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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Units – Activity
– Historical : • Curie (Ci) = 37 000 000 000 disintegrations per
second
– Modern: • Becquerel (Bq) = 1 disintegration per second
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Figure 1
Radiation effect on DNA
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Possible outcomes of a cellular radiation exposure in a normal cell (From R. Mitchel, AECL)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Is the risk proportional to dose ??
(Linear or not ??)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Human data
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
32Bone sarcoma in Radium dial painters (Linear scale)
How to modify the perception of radiation risk
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Bone dose
Bone sarcoma in Radium dial painters (Log scale)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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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Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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Cancer incidence mapRadon map USABlue : low riskYellow : Moderate riskPink : High risk
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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)
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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.
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
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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.
Ottawa U – I. E. - International Centre for Low-Dose Radiation Research (Jan 2002)
49http://www.epa.gov/iaq/radon/images/zonemap2.jpg