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DOSE-EFFECT CURVES; DETERMINISTIC AND STOCHASTIC EFFECTS OF RADIATION Module IX.

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Presentation on theme: "DOSE-EFFECT CURVES; DETERMINISTIC AND STOCHASTIC EFFECTS OF RADIATION Module IX."— Presentation transcript:

1 DOSE-EFFECT CURVES; DETERMINISTIC AND STOCHASTIC EFFECTS OF RADIATION Module IX

2 Module Medical IX. 2 Biological effects of radiation in time perspective Time scale Fractions of seconds Seconds Minutes Hours Days Weeks Months Years Decades Generations Effects Energy absorption Changes in biomolecules (DNA, membranes) Biological repair Change of information in cell Cell death Organ Clinical death changes Mutations in a Germ cell Somatic cell Leukaemia or Cancer Hereditary effects

3 Module Medical IX. 3 Radiation effects Radiation effects Early (deterministic only) Local Radiation injury of individual organs: functional and/or morphological changes within hrs-days-weeks Common Acute radiation disease Acute radiation syndrome (LD 50/60 ~ 3.5Sv LD ~ 5 Sv) Late Deterministic (Above D Q, cummul. ) - Rad. Dermatitis - Rad. Cataracta - Teratogenic (D Q,F ~0,1Sv) Stochastic (Probability increases with dose) - tumours, leukaemia - genetic effects

4 Module Medical IX. 4 Det Deterministic (a) and stochastic (b) effects of radiation

5 Module Medical IX. 5 Sources of data on human effects of radiation overexposure Note: * Effects of radiation exposure are not proved in these population groups, but studied recently (M - million)

6 Module Medical IX. 6 Typical dose-effect relationships for deterministic effects in population Typical dose-effect relationships for deterministic effects in population

7 Module Medical IX. 7 Threshold doses for some deterministic effects in the most radiosensitive tissues Bone marrow Depression of 0.5 > 0.4 haematopoesis Testes Temporary sterility 0.3 0.4 Permanent sterility 3.5-6.0 2.0 Tissue and Total dose Annual dose rate received Tissue and Total dose Annual dose rate received effects single brief in highly fractionated or effects single brief in highly fractionated or exposure (Gy) protracted exposure exposure (Gy) protracted exposure for many years (Gy/y) for many years (Gy/y)

8 Module Medical IX. 8 Tissue and Total dose Annual dose rate received in received yearly in Tissue and Total dose Annual dose rate received in received yearly in effects single brief highly fractionated or effects single brief highly fractionated or exposure protracted exposure exposure protracted exposure (Gy) for many years (Gy/y) (Gy) for many years (Gy/y) Threshold doses for some deterministic effects Ovaries Sterility 2.5-6.0 > 0.2 Lens Detectable opacities 2.0 > 0.1 Visual impairment 5.0 > 0.4 (cataract)

9 Module Medical IX. 9 Time of onset of clinical signs of skin injury depending on dose received dose received Symptoms Dose range Time of onset (Gy) (day) (Gy) (day) l Erythema 3-10 14-21 l Epilation >3 14-18 l Dry desquamation 8-12 25-30 l Moist desquamation 15-20 20-28 l Blister formation 15-25 15-25 l Ulceration >20 14-21 l Necrosis >25 >21 Ref.: IAEA-WHO: Diagnosis and Treatment of Radiation Injuries. IAEA Safety Reports Series, No. 2, Vienna, 1998

10 Module Medical IX. 10 Acute radiation syndrome (ARS) l ARS is the most notable deterministic effect of ionizing radiation l Signs and symptoms are not specific for radiation injury but collectively highly characteristic of ARS l Combination of symptoms appears in phases during hours to weeks after exposure - prodromal phase - prodromal phase - latent phase - latent phase - manifest illness - manifest illness - recovery (or death) - recovery (or death) l Extent and severity of symptoms determined by - total radiation dose received - total radiation dose received - how rapidly dose delivered (dose rate) - how rapidly dose delivered (dose rate) - how dose distributed in body (whole vs partial body irradiation) - how dose distributed in body (whole vs partial body irradiation)

11 Module Medical IX. 11 Principle syndromes contributing to death after acute whole body radiation exposure death after acute whole body radiation exposure

12 Module Medical IX. 12 Special deterministic effects Teratogenic effects of radiation

13 Module Medical IX. 13 Frequency of severe mental retardation in prenatally exposed survivors of A-bombing in Hiroshima and Nagasaki % Sv

14 Module Medical IX. 14 Microcephaly: Hiroshima data Foetal dose, mSv %

15 Module Medical IX. 15 Stochastic effects Cancer induction and genetic effects

16 Module Medical IX. 16 Phases of cancer induction and manifestation

17 Module Medical IX. 17 Stochastic Effects of Radiation Exposure l Frequency proportional to dose l No threshold dose l No method for identification of appearance of effect of ionizing radiation in individuals l Increase in occurrence of stochastic effects provable only by epidemiological method

18 Module Medical IX. 18 Stochastic effects of radiation exposure (continued) l Stochastic effects observed in animal experiments l Dose-effect relationship for humans can be studied only in human population groups l Dose-effect relationship in low dose range (below 100 mSv) not yet verified l Extrapolation down to zero excess dose accepted only for radiation protection and safety

19 Module Medical IX. 19 Human data on radiation cancerogenesis

20 Module Medical IX. 20 Latency periods for radiation-induced cancer

21 Module Medical IX. 21 Risk of leukaemia depending on age at exposure to A-bomb

22 Module Medical IX. 22 Age dependency of incidence of leukaemia in British population and radiotherapy patients

23 Module Medical IX. 23 Cancer deaths attributable to A-bomb Cancer deaths attributable to A-bomb In 86 572 survivors of Hiroshima and Nagasaki, 7827 persons died of cancer in 1950-90 Observed ExpectedExcess (%) All tumours 7578 7244 334 (4.4) Leukaemia 249 162 87 (35.0) All cancers 7827 7406 421 (5.4) Ref: Pierce et al, Rad.Res. 146: 1-27, 1996

24 Module Medical IX. 24

25 Module Medical IX. 25 Cancer mortality of nuclear industry workers

26 Module Medical IX. 26 Childhood leukaemia around UK nuclear facilities l STUDY GROUP: 46 000 children (followed till the age of 25 yrs) born to parents working in nuclear industry FINDINGS: 111 cases of acute leukaemia observed, i.e. fewer than expected in a group of this size and age l Study found 3 cases of leukaemia in children of male workers who had received a pre-conceptional exposure of 100 mSv or more l Two of these three cases had already been identified in the 1990 Gardner report (proposed theory that paternal pre-conception radiation leads to increased risk of leukaemia in offspring) l Conclusions No substantial evidence found to support Gardners theory Study did not confirm theory Ref. ICRF, LSHTM & LRF: Nuclear Industry Family Study (NIFS). BMJ, 28-05-1999

27 Module Medical IX. 27 Lifetime mortality in population of all ages from cancer after exposure to low doses * For general public (all age groups) only Summary factor of cancer risk for working population taken to be 400x10 -4 Sv -1 Reference ICRP, Publ. 60, 1991

28 Module Medical IX. 28 Nominal probability coefficients for stochastic radiation effects Ref. ICRP, Publ. 60, 1991

29 Module Medical IX. 29 Genetic radiation damage l Increase of chromosome aberrations in human spermatogonia following radiation exposure of testes has been detected l inheritance of radiation damage in human population (including A-bomb survivors) not yet detected

30 Module Medical IX. 30 Review of topics discussed l Biological effects of radiation in time perspective l Main characteristics of deterministic and stochastic effects l Sources of data on human effects of radiation overexposure l Threshold doses of deterministic effects in the most radiosensitive tissues l Teratogenic effects of radiation: severe mental retardation, microcephaly l Phases of cancer induction l Sources of human data on radiation cancerogenesis (3 groups) l Latency periods of radiation induced cancers (lag 2 & 10 yrs) l Risk of cancer depending on age at exposure (reverse dependence) l Cancer deaths attributable to A-bombs – 5.4% in 40-yr follow up l Cancer mortality studies of nuclear industry workers and offspring – leukaemia probable in workers l Genetic effects of radiation – not proved in human population


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