Long-Term Low Dose Effects of Ionizing Radiation :Long-Term Low Dose Effects of Ionizing Radiation Estimates of Risks


“Low Level” Radiation Exposure :“Low Level” Radiation Exposure Single exposure of 10 rad or less Larger exposures delivered over periods of days or longer (low dose rates)


Slide 8:STOCHASTIC EFFECTS: In low dose ranges—hereditary effects, carcinogenesis. NON-STOCHASTIC EFFECTS: Various somatic effects, including erythema, epilation, cataracts, impaired fertility, etc.


RISKS OF LOW-LEVEL RADIATION EXPOSURE :RISKS OF LOW-LEVEL RADIATION EXPOSURE Genetic Effects Induction of Cancer Effects on the embryo


CANCER INDUCTION :CANCER INDUCTION


GENERAL CONCEPTS :GENERAL CONCEPTS Considerable time may elapse between radiation exposure and cancer development. In human beings the length of this latent period may be 10, 20, 30 or even 40 years.


Variable Radiation Sensitivity :Variable Radiation Sensitivity Cancer can be induced in almost all body tissues but they vary considerably in their sensitivity.


Latent Effects :Latent Effects 4. Whole body exposure produces more solid tumors than leukemias. Solid tumors also have longer latent periods and periods of expression.


Radiation Induced Cancers :Radiation Induced Cancers Cancers induced by radiation are indistinguishable from those that occur spontaneously, hence their existence must be inferred on the basis of statistical excess.


Slide 15:Radiation cancer is difficult to demonstrate at high doses and essentially impossible to quantify at low doses even with large populations.


High Background of “Spontaneous” Cancers :High Background of “Spontaneous” Cancers Reason: The observed number of cancers in the control population is so large with respect to the number of cancers induced by radiation that the radiation effects become undetectable.


DOSE RATE EFFECTS :DOSE RATE EFFECTS


Slide 25:Hall, R.J., Radiobiology for the Radiologist 5th Ed. Lippincott Williams & Williams, Philadelphia, PA 2000, p. 173


Thyroid and Breast Cancers :Thyroid and Breast Cancers The incidence of radiation-induced human breast and thyroid cancer is such that the total cancer risk is greater for women than for men. For other cancers, the risks are about equal.


Example of Linear-, Non-Threshold Estimation of Risks at Low Doses :Example of Linear-, Non-Threshold Estimation of Risks at Low Doses 100 rad to breast  1000 women Observed = 40 cancers Expected [Background] = 22 Excess = 18


Linear Extrapolation of Risk Estimation :Linear Extrapolation of Risk Estimation 100 rad  1000 women  18 cancers 1 rad  100,000 women  18 cancers


Slide 30:LINEAR EXTRAPOLATION OF RISK ESTIMATION 100 rad  1000 women 1 rad  100,000 women   Expected = 22 Expected = 2,200   Excess = 18 Excess = 18   22 vs. 40 2200 vs. 2218 vs. 22


Age Dependency :Age Dependency Age is a major factor in the risk of radiation-induced cancer (breast, lung, and leukemia in A-bomb survivors; in utero irradiation).


Slide 38:R.J. Hall, Radiobiology for the Radiologist 5th ed. Lippincott Williams & Williams, Philadelphia, PA 2000, p. 150


Treatment of Hyperthyroid Disease in Humans with 131I Radioiodine (Na131I) :Treatment of Hyperthyroid Disease in Humans with 131I Radioiodine (Na131I) Thyroid Gland Dose ~ 50-100 Gy No significant increase in thyroid cancer or leukemia compared to “hyperthyroid” control cohort.


EXPRESSION OF RADIOSENSITIVITY :EXPRESSION OF RADIOSENSITIVITY Absolute Risk Breast and thyroid are well ahead of bone marrow and lung Relative Risk The sequence is probably: Thyroid, bone marrow, lung, and breast.


Somatic Effects :Somatic Effects Approximately 450 cancer deaths/million/rem Natural incidence of cancer deaths is 200,000/million


Slide 42:Health Effects of Exposure to Low Levels of Ionizing Radiation – BEIR V National Research Council. National Academy Press, Washington D.C., 1990, P. 357.


Slide 43:Hall, R.J., Radiobiology for the Radiologist 5th Ed. Lippincott Williams & Williams, Philadelphia, PA 2000, p. 157


Slide 44:Health Effects of Exposure to Low Levels of Ionizing Radiation – BEIR V National Research Council, National Academy Press, Washington D.C., 1990, p. 357


The radiation-induced cancers among A-bomb survivors (estimated average radiation dose = 28 rads) was approximately ___ percent of the cancers naturally occurring in that population. :The radiation-induced cancers among A-bomb survivors (estimated average radiation dose = 28 rads) was approximately ___ percent of the cancers naturally occurring in that population. a. 5.1% b. 51% c. 510%


Slide 47:Radiation induced cancer deaths in the Japanese A-Bomb survivor cohort (1950-1990)a,c % Ca’s Radiation Total CA Deathsb Radiation Induced Induced _____________________________________________________ Solid Tumors 7,578 334 4.4% Leukemia 249 87 35% Combined 7,827b 421 5.4% _____________________________________________________ 86,572 individuals are included in the Life Span Study of survivors (whole body dose received by this group was >10 rads with an average dose of 28 rads). By 1991, approximately 38,600 had died; approximately 20% from cancer. Calculations estimate that 1.1% of the deaths in this population resulted from the radiation exposure From UNSCEAR report to the United Nations in 2000.


Earlier Epidemiology Studies :Earlier Epidemiology Studies “[most] of these studies was considered by the Committee to constitute reliable evidence at present for use in risk estimation, for various reasons, including inadequate sample size in some instances, inadequate statistical analysis, and unconfirmed results.” BEIR 1980, p. 138


Populations exposed to very low levels of irradiation :Populations exposed to very low levels of irradiation DOE’s Hanford Facility Portsmouth Naval Nuclear Shipyard Tri-state study of leukemia deaths Utah residents exposed to fallout Project Smoky Three-Mile Island


Project “Smoky” :Project “Smoky” 1957 Nevada atmospheric A-bomb test 3,153 Military personnel Dose estimate – Most under 5 rem Leukemia – Observed 8 cases expected 2-4 cases


BEIR V :BEIR V … the possibility that there may be no risks from exposure comparable to external natural background radiation cannot be ruled out. Page 181


GENETIC MUTATION :GENETIC MUTATION


Estimation of Genetic Effects :Estimation of Genetic Effects Conclusions are largely “mousebound”. How are mouse numbers converted to human numbers? Some evidence of similarity from in vitro studies of imitation and chromosome changes.


Genetic Effects :Genetic Effects Must be estimated on the basis of data from animal experiments because NO Conclusive Human Data Exists.


Effects for Which No Relationship with A-Bomb Exposure Has Been Shown :Effects for Which No Relationship with A-Bomb Exposure Has Been Shown Increased birth defects in the F1 generation. Increased F1 mortality. Infertility. Accelerated aging. Altered immune function. Diseases other than neoplasm.


EFFECTS ON THE EMBRYO :EFFECTS ON THE EMBRYO


Radiation Effects on the Embryo :Radiation Effects on the Embryo Radiation dose Dose-rate Stage of gestation


Classical Triad of Effects of Radiation on the Embryo :Classical Triad of Effects of Radiation on the Embryo Growth retardation Embryonic, fetal or neonatal death Congenital malformation


Slide 68:Hall, R.J., Radiobiology for the Radiologist 5th Ed. Lippincott Williams & Williams, Philadelphia, PA 2000, p. 187


Embryo is Radiosensitive :Embryo is Radiosensitive Embryonic cells have high rates of cell division and cell differentiation. Composed of relatively few cells.


NCRP Report 54, page 6 :NCRP Report 54, page 6 Animal experiments have shown that irradiation during the pre-implantation period generally produces an all-or-none effect, i.e., either very early embryonic death (pre- or immediately post-implantation) is caused, or there is apparent normalcy (including growth rate, fertility, and longevity) of survivors.


Slide 71:Hall, R.J., Radiobiology for the Radiologist 5th Ed. Lippincott Williams & Williams, Philadelphia, PA 2000, p. 187


Radiation and Congenital Malformations :Radiation and Congenital Malformations Radiation produces no unique abnormalities. High rate of spontaneous abnormality (4-6%).


NCRP Report 54, page 7 :NCRP Report 54, page 7 Noting that the excess risk of adverse effects arising from doses below 10 rad probably is not statistically detectable in experiments involving manageable numbers of animals, one must decide on a level above which scheduling is indicated. Doses below 5 rad to the human embryo-fetus are considered by many to represent an acceptable risk when compared to the potential medical benefit of the examination to the patient.


10 Day Rule :10 Day Rule It must be emphasized that both the ICRP and NCRP recommended application of the 10-day rule only to those studies that do not contribute to management of current disease. It, therefore, follows that studies which do contribute to diagnosis or treatment of current disease should be performed in fertile women without regard to stage of the menstrual cycle. The ACR supports the American College of Obstetricians and Gynecologists’ 1977 Guidelines for Diagnostic X-ray Examinations of Fertile Women.


Slide 77:Hall, R.J., Radiobiology for the Radiologist 5th Ed. Lippincott Williams & Williams, Philadelphia, PA 2000, p. 188


Slide 79:Hall, R.J., Radiobiology for the Radiologist 5th Ed. Lippincott Williams & Williams, Philadelphia, PA 2000, p. 187


Slide 80:Health Effects of Exposure to Low Levels of Ionizing Radiation – BEIR V National Research Council. National Academy Press, Washington D.C., 1990, P. 357.


Fetal Irradiation :Fetal Irradiation Therefore, one concludes that from preconception to birth there is no period during which a radiological examination of the lower abdomen and pelvis of a woman of reproductive capacity can be conducted with no risk.