Time-series analyses of air pollution and mortality in the United States: a subsampling approach.

BACKGROUND: Hierarchical Bayesian methods have been used in previous papers to estimate national mean effects of air pollutants on daily deaths in time-series analyses. OBJECTIVES: We obtained maximum likelihood estimates of the common national effects of the criteria pollutants on mortality based on time-series data from ≤ 108 metropolitan areas in the United States. METHODS: We used a subsampling bootstrap procedure to obtain the maximum likelihood estimates and confidence bounds for common national effects of the criteria pollutants, as measured by the percentage increase in daily mortality associated with a unit increase in daily 24-hr mean pollutant concentration on the previous day, while controlling for weather and temporal trends. We considered five pollutants [PM10, ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), and sulfur dioxide (SO2)] in single- and multipollutant analyses. Flexible ambient concentration-response models for the pollutant effects were considered as well. We performed limited sensitivity analyses with different degrees of freedom for time trends. RESULTS: In single-pollutant models, we observed significant associations of daily deaths with all pollutants. The O3 coefficient was highly sensitive to the degree of smoothing of time trends. Among the gases, SO2 and NO2 were most strongly associated with mortality. The flexible ambient concentration-response curve for O3 showed evidence of nonlinearity and a threshold at about 30 ppb. CONCLUSIONS: Differences between the results of our analyses and those reported from using the Bayesian approach suggest that estimates of the quantitative impact of pollutants depend on the choice of statistical approach, although results are not directly comparable because they are based on different data. In addition, the estimate of the O3-mortality coefficient depends on the amount of smoothing of time trends.

Potency factors for risk assessment at Libby, Montana.

We reanalyzed the Libby vermiculite miners' cohort assembled by Sullivan to estimate potency factors for lung cancer, mesothelioma, nonmalignant respiratory disease (NMRD), and all-cause mortality associated with exposure to Libby fibers. Our principal statistical tool for analyses of lung cancer, NMRD, and total mortality in the cohort was the time-dependent proportional hazards model. For mesothelioma, we used an extension of the Peto formula. For a cumulative exposure to Libby fiber of 100 f/mL-yr, our estimates of relative risk (RR) are as follows: lung cancer, RR = 1.12, 95% confidence interval (CI) =[1.06, 1.17]; NMRD, RR = 1.14, 95% CI =[1.09, 1.18]; total mortality, RR = 1.06, 95% CI =[1.04, 1.08]. These estimates were virtually identical when analyses were restricted to the subcohort of workers who were employed for at least one year. For mesothelioma, our estimate of potency is K(M) = 0.5 x 10(-8), 95% CI =[0.3 x 10(-8), 0.8 x 10(-8)]. Finally, we estimated the mortality ratios standardized against the U.S. population for lung cancer, NMRD, and total mortality and obtained estimates that were in good agreement with those reported by Sullivan. The estimated potency factors form the basis for a quantitative risk assessment at Libby.

Pleural and peritoneal mesotheliomas in SEER: age effects and temporal trends, 1973-2005.

We analyzed mesothelioma incidence in the Surveillance, Epidemiology, and End Results (SEER) database over the period 1973-2005 using extensions of the age-period-cohort (APC) models. In these analyses, the usual non-specific age effects of the conventional APC models were replaced by hazard functions derived from two multistage models of carcinogenesis, the Armitage-Doll model and the two-stage clonal expansion (TSCE) model. The extended APC models described the incidence data on pleural and peritoneal mesotheliomas well. After adjustment for temporal trends, the data suggest that the age-specific incidence rates of both pleural and peritoneal mesotheliomas are identical in men and women. Driven largely by birth cohort effects, age-adjusted rates of pleural mesothelioma among men rose from about 7.5 per million person-years in 1973 to about 20 per million person-years in the early 1990s and appear to be stable or declining thereafter. Age-adjusted rates of pleural mesothelioma among women have remained more or less constant at about 2.5 per million person-years over the period 1973-2005. Age-adjusted rates for peritoneal mesothelioma in both men (1.2 per million person-years) and women (0.8 per million person-years) exhibit no temporal trends over the period of the study. We estimate that approximately 94,000 cases of pleural and 15,000 cases of peritoneal mesothelioma will occur in the US over the period 2005-2050.

Combining perfluoroalkane acid exposure levels for risk assessment.

Perfluoroalkane acids are present in biologic samples from >90% of people in the developed world. Because people may be exposed to multiple perfluoroalkane acids, it is reasonable to consider whether the exposure levels of these agents can be combined for risk assessment purposes. To investigate this possibility, we considered whether the literature on perfluoroalkane acids could be used to justify a scaling system analogous to the Toxic Equivalency Factor (TEF) system used for polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans. We evaluated pairs of studies performed with different perfluoroalkane acids in the same species using the same design and found that endpoints for perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorobutanesulfonate (PFBS), and perfluorodecanoic acid (PFDA) could be discordant. We evaluated pairs of rat studies of PFOS, PFOA, and PFBS performed with the same design for which dose-response curves could be modeled for the concordant endpoints, but we were unable to identify a scaling system that gave values consistently within an order of magnitude for the same compounds. Currently available data do not support the combining of exposure levels of perfluoroalkane acids for risk assessment, although re-evaluation after additional data are available is recommended.

Categorization and nomenclature of vitreous silicate wools.

There is substantial interest among government agencies in categorizing fibers for hazard classification purposes, particularly the commercially important synthetic vitreous fibers (e.g., rock wool, slag wool, glass wool, and refractory ceramic fibers). The intent of this categorization is to partition the population of fibers into distinct categories, which are mutually exclusive, collectively exhaustive, easy to understand and implement, and homogeneous with respect to potential biological activity. This paper identifies criteria for categorization, summarizes historical systems for categorization (e.g., by origin, chemistry and structure, physical form and morphology, and application), analyzes the current categorization schemes used by the European Community (EC) and the International Agency for Research on Cancer (IARC), and proposes an improved partitioning method based upon biopersistence/durability. The proposed basis for categorization incorporates the best features of the EC and IARC methods, eliminates some of their inconsistencies, exploits available knowledge of fiber toxicology (much of which was developed in recent years), and is practical to implement.