Maximum Likelihood Analysis of Bioassay Data from Long-Term Follow-Up of Two Refractory PuO2 Inhalation Cases

Abstract

The U.S. Transuranium and Uranium Registries' tissue donors 0202 and 0407 are the two most highly exposed of the 18 registrants who were involved in the 1965 plutonium fire accident at a defense nuclear facility. Material released during the fire was well characterized as "high fired" refractory plutonium dioxide with 0.32-μm mass median diameter. The extensive bioassay data from long-term follow-up of these two cases were used to evaluate the applicability of the Human Respiratory Tract Model presented by International Commission on Radiological Protection in Publication 66 and its revision proposed by Gregoratto et al. in order to account for the observed long-term retention of insoluble material in the lungs. The maximum likelihood method was used to calculate the point estimates of intake and tissue doses and to examine the effect of different lung clearance, blood absorption, and systemic models on the goodness-of-fit and estimated dose values. With appropriate adjustments, Gregoratto et al. particle transport model coupled with the customized blood absorption parameters yielded a credible fit to the bioassay data for both cases and predicted the Case 0202 liver and skeletal activities measured postmortem. PuO2 particles produced by the plutonium fire are extremely insoluble. About 1% of this material is absorbed from the respiratory tract relatively rapidly, at a rate of about 1 to 2 d (half-time about 8 to 16 h). The remainder (99%) is absorbed extremely slowly, at a rate of about 5 × 10(-6) d (half-time about 400 y). When considering this situation, it appears that doses to other body organs are negligible in comparison to those to tissues of the respiratory tract. About 96% of the total committed weighted dose equivalent is contributed by the lungs. Doses absorbed by these workers' lungs were high: 3.2 Gy to AI and 6.5 Gy to LNTH for Case 0202 (18 y post-intake) and 3.2 Gy to AI and 55.5 Gy to LNTH for Case 0407 (43 y post-intake). This evaluation supports the Gregoratto et al. proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles.

Application of Markov chain Monte Carlo analysis to biomathematical modeling of respirable dust in US and UK coal miners

“…These distribution estimates provide useful information to further characterize the variability in lung burden predictions in worker populations. The distributions of parameter values estimated in the current analysis are consistent with those reported in other human studies (Gregoratto et al, 2010(Gregoratto et al, , 2011Avtandilashvili et al, 2012), and as such would be expected to provide similar estimates of the long-term retained lung burden at similar exposure conditions.…”

“…This model structure has been shown to improve the estimates of the long-term retained lung burdens of poorly-soluble particles in humans, including those with relatively low inhaled particle exposures (Gregoratto et al, 2010(Gregoratto et al, , 2011Avtandilashvili et al, 2012). This sequestration model also improves the biological basis of the particle retention description in the alveolar region, and increases the parsimony of the model structure and parameters.…”

Application of Bayesian Inference to the Bioassay Data from Long-term Follow-up of Two Refractory PuO2 Inhalation Cases

“…A previous maximum likelihood analysis (Avtandilashvili et al 2012) demonstrated that when implementing HRTM to fit these data, substantial modification of both the structure of the alveolar-interstitial region and the assumed characteristic rates of particle transport to the bronchioles and thoracic lymph nodes was necessary (Fig. 2).…”

“…A detailed description of a plutonium fire accident and case histories of two USTUR tissue donors, 0202 and 0407, were given elsewhere (Avtandilashvili et al 2012).…”

“…In a previous paper (Avtandilashvili et al 2012), the bioassay data from long-term follow-up of two U.S. Transuranium and Uranium Registries (USTUR) tissue donors, 0202 and 0407, involved in a plutonium fire accident at a defense nuclear facility (DNF) were used to examine the applicability of the current ICRP HRTM and its proposed revision to this particular exposure scenario. A maximum likelihood fitting method was applied to these data to obtain single values of the revised particle transport model parameters along with material-specific absorption parameters.…”