DOSEEFFECT CURVES DETERMINISTIC AND STOCHASTIC EFFECTS OF RADIATION

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

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

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

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

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) Module Medical IX. 5

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

Threshold doses for some deterministic effects in the most radiosensitive tissues Tissue and effects Total dose single brief exposure (Gy) Bone marrow Depression of haematopoesis Annual dose rate received in highly fractionated or protracted exposure for many years (Gy/y) 0. 5 > 0. 4 Temporary sterility 0. 3 0. 4 Permanent sterility 3. 5 -6. 0 2. 0 Testes Module Medical IX. 7

Threshold doses for some deterministic effects Tissue and effects Total dose received in single brief exposure (Gy) Annual dose rate received yearly in highly fractionated or protracted exposure for many years (Gy/y) Ovaries Sterility 2. 5 -6. 0 > 0. 2 Lens Detectable opacities 2. 0 > 0. 1 Visual impairment 5. 0 > 0. 4 (cataract) Module Medical IX. 8

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

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 - latent phase - manifest illness - recovery (or death) l Extent and severity of symptoms determined by - total radiation dose received - how rapidly dose delivered (dose rate) - how dose distributed in body (whole vs partial body irradiation) Module Medical IX. 10

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

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

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

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

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

Phases of cancer induction and manifestation Module Medical IX. 16

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 Module Medical IX. 17

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 m. Sv) not yet verified l Extrapolation down to zero excess dose accepted only for radiation protection and safety Module Medical IX. 18

Human data on radiation cancerogenesis Module Medical IX. 19

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

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

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

Cancer deaths attributable to A-bomb In 86 572 survivors of Hiroshima and Nagasaki, 7827 persons died of cancer in 1950 -90 Observed All tumours 7578 Leukaemia 249 All cancers 7827 Expected 7244 162 7406 Excess (%) 334 (4. 4) 87 (35. 0) 421 (5. 4) Ref: Pierce et al, Rad. Res. 146: 1 -27, 1996 Module Medical IX. 23

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Cancer mortality of nuclear industry workers Module Medical IX. 25

Childhood leukaemia around UK nuclear facilities l l 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 Study found 3 cases of leukaemia in children of male workers who had received a pre-conceptional exposure of 100 m. Sv or more 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) Conclusions n No substantial evidence found to support Gardner’s theory n Study did not confirm theory Ref. ICRF, LSHTM & LRF: Nuclear Industry Family Study (NIFS). BMJ, 28 -05 -1999 Module Medical IX. 26

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 400 x 10 -4 Sv-1 Reference ICRP, Publ. 60, 1991 Module Medical IX. 27

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

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 Module Medical IX. 29

Review of topics discussed l l l Biological effects of radiation in time perspective Main characteristics of deterministic and stochastic effects Sources of data on human effects of radiation overexposure Threshold doses of deterministic effects in the most radiosensitive tissues Teratogenic effects of radiation: severe mental retardation, microcephaly Phases of cancer induction Sources of human data on radiation cancerogenesis (3 groups) Latency periods of radiation induced cancers (lag 2 & 10 yrs) Risk of cancer depending on age at exposure (reverse dependence) Cancer deaths attributable to A-bombs – 5. 4% in 40 -yr follow up Cancer mortality studies of nuclear industry workers and offspring – leukaemia probable in workers Genetic effects of radiation – not proved in human population Module Medical IX. 30