adjacent totest sites, average doses of the order of 5 rnrem/year
are found in man for the years 1955 and 1956.'O Dosefrom IIs1in soft tissues is of the order of lo4 times the
thyroid dose.D84Therefore the average annual gonaddose in the United States for the years 1955 and 1956
was of the order of p rem.
90. In areas near test sites, short-lived iodine isotopes
will reach the thyroids. From the half-lives and averageenergies of these isotopes, the thyroid dose delivered canbe computed as 4 times the dose from IIS1if radioiodine
is inhaled about 10 hours after the nudear explosion,83
but after 10 days the contribution is negligible.

m. ESTIVWIONO F DOSES FROU FUTLRE FALL-OUT
91. Data on present fall-out rates and accumulated
deposits and the human burden of fission products
allow the estimation of present dose rates. However, forevaluation of future genetic and somatic effects it isrequired to estimate the 30-year and 70-year doses. Thisestimation can of course be based on computations onlyof future fall-out rate and deposit and not on experimental data.,.It is possible, however, to make these computations using available data and certain assumptions
which have at present little if any support in physicaldata. The results must therefore be considered only inconnexion with these assumptions and necessarily cannot
be any more valid than these.
92. Once the values for the future average world-wide
fall-out rate and deposit have been calculated, the next
step is to evaluate the doses received by human beings.
This requires calculations based on factors, some ofwhich are uncertain and others which cannot be generalized for the world's population, such as agriculturd conditions and practices or living and dietary habits.
93. Owing to all these faciors the evaluation of doses
is rather uncertain. Furthermore, no indiczition. based on
experiments, can be given as to the degree of uncertainty
involved in the evaluations, but an attempt has been
made to choose the more pessimistic of the possible
alternative assumptions, and the over-all calculations
may therefore overestimate the doses to be expectedfrom future fall-out.
Estir~latiotzof fall-oui rate and deposit in the future
94. A major part of the long-lived components of fallout arises from the stratospheric resen-oir, which isbuilt up by "high yield e s p l ~ s i o n s " .I~t ~has been reported that asout 10 per cent of the deposited Srg0comest ~areas~ ~ ~far from test sites
from tropospheric f a l l - ~ uin(Sweden and Unitcd Kingdom). In the United States
the contribution is estimated to be about 30 per cent."
which may be taken as representative for areas relatively
dose to test sites. Only a small error, therefore, is introduced in considering that all the Sr" fall-out arises fromthe stratospheric resen-oir. As Cs13' and SrgOhave approsimately the same half-life and fission yield. andsimilar gaseous precursors in the fission chain. thefollowing evaluation will be assumed to apply for bothisotopes.

95. The material balance of SPOin the stratosphereearth system can be described by the following generalequations :where:
n is the injection rate of Sr90 into the stratosphereper unit area (mc/km2*year). (n is as a convention
assumed t o be uniform for all the earth's surface.
This assumption implies a relatively fast latitudinal
stratospheric mixing.)
0 (t) is the Sr90 content of the stratosphere, expressed per unit area (mc/km2).
Fr(t) is the world-wide average fall-out rate of Sr90
per unit area (mc/km2. year).
Fd(t) is the world-wide average accumulated depositof Sr9O per unit area (mc/krnZ).
X is the disintegration constant of Sr90 (0.025/
year).
96. These equations do not imply any particular relation between the stratospheric content and the fall-out
rate. nor do they imply any specific function for thevariation of 11 with time. The equations, therefore, cannot be fully resolved. At present, data on n are notavailable to the Committee. The computations will therefore be carried out for hypothetical cases of future
values for 11. Equation ( 5 ) implies that no leaching or
weathering occurs.
97. Analysis of fall-out material has shown that Sre0
can remain in the stratosphere for many years before
being deposited on the earth. The depletion mechanismof the stratospheric reservoir is not yet adequately
known. I t has been estimated from measurement of fallout rate and stratospheric content that the annual SrgO
fall-out is about 12 per cent of the stratospheric c ~ n t e n t . ~This annual fraction corresponds to a mean residence
time of about 8 years, which is in agreement with a valueof 10 k 5 years derived from unpublished data.87 The
concept of a constant fractional removal per year of thestratospheric content is inconsistent with ~neteorologicalprinciple. However, nothing better can be offered atpresent. If the concept is to be used, a mean residence
time of about 5 years appears to be the best value anda reasonable upper limit is about 10 years.84 The lattervalue has been used in the calculations to follo\v. since
it tends to yield results on the pessimistic side.
98. For the calculations it will be introduced asworking hypothesis that the annual fraction does notchange with time:
Fr(t) = k Q(t)where k = O.l/yea_r. I t can b_e seen that all the following equations for F,(t) and Fd(t) that depend on thevalue of k will give higher results for lower vziues of k*.
99. As the radioactive material is in the form of
microscopic particles of various sizes, it might be espected that the residence time of this material in thestratosphere \\rill be a function of the size spectrum of
the particles. This has importance especially in the eventthat no new material is introduced into the stratosphere.
because the depletion would then continuously change
the size distribution.
*Using k = 0.2/year in the follo~vingconputztions gives
doses that are 0 to 10 per cent lolver than those obtained using
k = O.l/year.

100. I t is now possible to presknt a model in which
equations (4) and (5) can be integrated. The hypothesesof the model are the following :I

mc/km2

III

1. year( a ) -All the SrSOfall-out comes from the stratosphericreservoir ;( b ) The fall-out rate is proportional to the stratospheric content ;(c) The SrsOdeposited on the earth is not acted uponby weathering effects or leaching :(d) The injection rate of SrS0into the stratosphere 12
will be constant in the future. Two hypothetical cases
giving two different values of tz will be discussed below.
101. The general solutions of equations (4) and ( 5 ) ,using equation ( 6 ) ,are :Fr(0) and Fd(0) are the values

I.

1

I

part of year are encircled.

Case 1: The tests stop ai the end of 1958
102. This implies that n = 0 for any subsequent time.
Using this relation, equations (7) and (8) will be :Fr(t) = Fr(0) e -ck + A)t(9)F'.(t)

1

1954
1955
1956
1957
Figure 2. Fall-out rate of S P determined by radiochemical
analysis.g*ll.l5~~~~**
Values obtained by extrapolation of data forfor the fall-out rate and accumulated deposit at the time
t = 0, which in the following will be taken as the endof 1958.

for the stratospheric depletion. This might have been thesituation during the last four years, as illustrated infigure 2. From equations (4) and (6) it follows that:

Fr(0) (e+ -e-(k +A)t) (10)= Fd(0)Using this relation, equations (7) and (8) will be:
Fr(t) = F,(O)
(15)
Fr(o)
(1 - e -At)
Fd(t) = Fd(o)e -At(1 6)

Equations (9) and (10) show that the fall-out rate decreases exponentially from the moment of interruptionof tests, while the fall-out deposit increases, goes througha maximum at a time:1
Fr(o) (k A)
tmDr= - lnk(Fa(0) F,(o)/k)k~

+

+ ,-

+

If the tests go on indefinitely, Fd(t) will reach anequilibrium value of:Fa(=) = Fr(0)(17)(about 13 years after tests stop) and then decreases,
eventually with the half-life SroO,X

The 90 per cent equilibrium value will be reached inabout 70 years.
105. Asszimptwn (b).;The period from the beginningof 1954 t o the end of 1958has been chosenDlo3because
the values of Fr(t) and F,(t) were small before 1954
and the error introduced assuming both to be equal t ozero would be small. The estimation of an average fl
for the period 1954 to 1958 inclusive implies in ourmodel computing a constant n such that it wsuld Prod-uce, in five years, the observed values of Fr(0) andFd(0) a t the end of:1958.
106. The total amount of Sr90 in the environment

Case 2: Tests continue
103. For the calculations of future fall-out rate anddeposit t ~ assumptionsoare used: (a) the rate of fallout of Srgo will remain in the future a t the constantvalue observed for the last four years, or (b) the rateof injection of Sr" into the stratosphere will remait] inthe future a t a value equal to the mean value for theyears 1954 to 1958 inclusive. If tests are stopped a t any
subsequent time T, then Fr(t) and Fd(t) would fromthat momenton,with either assumption,be determinedb y the equations:~ X ) ( t - T)
Fr(t) = F , ( T ) ~ - ( +(12)

F (T) (e -A(C
Fd(t) = F , ( T ) ~-A(' - TI + Lke-(k i A ) ( t - T ,1

is F,(t)- TI -+ Q(t) = F,(t) + +F. (t) Therefore.

(averagefor the period 1954 to 1958) is an Z determined by! .
F (0) = Ti (I - e-Ar)
Fd(o)
(18)

(13)

++

104. Asstimption (a). In the model adopted. thisassumption implies that Q will remain at an equilibrium
value, which has been caused by large initial injections,follo\ved by a constant injection rate that compensates--.

where 7 is 5 years, and Fr(0) and FdO) arerate and deposit a t the end of 1958. Under tfilsassump*>
tion the solution of equations (7) and (8) Is:-~'
5

111

-

F,(t) = F,(o)e -ck

+

fik
k+X
+-

Fd(t) = F,(o)~-Y +-108. The world-wide average of the fall-out rate of
SrgOwas estimated from the latitude distribution curve,
figureI t was assumed that the fall-out rates at thepoles were zero. As measurements seem to indicatethat the fall-out rate has been fairly constant over thelast four years (see figure 2),D104the rate of 1.5 mc/km2.
year obtained from the data from 1956 and 1957 has also
been assumed valid for 1958.

(( e - ~ t - e - ~ +4t)

k

X

-A

+f(m+me-(k+"')(20)
If tests go on indefinitely F,(t) and Fd(t) will reachthe equilibrium values:-

109. The world-wide average of the accumulated fallout deposit of SrsOhas been obtained from soil, pot and
The values obtained were
gummed film data.5~9-13~'0~"2'3
extrapolated to the end of 1958 using the quoted value
1.5 mc/km2.year for the average fall-out rate: giving as
an average about 5 mc/km2 as the average accumulated
deposit at the end of 1958.

Ti

Fd(") =

h(li + A)
The 90 per cent equilibrium values will be reached inabout Is' and 100 years, respectively.

110. Population weighted averages have been calculated using the same data as in paragraphs 108 and 109,
and the latitudinal distribution of the world's population
as obtained from a detailed population map.s6At present,
the maximum fall-out level occurs at the same latitude
as the maximum population density and the population
weighted averages for fall-out rate and deposit are atpresent higher than the area weighted averages by afactor of about 2. I t is possible that this may change inthe future and that in the event of cessation of tests it
may approach unity. However. no allowance for thispossible reduction has been made in the present calcula-

Values of F,(O) and Fa(0)107. I t is dii3cult iron1 the available data to computea world-wide fall-out rate and deposit, partly because
large areas of the earth are insufficiently covered by the
net-work of stations collecting data and partly because
the different stations and laboratories do not all operatewith comparable collection and evaluation methods. The
estimation is especially difficult for the fall-out deposit,
as many stations have only operated for less than
two years.

Population weighted
fall-out rate of srgO
Fr (t)
8.0'

7.0

mc/krn2-.

rate-fromtests up to the end of 1958year

- ---- rate.according assumption atp..................rate according to assumption b
Time for cessation of'tests.........:.................................
at fie end of fie year given
Equilibrium value'

6.8 mc/km2. year

for the different curves.

------------Equilibrium value
3.0 mc/km

2

.

year

I

I

80

90

I

I

100 -t years

Population weighted accumulated fall-out deposit
Fd (t)
mc/km2
150

*.f

*:

~ ' k ~ u i l i b r i u valuem
272 mc/km2

:

:t'
.*.

:a
.

t

z

,.+-

:

*+*.

:
:

.SO

-

0

.+-*

19sa

t

t

-

L

CIP----

Equilibrium value
120 mc/km2

I

I

I

.

1

I

I

r

10

20

30.

40

50

60

70

tions.** The population weighted values of the fall-out
rate and of the accumulated deposit at the elid of 1958
are accordingly taken as :F,(O) = 3 mc/km2*year

Methods for dose estimutions***111. The equations derived above give the variationof the fall-out rate and deposit with time for the different cases studied (see figures 3 and 4). The computationof doses to human beings also requires information on
the behaviour of SrsOand Cs13' in the food-chain, andthis introduces new uncertainties. The main information
required is the extent to which the dose rate is correlated
to fall-out rate and to fall-out deposit and the values ofthese correlation factors. At present the available information is insufficient and has to be complemented bysome assumptions.
- F o r population weighted avenge fall-out rate and accumu(wiUlout
rated deposit the symbols F r ( f ) and R ( t ) arebar). As F,(0) and Fa(0) are a factor of 2 higher than F,(O)and Fd(0), respectively, it can be seen from equations (7). (a),(14) and (18) that also F,(t) and Fa(t) are a factor of 2
higher t i a n F,(t) and Fd(t).
the dose estimations population weighted average-Forfall-out rate and accumulated deposit F,(t) and Fd(t) will
be used.

r
80

I

I

I

90

loo

t years4
i112. I n the following paragraphs dose computations
will be considered for:( a ) =ternal irradiation of gonads caused by CP":(b) Internal irradiation of gonads caused by CS'~';(c) Internal irradiation of bone marrow caused
by Sreo.
In addition to the cases of (1) cessation of tests at theend of 1958 and (2) continuation of tests until equilibrium is reached, the doses for cases of (3) interruptionof tests at different times in the future are also given as
percentages of the equilibrium dose.
External irradiation of g o d s caused by CsJS'
shows that the exposure rate
113. Equationfrom external irradiation is proportional to the accumulated fall-out deposit :I = c X E-t X FTd(t)(1)
atake care
Takingof shielding, leaching and weathering effects, the dose
rate is given by:dD(23)(;if)e= c x cl x E, X Fz(t) = g. X FI(t)mrad. km2
Here c a 0.1 year.mc*i\?Iev and c1 will be assumed tobe 0.1.D'5 In the case of exposure from Cs'" the113

1deposit according to assumpti03 a

Time for cessation of tests at the end of
the year given for the different curves.

f*.
::....*...

:

100- - --

deposit.from tests up to the end of 1958.............. deposit according to assumption b

+
:
'

-

-

be used for EY is 0.92 X 0.89 X 0.661 NIev (92 percent of the disintegrations give y-ral-s of energy 0.661
Mev and of these y-rays 11 per cent are converted.)T h e dose rate from deposited Csln is therefore:($)a=ge~Fd(t)mrenl/year ior a fall-out rate of 1 mc/km2. If in the
future the dose rate is proportional to the fall-out rate,
then:

(z),

= g, X F,(t) = 0.3 X F,(t)=0.005 X Fd(t) mren~/year (24)(26)

Total irradiation of gonads caused by Csln

Iniernal irrdiatit'cnz of g o d s catlsed by CslS7
114. The human burden of CslSi at present depends
primarily on the fall-out rate of ~s thus giving~
the dose rate:

115. The total dose rate for the gonads from Csl37 is
dD
~
~
,
~
~glFr(t) ~(2 7)
d t = geFd(t)(25)

The 30-year doses for the two assumed injection rates(assumptions a and b) and for the different cases considered for cessation of tests are therefore given by+

Calculations from exoerimental data show that the average gonad dose rate >mounts to about 1 mrem/year in
the United Kingdom and the United States during 1956
and 1Fj7.DiaThe observed fall-out rate of SrBOin thosecountries was about 3 mcfim2 during the same years
Assuming the same fall-out rate for(figure 2)
Cs13' as for Sfl0 (probably an underestimate), the dose
rate due to internal irradiation from Cs13' is 0.3
TABLEXI I.

so

3o

+

ao

DIO = /%t= g . f ~ ~ ( t ) d t g l / ~ ~ ( t ) d t (28)7"0"0The equations for Fd(t) and F,(t) to be inserted in t h edifferent cases can be found elsewhere in annex D,
identified by their numbers as given in table XII.

EQUATIOSSFOR USE IN FORMULAS (28), (34) Ah'D (35)F ,(1)

FdCl)

Asrumpl. a

Tests stop end of 1958..

.....

Assumpl. b

Assumpl. a

Assumpr. b

(9)

(10)

Tests stop end of 1968, T=10(16) and (13) (20) and (13)(15) and (12)Tests stop end of 1978, T = 20

(16) and (13) (20) and (13)(15) and (1 2)(19) and (12)Tests stop end of 1988, T = 30

(16) and (13) (20) and (13)(1 5) and (1 2)(19) and (12)

(1 5)

(19)

. .

Tests continue.. .... . .. . .

(1 6)

The 30-year doses beconle functions of the time for thestart of integration, i.e., of the time of birth of the persons concerned. It can be shown that the maximum occurs for persons born at the end of 1958.7 If tests
continue, the maximum doses occur when equilibrium
conditions are reached for fall-out rate and deposit.
I n order to compute the total of individuals geneticallyaffected by a given series of tests, it is necessary to add
up the D,, values for all population groups born insuccessive years. Because the doses are almost completely delivered over only a few decades for tests ceasing at the end of 1958, these sums of D,, values overall successive population groups are satisfactorily approximated for the present purpose by the maximum
values of D,, in table XIII, if these are assumed toapply over a period of 30 years.

116. Any estimation of future levels of Sr" in humanbone is extremely difficult because it depends both on
estimations of the SrOOfall-out rate and deposit in the
future and on estimations of how these levels will influin bone. This last problem
ence the concentration of SrgO
is particularly uncertain, as the uptake in the bone isvery much dependent on the dietary habits and the foodi T h i s becomes slightly incorrect when the cessation date islater than about 1978. Even for cessation in 1988, however, theapproximation is good if the tropospheric contribution to thedoses is added.
* T h e bone marrow dose from external and internal Cs"'
can be calculated by integration of equation (27) over 70 years.
The dose contribution is of the order of 10 per cent or less thanthat from SrDDin bone and has accordingly been neglected intable XIII.

(20)(19) and (12)technology in a given r e g i ~ n . ~ ~As" - ~it ~has* been discussed in paragraphs 37 to 36: the uptake of SrgOin
different plants at different locations may be dependent
on a number of factors, such as fall-out rate, accumulated deposit and the amount of available calcium in soil.
117. The following paragraphs provide calculationsof the equilibrium diet-bone concentrations to be expected in humans subsisting on each of two foods :milk
and rice. In actual practice, a population does not subsist
entirely on either milk or rice, and these calculations
should. therefore, be accepted as approsimations basedon conditions which would not in practice be realized.
118. The concentration of SrgOin human bone in equilibrium with contatnirlated food can be estimated using
formula (3) in paragraph 30 if milk is the main sourceof calcium in the diet:
Cff = DF(mllkbone) X Cp,f = DF(mllk+bane)
X (a>f.l(Fd 3fd) $ bMfd)
where C z is the concentration of Sr90 in newly formedbne,
the discrimination factor from milkbone, DF(t o bone and the rest of the symbols are as in paragraph 40.
119. I t will be assumed that, in the future, theaccumulated deposit, Fd(t), will be the determining
factor for the milk ~ontamination.~'6Using a valueof ah, intermediate between those determined for
Perry, N. 17.,Ddand in the United IXingd~rn,~"andDFbak -bone) = 0.5 (table III),D" a simplified equation will be:
Cfr 0.15 X Fd(t)(30)
where Cr: is given in strontium units myhen Fd(t) isin rnc/km2.

-

+-

-

Estimated doses
124. Table XI11 shows the results of the computations for the different cases. The numbers should only
be considered in connexion with ail the assumptions anduncertain factors discussed in the preceding and following paragraphs.
125. For the estimations of future fall-out rate andaccumulated deposit the regional values can be expected
to differ by a factor of about 4?, to 2 depending mainly
upon latitude.D1s In some areas of the world the tropospheric fall-out may tend to raise the upper limit of thisrange, especially in the vicinity of test sites.
126. The uncertainties in the calculations of doses,
based on the estimated fall-out levels, may be considerable, but are difficult to evaluate because of insufficient experimental data. It seems: however, that theexperimental data indicate an uncertainty in the percapita mean marrow doses of a factor of about 3
merely because of regional variations in the conversion
factors from fall-out deposit to bone concentration of
Spo.D11e-i20

120. I n the cases where rice is the main source of

SF0 in the diet, a formula has been derived to cover
the rather unusual method of farming this grain in

T a.~ a n where,most of the ~ l a n tmaterial from earlier"cropsis ploughed down in B homogeneously cultivatedsoil.3'

Cg is the concentration of SrqOin newly formed bone.
DF{=II, ~ . I , I and DF(d, -bane), the discrimination factors from soil t o nce and from rice to bone, are taken
as 0.5 and 0.17 r e ~ p e c t i v e l y ~ ~A
~ .is~ "the. amount ofavailable calcium in the soil, approximately 95 X 10"
g/km2 (with outer limits approximately 30 X lo6 and230 X lo6g/km2)."The formula will in this case be:
CE 0.9 X Fd(t)(32)
where CE is given in strontium units when Fd is in
rnc/krn2.
121. I t is evident that the equations (30) and (32)for concentrations of SroOin bone are uncertain. The
neglect of folizr retention and of sources o i Sro0otherthan milk tend to give bone concentrations that are too
low, especially in the immediate future. I t must be
VII. CALCULATIOXOF BIOLOGICAL EFFECTS**
emphasized that the bone concentrations are calculated
127. The frequency of certain possible consequences
only for newly formedofradiation has been estimated on the following basis :122. The mean bone marrow dose is assumed to be
1 mrem/year for a bone concentration of 1 strontium
Leilkernia, assunling a litlear dose respome
unit.DE4 Therefore the dose rate in bone from SrBO
relationslzip arld ?LO threshold
will be :128. In this case, the number of individuals affectedannually ( R , ) is calmlated from the appropriate 70year mean narrow dose (D,,), the dose effect constantwhere CBis the conce~ltrationof Srw in nexvly formed( K , ) for leukemia as derived in annes G , paragraphbone, as given by equations (30) and (32) for the two
50, and the assumed world population ( P ) , and dividing
diets considered. The 70-year doses for the two asby 70 to give a mean annual rate. Thus:
sumed injection rates (assumptions a and b), and forthe different cases considered for cessation of tests are
therefore obtained by integration over 70 years ofequation (33), giving, for the hypothetic milk diet:I<, is here calculated on the ass~unptionthat a leukemia
70
incidence of 1.5 cases per million per year per rem continues after each element oi radiation exposure for the(DTo), = 0.15
Fd(t) d t
(34)
remaining life of the individual, or for an average period0of 35 years in a population living to age 70. K1 has thus
and for the hypothetical rice diet:a value of 52 cases per million per rem.
70( a ) I n estimating on this basis leukemia ascribable(35)(Dm):=
0.9
Fd(t) d t
to natural radiation, Dr0is 7 rem (annex C. table S X V )0and R1 is calculated for P = 3 X lo9and 5 X 10". giving
values of R , of 15,SOO and 26.200. (The natural occurThe equations for F d ( t ) to be inserted in the different
rence of leulcemia is calculated on a basis of 50 deaths
cases can be found elsewhere in annex D, identified byper million per year.)
their numbers as given in table XII. The doses are calculated for persons born at the end of 1958, which give( b ) Leukemia ascribable to fall-out from weapon
approximately the mz~imum70-~eardoses. If tests contests, if such tests stop in 1958. is calculated withtinue, however, the masimurn doses occur when equiP = 3 X lo9 and with values of 0.16 and 0.96 for Dio.
librium conditions are reached for accumulated deposit,
These are estimates for milk and for rice diets (table
and have accordingly been calculated for that case.
X I I I ) , and would correspond to incidences of 360 and
2,160 cases per year. Because most of the dose is actually123. T o use the equations (30) and (32) in thesedelivered during a few decades, the total of induced
computations implies the assumption that the wholecases would about equal 70R, and so \i-ould be 25900 toskeleton has. at any time, the same concentration of
151,000.
SrSOas bone which is newly formed at that time. The
Committee is aware that this assumption is not consistent(c) Leukemia attributable to fall-out in equilibriumwith the rather long biological half-lives o i calcium andconditions reached after prolonged testing is calculated
strontium. It is, however. a satisfactory approximation
for P = 5 X 10" The values of D,, (table XIII) range
for the purpose of the present calculations. which itfrom 1.3 rem under assumption a and with a nflE diet,greatly simplifies. 3Ioreover, this extreme assumption
to 17 rem under assumption b and with a rice diet,tends to over-estimate the average 70-year dose, and so
giving- - incidences of 4,880 and a,S00 cases Per Yearthe calculations may be taken as an upper limit for those**For the purpose of table TI, chapter VII, of the report the
population cohorts receiving the maximuin 70-year
finures calculated in the following pragraphs have been
exposure.
r&nded off.

1
j

1.

i

11

DOSES FROM STRATOSPHERIC FALL-OUT' (computed from population weighted \vorldTABLE
XIII. ESTIMATED
wide average values of stratospheric fall-out rate and d e p ~ s i t ) ~&wfically signifianl dare:
Jiarinurm faany 3Sfa-yearperiod (rcm)

Per capita mean m a n d dose:
Afaximum for ony 7 b j c a r prriod ( r m )Estimates for countries
drrisirrg most ofd i c u r y colcium from milk*

LVeapon tesrs cease a t end of 195.8.. ....................
Weapon tests continue until equilibrium is reached
in about a hundred pears. ....................

0.(110Eslirna:6sfor countries
derivirrg most of
dietary cokiam from rice=

0.16

0.96

Assump. ad

Assump. bd

Assum*. ad

Assurr~p.bd

Assunrp. od

Assump. bd

0.045

0.10

1.3

2.8

7.5

17

Eslirnnlcd perccntoges of fkc maximrorr doses for conlitrued =capon tesls

Weapon tests cease:1958 ......................................
1968 ........................................
1978 ........................................
1988......................................
Weapon tests continue ..........................

Assump. ad

Assump. bd

Assump. od

Assxmp. bd

22
45
63
72
100

10
33
55
62
100

13
24
34
42
100

6
16
26
35
1GO

* The methods used for calculation of these doses are given inparagraphs 91 to 123.
b Regional values may difier by a factor of l / j to 2 tram theestimated population weighted world-wide average values becauseof the latitudinal variation of fall-out rate and deposit. In someareas of the world the tropospheric fall-out may tend to raise
the upper limit of this range, especially in the vicinity of test sites.
The extenr to which these estimates apply to populations ofdilierent dietary habits and to those living in areas of differingsoil conditions is discussed in paragraphs 116121.
Assumption a is that the injection rate is such as t o m a i n d n
a constant fall-out rate of S F and Csls, whereas assumption bis that nneapon tests equivalenr in release and stratospheric injection of fisslon products to the whole sequence of weapon tests
from the beginning of 1954 to the end of 1958 will be repeateda t constant rate. This second assumption d l give an equilibrium
value for the fall-out rate and deposit a proximately a factor of
2 higher than that calculated by using t i e first assumption.

Estimates for milk diet with assumption b and for rice
diet with assumption a are 10.500 and 28,200 cases per
year.

This report affords only very incomplete evidence as tothe likely variation of individual marrow doses fromthe mean values, and 110 estimate is given or' the way inwhich the risk of leukemia might increase once a threshold dose was exceeded. These results, on the hypothesisthat a 300 renl threshold exists, therefore give only ageneral indication of the relative hazards in different
circumstances.

@

Leukemia, assuming a threshold of 400 rent
129. On this hypothesis, cases of leukemia might result if the 70-year dose exceeded 400 r at any point in
the marrow. The maximum dose in marrow might. in asmall cavity, equal that in surrounding bone; and it ispossible that such bone might, owing to irregularities inmineralization, receive a dose oi up to twice the meanbone dose. which in turn is estimated to be about 2.5
times the mean marrow dose (taking a mean bone doseof 2.5 mrem per year per strontium unit*** and a mean
marrow dose of 1 mrem per year per strontium unit).
The maximum marroiv dose might thus equal 5 times themean marrow dose.
( a ) With natural radiation, a threshold of 400 rem
will only be exceeded in an individual receiving 400/7,
o r 57 times the normal D,, of 7 rem.
( b ) With fall-out from tests ending in 1958, the mean
marrow doses of 0.16 and 0.96 on milk and rice dietscorrespond to maximum marrow doses of 0.80 and 4.8.
The threshold urould thus be exceeded by individuals
receiving 400/0.8 and 400/4.8. or 500 and 83 times,
the average values of D;,.
( c ) Under equilibrium conditions of fall-out after
prolonged continuation of tests, the mean 70-year marrow doses would range from 1.3 to 17 rem, and thecorresponding maximum marrow doses would be 6.5 and85 rem. A threshold of 400 rem would thus be esceeded
by individuals receiving 62 times the average value formilk diet with assumption a, and 4.7 times this value forrice diet with assumption b.
-A mean osteocyte dose of 2.5 mrem per year per strontium
unit has also been used for the purpose of the calc~~lationsofthe numbers given in note to table 11, chapter I I I .

Major genetic-def ects
130. For the purpose of these calculations it is assumed that, by the time any mutations currently occurring came to be expressed as damage in the population,
the world population would have become stabilized at
P = 5 X lo0,half of whom were below the mean age ofreproduction.
The total number of births would be 5 X 109/70 and aof these would be affected by major genetic
part (Kg)
defects (annex H, table XI), the value of K, being
assumed from present experience to lie between 1 and
4 per cent of all births. The normal occurrence of such
defects would thus be from 715,000 to 2,860,000 per
year.
The total number of births affected by a 30-year
gonad dose D 30 is given by
Daa
P

I

where D? is the representative doubling dose and isassumed to lie in the range 10 to 100 rem. Under
equilibrium conditions, the evaluated rate of suchbirths would be
I3 30
P- x KgX(38)I32
2 X 30(a) Radiation from ?zatz~ralsources
For D 3 0 = 3 rem (annex B, table XXV) the rate of

I!
I

3
affected births is

2.5 X 109

(1 t o 4)X(10 to 100)

X

100

30

= 25,000 to 1,000,000 per year.

(b) Fall-out, tests slopping i n 1958
T h e total gonad dose is about equal to the nlasimum
30-year dose of 0.01 rem (table X I I I ) so that the total
0.01
number of afiected births is(1 to 4)X

X-

(10 to 100)
2.5 X 109 = 2,500 to 100,000 births.

100

No rate can appropriately be given since these births
will occur over a period prolonged beyond the 30-year
interval over which the dose is integrated.
(c) Fall-out, tests continuing for a prolonged period

The values of Dso are 0.06 rem and 0.12 rem on
assumption a and b (table XIII)i, giving rates ofRates are thus 500 to 20,000 on assumption a and1000 to 40,000 on assumption b. Rates can here be
given since equilibrium conditions are postulated.

VIII. NOTEON IXFORLIATION WNMENT
131. A document (A/AC.82/INF.3) entitled: "Anapproach to a general method of computing doses andeffects from fall-out" was prepared by the Secretariatof the United Nations in collaboration with a group of
experts of the Committee, as a working paper. It wascompleted just before the Committee's last session (9-14June, 1958). The Committee has not had sufficient time
to study and eventually to accept this work which wasconsidered to be of substantial scientific interest; it has
decided to make this paper available because it will be
useful to scientists engaged in calculations of gonad orbone marrow doses and their biological effects.07

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3. Martell, E. A.. U N document ,4/AC.82/G/R.21.
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109 (1957).
57. Killp, J. L:. Eckelmann. W. R.. and Schulert, A. R..
Science 125, 219-225 (1957) and U N document
A/AC.82/G/R.91.
58. M i t c h e l l , ~ .H.. Hamilton. T. S . Steggerda. F. R..
and Beau, H. Mr.,J. Biol. Chem. 158, 625-637(1945).
59. Hine, G. J. and Bro\vnelI. G. L.. editors : Radiafiorr
dosilrretry. Academic Press, Inc., New York (1956),
p. 899.
60. Hindmarsh, M., Lamerton. L. F., O~ven.AS.. Spiers.
F.W., and Vaughan, J., EN document A/AC.82/
G/R.114.
61. Engstrom. A., Bjornerstedt. R., Clemedson. C.-J..
and Nelson. A. :B o w a d radiostroltrizcuz. Alrnquist
and Miiksell, Stocld~olm; John Wiiley and Son, Inc.
New York (1958).
62. Communicated by R. Bjornerstedt and A. Engstrom, 1958.
63. Co~nrnunicatedby 1W. G. Marley. 1958.
64. Nishita. H.. Ken-alewsky. B. W..
Steen, A. J. andLarson. K. H.. Soil Sci. M, 317-326 (1956).

65. Anderson, E. C., Schuch, R. L., Fisher, TV. R., andLangham, JV., Science 125, 1273-1278 (1957) andUN document A/AC.82/G/R.123.
46. Hood. S. L. and Comar, C. L. University of Tennessee Report ORO-91 (1953), also Arch. Eiochem.
Biophys. 45,423-433 ( 1953).
67. International Commission on Radiological Protection, Recommendations, revised December 1, 1954.
Brit. J. Radiol. Suppl. 6 (1955).
68. Burch, P. R. J., Brit. J. of Radiol. Suppl. 7, 20-26( 1957).
69. Rundo, J., U N document A/AC.82/G/R. 167.
70. Sievert, R. M., Proc. Int. Conf. Peaceful Uses
Atomic Energy, United Nations 13,187-195 (1956).
71. Communicated by I. H. Tipton. 1958.
72. Com~nunicatedby W. G. Marley and E. E. Pochin,
1958.
73. Bergh, H., Finstad, G.. Lund, L.. Michelson, O., andOttar. B., U N document A/AC.82/G/R.113.
74. Bergh, 13.. Finstad. G., Lund. L.. Michelson. O., andOttar. B., Norwegian Defence Research Establishment Revorts No. KIR-173/57, KIR-176/57, KIR75. Best C. H. and Taylor, N. B.: Tlze physiologicalbasis of medical practice, 6 ed. The Williams andllilkins Comp., Baltimore (1955) p. 806-817.
76. Egypt: Preliminary Report to the United Nations
Scientific Committee on the Effects of Atomic Radiation. UN document -4/AC.82/G/R.46.
77. Gunther, R. L. and Jones, H. B., United States
Atomic Energy Commission report UCRL-2689 andaddendum, ( 1954).
78. White, M. R. and Dobson. E. L., United States
Atomic Energy Commission report UCRL-3355(1956).
79. Van IIiddelsworth,L., Science 123,982-983 (1956).
80. Comar. C. L.. Trum. 13. F., Kuhn 111.U.S.G., Wassennan, R. H., Nold, M. M., and Schooley, J. C.,
Science 126, 16-18 (1957).
81. Communicated by W. G. Marley, 1958.
82. Hine, G. J. and Brownell, G. L., editors: Radiation
dosimetry. Academic Press Inc., New York (1956)
p. 865.
83. Dunning, G. If..
Nucleonics 14, No. 2.38-41 (1956).
84. Communicated by L. Machta, representative of theWorld Meteorological Organization to the United
Nations Committee on the Effects of Atomic Radiation. 1958.
85. Lewis. C.: T h e Atlzerican Oxford Atlas. Oxford
University Press, New York (1951).
86. Sievert, R. M.. Gustafsson, S., and Rylander. C. G.,
Arkiv for fysik 12,481-499 (1957) and U N document A/AC.82/G/R.147.
87. Alba. F., Brodjr, T.. Palacios. A., and Tejera. -4..
U N document A/AC.82/G/R.187.
88. Data submitted by the United States delegation to
the United Nations Committee on the Effects ofAtomic Radiation ( 1958).
89. Data sublllitted by the United Kingdom delegation
to the United Nations Colnrnittee on the EEects ofAtomic Radiation (1958).
90. Data submitted by the Japanese delegation to theUnited Nations Committee on the Effects of Atomic
Radiation (1958).

91. Communicated by W. E. Grurnmitt, 19%.
92. Hardy. Jr.. E. P., United States Atonlic EnergyCoinmission Report HASL-38 ( 193.3).
93. Communicated by J. H. Harley. 19%.
A.. ~ a ~ e r aR.,s .Palacios, A.,
91. Alba A., F..
Rickards C., G., Tejera R.. -4.. and de Velarde.
E. G. B., UN document A/AC.82/G/R.l&.

rod^:^.

TABLE
XIV.
ConnLry

Argcnlina

Denmark

Sampling method. ...........

Stainlesssteel pot

Plate

Sampling period.. ........... I month......

96. Russell, R. S. and Alilbourn. G. 31.. Kature. 180,
322-324 ( 1957).
97. UN document A/AC.82/IXF.3. Copies oi thedocument may be obtained bv writing to the United
Nations, X e v ~york 17. N. P.. U.S.A.

E S T E ~ AIRRADI;\TION
LDUE TO FALL-OUT
Mexicofi-clhnlunds

Noway

Srr&n

Uniled Stairs

Gummedfilm

Stainlesssteel pot

Stainlesssteel pot

FunnelGummed film

24 hours (if 1 month or Dust: 24 hrs., 2 to 3 days
morehn0.5 aftereachpre water after
mmpreeipita- cipitationeach precipition is coltation
lected)2 days24 hours

Period of mmwement. ...... Jan. to Sept. J a to Dec.
Totnl accumulatedactivityirom
fall-out (mcjkm2)s...

95. Blok, J.. UN document A/AC.82/G/R.l84.

FranceJapan

Funnel com- Polyethylene
bined with sheet and pory mmed 6lm cclain bay

1957

1956

Aprii 1955 toJuly 1957

ilb

60

50b

4 to Ndays 24 hours
or during
precipitationbhy 19% to &lay1956 to Nov. 1955 to OcL 1958 to A p d 1953 to OcL 1952 toJune 1957
Oat. 1957 Oct. 1957 Sept, 1957 June 1957
June 1957"Infinite plane" exposure during a 30-year period, from thetoW fd-out during the period of measurement ( m d ) .
Factm of redoction due toweathering.

...............

Factor of reduction due toshielding by buildings ......
Total reduction factor..

......

3

7

6*Activity a: the end of t h e period of measurement, comprising local tropospheric a n d stratospheric fall-out deposited duringthat wrinrl.
r--b Extrapolated t o 1 January 1958.

Dose for infinite time. This dose is only slightly different from t h e 30-year dose.
March-October 1957.

d From fall-out during the period

TABLE
XV.

Sr90 FALL-OUT ON THE GROUND-Countrv

dipnfinr

Snmplin: mctho3..

BelgiumPram..... Stainless Aluminium Funnel
steel p3t

potbined mthgummed6lm

Japn

Hmico

N&h&

Polyethylene. .
sheet and

Gummed6lm and

Staidesporcelainpoteteei pot...-.- -,Son'etUnitd Arab
Union o j Socialid
Pd blic
liniledNorwq So& A f r h &publiu($a) Kingdo2
Staideseke] pot

Porcelain
pot

Gauze

GummedFwei

6lm

Linitai
Sfatea(a) Gummedpaper(b) stnitdeb9
steel pot(c) Gal~auized

tray

.UU

.... . 1 nonih~ ~ W d i~r a~ i o d . . .

.

Period d measurement. Jaa-&pt.
1957

24 h o w

24 horn

Dust: U k..
2 to 3 days
water d ~ c r
precipitation
whprecipitstion~p.-Nov.
1967

Apt. 1955- (a) May 1954- hk.-Oci. (a) Julyblar.1956- Jan.-Apr.
1956
July 1957
Aop.1956
1957
1965Jnne 1957(b) Oct. 1956NOT. 1956
June 1957(bl Dec.
1958Nm. 1957

I month. or
a h : each

2 days24 hours

24 hours

24 hours(0) Up to Mar.-Dee.
end 1955
1957(a) JulySepl. 1957

1 month(a) 24 h o r n@) 1 w t - 1 mo(c) 3 to 7 days

May 1 9 w (a) Oct. 1951Apr. 1957
June 195i(b) Feb. 1954Gpt. 1957(c) hiar. 1955Nov. 1957

htethod of determinntionof Sr*.

.............. W.chem. Fhd.chem. Cdcnlation\ (a) CdculaadYi3

tion*(b) Radchem.
analysisdysis

Cdculation*(a) Qlcula-tio~

Cdculation*(b) Radio&em.

Rad.chem. Bad.chem. B3d.cheehem.
andysisnnalyais
adyeis of
dpoOaed poded
smplesssmplesBad.chem.
malysisanal*(a) CalculsLion*[improved)(b) and ( 4Radrhem.

dais
Accumulated d e m i t d
8 P during the priodof measurement (no/hn3 ................

1.4

15

2O
.

8.Ob

0.6

Approx. 5 3

2.4(034.9)0.28(0)l.S(0.8-33)

7 s(a) 6.8(42-21)(a)(c) 9.01
rate of EP( s c l l r m r - yeu)

Fnht

.....

1955: 0.6
1956: 0.7

1954: 1.0
1955: 0.7
1956: 3.8

Using Hunter and Ballou curves 8.
b Assumed a deposit of 0.4 mc/km2 prior to May 1954.
Assumed a deposit of 0.7 mc/km? prior t o May 1954.

* New York City.

Pittsburgh.
Mean value from 4 funnel stations.
Mean value from 8 pot stations.

(a) Appro% Sept. 19562.3
Aw.1951:(b) 2.3
0.9@) 2.8(234.3)

1.4

1954: 2.0
1955: 23
19%: 2.V

1957 3.W(1.9-0.2)

TABLEXVI.

~IISCELWNEOUSDATA ON Sr90
Union ofco~abydrprntinn

Brad

Cwda

Japan

6+ in air a i ground lerel( l e a 4 1 ) ............

YrricoNonmr

Sdm

Xov. 1955 to
Xov. 1956:
53(25-106)'

1956:
4.6
(4.5,4.6)

B F i n milk (lyle/pCa). .. Apt. to June
1957:
34
(3.1, 3.9)

Ftst month
195i:
2.7M.3

1956: 5.0
(lSll.6)
1957: 8 2
(2.5-19.8)

1956: 2.4
(2.1.2.7)
195i: 2.9

Oct. to Dec.
1966:
1.2(0K-l.S)
Od. to Dec.
1957:
3.0(2534

1957: 7.9d
(45-155)

Summerl956:
13b(0.~3-2.0)

S o ~ S ~ i r f Unifrd

Cn'ledLidom

S!a!crMar. to Dee.

dpri1 1952 :o

1955:
60-110&pi.-SOT.
1957:
6.3-100

Ju. 1856:
C

1953: 6.4
(3.0-112)19%: 20(1.0-60)
1955: 41
(3.6-120)
June to Inp.
1956:
75

Feb. to Job

March 1955:

1952
6.0
(3512)

l.i(O.5-2.9)
July 1956:
4.7 (1.9-10)&rmblicr

1953: 14(0.4-24).
1965: 4.8
(0.8-7.5).
1956: 6.9
(2.9-12).

July 1956 to 1965: 3.9
J w 195i:(1.8-6.0
4.9
1956: 5.4
(2.2-8.0)(2.9-103)1956:

vcgebbks
9.4 (1.1-23)
Whiie rice:49 (36.82)
B r o m rice:
154 (81-250)
Rice bran andM
450 @9o-Mo)
195i:
Brmn wheat:
102 (153.170)

wha(Bau:53

Corn. 1956: Dea h m . prom
62(226.6)

195k 4.4(1.E4.9)
1855: 4.:(1.0-11.7)
1956: 2.6
F& 1956 to
196;:

Fdmka
3.4 (0.4-11.4)

Muine:
0.29 (OJ9,0.38)

Calculated from total &activity measurements.

b Preliminary data, probably too low because of the leaching method used (1 M ammonium acetate).

Sampled in October each year.

* In units of @/I.
Grown on normal soil.
' Grown on acid hill soil.
Lowland sheep.
Highland sheep.

1956: 11.0
(8.0439).
526.7-16314
1956: 13.0
(i.5-16.6).
48('24-1W)hCons and
Sheep
1954:33(1.7-7.0)
1955: 7.5 ::(0.51-24)

Country

Japal:

Norway.

Union ofSomct Socialist
Rrpfrblics

Dm. 1956 to
May 1957

Oct. 1956 to
Dec. 1957

Second half1957

4.6 (4.14.6)

0.5
0.8 (0-1.3)
0.7 (0.2-1.1)
0.4 (0.3-0.5)
0.3 (0-0.7)

CasadaPeriod oi measurement.. .. June 1956 toJune 1957
Age Froup
Stiltborn to 1 month.. ...
month to 1 year. ......
1 Year to 5 years.. ......
5 ~ ~ t 0 2 0 y e......
ar~hfore than 20 years.. ...

0.7 (0-1.1)
1.6 (1.4,l.g)
3.1 (0.1-3.8)
0.1
0.4 (0.1-0.6)

0.73 (0.2-1.25)
0.U (0.04-1.73

Ui:ifcd Kingdom

Oct. 1955 to

Dec. 1936
0.44 (0.150.8)
0.70(0.15-1.3)
0.85 (0.51-1.45)
0% 280.15-053)
0.11 (0.064.2)

2.3 (1.6-3.2)b' Preliminary data, determined without using low-level counter.

Cnifcd SIafcs

Jan. toJune 1957

Dec. 1955 toJuly 1956

0.54 (0.44.7)
1.5 (0.9-3.4)
1 3 (0.4,?.2)
0.39 (0.3-0.5)

0.57 (0.45,0.70)
0.83(0.71-0.97)
0.51 (0.10-1.7)
0.47 (0.13-1.4)
0.04 (0.02-0.11)

b Age 0 to 5 years.

TABLE
XVIII. Cs137 FALL-OUT ON TI-IE GROUND(Determined by radiochemical analysis)

CouufrYJapan

Sampling method.. ........................

(a) Precipitation collection

SwcdcnUnited Kingdom

FunnelFunnelSampling period.. .........................

(a) 40 to 8 3 days

4 to 30 days or during
precipitation

3 months

Period 01 measurement. ....................

(a) March to June 1957(b) Aug. 1957

April 1953 to June 1957

Jan. 1956 to hlarch 1957

Accumulated deposit of Csln during the periodof mewurement (mc/kmz) ...................

(b) 6.5.........

(a) 2.3

Fall-out rate of Csln (mc/l:m2.year)

TABLE
XIX.
CaurJryJapan

Period of measurement. ....... 1956 t o 1957

Vegetables and fruit.. .........

(b) Soil

July 1955 to June 1957: 1.3

CslU IS FOODSTUFFS XXD THE IIUM~XT
BODY(In units of ppcCslU/gK)
MexicoNormaySwdcn

Unitui Kincdom

Unifcd .%airs

Dec 1956

1957

1956

June 1956 to July 1957

1956

6.4
(3.3-1 1)

Cereals and rice.. ......
Human body.. ...............

30-60

Human urine.. ...............

34(9-78)In units of ppcCsl~7/l.

11(7.2-14)

T-ABLE
XX. ~'IISCELLANEOUS DATA ON FALL-OUT
CantafryB d g i ~ i n Brazil

Denmurk Smnu

Period of measurement of air 1957 %layto
concentrations of fission
July 1956
products. ................

1956

hlaximum concentration o! 14.8 '. .fission prodacts in air at: ground level (lo-%/I). ....

?1.9b

?dean concentration oi hssion

7.5

1957

Inliu

It&

Japan

Feb. t o Nov. 1956 a) 1955
tob) 1956
Jan. 1958 C) 19.5

Aug. 1956
87b

17.9b

33.P

a) 14.id

A-etherlands N a r a y

Sirdn

Re d l i c(9,)

31ay 1956 Mar. 1956

April 1952
toJa.1956

totoDee. l9.Z Oct. 1957
l?Obb) 177.3.
C) i53.6"
0.5

5.8

10

5.6

products in air at groundlev4 (10-16cll) ............

12.6a) 5.99b) 37.1c) 54.1
Sept 19%

Cantent oi I131 in thyroids ofcatUo bpc/g).

...........

100-800

hfay toSept. 1956
11 (0-129)
Oct. 1956
344 (3-1290)

Average over 1 month.

b Average over 24 hours.

L-,,ifcd
K ; , , ~ ~Annex E

METHODS OF RIEASURERIENTParagraphs

I. INTRODUCTION.............................................. 1
Direct measurements ....................................... 3
Indirect measurements ...................................... 5
11. SAMPLING................................................. 6................. 11111. &~DIOCHEMISTRY A N D ACTIVITY
MEASUREMENT
I. INTRODUCTION
1. The ultimate purpose of radiological measuremerits of concern to the Committee is the estimationof tissue dose from natural sources, man-made sourcesand environmental contamination. I n some cases, however, measurements of radioactivity are also of primaryconcern. I t is emphasized that new and improved methods are constantly being developed.
2. I t is customary to classify measurements of thisnature into categories relating to the method used, i.e.,
direct or indirect. Direct exposure rate measurements arethose made with ionization chambers or instruments calibrated in terms of air ionization. Indirect methods arethose where =F'osure rate is calculated "ommeasurement. The rates of exposure from medical andindustrial practice and from terrestrial and cosmic radiation are sui3ciently high to allow direct measurement.
rates from otherare low and the dose
rate must usually be estimated indirectly by activity
measurement and subsequent calculation.

Direct nlearuretnents
3. Routine
determination of external
ures usually involves the measurement of gas ionization,
between energy absorption and ionias thezation is relatively independent of energy. Any ionization chamber with an air equivalent wall may be used forthe measurement, but it must be standardized periodically against a free air chamber.'
3. Scintillation counters, films and geiger counters
can be used for rough estimation of exposure or exposure rate, but they can give erroneous results in mixed
radiation fields. They can be valuable, however, if thecomposition of the field is known and they have beencalibrated under similar conditions.
Indirect nreanireritcltts
5. The indirect determination of exposures fromradioactive sources, such as deposited fall-out or radioisotopes in the body. is more complex. I t involves consideration of methods of sampling, radiochemistry andcross-referNorE: Throughout this report and its
ences are denoted by a letter iollowed by a number: the letterrefers to the relevant technical annex (see Table of Contents)
and the number is hatof the relevant paragraph Within eachtechnical amex, references are made to its indi%+dualsdentificbibliography by a number without any preceding letter.

activity measurement. Methods for these are outlined in
the following sections. The necessary dose computations
are described in annexes BI CI and D.

11. SAMPLING

6. ~h~ determination of activity in the atmosphere,
fall-out deposit. soil, foodstuff and human tissue requires
the collection of samples representative of a given geographic region. Although this is difficult from a technical and statistical viewpoint, there are recognized methods.lJ I t is recommended that the sampling of the environment and the biological materials be co-ordinated.
may be present in the atmo7. Radioaai\,esphere in gaseous or particulate form, each requiring its
For measurement of radioaaive
own sampling
be obtained by colleainga meagases, the sample
sured volume of air in a suitable containeel or by drawing a measured vo]unle of air through an activated charprecod t r a p . 4 , ~ ,~~~h~filters4.5,8-1i andcipitators are suitable for collection of airborne particul a t e ~ . ~These+methods may also be used for very roughestimates of gaseous activities having solid daughter^.'^^'^
Deposited fall-out activity may be collected periodicallyby a high-walled ~ot'?-''"~-~' or high-walled funI E ~ , or
~ the
~ - accun~ulated~ ~deposit may be obtained fromsoil samples. 25.26.Dl4
8. I t is not possible at present to state the absolute
efticiency of any device for the collection of fall-out deposition. The high-walled pot is recommended as anarbitrary basis of comparison for other methods.
9. Samples of foodstuff should represent the regional
diet. and should be selected with reference to the isotope
interest. ~ l t h o u g hit is advisable to take samples
frequently, it is more economical to analyse a composite
representing one or more months' collection.
10. The itt vivo measurement of radioactive strontium
or radium by whole body spectrometry is inadequate a t
present. Therefore samples of bone are required for estimation of the skeletal burden in man. Specifications f o r
sampling have been given.25~D66

111. R~IOCHEMISTRTA S D ACTIVITY%IEASL~RE~IEP~T
11. R ~ , - may
J ~ ~be measured by alpha counting in an

ionization ~hamber"*'~*'~or scintillation c ~ u n t e r . ~ ~ * ~ ~The techniques suitable for air samples are also adequate for samples of exhaled breath ior evaluation of124

kthe radium body burden. Standards may be prepared
REFERENCES
from commercially available radium solution^.^^^^^
1. United States Department of Commerce, National
12. The determination of strontium activity in the
Bureau of Standards Handbook 62: Report of thevarious materials described above involves preparation
Internaiio~tal Coi?z~itissiotton Radiological Unitsof the sample, separation of strontium and measurement
and Mearz~rrme~lts( I C R U ) (19 57).
of the activity.
2. Deming. Mr. E.: Some theory of sa~tzpling.John
13. The preparation depends on the type of sample:
Wiley and Sons, Inc., New York (19 j0).
(a) soil from which strontium is removed satisfactorily
3, snedecor, G.
: Statistics. Iowa State College
by a 6M HCl leach; and ( b ) rainwater. foodstuffs andPress, Ames, Iowa, 4th ed. (1946).
bone, which are best treated by wet or dry ashing with
4. Goldman, F. H., and Jacobs, 31. B. : Chenrical ,)wthsubsequent solution in mineral acid. Following thisods b r ktdustrial hygime. Interscience, London
treatment strontium is radiochemically purified. YS0 is(1953).
allowed to grow to equilibrium, is separated from the
5. Elkins. H. B.: The clretnistry of indusfrirrl toxicoparent and measured in a beta counter, thus giving thelogy. John Wiley and Sons. Inc.. New York (1950).
SrgOcontent of the sample.'5*26*33-39
The activity of any
SF9present can be determined by difference. A moder6. Harley, J. H., Jetter, E., and Eisenbud, M., A.M.A.
ately low background counter (5 to 10 cpm) is satisfacArchives of Ind. Hyg. and Occupat. Med., 4, 1-9(1951).
tory for all samples but human bone, which requires
counters with a background of about 1 cPm. The count7. Grove, W. P., and Clack, B. N., Brit. J. of Radiol.,ing procedure must be calibrated with an absolute standSUPPI.7, 120-123 (1957).
ard in order to convert the values obtained to disintegra8- ~~J. B.,~~~~12,h N ~, 1,. ~62-65 (1954).
l~~are available fortion rate. Reference samples for SrDO
g.
Harris,W.
B.,
LevinelH.
D.,
and=isenbud,inter-calibration purposes through the Secretariat of the
A.hl.A. Archives of Ind. Hyg. and Occupat. Med-,
United Nations Scientific Committee on the Effects of
7.490-502 (1953).
Atomic Radiation and also ~ornrnercially.~~
10.
Steward, N. G., Crooks, R. N., and Fisher, E. M. R.,
14. The determination of total beta activity involves
UN
document A/AC.82/G/R.20.
only preparation of the sample and measurement of the
11. Hultqvist, B. :Stzrdies on naturally occurring ion&activity. ~~i~~~~~~
activity may be concentrated
ing radiations. Kungl. Svenska Vetenskapsakademfactorily by e v a p ~ r a t i o nor~ ~by~ ~absorption~
on ioniens Handlingar, Series 4, vol. 6, No. 3. Stockholm
exchange resin^.?^.^^ Air filters or the residues from(1956) and UNdocument A/AC.82/G/R.15, Part4.
rainwater may be counted directly or dry-ashed prior to
12. Alba A. F., Beltkn. V., Brody, T. A., Lezama, H.,
measurement of activity.23*~3*38.40
Useful infomation
Moremo M., A., Tejera, A, and Visquez B., M.,
may be obtained by determination of beta or gamma
U N document A/AC.82/G/R.5.
activity. The conversion of counting data to disintegration rates is difficult;the best standardization is accom13. Labeyrie, J., U N document A/AC.82/G/R.16, Part
plished with mixed fission products from a short irradia1-1.
tion but natural potassium is more generally available
14- &fartell,E. A., UN document A/AC.gZ/G/R.21.
and has suitable radiation characteristics.
15. Wilkening, M. H., Rev. Sci. Inst. 23, 13-16 (1952).
15. The Cs137burden of humans living in a
16. Harley, J. H., Nucleonics, 11, No. 7, 12-1j (1953).
nated environment can best be measured in vivo with a
17. Shirvailtar, V. V., and Vohra, K. G.. UN document
whole body s p e c t r o m e t e r . 4 ~ ~ 5G~~~~ spectroscopy is
A/AC.S2/G/R.32.
also useful for direct determination of this radioisotope
18.
Hvinden. T., U N document A/AC.82/G/R.92in other material^?^*^^ Radiochemical separation techniques have been described which allow measurement of
19. Harley, J. H., Hardy, Jr., E. P., Whitney, I. B.. andthe caesium beta or gamma activity without energy disEisenbud, M.. U N document A/AC.82/G/R.93.
c r i m i n a t i ~ n Adequate. ~ ~ ~ ~standards~ ~ ~ ~ ~have~ not been
20. ~ l ~J.,k UN, document A/AC.82/Gfl.l%.
available until re~ently.~'
An accuracy of 2 25 per cent21. Boulenger, R., UN document A / A c . ~ ~ / G / R . ~ o ~ .
may be obtained by comparison of the beta activities of
22. Stewart, N.G., Osmond. R. G. D.. Crooks. R. N.,
the Cs131 Wid7a s r w standard.
intercomparison
proand Fisher, E. M.. UN document A/AC.82/G/
gramme for development of CslJ7standards is desirable.
R. 143.
16. The 113' burden in humans can best be measured
23.
Edvarson,K., U N document r\/AC.82/G/R.149.
in vivo by scintillation counting of the thyroid with2
4.
Welford,G.
A., and Harley, J. H., Presented at theenergy discrimination.48-51 ~lgamma~ spectroscopy~,isAmericanChemicalSociety Meeting in San Franuseful f o r direct determination of this radioisotope incisco on April 14, 1958. To be published in Analytother materials, though radiochemical techniques haveical Chemistry.
been described which allow measurement of the sepa25. Bryant, F. J., Chamberlain, A. C., Morgan, A.. and. ~ ~ ~ ~ ~standards are comrated iodine a ~ t i v i t y Adequate
Spicer, G. S., U N document ~/Ac.82/G/R.30.
mercially available.54
26.
Hamada, G. H., and Hardy, Jr., E. P.,united States
17. The determination of radium involves preparation
Atomic Energy Commission report HAS=33
of a sample solution as for SrgOfollowed by measure( 1958).
ment either by a radon emanation techniqueo6 or by
27. Curtiss, L. I?., and Davis, F. J., J. Res. Nat- Bur.
radiochemical separation and alpha counting of theStand. 31, 181-195 (1943).
radi~m.~Standards~ ~ ~ ' are commercially a ~ a i l a b l e . ~ ' * ~ ~28. Pradel, J., UN document ~ / ~ ~ . s Pa*~ / ~ f i ~ ~18. The current radiochemical literature describes
1-3.
methods for many other nuclides, (fission products, in29. Pittendrigh, L. W. D.. Atomic Energy Research
duced activities, fissionable materials and natural isoEstablishment, Harwell, England, r e p r t!opes) which would appear to be completely satisfactory
HP/?vI 83 (1954).
m most instances.
12530. Van Dilla, M. A,, and Taysum, D. H., Nucleonics
13, NO. 2, 68-69 (1955).
31. Standard samples are available at National Bureauof Standards, United States Department of Commerce. Washington 25, D.C.. U.S.A.
32. Standard samples are available at The Radiochenical Centre, Amersham, England.
33. Health and Safety Laboratory, Ma~izialof Stattdard
Procedr~ves.United States Atomic Energy Commission report NYO-4700 (1957).
34. Michon. G.. UN document ~ / A c . 8 2 / G / R 1 6 Part
1-2.
35. Kurchatov, V. V.. UN document A/AC.82/G/R.40.
36. Canada: Report to the United Nations Scientifc
Committee on the Effects of Atomic Radiation,
UN document ~/Ac.82/G/R.98.
37. Netherlands: Report to the United Nations Scientific Committee on the Effects of Atomic Radiation,
U N document A/AC.82/G/R110.
38. Osmond. R. G., Pratchett, A. G., and lliarricker,
J. B., UN document A/AC.82/G/R.132.
39. Saito, N.. UN document A/L4C.82/G/R.135.
40. Lockhart, Jr., L. B., Baus, R. A., and Blifford, Jr.,
I. I<., UN document AC.82/G/R.124.
41. Anderson, E. C., Brit. J. of Radiol., Suppl. 7, 27-32(1957).
42. Burch, P. R. J., Brit. J. Radiol., Suppl. 7. 20-26(1957).
43. Rundo, J., 1956/1957, UN document -4/AC.82/
G/R. 167.
44. Owen, R. B., Brit. J. Radiol. Suppl. 7,33-37 (1957).

45. Marinelli, L. D., Brit. J. of Radiol. Suppl. 7. 38-43(1957).
46. Iredale, P., and Humphreys, D. L. O., UN document A/AC.82/G/R.152.
47. Booker, D. V., Phys. in Med. and Biol. 2, 29-35(1957).
48. Gunther, R. L., and Jones, H. B.. United States
Atomic Energy Commission report UCRL-2689
and addendum (1954).
49. Franco, V. H.. Botelho, L., Ciode, W., Baptista,
A. R4.. Fernandez, M. A. P., and Martins, M. L..
Proc. Int. Conf. Peaceful Uses Atomic Energy,
United Nations 10, 298-307 ( 1956).
50. Francis, J. E.. and Bell, P. R.. Proc. Int. Conf.
Peaceful Uses Atomic Energy, United Nations 14,
193-203 (1956).
51. Hine, G. J.. Burrows, B. A., and Ross, J. F., Nucleonics, 15, No. 1,54-56 (1957).
52. Schrodt, A. G., Proceedings of the Second ,4nnual
Meeting on Bio-Assay and Analytical Chemistry,
October 11 and 12, 1956. Los Alamos Scientific
Lab.. N. Itex.. report WASH-736 (1957).
53. Bergh, H., Finstad. G., Lund, L.. Michelsen. O., andOttar, B., UN document A/AC.82/G/R.113.
54. Standard samples can be obtained from KuclearChicago Corporation, 223 West Erie Street, Chicago
10, Ill., U.S.A.
55. Hudgens, J. E.. Benzing, R. O., Cali, J. P., Moyer.
R. C., and Nelson, L. C., Nucleonics, 9, No. 2, 1121 (1951).
56. Harley, J. H., and Foti, S., Nucleonics. 10, No. 2.
45-47 (1952).
57. Kirby, H. W., Anal. Chem. 25, 1238-1241 (1953).

ANXEXF

FUNDAMENTAL RADIOBIOLOGYTABLEOF CONTENTS
Paragrapl~sI. DISSIPATIONO F PHYSICAL ENERGY

Introduction-Direct and indirect effects ................. 1
L E T and RBE ....................................... 4
Dose-eff ect relations ..................................
8
Time intensity factor ................................. 12
Inactivation by transmutation of radioactive elements
15......

11. RADIATIONCHEMISTRY ................................. 17
Indirect effects ...................................... 18
Direct effects ........................................ 28
Effect of LET ....................................... 36
Oxygen effect ....................................... 38
After-effects ........................................ 39
Radioprotection ..................................... 42
Restoration ......................................... 48
Present status of the "target" theory ..................... 51

111. BIOCHEMICALEFFECTS.................................. 52

Cellular constituents .................................. 53
Biochemical mechanisms .............................. 59.

I V CYTOLOGICALEFFECTS ..................................
66
Nucleus ............................................ 67
Cytoplasm .......................................... 72

V. BIOLOGICALEFFECTS .................................... 87

Homogeneous cell populations ......................... 88
Differentiating cell populations ......................... 113
Adult organisms ..................................... 120

VI. VARIABLESIN RADIATION EFFECTS

Physiological conditions ............................... 128
Comparative sensitivity of living organisms .............. 138
Adaptation to radiation ............................... 146
Secondary effects ....................................153

V I I. ALTERATIONSOF RADIATION EFFECTS BY FOREIGN AGENTS
Protection .......................................... 159
Sensitization ........................................ 170
Recovery ........................................... 173......................................... 188
VIII. CONCLUSIONS
I. DISSIPATION
OF PHYSICAL ENERGY(Space and time factors)
Iniroduction-Direct atrd indirect effects
1 The effect of radiation is induced by the processes
pf absorption. when the energy of radiation is dissipated
In the irradiated matter .Apart from excitation. the ionization of molecules is believed to be largely responsible
for the initiation of primary chemical reactions There
are at present two major theories of the mechanism of
a d o n of radiations on living organisms : the theories of
direct and indirect action. The first one claims that
effective ionizations take place in key cellular structure
or in their immediate vicinity: the probability that their
a!teration causes cellular damage is dependent on thelr
pological specificity. This has often been called thetarget theory". and. since Dessauer . Crowther. Hol~veck.

.

and Lacassagne . Timofeeff-Ressovsky and Lea. the concept has had the support of many physicists ; it is being
constantly revised to take into account many new fundamental acquisition^?^^^^*^^^*^*^.

2 The "theory of indirect action." on the contrary.
claims that the biologically specific cellular structures arealtered as a result of their chemical reaction with free
radicals formed in irradiated water or other molecdes
not belonging to these stru~tures.~
As with most conflicting theories which have had ardent supporters O? .
both sides (another good e - m p l e is the corpuscular and .;.'
electromagnetic theories of light). it is very .probab@.l ..
that the two are complementary . Indeed. it IS almost&':certain that the same cellular component can beaffec&d_.*' ;in a way which is liable to produce identical b!pL%?$*@$
effects by both mechanism^.^*^^." >lethods have been *%.',! .F).
.... ;;

.

A,&
I.)

.-(

developed in recent years which enable the existence of
unpaired electrons resulting from the ionization process
to be demonstrated not only in crystalline amino acids
and other small molecules, but also in proteins, plant
embryos and other kinds of cells.

3. An attempt will be made to draw a brief picture ofsome fundamental aspects of the problem.
Linear energy trarrsfer (LET) and relative biologicaleffectiveness (RBE) of different kinds of radiation
4. The efficiency of radiation per ionizatiort to inducea particular effect is often found to vary for different
types of radiation. Let us at first consider an event whichis caused by one ionization such as the inactivation of an
enzyme or virus : in the case of small structures in vitro,
the radiation producing a low ion density will be more
effective than that giving a high ion density, becausesome of the ionizations of the latter will be wasted.
On the contrary, a radiation with a ligh density ofionization will be more effective when several ionizations
are simultaneously or in a relatively short time neededin the sensitive structure. Thus, the relative biologicalefectiveness (RBE) of radiations varies with theirlittear energy transfer (LET). This term describes thespatial distribution of the transfer of physical energy
in matter-and accounts for the loss of energy of theradiation, not only through ionizing processes, but also
through other processes such as dissipation of heat or
excitation of atoms. I t is a theoretical implication ofthese facts that some of the primary effects of radiations
take place within a shorter time than that needed forthe processes initiated by ionization or excitation to lose
their initial spatial distribution (perhaps as short as 1
millionth of a second) ; and also that the primary biological receptors of radiation are not themselves homogeneously distributed throughout the cell.'?

5. In mice, the relative biological efficiency (RBB)
increases greatly with ion density, for killing with low
intensity radiation, for shortening of the life-span, forinhibition of tumour growth, and for cataract induction :the increase, however. is smaller when one considers
effects on the gonads (sterilization), on the skin(epilation), on the blood white-cell count, or on the
induction of many chromosome abnormalities in
Dro~ophila.'~*l'*~~Some chromosome abnormalities inTradescantia have a very high incidence with highdensity irradiation.'$ Mutations in micro-organisms andsome in Drosophila are only slightly influenced by the
LET.12

6. Reviews on the subject by Lea1 and Zirkle12 haveshown that much could theoretically be achieved by comparing the effects of ion density. Lea had attempted touse the data available to him at the time, on the decrease
in incidence of chromosome breakage with decreasing
ion density, as an argument for the target theory.
However. it appears from Zirkle's paper that changes
in RBE-for comparable effects are often very difficult
to include in a general theory, because in many instances
the direction of change in RBE is not the same forsimilar effects in different materials and the RBE may
be strongly dependent on conditions of irradiation suchas the oxygen tension. It is at present very difficult tomake definite generalizations.

7. The mode of dissipation of radiation energy insideliving cells is not yet understood, although our knowledge of the physical aspects of energy loss is adequate

and hypotheses on the distribution of free radicals along
the radiation tracks have been suggested. However? it is
not clearly understood how this physical energy becomesapparent in chemical changes sudl as ionization andexcitation. I t might be of interest to use inert structuralmodels or do such experiments as comparing the L E T
for a virus inside and outside the host cells to get a better
picture of the sequence of events. When completely
understood, the use of radiations of different L E T may
lead to precise estimates concerning the size of thebiological structures affected.

Dose-effect relations

8. When a homogeneous substrate is irradiated, the1energy is distributed in an unpredictable way and theprobability of a molecule being hit depends on its concentration and on its volume. The concentration of theintact substrate decreases as radiolysis proceeds, andit can be predicted on theoretical grounds for low density
radiations that, if one ionization suffices to cause theeffect, the expression relating the remaining intact
structures ("survivors") to dosage will be exponential.
When a relatively small number of ionizing events isneeded, the number of responses observed will, however,This
be approximately proportional to the dosage.16-17*18
sort of effect has no threshold-which means that any
dosage, however small, is effective in producing somealteration.

9. On the contrary, if several ionizing events or "hits"
are needed, the response only becomes manifest after acertain dosage has been accumulated in the sensitive
structure: the dose effect curve is thenIn this case there is a threshold which, however, may
only be statistical, as when two identical cellular s-uctures need to be irreversibly altered for the effect tobecome manifest, which is so for recessive lethal mutations in yeasts.1° Other threshold effects appear whenrecovery of the altered structure or replacement of killedcells takes place, as is often the case in multicellularorganisms where many interferences may take place
between the primary physical event and its biologicalexpression.
10. The meaning of the dose-effect relationship isoften difficult to understand because the curve may
change quite dramatically when the conditions of irradiation are altered (aerobic or anaerobic irradiation;change of culture medium) : this difficulty is most likely
to occur when one studies a complex phenomenon likecell death, whose cause may be multiple and not identicalin different ~ i r c t m s t a n c e s . ~ ~11. However, several radiobiological processes are
known to give exponential dose-effect curves under
specific environmental conditions, as in the case of many
lethal effects on viruses and on micr~-organisms.'l*~
Diploid yeast
or mammalian cells2' in tissue
culture have a sigmoid dose-effect curve when s-irradiated. In the case of diploid cells, the sigmoid type of
curve is consistent with a 2 hit process, the exponential
response being explained on the assumption of a single
hit. One of the best present arguments ior the "target"
concept comes from the fact that in the case of small
viruses the "target" size can be estimated with a good
approximation21 and that survival curves of protectedbacteriophage are very similar in vitro and during theyery first minutes of infection.?' These results can beiIexplained on the basis that the primary ionization takes
place inside the sensitive structure. In the case of amutation this is the gene. It is, however, difficult toaccept the concept without modification at the present
time, on account of the possible contribution of diffusable radicals from water or other molecules in theimmediate vicinity of the target. However, it is believedthat radicals only diffuse for distances of about 30X.
As most effects have not been fully expressed when theradiation has ceased to be delivered, there is a timeinterval during which restoratiori may occur, andwhether this takes place or not may alter the doseresponse curve. Very little is known about what happens
during this time: the chain of events may be relatively"simple" in the expression of a point mutation in microorganisms or perhaps even in a mammalian germinal
cell, but it is certainly very complex when the inductionof malignant growths is considered. The number ofmutations in bacteria,21D r ~ s o p h i i aand
. ~ ~perhaps mouse
populations." incremes linearly with radiation up tomoderate dosages, as do certain of the chromosome
aberrations2' and perhaps the induction of leukemia.zs~29
However. the determinations do not extend as low as the
background radiation, and much uncertainty remains atthese low levels, although it is highly probable that thebackground radiation causes some of the mutations
which occur naturally, thus contributing to some extent
to the evolution of living organisms and to their load ofmutational hazards. This nreanr that as far m w e know
at present, biological effects will follow irradiation, however small its amount. It has thus become very importantto establish with great accuracy the shape of the doseeffect curve in the lower dose range. in order to estimate
the contribution of the natural Fahiation for di-fferent
effects. The number of experimental animals needed toobtain a good accuracy increases enormously as the dose
decreases and the response b ~ ~ m smallere sor less
frequent. For human populations, as each individual isimportant, the only reasonable "experimental sample",when small doses are concerned, is the total populationof living human beings. In this case, the only ~ o u n dprocedure is to get a better understanding of the fundamental processes which are occurring. Thk may actually
be the only w a y of anstverirrg some of the basic problems
underlying low dosage irradiation.

given dose is f r a ~ t i o n a t e d .A~ ~change of intensity by afactor of one million does not alter the number of phage
induced in E. C O ~ ~ . K , , . ~In' *contrast,~~
the number of
certain chromosome aberrations in Tradescantla micro- like chromosome exchanges,
spores or Vicia seeds34136
which require the simultaneous occurrence of two breaks-are often highly dependent on the time taken to deliver
the dosage: more exchanges are obtained for higher
intensities. When the duration of irradiation is increased, one reaches a time for.wFch the effectivenessdoes not decrease any more; thls hme is related to thelapse during which the breaks remain open. Hot~ever,this picture is complicated by the fact that the rate ofrejoining depends on respiratory activit~.~'The killingof complex organisms like mammals, being the result of
extremely complex cellular damage, 1s very efficient forhigh intensities but much less so for low ~ n e s . ' " * ~ ~ ~ * ~14. The time during which radiation is delivered becomes very important ~f the system being studied undergoes some change during this time: the radiosensitivityof many cellular processes varies during the mitotic
cycle and one can expect a greater radiation effect if theintensity is high during the most sensitive period of thiscycle. Secondary biological reactions may interfere withthe expression of damage and, if recovery or selection
occur, one can expect a greater effect if the intensity ishigh for the same given dosage. For these reasons,it does not appear justijid.de, unless the ftcndantentd
pathways of radiafion damage are known, to consider
tltat an effect observed after high interzsity irradiation
will necessarily follow the applicatiotl of the same dosage
at low intensity.

Inactivation by transntutatiotr of radioactive elemeltts
15. Certain radioactive substances taken up by theorganisms in specific structures may affect them not only
b!? the radiation they
but also by the fact that theis often accompanied by
mission of theserecoil effects or transmutation into an atom having new
chemical properties. Thus P-32 can be incorporated into
important biological structures like viruses or chomosomes, and in the first case it has been shown that theinactivation due to transmutation of P-32 into S-32 ismore efficient than the one due to the /3 particles beinge ~ n i t t e d . ~ ~It- ' is~ conceivable that strontium could reTime intensity factor
place calcium or magnesium, which are probably structural constituents of chromosomes.4BI t has been claimed
12. The time taken to deliver a given dosage of radiathat
a low calcium environment increases the number oftion can be varied in order to give very high or verq. lowv
spontaneous and induced chromosome breaks in Tradesintelzsities per unit time. A &ange in intensity will notaffect the end result when separate ionizing events con~ a q t i a . " ~I f* ~these~ facts were of general application,
the disintegration of strontium-90 or strontium-89 might
tribute i&ependelttly to the observed effect ; this should
affect cells not o d y by emitting P radiation. but also byhold true for some of the exponentially respondingtransmuting to yttrium, which has new chemical properevents although it is not true for all. On the contrary,ties. Such possibilities will have to be discussed, andin the case of events responding by sigmoid curves, sevthe role of trace amounts of metals and o f &dine
era1 ionizations may be needed almost sinncltaneouly
e a r t h ift intp~rtatttcelllklar structltres shoftld be kflown(this is the case when recovery processes exist) ; here,
before one dismisses its possible intportance biologicd
a given dose becomes less effective if delivered in aeffectsof radionuclides which, apart from emittill9 l a d long interval of time.31n3z.39 However, this is not dx~ays
atio?t, !rave a specigc fzbncti0~.
the case, and for inactivation of both homologous chromosome regions of a diploid cell. it is known that pro16. ~ l t h Cads
~ ~ ~hash not been found by ? d i e
traction of irradiation does not alter the effect.
aulography in the bone marrow cells of rats ~revlously
injected with 200 pc,40 nuclear aberrations have been
13- The physiological conditions of DrosopItila sperm
observed in allium which had been grown in the presence
are very constant for a considerable length of time, andof S1--90,~'and further work on the subject. should be
lt has been found that the induction of mutation byirradiating the males does not vary with the intens~ty done to settle this problem. which is of greatm?ortancein understanding the possible cellular damage. Inducedof irradiation.30 The same is true for the induction of
by radionuclides. Their specific radioactivity lnslde cellumost malformations in the mouse embryo. Howvever, inlar structures as well as their rate of turnover and their. Some cases the severity of malformations is greater i f a

i

I

-

,
a

.

!

,

-

X'

129
-

chemical function may be important in inducing cellular
damage.

11. RADIATIONCHEMISTRY
17. It is only by understanding the mechanisms ofaction of radiations on the different cellular constituentsthat one can hope to understand what is happening in
irradiated cells and also to use these basic findings in the
search for protecting agents. Much useful informationon the chemical effects of radiation has been gathered bysubmitting various chemicals to irradiation in vitro(radiation chemistry) ; however, on account of our very
incomplete knowledge of cellular structure and chemistry: biological constituents should be studied after
irradiation of the living organisms (radiation biochemistry) if one is looking for full understanding of radiobiological processes. Furthermore, as will be pointed
out, specific constituents and not bullc chemical properties should be studied whenever-pcssible. Molecules may
be altered by indirect and direct effects of radiation.
Indirect effects
18. I t is known that the most abundant of all biological constituents is water: it constitutes 70 per cent of
most living cells except for certain plant seeds and may
sometimes constitute more +an 95 per cent, but an unknown proportion of it is bound water ahd constitutes
part of the cellular structures. This has prompted muchresearch into the radiochemistry of water.
Effects of radiation on water and substrates in aqueous~01ution~~~~~
19. I t is usually accepted, although-by no means
demonstrated. that water when chemically pure undergoes ionization and, as a result of this-and of secondary
reactions, the sequence of which is hypothetical-splits
into OH0 (hydroxyl radicals) and H0 (hydrogenatoms), which recombine: in the absence of any impurity, nothing apparently will have happened because
the radicals cannot enter any other reaction. Traces ofH2 and H,O, are thought to be formed during thisprocess. The formation of radicals takes place in the
short time ~f 10-l1 -lo-'? s e ~ . ~ ~20. The existince of OH0 radicals has been demonstrated: certain radiation reactions leading to the polymerization of acrylonitrile can best be explained on thebasis of an OH0 radical mechanism, as also the oxidationof benzene to p h e n ~ l . ~ l * ~ ~21. On the other hand, the existence of free H atoms
is still questioned on account of the high osidizing powerof radiation on substrates in aqueous solutions ; several
mechanisms of radiolysis have been suggested, which
do not make necessary the postulation of the existenceof HGatorns.jl It may be easier to interpret many biochemical reactions of radiation when a better understanding of the radiolysis of water has been achieved.
This should certainly be of great importance for the
logical approach to protection mechanisms. Although
the existence of a free hydrogen atom is doubted bysome, many authors have assumed that it does exist,
and much present thinking is based on this assumption.
I t will make the discussion easier if we tentatively adoptv,
a mechanism involving this radica!
this ~ { e ~ wheneveris suggested. If oxygen is present as it is when a solution is in equilibrium in air, O,HO (perhydrosy radical)(hydrogen peroside) are also formed In addiand H202
tion to H0and OH0.51

22. When the water contains various solutes, these
are the site of chemical reactions due to HG,O H 0 and
O,HO radicals formed in the solution through the radiolysis of water. These radicals have reducing or oxidizing properties and can react with the substrate,oxidizing or reducing it or transforming it in turn toa new free radical. Thus, if many solutes are present,
they may be altered by radicals coming either fromwater or from the other solutes: this last mechanisnl
although not too well studied could very well be of some
importance in very complex systems. When macromolecules are irradiated, the yield of altered molecules perion is usually smaller than expected from what happens
to smaller molecules of similar chemical properties : thisis thought to be due to the fact that bonds, broken inthese structures, are not able to come apart (they areheld together by the other intact bonds in the structure
or cannot come apart by normal diffusion processes) andthe radicals formed presumably recombine. Such a "cageeffect" would be chiefly expected in concentrated solution
and in complex cellular ~tructures.~'
There are probably
also some biologically inert chemical groups whosealteration ~vouldnot impair the biological activity ofsome n~acrom~lecules.~~
23. Although some reduction reactions occur whensubstrates are irradiated. most reactions appear to beo ~ i d a t i v e . ~ From
~ * ~ " experilnental data it is apparent
that a substance is reduced only when it possesses a very
high normal redox potential (greater than 0.9 - 1.0 for
effects of X-rays in the absence of ~ x y g e n ) . ~ 'Nature of the chenrical efects
24. Ionizing radiations may alter inorganic as wellas organic substrates. The following reactions can betaken as examples

Oxidiziftg reactions may be effected by OH0 radicals(a) By simply removing an electron from an ion
Fez' + Fe3+-a reaction used for chemical dosimetry ;(b) By removing an H atom, leaving a radical which
can combine with another ones1
2CH3 COOH + 2C0H2COOH + COOH-CHZ-CH, -COOH ;(c) By substitution of a hydrogen by an OH0 as in
the oxidation of benzene to p h e n 0 1 . ~ * ~ ~ ~25. In a similar manner, small organic molecules likealcohols, aldehydes or acids undergo oxidation, and thelast-named compounds are often d e c a r b o ~ y l a t e d . ~ ~ ~ ~ ~They are also sometimes capable of undergoing polymerization by the formation of a chemical bond possibly
between two radicals as in the second reaction above:
acetic acid is capable of giving succinic and even still
more complex organic acids. Amino-2cids may be osidatively deaminatedIs1and if they have sulfhydq-l groups
these are oxidized to disulfur (S-S)=' and sometimes tosulioside, as in the case of cy~teine.~O*~~
26. Rcdztckg reaciions may be obtained as folloi~~s:(a) O H 0 radicals may act on strongly osidizing
agents (this is the case for iodate and ceric
salts) .51(b) I n certain cases. organic redox indicztors havebeen reversibly bleached in the absence of osygen.62The mechanisms are at present difficult tounderstand on account of the questionable existence of the free H atom.

( c ) Coenzyme I (Diphosphopyridine nucleotide)can be reduced by radiation to an abnormal
derivative (probably a dimer of the natural molecule) but only in the presence of a hydrogen
donor like ethanol,a3

27. C o ~ > ~ p lnnrolecrrles,e-~such as enzymes and otherproteins,05 nucleic acids, lipids and polysacharides, arealso altered in aitro as a result of the action of ionizing
radiations; enzjmes and desoxyribonucleic acid (in thecase of the transforming principle of bacteria) may loseI n most cases the nature
their biological pr~perties.O~*~~of the reaction has not been analyzed and cannot be
until we know more about the structure of these macromolecules.
( a ) One of the most sensitive cl~emicalgroups ofproteins is the sulfhydryl group (-SH) : two
adjacent groups are oxidized by OH0 to -S-S
resulting in the loss of biological activity when,
as in some enzymes, this activity is associatedwith the reduced form. S-S bridges also cause
cross-linking reactions between two adjacent

25. In the case of a direct e f i e c t , ' ~the~ ~ ionization
caused by the radiation concerns t5e molectile or structure under study. It is probable that the energy released
in one part of such a nlolecule ti-ill be transferred overh\e whole structure and ionizaticn or excitation phenomena will not necessarily occur ai the point of firstinteraction. If the molecule beco~nesionized, reactive
free radicals may be formed and the existeilce of unpaired electrons has been proved in experiments usingparamagnetic resonance; in the absence of water, theseradicals are found to exist for periods as long as \\-eelis
or months."*s4 In the case of water solutions, the lifeof the radicals is much shorter ( a few minutes). Suchstctdies have also been made in irradiated cells, indicati~l~the existence of free r a d i ~ a l s . ~ * * ~ ~29. Cross-linlcing between macromolecules may occur,
as in polyethylene, probably by the reaction of an ionizedmolecule on a normal one.sa The absence of an electronfrom a chemical bond may make this bond unstable
and cause it to be hydrolyzed or broken, and some ions
may also react with normal molecules causing them tocross link, as in some synthetic polymer^.'^ The absorption of energy from the ionizing radiation does not always result in the esptllsion of an electron: when ionization does not occur, the group of atoms may become
excited for a period perhaps as short as
sec. thus
being rendered 1110re reactive with other molecules and~~is thesusceptible to chemical a l t e r a t i ~ n .Escitation
only process responsible for the alteration of substances
by ultraviolet or visible radiations, and the use of thesetypes of radiations is thus extremely useful in thisrespect.
30. Tlze pltysical state of a proteiir rtwleclrle can bemade to vary, and it has been shown that when an
originally globular protein like pepsin is unfolded at an
air-water interface and is irradiated as a inonomolecularlayer it is much more sensitive than when the "stretched"molecules have been compressed into fibresss

molecule^.^^^^^( b ) Other specific osidation reactions of some macromolecules have been found, including the deamination or decarbosylation of proteins,B0and theosidation of structures containing double bonds:
as in the case of unsaturated fatty acids;66 butlarge dosages have usitally been necessary inorder to make measurements possible.
( c ) Cross linking may occur through the formationof a carbon to carbon linkage as the result of the
combination of two macromolecular free radicals,possibly formed by direct or indirect action."-i'This process has, however, mostly been studied in
artificial high polymers like polyvinylalcohol, but
it is also very likely to take place in cells where thelocal concentration or the orientation of macromolecules relative to each other may be advantageous for such a process, as in chromosomes orduring the formation of other oriented cellular
Distinctioir between direct and indirect efects
structures. There is in fact good evidence for its
occurrence in protein73and in DNA.14
Dilution effect( d ) Some effects of ionizing radiations on complex
31. It is possible to distinguish between direct andmolecules of biological interest have been defiindirect effects in a simple system by increasing the connitely shown to be due to OH0 radicals: this iscentration of the molecules under study. In the case ofso for the inactivation of ribonuclease, carboxyindirect efi'ects, the yield of altered solute molecules
peptidase or the S H enzymes. These effects candecreases with increasing concentration of the s o l ~ t e . ~ ~ ~ ~ ~be duplicated by chemically produced OH0.76I n
I t has thus been calculated that in a 1 per cent solution
the case of bacteriophage SIsi6 or catala~e,'~ of thP enzyme carboxypeptidase, more than 90 per centhowever, it has been suggested that they becomeof the inactivation is indirect; in a 20 per cent solution,
inactivated as a result of a reducing mechanism
only 60 per cent of the effect is indirect.OO
but, on account of the ~roblematicexistence ofindependent H atoms 6 usual conditions of irDesiccation aizd protection
radiation, one can probably not be certain of the
32. One can also obtain information on the relative=act mechanism, since new experiments7' mayimportance of direct and indirect mechanisms by comyet lead to other interpretations. In many cases
paring the yield of a radiation reaction on the samethe mechanism of inactivation has not been
substrate after desiccation, in a completely protected
worked out.
solution and in the absence of any protector. although( e ) The physical chemical properties of these moleit is probable that one will not be able to secure absolute
cules may be altered: the asymmetry of nucleic
protection against indirect effect^.^'of fibrous proteinss0 or of hyaluronic
acidT9may be decreased, possibly but not necesTenlperature c o e h i e n t ssarily as a result of a depolymerization ; the absorption spectrum of these various compounds
33. One can expect, if diffusible free radicals p1ay.a
IS often altered. indicating a chemical alteration
part in the indirect effect. that the contribubon of tbls
of the chromophore group ; ' W e stability of protype of effect could be reduced considerably by freezing
teins and nucleic acids towards heat or otherthe solution.92 This has been experimentally proved.
denaturing agent is usually decreased.1°
However, irradiation of dry substances at differentarise by the oxidizing action of O,HO on organica ~ i d s . " , l ~The~ ~ rate~ ~ ' of inactivation of certain non-SH
enzymes does not appear to depend on the presence ofoxygen, but S H enzymes are far more radiosensitive
when oxygen is present.lo5 Other biolc~gicalmaterials
Oxygen effectsuch as the desoxyribonucleic acid0"68*10zo r bacteriophageT6( a desoxyribonucleoprotein) appear to be inac34. The existence of an oxygen effect (paragraphtivated by ionizing radiations, by mechanisms chiefly38) was considered until recently as a criterion for pdirect effects; however, as the radiosensitivity of dr~ed independent of the presence of oxygen. This is also true
proteins and polymers varies with oxygen t e n s i ~ n , ~ ~ J "for the induction of bacteriophage in E. Coli K12?7J06
But it has been shown that DNA irradiated in the presthis is no longer a good test until more is known about
ence of oxygen is capable of forming hydroperoxides
the mechanism of oxygen effects.
which arise almost certainly from the indirect effect of
35. A major problem in radiobiology is to determine
the perhydroxyl radicals on pyrimidine bases.lo7 Howthe relative contribution of direct and indirect effects3 ever, the excited DNA molecule itself can form similar
and its solution will also be of great help in developing
compounds by reacting with molecular oxygen and thismethods of chemical protection. A first attempt has been
will result in the direct formation of hydroper~xides.'~'made with yeasts; it can be shown that when they are
It has recently been shown that dehydrated proteins
irradiated in the dry and hydrated state the order of(trypsin) also show an oxygen efect when irradiatedmagnitude of both types of effects is very similar.9s with sparsely ionizing radiation ( X or y rays) ; thisHowever, the molecular organization of most structures
may be due to 0,- ions.03(chromosomes, cytoplasmic particles, nucleoli, cell membrane) is hardly understood, nor is the contribution tothese structures of free or bound water and the possi39. I t has often been observed that the molecules
bility of diffusion of the free radicals formed during
under study continue to undergo alteration after theirradiation into or around them. A better understanding
exposure to irradiation has ceased. This is the case forof all these fundamental problems would undoubtedly
the oxidation of tyrosine,loDor for the inactivation of
be of great value.
some proteins,l1° nucleic acids.67bacteriophage,lll othern u c l e ~ p r o t e i n shyaluronic~~~
acid.I9 Pneumococcal DNA
E f e c t of LET
whentestedfortransforming
activity does not appear
36. According to the type of radiation used, yields per
to show any after-effect after irradiation in 1 per cention pair fornled may vary as a result of different LET.
yeast extract.6s
I t has been calculatted for water solutions that radiation
giving high specific ionizations ( a particles, slow neu40. The after-effect seems to be the result of a pritrons. soft electrons) produce high concentrations of H0 * mary process taking place chiefly in the presence of disand OH0 radicals along the ionization track;96 theirsolved oxygen but it may not be sufficient injtself toefficiency per ion pair in water solution will thus beinactivate the molecule. It could be due to the H,Ollll
smaller, \\*hen they are compared to y or x-rays or highor to the organic hydroperoxidesi12 formed in the soluenergy electrons. In the first case, the radicals, beingtion, but other hypotheses have been presented.
more densely distributed in space, will have a higher
41. The case of desoxyribonucleic acid has been theprobability of recombining or neutralizing each other,most studied: many mechanisms-such as the oxidative
and this explains the lower yield of reactions such asformation of labile phosphate l i d s with the sugar rings
the oxidation of tyrosine, the inactivation of the enzymeof the macromolecular chain or the slow unwinding ofcarboxypeptidase or of several viruses when the highthe double helical structure of desoxyribonucleic acidspecific ionizations are used.'"have been po~tulated.~~'~"~J'O
Although H,O, formed
37. These densely ionizing particles form Hz, O,,
in the solution does not appear to be necessary in the
may have a very
case of desosyribonucleic acid,ll"tH20, and presumably HOq as a result of the radiolysis
of H 2 0 2in water. evert in the absence of oxygeri and there
pronounced effect on bacteriophag? S, which becomes
more sensitive to this agent after irradiations; S,, also
are instances where H 2 0 2has been shown to be responbecomes more sensitive to some reducing agent likesible for part at least, of the effect of these particles; it
ascorbic acid.i6 As the after-effect does not appear tohas been estimated that local concentration of H,O,
occur after irradiation in the dry state (in the case of
may reach molarity along the track of a particles.96
DNA)S5 it does appear to be the consequence of an
indirect effect of irradiation. One will not be able to
Oxygen effectestimate
its contribution in irradiated organisms until
38. In aerated water solutions, irradiated with X or :/one knows more about direct and indirect action irz viz~o.
rays, H,O, is fornled, and it is thought that the radical
O,HO (perhydrosyl) is also produced as a result of the
reduction of molecular oxygen by an H 0 atom :51J'7*"00
in these, the radio-oxidation yield of many substrates is
I?r water so1l.t'ton
strikingly increased, sometimes by a factor of 5 to 6. In
42. I n a radiation-induced reaction taking place inthe case of the more densely ionizing particles, as thesewater, the fact that the major part of the effect is ofradicals are formed even in the absence of oxygen, one
indirect origin has iundarnental as well as important~ ~ ~instances,~"finds hardly any oxygen e f f e ~ t . ~In~ some
practical consequences.
new osidation products appear, as when irradiated ala43. Any other solute, reactlng with the free radicals
nine becomes oxidized to pyruvic acidlo' (the latter
fornled at the expense of the water molecules. will
also occurs as a natural oxidation product of alanine
render them less available to the substance under study
through the action of aninoacid osidase) .51 In some degradation reactions of polymetacrylate, oxygen is necand protect it possibly by a competitive r n e ~ h a n i s r n . ~ ~ ~ ~ 'Many organic or inorganic compounds are efficient inessary;s7*102organic hydroperoxides or peracids also
temperatures shows that the direct effect of ionizing
radiation also varies with the temperature, which makes
the use of temperature coefficients more hazardous, butnevertheless useful.82

I

4

:

vitro, amongst these thiourea, aniline, phenol, cysteamine
which is not the natural one and which cannot be restored
and S-2-Aminoand its osydation derivative cysta~nine,~~to an active biological compound by natural processes.63
ethylisothiuroniumOBrOHBr ( S T ) .lls
Coenzyme I is reduced by X or irradiation to an unnatural rroduct only in the presence of alcohol which is
44. Substances capable of reacting with essential
osidised to acetaldehyde :the reaction cannot be reversed
groups of enzymes may, when present during irradiaby enzymatic osidation. The great majority of radiotion, protect the group ; removal of the agent after irradichemical
reactions are apparently irreversible ilr vitro.
ation uncovers an unaltered group and this has been
If a radiation reaction similar to the last one describedshown to be the mechanism in the case of SH enzymes
were to take place itt slivo, natural enzymatic processes
protected in vitro by some SH r e a g e n t ~ . ~ ~ Many*'l~could restore the srcbstrate to its natural state, and the
enzymes are also protected by their substrate,'" theiracetaldehyde
formed could be reduced again to ethanol.
coenzvme or by competitive i n h i b i t ~ r s , ~ ~ probl~l~~*l~~ably &so becaise thh biologically active sites 01 thePresent staftis of the "target" tlzeory
enzyme molecules are maslied by the protector. I t has
51. According to its original meaning given by Crowbeen suggested, furthermore, that the S H group ofther in 1924, a "target" in radiobiology is a sensitive cellcystearnine can protect S H groups of enzymes by beular Structure whose inactivation by One Or several ionicoming linked to them reversibly through s - S bridges.
zations (hits) would result in the observed biological
Similar dissociable complexes can be postulated in othereEects. 131When ionization takes place exclusively in the
instance^.^^^*^'^
sensitive structure (direct effects) the dosage to effect'j- I f organic
originating from irradiatedrelationship has enabled one to calculate a target volume.
molecules are prevented to diffuse from one another, one
1, the case of dry or highly protected small viruses whichfavours their rejoining. This is also a possible mechare inactivated by a single efficient ionization, it has been
anism of radioprotection and it can probably be achieved
their volume and molpossible on this basis toby freezing at low t e i t ~ j e r a t t w e . ~ ~ ~ecular weight and obtain values in agreement with those
46. Reducing the oxygen tension will inhibit thoseobtained by other methods. As water is a major cell coneffects of radiation which are known to be increased instituent, it can be expected that part of the biological efosygen. There are many ways of producing anoxic confect of radiations is of an indirect nature: this raises
new problems as to the applicability of the target hypoditions, including the use of chemicals, such as hydrosulfite, cysteine or ~ y s t e a m i n e , l " ~and*~~of~ more usual
thesis to living cells. If all indirect effects could be suprespiratory inhibitors. I n vivo, many reducing organicpressed, as it is thought they are in dried seeds, there
would be no problem. A t present there is no certain way
substrates which consume the cellular oxygen by way ofof doing this : loading the organism with chemical prothe normal respiratory processes probably also produce
tectors, freezing the cells or reducing the oxygen tension
anoxic c ~ n d i t i o n s . ~I t~ is~ 'difficult~~at present to know
may not do it efficiently because it cannot be foreseen to
the exact contribution of these mechanisms in the case ofwhat extent a chemical protector will reach the cellularcertain protecting agents like cysteine or cysteamine ; itstructure under consideration. and because free radicals
is probable that it varies according to the type of submay remain frozen at or near their site of origin until
strate. the presence of other solutes and the concentrathe cells are thawed for biological assay. Therefore,tion of the different substances.
more kno~vledgeis needed about the relative importanceof
indirect effects and about the distances over which
In the d r y state
free radicals may diffuse before being neutralized o r
47. However, it is possible to protect molecules in the
before reaching the cellular targets. I n order to have a
dry state. I t has been shown that the four first substances
clear-cut criterion which can be observed, the biochemical
listed above, (paragraph 43) when i n c o ~ o r a t e dinto aor biological reactions controlled by the targets should besynthetic polymetacrylate, protect it during irradiation
well defined. Probably, when these conditions are satiseven when in the dry state.5s I n the solid state. no water
be possible to use the target concept as a usefied, it
radicals being present, the protective action is probably
ful analytical tool. JVorIi in this direction is in progress.
due to a transfer of energy through the polymer mole111. BIOCHEMICALEFFECTS
cules to the radioprotector. This would be the mechanismof protection in the case of a direct action of radiation
52. ~h~ seq,4ence of cjze,,zical evellts from the momenton the molecule. The ribonucleic acid of tobacco mosaic
when the cell constituents are subjected to radiation up
virus also appears to be protected against direct
to the time the biological effects become apparent can
by cysteine.lsO
conceivably be discovered with biochemical techniques.
The search for an immediate or initial biochemical event
will thus be the first step in this attempt. Two approaches
Restoration'Ons N d ~ i n gthe effects On
been usedhave
48. Redoration is a process starting in the irradiatedstituents and on biochemical mechanisms.
material, by which the original product can be obtainedwith its normal characteristics.
Cellular constituents
49. Reducing agents when added after irradiation
53. ~h~fordamage to important
have been
to be capable of restoring the full encellular constituents can be done by assaying, as Soon as
zymatic activity of a number of S H enzymes. The respossible after irradiation, the biological or the physicotoration is complete only at very low dosages :as dosageof various cell componenb of m h dchemical1s increased, reversibiity is less and less complete, wh~ch the integrity appears to be important for the econo.my ?£shows that different sites of one molecular species are
the cell. E~~~~~~or nucleic acids can be mamined tn thls
altered with different efficiencie~.~~way, but although high doses have been used no definite
clues have so far been reached. despite the very great
50- Although some compounds are normally oxidized
tonumber of observations. The general conclusionof reduced during normal cellular processes, the radiopoint to the apparent radioresistance of the ma~Orltyof. biological oxidations or reductions may lead to a productseeems133

cellular proteins ;and even sulfhydryl groups, which arevery radiosensitive in dilute solution. 13"134 do not appear
Similarly, esto be considerably dainaged itr vivo.12G*133
sential coeazymes and vitamins do not seem significantly
altered immediately after irradiation.lta This is due tothe fact that only a very small percentage of the constituents are affected unless very high dosages areapplied.126
54. I t must be realized that in such attempts to identif y radiosensitive molecular species by looking for theoxidation of SH groups or changes in molecular asymmetry these molecules are usually considered in bulk, andeven when specific analysis is undertaken, it is often
found, as is the case of coenzyme A, that no alteration
can be detected.l3"hesenegative findings do not exclude the possibility that a small number of molecules of a
type controlling key mechanisms (cell division for esample) or having a particular location may still be altered-but at present, general knowledge about the existenceof such specific molecules is lacking.
55. In the case of genetic constituents (desoxyribonucleoproteins), which presumably constitute a class ofrelatively few molecules each having a very high degreeof biological specifiaty. the alteration of a single unit
would result in some cellular damage which would become expressed at the end of the chain of reactions it
initiated.
56. The question of the radiosensitivity of nudeic
acids in G o seems still to be controversial, althoughevidence indicates that nucleoprotein complexes areprobably dissociated in many tissues as a result of moder~ ~been~~~calculated, on the basis of
ate i r r a d i a t i ~ nI.t~hasin vitro measurements, that a dosage of 100 r could
damage 100 to 200 molecules of DNA in a mammaliancell.137and this figure does not disagree with the data
indicating the stability of p~leumococcusDNA when
~ ~ dosages,
used in these experiirradiated in v i v ~ l thements not being sufficient to cause any significant inact i v a t i ~ n .Thus,~ ~ a very much lower dosage than 1 r
would be theoretically sficient to alter permanently
some genetic constituent in a single cell. In this case,not all cells would have one of their DNA molecules
affected. However, nothing is known on the possible
interactions that intact cells could have on the affected
ones, either by influencing their recovery processes orby competing effectively with them (selection). Knowledge on the behaviour of an affected cell in a normal
population nrould be of great interest to understand low
dosage effects.
57. There is no reason to believe that ribonucleoproteins are not as radiosensitive as the desoxyribonucleaproteins, but very littie is known about the number ofunits of each type which a cell is likely to possess andeven less of the specific reactions they control. Chromosomal ribonucleoproteins could very well be concernedwith the duplication of genetic material in dividing cells,
as suggested by recent work on bacteriophage syntheSiS.138,139,140

58. Still less information is available concerning thepossibility of other cellular constituents playing key
roles; many remain to be discovered and further fundamental research is required.
Bioclre~rrual nrec1io.nistn.r
Energy-fornzing syste~ns
59. More information is available from the study ofintegrated biochemical reaction chains. like those ofglycolysis and respiratioa. when studied at various times
after irradiation. These systems result in the building up
of compounds rich in chemical energy which can be used
for biosynthetic reactions and cellular work. I n radiosensitive organs like bone marrow, spleen and thymus, suchreactions as aerobic phosphoqlations seem already to
be impaired thirty minutes after irradiation by 50 r (effects on mitochondria), but it cannot yet be statedwhether these radiobiological processes are the cause or
the result of other biochemical damag'e."1J42
Syntlzetic nteclzorrisnzs
60. In dividing tissues, the most constant finding is
an inhibition of the synthesis of desoxyribonucleic
In micro-organisms like yeasts, theacid.
homogenity of the population makes experiments moreeasily interpretable: and it has been found that this inhibition is only temporary and that synthesis resumes
after various lengths of time.144In other instances, there
may be a short time-lag before this inhibition occurs.
However, the mechanism of DNA synthesis, although
beginning to be experimentally approached, is not understood. As has already been pointed out, it may be dependent even in normal cells on protein or ribonucleic acidmetabolism; and in bacteriophage it is probably dependent on such metabolism by the host cell. The natureof the initial step of radiation damage remains to be
determined. On the basis of bacteriophage inactivation,it has been suggested that the DNA model, or template.
on which the new molecules are thought to be formed,
has been altered in such a way as to make its reduplication impossible. The temporary inhibition of DNA synthesis may lead to abnormal DN.4 formation and this isperhaps related to the killing of cells and to mutation,
but in what exact manner is not known.
61. So far, the syntheses of ribonucleic acid and proteins and lipids in bulk do not appear to be consistently
impaired by radiation and may even be enhanced, butthese compounds are very complex and their study inbulk form, the manner in which it has mostly been carried out so far, cannot be regarded as adequate. Proteins and RNA, bound to the chromosomes and othernuclear and cytoplasmic structures. are probably very
complex and each fraction should be studied independently.14' This will only become possible, however, whenmore is known about the chemical composition of cellular
structures and when refined analytical procedures areavailable.
62. The inhibition of ittdzcced proteitt syrztltesis in micro-organisms has usually been found to be resistant toradiations, except in the case of hydrogenlyase in E.
C01i.l~~In mammals, a few cases of induced synthesis of
enzymes are known :the tryptophane peroxidase zctivityof rat liver can be increased if the animal is injectedwith large amounts of tryptophane. This process is inhibited by radiations, but this inhibition only becomesapparent after two or three days.lS0However, if tryptophane is not given to the animal, an i~zcreasedactivity ofthe peroxidase during the first few hours after irradiation can be observed, but this increase does not occur inadrenalectomised rats and is therefore due to a secondary~ ~ . ' ~are~ therefore two conadrenal s t i m u l a t i ~ n . ~There~I t hasflictincr mechanisms which have O D D O S ~effects.
furthgrmore been shou~nthat the oiiurrence of infection
in irradiated mammals can be related to an impaired sJnthesis of a,?ttibodiesif irradiation takes place before theinjection of the antigen
this is not necessarily due to the depletion of antibody-forming cells, but
131*1431"13145:'iG*"'9"R."Brmight be related to the inhibition of the induced sy~rthesisof a specific protein, a complex process generally considered to be related to the metabolism of ribonucleic
acid, but which is not understood. The con~pleteprocess
o i immunological response (the sequence of events between the invasion of the organism by an antigen and thesynthesis of a new specified antibody) is also not properly understood and the cells rvhich are concerned are
just beginning to be identified. The process of induced
synthesis is believed to be related to ribonucleic acidmetabolism, and in micro-organisms it is quite sensitive
to U.V. light absorbed by their constituents which affects
the synthesis not only of the new proteins but also ofribonucleic acid.lS3

I

chromosonle and in this case the damage would be visible.
Two types of mechanisms ior chromosoiiles breakage
appear to be possible;35 the first would be the result of
the breaking of weak ionic bonds, the second the rupture
oi stronger covalent bonds. I n the first case; restitution
is possible in the absence of external energy sources ; inthe second, energy of respiratory origin is necessary.
This interpretation is by no way deiinitlve: it is the one
which best fits the present esperimental data, but its
simplicity is obviously a reflection o i our ignorance ofthe over-all n~olecularstructure of chrolllosornes and o ithe dynamic mechanisms of chromosollie function. I t ispresumed that ionization must take place in the gene~tselfor in its immediate vicinity to cause a muration.
69. Less defined damage, making the chromosomes
stick to each other, is also observed; the result of thisstickiness is, as is often also the case for well-definedabberations, an uneven distribution of chromosomes behveen the daughter cells, which affects the process of
Staining abmitosis or the survival of the cells.162*1Bi
normalities of the nucleus have frequently been obseTVed."A168

E f e c t s 012 traltsport mechaninns in the cell njel~tbrane
63. Enzymatic systems at the surface of the cell membrane take a prominent part in the active transport ofmetabolites through the cell membrane,'54 but, although
cell pernleability has often been said to be affected after
irradiati0n,'~"'~9ewcritical cxperiments have been performed. I t has been shown, for instance, that lethal irradiations and still higher dosages have often led to a
70. New techniques have only recently been developed
leak of potassium ions into the medium ; this has been
for mammals, making possible in them the identification
proved in erythrocytes, in muscle but not in liver.15i Simof all the chromosomes in a sufficient number of cells
ilar phenomena. if existing in nerve cells, could be a basis€or the quantitative study of aberrations, which would
for esplaining some of the nervous symptoms of irradilead to the establishment of dose effect relationships ination. Surface mechanisms can be affected in yeasts bymen. Observations of this kind will be extremely laborU.V. light 365 mp. without apparently producing otherious and one cannot expect much information beiore
effects than delaying mitosis ;these surface lesions cause
many competent observers have been trained.
considerable loss in potassium.15s
71. The n~orphologyas well as the number of riiccleoli
64. The loss of small organic molecules like adenosine(small nuclear spherules characterized by their hightriphosphate has been shown to occur from irradiatedcontent of ribonucleic acid) may be altered in mammamicro-organisn~s,'~~and techniques of tissue culture willlian cells.lsO The total cellular volume may increase as
make it possible to establish whether such behavioura result of irradiation, as the volume of the nucleus often
applies also to mammalian cells. I n mammals, it is known
does; the nucleoli may become swollen, fragmented orthat amino acids and other small molecules (taurine for~ a c u o l a t e d . ~The
~ ~ ~precise' ~ ~ function of the nucleoli
instance) are released in the blood stream and ~ r i n e , ' ~ ~ * ' ~in' normal cells is far from completely known, but it
and this might be the result of impaired permeability.
may be related to such diverse processes as cell diSer65. The exact significance of these various biochementiation, protein synthesis and coenzyme synthesis, andical effects is difficult to discuss because our present
their obvious relationship with the chromosomes in many
instances make these organelles of prominent interest
knowledge of the sequence of biochemical mechanisms
for the proper functioning of the cell.lil
taking place in a normal cell and their interrelationshipis still very fragmentary.
EFFECTS
IV. CYTOLOGICAL

72. Nuclear swelling is often accompanied by cytowelling, and giant cells are often observed after
plasmic
tion, cytologists have tried for the last half century toirradiationof micro-organisms as well as of mammalianidentify abnormal cell structures.
cells.17' The fact that the dry weight or total nitrogenilcreases at the same time indicates that many synthetic
Nucleusreactions have not been interrupted. Swelling of cells
67. I n tlze cell nucleus. the most conspicuous damage(or elongation of bacteria) appears to be the result of
is in the chrotnosomes, which are very sensitive and frean impaired cytoplasmic deavage.':3~"'*lT5*1i8*17This
quently grossly altered ; irradiation as low as 25 r or evencellular swelling has often been the basis o i a misinterless is svfficient to induce chromosome aberrations inpretation : many references to the stinaulatiort of growthembryonic nerve cellsi6?or in many plant t i s ~ u e s . ~of~irradiated~ ~ ~ ~ ~organisms can be cited. Actually, as in the
68. Irradiation causes the breakage of chromosomes,
case of seedlings, this is merely the result of the elongawhich probably occurs during exposure; this is followed
tion of non-dividing cells :1i6*xi*lT8
the inhibition of one
by normal or abnormal recombination of the broken
process (cell division) may result in the increase ofends; but these may remain separate. As not only theavailable energy or building blocks for other reactions,.
molecular integrity but also the order of the genes onthus merely shifting one steady state to a n p t h e ~Thethe chromoson~esis important, this damage may lead toenergy of radiation and its random distribubon 1s suchgenetical effects simulating mutations. Point mutatlons
that the chances of obtaining deleterious reactions appear.
are molecular alterations of genes usually not accomgreater than those for specifically removing inhibitory
panied by visible aberrations, and they may perhaps
processes. another logical mechanism by ybch s~lnulaconcern only a very few sub-units (nucleotides) oftion could be explained. Effects of radiation should al-.
however, a point mutation could
genetical material :1s5+36
ways be thoroughly analysed before they can be as:umed,
occur at the point of breakage and reunion of theto be useful to the irradiated subject.
66. I n order to explain the biological effects of radia-

I

j.
f.

ill(2

i.2

13

.

.

73. The cell cytoplasm is known to contain a varietyof particular structures, the exact identity of which has
not yet thoroughly been worked out.lS0
74. Mitochondria are the largest of cellular particles ;they contain most of the enzymes and coenzymes responsible for cellular respiration which release the majorpart of energy used in biochemical reactions ; they also
have important functions in lipid metaboli~m?~'They
have been observed to swell or show abnormal staining
a finding which has
in irradiated spleen ceUs,lsl~lsz~l83
been supported by biochemical evidence (inhibition ofoxidative phosp1~orylation),18~~1S5
If, after irradiation,
the behaviour of the ~ a r i o u s biochemical functions
which are attributed to mitochondria were compared,
it should be possible to draw a consistent picture of theiralterati~ns;~~%nfortunately
the experiments have seldom been carried out in comparable conditions.
75. The following have been described :( a ) An inhibition of respiration and phosphorylations
chiefly in thymus and spleen ; the phosphorylation
processes appear to be more sensitive than respiration.lS4'186.1S7( b ) L4n increase of spleen adenosine-triphosphatasewhich seems to be independent, at least initially,of the inhibition of phosphorylation.ls6(c) -An altered lipid metabolism characterized chiefiy
by an increased synthesis of the phospholipids ofthe liver;188however in spleen and thymus it isslightly lower or remains normal. It must beemphasized, however, that lipid synthesis may
not necessarily be linked to mitochondrial integrity, as suggested by a number of experiments.
189.190,191

76. Thus, the different reactions to radiation of threedifferent mitochondria1 functions do not appear to respond identically. This raises the problem of the identity of the mitochondria performing all these threefunctions. Much better controlled worlc, where several
properties of the same particles are investigated in
identical conditions, could help to solve this important
problem, and radiations could perhaps in this instancebe useful as an analytical tool: the site of lipid metabolism could be a radioresistant type of mitochondrion.
77. It must finally be kept in mind that respiratory
processes appear, as in yeast, to be controlled by nuclearo r cytoplasmic factors ;lg3the latter may or may not be
identical with the cytoplasmic particles carrying the
respiratory enzymes themselves. An alteration o i thesecontrolling mechanisms could very well be the origin oi
late radiation effects on these functions.
78. Microsomes form another class of smaller, cytoplasmic structures organized in a reticulum. as seen by~ ' ~ have
~ ~ ~ a strong affinity
the electron m i c r o s c ~ p e . ~Theyfor basic dyes. a condition which is strikingly augmented
in tissues undergoing differentiation and actively synthesizing protein; in the course of these processes,
ribonucleic acid, chemically related to the desoxyribonucleic acids constituting the nuclear genes, undoubtedly
plays an important part. There does appear to be a functional relationship between microsomes and nucleoli,
but its nature is not understood. These particles are atpresent considered to be the major site of protein~ynthesis.1'~

79. Surprisingly, electron microscopy has not beenmuch used for the study of the structure of the irradiatedcytoplasmic reticulum and the scanty observations so far

performed in the thyroid and in the testes have not revealed any damage to this reticulum.196
80. If the microsomes are considered irom a dynamic
point of view and the cellular functions to which they
are related are studied, several conclusions can betentatively reached.
81. In general, protein sy~thesisdoes not appear to
be impaired immediately after irradiation,lgS and it is,on the contrary, often enhanced : however, this increased
activity is often followed by a depression, as in the caseof the synthesis of the protein moiety o i hemoThis bimodal response to radiation, often
globin.1Di~1s9
found for protein synthesis, makes it difficult to interpret the variations of the serum proteins200in irradiatedanimals where a very complex picture is often obtained
and when the many results available are difficult tocompare on account of different methods and timing of
the experiments.
82. The inhibition of the induced synthesis of tryptophane oxidase and antibodies are perhaps also related tomicrosome activity.150
83. Cholesterol synthesis is also related to the integ~ ' is often enhanced after irrarity of m i c r ~ s o m e s ~anddiation: when it is inhibited as in spleen, this only
becomes apparent after twenty-four hours.97
84. In most cases, the effects of radiation on microsome function probably do not become expressed immediately after irradiation. It will not be possible to understand these late effects until the fundamental facts aboutprotein synthesis and their relation to nuclear activity
are known. Experiments on enucleated unicellular organisms have shown that the nucleus has a definite but
remote control over the cytoplasmic ribonucleoproteins :Ii1 the irradiation of non-nucleated cytoplasm in
the amoeba has shown that at least ultra-violet lightaffects cytoplasmic ribonucleoproteins quite rapidly.'OZ
85. Lysosomes form a type of cellular particle chiefly
studied in liver; they are intermediate in size between
microsomes and mitochondria ;Is0 they are characterized
by a high content of iron and by their association withseveral enzymes like desoxyribonuclease 11, ribonuclease, cathespin, glucuronidase, and acid phosphatase.
As the activity of the first three of these enzymes has
been found to increase in tissue homogenates o r in theit could be
blood stream after irradiation,203*2M~z05~206~~0isuggested that this is a result of damage to the lysosomes ;critical experiments in which enzymes are assayed simultaneously in an irradiated animal might prove this hypothesis. In the case of cathepsin, the increased activity
can be related to the disappearance after irradiation of an
enzyme inhibitor normally present in the blood.-"01208
86. C h l o r ~ p l a s t sthe
, ~ chlorophyl-containing~~~~~~
cytotheplasmic particles of plant cells, and ki~retoson~es,"~particles related to flagella in protozoa, are both endowedwith genetic continuity: this gives to these structures
great theoretical importance. If the speed of multiplicatlon of these structures can be reduced to a greater extent
than that of cell division, one can expect to find that someof the daughter cells have completely lost them. The reverse could also be true, and recent work on moderate!^
irradiated grasshopper testeslg6has shown in the electron
microscope the appearance of supernumerary tail filaments and centrosomes, probably related to the kinetosomes of protozoa. These obsenlations have led theirauthors to an interesting theory of radiation damage
based on the synergistic action of non-specific moleculardisplacements leading to the formation of abnormal

i
,
1

!

s t r u c t ~ r e s . 'Extensive~~
work on irradiated plant cells
has led to the demonstration that the activity of several
enzymes bound to the chloroplasts were altered.?ll

V. BIOLOGICALEFFECTS
87. The effects on homogeneous populations of cells
will be considered first, and then those on complex
organisms.

ing of the critical period in other cell^.?^^*?^^ Also, in eachcell type. although the general course of nitosis is quite
similar, the duration of each phase and sometimes theexact denomination of the stage considered may varyto a considerable extent, which makes exact comparisonsvery difficult.

92. The exact cause of the inhibition of mitotic division is not known. It has been suggested that it is related
to the inhibition of DNA ~ y n t h e s i s * ~which~ ~ ? ' ~occurs
frequently- but some instances where cell division is
Ho~nogeneouscell popt~lations
inihibited with apparently normal DNA metabolism will
88. Cell populations such as micro-organisms, proforce us to reconsider this vie^."^ DNA synthesis, astozoa, unicellular algae, cultures and surviving suspenstatedpreviously, is a complex process; it is perhaps
sions of cells from multicellular organisms like fibroassociated with chromosomal protein'2s or RNA synblasts, bone marrow cells, gametes and certain cancerous
thesis,138of which next to nothing is known. I t has beencells have been extensively studied.1*213*214*'15*217*218
suggested on the other hand that an interference of radiRecent techniques make possible the culture in liquid
ation with the oxido-reduction of sulfhydryl compounds
media of almost any type of mammalian cell
these
known
to occur during cell division^*^^*'^^"^^ might also
cells are capable, in vitro, of forming organized strucbe
one
cause
of its inhibition ; inhibition of mechanisms
tures recalling the original tissue they come from,216
ofcytoplasmiccleavagezz6 or of spindle formationzi
which should be of great value in studying problems of
are
other
plausible
hypotheses.
cellular organizations and in understandig multicellularorganisms. These cell populations have been irradiatedMufatiomin rather comparable conditions, and they have beenshown to react in very similar ways.
93. I t has been stated earlier that cells which do notdie after several divisions are said. to recover. This
89. When fundavtental Properties of the cells such as
statement is very imprecise, because all that is known issurvival, cell multiplication or mitosis, increase in drythat these cells look as if they had recovered. However.
weight, differentiation of non-mature cell types, cellin certain instances although they continue to have amovements, or permeability of the cell membranes arequite normal appearance, they have undergone wttttation.
studied, one can usually describe a comnton pattern ofThese changes have been observed most clearly inreaction to radiation.
bacteria, moulds, and other unicellular autotrophic or
90. O n the other hand, cells performing specialized
heterotrophic organisms ; and very recently, the studies
functions may react to radiation in a specific mannerof cultures of isolated mammalian cells have suggested
related to this function. In multicellular organisms, imthat such mutant forms also =ist amongst the surportant i?zteractions between the different tisslies havev i v o r ~ These. ~ ~ ~mutations are characterized by the factthat the surviving cell as well as most of its descendants
also to be considered.
have been affected in a way which makes them permnutiently incapable of performing some biochemical reMitosis (i.e., cell division)action. If this biochemical reaction (for instance, the91. Cells are rarely killed immediately, but usually die
formation of an essential building block) is necessary
after having attempted division or after having underfor the cell to grow and multiply, the mutation will leadgone one or several divisions. Mitosis itself is interferedto the arrest of growth and multiplication, and finally thewith and is usually delayed, if irradiation happens earlycells will die, if this essential building block is not proenough in the mitotic cycle. This has been examined mostvided in the culture medium. It is believed that there is aelegantly by direct observation on hanging drop prepaperiod of time following irradiation dtiring which therations of neuroblasts from grasshopper embryos.167 process of mrrtation is not fully e~tablished.'~?~~~~.~~~"~~
These experiments have shown the existence of a very
What takes place during this time is not known-but it iscritical stage of cell division during the period when thepossible, at least in the case of ultra-violet irradiation ofchromosomes condense as visible threads and when both
micro-organisms, that the expression of damage depends
the nuclear membrane and nucleolus disappear. Irradiaon the synthesis of some protein. Although this tirnetion before this critical stage usually makes the wholelag gives the possibility of interfering with mutaprocess stop for a duration depending on dosage; afterg e n e s i ~ ? ~ ' * ~ ~subject~ - a which will be discussed more
it has passed this stage, the mitotic events do not appear
thoroughly in another section-it is generally accepted
to be interfered with if dosages are small. It is remarkthat this damage once fzrlly established cannot be r e v e r ~ e dable that, if applied at the right moment before the critby non-genetical processes. I n addition to induced muical period, dosages as small as 8 or 16 rad will delay the
tants
there are always a certain number of spontaneoru
progression of mitosis in this type of cell. These observaones,
which arise in the absence of any added external
tions are essentially similar to the previous analyses on
agents.
fibroblast c ~ l t u r e s ; ~they~ ~ *also~ = fit~ rather well withthe experiments on irradiated gametes of the sea94. Back nzlitation (reverse mutation), the apparent
urchins, where cleavage of the fertilized embryos obreversal of the previous mutation and the evolution fromtained by the conjugation of irradiated gametes (either
dependency to independence of some specific metabohte?
pr both of which have been irradiated) is also delayed,
may occur spontaneously or by irradiation of the mul f irradiation occurs before early prophase in this case.222
tant; apparently there is what could be called a true
If irradiation occurs aftenvards, it is the subsequent
recovery of the cell o r at least of that part of thecleavage which is slowed down. This general picture ofwhich had first been altered.g37However, the spontaneous phenomenon has a small probability of occurring
mitotic delay may be subject to some alteration when
and the process of back mutation, zcnless it could be dzdifferent types of cells are considered; less direct
methods of observation may have led to a different timrected, is not a ~racticalrecovery process.
.
----.:1771178

199. I t has bcen shown in many cases that potas95. Other mutagenic agents (lower ener radiation
like ultra-violet light,z3Smanytoxic compoun s and chemsium leaks out of many irradiated cells like erythroical analogues to normal building b l o ~ k s ) ~are~ d~ ~ ~ c' ~y t e ~ , ~and~ cardiac~ * ~ ~ ~ * ~but
~ not
~ out of liveror kidney,2s1or striated muscle.240
useful in helping to clarify the mechanism of mutations.
Chemical analogues, for instance. compete with normal
100. The entry of glucose or amino acids into cells isbuilding blocks and may often replace them in importantalso dependent on surface enzymes, and it should bemacromolecules like nucleic acids. sometimes preventing
clarified whether an inhibition of these systems might
their reduplication or their normal functioning. Comaffect secondarily synthetic or energy-forming mechaparison of ultra-violet lights of different wavelengths will
nisms. In micro-organisms (E.Coli, yeasts), it is known
indicate which of them is most effective and enables thethat the induced synthesis of many enzymes is not innature of the chemical groups absorbing the energy tohibited by X-rayszs2 for doses which conlpletely arrest
be determined. The use of these agents is of very greatcellmultiplication. which indicates that the inductor subimportance in elucidating the mechanism, not only ofstrates are still capable of penetrating into the cells.
mutation, but also of chromosome breakage and of miHowever, quantitative studies have not been performed.
tosis, which they are capable of d i ~ t u r b i n g . ' ~ ~On the other hand, it has been proved that in similarorganisms (E.Coli) irradiation leads to the diffusion of
96. Genes presumably control the biochemical mechainto the outside medium, as well as
many n~cleotides'~~nisms (many of which are located in the cytoplasm)of potassium, which has already bcen discussed (pararesponsible for producing enzymes or other specificgraph 63).
cellular constituent^.'^' It is possible to ima~linethat, as aresult of irradiation, the block in the reaction chain
101. In mammals, it has been found that when glucose
between gene and enzyme-forming system could occur
is injected under the skin immediately after irradiation,
in some intermediate cytoplarrrtic structure. Ii this strucits entrance into the blood stream is slowed d o ~ n . ~ ~ ~ture is one which, like the chromosomes and the genes
The passage of metabolites from the hypodermal region
they carry, has to reproduce itself at each mitosis in
into the blood capillaries could be a more complex pheorder that each daughter cell be identical to its parents,
nomenon, because it involves the passing of the moleculeand if damage has rendered the reduplication of thethrough an organized tissue. The same applies to theoriginal structure impossible, one will obtain a cytoinhibition of the intestinal absorption of glucose, whichplaslnic ntutation. Nothing much is knoivn about these,is diminished three to six days after total body irradiabut the induction in yeasts of respiratory deficient strainstion in rats. However, in this case the inhibition is acby poisons or radiation and the demonstration that thiscompanied by important cytological
The case
deficiency is not necessarily of nuclear origin, indicates~ ~the barrier separating the eye from the blood stream"55
the existence of heritable cytoplasmic c l ~ a r a c t e r s . ' ~ ~ * ~ofas well as many otherslJ6 have also been studied withsimilar results.

P

97. CrlH $nobility can be stopped by irradiation, but

Cell deatlz

usually very high dosages are needed for such an effect.
Irradiation of spermatozoa2" may result in the loss of
motion, probably as a consequence of the inhibition ofphosphorylation ;='= this causes them to become infertile.
but the dosages are much larger than the ones required
to delay cleavage of the fertilized egg. Nothing specificis known of the effects of radiation on the cellularmigrations IT-hich occur in the developing embryo.
On the other hand, radiation is Icnown to inhibit phagocytosis in mammalian polymorphonuclear white blood
but phagocytosis is a complex phenomenon andthis effect is not necessarily due to the inhibition of
movements. Alterations of cytoplasmic or nuclear movements inside living cells might also give useful indications. but so far their quantitative measurement isdifficult.

102. Irradiated cells die either immediately (i.e., during irradiation) or after a certain delay: in the former
case, much higher dosages are needed, and death can be
attributed to a general denaturation of cellular constituents. Many conflicting results on cell death have appeared in the literature : this can be accounted for by thedifficulty in defining cell death: in micro-organisms, forinstance, death has been defined as the inability to form
visible colonies on agar plates. Furthermore, the primarycause of cellular death may differ from one system toanother, and it is not necessarily unique; any of thecytochemical. biochemical, physiological o r geneticaleffects of radiation so far discussed could each take partin killing the cell. A mutation in a micro-organism leading to the inability to form an essential building block
will be "lethal" otzly in the case where the culture medium
does not contain this substance.

Aleltrbra~rcpheflotrte~iaajzd io)tic equilibria

103. Delayed death of dividing cells occurs after one
or several cellular divisions have taken place,220~'56~z57
and it may often be linked to chromosome damage.2ss
but it could also be due to nutritional or other deficiencies, such as occur in a non-dividing population. Delayed
death is caused by much more specific damage than immediate death, and its study is thus of far greater interest. The doses required for obtaining delayed deathmay be different not only for cells of different species.l
but also for closely related cells such as different strainsof the same bacterial species.25g

9s. The statement frequently made that radiation
alters the cell permeability needs to be specified. The
evchange of inorganic or organic molecules and ions
between cells and their natural environment is a very
complex process, because many substances have to beconcentrated inside the cell aga~nsta concentration gradient, a process which requires energy.15' and inhibitionof permeability could result from the inhibition ofenergy-forming systems. This is the case for K+ orscarbohydrates: in the case of the latter, c o n ~ ~ l eenzvmatic systems. located on the cellular membiane, ha;ebeen described, and it would furthermore not be surprising that this organized structure be upset by radiationas are other patterns of cellular organization.

10-4. Recent experiments on cultures originating fromdifferent single mammalian cells have shon-n a very similar sensitivity ;231this probably results from the fact thatin these abnormal conditions cells undergo relatively

rapid division, whereas in the whole organism thisprocess may be estremcly sloiv and may differ from one
tissue to another. When penetrating radiations are used,
it can be assumed that each cell of an irradiated population receives the same amount ot' radiation. I n an average-sized mammalian cell, submitted to an irradiation of
1 r, severd hundreds of ionizations occur. and the probabiiity of a structure being damaged will depend on several factors, including its size and the radiosensitivity of
its constituent molecules in vivo. I t has been calculated
that 100 r to a mammalian cell nucleus produce 100-200
hits into the DNA: 1.000 r to a bacterium will produce of the order of 5 to 20 direct hits in the DNA alone.
and every radical which might reach the D N A could
damage another molecule.6g Alterations of D N A could
be one cause of late cell~dardeath, but other cellularconstituents are also damaged. It can be shown thatsome cells die while others recover and apparently behave
again like normal ones. This probably results from differences in the distribution of the energy to "critical"
and to less "critical" molecules and it has to be remembered that it is the remaining physiological activity ofeach cell constituent which will determine the final biol o"~ + Aeffect.

Effects olt virtues and I< particles in Para~zecia
105. Radiation effects on such specialized biologicalsystems may at first appear to be out of place in a general survey as this one, aiming at understanding radiation hazards to man. However. these systems are very
closely related to chromosomes (and presumably thegenes they carry) and to many cytoplasmic particles;
they consist of nucleoprotein, and the mechanism bywhich viruses reproduce autocatalytically offers the bestmodel at present available for the study of the reduplication of cellular nucleoproteins. Viruses are very important in radiobiology, because they can be studied bothas chemical entities irz vitro and they can be irradiatedindependently of the cells they multiply in. Bacterial
viruses (bacteriophage)some of the animal viruses and the cytoplasmic K particle of Paran~ecica"~
are desoxyribonucleoprotcins. like the bullc of the chromosomes: plant viruses and some animal viruses areribonucleoproteins, others are desoxyribonucleoproteins.
,2601261

106. Bacterial viruses are the ones most attention has
been paid to, and the following fundamental facts havebeen discovered and have in some cases been confirmed
using other viruses.
107. Ionizing or ultraviolet radiation applied in vivo
or in vitro inactivates them, i.e. interferes with thepossibility of their being self-dztplicafed inside theCel~.?60,263.?62

110. Esperiments like these may have very generalimplications for the understanding of damage and ofrecovery processes talcing place in cells of more complex
organisms and therefore should be vigorously encouraged.

Eflects ool~lysogexic cells
111. Certain types of bacteriophages invade their hostbut do not multiply in the usual way; on the contrary.
they appear to become integrated into the bacterial
desosyribonucleoprotein and thus reduplicate cim~~ltaneously with the bacterial nuclear material without causing any apparent trouble to the cell. However, estrenlely
low dosages of irradiation as well as a variety of otheragents induce the transformation of this "prophage" toa virulent bacteriophage, which will multiply and h d l ylyse the infected
I n certain strains of lysogenic
bacteria, a dosage of 0.1 r may give a measurable induction, and the linearity of the dose-response curve for this"genetic" effect has been demonstrated down to suchWhat
~ J ~characterizes induction is that it
low d o s a g e ~ . ~takes place in almost 100 per cent of lysogenic cells.
whereas mutation only talces place in a small number.
112. Experiments on infected micro-organisms havealso shown that a virus is capable of becoming integrated
into the genetic material of the host and of transducing
some genetic characters from one genetic type of host
~ *not~ ~unlikely~that processes similar
to a n ~ t h e r . l I~t isto bacterial transformation by DNA or to transduction
involving the transfer of genetic material from one typeof cell to another, also exist in mammals. If such phenomena were discovered, directed reversed nztctations
might become possible iiz ~narnnzals.

Differetitiating cell populations
Embryonic developntent
113. Gametes arise from the differentiation of stem
cells, the oogonia or spermatogonia, which takes placein the gonads. This differentiation (oogenesis or spermatogenesis) is a process during which the double genetic
equipment (diploid) existing in the stem cells as well as
in the somatic cells is halved evenly through the complex
process of meiosis to give daughter cells, which willproduce gametes containing only one gene of each kind
(haploid). Fertilization will result in the fusion of theparent nuclei, and the usual diploid number of thesomatic cells is thus obtained.
Irradiation of galiretes
114. W e have seen that when either of the gametes isirradiated, the first cleavage of the fertilized egg isdelayed: if the embryo is then left to develop. thecleavage divisions usually proceed apparently quite
normally up to the blastula stage. However, embryonicdevelopment usually comes to a permanent stop before
the completion of blastulation or during early gastrulation: this is one of the numerous examples of delayed
death.269The fundamental biological situatioll is t!lat
gastrulation is the first stage of development dun%
which cellular differe~ttiatio~roccurs : this process is preceded by a striking increase in the metabolism of rib?nucleic acid (both in the cytoplasm and n u c l ~ ~ l u s ) . 1s
the case in most biological processes where Intense protein synthesis and differentiation is taking
Furthermore, during gastrulation important cellular
movements lead to the formation of three dieerent c d u lar layers which ultimately become organized in tissues

108. F o r certain strains, non-irradiated bacteriophages are capable of growing in bacteria heavily irradiated by X-rays or ultraviolet radiation, indicating veryclearly that the self-duplicating strzlctzrre itself has to beaffected and that the bacteria remain capable of supporting phage m ~ ~ l t i p l i c a t i o n . " ~ * ~109. If the conditions of infection are such that there
are several ultraviolet inactivated bacteriophage per cell.
for certain strains of bacteriophage. the intact parts ofeach virus can recombine into a complete new unit,
which is again capable of duplication (this is called
nttfdtiplicity r e a ~ t i v a t i o n )This. ~ ~ ~is a crude and probably quite inaccurate way of explaining a compIex
mechanism of which little is known. This type of reactlvation has also been described for X-rays.'66
139

and organs. Some of the cells in certain layers are capaof the embryo is the following : irradiation of the motherble of inducing specific differentiation processes inafter fertilization but during the pre-implantation period
others. There is not just a change in the "geographical"
leads to a high incidence of prenatal death : however, therelationship of the cells as a result of these movements,
survivors have very few major abnornlalities :this meansthat only the slightly affected embryos survive. I n conbut their apparent uniformity- up to the stage of the
trast. if irradiation occurs after the embryo is implanted
blastula is lost: this is demonstrated by the fact that thein utero, during the period of organogenesis, death
nuclei lose the general potentialities they had until
then.z71
usually occurs onlv after birth--but it is much less frequent: on the othe; hand, there is a very marked increase
115. The cause of the death of embryos obtained fromofmalformations of the embryo. During early embryonicoocytes fertilized with irradiated sperm appears certainly
development (if irradiation takes place during theto be related to nuclear daniage: the sperm cell contains
formatioil of the neural folds), malformations may oconly very little cytoplasm, and the damage can remain
curin the eyes, brain and medulla but also in the kidney
hldden, as it may do in mutations, over many cellularandliver. Irradiation at a slightly later stage of organogenerations. Cell divisions appear to be blocked as a
genesisgives rise chiefly to abnormalities of the skeleton
result of incomplete fusion of the maternal chromosomesof various types. There appear to be short critical periods
with the abnormal ones of male origin, a situation leadof development during which certain types of abnoring eventually to abnormality and uneven distribution
malities arise with very great frequency.278
of chromosomes between daughter cells.2681z'2.27ss2741275
It is important to notice that thve process of cell division
118. The -act mechanism of
which
these
becomes inhibited at a stage of development where theare all possible in humans, is far from being well undergenetic material is presumed to initiate differentiation.
stood on account of our ignorance of many- importantI f , however, the fusion of the abnormal paternal chromofacts concerning embryonic development, such as thesomes with the normal maternal ones is c o n l ~ l e t e Prel~
nature of i,ductiow (interaction bet~jreenneighbouring
vented (which can be done by using higher dosages oftissues), the cause of morphogerletic movetnents or theradiation), a situation arises where the abnormal nucleus
nature of gertetic expres&on, that is, the mechanism byis eliminated, and in this case an apparerttly nor?tzd which one single cell is capable of becoming differentiembryo will develop if the species studied are capable ofated into a multitude of daughter cells performing aparthenogenetic d e v e l ~ p m e n t . ~This~ ~ ~is"one~ ~exam~~~variety of functions.
ple, amongst others, where dosage-effect relationships
Dosage-efect relatiorlrlzips
appear to be non-linear and even paradoxical : higher
dosage producing less lhal damage than lower Ones.
119. These have been studied in certain cases, and for
The =planation ismechanisms
most bone abnornlalities they have been found to be ofment, secondary to the initial damage to the chromatin
the sigmid fype.~eo
the case of the decreased weightare observed : this damage, however, is probably relatedof the foetus at birth, the dosage relationship is lillear,~sO
in a simple way to the amount of irradiation received.
,d litter size appears to fall ofi logarithmically
A similar paradoxical situation may be found in the
dosage to he gametes.z8~ A constant finding is that aexperimental inductions in the embryo of certain abnorhigher dose not onlyincreases he incidence but also themalities such as m i c r ~ p h t h a l m i aand
~ ~ ~this can be logdegree of malformation and the lengh of the sensitive
ically explained by the existence of some competition
period during which a specific response can be inwith other lesions at higher dosage.
d~ced.'~OIt has been shown that a dose as small as 25 r
116. In the wasp H a b r o b r a c o ~and~ ~ in~ ~silk wormzT7 to the mouse embryo has led to the induction of minor
but nevertheless well defined abnormalities. It is difficult
the reverse situation is possible, and the fusion of aat present to know how such small doses could affectnormal sperm cell with a highly irradiated egg cell may
human embryos, but it can be expected that very minutelead to an androgenic embryo (containing only its
malformations of the brain, which could perhaps not befather's chromatin). Experiments such as this point
detected in experimental animals, will result in someagain to the very important role of radiation damage tokind of psychological disorders. Responses to lower
the cell nucleus. Nuclear damage (genetic) is probably
dosages still could probably be detected if a greater
also responsible for the various forms of abortion or of
number of animals and more refined tests were used.
malformations of offspring born of parents, one or both
The case of leukemia, also believed to be inducible byof which have been irradiated. In this case, the developirradiation of the human embry0,2~'is discussed in detailment of the embryo ceases at some stage of organogein chapter V and annex G.
nesis, sometimes even after birth. However, as different
stages of gavtztogenesis have different radiosensitivities,
Adult orgattis~rrs
one espects to have a different probability of abnormal
offspring when mating occurs at different times after
Difierelltiot.H
irradiati~n.?'~The longer the time lapse before concep120. Some undifferentiated cells are carried on intotion. the smaller the probability of abnormal developthe adult organisms and these stem cells go on differenment, because it has been found that the earlier stages
throughout life: the white blood cells are formed~ ~ ~ ~ tiating' ~are the least sensitive ones, at least in m i ~ e . Within the bone marrow and in the lymphatic tissues (lymph
slight irradiation, development may in many cases pronodes and spleen and other organs). Thc lymphatic
ceed and this will result in more or less dramatic extissues are considered to be of major importance in antipressions of genetic damage visible in the offspring.
body formation. The red blood cells originate from bone
Irradiatioi~after f ertilizatiorl
marrow and during embryonic life from spleen andliver. In rodents, myelopoesis and erythropoiesis con117. If irradiation is given at different stages of emtinue in spleen during adult life, but not in man. This isbrvonic developjnertt, the inhibition of cell division andone of many physiological differences it is essentid not
differentiation and cell death may cause the developto overlook when one transposes the results from esperiment to be either completely or partially stopped. In themental animals to man.
mouse, the pattern of response to irradiation (200 r )140

121. Adult organisms contain other tissues coirtkuoztsly regz;rerating from stem cells, such as epithelia(skin, gut, etc.) or bone: finally there are tissues inwhich fez,cell dkisions take place (liver, kidneys, pancreas, brain, or conjunctive tissue).

mutations or in chromosome damage of non-germinal
cells either as a result of death or loss o i specific cellfunctions.

122. -4s in the case of isolated cells. esperimental evidence points to the particz~larradiosensitivity not o~rlyof
rapidly dividing cells, but also of the e~tlbryonicor stew
cells whirl1 are still due to wtdergo cellrclar diferentiatio~r.'~This can be shown when one observes the survival or the cytological alterations of these cells. The
mature lymphocyte, however, which does not belong toeither of these classes is an exception to this rule; its
great sensitivity to radiation^'^^^*^^ is not well understood but may be related in some way to the fact that thenucleus is surrounded by unusually little cytoplasm
which may diminish spontaneous recovery mechanisms
or to the fact that it is a cell with a very short lifeexpectancy. It is also sensitive to many other stimuli.
The situation is diiTerent from that in the spermatozoon,
whose haploid nudeus plays an important role both incell division and in differentiation processes which do
not occur in the case of the lymphocyte, whose diploidnudeus may be more resistant than the sperm nucleus.

127. These effects. as well as their possible genetic
origin, are discussed iil chapter V and in annex G.

Mutations in nrulticellular orga~cisnts
123. Genetic mutations are found when gametes orthe cells they originate from have survived irradiation
and undergo f e r t i l i z a t i ~ n . ' ~ ~ J ~123. Many mutations are not lethal, and genetic abnormality of one of the gametes is believed to be thecause of many forms of congenital malformations: inthis case. embryonic development is only very locallyinhibited, and this leads to abnormalities such as harelip, cleft palate, spina bifida or the many deficiencies of
the nervous system like congenital blindness, deafness ormental deficiencies. Hereditary diseases due to well defined biochemical deficiencies are also known to occur inand in a few instances they have been quite
thoroughly anal~sed:in man the missing enzyme hassometimes been identified, as in galactosen~ia?~~
and inphenylpyruvic 01igo~hreniaz87,a form of mental deficiency related to abnormal phenylalanine metabolism.

Mutations in sontatit cells
125. Mutations in somatic cells will affect the lineageo i these cells but will not be carried to the offspring.
These mutations have been shown to talte place at afrequency oi the same order as that found in the germ
cells before meiosis (gonia)2JJ8Wg0.20' and they havebeen found to occur in irradiated tissue culture; suchmutations might play an important part in the determination of malignant growths.

Carciizoge)tesis and other sotnatic efects

VI. VAFSABLESIX UDIATIONEFFECTS

Physiological conditiofts
128. Physiological conditions may vary in many ways
and this can iduence radiation responses.'l129. During cell division (nlitosis and wzeiosis) there
are different phases of radiosensitivity which one has
attempted, not too successfully so far, to link to thedifferent phases of new chromosome formation andnucleic acid synthesis which occur during these events.
The survival of cells, the incidence of mutation and thealterations of chromosomes all undergo striking changes
in radiation response, depending on the stage of thedivision cycle during which the organisms are irradiated,
but it is difficult to generalize as to which is the criticalstage since it can vary from one effect, or from one
organism, to a n ~ t h e r . " ~ * ~ ~ ~ * ~ ~ *130. The induction of abnormalities or the lethal
effect in developing embryos after irradiation of immature gametes of either sex, is strongly dependent on thestage of gametogenesis during which irradiation takes
place. The first meiotic division is the period when it ispossible to induce the greatest number of dominant
the case of the male,lethals in the mouse o o ~ y t e . =In~ ~spermatogonia are the most sensitive and it seems thatthe degeneration occurs during the interphase or the
first prophase following irradiation. The period of greatest sensitivity for various effects induced during embryonic development need not be identical.
131. TIle age o f cells and orgallhnrs may affect theirradiosensitivity: in an aged bacterial szcspettsion, when
the cells have reached their stationary phase, they become less sensitive to radiation;m5 but what is usuallycalled an old culture is simply an "undernourished" onewhich has ceased to divide because the stationary phase
only begins when some nutrient begins to be deficient;modem continuous cultures in media constantly renewed. By means of the chemostat might help to demonstrate whether aging occurs in micro-organisms or cellular suspensions of dividing cells of more complex
organisms. The possibility of aging would exist if thedaughter cells were not identical; and such a condition
would arise if cytoplasmic material endon-ed with genetic
continuity were not distributed evenly between daughter
cells. I t is probable that in aged cultures the radioresistance is greater because the bacteria have stopped
dividing.

126. I t is very probable that the mechanism of m t a tion in higher organisms is very similar to that in microorganisms; and the importance of fundamental studies
in bacteriophage. microbial or fruit-fly genetics is that132. In the case of higher orgafristtts,there is u s u d l ~a great sensitivity during foetal life and the LDso is lessthey enable us to get answers much more rapidly and inthan half that of the adult, and. as has been alreadymuch better defined environmental conditions than can
shown. the type of lesion depends on the time
be hoped for in the case of the higher animals. Tissue
bryonic development during which the radiation Is deculture, which is complex in the case of these organisms,
livered. In certain strains of mice. 200 r on the ninth
may become of primary importance for the study of
day of gestation is 100 per cent lethal: on the tenth
genetical mechanisms in mammalian cells, since suchgreater
twice this dosage is required and after b*!istudies have become possible by culturing isolated mamdosages still are needed. The sensitivl9' conti?ues to de- malian cells in the same way as micro-organisms : mutaat
tlons have been induced in such cultured cells.29z*231 crease until adult life is reached: the LDso Is
for CAFz
forty days and reaches 670 r at 140
Many somatic effects may have their origin in such

--

141

mice.'96~29i~2g8
The sensitivity then remains very constant
up to the last months of life-~vhen it again increases
sharply. A similar pattern of response exists in rats ;'"DrosophilaSoOand birds,301on the other hand, have amuch more constant radiosensitivity throughout theiradult life.
133. These variations of resistance with age may be
due to changes in mitotic rate (there are no divisions ?fsomatic cells in Drosophila) or to changes in metabol~c
activity of different tissues, or to the fact that foetal
tissues are undergoing active differentiation, or because
the recovery processes of the aged cells have become
inefficient.
134. Nutritional a,ld other pltysiological conditiotls.
Starvation of micro-organisms may render them moreresistant, as seen in paragraph 131, but in other mstances, or in reference to other types of effects, they
can become more sensitive: fermentation by yeasts cultivated in a medium poor in ammonium salts is inhibitedby doses which do not affect the same process when thesenutrients are normal.302
135. There are felt? data on the effects of nutritional
conditions on the radiosensitivity of the mammal,
although a certain number of radiation effects concerning adrenal metabolism (weight, ascorbic acid, cholesterol) have the same sensitivity after one or seven days
fasting.303
136. Other conditions: Anaemia apparently renders
mice more sensitive to radiation, as is shown by the lower
LD,, of certain anaemic strains. Exercise, on the otherhand. does not seem to have much effect in mice.304
It is possible, however, that in human populations, undernourishment and strain may affect the recovery
processes.

organisms cannot be compared on exactly the same basis,but it often takes as much as 100,000 r or sometimes
much more to prevent 50 per cent of the organisms ofmany species from developing colonies. and certain protozoa may need more than 300,000 r to kill them.
139. Various factors may explain these difierences.
I n cold blooded animals, either low nletabolic rates or
low cell division rates imply that radiation damage willtake longer to develop; but this will not hold true formicro-organisms, which divide much faster than mammalian cells and resist much higher doses.
140. There may also be varying oxygerr tensions indifferent organisnls which could account for different
radiosensi tivities.
141. In the same species, organisms of different
genetic strains may vary in radiosensitivity to lethal
effects. This has frequently been observed in microorganisms but it holds true also for mammals, where different strains of mice have different LD,0/,0.318~319I t has
also been shown that similar genes in different speciesof Drosophila may mutate at rates which can diEer by
I t has furthermore beena factor as high as 2.236*Q5*316
shown that the f requenq of production of developmental
abnormalities may depend very much on the genetic
strain: in Ea1b.C mice. certain malformations of thespine occur in 100 per cent of animals irradiated with
200 r during the 8th y day of gestation, whereas in the
hybrid (C57XNB) F, no such malformations occur.31i
For practical purposes, tl& ftteans that obsewations obtained frotn one h~mrara~opztlationdo not necessarily
apply to a genetically di8ereizt population.
142. I n some organisms such as adult insects where
no cell divisions take place. one expects, and finds, ahigher radioresistance ;but in this case the gonads, where
cell divisions do take place, appear also to be rather
radioresistant; on the other hand, we have seen thatembryonic cells may be very sensitive,320as in grasshoppers.

137. Oxygen iensioa. The irradiation of water sohtions in the presence of oxygen results in the formationof D,HO radicals, in addition to H 0 and OH0. This
radical could also be formed in vivo. This would explainthat when the oxygerz tension is diniinished, a lower
143. The presence of natural radioprotectors may be
response to irradiation occurs ;305this is true for the
yet another factor: some organisms like insects are
survival ofand of birds,308for certain
known to lave a higher concentration of aminoacids
m ~ t a t i o n s ~but
~ ~not~ ~all,s1o
l l for chromosome damage,s1'(which are fair radioprotectors) in their body fluids.
for various effects on embryonic d e ~ e l o p m e n t ? and~ ~ * ~ ~The~ degree of oxygenation of the tissues should also betaken into c o n s i d e r a t i ~ n . ~ ~ ~for certain biochemical reactions dependent on oxygen.
Chemical metabolites or poisons whose presence in tissues
144. Finally, the number of sets of genes (ploidy)
reduces the oxygen tension may have similar effect.
has
certainly something to do with radiosensitivity, as
Lowering the oxygen tension may reduce the response
has been demonstrated for yeast and certain other microto irradiation by a factor of 3 to 5 in the case of highorganisms, in which diploid strains (containing bvo sets
energy radiation ha&g a low ionizing density (X andof genes) are more resistant than haploid ones (containy rays. fast neutrons); when the oxygen tension is
Not only the number of sets ofing
only one set).32av3?1
increased, these effects are not enhanced, which indicatesthat in air the osygen tension is sufficient for the m ~ x i - genes, but the number of chromosomes and their lengthappear to be important ; the greater their number or themum effect. In the case of the densely ionizing a particles
shorter their length, the more resistant the organisms
or s l o ~ neutrons,t~there is no oxygen effect.305
seem to be. This holds true at least in the case of theplantswhich have been studied in this respect.g2'
Co~r~parative
radioserisitivity of living orgatlisitls
145. Many of these suggestions are mere working
138. When the survival rates after irradiation of difhypotheses and nothing systematic hx ever been done tothe senferent types oforganisms arefind out about these different factors. Work in this direcsitivities are found to vary very widely.314 hfanm-mls tion may lead to theof bener ,vays of proappear to be the most sensitive of all classes of organisms
tection.
and doses able to kill 50 Der cent of animals in thirtv
days (LD,,/,,)
range f;om about 200 rad for thi
Adaptation to radiotiof8
guinea pig to 900 rad for the rat. the best estimate forman being 400 f 100 rad. Cold blooded animals have146. Little is known about the possibilities of organan LD,J,, which can rise to 3,000 r for the triton andisms becoming adapted to radiation: the follo~vingsugperhaps 20,000 r for the snail. Bacteria and other microgestions may ho~veverbe made.

117. Increase in catalase (an enzyme destroying hydrogen peroside and possibly neutralizing other peroxides) in algae from the Bikini area has led to the
hypothesis that this might be the result o i some adaptive
enzymatic processes induced by the unusual amount of
peroside detectable in the sea
1%. Selcctio~tmight be expected to lead, in certain
populations of mised species, to the predominance of themost resistant strain. Furthermore, it is quite conceiv&le that irradiation itself induces a mutation which increases or decreases the radiosensitivity of an originallyhomogeneous population of cells. However, work doneon D r o ~ o p h i l a ?and~ ~ yeasts324does not indicate thatbreeding in a high radiation background leads to theappearance of more resistvlt genes. The U\' irradiationof E Coli B, on the other hand, has selected a small
number of radioresistant mutants (B/r)2z9 occurring innormal cultures as a result of spontaneous mutations withthe rate of about 1 X
mutations per bacterium per
generation ; one would expect that under chronic irradiation one could select this strain to some extent.
149. Tumours have oiten been claimed to becomeradioresistant when treated with X-rays; it is howeverdifficult at present to give any sound explanation forsuch a behaviour ; adaptation of the cells has been given
as one reason3?5,=6,=,a~ but it is d i c u l t to dismiss thefact that the oxygen tension may decrease as a result of
pathologic changes in the blood vessels and that the polyploidy of the tumour cells may enhance their radioresistance.
150. Another possible interpretation is that tumour
cells may become incapable of further cell division itt
vivo, although when cultured they can resume division.
Recent experiments tend to indicate that small dosagesof X-rays (25 r ) to embryonic mice makes them somewhat more resistant to exposure to X-rays during theiradult life; this is however true only for females, themales appearing on the contrary to be adversely afi e ~ t e d . ~This' ~ apparent beneficial effect of low dosesof X-rays on females is compensated by the fact thatthe nunlber of litters they were able to bear fell from 5
for the control to 0.5 for the SO r group; furthermore
the number of young per litter was also greatly reduced-it may therefore be the fact of not bearing offspringwhich is responsible for the increase in life-espectan~y.~~O151. The study of the biology of species living inregions of high natural radioactivity may lead to some
information concerning this problem. However, suchworlc, although it may lead cluite rapidly to definite ideas
conccming tGe beha6our of short lived organisms or to
the identification of pathological symptoms in man, willneed to be carried on over many years or decades for thereactions of humans to such conditions to be understood.
The mechanism of possible changes in these populations
will need to be worked out in the laboratory where
genetic strains as well as experimental conditions can be
accurately controlled.

by higher crop yield, is reported with various contradictory results.33A,""633"Secondary efects
153. One important problem is to know whether irradiation applied to one site oi a cell or organism can
induce an efFect in another part.

154. Such secondary effects can be espected on account of the close physiological relationship behveen the
different cellular organelles. It is known that i i the normal isolated nucleus of an amoeba is put into the irradiated cytoplasn~of another amoeba that had previously
been enucleated, mitosis is inhibited in the reconstitutedamoeba at cytoplasmic dosages only three times thoseIt
producing the same effect in a normal 0rganism.~~7
has also been shown that unspecific chromosome darnage
can be induced in an intact frog oocyte nucleus introduced in the irradiated cytoplasm of another o ~ c y t e ~ ~ ~and ultra violet irradiation of the cytoplasm of the giant
unicellular Acetabtilaria klediterranea induces very
rapidly some cytochemical alterations in the nucleolus
which had been shielded during irradiation (this last
HOWeffect is hardly apparent in the case of
ever, nuclear damage to Acetabularia is also demonstrated if only the nucleus is irradiated. In the course ofexperiment on eggs of Drosophila, the much greater
sensitivity of the nucleus when directly irradiated isevident: it takes much more energy to kill the offspringby irradiating the cytoplasn~of &e egg alone than byirradiating the nucleus :340 the same holds true for attempts to induce chro~nosomedamage by micro-irradiating other parts of the cell.3" Primary nuclear damage
appears to play a prominent role in processes where
nuclear activity is important as in cell division, mutations
or inany lethal effects. However, this does not mean thatthe cytoplasm does not participate in radiation damage.
In some cells where no division occurs, cytoplasmic
processes may become efficiently inhibited: this is thecase of non-nucleated cytoplasnls of Anroeba and Acetabularia which survive for shorter periods than if theya nucleus :20',34%343 In this case, the role of thenucleus could be associated with some repair processes
wl~icl~cannot take place as efficiently in its absence, perhaps on account of the fact that the synthesis of cytoplasmic ribonucleic acid becomes seriously impaired incytoplasm which has been deprived of its nucleus forsome time?"
Peroxide fortnatiorz in irradiated cells

155. One of the possible agents for these secondary
effectscould be organic or other peroxides arising during
irradiation. It has been found that. bone marrow cells
incubated irt vitro produce peroxides when the cells
originate from an irradiated rabbit."' The si,gnificanceof this finding is difficultto understand on account of thefact that many tissues (although not bone marrow) ffom
non-irradiated rabbits also produce peroxides ha v~fro.
152. In certain experiments, the conclusion has been
Not much is known of the effects these ~ e r o s i d e rnlghtsdrawn of the favourable effect of small doses of radiation
have on other cellular populations. It has, however, been("biopositive influence", "stimulating effect") bothdemonstrated that many lysogenic bactena -show a. ~ ~ ~ *diminished~ ~ ~ ~response~ ~ when put in the presence ?I ~ t a l a s efrom =ternal and internal s o ~ r ~ e sHowever,further analysis usually explains this as a consequence(catalase reactivation after U.V. and X i r r a d ~ a ~ o n ) . ~ ' ~of pathologically shifted functional equilibrium, where
Another argument for the formation of peroxides in
one biological function, taken in isolation, may appear
irradiated organisms is that even with small dosages
to be stimulated. Also, the possibility of stimulating the(17,000 r ) to yeasts grown in anaerobiosis. these organinitial stages of plant development and growth, followed
isms synthesize catalase or ~erosidasewhen kept inanaerobiosis, a condition during which they normally
only have traces of the enzymes.340The synthesis of new
enzymes is believed to be induced by peroxides formed
during irradiation.
156. Radiation is also capable of inducing the formation of peroxides outside the cells, and irradiation by
X o r U.V. rays of organic culture media is mutagenic
f o r the bacteria which are cultured aftenvards; theeffect can be prevented by catala~e.~'~157. I t has been found repeatedly that the rtucleic acidnzetabolisna of a carcinoma is temporarily decreased asa result of irradiation of the animal bearing it, although
it had been completely shielded during the irradiation.
It has also been demonstrated that tumours originating from non-irradiated thymus cells can develop i fthese cells are grafted on a totally irradiated host whose
thymus had previously been removed;350 damage (byradiation or other means) or removal of the thyroid
may lead to pituitary cancer.351 No h a 1 explanationof effects of this type can be given ; the first mentioned
could be due to diffusible organic peroxides produced
during irradiation and very small quantities of peroxides
have been found in irradiated mice.352
158. On the other hand, normal regulatory processes
located in the irradiated part of the animal can certainly
be affected: hormonal effects, which are dealt with inchapter V, must be considered.3G3Stimulation of thepituitary as a result of thyroid disfunction is probably
the cause of the pituitary tumour mentioned above (paragraph 157). Tlze exact relationships between lzorntones
and biochemical processes in norinal organisms should
be known to understand many effects of radiation in the
mammal.

VII. ALTERATIONSOF RADIATION EFFECTS BY FOREIGNAGENTS

Protection
159. Protecting agetrts are those whose presence drrring irradiatiorr decreases the response of an organism
to radiation. Man experiments reported earlier (paragraphs 38,42 to 4 ) constitute a basis for finding chemicals capable of protecting living organisms against
radiations. However, our ideas on the mechanisms ofprotection in vivo are often conflicting, for the simple
reason that the fundamental processes of radiobiology
are not understood.

5

capable of decreasing the intracellular oxygen tension
can be expected to afford protection against direct o r indirect effects which are oxygen dependent ;35i ( d ) finally,a protector might conceivably give more chemical stability to a macromolecule and favour the rejoining of brokenbonds or divert energy from it. I t is, however, at presentvery difficult to choose between any of these possibilities.
162. Very many experiments have been performed,
very many chemicals have been tested and many effects
have been found susceptible of a certain amount o iprotection.
163. The sunn'val of unicellular and multicellularorganisms have been quite considerably increased by theuse of various agents. SH and allrirro reagents (cysteine,
cystearnine or cystamine, glutathione) or the methyl
derivative, methionine, as well as thiourea have beenused successfully on micro-organisms a l d mammals.
Very similar possibilities have been found with
S-2-aminoethylisothiuronium . Br . HBr (AET)U8
which is less toxic and may thus be used in many mammals, including monkeys and dogs.359AS far as is known,
there have been no attempts to use this compound inman. Further analysis has shown that at neutral p H arearrangement of the A E T to guanidine form occurred,
so that the effective compound was 2-mercaptoethylguanidine hydrobromide (MEG) .360
35513s6*358

164. These protecting agents appear to have greater
efficiency in promoting recovery processes rather thanin preventing the initial damage observed: this is moststriking in the case of the white blood cells and of themetabolism of spleen nucleic acid which seem to follow
a similar pattern of response.s01
165. The nutnber of chrornosonre a b e r r a t i o t 1 3 ~ ~ ~ ~ ~ ~ *and in some instances the number of ~nutatiortsn8 have also been reduced when similar protective
agents were used during irradiation. Successful experiments on plant cells have been reported. but cysteine does
not reduce chromoson~eaberrations in mousealthough nucleic acid integrity does appear to be proin the same organ.
tected by thiourea or cysteamineSBG
I n Drosopitila, however, and in micro-organisms, mutations have not so far responded to the protective actionof cysteine or ~ y s t e a m i n e .In~ ~micro-organisms~
a protective action probably exists, but it is often difficult tointerpret the experiments because increased survival asa result of protection could lead to an enhanced opportunity for a mutation to become e~pressed."~367*3a8.3e9160. The idea of protecting organisms against radiations arose about a decade ago, as a result of the discovery of the indirect nature of radiation effects ondilute solutions. However, as stated earlier, it is verymuch doubted at present whether effects of radiation onorganisms necessarily occur through indirect mechanisms, I t can furthermore be expected that the relative
contribution of direct and indirect mechanisms will vary
for different biological effects and in each case the possibility of protection may thus be different.3s5~S58~S58

166. These agents have in common the properties o ihaving an amino-group and a sulfur atom (which often
is in the form of a sulfhydryl group) and both these are
believed to be important.370However, they can act independently because many amines are also found to besatisfactory protectors in the absence of a sulfhydryl,
and a sulfhydryl group alone may be efficient in someinStanceS.370~371.~~
I t has often been suggested that thesulfhydryl group decreases the intra-cellular oxygen
tension and this has been found to be the case in few
living systems protected with cysteine or cy~tearnine.~'~161. There are many possible ways by which radiation damage might be diminished: ( a ) loading the organism with chemicals capable of reacting with HO, OH0,
and O,HO radicals may divert these from reacting with
important cellular constituents; ( b ) protecting agents
could also act by covering the sensitive site of cell constituents, and this type of mechanism could be operative
both for direct and indirect effects(ch) all agents

167. Many other agents have been used with a varying
degree of success and the mechanism of action of someof these does seem to be dependent on the decrease ofcellular oxygen, as in the case of the protection of micro~ ~ certain number o iorganisms with h y d r o s ~ l f i t e .hnatural metabolites (succinate, glucose, alcohol) haveprotecting properties in a few instances, probably by
consuming the cellular oxygen in the course of theirnormal enzymatic ~xidation.~'%oxia can arso be ODtained with a certain number of drugs like morphine
which depress the respiratory centres : in that case aprotecting effect is also found.3i3 Cyanide, a strong inhibitor of respiratory enzymes, has been found to be an
efficient protector of mice, although it would tend toincrease the intr2cellular tension of oxygen.374On theother hand, seeds irradiated in its presence show agreater mutation rate when it is used in low concentrations, but a smaller one when the concentration is increased.3T5However, in these conditions an increased
number of chromosome breakages is observed.376

3 parwhich appear later are also temporaT and dispIav -pent recovery. In irradiated mammalj. bone mar;o\~andgonads can recover at the expense of the sun.iving cells
which multiply and repopulate thesebut permanent damage, leading for instr?nce to iore
rapid aging,to an increased radiosensitivity or to the developmentof cancer, may have been established,

171. The lapse of time existing befiveen irradiationand the biological expression of the primaT damage:
gives an opportunity of preventing the developmat or
the lesion or of enhancing the spontaneous
processes.
165. I t is not clear at present to what extent the pro175. Recovery agents are those which are efiective
tection is complete, because although damage is not lethal
when given after irradiation. Various methods for proit may well be present and only become apparent at amoting the recovery of irradiated organisms have beenlater stage. It has been shown that rats, protected during
described and can roughly be classified into two groups :irradiation, develop a large number of tumours ;3"J78*176. (a) Those whose object i s to destroy some i)tter3is~sB0 these might have developed in the non-protected
before the damage is definitively
mediate co~~zpol~rzd
animals had they lived, as in the case of mutations inestablished : as in the phtorestoration of a great number
micro-organisms; and it is difficult to know if the priof effects of ultra-violet light,388*388the cafa/ae restoramary events of induction of cancer have or have not beenof lysogenic bacteria treated with ultra-vi~letlight3"
diminished. Nothing much is known on the protection
or, in one instance, the effects of X-rays.387 The first ofagainst other late damage or against the early aging ofthese processes, in the case of ultra-violet irradiated batirradiated organisms.
teriophage is only possible if illumination takes place In
169. Protecting agents are much less efficient in thethe presence of extracts of normal bacteria; the second~ ~ "seens (paracase of alpha rays or n e ~ t r o n s . ~ ~ ~ *wasappears to lead to the destruction ofgraph 37) in these cases reduction of the oxygen tension
formed during irradiation.
is not expected to have any effect.
177. Restoration achieved in some instances by coolingor heating the irradiated cellssmmay inhibit the esPression of injury before it is definitively established but
none of these mechanisms is properly
170. Radiosensitizing agents have been used in cancer
therapy, but the fundamental aspects of sensitization
178. ( b ) Those whose object is to re@ce a da*rpged
are certainly much less known than in those in the caseto m?crocompound or cell. The provision ofof protection. There are a few instances of enhanced
organisms which have lost the capacity of syntheslzIng
reactions to irradiation in the course of in vitro experithem could be considered as one possible mechanismm e n t ~but, ~these~ ~ are not at present susceptible to applirecovery; recovery is however only apparent, because
cation ifa vivo. It has, for instance, been shown that thethe fundamental damage has not been
oxidation of ferrous sulfate by X-rays is enhanced in
179. True recovery would depend on the p ~ ~ s i b i l i t ~the presence of various alcohols or of benzene.
of replacing the damaged molecules or cells by "On171. As a result of the systematic study of many
ifradiated ones. Experiments on bacterial transforma'chemicals, it has been found that s y n k a ~ i t , ~a~derivatlons or on genetic recombinations in micro-organisms
tive of vitamin K, increases the radiation induced mitotic
have shown that it is possible to control some alteration
inhibition in chick fibroblasts cultured in vitro; this efEectof them genetic characters. The mechanisms of thewas carried on in the absence of synkavit for several
greater radioresistance of diploidwith haploid
generations; and if rats are treated with the compound
cells may well have their origin in closely related me&before irradiation their mortality is increased. Synkavit
anisms. O n these grounds, the use of intact des05~ribOis also capable of increasing the permanent regression
nucleic acid to replace the irradiated compound insldethe
after irradiation of experimental tumours in the rat or
chrpmosome becomes a possibility. One successful -of cancer in man. All that is known about the mechanism
periment of saving ultra-violet irradiated salmonellaof action of this agent is that it becomes concentrated inwith intact D N A has been reported.389
the tumour as compared to the other tissues and that in
180. It is possible to replace whole cell populations
tissue cultures its eEect can be abolished by guanosine;
irradiated animals and thus promote their survival ;ofthis may indicate some interference with nucleic acid
this can be done by injecting intact bone rnzrro\v
metabolism. If one increases the oxygen tension of tua non-irradiated donor into the circulation of a lethally
mours where it is usually low, one increases their radioirradiated one. This type of experiment was .at firstsensitivity, a finding which has proved to be useful inperformed as a consequence of the demonstration
cancer therapy.38s
the death incidence of mice firas considerably decreased
the172. I t is not known to what extent natural radiowhen hematopoietic organs (like bone marro\v
sensitizers might accumulate during certain steps ofhind limb, spleen or liver) are shielded during irradiato benormal metabolic processes and thus alter the radiotion. Bone marrow injections have sincesensitivity.
successful in dogs, hamsters, ~ n o n k e ~ s .Only
3 ~ ~ ti'Sues
containing cells capable of forming gran.locfles
polymorphonuclear white blood cells), red blood
cellular173. When organisms are irradiated, many processes,
or platelets are capable of this activity. These
inhibited at first, recover. The synthesis of desoxyribosuspensions are effective in preventing acute death
nucleic acid is often decreased immediately after irradiX or y rays but apparently death caused by neutrons
ation, but only temporarily ; other biochemical effects
is much more difficult to1S1. As a result of injected bone marrow, the blood
cells and platelets tend to reach normal values again! theweight of the body, of the thymus and spleen increases
2nd immunological defence which had disappeared also
becomes functional again. However, many of the lesions
caused by radiation are not diminished after bone marrow injection: the greying of hair is not influenced andthe fertility of gametes is not restored,SoStumours develop with greater frequency in protected or parabiotic
animalSJ9G,S07,3D8 and the normal life-expectancy of theanimal remains decreased.394 All these facts seem todemonstrate that only acute death has been prevented
by the graft.

185. Experiments on cell transfer have been madein attempts to replace leukemic cells, which can be
destroyed by high dosages of irradiation, by normal
marrow tissue with the hope of preventing further development of leukemia Experiments performed on mice
have shown that such a treatment is capable of increasing
considerably the survival time of experimental leukemic
mice.406One such attempt is now being made in a caseof human leukemia.
186. The multiplication of donor cells in the irradiatedhost has unquestionably been established; however, thisdoes not necessarily exclude a possible effect o i subcellular fractions. The idea of the possible recovery
capaaty of bone marrow or spleen nucleoproteins was
put fonvard a few years ago but was later abandoned on
the ground that a small number of intact cells were present in the fractions injected407 I t is, however, not possible at present to exclude the possibility that sub-cellular
fractions do play a role in these recovery phenomena
and, on account of the tremendous importance of proving
or disproving this hypothesis, both for fundamental andapplied purposes, worlc on the biological activity of
nucleoproteins in normal or irradiated mammals is ofgreat interest and should certainly be very actively
pursued.
187. It will probably become possible to enhancesimilar recovery processes in human beings, but this zuillcertainly require a much better understanding of immunological processes and of interactions between cellular populations before it becomes a reality.

182. Important immunological problems are brought
up by such experiments as they were in the case of thefirst blood transfusions: it is well known that mammals
are only able to accept definitively grafts from subjects
belonging to the same genetic strains (iso!ogous grafts).
For instance, one has known for a long tlme that grafts
from one human being to another (homologous grafts)
are usually eliminated rather rapidly. as in the case ofskin grafts ; this is also the case when grafts are madebetween different species of animals like rats and mice(heterologous grafts). This incompatibility originatesfrom the fact that mammals possess imlnunologicaldefence mechanisms which make them synthesize newantibodies to any foreign protein entering their blood
circulation. However, it has been found that the immunological response of mammals is strongly inhibited in thedays following total body irradiation, and in these circumstances both homologous grafts (from other strainsof mice) and heterologous grafts (from rats) of bone
VIII. C o x c ~ t . s ~ o x smarrow are capable of saving lethally irradiated mice.
188. Radiobiology has certainly made great headway
Cells of the donor animal have been characterized in thewithin the last fifteen years. It has had, like cancer
receptor animal by specific genetical or imnrnunologicalresearch, strong governmental support in many countries,
identification ;3s0J99and the repopulation of the myeloid
and both these aspects of medicine have the common
and of the lymphoid tissue has been demonstrated. In
feature that litany cellular mechanisn~sappear to be
the case of heterologous grafting of thymus tissue fromsimultaneously concerned. This is why effects of radiarats into irradiated mice, the cells appear at first to betion are as diverse as are cellular functions. The visible
exclusively of rat origin but the later appearance of andamage will probably depend on which particular mechagglutination reaction with specific mouse antisera inanism is most sensitive at the time of irradiation. on its
dicates that thymus cells of mouse origin may be rerelative importance to the over-all economy of the cellcovering."00
and on the possible interference of other less damaged
153. The survival of the animals injected with boneprocesses. Mutations, carcinogenesis, and the inhibition
marrow becomes, however, dangerously compromisedof mitotic activities, of cellular differentiation and ofafter a certain time, because, whether homologous or
immunological processes. to name but a few examples
heterologous grafts are used, the incompatibility betweenof radiation damage, affect extremely complex cellularthese and the 'cells from the receptor animals reappears.
mechanisms, which, despite the efforts of many able
The discussion has arisen as to whether the recovered
scientists, remain one of the most provocative challenges.
cells from the irradiated organisms are again able toI t thus becomes vital, if effects of radiation are to besynthesize antibodies against the injected cells or
understood and possibly prevented. that the functio~~ing
whether these are making antibodies against the cells ofof normal cells and the organization of cellular populathe irradiatedtions be knotvn. Radiobioloe-v is not a science in itself;
184. There have been recent attempts to stimulate
it is but an applied scienceu;nd it rests entirely on ourbone marrow regeneration. It has been showll that alknowledge of the great principles of biology whichkosyglycerols obtained from bone marrow, as well as
cannot be studied independently of one another. The
some of their derivates, stimulate the white blood cells
understanding of some aspects may at times progresscounts of patients irradiated for therapeutic purposes:
more rapidly than that of others, but in the long run all
this increase seems to concern the neutrophil polynorthese have to be integrated iilto one harmonious picture.
phonuclears and has also a beneficial effect on the platelet
The problein is not merely to push forward the study
count.'03 I t has also been found that the bactericidal
of genetics or of carcinogenesis, because it is obvious
properties of the blood serum mere diminished in irradithat these problems are dependent on most othcr aspects
ated rats ; this could be due to 2 loss of properdin, preof cell physiology. Our ignorance of fundamental biology
sumably a natural non-specific antibody. Treatment of(taken in its widest possible sense) is undoubtedly thethese animals with a fraction from serum rich inmajor factor limiting our understanding o i radiation
properdin appears to increase the s u r \ ; i ~ a l . ~ ~ ' ~ ~ ~ ~effects on man.

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152~

Annex G

MAMRIALIAN SOMATIC EFFECTS

Paragraphs

I. SHORTENING
OF THE LIFE SPAN I N EXPERIMENTAL ANIMALS. 1
The acute LD,, . . . . ... . . . . . . .. . . . . . . . . . . . . . . . .. . . .. . . . 8
Acute effects in single organs. .. . . . . . . . . . . . .. ... . .. . . ... . 9
Recovery from whole-body exposure . .. . . .. . . . . . . . . . .. . .. 10
The experimental effect of single doses on long-term survival. .. 11
The experimental effect of single doses on short-term survival.

The experimental effect of chronic exposure on long-term
SUMV~. .. . . .. .. . . .. . .. . . . ...... . . . . . . . . .. .. .. .. . . 14

Article: "Shorfedng of life by chrortic irradiation: the ezperimental facts", by R H . MOLE

. . . . ... .. ... .. . .. . . . . .. . ..... . .. .. .. 27
Atom bomb survivors in Hiroshima.. . . .. . . . .. . . . . .. .. . .. 28

Leukemia in man. . . .

Article: "Leukentio irt Hiroshifrur City Atorrric survivors", byNIELWALD. . . .. .. . . . . . . .. . . . . . .. . . . . .. ... . .. . ... .. 33. . .. . . . . . . . . . . . . .. . . . ... . . . .. .. 34
Leukemia in children . .. . . .. . . . . . . . . . . . .. . . . . . . . . . . . .. . 35
Leukemia after X-ray therapy for ankylosing spondylitis.. . . 40
Leukemia in radiologists

Theoretical considerations for estimation of radiation hazards 47
REFERENCES

I. SHORTENING
OF TIIE LIFE-SPAN IN( b ) The intermediate period whose duration of 1.5-2
years depends on the radiation dose, and during which
practically no deaths occur;(c) The terminal period during which the population
dies out rapidly.

EXPERIYEXTAL A N I X A L S

The experintental effect of single doses
on sltort-term szwvivol
1. The short and long-term effects of whole-body exposure to a single dose of radiation have been studied
in a variety o i mammals. JVhen "survival time" (duration of life after exposure) is studied as a function ofradiation dose, the rcsults with all species have shown
fundamental similarities that may be illustrated herewith the data of a hypothetical experiment.
2. The plan and results of the hypothetical experimentare shown in table I and figure 1. The animals wereyoung adult males, 100 days old on irradiation. They
were of a species with a relatively short life span of
2% years. Slightly different results would be obtainedwith females. Greater effects per unit of radiation dosewould be obtained with immature animals or with sickanimals.
3. The mortality-time curve (figure 1) illustrates
three major periods :( a ) The acute period lasting about one month, forwhich the LD,, is 600 rein ;4. Long-term somatic effects develop during the intermediate period and some of them become "limiting
factors" for survival in the terminal period. The complete quietude of the intermediate period indicated infigure 1 is therefore misleading-the intermediate period
is, in fact, a period of increasing morbidity. The rate ofincrease may be slow or fast, depending on the radiationdose and also on various biological factors, many ofwhich are predetermined genetically.

5. The long-term decrease in life-span, illustrated infigure 1: is dealt with quantitatively in the sixth column("Days") of table I. The decrease is not proportional tothe acute mortality (column 4). The decrease can also
be expressed as a percentage of the normal life span(column 7), which in the present experiment was 900
days. It is useful to express life-shortening in per centof normal life span for purposes of comparing resultsof experiments involving species that differ in life-span.

The animals (males, 100 days old) received a single whole-body exposure on =perimentday 0. The table records the doses given to the various groups, and the resulting changes intheir median life-spans.

hdiationGroup

Num+r oflire anrmals

dare

?em

-

1 .........
2
3 .........
4 .........
5 .........
6 .........

.........

DOY 0

Long-term decrease inlife-span

Median s u w i dlime of animals
dior on day 30
dars

Day 30

Daw

0
300
500
600
700
800

100
100
100
100
100
100

100
100
82
50
11
0

Per unl of

-

~

800
710
650
600
530

90
150
200
270

-

-

&aP

A

10
17
21
30
A

The ditTerence between the datum for group 1 (800 days) and the data for other groups
in column 5 (median survival time).
The l i e span of the controls (group 1) was 900 days

6. The dependence of biological effect on radiationdose is illustrated in figure 2. In the case of acute mortality (deaths within thirty days of exposure calculated
from table I, co~umn4), the dose-effect curve shows athreshold-the first deaths occur somewhere between
300 and 500 rem. In the case of the long-term decreasein life-span (per cent of normal life-span) the courseof the curve as drawn does not show a threshold andindicates that even at the smallest radiation doses there
is some decrease in life-span (see paragraph 11).

7. Biological effects not only depend on radiation dose
but also on dose rate. I n the hypothetical experiment, theanimals received a single dose at 50 rem/min. The same
results would have been obtained with dose rates of 5or 500 rem/min. Below 5 rem/min., however, the effectper unit dose diminishes. In the case of acute mortality.
it does so relatively rapidly. It may do so quite differently in the case of the various lcinds of late injuries,
including those shortening the life-span.
Tlre acute LD,,
8. Recent determinations of the acute LDSO(sing!e,whole-bodyfor mature mammals are given In

table 11. Values for immature and senescent aniplals
would be lower than those tabulated. It has been pointed

TABLE
11. ACUTEX-

GMIbf-4-R4Y LDso

OF MATURE MAMMALS'
SPCCUSswine..

z ~ (rods)
r

1w310
210
Goat .........................
Dog- ......................... 240-320
Alan. ........................
300 (?)
Guinea pig.. .................. 380490
Monkey.. ....................
520&louse.. ...................... 520470
Hamster.. .................... 590-800~ ~ b b i t.....................
..
680-750....................... 790-S20........+a.e..........

NU=.& pf
dcrmnrnclrons

4
1

6
0
3
1

7
3
3
2

The original reports are listed in reference 1. All doses are
estimates for the middle-longitudinal 2xis of &e animal underconditions of approximately homogeneous soft tissue d o e distribution. The dose rates ranged from 5-60 rads/min. The LD6ois that d o e killing half the animals within 30 days of exposure.
Almost all of the deaths occur within three w e e k .

154

-

800

-

t

+ .;
I

4
B

-

HYPOTHETICAL EXPERIMENT

-

-

-

-

-

-

-

E

S

B
3

-

U

-

-

I

A

I

1

I

0 30

I

I

I

200

I

400

r

I

600

I

800

DAYS AFTER IRRADIATION
Figrcre 1. Hypothetical experiment-Cumulative mortality after a single whole-body exposure.
The dose in rem is specified for each curve.

1

100

I

I

1

I

1

I

I

-

-

80 -

-

ACUTE MORTALITY

w

-

U

60-

HYPOTHETICAL EXPERIMENT

Sr

ka

H

EU
9:

40

-

-

20

-

-

W

PC

LONG TERM DECREASEIN LIFE SPAN

-

0
1

100

I

I
300

I

I
500

I

I

700

RADIATION DOSE (REM)
Figure 2. Hypothetical experiment-Effect as a function of dose. Acute mortality shows athreshold whereas long term decrease in life-span does not.

I

out1 that the values fall into two groups. Those for the'.largerJ' mammals are in the range 200-300 rern ; thosefor the "smaller" mammals are in the range 400-800 rem.
The only monkey listed (M. mulatta) falls into the"small" animal class. The estimate for man is close to thedeterminations for the guinea pig and dog, suggestingthat studies with these species may be of speaal importance. I t is to be noted, however, that the figure for man
is speculative.
Acute effects in single orgalis
9. A very great number of somatic effects have been
described that occur within hours, days, or several weeks
of irradiation. Doses as low as 5 rem, for example, havea measurable although brief effect on the mitotic index
of the skin of mice.2 In the range from approximately
25 to 200 rern, simple qzcantitative relations between
somatic effect and radiation dose have been demonstrated
in such organs as the lymph node, spleen, thymus, testis,using both microscopic and gross methods
and inte~tine,~of examination (e.g., weighing). In these examples, restitution occurs relatively quickly, during the course ofsome days or weeks, and often seems complete.
Recovery from whole-body exposure
10. When two or more exposures instead of one are
employed, some restitution occurs during the interval(s)between them. One method to study the rate of restitution is to give a non-lethal dose on day 0 and to determine
the LD,, on various days thereafter. Suppose that theLD,, of unirradiated animals is 600 rem. Furthermore,
suppose that after 300 rern on day 0 the LD,, is :(a) 300 rern on day 1 :( b ) 450 rern on day 2 ;(c) 600 rern on day 8 :(d) 600 rern on day 20.

TABLE111. T n r ~FOR 50 PER CENT RECOVERYFROM A SINGLE THOLE-BODY EXPOSURE TO X-RAYS'

Nu&

12. The data in figure 3 are based on exposure inyouth or early adulthood. Comparable data for exposure
during middle age or old age are not available.
13. I t is Anown from clinical as well as laboratory

evidence that partial-body exposure decreases the life. spanmuch less than whole-body exposure (when theeffects of roughly similar doses in rads are compared).
There is a paucity of information, however, concerning
the quantitative dependence of the life-span on (a) theregion or organ irradiated and (b) the absorbed dose.
The data from an experiment of this type are given intable 1V.O hllore information of this kind is needed.

TABLE
IV. DECREASE LIFE-SPA-KPARTIAL Ahm WHOLE-BODY X-RAY EXPOSURE
COMPARED IN THE U O U S E ~Region cxjmscd

I t may be concluded therefore that acute recovery from300 rem was complete by day 8, since by then the LD,,
had returned to "normal", and half-complete by day 2.
Experiments of this type (table 111) have shown that therate of recovery depends on genetic factors, and therefore varies with the strain and species of animal.' The
rate also depends dn the magnitude of the dose-large
doses may. so to speak, inhibit the recovery process
per se.

Animaltime of puberty or young adulthood are summarized infigure 3.5 The radiation dose is expressed as a percentageof the acute LD,,, e.g., a dose of 300 rem is called 50
per cent if the acute LD,, is 600 rem. In the various
experiments, the LD,, (in r ) varied from 500 to 800 r.
The curve fitted to the points in figure 3 is on the assumption that life-shortening is directly proportional
to dose. For mice and rats it appears that life is shortenedby about 10 per cent following a "25 per cent dose".
The curve drawn through the points in figure 3 runs
straight to the origin, indicating that radiation decreases
the life-span no matter how small the dose may be. I t is
to be noted that the figure only suggests this conclusion,
but does not prove it.

ofsbainr

X-ray dose(~nn)

50 gn unt
relime(days)

Mmc
Young ................
Adult .................
Adult.. ...............
Rat .....................

1
6
1
2

260
200-400
310

7.4
1.6-3.0
12.0
4.9 and 8.5

Munkcy (M.mulotla). ....

1

260

4.8

600

Recovery measured undcr the particular conditions describedin paragnph 10. The original reports are listed in reference 4.

The experimental eflect of single doses
on long-term sr~rvival
11. Data on life-shortening in mice and rats after asingle whole-body exposure to X- or gamma-rays at the

Dose

(?em)

Control.. .................
0
Entire animal.. ........... 530
Entire chest.. ............. 720
One-half chest. ............ 570
and caudal. ............... 1140
2cm. of trunk ............. 1700

JfcdiarSins canfly
sumidtinu
digad
after czporure from Mlbd
(dous)(P 6 .05)

676
582
646
654
591
525

Yes
No
NO
Yes
Yes

-

Female mice, 170 days old when irradiated. With the doses
employed there m-ere no acute deaths. Data from reference 6.

The experiw~e+ital
efect of chronic exposure
on long-tertn sun~i-~al
14. The experimental literature on the shortening oflife by chronic exposure to radiation, and its bearing on
the ma-ximum permissible dose for man, are discussed
in the article by R. H. Mole,7 presented in its entirety
following paragraph 15. Among other details, the reportconsiders whether a threshold dose c ~ i s t sbelow which
the life-span is unaffected. The report finds the evidence
equivocal. A significant conclusion might be established
for animals if very great numbers of them were used insuch experiments. The report points out, however, thateven if such a conclusion \\-ere established, its application to the human caserequ3e a theoretical basis
to justify such an extrapolation. Such justification islacking at present.
15. Of the experimental groups referred to in paragraph 14, two (mouse. guinea pig) that received less than
1 rern per week lived a greater total number of days thantheir respective controls. In a more recent experiment8
with Sprague-Da\vley male rats exposed throughout

1

50

-

I

I

I

I

t

I

1

SINGLE DOSEDOSE IN PERCENT OF LD- 30 DAYS

Figure 3. Life shortening (percentage) in mice and rats after a single, whole-body exposure
to X- or gamma-rays. The dose is expressed as a percentage of the acute LDm The figure istaken from reference 5 where the original reports are listed.

I
I
I

adult life to 0.8 r/day of CoeOgamma-rays, the mediansurvival times were as follows :Tmpcrature ofennironmnu

Srtrpkal time (days)

CWd

5O C.. .................. 240
2S°C .................... 460

Inadiakd

305
600

Although there were only twenty-two animals per group,
the differences between the irradiated and control groups
were consistent throughout the course of the experiment.

I

1

I

Medical Researclt Coutrcil Radiobiological Research Unit
Afonric Energy Research Establishment
Hanuell, Berks., EnglandI t is probably true to say that more is known of thebiological effects of radiation than of any other environmental hazard except bacteria. Certainly the chronic
toxicity of no chemical substance has been investigatedas thoroughly as the chronic toxicity of whole-body irradiation by penetrating gamma-rays or fast neutrons.
The incentive has been obvious : the very large industrial
hazard during the mar-time development of the atom
bomb, and afterwards the increasingly widespread risk
associated with the remarkable development of atomic
energy as a source of industrial power and of a uniqueseries of military weapons. Chronic toxicity =perimentsin the strict sense must cover the whole life-span of the* UN document A/AC.82/G/R.l15:also published in Nature

180,456-460, 1957. For table 1, figures 1 and 2, and bibliographyreferred to in this article, see immediately following the arncle.

experimental animal and thus take years to carry out,
even with the relatively short-lived laboratory mouse.
The results of war-time work in the United States havebecome generally accessible in the past few
andwork carried out in this laboratory is just beginning to
A brief survey of the experimental resultsbe p~blished.~
relating to shortening of the life-span may provide a few
facts in a field of current general interest and perhaps
raise the academic question of how the results of chronic
toxicity experiments, as such, may be generalized-aquestion which needs an answer before they may be
used to help solve the practical problem of setting safe
limits to the environmental exposure of man to irradiation.

Daily irradiation has been given to animals in a variety
of ways. for details of which the original reports should
be consulted.'-' The more important experimental features are summarized in table I. There are two importantdifferences between the experimental arrangements ofHenshaw et aL3 and Evansz on one hand, and those ofLorenz et aL4 and of this laboratory on the other. I n thefirst two sets of experiments, the animals had to betransferred individually each day from their living cages
to the irradiation boxes and back again. and each daily
dose of radiation was given in a few minutes. In thesecond two sets of cxpenments, the animals mere irradiated in their living cages, undisturbed by additional
handling with its accompanying traumatic effects, andthe daily dose of radiation was spread over 8-24 hours.
In general, the experimental animals were examinedture of the data, it would be difficult to have a clearer experimental demonstration of the existence of a threshold.
(2) The biologist, almost as a reflex, attempts to fit
a Gaussian cunre to quantitative data. Such a curve isshown as a dashed line in figure 1, and clearly fits all theexperimental data very well. The meaning of the fit atweekly doses of less than 10 r., where none of the points
differs significantly from the base line, is less clear.
( 3 ) Boche (1946, 1954)' suggested that shortening
Reszclts ar~dtheir ittferfiretaiiotz
of life-span was proportional to the total accumulated
By chronic irradiation is meant daily irradiation five,dose,
six or seven days a week at dose-levels which allow surt - to = kdt
vival for at least six months. All the experiments on
where t and t,were the mean life-spans of irradiated andchronic irradiation for the duration of life which havecontrol animals, d was the daily dose of radiation andever been carried out, so far as is known, are referred tok was a constant. This curve (k = -0.04 for gammain table I and, where possible, shown in figure 1. The durays) is shown in figure 1 as a dotted line, which also
ration of life of an irradiated group of animals has beenfits all the experimental points very well.
expressed as a proportion of its corresponding control
and plotted against the weekly dose of radiation on a
Curves 1 and 2 are empirical : curve 3 has some claim
logarithmic scale. The results from this laboratory are
to a theoretical basis. the idea that the bigger the totalshoum in black symbols. They provide the first dirkt
dose of radiation the bigger the effect, that is, the shorter
experimental comparison between gamma-rays and fast
the mean life-span. For daily exposures which kill inneutrons for chronic irradiation, where the dose of fastless than six months, however. the converse is found toneutrons was measured in terms of energy absorbed in
be tr~e.'~~*l'This is not as paradoxical as it may seem,tissue. The relative biological efficiency factor for theonce the importance of recovery processes is apprecifast neutrons used as compared with cobalt gamma-rays
ated; but it makes data on the effects of high daily doses
was 13.
(on shortening of life by much more than 50 per cent)This factor has been applied to the other two fastof little value in helping to decide which is the best ofneutron experiments, where the fast-neutron dose wasseveral curves, each purporting to describe the effects
measured in arbitrary units and where a somewhat unof low daily doses.
certain conversion factor (table I) has to be used forCurves 2 and 3 are clearly so dose together that overestimating the tissue dose. In this way the results of a l ltheexperimentally determined range they cannot be disthe experiments with fast neutrons as well as those withtinguished.
(The possibility that this algebraic similarity
gamma-rays from other laboratories have been plotted,
has
a
much
wider
biological significance is being investiusing open symbols, together with our own results ingated.)
Each
curve
appears to fit all the points better
figure 1. The agreement, when mice were used as experithan
thestraight
line
of curve 1, but this may be a spurimental animals, is remarkable, and suggests, in spite
ous
consequenceofexperimental
uncertainties. In twoof the various uncertainties in the comparisons, thatexperiments the exact conversion factor from arbitrary
chronic irradiation shortens the life of mice in a reprounits of fast neutrons to rads is unkown (see above)
ducible manner.
and factors numerically different from those used (tableI t should be noted that there are eight experimentalI) but just as plausible (see literature) would make thepoints at weekly doses of less than 10 r. or its equivalent
fit look less good. There seems to be no intrinsic reason
in neutrons, and that the duration of life in none ofwhy different mouse strains should behave identically,
these experimental groups was significantly different
and the curvilinear arrangement of the experimental( P 2 0.05) from its control.
points may merely reflect differences of strain andof dose.
The experimental results have bee11 put down as they
were obtained. hfore sophisticated analyses of some ofEach of the second two formulations indicates that~ * ~pur* ~ ~ ' ~there is no absolute threshold for shortening of life bythese results have been made e l s e ~ ~ r h e r e . ' ~Thepose of such analyses has usually been to find some reguchronic irradiation. The apparent threshold suggested
larity in the results which would all~urextrapolatioils to
by curve 1 may be thought of either as an absolute o r as
daily doses smaller than, and to species other than, thosean effective threshold, depending on whether shortening
used experimentally.
of life is considered in proportional or absolute terms.
If time is necessary for the effects of daily irradiation
to show themselves. and if this time is longer the lower
Three curves have been fitted to the mouse data andthe daily dose, then an effective threshold ntwt be
are shown in figure 1.
reached at a dose-level which takes longer than the life( 1) The straight line which provided the relative biospan to produce its effect. If so, each species would be
logical emciency factor of 13 from our second experiexpected to have its own threshold. and the longer thement (Xearq. ei d.,11, table I ) is clearly a good fit to its
natural life-span the lower this would be. The only releresults, and is.also reasonably close to the only experivant esperimental data are those of Lorenz ef al.' on
chronic irradiation of guinea pigs and these are included
mental group in our first experiment with a markedly
decreased sun-ival-time. The simplest interpretation of
in figure 1. The effect of 1.1 r dzily was possibly greatersuch a linear relation is that there is a threshold of bethan in mice (though still not significantly different fromtween 1 m d 2 r. daily below which no shortening of aits control) and the apparent threshold possibly a little
mouse's life will be produced by daily irradiation. This
less. The difference in life-span between mice and guinea
may be considered confirmed by the repeated experimenpigs is probably not large enough to decide the point,
tal failure to find a demonstrable shortening at n~eeltly and in an event there are no confirmatory data for guinea
doses of less than 10 r. (see above). Considering the napigs as there are for mice.
daily and the time of death noted. Post-mortem examinations to determine tumour incidence and the cause ofdeath were usually made, but the =perimental reports
cliff er very greatly in the detail with which these findings
are given. For this reason, and since shortening of lifespan is often considered the most sensitive experimental
index of the toxicity of chronic irradiation, survival-timeis the only experimental end-point considered here.

,iThe data for guinea pigs do show that species differences occur. Bochel suggested on. admittedly tenuous
evidence, that the constant k (curve 3) is a t , where a isthe same for all mammals. If this were true, the mouse
data should not agree so well, since to for the different
mouse strains differed. If the mean mouse t, is 600 days,
a = 7 s le5(rather different from Boche's own estimate)! and this has been used to construct the theoreticalcurve for guinea pigs (at, = -0.09 curve 3, figure 1 ) ;the fit to the experimental points is poor.

In any event, too much should not be read into theresults because of the nature of the experimental material. First, the results have all been espressed in termsof mean survival-times. This is really a rather unsatisfactory parameter to use, as may be seen from figure 2,
which illustrates the shape of the mortality curve of
normal control female CBA mice. The shape of thehuman mortality curve in the more materially advanced
human civilizations is similar. but that of mice with ahigh spontaneous incidence of leukemia may be very
different.'3l2 The mean survival-time and its statistics
are markedly affected by the occasional early deaths andno great precision in mean survival-time can be expected.
A small decrease in mean survival-time could occur
either because of a small increase in the frequency ofearlier deaths or because of a small reduction in life-spanof the upper two quartiles. In fact, an analysis of causeof death in relation to duration of life is imperative inorder to see whether irradiation decreases life-span byincreasing the frequency of particular causes of death
which kill earlier than the average, or merely by making
all causes of death kill at an earlier age.0
Second, the nature of a chronic toxicity experimentusually, if not invariably, makes it impossible to randomize treatments and to ensure that the only difference
between experimental groups is the treatment being investigated. F o r example, if animals are arranged at different distances from a source of radiation, the animals
will occupy different parts of a room for their whole
lives and it will be impossible to be sure that environmental temperature, humidity, degree of air movement
and other relevant factors possibly not even thought ofare exactly the same for each different dose-group. Thus
the differences in, say, mean survival-time between different groups, mill be due to the differences in radiationlevel plus any other relevant environmental differences.
This is not just a theoretical point. Differences of theorder of 5 per cent in the mean survival-time of female
CBA mice have been found during the past few years
not only between different "lots" of controls but also
between two sets of randomly chosen controls kept, so
far as could be, in the same environment but some 20
feet away from each 0ther.O The apparent increase insurvival-time at the lowest daily dose used by Lorenz
et al.' (figure 1) may well be due to the fact that the
animals at this dose-level were kept without air conditioning in a different room from all the other groups,
including the controls. Such variability is to be expectedby the biologist, but it should also enjoy caution in extrapolation of the results of analysis of intrinsically in=act data.
Replication on a sufficiently large scale, though often
completely impractical, could overcome this particulardifficulty. I n fact, however, replication is almost completely lacking from the =periments listed in table I.
The logic of experimentation is that experiments arerepeated and give the same result. Yet with the esceptionof a still unfinished investigation,^^ no one concernedwith duration-of-life irradiation experiments has everrepeated his esperiment even once--for whi& there areperhaps understandable reasons. The nearest to ppetition so far has been the two =periments carried out inthis l a b o r a t ~ r y , ~where* ' ~ although the same mouse strain
was used the radiation doses were different. Fromthis
point of view the value of figure 1 is to demonstrate thatan esperiment has been done, that is, that the same result
has been obtained several times over.
Lastly, it should be pointed out that in all the experiments considered here irradiation has been for the durntion of life. This may not be the most appropriate experi~ +well' ~ as olderq4.16
ment to carry out. R e ~ e n t , ~ * asevidence has shown that, in some circumstances at least,
not all radiation is of equal value, the first of a series ofdaily doses having proportionately greater effects inshortening life and inducing leulcemia than the later
daily doses. This is presumably one aspect of the time
factor: time is needed for the effects of irradiation todevelop to the point where biological damage can bed e t e c t e ~ l . ~ ~and/or~ ' + - ~ ~the reactivity of the biologicalobject may change with age." But if the phenomenon istrue of weekly doses of less than 50 r., which has not yet
been demonstrated, formulae which give equal weight toeach of a series of doses as Boche's, cannot be properly
estrapolated. Further, if at relatively high daily doses
much of the radiation is wasted, so far as producing aneffect is concerned,ll then an observed linearity of response against total dose (curve 3, figure 1) may imply
a decreasing ability of radiation to harm as the daily
dose decreased.
There has also been very little work yet on the problemof whether the effect of chronic irradiation is alteredby changing the distribution in time of, say, a constantweekly dose. The data of table I and figure 1 suggest thatit matters little whether a daily dose is given in a few
minutes or spread out over many hours; but other as~ ~ * ~ ~ that the deyet uncompleted o b s e ~ - v a t i o n s suggest
layed effects of irradiation may depend as much on theway the irradiation is given as on the total dose. I nthese experiments there was no wasted radiation: on
the contrary, as much time as possible wvas allowed forthe full development of any damage that radiation may
have caused. Such experiments may give a relation between shortening of life and dose of radiation very
different from those shown in figure 1, and indeed thismight well be anticipated by anyone aware of the normal
complexity of biological phenomena. Dose-response
curves should not be extrapolated without fully realizing
the nature of the =perimental material on which they
are founded.

Possibilities of extrapolation
It should first be emphasized how unusual it is to pay
any attention to the ends of a biological dose-response
curve. Normally, the aim of the biologist is to work In
the middle ranges and, if irregularities appear at theends, this is regarded as just to be expected, not necessarily deserving investigation.
The current maximum permissible level of radiationfor occupational exposure of man, 0.3 r. weekly (Recommendations of the Intenlational Commission on Radiological Protection), is indicated in figure 1. Extrapolation suggests that this dose-level would shorten the liyesof mice by nil, 0.02 or 0.2 per cent, depending on whlchof the three curves described earlier is taken to becorrect. As already shown, the experimental data on
chronic irradiation at low doses are not sufficiently exact
to distinguish between the curves, and the adequacy of
fit at high levels of irradiation seems quite irrelevant.
Thus the value of any attempt at extrapolation must
depend on whether there is some theoretical reason for
preferring one mathematical form to another. When thisquestion is settled, there is the additional problem of
extrapolating from one species to another.
One principle of selection often used nowadays ingeneral discussion on radiation as it affects mankind, andat first sight self-evidently sound, is to take the mostpessimistic assumption suggested by experiment or
theory for the relation between dose and effect. Lorenzs
used a very similar criterion when discussing the effects
of daily irradiation on the difficult tissues and organs ofdifferent species. He concluded that man should be considered to be as sensitive as that species of animal foundexperimentally to be the most sensitive. Clearly this is
no absolute criterion; as the range of species examined
is widened, the apparent sensitivity of man must decrease. A consistent use of this criterion would involve
denying the possibility of chemotherapy, or of selective
killing by pesticides. I t does not seem realistic to maximize pessimism as a means of choosing the best doscresponse curve.
The most plausible reason for thinking that species
differences among mammals in their reactiolls to irradiation are likely to be smaller than in their reactions tochemical agents is that the penetration of radiation into
cells is not affected by the series of permeability barriers
which every chemical agent has to pass before reaching
the site of its acti~n.'~The uniformity of the acutely
killing dose for all mammals gives supporting evidence.
However. the chronic toxicity of radiation would be expected to depend on a balance between the continuing
damage produced by the radiation and the ability of theirradiated animal to keep pace with the damage by repair.
The ability to repair and its rate must depend on manyof the structural and metabolic features which distinguishstrains and species, and, for this reason, strain andspecies differences in the dose-response cunres forchronic irradiation might be expected. Some of the ex-perimental facts can best be understood in this way.6

An alternative view is to assume that the chronic toxicity of radiation is due to processes where repair ofdamage does not occur, like genetic mutation. It may
then be plausibly argued that the genetic material of all
mammals is very similar, both physically and chemically,
and that therefore dose-response curves mill in general
be the same for all species. Such a view would suggestthat damage should be proportional to total dose, as in
Boche's formula (curve 3, figure 1). and u-ould beconsistent with the somatic mutation theory of carcinogenesis and the iact of carcinogenesis by ionizing radiation. But there are difficulties in the way of equating
damage and total dose, as already suggested, and reallyvery little evidence in support of the mutation theory ofcarcinogenesis, The theory is an easy one to accept: buteven with the most recent advances in technique its
testing seems almost impossible to envisage. However,in the experimental animal there is no simple relation
between carcinogenesis and dose of radiation, and formouse leukemia there is good evidence of the great importance of an indirect mechanism.lg Rforeover, theexperimental evidence suggests that radiation shortens
life apart from inducing cancer, and this is not easy tounderstand in terms of mutation.
If the results of animal experiments are to be carriedover to man, there must either be very good evidence
that all mammals behave alike, or sufficient human evidence of similarity with experimental animals to inspire
confidence in the process of filling the human gaps fromanimal experience. I t will at least be generally agreed
that experimental dose-response relations which cannot
satisfactorily account for all experimental results are
scarcely worth applying to the human case. I n the absence of a satisfactory theory, it seems pointless to
expend the enormous experimental efiort required todefine the relation between daily dose and life-span formean survival-times of 95 per cent and more of thecontrol: it is only in this region that extrapolation to
man is of any particular interest.
I urould l i e to thank my colleagues for allo\ving me
to make use of unpublished material.

TABLEI.
Of preceditrg paper by R. H . Mole".

Unit of irradiation cxbos~trc
LYPf ofdose Symbol
inadratwn(conansion
Dwofion used i a
G-Gamma rays fubr to Days/of daily Fie. 1
N=fast nc:rfro,rs
rods)
wcrk
dose
Smrrcr andRrfncncr

t%:nn:.dJicuscsbai?:

Shf0f

irradiation(dous)

lif~-s9cn

fiom

sfor;ofminutesminutesOn

Evans (ref. 2). . . . . .. .

5

minutes•

Lorenz et d.(ref. 4). . . Radium G
Neary et al. I (ref. 6). . Graphite N
reactorGraphite N
Neary ct al. I1 (ref. 13) . .. reactor
G[Wo
Thompson d d.(ref. 16). . 6JCo
G

8 hr.
7
6-7 1 6 2 4 hr.

0

rad

7

1 6 2 4 hr.

A

r.
r.

7
7

24 hr.
21 hr.

+.

Henshaw rt al (ref. 3). . . ./z$hite( reactor.

Lorenz el a1 (ref. 4).

.. Cyclotron N K (2.5)
r.
...
.. . .
rad.... . . RadiumGr.

{c$males

4%

28-42

- . 52-85

CBA

0

CBd
Rats (SpragueDawlcy, females only)
Guinea pigs
(hybrrd)

{

hr.

820

hledin-

475
420

500

hIediallb

75-95

703
780

240
500

&rean
Meado

90-120

585

42+

Mean

137-196

1,372

112

Mean

only)

LAP- 2

replingsunidtimc

-.

?

{ziss
.

.*

a c r 3 8 o o 0,

irradiario~r
-

6
6

G
r.
N r. (2.0).,..,.A>

5-0.ofonimals

blean survival times calculated from data provided by Hollaender and Stapleton (1948, personal communication) have beenused in fig. 1.
b Mean survival-time of the two strains combined were also
reported and have been used in fig. 1 because standard errors
were also given. However, irradiation stopped when 8-30 per centof an experimental group nxs still alive, so that the mean survival
times include variable proportions of radiation-free time.
There were real st. differences in control life-span and pm
sibly also in the effects of irradiation. The data have been pooled
to make thcm comparable with those of the other authors.
The data of Henshaw (ref. 7) have not been included because
the mean life-span of his controls %as less than a year. The dataof Boche (ref. 1) have not been included for a variety of reasons:his monkeys had tuberculosis, his mice salmonellosis; the dogs
and rabbits were irradiated in small numbers and irradiation
stopped after two years, long before the end of the natural lifespan; irradiation of the rats also ceased after two years when
16-36 per cent of the lower level and control groups were still
alive and were filled, which prevents estimation of mean survivaltimes.
Evans's X-ray data (ref. 2) have not been included becausemean survival-times were not given. The control life-span was
not given by H a p and Simmons (ref. 5). In each of Sacher's(ref. 5) and bfole s (ref. 1I ) experiments with daily X-irradiationof mice, one experimental group survived about seven months;
they are omitted because no groups surviving longer are available and because the relative brological efficiency for X- t ogamma-rays for chronic irradiation is not known.

BIBLIOGRAPHYFOR PRECEDING PAPER BY R. 13. MOLE

14. Mole, R. H., in "Progress in Radiobiology", edit.
J. S. Mitchell. B. E. Holmes and C. L. Smith(Oliver and Boyd, Edinburgh, 1956).
15. Mole, R. H., Brit. 1.Radiology, 30, 40 (1957).
16. Thompson, J. F., Tourtellotte, W. \V., Carttar.
M. S., Cox, R. S., Jr., and Wilson, J. E., Anrer. I.
Roentgelzology, 69, 830 (1953).
17. Mole, R. H., Proc. V I Int. Haematology Congress,
Boston (in the press).
18. hlole, R. H.. Brit. J. Radiology, 26, 234 (1953).
19. Kaplan, 1-1. S., Carries, W. Ha,Brown, M, B.,andHirsch, B. B., Cancer Research, 16, 4 2 (1956).

1. Boche, R. D. (1946), cited by him in "Biological
Effects of External Radiation" (edit. H. A. Blair),
N N E S VI-2 (McGraw-Hill. New York, 1954).
2. Evans, T. C., Nucleonics, 4, 2 (1949).
3. Henshaw, P. S., Riley. E. F., and Stapleton, G. E.,Radiology, 49,349 ( 1947).
4. Lorenz. E., Jacobson, L. O., Heston. W. E.. Shimkin, M., Eschenbrenner, A. B., Deringer, Margaret
K., Doniger, Jane, and Schweisthal, R., in ''Biological Effects of External X- and Gamma-Radiation"(edit. R. E. Zirkle), NNES IV-22B (McGraw-Hill,
New York, 1954).
5. Sacher, G., I.
Cancer Inst., 15, 1125 (1955).
6. Neary, G. J., Munson, R. J., and Mole, R. H..
"Chronic Irradiation of Mice by Fast Neutrons"(Pergamon Press, London, 1957). In the press.
7. Henshaw, P. S., J. Nat. Cancer Inst., 4,513 (1944).
8. Lorenz, E., in "Biological Effects of External Xand Gamma-Radiation'' (edit. R. E. Zirkle, NNES
IV-22B (3IcGratv-Hill, New York, 1954).
9. Blair, H. S., "Peaceful Uses of Atomic Energy",
11, 118 (United Nations, New York, 1956).
10. Sacher, G., Radiology, 67, 250 (1956).
11. Mole. R H., I. Nut. Cancer Inst., 15,907 (1955).
12. Sampford, M. R., Biornetrics, 8,13 and 307 (1952).
13. Neary, G. J., Munson, R. J., Hulse, E. V., and Mole,
R. H. (unpublished observations).

at.

11. LIFE SHORTENING EFFECTS IN M A X
16. Data were examined relating to the mortality of
medical specialists in order to learn if those exposed to
X-rays had a shortened life-span. In one extensive
analysi~,~utilizing the mortality data for specialists 3574 years of age who died during 1938-1942, the nrortalify
ratio was calculated for each specialty. The mortality
ratio is the ratio of the number of deaths observed to thenumber that specialty would =perience if subject to thespecific death rate calculated for all physicians. These
mortality ratios are given in parentheses in the last coluinn of table V. I t is seen, first. that specialists havq alower mortality than physicians in general ; the specialist
mortality ratio is only 0.78. Secondly, the various specialties appear to have different mortality ratios, from
0.99 to 0.62.
17. The mortality ratios of the various specialties
were r e c a l ~ u l a t e dusing. ~ ~ the death rate for all special161

ists instead of all physicians (table V). The ranking of
the mortality ratios by this method agreed with that ofparagraph 16. Eight specialties had mortality ratios
greater than unity, but in no case was the difference
statistically significant.
18. The extent to which repeated small exposures to
X-rays shorten the life of man is a matter of speculation. In the past, radiologists were so exposed, but fromthe mortality statistics it cannot be demonstrated thatthe life-span of this group of mcdical specialists has beenshortened relative to that of other medical specialists1'
although this has been suggested.*?I t is known, however,that the incidence of leukemia is increased in these men.

the incidence rate of cancer to radiation dose and to timeafter exposure. For introduction, the method of calculating the incidence rate and the influence of certain
variables on it will be discussed briefly.
20. The prevalence of cancer may be defined as thenumber of cases per unit of population at a specified
time, e.g. 15 cases per 10,000 on January 15.
21. The cancer incidence rate R may be defined as
the number of new cases per unit of time and population
occurring during a specified interval of time, e.g., 5 per
10,000 per annum. Alternatively, it may be said that an
estimate of the probability that an individual in the
population will acquire a cancer equals 5/10,000 or 5 x
lo-' per annum. R is an important statistic in the calcu111. CANCER
IN M A N
lations to be made below.
19. It is generally agreed that the incidence of can22. The total effect of exposing a population to radiacer* in man can be increased by exposure to ionizing tion is estimated in terms of the total number of cases,
radiation Quantitative data will be considered relating ,,'- induced per unit of population. If the rate after
exposure is constant at R, and if prior to exposure it*Cancer is a generic term and, as used here, includes leuwas
constantly R,, then (R-R,,) is the number of extra
kemia and all forms of so-called neoplastic o r malignant disease.

FAST

NEUTRONS

rads / week

Figrrre I (of preceding paper by R H. Mole). Mean survival-time (per cent of control) andweekly dose o i radiation (logarithmic scale).
The symbols are given in table 1. The curves are numbered 2s in the test, where they are
discussed. The gamma and neutron scales are in the ratio 13 :1 (see t e s t ) .

AGEFigure 2 (of preceding paper by R H. Mole). Cumulative mortality of female CBA mice(four different control groups 1951-54). All times plotted from same starting age of 70 days.

Rank

1.
2.
3.
4.

5.
6.

7.
8.
9.
10.
11.
12.

Specially

Obseror4 &allrr

Expected & a l hMoriality rafi*

Tuberculosis.. ..............................................
Dermatology ................................................
Roentgenology and radiology. ................................
Anesthesiology..
Orthopedic surgery, proctology, urology and-idustrial surgery.. ..
Neurology and psychiatry.. ..................................
Public health.. .............................................
Suwry ....................................................
Obstetric3 and gynecology.. ..................................
Eye, ear, nose and throat ....................................
Internal medicine and pediatrics.. .............................
Pathology and bacteriology.. .................................
Au

43
60 (58)b96 (91)b
17
199
142
99
360
112
502
378
38
2.046

34.2
47.8
82.4

1.26 (0.99)
1.25 (0.98)
1.16 (0.90)- (0.88)
1.11 (0.86)
1.07 (0.83)
1.OS (0.83)
1.04 (0.81)
0.96 (0.75)
0.96 (0.75)
0.89 (0.69)
0.79 (0.62)"
1.oO (0.78)............................................

The ratio of (observed deaths i n a specialty at ages 25 to 74
years) t o (expected W h s a the basis of age spccifi deollt rates ja
all specialists, 1938-1942). The ratios a-ere calculated from data
made available by Dr. &I. Spiegelman. The figurs in parentheses
are the published9 mortzlity ratios for specialists based on the

-

179.1
133.0
94.3
346.7
116.3
523.4
423.6
48.1

age specificdeath rates for all ph sicians (instead of all specialists)a t ag-et 35 to 74 (2,046 deathsf Note that the ranking of themortality ratios is the same for both methods of calculation.
b Omitting deaths from leukemia.
Pathology only.

cases per unit of population per annum. In a period of
T years,
Nx = (R - R+)T
(1)
Although simple in principle, the use of equation ( 1) issomewhat difficult in practice. First, R is not a constant,but varies with times. In general, exposure is followedby an initial period during \~+ich few if any radiationinduced cases occur. The duration of the initial period
may be shorter after large doses than after smaller ones.
Thereafter, depending on the particular cancer studied
and the nature of the population, there will be a second
period during which the vast majority of radiationinduced cases occur. This period might last for five years
or for twenty-five. We are now only in the process ofIcamin what the duration of such periods may be.
Second y, precise values of R, may not be available. In
the case of some kinds of cancer there is some evidence
that R. is changing relatively rapidly (e.g. leukemia).
F o r these, it would be necessary to estimate the changes
in R, as a function of time independently of the changes
in R. Thirdly, the numbers of radiation-induced cases
actually dealt with are very small, as will be seen below.

f

3.Having obtained a method for estimating N,,it
becomes feasible to investigate how N, depends on thedose of radiation, D. Is N,, for example, a simple linear
function of D, is it a non-linear function or is there athreshold dose below which radiation is without effect?
Before a t t a c h g such a problem, it is important to notethat the same dose may result from a single exposure,
multiple exposures, or a long period of continuous exposure. Such differences in dosage may lead to majordifferences in the end results and therefore must be
esplicitly dealt with when making comparisons or
ex-trapolations.
24. It is worth special note that the factor of time hasentered the problem in more than one way. I n equation(1) paragraph 22, there is the term T, often referred toas period at risk. In paragraph 23, the role of time indosage is considered ; this may be referred to as periodrclder exposure. The period under exposure may lastfor only a minute and thus be an insignificant fractionof the years at risk. On the other hand, in the case oflong-lived isotopes, for example, the period under exposure may be a matter of many years and thus partiallyor even completely overlap the period at risk.

wise expressed? Should the integral absorbed dose beconsidered ?
(b) Tettrporal factors. 'Mihat allowance, if any,
should be made for multiple or continuous exposure?
Is each successive year at risk of equal significance?
(c) Co,tstitutional factors. What is the nature of theirradiated population with respect to age, general health,genetic constitution, etc. ?
(d) Dose-effect curve. I s there a threshold? I s theeffect a linear or some other function of dose? Can afactor be determined that will relate hTxto D ?

Leukemia in vron
27. Demographic data relating the incidence of leukemia to radiation exposure come from four populationgroups whose exposures were either a hazard of war or
profession, or were incurred during diagnostic andtherapeutic medical procedures.
Atont borttb survizvors itr Hiroshima
28. The most recent information on the incidence of
leulcemia in the Japanese survivors of the 1945 atomic
bomb is given in a report which is reproduced in paragraph 33 below. From the condensed summary in table
VI of the Hiroshima data, it is seen that the incidenceof leukemia in the population exposed at 0-1,499 metresfrom the hypocentre has been twenty times greater thanin the population exposed a t 1500 metres and beyond.
Thus a t the end of 1957, N (0-1,499 m.) = 5570;
N ( > 1,499 m.) = 280. N is the total number of cases
per million persons present at the time of the explosion.
Taking the cases at 1.500 metres and beyond as a crude
estimate of the natural incidence of leukemia, the nurnber of cases N , due to radiation may be estimated as
5,570 - 280 = 5,290, or in round numbers 5,300 per
million.

TABLE
VI. LEUKEIIIAIN SIJRITVORS AT HIROSHIMA,
1948-1957'

1.500 and

Period of oascl

25. Constitutional factors are l a o w n to influence theproduction of cancer in man. These include race, age,sex, nutrition and other environmental and genetic influences. All of these factors have to be taken into
account in discussing the production of cancer in man
through exposure to ionizing radiation, especially whencomparing the effects in one group with those in another.
26. The tot21 of all human data that can be used forthe quantitative analysis of cancer-induction by radiation is meagre. For esample. only sixty-eight cases ofleukemia are involved in the Hiroshima data of table
VII. It is im~ortantthat full use be made of suchdata while at the same time recognizing and giving due
weight to their limitations. In the, case of the calculations. extrapolations and applications that follow, thereader is urged to note the simplifying assumptions that
may have entered into the analyses, especially in regard
to the follo\vmg items :(a) Absorbed dose. In what organ is the absorbed
dose to be determined? If the dose is not uniform
throughout the organ, ho\v shall it be averaged or other-R (average of cases per year per 106).

Tofol

. 84

&1,399beyond557

28

Data from reference 13. The full report from which theseand the data of table VII were taken is s v e n below.
b 10,051 persons were esposed at 0-1,499 metres; 85,768 were
esposed at 1.500 metres and beyond.

29. The data in table VI indicate that t l e biennial rateof leukemia in the heavily esposed population reached
its ma.imum in 19j0-1951 and has been declinillg siilce
then. If this tendency continues. practically all cases ofha\.e occurredradiation-induced leukemia
bv 1960, within fifteen years of exposure, so that at
1Gase ~ 0 ' ~ cente r of them may be said to have occurredalready, within ten years of exposure. In these circurnstances. the annual rate of leukemia taken by itself is notTABLE
VII. LEUKEVL~INCIDENCE FOR 1950-5;
Duiance from

%?

zonc

A

under 1,000
1,000-1,699
1,500-1,999
2,000-2,999
over 3,000

B
C
D
E

L
(Cores of

Nb

Dose
(red

Persons
ez$osed2cuRc11:su)s/t(tofal rases
per I@)

1,300
500
500
2
0

1,241
8,810
20,11332,69232,963

15
33
8
3
9

3.9
5.7
2.8
1.7
3.0

12,087 f 3,143
3,746=t 647
398 f 139
92 f 52
273 f 91

Based on data in reference 13. Prior to 1950 the number ofcases m a y be understated rather seriously.
b

AFTER E-XPOSURE AT HIROSHIJLL~

The standard error is taken as N (V La).

a good index o i the total radiation efiect ; it is the total
number of case N , that should be employed as such ameasure.
30.
thethe -pased population
segment thatthe hypocentre has had thegreater incidence of leukemia. However, the quantitative
relation between leuketrtia hcidence i?z Hirosliima andradiatiotr dose is not yet known. Before such a relation
can be formulated it will be necessary to have better
estimates of the absorbed dose in rev&than have been
available hitherto. The estimates must be made both forthe various dose zones in which the ~ 0 ~ u l a t i owas
n distributed, and, also, for every individ&dAcaseof leukemia,
taking into account both its position within the zone andthe shielding immediately around it. Such work is underway.
31. None the less, using such data as were available,
estimates have been made of the ~ o t e n c vof this bombradiation in causing leukemia.li ~ g exp&edepopulationsof Hiroshima and Nagasaki were considered to have been=posed in a 'lumber 'Ones forof which a mean
The extra probabilify of leukemia
dose wasoccurring in an =posed Person Per rem and Per Yearafter exposure was thenfor the population of each zone :''average estra number of new cases per year
(1948-1955)-

number of persons exposed X dose (rem)I n zones A (1,300 rern), B (500 rem), and C (50 rem),the values of PLwere calculated to be 0.9,0.7, and 0.7 X
l W , respectively. This finding was taken to support thesuggestion that the extra leukemia incidence is directly
proportional to radiation dose, and conversely, to argue
against the existence of a threshold for leukemia
induction.
32. PL might be used in estimating N,, the total number of extra cases of leukemia that follow a dose ofradiation. The average value of P, in paragraph 31 is
0.8 X 10-8 based on statistics for the years in which theleukemia rate is considered to be maximal. Taking 15
years to be the entire period of leukemia production(period at risk), the total number of cases (per individual exposed per rem) = 15 X 0.8 X lo4 = 12 X
lVa, O n this basis if each of a million persons receives
1 rem, a total of 12 extra cases of leukemia will eventually develop.
33. I t is of interest to apply the above method to thelatest data on leukemia incidence in Hiroshima, using
the same zoning system and estimates of dose (table

S.

(Radiationind-d casts*I@)

11,814
3,473
125
-181
ControlPL-vJrcm(-\-Jl@/ytar/,tm)

9.1
6.9
2.5
-90

1.14 x 104
0.86 X 104
0.31 X 104-11 X 104--

It has been noted ' 5 . l6 that almost all cases of leubmia inthis zone occurred in patients who had severe radiation cornplaints, indicating thar their doses were greater than 50 rem.

VII). Contrary to previous findings, the present findings
indicate that PL decreases marltedly as the dose falls,
that therefore leukemia incidence is not a linear function of dose, and that a threshold for leukemia inductioi
might occur. In fact, according to bble VII a dore of
2 rem is associateda decreased leukemia rate. I t is
to be emphasized again, however, that the estimates ofdose employed in the present and previous analyses aremuch too uncertain to permit drawing conclusions relative to the vital points in question. The calculations are
made only to illustrate how variable the results may belvhen inadequate data are utilized.
LEUKEXIAIN HIROSHIJIACITYAMXIC BOMBSURVIVORS*byNIEL ~ V A L D ~Atotraic Bomb Casualty Co~tt~tiissiotl
Hiroshima, Japan

It has become generallythat an increased
incidence of leukemia follows the acute or chronic aposure of various experimental animals and of man toionizing radiation.l Recently an a n a p t has been madeto establish a
between the probability of radiation-induced leukemia and the unit-dose ofradiation received. on the basis of data from studies ofvarious groups of'radiation-exposed human beings.?
The survivors of the atomic bombings in Hiroshima
and Napsaki, Japan, comprise two such groups. Reports
concerning the occurrence of leukemia in these populations over a period through June 1956 have been published at intervals by various staff members3 of the
I n addition. an
Atomic Bomb casual^ Commi~sion.~
unpublished compilation of certain specific detailed information requested by the British Medical ResearchCouncil was prepared in September 1955.JAn analysisof these data appeared in a publication of the Medical
Research Council6 and a portion was also published in areport of the National Research Council.'
Since that time a review has been made of all theleukemia cases known to the Atomic Bomb Casualty
Commission, and a master list has been compiled. Someof the cases on the September 1955 listing have been
dropped for various reasons, and many cases have been
added. No detailed official report has been publishedrecently in the hope that more adequate dosimetry data
might become available. This wish is nearing fulfilmentof
because of the joint initiation of a large- programme~*Science In, 699-700,19% for table 1 and bibliography referred to in this article, see immediately following the article.
t. Present address :University of Pittsburgh, Graduate Schoolo i Publ~cHealth. Pittsburgh, Pa.

dosimetry studies in 1955 by the Atomic Bomb Casualty
Commission and a group of interested organizations
including the Atomic Energy Commission's Division of
Biology and Medicine, the National Academy of
Sciences - h'ational Research Council, the U.S. Air
Force School of Aviation Medicine, Los Alamos Scientific Laboratory, and Oak Ridge National Laboratory.
The programme is designed to make possible the assignment of a specific neutron or gamma ray dose or bothin rads to the record of each survivor in the Atomic
Bomb Casualty Commission's files for whom sufficientpertinent information is available.
A detailed interim report on leukemia in the Hiroshima atomic bomb survivors is presently being prepared by various staff members of the Atomic Bomb
Casualty Commission and the National ResearchCouncil. I t will include the best currently available dosimetry information resulting from the &fore-mentioned
collaborative effort, However, because of the presentinterest in data pertinent to radiation leukemogenesis andthe desirability of making available current irlformation
obtained by the Atomic Bomb Casualty Commission,table I, summarizing results of the leukemia survey inHiroshima as of December 1957, is presented at thistime.
Certain limitations of these data should be pointed
out. The programme was initiated in 1917 but the present level of intensity of effort was not achieved until
about 1950. Therefore, while it may be assumed thatthe numbers of cases shown for the years 1950 through1956 are fairly accurate, the numbers that arose in thepreceding years may be understated rather seriously.
With respect to 1957, it is probable that additional cases
remain to be discovered with onset in that year.
The denominators of the incidence rates are estimates,
subject to errors of presently unknown magnitude. The

3 June 1953 Residential Census of Hiroshima was conducted by the Hiroshima Census Bureau and was presumably of a reasonable degree of accuracy. The categorizatton by distance from the hypocentre was madeon the - basis of Atomic Bomb Casualty Commission
investigations of 50.8 per cent of the males and 44.6
per cent of the females who reported themselves exposedto the bomb. However, it was found that 3.1 per cent of
those reportedly exposed were in fact not in the city atthe exact time of the bombing.
Apart from the uncertainties regarding the population
on 3 June 1953, it may be incorrect to assume that
migration in and out of the city during the period from1950 to the present was the same for persons exposedin different distance categories. However, despite thecurrent lack of pertinent information, the simple expedient of multiplying the June 1953 population values by
eight to obtain estimates of person-years at risk has been
adopted since the census date is roughly near the midpoint of the interval under study. This procedure seems
reasonable at present, although the magnitude of any
resultant error is hard to estimate.

In addition to the above-mentioned points, which hare
to do with the intrinsic accuracy of the data presented,
a further caution should be strongly emphasized. The
uncertainties involved in inferring radiation dose fromdistance alone are too large to support conclusions
beyond the previously reported qualitative one that thosesurvivors who received large doses of radiation-that is,
who were within 1,500 metres of the hypocentre, had asignificantly higher incidence of leukemia than thosebeyond that distance, who recei\-ed relatively little ornone.s The relationship of incidence to distance as presented in table I cannot be given a more quantitativeinterpretation because there are too many variables, as
yet unresolved, which cannot be ignored.

TABLE
I.
Of preceding paper by Niel Weld
LEUKE~IIA
LV HIROSHIMAATOMIC BOMB SURVIVORS ~ ' H OWERERESIDENTS OF HIROSHIBIACITYAT THE TIME OF DIAGNOSIS(DIAGYOSESVERIFIED BY THE ATOMICBOMBCASUALTY
CO~IIIISSION)
Year of On+&

Total

1945 .......................
1946
1947. ......................
1948 .......................
1949. ......................
1950 .......................
1951 .......................
1952... ....................
1953. ......................
1954 .......................
1955 .......................
1956
1957 .......................

Under
1.000

1.0001.499

1.5W

2.000-

1

2
1
1

1999

2999

Om
31UX)

.........a+............

.......................

TOTAL

3
7
5
9
11
11
12
6
8
6
5
83

....... 95,819
Estimated
Number of cases uith onset in
1950-1957 ................
68
Estimated person-years at risk. 766,552
Annual incidence of leukemia
per100,OOO...............
8.9

1

9

7

1
3
1
10

1,241

4
1
5
7
5
6
2
4
1
3
39
8,810

20,11332,63232,963

15
9,928

33
70,4808
160,904

3
261,536

9
263,i04

151.1

46.8

5.0

1.1

3.4

2
1
3
3
3
2
2
1
1
18

1
1
2
1
2
1

1
1

1

1
1

2
1

Based on Hiroshima Census Bureau's Daytime Population Census of Hiroshima City,

S , June 1953.

166

For example, the presently available estimates of the
air dose in Hiroshima have a large uncertainty, themagnitude of which is itself not yet definite. Also, experimental dosimetry studies at Oak Ridge National
Laboratory emphasize the need for detailed information, such as is being collected by the Atomic Bomb
Casualty Commission, concerning the shielding situationof any particular survivor at any distance. I t is conceivable that the radiation received within a light framehouse (the most common shielding situation) may varyfrom an amount almost equalling the outside air dose to
one equal to the outside air dose attenuated by perhaps
a factor of 'nvo, depending on the position of the personin the house.
I n determining the relationship of radiation exposure
to the incidence of leukemia, such detailed data must be
examined not only for each leukemic survivor, but also
for enough of the population at risk to permit calculation of statistically significant incidence rates. Until thisinformation becomes available from the dosimetry programme, it is premature to attempt precise quantitatio?
of dose-effect relationships in radiation leuliemogenesls
on the basis of the Hiroshima and Nagasaki radiationpop~lations.~
BIBLIOGRAPHYFOR PRECEDING PAPER BY NIEL WALD

1. J. Furth and E. Lorenz. Radiatio~z Biology (McGraw-Hill, New York. 1951), vol. 1,pt. 2.
2. E. B. Lewis. Scietzce 123, 965 (1957).
3. J. H. Folley, W. Borges, T. Yama~vaki,Am. J. Med.
13. 311 (1952) : R. D. Lange. W. C. Moloney,
T. k'arnawaki, Blood 9, 574 (1954) ; W. C. Moloney,
and M. A. Kastenbaurn, Science 121, 308 (1955) ;N. Wald, Acta Haematol. Jap. 20, 152 (1957) ;N. W-ald et al., "Proc. Intern. Soc. Hematol., 6thIntern. Congr. Boston, 1956" (Grune and Stratton,
New York, in press).
4. The Atomic Bomb Casualty Commission is a fieldagency of the National Academy of Sciences National Research Council, operated with funds supplied by the U.S. atomic Energy Commission.
5. "Listing of Leukaemia Cases in Hiroshima andNagasaki" (Atomic Bomb Casualty Commission,
Hiroshima. Japan, Sept. 1955).
6. "The Hazards to Man of Nuclear and Allied Radiations" (~Vled.Research Cozcrzcil (Brit.)Cntd. 9780)( H . M . Stationery Office, London, 1956). appendix A.
7. "Report of the Committee on Pathologic Effects ofAtomic Radiation'' Natl. Acad. Sci.-Natl. ResearchCozmcil, Publ. N o . 452 (Washington, D.C., 1956).
appendix I.
8. Grateful acknowledgement is made for the biostatistical assistance of Mr. Seymour Jablon. National
Research Council, and also for the aid of Dr. Lowell
Woodbuq. head of the Biostatistics Department of
the Atomic Bomb Casualty Commission, and his staff.
-4ppreciation is also expressed for the help of
Dr. Robert ill. Heyssel. who provided the hernatological data for 1957, and for the co-operation of thephysicians of both the Atomic Bomb Casualty Commission and the city of Hiroshima, who make thelong-term Hiroshima leukaemia study possible.

L e t ~ k e ~ t zitr
i a radiologists
34. The most recent estimate of the leukemia death
rate for United States radiologists (ages 35 to 74 years)

is based on the data of 1938-1952. inclusive.14 During
this period there were 17 deaths, corresponding to an
average annual rate of 610 per million. The rate observedin the population at large (corrected for age distribution) was 121 per million.
3j. Two reports have associated leukemia in children
with previous X-ray exposure during infancy or the
prenatal period. I n the first,'' a study was made of 1,700
United States children treated during infancy for a condition known as enlargement of the thymus gland. The
untreated siblings of the irradiated children served ascontrols. There were 17 cases of cancer, including 7 ofleukemia in the irradiated group; there were 5 cases ofcancer, but none of leukemia in the control group(tables VIII and IX).

TABLE
VIII. EYPECTED
m OBSERVEDU T E S FOR CA-YCER8

All cancers.. ...........
Leukemia.
Thyroid cancer. ........

2.6
.6
.08

.............

a17 (119)
7 (? 8)

6.

2.7
.6
.08

5
0
0

Data from reference 17.

TABLE
IX. DISTRIBUTIONOF NEOPWSL~ACCORDING TO m O U N T OF R ~ D I A T I O N ~--Number treated. ............ 604
Cases of leukemia.. ..........
2
Other cancers. ...............
0
Carcinoma of thyroid. ........
0
Adenoma of thyroid.. ........
0

801
5
4

313
(?I)
0

6
6

0
3

Data from reference 17.

36. In a British studyls of the history of 547 mothers
whose children had died before the age of ten fromleukemia and other cancers, it was found that 85 of themothers (15.5 per cent) reported that they had had
diagnostic abdominal radiography involving the foetus
during the relevant pregnancy. In a comparison series of
547 mothers with healthy and living children only 45(8.3 per cent) reported radiologic exposure during therelevant pregnancy (table X)

.

TABLE
X. LEuKEJ~L~
Ah3 CANCER INCIDENCE
OFFSPRING RELATED TO X-RAY EX-4lffNATIONS I N
THEIR MOTHERS DUREYG THE RELEVANT PREGN-ZNCP~
hrzmbn of molhcrs andfoetuses cx&+osrd lo
Tybe of c a w in child

Numberof cases.......... 269
Controls (living). ... 269
2. Other cancers.. ....... 278
Controls (living). ... 278
3. Total cancer.. ........ 547
Total control. ........ 547
1. Leukemia..

aAbdominal
Examinolion o f
c ~ m i n a i w n other Bar& of body

42
24
43
21
85
45

25
23
33
32
58
55

Data from reference 18.

37. The suggestion has been made that a proportionof the leulcemias and cancers in the first group, namely

7.2 per cent, may have been caused by the exposure
during intrauterine life of the patients in question.
However, radiological examination of other parts of the
body was not correlated with increased cancer incidence.
38. The data indicate a correlation between leukemia
and other cancers in childhood and irradiation of the
foetus, although alternative possibilities cannot be excluded. It is possible that some mothers who give birth
to leukemic children might be in greater need for diagnostic X-ray sen6ce during pregnancy and that in thepresent cases leukemia or cancer may have resulted independently of exposure sustained during intrauterine life.
39. In any event, the clinical indications for the X-ray-aminations of the mothers of these particular children
are not known, nor is information available on the typesof examinations performed and on the actual doses of
X-ray received by the mothers and the foetuses. Additional data and final evaluations of their significance are
known to be in course of publication (British Medical
Journal).

Leukemia after X-ray therapy f or anky1osi)tg spoidylitis
40. A dependence of the incidence of leukemia onradiation exposure has been demonstrated in a study of
13,352 cases of ankylosing spondylitis treated during
1935-1954 at 82 radiotherapy centres in Great Britain.l0
I n this series. 28 patients were certified to have died ofleukemia and 12 of aplastic anemia, as of 31 December
1955. The numbers of expected deaths were 2.9 forleukemia and 0 3 for aplastic anemia. (The over-all
death rate per million persons for leukemia in Englandand Wales has been as follows: 21 in 1935, 34 in 1945,
49 in 1954). A thorough study of the series led to thef o l l o ~ ~ ~tabulat~oning
of cases with blood disease :
,Woks

Group

Leukemia (A). ...................... 35
Probable leukemia (B). ............... 5
Aplastic anemia.. ....................
42
Undecided ..........................

F c d s

1
0

0
2

.

41. T o study the distribution of cytological types, allavailable cases of leukemia in patients with ankylosing
spondylitis, both treated and untreated were tabulated :X-ray hcokd series
prr

Lymphatic leukem'ia.. ... 3 (8)M yeloid leukemia. ...... 31 (78)
Monocytic leukemia.. ... 6 (15)Type unspecified.. ...... 9

ment, but some ( 1,119) received as many as four courses
over a period of years. Preparatory to examining therelation between leukemia incidence and radiation doseelaborate studies were made so that for each course oftreatment in each case there could be determined :(a) T h e spinal dose: the mean dose to the spinal marrow, based on the average of 3 points (upper sacral, middorsal, mid-cervical).
(b) T h e integral dose: the integral dose to the wholebody.
The distribution of doses in the entire population of
11,287 men mas estimated from the doses of a randomly drawn sample of 1,878 men. The dose of eachleukemia case was determined individually. F o r multiple
courses of treatment due allowance was made for theyears at risk a t each dose level. Dose-classes were thenrem), andestablished (e.g., 2 5 M 9 9 rem, 500-749
the crude incidence of leukemia determined in each class.
In addition, the standardized incidence of leukemia wasdetermined, i.e., the incidence standardized for age.
44. I n studying the dose-effect relationship, the following assumptions were made :(a) The significant parameter of dose is the meandose to the spinal marrow. (The spinal marrow was
always irradiated : the amount of irradiated extra-spinal
marrow was variable.)(b) There is an absolute waiting period of one year
after exposure during which no cases occur. Thereafter,
each year at risk has equal weight. (The authors considered this to be an over-simplification, but used it as apractical method of dealing with the many cases that hadreceived multiple courses of treatment).
(c) Fractionation of dose did not diminish its
effectiveness.
(d) The probability of inducing leukemia is directly
proportional to the number of man-years at risk. The
number of man-years at risk equals the product of(number of individuals given a particular dose) X(mean years since exposure-1 )(e) constitutional- factors . may predetermine agreater radiosensitivity in this population, but no allowance can be made for it.
45. Results from these studies are summarized intable XI and figure 4. I t is clear that the incidence ofUntreakd wriw
9-3 (38).i (50)1 (13)
0

'

80a

C

There is a relative deficiency of the lymphatic type ofleukemia among the X-ray treated cases, and the differaence between the two series was found to be just significant (P = 0.05).
a5
42. Only male cases of leukemia and "probable leukemia" (groups A and B) were available in adequate% a%numbers for further statistical analysis. After a single
course of treatment, the evidence of 10 cases indicatedthat leukemia occurred within 5 years. When all cases
Q
20were cons-idered, i.e. those receiving multiple courses
over a period of years as well as those receiving a singlezcourse in a mo~?thprso, it was noted that leukemia wasdiagnosed wlth~n3 years of the last treatment in 35 of1OF
37 cases.
500. KlOO
IS00
2Ka
2500
n u n dco.suinat marrow (r.)
43. The radiological treatment of ankylosing sponFiglire 4. The incidence of leukemia, standardized ior age, in
dylitis usually consisted of irradiating the spine and therelation to the mean dose of radiation to the spinal marrow : alljoints.
cases other reregion of themale patients in the study series and 'A' and 'B'cases of leugions were also treated. Most (7,215) of the ~ztients kemia, =duding co-existent cases. (Figure 4 is Figure 1 in thein the present series received only one course or' treatoriginal reference 19.)

1=
.
1

I:

I

168

involves the precise relation between the total numberof radiation-induced cases N , and the radiation dose D,
throughout an extended range of dosage. At present,such a statement cannot be satisfactorily made for any
kind of human cancer. For certain purposes, however?
a very crude estimate may be better thm none at all andhvo methods have been proposed with this end in mind.

leukemia increases with radiation dose and that the relation between them is not linear. The curve through thepoints in figure 4 is drawn to reach the control rate atzero dose without indicating a threshold for the induction of leukemia. I t should be noted. however, that only
one case of leukemia received a dose of less than 400
rern and that this case had lymphatic leukemia and had
had large doses oi extra-spinal irradiation. Therefore
the course of the curve between this dose and zero must
be regarded as practically undetermined. The slope ofthe curve between 750 and 1.250 rern appears to be relatively constant and is equal to about 0.6 new cases per
year per 106 men per rern to spinal marrow.
46. The data for the limited group of patients thatreceived irradiation to the spinal axis only are given intable XII. In this group, 1s patients developed leukemia.
-4nalysis of these dataz0suggested a threshold of 51 rernby one method and of 130 rern by another. These estimates, however, are subject to great uncertainty owing
to the small number of cases in the series and the lack ofdata for the range in question. Statistical analysis indicated that the threshold might lie anywhere between
0 and 460 rem. The slope of the dose-effect curve wasabout the same as that given in paragraph 45.

48. The first method assumes (1) that all cancer iscaused by ionizing radiation and (2) that the annual
cancer rate is directly proportional to the annual radiation dose. The total cancer incidence rate R in the UnitedStates, for instance, is now about 2,800 cases per annum
per million population. The annual background radiationdose rate is about 0.1 rem, and the dose rate from othersources is perhaps another 0.1 rern. The average annual
dose rate per individual is thus about 0.2 rem. The
potency factor k is, therefore,i.e., 1 rern will produce a total of 14.000new cancer cases
when a population of one million has been exposed.
Such a figure appears to be absurdly large. It has beensuggested that such a calculation applies only to certain
kinds of cancer but not to others. There appears to be
no scientific basis for such a selection, however.

TIteoretical consideratiotls fur estiinatiotz of radiatioia
hazards
47. The quantitative statement of a radiation hazard

THENU?rIBERS O F PATIENTS WHO DEVELOPED LEUI(EMI.4, AND T H E CRUDE -4YD STAhmARDIZEDINCIDENCE R4TES: AFTER DIFFERENT MEAN DOSES OF THEIWPEUTIC RADIATION TO THE SPINAL hLZRROW:hLXE 'Af Ah?) 'B' CASES, EICLUDIKG CO-EXISTENT CASES

TABLE
XI.'

Atcan dose to spinal marrow (r.)-?io. of men dmebping leukemia'A' cases. ....................... 'A' and 'B' cases.. ............... Crride incidence per 10,000 men per year
'A' and 'B' u s e s . ................ 0 4 9Standardized incidence per 10,000nren
per year'A' and 'B' cases. ................ 0 -49
a

1
1

2
3

6
6

3
4

7
8

2
3

3
3

1
1

2
2

3
4

1
1

1
1

3
3

2
7

2 - 16

4 -59

6.99

12.18

63 -65

5.98

1 -98

4 -66

7.21

14-44

72.16

5 -98

the same period, calculated from the mortality from leukemia
experienced by the whole male population of Britain.

This table was table 19 in the original reference.19

b The rate given for 'zero' therapeutic dose is the corresponding

rate among men of the same age-distribution and observed over

THEINCIDENCE O F LEURE&fIAAFTER DIFFERENT bfEXN DOSES O F THER4PEUTIC RADIATION TO T H E
SPLUAL >lr\mOTF: b L a E 'A) -4ND 'B' CASES GIVEN ONLY SPINAL IRR.IDIATION, EXCLUDING CO-EXISTENT CASES

TABLE
XII.'

Mean dose lo spinal t n o n m (r.)
Less

No. of man-years a t risk following exposure t o dose

250499than250

1.2501.499

1,5001.749

1.7501.999-

5,404 7,673 6,553 8,262 7,111 2,782

897

566

679 40,247

2
2

1
1

1

5 W
749

7509991.0001.249

2.000

0

or

AIL
dosrc

No. of men developing k~tkonia'A' cases. ................................
'A'and 'B' cases. ......................... Crude incidence per 10,000 men per year
'A'and'B'cases .......................... 0.49
Standardized incidence per 10,000 nren per year
'A'and'B'cases .......................... 0.49
a

0
0

2

2

3
3

4
5

0
0

1

17
18

1 -53

4.72

6-75'

8.12d

4 -47

1-44

1-83

6-82.:

8-70d

4 -47

This table was table 20 in the original reference.19

b Average dose, 2,290r.

For the group receiving 1,000-1,499r. the crude incidence
is74 91 ;standardized incidence 5 -06.
For the group"receiving 1,000-1,749 r. the crude incidence-

44

is 6.31:standardized incidence 6.82.
d For the group receiving 1,500r. 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 16-07;standardized incidence 16.82.

49. The second nlethod uses the results of the British
study of leukemia incidence in a radiation-treated population, discussed above. (The data for Hiroshima haveriot been used owing to the uncertain dosimetry.) To
compensate for the paucity of data, a number of assumptions are made in the following analysis :( a ) The significant parameter of dose is the meandose to the entire red marrow. I n uniform whole-body
expowre, the doses to the entire red marrow and thespinal marrow are the same. When only the spinal marrow is irradiated, the mean dose to the entire red marrowis probably about 40 per cent of the spinal dose.
( b ) The total number of years at risk is 15, and eachyear has equal weight. This assumption was arrived atfrom the following considerations. The mean period of
observation in the British study was 5 years ; this would
set a lower limit for all types of cases. Those 10 cases ofleukemia that received only one course of treatment all
occurred within 5 years of that treatment. For the population exposed at Hiroshima the cancer rate began falling
after 8 years. and a complete period at risk of 15 years
has been suggested. The maximum duration of theperiod at risk cannot be greater than the duration of life
after exposure. In the case of a population of children,
this could be 65 years, in the case of the usual mixed
population, the average would be about 35 years.
(c) Fractionation or protraction of dose does not dirninish its effectiveness.
(d) Constitutional factors may be neglected.
( e ) b ~ c e productionr
is a linear function of radiation dose. Linearity has been assumed primarily for purposes of simplicity. In the case of the British data fordoses below 1,300 rem, a linear relation provides a fairly
accurate fit.
( f ) There may or may not be a threshold dose. The
two possibilities of thrcshold and no-threshold have beenretained because of the very great differences they engender.
50. The potency factor k, equal to N J D , can now be
calculated. For a single exposure of the entire red marrow to 1 rem, the average annual leukemia rate is estimated to be 1.5 cases per million persons exposed. If thetotal number of ears at risk is assumed to be 15, k isequal to 1.5 X 1 , or approximately 20 cases per million
exposed per rem. 'These calculations are based on observations following single large exposures. However,under conditions of prolonged exposure at lower dose
rates, the period of risk may be longer. I n the calculations of chapters V and VII where a maximunt estimate
is wanted, the period at risk is assumed to equal theaverage remaining life-time of the exposed population(35 years). The value of k has therefore been taken as
52 cases er million per rem in the calculations in paragraph 12 of annex D and in paragraph 61 of chapter Vof this report.
51. The use of k to predict the number of cases ofleuliemia depends on the magnitude of the threshold.
If there is no threshold. N, is equal to the product of k,D, and the number of persons exposed. If a thresholdis assumed. there will be no cases in persons who havereceived less than that dose.
52. Besides the alternative possibilities of a linear relation with or without a threshold, it is possible that a
non-linear relationship may exist, as has been found,for example, in the case of many chromosonie abnormalities.?l As noted in paragraph 35 and illustrated infigure 4, the incidence oi le-A-eniia i : ~tile British study

2'

C

170

was a curvilinear function of dose. not a linear one.
A curve providing a good fit to these data is obtained
when leukemia incidence is considered to be proportional to the square of the radiation dose. In general,
curves of this type predict a finite incidence of leukemia
at small doses. However, this incidence may be verymuch lower than that predicted by a linear function
based on all of the same data.
33. The methods used above to estimate the risk ofleukemia after radiation exposure are of general use.
They may be applied both to other cancers and also to
non-cancerous lesions such as occur in the eye (cataract). the skin and in the bones. Their use is contingent
upon the availability of adequate statistical estimates of
the incidence of the disease in question related to theradiation doses received by the population at risk. I t may
be noted that such methods do not depend on detailed
knowledge of how tile radiation induces the lesion within
the cell, e.g. by somatic mutation or some other allegedor hypothetical mechanism. At present, adequate statistical data are not available for bone tumours or fortumours of other organs to make such estimates of risk.
However, it is known that pertinent studies are under
way for bone tumours in man that are caused by radioactive substances.
REFERENCES
1. Bond, V., and J. S. Robertson, Annual Review of
Nuclear Science 7,135-162,1957.
2. Knowlton, N. P., and L. H. Hempelmann, Journalof Cellular and Comparative Physiology 33, 73,
1949.
3. Conard, R. A., Radiation Research 5. 167-188, 1956.
De Brupn, P. P. H., and 11. M. Tornova-Svehlik,
Radiation Research 6, 573-584, 1957.
Kallman, R. F., and H. I. Kohn, Radiation Research
3, 77-87, 1955.
Kohn, H. I., and R F. Kallman, British Journal ofRadiology 27, 586-591, 1954.
Patt, H. M., hf. E. Blackford, and R. L. Straube,
Proceedings of the Society for Experimental Biology and Medicine 80, 92-97, 1952.
Oakberg, E. F., Radiation Research 3, 369-391,
1955.
Trowell, 0. A., Journal of Pathology and Bacteriology 64,687-704,1952.
Schrek, R., Radiology 46,395-410, 1946.
Storer, J. B., P. S. Harris. J. E. Furchner, andW. H. Langham, Radiation Research 6, 188-285,
1957.
Patt, H. hii., Annals of the New York Academy of
Sciences 59, Art. 4, 649-664, 1955.
4. Kolln. H. 1. and R. F. Kallman, radiation Resear&
7,85-97, 1957.
5. Blair, H. A., Collected data pertaining to shorteningof life span by ionizing radiation, available as University of Rochester Report U R 4 2 , 1956. See
also: Blair, H. A.. Proc. Internat. Coni. PeacefulUses of Atomic Energy 11, 118-120.United Nations
1956.
6. Communicated by R. F. Kallrnan and H. I. Kohn,
1958.
7. Mole, R. IX.U N document A/AC.82/G/R.115.
Also published in Nature 180,45640, 1957.
8. Carlson. L. D.. W. J. Scheyer. and B. H. Jackson,
Radiation Research 7, 190-197, 1957.

9. Dublin, L. I., and M. Spiegelman, Journal of theAmerican hledical Association 137, 1519-1524,
1948.
10. Communicated by G. A. Sacher, 1957.
11. Seltser, R, and P. E. Sartwell, Journal of the American Medical Association 166. 585-587, 1958.
12. Warren, S., Journal of the American Medical Association 162, 464-468, 1956.
13. Wald, N., Science 127,699-700, 1958.
14. Lewis? E. B., Science 125,965-972, 1957.
15. Hempelmann, L. H.. in Hearings before the special
subcommittee on radiation of the joint committee on
atomic energy, Congress of the United States, Part
1;989,1957. U N document A/AC.82/G/R.130.
16. Pathologic Effects of Atomic Radiation. Report of
the Committee of the National Academy of Sciences

National Research Council, Washington, D. C.,
1956. Appendix I, pp. 1-13. Un document A/AC.82/G/R. 11.
17. simpson, C. L., and L. H. Hempelrnann, Cancer 10,
42-56,1957.
18. Stewart, A., J. Webb, D. Gies and D. Hewitt,
Lancet ii, 447, 1956.
19. Court-Brown, W. M., and R. Doll, Leukaemia andaplastic anaemia in patients irradiated for anh710sing spondylitis, Medical Research Council, Special
Report Series No. 295. London, H.M.S.O., 1957,
See also UN document A/AC.82/G/R.loj.
20. Court-Brown, W. M., and R. Doll, Lancet 4, Jan.
1958.
21. Lea, D. E., Actions of radiations on living cells,
Cambridge University Press, 1946.

Annex H

T H E GENETIC EFFECTS OF RADIATION

I. MUTATION..............................................
1. THEMECHANICS OF MUTATION

The gene ...........................................
Gene mutations ......................................
Chromosome breaks ..................................
The hereditary material ...............................
Linearity of dose-mutation curve .......................
Mechanism of mutation ...............................
Other possibilities of interference between irradiation andits effects at the cellular level ........................
Comparison between natural and radiation-induced mutations~ e t e h i o nof mutation .................................
2. MUTATIONRATESNatural mutation rates ...............................
Natural mutation rates in man .........................
Radiation-induced mutation rates .......................
Radiation-induced mutation rates in man .................
3. THE REPRESENTAT~X DOUBLING DOSE .....................
Estimates of the representative doubling dose for human............................................
genes
4. ESTIJIATESOF TOTAL RATE OF RADIATION-INDUCED ~ I U T A T I O N S
I N THE GENOME O F MAN.................................

11. T H EGENETIC CONSEQUENCES OF IRRADIATION
1. THECONNE-UON BETWEEN MUTATION ~3x1
GESETIC DAMAGE :SELECTION........................................... 75
2. APPROACHESTO QUANTITATIVE ASSESSMENT OF T R E GENETICCONSEQUENCES OF IRRADIATION OF HUMAN POPULATIOXS.. .. 80
3. THE CURRENT SOCL~LBURDEN OF GENETIC ORIGIN IN HUMAN
POPULATIONS, ITS CONNEXION \f71TH MGTATION AND RADIATIONEXPOSURE.

............................................ 87

Specific traits ....................................... 88
Biometrical characters ................................ 95
Fertility ............................................ 104
Pool of recessive mutants. ............................. 106

Table

I. Measured or calculated values of natural mutation rates in man
11. Measured or calculated values of natural mutation rates at single
loci of organisms other than man
111. Measured or calculated values of total natural mutation rates forclasses of loci in organisms other than man
IV. Rates of radiation-induced mutations at single loci in organisms
other than man
V. Total rates of radiation-induced mutations in classes or' loci inorganisms other than man
VI. Sunreys of human populations for purposes of radiation genetics
VII. Content of DNA in various types of cells
VIII. Calculated doubling doses in organisms other than man
IX. Comparison of approaches to quantitative assessment of mutational damage
X. Some over-all estimates of social burden

XI. List of specific traits, with estimated incidences :Category I(a) Autosomal dominant traits( b ) Autosomal recessive trsts(c) Sex-linked recessive traits(d) Summary of traits of Category I

XII. List of specific traits, with estimated incidence: Category I1XIII. List of specific traits, with estimated incidences : Category 111
XIV. Dominant conditions identified in the Northern Ireland population but not included in Categories I and I1 for the reasonsstatedXV. Classes of biometrical character

Table XVI. Calculated consequences of changes in the parameters governing birth-weight distribution

recognizable for the organism as serious somatic effects.
ranging from death or incapacity of cells fulfiling vital
specialized functions to unrestricted proliferation.

I. MUTATION
1. THEMECHANICS O F MUTATION

Chrottzosome breaks

The gene

1. The conventional concept of the gene has been thatof a functional hereditary unit. I n recent years this concept has required a more precise definition. since sensitive tests of allelism have indicated that a single f m c tional gene may be separable into component dements byrecombination and so shown to be capable of many
pseudoallelic differences?*= Single mutational events
which modify or prevent the action of the functional
unit may affect different large or small parts of thisunit.s During the same period, it is notable that featuresof the genetics of natural populations have indicated theextent to which individual functional genes can be invalved in larger complexes and lack complete
Possibly the most striking manifestation of this is atpresent in Salmonella typhimurium, in which it appears
possible that there are integrated linear sequences of adjacent gene-structures responsible for whole sequencesof biochemical operations, assembly-line fashion.'
Geftemutations

I

2. Take in its widest sense, mutation means any
change of the genetical constitution not due to recombination, ranging from whole genomes to alleles. Often
mutation is used in a more restricted sense, viz. as changeof the action of some specific gene. This is commonlyreferred to as p& mutation, which, however, may be amisleading term, as it is known, especially from the work
on Drosophilo by Dubinin and other^,^^^ that a change ofthe position of a gene may change its habit of action.
Moreover, the idea of a point mutation, as distinct froma deletion or rearrangement, was formerly based upon
the smallest unit of structure microscopically risible.
Because recent structural analysis of the gene has se.med
to penetrate almost as far as the much Smaller ultimate
units of its ph~sico-chemicalstructure, believed to be
the single nucleotides, it has already been suggested thatthe term "point mutation" be resenred for mutational
events invol~ingonly one such unit.8 Such ideas do notby themselves affect the distinction between intragenic
and intergenic mutationsg and may, indeed, dar$ these ;for example, it remains possible that further investigations of genes and chrom~somes'~
will lead to a distinction between a structural backbone and separate attachedgenes. There is no doubt that advances in this field will
eventually add greatly to the refinement of current ideas
concerning all aspects of mutation.

3. I n man, the primary genetic concern is with alltransmissible hereditary changes which simulate thechange to a new allele. These are perhaps best grouped
together under the term "apparent gene mutations",
whatever their structural nature. However, other formsof genetic damage require consideration in connexion
both with SOmatlc effects and with the requirement that
mutations must sunrive transmission through the germ
cells if they are to be observed. These latter forms ind u d e both gene mutations and chromosome structuralchanges in somatlc.ceU.s, which may well have a sensitivity to the radiation-induced process quite similar tothat of germ line cells?c4 hlutations and chromosomechanges in these cells could bring about consequences,

4. It remains a major question to what extent chromosomal or other genetic effects may be responsible forcell death or damage in somatic or germinal tissues ofman.11 Visible chron~osomalalterations resulting from
irradiation have been studied in cytoIogically favourable
material, principally of plants and of insects. They commonly arise through one or more chromosome breaks inthe cell rejoining in some new configuration. A frequent
result is dominant lethality through loss of substantial
chromosome parts or interference with cell division.
In spite of the difficulties of objective numerical scoringof cytological phenomena, many quantitative investigations have been made upon them :I2 it has been shownthat the more densely ionizing radiations are relatively
more effective in produang them12*13and that the numbers obsenred or recovered can be considerably affectedby various post-irradiation treatments if these are applied sufficiently early.12p14In this way, recent work hassuggested that there are some breaks at ionic bindings,
which reheal very rapidly, and others at co-valent bonds,
which heal more slowly,14as well as two separate effectsof radiation, one in causing the breaks and the other in
affecting the rejoining mechanism.14 The effects of oxygen, both at the time of irradiation and during the subsequent rejoining process, have played an important andcontroversial part in thislt would be ofinterest to learn to what extent inx-estigation of postirradiation modifiers of the rejoining process
biochemid
to those observed \+-ith
modifiers of fie cell lethality induced by irradiation.

5. Many investigations have connected ploidy withradiation resistance in unicellular organisms,
the extensive work of Mortimer and his colleagues onyeast;16 and this, together with the increased RBE of
the more densely ionizing radiations, has led to the idea
fiat much radiation-induced cell lethality has its
in dominant genetic changes. Certain cases are. however,lcnown inthis is not true; instead, lethality resultsfrom an imbalance or block in metabolism (as in very
heavily irradiated Habrobacon eggs,17) or a generalized
failure of the mitotic process hardly to betoindividual processes of the break-rejoin type. On thebasis of a turo-hit killing curve for mammalian tissue
cultureof various ploidies, Puck has recently argued that radiation-induced death in these is ,-hromosomal in origin ;lS,lg4cytological evidence will perhaps
be required before such a conclusion can be considered
as finally established. However, the reduction in growthrate observed by Puck et al. in colonies derived from
diploid mammalian tissue culture cells which had survived X-irradiation already provides printa fmie e+dence that even at doses of the order of 100 r, mostsurviving cells have suffered dominant deleterious
changes.lBJs bIoreover, Bender has recently demonstrated a rather high sensitivity of tissue culture cells
derived from human kidney to chromatid breaks inducedby X-raJrs.19
The hereditary tlurterial

6. Recent years have remarkably advanced the knowledge of genetic material and of the role played in it bydesoxyribonucleic acid (DNA). Indirect evidence from174

difierent sources has long led cellular physiologists tobelieve that DNA, in close association with protein,
forms part of genes and chromosomes ; this has included
the relative DNA content of haploid and diploid cells of
various tissues of an ~rganisrn,~"cytochemical evidence,of the presence
including thethe association of DNA
of DNA to the cell
More recently, a very
syntllesis with cell
between the asclose association
similation of radioactive .racers incorporated in DNA,and chromosome division.''' In addition, other evidence
has inclined many geneticists to believe that D N A may
be the actual material whose configuration constitutes
genetic information ;this evidence includes :( a ) The transformation of hereditary characters ofcells of P n e n s ~ o c o c c u sand~ ~ Haevrophilus" bacteria byapplication of solutions of pure DNA.

( b ) The role played by DNA in the growth andheredity of the coliphages of the T s e r i e ~ . ~ ~ * ? ~( c ) Indications from current work that increased
mutation in microbial systems occurs under conditionsof deficiency for an essential constituent of DNA suchas thymine, or in Presence of a competitive analogue ofa constituent, such as bromo~racil.~'~ 1 such
1 phenomena carry the promise of ne,v lines ofinvestigation of the mechanisms of gene mutation.

7. Concurrent investigations have remarkably advancedof the chemistry and structure ofDNA,
the X-ray diffraction studies of
Wikins et d.?sand the complementary biochemical relationships uncovered by Bargaff
and 0the~s.29leading to
the remarkable double helical structure proposed by
Crick and Watson,so so suggestive of the exact replicative process required for the transmission of hereditarycharacters, and already so productive of fresh ideas concerning the mechanics of mutation.

8. while none of these arguments is alone conclusive,andit is recognized that the gelletic material ofof higher ol.ganisms is organized into very substantial stainable structures. which must be more complphysically andthan the fine DNA fibrils
visible only under the electron m i c r o ~ c o p enonetheless.~~very many geneticists believe that the ultimate carrier ofgenetic information is likely to be the arrangement of
nucleotides in DNA.

9. I n that event, total radiation-induced mutation
rates, in the widest sense of change of the hereditary information. might be expected to be quantitatively correlated with the DNA content of the cells of the germ
plasm together with the biochemical operations whichconstruct and maintain DNA. It at least seems reasonable that when comparisons of mutation rates between
different species or physiological conditions are made,parallel DNA comparisons should be kept in mind. The
D N A contents of some relevant types of cell are listed
in table VII. hlost kinds of cell nuclei contain enough
D N A to form a structural molecule of great length which
could only be packed inside the nucleus by much folding.
This has given rise to the recent suggestion, now appearing on purely structural grounds, that the chromosome
may consist of a multi-stranded structure.''' I f the structure turned out to be, say. a proteinaceous backbone with
attached DNA molecules as side arms forming the genes(a possibility which is not excluded). the distinction
between inter- and intragenic mutations could eventually

come to have a very real physical basis, and the t\vo kindsof mutation could differ in mechanisms.

Linearity of dose-rjurtation ctrwe

10. The esperimental justification for speaking ofradiation-induced mutation rates at low doses rests upon
Drosophila data, in which the linearity oi fie dosemutation cunre, when it is investigated under suficielltly
rigorous conditions, has been confirmed down todoses of 25 rad for irradiation of spermatozoa by tilepainstaking work of Stem and his ~ ~ l l a b o ~ ~ t ~ ~ ~ , J l following earlier experimenter^.^'-^^ Mulle?' has recently argued cogently that there is no point in pressirlg
the test of linearity below 5 rad, and has indicated that
this limit could be reached in Drorophilo by techniques
at present available. Many geneticists ,%,auld agree
the implication of the cited passage, that linearity canalready be safely accepted, without the enormous iabo~lr
involved in its extension to still lower doses-at least in
the absence of a definite proposed basis for expecting a
non-linearity. However, it must be borne in mind thatlinearity has not been tested in this range of doses forspermatogonia~irradiation.
the case of irradiation ofthese cells it is still difficult to conceive a priori of a nonlinearity at low dose, followed by a linear portion of thecurve at medium or high exposures.'However. OakbergS8
has shown that some classes of spermatogonial cells of
the mouse are very sensitive to the lethal effects of low
doses ( 5 rad - 100 rad) of gamma-radiation. If thesesame classes were to turn out also to be unusually sensitive to the induction of mutations by radiation, the curveof recovered mutations as a function of dose might turnout to be linear in the range of moderate doses. but tohave considerably higher slope in the very low dose
range where an appreciable proportion of the cells surviving irradiation belonged to the sensitive group.

I

ll. The Committee has beenof current
periments upon mice which will enable the linearity ofthe dose-mutation curve for irradiation of spermatogonia, oogonia and oocytes to be checked down to 37.5
Attention must, however, again be drawn to thedependence of the whole quantitative assessment ofgenetic effects of low doses upon an assumed linearity
andirradiationa particular type cell in a dosera"geinyestigated.

Mechojrism of nzzctation

12. Many attempts have been made to affect theprocess of induced mutation after its initiation by exposure to ionizing radiation. Some of these have beensuccessful to a greater or lesser degree,4- and this fact
is of cardinal importance as demonstrating at least thepossibility of interference between the irradiation and its
principal genetic consequence. Unfortunately, in manyof these cases the precise genetic nature of the mutational
event is not known ; association with chromosome breakage or rejoining may therefore be suspected. Moreover,many of the esperiments refer to microbial material. In
which it is possible that the gene structures are far more
esposed and more easily able to be reached and affectedby external agents than are the mammalian chromosomes. Nevertheless, it is a hopeful sign that recent experiments reported to the Committee have extended thedemonstration of post-irradiation interference to a wellknown class of apparent gene mutations, the sex-linked
recessive lethals of Dr~sophiZa.'~These experiments
seem to show that a finite interval of at least some tens

175

of rnhutes exists in Drosophila before .'fixation" ofradiation-induced mutations.

13. In comesion with any possibility of ultimate
practical use of chemical or other modifiers of induced
mutations, it is well to remember that, in many populations. the largest man-made exposures of the gonads
occur through comparatively large doses delivered relatively infrequently in the course of medical work at
controlled times. The possibilities of modifying the mutational effects of radiation should be considered in thelight of the more general discussion of modifiers ofradiation effects in chapter IV and annex F of thisreport.

Other jossibiliiies of interference betweejz irradiation
altd its efects at the celltrlar level

either individual genes,$' strains.jS or physiological cond i t i o n ~result~ ~ in altered natural rates. Very little correlation is also found between radiation-induced mutability
and the natural rate in the sample of thirty biochemical
back-mutations examined by Glover.53 However, thewide variations in the ratio of radiation-induced to natural mutability found both in the work of Glover onbacteria and in extensive work on plantss0 do not seemto be correlated with the type or severity of the forward
or back-mutation involved, and it is generally acceptedthat the ratio of visibles to lethals is much the same fornatural and radiation-induced mutations in Drosophila,
although no explicit study of this point has. been made.
Atoreover, a very detailed investigation by Giles" of
purple-adenine and other mutants in Neurospora has
shown no evidence for a qualitative or quantitative difference between radiation-induced and spontaneous mutations at the same locus. The evidence of Stadler primarily
relates to the compound A locus ;consequently,a possible
esplanation is that A has a very low sensitivity to radiation-induced point mutation. I t is therefore reasonable
to accept as a tentative assumption that spontaneous andradiation-induced mutations are qualitatively similar :wide differences in the two mutation processes exist but
are functions of individual loci, and are not appreciably
correlated with the type or severity of effect exerted by
the mutant allele.

14. Interference with and control of genetic consequences of irradiation does not end with the completionof the mutational process. However, to look further
requires that the completed mutations be detectable. The
number of conditions in which carriers of unexpressed
deleterious genes can be detected has recently increased
this trend is closely associated with advances
greatly ;46147
in general biochemical and immunological genetics, and
it is to be hoped that Governments will foster and encourage its progress. -4second field closely related to thisand other aspects of the present subject is that of human
17. In connection with this problem, attention may be
chromosomal cj-tology. We are indeed a long way rebacdrawn to certain organisms such as Aspergill~ts,~?
moved from the beautiful situation which prevails in, ~which~ ~ ~ very sensitive tests
teria,"=and c ~ l i p h a g e in
Diptera where giant salivary gland chromosomes canof allelism are possible : tests which may be calculated51
be studied in minute detail : nevertheless recent technicale ~ ~can~ ~ ~ in some cases to be adequate for resolution of recombinaadvances in the field have been c o n ~ i d e r a b l andtion distances corresponding to one nucleotide pair if
give US great hopes of progress. Such advances may bringabout radical changes in human genetics and especially genes are primarily constituted of DNA. Such investigations might eventually shed much light on the real maghuman radiation genetics.
nitude of the structures disturbed by various types of
15. Other radical possibilities for dealing with radiamutational event of different origin, and indirectly on
tion-induced mutation, besides the cumbersome andthe "quality" of mutations caused by different agents.
often painful process of selection, beyond question exist.
Unfortunately, all the above organisms are microbial andAn example which must be considered, in the light of
not necessarily representative of the larger chromosomes
teclmological advance, is that of the natural or controlledof higher organisms.
transfer of genetic characters. This phenomenon is wellestablished in microbial materials," although usually but
18. In man, little information yet exists concerning
not always with very low frequency,51and as an eventual
the relative sensitivities of genes to specific mutagens.
aid in the elimination of harmful genes or their conseHowever, a notable beginning has been made upon thequences it cannot be'entirely dis~llissedas speculation.
* l ~ ~has analysed the mean
problem by P e n r o ~ e , ~ ' whoparental age at birth of propositi showing various conditions. and correlated these shifts with hypotheses as
Conzparison between xaturalto the principal kinetically different classes of mutagens,ana? radiation-kdziced nuta at ionssuch as natural radiation (expected to raise both mean
16. There has been a widespread belief among genetpaternal and maternal ages by an equal small increment).
icists, based largely upon the classical work of Stadler
copy-error (expected to raise mean paternal age somein corn" that radiation produces in general a differentwhat), or chemical mutagens (which might under some
type of mutant allele from those which occur naturallycircumstances raise the mean maternal age in such a way
more &reme, less likely to be reversible, more frethat incidence increased more than linearily with age).
quently a loss of function. However, Stadler's work may
Thus the prospect already exists of the analysis of
not be entirely typical even of plant material.ls8 Muller
human genes in ternls of sensitivities to different kinds
has recently reviewed the evidence against existence ofof mutagen.
Certainly, both the mechanism ofsuch a distin~tion.~
production and the distribution among loci of radiationinduced and natural mutations differ:53 there is also
some indication of small differences in the proportions
19. An apparent gene mutation can be detected if itof mutation to the different alleles at a single
results in a new allele ~ - h i c hdiffers so much in its action
Minute one-hit deletions do occur under the action of
from the original one that it can be scored by appropriate
radiation." and some radiation-induced point mutations
methods. There exist different alleles (isoalleles) whoseb Drosophilc may be associated with breaks or structural
phenotypic effects cannot at present be distinguished butchanges near them.56 3loreover, evidence in Drosoplzila
which may differ in other respects as. for esample. mutais against any appreciable correlation between naturalbility.OS Studies of natural and induced mutations are
mutation rate and radlatlon-induced mutability whererestricted to those which can be distinguished pheno-typically, and measurements oi their frequency will consequently be minimum figures for the total mutation
rates of the genes concerned.

20. I n Drosoplzila as well as in mice the rate of visible
mutations at specific loci has been studied after matingsof the stock to be tested with animals of the opposite sex
containing the marker genes whose mutation frequency
is to be examined. By this method the visibles scoredinclude both those which are recessive lethals in homozygous condition and those which are homozygous viable,
provided only that they are visible and viable as heterozygotes with the allele in the marker
As reported
by R u s ~ e 1 1 six. ~ ~out of twenty-one tested mutants induced in spermatogonia of mice were lethal, seven weresemi-lethals and eight were viable. The corresponding
data from Alesander'sio test of mutations in spermatogonia in Drosophila yielded three lethals, one semilethal and four viable. Excluding rare heterozygotes
combining a recessive viable visible with a recessive
lethal visible, what could be scored in any corresponding
study in man might be only those recessive visibles notrendered unscorable by their association with recessive
lethals. Supposing the same relationship behveen viable
and lethal visibles as in mice, one might easily underestimate the total mutation rates of genes in man by a factorof two or three.
21. I n estimating mutation rates it must also be bornein mind that the same phenotypic effect need not mean agenetically identical condition. In man, as in many otherorganisms, several different genotype? may exist whichgive rise to indistinguishable phenotypic expressions. I n
the case of man one must think of classes of genes eachcausing a similar effect, rather than of specific single
genes. The number of genes in each such class may varyconsiderably, causing a strong variation between theobserved rates of natural mutations in the various classes.
Thus in man? because test breeding cannot be used topin down an alteration to a specific locus, a mutation rateis always in fact measured for the whole class of genes
giving rise to one altered condition, recognizable trait,or clinical entity.

22. I n recent years many important studies of themutational process have been made in unicellular organisms. There are, however, several major problems inthe measurement of gene mutation rates in single cellmaterial, including a lag between application of radiationor other mutagenic agent and the observable expressionof mutations which enables them to be counted : this lag
can be due to various factors, segregational or physio10gical.~' Furthermore, there is always a possible effectof non-mutant cells upon the survival of mutants during
tests.72 A different problem, peculiar to back-mutations,is the difficulty of distinguishing apparent back-mutation
at the same locus from suppressor or modifier effect.
For this problem, which is related rather closely to theimportant question of the reversibility or otherwise ofradiation-induced as compared to spontaneous mutations, there are great advantages to microbial material
in which both kinds of forward and reverse mutations
have been and are being explored. Both radiationinduced and spontaneous mutation rates have beenmeasured with relatively high precision in unicellularorganisms, especially bacteria, under a variety of conditions ;73374it is to be hoped that the techniques andmethods developed ~villyield equally valuable results
when applied to the clones of mammalian tissue-culture
cells now available.

Natural i;tlctatio~trates
23. The basic difficulty in any quantitative stud,^ ofnatural mutation rates is to obtain large enough numbers,
for these rates are low (tables I, 11) and cannot of
course, be raised artificially for purposes of study.
Consequently, investigation has been confined to organisms which can be handled or are present in rather large
numbers, such as bacteria, Drosopltila, and humans. The
limit to the information on natural mutation rates which
can be derived from the very extensive and careful control observations in mice, in the work both of Carter,
Lyon and Philips'' and ofillustrates the difficulty. Because chromosome structural changes occur
naturally at much lower frequencies even than apparent' ~ ~the~ ~ study~ ~ " of rates has been
gene r n u t a t i ~ n s ~ andconfined almost entirely to the latter events, only thesewill be considered here. In man, individual cases, once
found, can be followed up with relative ease even inlarge populations, because the family and individual areindentifiable by name, etc. As a result, it is possible that
more information about natural mutation rates for single
phenotypic entities exists for man than for any otherorganism. I n man, however, as in other organisms, thebasic ~roblemof small numbers governs considerationof thekeld.
The rate and variation of natlcral mutatiom inexperimental organisnzs
23. In other organisms than man, it has been possible
by experiment and test breeding to examine more closely
the variations in natural mutation rates as well as theabsolute magnitudes. The general ranges of the latter do
not vary very widely (table 11).

Physiological variation.s
25. As noted above in another contest, physiologicalvariables affecting natural mutation rates of individualloci have been examined in bacteria by Novick andSzilardia who concludcd that the number of mutations
increased as a function of chronological time rather thancell division. This may, however, not be generally true:79
moreover, the genetic material of bacteria may not be
entirely representative of that of higher organisms.
Moreover, the general lack of systematic variation of
doubling dose among species of widely different generation times, militates against any assumed dependence of
number of natural mutations upon chronological time.
26. Work on physiological variables in DrosopIzila
has been carried out in relation to mutation at classes ofloci, such as the recessive lethals, rather than at single
loci. Differences behveen natural strainslT4and between
sesesaOand dependence upon ageB0have been established
for a number of organisms. These variations in natural
mutability are not known to be correlated with variationsin the radiation-induced rates.
*Strictly, the term mutation rate refers to the rate of occurrence of mutational events and not to the irequency of mutant
gametes among tested gametes, although it is also c o m m o n l ~used to refer to this latter measure. The distinction must,however, be borne in mind in certain situations: for e??mple.
if it is desired to compare true natural mutation rates esbmatedfor free living unicellular forms of life 11-ith the frequencies ofappearance o l mutant gametes in higher organisms, slnce thelatter do not directly reflect the rates of occurrence of mutational events in the germ line cells (see table 11).

Va.riatiots between lociIndirect ~twilzods:autosonz.al recessives (fable I )27. The difficulty, even in Dt.osophila, of obtaining
enough data to document significant variations in natural
mutation rates between loci other than esceptional unstable genes further underlines the basic problem of
numbers in the investigation of natural mutation rates.
Variation between loci, and in certain cases between
i s d e l e s at the same locus is, however, well-known inthis organism.6s I t has been far more extensively documented in the bacteria, at least for back-mutations; therates of these vary from 10-6 to the lower limit of detection near lVlO:they are correlated with mutability byradiation to only a very small extent.53

31. The mutation rate for autosomal visible recessives
is calculated indirectly, by a process originally due to
Haldane.s4 The observed number of propositi, together
with an estimated selective disadvantage in the homozygote, is used to calculate the rate of disappearance of themutant alleles concerned from the population, and abalancing rate of fonvard mutation is inferred from anassumption of genetic equilibrium. The uncertainties
concerning possible existence of small selective effects
in the heterozygote and of large departures from equilibrium render extremely uncertain the values obtained inthis way: indeed, perhaps the most notable use of such
figures has been to deduce a prior; expectation of heterOSIS from a few "unreasonably high" calculated mutation
rates, although most of them lie in the same order ofmagnitude as those for dominant entities (see table I).

2s. In extreme cases variations between loci may
originate in genes which are themselves unstable or confer instability upon others. \ f i e r e mutator genes affectall or a large part of the genome, they may in addition
be partially responsible for variations in spontaneous
mutability between strains. Again, such genetic modifications of spontaneous mutation rates is not known to becorrelated with change in radiation-induced rates.
Natural 9nutatio~crates ifa nzalz

29. Penrose, Nee1 and others have tabulated a numberof calculated rates for single clinical entities in man (seetable I ) . In examining these values, it is necessary to
bear in mind the limitations of the data and of themethods of calculation by which they are obtained.
Direct methods: autosonzd donzinattts a ~ z dsex-litzked recessives (table I )30. In the case of clear-cut autosomal dominant visible entities, the mutation rate is in principle directly
estimated by observation of propositi whose parents andother close relatives are normal. The various technicaldifficulties such as failures of ascertainment and occurrence of phenocopies. degree of penetrance, and the proportion of cases not due directly to fresh mutation havebeen discussed in the l i t e r a t ~ r e The. ~ ~ experimentally~~~
ideal dominant visible combining full penetrance, complete ascertainability and responsibility for total sterility
would be o i reduced value, since it could not be proved
directly to be genetic in origin. Moreover, in practicestudies are commonly made upon the natural mutation
rates in those populations where they are known to behighest, simply in order to obtain enough documented
cases to make the results statistically significant. It istherefore questionable whether the observed rates are
representative. They cluster around 10-Qer gamete ina distribution which is rather skew. If a population of
10' is surveyed during five years for an ideal condition,observable during thirty years, it already constitutes aconsiderable labour, and yet significant results are unlikely to be obtained unless the mutation rate exceedslo6. In practice, no such ideal conditions exist. I t is very
probable that some of the well-documented human mutationss3 have much lower frequencies. Perhaps the possibility should be faced that the sample of spontaneous
mutation rates which have been measured in man is not
representative, and that the true centre of gravity of therates for this group of entities lies at or below lo4 rather
thvl near lo-' per gamete. This encourages the suspicion
thzt among the autosomal recessive visibles for whichrates have been calculated indirectly, more than hitherto
suspected might show heterozygous advantage. There isneed for Governments to foster extension of the scope ofexisting methods, especially to conditions which are rare
or of weak or irregular expression.

Lower limit to detectiort of recessives

32. An autosonla1 recessive with a selective disadvantage of only 1 per cent in the heterozygote, in a population whose coefficient of inbreeding was 0.01 per cent,would, if its mutation rate were lo4, show up phenotypically in no more than about l in lo6 of the population. Even if the condition were fully penetrant, a mutation rate would be very difficult to estimate. Such genes,
if their natural mutation frequencies were in the rangeof lo-?, could hardly be observed at all. There is therefore reason to believe that the best documented sample ofrecessives for which indirect estimates of mutation rate
are available may be unrepresentative. If this is because
they show very slight heterozygous advantage, the mutation rates calculated for them are also too high ;but thenthere is a fallacy in the converse argument, that because
many of these turn out upon investigation to be heterotic,
most human mutant alleles are so.

33. The study of consanguineous marriages does notlead to estimates of natural mutation rates but to estimates of the numbers of recessive alleles present in
populations. In principle, these marriages constitute a
test-breeding for the presence of recessive alleles throughthe associated degree of homozygosity ($$s for firstcousins) which they bring about. It may, however, bequestioned whether a truly comparable control group canever be obtained, although internal controls by comparison of different degrees of consanguinity are usuallyavailable. The limited number of studies made -hOW as
yet no very consistent picture. Of them, those by Sutter~ Othe most extensive.
and Tabah6"= and by S c h ~ l l ~areand that by Books7 the most intensive. Morton, Crowand M ~ l l e r by
. ~ ~an ingenious argument, have shownhow to present the over-all reduction in viability, which
is observed in three of the surveys, in the form of anequivalent number of alleles n-hich ~vouldbe lethal if
homozygous, or lethal equivalents, carried per head of
population. From the surveys analysed by them they
conclude that 3-5 lethal equivalents acting before maturity were present per individual in the population, afigure with which the survey reported by Schull is insatisfactory agreement. Unfortunately, the intensive
examination carried out by Book shom-s an entirely different picture of viability, although in a very small
sample: the total deaths. includiig prenatal and up to
age 30, in Book's sample, were zlnlost identical in thecousin marriages and the controls.

31. The content of deleterious recessive genes of a
population: whether expressed in lethal equivalents orotherwise, is an important parameter indicative of its
genetic state. I t is also a valuable standard of comparison
for actual or postulated mutation rates. There is, however, another possible use for it. Comparison can bemade of the total recessives in lethal equivalents, derived
from vital statistics only, with intensive investigationof all the known recessive lethals present, such as that
undertaken by Book. (Ideally, the total reduction in viability and fertility up to the second generation beyond
the cousin marriages should be employed, (see paragraph 113 below) and the intensive examination should
cover all known recessive conditions.) I n this way it
might be possible to obtain some idea of what proportionof recessive damage is covered by the lcnown effects,
and what proportion remains unltnown : a factor of great
importance to our confidence in any estimates or predictions, based as they must be upon current limited knowledge. This possibility is discussed in more detail inparagraph 113.

35. It is clear that improved recording of such consanguineous marriages, in maternity hospitals or centresof vital statistics, would be of great value and should be
encouraged by Governments if they wish to be aware of
the general state of genetic well-being of their peoples.
36. The Committee has been informed of large-scalecurrent or pIanned surveys of consanguineous marriages
both in Japan, where the frequency of these is high, and,as regards vital statistics, in Canada.s"go

37. I t has. unfortunately, not been possible so far toestablish total natural mutation rates in man for verylarge classes of genes, such as that formed by the sexlinked recessive lethals of Drosophila. Such large classes,
if they could be investigated upon a firm genetic basis.
might more easily provide adequate numbers for reliable
statistical analysis than can be obtained from the laborious search for specific rare conditions. I n this connexion,
it is of interest that Lejeune and Turpins' have recently
attempted to interpret the decrease of sex-ratio at birthwith age of either parent in terms of a mutational
hypothesis. There is, however, no certainty that the secondary sex-ratio does decrease with the age of themother,'86 and the combined data upon irradiated andaged fathers appears at present to involve contradictions.
Since there does appear to be a decrease in sex-ratio withage of the father,la6Js7 it seems a reasonable possibility
that mutations to sex-limited detrimental autosomal
dominants are concerned and that they are due to natural irradiation or other non-cumulative, time-independent causative agents (Penrose's Class I,=' see paragraph 18 above). I t would evidently be of great value
if clear-cut interpretations could be established in someother mammal, such as the mouse, since secondary sexratio data are widely recorded in large populations,although not always in a form suitable for geneticalanalysis, and they are relatively free from the ambiguities of fine diagnostic distinctions. The possible interpretation of sex-ratio data is further discussed in paragraph 64 below.
Mutator afzd unstable genes
38. I n any consideration of variations in spontaneous
mutation rates, the evidence of mutator genes and unstable genes, well-established in corn, in Drosophila andin bacteriaag?must be borne in mind. together with thefact that these commonly do not affect the rate of induc-tion of mutations by irradiation. Minor efiects of thiskind might be more common than are supposed andcould perhaps give rise to some variations in natural
mutation rates between human populations. If that wereso, these in turn could be expected not to give rise to any
corresponding variation in radiation-induced rates.
Although variations in frequencies of appearance ofmutant phenotypes between difierent human populations
are well !mown to occursg3they have been inadequately
documented, especially for dominant conditions. I n thecase of recessives they are usually attributed to past
selective differences, although it is conceivable thatgenetic drift also plays a part.g'
Rads'atio?t-inducedinutation rates

39. Radiation-induced gene mutations have not yet
been observed with certainty in man, and so no quantitative dose-mutation relation exists for the genes responsible for any specific clinical entity. In consequence,quantitative assessments of the mutational affects of theirradiation of human populations must rely at present
upon tenuous arguments and upon extrapolations which
are often of uncertain validity. I n any event they depend
upon the well-established results of the investigation ofradiation-induced mutation in other organisms.
Mag~iitrrdeand variatio~tof radiatiolt-induced ?~tutatio?trates in orgaglisnrs other than matt
40. Since the field of mutational radiation genetics
was opened by 1\Iuller in 1927,95it has been establishedin all the many organisms tested that ionizing radiations
can induce apparent gene mutations: hence the same isbelieved true of man. X-ray induced mutation rates havebeen measured for a large number of single loci, especially in Drosophila. Both the range and average of suchrates are lcnown for a wide variety of individual visible
markers through measurements made under very carefully controlled conditions, and so also is the total rate
for certain large classes of markers such as the sexlinked recessives of Drosophila. A number of rates
observed in experimental species are listed in tables 111,
I V and V.
41. I n mammals, the most extensive investigation of
the X-ray induction of mutations at single loci so far
in which the rates at
carried out is that for mice,",75~i6*96
seven autosomal recessive visible loci have been in\-estigated in spermatogonia; the average of these rates isfound to be about fifteen times the average for a comparable group of loci in D r o s ~ p h i l a . ~ ~42. Extensive research has been conducted upon thevariation in sensitivity to radiation-induced mutation
with physiological condition. In the male it has now been
established that the mutability is low in spermatogonia,
rises to a pcak during the time of formation of spermatids, falls to a second minimum in immature spermatozoa, and then rises up to the time of ejaculation, bothin Dros0plzila~7~~~
and the mouse.B9 In the female
Drosophila, the oogonia show a mutability similar to thatof spermatogonia while late iiocytes are very mutable.37J00 The subject has recently been reviewed by
Glass.lo0Drosopltila is also the only organism for which
extensive determinations exist of the relative ratqs ofmutations in different selective and other classes, either
at single loci or summed over large parts of the
43. & I ~ l l ehasr ~ pointed~~
out that evidence in Drosophila indicates that mcltation rates in somatic and gonialcells are about equal. Estensioll of fllis principle to otherspeciesl~4and eventually to man might malie possible
very i n f o r l ~ a t i ~conclusions
efrom investigations On
somatic mutation rates in vivo in man.
Calculations have been 11lade by Haldanelos andthe practicability of observing nototherssingle locus rates but total rates over a large part of the
genome in a mammal such as the mouse. Such an experiment upon the very large scale necessary might beof considerable value at this juncture in the process of
extrapolation to man ; it would, however, involve theexpenditure of a great many scarce mouse-geneticistyears. The Committee has been informed of the existence of a pilot experiment on these lines.lO"

45. l-he collcept of genes as finite structures of different sizes which carry hereditary information largely
in he form of different arrangements of nucleotides in
DNA has recently made possible one particularly interesting interspecies comparison concerning induced mut a t i o n s . l ~ There~ l ~ ~ is evidence that in mice the total rateof induction of recessive lethal mutations in sperm ishigher ballthe corresponding rate in Drosop]%ilaby afactor of about 20.157 The same is true for the rate of
mutation per locus ayeraged over several different loci,and in addition there is a similar difierellce of aboutti\-enty-fold in the same direction in the DNA content
per nucleus. This suggests that perhaps mouse genes are
not more numerous but are larger than Drosophila genes-that the extra DNA has gone into building genes thatare bigger and more complex rather than more numerous.
The possible application of such an idea to man, an
organism in which mutational events cannot in generaleven be assigned to definite loci by test crosses, but which
has a DXA content per nucleus similar to that in themouse, might lead one to expect rather high mutation
rates, both spontaneous and induced, when measured
atperclinical entityt', as well as all the complesities andpeculiarities of large multiple allelic series. of which a
notable example has been uncovered by Dunn in the
t-alleles of the mouse.10s Penrosess has already drawn
attention to the possibili~of some unusually complex
genes in the X chromosome of man, in connexion withvery high observed natural mutation rates.
Radiation-induced r.trutatio~zrates in v~arr
S u r v e y s o f radiatioiz-iprduced gelle atutations in man
46. Whatever approach is adopted to the problem ofradiation-induced mutation rates, the gonad doses received both by control and by experimental groups
have to be known.
47. I n principle, the simplest method to obtain a qua,]titatix: relation between dose and radiation-induced genemutaoons in man is '0 ma'
a ~ o m ~ a r a t i vSurveyeofthe Progeny of an irradiated ("experimental") and a
com~arableu?-irradiated("control") population. Thosesurveys published so far are concerned only with thefirst generation born of irradiated parents. Hoivever.
it isto Show that. as human matings cannot be conaami?ati?n of the first generation provides
more information m itself than examination of subsequent generations.
48. I n the last analysis, all the obsened quantities
come do~vnto variations in frequency, and therefore:(a) All studies must be accompanied by the esamination of a control san~plepresumably issued from genetic
stock identical to that of the irradiated sample. This con180

dition greatly restricts the value of the results ~ublishedso far.
(6) All the results obtained are subject to an inevitable sampling error which necessitates the collection ofa v e v large amount
dataA number of quantitative characters. such as birthweight, size and various anthropometric measurements,
as well as statistical data, such as neo-natal mortaliq-.
have been suggested and examined. Unfortunately, theprecise genetic component in these variables is notknown ; on the contrary, they are known to be dependent
upon factors which are economic (standard of living).
demographic (age of parents. order of birth, etc.) andsociological (medical care).
49. The characters that can be utilized may be groupedin ~ I V O categories, according to whether they are connected with dominant (or sex-linked) visible mutations
or with dominant (or sex-linked) lethal mutations. The
detection of ~ i s i b l edominants is carried out in practiceby the observation of maiformations at birth. I t is in factreasonable to assume that an increase in the frequencyof dominant mutations associated with visible effects
would manifest itself to some unknown =tent as anincrease in frequency of malformations. The same would
be true of visible sex-linked recessives in boys born toirradiated women. Lethal mutations may be revealed infour ways :( a ) Increase in frequency of miscarriages (\-irtually
impossible to determine with certainty) ;(b) Increase in frequency of still-births (much morefeasible but subject to the demographic considerations
mentioned in connesion with neo-natal:(c)Reduction in fertilit)., or eren steriliq (\4rtually
inlpossible to measure in man) ;Disturbance in theof the seses at birth(deviation in the sex-ratio, an easily obsen-able criterion).

jo. The various studies \vhi& ma,, be taken into account at the present time are listed, together with pertinent results, in table VI. Given the very uneven qualityof the data presented by the various authors, and theparticular way in which they were arranged by each ofthem, it is impossible to add together the figures fromthe separate surveys. In general. none of the investigations makes a definitive demonstration of a genetic phenomenon. Only the decrease in the sex-ratio. which isfound in the three studies of irradiated mothers. seems
to be acceptably established as a reality. Although no ..
one of these studies concerning sex-ratio yields statistically significant results by itself, the fact that all
three deviate in the same direction gives some confidence
conce,~ng the realit,. of the
A~~~~~~~
ofthe studies to date rdse the possibility of an increase inco,snital malformations among the offsprillg of irradiated persons, the findings in this regard are much lessconsistent than those concerning
the sex-ratio. In thiscomesion,
it must constantlybe
in mind,vhere many comparisons are being
behveen M70
groups, on the basis ofalone oIle in twenty ofthese comparisons will
differencesthej per cent leXrelof significance+
observations
regarding the possibility of an increase in congenital
defect or early death are highly desirable.
51. In summary, it seems possible, although only withgreat difficulty, to distinguish a detrimental effect ofirradiation on the first generation issuing from irradiated parents. The possibility of firm demonstration and-.

measurement of this phenomenon suggest that all thesestudies be extended on the largest scale possible, wherever practicable surveys can be made with a reasonableprobability of yielding positive significant results in acomparison with adequate controls.

52. I n view of this possibility of future surveys of theprogeny of irradiated persons, it seems worthwhile toindicate the criteria which determine the value or "resolving po\ver" of any such study. In brief, five points must
be considered :( a ) The dose to the parents of the individuals understudy ;( b ) The number of individuals whose parents havebeen so esposed :( c ) The number of characteristics of genetic significance to be recorded ;(d) The manner in which information on these characteristics is collected;(e) The availability of a suitable control group.
53. To illustrate the manner in which ( a ) and (b)may be taken into consideration, a particularly simple
hypoethetical case has been selected, that of the detection of an ideal autoson~aldominant visible allele causing
complete sterility :Suppose the gene concerned to mutate at a rate m
per gamete in the control population and at an increased rate fm per gamete in the irradiated population. If the doubling dose for the mutational step
concerned is D2rad and the mean genetically significant exposure per parent of the irradiated group is
D rad, thenf - 1 = D/Dz
If P progeny of the irradiated group and Q of theunirradiated are examined with complete ascertainment for the visible allele. the numbers ex~ectedto beobserved are respective$ 2mfP and 2m&. The observed difference in rate between the two groups is
A = 2m( f - 1) and has an allproximate
variance dueto the limited s&nple size of
uA2 = 2m(f/P+ I/Q)In cOnsequencel even if
are considered,

other

i
:
>
-

I
of

calculated R values for the various exposure classes,
which add up to 2.3 X 1V2on the assumption that the
representative doubling dose is 30 rad. With respect
to the possibility of significant findings based on mutation at alry otle locus, then this study (and any otherstudy to date) is far below the level of significance.
54. Where multiple traits are involved in the inquiry,
the power of the study is a function of the precise number of traits under consider?tion. For example, if one
were to make the over-simphfied assumption that mutation at any one of 100 loci resulted in completely penetrant, dominant mutations responsible for congenital
defect, assuming independence In the ~xpressionof mutation at these loci, the calculated resolving power of thepreviously mentioned study becomes 2:3,.and the failure
to observe a significant effect of radiation on the frequency of congenital malformations in the aforementioned study might indicate that the assumed doublingdose was too low.
55. The sex-ratio is one of the more conveniently
studied indicators of possible genetic damage. Information on this point is relatively easy to collect and has ahigh degree of objectivity. The calculations corresponding to those of paragraph 53 are relatively simple andproceed as follows :Suppose a group of mothers receive gonad doses
averaging Dmprior to conception of children, and suppose the irradiation causes a shift in the secondary
sex-ratio s which is linear with the dose
Suppose Pmprogeny of these mothers are esamined. the variance in the determination of the sexratio of the progeny of the group, due to limited sample size, will be$ = s(1 - s)P,Since s is always approsimately 5, this may be
1

=-

4Pm
If such a group is compared with Q, progeny of acontrol group the variance of the observed differenceis

If we require that x" 4 for a significant increase of
mutation rate in the irradiated group t o be established, and denote x2/4 by R, then for a significant
increase in mutation rate a t a single locus,

and the significance of the observations is determinedby

In terms of D and D?

If we require ~2 3 4 before the shift can be considered significant, thenFor esample, in the study of Nee1 and Schull,lll
the progency of irradiated parents numbered 3.3 X lo4
and the progency of control parents. 3.2 X lo4.while
the average excess radiation exposure to the combinedparents of the former group is about 17 rad. Becauseof the known heterogeneity of Lxposures. R for any
single locus must be computed by adding together the

Similar formulae can be derived for comparison of theprogeny oi irradiated fathers with controls. whereA number of completed surveys, irrespective of thesignificance of their results, all show decreases in swhen the mother is irradiated from which values of
k of the order of - 1 X 10-*/rad can be derived. If thisfigure is adopted for purposes of calculation, thenO n the basis of the present limited information, valuesof Rf have been calculated using a similar numericalvalue of k but of opposite sign

Clearly, if kf and km do in fact differ in sign, thensignificant results may occasionally be obtained by thecomparison of progeny of irradiated mothers withthose of irradiated fathers, even where neither groupdiffers significantly from the controls. On the basisof the numerical values adopted here, the same condition upon significance would then become

where Pf is the number of progeny of irradiatedfathers examined and Pa is the number of progenyof irradiated mothers examined. The resolving powerof comparisons with controls of progeny both ofwhose parents have been exposed will, under these circumstances, involve Df - Dm and be relatively poor
if the doses to the hvo parents are quite similar. If kf
and kcm were to have the same sign, the situation would
be reversed. By way of a numerical example, the data
of Turpin and Lejeune117~11s~105
may be considered.
I n this study, Pa is 136 and Q, is 236. For the purposes of this calculation, Dmand Df will both be set at
450 rads. Then R, may be calculated to be 0.175. The
calculated Rf for the same data is 0.52. In passing,it might be noted that because of the many somatic
factors thought to influence sex-ratiot one would as amatter of principle have more confidence in the genetic
origi? of a sex-ratio change among the offspmg oflrrad~atedfathers than among oiispring of irradiatedmothers.

56. That comparisons of the progeny of irradiatedand non-irradiated groups must be carried out on rather
a large scale, if there is to be any prospect that they will
yield significant positive results, is emphasized by thehigh proportion of non-significant results obtained in thecompleted surveys of table VI. Moreover, they may
require rigorous and complex analyses of controls,111
and therefore involve considerable effort of a very specialized kind. While negative results on a sufficient scale
can be of great value in excluding the most alarming
possibilities,''' onIy positive ones will suffice for a quanhtative relation between dose and mutation frequency.
I n this connesion, a survey of the high radiation area ofKerala113*lg5appears to have a potentially somewhat
greater resolving power than any previously made, if anequally intensive investigation over a ten-year period isassumed.
57. -kt its first session, this Committee requested advice from the World Health Organization about the possibility of setting up a standard of recognition for one

or more clearly recognizable medical conditions thought
to be largely or solely genetic in origin. I n their discussions of this, the geneticists of the study group t ~ h i c hframed the reply of W-HO made clear that they strongly
questioned the feasibility of using a single condition as
an indicator of the mutation level in large p0pu1ations.l~~
Their feeling appeared to be based in part on the manifold
uncertainties which exist concerning almost every single
likely indicator condition,l1° and in part upon the belief
that reliability of results in this field depends upon intensive study of every case. The study group recommended
that simultaneous investigations always be carried out on
several conditions.l13 Indeed, the sense of the document
cited is such as to cast some doubt upon the practicability of such surveys, in view of the associated difKculties of obtaining sufficiently large numbers. I t does not,however, rule out large-scale survey plans ii the urgencyof the situation warrants them. Moreover, if the objective were to survey one population serially in time so as
to be able only to establish limits of possible relative
increases in the mutation rate, tvithout any interpretation
as to cause, some of the difficulties might diminish.'1°
One such difficulty seem to lie in combining the intensive
examination of cases. which is the classical a ~ ~ r o a cofh
human genetics, with' the extensive survey ofL;ery large
populations which is required if adequate numbers areto be obtained for studies of mutation rates at or near
the spontaneous rate in man. This dficulty is emphasized by the sharp limit of about 3 x lo6 set in discussion
upon the size of human population which can be coveredby an institute conducting epidemiological surveys of theclassical type (see also ref. 11).

58. The difficulties of comparative surveys of highresolving power have led Penroseg3to propose a modified
approach, by which a given class of mutant propositi
would first be collected from a large population heterogeneous in radiation exposure as well as in other respects. and only then would personal histories, including
radiation histories of the parents, be compiled for the
propositi and a comparable control group. The method
is a powerful one for the wider field of general human
genetics. since it can serve as a basis for quantitative
investigations of other mutagens than radiation. As applied to the radiation problem, this same possibility ofalternative and perhaps unknown causes complicates the
choice of a legitimate control group. Moreover, the burden of work is in part thrown into a sphere where rather
considerable difficulty also prevails : the quantitative
compilation of individual histories of irradiation.ll'
In order to obtain a quantitative dose-efiect relationfrom a survey of this type, it is necessary to know not
only the incidence of the condition under investigationin the general population, but also the general incidence
in that population of individuals having similar radiation
exposures to those of various classes of propositi. Many
features of the approach are exemplified by the recent
work of Steward et al.l15 on a somatic radiation problem.
Possible aids ill extrapolatwn of radiatiolt-ir~dztced
17zzttationrates fronz otlzer species to Inan
59. I n view of the difficulties of a formal human radiation genetics. it is necessary to consider possible ways
in which radiation-induced mutation rates can be measured in systems closer to the in vivo germ cells of man.
In this connesion a new field of work has been openedby the ability of Puck and his collabor~torsto growcolonies of tissue-culture cells, the majority of which
are viable and able singly to give rise to fresh colo-n i e s ~ x , ~ ?The? well-developed methods of microbial
genetics can in principle now be applied to such cultures
both for natural and radiation-induced mutations, although certain features are believed by many workers
still to limit the applicability of the material to thisproblem :(a) Tissue-culture cells usually need a more complex
medium than the whole organism from which they
originate.
( b ) Well-established l i e s tend to be poly- or aneuploid. They resemble both each other and the malignant
HeLa strain, with which Puck first developed his techniques. I n certain types of radiation experiment, thisdifficulty may be circumvented, as in the work of
Bender,lg who used tissue-culture cells very recently derived from human kidney (within four transfers) in acytological study of induced chromosome breaks. But
the repeated propagation of lines of stable diploids fromsingle cells appears to be a prerequisite for systematicstudies of gene mutation in human tissue-culture.
( c ) Some workers in the field doubt whether any lineof normal (i.e. non-malignant) cells has really been successfully propagated as such (but see Puck)( d ) It is not yet known what is the exact relevance ofstudies on the mutational behaviour of somatic cells
in vitro to that of mammalian germ c d s in vivo.
Points ( b ) and (c) can perhaps be circumvented inpart by applying the technique to cultures derived as
freshly as possible from normal tissues. However, adifficultyof principle remains : the tissue-culture cell is afree living organism, whereas the ancestral tissue cell ispart of an organism so that its growth. division and differentiation are subject to the developmental controls ofthat organism. In view of the close connexion of all, andespecially the genetic, effects of radiation upon the cellwith the process of cell division, some initial caution ininterpretation is undoubtedly required. Nevertheless, thefuture role to be played by the tissue-culture methods inthe making of comparisons between species so as toprovide a basis for extrapolating from the known in vivo
mutation rates or rates of occurrence of gross structuralchanges, does not seem open to doubt.
.18*121*"211B4

60. There is some e v i d e n ~ e ' ~ ~thatJ ~ ' the frequenciesof radiation-induced mutations in somatic cells is similar
to that in gonial cells. If this correlation could be extended to the variation between species, attempts tomeasure induced and/or natural mutation rates in humansomatic cells in vivo might provide information of greatvalue as a guide in estimating mutation rates in humangenes.
Continired need of research in fulldarnental genetics
61. It cannot be too strongly emphasized that there islittle basis either for planning or for interpreting ad hocradiation genetic surveys in man, or for making calculations concerning radiation-genetic effects in man, except the great volume of fundamental research uponother organisms which has been carried out for its intrinsic interest alone, and directed wholly as a contribution to human understanding. This foundation must be
extended and strengthened, and must not be weakened
in the interests of the applied superstructure.

62. Provided that the dose-mutation rate relation has
a linear form
rn = m,kD+

the relative increase of mutation rate per unit dose isreadily expressed by the ratio k/m,. Another convenient parameter t o use js the reciprocal of this ratio,
mo/k, which is the radiation dose required t o produce
a number of mutations equal to those occurring naturally, or the "doubling dose" (Dz). For a whole seriesof mutations r n ~whose effects sum up or are collectively observed Z ml = 2 mol D z ~ ,

+

1

1

1

v
L4

and one can define a mean D as

m01
=

7 k,

fS ,.

This procedure can be used to estimate a D, for as
representative a group of human genes as possible. I t
is not necessary to know how many genes are involved
or of what kinds, provided that they can reasonably be
assumed to be a representative sample a?d provided
that there is assumed to be no correlatlo? between
Dz,, k l or m o tand thedegree or kind of manifestation.
The representative D2 should then express the doseeffect relation for a n y set of radiation-induced mutational events in so far as this itself depends upon asufficiently representative sample of human genes:
usually the sets will be of a kind in which the mutations at a very large number of loci a r e summed, bothin calculating and in making use of Dt.
Estinzutes of the representative doubling dose
for lrurlran genes
Gerreral levels in other species

63. I t has been pointed out1isJ50 that a number ofdoubling doses calculated for different species clusteraround the range 3 0 4 0 rad (table VIII). However, thesignificance of this fact for present purposes is limited
by several considerations :(1) The majority of the experimental radiation exposures concerned were of gametic cells. Where irradiation of gonial cells is concerned, it is true that the best
estimate that can at present be made for a group ofgenes in the mouse (the only mammal so far investigated) is of the order of 30 rad, but this must be compared, for instance, with values for Drosophila ranging
up to 400 rad (see table VIII).
(2) No satisfactory interpretation of the observed
concurrence or range of values exists, and consequently
any empirical extrapolation to man would have to rest
upon an unsure basis.
(3) The lack of correlation of observed doublingdoses with life-span can be interpreted as an indicationthat mutation at a constant rate in chronological time is
not the dominant factor in determining the natural rates
in the ~xperimentalspecies. But man is so much longerlived than the experimental organisms that in his casean appreciable fraction of natural mutations is alreadyquite likely to result from time-independent causes suchas irradiation from natural sources. (See P e n r o ~ e l 'for~a preliminary investigation of this point).
Sex ratio

64. Observations have been made of a shift of the sexratio in the progeny of irradiated mothers (see paragraphs 50, 55). In a first attempt to make use of theavailable data, Lejeune and TurpinlZohave proposed acomparison between the effect of irradiation and theeffect of aging. These authors have calculated a significant decrease of the sex-ratio with the aging of themother alone, the partial regression coefficient being-3.36 X 1 P for an aging of five years. Taking a value
for one rad as an estimate of the decreaseof -6 Xof the sex-ratio following irradiation of the mother(table VI), and assuming that both decreases are related to the same -tent to newly arising sex-limited
detrimental mutations, they have proposed a doublingdose of-3.36

X 10-4 X 6- 6 X 10-5

+ 30 rad / From age 0magnitude as that calculated from purely mutational
experiment. Establishment of such facts would greatly
strengthen interpretation of corresponding observations
upon man.
68. Although today it is not possible to assign any
definite confidence to the use of the sex-ratio as an indication of mutation rates, it must be borne in mind thatthe parameter, even if not totally satisfactory, is the only
one easily surveyed in entire populations, and that it
represents the "cheapest" genetic trend available to research workers in terms of technical effort expended insurveys.

to age 30 years.

Unfortunately, as these authors themselves recognize,such a calculation cannot be considered as legitimate
before many problems have been solved. The needs
include :(1) A good estimate of the gonad dose effectively received by the mothers ;(2) A better estimate of the decrease of the sex-ratiowith irradiation, including a test of linearity of the relationship between these quantities, which is implicit in all
current calculations concerning sex-ratio ;(3) An explanation of the apparent contrast between
the sex-ratio's decrease with the father's aging1"JS7 andthe possible increase observed after acute irradiation of
the father's gonads ;111-124(4) The study of other variates such as birth rankle%
which might interact with the real effect of the aging of
the mother.

65. Only some preliminary data relevant to the problem of irradiation of the father are available, but these
indicate that a sex-ratio decrease after chronic irradiation may perhaps have occurred in manlZ6and in themouse.lZ5 The latter body of data, although not significant at the 5 per cent level, yields at face value a
representative doubling dose in satisfactory agreementwith other data for this speaes.
66. In summary, while the possibility esists in principle of deriving a representative doubling dose by comparing the changes in secondary ses-ratio when parents
either age or are irradiated, the relevant phenomena are,at present, not sufficiently well established either quantitatively or qualitatively for this procedure to be reliable.
Yet relevant surveys of the secondary sex-ratio are more
readily and widely carried out in human populations thanare others which must depend upon finer diagnostic
distinctions. Consequently, more extensive quantitative
data concerning comparable irradiated and non-irradiated human populations should continue to be sought.
I n particular, it may be worth attempting to search for adecrease of sex-ratio among the progeny of not too
h e a d y !rradiated human males ; the conclusion of sucha test might go far to determine the utility of the parameter in considerations relevant to the human genetic
radiation hazard.
67. I t is not at present certain, even in Drosophila,
whether the postulated genetic causes of shifts in the
sex-ratio play .the. quantitative roles expected of them ;and data of thls kind are needed. It is also possible thatfurther investigations upon experimental animals, especially vnong the progeny of male mice irradiated at low
doses, together with slmllar observations upon irradiatedfemale mice, may show that in both cases a doubling dosecan be derived from sex-ratio shifts which is of the same

69. A reasonable probability now exists that, in anintermediate dose range, the radiation-induced incidenceof leukemia is a linear function of the Exposure of thebone marrow, whatever the manner of delivery of thedose. Upon this hypothesis, it has been calculated that
30-50 rad mean exposure of the red marrow might
suffice to double the natural incidence of leukemia
among an adult group??'
70. Leukemia certainly involves a transmissible hereditary change in the tissue cells concerned. a "mutation"in the widest sense of the word. Whether the processof its induction in somatic cells corresponds qualitatively
or quantitatively in any way to the process of apparent
gene mutation as it is normally thought of in g e m cells
is extremely doubtful. Nevertheless, it is not entirely
excluded from providing an indication of the relative
sensitivity of human cells to natural and radiationinduced genetic changes. The indication must, however.
be regarded with great reserve : even if the most helpful
possibility eventually proved true, and leukemogenesis
were primarily a process of somatic gene mutation, asingle very atypical gene in a somatic cell might beresponsible, and might be entirely unrepresentative oftransmissible germ-line mutations.
Survey of Japatiese cities
71. Although the results were negative, the extensive
observations of Neel and Schulllll in Nagasaki andHiroshima provide some evidence of a lower limit for
the representative doubling dose for human genes. atleast for the dominant mutations which would havebeen observed by these authors. A difficulty of the typeof sunrey conducted by Neel and Schull must be mentioned here: in order to obtain significant data, it isnecessary to continue collection of it for some considerable time. Among a population who have been
subjected to heterogeneous, hea\y esposure, there may
perhaps be some infertility of a progressive kind selectively induced among the most heady exposed groups.
In that event, incipient positive results may be masked
by later data collected in the attempt to make the observations more significant. I t is possible that the si@cance of the observations made in this kind of survey,
because of its scale, complexity and uniqueness, canonly be evaluated adequately by the authors. I t thcrefore seems reasonable to accept the opinion of Neel and
Schull that their negative results make it improbablethat the representative doubling dose for human genes
irradiated in gonial cells lies below 10 rad.

The trafztral exposlire
72. The representative doubling dose for human genes
undergoing chronic irradiation cannot be less than thegenetically significant exposure of natural origin. In
most areas this is about 3 rad per generation. I n exceptional areas, the natural radiation may contribute soheavily to the natural mutation rate that the observed
representative doubling dose would be increased.*
Clcrrent best estimates

73. Iiot one of the arguments in paragraphs 63-71
gives a reliable estimate of the representative doubling
dose, yet each depends upon a different, independent
set of unproven ideas. This Committee recognizes aneed, in our existing state of knowledge. to make use of
every available source of information, however tenuous.
I t considers that the separate arguments and repeatedindependent observations of small changes, in spite of
the statistical limitations upon their significance. provide
a reasonable indication \\-hen taken together; the representative doubling dose for human genes irradiated inpregametic cells is likely to lie between 10 and 100 rad.
There is supplementary evidence that it cannot be lessthan 3 rad. The Committee notes that the value 30 rad iscompatible with the whole of the probable range cited,within a factor oi about 3 : it therefore has a certain
degree of utility for purposes of calculation wherevera "most probable" value of the representative doublingdose is required.

XfUTATIOKS IK THE G E S O J I E O F .\IAN

74. Because radiation-induced mutation has not yet
been observed with certainty in man. it is not possible
to give a satisfactory estimate of total induced mutation
rate: indeed, this is hard enough even in Drosophila.lo8
Nevertheless, it could be hoped that the total rate mightbear some relation to total genetic material : such a hope
has recently been supported by the only available comparison, that between calculated total induced recessive
lethal rates asd DNA contents in the mouse107 andDrosophi1a.i The DNA content of human cells is about
6/5 that of mouse cells, according to V e n d ~ e l yHence.
.~~upon the stated hypothesis, it might be expected thatroughly one recessive lethal per 250 rad would be induced in human sperm by irradiation. Again by analogy
with both the mouse and Drosophila, which behave
alike, it might be expected that in spermatogonia only
about one quarter as many gene mutations would occur.
However, in Drosopl~ilait has been estimated that the
total rate of mutation to appreciably deleterious alleles
is about four times the recessive lethal rate.'Os In theassunlptions made so far, it has been possible to rely
upon common quantitative behaviour of two diverse
species. But the induced mutation rates for single lociof mice, as well as the total recessive lethal rate, aregreater than those of Drosoplzila by a factor of 20,

corresponding approximately to the ratio of DYA contents per cell. This has suggested that perhaps the individual genes of the mouse are not more numerous
but are larger and more comples than those of Drosopltila. In turn, the ratio of total to recessive lethal mutations might be very greatly affected. That this isperhaps not SO is suggested by comparison of theinduced mutations at sets of v~siblerecessive loci inthe two organisms. In both cases, some hvo-thirds ofthe experimentally induced mutations have been foundupon investigation to be lethal. The similarity could be
a property peculiar to visible loci : but it at least suggeststhat the ratio of total to recessive lethal mutation rates
may be the same for these tsvo and possibly other species.
I f the Drosophila ratio is applied to man on these tenuous grounds, a total induced rate of appreciably deleterious mutations of about one for every 250 rad applied
to the gonial cells is suggested. It will be clear to thereader that based as it is upon so many tenuous hypotheses, this figure. must be regarded with the very greatest
reserve. In particular, it applies only to the sum ofoligogenes with individually detectable effects m dneglects the polygenes involved in quantitative inheritance, an especially serious omission for organisms
which may have considerably larger and more complex
genes than Drosopltilu, and may therefore be relatively
much more liable to small changes giving rise to many
isoalleles even at known loci.

11. T H E GENETIC CONSEQUENCES
OF IRPL4DIATIOX

75. The fate of a mutant allele newly introduced into
a population is determined by selection. Hence the connexion between mutation and the genetic damage due
to it depends primarily upon the selective properties ofthe mutant alleles concerned and, in particular. upon
the degree of dominance or recessivity of these. Our
ignorance of the relevant facts in man is very complete
and urgently requires rectification.

* T h e parameter of biological interest is, of course, the ratio

76. I t is useful to precede inquiry into the action of
the selective process upon mutant alleles by an inquiry
as to the origin of genetic variation in natural populations and its connexion with fitness. The question is an
old one. especially in connexion with plant material,
where the great extent of natural genetic variation was
early observed, and where breeding experimexits earlygave rise to the controversial notion of "hybrid vigour".
I-Io~vever,much of the agronomic literature is primarily
concerned with the rxxternally applied criterion of "yield"
rather than with fitness. hloreover. natural populationsof plants differ decisively from those of animals in the
aspects of genetic structure which are of immediateconcern here.

per unit dose. In man the spontaneous and induced componentsof the natural rate cannot be separated, and it is convenient todefine the representative doubling dose in terms of the total
natural rate. However, in situations such as that described here,
the distinction bet~\.een the spontaneous and natural rate
becomes of importance and must be maintained.
ti\ figure for tht total rate of induced recessive lethals ha:
also been given for yeast by the careful work of Bfagni."Vtappears at first sight to disagree with the hypothesis put forward
here, because of the exceptionally low DNA content of theyeast cell (table VII). However, yeast is known to possess 3.
relatively extensive non-chromosomal genetic apparatus."' It
has therefore not been used here for comparison.

77. What may be called the classical view of theadaptive norm of a natural population supposes the
optimal allele to be homozygous at most loci: this situation of mzximum fitness is disturbed by mutation.
continually restored by selection : rarely, due to chance,
to change in external conditions in time or space, o r tochange in other parts of the genotype, a mutant allele
will prove itself advantageous, displace the fornler predominant allele at the same locus, and become the new
wild-type allele (see review in ref. 130). I n recent
years this view has been increasingly strongly challengedof the spontaneous mutation rate to the induced mutation ratetion: the expressions o i these alleles also contribute toby some,'30 especially in conncxion with the accumuthe
genetic component of human ills.
lation of extensive evidence concerning the prevalence
and the superiority in many respects of structural heterozygotes in natural populatio~lsof D ~ o s o p l z i l a a, ~ ~ ~ ~81.
~ ~As
~ yet, nothing is known of the rate of induction
by radiation of the mutations responsible for any specificfinding which is itself, however, compatible with thecondition in man. I n consequence, the discussion whichclassical ~ i e wof genic homozygosity as the adaptive
norm. I t has also been argued on more general grounds1ss follows will be restricted to broad categories of effects.
Only by such a grouping together of the consequencesthat heterozygosity is the adaptive nonn at most loci andof mutation at a large group of loci can a representativethat heterozygotes are in fact intrinsically better able torate of induction of mutations per gene, or a representaadapt themselves and maintain their own stability in thetive doubling dose, be applied: these are the only two
face of changing environmental conditions. A recent
parameters expressing a dose-effect relation so far
experiment byseems to indicate that evenavailable.
random unselected radiation-induced heterozygosity ingeneral confers an advantage, at least upon individuals
82. I t is natural, in applying the results of an exotherwise homozygous for certain pairs of arbitrarily
perimental science, to try t o use a synthetic approach,chosen chromosomes in laboratory populations ofassessing an effect from the accumulated knou-ledge
Drosophila.
of various causes. In the present instance, this means
attempting t o assess the magnitude of the social con78. These two views lead to different general expecsequences of increased mutation by using mutation
tations concerning the consequences of mutation. On
frequencies per rad a t particular loci t o build up a
the first, most mutants alleles will contribute to the
combined estimate from the effects of induced mutalimited degree of heterozygosity, will be harmful, andtion a t all loci. T o use this method, let the total
will require to be eliminated, diminishing the fitness ofmutation rate to the set of alleles responsible for a n y
the population. On the second, mutational events, alspecific condition denoted by i be k,D, where D is thethough the majority of them will still be harmful andgenetically significant dose of radiation to the populawill require to be eliminated, will scarcely affect thetion. By a theorem originally due to Haldane8.i there
great degree of heterozygosity already existing, and willmust on the average be klD subsequent eliminations
diminish the existing reproductive fitness to only a corof the mutant alleles through differential failure of
respondingly small extent. However, this is a consereproduction. These are often referred to a s genetic
quence of the fact that since the mating of diploid
deaths, although they may take place through pheheterozygotes produces some homozygotes, on thenomena such as very early'abortions, which are of no
second hypothesis the population must pay for its built-insocial significance, as well as through more or lessadaptability and plasticity by a permanently reduced
severe disabilities or even premature death. Suppose afitness due to these.
fraction p l are eliminated by socially serious expres79. Unfortunately, while evidence now exists for the sions and think of p, as including some weighting factor
second view of natural populations of Drosophila, thiswhereby such qualitatively diverse end-results a sparticular organism has certain features (principally
death, physical disability, mental deficiency, etc. m a ychromosomal inversions) which bestow upon it a special
somehow be quantitatively compared. Then the concapacity for carrying structural heterozygotes, together
tribution t o the social burden is kIp,D and the wholewith all the consequences which may flow from thiscontribution of the dose D t o the future social burden
capacity; these features include the absence of crossingis HklptD over all such specific conditions. The above
over in the
coupled with a mechanism forargument continues to hold whether the mutation ineliminating undesirable products of cross-over between
volved is to an allele which from the selective point ofstructurally different chromosomes from the egg in theview is conditionally or unconditionally deleterious,
female.ls8 There is no reason to suppose man to possess
although if the mutant allele is only conditionallyeither this particular structural mechanism or an optimal
deleterious then (a) it cannot be eliminated in thosedegree of genetic heterozygosity, although the possibility
situations in which it is selectively favourable, andis not excluded that equivalent mechanisms may be( b ) the total elimination rate a t any one time may
found. Hence the Committee is compelled to assume that
greatly exceed the mutation rate, because the increased
the general genetic structure of human populations corfertility of carriers under the selectively favourable
responds more closely to the classical model in so far
conditions increases the gene frequency. If the natural
as this relates to known genes having individually demutation rate m, is known, then k t can be re-expressed
tectable effects. There is, however, no basis in ourin terms of the doubling dose D2, by jCIDzl = m i andpresent limited state of knowledge for deciding whether
for all mutations or a large class of them a mean
the genes responsible for quantitative inheritance dod s b l i n g dose I 3 2 can be defined by the equationo r do not maintain themselves by overdominance in so
kDz = m where k = Tk, m = fml. I t is unfortunate
far as they affect the over-all fitness. I t must be emthat in man we do not know any individual k lor D?,.
phasized that upon all the hypotheses discussed here, theStill more unfortunately, the fractions eliminated bygreat majorlty of radiation-induced mutations will be tosocially serious expressions, pl, are unknown and may
alleles which are UI the first instance harmful and undepend upon rather small positive or negative fertility
likely to be retained in the popuhtion.
differentials in those ~ v h ocarry the mutant allele without expressing it, if they greatly out-number those inwhom it is expressed. Nor can a mean p, be estimated
2. APPROACHESTO QUAXTITATIVE ASSESSMENT
for mutant human alleles. As a result, the synthetic
O F THE GENETIC COSSEQUEXCES O F IRRADIATION
approach leads t o an estimate in such terms t h a t i t
OF HEMAN P O P U L ~ T I O ~ S
cannot as yet be satisfactorily related to the social
consequences.
80. On the classical basis, the irradiation of humanpopulations is espected to result i11 mutations to alleles
83. There is an alternative formulation of the problem
whose expressions are harmful and lead to their eliminaby an analytic approach. based upon analysis of thepresent social burden in terms of naturally occurring
hereditary defects. In this, it is asked, ( a ) what is thesocial burden bl due to a given condition denoted by i,whose occurrence is related to the presence of adverse
genes? ( b ) Of the genetic burden bi, what fraction f
is due to recurrent mutation? ( c ) By what fraction gi
will this be increased immediately or in the future by agiven fractional change c, in the natural mutation ratem i Z If the change ci is caused by a genetically significant
dose D to the population.

For all conditions or a large class of them the total
genetic burden may be written b = f bl, that due torecurrent mutation fb = flbland that due to a givendose D asfglflbI. If it is assumed that g l = cl, this-.
may be written as

TIt may be assumed that bi and f t are independent of
D,,. Then the increased burden may be written

D/a2 $fib, which may be written (D/Dz)
f bwhere f = %fibl/ ?blT h a t is, the genetic burden due to a given dose
equals( p e of genetic burden
X ma~ntainedby recurrent
doubling dosemutation)

given dose

The relation behveen induced mutation rate and exposure enters here only through the representative doubling dose. In the present state of knowledge, the analytic
approach is more certain than the synthetic approach,because the relation between induced mutation rate andexposure enters only through the representative doubling dose.

84. Even supposing the necessary quantitative relations between mutation rate and dose or radiation exposure to be known. calculation of the social consequences still requires knowledge of one of the sets oi
parameters, pi or f dependent upon selective behaviourof the mutant alIeles. The hvo approaches are comparedfrom this point of view in table IX. I t will be seen that,
under conditions in which mutation contributes a largepart of the social burden, f l is relatively well known
but pi is not. Moreover, there is some reason to believethat most heterozygous carriers of individually detectable, socially deleterious recessive alleles are slightly~ * is' ~true,~ most f iless fertile than a ~ e r a g e . ~ ~IfJ ~thisare kno~cnbut most p1 are not. It is concluded that, formost purposes, the analytic approach starting from thecurrent social consequences of unfavourable alleles is tobe preferred to the alternative method at the present
stage of knowledge.

85. Certain assumptions are implicit but not stated in
the analytic approach to the problem adopted here :First. it has been assumed that the genetic componentof the social burden is directly related to the expressed
effects of unfavourable alleles. However, the actualsocial burden realized in a population will be modified
by environmental factors such as the cutent of caredevoted to those affected. For this reason, the actualsocial burden resulting from a given genetic situation
may be heaviest in those countries having the best medical care of the afflicted.
Second, the genetic component of today's social burden has been assumed to be related to the present natural rate of occurrence of mutations and to present
selective conditions. Certainly this assumption is not true-the number and distribution of recessive alleles isdetermined by a long history of past mutation rates andpast conditions of selection-yet with our present limited
knowledge of the distant past and future no alternative
assumption seems to present a possible basis of calculation. A number of considerations indicate that theerrors involved may not be too serious :( a ) Because of recent improvements in medical carethe present genetic burden may be below equilibriumwith today's rates of elimination of undesirable alleles,
so that the effects of a given increase in mutation rates
are underestimated. On the other hand, further improvements in medical care are likely in the future to reduce
the socially serious effects of mutations. This process
cannot by itself affect the influence of mutation upon
the Darwinian fitness of the population, but may affectthe future social burden due to present mutations if it
occurs without a corresponding effect upon the rates of
elimination of the socially deleterious alleles. If thiselimination takes place largely through rather trivial
effects in heterozygous or other carriers of unexpressed
alleles, alleviation of the expressions in grossly affectedindividuals might be accomplished with little influence
upon the process of elimination. We would then haveoverestimated the future social burden from present
mutations. Thus the two sources of error due to improving medical care act in opposite senses.

( b ) I n spite of changes in diet and living conditionsof all kinds, there is no reason to suppose that natural
mutation rates have changed very greatly; for example,
chondrodystrophy, which, in man, is largely a dominantdisease, has been prevalent at a low frequency sinceancient times.139 Selection has, by contrast. certainly
undergone great changes. This fact is relevant to therecommendation, contained in the report of a WHO
study group submitted to this Committee.ll that research
be initiated upon selection in primitive communities
while the opportunity to do this still exists." But manyof the specific detectable conditions with which we s h l lbe concerned here either arise from dominant alleles,and hence do not in general persist for so many generations as recessives, or else they confer a reduction in
selective fitness which has not yet been greatly modified
by advances in medical practice. The working assumption may therefore be not too greatly in error for thebroad categories of effects to be considered. I n point o ifact, the effect of improved living conditions and improved medical care is far from obvious. Penrosel'O haspointed out that, besides preserving less fit individuals,
this change may in recent years have removed the selective advantage of alleles which confer a degree of protection against an infectious disease in the heterozygote
while being grossly deleterious in the homozygote: theclassical example is siclcle cell anaemia.141 HOWmany
such situations exist is debatable. However, the consequences of improved medical care could be called eugemc
rather than dysgenic in such cases. It must also be bornein mind that the total potential intensiq of selection in
populations has, at least in recent years, not been e a n g ing anything like as rapidly as the qualitative.basls of
it.142,143 I t may be observed here that the possible dys--

genic effect of future improvements in social and medicalcare is limited by the fact that no more deleterious
mutant alleles can be saved for later generations thanarise by mutation; moreover, a subsequent withdrawalof improved medical care by some social catastrophe will
not cause more losses than would have occurred anyway
had it never been present. Only the distribution in time
will be altered. Thus, in a constant population, the dysgenic efiect of a changing selection does not increase
the total number of seriously affected individuals but
by contrast, the dysgenic effect of increased mutation
does increase the total number of seriously affected individuals. Finally, it has been assumed that radiationinduced mutations and spontaneous mutations are qualitatively similar: that there is no correlation between D,!
and the degree or kind of manifestation ( f i , bi. pi) of agiven mutation. This assumption has been discussed inanother section and is acceptable to the Committee.

86. On the basis of the above arguments, the Committee considers :(a) That the most satisfactory assessment of thegenetic consequences of irradiation of human populations which can be attempted at the present time must be
based on the present social burden due to hereditaryconditions. Because it must employ the representative
doubling dose, it must be restricted to rather broad
categories of effects ;(b) That the sources of error in an assessment of thiskind may not be too serious ;(c) That two principal sources of error are related tothe extent to which selection changes in the transition
from a technologically primitive to a technologically advanced environment and to the extent to which alleles
responsible for socially serious conditions may confer
small favourable differentials of fertility in the heterozygous, impenetrant or other "carrier" states. Both require to be investigated.
3. THECURREKT SOCIAL BURDEN O F GENETIC ORIGIN I N
H U N A N POPULATIONS, ITS CONNEXION WITH &IUTATION
AND RADIATION EXPOSURE

87. I n order to make use of the representative
doubling dose discussed earlier, there will be consideredhere only broad categories of damage, each of which
may be caused by mutation at any one of many loci.
such as the sums of specific clinical conditions or traits
within various genetic categories, or biometrical characters such as intelligence, life-span or birthweight, eachlikely to be dependent upon many genes, or fertility.
Specific traits
88. For the present purpose, the available information
concerning the incidence in man of specific diseases ordisabilities of genetic origin is severely limited. Only
very few sizeable populations have been surveyed, notably in den marl^,'^^ Michigan, U.S.A. and Northern
Ireland.14* hIoreol-er. good quantitative data are only
available for clear-cut traits or disorders. and, even here,
the genetic interpretation of the facts is almost neverstraightfon~ard.l10In the past, various estilnates havebeen made of the frequencies of such specific traits, but
the basis of the estimates has not aln.ay-s been clear.
Sometimes it has been uncertain n-hether the trait irequencies referred to were those at birth or in the whole
population. The latter estimate would aln-ays be expected
to be lower, particularly if the trait \\-as severe in its

effects. Independent over-all estimates, both in the literature and in reports to this Committee, seem to be inreasonable superficial agreement with each other and aresummarized in table X ; each of these implies consideration of one or another category out of a total of some
500 dear-cut disorders or traits.133 However, it has seldom been specified which traits are included and which
excluded in them.
S9. I n order to formulate, upon a precise basis, overall estimates to which a representative doubling dose canreasonably be applied, the Committee has made use in thepresent report of a single, definite list of traits and theirestimated frequencies of appearance in a single populathe popution, namely that compiled by Stevenson""orlation of Northern Ireland. I n so doing, it is recognizedthat the frequencies of specific traits will be different inother populations, so that some listed here may not occur
at all, and others not in the present list will be prevalent.
Nevertheless, such comparisons as can be made of the
population frequencies of traits in different parts ofEurope, North America and Japan suggest that, while
the contributions of individual traits to the total may
differ considerably in different populations, the totals,
and their division into principal categories, will not vary
appreciably so long as present methods of detection are
employed.
90. The list of traits compiled by Stevenson has beenbroken down into separate categories in the following
manner, which differs somewhat from that used in theoriginal compilation.lM
Category I (table XI (a)-(b)): Category I includes
traits detern~inedby single, harmful mutant alleles. The
majority of these are dominant with a ligh degree ofpenetrance, but some are autosomal recessive and a few
are sex-linked. Most are not recognizable in the affected
person at birth. I t seems reasonable to assume that inrespect of these traits there is no significant selective
pressure in either direction against apparently unaffected
carriers of the mutant alleles, although this cannot be
proved in our present state of knowledge. I t would
therefore be expected that the ultimate consequence ofan increase in mutation rate at each or all of these lociwould be a direct effect upon trait frequency. About 110
different mutations are required to explain these traits.
No doubt some similar, but separately identifiable, traits
are determined by alternative alleles. Of these mutant
alleles about 72 are dominant, 30 autosomal recessive
and 8 sex-linked recessive. The estimated total of liveborn affected is 1.1 per cent.
Category 11(table X I I ) : Category I1 includes a considerable number of traits mostly detectable at birth.
A proportion of them sometimes determines intrauterine death, but this fraction of these conditions isignored in the present contest. Maternal health andintra-uterine environment appear to play a considerable
part in determining whether and to vhat degree they are
expressed. Their familial patterns in a community seldom satisfy the criteria of a single mutant expression.
In all there is a familial concentration of cases greaterthan would occur by chance. In sorne, the family patternapproaches some of the criteria of those included in
category I, and it will be clear to the reader that arbitrary decisions have had to be made. The estimated toralof 1i1-e born affected is 1.0 per cent.
Category 111 (table X I I I (a) - ( b ) ) : Category 111
comprises t ~ v ounequal classes of traits. The first andsmaller proportion (categoq- 111 (a) : table XI11 ( a ) )consists of traits which appear to follow closely the es-

pected family patterns of a single recessive mutant genes,
but show a frequency too high to be explained on a basisof mutation pressure alone, unless it is assumed that
mutation occurs many times more frequently at the relevant loci thvl at those loci giving rise to dominant mutations in man or than in the general range of all types ofmutation in experimental animals. I n the data forand elsewhere in the United ~iNortherndom, only fibrocystic disease of the pancreas and deaf
mutism clearly fall into this category, although otherconditions well-known elsewhere such as sickle cellanaemia and thalassemia also belong to it. I t is possible,
although neither provable or disprovable at present, thatthe gene frequencies in these conditions are maintained
mainly by relative selective advantage in the heterozygous carriers. In deaf mutism several independent
mutants contribute to the trait frequency. The two conditions together determine about 37 per cent of the totalfrequency of recessive traits at birth in the population
have a combined
studied by Stevenson (lot. Cif.)frequency of 0.09 per cent of all live births. The secondand larger proportion (category I11 ( b ) ; table XI11
define and limit.
'I1 is(b , )
examples of serious, "constitutional," diseases are listed
in the table, but it is difficult to know where to draw theline thereafter. I n different communities the frequencies
will vary considerably. I t is impossible to estimate frequencies without malting some arbitrary decisions as towhat will be included: as an example, admission to hospita1 might be made a criterion. Furthermore, the frequencies depend on the ages to which people live in populations, as in the cases oi diabetes and the primary presenile psychoses. Finally, there are environmental factorsof importance which vary in different populations. I nsum, at least 1.5 per cent of those liveborn will sufferfrom one or another of this group of disorders.

I

91. I t must be emphasized that the list of traits, trait
frequencies and categories outlined above and in tables
XI-XI11 :( a ) Represents only tangible or detectable genetic
damage, which in principle, although in practice withgreat difficulty only, can be assessed by "counting
heads" ;( b ) Includes only defects of such severity as to be atleast very inconvenient to their possessors ;('1 Isanlist, even of such 'Onditions ;( d ) Ignores matemal/foetal incompatibility andmongolism ;in the latter the genetical component appears
to be weak, and in the former the relative frequency of
the alleles, which is the most important factor in determining proportions of affected infants, would probably
not be affected appreciably by increased mutation rates;( e ) Exdudes a group of individually rare or mild
traits which mostly appear to be determined by simple,
irregular, dominant genes and are listed in table XIV.
Nevertheless, the list gives rise to the expectation thatsome 4 per cent of the liveborn suffer or will suffer fromdefects predominantly of genetic origin. Certain comments are pertinent to this estimate :(1) Any present over-all estimate of total genetic
damage must of necessity be minimal. However, eventhough more sophisticated methods of detection can be
expected to increase the present estimates, it is unlikelythat in the near future more than a very small numberof new specific traits will be discovered, relative to thetotal so far known. (See also paragraph 104 below.)( 2 ) The present estimates refer to those born alive.
In addition, approximately another % to 5 per centfoetuses alive after the twenty-eighth week of pregnancy
are born dead mainly by reason of detectable developmental defects which may be of genetic origin.
(3) In about half of the affected liveborn, the defectwill
detectable
at or soon after birth, but in the other~ be ~
half the expression of the genotype will only be apparent
in later childhood or in adult life.
92. l-he division of the 4 per centlive-births
into categories as outlined above may be summarized asfollows :Category I: About 1 per cent of defects due to single
mutants of classical type (majority not recognizable atbirth) ;Category 11: About 1 per cent showing no consistentfamilial pattern compatible with a simple genetic hypothe ~ andi ~often having an environmental component intheir aetiolog~(majority recognizable at bidh) ;Category 111 :About 1.6per cent either ( a ) show trait
frequencies too high to be maintained by mutation pres( b ) determine constitutional illnesses whosesure,
frequency is also unexpectedly high in relation to theirseverity.
This division into categories is of great importance forpredicting the results of increased exposures of populations to ionizing radiations. The supply of recognizably disadvantageous mutant alleles in a population may be maintained either by recurrent mutationsbalanced by selection or by selective advantage amongindividuals in whom the disadvantage is not expressed;that is, by a balance between opposing selective forces.
A reasonably small increase in mutation rate cannot
be expected to affect greatly the pattern of gene elimination and so should cause at equilibrium an equal
fractional increase in the genetic damage due t o alleles
maintained in the first manner (corresponding t o traits
in category I above, together with an unknown fractionof those in categories I1 and 111), but a much smaller
increase in the genetic damage due to alleles mentioned
in the second n ~ a m ~ (correspondingert o an unknown
fraction of the traits in categories I1 and I11 above).
I t follows that permanent exposure of a population t oan extra genetically significant dose D per generation
may be expected eventually to give rise t o an increasein the incidence of live-births who are or xi11 beaffected of between D/D2 per cent and 4D/D2 percent where D 2 is the representative dose. If the increased irradiation were to occur in only one generation to a population of fixed breeding size P, it follows,
by a principle of detailed balancing, that the calculated total number of affected live births is expected
to lie between
DP
D
4P-X-and-XI32
100
Dz 10093. must be borne in mind that the mutant allelesconcerned in the above estimates range all the way frpm
severe dominant to true recessive, and the time durlngwhich the genetic damage either climbs to equilibrium orcompletes its expression after exposure of a single generation varies in turn from one or two to many tens ofgenerations. Thus, in the case of irradiation of thepresent population, the damage may well become expressed under social and technological conditions which
189

-

.

cannot even be imagined today, and which map grossly
affect the relation between gene elimination and its social
consequences. Some geneticists therefore question theutility of assessment of a hazard so far in the future.lc6

and confers greatest uncertainty. Mather's calculation isa useful guide to the upper limit of the social burden
expected to be conferred by radiation-induced genetic
changes in the variance of intelligence (but see footnote
to paragraph 102 below).

94. I n conclusion, it must be emphasized that even forthis most tangible kind of genetic damage, far more
Relatiotrship of gettetu cotnponertt ofwork is ~leededon family studies, on sib-correlations,variartce to ?nutation
incidence in consanguineous marriages, twin studies etc.,
so as to establish more accurately the genetic nature of
97. The relationships of selection, genetic variability
the traits listed here and other conditions. I f Governand mutation in a character of relatively low selective
ments wish to h o w the genetic health of their peoples it
importance (bristle number) have been smdied by\%'illbe necesrxy for them to Support the necessa~lvork. erd authors in ~ ~ ~ ~ ~ ppartidar,
h ; l ~ Clayton.
~t has been argued that, at present, ~ o ~ u l a undert ~ o ~ ~Robefison1SJ halle been able to show that thereview by single institutes of human genetics cannot conadditive genetic variancein an outbred pop*tion,
fromveniently exceed 3 X 10°.ll However, the problems reflies were originally dramrn,
which theirlated to both the scale and scope of such work involvethe spontaneous increase in genetic variancequestions of general medical education and co-opeation
per generation by a factor of l,m,and observat~onsby
as well as legal and administrative aspects which merit(quoted by Matherlsi,l~6~
suppan this concluthe attention both of Gove131menfs and public healthirradiated and unirra&ated popula,ion. By
authorities. For example, a number of human geneticists
tions, Clayton and Robertson further showed that somefeel that the present Manrial of the Itttertlational Stafiswould have been needed to produce an incrementtied Clmsifiation of Diseases, Injuries and Causes o jequal to the natural variance. w i t h selective neutrality
Death is inadequate in its present scope and form forsuch a genetic variance in the natural population is perscientific purposes in the classification of congenital
fectly compatible
m esrablished equilibrium beconditions.
tween mutation and a degree of inbreeding due to limited effective population size. For a character of greater
selective importance the genetic variance displayed by
Bio?netrical clzaracters
the population would exceed the increment per genera95. Many important characteristics of man, amongtion by a correspondingly smaller factor. Haldanel" haswhich specific mention must be made of intelligence, lifepointed out that, in the cited case of birthweight, selecspan and birthweight, vary continuously in natural p o p tion removes 10 per cent of the obsen~ablevariation perlations about some mean which is often close to a selecgeneration. If this selection makes no distinction between
tively optimal value. Where this is true, selection may
variation or' genetic and of environmental origin, it poses
act on the phenotype quite largely by reducing thethe question: HOWis the genetic component of variancevariance, rather than by shifting the mean; to thatmaintained?
extent, it is normalizing or stabilizing ~e1ection.l~~Suchasdiscussed the theoretical
98. R o b e r t s ~ n ~ ~ %recently
quantitative variation is often influenced by many genes
for
optimalcentral phenotype.
inwhose separate effects cannot be distinI t appears that this process cannot of itself maintainguished, in contrast to those exhibiting specific qualitagenetic variability, even though heterozygotes have intertive effects and discussed above. T~~~~
genes can onlybemediatevalues of the character (see Fisherls0). The
studied statistically, principally through that part of thegenetic variation must therefore be maintained either byvariance of the character for which theyare responsible,
the selective advantage, in some circumstances, of thehi^ variance may be of considerable importance as aheteroz~gotesas such (i.e., the majority of the genes aresocial burden or loss of population fitness. Discussion
individually heterotic) or by mutation. Lerner13' has arof the consequences of possible shifts in the mean ofgued for expecting heterosis among genes of this kind,such characters will be deferred t~ paragraph 99 below.
his argument being based partly upon an anticipation of
96. The genetic component of the variance has been
improved buffering or canalization in the developmental
tentatively estimated in the case of birthweight byprocesses of heterozygotes and partlyupon experimental
Penrose and by Robson as some 40 per ~ e n t , ~ ~ ~ . ' ~ " h aevidence (of which, however, a considerable fraction isof .it associated with maternal genotype, and in the casedrawn from Drosophila) and general experience of inof intelligence asor perhaps as high as %.lS0 In each
breeding. Paxman1Si.1B6has, on the other hand, failed toof these cases, the more extreme phenotypes of the disfind evidence of such heterosis, despite a search for it.
tribution are observed to be associated with a loss inThus evidence of the necessary heterosis is by no means
viability or reproductive fitness and with social burden.
conclusive and further data are much needed. A t theThus on the basis of P e n r o ~ e ' s land
~ ~ Karn and Pensame time, the high rate of selective elimination doesrose's1'' work it can be estimated (see appendix) thatnot seem compatible with replacement by mutation at
the genetic component of this variance was associatedthe low rates observed in experiment. This difficulty may
with the occurrence of some 1.6 per cent of stillbirths
ivell, however, be less than it seems, because where manyand neo-natal deaths among males. MatherlS2has calcugenes of similar effect contribute to the variation of alated that on an intelligence quotient scale normalized
character, only a portion of the total genetic variability
to mean 100 and standard deviation 15, 2.3 per cent ofpresent in the population is manifest as variation actuallychildren will fall below intelligence quotient 70. and aobservable by difference among the phenotypes of the
doubling of the heritable component of variance, assumindividuals. In a polygenic system, alleles at different lociing no shift in the mqan, would increase this number by
can =ert their actions in opposite directions and thus
a factor which may Ile between 2.2 and 2.9 ; this calcubalance out one another's effects, so that some of thelation depends upon the assumption of a Gaussian disvariation lies hidden as balanced differences within thetribution of the measured variable at the tails of the
genotypes of the individuals.19i The proportion of the
distribution, where the assumption is itself least sure
total variability so hidden increases directly with the

s,

190

number of genes in the system, and it may go up evenhigher if the genes are linked. The hidden variability isreleased by recombination of the genes which balance one
another, to become exposed as phenotypic differences,and this rather than mutation is the immediate source ofreplenishment of the observable variation eliminated bynatural selection. Ultimately replenishment must depend
on mutation : but, by virtue of the reservoir of hidden
variability, the accunlulation of new variation from mutation need balance loss through selection only in thelong term. Thus the rate of selective elimination observedat any given time need not provide a reliable indicationof the rate at which new variation is arising by mutation.
Furthermore, the selective elimination of any fractionof the observable variation represents the loss of a muchsmaller fraction of the total genetic variability. Thus withbirthweight. 10 per cent of the observable variation iseliminated in each generation, but this loss could represent as low a fraction as 1 per cent of the total genetic
variability for this character in the population if it
depended on the simultaneous action of no more than
10 polygenes. Mutational increments quite low in relation
to the total variability might thus suffice to maintain theplygenic variation of a character against the erosion of
selection. This is a matter on which more data areneeded ;but pending their appearance it would seem conof the genetic variability
servative to suppose thatof most quantitative characters is the greatest fraction
which it is necessary to envisage as replenished by mutation in each generation, and the fraction may indeed generally be very much smaller than this. The Committeeemphasizes, however, that there is at present no satisfactory experimental basis for determining whether thisfraction is large or small even in experimental species,
much less in man. Clearly, further data are much neededin this whole area.

xo

Shifts ilr mean vaktes of metrical characters
99. Besides contributing to the variance of a metricalcharacter, genetic factors may impose a social burden byaffecting the position of its mean. Three quantities must
be considered : the population mean, the selective optimum and the social optimum. The three may all differ,as is illustrated in table XV for the characters mentioned
in paragraph 95.
100. The great majority of well-studied single-locus
mutants in experimental organisms are hypomorphic ;15e*160
that is, they appear to lead to a reduction in
the function or character most immediately affected.
There is good a priovi reason to expect this, as random
interference with a complex machine will more often be
destructive than constructive. In consequence it might be
expected that most mutations and mutant alleles would
act so as to diminish the population mean relative to theselective optimum. However, it must be questioned
whether there are sufficient grounds for extrapolating
this view to polygenes affecting quantitative characters.
Provided that the changes are not so large that they
excessively disrupt the organism's general control of thedevelopmental channels concerned, is it not just as reasonable to suppose that a particular organ of social
import-for
example, the brain-may in fact benefit
from hypomorphic changes in most other organs, due to acompensating diversion of resources, so that many suchchanges would be hypermorphic for it ? Among the characters of table XV, it is of interest that the facts concerning birthweight151 fit the classical expectation, but thatthose concerning intelligencelsl possibly do not.
101. I n the case of birthweight, it can be calculated(see appendix) that the di&erence by which Karn andPenrose observed the selective optimum to cxceed the
population mean in males is associated with 0.4 times as
many deaths at or near birth as the total variance andabout 0.7 times as many as the estimated genetic component of variance. What proportion of this deviation is
genetic in origin is not known, but it is clear from thearguments outlined above that recurrent mutation could
easily be the principal cause ; if so, co~ltinuedapplicationof a doubling dose to every generation might eventuallybring about an increased incidence of some 1.2 per centin the deaths at or near birth. This selection acts so as todiminish the difference between the mean and the selective optimum by about 7 per cent per generation.15' If it
does not distinguish between genetic and environmental
components of the difference, the genetic effects of analtered mutation rate upon the mean must be expected to
be spread over some ten generations, and any shift to a
new equilibrium value will take a comparable period oftime.
102. The case of intelligence is somewhat different.
Here the social optimum lies far away from the selective
optimum, and it is not simple even to decide what must
be computed to assess the social implications of a givenchange. Moreover, the genetic picture is complicated bya high degree of phenotypic assortative mating.lS8 For
the purposes of this report Mather's calculations152basedon United Kingdom figures have been available. Mather
based his calculations concerning the effect of increased
variance upon an unchanged mean but he also considered a situation in which increased mutation was
associated also with a falling mean. such that the effects
mediated through mean and variance were roughly comparable in magnitude. However. there is no indication in
the figures at present available for the United Kingdom
nlies below the selective o ~ t i that the ~ o ~ u l a t i omean
mum; thtlsLgives rise to a presumption that increased
mutation might not depress the mean appreciably. I t
seems important to try to find out if this situation is true
and, if so, whether it is peculiar to the somewhat special
demographic situation in the United Kingdom or is moregeneral, since it raises a question as to how such a position might arise and be maintained.15s I n the meantime,it seems premature to attempt here any assessment of the
expected effects of increased mutation rate upon mean .
intelligence. The social consequence of hereditary shifts
in intelligence probably occur mainly as a result of shift
in the numbers at the extremes of the I.Q. distribution(of which only changes at the lower end are numericallycited in para. 96 above) ;* a change in variance will in any
event affect these more markedly than an equal change
in the mean. Part of the difficulty in discussing shifts ofthe mean intelligence as measured by intelligence quotient may lie in the need to consider small intelligencequotient differences; it is possible that present tests ofintelligence are not sufficiently well-developed and freefrom bias associated with other variables to serve as
suitable material for close quantitative analysis. The
problem of further progress in this field may thus depend upon developments in pure human biology. I n any*An increase in variance without change in mean also causes
an increase in the classes of highest I.Q.upon which it has been
claimed that much of human progress depends. Any judgement
concerning the relative value of this increase is a social one;it has therefore not been computed here and np attempt has
been made in this report to offset its value a w n s t the soclal
burden represented by a calculated increase in the numbers ofindividuals with I.Q. <70. It must be borne in mlnd e a t there
is some reason to believe that the distribution of variance due
to new mutations would not be symmetrical, and that most of
the increase would be in the direction of lowered ~ntelllgence.

over-all discussion of intelligence, it is necessary to bearin mind that it is affected not only as a biometrical character by many genes with small interacting effects, but
by known specific loci, radiation-induced mutations at
which will almost always cause serious harm to any individual in whom the mutant alleles are expressed.
103. In the case of the life-span, the d a b of Russell'"on the progeny of male mice irradiated by fast neutrons
suggest the existence of the kind of effect which would
be expected from classical hypomorphic mutations ; thatis, the occurrence of radiation-induced mutations to aseries of weakly dominant alleles which collectively
cause a shortening of the life span. However, the magnitude of any corresponding effect which might be expected in man is entirely unknown. I t might seem at firstsight as if increased variance in life span I \ ~ o u I ~confer
little or no increased social burden, but be selectively
neutral as long as it affected only groups be~olldthe ageof child-bearing. However, if themechanism of shortening were related to an effective contraction of time-spanof the physiological processes, the reproductive period
might be adversely affected. and the selective o~timutn
for life-span might then be very long. It is essential thatthe work of Russell be confirmed and extended in orderto have an adequate experimental basis in other organ,isms for consideration of the possible implications forman. Russell's experiments are in line with effects observed in irradiated mammalian tissue culture cells andother organisms, among which the survivors frequently
carq7slightly deleterious dominant alleles,ls"84 as well aswith observed correlations between the life-spans ofrelated individuals suggestive of genetic iIlfluenCes.l~sFertility
101. The most direct expression of the effect of undesirable mutations is tllrough the net reproduction per
generation or fertility differentials. Penroseo3 has suggested that, in man, some 50 per cent o f the zygotes ofeach generation fail to contribute to the next one byreproduction, and has suggested, by analogy with othermetrical characters, that some half of this might be ofgenetic origin. Penrose also points out that, on the same
be due to theanalogy, much of the infertility mightpresence of conditionally deleterious alleles 1%-hicharenot primarily maintained by mutation and are essentiallyby changes in mutation rate. However, one
may compare such a rate of elimination with an estimateof the total rate of mutation to unconditionally deleterious alleles such as was derived in paragraph 74 above.
105. Applying a representative doubling dose of 30
radthe estimate of paragraph T4! therate
mutation
would amount to%(i.e.? a ~ ~ r o x i m a t e30/2j0)l~
Per haploid gamete or %per diploid zygote. At equilibrium, these C O L I be
~ ~ eliminated by % of zygotes failing to reproduce. These estimates of mutation are therefore consistent with that ofPenrose concerning fertility, and with the assumption ofgenetic equilibrium, which suggests the possibility that atpresent of d l rygotes fail to contribute to the ncxt generation because of the presence of deleterious alleles
maintained by recurrent mutation. Taking this to be anof a doubling doseupper
to each generation mlgllt eventually extend the fractionof non-contributlng zygotes f ram 5 to % and require aof average
size for a previously constant population to maintain itself. This appears to bewell within human capacity. If it be further supposedthat thc mixture of donllnants and recessives concerned
has an average persistence in the population of 10-100

generations, then exposure of one generation to 10 or
100 times the doubling dose would impose the equivalentof the same load for a period of 10 or 100 generations.
Such doses are ofmagnitude 300-3000 rad, and in arange which is such as to render further considerationsof genetic problems redundant. It therefore seems probable that the human race has ample breeding capacity to
the genetic consequences of any foreseeable

Pool of recessive nrlitants
106. Examination of the offspring of consanguineous
tnarriages can give information concerning the total ofdeleterious rcccssive mutant alleles in a population, andMorton, Crow and &IulleIgBhave recently sholvn how theresults of statistical suneys of this kind can be expressedin the form of a number of lethal equivalents per m a ber of the population. In the absence of a figure operationally equilralent to the total number of genes per
individual, this information does not relate directly tothe social burden upon the population nor, lTithout assuming an average dominance, can it be related to thenatural mutation sate. The number of lethal equivalents
per head is, however, in its own right, a most importantparameter describing the genetic state of a population,
derivable from a purely demographic type of information. Governlllents would do well to investigate it intheir populations.
107. I t is also possible in principle to compare thenumber of lethal equivalents, derived from vital statistical information, with the number of recessive deleterious genes found in the direct intensive surveys ofsmaller numbers of consanguineous marriages. IdealIy,such studies should cover the whole period during which
identical alleles are together and so liable to give rise toan effect through homozygositl'; thus not only the number and viability but also the fertility of the Progeny ofconsanguineous marriages should be i~~vestigated: a preliminary study of this kind has been initiated by
Fraser-lg3 Such a comparison could be of great importance as indicatingurhat fraction of the total recessive
deleterious pool we know about, through recognizable
specific effects. At the present time the evidence of bothkinds is very scanty. By direct examination of a north
Swedish population, Book has estimated that about threerecessive deleterious genes are carried per individual-s7
However, using the criteria of Stevenson, this figure
would be only 0.8-1.7.'" Stevenson, himself, in a somewhat smaller sample, has found 0.5-0.9.1U I t is not possible t~accurately >:hat is the reproductive
fitness of the afflicted individuals, relative to the general
population, but it is reasonable to suppose that the average would lie between 20 per cent and 80 per cent.
Probably, therefore, the best direct intensive investigations today sholv up about 0.2-0.8 p ~ s t - ~ ~ lethaltalquivalents per individual in the generalpopulation.
Following I\Jorton. Crow and Mullerls analysis of thework of Sulter and Tabah,ss,ss but excluding stillbirths
and nm-,-natal deaths, it is likely that a total of some
2-2.8 post-nabl lethal equivalents per individual are present in their population. This suggests that present recognition encolnpasses sonle\vhere behreen j per cent anddamage40 per cent of the total deleterious
which arises. These numerical figures reflect the strictness of the particular criterion employed by Stevenjon
in his use of the term arecessire.y.
108. The specific genetic conditions whose incidence
is reported by Stevenson are divided into dominant and192

recessive conditions ; a most striking feature of the datais that the total inadence of rare dominant conditions
exceeds that of recessives by a factor of 10. If a correction is applied for those recessive conditions not atpresent recognized, using the figures derived in the preceding paragraph, the ratio of total incidence of recessive conditions to total incidence of dominant conditions
shifts from 0.1 to between 0.25 and 1.3 and the total
incidence is increased by a factor of between 1.2 and 2.3.
The calculation is now relatively insensitive to the exact
providedthat it is thecriterion of recessivity- employed,- same throughout. It perhaps serves to give some idea ofthe limits of confidence which can be placed upon current estimates of the genetic social burden due to specificrecognizable conditions.

109. I t is of some interest to compare the ratio of theobserved rates of elimination of deleterious recessive anddominant alleles, corrected as in the previous paragraph,with that to be expected from equilibrium with fonvard
mutations. In mice, the ratio of recessive to dominantlethals occurring naturally appears to be about 2.5 :1 or
3 :1.10iJ6" It is very different for Drosophila, perhaps as
low as 0.1 :I, but if Drosophila has much less complex
genes t4an mouse or man, it may be a poor guide.)
If the ratio of natural rates is similar in man and mouse,
the corrected ratio of elimination rates, between 0.j :I
and 2.8 :1, is in reasonable agreement with it, but suggests that the recessive alleles might, if anything, tend
to be on the average slightly deleterious rather thanadvantageous in the heterozygous state.

TABLE111. MEASUREDOR C~~LCULATEDV ~ U E SOF
TOT-4L N-4TURAL 31UT-4TION RATES FOR CLASSESO F LOCI I N ORGANISMS OTHER THkV &L4N
Trait studkd.

Rare domirant
Porcupine. ..............................
Sex-linked recessives (direct)
Hemophilia. .............................
Duchenne's type muscular dystrophy.. ......
Autosomal recessives (indirect)
Albinism. ...............................
Ichthyosis congenita.. ....................
T o t d colour blindness.. ...................
Infaotle amaurotic idiocy.. ...............
-4myotonia congenita. ....................
True microcephaly.. ......................
Phenyketonuria.. ........................
Average of 7 loci.. .......................
a

Mutants pn
leslrd game&C h s s of nrufanfsstudied

Autosomal dominants (direct observation)
Epiloia ................................
~ c h o n d r o ~+lal a ...........................
-'
Aniridia.. ...............................
Retinoblastoma ..........................
Partial albinism with deafness.. ............
Microphthalmos ..........................
Neurofibromatosis ........................
Average of T loci. ........................

D. inelunogasterSex-linked recessive lethals:
1.0 x 10-3

aged sperm.. ........

2.0 x 10-3

range for various wild
type stocks. ....... 0.7-1 1 s 10-3
mutable Florida stock
1.1 x 10-3

<10-9~XXY females. .......

3 x 10-5
4-10 s 10-5
2.8 x 10-5
1.1 x 10-5
2.8 x 10-6
1.1 x 10-5
2.0 s 10-5
4.9 x 10-5
2.5 s 10-5
2.4 x 10-5

young sperm.. ......

7.0 x 10-3
1.8 x 10-3

Spencer and Stern32{Uphoff
and Stern31
Caspari and Sterns${Uphoff and Stern81
Demerecli4
Demerecl74
Muller et al.171
Mullerlos

TABLE
IV. GTESOF UDIATION-I~DUCED

MUTATIONSAT SINGLE LOCI I N ORGANISMS OTHER THAX NAN

Very rough estimate: see ref. 83,

TABLE
11. ~~IEASURED
OR CALCULSTEDVALUES OF
NATURAL MUTATION RATES AT SINGLE LOCIO F ORG-4NISMS OTHER THAN h U N
Mtrfanls per&sled somete

Mufonts strcdicd-~-

D. melanogasterAverage for 9 seslinked recessive
visibles in XXY
female. ........

3 x 10-58 Iluller, Valencia andValencialTl

Average for 4 autosomal recessive
visibles in Oregon-R females.
2.5 x 10-6
Average lor 4 autosomal recessive
visibles in Oregon-R males.. ..
4.5 x 10-5
Average for about
12 sex-linked recessive visibles
in Oregon-R females. .........
2.4 s 10-6
White eye..
0.1-3.7 s 10-5
8 ses-linked recessive visibles inmutable Florida
stock. .........
~Ufce-4verage of 7 autosomal recessive
visibles in maleca. 7 x 10-6
Bacleria
Average of about
30 biochemical
back-mutations.
4.5 s 10-9.

......

Glass and Ritterhofl7"

Average of 9 recessive
visible autosomals
in oocytes, oogonia

1.4 x 10-8

Average 01.9 recessive
visible autosomals:
spermatogonia . .
1.5 x 10-6
mature sperm.. .
6 x 10-8
mature sperm.. .
4.4 x 104
mature sperm..
5.2 x 10-8
White eye mature
sperm.. ......... .0.&1.2 s 10-7
D. cirilis
A v e r a g e of 7 s e x l i n k e d recessive
visibles:mature spern~
7.6 s 10-8.

...

Glass and Ritterhof172

Glass and RitterhoPT?
Bonnier and Lihingl"

Muller, Valencia andValencial"

Alesander70.4lesanderiO
Pattersonl7j
Demerecli6
Bonnier and L ~ n g l 7 3

Gin611177

E.

Average of about 30
biochemical backmutations. .......
Mice
Average of 7 recessive
risible autosomals:
spermatogonia . .

2.7 s 10-10 Glover in Demerecet al.3

2.5 x 10-7

Russel176

TABLE
V. TOTALRATES OF RADIATIOS-INDUCED
Russe1176, Carter et a1?5

BIUTATIOKS IX CLASSES OF LOCI IX
ORGANISlIS OTHER THAN 3L4N

Glover in Demerecet ~ 1 . 5 ~ D ,nzelanogasterSex-linked recessive lethals
inaged
snerm... . . . ............ 2.3
1 0 - U n- hr o f f and Stern31---.. .,--.....
.. s
....
young sperm. ........ 2.8 s 10-5 Uphoff and Sterns1

Range of abo1-e. .. lo-" to 4 s 10-8 Glover in Demerecetal.53
a But approximately 5 x lo4 if allo\r.ance is made for the factthat the Kte of sex-linked recessive lethals was abnormallv hiehin this experiment. Droso@hilarates vary very widely wit& staieof life, cell-development, etc.

~ - - --~--

Na~rrberof irrntlinladpnrcnls

Rcjero~~cr

Dose rnnga
i~rrsds

Ab~~rlior~s
Irrad.

Control

Irrnd.

Slill-bb-llts

innlf~ttrnlions"(livc bir1h.r)
C o ~ ~ l r o l Irrud.
Co~rlrolS.x-ralio(live births)
Irrud.
Colrtrol--

Survey of p r c ~ ~ ~ a n c i cNecls
and Sch~~ll'l' approx. 27,000 O
i l l I l i r o s l ~ i ~;111dn;~Nagasaki

Survey of olTspringof Fre~ichpiltic~ltsapl)l'ox. 14,000 8

l'urpin, L e j e ~ r ~ ~ candRethorell7. 1~05-

I
- - - - t~;~scdL I ~ O Iscv-

546

408

300

294

rc.yrcssio~l lines

8-200

33,181

31,55933,52731,904cr.11 doses: forraw d a t n YCC
I . 1 I C a p
ter V11.

8

-

7

9
405

8
696

8-200

47

289 d

4-450''

-

18

7
-

5
-

5
-

-

1

63
-

130
-

D i n ~ i n ~ ~ tofi osex-rationfor irradiatedmothcra sig-ni6ca~~t
conlpa~ecl L oirrr~tliatedfathers ( x 2 = J.2), notsignificant con~pnrcd to controls.
k I ~ t w c e n 6 X 10*/rntl and
12 X I0 -5/r:1d.

254

13G

236

136

236

1.16

236

No;~cco~~~~(.~alcc~~ofi~~cnn

46

-

-

-

225

--

358

452
742
405
696
405
696
---26

97 O

40-450"Obscrvatio~lsincl~~tle
scx-ratio, frcqucncy of stillbirths and 11co11atnl
dc;ttl~s,birtIiwc.i):l~t,o c c u ~ r c ~of~rc
c o n ~ c ~ ~ rnalfor~~~ations,ital
all(\,fora r.~~~tlom
30% sanlple reexn~nincda t age 9 ~ n o ~ ~ t lcertainls,bodilymcast~rcn~cnts
and the occurrence
notof adclitional n~allormatio~~sapparent a t birth.
Non-sig~~ifiwnt
dccrcase i l l sex-ratiok = -5.5 X IO*/md for irradiated mothers: arriong earlier
births12' lc wiis -8 x 10-6 ant1
significant.
Sligllt IIOII-significn~lt
ic~crcasefor irradiatctl fathers in earlier birtlls12S.

I62

Inquiry by qucstionr~aire.
Follow-up 011 progenyof women trc;ltcd forsterility
Surveys ofchildre~lof
Anicrican
ri~tliolo~ists

I<aplan119

311 O

ca. 60

91

2

513

3

-

No control as yet. Very low ses-rntic*
sig~lificantlydilTcrcnt fro1110.51 5,
IC -8 X lO-'/riltl.

191

-

-

-

513

513

409

Aborlions nrrtl Slill-births
Irrad.
CoirlrolCrow1@

RIacht and
Lawrence~~

654 d

5,461 dUnknowrl
accuniulalion ofmany s~ualldoses

No data on malformations or scxratio. Inquiry by questionc~airc.

274

215

-

-

1,653

1,348

-

766

-

-

328

216

2,090

5,461

:4,484

5,461

4,484

4,127

548

-

1,766

3,390

Non-significant incrcase i~dstill-births
a ~ ~abortions.
tl
Significnnt increase in n~alformalio~ls( x 2 c.6.7) incl~~tlcs
many very slighttnalforl~~ations
or other discnses,
if restrictedI)t~tr c n ~ a i sig~iilicant~~s
to cardiac ~nalfor~nations
only. Inq~liryby question~~~~ire.

7
7
a Enrlicr literalure surveys by M a ~ ~ r e r and' a t ~ yMurpl~yant1 G o l c l s t e i ~ ~respectivclyl~rcvcalerl!'andmalforrnotions anrollg r ~ ~ o i l ~whoe r s llad rcccivcd heavy doses, bul229
417
without co~ltrols.
b Taking the gonad dose to be 1 /3 the skin dose.

-TABLEVII. CONTENTO F DNA I N V-4RIOUS TYPES O F C E L L S ~ ~ ~Organism and cell !j9pcs

gm DNA-phosphorus

gm DNA

per u l l

Bacteria.. ...... B. h t . aerog.
2 x 10-15
E.coli
2.3 x 10-15(compare T2 bacteriophage
Microbes. ......Penicilliun~
Aspergillus
Yeast
Drosoplrila.. ... Salivary glands d
2.6 r 10-110
2.8 x 10-u
Diploid cells (limb)
0.6-1.0 x 10-12
Rat.. ......... .Diploid cells
Mouse. ........Submaxillary glands (diploid) 0.7-1.4 x 10-12
8.7 s 10-19
hlan. .......... B.M.
Leukocytes
8.6 x 10-19
RBC
7.0 x 10-13
Liver
1.0 x 10-13
Kidney8.7 x 10-15

per cell3 x 10-16 per particle)
I .5 x 10-13 per spore
1.9 x 10-12 per spore
6.2 x 10-15
1.7 x 10-13

For a further extensive table, see ref. 21.

TABLE

Organism

VIII.

CALCUJ-~TED DOUBLING DOSES I N ORGAhTSYS
OTHER THAN l
f
~
~
~
Loci

Zea-mays. ......... .4 recessive visibles
Oenolhera, Prusus.. ..Self-incompatibility
Drosophila ..........Sex-linked lethals
Mouse.. ........... . 7 recessive autosomal
visiblesDominant lethals~

C a d i l i o n s of+radiated cell

Doubling
dose ( r 4

Rcf.

PollenPollenspermatozoa
aged spermatozoa
o6cytes and o6gonia

28
60
50
140
390

179
180,181
31-33
31-33
171

spermatogoniat h r o u g h spermiogenesis except timeof peak sensitivity
spermatogonia

Approximate calculation for natural rate corresponding to age of mice used in 76,69, 75.

TABLEIX.

CONPARISON
OF APPROACHES TO QUANTITATIVE ASSESSXENTO F hIUTATIONAL DAMAGE

KnwsIcdgc
o f fipi = 1Higher than average. .....
Lower than average.. .... .Small but unknown

Small but unknown
f:=lRrZatirc effccio f
mlrloti~n~p~nfrequency ofcondifion

Small

Large

TABLE
X. SOMEOVER-ALL ESTIBL4TES O F SOCLiL BURDEN
AuthorShensonlt4

Class of trails

I n populalioa

Rare heterozygotes.. ................. 1.36 X 10-2
Rare homozygotes. ................... 1.0 X 10-3
Rare sex-linked. ..................... 1.6 X 10-4
Common traits of hard interpretation.. . 1.0 X 10-2

U.S.A. Panel16 Tangible defects of genetic origin (1/2
total) .............................
Kernpls. 191
Physical malformations and defects.. ...
Severe hereditary afflictions.. ..........

~TABLE
XI . LISTOF SPECIFIC TRAITS. n?m ESTIM-ATED INCIDENCES: CATEGORYI(A) ALTOSOM.~.
DOJIINAST TRAITS

Phenotype
Ircc:unfY

pcr million
Remarks

Trait

Achondroplasia ............................. Chondrodystrophy 'Foetalis'
Arachnodactyly ............................. RrIarian's syndrome
Brachydactyly (major) ...................... Hands and feet affected-mean stature reduced
Ectrodactyly ............................... Including all types of 'split hand'hlultiple exostoses .......................... Only a minority are troublesome
Osteitis deformans ..........................
Osteogenesis imperfects.. .................... Fragilitas ossium. Several types. all irregular dominantgenetical relationship not known
Cranio-facial. cranio.cleidal. mandibulo-facial
dysostoses ................................ A series of separate disorders individually uncommon
Hypertelori sm ..............................
Ataxia ..................................... Dominant hereditary ataxia-agroup of which Friedrich's
is the best defined
Epiloia .................................... Tuberose sclerosis (9 living sporadic cases in N.I.)
Huntingdon's chorea ........................ (Three families in N Ireland known)
Hydrocephaly internal obstructive ............ Includes stenosis of and forking of aqueduct of Sylviusprobably each due to irregular dominant gene
Peroneal muscular atrophy ................... Charcot-Maric-Tooth discase
Spastic diplegia .............................
Dystrophia myotonica .......................
h l u x u l a r dystrophy, limb girdle .............. Faces affected
Myositis ossificans ..........................
Deaf mutism (Deafness total hereditary) ....... Estimated 3 per cent of all hereditary deaf mutism due todominant genes
Deafness perception ......................... Early onset dominant type
Deafness and cataract ....................... Severe early onset deafness and cataract
Deafness ................................... Absence of or atresia of external auditory meatus
Neurofibromatosis ........................... Von Redclinghausen's disease
Polyposis of colon, multiple ..................
Alopecia areata .............................
Anhidrotic syndrome ....................... Anhidrotic "ectodermal" Dysplasia
Cephalo-facial haemangiomatosis .............. Naevoid Amentia
Epidermolysis bullosa .......................
Pityriasis rubra pilaris .......................
Telangiectasis haemorrhagica .................
Tylosis palmaris et plantaris ..................
Urticaria pigmentosum ......................
Xanthoma tuberosum multiplex .............. Cutaneous xanthomatosis and essential hypercholesteraemia
Willebrand's disease ......................... I-Iaemophilia-like syndrome
Polycythaemia vera .........................
Spherocytosis ............................... Acholuric jaundice
Thrombocytopenia chronic recurrent ..........
Porphyria .................................. Dominant type genotype detectable but seldom causes illness.

Diabetes (insipidus) .........................
40
500
Cystic disease of lungs....................... (Included here "congenital" bronchieaasis)
hlegacolon ................................. Hirschsprung's disease100
Aniridia .................................... Dominant very irregular degree of manifcstatio~and~prob60
ably several dominant mutants can cause
Cataracts "congenital" ...................... Types detected at birth or early-probably several different
types
160
2.000
Cataracts. senile and pre-senile ...............
Choroidal sclerosis .......................... Several types varying in severity and depending largely on
location for disability caused
500
Colobornata ................................ Common-vary from slight iris defect t o big defects OGAS
250
choroid and retina involving macula
140
Corneal dystrophies ......................... Several types of very variable severity
Fundal dystrophies ..........................
150
100
Glaucomas. infantile and juvenile .............
Hypermetropia ............................. Can only be arbitrarily accepted as a segregating trait a t
about 10100
Keratoconus ................................
20
100
Macular dystrophies ......................... At least two dominant types occur
Nystagrnus ................................. Familial idiopathic non-albinotic usually lateral
700
150
Retinitis pigmentosa ........................ Relatively mild regular dominant type
Retinoblastoma .............................
58
6
Subluxation of the lens ...................... Primary and not part of Marfan's syndrome
Optic atrophy ..............................
7

-

TOTAL

9.555

TABLE
XI . LIST OF SPECIFIC TRAITS. WITH ESTIMATED INCIDEKCES: CATEGORY
I (continued)(B) AUTOSOM.
4 ~ RECESSIVE.
TRAITSPh=**
ficoufnfy

Trait

pn mason
Birihr
L i..?'ng&marks................................... Usual type with ocular signs. More than one mutant(?allele). can cause
Alkaptonuria ...............................
Methaemoglobinaemia .......................
Phenylpyruvic acid amentia .................. Phenylketonuria
Porphyria congenital ........................ Recessive light :ensitive type
Galactosuria ...............................
Gargoylism .................................
Amaurotic idiocy ........................... Warran-Tay-Sachs disease. Various types with difierent agesof onset. Different loci mutants? Alleles?
Hepato-lenticular degeneration ............... Wilson's disease
Albinism

Lawrence-hloon-Biedl syndrome ..............
Microcephal y. true
Microcephalic imbecility
AtaxiaChoreo.athetosis
M yodonic epilepsy
Spastic diplegia
Spastic diplegia familial often with oligophrenia
Muscular dystrophy limb girdle type .......... Face not affected
Poikiloderrnia
Epidermolysis bullosa dystrophica .............
Ichthyosis congenita ......................... May be more than one type
Anophthalmos
Corneal dystrophies
Severe recessive type
Glaucomas
More than one recessive type with buphthalmos
Macular dystrophies......................... Juvenile and adult types
Miaophthalmos ............................ Pure type as distinct from those associated u-ithrother eye
defects Mental deficiency often associatedMyopia. highSegregating traits overlapping with ordinary refraction v w i ations 3-6 types with other associated defects induded
here. e.g. with microphakia and spherophakia
Optic atrophy
Very early onset type
Probably several independent mutants contribute
Retinitis pigmentosa..........................
.....................................

............................
..........................

.............................

..............................

..............................
.........................
.................................

...............................

.

.

..............................
........................

TOTAL

130
5
5
100
50
50
20

130
3
5
30
5
2
4

50
10
40
40
40
70
50
50
30
10
20
10
100
5
15
10

5
3
6
21
20
15

100

100

150
50
60

150
50
60

6

18
16
3
6

50
5
15
10

-

-

1.260

738

(C) SEX-LI~XEDRECESSIVE T R ~ I T S
Phcnolypr

frrpuf=f~

pn m d w a
Trait

Rcnzarks...........................
.. ...............................

Diabetes insipidus
Haemoph~l~a
Christmas disease
Iclithyosis vulgarisMuscular dystrophy ......................... Duchenne's type
Megalocornea .............................. ? Only sex limited
Optic atrophy .............................. Leber's typereally sex linked
Retinitis pigmentosa ........................

...........................
..........................

TOTAL

OFRTRAITSYOF CATEGORYI(D) S U ~ ~ A W
Frcgucncj* grr miliion-%utosomaldominant .......................................
.A utosomal recessive........................................
Ses-linked recessive ........................................

9.555
1.260
397

i.100
738
155

BirthsLioinr

50
100
10
6
176
20
15
20

5
66
4
6
24
20
10
20

-

-

397

155

TABLE
XII. LIST OF SPECIFIC TRAITS, WITH ESTIMATED INCIDENCES: CATEGORY
11
Pknorypc
frepurncy

per nill lion

Tr~i!

Remarks

Bir!h-4bsence of limbs or pans of limbs.. ........... .Congenital endogenous amputations
200
Cleft palate and hare lip, together or separately. .Not including these anomalies occurring as parts of syndromes or
associated with other gross defects
9iO
Congenital dislocation of hip.. ............... .Mostly limited in effects to females
900
Osreonecrosis. ...............................Includes osteochondritis di-cans and local, e.g. dk-si~f,Kienbock, Kohler, Perthe and Schlatter
200
Radio-ulnar defects.
.Varying degrees ol absence and deformity, radius usually:primaryand determining also hand defects
205
Talipes-equino-vans, ........................ .Excluding, where recognized, those with neurological determining
causes and when part of severe syndromes e.g. anencephalus
800
Vertebrae, defects and fusions.
.A large group including I<lippel-Fiel syndrome, Sprengel's anomaly
400
etc.
Psoriasis. .................................. .Not known if all of one ori-gin-varying age of onset, duration of
attacks and severity
3,000
Ichthyosis vulgaris.
1,100
Deafness, otosclerotic..
200
Anencephalus. ...............................
i.e. The live born with these defects usuallyl
360
Occipital meningocoele.. .....................
80
dying shortly after birth, with and withHydrocephalus (Arnold-Chiari).
spina bifida or rachischisis
300
Lumbo-sacral spina bihda.. ...................
800
Other central nervous system malformations.. ...
320
Cardiac malformations. ......................
1,200
Digestive tract malformations. ................
630
Urogenital tract malformations.
200.........................

...............

..........................
.......................
...............

...............

(A)

80
700
900
200
205
700
200
3,000
1,100
200

-

-

100

-

400
100
40

- -

T O T . TUIT~FREQUESCYTABLEXIII.

LLiling

9,825

8,725

LIST OF SPECIFIC TFbiITS, WITH ESTIMATED INCIDENCES: CATEGORY111

Remarks

Deafness total from birth. ................... .97 per cent of all genetic deafness a t birth. A number of independent
mutants involved. Relative fertility of homozygote about 1/3
Fibrocystic disease of pancreas.. .............. .A generalized disorder of external secretory glands. For practical
purposes, relative fertility of homozygote is zero
TOTAL TRAIT FREQUESCY

BirthsLinn g

264

264

600
15
864

279

TABLE
XIII. (B) LIST OF SPECLFIC TRAITS, WITH ESTDIATED INCIDENCES: CATEGORY
111 (continued)
Phcnarypc
ficq~f"~
per mrllron
Trai:.......................

Marks

Anaemia, pernicious..
.Addison's anaemia
Diabetes mellitus.. ..........................
Exophthalmic goitre.. ........................Graves's or Basedow's disease
Manic depressive reactions. .................. .Based on severity requiring hospital admissions
Schiiophrenia..
.Based on severity requiring hospital admissions
Epilepsy. .................................. .Secondary to disease or injury.............................

T ~ A PHENOTYPE
L
F~EQUENCF

Births

Li?ing

1,300
4,000
4,000
1,300
2,500

1,000
3,000
1,500
2,500
1,100
1,200

14,80010,3001,700- -CO-WITIONS IDENTIFIED I N THE NORTHERNI R E L ~POPULATIOND
BUT XOT IKCLUDEDTABLE
XIV. DOMINANT
IN CATEGORIES
1 AND I1 FOR THE REASONS STATEDTHELR EFFECTS ARE SLIGHT (most are common)
A BECAUSE

Hand dejects: Brachydactyly thumbs, brachydactyly 1st finger, brachydactyly l s t , 3rd, and 4th hgers: mmptodactyly; clinodactyly; polydactyly (not part of syndrome) of radial side and of ulnar side (more common) of hands; syndactyly and symphalangim
mostly 3rd and 4th finger (hundreds of cases of the above types are known but have not been sought out for special investigation);
Dupuytren's contraccure familial.
Foot defects: Garber's toe deformity; hallw valgus (familial cases may be associated with metatarsal anomalies); hammer toes
(many are familial); syndactyly and symphalangism.

0 t h skelhl:

Diaphyseal achalasia, epiphysitis punctata.

Teeth anomalies (Other than parts of syndromes): Defective or absent enamel (various types) ;opalescent dentine; additional teeth(many types); absence of permanent incisors and pre-molars; some such anomalies are present in about 1.3 per cent of the population.
Skin and kuir anomalies: Adenoma, cystic multiple benign; cysts, epidermoid; dermatomyomat multiple; anonychia and hypoplasia of nails; leukonychia totalis; pachyonychia congenita; hair, white patches; hair kinky; hair woolly; hydroa aedvale; porokeratosis

Eye anomalies: Eyelids-spasm, absence of tarsal plates, uncomplicated ptosis; absence fstula of lacrymal ducts; retina, opaquefibres; strabismus convergent and divergent (primary).
Miscellaneous:

Pelger's anomaly, elliptocytosis.

Ear anomalies:

Cat's ears, microtia; pre-helicine pits; lobule pits: accessory auricles.

BECAUSEEVEN IF THE EFFECTS ARE SEVERE, THE ASOU.4LIES ARE PROBABLY PRESENT LT LESS T E 4 N FIVE PERSONS PER ?dUL.IOK

B.

Skektul: Osteo-petrosis (Albers-Schbnberg) ; phocomelia; ankylosing spondylosis; polyostotic fibrous dysplasia (Albright's disease) ;multiple enchondroma; fibula absence or defect; oxycephaly; acrocephaly; syndactyly.
Skin: Ichthyosiform congenital erythrodermia; keracosis follicularis spinulosa( Darier's disease) ;monilethriu; urticaria pigmentosa;
tylosis palmaris et plantaris; pili torti; ma1 de hleleda; lipodystrophy progressiva without gargoylism.
Miscellaneons:

Milroy's disease: periodic paralysis; dominant microcytic anaemia; Waardenberg's syndrome: anotia.

TABLE
XV. CLASSESOF BIOIIETRICAL

CHARACTER-

Prrtumed posiliol: ofsocial optimum

Charackr

Birrhweight ................................. At selective optimumIntelligence (measured as intelligence quotient) . 4-.

Life-span ...................................

"+=

Position ofs c k d i x o$!itnum

Position of
gopulation mean

Intermediate finite value
Intermediate finite value

Below selective optimumljl
Near and possibly even above
present selective optimum:*far below social optimum
Below social optimum: probably
below selective optimum

Unknown: perhaps+ cca"+-" implies positive and indefinitely large, always greater than the population mean.
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126. Macht, S. H., and P. S. Lawrence, Amer. J.
Roentgenol. 73, p. 442 (1955).
127. Court-Brown, W. M., and R Doll Leukaemia andAplastic Armentia itr Patients Irradiated for Ankylosing Spondylitis, H . M . Stationery Office, London ( 1957) and UN document A/ACS2/G/R. 105.
128. bfagni, G. E., C. R. Carlsberg, Lab. Physiol. Serv.
26, p. 273 ( 1956).
129. Ephrussi, B., et al, Ann. Inst. Pasteur, 76, p. 351,
419,510, 77, p. 47,64 (1949).
130. Dobzhansky, Th., Cold Spring Harbor Symposia
on Quantitative Biology, 20, p. 1 (1955).
131. Dobzhansky, Th., 0. Pavlovsky, B. Spassky and
N. Spassky, Genetics, 40, p. 792 (1955).
132. Dobzhansky, Th., and H. Levene, Genetics, 40,
p. 797 (1955) and references therein.
133. Lerner, I. M., Genetic Honteosta~is,John Wiley,
New York (1954).
134. Wallace, B.. Proc. Nat. Acad. Sci. U.S.A., 43, p.
404 (1957).
135. For indication of cross-over in Drosophila malesby X-rays or chemical agents, see U N document
A/AC.82/GfR.90.
136. Sobels, F. H., and H. von Steenis, Nature, 179, p.
29 (1957).
137. ~ h i t t i n ~ h i lM.,
l , J. Cell Comp. Physiol. 45, Suppl.
2, p. 189 (1955).
138. Sturtevant, A. H., and G. IV. Beadle, Genetics,
21, p. 554 (1936).
139. Kemp. Tage, Getretics and Disease, klunksgaard,
Copenhagen ( 1951) .
140. Penrose, L. S., Adv. Sci., 11, p. 387 (1955).
141. Allison, A. C., Ann. Hum. Genet. 19, p. 39 (1954).
142. Crow, J. F., Human Biology, 30, p. 1 (1958).
143. Neel, J. V., Human Biology, 30, p. 43 (1958).
144. Stevenson, A. C., UN document A/AC.82/G/
R. 104.
145. The Biologica,l Egects of Atovric Radiation, Summary Reports : Nat. Acad. Sci.-Nat. Res. Council,
U.S.A. (1956), U N document A/AC.S2/G/R. 1.
146. Reed. T. E., Jap. J. Hum. Genet. 2 (Supp.), p. 48,(1957).
147. Pansel F., Dig Erbchorea, Thieme. Leipzig (1932).
148. See Haldane, J. B. S., Caryologia, Supp. to Vol.
XI, Proc. 9th Int. Cong. Genet., p. 485 (1953).

&149. Penrose, L. ,Caryologia, Supp. to Vol. XI, Proc.
9th Int. Co
enet., p. 521 (1953).
150. T h e Hazards to Man of Nzrclear and Allied Radiations, H.M. Stationery Oftice, London (1956), UN
document A/AC.82/G/R.2.
151. Karn, 31.N., and L. S. Penrose, Ann. Eug. 16, p.
147 (1952).
152. Mather, K., Appendix G of ref. 124.
153. Clayton, G. and A. Robertson, h e r . Natur. 89,
p. 151 (1955).
154. Haldane, J. B. S., Caryologia, Supp. to Vol. XI,
Proc. 9th Int. Cong. Genet., p. 480 (1953).
155. Robertson, A., J. Genet., 54, p. 236 (1956).
156. Fisher, R. A., Genetical Theory of Natural Selection, Clarendon Press, Oxford, 1930.
157. Quoted by Mather in Appendis F of ref. 150.
158. Penrose, L. S., Proc. Roy. Soc. (B) 144, p. 144(1955).
159. &fuller, H. J., Genetics, Ettgeftics ajrd the family,
1, p. 106, Proc. 2nd. Int. Cong. Eug., p. 7 (1921).
160. Muller, H. J., Vol. I Radiation Biology, p. 351,
ed. A. Hollaender, McGraw Hill (1954).
161. OF cit. ref. 158, Fig. 14 and data in references.
162. Russell. W. L., Proc. Nat. Acad. Sci. U.S.A., 43,
p. 324 (1957).
163. Beeton, M., and K. Pearson, Biometrilta, 1, p. 50(1901).
164. Bateman, A. J., Nature, 178, p. 1278 (1956).
165. Turpin, R., J. Lejeune and M. 0. Rethore, Acta
Genet. et Stat. Med. 6. p. 204 (1956).
166. Crow, J. F., Amer. J. Roentgen., 73, p. 467 (1955).
167. Murphy. D. P.. and L. Goldstein, Amer. J. Roentgen., 22, p. 207 (1929).
168. Maurer. Zbl. Gynk., p. 819 (1933).
169. Penrose. L. S.: Appendix C of ref. 150.
170. Penrose, L. S.. op cit. ref. 111, p. 210 and references contained therein.
171. Muller, H. J., J. I. Valencia and R. &'I.
Valencia,
Genetics 3j, pp. 125, 126 (1950).
172. Glass, H. B., and R. K. Ritterhof, Science 124, p.
314 (1956).
173. Bonnier, G., and K. G. Liining, Hereditas, 35, p.
163 (1949).
174. Demerec, hl., Genetics, 22, p. 469 (1937).
175. Patterson, J. T., quoted by Alesander in ref. 70.
176. Demerec, M.,Cold Spring Harbor Symposia on
Quantitative Biology, 2, p. 110 (1934).
177. Girvin, A., Univ. of Texas Publ. 4920, p. 42(1949).
178. Based on a table compiled by H. C. Waddington
and T. C. Carter, Appendix H of ref. 150.
179. Konzak. C. F., and W. R. Singleton, Proc. Nat.
Acad. Sci. U.S.A. 42, p. 78 (1956).
180. Lewis, D., Heredity, 2, p. 219 (1948).
181. Lewis, D., Heredity. 3, p. 339 (1949).
182. Stem, C. et al, Genetics 37, p. 413 (1952).
183. Muller. H. J., J. Cell. Comp. Physiol. 35, Supp. 1,
p. 205 (1950) and unpublished (with Campbell).
184. Fraccaro, M., Ann. Hum. Genet. 20, p. 282 (1955).
185. Robson, E. B.. Ann. Hum. Genet. 19, p. 262(1955).

186. Novitski, E., and L. Sandler, Ann. Hum. Genet.
21, p. 123 (1956).
187. Lejeune, J., and R. Turpin, Comptes Rendus Acad.
Sci. 244, p. 1833 (1957).
188. Caspar, A., and \V. R. Singleton, Rec. Genet. SOL
Amer. Genetics ( 1957).
189. Neel, J. V., p. 144 of ref. 11.
190. Schull, W. J. (in press).
191. Kemp. T., Cold Spring Harbor Symposia on
Quantitative Biology, 15, p. 129 (1950).
192. da Cunha, A. B., Adv. Genet. 7, p. 93 (1955).
193. Clark Fraser, F.: UN document A/AC.S2/G/
R.218.
194. Puck, T. T., D. Morkovin, P. I. Marcus and S. J.
Ciecura, J. Esp. hied., 106, p. 485 (1957).
195. Eharatwal, D. S., and G. H. Vase, UN document
A/ACS2/G/R. 166.
196. Mather, K., Proc. Roy. Soc. B., 145, p. 293 (1956).
197. lIather, I<.. Symp. Soc. Exp. Biol., 7, p. 66 (1953).
198. Penrose, L, S., Amer. J. Hum. Genet., 9, p. 167(1957).

Calculations concernirtg survival at or near birth and the
distribution of birth-weights
110. Both Karn and Penrose151and Fraccaro18' havefound in samples of several thousand births that the distributions both of survivors S and non-survivors N
through birth and the subsequent 30 days are Gaussian.
Under these conditions the influence of the mean andvariance of the over-all birth-weight distribution uponsurvival at or near birth can, at least approximately, betreated algebraically. Suppose birth-weight w to be measured from the birth-weight at which S is maximal.
Let S = S o exp - w2/2u92

N = N. exp - 1/2(-)lq*
Then the curve determining survival is
S
-=

N

1(

1
-exp - so

exp
2u,2
No
2
1
1
1
where - = - - 0 ~ 2
u32 ud2
and the over-all survival is 1 - Ewhere
174 Nok =a 3 0 f u4NO
Moreover, optimal survival is a t o,,, =and at this point~ 4 2 '732

-m'Ug2uca - 432

Then the survival a t w = a,,, is 1 - kml,

N./s, exp - 1/2
where k,l,

( ""-2 1
'74"

=

I

+ NJS. exp - 1/2 (u,2 - .a2

andk in terms of (1) the variance 422 of the over-all distribution of birth-weights
T(W) = S(W) N (W)and(2) the difference m between the mean of the over-all
distribution of birth-weights and the birth-weight for
optimal survival, andCalculated numerical changes in r and in for 1 percent changes in variance and in departure of meanfrom optimal birth-weight are given in table XVI
calculated from the data of Kam and Penrose andFraccaro.

-I t is desirable to express the relation between k,,,

.

-

+

(3) the variance u12 which determines the shape of thebirth-weight-survival relation.

In terms of the parameters describing S(W) andN(W)If it is assumed that is small by comparison withunity, it -is. possible to write

k

(

0 4

m'2

)+om

r=-=exp 112
kml, at
4 4 2 - 43
and so since a 2 = a52 o(E)and a42 can be eliminatedin terms of a12 and ~ 7 3 ~+'Comparison ofas observed by Karn and Penrose
with values calculated from the above formula andthe parameters of their experiments gives
To&

Males
Females

2.07
2.21

C
'&

2.23
2.36

111. On the basis of equ. (1) it is possible to estimate
the consequences of small shifts in the mean or variance of the distribution of birth-weights, assumingthat the survival curve (k,,,, ul) remains constant, by
the relations

T-ABLE XVI.

112. I t has been estimated by Robsonla and byPenrose'4Q that some 40 per cent of the variance ofbirth-weight in a United Kingdom sample was due
to genetic factors, either of the mother or of the foetus.
Possibly only a small fraction of this is maintained byrecurrent mutation. The other extreme possibility isthat recurrent mutation maintains the \\?hole of thegenetic component of the variance 412. In that eventa 10 per cent change in mutation rate might lead toa 4 per cent change in 422 and so to changes in survivala t and near birth amounting to 0.2-0.7 per cent. If therepresentative doubling dose for the polygenes concerned were to be 30 rad, this would then correspond
approximately to the genetical influence of natural
sources of irradiation upon survival a t or near birth.
113. The part played by genetic factors in maintaining the difference between the mean birth-weight andthat for optimal survival is not known, but the mostextreme possibility is again that recurrent mutation
may be responsible for the whole of m. In that eventa similar change in mutation rate might lead tochanges in survival a t or near birth amounting to
0.2-0.8 per cent. These calculated upper limits apply
to regions in which the total loss of infants a t or nearbirth is in the range 4-7 per cent. They are illustrativeof the need to resolve the underlying and more fundamental problem of the part played by mutation inmaintaining the current distribution of birth-\$-eights
against the pressure of selection acting through thisphenotype.

CALCULATEDCONSEQUENCES OF CHAKGES IN THE PARAMETERS
GOVERNING BIRTH-WEIGIIT DISTRIBUTION

Swrcy Sampk

IGrn and Penroseljl.. ............................

...........

Chnngcs due fo 1 pn cear chongc in a12

Changes due lo I pcr cetrl chczgc in m

Fractional change
in r (parcnr)

A b ~ l u fchongctin fr (pcr cent)F r a c f i d chaalc Aberrlc change
in r (p,cent)in k Cpcr ccnl)

hlales 1.5
Females 1.3
Males 1.6
Females 2.9

0.072
0.053
0.11
0.18

0.50
0.84

0.024
0.034

Annex I

LIST OF REPORTS
S U B M I T T E D T O T H E CObIMITTEE
1. This annex lists reports received by the Committee from Governments, specialized agencies, the International
Commission on Radiological Protection and the International Commission on Radiological Units and Measurements.
Abstracts have been inserted where appropriate.
2. All those reports are included of which a sufficient number of copies for distribution in the A/AC.82/G/R.
document series were received before 1 March 1958.
3. The list also includes reports received after 1 &larch 1958, preliminary copies of which were submitted to theCommittee prior to that date.
Document
hrumbnCoulitry and Ti&

A pfrorimate
No. of pages

A/AC.82/G/R.
1.

2.

3.

4.

USITEDSTATESOF AMERICA.The biological efezts of atomic radiation
Summarizes general survey in which committees of experts covered the following
subjects: genetics; pathology; meteorology; oceanography and fisheries; agriculture
and food supplies; disposal and disposers of radioactive wastes.
UETTEDKINGDOMOF GREATBRITAIXAND NORTHERN-~REL.~NI).T h hau~ldsto manof nuclear and allied radiations
General report covers both somatic and genetic hazards associated with radiation,
present and foreseeable levels of exposure, and an assessment of the hazards in termsof associated actual and permissible levels.
BELGIUM.Prelinzinary report on modern methods fur the evaluution of the biological e m t s
of small doses of external radiution or absorbed radioactive materials
Concludes that the most hopeful measurements are those of:
1. DNases and cathepsins in plasma and urine.
2. DNA synthesis in vitro by bone marrow or biopsy specimens.
3. Platelet counts.
4. Antibody synthesis.
and that the Committee should re-emphasize the need of appropriate fundamental
research in radiobiology.
JAPAN.(Report consisting of eight parts, as follows:)(Part 1.) Researches on tlze efects of the H-bomb explosion at Bikini Atoll 1954 on
animal ind~istryand sericzrllure in Japan
Gives negative results of analysis by absorption method of radioactivity in milk,
eggs and agricultural products following the Bikini explosions of hlay 1954. Related
experimental feedings of animals with radioactive ashes were analysed chemically.
(Part 2.) The radioactive contamination of agricultural crops in Japan
Gives results of soil and crop analyses for total radioactivity before and after May
1954 Bikini explosions, after subtraction of K'0 content, and with some radiochemical
analysis. Radioactivity after the explosion was detected in soil, crops and other vegetation which are distributed all over Japan. The possible route of contamination is
discussed.
(Part 3.) A preliminary report of reconzmendations on the modern methods 4 estimating
the biological activity of small radiation dose
Several current hematological findings in Japan are summarized and discussed.
(Part 4.) The airborne radioactivity i n Japan
Analyses of airborne radioactivity by filter and by electrical precipitator are describedand compared. Results of analyses 1954-1956 show poor correlation between peaks ofcontamination and trajectories of high-level air masses.
(Part 5.) Report on the systemtic observations of the atmospheric radioactivity i n Japan
Describes methods of collection and analysis of fall-out in dust, rain and snow, andof airborne radioactivity, as used in a wide survey a t meteorological stations. Resultsfrom April 1954-March 1956 are summarized and discussed and the cumulative depositions of Sr9O is calculated.
(Part 6.) On the distribirtion of natrtraliy radioactive ttuclicdes in Japanese islands
Surveys of the distribution of naturally radioactive nuclides in Japanese waters andminerals are reviewed and summarized.

205

Document-umberCountry and Titk

A fifiroximate
No. of pages

A/AC.82/G/R.
JAPAN (coratinzled)

5.
6.

7.

8.

9.

10.

11.

12.

13.

14.

14/Add.l(Part 7.) RadiocIrentual analysis of radioactive fall-out observed i n Japan
21
Present methods and results of radiochemical analyses of ash from the fishing boat
No. 5 fukuryu Maru and of rainwater and soil samples in Japan.
24(Part 8.) Fission prodwts i n water we5 and q u a t u organisms
Describes fall-out distribution and uptake generally, with special reference to waterand aquatic organisms and to the problem of Sr90.
~ ~ E S I C O First.
report on the studies of radwactke fall-out
15
Gives full description and comparisons of sticky paper and pot methods, preliminary
results May-July 1956 for total beta activity and intended expansion of programme.
2
UNIONOF SOUTHAFRICA.Preliminary report on radioactive f&out
The preliminary result of the measurement of total beta activity of fall-out by
porcelain dish method is described and results are given for January-June 1956. Sr90
deposition was estimated by chemical analysis.
UNITEDSTATES.
Radioactive fall-out througlz September 1955
13
Summarizes analysis of daily samples obtained up to end of September 1955 fromtwenty-six stations in United States and sisty-two elsewhere by gummed film method
calibrated against collection in high walled pots (see document A/AC.82/INF.l).
Cumulative deposition of mixed fission products, integral gamma doses and Sr90 deposits are calculated and compared with other findings, including Sr90 content of soils
and milk.
CHINA.Reports by the d t o m u Energy Council of the Executive Y u a n of the Republicof China
8
Briefly notes the radium content of certain Chinese and other waters and the occurrence of radioactive sailfish and dolphin in seas off Taiwan, June 1954.
CANADA.
Report on waste disposal system ai the Chalk River P h n t of Atomic Energy ofCanada Limited
15
Describes procedures and results of ground dispersal of radioactive wastes from anatural uranium heavy water-moderated reactor.
15
The Canadian progranzme for the investigation of the genetic effects of ionizing radiation
Describes a proposal to modify the sy,fem of recording of the national vital statistics
so as to render useful for genetic analysls the information contained in certificates ofbirths, marriages and deaths (see also document -4/AC.82/G/R. 58/Add. 1, annex 12).
UXITEDSTATES.Pathologic effects of atomic radiation
100
Present knowledge of the pathological (non-hereditary) effects of radiation is surveyed extensively by a committee. Includes separate sections by sub-committees orindividual members on: acute and long-term hematologcal effects: toxicity of internal 7
emitters; acute and chronic effects of radioactive particles on the respiratory tract;
delayed effects of ionizing radiations from external sources; effects of radiation on theembryo and foetus; radiation in a disturbed environment; effects of irradiation of thenervous system: radiation effects on endocrine organs.
Levels of strontitrm-90 i n Canada
7
CANADA.
Gives figures for Sr90 and S@ in milk powder a t seven stations, November 1955May 1956. The Sr90 level averages 4.8 ctpc/grn Ca. Cumulative total beta activity andcalculated SrOO content of fall-out analysed by United States AEC from gummed
papers, are summarized annually for 1953 to 1955. Independent Canadian measurements by methods which are not described differ from these by factors 2-5.
NEW ZEALAND.
-Wok by New Z m h d
12Gives brief notes in reply to the questions contained in individual paragraphs ofannexes to letter PO 131/224 of 9 April 1956 (annexes derived from A/AC.82/R.10).
Other sections describe: measurements of radioactivity (only radon found) collectedfrom air a t Wellington by filter and by electrostatic precipitator February 1953-May
1956, also by an impactor method in 1953 and in rainwater on certain dates November
1955-AIay 1956; results of measurements of total beta activities of fall-out by sticky
paper method May-July 1956.
NORW-4~.
Report of three parts
9
Suggests taurine biochemistry and lens opacities as biological indicators for low
doses. Gives notes on disposal of small amounts of radioactive wastes. Describes andgives results of analyses by pot method in 1956 of total beta activity due to fall-out
on ground. in air, in drinking water and accumulated in snow falls. Includes someanalyses for Sr90.
Addetzdum to Part I
7

Document~VztmberCountry and Title

Approximate,Yo. of pages

SWEDEN.Report of fifteen parts
The fifteen sections cover: consumption of the doses to the gonads of the populationfrom various sources; thorough survey of natural radioactivity including estimates ofu-eeldy dose-rates; measurements of gamma radiation from the human body; measurements of fall-out (1953-1956) including total beta activity, gamma ray spectrum andmigration of SrgO into soils, plants and grazing animals, content of certain isotopes aswell as research upon certain related physical quantities; considerations of occupational (medical) exposures. Methods used are extensively described throughout.
Corrigendzcm to parts 1 and 9
Corrigendum to part 9
FRA~-CE.
Report of three parts
The report includes three main parts:
1. hlethods of measuring: the radioactivity produced b y nuclear explosions andnuclear industry; natural or artificial radioactivity in living beings; the atmosphericradon.
2. Reports on measurements relative to: natural radioactivity of rocks: radioactivity of soil and water; natural and artificial radioactivity of air, water and soil;
occupational radiation exposure.
3. Studies on genetic effects of radiations and on the descendants of patientstreated with pelvic radiotherapy.
Addendum to above report
Czacaos~ov.-isu.Nalural radioacti-jily of water, air and soil in the Czechoslmak Republic
Briefly draws attention to deviations from reciprocity and to the partiaI reversibilityof many radiation induced phenomena, to the possible use of organisms in a state ofabiosis as integral dose-indicators. to certain specially radiosensitive organisms andresponses, and to questions of threshold. An extensive survey reviews many studies
of natural radioactivity.
KOREA,REPUBLICOF. Report concerning the request for information on natzrral radiation
background
Describes counters used for monitoring radiation background and gives results (cpm)from January 1955 to June 1956.
AUSTRIA.Information prepared by the Austrian Government relating to the effects ofatomic radiation
Describes radioactive warm springs a t Bad Gastein, giving activity levels in waterand air. Outlines wide scope of biological and instrumental research a t Gastein Institute.
UNITEDKENGDOM.
Th8 radiological dose to persons in the United Kingdom due to debris
fronz nuclear test explosions prior to Jantrary 1956
Summarizes measurements of total beta activity and Sr" content of fall-out a t
ground stations, in rainwater and in the air over the United Kingdom during 19521955. Includes calculations of time-integrated gamma ray doses.
Corrigendum to above report
UNITEDSTATES.
Project Sunshine Bulletin No. 12
Presents and discusses results of SrQOanalyses since 1 December 1955. Includes Srw
concentration in human and animal bones, animal products, vegetation, soil, precipitation, other water, and air.
Siunzmary of analytical results from the Has1 Strontium Progranz to June 1956
Summarizes the data of research on Sr9O conducted by Has1 since 1951. Includes the
Srgo content in fall-out, soil, vegetation, human and animal bones, human urine, milk,cheese, clrinking water, and fish. Fall-out measurements and samples cover not only
United States of America but also several other countries.
ARGENTINA.
Preliminary report on possible methods of estimating tlte biological effects ofsmall doses of radiation
Among biological effects of small doses of radiation, emphasizes especially: measurement of DNA synthesis using P32 and Cld radio-autography, histochemical andelectron microscopic examination of changes in lymphocytes and other components ofperipheral blood.
UNITED
STATES.
The effect of exposz~reto the atontu bombs on pregnancy termination in
Hiroshima and Nagasaki
Gives full account of survey of pregnancies in Nagasalu and Hiroshima from 1948
to 1954: sex ratio, congenital malformations, still births, birthweights. neo-natal deaths,
certain anthropometric measurements a;t nine months, and autopsies were compared~ i t parentalhirradiation histories. No significant correlations were found.

207

DocudNumberQ
Country and Tille

Approximak
No. of pages

A/AC.82/G/R.
HUNGARY.Unztsual radioactivity observed i n tire atmospheric precipitation in Debrecen
25.
(Hungary) between 22 April-31 December 1952
Describes methods and discusses results of measurements of total beta activity offall-out at Debrecen, April-December 1952.
BELGIWI.Report consisting of five parts26.
1. Gives results of clinical observations of patients treated with X-rays, Ra or 1181
and of persons occupation?lly exposed.
2. Gives results of studles relating to: the medical and physical control of persons
occupationally exposed: the absorbing materials; and the radioactive contaminationof the atmosphere.
3. Considers preventive or curative methods of syndromes of acute irradiation.
States results of doses received by the occupationally exposed personnel of the Institut
du cancer of Louvain, Belgium, and of hematological examinations of them.
4. Describes methods for measuring the radioactivity in rain and surface waters.
Gives results of measurements of radioactivity in rainwaters.
5. Describes method for measuring the radioactivity of atmospheric dust by continuous filtering of air.
SWITZERLXSD.
Letler from the "Service fakral de l'ltygid?~publique", Bern
27.
Gives brief description of studies on atomic radiations conducted in Switzerland.
ARGENTINA.Information summary on the preliminary work carried out in Argentina
28.
for the measztremettt and study of radioaciive fall-out
Gives summary description of methods tried in Argentina for measurement of total
fall-out radioactivity and airborne radioactivity.
AUSTRALL~.
(Report consisting of six parts, as follows:)
29.
(Part I.) H u m a n genetics
Report gives recommendation as to the kind of human mutations which could bescored: several dominant autosomal genes should be investigated (gives list of suchgenetical abnormalities).
(Part II.) PIant genetics
Gives plan of research to be organized.
(Part I I I . ) Radio-biological unit in the University of Adelaide
To be established.
(Part IV.) Natural radiation background and environmental contamination
Describes future organization of investigations on natural radiation background andcontamination; radioactivity of food will be determined.
(Part 17.) Occupational exposure i n Australia
Describes monitoring system in application since 1940 and summarizes observations
done by the use of film badges (gives statement of per cent of personnel having received
a specified per cent of the permissible dosage).
(Part VI.) Health and safety precazttio9ts i n uratti2rnz mining and milling i n Aztstralia
Describes health and safety precautions in uranium mining and milling.
30.
UNITEDKIXGDO>I.Radio-strontium fall-out i n biological materials i n Britain
Describes methods for determination of Sr90 in soils and material of the biologicalcycle: gives results of measurement effected in England up to spring 1956.
31.
FEDERALREPUBLICOF GERMANY.
Replies to the questions put by the United Nations
Scienti$c Conzvzittee 072 the Effecls of Atomic Radiation
1. Levels of natural radiation background.
3. Summarizes long-term research in biology and medicine under the direction of
Langendorf (genetic effects, restorations, physicochernical effects); Rajrdski (effects
of natural radioactivity, accumulation of nuclides in tissues); Alarquardt (research on
natural mutation rates and their modification by irradiations): Other institutes(pathological and physicochemical effect). No details given-refers to scientificpublications.
32.
INDIA. Procedure used i n India for collection of fall-out samples and some data on fall-out
recorded i n 1956
Describes methods for measurements of airborne actix-ity by filtration, and of deposited fall-out with daily and monthly collection. The information includes tables
p i n g results.
33.
External radintio7t dose received by the inlzabitants of nzonozite areas of TravancoreCochin , Izzdia
Contains results of a survey to measure the radiation level of the Indian State ofTravancore. The radiation level due to gamma-rays a t about three feet above theground level ranges from 6,000 to 100 mrad/year, approximately. The main contributors are thorium and its decay products.

13

50

6
2
17

46

6

12

9

Document
Number-1

A fifloximate
No. of pages

Counlry and Title

A/AC.82/G/R.
t34 and Add.1 $BRUIL. O n tlze intensity levels of natural radioactivity in certai??selected areas of Brazil
States that Brazil has areas of intensive natural background where thorium sands
are present. Gives description of a survey on four sample areas which were selectedwith regard to:( a ) The geological structure and genesis of their active deposits;(b) The extension, configuration and intensity of their radiometric levels:(c) The extent and variety of possible biological observations and experiments.
34/Corr. 1
Corrigendum to above report.
~~'IETEOROLOGICALORGANIZATION.
Summary of comments of W h f O on proWORLD35.
cedures for collection and analysis of atmospheric radioactivity data
Comments on meaurements of fall-out and airborne activity: stresses the importanceof co-operation between meteorologists in selecting sites wherefrom to obtain samples.
BUZIL. ~lfeasurementsof long-range fall-out in Rio de Janeiro
36.
Gives information on measurements of airborne activity done in Rio de Janeiro,
including tables showing decay curves of activity of samples and concentration offission products in air during the period May-July 1956.
37.
UNIONOF SOVIETS O C L ~ I SREPUBLICS.
T
O n the methods of indicating the changes produced i n the organism by small doses of ionizing radiation
Gives an enumeration of many methods which might be used as tests for small
dosages: but these are based on certain symptoms which have not yet been worked
out to give a quantitative response, i.e. vegetative-visceral symptoms, nervous symptoms (like the increase in threshold of gustatory and olfactory sensitivity, etc.), skinvascular reactions, electroencephalogram.
Blood symptoms are also described (alterations of thrombocytes and lack of aleucocptosis response t o the injection of Vit. B-12).
Certain "immunological" symptoms are quoted, like the bactericidal properties ofsaliva and of skin.
38.
BRAZIL.Absorptio?~czrve of fall-out prodrlcts
Is connected with document A/AC.82/G/R.36; gives absorption curve for fission
product of an airborne activity sample obtained by filtration.
39.
USSR. Content of natural radioactive substances in the atnzospkere and in water in the
territory of the Union of Soviet Socialist Republus
Studies content of natural radioactive substances in the atmosphere and in waters;geochemical considerations on mechanism of contamination of waters and descriptionof radio-hydrogeological methods. Gives methods of measurement of airborne activity
and results, and includes tables giving content of natural radioactive products in air
and waters.
40.
Study of the atmospheric content of strontium-90 and other long-lked fissions prodiccts
Gives measurements of airborne fission products (Sr90, CslE, Ce'44 and Ru106):
methods for collection of samples and their radiochemical analysis; results andcomments.
41.
O n the behaviour of radioactive fission prodzlcts i n soils, their absorption by plants andtheir accumulation in crops
Report of two parts:
Part I.-Experiments of absorpuon and desorption by soil of fission products and
Yw, Cs137, Zr95
Nb9j and Ru106
Rh 106 areespecially of isotopes such as Sr9O
described. Theoretical analysis is also described.
Y90 is absorbed through ion exchange reaction, and is
I t was observed that Sr90
completely or almost completely displaced from the absorbed state under the action of
a neutral salt such as CaCl?. Radioactive equilibrium between SrgO and Y9O is destroyed during the interaction with soil.
Displacement of absorbed radiocesium is greatly affected by the potassium ions, but
not highly affected by N a N 0 3 or CaCl2 compared with SrgO
Y90. Zirconium andruthenium absorbed by soil exhibit a much lower susceptibility to desorption into
neutral salt solution, though their absorption is less complete. The disturbance of theequilibrium occurs also by absorption or desorption.
Part II.-The results of experiments on uptake of fission products by several agricultural plants are described. In water culture, the bulk of radioactive isotopes ofcesium and strontium is held in the above-ground organ of plant, while Zr, Rh andCe are mainly retained in the root system. Sr and Cs are likely to accumulate inreproductive organs of plants in larger quantities than Zr, R u and Ce. The plant uptake is affected by the concentration of hydrogen ions in the solution. Plants' uptakeof fission products from soils is considerably smaller than from aqueous solution, and

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cesium was found to be less absorbable from soil, compared with other isotopes, while
cesium is among the fission products most strongly absorbed by plants in water
culture. These facts can be explained by the absorptive and desorptive capacity of theisotopes of the soil. The properties of soil as well as the application of lime, potassium
or mineral fertilizers greatly affect the plant uptake. When a soluuon of fission
products was applied to leaves of a plant, radio-isotopes were observed to pass toother organs. Radiocesium was the most transmovable among the isotopes tested.
MEXICO.
First studies oft radioactive fall-out
Revised form of UN document A/AC.82/G/R.5.
JAPAN. The effect of momentary X-ray exposure in a s
d dose upon the peri$heral
blood picture
Decrease in lymphocyte number after single 60 mr exposure in humans. Decreasein lymphocyte count varies from 10 to 50 per cent-the maximum drop occurs thirty
minutes after irradiation, and may be followed by an increase in lymphocyte count.
Hematological e J ~ t sof single exposure to small doses of X-ray
Hematological effects during routine chest examinations. Dosages up to 3r. Most
constantly observed are: increase in neutral red bodies and Demel's granules inlymphocytes and late decrease in mitochondria1 index of lymphocytes during thefour-hour period following the irradiation. The cytochemical identification of thesevarious granules and their biological si_gnificanceshould be established unequivocally.
Morphological changes of platelets in chronic radiation injuries
Platelet morphology in chronic irradiation injury in rabbits (chronic 0.115 r/day or
0.231r/day), X-ray workers (dosage not evaluated) and persons exposed to atomic
bomb within 4 km from epicentre (nine years after the exposure).
Even if platelet count is normal, area index (proportional to average area) is increased markedly, and may remain so nine years after irradiation and is not necessarily related to low platelet count. Other morphological changes are also shown.
This observation should be repeated by other groups.
EG~TT.Preliminary report on environnrental iodine-131 measurement in sheep andcatlle thyroids in Cairo, Egypt
Contains measurement of radioactivity of 1131 deposited in thyroids of sheep andcattle which were brought from all over Egypt, Sudan and north coast of Libya.
Sampling was made during the period from hlay to October 1956.
USSR. Preliminary data on the effects of atomic bomb explosions on the concentration ofartiJicia1 radioactivity i n the lower levels of fhe atmosphere and i n the soil
Contains description of methods of measurement of radioactive products in the air
a t ground level and high altitude and gives results of observations.
Also contains the following conclusions:(1) The existing technique for detecting the presence of artificial radioactivity inthe lower atmosphere and the technique for determining the integral activity ofaerosols deposited on the earth's surface makes it possible to estimate the level ofcontamination of the soil by radiostrontium (strontium-90).
(2) The accumulation of radiostrontium in the soil in various areas of USSR territory is attributable partly to the explosion of atomic bombs in USA and partly to
explosions set off in USSR. The lower limit of activity of the strontium-90 which has
accumulated in the past two years (19541955) is as high as about 30 millicuries per
km2 in certain towns (cf., for example, Adler).
(3) Since radiostrontium is readily caught up in the biological cycle, suitable projects
must be put in hand to determine the permissible levels of contamination of the soil
with radiostrontium (strontium-90) and other biologically dangerous isotopes.
Programme of scientific research on the e f a t s of ionizing radiutions on the health ofpresent and futzrre generations
Describes a programme of research intending to study the effects of radiation a t
dosages 1 or 2 orders of magnitude above background intensity, of contamination of
the air and soil and life in areas of high natural radioactivity.
Summaries of papers presented at the Conjerence on tlze remote consequences of injuriescaused by the action of ionizi?zg radiatiolt
34ostly concerned with effects of various radionuclides and external radiation ondifferent mammalian populations (Hematology, carcinogenesis, f~rtility mostly
studied). Twenty-two papers are summarized.
Contribzrtions to the s t l ~ d yof the metabolism of caesiunt, stro?ztit~mand a mixtztre ofbeta-emitters it^ cows

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The metabolism of Csl37, S14989.90 and a number of mixed beta-emitters has beenstudied in cows (milk, urine, faeces, tissues).
Str07ztil~m:about 10 per cent given is absorbed in intestine and 1.45 per cent isretained in bones, and twenty times less in the soft tissues. The rest is excreted bymilk or urine.
Caesizrm: about 25 per cent given is absorbed in intestineone fifth of this is retained in muscle and less than one tenth of this amount in other organs or skeleton;
the rest is eliminated in the milk or urine.
51.

UNITED
IGNGDO~I.
T h e genetically signi$cant radiation dose from the diagnosis use of
X-rays in England and Wales-A prelinzinary sztrvey
Contains an analysis of number of X-ray diagnostic examinations performed perannum in England and \Vales, and a subdivision obtained from five selected hospitals
into types of esaminations. and into age and ses of the patients examined. In addition,
an assessment is made of the minimum dose received by the gonads in each type of
examination, and the probability of reproduction as a function of age. The results showthat it is unlikely that the genetically significant radiation dose received by the population of England and Wales from X-ray diagnosis amounts to less than 22 per cent ofthat received from natural sources and it may well be several times greater than thisfigure. Most of this radiation is received in a few types of esaminations, undergone byrelatively few patients, and by foetal gonads in examinations during pregnancy.

52.

RoM~NI.~.
Organization and results in radiobiological research work in the .RomanianPeople's Republic
Describes the following:(1) and (2) Protective effects of narcosis during irradiation only.
(3) After 325 r, up to eleven days narcosis increases biological effects (does not state
what criteria of biological effect).
(4) Hibernation (25' C) protects. Hibernation between 18'-25' C enhances effect.
Does not state if this is during or after irradiation.
(5) Hematological tests after 350 r.
( 6 ) Caffeine or aktedron during irradiation enhance effect; caffeine or alitedron
after irradiation diminish effect.
Suggests roentgenotherapy under conditions of protection (narcosis). Gives programme for radiobiology research in 1956-1957.

53.

USSR. Report consisting of two articles:
Part 1. The effects of ionizing radiations on the electrical activity of the brain( a ) Grigorev's research work states: gamma-rays depress electrical action of humanbrain. Does not confirm Eldrid-Trowbridge, who do not find effect on monkey.
(b) Describes effects of beta-rays of P32 (0.05 mc/kg up to 1 mc/kg) on electroencephalogram of dogs. This was followed by radiation sickness (if dose > 0.5 mc/kg)
and by hematological effects. A special implantation method of the electrodes is used.
Injection of 0.09 mc/kg gives change in amplitude five minutes after the injection(reduction in amplitude). After 0.5 mc/kg lowering of electrical activity lasts forseveral days. For dosages above 0.1 mc, part of the repression of brain activity isprobably a result of the radiation sickness induced by such high dosages.
Part 9. On the beta-radiation mtirn'ty of human blood
Report on radioactivity of human blood: 100 cc of normal blood have a radioactivity of 1.7 to 3.64.10-10 curies (due to K"). Permits the determination of K
content of whole blood. Same values are found in different pathological conditions.
No data on people working with radioactive material.

54.

UNITED
STATES.
Some efects of ionizing radiation on human beings

55.

A report on the Marshallese and Americans accidentally exposed to radiation fromfall-out and a discussion of radiation injury in the human being. Gives general andclinical symptomatology in relation to the estimated dosage and to internally deposited radionuclides.
Background radiation-A literature search
The results of literature search about background radiations dosage to human beings
are described and classified into three categories:(1) Cosmic radiation; (2) terrestrial radiation sources: and (3) radiation from internal
emitter. The cosmic radiation is important for the evaluation of natural background,since i t is estimated very roughly to contribute about a quarter of total backgroufld
dosage to the human population a t sea level and high latitude. However, its intensity
varies with various factors, such as altitude, geomagnetic latitude, barometric pressure,

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STATES(continued)
temperature etc. Facts directly related to biological effects of cosmic rays are also
reviewed.
Radiations from naturally-occurring radioactive isotopes form another importantpart of the natural background. The contribution which comes from land is mainly
due to IC40, Razz6, ThB2 and Urn and the decay products of the last three nuclides.
The radium concentrations in surface water and public water supplies in various
districts are tabulated. The atmospheric concentration of Rn and Tn is greatly dependent on the locality, atmospheric condition and degree of ventilation, if indoor.
The population dose due to the natural background radiation is difficult to evaluate
in general, because of the statistical nature and varying conditions involved in nations.
Operation Troll
Operation Troll was conducted to survey the radioactivity in sea water and marine
life in the Pacific area during the period from February to hlay 1955. The general
conclusions obtained are as follows:
1. Sea water and planlcton samples show the existence of widespread low-level
activity in the Pacific Ocean. Water activity ranged from 0-570 d/min/litre andplankton from 3-140 d/min/g wet weight.
2. There is some concentration of the activity in the main current streams, such as
the North Equatorial Current. The highest activity was off the coast of Luzon, averaging 190 d/min/litre down to 600 m (1 -April 1955).
3. Analyses of fish indicate no activity approaching the maximum permissible levelfor foods. The highest activity in tuna fish was 3.5 d/min/g ash, less than 1 per cent of
the permissible level.
4. JIeasurements of plankton activity offer a sensitive indication of activity in theocean.
5. Similar operations would be valuable in assessing the activity from future tests
and in gathering valuable data for oceanographic studies.
Go7zadal dose i n roentgen examinations-A literature searchContains results of literature research which show the estimated contribution of
gonadal dose by standard medical roentgenographic procedures. Contribution to the
gonadal dose of certain examinations, such as examinations of teeth, skull, chest andextremities, is relatively insignificant, when compared to the case of pelvic and abdominal examinations. I t should be noticed that the dose to the foetal gonad isimportant genetically.
WORLD
HEALTFIORGANIZATION.
Ex't of radiafiotl on human I t e r e d i t p
Report of a Study Group (Copenhagen, 1-11 August 1956).
1. Document A: Reply to a question raised by the United Nations Scientific Committee on the Effects of Atomic Radiation.
2. Report of the study group concerning general questions and recommendations
for future progress and research.
3. Annexes 2-9 and 11-12 of the above report, being papers presented by various
members of the group.
These annexes were:Types of mutation a t known gene loci and possibility of hitherto unrecognized
mutations being induced. Irradiation of animal populations: results and work neededT. C. Carter.
Some of the problems accompanying an increase of mutation rates in Mendelian
populations-Bruce Wallace.
Exposure of man to ionizing radiations, with special reference to possible genetic
hazards-R. M. Sievert.
Detection of induced mutations in offspring of irradiated parents-J. Lejeune.
Gonad doses from diagnostic and therapeutic radiology-W. hI. Court Brown.
lllutation in man-L. S. Penrose.
Possible areas with sufficiently different background-radiation levels to permit detection of differences in mutation rates of "marker" genes-A. R. Gopal-Ayengar.
Comparisons of mutation rates a t single loci in man-A. C. Stevenson.
Effect of inbreeding levels of populations on incidence of hereditary traits due toinduced recessive mutations-N. Freire-Maia.
Detection of genetic trends in public health-Harold B. Newcornbe.
Annexes 1 and 10 of the above report of the WHO Study Group on the effect ofradiation on human heredity.
These annexes were:
Damage from point mutations in relation to radiation dose and biological conditions-H. J. hquller.

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60/Add. 1
61.

61/Add. 1
62.

63.

64.

65.
66.
67.

Some problems in the estimation of spontaneous mutation rates in animals andman-James V. Neel.
NETHERLANDS.
Radioactive fall-out nzeasurenrents in the Netherlands
Describes methods used for collecting samples of airborne r a d i o a c t i v i ~and of
deposited fall-out, and methods of measurement.
Includes tables of results for 1955 and 1956; calculation of gamma doses andquantity of strontium-90 computed from total activity.
UNITEDKINGDOM.
Genetic research i n the United Kingdom
Relevant programmes of genetic research in the United Kingdom and their investigators concerned are listed under the headings:(i) Fundamental research upon mechanisms;(ii) Population structure;(iii) Quantitative data on human mutation.
Suggestions for research in radiation genetics
General considerations are reviewed and a list of suegested programmes of researchin the fields (i) to (iii) is appended.
JAPAN. Current and proposed progranznzes of research and investigation related to radiation genetics i n Japan
A brief survey of current and planned research in Japan relevant to radiation
genetics, covering both human surveys and experimental work.
Table 1 (2) to abwe report:
Experimental data with beta radiation
Radiochenzual analysis of Sr90 and Csl37
Discusses methods of radiochemical analysis of Sr90 and Csls, including separationof strontium by precipitation and by ion exchange. Experiments for determining thebest conditions for ion exchange separations are reported.
Review of the recent researches on the biological effects of ionizing radiation in Japan
Contains brief abstracts of fifty-five papers from the Japanese literature dealing
with (1) research on biological indicators of the effects of ionizing radiation in small
and large doses, and (2) research on counter measures t o alleviate radiation injury.
Classical and more modern morphological, histochemical and biochemical methodsof observation were used for the assessment of radiation damage. Most studies were
performed on mammals. It is emphasized that it is very difficult t o obtain reliablebiological indicators of damage by small doses and that haematological methods arestill the most suitable in man.
UXITED
STATES.Shortening of life i n the ofspring of nmle mice mposed to neutronradiation from a n atomic bomb
Length of life in the offspring of male mice exposed t o moderate doses of acuteneutron radiation from a nuclear detonation is shortened by 0.61 days for each rep
received by the father over the dose range tested. This figure excludes death before
weaning age. The 95 per cent confidence limits are 0.14 and 1.07 days per rep. p t r a polating t o a proportional shortening of life in man gives twenty days per rep received
by the father as the point estimate and five and thirty-five days as the 95 per centconfidence limits. The offspring were obtained from matings made from nineteen to
twenty-three days after irradiation and, therefore, represent the effect of irradiation
on germ cells in a post-spermatogonial and sensitive stage of gametogenesis. It is probable that irradiation of spermatogonia (the stage that is important from the point ofview of human hazards) would give a somewhat smaller effect. However, since thepresent data show an effect on the offspring which is as large as the shortening of lifein the exposed individuals themselves, it seems likely that, even when allowance ismade for the conditions of human radiation exposure, shortening of life in the immediate descendants will turn out to be of a magnitude that will warrant serious
consideration as a genetic hazard in man.
Gamma-ray sensitivity of spermatogonia of the mouse
Relates the depletion of spermatogenic cells t o killing of spermatogonia, the repopulation being related t o the maturation of surviving cells.
Some delayed efects of low doses of ionizing radiations in small laboratory animals
A quantitative study of the life span, the incidence of leukemia, tumours (lung, liver,overy), and lens opacities as a response to low dosages (less than 100 rads).
Eflects of low-level radiation (1 to 3 r ) on mitotic rate of grasshopper neurobhts
A study of the inhibitions of mitotic rate and of its possible relationship with thealteration of chromosome structure.

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68.
69.

70.
70ICorr. 1
71.
72.

73.

74.

75.

76.

76/Rev.l77.

78.

Effects of low doses of X-rays on enzbryofzic development i n the mouse
Effects of 25 r applied during different stages of embryonic development on skeletal
malformations appearing in the young.
S ~ D E NDoes. there exist mutational adaptation to chronic irradiation?
,haccount of an experiment in which a population of Drosophila heavily irradiatedfor many generations was compared with a control unirradiated population in respectof radiation-induced mutability. NO significant differences were found.
JAPAN. Radiological data i n JapanThe report is a compilation of data on radiation exposures in Japan. Data are arranged as suggested b y the Scientific Committee a t its October 1956 meeting.
Corrigendz~?nto above docu?nent
UXITEDSTATES.
Occupatio~zalradiation exposures i n Atontic Energy projects
A series of five tables concerning yearly exposures from 1947 to 1955 from external
and internal radiation sources.
Worldwide effects of atomic weapons(A comprehensive preliminary report on the Sr90 problem up to 1953).
-4 preliminary report discussing the various aspects of long-range contamination
due to the detonation of large numbers of nuclear devices. An improved methodology
for assessing the human hazard is developed, and an extensive experimental programme is proposed.
maximum pervzissible radiation exposures to man
A preliminary statement of the U.S. National Committee on Radiation Protection
and Measurement. The recommendations given by the Committee in National Bureauof Standards Handbook 59 have been revised and the maximum permissible doselevels have been lowered. The concept of "accumulated" dose for occupational conditions differs from the ICRP recommendations of 1956. For the whole population anannual additional exposure of 2.5 times the exposure from natural radiation sources
is allowed.
Gonadal dose produced by the medical m e of X-rays
A survey of diagnostic X-ray exposure with an attempt to estimate the geneticallysignificant dose in the United States. The estimate has been made under the assumption that patients undergoing X-ray examinations have a normal child expectancy. The
authors have assumed that the genetically significant dose can then be evaluated as
approximately equal to the average gonad dose for patients below the age of 30.
Using exposure data which are considered fairly representative of American practicethey arrive a t 130-140 mrem/year and 50 mrem/year as being the most probableand the minimum figure respectively.
Summary of current and proposed programmes of researclz i n the U.S.A. related toradiation genetics
A survey by investigator and title of current and proposed programmes of researchin the United States related to radiation genetics.
FOODAND AGRICULTURE
ORGAATZATION
OF THE UNITEDNATIONS.Principal calcium
contributors in national diets in relation to effects of atomic radiationfrom Sr90
Gives a general idea of foods contributing to the calcium uptake of human beings invarious parts of the world in relation to the different food habits of these people. Data
still quite preliminary.
FAO. Principal calcium conlributors i n national diets in relation to effects of atomic
radiation from strontium-90
This paper replaces the preliminary note circulated as U N document A/AC.82/G/R.76.
NORWAYAND SWEDEN.Radioactive fall-out over the Scandinavian peninsula between
July and December 1956
In this report, fall-out and rain precipitation figures over the Scandinavian peninsula are discussed. Accumulated monthly fall-out is reported for the period JulyDecember 1956.
BELGIUJL.
Information in eight parts on 1l.unzan getzetics submitted by Belgium
Contains the Belgian memorandum on human genetics prepared for the Geneva
meeting in April 1957 and a preliminary report on radioactive regions of Katanga(Belgian Congo). Besides this several reprints of Belgian contributions to radiobiology
are presented. The topics included are:(1) Steroid metabolism in irradiated rat.
(2) Endocrine response of irradiated animals studied by intraocular grafting.

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BELGIUM(contkzced)( 3 ) Doses and hazards due to medical radiology.
(4) hfetabolism and toxicity of cystamine in the rat.
Part 1. Current uncertainties in the field of human genetics.
Part 2. A preliminary survey of vegetation and its radioactive content in the
Katanga area.
Part 3. Influence of irradiation on the blood level of 17-hydrov-corticosteroids
during the 24 hours following irradiation.
Part 4. Skin and depth doses during diagnostic X-ray procedures.
Part 5. General discussion of the need for methods of effective dose reduction indiagnostic X-ray procedures.
Part 6. Chemical protection ( a ) metabolism of cystamine
Part 7. (b) the effectiveness and toxicity of cystamine.
Part 8. Experiments on the ascorbic acid and cholestrol content of the suprarenals of the rat following irradiation of normal and hypophy~ectomi~4
animals.
79.

80.

81.
81/Corr.l
82.
83.
83/Add.l
84.
85.
86.

87.

88.
89.

SWEDEN.A suggested procedure for the collection of radioactive fall-out
Proposes new method for evaluation of the external thirty-year dose due to thedeposition of gamma-emitting isotopes, based upon a single beta measurement foreach sample and one caesium ratio chemical determination in a pooled sample.
A second part of the report describes a collecting procedure using ion exchange resins.
ARGENTINA.
A geological, radiotnetric a d botanic survey of the region "Los Clut+iores"in the province of Mendom of Argentine RepublicRadiometric data on the above-mentioned region are shown on the attachment to
the document.
Measurements of the cosmic ray intensity in three latitudes of Argentine Republic
Data on the intensity of the cosmic rays in three points of observation a t different
latitudes in Argentina.
Corrigendum to above report
On the absorption of the nucleonic cotnponent of the cosmic radiation at -15' geomagnetic latitude
Mt~tationsi n barley seeds induced by acute treatments by gamnza rays of cobalt-60
A report of experiments on the induction of mutations a t a number of loci in barley
by irradiation of seeds with gamma-rays of Cow a t 10 r/min.
Addendum to above report
Mutations i n barley induced by formaldehyde
A report of experiments on the induction of mutations a t a number of loci in barley
by formaldehyde.
Spontaneous mutations in barley
A report of experiments on spontaneous mutations a t a number of loci in barley.
A study of radioactive fall-out i n Argentine Republic
Describes the methods used in Argentina for fall-out collection and measurement.
Value for strontium-90 and total beta activity are given for the first two monthsof 1957.
A research programme i n Argentina on the genetic influence in the plants of the ionizing
and ultra-&let radiatwt~
A brief summary of projected research in Argentina on the genetic effects of ionizing
and ultra-violet irradiations of plants, comprising both surveys of areas of highnatural background and a broad range of laboratory experiments.
Programme of physical oceanography for the International GeophysiGal Year
Information on the general programme to be developed i n Argentina on items of interest
to the Scientific Committee on the Efects of Atomic Radiation
A brief general survey of Argentina research activities related to the effects andlevels of ionizing radiations.

90.

NETHERLLP.~~.
Che?nual steps involved irz the production of mz~tationsand chromosome
aberration by X-radiation and certain chemicals in Drosophila
A survey of comparative studies of X-ray and chemical mutagenesis in Drosophila,
made in an attempt to throw light on possible intermediate chemical steps in the induction of chromosome breaks or mutations by ionizing radiation.

91.

UNITEDSTATES.
Strontiz~m-90in man
Radiochemical analyses of strontium-90 in human bone have been reported. The

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97/Corr.l
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99.

100.

values are in accord with the predicted levels based on fall-out measurements andfractionation through the food-chains.
Radioactive faldout irt Norway
NORWAY.
Contains information on methods and results of measurements of fall-out in Nonvay.
Summary of analytical results from the H A S L Stro?ttiz~mProgram July throughDecember 1956
Summarizes data on samples collected by the U.S.A. fall-out network since September 1955 up to September 1956. In addition, i t summarizes the data of the samples
collected for the strontium programme during the period July-December 1956.
Environmental radon cotzcentratwns-An interim report
Preliminary data showing ambient concentrations of radon in the metropolitan New
York area are presented. An attempt has been made to define the variability ofconcentration of radon in the general atmosphere with location, time, and weather
conditions. Samples have been analysed from the outdoor air, inside of buildings, andabove and below the surface of the ground. Comparisons with the data obtained byother investigators are also shown.
The radium content of soil, water,food cnd humans-Reported odues
hlari?te biology-EJectsof radiution-A selected bibliography
Twenty-four references concerning investigation on the distribution and metabolism
of fission products in marine organisms.
Sea disposal operatwtt
Some atomic energy activities in the United States have been disposing of radioactive wastes a t selected ocean disposal sites since as early as 1946. It is the purposeof this report to describe the extent of these disposal operations including a summaryof types of packaging used and of places where the wastes are dumped. The status ofrelated oceanographic research (1956) is briefly touched upon.
Corrigendum to the abme report
C-&-~U)A.
Radiochemical procedures for stroniiunz and yttrium
A detailed ion exchange ~rocedureis given for the determination of radiostrontium
in different samples. Methods are described for the treatment of various organic
materials.
Lmels of strontiz~m-90i n Canada u p to December 1956
Reports the results of radiochemical analysis for strontium-90 activity in milk
and milk products and human bone. Natural strontium content determinations in milk
and bone are also reported.
USITED KINGDOM.
The determination of long-lived fall-out in rainwater
Describes radiochemical procedures for the determination of S 9 , Sr90, Cs137 and Cel4J
activities in the rainwater.

101.

DENMARK.
kfeasurenzent of activity of airborne dttst. Measurements of fall-out depositedon the groundResults of daily measured radioactivity in air (electrostatic filter method) and in
precipitations (collection of rainwater) in Copenhagen for rhe period 1956.

102.

AUSTRIA.Radiologicd data. Demographic data.
Contains data on RBE dose rate in the gonad due to both natural and artificial
sources. Demographic data on the whole population and of special groups are given.

103.

UNITEDKINGDOM.
Modifiation of imnzunological pheno7ttena and pathogenic action of
infectious agents after irradiation of the host
Evidence is given that whole body irradiation before the repeated injection of antigen
both diminishes the peak-concentration of antibody and delays in time the appearance of the peak. The lowest efficient dose was 25r. The tolerance of heterogenous skin,prafts or bone marrow cells has been also shown after irradiation; the duration of~nhbltionof immune response is proportional to dose received.
Some data, esti~natesand rejkctions on colzgetzital awd hereditary anomalies i n the
fioPu.ktion of Northern Ireland
Presents an extremely detailed and thorough medico-genetic survey of the population of Northern Ireland using data accumulated over a number of years, together
with very pertinent analyses of the data, the problem of genetic disability and its relation to radiation effects.
Leukemia and aplastic anaemia in patients irradiated for ankylosing spondylitis
The incidence of leukemia and of aplastic anaemia was investigated in patients

101.

105.

Country and Title

A moximate
No. of pages

treated in Britain for ankylosing spondylitis by means of ionizing radiations during theyears 1935-1954.
Relationship behveen radiation dose and incidence of leukemia was evaluated. The
answers suggest the adoption of working hypothesis that for low doses the incidenceof leukemia bears a simple proportional relationship to the dose of radiation, and that
there is no threshold dose for the induction of the disease. The dose to the whole bonemarrow which would have doubled the,expected incidence of leukemia may lie within
30 to 50 r for irradiation with X-rays.

Information on radiological data
NORWAY.
Summary tables on radiological data in Nonvay with an extensive set of data on
X-ray and natural radiation exposures.
Addendum to above report
NEW ZE-UND. New Zealand report to U.N. Scientifi Comnzittee on Atomu Radiation:
E m t s of atomic radiation measured in New Zealand to 31 July 1957
A set of notes on the current status of various programmes in New Zealand 1vi:hin
the field of interest on the Scientific Committee on the Effects of Atomic Radiation,
including preliminary measurement of radioactive fall-out, C" airborne activjty,
natural and artificial radioactivity, and occupational gonad exposures.
USITEDSTATES.Current research findings on radioactive fall-ozct
General survey of the fall-out problem, especially Srw distribution and uptake inthe human body.
Dosages from natural radioactivity and cosmic rays
NETI-IERLANDS.
Four reports on quantitative determination of radioactivity
A group of tables containing figures for the radiation doses from natural and manmade sources in the Netherlands.
NORWAY.
0 1 1 the deposition of nuclear bomb debris in relation to air concentration
Studies the relation between the deposition of fall-out and the airborne activity.
I t appears that in 1956-1957 the fall-out in the Oslo area was roughly proportional tothe product of precipitation and airborne activity a t ground level.
Radioactive fall-out in Norway u p to August 1957
Gives the results of measurement of fall-out materials in air. precipitation, waterand other samples. Measurement of airborne activity a t high altitudes are included.
Srw values are computed from total beta activity, a small number of samples havlng
been checked by chemical analysis. Samples of water, milk and urine have been
analysed for iodine-131.
Radiochemical analysis of f&out in Norway
andDescribes the methods used in Nonvay for determination of Srw, Csln andcontains data of Srw and Csln activities in water and milk and of 1'31 in milk, in the
period February-June 1957.
UNITEDKIXGDOM.The relative hazards of Srw and Ra*
Methods for calculations of the doses received by soft tissue cavities in bone
containing Srw and Ram are presented. Non-uniformity factors are given for the dosefrom Sr90. Calculation of the maximum permissible body burden for radium on thebasis of a given maximum permissible dose-rate to bone gives a wide range of values,
depending on the assumptions made. In the case of radio-strontium, the range of possible values is less. I t is suggested that radium be no longer taken as the basis for the
calculation of maximum permissible body burden of Srw.
Sltortening of life by clzronic irradiation: the experimental facts
A survey of all published experimental results relating to shortening of life-span ofmice due to chronic irradiation.
The comparison of effects between gamma-rays of cobalt-60 and fast neutrons ismade; the R.B.E. factor used for fast neutrons was 13.
A good agreement of experimental results has been found indicating that chronic
irradiation both with gamma-rays and neutrons shortens the life of mice in a reproduc~blemanner. No statistically significant data were found below the weekly doseof lor.
The possibility of extrapolation and the possible dose-effect relationship is discussed.

BELGIUM.
Report on health protection i n uranium mining operations i n Katanga

Document

NumberCounlry and Title

INTERKATIONAL
COX~IISSION
ON RADIOLOGICALPROTECTION
A ~ DINTERNATIOKAL& P o s u ~ ~ of man toCoual1sslo~ON RADIOLOGICAL UNITSAND ~,IEASURE~IENTS.
ionizing radiation arising from medical procedures
Gives a survey of the present exposure of the gonads due to X-ray diagnostic procedures. Some 85 per cent of the diagnostic dose arises from six to seven types of
examinations, which are discussed separately. Estimates of the genetically significant
dose are given for some countries. I t is recommended that the basic studies be extended and that more detailed analysis be obtained through sampling procedures
rather than through the systematic recording of the radiation received by every
member of the population. Methods for dose reduction are discussed.
POL^^. Report on meusurements of fall-out i n Poland
Continuous measurements of global beta activity of fall-out are reported for four
stations in Poland.
Effect of a lethal dose of radiation on the antor~ntof reducing steroids in the
BELGIUM.
blood of the rat
Indicates that lethal irradiation shows, in the blood, an increase of reducing steroids.
This reaction presents a maximum which is not necessarily linked to the variations of
the ascorbic acid and of the cholesterol in the suprarenals.
Action of hydrogen peroxide on the growth of young barley plants
The growth of coleoptiles of young barley plants treated with hydrogen peroxide
is affected in the same way as when the plants are irradiated n-ith X-rays.
Action of cystantine and glutathwne on X-ray irradiated barley seed
The cystamine and glutathione diminish the effects of X-rays on barley grains;
mitosis are still possible after doses which would inhibit them in the absence of theseagents.
Action of X-rays on the growth of internodal cells of tlte alga Chara Vulgaris L.
Irradiation of internodal cells of alga CIzara Vulgaris L. increases the elongation ofthese cells for doses up to 150 kr; above this dosage elongation is inhibited (c.f. document A/AC.82/G/R.156).
UNITEDSTATES.Radioactivity of People and foods
Potassium and caesium activities measured with whole body counters are reported.
The amount of caesium-137 now present in the population of the United States showsno marked dependence on geographical location.
Atmospheric radioactivity along the 80th meridian, 1956
Radioactivity levels a t the various sites during 1956 are reported for three different
collecting systems: air filters, cloth screens and gummed films. Estremely wide variations in the gross radioactivity of fission products in the air have been noted, n-ith
the highest levels occurring in the Northern hemisphere. Preliminary results of radiochemical analyses of a few filter collections are included.
Radioactive co?ztamination of certain areas in the Pacific Ocean from nuclear tests
Contains a summary of the data on contamination levels in some areas of the
Pacific Ocean and results from medical sun7eys of Marshall Islands inhabitants.
Data on gross beta activity, individual isotope contamination and external gammaexposure are included.
UNITED
KINGDOM.
Radwstrontium in soil. grass, milk and bone in the United Kingdom:
1956 results
Results of strontium-90 analysis of soil, grass and animal bone for twelve stationsin the United Kingdom are given. Human bone specimens obtained in 1956 have also
been measured.
- ~ G E N T ~ T ACalcium.
and potassium content of foodstuffs in the Argentine Republic
Describes the methods and results of I< and Ca analysis of food in Argentina.
I t shows that 80 per cent of the dietary Ca is provided by milk.
UNITED
KIXGDOM.
Ionizing radiation and the socially handicapped
Collects available data and calculations concerning the numbers in various classesof handicapped individuals in the United Kingdom and the relationships of thesenumbers to genetic factors, mutation rates and radiation levels.
C-4~-=A.Dose from unsealed radio-nuclides
Calculations based upon information on shipments of radioisotopes show that the
gonad dose to age 30 from unsealed radio-nuclides during 1956 in Canada is about
0.5 per cent of the dose from the natural radiation sources. The main dose arises fromiodine-131.

Documen:
hiumber

Colrntry and TiUc

dpProxim&
NO. of pages

A/AC.82/G/R
130.

13O/Add.l
131.

132.

133.

134.

135.
136.

136/Corr.l
137.

138.

138/Corr. 1
139.

2,000
USITEDSTATES.Tlae nature of radioactive fall-out and its eflects on man
An extremely diverse and extensive collection of infomation and expert opinion
given as public testimony before a governmental committee, and presented without
further evaluation.
Index to above report.
51
Radioactive strontium fall-out
26
General survey of the fall-out problem, especially strontium-90 distribution anduptake in the human body.
21
UNITED
KINGDOM.
Tlte determination of long-lived fall-out i n rainufater
A method is described for the determination of long-lived isotopes in samples ofrain water. Some attention is paid to the development of the method, including detailsof the checks to ensure radiochemical purity of the final sources used for counhng.
WORLDMETEOROLOGICALORGANIZATION.
ExcerPt from a letter dated 6 November 1957
received from the Secrehry-General of the WMO-Interinz international reference
precipitation gauge
Brief report of the discussion held by the Executive Committee Panel on Atomic
Energy and by the Commission for Instruments and Methods of Observations of the
WMO on subjects related to the effects of atomic radiation.

7

ITALY.Report on genetics 1950-57-A brief report on the research work done i n the jieldof genetics i n Italy
Extensive notes reporting relevant research work in the field of genetics carried out
in Italy during the period 1950-1957.

47

J A P A N . Analysis of Sr90, Csln and Pu239 i n fall-out and contaminated materials

The report gives radiochemical procedures for Sr'Jo,Csln and Pu239 from air filter ash.
The counting equipment is described briefly.
Primary estimate of tlre dose given to tlze lungs by the airborne radioactivity originatedby the nz~clearbomb tests
The report gives method and results of measurement of airborne radioactivity forTokyo from 1955 to 1957. Values are obtained for gross alpha and beta activity andradiochemically determined concentradons of strontium-90 and plutonium-239. A
method for computation of the dose to the lungs is described. The mean dose during
1955-1957 was of the order of magnitude of 10-2 rem/year.
Corrigendum to above report
A measure of future strontium-90 level from earth surface to human bone
Calculation of the future strontium-90 level is made on the basis of present data on
cumulative ground deposit and food contamination.
The cumulative ground deposit (mc/km2) is calculated assuming that:
1. The total amount of fission products from future tests is known.
2. 20 per cent of airborne strontium-90 falls to the earth's surface every year.
3. The distribution of fall-out is homogeneous.
The metabolism of strontium-90 through the food channel and food habit factor
related to calcium and strontium source are taken into consideration.
The future human skeletonal dose and maximum permissible level of ground deposit
are then calculated.
Sufiplemental review of tlte recent researches on tke allwiatio?~of radiation luzards
This is an addition t o G/R 63 and gives abstracts of new developments of radiobiology in Japan. Work on protection by amino acids, cysteamine and some newderivatives of this last compound is reported. Work on the therapeutic effect of aprotein diet and of adrenochrome preparation is also reported.
Corrigendum to above report
Experimental studies on the development of leukemia i n mice with frequent administrations of small doses of some radioactive isotopes (P2, S F , Gel")
The development of leulcemia is described in three strains of mice in which thedisease has not been observed under control conditions. Nine cases of leukemia havebeen observed among forty-six animals surviving tn-enty-one weeks and longer
following the first of repeated administrations of P32 a t three dose levels (0.1, 0.3, and
0.5 pc/gm). Latent periods varied with total dose administered. Larger doses weremore effective than small doses. The leukemia was primarily of the myeloid type.
Radiostrontium (Sr90) and radio-cerium (Cd") were much less and practicallyineffective in producing this disease in these animals. Sarcoma of bone was foundstrontium-treated animals. I t is concluded that leukemia is the result of severe damage

7

7

1
14

3

1

9

DOCUW

Country and Title

NumberApproximate
No. of pages.4/AC.82/G/R
JAPAN (continued)

to the haematopoietic tissues in the bone marrow and lymph nodes. There are many
tables and figures, including results of radiochemical analyses of various bones a tvarious intervals following injection.
Corrigendum to above report
Experinzental studies on radiation i ~ t j u r yby colloidal radioisotope-liver injury bycolloidal radioactive chromic phosphate CrP:2O4
Describes morphological observations on the liver of rats which mere injected intravenously with various concentrations of colloidal suspensions (particle size 0.1-1.0
micron) of radioactive chromium phosphate (CrPS204). Even wirh high doses (5.5
pc/gm) liver injury did not become manifest until twenty days after injection andcorrespondingly later with lower doses. Changes in the liver are described but notillustrated. They are greater in the liver than in other organs containing reticuloendothelial cells. The lesions are said to resemble those of virus hepatitis. Large dosesof chromium phosphate also produce lesions in the bone marrow with concomitantchanges in the peripheral blood.
Corrigendum to above report
Radiological data i n Japan II-Concentrations of Sr90, C s m , PuB9 and others i n various
nzaterials on earth's surface
Contains data on concentration of Sr90 in rainwater, soil, foodstuffs and human bonein Japan obtained by radiochemical analysis in some cases and by computation fromthe total beta activity in other cases. Besides Sr90, data on Csl37, Pu239, Zns, Fe55 andCdlu are also included.
Corrigendum to above report
Addendunt to above report
U ~ T E STATES.
DRadioactive fall-out
General survey of the fall-out problem, especially Sr90 distribution and uptake inthe human body.
The world-wide deposition of long-lived fission prodztcts from nuclear
UNITEDKINGDOAI.
test explosions
A network of six stations in the United Kingdom and thirteen in other parts of theworld has been set up for rainwater co!lection. Samples are analysed for S F , Srw,
Celn and Cel44, This report contains an account of the results obtained so far, andsome discussion of the present and future levels of SrQ0in United Kingdom soil.
NORWAY.
Radioactive fall-out u p to November 1957
A review is given of the monitoring in Norway of airborne activity and fall-out ofradipactive dust; also radioactive contamination in drinking water is reported.
SI~-EDEN.
Uptake of strontium and taesiunz by plants grm'tt in soils of diflerent textureand different calcium and potassiunt coliteltt
The radioactiue fall-out i n Sweden u p to 1.7.1957
Additional data to the report G/R.l5 for the period up to June 1957 are given. The
total beta activity, accumulated Srw and Csln amount and Srw content in soil aremeasured.
Gamma radialion from some Siiedish foodstufls
Significant increase of gamma radiation from milk, beef, cattle-bone and vegetables
was found during the period 1952-1956. No increase of gamma radiation from children
in the corresponding period could be observed.
Progress report on the metabolism of jission products i n ruminants
The excretion of radioactive fission products (Srw and 113') in milk after per oral
administration is measured.
A method for monthly collection of radioactive fall-out
Describes a collecting procedure using anion and cation exchange resins.
The computatio~zof infinite plane 30-year doses front radioactive fall-out
Proposes new method for evaluation of the esternal 30-year dose due to the deposition of gamma emitting isotopes, based upon a single beta measurement for eachsample and one CslS' ratio chemical determination in a pooled sample.
The control of irradiation of populations from natural and a r t i r n l sources
Describes an automatic system for continuous indication and recording of very low
radiation level. Suggests the use of such instrument for public control purposes.

Documenl
NumberCoun;ry and Titk

Approrim
No. oj Pages

152.

UXITEDKINGDO~I.
Tlte analysis of low level gamma-ray activity by scintillatio?~
speclrometry
The application of gamma-ray spectrometry enables measurement of the gammaactivity of 10-11curies or less.

153.

USITEDSTATES.The Chicago Sunshine method: Absolute assay of strontiztm-90 i n
biological materials, soils, waters and air filters
Contains a survey of Chicago sunshine research programme on the distribution ofstrontium-90 in the biosphere. Methods of sample treatment, counting and evaluationof data are reported. Detailed description of analytical chemical procedures is added.

154.

ARGENTIXA.
Normal calcium content of Sun Juan wines155.

BELGIUM.
Recent research on the chemical protectors and particularly on cysteaminecystamine. (Document in English)
Discusses the possible mechanisms of action of chemical radioprotectors particularlyof those above-mentioned.
Effect of X-rays on the growth of internodal cells of the alga Chara vulgaris L
A complicated doseeffect relationship is shown when non-dividing internodal cells
are irradiated and their growth tested (cf. document A/AC.82/G/R.122).

156.

157.

ARGENTINA.
Radioactive fall-out from the atmosphere in the Argentine Republic during
1957
Includes tables of results for first three-quarters of 1957. Total activity and strontium-90 content is measured.

158.

159.

Tlte action of various drugs on the suprarenal response of the rat to total body
BELGIUM.
X-irradiation. (Document i n English)
Describes strict difference in action of radioprotectors (cysteamine) or narcotic
drugs (morphine and barbiturate) in preventing adrenal changes of irradiated animals.
Nervous co?ttro2 of the reaction of anterior lzypophysis to X-irradiation as studied i ngrafted and newborn rats. (Document i n English.)
Indicates that the changes of suprarenals after irradiation are consequence of aneuro-humoral chain reaction. The reaction of adrenals seems to have negligible importance in the pathogenesis of radiation disease.

160.

USSR. Draft of Chapter F prepared by tlre delegation of the U S S R to the Scientific Com-

161.

162.

163.

mittee on the Effects of Atomic Radiation
A sensitive method for detecting the effect of radiation upon the human bodyJAPAN.
Discovers a new extremely sensitive biological indicator of the effect of ionizing
radiation. The acute dose of 50 mr and even less results in significant changes of thephosphene threshold of the eye. Approximately linear relationship between the effectand the logarithm of the dose from 1 mr to 50 mr is derived. Summation of the effectof repeated exposure is found.
UNESCO/FAO/WHO. UNESCO/FAO/WHO report on sea and ocean disposal ofradioactive wastes, including appendices A , B and C
Summarizes contributions made by different authorities.
Appendix A : R. Revelle and &I. B. Schaefer. General considerations concerning theocean as a receptacle for artificially radioactive materials.
Contains general account of the processes in the oceans and indicates the necessityof research on certain basic problems which would enable the prediction of the consequences of the disposal of large quantity of radioactive material to the sea.
Recommends measures of an international character in order to assure safe liquidation of atomic wastes.
Appendix B: Report prepared by FA0 and WHO. Discusscs the following questions:
1. The geochemical cycle of various elements between the water and the sediments.
2. The affinities of the various species of organisms in the oceans for different
elements which have radioactive isotopes.
3. The possible rate and distance of vertical and horizontal transport of radioactive
isotopes by marine organisms.
4. The distribution, abundance and rate of growth of the populations in the oceans.
Appendix C: Abstracts of eight other contributions to the report on sea and ocean
disposal of radioactive wastes.
USSR. Data on the radioutive strontium fall-out on the territory of the U S S R as to theend of 1955

Courrtry and Ti&

A/AC.82/G/R
164.

MEXICO.
Third report on the studies on radioactive fall-out
Presents fall-out data for thirteen stations in Mexico covering the period fromMarch to October 1957.
Computes approximate figures for infinite gamma dose and Sr90 precipitation.
Gives preliminary results of Sr90 and Csl37 content in milk.

FAO. General considerations regarding calcium availability i n the broad soil groups of
the world in relation to the uptake of radiostrontit~m

165.

Classiiies soil groups with low calcium level. Recommends the investigations of thefactors influencing Srw uptake by plants growing on such soils.
166.
.

167.

IS~IA.,Weasurements on the radiation fields in the Monazite areas of Kerala in India
Presents results of measurements in the monazite area with high thorium content.
As this area is one of the most densely populated areas in the world, the study of therelation between high level radiation background and eventual biological effect would
be of great value.
The average dose is 1500 mrad per year, exceeding three times the maximum permissible dose recommended by NCRP (USA).
UXITEDKINGDOM.Measureme?ats of Csl37 in human beings i n the United Kingdom
1956/1957~ e s k i b e sthe method of determining the Csln content in the human body using
gamma-ray spectrometry.
~ ~g potassium.
~
The average present value is 34.0 f 7 . 6 perJAPAN. An enumeration of future Sr90 concentration in foods and bone

Gives amendments and corrections to the report A/,'iC.82/G/R.137 based upon
new available data.
BRUIL. On the nature of long-range fall-out. (Document in English.)Describes one surprisingly high value of daily collected fall-out activity due to asingle big and highly active particle.
Corrigendum to above report
UXITEDKINGDOM.
The disposal of radioactive waste lo the sea during 1956 by the United
Kingdom Atomic Energy Authority
Summarizes the discharges of liquid radioactive wastes to the coastal sea fromWindscale Works during 1956.
The results of monitoring indicate that the average activity of the samples remains
well below the permissible level.
A summary of the biologital inoestigaiions of the discharges of aqueous radioactioe
waste to the sea from Windscale W m k s , Sellafield, Cztmberland
Summarizes the results of preliminary hydrographic and biological studies and of
regular monitoring of the marine environment in the period 1952-1956. About 2,500
curies of radioactive wastes monthly has been discharged during this period. Due tothe favourable local conditions, the upper limit for safe liquidation is determined tobe more than 45,000 curies per month.

The estimation of the amount of Sr" deposition and fhe external infinite gamma
dose in Japan due to man-made radioactivity
SWEDEN.Transfer of strontizrm-90 from nzother to foetus at various stages of gestationin miceShows that no significant fixation of SrQoby the foetus can be detected before thefifteenth day of gestation. The increase of radioactivity corresponds to the intensityof ossification processes.
The recovery phenomenon after irradiation i n Drosopltila melanogaster
I. Recovery or diferential sensitirdy to X-rays
Experimental results-lon-er rate of chromosome aberrations induced by X-ray jf
irradiated in anoxia in comparison with irradiation in air-support the hypothes~sof recovery.
The recovery phenomenon after irradiation i n Drosopkila melanogasterIndicates that both the spontaneous recovery and the differential sensitivity inspermatogenesis in Drosophila are responsible for the changes in the rate of chromosome breaks under different corlditions of irradiation.
The recovery phenomenon after irradiation in Drosophila melanogaster
Chromosomes breakage per se or their rejoining by recovery seems to have no
genetic consequences.
JAPAN.

Documeni
NumberCountry and Tille

SWEDEN (continued)
Reports on scientiJic observatio7zs and experiments relevant to the effects of ionizing
radiation zbpon ma?z and his environment already under way in Sweden
Report on experiments on the in3uence of selection pressure on irradiated populationsof Drosophila melanogaster
Attempts to determine the influence of high selection pressure in a population on
the spread of radiation-induced genetic changes. No results are as yet available.
Studies on the mutagenic efect of X-rays
Summarizes the results of the work on.radiation-induced chromosome breakage
under various conditions (I<. G. Liining).
Does there exist mzctational adaptation to chronic irradiation?
The results do not confirm the assumption that under the increased radiationbackground mutational adaptation occurs due to incorporation in the population of
mutational isoalleles with lower mutability.
Some results and previews of research in. Sweden relevant to human radiation genetus
Summarizes the present state of knowledge and recommends:
1. Large-scale international investigation of genetic consequences in females who
have been controlled by means of X-rays due to congenital dislocation of the hlp.
2. The study of genetic effects of radiation on human cell cultures.
Summary of papers of Lars Ehrenberg and co-workers with regards to the questionsof the U.N. Radiation Committee
Summary of papers of L. Ehrenberg and co-workers on genetic effects of radiation.
Studies on the eflects of irradiation on plant material carried out during recent years
at the Institute for Physiologic Botany of Uppsala University
Swedish mutation research i n plants
Dr. Gunnar Ostergren and co-workers
Study on experimentally induced chromosome fragmentation (G. Ostergren).
Investigations carried out by Dr. C. A . Larson (human genetics)
Some notes on skin doses and bone marrow doses in mass miniature radiograplzy
Investigations into the health and blood picture of Swedish women living i n lzouses
representing different levels of ionizing radiation
No difference was found either in general health-state or in blood picture among
thevarious groups of individuals (over 2,000women) living in different types of dwelling.
Other haemopoetic functions: Read-off metlwds i n radio-huematological control
Proposes a statistical method of evaluating total white-cells count as a control
test of radiation damage;

FR~NCE.
Atomic Energy Commission. Centre of Nzbclear Studies at Saclay, Gf-surYvette (Seine et Oise), France. Ilfeasurenzent of environ?nental activity: Methods andresirlts
Gives results of measurements of both natural and artificial radioactivity in theenvironment.
Corrigendum to above report
Biologual methods available for use in the quantitative detection of ionizing radiatwns
Surveys and evaluates the biological methods usable for the quantitative estimationof absorbed dose.
SWEDEN.Bone and radiostrontium
The local radiation dose to the bone tissue and to the bone marrow after adrninistration of bone-seeking isotopes is discussed. The figures are compared with the maximum
permissible body burden.
Radiation doses to the gonads of fitients in Swedish roentgen diagnostics. Summeryof studies on magnitude and variation o; the gonad doses together with dose reduczng
measures.
THE NETHERLANDS.
Report of the Committee of tlze Royal Netherlands Academy of
Sciences concerning the dangers which ntay arise jroln the dissemination of radioactive
products through nuclear test explosions
Report on the amount of radioactivity, its world-wide spreading and its biologicalrisk as a consequence of test explosions.
Radioactive fall-out measurements i n the Netherlands until December 31, 1957
Corrigendum to above report223

Docir ment

A pp~oximate
No. of pages

NumberCountry and Tiile

185.

NEW ZEALAND.
Report on some aspects of radiation protection work in New ZealandContains :1. Description of radiation protection measures in New Zealand.
2. Results of routine monitoring of radiation workers.
3. Preliminary results of statistical study on genetically significant gonad dosefrom X-ray diagnosis.

186.

FRANCE.Doses received by the genital organs of children during X-ray examinations
Suggests the improvement of the radiological techniques and certain protective
measures for decreasing the gonad dose from radiography.

187.

~IESICO.Summary of radioactive fall-out data recorded i n i k k o

188.
189.

BRAZIL.Su~?zntarptro?1tiunz-90
analysis i n dry milk and h u ~ n a nurine
On the cotnposition of long-range fall-out particles
A single fall-out particle of large dimensions and relatively high activity was foundby daily monitoring of fall-out. A detailed investigation of the nature and activity ofthis particle is presented.
On the uptake of M s T h I in naturally contaminated areas
Gives preliminary results of an investigation on the uptake of natural radioisotopes
by plants and animals in thorium-bearing area.

190.

191.
192.
193.

UNITED
A R ~ RREPUBLIC.
Radioactive fall-out i n Egypt: December 1956-February 1957
Radioactive fall-out i n Egypt: ~Varch-December1957
Sonze somatic changes obsmed in Culex ,%tolestus Forskal 1775
Shows differences in the uptake of P32in dependence upon the development stage
and sex. The explanation of sex-difference is discussed.

194.

FRANCE.
Gofzad doses i n radiodiagnosis
Summarizes the systematic study on the gonad dose due to diagnostic examination
by means of X-rays.

195.

ITALY. Data orr radioactive fall-out collected i n Italy (1956, 1957, 1958)

196.

USSR. Draft chapter on "Genetic Effects of Radiation" for the report to be transmitted by
the Scientifi Committee on the Effecis of Atomic Radiation to the General Assembly
i n 1958
Draft chapter on "Conclusions and Recommendations" for the report to be transmitted
by the Scientific Committee on the Effects of Atomic Radiation lo the General Assembly
i n 1958
Contanzination of the biosphere i n the vicinity of Leningrad by the products of nuclear
exp'losions
Contains the description of methods used for monitoring the fall-out deposition.
Results for the period 1953-1957 are given. Data on specific activity of water fromthe river Neva, the sea and the water supply system are also included. Accumulated
radioactivity on the ground and external dose from radioactive deposit are thencomputed. Special attention is given to the contamination of the biosphere by SrgO.
Data are based on Hunter and Ballou's calculation.
Study of the strontium-90 content of the atmosphere, soil, foodslufis and hunzan bones
i n the U S S R
The strontium-90 content of the air, soil, milk and cereals in various districts of the
USSR was determined by radiochemical analysis. Preliminary results on the Srw
content in bones from children in the hiloscow district give the average value of 2.3
S.U. in the second half of 1957. A few data on Cs137 concentration in the air are attached.
Uptake of radioactive strontium by plants and its accumulation i n various agricultural
crops
Detailed analysis of SrgO uptake by plants in relation to their biological characteristic (plant species, vegetative period) and the properties of the soil.
Both factors can influence to a large extent the incorporation of Sr90 during thebiological cycle.
Some results of a study of the bone system after injury by radioactive strontium
Revi$n.s the experimental results obtained in the studies on the effect of bone-seeking radloisotopes. The progressive pathological changes leading to the developmentof bone tumours are described. The disturbances in the osteogenetic processes during

197.
198.

199.

200.

201.

Document
NumberCminlry and Title

Approximate
No. of pages

USSR (coj~tinued)
the initial stages after contamination are marked pretumorous changes; their histological characteristic and their pathogenetic significance are discussed.
Blasto?nogenic efecfs of strontiz~m-90
Summarizes and evaluates the results so far published on the cancerogenic effect ofstrontium-90 in bone. In particular, the minimum and optimum tumour-producing
doses, the latent period and the distribution of strontium-90 are discussed. The
connexion between the blastomogenic effect and the development of leukemia isbriefly mentioned.
The radiation hazards of explosions of pure hydrogen and ordinary atomic bombs
Compares the hazards of the long-lived radioactive substances dispersed throughout
the world after the explosion of a fission and a pure fusion bomb. Radiation doses to
the gonads and bones are calculated and the number of persons affected (hereditarydiseases and leukemia) then computed. The conclusion is drawn that a pure fusionbomb cannot be regarded as less dangerous to mankind than a fission bomb.
Towards an assessntent of the hazard from radwactit~efall-out
An attempt to assess the various forms of hazard involved in the contamination of
the earth's surface with long-lived radioactive fission products. The particular importance of strontium-90 is stressed. Effects of small doses of radiation and theconcept of maximum permissible dose are discussed.
Nature of the initial e f a t of radiation on the hereditary structz~res
A survey of the present knowledge of the nature of the primary mechanisms throughwhich ionizing radiation damages the hereditary structures.
Radiation and human heredity
Emphasizes the importance of the basic scientific principles of radiation genetics
for the assessment of radiation-induced changes in human heredity. The natural
mutation rate for various hereditary abnormalities is compared with the observations
so far available on irradiated human population. The comparison of natural and induced mutagenesis both in experimental organisms and in men is the basis on which
the doubling dose for man was estimated as approximately 10 r. The lack of exact
knowledge and the urgent need for it is stressed.
The effect of radialion on the histological structure of monkey testes
Presents the results of histological analysis of monkey testes two years after cxposure to a dose of 150-450r. While the recovery process proceeds rapidly and is apparently complete in animals irradiated after the attainment of sexual maturity,
harmful disturbances have been found in young animals even avo years after exposure.
The cytogenetu efects of radiation exposure on spernultogenesis i n monkeys
Presents the results of cytological analysis of monkey testes two years after exposure to a dose of 150-450r. Ex~ensivedamage to the spermatogenesis was found.
The frequency of chromosome re-arrangements in mammals considerably exceedsthat in Drosophila after exposure to the same dose, being 65 per cent and 1.6 per centafter 500 r respectively.
B E L G I ~Radioactive~.
fall-out measured at the C E N during 1955-1956 and 1957
Describes methods and results of fall-out measurements in the period 1955-1957.
Average dose received by the personnel of CEN, dfOL,front 1954 to 1957
Summ,arizes the results of monitoring the professiorlal exposure in nuclear energy
education centre in Belgium. Film strip enables the differentiation of the proportionof the exposure between beta, gamma and neutron radiation. Only average doses ofthe personnel are given.

FUNCE. Study of the gonad dose during systematic X-ray exantinations (Preliminary
note dealing only with the irradiation of male gonads)
Measurement of the gonad dose resulting in males from systematic standardized
X-ray examination of the chest indicate that the exposure is very low. An average of
9 mrem for a period of 30 years is computed. The dose to the lungs is discussed withrelation to the increase in frequency of lung cancer.
Determination of the absorbed dose/exposz~redose ratio i n bone and niziscle by theequivalent-gases ,method. Principle of the metltod and preliminary results
Describes the method for determination of the dose absorbed in various tissues
using ionization chambers filled with gas mixtures of equivalent density.

Document

Counfry and Tit&

Number

A fipIoximate
No. of pages

A/AC.82/G/R

FRANCE(continued)
213.

Recovery folZuwing the uctwn of ionizing radiation
The authors first discuss the problem of recovery which they consider hypothetically.
They attempt to show that it is a phenomenon which, although appearing very
complex a t first glance, can be simplified by relating the recovery to a definite effect.
They contribute a series of experiments showing that recovery is a very general
phenomenon, common t o all living things, and related t o the metabolic activity ofliving matter.
They report a new method of experimental analysis which greatly facilitatesinterpretation of the results. They believe that the study of recovery should be developed on a much larger scale.

26

Appendix

LIST O F SCIENTIFIC EXPERTS
The scientific experts who have taken part in the preparation of the report while attending Committee sessions
as members of national delegations are listed below. The Committee must also express its appreciation to the many
individual scientists not directly connected with national delegations whose voluntary co-operation and good willcontributed in no small measure to the preparation of the report.
ARGENTINA:
Dr. C. Nuiiez (Representative)
Dr. D. J . Beninson
Professor E. Favret
Dr. N. Nussis
Dr. J. A. Olarte
AUSTRALIA:
Dr. C. F. Eddy (Representative-first
Mr. D. J . Stevens (Representative)
Dr. A. R W. Wilson

Dr. A. Halawani (Representative)
Dr. H. T. Daw

session)BELGIUM:
Professor Z. Bacq (Representative)
Mr. R. Boulenger
Dr. M. Errera
Professor F. Twisselman
BRAZIL:
Professor C. Chagas (Repesetrtative)
Dr. B. Gross
Professor N. Libanio
Professor C. Pavan
Father F. X. Roser, S.J.
CANADA:
Dr. E. A, Watkinson (Representative)
Dr. R. K . Appleyard
Dr. P. M. Bird
Dr. W. E. Gnunmitt
Dr. Colin Hunter
Dr. G. H. Josie
Dr. C. A. Mawson
Dr. H. B. Newcombe
Dr. F. D. Sowby
CZECHOSLOVAKIA:
Professor F. Hertik (Representative)
Professor F. BEhounek
Dr. M. HaSek
Dr. L. Novik
Professor V. Sobek
Dr. I. Ulehla
Dr. V. Zelenf

Professor L. Bugnard (Representative)
Dr. A. Allisy
Dr. J. Coursaget
Dr. H. Jammet
Dr. J. Labeyrie
Dr. J. Lejeune

INDIA:
Dr. V. R. Khanolkar (Representative)
Dr. A. R. Gopal-Ayengar
Dr. A. S. Rao
JAPAN :

Dr. M. Tsuzuki (Representative)
Dr. Y. Hiyama
Dr. D. Moriwaki
Dr. K. Murati
Dr. M. Nakaidzumi
Mr. S. Ohta
Dr. N. Saito
Dr. E. Tajima
MEXICO:
Dr. M. Martinez Baez (Representative)
Dr. F. A. Andrade
Dr. H. Zalce

Professor R. M. Sievert (Representative)
Dr. B. A. A. Aler
Dr. R. G. Bjarnerstedt
Professor G. Bonnier
Professor T. 0. Caspersson
Professor C. A. T. Gustafsson
Dr. A. G. A. Nelson* Now in the United Arab Republic.

UNIONOF SOVIETSOCIALISTREPUBLICS:
Professor A. V. Lebedinsky (Representative)
Professor K. K. Aglintsev
Professor B. M. Isaev
Professor P. M. Kireev
Professor A. N. KraevsLy
Professor A. bZ. Kuzin

UNITEDKXNGDOM
OF GREATBRITAINAND
NORTHERNIRELAND
Professor W. V. Mayneord (Represetltativefirst session)
Dr. E. E. Pochin (Represelztative)
Dr. T. C . Carter
Mr. A. C. Chamberlain
Dr. W. G. Marley
Mr. N. G. Stewart

Dr. Shields Warren (Represe~rtative)
Professor G. W. Beadle
Dr. A. M. Brues
Professor J. Crow
Professor Th. Dobzhansky
Dr. C. L. Dunham
Mr. Merril Eisenbud
Professor Sterling Emerson
Professor G. Failla
Dr. J. H. Harley
Dr. J. S. Laughlin
Professor J. V. Nee1
Dr. M. Zelle