EPA Radiogenic Cancer Risk Projections for the U.S. Population

1. EPA Radiogenic Cancer Risk Projections for the U.S. Population Michael Boyd Radiation Protection Division U.S. Environmental Protection Agency 2011 OAS Annual Meeting Richmond, VA August 24, 2011

2. EPA’s Risk Estimates • Old “Blue Book” published (1994) • Addendum on uncertainties with some revisions (1999) • FGR-13: radionuclide specific estimates (1999)

3. NAS BEIR VII Rept. (2006) • Co-sponsored by EPA and several other Federal agencies • Developed models for estimating low dose, low-LET radiogenic cancer risk as a function of: • Dose • Cancer site • Sex • Age-at-exposure • Age-at-diagnosis (death) • Developed quantitative uncertainty distributions

4. BEIR VII Treatment of Low Dose Issue Endorsed LNT: “…the balance of evidence from epidemiologic, animal and mechanistic studies tend to favor a simple proportionate relationship at low doses between radiation dose and cancer risk.” Derived a DDREF of 1.5 for solid cancers based on a “Bayesian” analysis of epidemiological and radiobiological data

5. BEIR VII Risk Models • Most models derived from Japanese Life Span Study (LSS) incidence data • Breast and thyroid risks from pooled analyses of medical and LSS cohorts • Most solid cancer risk models were assumed to have the same age and temporal dependency • Two models for most solid cancers, EAR and ERR: • The excess absolute risk (EAR) adds to the baseline cancer incidence or mortality rate • The excess relative risk (ERR) multiplies the baseline cancer rate

6. Cancer Risk Coefficients • Excess absolute risk (EAR): rate of radiogenic cancers per unit dose • Excess relative risk (ERR): fractional increase in cancer rate per unit dose; i.e., radiogenic cancer rate per unit dose divided by baseline rate in the population

7. EPA Modifications and Additions to BEIR VII Approach • Additional cancer sites (bone, kidney, skin) • High-LET (α-particle) risk estimates • Stationary population • Weighted arithmetic mean of ERR & EAR estimates rather than geometric mean • Breast cancer analysis • Risk estimate for prenatal exposures • Expanded uncertainty analysis

8. Risk (Gy-1) from Uniform, Whole-Body Irradiation

9. Age-Dependence of Risk from Whole-Body Irradiation Incidence —— Mortality – – – – Incidence ——— Mortality ———

10. Life-Table CalculationsAge- and Sex-Specific Survival Functions • Life-tablecalculation: corrects for competing causes of death • Survival function, S(a,ae): probability of surviving to age a, conditioned on being alive at age of exposure, ae • r(a,ae) = f(D) g[a,ae,r0(a)] S(a,ae) • Lifetime Attributable Risk due to an exposure at age ae: LAR (ae) = ∑r(a,ae) • Population risk:∑ N(ae) LAR (ae)

11. Stationary Population • Age distribution constant • # births = # deaths, each year • N(a) = N0 S(0,a) • Risk per Gy for (small) acute exposure = that for chronic low dose rate exposure • Stationary population“older” than the U.S. population ===> estimated radiogenic cancer risk is lower

12. Averaging Model Projections • Weighted Arithmetic Mean AM = w(EAR) + (1-w)(ERR) • Weighted Geometric Mean log GM = w log (EAR) + (1-w) log (ERR) • GM ≤ AM • For most sites, BEIR recommended GM and w=0.3, GM = (EAR).3 (ERR).7 Exceptions – Lung (wts. reversed), Thyroid, Breast

13. LAR Projections for Incidence (x10-4 Gy-1)

14. Other Revisions & Extensions to BEIR VII • Thyroid: Model primarily based on NCRP Thyroid Report (NCRP No. 159) • Skin: Model projection for BCC but not included in total incidence estimate • Alpha-particles • For most sites, RBE=20 • For leukemia, RBE=2 • Bone cancer • Model based on studies of patients injected with 224Ra • Low-LET estimate derived assuming that RBE=20

15. Major Sources of Uncertainty • Sampling errors • Transport of risk from the LSS cohort to the U.S. population • DDREF • Age/temporal dependence

16. Uncertainty in Low-Dose “Extrapolation” BEIR VII/EPA implicitly assumes: (1) LQ dose-response: R = α D + βD2 (2) β/α, DDREF same for all solid cancers 95% CI on DDREF then turns out to be ≈ a factor of 2, up or down

17. Uncertainties

18. Other Data Pertaining to Low Dose Risks I. Radiobiology • Experiments indicate novel phenomena not easily reconciled with standard paradigm for radiation carcinogenesis • Adaptive response, bystander effect, genomic instability, etc. • Mostly based on cellular studies, inconsistency among laboratories – significance for human carcinogenesis unclear • May produce increased as well as decreased risks

19. Other Data Pertaining to Low Dose Risks II. Epidemiology • Epidemiological data on cohorts receiving fractionated or chronic exposures show excess risks, generally consistent with a DDREF of about 1. • Fractionated: Multiple fluoroscopies (breast cancer) Scoliosis patients (breast cancer) Tineacapitis patients (thyroid) • Chronic: British nuclear workers (leukemia, solid cancers) Chernobyl liquidators (leukemia) Techa R. Cohort (leukemia, solid cancers) Taiwanese apartment dwellers (leukemia) Semipalatinsk test-site residents (solid cancers)

20. Future Plans • New “Blue Book”: Available on RPD web-site at www.epa.gov/radiation • Addendum on RBE for low energy electrons and photons to be published by ORNL • Important for 3H betas, medical X-rays, & perhaps certain external radionuclide exposure situations • NCRP committee also working on such a report • New Federal Guidance Report on risks from external and internal radionuclide exposures • Replace FGR-13 • Use new risk models in combination with latest ICRP dosimetry