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INTERNAL EMITTERS:ARE WE IN THE KNOW?

WILLIAM J BAIRAPRIL 20, 2004

12th Annual J. Newell StannardLecture Series

Sierra Nevada-Northern CaliforniaChapters of Health Physics Society

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INTERNAL EMITTERS:ARE WE IN THE KNOW?

• SOME HISTORY• CURRENT STATE OF KNOWLEDGE• NEEDS• FUTURE PROSPECTS

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WHY INTERNAL EMITTERS?GREATEST SOURCES OF RADIATION EXPOSURE

BACKGROUND RADIONUCLIDESNUCLEAR WASTE (TRANSPORT & STORAGE)POWER REACTORS5000 CONTAMINATED COLD WAR SITESMEDICAL RADIOISOTOPESCONSUMER PRODUCTSRESEARCH & INDUSTRYDISASSEMBLY OF WEAPONSSPACE VEHICLESORPHAN SOURCESTERRORIST ACTIVITIES

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“RADIATION” AS IN THEPUBLIC’S FEAR OF RADIATION

IS SYNONYMOUS WITHINTERNAL EMITTERS

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INTERNAL EMITTERS• ENERGY DISTRIBUTION IS

DEPENDENT UPON BIOKINETIC ANDRADIOLOGICAL PROPERTIES OF THERADIONUCLIDE

• ENERGY IS DISTRIBUTED OVER TIMEAND GENERALLY IS NON-UNIFORM INBODY OR TISSUE

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HANFORD INTERNAL EMITTERCONCERNS IN 1954

• RADIONUCLIDE EMISSIONS– IODINE-131– RUTHENIUM-106 “HOT PARTICLES”

• WORKER EXPOSURES– PLUTONIUM-239 DIOXIDE

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TRANSMUTATION EFFECT

• HYPOTHESIS: CELLULAR DNA DAMAGE OCCURS WHEN

INCORPORATED RADIONUCLIDES SUCHAS 35S DECAYS AND BECOMES ANOTHERELEMENT, 35CL.

• RESULTS: INCONCLUSIVE

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BEAGLE 239PU EXPOSURE

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CURRENT ISSUES HEALTH CLAIMS

• NUCLEAR WORKERS (51,000)“ENERGY EMPLOYEES OCCUPATIONAL ILLNESSCOMPENSATION PROGRAM”:DOSE RECONSTRUCTION & “AT LEAST AS LIKELYAS NOT” GUIDELINES (COMPENSATION)

• DOWN WINDERS (LITIGATION)• WEAPON TESTS FALL-OUT (COMPENSATION)• RADON (MITIGATION)• HOT PARTICLES (LITIGATION)• DEPLETED URANIUM (LITIGATION)

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THE STATES OF KNOWLEDGE

• KNOWN KNOWNSTHINGS WE KNOW WE KNOW

• KNOWN UNKOWNSTHINGS WE KNOW WE DO NOT KNOW

• UNKNOWN UNKNOWNSTHINGS WE DON’T KNOW WE DON’T

KNOW

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THE QUESTION!

HAS THE LARGE MASSOF INFORMATIONGENERATED ON

HEALTH EFFECTS OFINTERNAL EMITTERS

PUT US IN THE KNOW?

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THINGS WE KNOW WE KNOWFROM HUMANS

• CANCERS- HIGH DOSES226-228Ra: RADIUM DIAL PAINTERS- BONE224Ra: ANKYLOSING SPONDILYTICS- BONE232Th: THOROTRAST PATIENTS- LIVERRADON: HARD ROCK MINERS- LUNG131I: MARSHALLESE AND CHERNOBYL- THYROID239Pu: SOVIET WEAPONS WORKERS- LUNG

• BIOKINETICS & DOSIMETRY: NUCLEARMEDICINE & ACCIDENTS

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THINGS WE KNOW WE KNOWFROM RESEARCH*

• ANIMALS: BIOKINETICS, DOSIMETRY &HEALTH EFFECTS– FISSION PRODUCTS– TRANSURANICS– URANIUM– RADON– POLONIUM– HOT PARTICLES

• CELL STUDIES: RADON, Pu, 210Po, 3H, 35s*PNNL, LANL, ANL, UC-DAVIS, ITRI, LBL, U of R, U of UTAH

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KNOWN KNOWNSSUMMARY

• BIOKINETICS & DOSIMETRY: LARGEDATA BASE FROM HUMANS & ANIMALS

• HEALTH EFFECTS: RISK ESTIMATES ATHIGH DOSES FROM HUMANS AND ANIMALS

• CELL & MOLECULAR: MINIMAL DATA BASE

• RADIATION: EFFECTIVE CELL KILLER,POOR MUTAGEN

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THINGS WE KNOW WE DON’TKNOW

• RADIATION CANCERS VS. OTHERCANCERS

• VALIDITY OF HEALTH EFFECTS CLAIMS BYEXPOSED WORKERS & PUBLIC

• NATURAL RADIONUCLIDE EFFECTS

• RADON & SMOKING SYNERGISM

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THINGS WE KNOW WE DON’TKNOW

• MECHANISM OF RADIATION INJURY

• INDIVIDUAL SENSITIVITIES

• SPECIES SENSITIVITIES

• EXTRAPOLATION FROM ANIMALS

• MEASUREMENT OF BODY BURDENS

• THERAPY FOR INTERNAL EMITTERS

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THINGS WE KNOW WE DON’T KNOW BUTPRETEND WE DO KNOW

• DOSE RESPONSES AT LOW DOSESLINEAR NO THRESHOLD THEORY

• HUMAN CANCER RISKS FROMINTERNAL EMITTERSA-BOMB SURVIVOR DATARISKS FROM HIGH DOSE HUMAN CASES

• CRITICAL TARGETS & DOSESBIOKINETIC & DOSE MODELS

• DOSES TO WORKERS & PUBLICDOSE RECONSTRUCTION MODELS

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THINGS WE KNOW WE DON’T KNOW BUTPRETEND WE DO KNOW

• QUANTIFICATION OF TOTAL HEALTHDETRIMENT FROM INTAKES OF INTERNALEMITTERS– COMMITTED EFFECTIVE DOSE

• RADIATION WEIGHTING FACTORS• TISSUE WEIGHTING FACTORS (DERIVED FROM A-

BOMB SURVIVORS + DDREF)– MODELS OF RESP. TRACT, G.I. TRACT, BONE– DOSE COEFFICIENTS

• DOSES FROM RADIOPHARMACEUTICALS– MIRD & ICRP MODELS & DOSE COEFFICIENTS

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THINGS WE DON’T KNOW BUTTHINK WE DO KNOW

VERY LIKELY WE ARE WRONG ABOUTSOME THINGS WE ARE CERTAINABOUT– SENSITIVE CELLS & TISSUES?– DOSE EFFECT RELATIONSHIP AT HIGH

DOSES?– INTERACTION OF RADIATION WITH DNA?

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THINGS WE KNOW BUT LIEABOUT

WHO WOULD DO THIS?SOME EXPERT WITNESSES?SOME ANTI NUCLEAR VOICES?

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THINGS WE DON’T KNOW THATWE DON’T KNOW

• WILL ONLY KNOW IN RETROSPECT• CONSIDER PAST SURPRISES

– MENTAL RETARDATION IN JAPANESE– NO GENETIC EFFECTS IN JAPANESE– LACK OF LEUKEMIA IN CHERNOBYL

PEOPLE– 238PU OXIDE MORE SOLUBLE THAN

239PU OXIDE IN LUNGS

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ARE WE IN THE KNOW?UNCERTAINTIES IN OUR KNOWLEDGE ARE

REFLECTED IN: • CONSERVATISM IN DOSE & RISK MODELS• CONSERVATISM IN RISK PROJECTIONS• CONSERVATIVE STANDARDS• CAVEATS• SCIENTIFIC DEBATES• PUBLICATIONS (INTERNAL EMITTERS- 70%

IN “HEALTH PHYSICS”)• UNRESOLVED HEALTH ISSUES

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PUBLIC ISSUES IMPACTED BYUNCERTAINTIES IN

KNOWLEDGE OF INTERNALEMITTER RISKS

• NUCLEAR WASTE--TRANSPORT &STORAGE

• STAGNATION OF NUCLEAR POWER• CLEAN-UP OF WEAPONS SITES• ORPHAN SOURCES• DIRTY BOMB!

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WHAT IS OUR HOPE FOR BEING“IN THE KNOW”?

• INTERNAL EMITTER RESEARCHPHASED OUT

• NEW MOLECULAR BIOLOGY BEGINS OBJECTIVE:

RESOLVE LOW DOSE AND LOW DOSE-RATE ISSUES

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NEEDS FOR INTERNALEMITTERS

• IMPROVEMENT OF BIOKINETIC AND DOSEMODELS:– ONGOING EFFORT (ICRP, NCRP, LABS, &

UNIVERSITIES)• BASIS FOR EXTRAPOLATION FROM

ANIMALS TO HUMANS:– BEING ADDRESSED BY NCRP

• INTERNAL DECONTAMINATION THERAPY– NO ACTION

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NEEDS FOR INTERNALEMITTERS

• QUANTIFY RISKS AT LOW INTAKES• IDENTIFY SENSITIVE INDIVIDUALS• DISTINGUISH BETWEEN CANCERS

CAUSED BY RADIATION FROM THOSEDUE TO OTHER CAUSES

(POTENTIAL OUTCOMES OF DOE LOW DOSERESEARCH PROGRAM)

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DOE LOW DOSE PROGRAM*(0 TO 10 RADS)

• GOAL: SCIENTIFIC BASIS FOR RADIATIONPROTECTION STANDARDS

• FUNDING: $20M PER YEAR, 10 YEARS• 70 PROJECTS• MAJOR THRUST: CHALLENGE THE LINEAR

NO THRESHOLD HYPOTHESIS• DATA SUGGEST MECHANISM OF ACTION

DOSE DEPENDENT

(* Program Mgr. Dr. A. L. Brookshttp://lowdose.tricity.wsu.edu)

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LINEAR NO-THRESHOLD THEORY

• PRIMARY LESION: DNA DOUBLESTRAND BREAK

• BREAKS ARE IN PROPORTION TODOSE

• RADIATION RISKS ARE ADDITIVE• RISK PER UNIT DOSE IS CONSTANT• NO THRESHOLD DOSE• DOSE DOMINATES BIOLOGICAL

VARIABLES

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ADAPTIVE RESPONSES• PRE-EXPOSURE TO LOW DOSES (1-10 RAD)

REDUCES CHROMOSOMAL DAMAGE BYSUBSEQUENT (WITHIN 5 HRS.) EXPOSURES(~50 RAD)

• OBSERVATIONS: REDUCE– CHROMOSOME ABERRATIONS IN MICE &

HUMANS– CANCER, GENETIC & TERATOGENESIS IN MICE

• NON-LINEAR: SUGGESTS RISK IS LESSTHAN LNT PREDICTS

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GENETIC SUSCEPTIBILITY• SOME INDIVIDUALS MAY BE MORE

SENSITIVE TO RADIATION DAMAGEBECAUSE OF GENETIC DIFFERENCES

• APPLICATION OF NEW GENE SEQUENCINGTECHNOLOGY

• POSSIBLE IDENTIFICATION OF INDIVIDUALSWITH GREATER SENSIVITY TO RADIATION-INDUCED CHANGES IN THEIR GENOME &THUS, TO CANCER

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NORMAL VS. RADIATION INDUCEDMOLECULAR DAMAGE AND

REPAIR

• IF DNA DAMAGE AND REPAIR FORRADIATION ARE SAME AS FOR NORMALDAMAGE AND REPAIR– POSSIBLE EVIDENCE FOR THRESHOLD EFFECT

• IF DNA DAMAGE AND REPAIR FORRADIATION ARE UNIQUE– POSSIBLE EVIDENCE FOR LINEAR RESPONSE

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GENETIC INSTABILITY• EXPRESSION OF CERTAIN

CHROMOSOME ABERRATIONS ANDMUTATIONS CAN OCCUR IN PROGENYOF IRRADIATED CELLS LONG AFTEREXPOSURE TO ALPHA RADIATION

• NON-LINEAR PROCESS

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BYSTANDER EFFECTUNEXPOSED CELLS MAY BE DAMAGED

WHEN ADJACENT CELLS AREEXPOSED TO HIGH LET RADIATIONS– DO IRRADIATED CELLS SEND SIGNALS

TO CAUSE INDIRECT DNA DAMAGE?– GREATER THAN LINEAR EFFECT, BUT

POSSIBLE MITIGATION BY ADAPTIVERESPONSE

– APPLY TO RADON RISKS?

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GENE EXPRESSION

Dose (cGy)

0 10 100 1000

Low DoseGenes

High DoseGenes

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APPLICATION TO INTERNALEMITTERS

• PROSPECTS– LESS UNCERTAINTY IN DOSE & RISK

ESTIMATES– IDENTIFICATION OF HIGH RISK

INDIVIDUALS– IDENTIFICATION OF RADIATION INDUCED

CANCERS– PREDICTION OF HEALTH

CONSEQUENCES

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APPLICATION TO INTERNALEMITTERS

• BENEFITS– ADDRESS HEALTH EFFECTS ISSUES– DECREASE PUBLIC FEAR OF

RADIOACTIVE MATERIALS– GREATER SCIENTIFIC BASIS FOR

STANDARDS & PROTECTION ?INCREASED CONFIDENCE

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SUMMARY & CONCLUSIONS• INTERNAL EMITTERS ARE GREATEST

SOURCES OF RADIATION EXPOSURE

• KNOWLEDGE IS INADEQUATE TO RESOLVECURRENT & FUTURE HEALTH ISSUES

• LOW DOSE PROGRAM HAS POTENTIAL TORESOLVE THESE ISSUES AND IMPACTRADIATION PROTECTION PRACTICES

• KEEP INFORMED