Still-births among the offspring of male radiation workers at the Sellafield nuclear reprocessing plant: detailed results and statistical aspects

Summary. This study investigates whether there was evidence of increasing risk of still-birth with increasing paternal exposure to ionizing radiation received during employment at the Sellafield nuclear installation before the child was conceived. A significant positive association is found between the total paternal preconceptional exposure to external ionizing radiation and the risk of still-birth (after adjustment for year of birth, social class, birth order and paternal age, odds ratio at 100 mSv 1.24 (95% confidence interval 1.04–1.45)). A summary of the principal scientific findings of this study has been published in the Lancet . This paper describes in detail the statistical methods that were used in the investigation and presents the results in full.     

Statistical Distributions of Daily Breathing Rates for Narrow Age Groups of Infants and Children

Children may be more susceptible to toxicity from some environmental chemicals than adults. This susceptibility may occur during narrow age periods (windows), which can last from days to years depending on the toxicant. Breathing rates specific to narrow age periods are useful to assess inhalation dose during suspected windows of susceptibility. Because existing breathing rates used in risk assessment are typically for broad age ranges or are based on data not representative of the population, we derived daily breathing rates for narrow age ranges of children designed to be more representative of the current U.S. children's population. These rates were derived using the metabolic conversion method of Layton (1993) and energy intake data adjusted to represent the U.S. population from a relatively recent dietary survey (CSFII 1994–1996, 1998). We calculated conversion factors more specific to children than those previously used. Both nonnormalized (L/day) and normalized (L/kg-day) breathing rates were derived and found comparable to rates derived using energy estimates that are accurate for the individuals sampled but not representative of the population. Estimates of breathing rate variability within a population can be used with stochastic techniques to characterize the range of risk in the population from inhalation exposures. For each age and age-gender group, we present the mean, standard error of the mean, percentiles (50th, 90th, and 95th), geometric mean, standard deviation, 95th percentile, and best-fit parametric models of the breathing rate distributions. The standard errors characterize uncertainty in the parameter estimate, while the percentiles describe the combined interindividual and intra-individual variability of the sampled population. These breathing rates can be used for risk assessment of subchronic and chronic inhalation exposures of narrow age groups of children.     

Bayesian analysis of discrete time warranty data

Summary.  The analysis of warranty claim data, and their use for prediction, has been a topic of active research in recent years. Field data comprising numbers of units returned under guarantee are examined, covering both situations in which the ages of the failed units are known and in which they are not. The latter case poses particular computational problems for likelihood-based methods because of the large number of feasible failure patterns that must be included as contributions to the likelihood function. For prediction of future warranty exposure, which is of central concern to the manufacturer, the Bayesian approach is adopted. For this, Markov chain Monte Carlo methodology is developed.     

Potential exposures and risks from beryllium-containing products.

Beryllium is the strongest of the lightweight metals. Used primarily in military applications prior to the end of the Cold War, beryllium is finding new applications in many commercial products, including computers, telecommunication equipment, and consumer and automotive electronics. The use of beryllium in nondefense consumer applications is of concern because beryllium is toxic. Inhalation of beryllium dust or vapor causes a chronic lung disease in some individuals at concentrations as low as 0.01 microg/m3 in air. As beryllium enters wider commerce, it is prudent to ask what risks this might present to the general public and to workers downstream of the beryllium materials industry. We address this question by evaluating the potential for beryllium exposure from the manufacturing, use, recycle, and disposal of beryllium-containing products. Combining a market study with a qualitative exposure analysis, we determine which beryllium applications and life cycle phases have the largest exposure potential. Our analysis suggests that use and maintenance of the most common types of beryllium-containing products do not result in any obvious exposures of concern, and that maintenance activities result in greater exposures than product use. Product disposal has potential to present significant individual risks, but uncertainties concerning current and future routes of product disposal make it difficult to be definitive. Overall, additional exposure and dose-response data are needed to evaluate both the health significance of many exposure scenarios, and the adequacy of existing regulations to protect workers and the public. Although public exposures to beryllium and public awareness and concern regarding beryllium risks are currently low, beryllium risks have psychometric qualities that may lead to rapidly heightened public concern.     

Dose-Response and Risk Assessment of Airborne Hexavalent Chromium and Lung Cancer Mortality

This study evaluates the dose-response relationship for inhalation exposure to hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate production facility, and provides estimates of the carcinogenic potency. The data were analyzed using relative risk and additive risk dose-response models implemented with both Poisson and Cox regression. Potential confounding by birth cohort and smoking prevalence were also assessed. Lifetime cumulative exposure and highest monthly exposure were the dose metrics evaluated. The estimated lifetime additional risk of lung cancer mortality associated with 45 years of occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was 0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI: 0.00143, 0.00302) for the additive risk model assuming a linear dose response for cumulative exposure with a five-year lag. Extrapolating these findings to a continuous (e.g., environmental) exposure scenario yielded an environmental unit risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for the additive risk model. The relative risk model is preferred because it is more consistent with the expected trend for lung cancer risk with age. Based on statistical tests for exposure-related trend, there was no statistically significant increased lung cancer risk below lifetime cumulative occupational exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average monthly exposure did not exceed the current Permissible Exposure Limit (52 microg/m3). It is acknowledged that this study had limited power to detect increases at these low exposure levels. These cancer potency estimates are comparable to those developed by U.S. regulatory agencies and should be useful for assessing the potential cancer hazard associated with inhaled Cr(VI).     

Exposure Reconstruction for the TCDD-Exposed NIOSH Cohort Using a Concentration- and Age-Dependent Model of Elimination

Recent studies demonstrating a concentration dependence of elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest that previous estimates of exposure for occupationally exposed cohorts may have underestimated actual exposure, resulting in a potential overestimate of the carcinogenic potency of TCDD in humans based on the mortality data for these cohorts. Using a database on U.S. chemical manufacturing workers potentially exposed to TCDD compiled by the National Institute for Occupational Safety and Health (NIOSH), we evaluated the impact of using a concentration- and age-dependent elimination model (CADM) (Aylward et al., 2005) on estimates of serum lipid area under the curve (AUC) for the NIOSH cohort. These data were used previously by Steenland et al. (2001) in combination with a first-order elimination model with an 8.7-year half-life to estimate cumulative serum lipid concentration (equivalent to AUC) for these workers for use in cancer dose-response assessment. Serum lipid TCDD measurements taken in 1988 for a subset of the cohort were combined with the NIOSH job exposure matrix and work histories to estimate dose rates per unit of exposure score. We evaluated the effect of choices in regression model (regression on untransformed vs. ln-transformed data and inclusion of a nonzero regression intercept) as well as the impact of choices of elimination models and parameters on estimated AUCs for the cohort. Central estimates for dose rate parameters derived from the serum-sampled subcohort were applied with the elimination models to time-specific exposure scores for the entire cohort to generate AUC estimates for all cohort members. Use of the CADM resulted in improved model fits to the serum sampling data compared to the first-order models. Dose rates varied by a factor of 50 among different combinations of elimination model, parameter sets, and regression models. Use of a CADM results in increases of up to five-fold in AUC estimates for the more highly exposed members of the cohort compared to estimates obtained using the first-order model with 8.7-year half-life. This degree of variation in the AUC estimates for this cohort would affect substantially the cancer potency estimates derived from the mortality data from this cohort. Such variability and uncertainty in the reconstructed serum lipid AUC estimates for this cohort, depending on elimination model, parameter set, and regression model, have not been described previously and are critical components in evaluating the dose-response data from the occupationally exposed populations.     

A Bayesian Model and Stochastic Exposure (Dose) Estimation for Relative Exposure Risk Comparison Involving Asbestos‐Containing Dropped Ceiling Panel Installation and Maintenance Tasks

Assessing exposures to hazards in order to characterize risk is at the core of occupational hygiene. Our study examined dropped ceiling systems commonly used in schools and commercial buildings and lay‐in ceiling panels that may have contained asbestos prior to the mid to late 1970s. However, most ceiling panels and tiles do not contain asbestos. Since asbestos risk relates to dose, we estimated the distribution of eight‐hour TWA concentrations and one‐year exposures (a one‐year dose equivalent) to asbestos fibers (asbestos f/cc‐years) for five groups of workers who may encounter dropped ceilings: specialists, generalists, maintenance workers, nonprofessional do‐it‐yourself (DIY) persons, and other tradespersons who are bystanders to ceiling work. Concentration data (asbestos f/cc) were obtained through two exposure assessment studies in the field and one chamber study. Bayesian and stochastic models were applied to estimate distributions of eight‐hour TWAs and annual exposures (dose). The eight‐hour TWAs for all work categories were below current and historic occupational exposure limits (OELs). Exposures to asbestos fibers from dropped ceiling work would be categorized as “highly controlled” for maintenance workers and “well controlled” for remaining work categories, according to the American Industrial Hygiene Association exposure control rating system. Annual exposures (dose) were found to be greatest for specialists, followed by maintenance workers, generalists, bystanders, and DIY. On a comparative basis, modeled dose and thus risk from dropped ceilings for all work categories were orders of magnitude lower than published exposures for other sources of banned friable asbestos‐containing building material commonly encountered in construction trades.     

Daily Inhalation Rate and Time‐Activity/Location Pattern in Japanese Preschool Children

Lack of data on daily inhalation rate and activity of children has been an issue in health risk assessment of air pollutants. This study aimed to obtain the daily inhalation rate and intensity and frequency of physical activity in relation to the environment in Japanese preschool children. Children aged four–six years (n= 138) in the suburbs of Tokyo participated in this study, which involved three days' continuous monitoring of physical activity using a tri‐axial accelerometer and parent's completion of a time/location diary during daily life. The estimated three‐day mean daily inhalation rate (body temperature, pressure, saturated with water vapor) was 9.9 ± 1.6 m³/day (0.52 ± 0.09 m³/kg/day). The current daily inhalation rate value of 0.580 m³/kg/day proposed for use in health risk assessment in Japan is confirmed to be valid to calculate central value of inhaled dose of air pollutants in five‐ to six‐year‐old children. However, the 95th percentile daily inhalation rate of 0.83 m³/kg/day based on measurement for five‐year‐old children is recommended to be used to provide an upper bound estimate of exposure that ensure the protection of all five‐ to six‐year‐old children from the health risk of air pollutants. Children spent the majority of their time in sedentary and light level of physical activity (LPA) when indoors, while 85% of their time when outdoors was spent in LPA and moderate‐to‐vigorous physical activity. The results suggest the need to consider variability of minute respiratory ventilation rate according to the environment for more refined short‐term health risk assessment.     

A Tiered Framework for Risk‐Relevant Characterization and Ranking of Chemical Exposures: Applications to the National Children's Study (NCS)

A challenge for large‐scale environmental health investigations such as the National Children's Study (NCS), is characterizing exposures to multiple, co‐occurring chemical agents with varying spatiotemporal concentrations and consequences modulated by biochemical, physiological, behavioral, socioeconomic, and environmental factors. Such investigations can benefit from systematic retrieval, analysis, and integration of diverse extant information on both contaminant patterns and exposure‐relevant factors. This requires development, evaluation, and deployment of informatics methods that support flexible access and analysis of multiattribute data across multiple spatiotemporal scales. A new “Tiered Exposure Ranking” (TiER) framework, developed to support various aspects of risk‐relevant exposure characterization, is described here, with examples demonstrating its application to the NCS. TiER utilizes advances in informatics computational methods, extant database content and availability, and integrative environmental/exposure/biological modeling to support both “discovery‐driven” and “hypothesis‐driven” analyses. “Tier 1” applications focus on “exposomic” pattern recognition for extracting information from multidimensional data sets, whereas second and higher tier applications utilize mechanistic models to develop risk‐relevant exposure metrics for populations and individuals. In this article, “tier 1” applications of TiER explore identification of potentially causative associations among risk factors, for prioritizing further studies, by considering publicly available demographic/socioeconomic, behavioral, and environmental data in relation to two health endpoints (preterm birth and low birth weight). A “tier 2” application develops estimates of pollutant mixture inhalation exposure indices for NCS counties, formulated to support risk characterization for these endpoints. Applications of TiER demonstrate the feasibility of developing risk‐relevant exposure characterizations for pollutants using extant environmental and demographic/socioeconomic data.     

Asset Decommissioning Risk Metrics for Floating Structures in the Gulf of Mexico

Public companies in the United States are required to report standardized values of their proved reserves and asset retirement obligations on an annual basis. When compared, these two measures provide an aggregate indicator of corporate decommissioning risk but, because of their consolidated nature, cannot readily be decomposed at a more granular level. The purpose of this article is to introduce a decommissioning risk metric defined in terms of the ratio of the expected value of an asset's reserves to its expected cost of decommissioning. Asset decommissioning risk (ADR) is more difficult to compute than a consolidated corporate risk measure, but can be used to quantify the decommissioning risk of structures and to perform regional comparisons, and also provides market signals of future decommissioning activity. We formalize two risk metrics for decommissioning and apply the ADR metric to the deepwater Gulf of Mexico (GOM) floater inventory. Deepwater oil and gas structures are expensive to construct, and at the end of their useful life, will be expensive to decommission. The value of proved reserves for the 42 floating structures in the GOM circa January 2013 is estimated to range between $37 and $80 billion for future oil prices between 60 and 120 $/bbl, which is about 10 to 20 times greater than the estimated $4.3 billion to decommission the inventory. Eni's Allegheny and MC Offshore's Jolliet tension leg platforms have ADR metrics less than one and are approaching the end of their useful life. Application of the proposed metrics in the regulatory review of supplemental bonding requirements in the U.S. Outer Continental Shelf is suggested to complement the current suite of financial metrics employed.