Radia%on and Human Health

Radia%on and Human Health Key Issues in Low Dose Radia%on Exposure for Fukushima Disaster James P. Seward, MD MPP Clinical Professor of Medicine, UCSF Medical Director Lawrence Livermore Na%onal Laboratory November 12, 2012 1

Issues to Discuss Types of Radia%on effects Pathways of exposure Linear no threshold dose model for cancer Radia%on Cancer Epidemiology Thyroid - - Solid Tumors - - Leukemia Health Implica%ons for Workers and Residents 2

Radiation Dose Concepts Adsorbed dose (Gray, Gy) is absorption of radiation energy per unit mass of tissue. 1 Gy = 1 Joule per kilogram Equivalent dose (Sievert, Sv) adjusts for biological damage by different types of ionizing radiation using a quality factor Most exposures in this presentation are: Low Dose (<0.1Gy = 100 mgy) Low Linear Energy Transfer (LLET) radiation γ, β, and X 1 Gy = 1 Sv (I-131,Cs-137, Sr-90) 3

Radioac%vity Becquerel (Bq) = 1 nuclear disintegration/ second (1 Curie = 3.7 x 10E10 Bq) Becquerels from ingestion or inhalation can be converted into equivalent dose using radionuclide, organ, and age conversion factors Example: 100 Bq of CS-137 ingested by an adult = 1.3 E-06 Sv whole body internal dose 4

Natural Background Radia%on Natural background radia0on dose approx 23 msv/year (range 1-10 msv) without known health effects 0.38 msv 2.3 msv 5

Human Contribu%ons to Background Dose 3 msv 6

Lethal, Worker, and Background Doses 7

Environmental Pathways for Radia%on Exposure Internal Dose from radioac%ve materials in the air 8

Response to Radia0on Determinis0c effects : early or late effects that have dose- effect rela0onship, i.e., a threshold dose increase in effects with increasing dose Acute Radia0on Syndrome Skin Burns Cataracts Developmental effects (IQ, microcephaly) Stochas0c effects : long- term random or chance effects - rela0onship, no lower threshold dose for effects Risk of Cancer Heritable Gene0c Defects (observed in lab animal studies not demonstrated in humans) Modified from REAC/TS 9

Approximately 160 Deaths or Illnesses from Acute Radia%on Syndrome among Chernobyl Workers The LD 50 for humans is 3-4 Gy for young adults without medical interven%on. EJH, Radiobiology for the Radiologist, 4 th Edi%on, 10

Determinis%c Effects Skin Burns Threshold 5 Gy Posterior Cataracts Recent Evidence for lower threshold Sterility M>3.5 Gy F >2.5 Gy In Utero Mental Retarda%on Malforma%ons Cardiovascular Increased rates of Stroke and Atherosclero%c Disease

What is the dose response rela%onship for radia%on- induced cancers? Linear No Threshold ( High Energy)._._._ Linear No Threshold (Low Energy) Linear Quadra0c (leukemias) Linear with Threshold Source: BEIR VII 12

Linear No-Threshold Hypothesis (LNT) for Cancer Causation Assumes that cancer risk is propor%onate to dose, no maber how small No threshold for risk best scien%fic assump%on of reality Derived primarily from extrapola%on of studies of high dose rate, high linear transfer radia%on (Hiroshima & Nagasaki, Medical Radia%on Therapy) Intended for radia%on safety standard segng Errs on safe side 13

Human Epidemiology Studies Support Linear Dose Response for solid tumors at doses above 100 msv Es%mated excess life%me risk of radia%on- related cancer mortality 0.04-0.05%/100mSv Japanese cancer mortality risk in unexposed popula%ons 26% (males) and 16% (females) Cancer mortality Risk for male exposed to 100 msv would be ~26.05% Increased Risk for radia%on exposed Infants and Children Some Japanese workers at Fukushima- NPP1 have exceeded 250mSv 14

Low Dose Radia%on cancer effects are not certain in epidemiological studies 80% Hiroshima & Nagasaki survivors exposed to <100mGy Survivor studies show solid tumor dose response over 0 150 mgy range But high dose rate of neutron and gamma Low dose occupa%onal and medical radia%on studies generally nega%ve for cancer increase Occupa%onal: UK, 3- country, Mayak (Russia) Wide uncertain%es Suggest trend for leukemia 15

Human Epidemiology Shows Increased Cancer Risk Above 100 msv Linear No Threshold ( High Energy)._._._ Linear No Threshold Low Energy) Linear Quadra0c (leukemias)? Linear with Threshold 100 msv Modified from: BEIR VII 16

Transmissible Reproduc%ve effects Hereditary gene%c diseases (stochas%c effect) not demonstrated in 30,000 children of Hiroshima and Nagasaki survivors mouse data demonstrate possibility for these effects at >250mSv exposure ra%o of induced to spontaneous muta%ons small at low dose levels Ovaries can repair minor gene%c damage 17

Radiation Damage to Chromosomes Indirect damage Radiation creates highly reactive OH free radicals 75 percent of radiation-caused DNA damage is due to OH free radical. Direct damage DNA molecule is struck by radiation, ionized, resulting in damage.

Chromosome Damage Interchange between two chromosomes forms a chromosome with two centromeres and fragment, followed by replication. 19

Poten%al Biologic Factors with Radia%on Carcinogenesis DNA repair Adapta%on Bystander effects Impacts on suppressor genes Tumor ini%a%on monoclonal hypothesis 20

Chernobyl vs.fukushima Complete meltdown/fire Very high emissions Broad Range of radionuclides No local Iodine prophylaxis Delayed evacua%on Prolonged regional low dose exposure Consump%on of contaminated food and dairy Subsequent collapse of USSR complicates research Limited reactor compromise Fewer emissions narrower range of radionuclides Limited Iodine need unclear? Progressive, but prompt evacua%on miscalcula%on on plume Early restric%ons on food products including dairy and fish Early efforts to begin dose reconstruc%on 21

Thryoid Cancer- - Chernobyl Iodine 131-8 day T 1/2 Thyroid gland Average thyroid dose- children near Chernobyl = 1.4 Gy Over 6000 Cases few fatal Young children highest excess rela%ve risk (ERR) = 11 ERR declines with age at exposure lible risk for adults ERR persists as individuals age 22

Es%mates of Thyroid Equivalent Dose in Japan (WHO Preliminary Assessment) Exposure in most of Fukushima 10-100 msv - - primarily inhala%on - - WHO - Tashiro(2011) Max 35mSv in children - Tokonami(2012) Max 23mSv in children Localized area with 100-200 msv to infants< 1 year old Rest of Japan 1-10 msv- - primarily inges%on Chernobyl data: increased cancer risk >50 msv 23

WHO Preliminary Dose Reconstruc%on Whole Body All Key Radioisotopes High Areas: 10-50 msv effec%ve dose mostly external Lower areas: 1-10 msv effec%ve dose- - - mostly internal 24

Health Concerns for >20,000 Fukushima Workers Exposures (mostly internal) up to 670 msv at beginning of reactor accident (no KI) (INPO Nov. 2011) UNSCEAR Preliminary report: 167 workers exposed over 100mSv (6 >250mSv) Uncertainty of dose measurements No clinically observable effects Psychological impacts Ongoing worker health monitoring needed 25

Interna0onal Commission on Radiological Protec0on Because of the uncertainty on health effects at low doses the Commission judges that it is not appropriate, for the purposes of public health planning, to calculate the hypothe%cal number of cases of cancer that might be associated with very small radia%on doses received by large numbers of people over very long periods of %me. ICRP Pub. 103; 2007 26

Es%mates of Total Cancer Create Controversy Stanford Study (Ten Hoeve and Jacobson: Energy Env. Sci 2012:5 8743-8757) 130 addi%onal fatal cancers worldwide, mostly Japan Wide range 15-1100 cancer deaths Addi%onal 180 (24-1800) non- fatal cancers Uncertain%es in dose es%ma%on, exposure assump%ons, etc. Difficulty in detec%on of small numbers in epidemiological studies 27

Ingested Cesium Radionuclides Principal Source of Long term Radioac%vity uptake Biological half life:~ 110 days in adults ~ 50 children Cs 137 Rad T ½ = 30 years Cs134 Rad T ½ = 2 years Uptake in vegetables, starches (rice) and seafood (fish, seaweed) Marshall Islands (US Nuclear Tests) showed most exposure to be from terrestrial food (effec%ve half life 12-20yrs ) Only 0.1% total human radia%on exposure from marine sources (integrated over 30 years) Effec%ve half life (radiological/biological) in reef fish 9-12 years Japan has recently lowered allowable Cs levels in food, including fish to 100 Bq/kg to keep popula%on dose <1mSv/ yr 29

Ques%ons? 30

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UNCLASSIFIED Background Science Program Cesium-137 is the main contributor to the present-day nuclear testrelated dose for resettled and resettling populations in the Marshall Islands About 85 to 90 % of the dose delivered to islanders from nuclear testrelated fallout contamination in the environment is derived from ingestion of Cesium-137 contained in locally grown foods, and the other 10 to 15 % is due to external exposure from residual Cesium-137 in soil UNCLASSIFIED

Effective dose (Sievert, Sv) weights equivalent dose by tissue-specific factors to create a dose figure that standardizes risk 33

Childhood Thyroid Cancer Incidence Belarus (Children <10 yrs old) Source: UNSCEAR 2008 34

Thyroid Cancer and Chernobyl Papillary Cell type Despite tendency to metastasize, treatable with low mortality 1% Cases will con%nue to accumulate for years to come Based on Chernobyl studies prophylaxis with iodine tablets recommended for an%cipated Iodine 131 dose > 50 msv 35

Other Cancers in regions around Chernobyl (consider latency period ) Leukemia o Expected as early effect based on Atomic Bomb survivor experience especially in children o No definite associa%on with Chernobyl vic%ms o Sugges%ve effect for childhood leukemia in contaminated areas of Russia Breast Cancer and other solid tumors o Several studies, but no clear trend for Breast Cancer o Possible increase in Russian study 36

Health Effects in 600,000 Rescue Workers/ Liquidators at Chernobyl Acute Radia%on Syndrome 28 deaths 1 st year 20+ subsequently 130 illnesses from Acute Radia%on Syndrome Cancer effects No consistent pabern of increase Sugges%on of leukemias and dose- related increases in solid tumors in Russian Studies Increased posterior sub- capsular cataracts at doses lower than previously documented Possible increase in cardiovascular disease 37

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Radia%on Doses around Fukushima appear be much lower than Chernobyl Importance of comple%ng Fukushima Health Survey and reconstruc%ng radia%on dosimetry Differing survey results: Thyroid Government: 1080 children in Iwaki and other prefectures highest dose 35 msv Hirosaki University: 65 people, highest adult 87 msv highest child 47 msv. Whole body Fukushima Prefect. Gov.: 10,468 people, highest 23 msv 39

Cesium a persistent health concern around Fukushima Cs 137 30 year half- life decays by β, γ Biological half life 110 days Behaves like potassium in human body, more heavily concentrated in muscle %ssue Taken up from soil by plants (rice,vegetables) Japan has recently lowered allowable Cs levels in food to 100 Bq/kg to keep popula%on dose <1mSv/yr 40

Implica%ons for Japan Dose reconstruc%on and iden%fica%on of popula%on at risk for thyroid cancer Risk for all cancers likely to be low and difficult to assess epidemiologically Lifespan studies of exposed groups Special aben%on to medical surveillance of plant workers Challenging of regaining trust, targe%ng appropriate services to the right popula%on, maximizing benefit, minimizing harm 41

Typical Doses of Diagnos%c X- Ray Procedures Conven%onal X- ray (chest, bone) 0.02-10 mgy Conven%onal Complex X- rays (GI, IVP) 3-10 mgy Computed Tomography 5-15 mgy Angiography 10-200 mgy with interven%on (stent) 10-300 mgy 42

Cardiovascular disease Increased risk of cardiovascular death from high dose exposure (MI and stroke) in long- term atomic bomb survivors HTN, high cholesterol pa%ents treated with radiotherapy to chest (Hodgkins, breast cancer) Lible evidence of increased risk from occupa%onal studies Possible mechanisms: Microvascular damage Inflamma%on 43

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Increasing Diagnos%c X- Ray 46