1 low-dose radiation and risk: a perspective philippe duport centre for low-dose radiation research...

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Low-Dose Radiation and Risk:

A Perspective

Philippe Duport

Centre for Low-Dose Radiation Research

Institute of the Environment

University of Ottawa

Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)

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Centre for Low-Dose ResearchInstitute of the Environment

University of OttawaFunding : US-DOE, Électricité de France, Central Research Institute of Electric

Power Industry, MDS-Nordion, CNS, CANDU

• Started in 1997

• Main objective: to assemble and analyze, globally, all published data on low dose radiation carcinogenesis in lab mammals

• Database of > 150 000 animalshttp://www.ie.uottawa.ca


http://www.ie.uottawa.ca/

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• What is ionizing radiation?• Radiation in the environment and in our body

• Low-dose radiation and cancer: Is there a risk?• If yes, how big is it?

– Animal experiments– Human data

• Natural radiation levels and cancer• Radiation workers• Medical irradiation and cancer

• The “ Healthy Worker Effect “

• Conclusions


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5


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Units – Activity

– Historical : • Curie (Ci) = 37 000 000 000 disintegrations per

second

– Modern: • Becquerel (Bq) = 1 disintegration per second


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Units - Dose• Complex system (absorbed, equivalent, effective dose)• Historical : Rem (Roentgen equivalent man)

• Modern : Sievert

Scale of effects (acute exposure)

Less than 0.200 Sv ?????

0.2 – 0.5 Sv (penetrating radiation)

0.2 – 10 Sv (alpha radiation)

No effect, increased or reduced cancer risk, depending on exposure conditions and individual susceptibility

0.50 Sv Blood count changes

1.00 Sv Vomiting (threshold)

1.50 Sv Death (threshold)


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Cosmic radiationExposure at Different Elevations

0

20

40

60

80

100

120

140

Sea Level DeathValley

Richland Denver Ledville (~3000 m)

mre

m /

year

1 mrem/year = 200 feet of altitude

4 mrem/year = 800 feet

500 mrem/year = some isolated populations

(10 mrems = 0.1 mSv)


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Natural Radioactivity in your body (disintegrations per second)

Nuclide Bq (alpha) Bq (penetrating radiation)

Uranium 1.1

Thorium 0.11

Potassium 40 4400

Radium 1.1

Carbon 14 15000

Tritium 23

Polonium 37

approx. 40 des/sec approx. 19 000 des/sec

Annual dose from internal radiation : 0.2 mSv = constant


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Natural Radioactivity in Food

Food40K 226Ra

Bq/kg Bq/kg

Banana 130 0.04

Brazil Nuts 210 27 - 260

Carrot 130 0.02 - 0.07

White Potatoes 130 0.04 - 0.1

Beer 15

Red Meat 111 0.02

Lima Bean 170 0.07 - 0.20

Drinking water 0 - 0.006


12Country averages : extreme cases not shown (e.g. Kerala (India), Ramsar (Iran)


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Unsuspected sources of radiation:

• Uranium, thorium in coal, released from U.S. coal-fired plants in 1982

– 800 tons of Uranium– 1970 tons of Thorium

• Radon decay products (mostly Po-210) accumulated on the ground, from Rn released from soil

– 40 tons equivalent-Pu-239 per year on the ground of the territory of Ontario


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Unsuspected sources of radiation:

• 10 000 Bq/m3 of Po-210 and PB-210 in

“ clean mountain water ” from Mont Blanc (Alps)

~ 20 mSv per 1000 litres consumed (adults)

~ 35 mSv per 1000 litres consumed (chidren)


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Annual dose limit for radiation workers

Annual dose limit for the public

Natural background radiationRadiation levels (average annual doses) from natural and man-made sources (adapted from Jaworowski Z, Radiation Risks and Ethics, Physics Today, Sept. 1999 – Graph expended by Rockwell T. from UNSCEAR figures)

Action levels (Public)

EvacuationIn case of incident


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Background Cancer

Over 30 % of us will develop cancer

About 25 % will die of cancer

Cancer risk is variable as a function of • Genetic Background• Environmental Exposures• Diet - Lifestyle


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Figure 1

Radiation effect on DNA


http://cnts.wpi.edu/RSH/Figures/Docs/MP98_Fig1.gif

http://cnts.wpi.edu/RSH/Figures/Docs/MP98_Fig1.gif

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Number of Events Occurring Daily in Each Cell of the Body:

Metabolism Radiation (1 mSv/yr)

Free radicals created near DNA

100,000,000

DNA alterations 1,000,000 (1 in 100) 0.005

Un/misrepaired alterations

100 (1 in 10,000) 0.000,01 (1 in 500 )

Mutations: Persistent un/misrepaired

1 (1 in 100) 0.000,000,1 (1 in 100)

Ratio of mutations, radiation to metabolism:

1 to 10,000,000


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Possible outcomes of a cellular radiation exposure in a normal cell (From R. Mitchel, AECL)


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Radiation-induced resistance

TreatmentAverage

Lifespan (Days)Life

Lost (Days)

Control 727 0

1 Gy 486 241

0.1 Gy, 24h, 1.0 Gy 578 149

Extension of latency period in mice developing acute myeloid leukemia(R. Mitchel, AECL, IRPA 10, 2000)


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Is the risk proportional to dose ??

(Linear or not ??)


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Possible dose-effect relationships

-4.00

-2.00

0.00

2.00

4.00

6.00

8.00

10.00

0 1 2 3 4

Dose (arbitrary units)Ris

k (

arb

itra

ry u

nit

s)

Threshold


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Relative risk of solid tumors in male BC3F1 mice after whole body irradiation with fission neutrons.Covelli, Rad. Res. 119:553-561, 1989.

0.0

1.0

2.0

3.0

0 0.5 1 1.5 2 2.5

Dose (Gy)

Re

lati

ve

Ris

k

200 mGy


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Relative Risk of all solid tumors in male BC3F1 mice following exposure to 5 daily doses of fission neutrons.Di Majo, Rad. Res. 138:252-259, 1994.

0.5

1.0

1.5

2.0

0.0 0.2 0.4 0.6 0.8

Dose (Gy)

Re

lati

ve

Ris

k


25

0.86

0.88

0.9

0.92

0.94

0.96

0.98

1

1.02

1.04

1.06

0.00 0.10 0.20 0.30 0.40 0.50 0.60

Dose (Gy)

Rel

ativ

e ri

sk

-11 sd

-9 sd

Figure 2. Relative risk for all cancers in mice exposed to gamma radiation (reticular tissue and solid cancers) (Ref: Ullrich & Storer, Radiat. Res. 80(2):303-342, 1979)

Probability that protective effect does not exist in that experiment: less than 1 in 1 millions million


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Bone sarcoma in C57Bl/Do albino female mice following injection of Ra-226 (Taylor et al. Radiat. Res. 95:584-601 (1983)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 2 4 6 8Dose (Gy)

Inc

ide

nc

e

Mean survival time (days)626727752766

600

650

700

750

800

1 2 3 4

Dose level

Age

at d

eath


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Survival time in mice exposed to very low dose rates of gamma radiation (Courtade et al., WONUC 1999)

0

50

100

150

200

250

300

350

0 61 129 224 320 445 609 629 673 803 932 1027 1095

Survival time (days)

Nu

mb

er o

f m

ice

Controls

7 cGy/y

14 cGy/y

Average background level in Toulouse (external radiation only): 0.2 cGy/y


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Human data


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Standardized mortality rate from breast cancer in TB patients after fluoroscopy (other than Nova Scotia), Miller et al., the New England Journal of Medicine, 321(19):1285-1289, 1989)

0

100

200

300

400

500

600

700

800

0 0.1 0.2 0.3 0.4 0.5 0.6

Dose (Gy)Lu

ng

can

cer

inci

den

ce p

er 1

06

per

s.ye

ars

Prob. that cancer incid. is the same at 1st & 2nd dose levels : less than 1 in 1000 millions


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LOW-DOSE LINEARITY: THE RULE OR THE EXCEPTION?Figure 6. The Canadian Tuberculosis Fluoroscopy Study of Miller et. al. A graphic plot by E.W. Webster of the study data showing the authors' "best fit" linear model and linear-quadratic model relationships. (Martha Heitzmann1 and Richard Wilson, BELLE Newsletter Vol 6, No. 1, March 1997) – Graph shown by E.W. Webster at Lauriston Taylor lecture, NCRP 121, 1995

Howe 1996 paper

Miller 1989 paper


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Cancer incidence and mortality after treatment of hyperthyroidism(Franklin et al. The Lancet 353: 2111-2115, 1999)

SIR (95% C.I.) SMR (95% C.I.)

All sites 0.83 (0.77 – 0.90) 0.90 (0.82 - .098)


32Bone sarcoma in Radium dial painters (Linear scale)

How to modify the perception of radiation risk


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Bone dose

Bone sarcoma in Radium dial painters (Log scale)


34Bone sarcoma in Radium dial painters

Linear scale Log scale


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Probable thresholds for alpha emitters :

• Osteosarcoma– In dial painters – D ~ 8 Gy (160 Sv)– In Pu-exposed Mayak workers - D ~ 2 Gy ++

• Liver cancer– in Thorotrast patients - D ~ 2 Gy (40 Sv)– in Pu-exposed Mayak workers


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British radiologists (Controls : all male medical practitioners)

Year of registration

1897 - 1920 1921 - 1935 1936 - 1954 1955 - 1979

Cause of death Obs Exp SMR Obs Exp SMR Obs Exp SMR Obs Exp SMR

All non-cancer 230 266 0.86 219 255 0.86 278 291 0.96 77 121 0.64

All cancers 60 34 1.76 51 41 1.24 85 76 1.12 32 45 0.71

All causes 290 300 0.97 271 296 0.92 368 367 1.00 113 166 0.68

SMR : Standardized Mortality Ratio = no. observed / no. expected


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Canadian National Dose registry StudyAshmore et al. Am. J. Epid. 148(6): 564-574 (1998)

Sont et al. Am. J. Epid. 148(6): 564-574 (2001)

SIR (95% C.I.) SMR (95% C.I.)

Females Males Females Males

Cancer incidence (all cancers)

0.88

(0.85 – 0.92)

0.74

(0.71 – 0.76)

Mortality

(all causes)

0.618

(0.59 – 0.65)

0.586

(0.57 – 0.60)

All cancers

0.715

(0.66 – 0.77)

0.65

(0.53 – 0.80)


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Relative risk o flung cancer in French Uranium miners

0

2

4

6

8

10

12

14

0 100 200 300 400 500 600 700

Exposure (WLM)

Rel

ativ

e ri

sk Threshold ?


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40


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Cancer incidence mapRadon map USABlue : low riskYellow : Moderate riskPink : High risk


http://www.usc.state.ut.us/Home/radon/natlmap.html

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Lung cancer incidence in Schneeberg (Germany)

012345678

<50 >50-<250 >250-<500

>500-<1000

>1000->1500

>1500

Indoor radon concentration (Bq/m3)

Od

ds r

ati

oraw

stratified

Action level (Bq)m3) :

Canada USA Europe Switzerland

800 150 400 800


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Medical uses of low-dose radiation

• Treatment of rheumatisms and asthma in radon spas (covered by national medical insurance in Germany and Austria)

• Clinical tests show that low-dose total or half-body irradiation – at doses well below cell killing - contribute to curing cancer and preventing metastases (Japan, France)


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Conclusions - 1

• Ionizing radiation is part of life.

• Sources of ionizing radiation are naturally everywhere, in food, air, water and our body.

• Life appeared and evolved in a radioactive environment.

• At environmental levels, there is no evidence of increased risk with increased dose, even when annual doses exceed current dose limits for radiation workers


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Conclusions - 2

• In fact, there are indications of decreased risk of cancer and non-malignant diseases at doses and dose rates well above current regulatory limits for the public and the workers.

• Populations in high background areas tend to have less cancers than those in low background areas.

• Low dose radiation is used in medicine: radon spas, cancer treatment and prevention.


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Question

• Are we doing more good than harm when radiation exposures are reduced to levels “as low as reasonably achievable” ?

or

• Is there any public health benefit at all in reducing radiation doses “as much as possible”?


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Position of the French Academy of Medicine (Nov. 2001)

Conclusion # 3: denounces the utilization of the linear no-threshold (LNT) relation to estimate the effect of doses lower than a few mSv (equivalent to variations of natural radiation in France) …

Conclusion # 5: recommends the introduction of the ADIR (Annual Dose of Incorporated Radioactivity (~ 0.2 mSv) resulting from homogeneous exposure of the human body to natural potassium-40 and carbon-14), as this dose equivalent is almost constant whatever the size of the individual and the geographic region.


49http://www.epa.gov/iaq/radon/images/zonemap2.jpg

1 low-dose radiation and risk: a perspective philippe duport centre for low-dose radiation research...

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