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

Issues to Discuss Types of Radiation effects Pathways of exposure Linear no threshold dose model for cancer Radiation Cancer Epidemiology Thyroid --Solid Tumors --Leukemia Health Implications for Workers and Residents

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)

Radioactivity 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

Natural Background Radiation Natural background radiation dose approx 2 mSv/year (range 1-10 mSv) without known health effects 3 0.38 mSv 2.3 mSv Per NCRP-160 (2009), average dose from nat. background in US is about 3.2 mSv.

Human Contributions to Background Dose 3 mSV

Lethal, Worker, and Background Doses Observable deterministic effects (e.g., beginning of Acute Radiation Syndrome) may occur at around 250 to 500 mSv (25 to 50 rads)

Environmental Pathways for Radiation Exposure Internal Dose from radioactive materials in the air

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

Approximately 160 Deaths or Illnesses from Acute Radiation Syndrome among Chernobyl Workers The LD50 for humans is 3-4 Gy for young adults without medical intervention. EJH, Radiobiology for the Radiologist, 4th Edition,

Posterior Cataracts Recent Evidence for lower threshold Deterministic Effects Posterior Cataracts Recent Evidence for lower threshold Skin Burns Threshold 5 Gy Sterility M>3.5 Gy F >2.5 Gy Cardiovascular Increased rates of Stroke and Atherosclerotic Disease In Utero Mental Retardation Malformations

What is the dose response relationship for radiation-induced cancers? ____ Linear No Threshold ( High Energy) ._._._ Linear No Threshold (Low Energy) _ _ _ _ Linear Quadratic (leukemias) ………… Linear with Threshold Source: BEIR VII

Linear No-Threshold Hypothesis (LNT) for Cancer Causation Assumes that cancer risk is proportionate to dose, no matter how small No threshold for risk—best scientific assumption of reality Derived primarily from extrapolation of studies of high dose rate, high linear transfer radiation (Hiroshima & Nagasaki, Medical Radiation Therapy) Intended for radiation safety standard setting Errs on safe side “There is no safe level of radiation dose” is as meaningful as “There is no safe level of exposure to the sun.”

Human Epidemiology Studies Support Linear Dose Response for solid tumors at doses above 100 mSv Estimated excess lifetime risk of radiation-related cancer mortality 0.04-0.05%/100mSv Japanese cancer mortality risk in unexposed populations 26% (males) and 16% (females) Cancer mortality Risk for male exposed to 100 mSv would be ~26.05% Increased Risk for radiation exposed Infants and Children Some Japanese workers at Fukushima-NPP1 have exceeded 250mSv Need visual Can elim statement about workers if keep worker slide later

Low Dose Radiation 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 occupational and medical radiation studies generally negative for cancer increase Occupational: UK, 3-country, Mayak (Russia) Wide uncertainties Suggest trend for leukemia

Human Epidemiology Shows Increased Cancer Risk Above 100 mSv ____ Linear No Threshold ( High Energy) ._._._ Linear No Threshold Low Energy) _ _ _ _ Linear Quadratic (leukemias) ………… Linear with Threshold ? ∧ ∧ 100 mSv Modified from: BEIR VII

Transmissible Reproductive effects Hereditary genetic diseases (stochastic effect) not demonstrated in 30,000 children of Hiroshima and Nagasaki survivors mouse data demonstrate possibility for these effects at >250mSv exposure ratio of induced to spontaneous mutations small at low dose levels Ovaries can repair minor genetic damage

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.

Potential Biologic Factors with Radiation Carcinogenesis DNA repair Adaptation Bystander effects Impacts on suppressor genes Tumor initiation monoclonal hypothesis

Chernobyl vs.Fukushima Complete meltdown/fire Very high emissions Broad Range of radionuclides No local Iodine prophylaxis Delayed evacuation Prolonged regional low dose exposure Consumption 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 evacuation—miscalculation on plume Early restrictions on food products including dairy and fish • Early efforts to begin dose reconstruction DIFFERENCE BETWEEN ATOMIC BOMB AND REACTOR - INSTANTANEOUS EXTERNAL RADIATION -REACTOR—GREATER PROPORTION INTERNAL RADIATION ESPECIALLY RADIOIODINE ECONOMIC COLLAPSE OF USSR ADDED MANY COMPLICATIONS TO HEALTH ASSESSMENT AND CONFOUNDING PUBLIC HEALTH ISSUES CURRENTLY CONTAMINATED ZONE FALLS PRIMARILY IN 3 COUNTRIES ( UKRAINE, BELORUS, RUSSIA) AND THAT POSES EXTRA LOGISTICAL DIFFICULTIES FOR LONG TERM EPIDEMIOLOGICAL STUDY OPEN REACTOR CORE AT CHERNOBYL AND PROLONGED FIRE GENERATE GREATER RANGE OF RADIOACTIVE FISSION PRODUCTS

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 relative risk (ERR) = 11 ERR declines with age at exposure little risk for adults ERR persists as individuals age THYROID CANCER FROM CONCENTRATION OF RADIOACTIVE DOSE IN THRYOID. BOTH INHALED AND INGESTED ( MILK/FOOD) RESIDENTS AROUND CHERNOBYL HAD NO WARNING OF RISK FOR SEVERAL DAYS AFTER RELEASES BEGAN IODINE PILLS CAN BLOCK UPTAKE OF IODINE 131, BUT NONE DISTRIBUTED INCREASED # OF CASES OF THYRIOD CANCER BEGAN APPEARING SEVERAL YEARS AFTER INCIDENT NOW > 6000 AND CLIMBING RISK IS VERY AGE DEPENDENT—UNDER 4 YEARS OLD 10 X/GRAY BUT ONLY 2X FOR 20 YEAR OLD. UN Scientific Committee on Effects of Atomic Ratiation concludes that overall there is little evidence for increased risk of thyroid cancer in people exposed as adults.

Estimates of Thyroid Equivalent Dose in Japan (WHO Preliminary Assessment) Exposure in most of Fukushima 10-100 mSv --primarily inhalation --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 ingestion Chernobyl data: increased cancer risk >50 mSv

WHO Preliminary Dose Reconstruction Whole Body—All Key Radioisotopes High Areas: 10-50 mSv effective dose—mostly external Lower areas: 1-10 mSv effective dose---mostly internal

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

International Commission on Radiological Protection “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 hypothetical number of cases of cancer…that might be associated with very small radiation doses received by large numbers of people over very long periods of time.” ICRP Pub. 103; 2007

Estimates of Total Cancer Create Controversy Stanford Study (Ten Hoeve and Jacobson: Energy Env. Sci 2012:5 8743-8757) 130 additional fatal cancers worldwide, mostly Japan Wide range 15-1100 　cancer deaths Additional 180 (24-1800) non-fatal cancers Uncertainties in dose estimation, exposure assumptions, etc. Difficulty in detection of small numbers in epidemiological studies

Ingested Cesium Radionuclides Principal Source of Long term Radioactivity 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 (effective half life 12-20yrs ) Only 0.1% total human radiation exposure from marine sources (integrated over 30 years) Effective 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 population dose <1mSv/yr

Questions?

Background – Science Program UNCLASSIFIED Background – Science Program Cesium-137 is the main contributor to the present-day nuclear test- related dose for resettled and resettling populations in the Marshall Islands About 85 to 90 % of the dose delivered to islanders from nuclear test- related 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

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

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

Other Cancers in regions around Chernobyl (consider latency period…) Leukemia Expected as early effect based on Atomic Bomb survivor experience—especially in children No definite association with Chernobyl victims Suggestive effect for childhood leukemia in contaminated areas of Russia Breast Cancer and other solid tumors Several studies, but no clear trend for Breast Cancer Possible increase in Russian study

Health Effects in 600,000 Rescue Workers/ “Liquidators” at Chernobyl Acute Radiation Syndrome 28 deaths 1st year…20+ subsequently 130 illnesses from Acute Radiation Syndrome Cancer effects—No consistent pattern of increase Suggestion 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

Woods Hole Oceanographic Institute study concluded that doses from Fukushima radionuclides in contaminated fish would be far below doses from naturally occurring radionuclides (mostly Po-210) in same fish.

Radiation Doses around Fukushima appear be much lower than Chernobyl Importance of completing Fukushima Health Survey and reconstructing radiation 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

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 tissue Taken up from soil by plants (rice,vegetables) Japan has recently lowered allowable Cs levels in food to 100 Bq/kg to keep population dose <1mSv/yr

Implications for Japan Dose reconstruction and identification of population at risk for thyroid cancer Risk for all cancers likely to be low and difficult to assess epidemiologically Lifespan studies of exposed groups Special attention to medical surveillance of plant workers Challenging of regaining trust, targeting appropriate services to the right population, maximizing benefit, minimizing harm

Typical Doses of Diagnostic X-Ray Procedures Conventional X-ray (chest, bone) 0.02-10 mGy Conventional Complex X-rays (GI, IVP) 3-10 mGy Computed Tomography 5-15 mGy Angiography 10-200 mGy with intervention (stent) 10-300 mGy

Cardiovascular disease Increased risk of cardiovascular death from high dose exposure (MI and stroke) in long-term atomic bomb survivors HTN, high cholesterol patients treated with radiotherapy to chest (Hodgkins, breast cancer) Little evidence of increased risk from occupational studies Possible mechanisms: Microvascular damage Inflammation

Increasing Diagnostic X-Ray