ABBREVIATIONS: BEIR = U.S. National Research Council Committee on the Biological Effects of Ionizing Radiations; CD2 = cytodynamic 2-stage; CL = confidence limit; LCM = lung cancer mortality; PY = personyear; RR = relative risk; SE = standard error; WF = U.S. white female; WLM = Working Level Month.
ABSTRACTEcologic U.S. county data suggest negative associations between residential radon exposure and lung cancer mortality (LCM) that are inconsistent with clearly positive ones revealed by individual data on underground miners. If this inconsistency is due to competing effects of induced cell killing vs. mutations in alpharadiation exposed bronchial epithelium, then linear extrapolation from miner data may overestimate typical residential radon risks. To investigate the plausibility of this hypothesis, a biologically based "cytodynamic 2-stage" (CD2) cancer-risk model was fit to combined 1950 to 1954 age-specific person-year data on white females of age 40+ y in 2821 U.S. counties (~90% never-smokers), and on five cohorts of underground miners who never smoked, conditional on a realistic rate of alpha-radiationinduced killing of human lung cells, and on linear-no-threshold dose-response relations for both processes assumed to affect cancer risk (alpha-induced mutations and cell killing). As summarized previously (Bogen, K.T., Hum. Exper. Toxicol. 17:691-6, 1998), a good CD2 fit was obtained that involved biologically plausible parameter values and (without further optimization) also predicted inverse doserate effects observed in the nonsmoking miners. The present paper reports mathematical details of the CD2 model used, as well as additional modeling results involving the same combined data set. The results obtained are consistent with the hypotheses that low-level radon exposure is nonlinearly related to LCM risk, and that current linear no-threshold extrapolation models overestimate LCM risk assoBogen ciated with relatively low residential radon concentrations (< ~200 Bq m -3 ). Testing this hypothesis would require more extensive individual-level epidemiological data relating residential radon exposures to LCM than are currently available.