The Effects of Low Dose Radiationradionucleide.free.fr/Stresseurs/Week_5_Lecture_09... · 2010. 1....

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

The Effects of Low Dose Radiation

Lecture 09. Seminar

Rafael Macian

“Radiation and Radioisotope Applications

EPFL Doctoral Course PY-031

23.11.06


EPFL/PSI

EPFL Doctoral Course PY-031: Radioisotope and Radiation Applications The Effects of Low Dose Radiation, R. Macian, 23.11.06 2/41

Dose Ranges

0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000

0 100 200 300 400 500 600 700 800 900 1000

0 10 20 30 40 50 60 70 80 90 100

0 1 2 3 4 5 6 7 8 9 10

0 0.1 0. 2 0.3 0. 4 0. 5 0.6 0.7 0.8 0. 9 1

0 0.01 0.02 0.03 0.04 0.05 0.0 6 0.0 7 0.08 0.0 9 0.1

(mSievert)

Experimental Radiobiology

Cancer Epidemiology

DOE Low Dose Program

Medical Diagnostics

Regulatory Standards

Total Body Therapy Total Tumor Dose

A-bomb survivors

Significant cancer risk at > 200 mSv

(UNSCEAR)

Human LD50

Typical mission dose on Int. Space Station

Typical annual dose for commercial airline flight crews

Bone (Tc-99m)Thyroid (I-123)

Chest X-ray

Dental X-ray

ICRP Negligible Dose

NRC Dose Limit for Public

Natural background

Site Decommissioning/License Termination

3-Mile Island Ave Ind

Occupational Limit NRC, EPA

EPA Clean-up Standards NRC Clean-up Standards


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.


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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).


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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.


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In-Utero Effects

Production of Malformations

in developing Embryos.

q Teratogenic Agents:

• Physical: Radiation.

• Chemicals: thalidomide.

• Biological: viruses.

q The observed effects depend on the stage of fetal development.

Same as above with lower risk plus possible functional abnormalities).

8-14 (fetal state)

Developmental abnormalities/growth retardation/cancer.

2-7 (organogenesis)

Intrauterine death.0-1 (preimplantation)

EffectWeeks Post Conception


EPFL/PSI


Radiation Risk

Risk relates Exposure to Probability of Biological Effects

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.

4 to 12In-Utero (cancer)

20 to 200In-Utero (all effects)

4 to 20Somatic (cancer)

2 to 4Genetic

Excess Cases per 10000 exposed per rad (10000 man-rad)Effect


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/PSI


Linear No Threshold Model

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.

Conservative Assessment of Risk

Simplification of Risk Estimates


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/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 theyare 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/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”.

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

(Report to Congress on the effects of radiation)


EPFL/PSI


Criticism of Current Practice

q Some regard the LNTM as conservative or even completely wrongfor 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/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/PSI


What do we really know ?.

The adverse health effects versus radiation exposure levels. Large uncertainty as the curve approaches zero radiation levels.


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/PSI


0

5000

10000

15000

20000

25000

No cancer detected

below this level

Occupational exposure

limit

Ave background Population Exposure limit


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/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/PSI


Detectability limits in Radioepidemiology

Number of people in study and control groups

EF

FE

CT

IVE

DO

SE

(mS

v)

510

-110

010

010

110

110

210

210

410

410

310

310

610 710 810 910 1010 1110

CHERNOBYL

DOSES

REGION OF DETECTABILITY

REGION OF UNDETECTABILITY

Theoretical limit of detectability

due to statistical causes

(90% confidence interval)


EPFL/PSI


Cancer Risk Picture

2.0

1.5

1.0

0.5

0.0 0.30.1 0.2 0.4 0.5

Radiation Dose (Sv)

Can

cer

Ris

k

(Bac

kgro

und

is s

how

n a

s 1.

0)

0.0

Background Cancer risk

Modified from BEIR VII, McClellan and Brooks

Background dose/yrBackground dose/yr

Ext

rap

olat

ed R

isk

Exc

ess

Ris

k

Ext

rap

olat

ed R

isk

Exc

ess

Ris

k

Background dose/40 yearsBackground dose/40 years


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/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 forobserved 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/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.


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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-natural-radioactivity/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

The Effects of Low Dose Radiationradionucleide.free.fr/Stresseurs/Week_5_Lecture_09... · 2010. 1....

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