EURADOS AM2021 (Virtual, 3 February 2021)

Possible effects of space radiation
exposure on the reproductive
system and fetal developmentin 25 minHiroshi Yasuda
保田 浩志

Research Institute for Radiation Biology and Medicine
広島大学原爆放射線医科学研究所

Contents
1. Possible space radiation exposure
and its biological effects in futureinterplanetary missions
2. Relative biological effectiveness(RBE) of high-LET particles withregard to reproductive potentials

Possible space radiation exposure
and its biological effects in futureinterplanetary missions

3Deep space exploration (DSE)
深宇宙ミッション

https://www.inverse.com/article/33217-mars-moon-phobos-baseMission to the moon
月へのミッション

https://www.nasa.gov/specials/apollo50th/back.html

Mars mission ‐ it’s long..
火星ミッション―これは長い..

ReturnSun

EarthOutboundMars

Fig. A typical route of Mars Mission planned by NASA.

Concern about space radiation exposure
宇宙放射線被ばくへの懸念

The space is full of energetic nuclei.
https://www.nasa.gov/image-feature/htv-6-captured-with-the-canadarm2

Radiation environment in space
宇宙放射線環境

Galactic cosmic raysGalaxy

Trappedparticles

SunEarthSolar wind
Magnetosphere

Usually, cosmic radiations in theEarth’s atmosphere are attributable
to the galactic cosmic rays (GCR).

Galactic cosmic rays

Radiation exposure in aviation
航空機高度での被ばく
Altitude[km]Interface of theStratosphere

StratosphereOzon layer

Atmosphericpressure

π πNInterface of thetroposphere

P

Cumulonimbus

γμPe

Troposphereπνμ

背景：新星出版社「飛行機のしくみ」

πNN

νSpace radiation exposure in LEO missions
低軌道宇宙飛行における宇宙放射線被ばく

Table. Assessed bone marrow dose rates (at 5 cm depth) received by
the astronauts who were involved in the NASA space programs
performed in the 20th century.

Program

Inclination[ °]Altitude[km]

Absorbed doserate[mGy d-1]

Dose equivalentrate[mSv d-1]

Mercury
GeminiApolloSkylabShuttleShuttleShuttleShuttleShuttle-MirISS

50
28.5
28.5
>50>50
51.6
51.6

430
<400>400<400>400~390
330~440

0.3
0.49
0.43
0.71
0.1
1.2
0.2
0.44
0.37
0.19

0.55
0.87
1.2
1.4
0.18
2.1
0.45
1.1
0.84
0.48

Courtesy of Dr. Francis Cucinotta (NASA-JSC)

Solar particle event (SPE)
太陽粒子現象 (SPE)Energetic particles (mainly protons)
are generated by a huge explosion(flare) on the Sun’s surface.

Predicted dose from SPE
SPEによる予測線量
100
Dose [GyEq]

1010.1
0.01
0.001
Aluminum thickness [g/cm2]
Fig. Predicted doses of selected organs as functions of the thicknessof aluminum shielding for the hypothetical largest SPE (comparableto the Carrington event) with RBE=1.5 [Townsend et al., 2006].

Organ dose limits for LEO astronauts (NASA)
低軌道宇宙飛行士のための組織線量限度 (NASA)

Table. Recommended RBE-weighted dose limits regarding thedeterministic effects for LEO astronauts [NCRP, 2000].

PeriodRBE-weighted dose limit [GyEq]
Bone marrow

Lens of the eye

SkinCareer-4.0

6.0

1 year

0.50

2.0

3.0

30 days

0.25

1.0

1.5

* These limits are applied to all ages. The career effective-dose limits forstochastic effects are given separately.

Effects of space radiation exposures on the reproductive
potentials of astronauts have not yet been considered...

Can they keep their reproductive potentials?
宇宙飛行士は生殖能を維持できるか？
Will you stayin my life?

Yes!
It’s under way
already…

Figure. Possible situation in a future interplanetary mission.

Threshold doses on reproductive organs
生殖器に関するしきい線量Table. Threshold dose estimates of the acute absorbed doses for 1%
incidences of morbidity for testes and ovaries after whole-body
γ-ray exposures [ICRP, 2007].
Organ/Tissue
TestesOvaries

EffectThreshold doseTime to develop

Temporary sterility〜0.1 Gy

3〜9 weeks

Permanent sterility〜6 Gy〜3 weeks

Permanent sterility〜3 Gy〜1 week

Threshold doses on human embryo & fetus
胚及び胎児に関するしきい線量
Table. Threshold dose estimates of the acute absorbed doses of lowLET particles for the deterministic effects other than cancer inthe human embryo and fetus [NCRP, 2013].
Post-conception
periodEffectThreshold dose

1 to 2 weeks

Embryo lethality

0.15〜0.2 Gy

3 to 5 weeks

Embryo lethality

0.25〜0.5 Gy

Fetus lethality>1 Gy

6 to 13 weeks

8 to 25 weeks>14 week

Permanent growth
retardation in the adult0.25〜6 Gy

Mental retardation anddecrease in IQ scores>0.5 Gy

Fetus lethality>1.5 Gy

Gross anatomic
malformation>0.5 Gy

Predicted dose from SPE – is this correct?
SPEによる予測線量 – これは正しい？
100Dose [GyEq]

1010.10.010.001

Is this RBE value
appropriate for thereproductive systemor embryonic/fetaldevelopment?
Aluminum thickness [g/cm2]

Fig. Predicted doses of selected organs functions of the thicknessof aluminum shielding for the largest-scale SPE (a hypotheticalCarrington event) with RBE=1.5 [Townsend et al., 2006].

Relative biological effectiveness(RBE) of high‐LET particles withregard to reproductive potential

18Difference of energy deposition patterns
エネルギ―付与のパターンに観られる違い

Fig. Illustration showing the difference of energy depositions to tissue cells
from photon (left), neutron (center) and heave ion (right).
Courtesy of NCRP

Linear energy transfer (LET)
線エネルギー付与 (LET) とは

The energy transferred from a radiation to thematerial per unit length of the track.
粒子飛跡の単位長さ（通常はµm）当たりに物質に付与されるエネルギー．
Low‐LET Medium‐
particle LET particle

High‐LET
particle

Courtesy of NCRP

Definition of RBE
RBEの定義The relative biological effectiveness (RBE) is definedas the ratio of the dose of a radiation in respect to thatof a reference radiation (usually γ/X-rays) required bythose radiations to cause the same level of biologicaleffect.
生物学的効果比 (RBE) は、対象とする放射線が、基準となる放射線 (通常γ/Ｘ線)に比べ、同じ生物効果を生じるのに要する線量の比として定義される．
//(1)[GyEq] (2)Relationship between LET and RBE
LETとRBEの関係

5RBE

432
1
00.1

110100

LET [keV/µm]
Fig. A typical LET dependency of RBE.

1000

RBE .vs. Severity
RBE .vs. 重篤度
Low-LET
particle withlow doserate

Severity

High-LET
particle

RBEHL = DLL/DHLDHLDLL

Dose [Gy]Fig. Relationship between dose and severity of a deterministic effect.
RBE is calculated as the ratio of the high-LET particle dose (DHL) tothe low-LET particle dose (DLL) at the same level of severity.

RBE .vs. Severity
RBE .vs. 重篤度
Low-LETparticle withhigh doserateSeverity

High-LETparticle

RBEHL = DLL/DHL
DHL

DLL

Dose [Gy]Fig. Relationship between dose and severity of a deterministic effect.
RBE is calculated as the ratio of the high-LET particle dose (DHL) tothe low-LET particle dose (DLL) at the same level of severity.

RBE .vs. Severity
RBE .vs. 重篤度
Low-LETparticle withhigh doserate

Severity

High-LET
particle

RBEHL = DLL/DHLDHLDLL

Dose [Gy]Fig. Relationship between dose and severity of a deterministic effect.
RBE is calculated as the ratio of the high-LET particle dose (DHL) to
the low-LET particle dose (DLL) at the same level of severity.

Variability of the RBE value
RBE値の変動性

Even for the same combination of two radiations,
the RBE value could considerably change due tothe following conditions:• Tissue/Organ• Biological endpoint• Ionization density• Dose rate
同じ線質の組み合わせでも、以下の条件が違うとRBE値は大きく変わり得る：• 対象組織／臓器• 着目する症状• 電離密度• 線量率、等Male reproductive organ – Testis –男性の生殖器 ―精巣―

Table. The RBE values of neutrons and selected heavy ions forspermatogorium killing in mice [Wang and Yasuda, 2020].

Energy orsource

RBE value

Heliumfrom 210Po

6.7

Rao et al. (1991)

Carbon400-670 MeV/u<3Alpen et al. (1981)

Oxygen400-670 MeV/u<3Alpen et al. (1981)

Neon

400-670 MeV/u<3Alpen et al. (1981)

Argon

400-670 MeV/u<3Alpen et al. (1981)

Neutron

1 MeV

5.7Gasinska et al. (1985)

Neutron

5.5 MeV

4.6

Gasinska (1985)

Particle

Courtesy of Dr. Bing Wang (QST)

ReferenceFemale reproductive organ – Ovary –女性の生殖器 ―卵巣―Table. The RBE values of neutrons and selected heavy ionsfor oocyte killing in mice [Wang and Yasuda, 2020].

Energy orsourceRBE value

Carbon80 MeV/u

1.3－1.5

Zhang et al. (2006)

Neon

450 MeV/u0.4－0.6

ICRP (1989)

Silicon

670 MeV/u

0.4－3.0

ICRP (1989)

Argon

570 MeV/u

0.4－2.2

ICRP (1989)

Neutron0.43 MeV

1.7

Straume et al. (1987)

Neutronfrom 252Cf

1.6 – 3.5

Satow et al. (1989)

Particle

Courtesy of Dr. Bing Wang (QST)

ReferenceEmbryonic/fetal development (HCPs)
胚又は胎児への影響 (HCPs)

Table. The RBE values of protons and selected heavy ionsfor embryonic/fetal development [Wang and Yasuda,2020].

Particle

EnergyBiological
endpoint

RBE value

Reference

Proton150 MeV

Embryo killinga

1.1-1.2

Szabó et al. (2018)

Helium

530 MeV

Fetal lethalityb

1.0-1.4

Ward et al. (1976)

Carbon290 MeV/uImpairmentc

1.0-2.0

Wang et al. (2005;2007; 2008)

Neon

400 MeV/uImpairmentc

1.0-2.1

Wang et al. (2005;2007; 2008)

Iron

500 MeV/u

Apoptosisd

3.7-4.2

Yasuda et al. (2011)a) Embryo killing in zebrafish; b) Fetal lethality in mice; c) Impairment of prenatal
neurophysiological accomplishment in rats; d) Induction of apoptosis in thedeveloping optic tectum in medaka fish.
Courtesy of Dr. Bing Wang (QST)Embryonic/fetal development (neutrons)
胚又は胎児への影響 (neutrons)

Table. The RBE values of neutrons for embryonic/fetal
development [Wang and Yasuda, 2020].

Particle

Energy orsource

BiologicalendpointRBE value

Reference

Neutronfrom 252Cf

Malformationa

2.3-3.1

Satow e tal. (1989)

Neutron

6.0 MeV

Chromosomalanomaliesb

4.7-7.4

Weissenborn &Streffer (1988)

Neutron

7.0 MeV

Micronucleusc

2.5-3.5

Pampfer et al.
(1992)

Neutron10 MeV

Apoptosisd

9.8

Ishida et al. (2006)

48

Kuhne et al. (2009)

Neutron~800 MeV/u Embryo killingea) Malformation in mice; b) Chromosomal anomalies at 1st to 3rd mitosis in onecell embryo in mice; c) Micronucleus induction in pre-implantation embryos inmice; d) Induction of apoptosis in fetal cerebral cortex in mice; and e) Embryo
killing in medaka fish.
Courtesy of Dr. Bing Wang (QST)

Lifestyle on the moon or Mars
月や火星での生活様式

Fig. Illustration of a possible lunar base in near future.

Lifestyle on the moon or Mars
月や火星での生活様式

π πnπnγppe

νμe

ν

πnnμν

Fig. Illustration of a possible lunar base in near future.

Summaryまとめ The deterministic effects of space radiation
exposure on the reproductive potentials of
astronauts need to be carefully considered inplanning of future interplanetary missions.
 It should be recognized that the RBE values ofhigh-LET particles in space could largely change
depending on particle energies and dose rates
as well as biological endpoints.
 More studies are desirable for selecting the mostappropriate RBE values in correspondence topossible exposure situations during the mission.

EURADOS AM2021 Winter School (Virtual, 3 Feburary 2021)“Possible effects of space radiation exposure on the reproductive system and fetal development”
Hiroshi YASUDA (Hiroshima Univ.)

Thank you for your attention.

Hiroshi YASUDA, Prof.
保田 浩志
Department of Radiation Biophysics,
Hiroshima University
Email: hyasuda@hiroshima-u.ac.jp