Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
“Radiation and Radioisotope Applications EPFL Doctoral Course PY-031
The Effects of Low Dose Radiation Lecture 09. Seminar Rafael Macian 23.11.06 EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06.1
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Dose Ranges (
Total Body Therapy
Total Tumor Dose
mSievert) A-bomb survivors
0
1000
2000
Typical mission dose on Int. Space Station
0
100
Experimental Radiobiology
Human LD50
3000
4000
5000
Significant cancer risk at > 200 mSv (UNSCEAR)
200
300
400
500
6000
7000
8000
9000
10000
Cancer Epidemiology 600
700
800
900
1000
DOE Low Dose Program Occupational Limit NRC, EPA
0
10
20
30
40
50
Typical annual dose for commercial airline flight crews Thyroid (I-123)
0
1
Bone (Tc-99m)
2
3 background 4 Natural
Site Decommissioning/License Termination
60
70
80
90
100
Medical Diagnostics
5
6
7
8
9
10
NRC Dose Limit for Public Dental X-ray Chest X-ray
0
0.1
0. 2
EPA Clean-up Standards
0.3
0. 4
0. 5
0.6
0.7
0.8
NRC Clean-up Standards
0.01
0.02
0.03
0.04
0.05
1
Regulatory Standards
ICRP Negligible Dose
0
0. 9
0.0 6
0.0 7
0.08
0.0 9
0.1
3-Mile Island Ave Ind EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 2/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Low Dose Radiation q Low Dose Radiation is delivered in doses that are small enough NOT to produce accute damage and fast cell and body responses. q It can be delivered by any type of radiation. q People are ususally exposed through: • Background Radiation Sources. • Occupational Exposure.
q Its effects are: • Genetic: transmitted to the offspring. • Somatic: suffered by the individual exposed. Carcinogenesis • In-Utero: fetal malformations. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 3/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Genetic Effects Mutation of the reproductive cells passed on to the offspring of the exposed individual. q Facts about Genetic Mutations induced by radiation: • Mutations take place in the sperm or egg cells. • Radiation is a MUTAGENIC agent (chemicals and viruses are also). • Radiation INCREASES the SPONTANEOUS RATE of MUTATIONS. • Radiation DOES NOT produce any NEW MUTATIONS. • Intensive studies of 70,000 offspring of the atomic bomb survivors have failed to identify an increase in congenital anomalies, cancer, chromosome aberrations in circulating lymphocytes or mutational blood protein changes (Neel et al. Am. J. Hum. Genet. 1990, 46:1053-1072). EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 4/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Somatic Effects Related to Cancer (Carcinogenesis). q Carcinogens are: • Physical: radiation. • Chemical: tobacco smoke. • Biological: viruse.
q Radiation induced cancer is well documented: • Early scientists working with radiation sources: leukemia, skin and bone cancers. • Uranium miners. • Japanese Bomb Survivors. • Patients treated with X-rays to cure espondilarthritis. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 5/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
In-Utero Effects Production of Malformations in developing Embryos.
Weeks Post Conception
Effect
0-1 (preimplantation)
Intrauterine death.
2-7 (organogenesis)
Developmental abnormalities/growth retardation/cancer.
8-14 (fetal state)
Same as above with lower risk plus possible functional abnormalities).
q Teratogenic Agents: •
Physical: Radiation.
•
Chemicals: thalidomide.
•
Biological: viruses.
q The observed effects depend on the stage of fetal development.
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 6/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Radiation Risk Risk relates Exposure to Probability of Biological Effects Effect
Excess Cases per 10000 exposed per rad (10000 man-rad)
Genetic
2 to 4
Somatic (cancer)
4 to 20
In-Utero (cancer)
4 to 12
In-Utero (all effects)
20 to 200
Genetic: 1 rem to reproductive organs 50 to 1000 times less than spontaneous risk. Somatic: Small risk compared to 1 in 4 for normal cancer risk. In-Utero: 5 to 30 times grater than normal exposure to 1 rem. Medical practice largest source. Limit for pregnan women 0.5 rem for entire preg. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 7/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Models For Radiation Risk q Based on Extrapolation of High Dose Effects to Low doses q Models: • Linear No Threshold Model (LNT). • Sub-linear Model: the end point for biological effect is zero rem. The number of projected cancers grows at a much lower rate than in the linear LNT model. • Threshold Model: radiation has no effect up to a certain dose (5 to 20 rem). After this, excess cancers may be observed. • Hormesis Model: Assumes that high doses of radiation increase the incidence of cancer, but below a value of about 10 rem may be beneficial to the person. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 8/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Linear No Threshold Model
Conservative Assessment of Risk
Simplification of Risk Estimates
q Based on the assumption that the damage caused by ionizing radiation is linear (i.e., directly proportional to the dose) at all dose levels. q LNT asserts that there is no threshold of exposure below which the response ceases to be linear. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 9/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Evidence For Hormesis q Some evidence for: • Studies of airline crews are exposed to higher levels of cosmic radiation due to altitude but show no overall increase in cancer in spite of higher exposure • Incidence of cancer is found to be low in high-lying areas which are less protected by the atmosphere against cosmic radiation • Genes that protect against radiation damage have been found to be activated in people exposed to radiation in these areas • Ramsar has naturally very high radiation (260 mSv) due to its geology but is found to have no increased cancer risk[2] • No chromosomal damage was detectable in animals with high radiation counts living around Chernobyl • Lower than expected increases in cancers have been found from Chernobyl[3] • In Taiwan, apartments built with radioactive rebar contaminated with cobalt 60 gave doses of an average of 400 mSv/year to the occupants. Mortality and cancers were considerably lower than in reference populations.[4]
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 10/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Evidence Against Hormesis q Some evidence against: • Pilots are more prone to brain, rectal and prostate cancers whilst flight crews are twice as susceptible to breast cancer, but are healthier overall than the general public (possibly because they are healthier when selected for the job due to health screening).[5] However there is a contrary suggestion and evidence that breast cancer in flight crews may be caused by jet lag[6]. • High-lying areas have reduced oxygen levels (oxygen is slightly carcinogenic); once this and other effects are accounted for there is actually an increase in cancer incidence with altitude which seems to be attributable to radiation.[7]
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 11/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Current Practice q A linear model has long been used in health physics to set maximum acceptable radiation exposures. q The United States based National Council on Radiation Protection and Measurements (NCRP) : “Radiation's effects should be considered to be proportional to the dose an individual receives, regardless of how small that dose is”. (Report to Congress on the effects of radiation)
q Regulations (USNRC 10CFR Part 20) requires that Exposure SHALL be held to the ALARA principle. q Risk assumed as directly proportional to dose, without any threshold EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 12/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Criticism of Current Practice q Some regard the LNTM as conservative or even completely wrong for predicting the effect of low doses of radiation.[1] They claim that there is no evidence supporting the assumption that there is no threshold, and that recent studies suggest changes in this assumption.
q The European Committee on Radiation Risk (ECRR) is a committee set up in 1997: • Sets out the basic standards regarding radiation protection in the European Union. • Includes several prominent critics of the dominant view of radiation risk such as articulated by the International Commission on Radiological Protection (ICRP) and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 13/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Scientific Basis for Challenge (Prof. A. L. Brooks, Washington State University) q Hit theory shift to bystander paradigm. • A cell does not have to be hit in order to be biologically altered.
q Mutation theory shifts to gene expression paradigm. • Radiation induces changes in gene expression that may alter subsequent responses in a large fraction of the cell population.
q Single mutation cancer theory shifts to tissue paradigm. • Tissues respond as whole and not as individual cell.
q LNTH challenged by adaptive response & genomic instability. • Adaptive response may result in protective, nonlinear dose-responses • Genomic instability or bystander effects could result in either super-linear or sub-linear dose-responses.
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 14/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
What do we really know ?.
The adverse health effects versus radiation exposure levels. Large uncertainty as the curve approaches zero radiation levels. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 15/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Radioepidemiological Facts q Response to low doses of radiation is different than to high doses: • Cancer has never been seen following low doses of radiation. • High dose studies are used to estimate risks from cancer. • These high dose risks are then extrapolated to estimate risk following low dose.
q Background radiation is often higher than the level of added radiation exposure. q There is a high and variable rate of cancer in the human population. q There is no way to tell a radiation-induced cancer from a spontaneous cancer. Radiation is a poor mutagen/carcinogen, but a very good cell killer EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 16/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
25000 20000 15000 10000 5000 0 No cancer detected below this level
Occupational exposure limit
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
Ave background
Population Exposure limit
The Effects of Low Dose Radiation, R. Macian, 23.11.06 17/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Problems with Data at Low Doses q Cell culture and animal data difficult to extrapolate to humans. q Human experience. • Not randomized controlled. – Would be highly unethical.
• Many assumptions in Life time study. – Poor dose information (to part or whole body). – Unknown co-existing conditions. – Poor statistics (small numbers).
• The natural incidence of cancer is much greater than any contribution from ionizing radiation: – 10000 people, 2000 natural cancers + 4 to 8 from 1 rem exposures.
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 18/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Problems with Data at Low Doses q Irradiated populations are: • people exposed from the atomic bomb explosions. • people exposed during nuclear and other radiation accidents. • patients exposed for medical reasons. • people exposed to natural radiation. • workers in radiation industries.
q Information is scanty (not much, less than needed) on: • Consequences of low doses delivered at low dose rates. – To detect an increase from a 20% spontaneous cancer incidence to 25% (corresponding to an exposure to ~1 Sv) > 1300 persons must be studied.
• Consequences of external high LET radiation. – (neutrons) and several radionuclides.
• Presence and influence of confounding factors. – especially if different populations are to be compared. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 19/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Detectability limits in Radioepidemiology 10 4
REGION OF DETECTABILITY Theoretical limit of detectability due to statistical causes (90% confidence interval)
EFFECT IVE DO SE (m Sv)
10 3
10 2
101
CHERNOBYL DOSES
10 0
10-1 10 0
REGION OF UNDETECTABILITY 101
10 2
10 3
104
105
106
107
108
109
1010
1011
Number of people in study and control groups EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 20/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Cancer Risk Picture
1.5
Excess Risk
Extrapolated Risk
(Background is shown as 1.0)
Cancer Risk
2.0
1.0
Background Cancer risk
0.5 Background dose/yr
0.0
0.0
Background dose/40 years
0.1
0.2
0.3
0.4
Radiation Dose (Sv) EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
0.5 Modified from BEIR VII, McClellan and Brooks The Effects of Low Dose Radiation, R. Macian, 23.11.06 21/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Summary q Both early and late effects and risks from high doses of radiation are well defined and understood. q The radiation risks associated with exposure to low doses of radiation are: • difficult to measure and • still have major uncertainties associated with them.
q Rapid advances in technology, techniques in cell and molecular biology are now making it possible to detect and understand biological changes after low doses of radiation. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 22/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Balanced Opinion (Prof. A. L. Brooks, Washington State University) q Radiation is not a major environmental carcinogen. It takes a large amount of radiation to produce an increase in cancer frequency. q Both non-linear and linear models must be considered in determining dose-response relationships for radiation-related human cancer. q Single hit, single DNA damage/mutation, single cancer biophysical model must be modified to accommodate modern molecular biology. q Additional research is needed to define mechanisms of action for observed low dose biological responses before they can be used in cancer risk estimates. q Scientific basis for radiation standards is needed to help define the shape of the dose-response relationships in the low dose regions. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 23/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
Criticism to BEIR-VII (Prof. A. L. Brooks, Washington State University) q Good review of the literature, summaries and conclusions, “The risk from radiation is small.” q Failure to acknowledge the differences between real data and extrapolated risks using the LNT-H. q Dismissal of new mechanistic biological data that demonstrate non-linear biology. q Failure to include the caveats in conclusions and public summaries. q Since the risk is small it takes a lot of radiation to produce excess cancers. EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 24/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 25/41
Laboratory for Reactor Physics and Systems Behaviour EPFL/PSI
References 1.
Luckey T (1999). "Nurture with ionizing radiation: a provocative hypothesis.". Nutr Cancer 34 (1): 1-11. PMID 10453435.
2.
http://www.ecolo.org/documents/documents_in_english/ramsar-naturalradioactivity/ramsar.html
3.
http://www.tcsdaily.com/article.aspx?id=091905D
4.
http://www.jpands.org/vol9no1/chen.pdf
5.
http://news.bbc.co.uk/1/hi/health/380274.stm
6.
http://news.bbc.co.uk/1/hi/health/154933.stm
7.
http://www.gfstrahlenschutz.de/docs/hormeng2.pdf
8.
Health effects of Exposure to Low Levels of Ionizing Radiation – BEIR-V (1990): http://www.nap.edu/openbook/0309039959/html
9.
Radiation and Life: http://www.uic.com.au/ral.htm
10. Radiation Reassessed: http://whyfiles.news.wisc.edu/020radiation/index.htm 11. Low Level Radiation Health Effects: http://cnts.wpi.edu/_uploads/documents/live/ps41.pdf
EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications
The Effects of Low Dose Radiation, R. Macian, 23.11.06 26/41
