1. Health effects of radiation exposure Tilman A Ruff Nossal Institute for Global Health, University of Melbourne Advisor: Australian Red Cross, AusAID/UNICEF Consultant: GSK Biologicals, Novartis Vaccines Medical Association for Prevention of War International Campaign to Abolish Nuclear Weapons Hunter’s Hill Inquiry, Sydney 4 July 2008

2. Overview Overview of radiation Overview of radiation Sources of environmental radiation Sources of environmental radiation Health effects of radiation Health effects of radiation

3. A Quiz… 1. One chest x-ray increases your risk of cancer T or F? 2. One CT scan increases your risk of cancer T or F? 3. The radiation dose of one CT scan of the abdomen & pelvis is how many times that of a chest x-ray dose? A. 250

4. Radiation Basics Radiation – Energy in transit: –electromagnetic waves (gamma-γ or x-ray), or –high speed particles ( alpha-α, beta-β, neutron-η, etc.) Ionizing Radiation – Radiation with sufficient energy to remove electrons during interaction with an atom, causing it to become charged or ionized –Can be produced by spontaneous radioactive decay or by accelerating charged particles across an electric potential (eg x-rays)

5. Ionising radiation

6. Introduction What is ‘radiation’? What is ‘radiation’? –Electromagnetic energy –Spectrum

7. Ionizing vs Non-ionizing Ionizing radiation has high energy and displaces electrons from their orbits creating charged atoms (ions)/molecules Ionizing radiation has high energy and displaces electrons from their orbits creating charged atoms (ions)/molecules –Creates DNA damage –Outright cell death –Bystander effect –Genomic instability Non-ionizing radiation creates heat due to low energy eg infrared, MRI Non-ionizing radiation creates heat due to low energy eg infrared, MRI

8. Radiation types

9. DNA injury … somatic and germ- line effects

10. Radioactivity Basics Radioactivity – The spontaneous nuclear transformation of an unstable atom that often results in the release of radiation, also referred to as disintegration or decay Units Curie (Ci) the activity in one standard gram of Radium = 3.7 x 10 10 disintegrations per second (S.I.)Becquerel (Bq) 1 disintegration per second – International Units (SI)

11. Sources of radiation Natural - earth/rocks, sunlight, lightning, heartbeats, CNS, space Natural - earth/rocks, sunlight, lightning, heartbeats, CNS, space Artificial - Artificial -

12. Ionizing Radiation Sources Average global dose: 2.4 mSv Average global dose: 2.4 mSv

13. Ionizing Radiation Sources

14. Evironmental Radiation Sources Occupational – pilots and flight crews, uranium miners, medical imaging workers Occupational – pilots and flight crews, uranium miners, medical imaging workers –Limit = 20 mSv/annum (cf 1mSv general public) Background (81%) – radon, cosmic, solar, terrestrial (K, U, thorium) Background (81%) – radon, cosmic, solar, terrestrial (K, U, thorium) –Australia 2.4mSv, USA 3.6mSv, Ramsar (Iran) 260mSv Human-made (19%) – mainly (79%) diagnostic & therapeutic (CT scans 50-65%) Human-made (19%) – mainly (79%) diagnostic & therapeutic (CT scans 50-65%)

15. Multiple exposure pathways External - often gamma External - often gamma Most easily measured Most easily measured –Direct contact – skin Internal Internal –Inhale – gas, dust, aerosol –Ingest Food – many radioisotopes bioconcentrated Food – many radioisotopes bioconcentrated Water Water Environmental source esp young children Environmental source esp young children –Wounds

16. Radiation Basics Radioactivity – 1 Becquerel (Bq)= 1 radioactive disintegration per sec Absrbed dose – 1 Gray (Gy) = 1 joule of energy deposited per kilogram Equivalent dose (biological effect) – Sievert (Sv) the unit of absorbed dose equivalent. The energy absorbed by the body based on the damaging effect for the type of radiation. Sv =Gray x Quality Factor

17. Radiation Quantities and Units Biological equivalent dose: Sievert (Sv) = joules per kilogram Biological equivalent dose: Sievert (Sv) = joules per kilogram –Relates to the amount of radiation harm in biological tissues Beta, gamma, and x-ray Sv = Gy Beta, gamma, and x-ray Sv = Gy Particle weightings (electrons = 1; neutrons = 5; alpha = 20) Particle weightings (electrons = 1; neutrons = 5; alpha = 20) Biological effective dose: Sievert (Sv) = equivalent dose weighted for susceptibility to harm of different tissues Biological effective dose: Sievert (Sv) = equivalent dose weighted for susceptibility to harm of different tissues

18. Production of Ionizing Radiation Radioactive decay Radioactive decay = radioactivity (α, β, γ) = radioactivity (α, β, γ)

19. Production of Ionizing Radiation Radioactive decay Radioactive decay 5730 yrs T 1/2 20 s

20. Production of Ionizing Radiation Radioactive decay Radioactive decay

21. U-238 radioactive decay

22. tissue injury: alpha- particle track … lung cells

23. Radon Produced from radium in decay chain of uranium Produced from radium in decay chain of uranium Escapes into air – short lived decay products emit alpha particles – stick to dust, inhaled, deposit in lung – high but localised radiation Escapes into air – short lived decay products emit alpha particles – stick to dust, inhaled, deposit in lung – high but localised radiation Second most important cause lung cancer Second most important cause lung cancer

24. Radon Average outdoor levels: 5-15 Bq/m 3 Average outdoor levels: 5-15 Bq/m 3 Global indoor average: 39 Bq/m 3 Global indoor average: 39 Bq/m 3 Action levels – generally 200-400 Bq/m 3 (Australia 200) Action levels – generally 200-400 Bq/m 3 (Australia 200) Risk of lung cancer increases by 16% per 100 Bq/m 3 increase in radon Risk of lung cancer increases by 16% per 100 Bq/m 3 increase in radon Relationship linear with no threshold Relationship linear with no threshold Risk synergistic with smoking Risk synergistic with smoking Some (weak) evidence of increased effect at low dose rate Some (weak) evidence of increased effect at low dose rate

25. Radon risk per 1000 of lung cancer by age 75 y Non-smokerSmoker 0 Bq/m 3 4100 100 Bq/m 3 5120 400 Bq/m 3 7160 WHO Factsheet 291 June 2005

26. Production of Ionizing Radiation Nuclear fission = splitting of atoms (radioactivity)

27. Production of Ionizing Radiation Nuclear fusion Nuclear fusion

28. Production of Ionizing Radiation Particle accelerators (cyclotrons, synchrotrons, linear accelerators) electrons, protons Particle accelerators (cyclotrons, synchrotrons, linear accelerators) electrons, protons

29. Cell Sensitivity Cells most affected: Cells most affected: –Rapidly dividing cells: small intestines, bone marrow, hair, fetus small intestines, bone marrow, hair, fetus

30. Varying tissue sensitivities

32. Health Effects of Radiation

33. Ionising radiation Capacity to damage core genetic blueprint - DNA Capacity to damage core genetic blueprint - DNA → cancer → other health effects → genetic damage Lethal dose can have equivalent energy to heat in a cup of coffee Lethal dose can have equivalent energy to heat in a cup of coffee Many different isotopes Many different isotopes Behave differently biologically Behave differently biologically

34. Biological Effects of Radiaton Acute effects (>100mSv) Acute effects (>100mSv) – hours/days/weeks) Chronic effects (no safe threshold) Chronic effects (no safe threshold) –Cancer, mutations

35. Biological Effects of Radiaton Deterministic effects (>100mSv) Deterministic effects (>100mSv) –Threshold –Increased dose = increased damage Stochastic (probabilistic) effects (no safe threshold) Stochastic (probabilistic) effects (no safe threshold) –Increased dose = increased probability of damage but not severity

36. What Radiation Affects Directly or indirectly, radiation affects the DNA in cells Directly or indirectly, radiation affects the DNA in cells DNA controls the cell’s function and ability to reproduce DNA controls the cell’s function and ability to reproduce

37. Possible Effects Destroy the DNA Destroy the DNA –Kill the cell Damage the DNA; cell can: Damage the DNA; cell can: –Repair itself (most likely) –Not function or function improperly –Undergo uncontrolled division (cancer)

38. Category of Effects Acute Somatic Acute Somatic –Immediate effects to the organism receiving the dose Delayed Somatic Delayed Somatic –Effects that appear years later to organism receiving the dose Genetic Genetic –Effects that appear in offspring????

39. Acute Somatic Effects <100 mSv <100 mSv –No detectable effects 100 - 1,000 mSv 100 - 1,000 mSv –Reduced red & white blood cell count 1,000 - 3,000 mSv 1,000 - 3,000 mSv –Nausea, vomiting, may not be able to fight infection

40. More Acute Somatic 3,000 - 6,000 mSv (300 - 600 rem) 3,000 - 6,000 mSv (300 - 600 rem) –More severe nausea and vomiting, hemorrhaging, diarrhea, loss of hair, cannot fight infections, sterility. At 4,500 mSv, about half exposed will die within 30 days, others will survive. >6,000 mSv (600 rem) >6,000 mSv (600 rem) –Same as above plus central nervous system impairment. Death within 30 days.

41. Delayed Somatic Effects 1. Cancer: solid tumors 1. Cancer: solid tumors –Increased risk –Latency period: 10+ y 2. Cancer: leukemia 2. Cancer: leukemia –Increased risk –Latency period: 5+ y 3. Degenerative effects (LSS, not sure at low doses) 3. Degenerative effects (LSS, not sure at low doses) –Life shortening (not sure) –Heart disease, stroke; digestive, respiratory, hemopoietic systems

42. More Delayed Somatic Effects 4. Cataracts 4. Cataracts –2,000 mSv single dose threshold 5. Birth defects (fetus exposed) 5. Birth defects (fetus exposed) –Effects depend on time of gestation 6. Sterility 6. Sterility –2,000 mSv temporary - male –8,000 mSv permanent - male

43. Cancer Risks Radiation is a recognized carcinogen with no threshold for its effect, BUT, the risk is relatively small, although not negligible. Radiation is a recognized carcinogen with no threshold for its effect, BUT, the risk is relatively small, although not negligible. Radiation dose does not produce cancer in every exposed person (stochastic) Radiation dose does not produce cancer in every exposed person (stochastic) Latency period: Latency period: –Solid tumors: 10 - 40 years –Leukemia: 2 - 4 years

44. Latency Period

45. Cancer Risks Normal cancer risk (Australia): Normal cancer risk (Australia): –About 1:2 men get cancer by age 85 –About 1:3 women get cancer by age 85 Normal mortality: Normal mortality: –29% of Australians die primarily from cancer –49.3 % die primarily or as a consequence of cancer Cancer in Australia: an overview 2006, AIHW

46. Cancer Risks Linear, no threshold Linear, no threshold Increased risk of cancer from 1 mSv of radiation: Increased risk of cancer from 1 mSv of radiation: –Solid tumor cancer risk about 1 in 10,000 –Leukemia risk about 1 in 100,000 Increased risk of cancer mortality about half those : Increased risk of cancer mortality about half those : –Solid cancer deaths: about 1 in 20,000  BEIR VII 2005

47. Cancer risks vary Infancy 3-4x increased risk cf 20-50y Infancy 3-4x increased risk cf 20-50y Female infants 2x risk of male infants Female infants 2x risk of male infants Female risk of cancer is 37.5% greater than males Female risk of cancer is 37.5% greater than males –50% greater risk of solid tumours –Less risk leukaemia  BEIR VII 2005

48. Low Dose Risk Data are good for risks from higher doses of radiation (>50 mSv); 10mSv in children Data are good for risks from higher doses of radiation (>50 mSv); 10mSv in children At lower doses, the effects are masked by natural high incidence At lower doses, the effects are masked by natural high incidence Extrapolate from high dose effects to low dose effects Extrapolate from high dose effects to low dose effects

49. Possible Extrapolations

50. Threshold Some effects do have a threshold dose for the effect to appear Some effects do have a threshold dose for the effect to appear –Sterility, cataracts Cancer does not seem to have a threshold Cancer does not seem to have a threshold

51. Linear-Quadratic Leukemia seems to obey this extrapolation Leukemia seems to obey this extrapolation

52. Linear - No Threshold If we can’t see the effects, are they really there? If we can’t see the effects, are they really there? If yes: the smallest dose may increase risk If yes: the smallest dose may increase risk If no: there is some level below which there is no effect If no: there is some level below which there is no effect Controversy among some radiation scientists Controversy among some radiation scientists –Orthodoxy vs heterodoxy eg hormesis

53. Fetal radiation risk There are radiation-related risks throughout pregnancy that are related to the stage of pregnancy and absorbed dose There are radiation-related risks throughout pregnancy that are related to the stage of pregnancy and absorbed dose Radiation risks are most significant during organogenesis and in the early fetal period, somewhat less in 2 nd trimester, and least in 3 rd trimester Radiation risks are most significant during organogenesis and in the early fetal period, somewhat less in 2 nd trimester, and least in 3 rd trimester LessLeast Most risk

54. Radiation-induced malformations Malformations have a threshold of 100-200 mGy or higher and are typically associated with central nervous system problems Malformations have a threshold of 100-200 mGy or higher and are typically associated with central nervous system problems Fetal doses of 100 mGy are not reached even with 3 pelvic CT scans or 20 conventional diagnostic x-ray examinations Fetal doses of 100 mGy are not reached even with 3 pelvic CT scans or 20 conventional diagnostic x-ray examinations These levels can be reached with fluoroscopically guided interventional procedures of the pelvis and with radiotherapy These levels can be reached with fluoroscopically guided interventional procedures of the pelvis and with radiotherapy

55. Central nervous system effects During 8-25 weeks post-conception the CNS is particularly sensitive to radiation During 8-25 weeks post-conception the CNS is particularly sensitive to radiation Fetal doses in excess of 100 mGy (threshold) can result in some reduction of IQ Fetal doses in excess of 100 mGy (threshold) can result in some reduction of IQ Fetal doses in the range of 1000 mGy can result in severe mental retardation and microcephaly, particularly during 8-15 weeks and to a lesser extent at 16-25 weeks Fetal doses in the range of 1000 mGy can result in severe mental retardation and microcephaly, particularly during 8-15 weeks and to a lesser extent at 16-25 weeks

56. Leukaemia and cancer… Radiation has been shown to increase the risk for leukaemia and many types of cancer in adults and children Radiation has been shown to increase the risk for leukaemia and many types of cancer in adults and children Throughout most of pregnancy, the embryo/fetus is assumed to be at about the same risk for carcinogenic effects as children Throughout most of pregnancy, the embryo/fetus is assumed to be at about the same risk for carcinogenic effects as children

57. Leukaemia and cancer The relative risk may be as high as 1.4 (40% increase over normal incidence) due to a fetal dose of 10 mSv The relative risk may be as high as 1.4 (40% increase over normal incidence) due to a fetal dose of 10 mSv For an individual exposed in utero to 10 mSv, the absolute risk of cancer at ages 0- 15 is about 1 excess cancer death per 1,700 For an individual exposed in utero to 10 mSv, the absolute risk of cancer at ages 0- 15 is about 1 excess cancer death per 1,700

58. Probability of bearing healthy children as a function of radiation dose Dose to conceptus (mSv) above natural background Probability of no malformation Probability of no cancer (0-19 years) 09799.7 19799.7 59799.7 10 109799.6 50 509799.4 100 1009799.1 >100PossibleHigher

59. Pre-conception irradiation Pre-conception irradiation of either parent’s gonads has not been shown to result in increased risk of cancer or malformations in children Pre-conception irradiation of either parent’s gonads has not been shown to result in increased risk of cancer or malformations in children

60. Pre-conception irradiation “at low or chronic doses of low-LET irradiation, the genetic risks are very small compared to the baseline frequencies of genetic diseases in the population. Additionally, they are consistent with the lack of significant adverse effects in the Japanese studies based on about 30,000 children of exposed survivors.” (BEIR VII phase 2) This statement is from comprehensive studies of atomic bomb survivors as well as studies of patients who had been treated with radiotherapy when they were children This statement is from comprehensive studies of atomic bomb survivors as well as studies of patients who had been treated with radiotherapy when they were children

61. The Evidence 1. Hiroshima and Nagasaki bomb victims (LSS) –Mortality data 1950-1997 reviewed in detail 93,000 survivors; equal numbers within 2.5km, and 3-10km of blast hyocentre 93,000 survivors; equal numbers within 2.5km, and 3-10km of blast hyocentre Less than half survivors were alive at 2000 Less than half survivors were alive at 2000 –Cancer incidence data from tumour registries became available for first time in 1990’s (prior data from death certificates) –35% survivors 100 to 4000 mSv show linear relationship to excess solid cancers –In utero exposure, excess solid cancers as low as 10mSv –65% survivors received doses <100mSv (c.w. 2.4mSv annual background) Statistical limitations make it difficult to evaluate cancer risk below 100mSv however radiation biology predicts the linear response is continuous with no threshold Statistical limitations make it difficult to evaluate cancer risk below 100mSv however radiation biology predicts the linear response is continuous with no threshold

62. The Evidence 2. Occupational radiation studies –UK National Registry of Radiation Workers; Three Country Study (Canada, UK, USA); –International Agency for research on Cancer* Excess RR 0.97/Sv non-leukemia cancers Excess RR 0.97/Sv non-leukemia cancers Excess RR 1.93/Sv leukemia cancers Excess RR 1.93/Sv leukemia cancers “1-2% of deaths from cancer among workers in this cohort may be attributable to radiation.” “1-2% of deaths from cancer among workers in this cohort may be attributable to radiation.” *Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.BMJ. 2005 Jul 9;331(7508):77. Epub 2005 Jun 29

63. The Evidence 3. Medical radiation studies –Mainly related to radiotherapy doses –Also pooled data A-bomb survivors Lung, breast, thyroid, stomach Lung, breast, thyroid, stomach –ERR lung 0.1-0.4/Sv –EAR breast 10/10 4 person-years/Sv –Thyroid ERR 7.7/Sv; risk only if exposed <20yo risk only if exposed <20yo no risk ca. with therapeutic radioiodine no risk ca. with therapeutic radioiodine –Leukemia ERR 1.9-5/Sv –Stomach ERR negative to 1.3 –CV disease in high dose Hodgkin’s and breast ca radioRx

64. The Evidence 4. Chernobyl –4000 thyroid cancers in children exposed, most due to radioiodine exposure from fallout –Predicted several thousand solid cancers; perhaps 2-3% rise in natural incidence (100,000 natural incidence) perhaps 2-3% rise in natural incidence (100,000 natural incidence)

65. Comparative Risks “Normal” fatal risks we face: “Normal” fatal risks we face: –Smoking (lifetime): 1:2 –Police officer: 1:2500 –Agriculture industry (per year): 1:2600 –Vehicle accident (per year): 1:6000 –Falls (per year): 1:20,000 –Home fire (per year): 1:50,000 –Airplane crash (one trip): 1: 1,000,000

66. What is ‘Safe’? Driving a car is “safe” Driving a car is “safe” –1:6,000 per year; 1:77 lifetime risk of death Taking an aspirin for a year Taking an aspirin for a year –1:6,000 per year Firefighter mortality-1:6,000 per year Firefighter mortality-1:6,000 per year Living at home is “safe” Living at home is “safe” –Falls: 1:20,000, Fires: 1:50,000, Poisoning: 1:40,000; Total: 1:10,000 Radiation (1 mSv) is “safe” Radiation (1 mSv) is “safe” –1:12,500

67. Years of Life Lost

68. Days of Life Lost

69. Hours of Life Lost

70. Medical Radiation Exposure Occupational limits Occupational limits –50mSv in one year –20mSv per annum averaged over 5 years ALARA principle ALARA principle Interventional procedures (coronary angio.) Interventional procedures (coronary angio.) –11 mSv per patient –0.05mSV per procedure total dose –0.5mSv per procedure eye dose

71. Medical Radiation Exposure A recap A recap

72. Medical Radiation Exposure Australian radiology statistics (Medicare) Australian radiology statistics (Medicare)

73. Medical Radiation Exposure Australian radiology statistics Australian radiology statistics

74. Medical Radiation Exposure Australian radiology statistics Australian radiology statistics

75. Medical Radiation Exposure Australian radiology statistics Australian radiology statistics –Australian CT services increased 140% (166%) since 1992* 431 (490) ca. per year; 1.3% of all cancers 431 (490) ca. per year; 1.3% of all cancers c.w. UK & Poland (0.6% cancers), Japan (3.2% cancers) c.w. UK & Poland (0.6% cancers), Japan (3.2% cancers) –Total population medical radiation dose 2006 1.7M CT @ 6.6mSv per scan = 11,220 Sv x 2 (CT accounts for 50% of all medical radiation) =22,440 Sv 1.7M CT @ 6.6mSv per scan = 11,220 Sv x 2 (CT accounts for 50% of all medical radiation) =22,440 Sv i.e. 1.07 mSv per capita i.e. 1.07 mSv per capita Berrington de González A, Darby S. Risk of cancer from diagnostic x-rays:estimates for the UK and 14 other countries. Lancet 2004; 363: 345-351.

76. Medical Radiation Exposure Procedure Effective dose (mSv) Equivalent CXR EBR (days) Equivalent aircraft flight hours Probability of fatal cancer Chest x-ray (PA) 0.021321:625,000 CT brain 31504563001:4200 CT chest 840012178001:1600 CT abdo/pelvis 11550167311001:1100 CT coronary angio 10500152110001:1250 Conventional coronary angio 3-111504563001:4200 Ba enema 8.743513238701:1400 mammography0.1515101:125000 Nuclear myocardial perfusion study 12600182512001:1000 Nuclear bone scan 4.42206694401:2800

77. Medical Radiation Exposure USA radiology statistics (NCRP) USA radiology statistics (NCRP)

78. Medical Radiation Exposure USA radiology statistics (NCRP 2006) USA radiology statistics (NCRP 2006) Per capita dose due to diagnostic radiation has increased 600% since 1980

79. Worldwide diagnostic radiation cancer risks United Nations Scientific Committee on the Effects of Atomic Radiation. Sources and effects of ionizing radiation. New York: United Nations, 2000.

80. CT Scanners

84. Cancer Risks-how good are we? Radiology 2004; 231:393-398

85. A Quiz… The Answers One chest x-ray increases your risk of cancer T or F? One chest x-ray increases your risk of cancer T or F? One CT scan increases your risk of cancer T or F? One CT scan increases your risk of cancer T or F? The radiation dose of one CT scan of the abdomen & pelvis is how many times that of a chest x-ray dose? The radiation dose of one CT scan of the abdomen & pelvis is how many times that of a chest x-ray dose? A. 250

86. References Calculate diagnostic procedure radiation dose: Calculate diagnostic procedure radiation dose: http://www.doseinforadar.com/RADARDoseRiskCalc.html Relative life risks: Relative life risks:http://www.physics.isu.edu/radinf/risk.htm

87. Nuclear industry workers 1 15 country retrospective cohort study of cancer mortality auspiced by IARC 15 country retrospective cohort study of cancer mortality auspiced by IARC Largest such study ever conducted Largest such study ever conducted Workers involved in fuel enrichment or reprocessing, reactors, weapons or isotope production (excl uranium mining) Workers involved in fuel enrichment or reprocessing, reactors, weapons or isotope production (excl uranium mining) 407,391 workers (90% male): 407,391 workers (90% male): – employed ≥ 1 y –monitored for external photon (X and gamma) radiation –> 90% whole body dose from external photons rather than neutrons or internal exposures Total FU 5.2 million person y Total FU 5.2 million person y

88. Nuclear industry workers 2 Doses to colon used for all and solid cancer, active bone marrow for leukemia analyses, lagged by 2 y for leukemia and 10 y for other cancers Doses to colon used for all and solid cancer, active bone marrow for leukemia analyses, lagged by 2 y for leukemia and 10 y for other cancers Doses: Doses: –Average 19.4 mSv –90% < 50 mSv – 500 mSv Total deaths 6516 from cancer other than leukemia, 196 from leukemia excl CLL Total deaths 6516 from cancer other than leukemia, 196 from leukemia excl CLL

89. Nuclear industry workers vs Japanese bomb survivors* 3 Cause of death, N Workers Survivors Excess relative risk per Sv 95% CI All cancers excl leukemia, 5024 0.970.14 -1.97 Solid cancer, 4770 3246 0.87 0.32 0.03 - 1.88 0.01 – 0.50 Leukemia excl CLL, 196 83 1.93 3.15^ 1.54” <0 – 8.47 1.58 – 5.67^ -1.14 – 5.33” Lung cancer1.860.26 – 4.01 *Men aged 20-60 at time of exposure ^Assuming linear dose response with no threshold “ Assuming linear-quadratic response

90. Nuclear industry workers 4 Mortality from all cancers except leukemia – central estimate 2-3 times higher than linear extrapolation from atomic bomb survivors Mortality from all cancers except leukemia – central estimate 2-3 times higher than linear extrapolation from atomic bomb survivors –Current recommended 5 y occup dose limit of 100 mSv → 9.7% (1.4 - 19.7%) increase in cancer excl leukemia –For leukemia excl CLL 100mSv → 19% (<0 - 84.7%) increase Cardis E, et al. BMJ 2005 (29 June 2005) BMJ,doi:10.1136/bmj.38499.599861.EO

92. ‘Routine’ radiation releases First large meta-analysis of data on childhood leukaemia and nuclear facilities First large meta-analysis of data on childhood leukaemia and nuclear facilities International peer-reviewed journal International peer-reviewed journal Multiple sites, different populations, different time periods, collected differently are difficult; findings more likely to be significant Multiple sites, different populations, different time periods, collected differently are difficult; findings more likely to be significant No major sources of bias identified No major sources of bias identified Countries with poorer environmental standards eg Russia, China and developing countries are excluded, so likely best case scenario Countries with poorer environmental standards eg Russia, China and developing countries are excluded, so likely best case scenario Effects robust to different types of analyses Effects robust to different types of analyses

93. ‘Routine’ radiation releases Point estimates are all above 1 Point estimates are all above 1 A number of important findings are statistically significant eg all of the results for childhood leukaemia incidence A number of important findings are statistically significant eg all of the results for childhood leukaemia incidence Association of young age and closeness to a nuclear facility with higher risk are biologically plausible, suggest dose-response effect Association of young age and closeness to a nuclear facility with higher risk are biologically plausible, suggest dose-response effect Heightened sensitivity of children to radiation, and leukaemia as most radiation sensitive cancer with shortest latent period support biological plausibility Heightened sensitivity of children to radiation, and leukaemia as most radiation sensitive cancer with shortest latent period support biological plausibility funded by the US DOE funded by the US DOE

94. German Childhood Cancer Registry data 1980 – 2003, <5y German Childhood Cancer Registry data 1980 – 2003, <5y Matched case-control study Matched case-control study 593 leukemia cases 593 leukemia cases Odds ratio for leukemia 2.19 (lower 95% CI 1.51) for residence within 5 km of nuclear power plant Odds ratio for leukemia 2.19 (lower 95% CI 1.51) for residence within 5 km of nuclear power plant

96. 1592 cases, 4735 controls 1592 cases, 4735 controls Odds ratio 1.47 (lower 95% CI 1.16) for inner 5 km zone Odds ratio 1.47 (lower 95% CI 1.16) for inner 5 km zone

97. Thank you!

98. Radioactivity of plutonium 1 millionth of a gram → fatal cancer 1 millionth of a gram → fatal cancer Half-life (T1/2) 24,400 years Half-life (T1/2) 24,400 years Decayed to 1/1024 th of original amount after 244,000y Decayed to 1/1024 th of original amount after 244,000y Neanderthals died out 30,000 y Neanderthals died out 30,000 y Last Ice Age glaciation 10,000 y Last Ice Age glaciation 10,000 y Settled agriculture 12,000 y Settled agriculture 12,000 y Writing invented 6,000 y Writing invented 6,000 y

99. BEIR VII 2005: Update on the risks of “low-level” radiation Radiation risks somewhat higher than prior estimate Radiation risks somewhat higher than prior estimate Cancer incidence and mortality risks Cancer incidence and mortality risks Risks by age and gender Risks by age and gender Some non-cancer risks, including heart disease and stroke at higher levels of exposure Some non-cancer risks, including heart disease and stroke at higher levels of exposure Various risk hypotheses studied Various risk hypotheses studied Detailed look at latest radiation risk literature Detailed look at latest radiation risk literature Synergisms with chemicals not examined Synergisms with chemicals not examined

100. Linear No-Threshold (LNT) BEIR VII re-affirms LNT hypothesis BEIR VII re-affirms LNT hypothesis Hiroshima-Nagasaki and 10 rem Hiroshima-Nagasaki and 10 rem Cellular level evidence for LNT Cellular level evidence for LNT Risk for low doses and low dose rates estimated to be somewhat lower than single dose risk Risk for low doses and low dose rates estimated to be somewhat lower than single dose risk Hormesis and thresholds considered but not endorsed as representing best scientific view of low-dose risk Hormesis and thresholds considered but not endorsed as representing best scientific view of low-dose risk Genetic variation in population combines with environmental factors Genetic variation in population combines with environmental factors

101. Risk Factors currently in use Generally used reference risk for workers: 0.04 fatal cancers per Sv (BEIR V with DREF = 2; note no DREF actually recommended in BEIR V) Generally used reference risk for workers: 0.04 fatal cancers per Sv (BEIR V with DREF = 2; note no DREF actually recommended in BEIR V) Generally used reference risk for general public: 0.05 fatal cancers per Sv Generally used reference risk for general public: 0.05 fatal cancers per Sv BEIR VII (average for men and women): 0.057 fatal cancers per Sv BEIR VII (average for men and women): 0.057 fatal cancers per Sv Incidence BEIR VII: 0.1 cancers per Sv Incidence BEIR VII: 0.1 cancers per Sv BEIR VII risks incorporate DREF = 1.5 BEIR VII risks incorporate DREF = 1.5 Risks for females ~1.5x higher than males Risks for females ~1.5x higher than males For children risks up to 15.4x higher than for 30 y olds For children risks up to 15.4x higher than for 30 y olds

102. Heritable effects (BEIR VII, p. 20) “Adverse health effects in children of exposed parents…have not been found” “Adverse health effects in children of exposed parents…have not been found” “there are extensive data on radiation- induced transmissible mutations in mice and other organisms” “there are extensive data on radiation- induced transmissible mutations in mice and other organisms” “There is therefore no reason to believe that humans would be immune to this sort of harm.” “There is therefore no reason to believe that humans would be immune to this sort of harm.”